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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!
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2175",leadTitle:null,fullTitle:"Risk Management - Current Issues and Challenges",title:"Risk Management",subtitle:"Current Issues and Challenges",reviewType:"peer-reviewed",abstract:"Every business and decision involves a certain amount of risk. Risk might cause a loss to a company. This does not mean, however, that businesses cannot take risks. As disengagement and risk aversion may result in missed business opportunities, which will lead to slower growth and reduced prosperity of a company. In today's increasingly complex and diverse environment, it is crucial to find the right balance between risk aversion and risk taking. To do this it is essential to understand the complex, out of the whole range of economic, technical, operational, environmental and social risks associated with the company's activities. However, risk management is about much more than merely avoiding or successfully deriving benefit from opportunities. Risk management is the identification, assessment, and prioritization of risks. 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Magnetic particles are currently one of the most important materials in the industrial sector, where they have been widely used for biotechnological and biomedical applications such as carriers for recovery and for detection of DNA, proteins, viruses, and cells (Perez et al., 2002; Kramer et al., 2004; Gonzales and Krishnan, 2005). The major advantage of magnetic particles is that they can be easily manipulated by magnetic force, which enables rapid and easy separation of target molecules bound to the particles from reaction mixtures (Mirzabekov et al., 2000; Gu et al., 2003; Kuhara et al., 2004; Xu et al., 2004). Use of magnetic particles is beneficial for complete automation of steps, resulting in minimal manual labor and providing more precise results (Sawakami-Kobayashi et al., 2003). Biomolecules such as DNA, biotin, and antibodies have been assembled onto magnetic particles and used as recognition materials for target recovery, separation, or detection.
The method chosen for biomolecule assembly is determined by the surface properties of the magnetic particles. Various methods of assembly onto magnetic particles have been reported such as electrostatic assembly (Goldman et al., 2002), covalent cross-linking (Grubisha et al., 2003; Gao et al., 2004) avidin-biotin technology (Gref et al., 2003), membrane integration (Mirzabekov et al., 2000; Tanaka et al., 2004), and gene fusion techniques (Nakamura et al., 1995b; Yoshino et al., 2004; Yoshino and Matsunaga, 2006). The amount and stability of assembled biomolecules and the percentage of active biomolecules among assembled molecules are dependent on the method used for coupling. However, the fabrication techniques have not been standardized. As applications for magnetic particles in the biotechnology field increase, magnetic particles with greater functionality and novel methods for their production are in demand.
Magnetotactic bacteria synthesize uniform, nano-sized magnetite (Fe3O4) particles, which are referred to as “bacterial magnetic particles” (BacMPs). A thin lipid bilayer membrane envelops the individual BacMP, which confers high and even dispersion in aqueous solutions as compared to artificial magnetic particles, making them ideal biotechnological materials (Matsunaga et al., 2003). To use these particles for biotechnological applications, it is important to attach functional molecules such as proteins, antibodies, peptides, or DNA. BacMP-specific proteins have been used as anchor proteins, which facilitate efficient localization and appropriate orientation of various functional proteins attached to BacMPs. We have developed several methods for modification and assembly of these functional organic molecules over the surface of BacMPs using chemical and genetic techniques. In this chapter, we describe advanced magnetic particles used in biomedical applications and the methods for bioengineering of these particles. Specific focus is given to the creation of functional BacMPs by magnetotactic bacteria and their applications.
Currently, magnetic particles offer vast potential for ushering in new techniques, especially in biomedical applications, as they can be easily manipulated by magnetic force. The important characteristics of these particles include (1) immobilization of higher numbers of probes onto magnetic particles because particle surfaces are wider than those of a flat surface, (2) reduction of reaction times because of good dispersion properties that increase reaction efficiency, (3) facilitation of the bound/free separation step with a magnet, without centrifugation or filtration, and (4) the use of automated robotic systems for all reaction steps. These characteristics offer great benefits for biomedical applications such as rapid and precise measurements or separations of bio-targets. Here, the methods for production of functional magnetic particles are introduced.
Commercialized magnetic particles are usually composed of superparamagnetic iron oxide nanoparticles (Fe3O4 or Fe2O3), which exhibit magnetic properties only in the presence of external magnetic fields. These particles are embedded in polymers such as polysaccharides, polystyrene, silica, or agarose. Micro-sized magnetic particles can be easily removed from suspension with magnets and easily suspended into homogeneous mixtures in the absence of an external magnetic field (Ugelstad et al., 1988). Furthermore, functional groups or biomolecules for the recognition of targets are conjugated to the polymer surfaces of magnetic particles (Fig. 1), and targets can be collected, separated, or detected by the magnetic particles.
Use of general magnetic particles
Biotin or streptavidin-assembled magnetic particles, on which complementary nucleic acid strands are immobilized, are widely used for the recovery or extraction of specific nucleic acids and are marketed worldwide. Moreover, magnetic particles can be used as supports for separation or detection of proteins or cells. For example, protein A- or protein G-assembled magnetic particles are suitable for antibody purification and are more efficient than column-purification techniques.
Currently, polymer magnetic particles marketed as Dynabeads (Invitrogen, co.) are one of the most widely used magnetic particles for biotechnology applications (Sawakami-Kobayashi et al., 2003; Prasad et al., 2003). These particles are prepared from mono-sized macroporous polystyrene particles that are magnetized by an in situ formation of ferromagnetic materials inside the pores. Dynabeads with diameters of 2.8 m or 4.5 m are the most widely used magnetic particles by scientists around the world, particularly in the fields of immunology, cellular biology, molecular biology, HLA diagnostics, and microbiology.
Antibody-immobilized magnetic particles have been used preferentially in target-cell separation of leukocytes (Stampfli et al., 1994; Schratzberger et al., 1997; Schwalbe et al., 2006; Nakamura et al., 2001) for in vitro diagnosis because of the simpler and more rapid methodology as compared to cell sorting using a flow cytometer. These commercially available magnetic particles are chemically synthesized compounds of micrometer and nanometer sizes. Several cell separation systems using nano-sized magnetic particles, such as 50-nm iron oxide particles with polysaccharide- (Miltenyi Biotech, co.) or dextran- (StemCell Technologies Inc.) coated superparamagnetic nanoparticles, are commercially available (Miltenyi, 1995; Wright, 1952). Because these particles are superparamagnetic and are preferred for high-gradient magnetic separation, specially-designed magnetic columns that produce high magnetic field gradients are required for cell separation (Miltenyi, 1995). Nano-sized magnetic particles are advantageous for assay sensitivity, rapidity, and precision. However, it remains difficult to synthesize nano-sized magnetic particles with uniform size and shape that adequately disperse in aqueous solutions. Consequently, advanced techniques and high costs are required for the production of nano-sized magnetic particles.
