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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:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"1483",leadTitle:null,fullTitle:"Soybean - Biochemistry, Chemistry and Physiology",title:"Soybean",subtitle:"Biochemistry, Chemistry and Physiology",reviewType:"peer-reviewed",abstract:"Soybean is an agricultural crop of tremendous economic importance. Soybean and food items derived from it form dietary components of numerous people, especially those living in the Orient. The health benefits of soybean have attracted the attention of nutritionists as well as common people.",isbn:null,printIsbn:"978-953-307-219-7",pdfIsbn:"978-953-51-4495-3",doi:"10.5772/1952",price:159,priceEur:175,priceUsd:205,slug:"soybean-biochemistry-chemistry-and-physiology",numberOfPages:656,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"840eecadb478078f679536ed332de9da",bookSignature:"Tzi-Bun Ng",publishedDate:"April 26th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/1483.jpg",numberOfDownloads:172709,numberOfWosCitations:182,numberOfCrossrefCitations:66,numberOfCrossrefCitationsByBook:4,numberOfDimensionsCitations:209,numberOfDimensionsCitationsByBook:6,hasAltmetrics:1,numberOfTotalCitations:457,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 19th 2010",dateEndSecondStepPublish:"June 16th 2010",dateEndThirdStepPublish:"September 21st 2010",dateEndFourthStepPublish:"November 20th 2010",dateEndFifthStepPublish:"February 3rd 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8,9",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"21099",title:"Prof.",name:"Tzi-Bun",middleName:null,surname:"Ng",slug:"tzi-bun-ng",fullName:"Tzi-Bun Ng",profilePictureURL:"https://mts.intechopen.com/storage/users/21099/images/system/21099.jpg",biography:"T. B. Ng obtained his Ph.D. degree from the Memorial University of Newfoundland in Canada. He pursued postdoctoral training at the University of California in San Francisco. He is currently a professor of biochemistry at the School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, China. His research interests encompass biologically active proteins and peptides of animal, plant, fungal and bacterial origins; polysaccharide-peptide complexe; polysaccharides;melatonin and derivatives; and natural products. He has supervised a large number of postdoctoral fellows and graduate students.He has published over five hundred papers in international journals and a number of book chapters.Some of these papers are about leguminous lectins, antifungal proteins, ribosome inactivating proteins, protease inhibitors, and peroxidases. He serves as the editorial board memeber of several journals including International Journal of Peptides, Journal of Biochemistry and Molecular Biology in the Post Genomic Era,and Frontiers in Cellulose Biotechnology. 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In mammalian cells, genetic information is stored in two locations: in the nucleus and in mitochondria. Nuclear DNA (nDNA) is organized into chromosomes of which two sets are present per cell: one paternal, and one maternal. In contrast, mitochondrial DNA (mtDNA) inheritance is (with few exceptions) exclusively maternal, and is highly redundant, typically a few hundred to a few thousand copies per cell. In many (but not all, (Noll et al., 1990)) cell types the bulk of ATP is produced by oxidative phosphorylation (OXPHOS) in mitochondria. Since mtDNA encodes components of four out of five mitochondrial respiratory complexes, it is not surprising that alterations in mtDNA result in (mitochondrial) disease (Holt et al., 1988; Lestienne & Ponsot, 1988; Wallace et al., 1988). Apart from mitochondrial disease, mutations in mtDNA are linked to a spectrum of diseases including cancer, diabetes, cardiovascular diseases and neurodegenerative disorders, as well as the normal process of aging (Wallace, 2005). Importantly, it has been established that not only mtDNA mutations, but also reduction in the mtDNA copy number can be pathogenic (Clay Montier et al., 2009; Rotig & Poulton, 2009). Understanding cellular mechanisms for the maintenance of mtDNA integrity and copy number is, therefore, of utmost importance since it can provide targets for clinical interventions aimed at prevention and treatment of human disease.
\n\t\tHuman mtDNA (Figue 1) is approximately 16.6 kbp long and encodes two rRNAs, 22 tRNAs and 13 polypeptides of which 7 are subunits of complex I (NADH dehydrogenase), 3 are subunits of complex IV (cytochrome c oxidase), 2 are subunits of complex V (ATP synthase), and cytochrome b (a subunit of complex III). The density of genetic information in mtDNA is relatively high, with very short intergenic regions. To increase this density some genes overlap, and some others lack complete termination codons, which are created by polyadenylation of corresponding mRNAs (Ojala et al., 1981). A short noncoding regulatory region in mtDNA harbours an origin of replication plus two promoters, one on each of the two complementary strands. These promoters generate polycistronic transcripts that are processed to produce mature rRNAs, tRNAs, and mRNAs and also are involved in the generation of the primer for replication of one of the strands.
\n\t\t\tThe map of human Mitochondrial DNA. OH and OL, origins of heavy and light strand replication, respectively; ND1-ND6, subunits of NADH dehydrogenase (ETC complex I) subunits 1 through 6; COX1-COX3, subunits of cytochrome oxidase subunits 1 through 3 (ETC complex IV), ATP6 and ATP8, subunits 6 and 8 of mitochondrial ATPase (complex V), Cyt b, cytochrome b (complex III).
It has been determined that mitochondria contain, on average, two molecules of mtDNA (Cavelier et al., 2000). However, mitochondria form a dynamic network which, in different cell types and under different physiological conditions, can assume a variety of conformations, the two extremes being “reticular” (mitochondria in the cell are fused to form a network of extended filaments) and “particular” (network is disintegrated into short fragments). In both conformations, mitochondria perpetually undergo the processes of fission and fusion, thus mixing their contents. Therefore, the above definitions of “reticulate” and “particulate” mitochondrial conformations are relative terms referring to a snapshot of the mitochondrial network in a cell. Nevertheless, these terms are useful as they describe the prevalence of either mitochondrial fission (“particulate” conformation) or fusion (“reticulate” conformation) in a given cell under given physiological conditions. In this light, the average number of mtDNA copies per mitochondrion determined in some studies (Cavelier et al., 2000) may simply reflect the extent of mitochondrial fragmentation under the assay conditions, which is defined by two factors: a) the mitochondrial conformation inside the cell, and b) the extent of mitochondrial fragmentation during isolation for the analysis of mtDNA content.
\n\t\t\tNuclear genetic material is represented by nucleoprotein complexes consisting of DNA wrapped around a core octamer of histones forming “beads on a string”. This nucleosomal chromatin is further organized to form chromosomes. In contrast, the mitochondrial genome lacks histones, which has led to the widespread belief that the observed high rate of mtDNA mutagenesis (approximately 10-fold greater than in nDNA (Brown, W.M. et al., 1979; Ballard & Whitlock, 2004; Tatarenkov & Avise, 2007) can be explained by the lack of “protective” histones. This belief lacks direct experimental support and remains controversial as it contradicts some experimental evidence, which suggests that histones may enhance, rather than reduce DNA damage (Liang, R. et al., 1999; Liang, Q. & Dedon, 2001), at least under some conditions, and that mtDNA-associated proteins are at least as protective against mutagenic insults as histones under other conditions (Guliaeva et al., 2006). Moreover, mtDNA may be physically covered with TFAM (Alam et al., 2003), an HMG-like protein involved in mtDNA transcription and replication, a notion which is consistent with the limited accessibility of mtDNA to methytransferases (Rebelo et al., 2009).
\n\t\t\tConsidering the endosymbiotic theory of mitochondrial origin from an ancient prokaryote, it is perhaps not surprising that recent studies revealed similarities in packaging of mtDNA and bacterial chromosomes. Thus, it has been established that in the ECV304 cell line the 3,500 copies of mtDNA are organized into ~475 nucleoids about 70 nm in diameter, each of them carrying 6-10 copies of mtDNA (Iborra et al., 2004). This organization insures similar DNA densities in mitochondrial and E.
Normal functioning of the cell and organism critically depends upon proper maintenance of mtDNA integrity and copy number. This is achieved through intricate coordination of the processes of mtDNA replication, repair, and degradation (turnover). Below, we will review each of these processes in some detail.
\n\t\t\tIt is generally accepted that replication of mtDNA is not linked to the cell cycle as strictly as replication of nDNA is. In fact, mtDNA replication occurs in all stages of the cell cycle and persists even in nondividing cells (Bogenhagen, D. & Clayton, 1977; Clayton, 1982). DNA polymerase γ ( Pol γ) is the sole DNA polymerase identified in mitochondria. This enzyme is heterotrimeric and consists of a single 140 kDa catalytic subunit encoded by the POLG gene and two 55 kDa accessory subunits, encoded by POLG2. As the only DNA polymerase found in mitochondria, Pol γ is responsible for both replication and repair of mtDNA. Several other proteins play prominent roles in the mtDNA replication process. These are the DNA helicase Twinkle, a mitochondrial single-strand-binding protein (mtSSB), which mediates unwinding of mtDNA through its physical interaction with Twinkle (St John et al., 2010), and a mitochondrial RNA polymerase, which generates primers for mtDNA replication with the assistance of mitochondrial transcription factors A (TFAM), B1 (TFB1M), and B2 (TFB2M). While the major players in mtDNA replication are fairly well known, the exact mechanism remains controversial (reviewed in (Holt, 2009)).
