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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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Plants have long been a source for traditional medicinal products. Indeed, greater than four billion people utilize plants to meet their primary health care [1-2]. There are >120 distinct drugs derived from plant sources representing >70% of the approved drugs in the past 20 years [3, 4]. The manner to exploit the scale and cost advantages of agriculture while diversifying the product offerings made available by plants has been under intense investigation since the early 1980s. Traditional transgenic approaches were initially pursued, but the challenges associated with the transformation and regeneration of viable recombinant crops delayed the appearance of initial products of medicinal promise until 1989 with the production of antibodies [5]and 1990 with the production of human serum albumin [6]. During this time, the concept of using plant virus genomes as expression vectors emerged. In early investigations, researchers recognized the natural capability of virus systems to change the translational priorities within infected cells such that virally encoded proteins were produced preferentially. This ability suggested that expression vectors could be constructed from viral nucleic acids to produce recombinant proteins throughout infected plants [7]. However, for this hypothesis to be tested, the genomes of viruses, starting with positive (+) strand RNA viruses, had to be cloned and characterized [8-10]. Soon after the first full-length “infectious” clones of a (+) strand RNA plant virus were constructed, and preceding traditional transgenic systems, the virus genome was converted into an expression vector [11]. Although limited with regards
The rapid replication cycle of the virus systems provided amplification of messenger RNA and the resulting proteins providing for a “burst” of recombinant expression that can provide impressive yields (reviewed in [12-15]). While these early vectors were useful in plant cell systems to produce recombinant protein products with potential market value [16], these early systems could not support large scale manufacturing nor did they exploit the advantages of agriculture to provide cost-effective products. This review will provide an overview of plant virus-based expression vectors, and provide select examples how virus expression systems have evolved to offer valuable tools for the production of medically important products [17]and support the study of plant structure and metabolic function (reviewed in [18]) in dicot- and monocotyledonous plants. The growing biomedical and agricultural markets have encouraged great creativity in the construction and testing of plant virus expression systems.
As an example of the market drivers for plant-based expression vectors, the biopharmaceutical industry market will be briefly reviewed. Recombinant proteins, including monoclonal antibodies (mAbs), enzymes, hormones, cytokines and growth factors, and vaccine antigens, are the source for new medical therapies and the pharmaceutical market. The global pharmaceutical market continues to prove to be robust, >$850B in 2010, in spite of generic pressure and biosimilars appearance [19]. Recombinant protein drugs, known as biologics, expanded their market to $149B, including $48B in sales of the top selling monoclonal antibody (mAb) products treating cancer and other disorders [19, 20]. The global cancer therapeutic market is projected to continue growth at 12.6% compound annual growth rate through 2014 [21]. Monoclonal antibody immunotherapy has revolutionized the treatment of many diseases – most notably cancer where the nondestructive nature of mAb treatment synergizes with many existing therapies to result in improved efficacy. These molecules make up the most promising part of product portfolios for biopharmaceutical companies and this market is predicted to grow by 11-14% compounded annual growth rate (CAGR) in the next five years compared with the rather tepid growth of ~3% CAGR of small molecule drugs [22, 23]. Indeed, in the midst of an economic downturn (2008-2010), the growth in mAbs continues to occur with sales of therapeutic mAbs being $48B in 2010 compared with $40B in 2009 and $37B in 2008 [24]. Adding the $10B of sales for mAbs used for diagnosis and research reagents raises the total mAb market to $58B in 2010. The clinical development of immunotherapy has been revived after several breakthroughs that have led to the approval of drugs and treatment for cancer. Indeed, four of the top 10 mAbs in terms of sales, are used for cancer treatment [24]. New drug targets and associated drug interventions are under investigation that will provide therapeutic options for traditionally underserved populations.
Recent successes and the growing market demand for more innovative biologic products to treat chronic patients has continued to fuel interest and investment to identify tools and strategies to accelerate discovery and product validation in immunotherapy fields. Further, clinical success is ultimately determined by established clinical endpoints indicative of survival. However, these results often require monitoring for months to years after the therapy has been given to the patient. These timelines are not conducive to the iterative and experimental process that is cancer therapy. Therefore, surrogate markers are sought: more rapidly appearing measurements that correlate with longer-term clinical endpoints. These functions require access to relevant clinical samples from diseased and healthy patients as well as adapting laboratory assays to more clinical formats. Surrogate markers require specific assays used to demonstrate efficacy of immunologic therapies and, as noted above, will fuel extraordinary market growth in the coming decade. These assays are highly empirical and require well trained staff, highly controlled conditions and consistency in procedure to ensure trends in data can be validated as statistically significant. Diagnostic assays incorporating recombinant proteins or exploiting mAb for detecting and assessing medical conditions was $776M in 2010 and is expected to grow at a CAGR of 47% through 2015 [25]. This growth in the use of biologics for immunotherapy and diagnostic products continues, in part, because of recent FDA approvals and physician implementation of several new immunology tools and immunotherapeutic products to diagnose and treat patients.
Plants have steadily gained acceptance as alternative production systems for biologics. The recent United States Food and Drug Administration approval of ProtalixBiotherapeutic’sElelyso (taliglucerasealfa) [20]represents the successful realization of the goal for plant-produced human biologics, initiated soon after the formation of Agrigenetics in 1981. This product, produced in engineered carrot cells, benefits from the simpler culture conditions required by plant cells compared with Chinese hamster ovary (CHO), insect, or yeast systems. However, it still requires the capital intensive production methods, requiring multiplicative costs for increased scale [26]. Nevertheless, the approval of Elelyso, demonstrates that plants can be used to source biologics that meet the stringent demands for high quality in human products, at competitive scale and costs. Indeed, Protalix indicates that the lower production costs associated with carrot cell systems will allow pricing of Elelyso to be 75% of Cerezyme, the leading product in this market sector [20]. This approval strengthens the regulatory case for plant-based production systems that was established by the 2006 approval of a DowAgrosciences, LLC vaccine by the US Department of Agriculture for the prevention of Newcastle disease in chickens [27]. As with the Protalix product, this recombinant vaccine was derived from a transgenic plant cell culture system.
Agriculture offers several advantages as a biologic production system. Plants allow capital-efficient design of upstream manufacturing capacity at various scales providing cost savings that cannot be easily matched by fermentation technologies. The market opportunities provided by follow-on biologics and the rising capital costs associated with production using traditional systems make plants particularly attractive. Considerable capital and time is required to construct the upstream facilities for cell culture production. The upstream facility must be linked with downstream capabilities supporting product purification and characterization. Although outdated, the published costs associated with these facilities are $300–$500 million and require from four to five years to complete construction, validation, and to gain regulatory approval [28]. Agriculture-based production requires less specialized upstream facilities, typically controlled growth chambers, linked with similar downstream production capabilities. The use of plants therefore reduces capital expenditures and also provides for more flexible use of space and capital.
The handling of plant biomass and its initial extraction requires unique biomanufacturing solutions [14]. Virus vector expression systems offer significant advantages at considerably reduced costs to current cell-based manufacturing systems, such as employed by Protalix and Dow AgroSciences, while avoiding concerns associated with stable plant transformation [29, 30]. Virus based expression systems have been extensively tested and shown safe and environmentally-friendly in both indoor and outdoor tests since 1991 [12]and multiple products completing early stage human clinical investigations [31, 32]. Additional advantages also exist compared with traditional cell-based fermentation approaches include: 1) speed and low cost of genetic manipulation; 2) rapid manufacturing cycles; 3) no mammalian pathogen contamination; 4) minimal endotoxin concentrations and 5) economical production [12-15, 33, 34].
Many different types of plant viruses have been converted into vectors for the production of recombinant proteins or peptides (for complete review, see [12-15, 33, 34]). As different viruses have distinct biological limitations and gene expression potential, each vector system has its own unique opportunities. This review focuses on virus vectors that have been particularly useful to produce recombinant proteins for biomedical, therapeutic and research, use. Many groups have sought to categorize virus based expression systems. For this review, we will organize our thinking by using two categories: “independent-virus” or “minimal-virus”. Independent-virus vectors are replication competent vectors that can be principally inoculated to plants as virus particles or viral RNA, multiply in initially infected cells and exploit virus encoded cell to cell and systemic movement activities to infect the majority of the phloem sink tissue of a host. In contrast, minimal virus systems are replication competent systems that have be modified in order to possess greater expression capabilies. The modifications are typically replacement of a virus-encoded open reading frame, not essential for genome replication, with the gene of interest such that the minimal-virus systems lack the ability to systemically infect a host. Examples of each system will be provided in the following sections with Figure 1 illustrating the genetic structures of independent and minimal virus systems derived from the tobacco mosaic
The genomic structure of wild type Tobacco Mosaic
Initial RNA virus vectors were functionally minimal-virus vectors that utilized a “gene replacement” strategy where a foreign gene of interest replaced the capsid protein (CP) gene of a virus [11]. These early vectors expressed foreign genes, but, as with other minimal-virus systems, lacked certain virus functionsthereby limiting activities. For example, brome mosaic virus (BMV) CP replacement vectors could not even move from cell to cell in an infected leaf [11], and although TMV-based CP replacement vectors could move from cell to cell, they could not move systemically in inoculated plants [35-37].
With greater understanding of virus function, plant RNA virus vectors were constructed to express a foreign gene product in addition to all required viral proteins [36, 38]. These vectors were the first independent-virus system that expressed recombinant products while moving systemically in a host plant. To construct independent-virus systems for (+) strand RNA viruses, vectors exploit subgenomic mRNA production to express foreign genes by using an additional subgenomic promoter inserted into the virus [38-40]. For viruses that used polyprotein processing, the foreign gene was inserted in translational frame with the existing virus open reading frame (ORF) and peptide sequences that facilitate the proteolytic processing of the fusion protein were present to insure release of the recombinant protein. Some independent-virus vectors are designed to express potential products as fusions to viral proteins, such as the potatovirus X (PVX) CP (reviewed in [41]). Often the fusion methodology employs the foot and mouth virus 2A translational cleavage sequence (see references in [42]). The apparent pausing of the ribosome, and the discontinuity of the peptide bond that results, allows proteins upstream and downstream of the 2A sequence to be differentially targeted, such as a single chain antibody accumulating in the plant apoplast while the CP was sequestered in its normal cytosolic localization [43]. Using these strategies, independent-virus systems have been derived from the genomes of
Most independent-virus vectors are functional in
As a more detailed example of an independent-virus system,
Active vaccination of Non-Hodgkin’s Lymphoma (NHL) patients with cancer antigens, in this case the idiotypic antibody expressed by the tumorogenic B-cells, has been shown to induce clinical remissions in human clinical trials [48]. However, more efficient and effective vaccines are sought. Full antibodies contain both idiotype-specific elements as well as constant sequences, shared by many antibodies, which may reduce the immunogenicity of the vaccine. In order to provide higher antigen content to vaccines, single chain antibodies (scFvs) were constructed from tumor-derived idiotypic antibodies to provide simpler and more sequence-focused vaccines for clinical testing. This vaccine strategy was shown to be effective in murine models of NHL [49]and a GENEWARE®-based production methodology was developed that could produce >80% of scFvs from human tumor samples [50]. Sixteen patients were enrolled in a Phase I clinical trial under the regulatory oversight of the US Food and Drug Administration [31, 51]. Vaccines were successfully produced for all patients and applied in two dosing groups with and without granulocyte-macrophage colony-stimulating factor adjuvant. The primary endpoint of the study was safety which, as the first parenteral administration of a plant-made vaccine, was an important outcome to monitor. The study results confirmed the safety of plant-derived vaccines, including plant-specific glycoforms present on 15 of the 16 vaccines. The secondary endpoint was determination of the immunogenicity of the vaccines in human subjects. Overall, 70% of the patients developed cellular or humoral immune responses to the scFv vaccines, with the adjuvant improving the frequency of responses, as predicted. The majority of the responses was shown to be vaccine specific and did not cross react with control idiotype proteins. These results demonstrated the flexibility of the TMV-based expression systems as well as the safety and effectiveness of the plant derived products [31, 51].