Magnetic particles are widely used not only as carriers for recovery or detections of bio-molecules, but also used as probes for magnetic detections, or agent for magnetic-field-induced heating. Especially, magnetic particles that have high saturation magnetization are ideal candidates for MRI contrast agents, and various kinds of magnetic particles have been developed and used for diagnoses. Recently, Mulder
Magnetotactic bacteria synthesize nano-sized biomagnetites, otherwise known as bacterial magnetic particles (BacMPs), that are enveloped individually by a lipid bilayer membrane (Blakemore, 1983). BacMPs are ultrafine magnetite crystals (50-100 nm in diameter) with uniform morphology produced by
Transmission electron microscopic (TEM) image and schematic diagram of
The molecular mechanism of BacMP synthesis involves a multiple-step process that includes vesicle formation, iron transport, and magnetite crystallization. This mechanism has been studied using genomic, proteomic, and bioinformatic approaches (Matsunaga et al., 2005; Nakamura et al., 1995a; Arakaki et al., 2003; Amemiya et al., 2007), and a comprehensive analysis provided a clear view of the elaborate regulation of BacMP synthesis.
Techniques for the mass cultivation of magnetotactic bacteria have been developed, allowing for a steady supply of BacMPs for industrial applications. Based on the molecular mechanism of BacMP formation in
The display of proteins on BacMPs was achieved using a fusion technique involving anchor proteins isolated from magnetotactic bacteria (Nakamura et al., 1995b). Figure 3A shows the procedure for producing functional magnetic particles through genetic engineering of these bacteria. Several proteins involved in the magnetic biosynthetic mechanism are embedded in the BacMP membrane. In
Preparation of BacMPs displaying functional proteins.(A) The functional protein gene is fused to an anchor gene for display of a functional protein on BacMPs. A plasmid harboring the fusion gene is introduced into
MagA was one of the first proteins experimentally demonstrated to be localized on the surface of BacMPs (Nakamura et al., 1995a; Nakamura
As research in this field progressed, a more effective and stable method for protein display was developed. To establish high levels of expressed proteins displayed on BacMPs, strong promoters and stable anchor proteins were identified using
An integral BacMP membrane protein, Mms13, was isolated as a stable anchor molecule, and its anchoring properties were confirmed by luciferase fusion studies. The C-terminus of Mms13 was expressed on the surface of BacMPs, and Mms13 was tightly bound to the magnetite directly, permitting stable localization of luciferase on BacMPs. Consequently, the luminescence intensity obtained from BacMPs using Mms13 as an anchor molecule was more than 1,000-times greater than when MagA was used. Furthermore, the IgG-binding domain of protein A was displayed uniformly on BacMPs using Mms13 (Fig. 3B).
Strong promoters and stable anchor proteins allowed efficient display of functional proteins on BacMPs. However, the display of particular proteins remained a technical challenge due to the cytotoxic effects of the proteins when they were overexpressed in bacterial cells. Specifically, transmembrane proteins such as G-protein coupled receptors were still difficult to express in magnetotactic bacteria. An inducible protein expression system is often used to control the expression dose and timing of transmembrane proteins. Recently, we developed a tetracycline-inducible protein expression system in
Currently, many types of functional proteins can be displayed at high levels on magnetic particles due to the modifications described above. Generally, immobilization of proteins onto magnetic particles is performed by chemical cross-linking; however, this can hinder the activity of some proteins. Because the amine-reactive cross-linker can bind to proteins in a random manner, the target proteins may become inactivated. Furthermore, protein orientation on the solid phase is difficult to control during chemical conjugation. To overcome these difficulties, protein display on magnetic particles produced by magnetotactic bacteria through gene fusion is a promising approach, and the techniques have expanded the number of applications.
Magnetic iron oxide particles, such as magnetite (Fe3O4) and maghemite (γ-Fe2O3), are widely used in medical and diagnostic applications such as magnetic resonance imaging (Gleich and Weizenecker, 2005), cell separation (Miltenyi et al., 1990), drug delivery (Plank et al., 2003), and hyperthermia (Pardoe et al., 2003). To use these particles for biotechnological applications, the surface modification of the magnetic particle with functional molecules such as proteins, peptides, or DNA must be considered. Previously, only DNA- or antibody-immobilized magnetic particles were marketed and used in biotechnology; it was suggested that the techniques for the immobilization of enzymes or receptors were more complicated and time consuming. However, as the methods for assembling functional proteins onto magnetic particles have become simpler and more efficient, the applications of magnetic particles have expanded. Here, the applications of BacMPs displaying functional proteins such as antibody, enzyme, or receptor are described.
Magnetic particles have been widely used as carriers of antibodies for immunoassay, cell separation, and tissue typing (Herr et al., 2006; Tiwari et al., 2003; Weissleder et al., 2005). The use of magnetic particles is advantageous for full automation, minimizing manual labor and providing more precise results (Sawakami-Kobayashi et al., 2003; Tanaka and Matsunaga, 2000). In particular, immunomagnetic particles have been used preferentially in target cell separation from leukocytes (Stampfli et al., 1994; Schratzberger et al., 1997) for in vitro diagnosis, as this provides a more rapid and simple methodology compared with cell sorting using a flow cytometer.
To immobilize antibody, protein A, which is the antibody-binding protein derived from
Z-domain was displayed on bacterial magnetic particles using gene fusion techniques and was used to detect human insulin from whole blood by sandwich enzyme immunoassays. The experimental procedure was fully automated using a pipetting robot bearing a magnet (Tanaka and Matsunaga, 2000).
Antibody-conjugated BacMPs also can be utilized for cell separation. In general, nano-sized magnetic particles, rather than micro-sized particles, are preferred for cell separation because separated cells with nano-sized magnetic particles on their surfaces can be used in subsequent flow cytometric analysis (Graepler et al., 1998). Additionally, micro-sized magnetic particles are more likely to have inhibitory effects on cell growth and differentiation after magnetic separation.
Magnetic separation permits target cells to be isolated directly from crude samples such as blood, bone marrow, tissue homogenates, or cultivation media. Compared to other more conventional methods of cell separation, magnetic separation may be considered a sample enrichment step for further chromatographic and electromigratory analysis. To enrich for target cells, cell surface antigens, such as cluster of differentiation (CD) antigens, were used as markers. CD8, CD14, CD19, CD20, and CD34 positive cells were efficiently enriched from peripheral blood (Kuhara et al., 2004; Matsunaga et al., 2006). The separated CD34 positive cells retained the capability of forming colonies as hematopoietic stem cells.
Schematic illustration of cell separation procedures. (A) The initial separation of peripheral blood mononuclear cells (PBMCs) from whole blood and the subsequent magnetic separation of target cells from PBMCs using magnetic particles followed the common procedure. (B) Target cells were separated directly from whole blood using magnetic particles in the procedure for direct magnetic cell separation.
