Phenotypes of trisomy and (partial or mosaic) monosomy 21. (Schinzel, 2001)
\r\n\tThere will be a chapter on secondary causes of sexual dysfunction disorders related to diabetes, cardiovascular disease, and obesity. A chapter on remedial measures to enhance sexual activity and maintain human relationships will be discussed. As there is a growing number of cancer survivors a chapter on cancer-related sexual dysfunction will be welcomed for including it.
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Dr. Sheriff has authored five books including a textbook on medical biochemistry with additional interest in human sexology. He had editorials written in the British Journal of Sexology, Journal of Royal Society of Medicine, Postgraduate Medicine, and Scientist. 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These are the two sex chromosomes or gonosomes (X,Y) and the 44 non-sex chromosomes or autosomes, respectively. Chromosomes of the latter group are numbered as 1 to 22, according to their decreasing size. Autosomes in somatic cells are comprised of two homologous, genetically identical chromosomes.
The time of the first conference for nomenclature in 1959 is called the pre-banding area. Individual chromosomes could not yet be ascertained beyond reasonable doubt. Thus it happened that the second smallest chromosome, chromosome 21, which had been analysed three times in the patient’s karyotype, was believed to cause Down Syndrome (DS). Later studies showed that DS is trisomic in the smallest chromosome. To avoid conflict between previous and subsequent publications, the position of the two smallest chromosomes (21 and 22) was switched, resulting in the definition of DS as trisomy 21.
The relative length of chromosome 21 is 1.9 ± 0.17 % of the total length of the human genome, and its size is approximately 60 Mb. Chromosome 21 belongs to the acrocentric chromosomes, i.e. the centromere is localised closer to the end of the short arm (p). The short arm 21p is heterochromatic but consists of different types of repetitive DNA (Figure 1)(Wyandt and Tonk, 2004).
The relative length of the short arm of chromosome 21 comprises 30 % of its total length (Figure 1). Variants in brilliant fluorescence after QFQ-staining are diagnosed in 2.0 % of band p11.2 and 10.0 % of band p13. Duplications in p12 show a frequency of 0.7-1.3 % and 0.1 % in the satellites of p13. Deletions in all three regions (p11.2, p12, p13) are rare (Kalz et al., 2004).
These frequencies are derived from population studies based on Europeans. Significant differences in comparison to other ethnic groups have been observed (Kalz et al., 2005). The polymorphic regions in the short arm of chromosome 21 allowed the first studies on the parental origin of trisomy 21 (Mikkelsen et al., 1980).
The long arm (q) of chromosome 21 is euchromatic, with the exception of the peri-centromeric region q11.1 and the distal telomere.
Chromosomes are usually presented and analysed in the metaphase of mitosis after
Structure and morphology of chromosome 21. Ideogram according to the ISCN (
only some (i.e. T-lymphocytes in a blood sample) can be stimulated
The central part of the centromere of chromosome 21 consists of α-satellite DNA that is almost identical to the centromere of chromosome 13 (homology 99.7%)(Figure 1). On both sides α-satellite DNA is flanked by β-satellite DNA. These two non-coding regions can vary significantly in size through duplication or deletion. They are irrelevant for the carrier, unless their length is less than 20 % of the average length of the region and thus prevents the normal development of the kinetochores. This would result in the failure of exact separation of the chromatids in the anaphase of mitosis (Waye et al., 1989; Mitchell et al., 1992).
Distal of the β-satellite DNA, satellite DNA class III is situated on the short arm (p11.2). Significantly varying in size, this band shows a specific absorption of DNA-dyes. Therefore, it is defined as a polymorphic region. It is followed in the short arm by the band p12, which is also named the nucleolus organising region (NOR) and contains the ribosomal RNA-genes. It is characterised by its slightly lateral expansion (satellite stalks). It is polymorphic and can be deleted or amplified (Tagarro et al., 1994a). The most distal regions of the short arms are the satellites (p13 or s), consisting of Sat I DNA with the telomeres at the ends (Tagarro et al., 1994b). Satellites are also polymorphic varying in size and staining characteristics. They also have the ability to duplicate.
In describing the structure of the short arm of chromosome 21, only the main components of the different bands are mentioned. Especially p11.1, p11.2, and p13 contain further subgroups of repetitive DNA.
