Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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1. Introduction
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The application of nucleic acid therapeutics sometimes requires the transfer of relatively large transgenes. For example, treatment of diseases such as hemophilia A, sickle cell disease, muscular dystrophy, or cystic fibrosis requires the transfer of coding sequences or complex regulatory elements, which can exceed 4.5 kilobases (kb). In general, transgenes are inserted into expression cassettes that can then be incorporated into either viral or nonviral vectors. The vector chosen depends not only on the therapeutic application but also on the size of the expression cassette. The size of the expression cassette depends on the size of the transgene and the requirement of specific regulatory elements necessary for appropriate transgene expression (for example, internal promoters, enhancers, insulators and other regulatory elements). Larger expression cassettes complicate gene therapy applications using viral vectors by
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limiting the types of vectors available due to encapsidation limitations,
increasing the complexity of the transferred nucleic acid sequence, which, for example, can inadvertently introduce splice donor and acceptor sites, and
reducing the titer of viral vector that can be produced.
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Due to these hurdles, gene therapy strategies utilizing large expression cassettes are limited in vector design. One avenue of decreasing the size of transgenes is to genetically engineer minimal complementary DNA (cDNA) cassettes by eliminating regions that encode for non-functional aspects of the encoded protein. For example, the cDNA of human dystrophin, the missing functional gene in Duchenne’s Muscular Dystrophy, is approximately 11 kb. Due to its large size, a truncated functional version termed, mini-dystrophin, is utilized, thereby reducing the transgene size to 6 kb. A similar strategy has also been evaluated for the cDNA encoding factor VIII (FVIII), mutations of which cause hemophilia A. The transgene size has been reduced by eliminating an entire domain, thus reducing the transgene size by >2.5 kb. A second strategy that has been evaluated involves dividing a larger transgene into smaller sub-transgenes that can then be incorporated into separate vectors to be delivered simultaneously. Nonviral gene-delivery systems, on the other hand, are not as constrained by the size of the expression cassette. Despite this advantage, nonviral vectors are currently not widely used because of inefficient gene transfer. However, rapid progress is being made with transposons circumventing limited transfer by capitalizing on their ability to integrate within the genome. For example, the Sleeping Beauty transposon has been used to insert a number of large expression cassettes into the human genome, including the 6.5 kb β-globin expression cassette for the treatment of sickle cell disease. Therefore, these vectors hold much promise for gene therapy applications with large expression cassettes.
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The gene therapy field has a reasonable level of understanding regarding how to transfer and manage some of the larger therapeutic payloads, and excellent progress has been achieved for some diseases. The transfer of the cDNA sequence encoding FVIII incorporates many of the strategies used to transfer large transgene sequences. Therefore, this chapter will focus on the methods developed to transfer the FVIII transgene. But the strategies described in this chapter can be, and have been, used to transfer similarly large nucleic acid sequences. For example, as shown in Figure I, several parameters have been manipulated to achieve safe gene transfer and high level expression. This chapter will describe
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the various gene transfer platforms, such as viral and nonviral gene transfer systems that are available and their likely applications to the transfer of large sequences,
various methods and techniques for modifying large transgene sequences for greater expression, and
the introduction of various accessory sequences, such as internal promoters in viral vectors and the WPRE sequence, both of which may aid in RNA expression and export from the nucleus.
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Because the transfer of the FVIII cDNA sequence has incorporated many of these parameters, it is an excellent model for developing strategies requiring the transfer of large nucleic acid sequences.
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Figure 1.
Schematic of a gene therapy expression cassette.
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The various parameters noted above can potentially be modified in order to achieve efficient gene transfer and expression of large nucleic acid sequences.
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2. Hemophilia A as a disease model for the transfer of large transgenes
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Hemophilia A is an X-linked bleeding disorder attributed to the loss of a functionally secreted FVIII protein. Approximately 1 in every 5,000 males have hemophilia A, equating to approximately 400,000 people across the globe (Doering and Spencer, 2009). The current treatment consists of repetitive prophylactic administration of recombinant or plasma concentrated FVIII as a means of protein replacement. However, this treatment doesn’t alleviate all the symptoms. Chronic joint pain can be experienced regardless of receiving optimal care. In addition, plasma concentrated FVIII historically has resulted in the transmission of blood borne pathogens (HIV, Hepatitis, etc.) to hemophilia patients and has thus, for the most part, been replaced with the administration of recombinant FVIII. Unfortunately, the recombinant form of FVIII is not available to a significant percentage (approximately 75%) of the individuals affected by the disease (Doering and Spencer, 2009). This is mainly due to the expense of treating hemophilia A, which on average can be $250,000 for recombinant FVIII product per year. Recombinant FVIII is costly because it is difficult to make resulting in periodic product shortages. It also has a low half-life in the circulation requiring repetitive multi-weekly administration to achieve prophylaxis. Further complicating the current therapy, some individuals who receive this treatment develop an immunogenic response in the form of neutralizing antibodies against the administered FVIII. These inhibitors make managing a bleeding episode in these individuals extremely complicated. Therefore, new therapeutic approaches are being developed to treat hemophilia A.
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A monogenic disorder, such as hemophilia A, is a prime candidate for gene therapy for a number of reasons. First, the gene responsible for hemophilia A has been isolated and well characterized, which has led to useful preclinical mouse (Bi et al., 1995) and dog models (Kingdon & Hassell, 1981) as well as a newly described sheep model (Porada et al., 2010). Second, the delivery of FVIII is not restricted to certain cell types. In fact, any tissue with exposure to the vasculature is an appropriate cellular target in that FVIII only needs to be secreted into the bloodstream for effectiveness. This makes a gene therapy approach relatively straightforward and achievable. Third, the therapeutic window is large. Only a moderate increase in FVIII (2-5% of normal equating to 2-5ng/ml) is required to be therapeutically effective while levels as high as 150% of normal have not been associated with adverse effects such as thrombosis (VandenDriessche et al., 2001). As a result, a number of viral and nonviral delivery strategies have been postulated.
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2.1. Previous clinical trials
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Three clinical trials to date have been conducted. Each utilized the human cDNA FVIII sequence, but all three differed in the manner whereby the nucleic acid sequence was incorporated into the patients’ cells. The first trial by Roth et al. (2001) admitted six subjects with severe hemophilia A. Dermal fibroblasts were biopsied from each patient from the upper arm, expanded in tissue culture dishes in a laboratory incubator and electroporated (exposed to a voltage shock in order to perturb the cell membrane layer), resulting in the incorporation of the cDNA sequence into the fibroblast cells. After culturing, stably modified clones were selected and implanted into the omentum of each patient. Transient FVIII expression was observed within three of the patients for up to 6 months, with one patient expressing 4 percent of the normal amount of FVIII twelve weeks after implanting the genetically modified cells. However, the levels of FVIII diminished to less than 0.5% of normal a year later. The second trial included eleven subjects (Powell et al., 2003). Four doses (2.8 x 107, 9.2 x 107, 2.2 x 108, and 4.4 x 108 TU/kg) of a retroviral vector based on the Moloney murine leukemia virus (MoMLV) were administered via peripheral vein injection over three consecutive days. No adverse effects were observed throughout the 53 week study. Yet once again only a transient expression of FVIII was achieved. Eight of the patients demonstrated greater than 1% of normal FVIII levels on two or more occasions yet these levels were not sustained throughout the study and could be associated with the administration of exogenous recombinant FVIII. The final trial was performed by GenStar Therapeutics. One patient was injected intravenously with an adenovirus, which contained the full-length human FVIII cDNA. The patient acquired an immune reaction to the virus and the trial was abruptly closed (Berlfein, 2003).
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2.2. The FVIII transgene
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The three clinical trials for hemophilia A used the human FVIII cDNA sequence instead of the wild-type FVIII gene sequence. This is due to the large size of the wild-type FVIII gene. In its entirety, the F8 gene is approximately 180 kilobases (kb) long and is comprised of 26 exons. It is transcribed into a 9010 base pair (bp) transcript with a short 5’ untranslated region (150bp) and a large 3’ untranslated region (1806bp), and a 7056 bp open reading frame the encodes the FVIII protein. The open reading frame of the FVIII transcript is translated into a protein containing a short 19 amino acid signal peptide, which is necessary for cellular excretion, and the 2332 amino acid protein with a distinct domain structure denoted A1-A2-B-A3-C1-C2. The B domain, comprising a total of 907 amino acids, is not found within the functional protein. Instead it contains sequence motifs recognized by both intracellular and extracellular proteases (Bowen, 2002). For example, FVIII is cleaved intracellularly after Golgi processing at two separate arginine residues within the B domain yielding a FVIII heterodimer composed of a heavy chain (A1 and A2 domains, as well as a shortened B domain) and a light chain (A3, C1 and C2 domains) held together by a calcium ion bridge. Further cleavage occurs extracellularly in which thrombin cleavage releases the remainder of the B domain resulting in FVIII activation (Lenting et al., 1998).
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Large transgenes, such as the FVIII transgene, complicate gene therapy applications using viral vectors by
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limiting the types of vectors available due to encapsidation limitations (see Table I) and
The different human cDNA transgene lengths chosen for the clinical trials are a reflection of these limitations. The GenStar Therapeutics trial, unlike the other two trials, utilized an adenovirus which has fewer encapsidation constraints than other viral vectors available for gene transfer. As a result, it was the only trial to utilize the full-length cDNA 7kb sequence. The Powell clinical trial, on the other hand utilized a retrovirus. Although retroviruses have the capability of encapsulating 7kb of exogenous DNA, incorporating a 7kb transgene into a retrovirus results in diminished viral titer making it difficult to achieve a high enough number of viral particles to be effective. Reducing the size of the insert, however, can increase viral titer (Yacoub et al., 2007). For this reason, many groups are using viral vectors and have reduced the size of the cDNA to approximately 4.5 kb. This can be accomplished by removing sequence that encodes the B domain, which has been found to be dispensable for the coagulation activity of FVIII (Toole et al., 1986).
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Table 1.
* A low frequency (up to 10%) of wild-type adeno-associated vectors has been found to integrate within chromosome 19 (Kotin et al., 1990).
Properties of major gene transfer methods used in gene therapy.
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As demonstrated above, the complications associated with the large FVIII transgene has led researchers to find innovative ways to apply gene therapy techniques to the transfer of the FVIII transgene. The following sections will discuss the methods that have been proposed for the pre-clinical testing of gene transfer technologies for FVIII. These methods will be outlined in reference to which vector is being used, since each vector is accompanied with its own set of limitations (Table 1). Both viral and nonviral vectors will be discussed, highlighting the strategies utilized to overcome the limitations experienced due to the use of a large transgene.
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3. Viral vectors
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Within the field of gene therapy, many viral vectors have been considered for the modification of cells, including both nonintegrating and integrating vectors. Nonintegrating vectors, such as the adenoviral and adeno-associated viral vectors, persist within cells extrachromosomally. As nonintegrating viruses, there is the risk that the vector genome will be lost, particularly if the modified cell divides. Yet, adenoviral vectors and adeno-associated viral vectors are appealing in that they efficiently transduce both dividing and non-dividing cells. If non-dividing cells are targeted then it is possible that long term expression can be achieved with these vectors. This quality allows these vectors to be able to target the most likely primary endogenous producers of FVIII, the terminally differentiated non-dividing hepatocytes.
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Since adenoviral vectors are not constrained by insert size, they were among the first to be used as therapeutic gene transfer vectors within clinical trials. However as mentioned previously in reference to the GenStar FVIII clinical trial, systemic administration of adenoviral vectors resulted in acute toxicity (as evidenced by elevation of liver enzymes) as a result of the induction of pro-inflammatory cytokines and chemokines directed against the viral capsid proteins (Aruda, 2006; Brunetti-Pierri et al., 2004; Schnell et al., 2001; Muruve, et al., 1999; Yang et al., 1994). This toxicity can be circumvented if adenoviral vectors are administered neonatally, capitalizing on the immaturity of the immune system during early development. Therefore, adenoviral vectors are now being considered for use within neonates to induce FVIII tolerance. This was recently achieved within hemophilia A mice after intravenous injection of 5 x 1012 vector particles/kg administered at three days of age (Hu et al., 2011). FVIII levels peaked at ~650% of normal on day six, but declined with animal growth as a result of episomal vector loss. Therefore, the single administration of adenoviral vectors within neonates was not able to achieve sustained therapeutic levels of FVIII. However, tolerance to the transgene and viral capsid proteins was achieved as noted by the lack of adverse effects after subsequent vector administration (Hu, 2011). It is worthwhile to note that this therapy could also be beneficial, in the absence of subsequent vector administration, to prevent the development of inhibitors to FVIII which currently complicates protein replacement therapy. In the context of gene therapy for hemophilia A, adenoviral vectors are only being considered for the induction of FVIII tolerance within neonates due to the extensive inflammatory response observed after presentation of the vector to the systemic circulation. This is unfortunate since the vector can withstand the large size of the FVIII transgene as well as any number of regulatory elements used within the field for expression enhancement or safety. Adeno-associated viral vectors, on the other hand, are being extensively evaluated for use within gene therapy.
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3.1. Gene transfer of FVIII with adeno-associated viral vectors
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The adeno-associated viruses are relatively small viruses, composed of a linear single-stranded DNA genome of approximately 4.6 kb. As of 2009, twelve different serotypes have been isolated from both human and non-human primates (a number which is expected to increase), all of which vary in transduction efficiency and tissue tropism (Youjin and Jun, 2009). Serotype 2 (AAV-2) was the first adeno-associated virus to be sequenced and cloned, and was therefore the first serotype to be used within gene transfer studies (Hermonat and Muzyczka, 1984; Laughlin et al., 1983; Samulski et al, 1982). Wild-type AAV-2 was found to encode two large open reading frames, composed of the replication (Rep78, Rep68, Rep52, and Rep40) and capsid genes (VP1, VP2, and VP3). To accommodate transgenes, these genes were removed leaving behind the inverted terminal repeats required for replication and packaging into a viron (Youjin and Jun, 2009). AAV-2 and other AAV serotypes have the ability to efficiently transduce both non-dividing and dividing cells (Hallek et al., 1998). This quality makes modifying hepatocytes in vivo possible, making them a potentially ideal vector for FVIII delivery. In this aspect, hepatocytes have been modified by a number of adeno-associated viral serotypes. For example, AAV-2, after intraportal administration, transferred a canine B domain deleted version of FVIII to liver cells, which resulted in partial phenotypic correction of hemophilia A mice. Although FVIII activity initially peaked to 8% of normal, expression was not sustained, declining to 2% nine months after injection (Sarkar et al., 2003). These findings, although confirmed independently by Jiang et al. (2006), are contradictory to similar preclinical and clinical studies for hemophilia B in which therapeutically effective levels of FIX are sustained over time (Manno et al., 2005 and Schuettrumpt et al., 2005). This is because FIX is a significantly smaller transgene than FVIII with a cDNA of 2.8 kb. This smaller sequence allows for the inclusion of larger regulatory elements (such as liver specific promoters and enhancers) within the adeno-associated viral vector that are not able to be incorporated after the inclusion of the FVIII cDNA sequence. Within the Jiang (2006) and Sarkar (2003) reports, a minipromoter was all that could be incorporated into the AAV-2 vector to promote FVIII expression. Therefore, it was concluded that regulatory elements, that were unable to be included in the AAV-2 vector (due to insert size restraints associated with adeno-associated viral vectors), were required to enhance FVIII expression. A follow up study evaluated additional adeno-associated viral serotypes (AAV-5, AAV-7, and AAV-8) to determine if other serotypes were more efficient at transducing hepatocytes than AAV-2. For the inefficient transfer of large transgenes, it was hypothesized that by increasing hepatocyte transduction, limited expression could be overcome without the inclusion of regulatory expression-enhacement elements. They found that AAV-8 was superior to other serotypes regardless of route of administration (intraportally or intravenously) producing near normal physiological levels of FVIII (0.58 + 0.2 IU/mL) six months post administration at a vector dose of 1 x 1011 vector copies / mouse (Sarkar et al., 2004). A similar comparison was performed by Jiang et al. (2006), comparing four serotypes (AAV-2, AAV-5, AAV-6, and AAV-8), within both mice and dogs. Within mice, transduction efficiency was found to be least with AAV-5 and greatest with AAV-8. However for dogs, no substantial difference was observed among the serotypes. Remarkably though, FVIII expression was sustained in some dogs (2 to 5% of normal) for up to three years, resulting in decreased occurrences of spontaneous bleeds (Jiang et al., 2006). This was a significant contribution to the field being the first multiyear report of therapeutic efficacy and safety within dogs. Albeit, high vector doses of 6 x 1012 and 2.7 x 1013 vector genomes/kilogram were required to yield these subtherapeutic levels of FVIII.
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Despite the phenotypic improvements noted above, the inclusion of regulatory elements to the vector for enhancing the expression of FVIII would have been the simplest way to address the limited hepatocyte transduction that was seen with AAV-2. Yet since adeno-associated viral vectors are restricted in their genetic carrying capacity, other avenues had to be evaluated to overcome this limitation. Some reports show packaging of genomes greater than 5kb within adeno-associated vectors (Alloca et al., 2008 and Grieger and Samulski, 2005). For example, it is reported that an AAV-8 viral vector was produced containing the B domain deleted human FVIII transgene as well as a full length promoter and enhancer, totaling 5.75 kb (Lu, 2008). However, extensive examination within this report as well as by Wu (2010) clearly showed that inserts ranging from 4.7 kb to 8.7 kb result in heterogenous virons of varying genome lengths, typically containing truncations at the 5’ end. Thus, increasing the size of the adeno-associated vector genome leads to the formation of defective viral particles encapsulating incomplete transgene sequences (Dong et al., 1996).