Protein G from
To increase cell separation efficiency, a novel functional polypeptide, which functions to minimize nonspecific adsorption of magnetic particles to cells, was developed for surface modification of BacMPs (Takahashi et al., 2010). Previous reports had shown that the hydrophilicity or neutral charge of the particle surface was important for the reduction of nonspecific interactions between the nanoparticle and the cell surface (Fang et al., 2009; Patil et al., 2007). The designed polypeptide was composed of multiple units consisting of four asparagines (N) and one serine (S) residue and was referred to as the NS polypeptide. Modification of the surface of a magnetic particle with the NS polypeptide resulted in reduction of non-specific particle-particle and particle-cell interactions. NS polypeptides on magnetic nanoparticle surfaces function as a barrier to block particle aggregation and minimize nonspecific adsorption of cells to the nanoparticles; they also add the ability to recognize and bind to target cells by working as a linker to display protein G on the nanoparticles (Fig. 5). When the NS polypeptide is used in a single fusion protein as a linker to display protein G on magnetic particles, the particle acquires the capacity to specifically bind target cells and to avoid nonspecific adsorption of non-target cells. CD19+ cells represent 4.1% of leukocytes and in peripheral blood were calculated to be less than 0.004% of the total cells. Analysis of magnetically separated cells using flow cytometry revealed that CD19+ cells were separated directly from peripheral blood with greater than 95% purity using protein G-displaying BacMPs bound to anti-CD19 monoclonal antibodies with the NS polypeptide. Purities were approximately 82% when the NS polypeptide was not present.
Effect of NS polypeptide on cell separation.(A) Schematic diagram of expression vectors for fusion proteins, Mms13-protein G (1), Mms13-(N4S)10–protein G (2), and Mms13-(N4S)20-protein G (3). (B) Correlation between the display of NS polypeptide on BacMPs and nonspecific binding of BacMPs to the cell surface. The number of RAW 264.7 cells separated using BacMPs displaying protein G (○), BacMPs displaying (N4S)10-protein G (×), or BacMPs displaying (N4S)20-protein G (△) were counted, and the ratio of nonspecifically separated cells was calculated. (C) Direct magnetic separation of CD19+ cells from whole blood using BacMPs displaying (N4S)20-proteins bound to PE-labeled anti-CD19 mAbs.
Display of fusion proteins (protein G and NS polypeptide) on BacMPs significantly improved recognition of and binding to target cells, and minimized adsorption of non-target cells. These promising results demonstrated that NS polypeptides may be a powerful and valuable tool in various cell associated applications.
Enzymes can catalyze various biochemical reactions with high efficiency and specificity and are therefore used in industrial production (Patil et al., 2007). However, the production and purification of recombinant enzymes can be quite time and cost consuming. If enzymes could be immobilized on magnetic particles, they could be reused following magnetic recovery from the reaction mixture. Enzymes and antibodies immobilized on BacMPs using bifunctional reagents and glutaraldehyde have been found to have higher activities than those immobilized on artificial magnetic particles (Matsunaga and Kamiya, 1987). The luciferase gene (luc) was cloned downstream of the MagA promoter and the effect of iron on the regulation of MagA expression was investigated; transcription of MagA was found to be enhanced by low concentrations of iron. As an initial proof-of-concept experiment for the recovery of enzyme-displaying BacMPs, luciferase was assembled onto BacMPs (Nakamura et al., 1995b). The genes for acetate kinase and liciferase were fused to the N- and C-terminus of the MagA anchor protein for simultaneous display of two different enzymes (Matsunaga et al., 2000). Acetate kinase catalyzes the phosphorylation of acetate by ATP. Therefore, this reversible reaction generates ATP in the presence of ADP and acetyl phosphate. The results presented in Fig. 6 are consistent with the hypothesis that ATP is generated in situ by acetate kinase present on BacMPs through phosphorylation of ADP to ATP (Fig. 6). Thus, protein-BacMPs complexes were constructed by joining the luciferase gene to the N- or the C-terminal domains of MagA, and also constructed bifunctional active fusion proteins on BacMPs using MagA as an anchor with acetate kinase and luciferase.
Simultaneous display of two different enzymes, acetate kinase (ackA) and luciferase (luc), onto BacMPs. (A) Schematic diagram of fusion genes, and (B) luciferase activity on BacMPs
A highly thermostable enzyme, pyruvate phosphate dikinase (PPDK), which converts pyrophosphate PPi to ATP, was also expressed on BacMPs. Pyrosequencing relies on the incorporation of nucleotides by DNA polymerase, which results in the release of PPi. The ATP produced by PPDK-displaying BacMPs can be used by luciferase in a luminescent reaction (Fig. 7). PPDK-displaying BacMPs were employed in a pyrosequencing reaction and a target oligonucleotide was successfully sequenced (Yoshino et al., 2009). The PPDK enzyme was recyclable in each sequence reaction as it was immobilized onto BacMPs which could be manipulated by a magnet. These results illustrate the advantages of using enzyme-displaying BacMPs as biocatalysts for repeat usage. Nano-sized PPDK-displaying BacMPs are useful for the scale-down of pyrosequencing reaction volumes, thus permitting high-throughput data acquisition.
Schematic diagram of the principle of pyrosequencing using PPDK-BacMPs. PEP: phosphoenolpyruvate, PPi: pyrophosphate, Pi: phosphate, PPDK: Pyruvate phosphate dikinase. PEP : phosphoenolpyruvate, PPi : pyrophosphate, Pi : phosphate, PPDK : Pyruvate phosphate dikinase
Along with immunoassays and cell separations, ligand-binding assays to study receptor proteins are highly desired applications for magnetic particles. Receptor proteins play critical roles in gene expression, cellular metabolism, signal transduction, and intercellular communication. In particular, nuclear receptors and transmembrane receptors can be major pharmacological targets. These types of receptors have been assembled onto BacMPs.
The estrogen receptor is a nuclear receptor serving as a ligand-inducible transcriptional regulator. In recent decades, it has been suggested that natural and synthetic compounds can act as steroid hormones and adversely affect humans and wildlife through interactions with the endocrine system. These compounds have been broadly referred to as environmental endocrine disrupting chemicals (EDCs). Several chemicals, such as plastic softeners (bisphenol A) or detergents (4-nonylphenol), were originally considered harmless, but now are suspected of having estrogenic effects. It is probable that many unidentified chemical compounds are potential EDCs.
To evaluate and detect these chemical compounds, estrogen receptor ligand-binding domain (ERLBD) was displayed on BacMPs (Yoshino et al., 2005). ERLBD-BacMP complexes can be used for assays based on the competitive binding of alkaline phosphatase conjugated 17β-estradiol (ALP-E2) as a tracer. The dissociation constant of the receptor was 2.3 nM. Inhibition curves were evaluated by the decrease in luminescence intensity resulting from the enzymatic reaction of alkaline phosphatase. The overall simplicity of this receptor binding assay resulted in a method that could be easily adapted to a high-throughput format.