\n\t\t\t\tElectron microscopic observations of purified mtDNA molecules led to the adoption of the strand-displacement model (Robberson et al., 1972). In these experiments, the observation of extensive single-strand regions in mtDNA suggested that synthesis of the leading strand is uncoupled from that of the lagging strand. The leading strand synthesis is initiated at a fixed point and advances about two-thirds of the way around the mtDNA molecule before second strand synthesis is initiated (Holt, 2009). Recently, however, analysis of mtDNA replication intermediates in both mammalian tissues and cultured cells by two-dimensional agarose gel electrophoresis revealed the presence of products consistent with a strand-coupled mechanism of replication (Holt et al., 2000). Subsequently, it was found that RNA is incorporated throughout the lagging strand (RITOLS mechanism, (Yasukawa et al., 2006)). This raised the possibility that the abundant single-strand regions observed in the earlier studies could be an artifact of RNA loss during DNA isolation and processing, and suggested that strand-coupled and RITOLS could be the only two mechanisms involved in mtDNA replication, thus excluding the earlier strand-displacement mechanism (Yasukawa et al., 2006). RITOLS appears to be initiated at several sites in the D-loop and proceeds unidirectionally (Yasukawa et al., 2006), whereas initiation of strand-coupled replication occurs over a broad region and is bidirectional (Yasukawa et al., 2005). However, the observation of stable non-replicative DNA-RNA hybrid loops formed by some mitochondrial transcripts casts a shadow on the authenticity of RITOLS in favor of the original asynchronous strand-displacement mechanism (Brown, T.A. et al., 2008).
\n\t\t\tMitochondrial genomes accumulate mutations approximately one order of magnitude faster than nDNA (Brown, W.M. et al., 1979; Ballard & Whitlock, 2004; Tatarenkov & Avise, 2007). This could be caused by a variety of factors, including an intrinsically lower fidelity of replication by mitochondria-specific DNA polymerase γ (Pol γ), a lower efficiency of mtDNA repair, or chronic exposure of mtDNA to noxious factors, such as Reactive Oxygen Species (ROS) or environmental genotoxins. However, attempts to experimentally link mtDNA mutagenesis to exposure to carcinogens (Mita et al., 1988) or to reactive oxygen species (Shokolenko et al., 2009) proved unsuccessful, leading to the notion that mtDNA may be resistant to mutagenesis. To confound things even further, several studies have reported that nDNA is at least as sensitive to oxidative damage as mtDNA (Anson et al., 1999; Anson et al., 2000; Lim et al., 2005), which undermines the earlier notion that the higher susceptibility of mtDNA to damage by ROS is the driving force behind its higher rate of mutagenesis (Richter et al., 1988).
\n\t\t\t\tThe current progress in our understanding of mtDNA repair pathways has been reviewed recently (Liu & Demple, 2010). Historically, the discovery that mitochondria are unable to repair ultraviolet (UV)-induced pyrimidine dimers (Clayton et al., 1974, 1975) and some types of alkylating damage (Miyaki et al., 1977), suggested that they may contain a reduced complement of DNA repair pathways. However, Anderson and Friedberg (Anderson & Friedberg, 1980) found uracil-DNA glycosylase activity in mitochondrial extracts, suggesting the presence of the base excision repair (BER) pathway. This was followed by a report of mitochondrial repair of O6-ethyl-2\'-deoxyguanosine (Myers et al., 1988; Satoh et al., 1988). This can be processed by direct reversal using O6-methyl guanine methyl transferase or by a nucleotide excision repair pathway. Subsequently, repair of a variety of mtDNA lesions by BER, including those arising from oxidative damage, was demonstrated (Pettepher et al., 1991; Le Doux et al., 1992; Driggers et al., 1993). Recently, long-patch BER of oxidative DNA lesions (Akbari et al., 2008; Liu et al., 2008; Szczesny et al., 2008), and mismatch repair (de Souza-Pinto et al., 2009) have been reported in mammalian mitochondria. The presence in mammalian mitochondria of a DNA end binding activity (Coffey et al., 1999), and a ligase capable of joining both cohesive and blunt ends (Lakshmipathy & Campbell, 1999) suggested the presence of a non-homologous end joining pathway in mitochondria. Similarly, detection of recombination intermediates indicated that mtDNA can be repaired through a homologous recombination pathway (Kajander et al., 2001; Kraytsberg et al., 2004). This notion was further supported by experiments on the induction of mtDNA double-strand breaks (DSBs) in vivo with the help of mitochondrially-targeted restriction endonucleases. In these experiments, DSB repair was accompanied by the formation of mtDNA deletions, some of which had breakpoints flanked by direct repeats, thus implicating homologous recombination in the repair (Srivastava & Moraes, 2005; Fukui & Moraes, 2008). To summarize, current experimental evidence suggests the presence in mitochondria of all major DNA repair pathways, with the exception of the nucleotide excision repair. Moreover, mitochondria appear to possess a unique mechanism for the maintenance of DNA integrity through degradation of damaged molecules (see below). Importantly BER, which is responsible for the repair of oxidative base lesions, is robust in mitochondria, as evidenced by observation that repair of 8-oxodG, the most prominent oxidative base lesion, is more efficient in mitochondria than in the nucleus (Thorslund et al., 2002).
\n\t\t\tUnlike the nuclear genome, the mitochondrial genome is redundant, consisting of hundreds to thousands of copies per cell. Therefore, a “repair or die” constraint is not imposed on mtDNA. Conceivably, a substantial fraction of damaged mtDNA can be lost without detrimental effects, provided that this loss is compensated for by replication of new genomes. In fact, the loss and resynthesis of mtDNA was observed more than 40 years ago by Gross and Rabinowitz, who described mtDNA turnover (Gross & Rabinowitz, 1969). Many cell lines are fairly tolerant to the loss of mtDNA, and can survive both a gradual loss of mtDNA through chronic treatment with ethidium bromide (King & Attardi, 1989), and acute destruction of a fraction (Alexeyev et al., 2008) or even all of their mtDNA (Kukat et al., 2008) by mitochondrially targeted restriction endonucleases. This is in a stark contrast to nDNA, in which persistent DSB can activate apoptosis. However, the hypothesis that turnover (degradation) of damaged mtDNA can be a mechanism used by mitochondria to deal with either excessive damage, or damage that can not be repaired did not take hold in part due to the lack of direct experimental evidence supporting it and in part due to discovery of mitochondrial BER (Pettepher et al., 1991), which shifted attention from unrepairable lesions to those that can be repaired. However, recent evidence reignited interest in mtDNA degradation.
\n\t\t\t\tEthanol has been reported to induce mtDNA loss in yeast (Ibeas & Jimenez, 1997). In mice, intragastric administration of ethanol induced oxidative stress and was accompanied by a reversible loss of mtDNA (Mansouri et al., 1999). The loss of mtDNA was approximately 50% in all organs studied. It could be partially prevented by the antioxidants melatonin, vitamin E and coenzymeQ, and was followed by adaptive mtDNA resynthesis (Mansouri et al., 2001). Lipopolysaccharide, a known inducer of in vivo oxidative stress also induced, mtDNA depletion (Suliman et al., 2003). Angiotensin II induced mitochondrial ROS production and decreased skeletal muscle mtDNA content in mice (Mitsuishi et al., 2008). Degradation of mtDNA was observed in the rat model of cerebral ischemia/reperfusion (Chen et al., 2001). Similar to mtDNA depletion induced by intragastric ethanol administration, mtDNA levels returned to normal within 24h of cerebral ischemia/reperfusion (Chen et al., 2001). Finally, H2O2-induced oxidative stress in hamster fibroblasts was accompanied by Ca2+-dependent degradation of mtDNA (Crawford et al., 1998). Taken together, these findings strongly suggested a link between oxidative stress (which may result in oxidative mtDNA damage) and mtDNA degradation, yet they stopped short of invoking degradation as protective mechanism. In an unrelated study, it was observed that mtDNA is resistant to mutagenesis induced by alkylating agents, and the authors suggested degradation of damaged mtDNA as one of the potential mechanisms for this resistance (Mita et al., 1988). However, mtDNA degradation under the experimental conditions of that study was not demonstrated (Mita et al., 1988).
\n\t\t\t\tRecently, we attempted to study the relationship between experimentally induced oxidative stress and mtDNA mutagenesis. In initial experiments, superoxide radicals were generated on the matrix side of the mitochondrial inner membrane by treating cells with sublethal concentrations of the complex I inhibitor rotenone (St-Pierre et al., 2002; Muller et al., 2004). However, exposing human colon carcinoma cells or mouse embryonic fibroblasts to rotenone for 30 days did not result in a significant increase in the rate of mtDNA mutagenesis (Shokolenko et al., 2009). Similarly, repeated treatment of HCT116 colon cancer cells with H2O2 failed to induce significant mtDNA mutagenesis. Instead, DNA lesions that manifest themselves as strands breaks under denaturing conditions (single-strand breaks (SSBs) and DSBs, abasic sites, etc.) prevailed over premutagenic base modifications by a factor of 10. Consistent with the hypothesis that unrepairable mtDNA molecules are degraded, treatment of cells with an inhibitor of BER methoxyamine, enhanced mtDNA degradation in response to both oxidative and alkylating damage (Shokolenko et al., 2009). The elimination of damaged mtDNA was preceded by the accumulation of linear mtDNA molecules, which may represent degradation intermediates, since, unlike undamaged circular molecules, they are susceptible to exonucleolytic degradation.