Routine diagnostic workup for identification of trisomy 21. a) Standard karyotype (47,XY,+21) by GTG banding (by kind courtesy of U. Mau-Holzmann, Tübingen). b) Interphase FISH showing three signals of chromosome 21 and two of chromosome 13 (LSI21:21q22.13q22.2; AneuVysion multicolor DNA probe Kit, Vysis).
According to the literature, the proximal heterochromatic region of the long arm (q11.1) of chromosome 21 consists of β-satellite DNA boarding the central α-satellite DNA and followed distal by Sat I DNA (Waye et al., 1989; Mitchell et al., 1992; Tagarro et al., 1994a, 1994b). The main part of the long arm is euchromatic. AT- and GC-rich bands have characteristic sequences and can be differentiated by their typical staining features (figure 1). These bands of single copy DNA are interspersed by non-coding repetitive DNA (SINEs and LINEs).
A complete or partially aneuploid chromosome is associated with a pathologic phenotype in the carrier, the expression of which depends on the type and amount of the aberrant genetic material.
In contrast to chromosome 22, chromosome 21 consists of a high number of AT sequences which contain a smaller amount of vitality-determining genes than the GC-rich ones.
GC-rich or housekeeping genes are expressed in most cell types. They lead to proteins that carry out various metabolic and structural functions. In contrast, the AT-rich genes are tissue-specific and are only active in certain cell types while being inactivated in others by methylation. This gene inactivation is accompanied by a more condensed structure of the chromatin and, consequently, the DNA of these genes is not accessible to the transcription factors. These AT-rich DNA regions show a higher staining intensity and can thus be localised by chromosome analysis.
Because of its high content of AT-rich regions, trisomy 21 is compatible with life, and in the majority of cases, leads only to retardation in the development of the carrier and not, as in trisomy 22, to lethality.
The gene map of chromosome 21 was initially constructed by combining the analyses of small structural aberrations with the results of different gene product analyses (dosage effect). Chromosome 21 was sequenced in 2000 (Hattori et al., 2000), and 225 loci (genes) were identified, which was less than expected. This might explain the relatively mild phenotype of the carriers.
In the following years, a high number of small regions in 21q has been analysed in order to localise the DS critical region (Figure 3)(Wong, 2011), but recent investigations revealed in contrast to the first assumptions that a direct genotype-phenotype correlation does not exist, since a large number of gene products from chromosome 21 also influences gene products and their function on heterologous chromosomes (Gardner and Sutherland, 2004; Weinhaeusel et al., 2011).
(AMKL acute megakaryocytic leukemia; TMD transient myeloproliferative disorder; DST duodenal stenosis; IA inperforate anus; HSCR Hirschsprung disease)Genotype-phenotype correlation in trisomy 21 based on partial trisomy 21 cases (from
DS was the first malformation complex that could be delineated as a chromosome abnormality in 1959. This was enabled by the new technology to prepare chromosomes in the metaphase of mitosis. In the early years, mitoses were analysed after direct preparations of bone marrow cells and long term cell cultures of tissue biopsies. Starting in 1960, the lymphocyte culture of peripheral blood was established. Thereby screening of handicapped persons on a large scale became possible. At the beginning of the 1980s, prenatal diagnoses were started for high-risk groups.
Any extension of the spectrum of investigations, any more precise definition of the localisation of the aberration and characterisation of the patients´ symptoms were combined with an improvement of the investigation methods.
The direct preparation of meristematic somatic cells was followed by long-term and short-term cell cultures of differentiated somatic cells removed postpartum, by the culture of amniotic fluid specimen and biopsy of chorionic villi, as well as the analysis of germ cells and their precursor stages in certain special cases, of polar bodies and early postzygotic stages like morula and gastrula in preimplantation diagnostics.
Initially, the presentation of chromosomes was only possible through homogeneous staining, which was succeeded by application of radioactive markers and subsequently of the differentiated characterisation of the chromosomal banding patterns (GTG, GAG, QFQ, RBG, RBA, CBG, and others).