In contrast to independent-virus vectors, minimal-virus systems are capable of functions supporting RNA replication, yet are lacking in one or more functions necessary for systemic infection. Although this vector was the first type constructed, researchers moved away from this approach in favor of the independent-virus vectors. However, as limitations emerged from independent-virus systems, including the size of genes that can be expressed, host range limitations and problems with systemic movement, researchers revised minimal-virus systems with new energy. The resulting vectors were found to be incapable of systemic movement in inoculated plants, thus they must be delivered to each and every plant leaf to allow cell-to-cell movement activities allow infection of all inoculated leaves. Standard abrasion methods are too tedious to deliver inoculum to each leaf, so new methods were developed. The most common method is Agro-infiltration of host plants to launch the infection process [33, 52-54]. This process introduces a DNA plasmid, containing the virus vector under the control of an appropriate transcriptional unit within normal Ti plasmid integration sites, into
The activity of viral movement proteins move the vectors from the initially infected cells to adjacent cells creating a more rapid and synchronous infection of inoculated leaves than independent-virus vectors. This eliminates the delays associated with systemic plant movement and can yield greater amounts of recombinant proteins in a shorter period of time than independent-virus systems [33, 54]. This approach increases the genetic load carried by the minimal-virus systems allowing efficient expression of larger recombinant proteins [55]. Minimal-virus systems have been developed from the genomes of
Examples of minimum-virus vectors include the systems developed using TMV genomes include those developed by(Figure 1)[63,64]. Two TMV variants were developed – one, actually an independent-virus system, employed the full TMV virus capable of systemic movement [63] and a second – lacked the virus coat protein as minimum-virus system [64]. The minimum-virus system (TRBO vector) produced significantly higher levels of the green fluorescent protein (up to 5.5 mg/g FW). This vector did not require the co-expression of a silencing suppressor and worked with very high inoculum dilution in infiltration medium. The RNA2 of cowpea mosaic virus (CPMV) was also adapted as a minimum-virus system which overcame the historic limitation of the insert size in CPMV vectors and allows expression hetero-oligomeric proteins from a single vector [65, 66]. However, the system also requires co-expression of silencing suppressors for optimal expression.
DNA viruses have been adapted to minimal virus systems. Both single and bipartite plant geminivirus systems have modified to produce recombinant proteins – usually at the expense of expression of the capsid or key movement or transmission proteins. Maize streak virus is an example of a single component virus which has been converted into an expression vector [67]. Bean yellow dwarf virus (BeYDV) has been developed into a single and dual-component replicon system that permits simultaneous, efficient replication of two DNA replicons and thus high-level accumulation of one or two recombinant proteins in the same plant cell [68, 69]. This system has been used to produce express immunoglobulin proteins and human papilloma virus HPV-16 and the p24 protein of HIV-1 [70]. The system requires co-expression of the silencing suppressors. Some geminivirus systems have been adapted to express recombinant proteins in non-
The most advanced minimum-virus system is magnICON®. This technology has been used to express a large number of recombinant proteins, including cytokines, interferon, bacterial and viral antigens, growth hormone, single chain antibodies (reviewed in [54, 72]). The ability of Agroinfiltration to introduce more than one expression vector into a host plant in the same inoculation allows the use of two magnICON® vectors to produce heteromeric recombinant proteins, such as mAbs. For production of mAbs, two non-competitive virus vectors are used: one based on turnip vein clearing tobamovirus (TVCV) and the second, potatovirus X (PVX [55, 73]). In mAb production, two magnICON® virus expression vectors each contain a separate mAb chain, heavy or light, and are co-delivered by Agroinfiltration. Each vector replicates independently and expresses mAb chains in the same cells that self-assemble functional mAbs at yields up to 1 g/kg fresh weight [33, 54, 55]. These vectors have been used for efficient large scale production of multi-gram batches of mAbs under Current Good Manufacturing Practices that have been tested in several challenge model systems, including non-human primates [14, 74].
Standard integrative plant expression vectors allow transformation of plant lines using
The present of sialic acid terminal sugars on glycan structures of human plasma proteins is correlated with their long half-life and the pharmacokinetic properties of effective recombinant therapeutics which must function in human plasma [80]. The capability to sialylate plant proteins has been demonstrated in transient and transgenic
The focus of the previous material was virus expression systems providing recombinant protein expression primarily in plant dicotyledonousplant species. This emphasis comes from the historical emphasis on dicot expression due to the availability of more facile systems. Yet monocotyledonous species, especially the cereals, are the most important of crops for feeding humans and livestock in many parts of the world. Further, maize, sugarcane, bamboo and other monocot species, are used extensively in the production of biofuels and other industrial products. Monocots possess unique morphological featuresand seed biology suggesting gene functions not present in dicots. Monocot species have also developed unique mechanisms for tolerance of adverse environmental conditions like drought and high salinity. In the past, most protein functions were proposed based on homology to better characterized dicot systems, such as
One of the challenges in developing any plant based expression system is to achieve high level expression without triggering the post translational gene silencing (PTGS) and related RNAi mechanisms that plants and other organisms have evolved (reviewed in [18]). These mechanisms have been observed to operate in transgenic plants, and even exploited to generate pathogen-derived resistance to viruses in cases where the silencing of viral transgenes prevents related viruses from infecting the transgenic host [85, 86]. The identification of plant viral proteins that are able to suppress these silencing mechanisms suggested that these mechanisms have evolved in part to prevent or slow viral infection.
Expression of proteins using viral vectors can also trigger PTGS, and is referred to as viral induced gene silencing (VIGS). Using VIGS, an endogenous plant gene can be silenced by inserting only a small portion of the target gene (100-500 nt in length) which creates loss of function phenotypes to study gene function. A wide range of viruses have been developed as VIGS vectors, originally, and most extensively, for dicot hosts [18, 87]. Shortly after the first dicot examples, a barley stripe mosaic virus (BSMV)vector, was used to silence the endogenous
BSMV, the type member of the hordeivirus family, infects many agriculturally important monocot species such as barley, rice, corn, oat and wheat [89-92]. It is known to be highly seed transmitted in barley, which could be a potential advantage for assessing gene function in seeds and early development. As showen in Figure 2, BSMV has a tripartite (+) sense RNA genome consisting of RNAs α, βand γ[93]. The virus uses well characterized subgenomic promoters for gene expression from each of its genomic RNAs [94].
As a more detailed example of a VIGS vector, BSMV was constructed by inserting fragments of the silencing target so that they would be expressed only as untranslated RNA on a subgenomic promoter following the γb ORF [88]. Although the strongest silencing in barley plants was observed using the barley
The general structure of BSMV genomic RNAs α, βand γ. Boxes represent the open reading frames on each RNA and are labeled with the the viral protein they encode. Arrows indicate the position of subgenomic promoters used to express the downstream proteins.
Coupling VIGS with high-throughput cloning and sequencing technologies has additionally allowed these viral vectors to be used in functional genomics. In this approach, cDNA libraries are constructed within virus expression vectors and gene function to be assessed by screening infected plant hosts for phenotypic or metabolic changes measured by various input and output focused screening assays. TMV and PVX VIGS vectors were the first to employed in this manner in the dicot
As with dicot expression vectors, monocot vectors include both minimal and independent virus vectors[103]. As noted above, minimal type BMV vectors have been constructed by replacing the coat protein ORF with a foreign gene. For example, French
BSMV has been developed to express recombinant proteins as fusions to several individual virus proteins expressed from subgenomic RNAs. To date these systemic vectors have not incorporated any sequences to liberate the foreign protein from the fusion protein. For example Lawrence and Jackson [106] expressed GFP as a fusion to the N terminus of the βb (TGB1) protein at levels sufficient to explore the function of the viral protein in cell-to-cell movement. Higher levels of expression however were achieved with fusions to the C-terminus of the BSMV γb protein. This includes systemic expression of a γb::GFP fusion protein used to study viral movement in barley [107, 108]. More recently, C-terminal γb fusions have been use to test the fungal ToxA protein activity in wheat, barley and
These efforts to develop independent viral expression vectors in monocots are extended by previously unpublished work described here. Our aim in this work was to improve foreign gene stability, increase the level of foreign gene expression, and generate free, non-fusion, foreign proteins that could function and localize independently of viral proteins.
Expression. of GFP::γb Fusion Protein from RNA γ
To test whether insert stability was related to the fusion orientation, we constructed a vector with GFP fused (indicated by the “::” in construct name) to N-terminus of the γb protein (γ.GFP::γb, Figure 3A). Co-inoculation of protoplasts and barley leaves with α and β RNAs (BSMV-GFP::γb) resulted GFP fluorescence and fusion protein accumulation to levels that were indistinguishable from co-inoculations with α, β and γ.γb::GFP (BSMV-γb::GFP) as shown in Table 1 (compare #3 and #4). However, as the infection in plants progressed beyond 7 dpi, GFP fluorescence and fusion protein accumulation were observed longer in γ.GFP::γb infected plants than in those infected with γ.γb::GFP. Specifically, GFP::γb expression is regularly observed in leaves 1-4 above the inoculated leaf by BSMV-GFP::γb, compared to 1-2 leaves for BSMV-γb::GFP (data not shown). Thus, the GFP gene is generally maintained and expressed by BSMV-GFP::γb to 18 dpi. We believe that the increased stability of fusions to the N-terminus of γb results from more restrictive requirements for the deletion of the GFP gene in order to gain a competitive advantage. For example, internal deletions in the GFP ORF have a one in three chance of maintaining the continuity of the ORF with γb, which is critical because γb is an important virulence factor for BSMV [111]. Thus, those deletions which result in a γb frame shift are likely to be less competitive than those viruses which maintained the full GFP ORF. In contrast, for C-terminal fusions of GFP to γb, all deletions within the GFP ORF would maintain γb expression and would presumably be more competitive than the parental virus due the reduced genetic load.
Genomic organization of BSMV γ RNAs engineered to express GFP. Vector components γ.γb::GFP and γ.GFP:: γb as designed to produce a fusion of GFP to the γb protein C and N terminus, respectively (a). The vector component γ.Δ
Inoculum | GFP expression | Systemic symptoms of BSMV infection | ||||||
Inoculation# | Vector RNA components | Tobacco Protoplasts | Barley Plants | |||||
Barley Plants | ||||||||
1 | α | β | none | γ | - | - | yes | |
2 | α | β | TMV-GFP | ***** | - | no | ||
3 | α | β | γ.γb::GFP | **** | systemic | yes | ||
4 | α | β | γ.GFP:: γb | γ | **** | systemic | yes | |
5 | α | β | γ.Δγa. Δγb.GFP | - | - | no | ||
6 | α | β | γ.Δγa. Δγb.GFP | γ | ***** | - | yes |
Comparative expression of GFP in tobacco protoplasts and barley plants using BSMV vector constructs
Expression of native GFP from RNA γ
To develop a BSMV vector able to express a free foreign protein, we tested a variety of novel vectors with the most promising of which described here. In each case, the BSMV γ RNA was modified to express GFP in combination with wild type BSMV α and β RNA. A three component vector with RNA α, β, and γ.Δγa.Δγb-GFP (a γ RNA containing a deletion of γa, the replicase protein ORF, and GFP in place of the γb ORF, Figure 3C) did not express GFP in protoplasts (#5, Table 1). However, the addition of wild type γ RNA created a four component vector, which was equivalent in GFP expression levels to TMV 30B (TMV-GFP [40]) in protoplasts (compare #6 with #2, Table 1). In contrast to its behavior in protoplasts, the four component vector did not express GFP systemically in barley, even though systemic viral symptoms were observed (#6, Table 1), apparently due to the loss of the GFP bearing component during systemic movement. This system may be amenable to expression in whole plants if delivered using an Agroinoculation strategy, or in transgenic plants expressing the γa and γb proteins to complement RNA α, β, and γ.Δγa.Δγb-GFP.