\n\t\t\t\tThe high rate of lesions (mostly, SSBs and abasic sites) in mtDNA induced by ROS suggests a mechanism by which mitochondria may maintain the integrity of their genetic information. In this model, oxidative stress induces in mtDNA lesions with a much higher (by the factor of 10, (Shokolenko et al., 2009)) frequency than mutagenic lesions. These lesions represent a block to transcription and replication of mtDNA, and when accumulated above a threshold level, they induce degradation of mtDNA molecule. Therefore, degradation of mtDNA molecule is triggered before it accumulates mutagenic lesions. This model provides a mechanistic explanation for the observations made by Suter and Richter (Suter & Richter, 1999), who found that the 8-oxodG content of circular mtDNA is low and does not increase in response to oxidative insult. However, fragmented mtDNA had a very high 8-oxodG content, which increased further after oxidative stress. It incorporates the previously suggested notion of a possible contribution of APE1 to mtDNA degradation (Tomkinson et al., 1988; Tomkinson et al., 1990). The model is consistent with the observations of Yakes and van Houten (Yakes & Van Houten, 1997), who found that oxidative stress promoted a higher incidence of polymerase-blocking strand breaks and abasic sites in mtDNA than in nDNA. Recent studies using qPCR for the analysis of mtDNA provide further support for the notion of mtDNA degradation in response to oxidative stress (Rothfuss et al., 2010). Therefore, degradation of severely damaged mtDNA emerges as a unique, mitochondria-specific mechanism for the maintenance of DNA integrity.
\n\t\t\t\tDegradation of damaged organellar DNA appears not to be unique to mammalian cells. Known examples of rapid organellar DNA turnover in plants and protists in response to ROS were reviewed recently by Bendich (Bendich, 2010).
\n\t\t\tIn most mammalian cells, mtDNA copy number is kept relatively constant at 1,000-10,000 copies per cell, depending on the cell type and physiological conditions (Copeland, 2008). However, antiretroviral therapy (Arnaudo et al., 1991) and genetic defects in the components of the mtDNA replicating machinery (Rotig & Poulton, 2009) were demonstrated to induce a pathologic decrease in mtDNA content of the cell. Also, mtDNA copy number can be decreased in response to increased mtDNA damage, which is not met with a corresponding increase in repair (Shokolenko et al., 2009). For patients with genetic mitochondrial DNA depletion syndromes (MDS), there is no treatment other than supportive therapy (Poulton & Holt, 2009). Liver transplantation proved inefficient in two major forms of MDS associated with liver failure: Alpers-Huttenlocher syndrome and deoxyguanosine kinase (DGUOK) deficiency. In the former instance failure to achieve a therapeutic effect appears to be linked to the inevitable brain involvement, which may not be apparent until after the transplantation. Attempts to correct the hepatocerebral syndrome resulting from DGUOK deficiency through liver transplantation were reviewed recently (Rahman & Poulton, 2009). Infant death was observed in 6 out of the 9 cases reviewed.
\n\t\t\t\tSince mtDNA copy number is maintained through an intricate coordination between two opposing processes, mtDNA synthesis and mtDNA degradation, we suggest that MDS should not be viewed merely as diseases of reduced mtDNA synthesis but rather as diseases of imbalance between synthesis and degradation of mtDNA. This view allows for a new, so far unexplored treatment strategy, i.e. inhibition of mtDNA degradation. Indeed, suppressed mtDNA replication due to mutations in Pol γ (patients with Alpers-Huttenlocher syndrome), Twinkle helicase (patients with progressive external ophtalmoplegia), or due to ingestion of nucleotide reverse transcriptase inhibitors (AIDS patients) results in the establishment of a new, lower cellular mtDNA content, which is characterized by reduced rates of both mtDNA synthesis and degradation. Conversely, suppression of mtDNA degradation should lead to a new steady state with increased mtDNA content, and therefore could be therapeutic in patients with MDS.
\n\t\t\tSouthern Blot analysis can be used for the quantitation of various types of damage to mtDNA. This method is based on the detection of strand breaks within linearized mtDNA. Strand breaks can be generated either directly by noxious agents (e.g., by alkylating compounds or oxidative stress), or indirectly, after the treatment of damaged DNA with lesion-specific glycosylases, which remove damaged bases thus creating abasic sites. Examples of glycosylases widely used for this purpose include E.
In other words, mtDNA break frequency (BF) in treated samples equals the negative natural logarithm of the ratio of mtDNA band intensities in treated and control samples.
\n\t\t\t\tSeveral important caveats have to be noted in relation to this technique:
\n\t\t\t\tPrior to analysis, circular mtDNA is linearized by digestion with restriction endonuclease.
The technique relies on measuring mtDNA band intensities in treated vs. control samples. Therefore, loading equal amounts of total DNA per well of the gel, which depends on accurate DNA quantitation is very important. Since nDNA shows much lower sensitivity to oxidative damage than mtDNA, hybridization of the membrane to nDNA probe in addition to mtDNA probe can be used in addition to visual inspection of ethidium bromide stained gels as loading control when studying oxidative mtDNA damage. However, hybridization to a nDNA probe is not useful as a loading control when studying, certain types of alkylating DNA damage, when the difference in the damage of nuclear and mitochondrial genomes is not as dramatic.
Isolation of mtDNA is impractical and is associated with the introduction of artifacts. Therefore, in this technique total cellular DNA is subjected to Southern hybridization. The use of a mtDNA-specific hybridization probe allows one to study only changes in mtDNA integrity. In a typical cell type studied by this technique, mtDNA constitutes only about 1-2% of total DNA.
Quantitative Southern Blotting under denaturing (alkaline) conditions, by itself, does not discriminate between SSBs and DSBs. Therefore mtDNA containing DSBs, which repair inefficiently and therefore lead to mtDNA loss (Kukat et al., 2008), will appear the same as SSBs, which repair much better (Fig. 2, Mix 1 vs. Mix 2, left side). To discriminate between SSBs (repairable mtDNA damage) and DSBs (mtDNA degradation) we introduced an approach that involves running the same DNA samples under both alkaline and neutral conditions (Shokolenko et al., 2009). Samples containing DSBs appear the same under both conditions (Fig. 2, Mix 2, left side vs. right side). In contrast, mtDNA containing SSBs appears like mtDNA containing DSBs under denaturing conditions, but under non-denaturing (neutral) conditions it behaves like undamaged control DNA (Fig. 2, Mix 1, left side vs. right side).
Specific types of DNA damage can be detected as follows:
\n\t\t\t\tDSBs convert circular mtDNA into a linear molecule. Therefore, qualitative detection of DSBs can be performed by Southern Blotting of total cellular DNA samples under non-denaturing conditions using linearised mtDNA as a standard. The increase in the signal corresponding to linear mtDNA is interpreted as a result of DSB. It is helpful to digest total DNA with a restriction enzyme that does not cut mtDNA (e.g., BglII for human DNA). In our experience, failure to perform this step results in an absence or in a severe reduction of the hybridization signal. However, the method is not quantitative for two reasons: a) DSB repair in mtDNA is inefficient, and most linear mtDNA is degraded fairly quickly (Shokolenko et al., 2009), and b) mtDNA can concatenate, at least in some cell lines (Bedoya et al., 2009), and electrophoretic mobility of linear concatemers is distinct from that of linear mtDNA monomers.
SSBs can be quantified as a difference in break frequencies detected using Southern Blotting under alkaline and neutral conditions (Fig. 2). Alternatively, it can be calculated as break frequency in sample ran under the alkaline conditions using the same sample ran under neutral conditions as a control.
Abasic sites. This type of lesion can be quantified as a difference in break frequency in two identical aliquots of the sample ran under alkaline conditions if one aliquot has been treated with methoxyamine prior to electrophoresis. Under alkaline conditions, abasic sites are converted into strand breaks through the process of beta-elimination. Modification of abasic sites with methoxyamine renders them alkali-resistant (Liuzzi & Talpaert-Borle, 1985; Scicchitano & Hanawalt, 1989). Alternatively, abasic sites can be quantified by comparing aliquots of methoxyamine-treated DNA run under the alkaline conditions after treatment with APE1 (control) and EndoIII (experimental). Methoxyamine-modified abasic sites are resistant to hydrolysis by APE1, but not by endoIII (Rosa et al., 1991)
Base modifications can be quantified using lesion-specific DNA glycosylases. One aliquot of DNA sample is treated with lesion-specific DNA glycosylase, whereas a second aliquot is left untreated. Monofunctional DNA glycosylases (e.g., uracil DNA glycosylase or methylpurine DNA glycosylase) convert a lesion into an abasic site, which can be converted into a strand break under the alkaline conditions thus allowing for the quantitation by comparing hybridization signals obrained from enzyme-treated vs. untreated controls. As indicated above, bifunctional DNA glycosylases, such as FPG or Endo III, will convert a lesion into a strand break allowing for quantitation using the same approach.