Today, a necessary requirement in diagnostic investigations is a high differentiation of the euchromatin (usually 550 bands per genome). By that way, structural aberrations of chromosome 21 can be safely detected microscopically, starting with a minimal length of 5 Mb. In the 1980s, fluorescence-in-situ hybridisation (FISH) as a new technique was introduced (Figure 2b). By FISH the characterisation of either the entire euchromatin or the centromeric areas or selected euchromatic bands with specific DNA-probes became possible. Simultaneously, this allowed the analysis of cells in interphase and the rapid investigation of larger amounts of cells without cell culture. This so-called rapid aneuploidy testing is especially important for prenatal diagnostics.
Further improvement of the investigation spectrum provided the development of the comparative genomic hybridisation (CGH) with the advancement to the microarray, which has been depicting an improvement and specification of diagnostics on the molecular-genetic level through development of specific tiling arrays.
The newest development is next-generation sequencing. This method is still known to be in trial tests, and its establishment in diagnostics is to be expected.
The various methods of investigation are often combined to improve diagnostics.
In addition to the predominance of standard trisomy 21 as the cause of DS, further types of aberrations exist. They differ in relation to the type of abnormality, and they lead to different prognoses as to the chances of development of the carrier and recurrence risks for the relatives of a carrier.
Therefore, the indication for a chromosome analysis is always given in the presence of the distinct phenotype of DS.
In this type of aberration, the carrier has 47 chromosomes, including three chromosomes 21. It accounts for nearly 90% of DS cases. Standard trisomy 21 typically occurs sporadically, therefore the recurrence risk is low.
The majority of free trisomy 21 cases (85-90%) originates from errors in maternal meiosis. In particular, maternal meiosis I is the most frequently affected stage of nondisjunction (>75%), whereas maternal meiosis II errors account for >20%. In 5% of free trisomy 21, paternal meiotic errors can be observed, here meiosis II nondisjunction is more frequent than meiosis I errors. In addition, postzygotic mitotic errors have also been reported (5%). The predominant influence of disturbed maternal meiosis is reflected by the decreased number of of chiasmata in meiosis I increasing with maternal age. Indeed, the reason for this association is unknown, however numerous hypotheses have been proposed (for review: Hultén et al., 2010).
Trisomy 21 due to an unbalanced translocation of chromosome 21 with a hetero- or homologous acrocentric, satellite-bearing chromosome (13, 14, 15, 21, 22) is called a Robertsonian translocation. However, the frequency of translocation partners varies and is a result of homologies in the heterochromatin of the short arm, thus leading to failures in the pairing of meisosis I. The resulting fusion products can be monocentric or dicentric with an inactive centromere.
In monocentric translocation chromosomes, the centromere can derive from each of the two partners or can be a hybrid structure originating from both of them.
Robertsonian translocations involve about 5% of the cases of trisomy 21. Approximately 75% are formed de-novo in the carrier, and 25% are familial ( for review: Gardner and Sutherland, 2004). Among these, translocation 21/21 is an unusual rearrangement, but in the majority of cases, it is not a fusion of homologous but the formation of an isochromosome.
In general rule, carriers of the balanced Robertsonian translocation display only 45 chromosomes, the unbalanced ones show 46, as in the majority of carriers, and two short-arm regions are lost. The loss of two NOR-regions does not lead to clinical symptoms in the carriers of balanced translocations.
Among the different heterologous translocations of the acrocentric chromosomes with chromosome 21, the combination with chromosome 14 (rob(14q21q)) is the most frequent one with about 60%. This is followed by the translocation rob(21q21q) or by the formation of isochromosome i(21q21q), respectively, in 35% of the cases. The other translocations are rare and do not exceed 5%. (for review: Gardner and Sutherland, 2004)
Current studies of meiosis are leading to new insights on frequency of formation and postzygotic selection of Robertsonian translocations in familial cases. These studies are largely based on analyses of translocation rob(14q21q) as the most common subgroup. According to these, women with a balanced translocation have an aberrant karyotype in about 20 % of their polar bodies as well as in the oocytes and men in 10-15% of their sperms. These frequencies decrease postzygotically in the course of the development of the embryo, therefore the risk of a child with heterologous translocation trisomy 21 amounts to only 8% if the mother is the carrier and to 4 % with the father (for review: Gardner and Sutherland, 2004).
It is noticeable that in families with translocations, children with a normal phenotype carry a balanced translocation more often than the normal karyotype if the origin is maternal (60:40), while the ratio is equal with paternal origin (50:50).