Subsequent-generation evaluation systems for EDCs can distinguish between agonists and antagonists (Yoshino et al., 2008). In one system, ERLBD-displaying BacMPs and green fluorescent protein (GFP)-fused coactivator proteins were used in combination, and ERLBD-displaying BacMPs were incubated with ligands and GFP-coactivators. Binding of the agonist to ERLBD induced a conformational change of ERLBD and promoted binding of the GFP-coactivator to an ERLBD dimer on the BacMP. Binding of the antagonist to ERLBD prevented the GFP-coactivator from binding to the ERLBD-BacMPs. Ligand-dependent recruitment assays of GFP-labeled coactivators to ERLBD-BacMPs were performed by measuring the fluorescence intensity (Fig. 8A). This method was used to evaluate 17-estradiol (E2) and estriol (E3) as full agonists, octylphenol (OP) as a partial agonist, and ICI 182,780 (ICI) as an antagonist (Fig. 8B). The full agonists showed dose-dependent increases in fluorescence. Octylphenol had lower fluorescence intensity than E2, and ICI 182,780 did not produce fluorescence. The method developed in this study can be used to evaluate the estrogenic potential of chemicals by discriminating whether a chemical is an ER full agonist, a partial agonist, or an antagonist. This novel method has important potential for screening for new EDC candidates and their effects in the environment.
Schematic diagram of the GFP-coactivator recruitment assay (A) and the assay results (B). Estrogen receptor ligand binding domain (ERLBD)-BacMPs were incubated with ligand and GFP-coactivator. Binding of agonist to ERLBD induced conformation change of ERLBD and promoted binding of GFP-coactivator to ERLBD dimmer on BacMPs. Binding of antagonist to ERLBD prevented GFP-coactivator binding to ERLBD-BacMPs. E2:17βEstradiol, E3:Estriol, OP:Octylphenol, ICI:ICI 182780
G protein-coupled receptors (GPCRs) play a central role in a wide range of biological processes and are prime targets for drug discovery. GPCRs have large hydrophobic domains, and therefore, purification of GPCRs from cells is frequently time-consuming and typically results in loss of the native conformation. The D1 dopamine receptor, which is a GPCR, was successfully assembled into the lipid membrane of BacMPs (Yoshino et al., 2004). D1 dopamine receptor-displaying BacMPs were simply extracted by magnetic separation from ruptured AMB-1 transformants. This system conveniently retains the native conformation of GPCRs without the need for detergent solubilization, purification, and reconstitution after cell disruption.
Additionally, display of the tetraspanin CD81 was demonstrated using the inducible expression system (Yoshino et al., 2010) described above. CD81 is utilized when hepatitis C virus (HCV) infects hepatocytes and B lymphocytes. Therefore an inhibitor of the human CD81-HCV E2 interaction could possibly prevent HCV infection (Pileri et al., 1998). This interaction was the motivation behind efforts to produce CD81-displaying BacMPs. Consequently, the interaction between BacMPs displaying truncated CD81 and the HCV E2 envelope were detected, suggesting that CD81-displaying BacMPs could be effectively applied to identify inhibitors of the CD81-E2 interaction.
Transmembrane receptors constitute the most prominent family of validated pharmacological targets in biomedicine. Receptor-displaying BacMPs were readily extracted from ruptured AMB-1 transformants by magnetic separation, and after several washings were ready for analysis. Moreover, BacMPs are well-suited for use in a fully automated ligand-screening system that employs magnetic separation. This type of system facilitates rapid buffer exchange and stringent washing, and reduces nonspecific binding.
The suitability of magnetic particles for use in fully-automated systems is an important advantage in solid phases of bioassays. Automated robots bearing magnets permit rapid and precise handling of magnetic particles leading to high-throughput analysis. Different types of fully-automated systems have been developed to handle the magnetic particles and to apply them to nucleotide extraction, gene analysis, and immunoassays.
Figures 9-11 show the layout of an automated workstation with which magnetic particles are collected at the bottom of microtiter plates (Maruyama et al., 2004; Tanaka et al., 2003). For fluid handling, the processor is equipped with an automated pipetter (1) that moves in the vertical and horizontal directions. The platform contains a disposable tip rack station (2), a reagent station (3) that serves as reservoirs for wash buffers, and a reaction station (4) for a 96-well microtiter plate, where a magnetic field can be applied using a neodymium iron boron sintered (Nd-Fe-B) magnet on its underside. One pole of the Nd-Fe-B magnet applies a magnetic field to one well (Matsunaga, 2003). Eight poles of the Nd-Fe-B magnet are aligned on iron rods, and 12 rods are set on the back side of the microtiter plate to apply magnetic fields to the 96 wells. The magnetic field can be switched on (magnetic flux density: 318 mT) and off (magnetic flux density: <10 mT) by rotating the rods 180°. The reaction station is combined with a heat block with a range of 4–99°C and is configured to perform the hybridization step. Heating and magnetic separation can be performed simultaneously in one well. This precise thermal control unit is suitable for DNA handling and has been used for DNA extraction, SNP detection in the genes for aldehyde dehydrogenase 2 (ALDH2) (Maruyama et al., 2004) and transforming growth factor (TGF) (Yoshino et al., 2010), detection of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), and determination of microsatellite repeats in the human thyroid peroxidase (TPOX) gene (Nakagawa et al., 2007).
Automated magnetic separation system, and magnetic separation is achieved in the bottom of microtiter plates.
Figure 10 shows the layout of an automated workstation with which magnetic particles can be separated on the inner surface of pipette tips. The automated system consists of an automated eight-way pipette bearing a retractable magnet mounted close to the pipette tips (1) a tip rack, (2) a reaction station for a 96-well microtiter plate, and (3) a luminescence detection unit. One rack can hold 8 × 3 tips for reactions. For automated magnetic separation, the suspension of magnetic particles is aspirated and dispersed using an automated pipette bearing a magnet. The automated pipette can move horizontally, and magnetic particles collected on the inner surface of pipette tips can be resuspended in the subsequent wells by the pipetting action (Matsunaga et al., 2007). As an advantage, this system can eliminate the carry-over of reaction mixtures to the following reaction steps. Due to precise liquid handling, this workstation is mainly used for highly-sensitive immunoassays, though its throughput capacity is less than the above system. Using this workstation, a fully-automated immunoassay was developed to detect EDCs (Matsunaga et al., 2003; Yoshino et al., 2008), human insulin (Tanaka and Matsunaga, 2000), and a prostate cancer marker (prostate specific antigen).
Automated magnetic separation system, and magnetic separation is achieved on the inner surface of pipette tips.