The advantages of Quantitative Southern Blotting include its robustness due to reliance on physical interactions rather than on enzymatic reactions and its ability to quantify some lesions (e.g., abasic sites), which can not be quantified by PCR-based techniques (see below). The disadvantages include the fact that the procedure involves multiple steps, is time-consuming, and requires relatively large quantities (1µg or more) of starting DNA.
\n\t\t\tAn alternative approach for the detection of DNA damage was developed by Govan (Govan et al., 1990) and modified by Yakes and van Houten for studies with mtDNA. This method, QPCR (a.k.a. QXL-PCR), is predicated upon the ability of the lesions present in mtDNA to block the progression of a thermostable DNA polymerase, resulting in a decrease of DNA amplification in the damaged template, when compared to undamaged control (Yakes & Van Houten, 1997). Similar to quantitative Southern Blotting, QPCR measures the fraction of undamaged amplifiable template, which decreases with increased number of lesions.
\n\t\t\t\tAnalysis of mtDNA damage by quantitative Southern Blotting under denaturing (alkaline) and non-denaturing (neutral) conditions. Behavior of the mtDNA samples that contain either no damage (Cont), SSBs (Mix 1), or a mixture of intact mtDNA and mtDNA containing DSBs (Mix 2) is presented schematically. Under the denaturing conditions (left side of the figure), mtDNA strands separate, and strands containing lesions in the form of SSBs, DSBs, or abasic sites fragment. The resulting fragments migrate faster than intact full-length (Fl) mtDNA strands in the agarose gel thus creating smears (Mix1 and Mix 2, left side). Under conditions depicted in this scheme, the intensity of the Southern Blot signal corresponding to intact mtDNA fragment from Mix 1 equals that of Mix 2, and represents half of the signal strength produced by undamaged control. When the same samples are analyzed under the non-denaturing conditions (right side of the figure), mtDNA fragmentation in Mix 1 containing SSBs does not occur. In contrast, mtDNA in Mix 2 containing DSBs fragments create a smear. As a result, the signal intensity for intact mtDNA in the Mix 1 under non-denaturing conditions is twice as high as that in the Mix 2. The arrow indicates the direction of electrophoresis; Fl’, full-length mtDNA strand complementary to Fl strand; 1, 2, 3, and 4 in Mix 1, subfragments into which Fl strand containing a lesion fragments; 1, 1’, 2, and 2’ in Mix 2, direct and complimentary strands of the subfragments resulting from a DSB in the Fl fragment.
Successful outcome of experiments with either quantitative Southern Blot or QPCR is heavily dependent upon the ability to accurately measure the amount of DNA used. Spectrophotometric methods (A260) appear to be inappropriate for this purpose because of the intrinsic difficulties associated with controlling the quantity and spectrum of contaminants in DNA preparations. Fluorescense based methods (PicoGreen and Hoechst 33258 dyes), unlike spectrophotometric techniques, show little sensitivity to such contaminants as proteins, single-stranded DNA, RNA etc., which are common to genomic DNA preparations and therefore are deemed the methods of choice. Also, when using QPCR, one has to control for changes in the mtDNA copy number. Indeed, a reduction in mtDNA copy number will manifest itself as DNA damage because of the reduction in the number of amplifiable mtDNA genomes in the template. This can be controlled for by amplifying of a short (about 300bp) fragment of mtDNA-encoded gene. The rationale is that encountering DNA damage in such a short fragment is an event with a very low probability and therefore profiles of amplification of such a fragment should be essentially identical between damaged and undamaged DNA. Therefore, variations in the degree of amplification of the small fragment are assumed to be the result of fluctuations in mtDNA copy number and the results of small fragment amplification are used for the normalization of the data obtained for the large (16 kb) mtDNA fragments.
\n\t\t\t\tThe success of the QPCR approach requires the measurements be made within the linear range of amplification. This requires optimization to find the optimal starting concentration of DNA template (Yakes & Van Houten, 1997). Alternatively, one can identify the range for linear amplification. However, both approaches require a significant amount of optimization. Recently, a real-time PCR approach has been extended to QPCR resulting in the development of the long-range PCR technique (LRPCR, (Edwards, 2008)). Two significant problems had to be addressed in the process: (1) the low processivity and polymerization rates of the DNA polymerases used in comparison to the length of the amplicons, (2) SYBR green inhibition of DNA amplification (Gudnason et al., 2007). In comparison to the earlier semi-quantitative protocols this represents a significant improvement in both the ease of data acquisition and the precision for quantification of mtDNA damage (Edwards, 2008). The most recent variation of the technique, the semi-long run real-time (SLR rt-) PCR method, further simplifies the procedure by amplifying relatively short mtDNA fragments using real-time PCR (qPCR) reagents and instruments (Rothfuss et al., 2010). In this procedure, the reduced length of amplified products enables the use of standard qPCR kits. The flip side of this improvement is the reduced sensitivity of the technique, which is directly related to the length of amplified fragments. Therefore, applicability of this technique for reliable detection of physiological (low) levels of mtDNA damage requires independent validation and is likely to strongly depend upon the instrument used. Indeed, a simple calculation shows that a fairly high level of mtDNA damage of 1 lesion/mtDNA molecule (16.5 kbp) translates into 0.061 lesion per 1 kbp fragment amplified in this method. Using “zero class” Poisson distribution used for the analysis of this type of DNA damage
\n\t\t\t\twhere D= lesion frequency per length of amplified fragment (1kbp), ln is natural logarithm, AD is amplification of the damaged DNA sample, and AC is amplification of the control sample) we arrive at the AD/AC =0.94. The corresponding shift in the threshold cycle (ΔCt, derived from the readout of the qPCR instrument) is 0.089. Therefore, a significant mtDNA damage of 1 lesion per mtDNA molecule results in less than a 0.1 threshold cycle shift between amplification curves of treated and untreated samples. This places a very high demand on the instrument’s ability to reproducibly amplify different samples. In our experience, a PCR block that allows for greater than 0.7 Ct spread between identical samples still conforms to the standards of the two major manufacturers of qPCR instruments. In this case, the instrument’s well-to-well variability exceeds the measured differences by a factor of 7.
\n\t\t\t\tThe strength of PCR-based techniques for the analysis of mtDNA damage is in the ability to work with very low starting quantities of DNA. This strength is turned into a weakness when relevant methodological precautions, such as the availability of distinct, dedicated workstations, for different steps of the procedure in physically separate laboratories (Santos et al., 2006) are considered. Another weakness of this approach is that it provides even less information about the nature of DNA damage than Quantitative Southern Blotting. E.g., abasic sites can be quantitated by Quantitative Southern Blotting under alkaline conditions by comparing lesion frequencies in DNA modified with methoxyamine vs. unmodified DNA. Methoxyamine modification protects abasic sites from being converted into strand breaks through beta-elimination under alkaline conditions. In contrast, native abasic sites, methoxyamine-modified abasic sites, and abasic sites converted into strand breaks through beta-elimination all will prevent copying by the DNA-polymerase in PCR-based techniques and therefore will be indistinguishable. Nevertheless, these techniques are the only ones available for analysis of mtDNA damage and repair when amount of the starting material is limited.
\n\t\t\tmtDNA integrity and appropriate copy number appear to be crucial for normal functioning of the cell. Therefore, understanding the processes that govern mtDNA replication, repair and degradation is of critical importance for our ability to prevent and/or clinically intervene in pathological processes associated with mutations in mtDNA and mtDNA depletion. Degradation of mtDNA is now emerging as a promising therapeutic target in the treatment of congenital mtDNA depletion syndromes and mtDNA depletion induced by antiretroviral therapy. However, the molecular identity of the nuclease involved in mtDNA degradation remains enigmatic. Future research will shed light on this and other remaining mysteries of mtDNA biology.
\n\t\tM.A. was supported by 1RO1RR031286, 1R21RR023961, and 1PO1 HL66299.
\n\t\tUser authentication is an important phase in security systems. Authentication is the determining process of a person is really, who claimed to be. Authentication technology affords the access to the systems after checking/verifying if a user’s certification matches the authorized certification in a database, usually provided with an ID of a user, and authentication is achieved when the user provides a certification. Generally, authentications can be according to their use: password-based, token-based, and biometrics-based. Each of has its advantages and disadvantages [1].
Biometrics systems based on human being’s measurements analyze statistic aspects of unique physical and behavioral characteristics, which can be consumed to identify or verify a human [2].
The term biometric is a Greek word, referring to bio means “life” and metric means “measurement.” Biometrics is used to achieve reliable authentication and identification that can be expressed as face fingerprints, iris, retina, signatures, gait, voice, etc. Recently, a new biometric field has gained its popularity because of its less drawbacks over other biometrics; it is the brain wave biometric or electroencephalography (EEG) [3].
However, without the drawbacks of both passwords-based and biometric-based, the EEG-based biometric authentication system combines their advantages [1]. EEG signals are dynamic, sensitive, and inexpensive and used to observe mental state that can be used to distinguish persons.