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For these reasons, several groups are attempting to overcome the packaging limitation with the use of two different vectors, one for the heavy chain and one for the light chain of FVIII. This strategy resulted from the demonstration of secretable biologically active FVIII following co-transfection within Chinese hamster ovary cells of two plasmids separating the heavy and light chains (Burke et al, 1986 and Yonemura et al., 1993). Within these cells the two polypeptide chains were able to reconstitute a functional FVIII heterodimer that was secreted into the cellular media. Although this strategy may be unique to hemophilia A gene therapy applications due to the structural properties of the protein, similar strategies could be implemented in other large transgenes. This strategy was first performed in C57BL/6 mice by intraportal administration (Burton et al., 1999). These mice were chosen since this strain does not elicit an immune response to the FVIII transgene, allowing expression to be measured without any contraindications. As a result, greater than physiological levels of FVIII were produced. These results were then extended into the hemophilia A mouse model where therapeutic levels of FVIII were achieved in a dose-dependent manner. High levels of transduction were noted with twelve percent of hepatocytes being modified with both vectors. Complicating the issue, a chain imbalance was noted with a 25 to 100 fold excess of light chain. This was found to be due to inefficient translational or posttranslational processing that could not be circumvented by changing the administration ratio of heavy to light chain vectors (Scallan et al., 2003). When extended to the hemophilia A dog model, only partial phenotypic correction was achieved, irrespective of adeno-associated serotype used. Although only modest levels of FVIII were observed in the dogs (ranging from 1 to 8% of normal), these levels were found to be sustained for at least two years (Sarkar et al., 2006).
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Another strategy used to overcome the inability of adeno-associated vectors to deliver large genes is trans-splicing. Trans-splicing attempts to repair the truncated FVIII mRNA in vivo by delivering the remaining downstream pre-mRNA. Within this strategy, a pre-trans-splicing molecule is delivered by an adeno-associated vector in which complementary mRNA sequences are located at the 5’ end of the molecule designed to be spliced with the preexisting truncated FVIII mRNA due to a strong splice site at the 3’ end. In this way, a shortened version of the transgene can be delivered in vivo to restore the disease phenotype. This method was performed in hemophilia A mice (Chao et al., 2003). Hemophilia A mice were created by inserting a neomycin resistance gene into the sixteenth exon of FVIII (Bi et al., 1995). As a result truncated FVIII mRNA is still expressed within these mice. By delivering a pre-trans-splicing molecule containing complementary sequence to intron 15, a functional FVIII pre-mRNA was spliced together in vivo resulting in phenotypic correction within eight of the ten injected mice.
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Despite these efforts the fact remains that nonintegrating adeno-associated viral vectors are unable to stably transduce cells. Therefore, many groups are focusing on the use of integrating viral vectors such as gamma-retroviral and lentiviral vectors. Lentiviral vectors, such as HIV and SIV, have been analyzed for their use within gene therapy since 1996 in which Naldini and colleagues revealed the ability of these vectors to overcome the need for cell division during transduction. Being able to transduce both dividing and non-dividing cells gives lentiviral vectors the same advantage as adeno-associated viral vectors. For this reason, lentiviral vectors are likely to make up a second generation of therapeutic vectors to be tested in clinical trials.
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3.2. Gene transfer of FVIII with lentiviral vectors
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Stable integration of a transgene can be achieved with integrating viruses, such as gamma-retroviral and lentiviral vectors. However, genomic integration of a viral vector has concerned the gene therapy community because of the possibility of cellular transformation due to integration of the transgene near an oncogene. This process has been termed insertional mutagenesis, and can cause misregulation of oncogene expression, which could subsequently lead to malignancy. Historically, insertional mutagenesis has been debatable due to the lack of data confirming its occurrence. However, recent data has confirmed the possibility of insertional mutagenesis due to retroviruses. First, retroviruses have been found to insert into the genome near promoters of transcriptionally active genes, setting the stage for the disrupted regulation of downstream genes (Wu et al., 2003). Second, direct proof of insertional mutagenesis has been documented in human gene therapy clinical trials for the treatment of severe combined immune deficiency syndrome that used gamma-based retroviruses (Hacein-Bey-Abina et al., 2003). In the initial clinical trials, of the 20 treated children, 5 have developed a T-cell leukemia-like disorder. The cause of the leukemia has been found to be due to integration of the gamma-retrovirus upstream of the oncogene, LMO2. Integration at this site disrupted the regulation of the oncongene increasing the expression of LMO2. The confirmation of insertional mutagenesis with gamma-retroviral vectors halted their use for clinical development for hemophilia. However, no direct evidence for insertional mutagenesis has been documented for recombinant lentiviral-based retroviruses. Instead, lentiviral vectors have been promising vectors for the delivery of the FVIII transgene because, like adeno-associated viral vectors, they are able to transduce both dividing and non-dividing cells, (Naldini et al., 1996) but unlike adeno-associated viral vectors are not as constrained by the size of the transgene. For these reasons, lentiviral vectors are ideal for gene therapy applications aimed for the treatment of hemophilia A.
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The first lentiviral vectors contained all of the viral genes except for the envelope gene (Naldini et al., 1996). Since then numerous safety measures have been taken to ensure the safety of the virus in the unlikely event of generating a replication competent lentivirus. Second generation HIV-based vectors removed 5 of the 9 viral genes, eliminating accessory genes (Quinonez & Sutton 2002). As an added precaution second generation lentiviral vectors have been designed as replication incompetent self-inactivating (SIN) vectors. This has been accomplished by removing 133 bps from the 3’ long terminal repeat (LTR). LTRs flank viral DNA at both the 3’ and 5’ ends and are involved in the integration process (for further discussion refer to Sinn et al., 2005). During the process of integration, the 3’LTR is copied and becomes the 5’LTR in the integrated sequence, which inactivates the integrated 5’LTR. Further safety measures resulted in the third generation lentiviral vectors, in which 2 more viral genes (the tat and the rev genes) were eliminated. To date these third generation lentiviral vectors have been used for gene therapy applications without any adverse complications (Cartier et al., 2010).
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Lentiviral vectors have a carrying capacity of approximately 7kb exogenous DNA. Although still constrained by encapsidation limitations, lentiviruses can be used to shuttle a number of transgenes that are restricted within the adeno-associated viral vector. However, as the insert size increases the viral particles produced (as measured by viral titer) can decrease (Yacoub et al., 2007). This phenomenon has been observed by several laboratories that use the 4.5 kb B domain deleted FVIII transgene. Because of this limitation, focus has been on reducing the insert size within the lentiviral vector. One component of the viral vector, which can be considered to be removed for this purpose, is the woodchuck post-transcriptional regulatory (WPRE) sequence (~ 600bp).
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\n\t\t\t\t\tZufferey et al. (1999) incorporated a WPRE sequence at the 3’ end of the transgene and demonstrated a 2- to 5- fold increase in expression. The enhancement in expression appears to be due to increased export of unspliced mRNA (Zuffery et al., 1999). Viral vectors used for the purpose of gene therapy utilize cDNA sequences, which are not spliced due to vector size constraints and therefore experience limited export of the mRNA. This limited export of unspliced transgene mRNA compounds the low level expression obstacle experienced historically. Thus, the inclusion of either splice donor and acceptor sites or a WPRE sequence appears to be ideal. As a result, the WPRE has routinely been incorporated into viral vectors. However, a recent report showed that the function of WPRE as a transgene expression enhancer may not be as advantageous as previously determined. The enhancement of transgene expression due to a WPRE sequence was found to be dependent on the promoter and cell line used. In general, the WPRE sequence enhances transgene expression, but in some instances no increase and even a decrease in transgene expression is observed. It was concluded that the function of the WPRE is more complex than originally assumed and should be evaluated in conjunction with every transgene (Klein et al., 2006). For this reason, the WPRE was evaluated in the context of an optimized high-expressing FVIII transgene and found to be negligible in regards to transgene expression as assessed by both transcript number and FVIII activity (Johnston et al., 2010). The effects were also negligible in regards to viral transduction. For these reasons, the WPRE can be considered for removal from some lentiviral backbones in order to reduce the insert size.
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To further overcome issues of FVIII expression several bioengineered FVIII constructs have been proposed, many of which target the efficient transport of FVIII from the endoplasmic reticulum to the golgi (Dorner et al., 1987). For example, removal of the B domain, besides shortening transgene length, was also found to be beneficial by increasing mRNA production 20-fold (Meulien et al., 1988). However, efficient secretion of FVIII requires N-linked glycosyl residues found within the B domain. Therefore, retaining these sites within a truncated B domain may be a preferred shortened FVIII construct (Miao et al., 2004). In addition to the above engineering schemes, amino acid substitutions within the A1 domain were incorporated in order to diminish binding to an ER resident protein chaperone, which resulted in enhanced FVIII production (Marquette et al., 1995 and Swaroop et al., 1997). A B domain deleted porcine FVIII transgene was also evaluated revealing a 10 – 14 fold increase in expression compared to a human FVIII transgene (Doering et al., 2002). Its subsequent transfer within hemophilia A mice resulted in high-level FVIII expression that could be sustained even after low-toxicity pretransplantation conditioning (Ide et al., 2007). Together, these studies demonstrated the ability of a high-expressing porcine FVIII construct to function in vivo. A comparison of these transgenes revealed the superiority of the porcine B-domain-deleted FVIII with a 36 to 225-fold increase in FVIII expression (Dooriss et al., 2008). These findings suggested that the current low-level expression obstacle could be eliminated if the sequences that are responsible for the enhanced secretion of porcine FVIII were identified. To accomplish this, human/porcine FVIII chimeras were constructed that revealed sequences within the A1 and A3 domains to be responsible for enhanced secretion of porcine FVIII (Gangadharan et al., 2006). The result was a hybrid human/porcine construct comprising ~ 90% human FVIII, designated HPFVIII, which has been shown to maintain the high-expression characteristics of the porcine sequence. This optimized HPFVIII transgene has recently been used to treat hemophilia A mice, which resulted in therapeutic levels of FVIII being observed after modifying hematopoietic stem cells (HSC) ex vivo with lentiviral vector (Doering et al., 2009). A codon optimized FVIII cDNA also has been reported and shown to enhance expression after in vivo administration to neonatal hemophilia A mice (Ward et al., 2011).
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Reduction in transgene titers due to issues associated with transgene size can be overcome by targeting various cell populations ex vivo then expanding the genetically modified cells. Therefore, despite diminished titer production, preclinical progress has been made with lentiviral vectors encoding the 4.5kb B domain deleted FVIII transgene. And, by targeting specific cells, viral transduction can be optimized and enhanced, which further overcomes the reduction in titer due to transgene size. In addition, ex vivo modification of cells is considered safer than the in vivo delivery of recombinant virus since it eliminates the possible transmission to germline cells, as well as avoiding any systemic toxicity that can result due to direct presentation of the vector particle (Van Damme et al., 2004). Ex vivo modification also eliminates the issue of modifying antigen-presenting cells, possibly eliminating the development of an immune response to the transgene.
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\n\t\t\t\t\tEx vivo gene therapy for hemophilia A has been analyzed within a broad range of cell types (Viiala et al., 2009). Cellular alternatives considered include embryonic stem (ES) cells, bone marrow derived mesenchymal cells, blood outgrowth endothelial cells (BOECs), and HSCs (as discussed previously). Stem cells are a reasonable alternative in that they have unlimited replicative potential and contain the ability to differentiate into a wide range of cells. However, the initial use of stem cells within the field of gene therapy resulted in low expression levels. This was thought to either be due to gene inactivation as a result of extensive differentiation (McIvor, 1987) or an inability to effectively transduce stem cells. Regardless, promising results were published utilizing an inducible system for FVIII within ES cells. However, both ethical and safety concerns have inhibited the continuation of these studies (Kasuda et al., 2008). This is due to the controversy surrounding the generation of ES cells from human embryos, as well as the formation of teratomas which arose from undifferentiated ES cells used for insulin production (Fujikawa et al., 2005). Fortunately, induced pluripotent stem cells (iPS) appear to be comparable to ES cells and have thus been considered to treat monogenic disorders in order to alleviate the ethical concerns surrounding stem cell usage. iPS cells are derived from adult somatic cells which have been reprogrammed to have stem cell characteristics. Significant progress has been made utilizing iPS cell-based therapy for murine hemophilia A (Xu et al., 2009). However, these methods are fairly new and still do not address the potential formation of teratomas. Therefore, many obstacles need to be addressed before this therapy can reach the clinics (for further discussion refer to Liras, 2011). Another cell type, bone marrow derived mesenchymal cells, initially yielded therapeutic levels of FVIII from transduced human mesenchymal cells within immunodeficient mice. Yet FVIII plasma levels deteriorated gradually in spite of the persistence of gene modified cells, suggesting transcriptional repression within this cell type (Van Damme et al., 2004). Human BOECs can be isolated from the peripheral blood of healthy donors and were considered as FVIII gene transfer targets because they express von Willebrand factor (vWF). vWF binds with high affinity to FVIII in the circulation and protects FVIII from degradation and uptake by antigen presenting cells (possibly eliminating the development of an immune response to the transgene) (Dasgupta et al., 2007). Therefore, it was hypothesized that modifying these cells to also express FVIII would result in the secretion of FVIII complexed to vWF, which would result in an increased half-life of FVIII, secreted at sites of injury. After transduction, BOECs expressed high levels of FVIII measured at 1.6 pmol/million cells/24hrs, which lasted for over thirty days in culture. FVIII was found to be stored within the same vesicles as VWF within the BOECs but was not found to be released upon agonist stimulation, unlike vWF. Instead, FVIII appeared to be released in a constitutive manner (van den Biggelaar et al., 2009). When BOECs were implanted into immunocompetent hemophilic mice, FVIII levels were within the therapeutic range for a total of 27 weeks. Afterwards, the levels declined to baseline due to loss of the implanted BOECs (Matsui, et al., 2007). Although a benefit for FVIII secretion with vWF was not directly tested, the proof of concept was shown for the expression of FVIII from BOECs. Another cell target, which has been considered, is skeletal muscle cells. Skeletal muscles cells are an ideal target for in vivo gene transfer in that skeletal muscle cells are terminally differentiated and provide a consistent source of FVIII persisting throughout the lifetime of an individual. For these reasons, Jeon et al. (2010) injected 107 lentiviral particles intramuscularly into the thigh of rats and found plasma FVIII levels to increase slightly above that of control mice for up to 4 weeks before deteriorating. Despite the need for follow up studies in order to achieve therapeutic levels of FVIII with this strategy, the results suggested that the in vivo administration of a lentivirus targeted at skeletal muscle cells may be an effective strategy for the treatment of hemophilia A. Most in vivo strategies, however, are aimed at targeting hepatocytes, the endogenous producer of FVIII. Lentivirus is administered via either the portal vein or intravenously. Unfortunately this strategy in the case of FVIII (a protein with extensive immunogenicity properties), results in the presentation of anti-FVIII antibodies due to the possible transduction of antigen presenting cells. To overcome this, a miRNA sequence was incorporated downstream of the WPRE sequence which would prevent expression within hematopoietic cells (including cells which make up the immune system). This method was found to be very effective in eliminating a FIX immune response (Brown et al., 2007), but alone was unable to do so with FVIII. Instead the FVIII-miRNA lentivirus had to be pseudotyped with the baculovirus envelope glycoprotein GP64, which has been shown to restrict transduction away from hematopoietic stem cells (Schauber et al., 2004). Combined, the miRNA incorporation and the GP64 pseudotyping were able to restrict FVIII expression to the liver, eliminating the presence of inhibitors, while resulting in about 9% of normal levels of FVIII (0.1U/mL), which was sustained in mice for a total of 60 weeks (Matsui, 2011). This study was significant in that it modified the current in vivo lentiviral gene transfer of FVIII making it safer by restricting expression within the liver.
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In contrast to focusing on transferring the missing or malfunctioning gene, constructs that encode proteins that can bypass the missing protein can be used to overcome the difficulties associated with the size of the transgene. In the case of hemophilia A, a smaller gene such as FVII can be used to bypass the need for FVIII. FVII is an extrinsic pathway coagulation factor that along with thromboplastin initiates the blood coagulation proteolytic cleavage cascade and has been shown in a recombinant form to be an alternative treatment for hemophilia A (Jurlander et al., 2001). For these reasons, Ohmori et al. (2008) transduced HSCs ex vivo with a simian immunodeficiency virus (SIV)-based lentiviral vector encoding an activated form of FVII expressed from a platelet specific promoter (the GPIbα promoter). As a result, FVII was found to localize to the cell surface following platelet activation within transplanted FVIII-deficient mice. Due to species-specific interactions, the murine TF was unable to interact with the human form of FVII resulting in unimproved hemophilia conditions within the FVIII-deficient mice. However, when a murine FVII was incorporated into the SIV-based lentiviral vector, the clot time and rate of clot formation were significantly reduced, decreasing the mortality rate after tail clipping (Ohmori et al., 2008). In addition, FVII was recently incorporated into an adeno-associated vector (AAV-8) being able to overcome the encapsidation limitations of the vector due to the shorter size of FVII. Yet it was shown that within hemophilic dogs, large doses of vector were required to be efficacious (Margaritis et al., 2009). Therefore, a bioengineered FVII variant with enhanced intrinsic activity was recently utilized in order to reduce the dose of in vivo administered vector. However, adverse thrombotic effects were observed in treated mice, which limits enthusiasm for this therapy. (Margaritis et al., 2011).
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4. Nonviral vectors
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Unlike viral vectors, nonviral vectors themselves do not risk evoking an immunological response, are less expensive to produce, and are less limited by the size of the transgene. As a result, naked DNA gene transfer was among the first methods to be utilized in a clinical trial for hemophilia A (Roth et al., 2001). However, this strategy results in transient gene expression because of limited uptake by target cells and further limited integration into the genome of these cells (a process that unless further manipulated occurs only randomly through nonhomologous recombination) (Essner et al., 2005). This issue can be overcome by promoting stable integration into the cell’s genome with the use of a transposable element. Transposable elements, although mostly inactive, are found to be littered throughout the human genome (Deininger and Batzer, 2002). In an active form, transposable elements (transposons) have the ability to jump from one location in the genome to another by a “cut-and paste” method through the enzyme transposase, which is encoded within the element. In order for a transposon to be utilized as a gene transfer vehicle, two components must be delivered to the target cell,
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the transgene flanked by inverted repeat/direct repeat elements that are recognized for integration, and
a transposase which can be encoded within the same plasmid or within a second plasmid.
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These plasmids can be taken up into cells after being complexed to a cationic polymer such as polyethylenimine (PEI).
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Although transposons can carry an expansive amount of DNA, transposons are still somewhat limited by insert size. Integration efficiency has been shown to decrease with the size of the transgene (Essner et al., 2005). This is due to both the difficulties in delivering plasmids containing larger inserts as well as the limitations of the transposase. For example, the transposase enzyme associated with the Sleeping Beauty transposon, the most notable nonviral gene-delivery system currently used, is only able to transpose up to 10kb.