Figure 11 shows the layout of an automated workstation with which magnetic particles can be collected onto a magnetic rod (Ota et al., 2006). This workstation is equipped with eight automated pestle units and a spectrophotometer that is interfaced with a photosensor amplifier. The magnetic rod that moves in both vertical and horizontal directions is composed of a neodymium–iron–boron (Nd–Fe–B) magnet pole and a covering sheath. DNA concentrations and purities are measured in the cuvette using an absorbance spectrometer that is integrated with the workstation. Light traverses the solution in the cuvette from bottom to top. When magnetic particles are collected from the reaction mixture, the core magnetic pole is sheathed, and then magnetic particles are suspended in the following step by stirring of the sheath without the core rod. The sheath is used as a pestle to gently mix the suspension of magnetic particles and solid samples. Using this system, DNA was directly extracted from dried maize powder using aminosilane-modified BacMPs. Furthermore, the quantitative detection of genetically-modified maize genes was examined by real-time PCR. This system offers rapid assay completion with high DNA yields and qualities comparable to those of conventional detergent-based methods.
Automated magnetic separation system, and magnetic separation is achieved onto a magnetic rod.
Magnetic particles have been utilized as biomolecule carriers since the 1970s when applied research examined bioreactors using enzyme-immobilized magnetic particles. Since then, various types of synthetic and bioengineered magnetic particles have been produced, modified, and enhanced. These magnetic particles have been widely used in place of centrifugation, filter, and chromatography separations, and applied to purifications of biological matter including target cells, proteins, and nucleic acids. More recent advances in the bioengineering of magnetic particles produced by magnetotactic bacteria have resulted in powerful tools for medical applications as well as basic research. This review focused on the applications of BacMPs for recovery or detections of bio-molecule. BacMPs are also available for other applications such as MRI contrast agents, and carriers for drug delivery systems, and so on. High potential magnetic particles will be developed combining with genetic engineering, and especially it is quite easy to control the kinds and numbers of proteins-displayed on BacMPs. Furthermore, it is possible to display artificially designed proteins or polypeptides onto BacMPs by the same methods. These approaches provide a new innovation in material science. Elucidation of the mechanism of magnetic particle formation in M. magneticum AMB-1 has provided a roadmap for designing novel biomaterials useful in multidisciplinary fields.
Mohs micrographic surgery (MMS) is a method used by physicians to obtain clear margins in the treatment of skin tumors. It was first described by a general surgeon, Frederick Edwards Mohs [1, 2]. Originally, this technique involved the application of zinc chloride paste to the excised tissue for overnight. The technique was later modified with the introduction of fresh tissue-frozen technique and the elimination of zinc chloride fixation [3].
MMS is characterized by complete evaluation of all tumor margins. It has been proven beneficial for various types of skin malignancies including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), lentigo maligna (LM) and melanoma in situ (MIS). This technique is especially useful in face, feet and hand regions to avoid wide excision, which may not be required for tumor control [4].
Recurrent tumors, tumors in the “h-zone” (central face, eyelids, eyebrows, nose, lips, chin, ear, hand, genitalia, feet, nail units, ankles and nipples/areola), tumors with more than 2 cm diameter and tumors with aggressive histopathologic findings are candidates for MMS. In 2012, appropriate use criteria have been established by American Academy of Dermatology (AAD) and other collaborating organizations [5]. According to these criteria, all BCC, SCC, LM and MIS located in the “h-zone” and the “m-zone” (cheeks, forehead, scalp, neck, jawline and pretibial surface) are appropriate for MMS except focal in situ SCCs with actinic keratosis and superficial BCC with less than 0.5 cm diameter located in the “m-zone.” In the “L-zone” (trunk and extremities), only aggressive, recurrent or large tumors meeting certain criteria are considered suitable for MMS.
Recurrent BCC have been shown to have subclinical extension which might not be possible to identify during conventional excision. MMS has been reported to achieve better cure rates with these cases. It has been reported by Hoorens et al. that tumor with an area more than 1 cm2, aggressive histology and patient age more than 80 are strong indications of MMS for BCC [6]. This aggressive biological behavior is characterized by sclerodermiform, infiltrative, micronodular or basosquamous histology. MMS technique for these tumors can achieve higher cure rates when compared to standard excision [7].
MMS can achieve better cure rates for SCC when compared to conventional surgery. Lower recurrence rates have been reported in SCC cases over 5-year follow-up periods with MMS. MMS has been shown to provide better margin control in cases with larger than 2 cm diameter, poor differentiation and perineural invasion in which tumors are frequently known to extend beyond their macroscopic margins. [8].
The role MMS in the management of invasive melanoma is controversial since it is difficult to identify the atypical melanocytes in frozen section. On the other hand, successful treatment of melanoma in situ (MIS) has been reported with MMS. The current standard in the MIS is wide local excision (WLE) with 0.5–1 cm margin. In a recent study by Nosrati et al., 277 patients treated with MMS and 385 patients treated with WLE were compared. No significant difference between the recurrence rate and melanoma-specific survival of the patients was found. This study is especially valuable since prior studies did not involve any direct comparison of these techniques [9]. The comparison of cosmetic and functional results of MMS compared to WLE is still not clearly understood. Further studies are needed in this regard.
Lentigo maligna (LM) is considered as a type of melanoma in situ. MMS that has been reported achieves similar cure rates compared to WLE in LM cases [10].
Lymphoepithelioma, trichilemmal carcinoma, spiradenocarcinoma, nerve sheath myxoma, cutaneous angiosarcoma, granular cell tumor, atypical fibroxanthoma and extramammary Paget’s disease are among other skin tumors which have been treated with MMS.
Conventional MMS begins with the removal of the tumor with a small free margin usually between 1 and 2 mm depending on the tumor location as opposed to standard excision of skin cancers, in which at least 5 mm of margin is preferred. The lateral borders are excised at a 45° angle to allow for flattening of the lateral borders of the specimen. Complete circumferential peripheral and deep margin assessment (CCPDMA) is performed following the excision. This technique provides the complete evaluation of all tumor margins as opposed to traditional margin assessment. Following mapping of the excised tissue lateral borders are delineated with a “mashing the pie pan” technique and are positioned at the same horizontal level as the deep margin (
Mapping of the excised tissue.
Flattening of the resected tissue with relaxing incisions indicated with arrows. a. b. Relaxing incisions. c. Flattening of the specimen.
Illustration of staged surgical excisions. a. preoperative view b. excision of the first layer c. positive tumor margin after the excision d. clear margin after the excision of the second layer.
There is a considerable amount of variations in the reported cure rates for MMS among different surgeons. Misinterpretation of the pathological slides, misoriented tissue margins, freezing artifacts, poor staining, difficulty of defining atypical cells in the presence of inflammation and scar tissues, inadequate amount of sectioning and problems with flattening the resected tissues are among the reasons for less than ideal outcomes of MMS. All of these can be related to poor training of the physicians and the technicians. Certain pitfalls can be encountered during interpretation of frozen sections. These include adnexal structures which are mistaken for BCC, sun-damaged skin resembling lentigo maligna and pseudocarcinomatous hyperplasia mistaken for SCC [20, 21].