These signals can be bound with a cryptography to empower the security, a scheme that can be used with brain wave signals is called fuzzy vault scheme, key-based cryptographic scheme uses error correction codes to generate polynomials to secure the key.
Biometric structure helps to find out the person with the physical-behavioral mechanism using statistics from person. [4], there are two types of biometrics: conventional and cognitive, conventional refers to physical and behavioral characteristics, such as fingerprint, voice, oder, DNA, face, iris, retina. Etc., cognitive refers to mental state signals as electroencephalography (EEG), these biometrics are unique for every individual. Physical biometrics is distinguished by “what the individual is” while behavioral is distinguished by “how individual do,” cognitive is “what individual think” [5]. Figure 1 illustrates biometric types.
Biometric types.
Electroencephalogram, EEG for short, is the human brain’s electrical activity. Nerve system of human, including the brain, consists of neurons, which are nerve cells. The electrical current transmitted signals by neurons to other neurons [6]. The changes in voltage resulting from the electrical current are then measured by electrodes. Patterns form waves used by EEG and are sinusoidal. Based on the frequency bandwidth can be classified into several bands. Each band of waves corresponds to different activities. Most common bands classification [6]: Delta (0.5–4) HZ, Theta (5–7) HZ, Alpha (8–15) HZ, Beta (16–31) HZ, Gamma(32-higher) HZ, the correspondence for each band, Table 1 describes each band and its activity.
Band name | Range in HZ | Activity |
---|---|---|
Gamma | 32–higher | Consciousness, higher processing tasks |
Beta | 16–31 | Awake, active thinking, concentration and arousal states, eyes opened |
Alpha | 8–15 | Relaxation, eyes closed |
Theta | 5–7 | Drowsy, meditating and sleeping |
Delta | 0.5–4 | Deep sleeping |
EEG bands description.
It is the measurement of electrical activity of the brain, sensor used to obtain these signals. Brain consists of millions of neurons, and these neurons express emotions and thoughts as signals [7].
“EEG measures the currents that flow during synaptic excitations of the dendrites of many pyramidal neurons in the cerebral cortex. Differences of electrical potentials are caused by summed postsynaptic graded potentials from pyramidal cells that create electrical dipoles between soma (body of neuron) and apical dendrites (neural branches) [5].”
The potentials are measured between two or more points called electrodes or sensors, which are placed on the scalp at different locations. EEG resembles waves, which is why the term brain waves is used when referring EEG signals. Padfield et al. [8], these EEG signals are unique for every individual and less exposed because it is under the scalp, which is hard to obtain and cannot be copied or manipulated [2].
Universality, uniqueness, permanency, performance, collectability, acceptability, and robustness satisfy the requirements of EEG-based biometric authentication method [7].
MI is imagining a motor action without any efferent information to neuromuscular system. Thoughts and actions are intimately linked. A confirmation of this prediction is found in the spatial patterning of activated cortical areas seen with functional brain imaging techniques such as PET and fMRI [9]. MI is widespread in BCI systems because it has naturally occurred discriminative properties and also because signal acquisition is not expensive [8]. It is widely used in sport training as mental practice of action, neurological rehabilitation, and has also been employed as a research paradigm in cognitive neuroscience and cognitive psychology to investigate the content and the structure of covert processes (i.e., unconscious) that precede the execution of action. The effectiveness of motor imagery has been demonstrated in musicians. There have also been conducted multiple studies on its uses in neurological rehabilitation in patients after stroke [10].
Marcel and Millan [11] investigate the use of brain activity for person authentication, using a statistical framework based on Gaussian Mixture Models and Maximum a posteriori model adaptation. Intensive experimental simulations are performed using strict train/test protocols to show the potential of method [11].
Fladby [12] performs an experiment with 12 participants for eight different tasks in three sessions. They extract features from time and frequency domain by analyzing EEG and then the proposed algorithm is applied as dynamic time warping as well as a feature-based distance metric [12].
He [7] proposes an EEG feature hashing approach for person authentication, by extracting the coefficients of the autoregression model from multiple EEG channels, Fast Johnson-Lindenstrauss transform that is based dimension reduction algorithm to hash vectors. For person authentication, a Naive Bayes probabilistic model is applied [7].
Nguyen et al. [13] investigated the person verification based on brain wave features extracted from EEG signals of motor imagery tasks. For each subject, left, right, and best motor imagery tasks were used. As for modeling, the Gaussian mixture model (GMM) and support vector data description (SVDD) methods were used [13].
Nieves and Manian [14] proposed a system use an effective time-frequency-based feature extraction method using the short-time Fourier transform (STFT) or spectrogram. Computed features on the spectrogram were energy, variance, and skewness. These features were used to train a SVM and neural network classifier. Using cross-validation for testing data for person authentication the classifiers are tested. Results using a different number of channels with optimum features presented [14].
Soni et al. [2] “design a system and implement it, so that users set patterns as an unlock pattern to obtain the access’s permission. This pattern can be any combination of eye blink, attention and various brain rhythms like Alpha, Beta, Theta and Delta. Provided two-level authentication. First level of which is brain waves. Once the correct pattern of brain signal is provided the system will ask for a pass key as a second level of authentication [2].”
Sjamsudin [15] “investigates the aspects of performance and time-invariance of EEG-based authentication. Two sets of experiments are done to record EEG of different individuals. The system implemented the use of machine learning such as SVM and deep neural network to classify EEG of subjects [16].”
Juels and Sudan [16] propose a novel cryptographic construction scheme defined as a fuzzy vault. Alice is a player lock a secret value in a fuzzy vault and “lock” it, using a set of element A. using set B of the same length Bob will try to “unlock” the vault, he gets the secret only, if A and B overlap substantially [16].
Uludag et al. [17] explore the combination of fuzzy vault with the fingerprint minutiae data, which try to secure the important data using the fingerprint data, such that only the authorized user can access the secret by providing the valid fingerprint [17].
Nandakumar and Jain [18] use the fuzzy vault to secure a multi-biometric template derived from a person’s templates. Exhibiting that a multi-biometric vault provides better recognition performance and higher security compared with a uni-biometric vault [18].
Khalil-Hani et al. [19] “propose a new chaff generation algorithm which is computationally fast and viable for hardware acceleration by employing simple arithmetic operations.”[19].
You et al. [20] proposed cancelable fuzzy vault algorithm based on the user’s transformed fingerprint features, which are used to generate a fuzzy vault [20].
DamaševiIius et al. [21] “combine an EEG based biometric with the fuzzy commitment scheme and BCH error correcting for person. Evaluating features that are covariance matrix of EEG data using EEG recorded from 42 subjects. The experimental results present that the system can generate up to 400 bits of cryptographic key from the EEG codes, while tolerating up to 87 bits of error [21].”
With the rapid development of technology, large institutions and government institutions, which have sensitive information and also applications, need systems with high security and reliable authentication way that is hard to/or possible to copy or manipulate brain wave biometric has these proprieties, in authentication it is very important that people accept the system (acceptability). With this in mind it is safe to say that a noninvasive method of capturing brain wave signals is the best way for biometric acquisition as for securing these biometrics.
In this chapter, the winning BCI competition Graz IV2a Dataset (2008) by burner is used [22], which is consists of nine subjects each performing four MI tasks randomly (this process called trial), each task is a class (left hand, right hand, foot, and tongue) corresponding to (1,2,3,4) respectively, the experiment is done by experts, with no feedback. For our system we use only left and right classes [22].
Each subject sat on comfortable armed chair in front of a computer screen at time (
The dataset is divided into two sessions each in separate day, one for training and other for evaluation, each subject performs 48 trial (each class 12 trial) for 6 runs, yielding in total 288 trial [22]. The sampling rate of the signal is 250 Hz, a bandpass filter was applied between 0.5 Hz and 100 Hz. The sensitivity of the amplifier set to 100 μV, to suppress line noise, a 50 HZ notch filter was applied, and artifact trials were marked. The signals were recorded from 25 channels, 22 EEG, 3EOG [22].
Extraction of EEG trials means the process of finding trial of interest of EEG signals by segment the signal according to the event associated with the dataset.
Events gives the time that the MI trail starts and ends to facilitate extraction of the task and the segment number, also the dataset that gives the artifact in each trial to eliminate it if need, in our case we need a clear signal so we eliminate these artifacts for the subjects. The proposed system segments the signals of each channel (C3, C4, Cz), these channels are the most effected by MI tasks. Also, because we use two classes only (left and right hand) the other two classes (feet and tongue) eliminated and their corresponding trials also eliminated. Figure 2 shows the signal of C3 channel before and after segmentation for three trials.
(a) Signal three channels before trials extraction; (b) signal after trials extraction (c) show the deference between original signal and extracted signal for three trial.
Artifacts can be defining as the unwanted signals that appear in EEG signals, they can be caused from various origins including body or eye movement, heart beating blinking, or frequency from utility, which is (50 Hz in Europe or 60 Hz in the United States) [23]. The utility frequency was removed already by applying notch filter while eye artifacts are left due to possibility of artifacts removal algorithms testing [22].
To handle eye artifact, there are three main approaches: avoidance, rejection, and removal [23].