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4.1. Gene transfer of FVIII with a transposon
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Transposons have been utilized as a nonviral vector for gene therapy of hemophilia A by a number of groups. The Sleeping Beauty transposon system was engineered from an inactive Tc1-like transposable element found within fish (Ivics et al., 1997). It has since been used to insert a number of large expression cassettes into the human genome, including the 6.5 kb α-globin expression cassette for the treatment of sickle cell disease (Zhu et. al, 2007). For hemophilia A, the Sleeping Beauty transposon/transposase system was utilized by Liu et al. (2006) to express the human B domain deleted FVIII cDNA within endothelial cells. FVIII levels remained at ~12% of normal after intravenous plasmid injection through the temporal vein of neonatal hemophilia A mice. However, the presence of inhibitors to FVIII resulted in only partial phenotypic correction (Liu et al., 2006). In order to circumvent the presence of inhibitors, the Largaespada group tolerized neonatal, one day old, hemophilia A mice to FVIII with a facial vein injection of 0.1U/g of recombinant human FVIII. Eight to twelve weeks later, two high pressure tail vein injections of a Sleeping Beauty transposon were administered. As a result, 16% of normal FVIII levels were seen within these mice at eighty-four days after plasmid injection, which was found to be sustained for 6 months. No inhibitors were detected and an improvement in clotting function was noted (Ohlfest et al., 2005).
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The high-pressure method of delivery is accomplished by injecting a high volume into the systemic circulation (termed hydrodynamic injections). Within the mouse, this results in DNA uptake followed by expression within the liver. Designed to overcome the difficulties of delivering DNA to the nucleus of a cell, high-volume high-pressure injection is not yet applicable for people (Essner et al., 2005). Therefore, other methods of transposon delivery are being explored. One method that is being studied is the cell specific delivery of a transposon by encapsulation within a nanocapsule. A recent report by Kren et al. (2009) utilized a novel dispersion atomization technique to encapsulate the Sleeping Beauty transposon system. The engineered nanocapsule was targeted to liver sinusoidal endothelial cells (LSECs) by coating the capsule with an endogenous ligand for the hyaluronan receptor found on LSECs. Inside the nanocapsule a single plasmid was encapsulated containing both a cis-acting transposase as well as the B domain deleted canine FVIII transgene. Eight-week old hemophilia A mice were injected with 25µg of nanocapsule via tail vein injection. FVIII levels were measurable for a total of 11 months.
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The size limitations of transposons have recently been expanded. Recently, a number of improvements have been made resulting in a hyperactive transposase, which appears to be able to improve transpositional efficiency to transgenes greater than 10kb (Zayed et al., 2004). These improvements will be useful for the transfer of large transgenes and expression cassettes within gene therapy.
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5. Conclusion
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Gene delivery systems are available for the routine delivery of nucleic acid sequences below approximately 3 kb. As the transgene size increases beyond this, the complexity of transferring the larger sequences increases as well. Many systems have been tested for transferring large transgene sequences and some have shown reasonable promise. In general, viral vectors efficiently transfer these larger sequences, but several hurdles hamper gene transfer, namely:
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limitations in the size of genetic material that can be packaged in a viral vector,
the inadvertent introduction of splice donor and acceptor sites, and
reduction of viral titer.
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Therefore, although efficient gene transfer systems are available, and clinical trials have confirmed the usefulness of some systems, there is still a need for improved gene transfer systems for large payloads. Even though optimal systems are not available, several strategies can be used to transfer large nucleic acid sequences. These strategies revolve around manipulating the various components of the expression cassette, specifically
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introducing the sequence into multiple viral or nonviral gene transfer system to determine the best for the specific transgene
modifying the transgene sequence, for example by deleting coding sequences that may not be important to the function of the expressed protein, and
removing various accessory sequences that may not be necessary, or incorporating accessory sequences with optimal expression properties, such as stronger promoter elements.
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The transfer of FVIII is an excellent example of how some of these limitations were overcome. The transgene that encodes FVIII is very large (7kb). Within the context of expressing FVIII for the treatment of hemophilia A, both viral and nonviral vectors have been tested. Viral vectors were first used to provide proof-of-principle that hemophilia A could be treated by gene therapy (VandenDriessche et al., 1999). However, the efficiency of FVIII gene transfer has hampered the progress of developing a gene therapy treatment for hemophilia A. Since then, the FVIII transgene has been truncated from 7kb to 4.5kb by removing the B domain, a non-functional region of the protein. A number of groups have focused on shortening FVIII even further by dividing FVIII into two smaller sub-transgenes, one encoding the heavy chain and another encoding the light chain. Besides focusing on the FVIII transgene itself, other components of the expression cassette have also been evaluated, such as removal of the WPRE sequence and testing of various promoters. Despite these innovative methods, viral vector design is limited, prohibiting the addition of other regulatory or safety sequences. Nonviral vector systems, on the other hand, are not as constrained by the size of the expression cassette. However, these vectors have been historically associated with inefficient and unstable gene transfer. The Sleeping Beauty transposon may be able to circumvent this disadvantage by stably integrating the transgene into the target cell’s genome. Overall, tremendous progress has been made to overcome the limitations associated with large expression cassettes. We now have a reasonable level of understanding, within the gene therapy field, of the limitations of the various gene transfer systems. The ability to transfer larger and more complex genetic expression cassettes will allow for more sophisticated approaches for targeting and treating diseases that currently are not being addressed because of transfer limitations.
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\n\t\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/17710.pdf",chapterXML:"https://mts.intechopen.com/source/xml/17710.xml",downloadPdfUrl:"/chapter/pdf-download/17710",previewPdfUrl:"/chapter/pdf-preview/17710",totalDownloads:2485,totalViews:183,totalCrossrefCites:0,totalDimensionsCites:3,totalAltmetricsMentions:0,impactScore:2,impactScorePercentile:77,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"November 19th 2010",dateReviewed:"April 2nd 2011",datePrePublished:null,datePublished:"June 22nd 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/17710",risUrl:"/chapter/ris/17710",book:{id:"224",slug:"gene-therapy-developments-and-future-perspectives"},signatures:"Jennifer Johnston, Christopher B. Doering and H. Trent Spencer",authors:[{id:"45593",title:"Dr.",name:"H. Trent",middleName:null,surname:"Spencer",fullName:"H. Trent Spencer",slug:"h.-trent-spencer",email:"hspence@emory.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction ",level:"1"},{id:"sec_2",title:"2. Hemophilia A as a disease model for the transfer of large transgenes",level:"1"},{id:"sec_2_2",title:"2.1. Previous clinical trials ",level:"2"},{id:"sec_3_2",title:"2.2. The FVIII transgene",level:"2"},{id:"sec_5",title:"3. Viral vectors",level:"1"},{id:"sec_5_2",title:"3.1. Gene transfer of FVIII with adeno-associated viral vectors",level:"2"},{id:"sec_6_2",title:"3.2. Gene transfer of FVIII with lentiviral vectors",level:"2"},{id:"sec_8",title:"4. Nonviral vectors",level:"1"},{id:"sec_8_2",title:"4.1. Gene transfer of FVIII with a transposon",level:"2"},{id:"sec_10",title:"5. Conclusion ",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\tAllocca, M., Doria, M., Petrillo, M, Colella, P., Garcia-Hoyos, M., Gibbs, D., Kim, S.R., Maguire, A., Rex, T.S., Di Vicino, U., Cutillo, L., Sparrow, J.R., Williams, D.S., Bennett, J., and Auricchio, A. (2008) Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice. Journal of Clinical Investigation, Vol. 118, 0021-9738\n\t\t\t\t\t5\n\t\t\t\t\t118\n\t\t\t\t\t1955\n\t\t\t\t\t1964\n\t\t\t\t\n\t\t\t'},{id:"B2",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAruda\n\t\t\t\t\t\t\tV. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006Toward gene therapy for hemophilia A with novel adenoviral vectors: success and limitations in canine models. Journal of Thrombosis and Haemostasis, 4\n\t\t\t\t\t6June), 1215\n\t\t\t\t\t1217\n\t\t\t\t\t1538-7933\n\t\t\t\t\n\t\t\t'},{id:"B3",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBerlfein\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003Clinical trial update. Hemaware, 8\n\t\t\t\t\t5September), 52\n\t\t\t\t\t53\n\t\t\t\t\n\t\t\t'},{id:"B4",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBi\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLawler\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAntonarakis\n\t\t\t\t\t\t\tS. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHigh\n\t\t\t\t\t\t\tK. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGearhart\n\t\t\t\t\t\t\tJ. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKazazian\n\t\t\t\t\t\t\tH. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A. Nature Genetics, 10\n\t\t\t\t\t1May), 119\n\t\t\t\t\t121\n\t\t\t\t\t1061-4036\n\t\t\t\t\n\t\t\t'},{id:"B5",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tB. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCantore\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAnnoni\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSergi\n\t\t\t\t\t\t\tL. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLombardo\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDella Valle\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tD’Angelo\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNaldini\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. Blood, 110\n\t\t\t\t\t13December), 4144\n\t\t\t\t\t4152\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B6",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrunetti-Pierri\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPalmer\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBeaudet\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarey\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinegold\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNg\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Acute toxicity after high-dose systemic injection of helper-dependent adenoviral vectors into nonhuman primates. Human Gene Therapy, 15\n\t\t\t\t\t1January), 35\n\t\t\t\t\t46\n\t\t\t\t\t1043-0342\n\t\t\t\t\n\t\t\t'},{id:"B7",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurke\n\t\t\t\t\t\t\tR. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPachl\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQuiroga\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosenberg\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHaigwood\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNordfang\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEzban\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1986The functional domains of coagulation factor VIII:C. Journal of Biological Chemistry, 261\n\t\t\t\t\t27September), 12574\n\t\t\t\t\t12578\n\t\t\t\t\t0021-9258\n\t\t\t\t\n\t\t\t'},{id:"B8",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurton\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakai\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColosi\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCunningham\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMitchell\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCouto\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999Coexpression of factor VIII heavy and light chain adeno-associated viral vectors produces biologically active protein. Proceedings of the National Academy of Sciences, 96\n\t\t\t\t\t22October), 12725\n\t\t\t\t\t12730\n\t\t\t\t\t0027-8424\n\t\t\t\t\n\t\t\t'},{id:"B9",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBowen\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002Haemophilia A and haemophilia B: molecular insights. Molecular Pathology, 55\n\t\t\t\t\t1February), 1\n\t\t\t\t\t18\n\t\t\t\t\t1472-4154\n\t\t\t\t\n\t\t\t'},{id:"B10",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCartier\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHacein-Bey-Abina\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVon\n\t\t\t\t\t\t\tKalle. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBougnères\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFischer\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCavazzana-Calvo\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAubourg\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Gene therapy of x-linked adrenoleukodystrophy using hematopoietic stem cells and a lentiviral vector. Bull Acad Natl Med, 194\n\t\t\t\t\t2February), 255\n\t\t\t\t\t264\n\t\t\t\t\t0001-4079\n\t\t\t\t\n\t\t\t'},{id:"B11",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChao\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMansfield\n\t\t\t\t\t\t\tS. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBartel\n\t\t\t\t\t\t\tR. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\thiriyanna\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMitchell\n\t\t\t\t\t\t\tL. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarcia-Blanco\n\t\t\t\t\t\t\tM. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWalsh\n\t\t\t\t\t\t\tC. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing. Nature Medicine, 9\n\t\t\t\t\t8August), 1015\n\t\t\t\t\t1019\n\t\t\t\t\t1078-8956\n\t\t\t\t\n\t\t\t'},{id:"B12",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDasgupta\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRepesse\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBayry\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNavarrete\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWootla\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDelignat\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIrinopoulou\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKamaté\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaint-Remy\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJacquemin\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLenting\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBorel-Derlon\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaveri\n\t\t\t\t\t\t\tS. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLacroix-Desmazes\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007VWF protects FVIII fron endocytosis by dendritic cells and subsequent presentation to immune effectors. Blood, 109\n\t\t\t\t\t2January), 610\n\t\t\t\t\t612\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B13",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDeininger\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBatzer\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002Mammalian Retroelements. Genome Research, 12\n\t\t\t\t\t10October), 1455\n\t\t\t\t\t1465\n\t\t\t\t\t1088-9051\n\t\t\t\t\n\t\t\t'},{id:"B14",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoering\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParker\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHealey\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCraddock\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarrow\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLollar\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002Expression and characterization of recombinant murine FVIII. Journal of Thrombosis and Haemostasis, 88\n\t\t\t\t\t3September), 450\n\t\t\t\t\t458\n\t\t\t\t\t1538-7933\n\t\t\t\t\n\t\t\t'},{id:"B15",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoering\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpencer\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Advancements in gene-transfer based therapy for hemophilia A. Expert Review of Hematology, 2\n\t\t\t\t\t6December), 673\n\t\t\t\t\t683\n\t\t\t\t\t1747-4086\n\t\t\t\t\n\t\t\t'},{id:"B16",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoering\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDenning\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoriss\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGangadharan\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJohnston\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKerstann\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Carty\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpencer\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Directed Engineering of a High-expression chimeric transgene as a strategy for gene therapy of hemophilia A. Molecular Therapy, 17\n\t\t\t\t\t7July), 1145\n\t\t\t\t\t1154\n\t\t\t\t\t1525-0016\n\t\t\t\t\n\t\t\t'},{id:"B17",body:'\n\t\t\t\tDong, J.Y., Fan, P.D., and Frizzell, R.A. (1996) Quantitative analysis of the packaging capacity of recombinant adeno-associated virus. Human Gene Therapy, 1043-0342\n\t\t\t\t\t17\n\t\t\t\t\t7\n\t\t\t\t\t2101\n\t\t\t\t\t2112\n\t\t\t\t\n\t\t\t'},{id:"B18",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDooriss\n\t\t\t\t\t\t\tK. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDenning\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGangadharan\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJavazon\n\t\t\t\t\t\t\tE. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Carty\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpencer\n\t\t\t\t\t\t\tH. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoering\n\t\t\t\t\t\t\tC. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Comparison of factor VIII transgenes bioengineered for improved expression in gene therapy of hemophilia A. Human Gene Therapy, 20\n\t\t\t\t\t5May), 465\n\t\t\t\t\t478\n\t\t\t\t\t1043-0342\n\t\t\t\t\n\t\t\t'},{id:"B19",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDorner\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBole\n\t\t\t\t\t\t\tD. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaufman\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1987The relationship of N-linked glycosylation and heavy chain-binding protein association with the secretion of glycoproteins. Journal of Cell Biology, 105\n\t\t\t\t\t6December), 2665\n\t\t\t\t\t2674\n\t\t\t\t\t0021-9525\n\t\t\t\t\n\t\t\t'},{id:"B20",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEssner\n\t\t\t\t\t\t\tJ. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Ivor\n\t\t\t\t\t\t\tR. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHackett\n\t\t\t\t\t\t\tP. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Awakening gene therapy with Sleeping Beauty transposons. Current Opinion in Pharmacology, 5\n\t\t\t\t\t5October), 513\n\t\t\t\t\t519\n\t\t\t\t\t0000-1471\n\t\t\t\t\n\t\t\t'},{id:"B21",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGangadharan\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParker\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIde\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpencer\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoering\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006High level expression of porcine FVIII from genetically modified bone marrow-derived stem cells. Blood, 107\n\t\t\t\t\t10May) 3859\n\t\t\t\t\t3864\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B22",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrieger\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSamulski\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Packaging capacity of adeno-associated virus serotypes: impact of larger genomes on infectivity and postentry steps. Journal of Virology, 79\n\t\t\t\t\t15August), 9933\n\t\t\t\t\t9944\n\t\t\t\t\t1098-5514\n\t\t\t\t\n\t\t\t'},{id:"B23",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHacein-Bey-Abina\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvon\n\t\t\t\t\t\t\tKalle. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchmidt\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLe Deist\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWulffraat\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Intyre\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRadford\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVilleval\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFraser\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCavazzana-Calvo\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFischer\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. New England Journal of Medicine, 348\n\t\t\t\t\t3January), 255\n\t\t\t\t\t256\n\t\t\t\t\t0028-4793\n\t\t\t\t\n\t\t\t'},{id:"B24",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHallek\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGirod\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBraun-Falco\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWendtner\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBogedain\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHörer\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998Recombinant adeno-associated virus vectors. IDrugs, 1\n\t\t\t\t\t5September), 561\n\t\t\t\t\t573\n\t\t\t\t\t1369-7056\n\t\t\t\t\n\t\t\t'},{id:"B25",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHermonat\n\t\t\t\t\t\t\tP. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuzyczka\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1984Use of adeno-associated virus as a mammalian DNA cloning vector: transduction of neomycin resistance into mammalian tissue cultured cells. Proceedings of the National Academy of Sciences, 81\n\t\t\t\t\t20October), 6466\n\t\t\t\t\t6470\n\t\t\t\t\t0027-8424\n\t\t\t\t\n\t\t\t'},{id:"B26",body:'\n\t\t\t\tHu, C., Clea, R., Suzuki, M., Lee, B., and Lipshutz, G.S. (2011) Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII. Proceedings of the National Academy of Sciences, 0027-8424\n\t\t\t\t\t5\n\t\t\t\t\t108\n\t\t\t\t\t2082\n\t\t\t\t\t2087\n\t\t\t\t\n\t\t\t'},{id:"B27",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIde\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGangadharan\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChiang\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoering\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpencer\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007Hematopoietic stem-cell gene therapy of hemophilia A incorporating a porcine FVIII transgene and nonmyeloablative conditioning regimens. Blood, 110\n\t\t\t\t\t8October), 2855\n\t\t\t\t\t2863\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B28",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIvics\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHackett\n\t\t\t\t\t\t\tP. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPlasterk\n\t\t\t\t\t\t\tR. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIzsvak\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1997Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell, 91\n\t\t\t\t\t4November), 501\n\t\t\t\t\t510\n\t\t\t\t\t0092-8674\n\t\t\t\t\n\t\t\t'},{id:"B29",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJeon\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOh\n\t\t\t\t\t\t\tT. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tO. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tS. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Delivery of Factor VIII gene into skeletal muscle cells using lentiviral vector. Yonsei Medical Journal, 51\n\t\t\t\t\t1January), 52\n\t\t\t\t\t57\n\t\t\t\t\n\t\t\t'},{id:"B30",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJiang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLillicrap\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPatarroyo-White\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQian\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScallan\n\t\t\t\t\t\t\tC. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPowell\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeller\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Murray\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLabelle\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNagy\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVargas\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCouto\n\t\t\t\t\t\t\tL. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPierce\n\t\t\t\t\t\t\tG. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs. Blood, 108\n\t\t\t\t\t1July), 107\n\t\t\t\t\t115\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B31",body:'\n\t\t\t\tJohnston, J.M., Moot, R., Doering, C., and H. Trent Spencer. (2010) Generation of an optimized lentiviral vector encoding a high-expression fVIII transgene for gene therapy of hemophilia A. Proceedings of the 13th Annual American Society of Gene and Cell Therapy Meeting, ABST#230, Washington D.C.\n\t\t\t'},{id:"B32",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJurlander\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThim\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlausen\n\t\t\t\t\t\t\tN. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPersson\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKjalke\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRexen\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJørgensen\n\t\t\t\t\t\t\tT. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tØstergaard\n\t\t\t\t\t\t\tP. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tErhardtsen\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBjørn\n\t\t\t\t\t\t\tS. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001Recombinant activated factor VII (rFVIIa): characterization, manufacturing, and clinical development. Seminars in Thrombosis and Hemostasis, 27\n\t\t\t\t\t4August) 373\n\t\t\t\t\t384\n\t\t\t\t\t0094-6176\n\t\t\t\t\n\t\t\t'},{id:"B33",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKasuda\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKubo\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakurai\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIrion\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhashi\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTatsumi\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakajima\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaito\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHatake\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPipe\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShima\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYoshioka\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Establishment of embryonic stem cells secreting human factor VIII for cell-based treatment of hemophilia A. Journal of Thrombosis and Haemostasis, 6\n\t\t\t\t\t8August), 1352\n\t\t\t\t\t1359\n\t\t\t\t\t1538-7933\n\t\t\t\t\n\t\t\t'},{id:"B34",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKingdon\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHassell\n\t\t\t\t\t\t\tT. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1981Hemophilic dog model for evaluating therapeutic effectiveness of plasma protein fraction. Blood, 58\n\t\t\t\t\t5November), 868\n\t\t\t\t\t872\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B35",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlein\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRuttkowski\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKnapp\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalmons\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGunzburg\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHohenadl\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006WPRE-mediated enhancement of gene expression is promoter and cell line specific. Gene, 372May), 153\n\t\t\t\t\t161\n\t\t\t\t\t0378-1119\n\t\t\t\t\n\t\t\t'},{id:"B36",body:'\n\t\t\t\tKotin, R.M., Siniscalco, M., Samulski, R.J., Zhu, X.D., Hunter, L., Laughlin, C.A., McLaughlin, S., Muzyczka, N., Rocchi, M., and Berns, K.I. (1990) Site-specific integration by adeno-associated virus. Proceedings of the National Academy of Sciences, 0027-8424\n\t\t\t\t\t6\n\t\t\t\t\t87\n\t\t\t\t\t2211\n\t\t\t\t\t2215\n\t\t\t\t\n\t\t\t'},{id:"B37",body:'\n\t\t\t\tKren, B., Unger, G., Sjeklocha, L., Trossen, A., Korman, V., Diethelm-Okita, B., Reding, M., and Steer, C. (2009) Nanocapsule-delivered Sleeping Beauty mediates therapeutic Factor VIII expression in liver sinusoidal endothelial cells of hemophilia A mice. Journal of Clinical Investigation, 0021-9738\n\t\t\t\t\t7\n\t\t\t\t\t119\n\t\t\t\t\t2086\n\t\t\t\t\t2098\n\t\t\t\t\n\t\t\t'},{id:"B38",body:'\n\t\t\t\tKumar, M., Keller, B., Makalou, N., and Sutton, R.E (2001) Systemic determination of the packaging limit of lentiviral vectors. Human Gene Therapy1043-0342\n\t\t\t\t\t15\n\t\t\t\t\t12\n\t\t\t\t\t1893\n\t\t\t\t\t1905\n\t\t\t\t\n\t\t\t'},{id:"B39",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLaughlin\n\t\t\t\t\t\t\tC. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTratschin\n\t\t\t\t\t\t\tJ. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCoon\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarter\n\t\t\t\t\t\t\tB. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1983Cloning of infectious adeno-associated virus genomes in bacterial plasmids. Gene. 23\n\t\t\t\t\t1July), 65\n\t\t\t\t\t73\n\t\t\t\t\t0378-1119\n\t\t\t\t\n\t\t\t'},{id:"B40",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLenging\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan Mourik\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMertens\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998The life cycle of coagulation factor VIII in view of its structure and function. Blood, 92\n\t\t\t\t\t11December), 3983\n\t\t\t\t\t3996\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B41",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiras\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011Induced human pluripotent stem cells and advanced therapies. Future perspectives for the treatment of haemophilia? Thrombosis Research, 10March), 1\n\t\t\t\t\t6\n\t\t\t\t\t0049-3848\n\t\t\t\t\n\t\t\t'},{id:"B42",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMah\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFletcher\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006Sustained FVIII expression and phenotypic correction of hemophilia A in neonatal mice using an endothelial-targeted Sleeping Beauty transposon. Molecular Therapy, 13\n\t\t\t\t\t5May), 1006\n\t\t\t\t\t1015\n\t\t\t\t\t1525-0016\n\t\t\t\t\n\t\t\t'},{id:"B43",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLu\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuack\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSarkar\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXu\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDing\n\t\t\t\t\t\t\tQ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXiao\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Complete correction of hemophilia A with adeno-associated viral vectors containing a full-size expression cassette. Human Gene Therapy, 19\n\t\t\t\t\t6June), 648\n\t\t\t\t\t654\n\t\t\t\t\t1043-0342\n\t\t\t\t\n\t\t\t'},{id:"B44",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tManno\n\t\t\t\t\t\t\tC. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPierce\n\t\t\t\t\t\t\tG. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArruda\n\t\t\t\t\t\t\tV. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGlader\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRagni\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRasko\n\t\t\t\t\t\t\tJ. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOzelo\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHoots\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBlatt\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKonkle\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDake\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaye\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRazavi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZajko\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZehnder\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRustagi\n\t\t\t\t\t\t\tP. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakai\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChew\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLeonard\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWright\n\t\t\t\t\t\t\tJ. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLessard\n\t\t\t\t\t\t\tR. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSommer\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTigges\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSabatino\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuk\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJiang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMingozzi\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCouto\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tErtl\n\t\t\t\t\t\t\tH. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHigh\n\t\t\t\t\t\t\tK. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKay\n\t\t\t\t\t\t\tM. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nature Medicine, 12\n\t\t\t\t\t3March), 342\n\t\t\t\t\t347\n\t\t\t\t\t1078-8956\n\t\t\t\t\n\t\t\t'},{id:"B45",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMargaritis\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRoy\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAljamali\n\t\t\t\t\t\t\tM. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDowney\n\t\t\t\t\t\t\tH. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGiger\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMerricks\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDillow\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEzban\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNichols\n\t\t\t\t\t\t\tT. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHigh\n\t\t\t\t\t\t\tK. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Successful treatment of canine hemophilia by continuous expression of canine FVIIa. Blood, 113\n\t\t\t\t\t16April), 3682\n\t\t\t\t\t3689\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B46",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMargaritis\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRoy\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFaella\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDowney\n\t\t\t\t\t\t\tH. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIvanciu\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPavani\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBunte\n\t\t\t\t\t\t\tR. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHigh\n\t\t\t\t\t\t\tK. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011Catalytic domain modification and viral gene delivery of activated Factor VII confers hemostasis at reduced expression levels and vector doses in vivo. Blood, 118\n\t\t\t\t\t4February), 1\n\t\t\t\t\t22\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B47",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarquette\n\t\t\t\t\t\t\tK. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPittman\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaufman\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995A 110-amino acid region within the A1-domain of coauglation factor VIII inhibits secretion from mammalian cells. Journal of Biological Chemistry, 270\n\t\t\t\t\t17April), 10297\n\t\t\t\t\t10303\n\t\t\t\t\t0021-9258\n\t\t\t\t\n\t\t\t'},{id:"B48",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMatsui\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMasaru\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLabelle\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHegadorn\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAndrews\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHebbel\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGalipeau\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHough\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLillicrap\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007\n\t\t\t\t\tEx vivo gene therapy for hemophilia A that enhances safe delivery and sustained in vivo factor VIII expression from lentivirally engineered endothelial progenitors. Stem Cells, 25\n\t\t\t\t\t10October), 2660\n\t\t\t\t\t2669\n\t\t\t\t\t0000-1066\n\t\t\t\t\n\t\t\t'},{id:"B49",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMatsui\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHegadorn\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOzelo\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurnett\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTuttle\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLabelle\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Ray\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\tP. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNaldini\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHough\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLillicrap\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011A microRNA-regulated and GP64-pseudotyped lentiviral vector mediates stable expression of FVIII in a murine model of hemophilia A. Molecular Therapy, 1February), 1\n\t\t\t\t\t8\n\t\t\t\t\t1525-0016\n\t\t\t\t\n\t\t\t'},{id:"B50",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Ivor\n\t\t\t\t\t\t\tR. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJohnson\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiller\n\t\t\t\t\t\t\tA. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPitts\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilliams\n\t\t\t\t\t\t\tS. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tValerio\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartin\n\t\t\t\t\t\t\tD. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVerma\n\t\t\t\t\t\t\tI. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1987Human purine nucleoside phosphorylase and adenosine deaminase: gene transfer into cultured cells and murine hematopoietic stem cells by using recombinant amphotropic retroviruses. Molecular and Cellular Biology, 7\n\t\t\t\t\t2February), 838\n\t\t\t\t\t846\n\t\t\t\t\t1098-5549\n\t\t\t\t\n\t\t\t'},{id:"B51",body:'\n\t\t\t\tMeulien, P., Faure, T., Mischler, F., Harrer, H., Ulrich, P., Bouderbala, B., Dott, K., Sainte Marie, M., Mazurier, C., Wiesel, M.L., van de Pol, H., Cazenave, J.P., Courtney, M., and Pavirani, A. (1988) A new recombinant procoagulant protein derived from the cDNA encoding human factor VIII. Protein Engineering, 0269-2139\n\t\t\t\t\t4\n\t\t\t\t\t2\n\t\t\t\t\t301\n\t\t\t\t\t306\n\t\t\t\t\n\t\t\t'},{id:"B52",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiao\n\t\t\t\t\t\t\tH. Z.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSirachainan\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPalmer\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKucab\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCunningham\n\t\t\t\t\t\t\tM. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaufman\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPipe\n\t\t\t\t\t\t\tS. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Bioengineering of coagulation factor VIII for improved secretion. Blood, 103\n\t\t\t\t\t9May), 3412\n\t\t\t\t\t3419\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B53",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuruve\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarnes\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStillman\n\t\t\t\t\t\t\tI. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLibermann\n\t\t\t\t\t\t\tT. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999Adenoviral gene therapy leads to rapid induction of multiple chemokines and acute neutrophil-dependent hepatic injury in vivo. Human Gene Therapy, 10\n\t\t\t\t\t6April), 965\n\t\t\t\t\t976\n\t\t\t\t\t1043-0342\n\t\t\t\t\n\t\t\t'},{id:"B54",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNaldini\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBlömer\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGallay\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOry\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMulligan\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVerma\n\t\t\t\t\t\t\tI. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTrono\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1996\n\t\t\t\t\tIn vivo gene delivery and stable transduction of non-dividing cells by a lentiviral vector. Science, 272\n\t\t\t\t\t5259April), 263\n\t\t\t\t\t267\n\t\t\t\t\t0036-8075\n\t\t\t\t\n\t\t\t'},{id:"B55",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhlfest\n\t\t\t\t\t\t\tJ. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrandsen\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFritz\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLobitz\n\t\t\t\t\t\t\tP. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPerkinson\n\t\t\t\t\t\t\tS. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClark\n\t\t\t\t\t\t\tK. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNelsestuen\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKey\n\t\t\t\t\t\t\tN. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Ivor\n\t\t\t\t\t\t\tR. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHacket\n\t\t\t\t\t\t\tP. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLargaespada\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Phenotypic correction and long-term expression of factor VIII in hemophilic mice by immunotolerization and nonviral gene transfer using the Sleeping Beauty transposon system. Blood, 105\n\t\t\t\t\t7April), 2691\n\t\t\t\t\t2698\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B56",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhmori\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIshiwata\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKashiwakura\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMadoiwa\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMitomo\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSuzuki\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHasegawa\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMimuro\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakata\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Phenotypic correction of Hemophilia A by ectopic expression of activated factor VII in platelets. Molecular Therapy,\n\t\t\t\t\t16\n\t\t\t\t\t8August), 1359\n\t\t\t\t\t1365\n\t\t\t\t\t1525-0016\n\t\t\t\t\n\t\t\t'},{id:"B57",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPorada\n\t\t\t\t\t\t\tC. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSanada\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLong\n\t\t\t\t\t\t\tC. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWood\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDesai\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrederick\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMillsap\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBormann\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMenges\n\t\t\t\t\t\t\tS. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHanna\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFlores-Foxworth\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShin\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWesthusin\n\t\t\t\t\t\t\tM. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGlimp\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZanjani\n\t\t\t\t\t\t\tE. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLozier\n\t\t\t\t\t\t\tJ. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPliska\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStranzinger\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJoerg\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKraemer\n\t\t\t\t\t\t\tD. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlmeida-Porada\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A. Journal of Thrombosis and Haemostasis, 8\n\t\t\t\t\t2Feruary), 276\n\t\t\t\t\t285\n\t\t\t\t\t1538-7933\n\t\t\t\t\n\t\t\t'},{id:"B58",body:'\n\t\t\t\tPowell, J.S., Ragni, M.V., White, G.C., Lusher, J.h, Hillman-Wiseman, C., Cole, V., Jolly, D., Ramanathan-Girish, S., Roehl, H., Lu, B, and Hurst, D. (2003) Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion. Blood, 0006-4971\n\t\t\t\t\t6\n\t\t\t\t\t102\n\t\t\t\t\t2038\n\t\t\t\t\t2045\n\t\t\t\t\n\t\t\t'},{id:"B59",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQuinonez\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSutton\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002Lentiviral vectors for gene delivery into cells. DNA and Cell Biology, 21\n\t\t\t\t\t12December), 937\n\t\t\t\t\t951\n\t\t\t\t\t1044-5498\n\t\t\t\t\n\t\t\t'},{id:"B60",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRadcliffe\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSion\n\t\t\t\t\t\t\tC. J. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilkes\n\t\t\t\t\t\t\tE. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCustard\n\t\t\t\t\t\t\tE. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBeard\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKingsman\n\t\t\t\t\t\t\tS. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMitrophanous\n\t\t\t\t\t\t\tK. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Analysis of factor VIII mediated suppression of lentiviral vector titres. Gene Therapy, 15\n\t\t\t\t\t4February), 289\n\t\t\t\t\t297\n\t\t\t\t\t0969-7128\n\t\t\t\t\n\t\t\t'},{id:"B61",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRoth\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTawa\n\t\t\t\t\t\t\tN. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tO’Brien\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTreco\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSelden\n\t\t\t\t\t\t\tR. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001Nonviral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia. New England Journal of Medicine, 344\n\t\t\t\t\t23June), 1735\n\t\t\t\t\t1742\n\t\t\t\t\t0028-4793\n\t\t\t\t\n\t\t\t'},{id:"B62",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSarkar\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXiao\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKazazian\n\t\t\t\t\t\t\tH. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003A single adeno-associated virus (AAV) murine factor VVIII. Journal of Thrombosis and Haemostasis, 1\n\t\t\t\t\t2February), 220\n\t\t\t\t\t226\n\t\t\t\t\t1538-7933\n\t\t\t\t\n\t\t\t'},{id:"B63",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSarkar\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTetreault\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGao\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBell\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChandler\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilson\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKazazian\n\t\t\t\t\t\t\tH. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJr \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype. Blood, 103\n\t\t\t\t\t4February), 1253\n\t\t\t\t\t1260\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B64",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSarkar\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMucci\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAddya\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTetreault\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBellinger\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNichols\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKazazian\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006Long-term efficacy of adeno-associated virus serotypes 8 and 9 in hemophili A dogs and mice. Human Gene Therapy, 17\n\t\t\t\t\t4April), 427\n\t\t\t\t\t439\n\t\t\t\t\t1043-0342\n\t\t\t\t\n\t\t\t'},{id:"B65",body:'\n\t\t\t\tSamulski, R.J., Berns, K.I., Tan, M., and Muzyczka, N. (1982) Cloning of adeno-associated virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells. Proceedings of the National Academy of Sciences0027-8424\n\t\t\t\t\t6\n\t\t\t\t\t79\n\t\t\t\t\t2077\n\t\t\t\t\t2081\n\t\t\t\t\n\t\t\t'},{id:"B66",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScallan\n\t\t\t\t\t\t\tC. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParker\n\t\t\t\t\t\t\tA. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPatarroyo-White\n\t\t\t\t\t\t\tS. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJiang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVargas\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNagy\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPowell\n\t\t\t\t\t\t\tS. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWright\n\t\t\t\t\t\t\tJ. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSarkar\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKazazian\n\t\t\t\t\t\t\tH. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Clelland\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCouto\n\t\t\t\t\t\t\tL. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003Phenotypic correction of a mouse model of hemophilia A using AAV2 vectors encoding the heavy and light chains of FVIII. Blood, 102\n\t\t\t\t\t12December), 3919\n\t\t\t\t\t3926\n\t\t\t\t\t0006-4971\n\t\t\t\t\n\t\t\t'},{id:"B67",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchauber\n\t\t\t\t\t\t\tC. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTuerk\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPacheco\n\t\t\t\t\t\t\tC. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEscarpe\n\t\t\t\t\t\t\tP. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVeres\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Lentiviral vectors pseudotyped with baculovirus gp64 efficiently transduce mouse cells in vivo and show tropism restriction against hematopoietic cell types in vitro. Gene Therapy, 11\n\t\t\t\t\t3February), 266\n\t\t\t\t\t275\n\t\t\t\t\t0969-7128\n\t\t\t\t\n\t\t\t'},{id:"B68",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchnell\n\t\t\t\t\t\t\tM. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTazelaar\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGao\n\t\t\t\t\t\t\tG. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYu\n\t\t\t\t\t\t\tQ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQian\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tS. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarnavski\n\t\t\t\t\t\t\tA. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLe Clair\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRaper\n\t\t\t\t\t\t\tS. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilson\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors. Molecular Therapy, 5\n\t\t\t\t\t1May), 708\n\t\t\t\t\t722\n\t\t\t\t\t1525-0016\n\t\t\t\t\n\t\t\t'},{id:"B69",body:'\n\t\t\t\tSchuettrumpf, J., Herzog, R.W., Schlachterman, A., Kaufhold, A., Stafford, D.W., and Arruda, V.R. (2005) Factor IX variants improve gene therapy efficacy for hemophilia B. Blood, 0000-0006\n\t\t\t\t\t6\n\t\t\t\t\t105\n\t\t\t\t\t2316\n\t\t\t\t\t2323\n\t\t\t\t\n\t\t\t'},{id:"B70",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSinn\n\t\t\t\t\t\t\tP. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSauter\n\t\t\t\t\t\t\tS. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Cray\n\t\t\t\t\t\t\tP. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Gene therapy progress and prospects: Development of improved lentiviral and retroviral vectors- design, biosafety, and production. Gene Therapy, 12\n\t\t\t\t\t14July), 1089\n\t\t\t\t\t1098\n\t\t\t\t\t0000-0969\n\t\t\t\t\n\t\t\t'},{id:"B71",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToole\n\t\t\t\t\t\t\tJ. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPittman\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOrr\n\t\t\t\t\t\t\tE. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurtha\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWasley\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaufman\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1986A large region (approximately equal to 95 kDa) of human factor VIII is dispensable for in vitro procoagulant activity. Proceedings of the National Academy of Sciences, 83\n\t\t\t\t\t16August), 5939\n\t\t\t\t\t5942\n\t\t\t\t\t0027-8424\n\t\t\t\t\n\t\t\t'},{id:"B72",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVan Damme\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChuah\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCollen\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVanden\n\t\t\t\t\t\t\tDriessche. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Onco-retroviral and lentiviral vector-based gene therapy for hemophilia: Preclinical Studies. Seminars in Thrombosis and Hemostasis, 30\n\t\t\t\t\t2April), 185\n\t\t\t\t\t195\n\t\t\t\t\t0094-6176\n\t\t\t\t\n\t\t\t'},{id:"B73",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVan den\n\t\t\t\t\t\t\tBiggelaar. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBouwens\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKootstr,a\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHebbel\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVoorberg\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMertens\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells. Haematologica, 94\n\t\t\t\t\t5May), 670\n\t\t\t\t\t678\n\t\t\t\t\t0390-6078\n\t\t\t\t\n\t\t\t'},{id:"B74",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVanden\n\t\t\t\t\t\t\tDriessche. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVanslembrouck\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoovaerts\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZwinnen\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVanderhaeghen\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCollen\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChuah\n\t\t\t\t\t\t\tM. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999Long-term expression of human coagulation factor VIII and correction of hemophilia A after in vivo retroviral gene transfer in factor VIII-deficient mice. Proceedings of the National Academy of Sciences, 96\n\t\t\t\t\t18August), 10379\n\t\t\t\t\t10384\n\t\t\t\t\t0027-8424\n\t\t\t\t\n\t\t\t'},{id:"B75",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVanden\n\t\t\t\t\t\t\tDriessche. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVanslembrouck\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoovaerts\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVanden\n\t\t\t\t\t\t\tDriessche. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCollen\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChuah\n\t\t\t\t\t\t\tM. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001Viral vector-mediated gene therapy for hemophilia. Current Gene Therapy, 1\n\t\t\t\t\t3September), 301\n\t\t\t\t\t315\n\t\t\t\t\t1566-5232\n\t\t\t\t\n\t\t\t'},{id:"B76",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tViiala\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLarsen\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRasko\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Gene Therapy for Hemophilia: Clinical Trials and Technical Tribulations. Seminars in Thrombosis and Hemostasis, 35\n\t\t\t\t\t1February), 81\n\t\t\t\t\t92\n\t\t\t\t\t0094-6176\n\t\t\t\t\n\t\t\t'},{id:"B77",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWard\n\t\t\t\t\t\t\tN. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBuckley\n\t\t\t\t\t\t\tS. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWaddington\n\t\t\t\t\t\t\tS. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVanden\n\t\t\t\t\t\t\tDriessche. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChuah\n\t\t\t\t\t\t\tM. K. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNathwani\n\t\t\t\t\t\t\tA. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Intosh\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTuddenham\n\t\t\t\t\t\t\tE. G. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKinnon\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThrasher\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Vey\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011Codon optimization of human factor VIII cDNAs leads to high-level expression. Blood, 117\n\t\t\t\t\t3January), 798\n\t\t\t\t\t807\n\t\t\t\t\t0000-0006\n\t\t\t\t\n\t\t\t'},{id:"B78",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWu\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCrise\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurgess\n\t\t\t\t\t\t\tS. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003Transcription start regions in the human genome are favored targets for MLV integration. Science, 300\n\t\t\t\t\t5626June), 1749\n\t\t\t\t\t1751\n\t\t\t\t\t0036-8075\n\t\t\t\t\n\t\t\t'},{id:"B79",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWu\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColosi\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Effect of genome size on AAV vector packaging. Molecular Therapy, 18\n\t\t\t\t\t1January), 80\n\t\t\t\t\t86\n\t\t\t\t\t1525-0016\n\t\t\t\t\n\t\t\t'},{id:"B80",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXu\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlipio\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFink\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAdcock\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWard\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMa\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proceedings of the National Academy of Sciences, 106\n\t\t\t\t\t3January), 808\n\t\t\t\t\t813\n\t\t\t\t\t0027-8424\n\t\t\t\t\n\t\t\t'},{id:"B81",body:'\n\t\t\t\tYacoub, N., Romanowska, M., Haritonova, N., and Foerster, J. (2007) Optimized production and concentration of lentiviral vectors containing large inserts. Journal of Gene Medicine, 1521-2254\n\t\t\t\t\t7\n\t\t\t\t\t9\n\t\t\t\t\t579\n\t\t\t\t\t584\n\t\t\t\t\n\t\t\t'},{id:"B82",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNunes\n\t\t\t\t\t\t\tF. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBerencsi\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFurth\n\t\t\t\t\t\t\tE. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGönczöl\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilson\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proceedings of the National Academy of Sciences, 91\n\t\t\t\t\t10May), 4407\n\t\t\t\t\t4411\n\t\t\t\t\t0027-8424\n\t\t\t\t\n\t\t\t'},{id:"B83",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYant\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMeuse\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChiu\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIvics\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIsvak\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKay\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system. Nature Genetics, 25\n\t\t\t\t\t1May) 35\n\t\t\t\t\t41\n\t\t\t\t\t0000-1061\n\t\t\t\t\n\t\t\t'},{id:"B84",body:'\n\t\t\t\tYonemura, H., Sugawara, K., Nakashima, K., Nakahara, Y., Hamamoto, T., Mimaki, I., Yokomizo, K., Tajima, Y., Masuda, K., Imaizumi, A., Funatsu, A., and Miyazaki, J. (1993) Efficient production of recombinant human factor VIII by co-expression of the heavy and light chains. Protein Engineering, 0269-2139\n\t\t\t\t\t6\n\t\t\t\t\t6\n\t\t\t\t\t669\n\t\t\t\t\t674\n\t\t\t\t\n\t\t\t'},{id:"B85",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYoujin\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJun\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009The treatment of hemophilia A: from protein replacement to AAV-mediated gene therapy. Biotechnology Letters, 31\n\t\t\t\t\t3March), 321\n\t\t\t\t\t328\n\t\t\t\t\t0141-5492\n\t\t\t\t\n\t\t\t'},{id:"B86",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZayed\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIzsvák\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWalisko\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIvics\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Development of hyperactive Sleeping Beauty transposon vectors by mutational analysis. Molecular Therapy, 9\n\t\t\t\t\t2February), 292\n\t\t\t\t\t304\n\t\t\t\t\t1525-0016\n\t\t\t\t\n\t\t\t'},{id:"B87",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhu\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKren\n\t\t\t\t\t\t\tB. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tC. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBilgim\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWong\n\t\t\t\t\t\t\tP. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSteer\n\t\t\t\t\t\t\tC. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007Erythroid-specific expression of beta-globin by the Sleeping Beauty transposon for Sickle cell disease. Biochemistry, 46\n\t\t\t\t\t23June), 6844\n\t\t\t\t\t6858\n\t\t\t\t\t1507-1521\n\t\t\t\t\n\t\t\t'},{id:"B88",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZufferey\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDonello\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTrono\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHope\n\t\t\t\t\t\t\tT. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. Journal of Virology, 73\n\t\t\t\t\t4April), 2886\n\t\t\t\t\t2892\n\t\t\t\t\t1098-5514\n\t\t\t\t\n\t\t\t'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Johnston Jennifer",address:null,affiliation:'
'}],corrections:null},book:{id:"224",type:"book",title:"Gene Therapy",subtitle:"Developments and Future Perspectives",fullTitle:"Gene Therapy - Developments and Future Perspectives",slug:"gene-therapy-developments-and-future-perspectives",publishedDate:"June 22nd 2011",bookSignature:"Chunsheng Kang",coverURL:"https://cdn.intechopen.com/books/images_new/224.jpg",licenceType:"CC BY-NC-SA 3.0",editedByType:"Edited by",isbn:null,printIsbn:"978-953-307-617-1",pdfIsbn:"978-953-51-6441-8",reviewType:"peer-reviewed",numberOfWosCitations:15,isAvailableForWebshopOrdering:!0,editors:[{id:"32217",title:"Prof.",name:"Chunsheng",middleName:null,surname:"Kang",slug:"chunsheng-kang",fullName:"Chunsheng Kang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1050"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"17705",type:"chapter",title:"New Vectors for Stable and Safe Gene Modification",slug:"new-vectors-for-stable-and-safe-gene-modification",totalDownloads:3237,totalCrossrefCites:0,signatures:"Francisco Martín, Karim Benabdellah, Marién Cobo, Pilar Muñoz, Per Anderson and Miguel G. 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1. Objective
The main purpose of this chapter is to acknowledge if Corporate Social Responsibility (CSR) acts as a Blue Ocean Strategy (BOS) in the mining industry. Additionally, this chapter introduces a comparative case study analysis of two mining operations in Peru. The conclusions indicate that CSR is the value innovation of BOS and there is a six-action framework to create responsible mining.
2. Introduction
Corporate social responsibility (CSR) has been defined broadly by dissimilar global agents without a consensus around its essence. Within the mining framework, three main dimensions are addressed in CSR: social, environmental, and economic. The approach estimates the consequences that mining firms may inflict within stakeholder groups in the following aspects: social, environmental [1], and economic [2]. Both firm’s and stakeholder’s perspectives regarding the meaning and reach of CSR are required by this approach within the mining industry. The relevance of the approach is substantial since conflict potentials between both company’s and stakeholder’s expectations and divergences will exist.
The mining industry has taken the lead on business engagement regarding CSR. This can be ascribed to the questionable nature of its expenditures and both environmental and social problems that are intrinsic to the mining venture. Leadership and vanguard at CSR by the mining industry reflect the rapid growth within the developing countries, specifically countries with weak governance, legislation, and institutional capacity [3].
In contrast, the blue ocean strategy (BOS) concept is introduced. Used as a business and marketing concept, BOS helps entrepreneurs and firms to develop a positioning strategy for a product or service that will distinguish itself from competitors. The main focus is to establish new zones or markets where a product or service can be developed where competitors have not yet addressed. In the development of the conceptual framework of their BOS, Kim and Mauborgne [4] stated that value innovation was the foundation of the BOS. Value innovation accentuates the quest for a low-cost and differentiated strategy simultaneously. It suggests observing market boundaries differently and developing products for each consumer segment by identifying common attributes. Firms ought to have higher activity standards than those of industry and offer higher value than competitors. Finally, the reduction and elimination of other activities are needed to deliver value at a low cost.
BOS is applicable for all types of innovation, not just value innovation. Moreover, CSR facilitates external knowledge and is frequently dissimilar from internal knowledge. Consequently, CSR can promote “creative leaps” and influence the innovation process [5]. Therefore, CSR is innovation and could be studied through the BOS lens. In the mining context, companies and communities are competing for natural resources such as water and land, and sometimes this completion results in a conflict. As a consequence, mining firms use CSR as a strategy to reduce social conflict and compensate the community for their impact. This being said, this Chapter aims to estimate whether CSR acts as a value innovation to create a BOS in the mining industry. To do that, the following questions arose: How CSR allows firms to reduce costs? And How CSR raises value to the community?
3. Literature review
3.1 Blue Ocean Strategy
BOS is focused on “creating uncontested market space and make competition irrelevant”. Profitable and continued growth has been the objective of straight on rivalry by firms. In today’s packed industries, contending head-to-head results in a bloody “red sea” of opponents battling over a shrinking profit pool, improbable to make gainful development later on. The creation of “Blue Oceans” is the key to conquer tomorrow’s victory [4].
Such strategic moves, called “value innovation”, create incentives in value for both the company and its consumers, releasing new demand and rendering rivalry insignificant. The “Four Actions Framework” used for creating brand new value propositions consists of the following: ‘Deleting’ factors that aged in competition and are taken for granted by clients; ‘lessening’ products or services that have been overdesigned in the race to beat the opposition, which the clients don’t appreciate; raising by deleting the understandings one’s industry forces clients to make by setting new guidelines well above contenders; originating through the discovery of the latest sources of value for customers, therefore originating new demand and strategic price shifts.
3.2 CSR as value innovation: reducing costs
Within the project cycle, how companies respond to the conflict has a significant influence. In the early stage of the cycle, leading firms are bound to withdraw from an investment (which may infer diminished social and environmental effects or the shift of effects on another area) and consider a foundational realignment of the project. On the other hand, at the late stage in the cycle, firms are bound to suit the plan or aggregate social responsibility projects, which provides impact compensation instead of reduction [6].
Likewise, lower costs, improve efficiencies, and add competitive advantages to public companies looking for investors at the Stock Markets are the effects of CSR activities focused on sustainability. A vast number of benefits arise for organizations who engage in CSR activities increased brand value, healthier and safer workforce, and larger access to finance. Consequently, five key benefits of CSR are presented by Solihin [7] for a firm to achieve social responsibility to both stakeholders and the environment: sales and market share growth, solid and strong brand positioning, corporate image growth, lessen operational costs, corporate appeal growth for investors and financial analysts.
3.3 CSR as value innovation for communities value
The community’s and firm’s expectations are on the opposite “course” in regards to CSR. While communities focus on sustainability, firms focus on exhibiting their responsible behavior within operations. According to Hsieh [8], firms that operate in developing countries are awaited to satisfy the highest expectations. Consequently, to address necessities and requests tailored to their needs, scholars have requested more awareness to comprehend the firm’s impacts considering stakeholder’s perceptions.
Even though mining is one of the main sources of employment in Africa, it is of the utmost importance that companies contribute to improving living standards within the communities they operate. Apart from issuing mandates to employ locals, there are a few approaches utilized to improve socioeconomic quality within a mining community: finance the construction of hospitals and schools, building roads and highways, and making use of local services [9].
4. Case studies
In the following section, both case studies are introduced, described, and assessed on context, strategies, and outcomes.
4.1 The Tintaya Copper Mine
Tintaya Copper Mine is run by BHP Billiton in Peru’s Espinar province Tintaya. Community members asserted that these land buys had been led in manners that were unscrupulous and unlawful. Also, community members started to protest about mine’s sensed environmental effects. By covering charges and agreeing to the Peruvian government, prerequisites, and laws, the firm thought they were maintaining their commitments through the community relationship policy. The firm thought they were overseeing everything admirably. In November 2000, the Peruvian NGOs sent a report to Oxfam Community Aid Abroad, Oxfam International’s Australian fellow member. The Mining Ombudsman answered by composing a letter to BHP Billiton authorities in Australia that delineated the communities’ complaints and requested an answer.
Before the Dialog Table, the local’s doubt regarding the mine’s local administration was profoundly instilled. In the following months after the December 2001 gathering, BHP Billiton and the community NGO alliance deliberately arranged their particular positions, while working mutually to distinguish an outside facilitator for the primary Dialog Table gathering. The facilitator they recruited would assume a crucial part in establishing the framework for an effective discourse process.
At the Dialogue Table’s debut meeting, the facilitator drove network individuals, NGO delegates, neighborhood government authorities, and BHP Billiton staff through an iterative and participatory issue distinguishing proof procedure. Toward the finish of the procedure, an accord was reached on the need to address four key issues of worry to the networks: loss of land, ecological effects, human rights infringement, and maintainable turn of events. At that point, Dialog Table members consented to frame four working commissions to examine complaints, define proposals, and execute changes in every one of the four zones. Three of the four commissions – the Environment, Human Rights, and Sustainable Development – were set up as progressing, changeless commissions, while the Land Commission would be broken down once its obligations were released. Each commission was made out of the networks’ chosen chiefs and intrigued inhabitants, city and NGO agents, and BHP Billiton corporate and neighborhood staff. At that point, with the assistance of the facilitator, Dialog Table members recognized a few key standards and guidelines – cooperation, agreement chasing, joint certainty finding, and secrecy – to manage their connections.