Complications such as tumor recurrence, hematoma, infection, cosmetic and functional deformities can be seen following MMS. Lips, nasal region and eyelids are among the most common sites for cosmetically poor results after MMS. Plastic surgeons should be consulted for reconstruction in cases where the primary closure of the defect with simple methods is not possible.
Mohs surgery is an important technique for the treatment of certain types of skin cancer. It is the modality of choice for high-risk basal cell carcinomas (BCC) and squamous cell carcinomas, particularly for the ones located in the facial region. This method achieves very high cure rates for both primary and recurrent BCC. Surgeons can usually avoid large deformities of the face region with application of this technique. This is an important tool that requires special training in the surgery and the pathology of the skin.
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\\n"}]'},components:[{type:"htmlEditorComponent",content:'Copyright is the term used to describe the rights related to the publication and distribution of original Works. Most importantly from a publisher's perspective, copyright governs how Authors, publishers and the general public can use, publish, and distribute publications.
\n\nIntechOpen only publishes manuscripts for which it has publishing rights. This is governed by a publication agreement between the Author and IntechOpen. This agreement is accepted by the Author when the manuscript is submitted and deals with both the rights of the publisher and Author, as well as any obligations concerning a particular manuscript. However, in accepting this agreement, Authors continue to retain significant rights to use and share their publications.
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\n\nWork - a Chapter, including Conference Papers, a Scientific Article and any and all text, graphics, images and/or other materials forming part of or accompanying the Chapter/Conference Paper.
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\n\nIntechOpen - Registered publisher with office at 5 Princes Gate Court, London, SW7 2QJ - UNITED KINGDOM
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Neutrophil effector mechanisms include the release of proinflammatory cytokines, reactive oxygen and nitrogen species (ROS and RNS), and granules containing degradative enzymes, which can cause further damage to the tissue and amplify the neutrophil response. Therefore, the modulation of neutrophil migration and functions is a potential target for pharmacological intervention in arthritis. The pharmacologic treatment options for RA are diverse. The current treatments are mostly symptomatic and have side effects, high costs, and an increased risk of malignancies. Because of these limitations, there is a growing interest in the use of natural products as therapies or adjunct therapies. Herbal products have attracted considerable interest over the past decade because of their multiple beneficial effects such as their antioxidant, anti-inflammatory, antiproliferative, and immunomodulatory properties. This chapter focuses on the role of neutrophils in the pathogenesis of arthritis and the action of substances from natural products as putative antirheumatic therapies.",book:{id:"5834",slug:"role-of-neutrophils-in-disease-pathogenesis",title:"Role of Neutrophils in Disease Pathogenesis",fullTitle:"Role of Neutrophils in Disease Pathogenesis"},signatures:"Elaine Cruz Rosas, Luana Barbosa Correa and Maria das Graças\nHenriques",authors:[{id:"64332",title:"Dr.",name:"Maria Das Graças",middleName:null,surname:"Henriques",slug:"maria-das-gracas-henriques",fullName:"Maria Das Graças Henriques"},{id:"197932",title:"Dr.",name:"Elaine",middleName:"Cruz",surname:"Rosas",slug:"elaine-rosas",fullName:"Elaine Rosas"},{id:"199677",title:"MSc.",name:"Luana",middleName:null,surname:"Correa",slug:"luana-correa",fullName:"Luana Correa"}]},{id:"46041",doi:"10.5772/57335",title:"An Insight into the Abnormal Fibrin Clots — Its Pathophysiological Roles",slug:"an-insight-into-the-abnormal-fibrin-clots-its-pathophysiological-roles",totalDownloads:3892,totalCrossrefCites:4,totalDimensionsCites:11,abstract:null,book:{id:"3836",slug:"fibrinolysis-and-thrombolysis",title:"Fibrinolysis and Thrombolysis",fullTitle:"Fibrinolysis and Thrombolysis"},signatures:"Payel Bhattacharjee and Debasish Bhattacharyya",authors:[{id:"88185",title:"Prof.",name:"Debasish",middleName:null,surname:"Bhattacharyya",slug:"debasish-bhattacharyya",fullName:"Debasish Bhattacharyya"},{id:"170045",title:"Ms.",name:"Payel",middleName:null,surname:"Bhattacharjee",slug:"payel-bhattacharjee",fullName:"Payel Bhattacharjee"}]},{id:"39110",doi:"10.5772/48250",title:"Laboratory Reference Intervals in Africa",slug:"laboratory-reference-intervals-in-africa",totalDownloads:4489,totalCrossrefCites:0,totalDimensionsCites:10,abstract:null,book:{id:"2607",slug:"blood-cell-an-overview-of-studies-in-hematology",title:"Blood Cell",fullTitle:"Blood Cell - An Overview of Studies in Hematology"},signatures:"Clement E. Zeh, Collins O. Odhiambo and Lisa A. Mills",authors:[{id:"141066",title:"Dr",name:"Clement",middleName:null,surname:"Zeh",slug:"clement-zeh",fullName:"Clement Zeh"}]}],mostDownloadedChaptersLast30Days:[{id:"66797",title:"Blood Transfusion Reactions",slug:"blood-transfusion-reactions",totalDownloads:2617,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Blood transfusion reaction/adverse transfusion reactions could be fatal/severe or mild, immediate or delayed, immunological or nonimmunological, and infectious or noninfectious, and attention is paid particularly to the incidence, possible causes and pathophysiology, clinical features, and management of each type with the aim of improving awareness and raising consciousness towards improving blood safety and judicious use of blood so as to forestall these blood transfusion reactions as much as possible. This chapter serves as a synopsis to adverse blood reactions, which are very common but apparently more often under-recognized and/or under-reported particularly in developing countries. This should sharpen the consciousness of all health practitioners involved in blood transfusion services towards taking measures at preventing transfusion reactions right from donor selection up to the infusion of blood into the recipients.",book:{id:"6905",slug:"blood-groups",title:"Blood Groups",fullTitle:"Blood Groups"},signatures:"John Ayodele Olaniyi",authors:[{id:"202764",title:"Dr.",name:"John",middleName:null,surname:"Olaniyi",slug:"john-olaniyi",fullName:"John Olaniyi"}]},{id:"49387",title:"Thalassemia — From Genotype to Phenotype",slug:"thalassemia-from-genotype-to-phenotype",totalDownloads:4877,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Thalassemia encompasses serious diseases with complex pathophysiology that is difficult to explain since it is considered a group of defects with similar clinical effects, still not a single disorder.",book:{id:"4729",slug:"inherited-hemoglobin-disorders",title:"Inherited Hemoglobin Disorders",fullTitle:"Inherited Hemoglobin Disorders"},signatures:"Ghada Y. El-Kamah and Khalda S. Amr",authors:[{id:"58735",title:"Prof.",name:"Ghada",middleName:null,surname:"El-Kamah",slug:"ghada-el-kamah",fullName:"Ghada El-Kamah"},{id:"176872",title:"Prof.",name:"Khalda",middleName:null,surname:"Amr",slug:"khalda-amr",fullName:"Khalda Amr"}]},{id:"51831",title:"Disorders Mimicking Myelodysplastic Syndrome and Difficulties in its Diagnosis",slug:"disorders-mimicking-myelodysplastic-syndrome-and-difficulties-in-its-diagnosis",totalDownloads:4511,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"Myelodysplastic morphology of blood cells can be encountered