For artifacts avoidance can be by asking the user to avoid movement during the recording that causes EEG artifact, which decreases the artifact’s number, but eye movement and blinks cannot be avoided.
Another way is to reject all corrupted trials by artifacts, which can automatically have done or manually. Manually can be done through visual examination, as the corrupted trials marked if they are corrupted or not by an expert. An algorithm is implemented in automatic artifact rejection, that can determine if artifacts corrupt a trial or not, and artifact rejection reduces the size of the training set. Last, is artifact removal, in order to remove the EEG signal artifact, some algorithms are used that leave the desired brain-originated signal intact.
After applying segmentation algorithm to segment signals of each channel into 3 s sub signal according to the event associated with the data set then remove all marked artifact trials, Figure 3 shows EEG signal for three trials after applying bandpass filter, the signal is filtered using a bandpass filter designed for a given frequency band. Using, for each channel, a 4th order Butterworth infinite impulse response (IIR) filter, IIRs are used to change the frequency component of a time signal by reducing or amplifying a particular frequency. This filter is used to pass only the band-limited portion of frequency content.
Signal of C3 channel after applying bandpass filter between (8–30 HZ).
The filtered signals are used to calculate spectrum PSD, in detail, estimate the PSD in the band between 8 and 30 Hz, this is based on the fact that the beta rhythm has distinct topographies and responses to the limb movements, compared with the alpha rhythm, the oscillatory power of the mu rhythm in the sensorimotor cortex ipsilateral to the tasks increased, while that of the beta rhythm in the contralateral sensorimotor cortex decreased simultaneously. The Welch’s averaged used for spectral estimation that is a modified periodogram method. With 1 s Hamming window and 50% overlap, Welch’s method can reduce noise. Each trial is divided into five bands and then the power and variance of each band are calculated, and energy of the whole trial is calculated.
The SVM method was used to train person EEG models using 10-fold cross-validation training and was used to train models on the whole training set and test on a separate test set.
SVM developed by Cortes and Vapnik [24] is a practical implementation of statistical learning theory capable of processing difficult problems of supervised learning, SVM is nonprobabilistic classifier; the two limitations of SVM are linear and binary features [25].
A decision boundary (plane) in SVM is used to separate the feature vectors. SVM classifier finds during training into two classes. The problem is to find the decision boundary (a linear hyperplane) that has the maximum separation (margin) between the two classes. The margin of a hyperplane is the distance between parallel equidistant hyperplanes on either side of the hyperplane such that the gap is void of data objects. The optimization during training finds a hyperplane that has the maximum margin. The SVM then uses that hyperplane to predict the class of a new data object once presented with its feature vector. See Figure 4 [26].
Model building.
It is an updated version of the ideas of the fuzzy commitment scheme [27]. In this scheme, a message
Polynomial is generated by using the code results from encoding a polynomial coefficient called secret that is a secret value using RS. Every EEG feature is projected onto the polynomial. Then it creates the chaff points using the proposed tent chaff points. Then shuffling the two point sets, to produce the vault. As the following algorithm:
Input: Parameters Output: A set Variables |
for output |
poly (
Figure 5 illustrates feature projection on polynomial produced by encoding the secret
Features projection on polynomial poly.
After projection of the feature onto the polynomial p using features as:
The genuine point list is comprised of:
To mask the identity of true points, chaff points are added using chaotic tent map. Let
Each chaff point and other genuine points do not need to put distance between them. The reason is that the chaff points are known for the two sides.
Finally, genuine Points and Chaff Points are combined, and the new matrix is shuffled. That represents fuzzy vault final matrix.
Figure 6 shows how chaff points hide genuine points; red circles in (a) are chaff points, (b) showing how attacker sees the final points projection.
How chaff points hide the polynomial.
The message vault is received and is attempted to decrypted it using input features produced from evaluation dataset. (
Input: A fuzzy vault R, Output: A value Variables : CH :chaff points,R :the vault ,Q:is the reconstructed polynomial regenerate chaff points CH for i = 1 to n do Temp= CH R(Temp)= [] Q=R Output S’ or null |
It is a method used to reconstruct polynomials; it is a method that computes the interpolation polynomial to form the system:
“The
space of degree
where the polynomials
The Lagrange polynomials for interpolation is:
After testing the system, it gives a good accuracy of classifying, which is 96%, but the run time of fuzzy vault authentication algorithm is kind of slow regarding that authentication must be fast to be practical for using it in real life; the reason of its slowness is because of the high number of EEG features, which result of many of multiple operations to compute Lagrange’s interpolation that slow the work of the algorithm that make the algorithm impractical, on the other hand, using the tent chaff points gives the system an advantage because it reduces the error occurrence when separating chaff points from the genuine points, which are the EEG signal features because the initial seeds are known by both sender and receiver so, the system can regenerate the chaff points again and rise them without or less effecting the genuine points, and in the traditional chaff point generation, it needs to keep distance from the genuine point, which requires more calculation, which this method does not. Also we have difficulties in converting the features that are float numbers into integers so they can be used in Galois field, which needs integers to deal with, another problem is the repeated numbers produced from the conversion into integers because the features’ values are close so they result in a repetition. The repeated values cannot use when reconstructing the polynomial because it results in division on zero, which is not acceptable because we need a unique number.
The system used nine healthy persons’ EEGs from the BCI Competition and extracted features from signals spectrum of beta and alpha band of EEG signal, then extracted features from three channels and used support vector Machine (SVM) to classify two tasks left hand and right hand that achieve 96.98% validation accuracy, using 10-fold cross-validation on the training set and then saved the model, these features are evaluated on a polynomial generated from the secret key, then chaff points using tent map are added, which reduce the error; for decoding, we use Lagrange interpolation for polynomial reconstruction and returning the key.
To measure performance, a confusion matrix was calculated from which its precision and recall are calculated, a part from using the confusion matric to find precision and recall, it is important to analyze the result by the help of the confusion matrix to analyze the results as it also gives a very strong, it gives the evidence where your classifier is going wrong. So for our model, we can see that our classifier goes in the right direction, which means the classifier can distinguish between subjects’ labels; Figure 7 illustrates confusion matrix for nine subjects.
Confusion matrix for the classification model.
The total validation accuracy is 96.98%, from confusion matrix; also, one can calculate the true positive rate (TPR) and the false negative rate (FNR) as shown below, by observing the table; TPR is high and FNR is low, which means the performance at its best. See Table 2.
Subject | TPR (%) | FNR (%) |
---|---|---|
1 | 95 | 5 |
2 | 98 | 2 |
3 | 91 | 9 |
4 | 99 | 1 |
5 | 98 | 2 |
6 | 99 | 1 |
7 | 99 | 1 |
8 | 98 | 2 |
9 | 93 | 7 |
TPR and FNR.