In a different approach, BSMV vectors expressing N- and C-terminus fusions of GFP to BSMV γb were modified to release GFP
BSMV Coat protein deletion vector and GFP expression. Genomic organization of BSMV β RNA engineered with a deletion of the BSMV coat protein, βa (a). Open boxes indicate ORFs, hatched boxes indicate indicateuntranslated ORF sequences, arrows indicate subgenomic promoters. BstB1 restriction site indicates the position of the βa sequences that have been deleted from the wild type β RNA. Western blot analysis of γb::GFP protein in barley leaves (b).
Genomic organization of BSMV γ RNAs and expression of free GFP or heterologous proteins from a cDNA library. Vector components γ.GFP::HA::2A-γb and γ.cDNA::HA::2A-γb as designed to produce a fusion of GFP or a heterologous protein with an HA epitope tag and the FMDV 2A sequence. The 2A sequence is designed to release the γb protein is during translation (a). Open boxes indicate ORFs, checkered boxes indicate the HA epitope sequence, grey boxes indicate FMDV 2A cleavage sequence, arrows indicate subgenomic promoters. Western blot analysis of GFP::HA fusion protein in barley leaves (b). Graph of rice cDNA sequences arranged according to size (c). cDNAs whose predicted proteins were detected by Western blot analysis are unshaded, while blue shaded bars indicate the lack of detectable HA tagged protein. Green bar represents the internal GFP::HA::2A control.
Coat. Protein Deletion Enhances Expression from γb Subgenomic Promoter
The coat protein (βa) of BSMV is not required for systemic infection. To determine the impact of βa deletion on βb subgenomic expression, a β genomic RNA containing a deletion of the βa ORF was constructed (β.Δβa, Figure 4A). In tobacco protoplasts, using β.Δβa increased GFP accumulation from the γ RNA 2-5 fold for viruses bearing the γb fusions (γ.γb::GFP, γ.GFP:: γb, γ.γb::2A::GFP, and γ.GFP::2A:: γb) or GFP substitutions of γb (γ.Δγa.Δγb.GFP) (Figure 4B and data not shown). Using β.Δβa also increased GFP fluorescence and accumulation for γb::GFP, GFP:: γb, γb::2A::GFP, and GFP::2A:: γb, in systemic barley tissue (data not shown).
Expression. of Epitope Tagged Heterologous Proteins from RNA γ Derived Vectors
To detect heterologous proteins, γ.GFP::2A-γb was modified to contain the hemagglutinin (HA) epitope tag fused between GFP and the FMDV 2A cleavage sequence (γ.GFP::HA::2A- γb, Figure 4A). In barley plants infected with BSMV RNAs α, β.Δβa, and γ.and γ.GFP::HA::2A-γb, Western blot analysis detected the HA tagged GFP (Figure 5B).The addition of the HA tag had no effect on the efficiency of the 2A cleavage sequence. These results suggested that the HA epitope tags would allow for the efficient detection of BSMV expressed heterologous proteins.
To test the flexibility of BSMV to express heterologous proteins in barley, plant genes, from a variety of subcellular locations were expressed as N-terminal fusions to HA::2A-γb (γ.cDNA::HA::2A-γb, Figure 5A). A total of 42 full-length rice genes were amplified from sequenced, cDNA library clones and inserted in frame with the HA::2A-γb ORF. All 42 γ.cDNA::HA::2A-γb RNAs were infectious when co-inoculated onto barley plant with BSMV RNAs α and γ.Δβa. For each vector, systemically infected barley tissue was tested in replicate for recombinant protein expression using two anti-HA antibodies. From the 42 genes, 38 genes showed confirmed expression of protein product in each plant tested (Figure 5C). In each case, the size of the protein detected in the Western blot was consistent with the size predicted for the post-cleavage heterologous protein, with the addition of the HA epitope tag and the 2A sequence. The 2A cleavage differed between the different heterologous genes, but cleavage rates of 60-95% were usually observed.
In our survey of 42 full length rice ORFs between 200 and 1800 nucleotides in size. The resulting gene products including proteins of 38, 46, 54 and 64 kDa proteins. Due to the average insert size of the library, proteins of 20-30 kDa were most commonly detected in our study. The flexibility of the BSMV expression vector was further demonstrated is ability to successfully express proteins of cytosolic localization (GFP and BMV CP) and those that are matured through the plant secretory pathway (including a lysozyme, interferon, human growth hormone and protease inhibitor). The maturation of these proteins demonstrates the ability of the 2A cleavage system to deliver proteins to distinct subcellular fates and still retain activity. In addition, these data also demonstrate the ability of the vector to express genes from both plant and animal sources successfully.
In summary, to develop a monocot vector capable of expressing free, heterologous proteins, we have tested a variety of strategies based on the BSMV γ RNA. All of the strategies relied on expression from the γb subgenomic RNA facilitating expression of >90% (38/42) recombinant proteins tested. The recombinant proteins were of a variety of sizes, ranging from 11 to 64 kDa. These data demonstrate that monocot recombinant expression vectors can be developed that show many of the flexile and attractive features of traditional dicot expression systems. These vectors can be deployed for testing the function of plant genes in both monocot and dicot species as well as express proteins of recombinant proteins of biomedical importance.
Primarily monopartite genomes with some multipartite examples | Primarily multipartite genomes with a monopartite example |
Independent and minimal-virus vectors demonstrated for whole plant expression | Independent-virus vectors only demonstrated for whole plant expression; minimal-virus vectors restricted to cell culture expression |
Vector delivery as infectious RNA transcripts or Agroinfiltration of DNA-based expression vectors | Vector delivery as infectious RNA transcripts |
Successfully used for gene silencing and gene overexpression | Successfully used for gene silencing and gene overexpression |
Systemic expression of foreign proteins primarily through non-genetic fusion strategies | Systemic expression of foreign proteins primarily through genetic fusions to virus proteins and inclusion of cleavage sequences |
Expression of single gene cistrons | Potential expression of multiple cistrons as β and γ gene fusions |
Systemic expression of wide range of gene sizes and classes of proteins | Systemic expression of wide range of gene sizes and classes of proteins |
Successful integration into cGMP recombinant protein production environment | Not integrated to date into cGMP production environment |
Comparison of properties of virus vectors for expression in dicot and monocotyledonous plant species.
The last few decades have seen tremendous progress in developing tools and expertise to produce recombinant proteins in plants. Although conceptually straightforward, the technical hurdles included not only improving our understanding of plant biology, development of expression systems, but also the perfection of purification and analytical methods to meet the specifications of research, industrial and medical applications. The successes described in this chapter involved a convergence of economic incentives, market forces and regulatory acceptance, the latter being particularly important for biomedical products. Throughout much of this time, transient viral expression systems have played a significant role. The adaptability of virus systems and their ease of use continue to help push the boundaries of recombinant protein expression in plants. Beginning with a few examples, highlighted in this review, a diverse array of viral vector systems have emerged capable of delivering target genes to a wide array of host species, and compliant with a wide range of regulatory and technical constraints. As shown in this chapter, expression successes initially observed in dicotyledonous plants have now been extended to monocotyledonous plants through the use of the BSMV genome. A comparison of the properties of virus vectors designed for recombinant protein expression in dicot and monocot plant species is provided in Table 2. Research continues to improve their effectiveness and ease of use. Indeed, the advantages of low development costs, flexible design, and relatively quick turnaround from conception to proof of principle to scale up, will continue to drive innovation and application of viral expression vectors. The synergy of customizing specific plant hosts for post-translational modifications offers a strategy to produce plant-sourced products which match the needs of the proposed end uses. Further, the unexpected discovery of viral vectors as tools to silence specific genes in plants has also been of tremendous value to the plant research community, and has effectively complemented their use in overexpression in a way that has only begun to be appreciated and applied in the last decade. The use of these two complementary approaches to address functional genomics in a high throughput fashion, and on a broad range of hosts, will likely emerge in the coming years.
The authors would like to acknowledge the support of Kentucky BioProcessing, LLC in the preparation of this manuscript and their continued leadership in the development and application of plant-virus expression systems in recombinant protein manufacturing processes. The excellent technical efforts of Mr. Paul Brosio and Dr. Long Nguyen are also acknowledged for their contributions to the novel BSMV overexpression vectors described within this chapter.
Maritime is an important industry. Over 80% of the total transport of all goods takes place by sea because it is the most economical and most massive mode of transport. The world’s seas provide free waterways. These are the largest absorbers of carbon dioxide and the largest producers of oxygen. The seas are the main source of food for one-third of the world’s population. Oil and diamonds, e.g., are extracted from the seabed. However, the seas are exposed to pollution caused by both natural disasters and human factors. Another paradox related to the seas is that the maritime industry lags significantly behind other industries in terms of digitalization. Some facts that support this statement are as follows: a large number of ships do not comply with the requirements of the Safety of Life at Sea (SOLAS) Convention. Some ships do not have modern electronic navigation aids such as Electronic Chart Display and Information System (ECDIS) nor (Satellite) Automatic Identification System ((S)AIS), for instance. Analyzes of accidents at sea have shown that the crew sometimes is not familiar with these devices. Digitization at land is more developed than at sea, and the main reason for this is the lack of profound investigation of Internet connectivity at sea, which can be hampered by sea surface movements, wave occlusions, rough weather, poor coverage, etc. Consequently, inter-organizational information systems (IOS) are used 75% in hinterland and only 25% in maritime. Internet of Things (IoT) is used considerably less at sea than at land. In road and rail transport, it is possible to track cargo at the level of a single unit or a container, while in maritime transport this is still not possible. As an example, we can use transport of dangerous goods. The casks (drums) with radioactive waste (plutonium, e.g.) can be tracked by Radio Frequency Identification (RFID) chips, Internet connection, and security backend web applications at the level of a single freight unit or a drum in the road and in rail transportation [1, 2], but not in maritime [3]. Furthermore, there are a large number of autonomous vehicles on roads (about 1.5 thousand) and in the air, i.e., drones (about 1.5 million), but only one autonomous ship (Yara), and another one is currently under construction [4]. Blockchain technology is not widely accepted yet, since there are various impediments like the lack of trust between stakeholders; government support; legislation; standards; along with the stakeholders’ readiness for risky investments in emerging technology. Some extensive desktop studies of academic writings shown that a very small percentage of articles deal with advanced info-communication concepts such as big data, virtual intelligence, robotics, 3D, virtual reality, digital security, etc., in maritime. There is no clear political strategy for further development of info-communication systems in maritime. This complicates maritime digitization in developed countries, and considerably more in developing ones. Concerning the latest, this chapter is organized in the following manner: Section 2 deals with smart adoption of advanced ICT&S in general, and in maritime business. Additionally, a case study has been conducted in several non-EU and EU countries in this respect, based on the Holtham’s & Courtney’s model. Section 3 considers rational blockchain adoption in maritime, with a focus on developing environments, concerning BMSCS, TradeLens, smart contracts, and Blockshipping. This section also encompasses a case study on blockchain smart adoption in maritime business in emerging economies, with emphasis on South Africa and Montenegro, while Section 4 gives some concluding remarks.