not only in myelodysplastic syndrome (MDS) but also in nonclonal disorders like viral, bacterial, parasitic infections, juvenile rheumatoid arthritis, polyarteritis nodosa, immune thrombocytopenic purpura (ITP), iron deficiency anemia, megaloblastic anemia, dysgranulopoietic neutropenia, congenital neutropenia, cases with microdeletion 22q11.2, malignant lymphoma, after administration of granulocyte colony stimulating factor, chemotherapy, steroids, smoking, alcohol, posttransplantation, copper deficiency also, together with or without cytopenia. Absence of cytogenetic abnormality in 50–70% of cases with MDS, some overlapping morphological and/or pathophysiological features make it challenging to differentiate between MDS and other diseases/disorders like aplastic anemia, refractory ITP, copper deficiency. Transient genetic abnormalities including monosomy 7 in megaloblastic anemia; increased immature myeloid cells in bone marrow of cases with copper, vitamin B12, or folic acid deficiency in the setting of cytopenia and dysmorphism may also lead to the misdiagnosis of MDS. On the other hand, there are also cases of transient MDS. In this chapter, a literature is be presented to draw attention of the readers on the disorders that mimic MDS. Additionally, our personal experiences are also be shared. Awareness of disorders mimicking MDS may prevent over- or underdiagnosis of MDS.",book:{id:"5276",slug:"myelodysplastic-syndromes",title:"Myelodysplastic Syndromes",fullTitle:"Myelodysplastic Syndromes"},signatures:"Lale Olcay and Sevgi Yetgin",authors:[{id:"184156",title:"Prof.",name:"Lale",middleName:null,surname:"Olcay",slug:"lale-olcay",fullName:"Lale Olcay"}]},{id:"64871",title:"Diagnosis and Classification of Myelodysplastic Syndrome",slug:"diagnosis-and-classification-of-myelodysplastic-syndrome",totalDownloads:3212,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by morphological dysplastic changes in one or more of the major hematopoietic cell lines. MDS can present with varying degrees of single or multiple cytopenias including neutropenia, anemia and thrombocytopenia. Presentation of MDS can range from asymptomatic to life threatening. MDS diagnosis and classification present important challenges, particularly in the distinction from benign conditions. French-American-British (FAB) classification proposed a classification based on easily obtainable laboratory information and was recommended in early and as modified by guidelines of new classification of World Health Organization (WHO). The strategy of diagnostic laboratory in MDS depends on morphological changes and is based on existence of dysplastic changes in the peripheral blood and bone marrow including peripheral blood smear, bone marrow aspirate smear and bone marrow trephine biopsy. The correct morphological interpretation and the use of cytogenetics, immunophenotyping, immunohistochemistry and molecular analysis will give valuable information on diagnosis and prognosis.",book:{id:"7138",slug:"recent-developments-in-myelodysplastic-syndromes",title:"Recent Developments in Myelodysplastic Syndromes",fullTitle:"Recent Developments in Myelodysplastic Syndromes"},signatures:"Gamal Abdul Hamid, Abdul Wahab Al-Nehmi and Safa Shukry",authors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"},{id:"273724",title:"Dr.",name:"Safa",middleName:null,surname:"Shukry",slug:"safa-shukry",fullName:"Safa Shukry"},{id:"277511",title:"Dr.",name:"Abdulwahab",middleName:null,surname:"Al-Nehmi",slug:"abdulwahab-al-nehmi",fullName:"Abdulwahab Al-Nehmi"}]},{id:"70780",title:"Laboratory Diagnosis of β-Thalassemia and HbE",slug:"laboratory-diagnosis-of-thalassemia-and-hbe",totalDownloads:1400,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"β-Thalassemia and HbE, each, is a syndrome resulted from quantitative and qualitative defects of β-globin chain, respectively. In addition to history retrieve and physical examination, diagnosis of these disorders requires laboratory information. Laboratory tests that are conventionally performed to diagnose the β-thalassemia and HbE are classified into two groups, based on the purposes, including the screening tests and confirmatory tests. The screening tests are aimed to screen for carriers of the β-thalassemia and HbE, while confirmatory tests are the tests performed to definitely diagnose these disorders. This chapter will explain all of these tests, the information of which will be useful for those who are working and interested in the β-thalassemia and HbE.",book:{id:"8450",slug:"beta-thalassemia",title:"Beta Thalassemia",fullTitle:"Beta Thalassemia"},signatures:"Thanusak Tatu",authors:null}],onlineFirstChaptersFilter:{topicId:"183",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82161",title:"Blood Groups More than Inheritance of Antigenic Substances: Susceptibility to Some Diseases",slug:"blood-groups-more-than-inheritance-of-antigenic-substances-susceptibility-to-some-diseases",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.104593",abstract:"Blood group antigens represent polymorphic traits inherited among individuals and populations. The objective of this chapter is to review articles that have reported; the association between blood group antigens and susceptibility to some diseases. Findings showed that O blood group had a greater frequency of severe infections such as E coli, cholera and blood group A was associated with incidence of smallpox and some bacterial infections. These are principally based on presence or absence of “H-like” and “A and B-like” antigens markers. Antigens A, B and H are connected to N-glycans of vWF and reduces the half-life of the protein (10 hours) for group O while non-O groups, 25 hours. The loss of A, B, and H antigens as malignancy progresses was linked to potential metastasis. Similarly, some tumors have A or A-like antigens this explains the propensity of group A to develop tumors. Blood type incompatibility between mother and foetus sensitizes the mother to develop alloantibodies that could potentially cause death of the foetus in utero, a condition known hydrops. Reviewed articles have reported close link between blood group antigens and susceptibility diseases. More studies are required to rationalize the mechanism associated to this.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Williams Bitty Azachi and Kuschak Mathias Dakop"},{id:"80344",title:"RH Groups",slug:"rh-groups",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.102421",abstract:"In 1939, a mother gave birth to a stillborn baby and underwent blood transfusion with ABO-matched blood from her husband. This resulted in a hemolytic transfusion reaction (HTR). Levine and Stetson postulated that a novel antigen was present in the baby and father, which was absent in the mother. Therefore, the mother’s immune system recognized this antigen and produced antibodies against it. This condition has been known as the hemolytic disease of the newborn for a long period of time. Since the antenatal management of the fetus has been developed, the term has been modified to hemolytic disease of the fetus and newborn (HDFN). This case led to the discovery of the antibody against the first antigen of the RH blood group system, the D antigen. To date, 56 antigens have been recognized within the RH blood group system. The five main antigens are D, C, c, E, and e. As observed in the above-mentioned case, the antibodies against these antigens are implicated in HTR and HDFN.