"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
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\\n\\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nOAI-PMH
\\n\\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\\n\\nLicense
\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\\n\\nPeer Review Policies
\\n\\nAll scientific works are Peer Reviewed prior to publishing. Read more
\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\\n\\nDigital Archiving Policy
\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
\\n\\n\\n"}]'},components:[{type:"htmlEditorComponent",content:'
The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Saxena and Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/8959.jpg",editedByType:"Edited by",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],equalEditorOne:{id:"287184",title:"Prof.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash",profilePictureURL:"https://mts.intechopen.com/storage/users/287184/images/system/287184.jpg",biography:"Dr. Hridayesh Prakash is a fellow of the Royal Society of Biology, London. Currently, he is an associate professor at the Institute of Virology and Immunology, Amity University, NOIDA. He has expertise in innate immunity with a special interest in macrophage immunobiology, tumor immunology/immunotherapy, cell-based immunotherapies, pulmonary infection biology, and radiation biology. \n\nDr. Prakash conducts research to exploit various immunotherapeutics for managing persistent bacterial and viral Infections and gastric cancer. He is unraveling the therapeutic potential of M1 effector macrophages against solid tumors. He is also studying various mechanisms that certain pathogens like Helicobacter pylori, Chlamydia, and Mycobacteria are exploiting for polarizing M1 effector macrophages towards the M2 phenotype during chronic and persistent infections. Under this major objective, he is now validating the therapeutic impact of M1 effector macrophages for the control of persistent infection-driven cancer (adenocarcinoma) progression. \n\nDr. Prakash is also exploring the palliative potential of macrophages against autoimmunity and chronic inflammatory disorders like IBD, radio-pneumonitis, pulmonary fibrosis, and radiation syndrome.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Maharishi Markandeshwar University, Mullana",institutionURL:null,country:{name:"India"}}},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8798",title:"Cells of the Immune System",subtitle:null,isOpenForSubmission:!1,hash:"4e8acf20a4e80bc7c97cb34d1672e53d",slug:"cells-of-the-immune-system",bookSignature:"Ota Fuchs and Seyyed Shamsadin Athari",coverURL:"https://cdn.intechopen.com/books/images_new/8798.jpg",editedByType:"Edited by",editors:[{id:"36468",title:"Dr.",name:"Ota",middleName:null,surname:"Fuchs",slug:"ota-fuchs",fullName:"Ota Fuchs"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3396",title:"Current Trends in Atherogenesis",subtitle:null,isOpenForSubmission:!1,hash:"914c59b8518185a41a0931cc0637c0bf",slug:"current-trends-in-atherogenesis",bookSignature:"Rita Rezzani",coverURL:"https://cdn.intechopen.com/books/images_new/3396.jpg",editedByType:"Edited by",editors:[{id:"63457",title:"Prof.",name:"Rita",middleName:null,surname:"Rezzani",slug:"rita-rezzani",fullName:"Rita Rezzani"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"67756",doi:"10.5772/intechopen.86600",title:"Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes",slug:"neutrophil-function-impairment-is-a-host-susceptibility-factor-to-bacterial-infection-in-diabetes",totalDownloads:1047,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Diabetes mellitus is a highly prevalent noncommunicable disease globally. One of the main complications of diabetes is the increased susceptibility to bacterial infection. Neutrophils play a crucial role in inflammatory response against bacterial infections, once they are the first cells recruited to the sites of injury. In diabetes, there is a failure in the neutrophil functions, including migration, ROS production, phagocytosis, and bacterial killing, which are associated with the high incidence of bacterial infections. Herein, we point out pieces of evidence revealing the primary molecular mechanisms involved with impairment of neutrophil functions in diabetes, with relationship with high susceptibility to bacterial infections.",book:{id:"8798",slug:"cells-of-the-immune-system",title:"Cells of the Immune System",fullTitle:"Cells of the Immune System"},signatures:"Daniella Insuela, Diego Coutinho, Marco Martins, Maximiliano Ferrero and Vinicius Carvalho",authors:[{id:"296748",title:"Dr.",name:"Vinicius",middleName:null,surname:"Carvalho",slug:"vinicius-carvalho",fullName:"Vinicius Carvalho"},{id:"303254",title:"Dr.",name:"Daniella",middleName:null,surname:"Insuela",slug:"daniella-insuela",fullName:"Daniella Insuela"},{id:"303255",title:"Dr.",name:"Diego",middleName:null,surname:"Coutinho",slug:"diego-coutinho",fullName:"Diego Coutinho"},{id:"303256",title:"Dr.",name:"Maximiliano",middleName:null,surname:"Ferrero",slug:"maximiliano-ferrero",fullName:"Maximiliano Ferrero"},{id:"303257",title:"Dr.",name:"Marco Aurelio",middleName:null,surname:"Martins",slug:"marco-aurelio-martins",fullName:"Marco Aurelio Martins"}]},{id:"42857",doi:"10.5772/53035",title:"Atherosclerosis and Current Anti-Oxidant Strategies for Atheroprotection",slug:"atherosclerosis-and-current-anti-oxidant-strategies-for-atheroprotection",totalDownloads:3122,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"3396",slug:"current-trends-in-atherogenesis",title:"Current Trends in Atherogenesis",fullTitle:"Current Trends in Atherogenesis"},signatures:"Luigi Fabrizio Rodella and Gaia Favero",authors:[{id:"118762",title:"Prof.",name:"Luigi Fabrizio",middleName:null,surname:"Rodella",slug:"luigi-fabrizio-rodella",fullName:"Luigi Fabrizio Rodella"},{id:"160911",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero"}]},{id:"42907",doi:"10.5772/54636",title:"MicroRNAome of Vascular Smooth Muscle Cells: Potential for MicroRNA-Based Vascular Therapies",slug:"micrornaome-of-vascular-smooth-muscle-cells-potential-for-microrna-based-vascular-therapies",totalDownloads:1824,totalCrossrefCites:2,totalDimensionsCites:4,abstract:null,book:{id:"3396",slug:"current-trends-in-atherogenesis",title:"Current Trends in Atherogenesis",fullTitle:"Current Trends in Atherogenesis"},signatures:"Kasturi Ranganna, Omana P. Mathew, Shirlette G. Milton and Barbara E. Hayes",authors:[{id:"63103",title:"Dr.",name:"Katsuri",middleName:null,surname:"Ranganna",slug:"katsuri-ranganna",fullName:"Katsuri Ranganna"}]},{id:"71468",doi:"10.5772/intechopen.91730",title:"Multiplex Technology for Biomarker Immunoassays",slug:"multiplex-technology-for-biomarker-immunoassays",totalDownloads:672,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"The simultaneous measurement of different substances from a single sample is an emerging area for achieving efficient and high-throughput detection in several applications. Although immunoanalytical techniques are established and advantageous over alternative screening analytical platforms, one of the challenges for immunoassays is multiplexing. While ELISA is still commonly used to characterise a single analyte, laboratories and organisations are moving towards multiplex immunoassays. The validation of novel biomarkers and their amalgamation into multiplex immunoassays confers the prospects of simultaneous measurement of multiple analytes in a single sample, thereby minimising cost, time and sample. Therefore, the technological advancement in clinical sciences is helpful in the identification of analytes or biomarkers in test samples. However, the analytical bioanalysers are expensive and capable of detecting only a small amount or type of analytes. The simultaneous measurement of different substances from a single sample called multiplexing has become increasingly important for the quantification of pathological or toxicological samples. Although multiplex assays have many advantages over conventional assays, there are also problems that may cause apprehension among clinicians and researchers. Hence, many challenges still remain for these multiplexing systems which are at early stages of development.",book:{id:"8959",slug:"innate-immunity-in-health-and-disease",title:"Innate Immunity in Health and Disease",fullTitle:"Innate Immunity in Health and Disease"},signatures:"Haseeb Ahsan and Rizwan Ahmad",authors:[{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"},{id:"412254",title:"Dr.",name:"Haseeb",middleName:null,surname:"Ahsan",slug:"haseeb-ahsan",fullName:"Haseeb Ahsan"}]},{id:"41447",doi:"10.5772/54726",title:"The Role of Cyclic 3’-5’ Adenosine Monophosphate (cAMP) in Differentiated and Trans-Differentiated Vascular Smooth Muscle Cells",slug:"the-role-of-cyclic-3-5-adenosine-monophosphate-camp-in-differentiated-and-trans-differentiated-vascu",totalDownloads:2272,totalCrossrefCites:1,totalDimensionsCites:4,abstract:null,book:{id:"3396",slug:"current-trends-in-atherogenesis",title:"Current Trends in Atherogenesis",fullTitle:"Current Trends in Atherogenesis"},signatures:"Martine Glorian and Isabelle Limon",authors:[{id:"161259",title:"Dr.",name:"Martine",middleName:null,surname:"Glorian",slug:"martine-glorian",fullName:"Martine Glorian"}]}],mostDownloadedChaptersLast30Days:[{id:"70362",title:"Resident Memory T Cells",slug:"resident-memory-t-cells",totalDownloads:964,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Until recently, T cells were thought to remain in circulation until recruitment of the inflammation and only a small number of T cells remained in the peripheral tissues without inflammation. However, studies have found that a group of T cells settled in the tissues and remained there for a long time. Those cells are named as tissue-resident memory T cells (TRM). TRM cells are transcriptionally, phenotypically, and functionally distinct from other T cells, which recirculate between blood, secondary lymphoid organs, and non-lymphoid tissues. They undergo a distinct proliferation that discriminates them from circulating T cells and their main cell surface markers are CD69, CD103, and CD49a. Upon exposure to the same or similar diseases, TRM cells provide a first line of adaptive cellular defense against infection in peripheral non-lymphoid tissues, such as skin, lungs, digestive, and urogenital tracts. This approach forms the basis of a novel vaccination strategy called “prime and pull”, which ensures long-term local immunity. On the other hand, abnormal activated and malignant TRM may contribute to numerous human inflammatory diseases such as psoriasis and vitiligo. Here in this chapter, we aimed to emphasize TRM cell location, migration, phenotypic structure, maintenance, and diseases associated with TRM cells.",book:{id:"8798",slug:"cells-of-the-immune-system",title:"Cells of the Immune System",fullTitle:"Cells of the Immune System"},signatures:"Hasan Akbaba",authors:[{id:"260489",title:"Dr.",name:"Hasan",middleName:null,surname:"Akbaba",slug:"hasan-akbaba",fullName:"Hasan Akbaba"}]},{id:"71769",title:"Immune Dysfunction during Enteric Protozoal Infection: The Current