The BHP Billiton designation was driven by CEO Paul Warner, a man who, unmistakably influenced the firm to follow through on his guarantees. Members deciphered his attendance as a sign that the organization was paying attention to the networks’ cases. An absence of trust in the kindness of the contradicting party was a conceivably destroying issue for both network individuals and BHP Billiton staff. After some time, and through recurred connections at the commission and entire gatherings, shared comprehension and regard between community leaders and BHP Billiton authorities gradually developed. Whether the organization has failed in the issues dissected, specialized examinations were required in each commission to decide and have suggestions to follow.
On December 21, 2004, a structured understanding between BHP Billiton and the five Dialog Table people group was agreed upon. The focal features of the structure understanding were the accompanying: First of all, each year the organization will contribute three percent of its benefit to develop the community. The Tintaya Foundation, an organization that was mutually managed by the firm and community, was created to fund different community activities including water system, specialized aptitudes preparing, and other rural improvement ventures. With this understanding, the mining firm was a pioneer at sharing direct profits among communities in Peru. Secondarily, to identify and alleviate environmental impacts from the mining activity, the firm and community associations will frame an ecological committee. Ultimately, the firm acknowledged that any activity performed within the community territory will be done with past assent from the proprietors. This being said, the “Previous consent” concept was first developed between a mining firm and a local community.
4.2 Quellaveco project
Quellaveco is an enormous scope copper mining venture situated in the south-eastern region of Peru, at the department of Moquegua. Social and ecological concerns in regards to Quellaveco’s operations were referred by the complainants as the following: water shortage, water quality corruption, and enlarged competition over water assets in an arid territory; environmental impacts of toxic wastes, health impact within local communities; and concerns over land invasion without landowner’s assent. The Environmental Impact Assessment (EIA) was introduced by the firm’s to the Energy Minister in May 2020 and approved in December of that year.
Both positive and negative effects of the venture were included by the organization and, despite the firm’s efforts to inform both the community and local authorities, couldn’t agree with the firm’s conclusion that “the net effect of the undertaking’s improvement is certain” and “the advancement of the open cut and its resulting loading up with water opens the chance of utilizing the establishment as a store”.
In March 2011, the provincial administration of Moquegua started a dialogue table involving 27 stakeholders from society, government and the company.
5. Discussion
To recreate the community value elements for creating a new value curve and to answer the two research questions, the Four Actions Framework is utilized. Four main questions are introduced to challenge the industry logic and business model with the goal to break differentiation and low-cost trade-off and creating a new value curve:
5.1 Which factors that are taken for granted by the mining industry should be eliminated?
Causes of social conflicts should be eliminated. A noteworthy influence on how firms answer to disputes arisen when they arise within the project cycle. When early in the cycle, conflict more presumably leads firms to withdraw from investments (which may traduce into decreased social and environmental effect or the transfer of effects to a different area) and evaluate an essential restructuring of the project. The most constant costs distinguished were those emerging from lost productivity because of delays [6]. In Quellaveco’s case, the reasons for social clashes were water assets and the utilization of freshwater from the streams without the community consent. The social conflict generated huge monetary losses to the firm. Interviewees calculated that around US$10,000 is lost for each day of postponement in lost wages and the expenses of keeping up an investigation camp. Additionally, the manager of the company suggested that the company should provide more CSR programs to avoid these operational costs.
Reputation concerns should be eliminated. Firms are most certainly to adopt the design or increase the social responsibility activities, the latest providing impact compensation instead of impact reduction when conflict arises later in the project cycle [6]. The value of intangible resources such as trust can be increased by the creation of a genuine solid reputation through certain and pre-planned activities and dealing with the corporate image. In BHP’s case, one of the community members of the NGO’s stated: “The community realized that the firm had numerous similar issues in Canada and Australia, so the organization didn’t want to keep being influenced by its awful reputation”.
5.2 Which factors should be reduced beneath the industry’s standard?
Environmental impact. In Quellaveco’s case, the community realized that the firm had the financial ability to reestablish the trajectory of the river. As a leader stated: “Economists, local engineers, and practitioners had a profound discussion with the firm about their interests. Thus, in the closure plan, the project evaluated leaving the open pit as a lagoon so the community could use it as a water reservoir. However, neighborhood engineers demanded the organization reinstatement of the trajectory of the Asana River as it was prior to the operations. After numerous researches, the firm embraced to execute the elective conclusion plan noted as Restoration of the Asana River Bed. The following would elude any social conflict and lose cash as an outcome of the conflict.
5.3 Which factors should be raised above the industry’s standard?
Relative power from community members should be raised. Relative power is crucial in the trusting process. If the trusted party is within a position authority, there is a deviation towards trusting because he can authorize an individual who abuses his trust. On the other hand, if the trusted party has little or no position of authority, he becomes vulnerable to the other’s party interests and would become less comfortable. Either way, prior to the dialogue table, community members did not have authority nor power. Once the dialogue table was settled, each participant had a vote. This means that a farmer from a rural village has the same power and authority that the other members, including the firm’s agents and the president of the region.
Secondly, stakeholder representation on decision-making committees should be raised. The following strategy exhibits that mining firms are aware of stakeholder’s interests. Within Quellaveco’s project, one of the last consensuses was that a Participatory Monitoring Committee will be created and framed by key stakeholders, civilians and institutions from local and regional governments will be made to screen the ecological effect during activity to oversee the environmental impact during the firm’s operations.
Thirdly, choice by agreement based methodology should be raised. Trust can be influenced by consensus, noticed. One of the government representatives at Quellaveco’s project stated: “The norm stated that any agreement should be done through consensus. We were looking for a discussion council to understand each party’s perspectives and to eventually join a consensus, not a voting session.”
In the fourth place, transparency should be raised. Stakeholder’s trust is increased by transparency; Expanding the stakeholder’s trust, a business separates itself and develops. Among non-employee stakeholders, trust creates considerable cooperative behavior, lowering operational costs, improving business reputation, and recruiting and holding new clients and skilled workforce. Call this the transparency-trust agreement. Within Quellaveco’s project, the firm’s agent stated: “The meetings were available to people in general, so the press could be there at any second, and some meetings were broadcasted live”.
Finally, support should be raised. The advantages of participation are ascribed to bigger trust, more prominent sentiments of control, better firm identity, and bigger goals. In the end, it upgrades trust and adds to a feeling of proprietorship and dominance, improving the acceptance system and dedication. On inspiration and active involvement, individuals lessen resistance to change and intensify acceptance of and commitment to both changes and decisions. In any case, there were numerous members from various firms: Those who were against and those who were in favor of the project.
Withing Tintaya’s case, an agent from the organization stated: “While the facilitator made a list of issues, everybody was questioned regarding their opinions on the issues. They conclude that there were four issues: human rights, land, sustainable development, and natural issues. Afterward, we asked each member which committee they would prefer to join.”
5.4 Which factors should be created that the mining industry has never offered?
“Create” didn’t emerge in the interviews. Alternately, the following three concepts had emerged: share, compensate and enhance.
Share profits. Within Tintaya’s project, the firm will annually share 3% of its profits with the community. Moreover, the firm created the “Tintaya Foundation” to finance community initiatives including technical training, irrigation, and different agricultural projects. With this accord, history was made since it was the first direct profit transfer from a mining firm towards a community in Peru.
Share norms of behavior. Trust cant be shaped without any previous foundation. Habitually, is created and evolved when two parties consistently agree to the equivalent moral and/or social norms and regulations. Within Tintaya’s case study, an agent from the firm stated: “The facilitator had more vision than us since he did not take any parties side. Since the earliest encounter, he helped set up a few guidelines of conduct. This seemed to be ordinary, nearly ridiculous. The rules were stated as follows: Listen to each other, and respect everyone’s opinion. Nonetheless, they were very useful”. The equivalent occurred within Quellaveco’s case: a participant created a guideline that established standards such as respect, transparency, equity, and participation.
Compensate by kindhearted concern. In both case study’s, the firms created a Social Fund, established as a non-profit organization formed by organizations representing civilians, intending to be recipients of social responsibility expenses to be made by the firm and give an appropriate use of the money to accomplish regional development.
Enhance resemblance. We are tribal at our core, which is the reason individuals trust easily those who look alike to themselves. Similitudes may incorporate values, group identity, personality attributes. Within Tintaya’s case study, the facilitator referenced: “We needed to create some systems and the proposal, which was agreed on by all, was to not leave a question unanswered. As a result, all the parties involved could express their purpose of existence clearly. Also, we felt that it would be a lot simpler for the firm to state its reason for existence and purpose. On the NGO’s side, it was intriguing because they also explained their identity, partners, financial background, and their sole purpose and objective. This system shattered various tales. If tales are not shattered, you can’t believe that the opposite party shares something with you. That is the most important lesson.
Enhance capability. The manager habitually evaluates capability upon the decision to trust or delegate authority to the individuals who work for them. Within Tintaya’s case study, a delegate from the NGO stated: “The community was not prepared for a negotiation. The community did not have a clue how to perfom upon arrival at the negotiation table to reach a solution”. Additionally, a delegate from the firm referenced: “We are a mining firm with top professionals. This being said, an unevenness in dialogue resulted since the community did not have the same opportunities”. Afterward, a leader of the community stated: “We decided as a group to search for assistance, so we could construct the capacity of the communities in how to participate in this type of dialogue. When this limit building was finished, the process starts managing easily”.
Enhance leadership. Relationship – oriented leadership, which suggests a moral implication, has a positive connection with trust, and associations as to administration – trust relationship varies measurably. Within the Tintaya’s case study, prior to the dialogue table, community members did not want the presence of the firm’s general manager since they couldn’t trust him. Hence, while the discussions were taken place at the Dialogue table, the firm assigned Paul Warner, a headquarter-based manager, a man who, as indicated by one delegate NGO, unmistakably had the power within the firm to follow through on his promises. Contrastingly, in Quellaveco’s case study leadership was generated from the base since the Regional Government started a dialogue table including 27 local stakeholders.
Enhance the alignment of interests. Before an individual place her trust in another person, she cautiously gauges the question “How likely is this individual to assist my advantage?” Trust is a reasonable response when an individual’s interests are aligned. In both cases, members had their interests, yet they found a common interest which was social development. For example, within the Tintaya’s case study, a community representative stated: “We assembled a Development Table were we identified the community’s social issues and attempt to discover a solution to them by working cooperatively”.
Enhance predictability and integrity. Sooner or later within the trust decision, trusters ask: Within Quellaveco’s case study, one of the community representatives stated: “The rule was as follows: If you had a commitment to do or a prior assignment to do it before entering to another understanding, do not let accumulate tasks. It implies we didn’t proceed to a new agreement before verifying if the past ones were finished. At this point, we all did a colossal effort to consent with agreements and be reliable. Similarly, within the Tintaya case study, before the dialogue Table, there was distrust. A delegate from the community stated: “We had consistently imagined that mining firms would enslave us with their laws and procedures. That was our point of view. Deceival was the feeling shared at the first encounter”.
Enhance the level of communication. Solid communication is crucial since trust is a relational concept. As anyone might expect, transparent communication frequently helps the decision to trust, whereas poor (or none) communication produces doubtfulness. When Tintaya’s case study, before the dialogue table, zero communication was found between the organization and the community. Nevertheless, following the dialogue table, the level of communication increase.
In summary, six strategies are found: Elimination, Reduction, Raising, Compensating, Enhancing, and Sharing. SeeTable 1.
Eliminate
Reduce
Raise
Causes of social conflict: Water resource (Quellaveco), Human Rights (Tintaya)
Environmental impact
Relative power of community members
Reputation concern (Tintaya)
Stakeholder representation on decision-making committees
Consensus based approach
Transparency
Participation
Compensate
Enhance
Share
Benevolent concern
Similarities
Profit
Capability
Norms of behavior
Leadership
Alignment of interests by Development Table
Predictability and integrity
Level of communication
Table 1.
CSR Strategies to reduce cost (Eliminate and Reduce) and raise value to community (Raise, Compensate, Enhance and Share).
CSR, as value innovation, is created both its cost structure and its value proposition to the community. Cost reductions are made by removing and lessening the factors mining competes on such water resources (Quellaveco), environmental impacts (Quellaveco and Tintaya), and land (Tintaya). Community value is lifted by raising, compensating, enhancing, and sharing CSR elements the mining has roughly offered. See Figure 1.
Figure 1.
CSR as value innovation.
6. Concluding remarks
CSR favorably influences both its cost structure and its value proposition to the community. Cost savings are made by eliminating and reducing the causes of social conflicts. Community value is lifted by raising, reducing, sharing, enhancing, and compensating elements the industry has never offered. So, CSR acts as a value innovation of BOS. See Figure 2.
Figure 2.
The six actions framework.
\n',keywords:"social responsibility, Blue Ocean Strategy, value innovation, mining industry",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73940.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73940.xml",downloadPdfUrl:"/chapter/pdf-download/73940",previewPdfUrl:"/chapter/pdf-preview/73940",totalDownloads:156,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 7th 2020",dateReviewed:"October 13th 2020",datePrePublished:"November 5th 2020",datePublished:"March 16th 2022",dateFinished:"November 5th 2020",readingETA:"0",abstract:"The main purpose of this chapter is to acknowledge if Corporate Social Responsibility (CSR) acts as a Blue Ocean Strategy (BOS) in the mining industry. Additionally, this chapter introduces a comparative case study analysis of two mining operations in Peru. The conclusions indicate that CSR is the value innovation of BOS and there is a six-action framework to create responsible mining. CSR favorably influences both its cost structure and its value proposition to the community. Cost savings are made by eliminating and reducing the causes of social conflicts. Community value is lifted by raising, reducing, sharing, enhancing, and compensating elements the industry has never offered.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73940",risUrl:"/chapter/ris/73940",signatures:"Cesar Saenz",book:{id:"9032",type:"book",title:"Corporate Social Responsibility",subtitle:null,fullTitle:"Corporate Social Responsibility",slug:"corporate-social-responsibility",publishedDate:"March 16th 2022",bookSignature:"Beatrice Orlando",coverURL:"https://cdn.intechopen.com/books/images_new/9032.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83880-939-3",printIsbn:"978-1-83880-938-6",pdfIsbn:"978-1-83880-940-9",isAvailableForWebshopOrdering:!0,editors:[{id:"232969",title:"Prof.",name:"Beatrice",middleName:null,surname:"Orlando",slug:"beatrice-orlando",fullName:"Beatrice Orlando"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"271122",title:"Dr.",name:"Cesar",middleName:null,surname:"Saenz",fullName:"Cesar Saenz",slug:"cesar-saenz",email:"csaenz@esan.edu.pe",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Objective",level:"1"},{id:"sec_2",title:"2. Introduction",level:"1"},{id:"sec_3",title:"3. Literature review",level:"1"},{id:"sec_3_2",title:"3.1 Blue Ocean Strategy",level:"2"},{id:"sec_4_2",title:"3.2 CSR as value innovation: reducing costs",level:"2"},{id:"sec_5_2",title:"3.3 CSR as value innovation for communities value",level:"2"},{id:"sec_7",title:"4. Case studies",level:"1"},{id:"sec_7_2",title:"4.1 The Tintaya Copper Mine",level:"2"},{id:"sec_8_2",title:"4.2 Quellaveco project",level:"2"},{id:"sec_10",title:"5. Discussion",level:"1"},{id:"sec_10_2",title:"5.1 Which factors that are taken for granted by the mining industry should be eliminated?",level:"2"},{id:"sec_11_2",title:"5.2 Which factors should be reduced beneath the industry’s standard?",level:"2"},{id:"sec_12_2",title:"5.3 Which factors should be raised above the industry’s standard?",level:"2"},{id:"sec_13_2",title:"5.4 Which factors should be created that the mining industry has never offered?",level:"2"},{id:"sec_15",title:"6. Concluding remarks",level:"1"}],chapterReferences:[{id:"B1",body:'Linnenluecke M, Russell S, Griffiths A. Subcultures and sustainability practices: The impact on understanding corporate sustainability. Business Strategy and the Environment. 2007;18(7):432-452'},{id:"B2",body:'Ambec S, Lanoie P. Does it pay to be green? A systematic overview. Academy of Management Perspectives. 2008;22(4):45-62'},{id:"B3",body:'Kolk A, Lenfant F. Business–NGO collaboration in a conflict setting: Partnership activities in the Democratic Republic of Congo. Business and Society. 2012;51(3):478-511'},{id:"B4",body:'Kim WC, Mauborgne R. Blue ocean strategy: From theory to practice. California Management Review. 2005;47(3):105-121'},{id:"B5",body:'Katila R, Ahuja G. Something old, something new: a longitudinal study of search behavior and new product introduction. Academy of Management Journal. 2002;45(6):1183-1194'},{id:"B6",body:'Franks D, Davis R, Bebbington A, Ali S, Kempl D, Scurrah M. Conflict translates environmental and social risk into business costs. 2014'},{id:"B7",body:'Solihin I. Corporate Social Responsibility: From Charity to Sustainability. Jakarta: Penerbit Salemba Empa; 2009'},{id:"B8",body:'Hsieh N. Does global business have a responsibility to promote just institutions? Business Ethics Quarterly. 2009;19(2):251-273'},{id:"B9",body:'Hilson, Gavin. 2001. Mining and Sustainable Development: The African Case. Minerals & Energy. Vol. 16 Issue 2, p27-36. 10p'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Cesar Saenz",address:"csaenz@esan.edu.pe",affiliation:'