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Amr J. Halawani"},{id:"80254",title:"Neutrophil-Specific Antigens: Immunobiology, Genetics and Roles in Clinical Disorders",slug:"neutrophil-specific-antigens-immunobiology-genetics-and-roles-in-clinical-disorders",totalDownloads:34,totalDimensionsCites:0,doi:"10.5772/intechopen.102431",abstract:"Neutrophils are the most abundant nucleated cells in blood circulation and play important roles in the innate and adaptive immune responses. Neutrophil-specific antigens, only expressed on neutrophils, are glycoproteins originally identified in studies on neonatal neutropenia due to fetal-maternal incompatibility and autoimmune neutropenia of infancy. The most investigated neutrophil–specific antigens are the NA and NB antigens that their incompatibilities also cause transfusion-induced febrile reactions and acute lung injury, a potentially fatal reaction, and in bone marrow transplantation, causing graft rejection. NA antigens are members of the immunoglobulin superfamily and are low-affinity Fc-receptors FcγRIIIb (CD16b). Fc receptors connect the F(ab), the antigen-binding fragment of the antibody molecules, to neutrophils and lead them to recognize and phagocytize the targeted antigens. The NB (CD177) antigen belongs to the urokinase-type Plasminogen Activator Receptor Superfamily (uPAR, CD59, Ly6), but its specific functions have not been fully determined. It is known, however, that NB antigen binds proteinase-3 (PR3 to the neutrophil membrane), a serine protease. In clinical studies, it was also demonstrated that NB expression is highly elevated in Polycythemia Vera and is unexpectedly expressed in some cancer tissues. Neutrophil-specific antigens are examples of antigens that have important biological and clinical activities beyond antigenicity.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Parviz Lalezari and Behnaz Bayat"},{id:"80716",title:"The ABO Blood Group System and Plasmodium falciparum (Pf ) Infection in Three Ethnic Groups Living in the Stable and Seasonal Malaria Transmission Areas of Burkina Faso (BF)",slug:"the-abo-blood-group-system-and-plasmodium-falciparum-pf-infection-in-three-ethnic-groups-living-in-t",totalDownloads:92,totalDimensionsCites:0,doi:"10.5772/intechopen.102475",abstract:"Genetic factors, including red blood cell polymorphisms, influence the severity of disease due to infection with Plasmodium falciparum (Pf). Studies show that these genetic factors associated with malaria susceptibility or resistance vary geographically, ethnically, and racially. We performed cross-sectional surveys in population living in rural villages from three ethnic groups. The blood group (BG) was determined genetically using two polymorphisms (rs8176719 and rs8176746). Out of 548 participants, 29.7% were Mossi, 38.2% were Fulani, and 32.1% were Rimaibe. The distribution of BG was, respectively, A: 25.5%, B: 26.6%, AB: 7.3%, and O: 40.5%. BG O was not only the common blood type overall, but was higher in Fulani (52.6%) than others. Fulani was associated with a reduced risk of infection and lower parasite densities than sympatric populations. The subjects with non-O blood were less susceptible to malaria infection. An association between ethnicity and malaria infection during the high transmission season as well as an association between the non-O blood group and malaria infections according to ethnicity was found. This was also true when ethnic groups were considered separately. Our results have demonstrated that the Fulani are not only less susceptible to Pf malaria infection, but when infected have lower parasite densities. Individuals with non-O blood are at lower risk of infection.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Edith Christiane Bougouma, Alphonse Ouedraogo and Sodiomon Bienvenu Sirima"},{id:"80474",title:"ABO Blood Group and Thromboembolic Diseases",slug:"abo-blood-group-and-thromboembolic-diseases",totalDownloads:40,totalDimensionsCites:0,doi:"10.5772/intechopen.102757",abstract:"Thromboembolic diseases are usually inherited in the family. The tendency to repeat in an individual is a phenomenon that allows it to be studied. The inheritance and recurrence of thromboembolic diseases, of course, have individual risk factors for this occurrence. In the past, the ABO blood group was only needed for transfusion and organ transplant therapy. Over time, scientists think that blood type is a risk factor for certain diseases, including thromboembolism. Many studies divide between type O and non-O blood groups, both of which are distinguished by the presence of antigens on the cell surface and antibodies in the plasma of individuals. Type O does not have A, B antigens but has antibodies against A, B antigens, and vice versa for the non-O type. Many studies have shown that the non-O blood group has a risk factor for thromboembolic diseases, commonly due to higher levels of von Willebrand factor (VWF) and factor VIII (FVIII). These thromboembolic events can occur in arteries or venous. Thromboembolic manifestations are often associated with cardiovascular diseases for arterial thrombosis; and deep vein thrombosis (DVT) and pulmonary embolism (PE) for venous thromboembolism (VTE).",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Yetti Hernaningsih"},{id:"78997",title:"ABO Blood Groups and Risk of Glioma",slug:"abo-blood-groups-and-risk-of-glioma",totalDownloads:59,totalDimensionsCites:0,doi:"10.5772/intechopen.100566",abstract:"Gliomas are one of the most common primary brain tumors and the etiology of gliomas remains unknown in most cases. The aim of this case–control study was to investigate possible association between incidence in relation to glioma and certain blood groups. This study included 100 histopathologically verified cases of glioma and 200 age and sex-matched controls without malignant diseases that were admitted to the same hospital. The results revealed that the patients with group AB were at 3.5-fold increased risk of developing glioma compared to the patients with other ABO blood groups. In this particular study, there was more male patients with glioma with the blood group AB. However, mechanisms that explain the relationship between the blood groups ABO and a cancer risk are unclear. Several hypotheses have been proposed, including the one with a modulatory role of blood group ABO antigens. In addition, the blood group ABO system regulates the level of circulating proinflammatory and adhesion molecules which play a significant role in the tumorigenesis process. Additionally, the recent discovery that includes the von Willebrand factor (vWF) as an important modulator of angiogenesis and apoptosis provides one plausible explanation as regards the role of the blood group ABO in the tumorigenesis process. To our knowledge, this is the first study that examined the relationship of blood group in patients diagnosed with glioma among the Serbian population. Moreover, for the first time our study results suggested that blood group AB increased the risk of glioma. The results of this study suggested that the blood group AB could be one of hereditary factors which had an influence on the occurrence of glioma. The further research is needed on a larger sample, to confirm these findings and the possible mechanisms by which the ABO system contributes to the pathology of glioma.",book:{id:"10728",title:"Blood Groups - More Than Inheritance of Antigenic Substances",coverURL:"https://cdn.intechopen.com/books/images_new/10728.jpg"},signatures:"Ana Azanjac Arsic"}],onlineFirstChaptersTotal:7},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:317,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,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:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{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"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:9,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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