We live in a time of massive progress in the field of info-communication technology and systems (ICT&S). The question is do we really need all these innovations and do they always make our lives easier and better. In order to get the best out of ICT&S, we need to know which of these technologies we actually need and how to use them purposely. When it comes to a business environment, it is very important that higher management structures are aware of these needs and discuss them with employees. This is especially important in maritime business, bearing in mind that, stakeholders in maritime are usually conservative and not early new technology adopters. Several studies considered ICT&S rational, intelligent or smart implementation and adoption of advanced ICT&S in maritime [5, 6, 7, 8, 9, 10]. On the Holtham’s & Courtney’s model, in this chapter, it has been examined how stakeholders in maritime assess key constructs in the model, regarding some developed and developing countries in Europe. The considered countries were treated as the European Union (EU) and non-European Union (non-EU) ones. Before presenting the methodology and the obtained results, the overview of the applied Holtham’s & Courtney’s model is given.
This model is composed of four constructs: knowledge, ICT&S strategy, system effectiveness, and ICT&S management. These constructs are supported by organizational culture and top manager’s mindset (Figure 1).
Adapted Holtham’s & Courtney’s model (source: Own).
Knowledge can be described as the understanding of a subject that one gets by experience or study, known either by one person or by people generally; or, as the state of knowing about or being familiar with something [11]. Furthermore, Cambridge dictionary depictures knowledge as awareness, understanding, or information that has been obtained by experience or study, and that either is in a person’s mind or possessed by people generally; or, as skill in, understanding of, or information about something, which a person gets by experience or study. Symbolically, knowledge is one of the steps in the so-called ladder of knowledge. This ladder of knowledge encompasses data, information, knowledge itself, and wisdom stairs. The data and information have easier explanations than the concepts of knowledge and wisdom. In this context, the focus will be on knowledge stair, as a key for understanding contemporary ICT&S and their rational implementation in maritime business. Knowledge here means consciousness about advanced ICT&S availability at the market, including the ICT&C purposiveness regarding particular business strategies, processes, and activities.
The ICT&S strategy brings together business and technology. Due to the Holtham’s & Courtney’s model, there are five different strategic orientations.
The system effectiveness can be achieved by setting and communicating critical success factors (CSF) [12] and developing them steadily. The first step is to use technology to create an effective operational platform, primarily with internal information. Then, the CSFs can be widened to foster improved skills to use technology. This will start with employees and then extend to suppliers and customers. Once when these two steps work well, the CSFs can be broadened to encompass external information about markets, customers, and competitors. After these, three steps comes business intelligence, which allows organizations to identify and manage risk while developing new products, services, and markets to ensure a successful future.
The ICT&S management is based on ICT&S builders, ICT&S managers, and ICT&S users. A person or management team that communicates the needs of ICT&S users into ICT&S builders or designers has to be engaged in the organization as a knowledge navigator, or information resource manager. There are business organizations, which recognized this triangle and which are working on filling and improving the personnel skills towards achieving this goal [13, 14].
These four constructs, which form the backbone of the Holtham’s & Courtney’s model are underpinned by organizational culture and top manager’s mindset.
Concerning the organizational culture, there is universal agreement that it exists and plays an important role in shaping behavior in organizations. However, there is little consensus on what organizational culture actually is. Here are quoted several expressions that can be used in absence of universally accepted one [15]: organizational culture is how organizations do things; organizational culture is the sum of values and rituals, which serve as glue to integrate the members of the organization; organizational culture is civilization in the workplace, etc.
Top manager or top management team’s role is to weave a fabric of horizontal (information, technology, people, and organization) and vertical (direction, knowledge, process, and climate) threads mutually intertwined. In organizations where knowledge is a core dimension, managers have frequently identified people’s skills as the major influence, along with organizational climate. Moving from the information-based to the knowledge-based enterprise is a major challenge for today’s companies [16]. Therefore, managers have to combine proper notions from several different domains: organizational behavior, human resource management, big data, analytics, artificial intelligence, etc. Technology is a key enabler, but not usually as significant as skills and climate. Top managers’ team mindset covers all considered constructs and it affects intelligent or rational use of ICT&S.
These constructs are used in the following analysis as independent variables. As a control variable is used non-compliance between technology-led potential and its everyday usage, while the dependent variable is intelligent use of ICT&S, which reflexes efficient and smooth communication between tasks, technologies, and employees [4].
Based on the Holtham’s & Courtney’s model, a survey was conducted among stakeholders in maritime in terms of how rationally they use the ICT&C in their business. Selected stakeholders from four EU (Croatia, Greece, Italy, and Slovenia) and from four non-EU countries (Albania, Bosnia & Herzegovina (B&H), Montenegro, and Serbia) were included in the survey. Forty experts (five per each considered country) from maritime administrative bodies, agencies, private marine companies, ports, and universities (maritime departments) were asked to evaluate the set of fifteen statements by means of Likert (1–5) scale (Table 1). The last two statements refer to the control and dependent variables in the model, respectively, while the rest of the statements correspond to the independent variables.
Construct | Statements |
---|---|
C1: Knowledge | S1.1: Knowledge is important for business success. S1.2: Knowledge and skills of employees are important for efficient and effective use of ICT&S? |
C2.1: ICT&S Strategy | S2.1: New ICT&S solutions adoption is risky for the organization. |
C2.2: ICT&S Strategy | S2.2: Analyzing carefully the existing ICT&S solutions prior to their introduction into the organization is important. |
C2.3: ICT&S Strategy | S2.3: The ICT&S reduces operational costs of the organization. |
C2.4: ICT&S Strategy | S2.4: The available ICT&S solutions can be adapted to the current business needs of your organization. |
C2.5: ICT&S Strategy | S2.5: The latest ICT&S solutions are the best ones. |
C3: System effectiveness | S3.1: Your customers intensively use ICT&S resources of your organization (web site and various online users’ apps). S3.2: The ICT&S allows you to become familiar with the current market trends in the area of your business. |
C4: ICT&S management | S4.1: The ICT&S functions are important for the successful functioning of the organization and its business success. S4.2: The usage of ICT&S for operational takes within your organization (accounting operations, database of employees, database of business partners, market analysis, etc.) is extensive. |
C5: Culture | S5: Positive organizational culture and clime are important for effective use of ICT&S. |
C6: Manager’s mindset | S6: Manager’s mindset is important for effective use of ICT&S. |
C7: ICT&S capacities versus exploitation | S7: There is a divergence between ICT&S capacities and their real application on a daily basis in your organization. |
C8: ICT&S intelligent exploitation | S8: The ICT&S serves as connective tissue among tasks, technologies, and employees in your organization. |
The survey content.
Source: Own.
The level of respondents’ agreement with the proposed statements is labeled due to the following scheme: (i) if the average score per group of experts from a certain country is between 1 and 2.5 then the level of experts’ agreement is “low”; (ii) if it is between 2.6 and 3.5, then the level of agreement is “moderate”, and (iii) if it is between 3.6 and 5, then it is “high”. The results of the survey are presented in Table 2.
The assessments of the constructs.
Source: Own.
According to the results presented in Table 2, it is obvious that all respondents evaluate knowledge, ICT&S management, and manager’s mindset as highly important for rational application of ICT&S in maritime organizations. When it comes to the system effectiveness and organizational culture, the experts assessed these constructs as high or moderate important for intelligent implementation of ICT&S. Control variable confirms validity of the assessments assigned to the dependent variable “intelligent use of ICT&S in maritime”. Namely, all experts highly agreed with the statement “the ICT&S serve as a connective tissue among tasks, technologies, and employees in your organization”, which in fact justify smart exploitation of ICT&S in maritime business. When it comes to ICT&S strategy orientation, the respondents are dominantly
In addition to the analysis of the degree to which ICT&S are used rationally in the maritime business, it was also examined which advanced info-communication platforms are available to the maritime organizations in which the respondents in this study work. The results of this part of the survey are presented in Table 3. It is evident that there are efforts to modernize ICT&S in maritime business, but also that some of the analyzed maritime organizations, i.e., countries are lagging behind, especially those that are not members of the EU. Namely, the non-EU countries have to reconsider their business development strategies and ensure funds for implementing new ICT&S and renewal of the existing ones. These countries should follow actual trajectories and scenarios towards efficient and effective digitalization in maritime [17].
Available ICT&S in the examined maritime organizations.
Source: Own.
Through this case study, it is shown that responders, who are employed in maritime administration and business organizations in four EU and four non-EU countries, have similar attitudes towards concerned constructs inherent to intelligent exploitation of contemporary ICT&S. They all identified knowledge, ICT&S management, system efficiency, organizational culture and manager’s mindset as key perpetuators of rational and purposeful use of the ICT&S. This speaks in favor of their sound education and awareness about the importance of ICT&S in today’s dynamic maritime business environment. Regarding ICT&S strategical orientation, the respondents are cautious, i.e., not prone to take risks of investing in new ICT&S solutions and experimenting in the market.
When it comes to the availability of common and advanced ICT&S in analyzed maritime organizations, it is shown that there are big differences among EU and non-EU countries. For instance, maritime organizations in Slovenia have almost all listed ICT&S except blockchain technology, AGVs, digital twins, are UxVs. The companies in Italy have, e.g., digital twins and UxVs. Croatia and Greece have also quite an extensive list of available ICT&S. On another side, explored non-EU countries are modestly equipped. The examination of the reasons for such difference and how it can be alleviated in order to avoid disruptions in maritime ecosystem and negative economic implications for the non-EU countries should be the subject of further, more profound studies. None of the considered maritime entities does have on disposal Blockchain-based Maritime Supply Chain System (BMSCS), e.g. Since BMSCS is the advanced emerging ICT&S platform in contemporary maritime business, the following text attempts to explain the basic principles of this platform, including its benefits and challenges.
Bockchain in maritime is a far broader system than cryptocurrency-based electronic financial transactions mechanism. In literature, it is named as Blockchain-based Maritime Supply Chain System (BMSCS) [18]. It includes smart contracts and payments, tracking and tracing cargo, empty containers placement, early risk assessment, and services that can create new added values in maritime (Figure 2).
BMSCS key components (source: Own).
Maritime is an indispensable link in global supply chains. Hereof, blockchain technology is likely to become unavoidable in shipping and port management, in striving to optimize global supply chains and make these more efficient and effective. The BMSCS should reduce the volume of administrative work, errors that occur due to manual work, delays in the delivery of goods, and consequently overall costs of transportation and delivery of goods. Due to some studies, the costs of global supply chains should be reduced by approximately 15% by implementing blockchain technology [19].