ESAN University, Lima, Peru
'}],corrections:null},book:{id:"9032",type:"book",title:"Corporate Social Responsibility",subtitle:null,fullTitle:"Corporate Social Responsibility",slug:"corporate-social-responsibility",publishedDate:"March 16th 2022",bookSignature:"Beatrice Orlando",coverURL:"https://cdn.intechopen.com/books/images_new/9032.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83880-939-3",printIsbn:"978-1-83880-938-6",pdfIsbn:"978-1-83880-940-9",isAvailableForWebshopOrdering:!0,editors:[{id:"232969",title:"Prof.",name:"Beatrice",middleName:null,surname:"Orlando",slug:"beatrice-orlando",fullName:"Beatrice Orlando"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"348198",title:"Prof.",name:"Arup",middleName:null,surname:"Kumar Sarma",email:"aks@iitg.ac.in",fullName:"Arup Kumar Sarma",slug:"arup-kumar-sarma",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"Indian Institute of Technology Guwahati",institutionURL:null,country:{name:"India"}}},booksEdited:[],chaptersAuthored:[{id:"77262",title:"Evaluation of Climate Change-Induced Impact on Streamflow and Sediment Yield of Genale Watershed, Ethiopia",slug:"evaluation-of-climate-change-induced-impact-on-streamflow-and-sediment-yield-of-genale-watershed-eth",abstract:"In the 21st century, changes in induced climate can significantly affect the water resources system in the watershed. Understanding climate change disrupts hydrological processes can facilitate sustainable water resource strategies to resilient impacts of global warming. The hydrological response of watersheds will be accelerated by climate change, altering the rainfall, magnitude & timing of runoff, and sediment yield. The study investigates climate change aspects on the hydrological responses using Soil and Water Assessment Tool (SWAT) model interfaced with Geographical Information System (GIS) of Genale Basin, Ethiopia. The calibrated SWAT was applied to simulate the impact of climate, and the SUFI-II algorithm was used for parameter optimization & finalization. The change of climate scenarios was built using the outcomes bias-corrected CORDEX RCM daily precipitation, min/max temperature for Ethiopia under RCP 4.5 and RCP 8.5. The average monthly change of streamflow from −16.47% to 6.58% and − 3.6% to 8.27% under RCP4.5 and RCP8.5, respectively (2022–2080). The monthly average sediment yield change was −21.8% to 6.2% and − 5.6% to 4.66% for the RCP4.5 and RCP8.5 scenarios, respectively, over 2022–2080. It implies that the climate change-induced impacts on sediment yield are more significant than streamflow and suggest substantial adaptive management in watershed systems.",signatures:"Tufa Feyissa Negewo and Arup Kumar Sarma",authors:[{id:"347544",title:"Ph.D. Student",name:"Tufa",surname:"Feyissa Negewo",fullName:"Tufa Feyissa Negewo",slug:"tufa-feyissa-negewo",email:"tufa1886@gmail.com"},{id:"348198",title:"Prof.",name:"Arup",surname:"Kumar Sarma",fullName:"Arup Kumar Sarma",slug:"arup-kumar-sarma",email:"aks@iitg.ac.in"}],book:{id:"10754",title:"The Nature, Causes, Effects and Mitigation of Climate Change on the Environment",slug:"the-nature-causes-effects-and-mitigation-of-climate-change-on-the-environment",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"347544",title:"Ph.D. Student",name:"Tufa",surname:"Feyissa Negewo",slug:"tufa-feyissa-negewo",fullName:"Tufa Feyissa Negewo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/347544/images/16730_n.png",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Guwahati",institutionURL:null,country:{name:"India"}}},{id:"347546",title:"M.Sc.",name:"Moses",surname:"Sithole",slug:"moses-sithole",fullName:"Moses Sithole",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"348146",title:"Assistant Prof.",name:"Terence Epule",surname:"Epule",slug:"terence-epule-epule",fullName:"Terence Epule Epule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/348146/images/system/348146.jpg",biography:"•\tAssistant Professor of Climate Change Adaptation and Sustainability Strategies in Africa: Mohammed 6 University Polytechnic (UM6P), Ben Guerir, Morocco\nJanuary 2021-ongpoing.\n•\tAssociate Professor of International Food Systems: UnilaSalle, Rouen, France. August 2019-December 2020.\n•\tPost-Doctoral Research Fellow/Lecturer: Department of Geography, McGill University. May 2016-July 30, 2019.\n•\tPost-Doctoral Research Fellow: Département de Géographie, Université de Montréal. May 2014-April 2016. \n•\tResearch and Project Assistant: Ecological modelling and carbon science laboratory (ECO MCS) : Institute des Sciences de l’environnement, Université du Québec à Montréal (UQAM), Montréal. Septembre 2010-April 2014.",institutionString:"Université Mohammed VI Polytechnique",institution:{name:"Université Mohammed VI Polytechnique",institutionURL:null,country:{name:"Morocco"}}},{id:"348462",title:"Prof.",name:"Abdelghani",surname:"Chehbouni",slug:"abdelghani-chehbouni",fullName:"Abdelghani Chehbouni",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"348916",title:"Dr.",name:"Isaac",surname:"Agholor",slug:"isaac-agholor",fullName:"Isaac Agholor",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Mpumalanga",institutionURL:null,country:{name:"South Africa"}}},{id:"349566",title:"M.Sc.",name:"Pawan",surname:"Thapa",slug:"pawan-thapa",fullName:"Pawan Thapa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"351571",title:"B.Sc.",name:"Yonten",surname:"Chophel",slug:"yonten-chophel",fullName:"Yonten Chophel",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"416107",title:"Ph.D. Student",name:"Somala",surname:"Karthik",slug:"somala-karthik",fullName:"Somala Karthik",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"416115",title:"Prof.",name:"M.S.",surname:"Sai Reddy",slug:"m.s.-sai-reddy",fullName:"M.S. Sai Reddy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rajendra Agricultural University",institutionURL:null,country:{name:"India"}}},{id:"416969",title:"Ms.",name:"Gummudala",surname:"Yashaswini",slug:"gummudala-yashaswini",fullName:"Gummudala Yashaswini",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"our-story",title:"Our story",intro:"
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
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Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"785",title:"Geomatics",slug:"geomatics",parent:{id:"118",title:"Environmental Engineering",slug:"engineering-environmental-engineering"},numberOfBooks:2,numberOfSeries:0,numberOfAuthorsAndEditors:40,numberOfWosCitations:18,numberOfCrossrefCitations:13,numberOfDimensionsCitations:23,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"785",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7465",title:"Trends in Geomatics",subtitle:"An Earth Science Perspective",isOpenForSubmission:!1,hash:"a32ff40d6c47e2b545b92d5075508c9c",slug:"trends-in-geomatics-an-earth-science-perspective",bookSignature:"Rifaat Abdalla",coverURL:"https://cdn.intechopen.com/books/images_new/7465.jpg",editedByType:"Edited by",editors:[{id:"222877",title:"Dr.",name:"Rifaat",middleName:null,surname:"Abdalla",slug:"rifaat-abdalla",fullName:"Rifaat Abdalla"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5246",title:"Geospatial Technology",subtitle:"Environmental and Social Applications",isOpenForSubmission:!1,hash:"79ea6b081cf0704d747c97857464d3fd",slug:"geospatial-technology-environmental-and-social-applications",bookSignature:"Pasquale Imperatore and Antonio Pepe",coverURL:"https://cdn.intechopen.com/books/images_new/5246.jpg",editedByType:"Edited by",editors:[{id:"4222",title:"Dr.",name:"Pasquale",middleName:null,surname:"Imperatore",slug:"pasquale-imperatore",fullName:"Pasquale Imperatore"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"51565",doi:"10.5772/64214",title:"Collaborative Uses of Geospatial Technology to Support Climate Change Adaptation in Indigenous Communities of the Circumpolar North",slug:"collaborative-uses-of-geospatial-technology-to-support-climate-change-adaptation-in-indigenous-commu",totalDownloads:1457,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"A literature review is conducted of geospatial technologies in community-based research on ice and mobility among Indigenous people of the circumpolar north. Numerous studies explore the use of traditional knowledge in the Arctic on sea ice, but limited evidence of community-based research in sub-Arctic communities and in freshwater ice systems is found. Geographical Information Systems (GIS) and remote sensing tools have been applied in a variety of ways in support of community adaptations. These include the production of living memory maps, ice classification systems, and geodatabases that reflect the relationship-building nature of collaborations between Indigenous traditional knowledge holders and scientists. Satellite imagery—particularly synthetic aperture radar (SAR)—is widely used to characterize traditional understandings of ice to help tailor geospatial tools, climate research, and early warning systems, so that they may be used more effectively to address community interests and needs. As numerous mapping platforms have been developed in the circumpolar north, there are important considerations with respect to data management, Indigenous rights, and data sharing. We see opportunities for further research in lake and river ice, and in further developing early warning systems to address the growing problem of unpredictable ice regimes in Arctic and sub-Arctic regions.",book:{id:"5246",slug:"geospatial-technology-environmental-and-social-applications",title:"Geospatial Technology",fullTitle:"Geospatial Technology - Environmental and Social Applications"},signatures:"Megan Sheremata, Leonard J.S. Tsuji and William A. Gough",authors:[{id:"182233",title:"Ph.D. Student",name:"Megan",middleName:null,surname:"Sheremata",slug:"megan-sheremata",fullName:"Megan Sheremata"},{id:"182238",title:"Prof.",name:"William A.",middleName:null,surname:"Gough",slug:"william-a.-gough",fullName:"William A. Gough"},{id:"182241",title:"Prof.",name:"Leonard J. S.",middleName:null,surname:"Tsuji",slug:"leonard-j.-s.-tsuji",fullName:"Leonard J. S. Tsuji"}]},{id:"51625",doi:"10.5772/64303",title:"Participatory Mapping to Disrupt Unjust Urban Trajectories in Lima",slug:"participatory-mapping-to-disrupt-unjust-urban-trajectories-in-lima",totalDownloads:1647,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"This chapter shares the experience of two action research projects ReMap Lima and cLIMA sin Riego, where mapping has been used with three main objectives: to make visible what is otherwise ‘invisible’; to open up dialogue between different stakeholders in the city and to arrive at concrete actions, collectively negotiated between citizens and policy makers. Two case study sites were chosen in Lima, Peru: Barrios Altos (BA) in the historic centre and José Carlos Mariátegui (JCM) at the edge of the city. The approach adopted applies a participatory action methodology based on grounded applications and advanced technologies for community-led mapping and visualisation. The chapter reflects upon three interrelated sites of the mapping process: the reading, writing and audiencing of maps and explores how these can provide opportunities to break away from the polar positions often established between Claimant/ marginalised group and the state, thus aiming to contribute to a process of spatial co-learning across typically confronted actors. The two case studies show different possibilities for interrogating the city to provide a spatially and socially grounded way of co-producing knowledge for action that can contribute to the planning of just urban futures.",book:{id:"5246",slug:"geospatial-technology-environmental-and-social-applications",title:"Geospatial Technology",fullTitle:"Geospatial Technology - Environmental and Social Applications"},signatures:"Rita Lambert and Adriana Allen",authors:[{id:"183462",title:"Dr.",name:"Adriana",middleName:null,surname:"Allen",slug:"adriana-allen",fullName:"Adriana Allen"},{id:"184062",title:"Dr.",name:"Rita",middleName:null,surname:"Lambert",slug:"rita-lambert",fullName:"Rita Lambert"}]},{id:"51416",doi:"10.5772/64250",title:"Satellite SAR Interferometry for Earth’s Crust Deformation Monitoring and Geological Phenomena Analysis",slug:"satellite-sar-interferometry-for-earth-s-crust-deformation-monitoring-and-geological-phenomena-analy",totalDownloads:1445,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Synthetic aperture radar interferometry (InSAR) and the related processing techniques provide a unique tool for the quantitative measurement of the Earth’s surface deformation associated with certain geophysical processes (such as volcanic eruptions, landslides and earthquakes), thus making possible long-term monitoring of surface deformation and analysis of relevant geodynamic phenomena. This chapter provides an application-oriented perspective on the spaceborne InSAR technology with emphasis on subsequent geophysical investigations. First, the fundamentals of radar interferometry and differential interferometry, as well as error sources, are briefly introduced. Emphasis is then placed on the realistic simulation of the underlying geophysics processes, thus offering an unfolded perspective on both analytical and numerical approaches for modeling deformation sources. Finally, various experimental investigations conducted by acquiring SAR multitemporal observations on areas subject to deformation processes of particular geological interest are presented and discussed.",book:{id:"5246",slug:"geospatial-technology-environmental-and-social-applications",title:"Geospatial Technology",fullTitle:"Geospatial Technology - Environmental and Social Applications"},signatures:"Giuseppe Solaro, Pasquale Imperatore and Antonio Pepe",authors:[{id:"4222",title:"Dr.",name:"Pasquale",middleName:null,surname:"Imperatore",slug:"pasquale-imperatore",fullName:"Pasquale Imperatore"},{id:"99269",title:"Dr.",name:"Antonio",middleName:null,surname:"Pepe",slug:"antonio-pepe",fullName:"Antonio Pepe"},{id:"182234",title:"Ph.D.",name:"Giuseppe",middleName:null,surname:"Solaro",slug:"giuseppe-solaro",fullName:"Giuseppe Solaro"}]},{id:"51731",doi:"10.5772/64527",title:"Estimation and Uncertainty Assessment of Surface Microclimate Indicators at Local Scale Using Airborne Infrared Thermography and Multispectral Imagery",slug:"estimation-and-uncertainty-assessment-of-surface-microclimate-indicators-at-local-scale-using-airbor",totalDownloads:1470,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"A precise estimation and the characterization of the spatial variability of microclimate conditions (MCCs) are essential for risk assessment and site-specific management of vector-borne diseases and crop pests. The objective of this study was to estimate at local scale, and assess the uncertainties of Surface Microclimate Indicators (SMIs) derived from airborne infrared thermography and multispectral imaging. SMIs including Surface Temperature (ST) were estimated in southern Quebec, Canada. The formulation of their uncertainties was based on in-situ observations and the law of propagation of uncertainty. SMIs showed strong local variability and intra-plot variability of MCCs in the study area. The ST values ranged from 290 K to 331 K. They varied more than 17 K on vegetable crop fields. The correlation between ST and in-situ observations was very high (r = 0.99, p = 0.010). The uncertainty and the bias of ST compared to in-situ observations were 0.73 K and ±1.42 K respectively. This study demonstrated that very high spatial resolution multispectral imaging and infrared thermography present a good potential for the characterization of the MCCs that govern the abundance and the behavior of disease vectors and crop pests in a given area.",book:{id:"5246",slug:"geospatial-technology-environmental-and-social-applications",title:"Geospatial Technology",fullTitle:"Geospatial Technology - Environmental and Social Applications"},signatures:"Serge Olivier Kotchi, Nathalie Barrette, Alain A. Viau, Jae-Dong\nJang, Valéry Gond and Mir Abolfazl Mostafavi",authors:[{id:"31099",title:"Prof.",name:"Mir Abolfazl",middleName:null,surname:"Mostafavi",slug:"mir-abolfazl-mostafavi",fullName:"Mir Abolfazl Mostafavi"},{id:"181360",title:"Ph.D.",name:"Serge Olivier",middleName:null,surname:"Kotchi",slug:"serge-olivier-kotchi",fullName:"Serge Olivier Kotchi"},{id:"188549",title:"Dr.",name:"Nathalie",middleName:null,surname:"Barrette",slug:"nathalie-barrette",fullName:"Nathalie Barrette"},{id:"188550",title:"Dr.",name:"Alain A.",middleName:null,surname:"Viau",slug:"alain-a.-viau",fullName:"Alain A. Viau"},{id:"188551",title:"Dr.",name:"Jae-Dong",middleName:null,surname:"Jang",slug:"jae-dong-jang",fullName:"Jae-Dong Jang"},{id:"188552",title:"Dr.",name:"Valery",middleName:null,surname:"Gond",slug:"valery-gond",fullName:"Valery Gond"}]},{id:"51786",doi:"10.5772/64528",title:"GIS Applications in Agronomy",slug:"gis-applications-in-agronomy",totalDownloads:3023,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Agronomy is a branch of agriculture that deals with soil and crop. Soil varies in space and is responsible for variation in the growth and yield of crops on the field. This variation in the yields of crops planted and monitored on the same parcel of land under the same environmental conditions has been a great concern to farmers. Spatial variations of soil nutrients status, as caused by topography, soil texture and management practices, have been observed across the fields. Hence, the need to separate the field into site specific management units using geographical information systems (GIS) for effective soil and crop management in order to obtain optimum productivity. Over the years, field sizes, farming direction, locations of fences, rotations and fertility programmes have changed the nutritional status of the farms. Consequently, the productivity of the soil has equally been affected. In spite of these factors, conventional agriculture treats an entire field uniformly with respect to the application of fertiliser, pesticides, soil amendments and other chemical application. The use of GIS will help farmers to overcome over- or under-applications of fertiliser and other agrochemical applications. The potential of GIS application in agronomy is obviously large. However, the GIS user community in the field of agronomy is rather small compared to other business sectors. To advance the use of GIS in agronomic studies, this Chapter in book tends to explore the applications of GIS to some fields in agronomy.",book:{id:"5246",slug:"geospatial-technology-environmental-and-social-applications",title:"Geospatial Technology",fullTitle:"Geospatial Technology - Environmental and Social Applications"},signatures:"Suarau O. Oshunsanya and OrevaOghene Aliku",authors:[{id:"175778",title:"Dr.",name:"Suarau",middleName:null,surname:"Oshunsanya",slug:"suarau-oshunsanya",fullName:"Suarau Oshunsanya"},{id:"176082",title:"Mr.",name:"OrevaOghene",middleName:null,surname:"Aliku",slug:"orevaoghene-aliku",fullName:"OrevaOghene Aliku"}]}],mostDownloadedChaptersLast30Days:[{id:"62267",title:"Identification of Karst Forms Using LiDAR Technology: Cozumel Island, Mexico",slug:"identification-of-karst-forms-using-lidar-technology-cozumel-island-mexico",totalDownloads:949,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Morphological relief analysis allows the identification of geomorphological forms and cartographic-environmental studies make extensive use of the medium (1:50,000) and large scale (1:250,000), where the topographical contrast is evident. However, at a detailed scale (<1:20,000) and for territories where the contrast of relief does not exceed 10 m in height, the morphological analyses must be adapted accordingly, because they contribute information to altimetry studies and to the topographic configuration of units. Thus, through visual interpretation and manipulation of high-resolution topographical LiDAR data from Cozumel Island, a relief analysis is presented at a detailed scale for the purpose of recognizing the geomorphological units of karst origin, using altimetry and slope cartography, digital models of elevation, and shading that permits the identification of 109 new exokarstic doline and uvala formations.",book:{id:"7465",slug:"trends-in-geomatics-an-earth-science-perspective",title:"Trends in Geomatics",fullTitle:"Trends in Geomatics - An Earth Science Perspective"},signatures:"Oscar Frausto-Martínez, Norma Angelica Zapi-Salazar and Orlando\nColin-Olivares",authors:[{id:"185429",title:"Dr.",name:"Oscar",middleName:null,surname:"Frausto-Martinez",slug:"oscar-frausto-martinez",fullName:"Oscar Frausto-Martinez"},{id:"258227",title:"MSc.",name:"Orlando",middleName:null,surname:"Colin - Olivares",slug:"orlando-colin-olivares",fullName:"Orlando Colin - Olivares"},{id:"258228",title:"MSc.",name:"Norma Angélica",middleName:null,surname:"Zapi - Salazar",slug:"norma-angelica-zapi-salazar",fullName:"Norma Angélica Zapi - Salazar"}]},{id:"64109",title:"Mathematical Analysis of Some Typical Problems in Geodesy by Means of Computer