Trends",slug:"immune-dysfunction-during-enteric-protozoal-infection-the-current-trends",totalDownloads:792,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Enteric protozoa usually cause severe morbidity and mortality in humans. Protozoal infections contribute to the high burden of infectious diseases. Despite recent advances in the epidemiology, diagnostic tool, molecular biology, and treatment of protozoan illnesses, gaps in knowledge still exist; hence, protozoal infections require further research. We are describing here some important enteric protozoal infections along with the immune dysfunction produced by them. Genus- 1. Entamoeba; 2. Giardia; 3. Cryptosporidium; 4. Cyclospora; 5. Cystoisospora; 6. Dientamoeba; 7. Blastocystis; 8. Balantidium.",book:{id:"8959",slug:"innate-immunity-in-health-and-disease",title:"Innate Immunity in Health and Disease",fullTitle:"Innate Immunity in Health and Disease"},signatures:"Renu Kumari Yadav, Shalini Malhotra and Nandini Duggal",authors:[{id:"176430",title:"Dr.",name:"Shalini",middleName:null,surname:"Malhotra",slug:"shalini-malhotra",fullName:"Shalini Malhotra"},{id:"315666",title:"Dr.",name:"Renu",middleName:null,surname:"Kumari Yadav",slug:"renu-kumari-yadav",fullName:"Renu Kumari Yadav"}]},{id:"69233",title:"Innate Immune Defense in the Male Reproductive System and Male Fertility",slug:"innate-immune-defense-in-the-male-reproductive-system-and-male-fertility",totalDownloads:824,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"To protect the male germ cells from adverse immune reaction, the male reproductive system adopts special immune environment such as immunoprivileged status. The male genital organs can be infected by various microorganisms via hematogenous dissemination and ascending genitourinary tracts. To overcome the immunoprivileged status, the male genital organs also adopt their own innate defense against microbial infection. The tissue-specific cells in the male reproductive system are well equipped with innate immune machineries, including pattern recognition receptors (PRRs) and their negatively regulatory system. PRR-initiated immune responses must be tightly regulated by the negative regulatory system for the maintenance of immune homeostasis. The immune homeostasis can be disrupted by unrestrictive innate immune response, which may lead to inflammatory conditions in the male genital tracts, an important etiological factor contributing to male infertility. This chapter describes the current understanding of the innate immune responses in the male reproductive system and their effects on male fertility.",book:{id:"8959",slug:"innate-immunity-in-health-and-disease",title:"Innate Immunity in Health and Disease",fullTitle:"Innate Immunity in Health and Disease"},signatures:"Fei Wang, Ran Chen and Daishu Han",authors:[{id:"295978",title:"Dr.",name:"Daishu",middleName:null,surname:"Han",slug:"daishu-han",fullName:"Daishu Han"},{id:"303373",title:"Dr.",name:"Fei",middleName:null,surname:"Wang",slug:"fei-wang",fullName:"Fei Wang"},{id:"309874",title:"Dr.",name:"Ran",middleName:null,surname:"Chen",slug:"ran-chen",fullName:"Ran Chen"}]},{id:"71781",title:"Innate Immunity and Autoimmune Diseases",slug:"innate-immunity-and-autoimmune-diseases",totalDownloads:819,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The innate immune response is responsible for the initial defense against invading pathogens and signs of damage; in turn, it activates the adaptive immune response to result in highly specific and lasting immunity, mediated by the clonal expansion of antigen-specific B and T lymphocytes. Inflammation is the acute response to infection and tissue damage to limit aggression to the body. It is a complex reaction of vascularized tissues to infection, toxin exposure or cell injury that includes extravasation of plasma proteins and leukocytes. Paradoxically, uncontrolled and prolonged inflammation can result in secondary damage and the development of immune pathology in the host. The components of the innate immune system have recently been studied as responsible mechanisms in various chronic diseases such as diabetes mellitus, atherosclerosis, asthma and allergies, among others. Autoimmune disease is an attack on auto tissues by the adaptation of the immune system. In general, such diseases are characterized by autoantibodies and/or autoreactive lymphocytes directed at antigens against themselves. The innate immune system is often considered an effector of self-reactive lymphocytes, but also provides protection. Studies in mice with specific gene-directed mutations show that defects in innate immune system proteins may predispose to the development of a systemic lupus erythematosus-like syndrome (lupus) characterized by autoantibodies against double-stranded DNA (ds DNA) or nuclear components. This seems to be due to a failure in the removal of apoptotic cells or nuclear waste. These observations imply that the innate immune system has a general protective role against autoimmune disease. For example, in systemic diseases such as lupus, innate immunity is important in the elimination of nuclear antigens and, therefore, in the improvement of tolerance to B lymphocytes. Alternatively, in specific organ disorders such as type diabetes 1 o Crohn’s disease, the innate immune system can be protective by eliminating pathogens that trigger or exacerbate the disease or regulate the presentation of antigens for T lymphocytes. Discuss various disease models in which the innate immune system could provide a protective role, deficiencies in the regulation of B lymphocyte signaling through the antigen/receptor or in the clearance of lupus antigens, (dsDNA and nuclear proteins), can lead to a disease similar to lupus. The repertoire of B cells seems to be very biased toward self-activity, as, possibly, that of the T-cell. This tendency toward self-activity is not surprising because B and T cells are positively selected against highly conserved autoantigens.",book:{id:"8959",slug:"innate-immunity-in-health-and-disease",title:"Innate Immunity in Health and Disease",fullTitle:"Innate Immunity in Health and Disease"},signatures:"Marcela Catalina Fandiño Vargas",authors:[{id:"312253",title:"M.D.",name:"Marcela Catalina",middleName:null,surname:"Fandiño Vargas",slug:"marcela-catalina-fandino-vargas",fullName:"Marcela Catalina Fandiño Vargas"}]},{id:"69097",title:"Assessment of Immune Reconstitution Following Hematopoietic Stem Cell Transplantation",slug:"assessment-of-immune-reconstitution-following-hematopoietic-stem-cell-transplantation",totalDownloads:1019,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for both congenital and hematological malignancies. Immune reconstitution after allogeneic hematopoietic stem cell transplantation is implicated in successful transplant outcomes such as overall survival and relapse-free survival. The reconstitution of immune cell subsets after HSCT occurs in different phases at different time points encompassing pre-engraftment, engraftment, and post-engraftment. The recovery of innate cellular immunity with the appearance of monocytes, dendritic cells, and natural killer cells in peripheral blood correlates with initiation of cellular engraftment. The cellular adaptive immunity is characterized by both thymic-independent expansion of T cells infused with graft and thymus-dependent expansion of naïve T cells derived from donor stem cells. The humoral immunity consists of B-cell reconstitution, which consists primarily of transitional and naïve subsets with the recovery of memory B cells that occur much later. In this review, we highlight the factors affecting immune reconstitution, the reconstitution of innate and adaptive immunity, techniques to assess immune reconstitution, and ways to enhance it.",book:{id:"8798",slug:"cells-of-the-immune-system",title:"Cells of the Immune System",fullTitle:"Cells of the Immune System"},signatures:"Meenakshi Singh, Selma Z. D’Silva and Abhishweta Saxena",authors:[{id:"217471",title:"Dr.",name:"Selma",middleName:null,surname:"D\\'Silva",slug:"selma-d'silva",fullName:"Selma D\\'Silva"},{id:"267032",title:"Dr.",name:"Meenakshi",middleName:null,surname:"Singh",slug:"meenakshi-singh",fullName:"Meenakshi Singh"},{id:"310438",title:"Dr.",name:"Abhishweta",middleName:null,surname:"Saxena",slug:"abhishweta-saxena",fullName:"Abhishweta Saxena"}]}],onlineFirstChaptersFilter:{topicId:"1034",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"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:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:"2753-6580",scope:"
\r\n\tThis book series will offer a comprehensive overview of recent research trends as well as clinical applications within different specialties of dentistry. Topics will include overviews of the health of the oral cavity, from prevention and care to different treatments for the rehabilitation of problems that may affect the organs and/or tissues present. The different areas of dentistry will be explored, with the aim of disseminating knowledge and providing readers with new tools for the comprehensive treatment of their patients with greater safety and with current techniques. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This series of books will focus on various aspects of the properties and results obtained by the various treatments available, whether preventive or curative.
",coverUrl:"https://cdn.intechopen.com/series/covers/3.jpg",latestPublicationDate:"August 4th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:2,numberOfPublishedChapters:139,numberOfPublishedBooks:9,editor:{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",fullName:"Sergio Gehrke",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}},subseries:[{id:"1",title:"Oral Health",keywords:"Oral Health, Dental Care, Diagnosis, Diagnostic Imaging, Early Diagnosis, Oral Cancer, Conservative Treatment, Epidemiology, Comprehensive Dental Care, Complementary Therapies, Holistic Health",scope:"\r\n\tThis topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. Subjects will include an overview of oral diseases and infections, systemic diseases affecting the oral cavity, prevention, diagnosis, treatment, epidemiology, as well as current clinical recommendations for the management of oral, dental, and periodontal diseases.
",annualVolume:11397,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"267724",title:"Prof.",name:"Febronia",middleName:null,surname:"Kahabuka",fullName:"Febronia Kahabuka",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZpJQAW/Profile_Picture_2022-06-27T12:00:42.JPG",institutionString:"Muhimbili University of Health and Allied Sciences, Tanzania",institution:{name:"Muhimbili University of Health and Allied Sciences",institutionURL:null,country:{name:"Tanzania"}}},{id:"70530",title:"Dr.",name:"Márcio",middleName:"Campos",surname:"Oliveira",fullName:"Márcio Oliveira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRm0AQAS/Profile_Picture_2022-08-01T12:34:46.jpg",institutionString:null,institution:{name:"State University of Feira de Santana",institutionURL:null,country:{name:"Brazil"}}}]},{id:"2",title:"Prosthodontics and Implant Dentistry",keywords:"Osseointegration, Hard Tissue, Peri-implant Soft Tissue, Restorative Materials, Prosthesis Design, Prosthesis, Patient Satisfaction, Rehabilitation",scope:"