In addition to these advantages, blockchain also has certain disadvantages. Maritime sector is generally risk-averse, tending not to be an early adapter of new potentially risky technology [20]. Some stakeholders in maritime want to keep their data secret, since “competition is fierce” and “a lot of industry actors are basically competing with the same service” [21]. In other words, some partners in the supply chain consider information as a competitive resource and are unwilling to share them. Positional data might be used to track vessels by identifying port locations, fueling locations, and routes [22]. This is particularly the case with tracking dangerous and hazardous goods, pharmaceuticals, or food. The use of blockchain does not guarantee that the information recorded in ledgers is correct and does not prevent tampering data prior to entering it into blockchain ledger, e.g., the contents of a container, fuel production, testing or combustion, and the like [23]. Due to the huge amount of data and traffic generation, including data storage, blockchain requires a wideband like G5 or G6 [24], while the internet speed can be low when the working stage is offshore. Further, blockchain causes high-energy consumption [25]. Blockchain in the maritime sector indicates the potential to reduce transaction costs in a number of areas, including reducing the need for intermediaries such as brokers and courier services and reducing related financial expenses and energy costs. However, one should not forget that this does not include the costs of the overall investment and expenses associated with blockchain implementation and adoption, especially in developing or emerging economies [26, 27].
The present level of awareness, knowledge, and expertise about blockchain is scarce among the stakeholders. Therefore, educational, training, or capacity-building programs are necessary at regulatory, administrative, and operational levels. Higher level of standardization across the global supply chain is necessary as well. The Digital Container Shipping Association (DCSA) conducts efforts in this regard, but further, more extensive, actions are necessary. In general, there is a hesitation by stakeholders in maritime sector to invest in blockchain systems in terms of technological integration, regulatory, organizational, and educational costs, since the maritime sector traditionally relies on its legacy systems. There appears to be a gap between what practitioners in the blockchain area suggest and what has been a range of state-of-the-art approaches in software engineering and information security research and practice [28]. Furthermore, the major liner shipping companies are the most likely parties to benefit from blockchain regarding the complexity of their blockchains and huge requirements on financial resources [29]. This can put other potential actors in the global supply chain at a disadvantage. The last but not the least, the basic attitude should be that technology, in this case, blockchain on the top of the global supply chain should improve the human condition, and not replace humans [30]. Therefore, human and ethical dimensions of blockchain technological development and more extensive deployment, should not be neglected.
In the following text, we shall present blockchain framework in maritime at the example of two applications: TradeLens and Blockshipping. TradeLens is used for tracking and tracing cargo along the global supply chain, early risk assessment, smart contracts, and value-added services created through an open platform. Blockshipping is used for empty containers’ optimal placement by autonomous intelligent software agents.
TradeLens is a new business model in shipping and port management. It enables one-to-many connections for all the actors, all individuals that are involved in a global supply chain instead of bilateral connections. Everybody come together in a maritime industry-neutral, open platform for every participant [31]. Maersk, the world’s largest international container shipping and logistics company, and IBM the technology leader in blockchain came together to provide a new, open platform solution underpinned by blockchain to help unlock some of the opportunities for a more efficient global supply chain. Maersk and IBM have a long history of working together, actually decades. In March 2017 these organizations collectively try to improve global trade through digitization. In January 2018, they launched an early adapter program; trials began, and in August 2018, they formally launched the TradeLens limited availability platform, shared among 92 participants. In December 2018, TradeLens is commercially realized, along with 1.5 million events per day published to the platform. Some types of these events are presented in Table 4.
Actual | Estimated | Planned |
---|---|---|
Start container tracking | Documentation cutoff: Vessel ETD | Import documents approval |
Start shipment tracking | VGM (Verified Gross Mass): Vessel ETD | Discharged from truck |
Booking confirmation | Cargo cutoff: Vessel ETD | Loaded on vessel |
Stuffing started | Rail ETD | Stuffing started |
Vessel ATA | Rail ETA | Stuffing completed |
Vessel ATD | Bill of Lading Available | Loading on vessel |
Loaded on rail | Vessel ETD | Gate in |
Rail ATD | Vessel ETA | Gate out |
Rail ATA | Discharged from vessel | Packed container selected for inspection |
Loaded on truck | Load on vessel | Packed container passed inspection |
+Add more | Custom release | Cargo specific certificate approved |
+Add more | +Add more |
The platform can track 120+ unique consignment shipments, while 60+ network members are onboard or in a process of accessing. TradeLens supports 18+ unique, standardized, trade document types. Some of these documents are listed in Table 5. In February 2019, enhanced document sharing, permissions, and notifications were released. The platform includes half a billion events on annual basis and this number grows with more and more network members.
Document | Party |
---|---|
Import documentation approved | Customs House Broker |
Customs release | Customs Authority |
Cargo geography-specific certificate approved | Customs House Broker |
Bill of lading available | Beneficiary Cargo Owner (BCO) |
Certificate of origin available | Beneficiary Cargo Owner (BCO) |
Packaging list available | Beneficiary Cargo Owner (BCO) |
Commercial invoice available | Beneficiary Cargo Owner (BCO) |
More than twenty million containers of cargo information are in the system today, which is roughly 1/5 of global trade and it is growing. The platform involves numerous parties and systems: ocean carriers, ports and terminal operators, inland carriers, shippers, consignees, beneficiary cargo owners, freight forwarders, 3PLs, custom authorities, government agencies, financial and insurance services, transportation management systems, Port Community Systems (PCSs), supply chain validity systems, supply chain, manufacturers, retailers, etc. They all collaborate and share information. TradeLens provides them with comprehensive, real-time visibility and immutability across the end-to-end journey of shipment. In other words, data is available immediately, along with the single simplified view across all shipments. For instance, a terminal operator publishes a piece of information about the fact that a container has been loaded onto a ship that becomes immediately available to everybody else in the supply chain. The idea is to build workflow based on smart contracts using chain code to derive cross-organizational workflow by excluding manual work.
Blockchain on which the platform is based, enables the trust in data that are available on the platform. It is an open and censorship-resistant distributed database model, secured by encryption and decentralization. Blockchain records information in blocks on a shared ledger, storing a synchronized copy of it on all the systems participating in the network, hence assuring its immutability. The trust anchors, which are the blockchain nodes, ensure through consensus algorithms that the information should be written on the platform as approved like valid. All information are auditable, verifiable, and temper proof; so, as soon as a piece of data is published to the blockchain it cannot be edited. The only way to edit a document is to create a new version of the document. Consequently, all the documents are fully auditable. Additionally, cryptographic hash of the data is written to the blockchain, and this is a part of the supply chain. It is important to say that private data remain private. TradeLens as an information-sharing model allows ecosystem partners to have access to the information they should access and vice versa. The platform offers a high level of flexibility through application of RESTful APIs (Application Programming Interfaces), back-end ERP (Enterprise Resource Planning), and secured front/back-end web services.
In the middle or at the very core of TradeLens solution, there is the platform and blockchain behind it. Below the platform is the network. The network is not a physical network. It is a set of entities that provide the data, including the data itself. The ocean carriers, ports, terminal operators, customs, shippers, inland transporters, etc., provide the data. On the top, above the platform are applications and services, i.e., RESTful APIs, back-end ERP, and secured web that enable people to exchange information. These are based on open published industrial UN/CEFACT standards that are defined at the platform level, so that third parties are allowed to build new value-added services and applications. This is the basic kind of model, through which TradeLens is moving forward as a paradigm shift in information sharing across the whole ecosystem. A conceptual framework of TradeLens as a blockchain-based solution in the global supply chain is presented in Figure 3.
TradeLens conceptual framework (source: Own).
What kind of information is shared across the platform, i.e., over the entire supply chain? This information is mostly shipping milestones. The information on: has a container been staffed; has the container be gated; what is the estimated time of arrival (ETA) of the container at the destination, and so on, are in fact shipping milestones. However, it is more than that. It is also the documents in maritime, both structured and unstructured (like PDFs, scans, images, etc.), by making them available to the participants along the supply chain. The documents need to change ‘hands’. They need to be approved, updated, and available to build workflow using smart contracts, like the bill of lading, clearance, insurance, etc. This is powerful in terms of driving cross-organizational data flow in maritime.
Within TradeLens, there is sensor data and IoT for referring to the container number, electronic seal, temperature inside it, for instance, etc. All of that is part of the underlined data that is made available to the participants who need that data. There is a whole concept of seamless and permission data-sharing model that is built on the base: what your role is, i.e., are you terminal, ocean carrier, shipper, inland transporter, etc. The default permission model allows people to share information, so that information is made available to those who need it, but it is not available to those who should not see it.
TradeLens is of utmost importance whenever planned actions turn into unplanned. For instance, the ocean carriers’ decision has implications not just for them but for all stakeholders further down the supply chain from customs brokers, port authorities, and terminal operators to inland transporters and consignees. With TradeLens, changes to the shipment are reflected immediately allowing supply chain participants to coordinate actions tightly, delivering the consignee’s inventory in time. TradeLens allows near-instant logistics adjustments so the disruptions are kept to a minimum. Global trade is an incredibly complex system, but TradeLens and blockchain create an industry-wide and innovative solution to alleviate this complexity and related impediments.
Smart contracts are programs stored on a blockchain that run when predetermined conditions met. They are used to automate the execution of an agreement so that all participants can be immediately certain of the outcome, without an intermediary’s involvement or time loss. They can also automate a workflow, triggering the next action when conditions are met [32]. Smart contracts work by following simple “if/when (…) then (…)” statements that are written into code on a blockchain. In the other words, a smart contract presents the lines of code that are stored on a blockchain and automatically executes when predetermined terms and conditions are fulfilled [33]. A network of computers executes the actions when predetermined conditions have been met and verified. These actions could include releasing goods, funds, or confirmations in maritime supply chain. The blockchain is updated when the transaction is completed. That means the transaction cannot be changed, and only parties who have been granted permission can see the results. Blockchain network controls access. Within a smart contract, there can be as many stipulations as needed to satisfy the participants, so that the task will be completed correctly. To establish the terms, participants must determine how transactions and their data are represented on the blockchain, agree on the “if/when (…) then (…)” rules that govern those transactions, explore all possible exceptions, and define a framework for resolving disputes. Then, the smart contract can be programmed by a developer, although organizations that use blockchain for business, provide templates, web interfaces, and other online tools to simplify structuring smart contracts. Key benefits of smart contracts are speed, efficiency, accuracy, trust, transparency, and security (blockchain transaction records are encrypted, which makes them very hard to hack; plus, each record is connected to the previous and subsequent records on a distributed ledger, and hackers would have to alter the entire chain to change a single record). In maritime supply chain, sea waybill or bill of lading can be converted into a smart contract, while it requires an agreement between shipper and carrier, and/or any other relevant and permissioned parties to view the consignment, transport equipment, and documents, as permissions allow [34]. The benefits of such smart contract include simplified transmission of shipping instructions; management of document status and versioning; faster submission of shipping instructions for creation of final bill of lading; quick sharing of documents with all permissioned parties; including immutability, traceability, and auditability of the documents involved.
Today the container shipping industry accounts for around 60% of all the world seaborne trade. This valuable industry has been troubled for years by challenges like overcapacity, low freight rates, security threats, and increasing environmental regulations. Currently, there are about 27 million containers in the world, which are moved from one destination to another on trucks, container cars, ships, rail, or waiting in the port, container yard, railway station, and the like. About 5 million containers are uncontrolled and nobody knows their precise locations; if they are currently in transit or waiting for collection. Consequently, no one knows if they are empty or loaded, which means that no one knows if a truck or a train is wasting time and energy carrying an empty “metal box” instead of carrying goods [35]. This is a huge waste of energy; it produces additional costs and negatively affects the environment.