Algebra",slug:"mathematical-analysis-of-some-typical-problems-in-geodesy-by-means-of-computer-algebra",totalDownloads:922,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"There are many complicated and fussy mathematical analysis processes in geodesy, such as the power series expansions of the ellipsoid’s eccentricity, high order derivation of complex and implicit functions, operation of trigonometric function, expansions of special functions and integral transformation. Taking some typical mathematical analysis processes in geodesy as research objects, the computer algebra analysis are systematically carried out to bread, deep and detailed extent with the help of computer algebra analysis method and the powerful ability of mathematical analysis of computer algebra system. The forward and inverse expansions of the meridian arc in geometric geodesy, the nonsingular expressions of singular integration in physical geodesy and the series expansions of direct transformations between three anomalies in satellite geodesy are established, which have more concise form, stricter theory basis and higher accuracy compared to traditional ones. The breakthrough and innovation of some mathematical analysis problems in the special field of geodesy are realized, which will further enrich and perfect the theoretical system of geodesy.",book:{id:"7465",slug:"trends-in-geomatics-an-earth-science-perspective",title:"Trends in Geomatics",fullTitle:"Trends in Geomatics - An Earth Science Perspective"},signatures:"Hou-pu Li and Shao-feng Bian",authors:[{id:"141289",title:"Prof.",name:"Shao-Feng",middleName:null,surname:"Bian",slug:"shao-feng-bian",fullName:"Shao-Feng Bian"},{id:"141296",title:"Dr.",name:"Hou-Pu",middleName:null,surname:"Li",slug:"hou-pu-li",fullName:"Hou-Pu Li"}]},{id:"51786",title:"GIS Applications in Agronomy",slug:"gis-applications-in-agronomy",totalDownloads:3022,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Agronomy is a branch of agriculture that deals with soil and crop. Soil varies in space and is responsible for variation in the growth and yield of crops on the field. This variation in the yields of crops planted and monitored on the same parcel of land under the same environmental conditions has been a great concern to farmers. Spatial variations of soil nutrients status, as caused by topography, soil texture and management practices, have been observed across the fields. Hence, the need to separate the field into site specific management units using geographical information systems (GIS) for effective soil and crop management in order to obtain optimum productivity. Over the years, field sizes, farming direction, locations of fences, rotations and fertility programmes have changed the nutritional status of the farms. Consequently, the productivity of the soil has equally been affected. In spite of these factors, conventional agriculture treats an entire field uniformly with respect to the application of fertiliser, pesticides, soil amendments and other chemical application. The use of GIS will help farmers to overcome over- or under-applications of fertiliser and other agrochemical applications. The potential of GIS application in agronomy is obviously large. However, the GIS user community in the field of agronomy is rather small compared to other business sectors. To advance the use of GIS in agronomic studies, this Chapter in book tends to explore the applications of GIS to some fields in agronomy.",book:{id:"5246",slug:"geospatial-technology-environmental-and-social-applications",title:"Geospatial Technology",fullTitle:"Geospatial Technology - Environmental and Social Applications"},signatures:"Suarau O. Oshunsanya and OrevaOghene Aliku",authors:[{id:"175778",title:"Dr.",name:"Suarau",middleName:null,surname:"Oshunsanya",slug:"suarau-oshunsanya",fullName:"Suarau Oshunsanya"},{id:"176082",title:"Mr.",name:"OrevaOghene",middleName:null,surname:"Aliku",slug:"orevaoghene-aliku",fullName:"OrevaOghene Aliku"}]},{id:"51468",title:"Increasing the Adaptive Capacity of Indigenous People to Environmental Change: The Potential Use of an Innovative, Web-Based, Collaborative-Geomatics Informatics Tool to Reduce the Degree of Exposure of First Nations Cree to Hazardous Travel Routes",slug:"increasing-the-adaptive-capacity-of-indigenous-people-to-environmental-change-the-potential-use-of-a",totalDownloads:1433,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The arctic and subarctic regions of Canada are experiencing amplified climate change impacts, which are disproportionately impacting Canadian indigenous populations’ ability to safely travel on land to acquire resources. Less predictable and more dangerous travel conditions are impacting not only the health and safety of individuals but also the traditional lifestyles that are vital to the cultural well-being of these indigenous communities. The University of Waterloo’s Computer Systems Group has developed a novel decision-support tool termed “Collaborative-Geomatics.” This web-based informatics tool can allow for the community to monitor, in real-time, the safety of travel routes. Using handheld GPS tracking systems, the utility of the geomatics system to present real-time travel conditions was carried out in a Canadian First Nations community, located along the Western James Bay coast. The results of this study showed that the collaborative-geomatics tool offers the potential to monitor and store information on the safety of travel routes, helping to promote adaptive capacity and aid in knowledge transfer within arctic and subarctic indigenous communities.",book:{id:"5246",slug:"geospatial-technology-environmental-and-social-applications",title:"Geospatial Technology",fullTitle:"Geospatial Technology - Environmental and Social Applications"},signatures:"Christine D. Barbeau, Donald Cowan and Leonard J.S. Tsuji",authors:[{id:"181883",title:"Ph.D. Student",name:"Christine",middleName:null,surname:"Barbeau",slug:"christine-barbeau",fullName:"Christine Barbeau"},{id:"186196",title:"Dr.",name:"Don",middleName:null,surname:"Cowan",slug:"don-cowan",fullName:"Don Cowan"}]},{id:"64719",title:"Architectural Design and Prototyping of Co-PPGIS: A Groupware-Based Online Synchronous Collaborative PPGIS to Support Municipality Development and Planning Management Workflows",slug:"architectural-design-and-prototyping-of-co-ppgis-a-groupware-based-online-synchronous-collaborative-",totalDownloads:1064,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Co-PPGIS has a wide variety of applications like municipal planning, emergency response, public health and security, etc. The main focus of this chapter is on the development and design of a Web Collaborative PPGIS (Co-PPGIS) infrastructure. As part of municipality’s planning and management services, Co-PPGIS is developed for real-time map sharing application system. Co-PPGIS is an effective and essential online meeting system for supporting group collaborations on geographic information such as maps and imageries, and capturing and sharing of local/domain knowledge in real time. Co-PPGIS permits amalgamation of geospatial data and collaborator’s input in the form of geo-referenced notations. It incorporates coherent components as map sharing, real-time chat, video conferencing, geo-referenced textual and graphical notations. The study aims to focus on public participation and geo-collaboration facilitated with information sharing, interactive geo-conferencing, real-time map, and data sharing with tools to draw features or add annotation to the map while discussions, uploading documents, and live communication. Co-PPGIS provides an efficient and reliable platform that will significantly reduce the time to acquire, process, and analyze data. The significance of this study is to contribute to existing public participation practices, to municipal planning, to decision-making, or to geographic information science.",book:{id:"7465",slug:"trends-in-geomatics-an-earth-science-perspective",title:"Trends in Geomatics",fullTitle:"Trends in Geomatics - An Earth Science Perspective"},signatures:"Muhammad A. Butt, Syed Amer Mahmood, Javed Sami, Jahanzeb\nQureshi, Muhammad Kashif Nazir, Amer Masood, Khadija Waheed\nand Aysha Khalid",authors:[{id:"3899",title:"Mr.",name:"Syed Amer",middleName:null,surname:"Mahmood",slug:"syed-amer-mahmood",fullName:"Syed Amer Mahmood"},{id:"242037",title:"Dr.",name:"M. Atif",middleName:null,surname:"Butt",slug:"m.-atif-butt",fullName:"M. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems. \r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
",coverUrl:"https://cdn.intechopen.com/series/covers/25.jpg",latestPublicationDate:"April 13th, 2022",hasOnlineFirst:!1,numberOfPublishedBooks:1,editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",slug:"j.-kevin-summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. Dr. Summers holds a BA in Zoology and Psychology, an MA in Ecology, and Ph.D. in Systems Ecology/Biology.",institutionString:null,institution:{name:"Environmental Protection Agency",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"38",title:"Pollution",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",isOpenForSubmission:!0,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"39",title:"Environmental Resilience and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",isOpenForSubmission:!0,editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",slug:"jose-navarro-pedreno",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",biography:"Full professor at University Miguel Hernández of Elche, Spain, previously working at the University of Alicante, Autonomous University of Madrid and Polytechnic University of Valencia. Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. Prof. Navarro-Pedreño is also a director of the Ph.D. Program Environment and Sustainability (2012-present) and a member of several societies among which are the Spanish Society of Soil Science, International Union of Soil Sciences, European Society for Soil Conservation, DessertNet and the Spanish Royal Society of Chemistry.",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null},{id:"40",title:"Ecosystems and Biodiversity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/40.jpg",isOpenForSubmission:!0,editor:{id:"209149",title:"Prof.",name:"Salustiano",middleName:null,surname:"Mato",slug:"salustiano-mato",fullName:"Salustiano Mato",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLREQA4/Profile_Picture_2022-03-31T10:23:50.png",biography:"Salustiano Mato de la Iglesia (Santiago de Compostela, 1960) is a doctor in biology from the University of Santiago and a Professor of zoology at the Department of Ecology and Animal Biology at the University of Vigo. He has developed his research activity in the fields of fauna and soil ecology, and in the treatment of organic waste, having been the founder and principal investigator of the Environmental Biotechnology Group of the University of Vigo.\r\nHis research activity in the field of Environmental Biotechnology has been focused on the development of novel organic waste treatment systems through composting. The result of this line of work are three invention patents and various scientific and technical publications in prestigious international journals.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorTwo:{id:"60498",title:"Prof.",name:"Josefina",middleName:null,surname:"Garrido",slug:"josefina-garrido",fullName:"Josefina Garrido",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRj1VQAS/Profile_Picture_2022-03-31T10:06:51.jpg",biography:"Josefina Garrido González (Paradela de Abeleda, Ourense 1959), is a doctor in biology from the University of León and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. She has focused her research activity on the taxonomy, fauna and ecology of aquatic beetles, in addition to other lines of research such as the conservation of biodiversity in freshwater ecosystems; conservation of protected areas (Red Natura 2000) and assessment of the effectiveness of wetlands as priority areas for the conservation of aquatic invertebrates; studies of water quality in freshwater ecosystems through biological indicators and physicochemical parameters; surveillance and research of vector arthropods and invasive alien species.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorThree:{id:"464288",title:"Dr.",name:"Francisco",middleName:null,surname:"Ramil",slug:"francisco-ramil",fullName:"Francisco Ramil",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003RI7lHQAT/Profile_Picture_2022-03-31T10:15:35.png",biography:"Fran Ramil Blanco (Porto de Espasante, A Coruña, 1960), is a doctor in biology from the University of Santiago de Compostela and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. His research activity is linked to the taxonomy, fauna and ecology of marine benthic invertebrates and especially the Cnidarian group. Since 2004, he has been part of the EcoAfrik project, aimed at the study, protection and conservation of biodiversity and benthic habitats in West Africa. He also participated in the study of vulnerable marine ecosystems associated with seamounts in the South Atlantic and is involved in training young African researchers in the field of marine research.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}}},{id:"41",title:"Water Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/41.jpg",isOpenForSubmission:!0,editor:{id:"349630",title:"Dr.",name:"Yizi",middleName:null,surname:"Shang",slug:"yizi-shang",fullName:"Yizi Shang",profilePictureURL:"https://mts.intechopen.com/storage/users/349630/images/system/349630.jpg",biography:"Prof. Dr. Yizi Shang is a pioneering researcher in hydrology and water resources who has devoted his research career to promoting the conservation and protection of water resources for sustainable development. He is presently associate editor of Water International (official journal of the International Water Resources Association). He was also invited to serve as an associate editor for special issues of the Journal of the American Water Resources Association. He has served as an editorial member for international journals such as Hydrology, Journal of Ecology & Natural Resources, and Hydro Science & Marine Engineering, among others. He has chaired or acted as a technical committee member for twenty-five international forums (conferences). Dr. Shang graduated from Tsinghua University, China, in 2010 with a Ph.D. in Engineering. Prior to that, he worked as a research fellow at Harvard University from 2008 to 2009. Dr. Shang serves as a senior research engineer at the China Institute of Water Resources and Hydropower Research (IWHR) and was awarded as a distinguished researcher at National Taiwan University in 2017.",institutionString:"China Institute of Water Resources and Hydropower Research",institution:{name:"China Institute of Water Resources and Hydropower Research",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:0,paginationItems:[]},overviewPagePublishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"10843",title:"Persistent Organic Pollutants (POPs)",subtitle:"Monitoring, Impact and Treatment",coverURL:"https://cdn.intechopen.com/books/images_new/10843.jpg",slug:"persistent-organic-pollutants-pops-monitoring-impact-and-treatment",publishedDate:"April 13th 2022",editedByType:"Edited by",bookSignature:"Mohamed Nageeb Rashed",hash:"f5b1589f0a990b6114fef2dadc735dd9",volumeInSeries:1,fullTitle:"Persistent Organic Pollutants (POPs) - Monitoring, Impact and Treatment",editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",biography:"Prof. Mohamed Nageeb Rashed is Professor of Analytical and Environmental Chemistry and former vice-dean for environmental affairs, Faculty of Science, Aswan University, Egypt. He received his Ph.D. in Environmental Analytical Chemistry from Assiut University, Egypt, in 1989. His research interest is in analytical and environmental chemistry with special emphasis on: (1) monitoring and assessing biological trace elements and toxic metals in human blood, urine, water, crops, vegetables, and medicinal plants; (2) relationships between environmental heavy metals and human diseases; (3) uses of biological indicators for monitoring water pollution; (4) environmental chemistry of lakes, rivers, and well water; (5) water and wastewater treatment by adsorption and photocatalysis techniques; (6) soil and water pollution monitoring, control, and treatment; and (7) advanced oxidation treatment. Prof. Rashed has supervised several MSc and Ph.D. theses in the field of analytical and environmental chemistry. He served as an examiner for several Ph.D. theses in analytical chemistry in India, Kazakhstan, and Botswana. He has published about ninety scientific papers in peer-reviewed international journals and several papers in national and international conferences. He participated as an invited speaker at thirty international conferences. Prof. Rashed is the editor-in-chief and an editorial board member for several international journals in the fields of chemistry and environment. He is a member of several national and international societies. He received the Egyptian State Award for Environmental Research in 2001 and the Aswan University Merit Award for Basic Science in 2020. Prof. Rashed was recognized in Stanford University’s list of the World’s Top 2% Scientists in 2020 and 2021.",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}}]}]},openForSubmissionBooks:{paginationCount:1,paginationItems:[{id:"11601",title:"Econometrics - Recent Advances and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11601.jpg",hash:"bc8ab49e2cf436c217a49ca8c12a22eb",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 13th 2022",isOpenForSubmission:!0,editors:[{id:"452331",title:"Dr.",name:"Brian",surname:"Sloboda",slug:"brian-sloboda",fullName:"Brian Sloboda"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:19,paginationItems:[{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",doi:"10.5772/intechopen.104846",signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"81271",title:"The Diversity of Parvovirus Telomeres",doi:"10.5772/intechopen.102684",signatures:"Marianne Laugel, Emilie Lecomte, Eduard Ayuso, Oumeya Adjali, Mathieu Mével and Magalie Penaud-Budloo",slug:"the-diversity-of-parvovirus-telomeres",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"79909",title:"Cryopreservation Methods and Frontiers in the Art of Freezing Life in Animal Models",doi:"10.5772/intechopen.101750",signatures:"Feda S. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. 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Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}},{id:"351158",title:"Prof.",name:"David W.",middleName:null,surname:"Anderson",slug:"david-w.-anderson",fullName:"David W. Anderson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",country:{name:"Canada"}}}]}},subseries:{item:{id:"95",type:"subseries",title:"Urban Planning and Environmental Management",keywords:"Circular economy, Contingency planning and response to disasters, Ecosystem services, Integrated urban water management, Nature-based solutions, Sustainable urban development, Urban green spaces",scope:"
\r\n\tIf we aim to prosper as a society and as a species, there is no alternative to sustainability-oriented development and growth. Sustainable development is no longer a choice but a necessity for us all. Ecosystems and preserving ecosystem services and inclusive urban development present promising solutions to environmental problems. Contextually, the emphasis on studying these fields will enable us to identify and define the critical factors for territorial success in the upcoming decades to be considered by the main-actors, decision and policy makers, technicians, and public in general.
\r\n
\r\n\tHolistic urban planning and environmental management are therefore crucial spheres that will define sustainable trajectories for our urbanizing planet. This urban and environmental planning topic aims to attract contributions that address sustainable urban development challenges and solutions, including integrated urban water management, planning for the urban circular economy, monitoring of risks, contingency planning and response to disasters, among several other challenges and solutions.
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He collaborates with the Environmental Resources Analysis Research Group (ARAM), University of Extremadura (UEx), Spain; VALORIZA - Research Center for the Enhancement of Endogenous Resources, Polytechnic Institute of Portalegre (IPP), Portugal; Centre for Tourism Research, Development and Innovation (CITUR), Madeira, Portugal; and AQUAGEO Research Group, University of Campinas (UNICAMP), Brazil.",institutionString:"University of Johannesburg, South Africa and WSB University, Poland",institution:{name:"University of Johannesburg",institutionURL:null,country:{name:"South Africa"}}},editorThree:null,series:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null},editorialBoard:[{id:"181486",title:"Dr.",name:"Claudia",middleName:null,surname:"Trillo",slug:"claudia-trillo",fullName:"Claudia 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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/348198",hash:"",query:{},params:{id:"348198"},fullPath:"/profiles/348198",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var t;(t=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(t)}()