Therefore, the global shared container platform (GSCP) is currently under development. As the world’s first blockchain-based container registry, it will allow the industry to help real-time track all containers worldwide. The platform will enable the industry players to manage efficiently all kinds of transactions related to container handling. The GSCP has several user groups like shipping lines, leasing companies, banks, financial institutions, blockchain container investment syndicates, transport service providers, beneficiary cargo owners (BCO), container terminals, container depots, repair shops, etc.
Through a secure login, each user group will have a unique set of functionalities that matches their exact needs. For example, if you are a shipping line export user, you can use GSCP platform to find street turn matching opportunities for ensuring that empty containers meet export demands. You will see an inventory list of all export bookings, which require an empty container to the customer location for stuffing, rather than transporting an empty container from the port or the depo. For convenience, the platform enables users to switch between list and map view. The user can apply one or more filters and inventory will update accordingly, for instance, only showing FEUs (40-feet units). Any set of applied filters can be saved in user’s filter presets. This way they are quickly accessible whenever the user needs them. Matching export containers with import containers is easy and swift. This enables both importer and exporter to save an empty container haulage trip, plus gate in and gate out fees at the terminals. The system identifies possible matches based on container size, type, boarding date, previous commodities carried, and availability. The platform also enables sending a request to the involved shipping line with the comment. The GSCP provides various ways to import booking and container data. The user can use EDI and API connection with the in-house booking or order platforms [36].
Blockshipping is, in fact, a shared pool of containers, which enables a “just in time containers” situation. Today more than 40% of all containers in transport are empty. Therefore, resources are wasted and costs are increased. With Blockshipping saving potential for the shipping industry might be at least 5.7 billion USD and reduction of CO2 emission can be 4.6 million tons yearly [37]. Blockshipping platform is a part of the so-called programmable economy. In such an economy, the interactions among different parties will not occur through mediation of a third trusted party, but automatically through autonomous intelligent software agents (AISA). These are also called dApps (distributed Apps) that run on blockchain and are authorized and instructed by the parties involved in the BMSCS to negotiate autonomously on their behalf.
Four key subsystems of Blockshipping are [38]:
Global Shipping Container Registry (GSCR), that holds real-time information about every container available through Blockshipping;
Empty Container Repository Engine (ECRE) that continuously calculates the next best-laden transport for each container. The engine also “understands” the position of every truck available to transport the empty container;
Autonomous Intelligent Software Agents (AISA) that run on blockchain and negotiate all agreements;
Smart Contracts (SC) that can be treated as rental contracts established through autonomous negotiations, which persist on the blockchain and govern the rental through binding self-enforcing rental agreements.
Blockshipping has developed a unique revenue-sharing model, while it issues two types of tokens:
Internal utility token, or Container Platform Token (CPT), and
External revenue share coin, or Container Crypto Coin (CCC).
The CPT will be used for clearing and settlement of transactions between the users of the platform. These transactions will relate to many different services and fees. A percentage of the revenue goes to a revenue share pool and is passed on to the owners of CCC tokens. Blockshipping exchanges the CPTs in the revenue share pool to Ether via USD. Then, Blockshipping uses smart contracts to convert revenue Dutch auction on the Ethereum blockchain in which Blockshipping offers the owners of the CCC tokens price for their tokens. The offered price will increase until all available Ethers are spent. After the auction, Blockshipping distributes the acquired CCC tokens to all the owners of CCC tokens on a pro-rata basis. In this way, token owners are rewarded regardless of their decision to sell or keep their CCC tokens [39].
The processes flow within Blockshipping is based on several simple and fully automated steps. The easiest way to make an explanation is to follow an example. Let us assume that the shipping line needs to rent a container to transport goods from Nairobi (Kenya) to Rotterdam (Netherlands). Blockshipping empty container repository engine identifies the best-positioned empty container in Nairobi and informs the shipping line about the options. The shipping line informs its autonomous intelligent software agents (AISAs) about the containers. The rental negotiations then happen unsupervised between the shipping line and the container owner through their autonomous agents. The agreements established by AISAs are persisted on blockchain in smart contracts that govern the rental in binding self-enforcing rental agreements. Blockshipping container platform tokens CPT are used to pay rental fees, while the fees are transferred from the shipping line wallet, in accordance with the smart contract and reserved payment. Smart contracts can be changed if conditions change. For example, if the rental period is extended when the container reaches its final destination in Rotterdam. Then, the smart Oracle blockchain enforces the smart contract. The rental ends and releases CPTs to the container owner’s wallet [40].
In addition to TradeLens and Blockshipping, there are a number of other blockchain applications in maritime. Some of these are given in Table 6. Concerning safety issues, semi-private blockchains are common. The consortium companies’ reputation speaks, in fact, about safety. Maritime, as conservative, assesses and recognizes the quality of operation in long run. As we said previously, stakeholders in maritime are not early adopters. However, trust between network participants is a bigger problem than safety. The blockchain is an unorthodox technology and cryptocurrencies are still highly volatile. In such a setting, maritime stakeholders do not like to disclose essential business information about customers, suppliers, and cargo. Many freight forwarders and intermediaries, e.g., earn their profit thanks to information asymmetry. Interoperability will be a smaller problem in terms of technology (since standards have been developing) than in terms of trust and smooth process flows at (inter-)organizational level.
No. | Blockchain | ||
---|---|---|---|
Consortium | Platform | Ledger | |
1. | Port of Koper, Slovenia | CargoX | Public |
2. | Malaysia’s West Port & LPR - Brazilian textile importer | 300cubits | Public |
3. | Maersk & IBM | TradeLens | Consortium (permissioned) |
4. | Abu Dhabi Ports and Port of Antwerp | Silsal | Consortium (permissioned) |
5. | EY & Guardtime | Marine Insurance Blockchain | Public |
6. | PIL, PSA & IBM | Proof of Concept (POC) | Consortium (permissioned) |
7. | Port of Antwerp with Belfruco, Enzafruit, PortApp, 1-Stop and T&G Global | Smart Contracts | Consortium (permissioned) |
8. | 2021.AI Den Danske Maritime Fond, EUDP, INVICTA | Blockshipping | Public |
9. | Port of Malmo & Port of Copenhagen | PortChain | Consortium (permissioned) |
10. | AAT, FileVersion Health, CROP | CargoChain | Consortium, (permissioned) |
Within this case study, we explored how maritime stakeholders in two developing countries, South Africa and Montenegro, perceive blockchain technology and its implementation in maritime. Through the methodological framework given in [26, 27] we conducted the survey, which included thirteen closed-ended questions, or statements on blockchain adaption. Concerned statements included the following blockchain dimensions: knowledge, infrastructure, standards, experts, diverse stakeholders, government and regulatory policy, social influence, loss of jobs, computing and storing capacity, complexity, opportunistic behavior, sharing information, and security. The respondents were from maritime companies, agencies, research organizations, governmental bodies, insurance companies, and universities. They are from the executive management level in industry and governmental bodies, and active researchers, professors, and lecturers from universities (10 from South Africa and 10 from Montenegro, all with more than 5 years of research experience). The respondents have had to express their (dis)agreement with the proposed statements via Likert 1–5 scale, where 1 represents the lowest level of (dis)agreement, and 5 the highest level of (dis)agreement. The rest of the offered numerical values are respectively in-between these two extremes. The statements and average values of assessments are given in Table 7. If the average score per group of respondents is between 1 and 2.5, then the level of (dis)agreement is “low”; if it is between 2.6 and 3.5, then the level of (dis)agreement is “moderate”, and if it is between 3.6 and 5, then it is “high”.
The assessments of blockchain adoption.
Source: Own.
Five statements with the highest “agree” and “disagree” assessment rates are categorized in different PESTEL (political, economic, social, technological, environmental, and legal) dimensions, along with their rank (Table 8).
P Political | E Economic | S Social | T Technological | E Environmental | L Legal |
---|---|---|---|---|---|
*Favorable government policies (rank 3) | *Hesitancy of sharing information (rank 5) | Awareness and knowledge about BC (rank 1) Skilled and expert resources (rank 4) | Infrastructure (rank 2) | *Hesitancy of sharing information (rank 5) | *Favorable regulatory policies (rank 3) |
Reduction of opportunistic behavior (rank 2) | Social Influence (rank 3) | Complexity and observability (rank 1) *Standardization (rank 4) **Ensuring privacy and security (rank 5) | **Ensuring privacy and security (rank 5) | *Standardization (rank 4) **Ensuring privacy and security (rank 5) |
PESTEL analysis.
- Constructs marked with ‘*’ correspond with two different PESTEL dimensions.
- Constructs marked with ‘**’correspond to three different PESTEL dimensions.
Source: Own.
The respondents consider awareness and knowledge about blockchain as a social dimension of the highest importance for its adoption in maritime. This is understandable, since knowledge is the biggest asset; the only one which grows with exploitation during the time. On the second place is infrastructure, which falls under technological dimension. This is reasonable since, without it, blockchain adoption is practically impossible. In the third places are favorable government and regulatory policies that fall under political and legal dimensions. This is of crucial importance since economic development in South Africa and in Montenegro is controlled by the government. On the fourth place is experts’ knowledge, which belongs to the social dimension of PESTEL model, and which is to a certain extent connected with awareness and knowledge, but it can be outsourced in the case of its lack, and under the assumption that awareness and general knowledge about blockchain are in place. The fifth place is the hesitancy of sharing information among the parties, and it falls under both economic and environmental dimensions of PESEL. This is understandable, since once blockchain becomes well established; the impact of this issue will be reduced.
The highest disagreement is observed regarding ‘simultaneous’ presence of blockchain complexity and observability. Majority of the respondents show suspicion regarding this paradox. Furthermore, the respondents do not agree with the statement that blockchain will reduce opportunistic behavior. South Africa and Montenegro are countries that are for decades in transition and suffer from the permanent reproduction of crisis. Consequently, the responders’ rather skeptic attitude towards this statement is completely understandable. The social influence is in the third place. The respondents do not believe that society can affect considerably the implementation of this advanced technology, and this belief is based on their experiences from transitional settings. The statement, which deals with the standardization issue, is “negatively” assessed, but it might be the case due to the experts’ belief that standardization must be achieved and that it cannot as such threaten blockchain key advantages. The need for ensuring privacy and security is assessed negatively. This means that some respondents strongly disagree with the statement that blockchain technology is still immature and vulnerable. Due to their response, one can conclude they believe that blockchain technology is at a high level of development and that is less vulnerable than it can appear due to its complexity and deployment at a global scale. This construct can correspond with technological, environmental, and legal PESTEL dimensions at the same time.
Since we collected only twenty survey responses, further research should include in-depth interviews or a survey upon a larger poll of experts and profound discussion on the respondents’ assessments, including comments and suggestions. In addition, the following investigation in the field should include experts from other developing and transitional countries (besides South Africa and Montenegro), including a longitudinal approach. Building new knowledge and transfer of existing one on blockchain technological and other crucial dimensions are necessary, particularly in developing countries, which suffer the lack of skilled personnel and expert knowledge, dominantly in the technological domain.
Maritime is lagging behind other areas of business and industry in terms of digitization. This is especially true in developing countries. Therefore, in this chapter, the results of two case studies on digitalization in maritime, conducted in developing countries, are presented, along with some comparative analyzes with developed countries in certain areas. These studies were conducted on a relatively small sample and in the future, longitudinal studies should be conducted on a larger sample and in a larger number of countries in transition. The results should be presented to ICT&S designers in developed countries in order to find solutions for intelligent design of ICT&S in maritime in perspective. These systems should provide benefits for all. If we strive for sustainable development, then it must ensure development for all. Entire continents cannot be excluded from the plans for further development of ICT&S, artificial intelligence, and virtual reality. This, of course, requires a broader platform, which includes standardization of ports and ships as basic maritime structures onto which ICT&S are built.
General knowledge about new technologies in developing countries exists, but there is a lack of expertise when it comes to hardware, software, network architecture, cyber safety, security, etc. Furthermore, developing countries suffer lack of funds for investments in advanced ICT&S. These countries are excluded from the strategic plans on the development and implementation of new ICT&S solutions. The governments should consequently invest more into attaining sound knowledge in contemporary ICT&S, including disruptive technologies like blockchain and its implementation in global supply chains. Standardization in maritime is the key enabler of faster modernization. In addition, profound research of internet connectivity at sea is of crucial importance for further development of IoT applications in maritime as the key condition for achieving equal presence of ICT&S applications on land and at sea. Maritime industry and high(er) maritime education institutions should cooperate much more closely to alleviate the gap between developing and developed countries in terms of achieving a higher level of graduates’ employability, while the sphere of digitalization can provide many opportunities in this respect. Rising awareness about digital transition in maritime and opening discussions among professionals and academics should become common practice. The involvement of legislatures and tight collaboration of key stakeholders in maritime emerging economies are necessary regarding harmonization of ICT&S deployment across global maritime ecosystem and overcoming the existing gap in digitalization.
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These physiological events occur smoothly in normal healthy individual and/or under normal conditions. However, in certain cases, these molecular events are retarded resulting in hard-to-heal or chronic wounds arising from several factors such as poor venous return, underlying physiological or metabolic conditions such as diabetes as well as external factors such as poor nutrition. In most cases, such wounds are infected and infection also presents as another complicating phenomenon which triggers inflammatory reactions, therefore delaying wound healing. There has therefore been recent interests and significant efforts in preventing and actively treating wound infections by directly targeting infection causative agents through direct application of antimicrobial agents either alone or loaded into dressings (medicated). These have the advantage of overcoming challenges such as poor circulation in diabetic and leg ulcers when administered systemically and also require lower amounts to be applied compared to that required via oral or iv administration. This chapter will review and evaluate various antimicrobial agents used to target infected wounds, the means of delivery, and current state of the art, including commercially available dressings. 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Matrix metalloproteinases (MMPs) play important roles in wound healing, and their dysregulation leads to prolonged inflammation and delayed wound healing. There are 24 MMPs in humans, and each MMP exists in three forms, of which only the active MMPs play a role in the pathology or repair of wounds. The current methodology does not distinguish between the three forms of MMPs, making it challenging to investigate the roles of MMPs in pathology and wound repair. We used a novel MMP-inhibitor-tethered affinity resin that binds only the active form of MMPs, from which we identified and quantified active MMP-8 and active MMP-9 in a murine diabetic model with delayed wound healing. We showed that up-regulation of active MMP-9 plays a detrimental role whereas active MMP-8 is involved in repairing the wound in diabetic mice. These studies identified MMP-9 as a novel target for therapeutic intervention in the treatment of chronic wounds. A selective inhibitor of MMP-9 that leaves MMP-8 unaffected would provide the most effective therapy and represents a promising strategy for therapeutic intervention in the treatment of diabetic foot ulcers.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Trung T. Nguyen, Shahriar Mobashery and Mayland Chang",authors:[{id:"183405",title:"Prof.",name:"Mayland",middleName:null,surname:"Chang",slug:"mayland-chang",fullName:"Mayland Chang"},{id:"191152",title:"Mr.",name:"Trung",middleName:null,surname:"Nguyen",slug:"trung-nguyen",fullName:"Trung Nguyen"},{id:"191153",title:"Prof.",name:"Shahriar",middleName:null,surname:"Mobashery",slug:"shahriar-mobashery",fullName:"Shahriar Mobashery"}]},{id:"63675",doi:"10.5772/intechopen.81208",title:"Wound Healing: Contributions from Plant Secondary Metabolite Antioxidants",slug:"wound-healing-contributions-from-plant-secondary-metabolite-antioxidants",totalDownloads:1331,totalCrossrefCites:7,totalDimensionsCites:20,abstract:"Plants by their genetic makeup possess an innate ability to synthesize a wide variety of phytochemicals that help them to perform their normal physiological functions and/or to protect themselves from microbial pathogens and animal herbivores. The synthesis of these phytochemicals presents the plants their natural tendency to respond to environmental stress conditions. These phytochemicals are classified either as primary or secondary metabolites. The secondary metabolites have been identified in plants as alkaloids, terpenoids, phenolics, anthraquinones, and triterpenes. These plant-based compounds are believed to have diverse medicinal properties including antioxidant properties. Plants have therefore been a potential source of antioxidants which have received a great deal of attention since increased oxidative stress has been identified as a major causative factor in the development and progression of several life-threatening diseases, including neurodegenerative and cardiovascular diseases and wound infection. Consequently, many medicinal plants have been cited and known to effect wound healing and antioxidant properties. This chapter briefly reviews antioxidant properties of medicinal plants to highlight the important roles medicinal plants play in wound healing.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Victor Y.A. Barku",authors:[{id:"261027",title:"Prof.",name:"Victor Y. A.",middleName:null,surname:"Barku",slug:"victor-y.-a.-barku",fullName:"Victor Y. A. Barku"}]},{id:"66793",doi:"10.5772/intechopen.85020",title:"The Impact of Biofilm Formation on Wound Healing",slug:"the-impact-of-biofilm-formation-on-wound-healing",totalDownloads:1434,totalCrossrefCites:7,totalDimensionsCites:16,abstract:"Chronic wounds represent an important challenge for wound care and are universally colonized by bacteria. These bacteria can form biofilm as a survival mechanism that confers the ability to resist environmental stressors and antimicrobials due to a variety of reasons, including low metabolic activity. Additionally, the exopolymeric substance (EPS) contained in biofilm acts as a mechanical barrier to immune system cells, leading to collateral damage in the surrounding tissue as well as chronic inflammation, which eventually will delay healing of the wound. This chapter will discuss current knowledge on biofilm formation, its presence in acute and chronic wounds, how biofilm affects antibiotic resistance and tolerance, as well as the wound healing process. We will also discuss proposed methods to eliminate biofilm and improve wound healing despite its presence, including basic science and clinical studies regarding these matters.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Rafael A. Mendoza, Ji-Cheng Hsieh and Robert D. Galiano",authors:[{id:"253607",title:"M.D.",name:"Rafael",middleName:null,surname:"Mendoza",slug:"rafael-mendoza",fullName:"Rafael Mendoza"},{id:"254018",title:"Dr.",name:"Robert",middleName:null,surname:"Galiano",slug:"robert-galiano",fullName:"Robert Galiano"},{id:"271116",title:"Mr.",name:"Ji-Cheng",middleName:null,surname:"Hsieh",slug:"ji-cheng-hsieh",fullName:"Ji-Cheng Hsieh"}]},{id:"63086",doi:"10.5772/intechopen.80215",title:"Medicinal Plants in Wound Healing",slug:"medicinal-plants-in-wound-healing",totalDownloads:2901,totalCrossrefCites:7,totalDimensionsCites:15,abstract:"Wound healing process is known as interdependent cellular and biochemical stages which are in trying to improve the wound. Wound healing can be defined as stages which is done by body and delayed in wound healing increases chance of microbial infection. Improved wound healing process can be performed by shortening the time needed for healing or lowering the inappropriate happens. The drugs were locally or systemically administrated in order to help wound healing. Antibiotics, antiseptics, desloughing agents, extracts, etc. have been used in order to wound healing. Some synthetic drugs are faced with limitations because of their side effects. Plants or combinations derived from plants are needed to investigate identify and formulate for treatment and management of wound healing. There is increasing interest to use the medicinal plants in wound healing because of lower side effects and management of wounds over the years. Studies have shown that medicinal plants improve wound healing in diabetic, infected and opened wounds. The different mechanisms have been reported to improve the wound healing by medicinal plants. In this chapter, some medicinal plants and the reported mechanisms will be discussed.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Mohammad Reza Farahpour",authors:[{id:"253340",title:"Prof.",name:"Mohammadreza",middleName:null,surname:"Farahpour",slug:"mohammadreza-farahpour",fullName:"Mohammadreza Farahpour"}]}],mostDownloadedChaptersLast30Days:[{id:"55736",title:"Haemodynamic Monitoring in the Intensive Care Unit",slug:"haemodynamic-monitoring-in-the-intensive-care-unit",totalDownloads:3369,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Monitoring is a cognitive aid that allows clinicians to detect the nature and extent of pathology and helps assessment of response to therapy. The cardiovascular system is the most commonly monitored organ system in the critical care setting. It helps identify the presence and nature of shock and guides response to resuscitation by detection of cardiac rate and rhythm, evaluation of volume state, cardiac contractility and systemic vascular resistance. Newer technologies allow greater assessment of oxygen delivery to vulnerable tissues. We discuss the nature, history, modalities and interpretation of the most commonly available haemodynamic monitoring methods in clinical use currently.",book:{id:"5756",slug:"intensive-care",title:"Intensive Care",fullTitle:"Intensive Care"},signatures:"Mainak Majumdar",authors:[{id:"86678",title:"Dr.",name:"Mainak",middleName:null,surname:"Majumdar",slug:"mainak-majumdar",fullName:"Mainak Majumdar"}]},{id:"51825",title:"Roles of Matrix Metalloproteinases in Cutaneous Wound Healing",slug:"roles-of-matrix-metalloproteinases-in-cutaneous-wound-healing",totalDownloads:3628,totalCrossrefCites:20,totalDimensionsCites:37,abstract:"Wound healing is a complex process that consists of hemostasis and inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Matrix metalloproteinases (MMPs) play important roles in wound healing, and their dysregulation leads to prolonged inflammation and delayed wound healing. There are 24 MMPs in humans, and each MMP exists in three forms, of which only the active MMPs play a role in the pathology or repair of wounds. The current methodology does not distinguish between the three forms of MMPs, making it challenging to investigate the roles of MMPs in pathology and wound repair. We used a novel MMP-inhibitor-tethered affinity resin that binds only the active form of MMPs, from which we identified and quantified active MMP-8 and active MMP-9 in a murine diabetic model with delayed wound healing. We showed that up-regulation of active MMP-9 plays a detrimental role whereas active MMP-8 is involved in repairing the wound in diabetic mice. These studies identified MMP-9 as a novel target for therapeutic intervention in the treatment of chronic wounds. A selective inhibitor of MMP-9 that leaves MMP-8 unaffected would provide the most effective therapy and represents a promising strategy for therapeutic intervention in the treatment of diabetic foot ulcers.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Trung T. Nguyen, Shahriar Mobashery and Mayland Chang",authors:[{id:"183405",title:"Prof.",name:"Mayland",middleName:null,surname:"Chang",slug:"mayland-chang",fullName:"Mayland Chang"},{id:"191152",title:"Mr.",name:"Trung",middleName:null,surname:"Nguyen",slug:"trung-nguyen",fullName:"Trung Nguyen"},{id:"191153",title:"Prof.",name:"Shahriar",middleName:null,surname:"Mobashery",slug:"shahriar-mobashery",fullName:"Shahriar Mobashery"}]},{id:"63086",title:"Medicinal Plants in Wound Healing",slug:"medicinal-plants-in-wound-healing",totalDownloads:2898,totalCrossrefCites:7,totalDimensionsCites:15,abstract:"Wound healing process is known as interdependent cellular and biochemical stages which are in trying to improve the wound. Wound healing can be defined as stages which is done by body and delayed in wound healing increases chance of microbial infection. Improved wound healing process can be performed by shortening the time needed for healing or lowering the inappropriate happens. The drugs were locally or systemically administrated in order to help wound healing. Antibiotics, antiseptics, desloughing agents, extracts, etc. have been used in order to wound healing. Some synthetic drugs are faced with limitations because of their side effects. Plants or combinations derived from plants are needed to investigate identify and formulate for treatment and management of wound healing. There is increasing interest to use the medicinal plants in wound healing because of lower side effects and management of wounds over the years. Studies have shown that medicinal plants improve wound healing in diabetic, infected and opened wounds. The different mechanisms have been reported to improve the wound healing by medicinal plants. In this chapter, some medicinal plants and the reported mechanisms will be discussed.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Mohammad Reza Farahpour",authors:[{id:"253340",title:"Prof.",name:"Mohammadreza",middleName:null,surname:"Farahpour",slug:"mohammadreza-farahpour",fullName:"Mohammadreza Farahpour"}]},{id:"67217",title:"Nursing Implications in the ECMO Patient",slug:"nursing-implications-in-the-ecmo-patient",totalDownloads:2528,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Effective care and positive outcomes of the extracorporeal membrane oxygenation (ECMO) patient necessitate optimal interdisciplinary management from the healthcare team, including expert care from specially trained registered nurses (RNs). It is incumbent upon the RN caring for the ECMO patient to excel in both time management and assessment skills, as this population often demands care delivery at the pinnacle of intensive care unit (ICU) acuity. Astute and nuanced monitoring of neurological status, bleeding risk with potential (often massive) transfusions, poor hemodynamics, and integrity of the ECMO pump itself are only the few specialized areas of focus that must share priority with traditional nursing considerations involving the critically ill, such as prevention of pressure injuries and bloodstream infections. These high-intensity medical foci must be balanced with ethical considerations, as the ultimate goal of returning the patient to their normal life is not always possible. These demands highlight the dynamic proficiency of the RN caring for the ECMO patient. The following chapter will highlight the importance of specialized nursing care in the critically ill patient supported with ECMO.",book:{id:"7878",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",title:"Advances in Extracorporeal Membrane Oxygenation",fullTitle:"Advances in Extracorporeal Membrane Oxygenation - Volume 3"},signatures:"Alex Botsch, Elizabeth Protain, Amanda R. Smith and Ryan Szilagyi",authors:[{id:"298623",title:"Mr.",name:"Alexander",middleName:null,surname:"Botsch",slug:"alexander-botsch",fullName:"Alexander Botsch"}]},{id:"66239",title:"Echocardiography Evaluation in ECMO Patients",slug:"echocardiography-evaluation-in-ecmo-patients",totalDownloads:2184,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Extracorporeal membrane oxygenation (ECMO) is a special form of organ support for selected cases of cardiovascular and severe respiratory failure. Echocardiography is a diagnostic and monitoring tool widely used in all aspects of ECMO support. The pathophysiology of ECMO, and its distinct effects on cardiorespiratory physiology, requires an echocardiographer with high skills to understand the interaction between the ECMO and the patient. In this chapter, we present the main application of echocardiography in ECMO patients and some general concepts on the ECMO working. ECMO, such as the standard cardiopulmonary bypass employed in cardiac surgery, V-V (veno-venous), can support the insufficient respiratory system by oxygenating and removing carbon dioxide from the blood. VA-ECMO (venous-arterial) can support haemodynamics by providing mechanical circulatory assistance. Today, ECMO can be used as bridge to decision, waiting for the development of the clinical conditions to support with other devices the evolution of cardiorespiratory failure or stop the assistance. Echocardiography (transthoracic (TTE) or transoesophageal (TOE)) can be used primarily to take decisions regarding appropriateness of ECMO support, therefore to control cannula insertion and confirm final position, to modify number and position of the cannulae in case of malfunctioning of these, and, finally, to assess clinical progress and suitability for weaning from ECMO.",book:{id:"7878",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",title:"Advances in Extracorporeal Membrane Oxygenation",fullTitle:"Advances in Extracorporeal Membrane Oxygenation - Volume 3"},signatures:"Luigi Tritapepe, Ernesto Greco and Carlo Gaudio",authors:[{id:"284893",title:"Prof.",name:"Luigi",middleName:null,surname:"Tritapepe",slug:"luigi-tritapepe",fullName:"Luigi Tritapepe"},{id:"294005",title:"Prof.",name:"Ernesto",middleName:null,surname:"Greco",slug:"ernesto-greco",fullName:"Ernesto Greco"},{id:"294006",title:"Prof.",name:"Carlo",middleName:null,surname:"Gaudio",slug:"carlo-gaudio",fullName:"Carlo Gaudio"}]}],onlineFirstChaptersFilter:{topicId:"173",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:332,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:142,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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\r\n\tEducation and Human Development is an interdisciplinary research area that aims to shed light on topics related to both learning and development. This Series is intended for researchers, practitioners, and students who are interested in understanding more about these fields and their applications.
",coverUrl:"https://cdn.intechopen.com/series/covers/23.jpg",latestPublicationDate:"August 17th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"280770",title:"Dr.",name:"Katherine K.M.",middleName:null,surname:"Stavropoulos",slug:"katherine-k.m.-stavropoulos",fullName:"Katherine K.M. Stavropoulos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRdFuQAK/Profile_Picture_2022-05-24T09:03:48.jpg",biography:"Katherine Stavropoulos received her BA in Psychology from Trinity College, in Connecticut, USA and her Ph.D. in Experimental Psychology from the University of California, San Diego. She completed her postdoctoral work at the Yale Child Study Center with Dr. James McPartland. Dr. Stavropoulos’ doctoral dissertation explored neural correlates of reward anticipation to social versus nonsocial stimuli in children with and without autism spectrum disorders (ASD). She has been a faculty member at the University of California, Riverside in the School of Education since 2016. Her research focuses on translational studies to explore the reward system in ASD, as well as how anxiety contributes to social challenges in ASD. She also investigates how behavioral interventions affect neural activity, behavior, and school performance in children with ASD. She is also involved in the diagnosis of children with ASD and is a licensed clinical psychologist in California. She is the Assistant Director of the SEARCH Center at UCR and is a faculty member in the Graduate Program in Neuroscience.",institutionString:null,institution:{name:"University of California, Riverside",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"89",title:"Education",coverUrl:"https://cdn.intechopen.com/series_topics/covers/89.jpg",isOpenForSubmission:!1,editor:{id:"260066",title:"Associate Prof.",name:"Michail",middleName:null,surname:"Kalogiannakis",slug:"michail-kalogiannakis",fullName:"Michail Kalogiannakis",profilePictureURL:"https://mts.intechopen.com/storage/users/260066/images/system/260066.jpg",biography:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool Education, University of Crete, and an Associate Tutor at School of Humanities at the Hellenic Open University. He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. He has published over 120 articles in international conferences and journals and has served on the program committees of numerous international conferences.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorTwo:{id:"422488",title:"Dr.",name:"Maria",middleName:null,surname:"Ampartzaki",slug:"maria-ampartzaki",fullName:"Maria Ampartzaki",profilePictureURL:"https://mts.intechopen.com/storage/users/422488/images/system/422488.jpg",biography:"Dr Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorThree:null},{id:"90",title:"Human Development",coverUrl:"https://cdn.intechopen.com/series_topics/covers/90.jpg",isOpenForSubmission:!0,editor:{id:"191040",title:"Dr.",name:"Tal",middleName:null,surname:"Dotan Ben-Soussan",slug:"tal-dotan-ben-soussan",fullName:"Tal Dotan Ben-Soussan",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBf1QAG/Profile_Picture_2022-03-18T07:56:11.jpg",biography:"Tal Dotan Ben-Soussan, Ph.D., is the director of the Research Institute for Neuroscience, Education and Didactics (RINED) – Paoletti Foundation. Ben-Soussan leads international studies on training and neuroplasticity from neurophysiological and psychobiological perspectives. As a neuroscientist and bio-psychologist, she has published numerous articles on neuroplasticity, movement and meditation. She acts as an editor and reviewer in several renowned journals and coordinates international conferences integrating theoretical, methodological and practical approaches on various topics, such as silence, logics and neuro-education. She lives in Assisi, Italy.",institutionString:"Research Institute for Neuroscience, Education and Didactics, Patrizio Paoletti Foundation",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:12,paginationItems:[{id:"83113",title:"Agoraphobic Dispositions towards Action Research: Teacher Education Students’ Perceptions and Experiences",doi:"10.5772/intechopen.106188",signatures:"Davison Zireva",slug:"agoraphobic-dispositions-towards-action-research-teacher-education-students-perceptions-and-experien",totalDownloads:1,totalCrossrefCites:null,totalDimensionsCites:0,authors:[{name:"Davison",surname:"Zireva"}],book:{title:"Active Learning - Research and Practice for STEAM and social sciences education",coverURL:"https://cdn.intechopen.com/books/images_new/11481.jpg",subseries:{id:"89",title:"Education"}}},{id:"83053",title:"Apologies in L2 French in Canadian Context",doi:"10.5772/intechopen.106557",signatures:"Bernard Mulo Farenkia",slug:"apologies-in-l2-french-in-canadian-context",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Bernard",surname:"Mulo Farenkia"}],book:{title:"Second Language Acquisition - Learning Theories and Recent Approaches",coverURL:"https://cdn.intechopen.com/books/images_new/11480.jpg",subseries:{id:"89",title:"Education"}}},{id:"82903",title:"Walking Accessibility to Primary Healthcare Services: An Inequity Factor for Olders in the Lisbon Metropolitan Area (Portugal)",doi:"10.5772/intechopen.106265",signatures:"Eduarda Marques da Costa, Ana Louro, Nuno Marques da Costa, Mariana Dias and Marcela Barata",slug:"walking-accessibility-to-primary-healthcare-services-an-inequity-factor-for-olders-in-the-lisbon-met",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Social Aspects of Ageing - Selected Challenges, Analyses, and Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11479.jpg",subseries:{id:"90",title:"Human Development"}}},{id:"82622",title:"Contemporary Geographical Gerontology: Reconciling Space and Place in Population Ageing",doi:"10.5772/intechopen.105863",signatures:"Hamish Robertson",slug:"contemporary-geographical-gerontology-reconciling-space-and-place-in-population-ageing",totalDownloads:13,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hamish",surname:"Robertson"}],book:{title:"Social Aspects of Ageing - Selected Challenges, Analyses, and Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11479.jpg",subseries:{id:"90",title:"Human Development"}}}]},overviewPagePublishedBooks:{paginationCount:0,paginationItems:[]},openForSubmissionBooks:{paginationCount:1,paginationItems:[{id:"11568",title:"Staphylococcal Infections - Recent Advances and Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11568.jpg",hash:"92c881664d1921c7f2d0fee34b78cd08",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"July 8th 2022",isOpenForSubmission:!0,editors:[{id:"59719",title:"Dr.",name:"Jaime",surname:"Bustos-Martínez",slug:"jaime-bustos-martinez",fullName:"Jaime Bustos-Martínez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:21,paginationItems:[{id:"83000",title:"Purine and Pyrimidine Pathways as Antimalarial Targets",doi:"10.5772/intechopen.106468",signatures:"Yacoba V.T. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11405,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. 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