Reciprocal translocations are caused by the exchange of euchromatic regions of chromosome 21 with the euchromatin of different autosomes or gonosomes. In addition to trisomic regions in various length and location of chromosome 21, unbalanced forms at the same time show partial monosomy for the exchanged regions of the second translocation chromosome. As a result, the phenotype in the carriers of unbalanced translocations is not consistent.
Caused by the rare occurrence of these translocations, there are no reliable data for their incidence, a frequency of less than 1:1000 standard trisomies can be assumed. According to the literature, the most common partners for a reciprocal translocation seem to be the chromosomes 18 and 22 (Schinzel, 2001).
This type of aberration is always formed de-novo in carriers with a noticeable pathologic phenotype. If the duplicated segment is only of small size or originated from a postzygotic mosaic, the impairment of the carrier may be mild, and he might have an almost unrestricted life opening the possibility of inheriting the duplication to his offsprings.
A duplication in the cells of the carrier can be caused by an unequal pairing of homologous chromosomes in the pachytene of meiosis I and an aberrant crossing-over as the consequence.
A paracentric inversion in the long arm of a parental chromosome 21 may present an increased risk for the formation of a duplication. According to published cases, the size of the duplicated region can vary significantly, and so far, no preferential sites for the exchange have been documented. With the few existing case reports, no data concerning the frequency of duplications can be given.
Investigations with FISH probes and applications of molecular-genetic methods for small euchromatic regions enabled the detection of structural aberrations in chromosome 21 in a size of less than 5 Mb. The amount of disorders that can be attributed to small duplications and deletions of chromosome 21 therefore has risen significantly within the last years. The phenotype of the carriers is predominantly not characteristic for the DS.
Meanwhile, extensive genotype-phenotype correlations on the basis of structural aberrations of chromosome 21 have been reported, which help to narrow down the DS critical regions (Figures 3, 4)(for review: Korbel et al., 2009). A small number of genes has been proposed to cause the specific DS features, and among them are: DSCR1, DYRK1A or APP (for further details see other chapters of this book).
The frequency of trisomy 21 mosaics after chromosomal analysis is about 3-5 %. This number is most likely too small since tissue-specific mosaics cannot always be detected.
Mosaics always originate from mitotic aberrations during the early postzygotic development of the conceptus. Their formation may be caused by an aberrant zygote loosing one of the three chromosomes 21 of a standard trisomy in a portion of the cells. Alternatively, the zygote can have a normal karyotype, but in a postzygotic mitosis, nondisjunction of chromosomes 21 takes place.
Structural aberrations of chromosome 21 as mosaics are always caused by postzygotic rearrangements. Carriers of mosaics with the aberrant cells occuring only in the gonads have an increased risk compared to the general population of the same age for the birth of a child with the aberration in all cells.
The risk of mosaic carriers for a retardation or affected offspring can not be specified because of the different types of aberrant karyotypes and their unequal distribution in the organism.
If the percentage of trisomic cells in all somatic tissues is small (0.5 – 5 %), the phenotype of the carrier can be normal.
Carriers with mosaics have a better prognosis than carriers of non-mosaic trisomies, but there is always a risk of uneven distribution of pathologic cells in the various tissues. Therefore, only the analyses of cells type stemming from different germ layers can lead to a reliable prognosis concerning the development of the patient.
A specific type of hyperploidy 21 is the tetrasomy where the chromosome 21 is present for four times. In the literature, only single cases have been published (Gardner and Sutherland, 2004). This abnormality can either consist of four free chromosomes 21 or of two normal chromosomes and in addition an isochromosome 21. The aberration is usually lethal in the conceptus in early pregnancy, but a mosaic constitution has been diagnosed in patients postnatally.
Many different cytogenetic as well as molecular-genetic techniques have been developed in the past to detect standard trisomy 21 and structural aberrations of chromosome 21. Whereas the “simple” detection of genomic imbalances can be performed with numerous molecular techniques (short tandem repeat typing, MLPA, molecular karyotyping), information on structural rearrangements is usually up till now achieved by classical microscopic methods, e.g. chromosome analysis and FISH. In future the development of high resolution next generation sequencing techniques will allow a nearly complete overview on all numerical and unbalanced structural rearrangements in one molecular assay.
Chromosome investigation is the conventional cytogenetic method based on cells undergoing mitosis to obtain metaphase spreads. The chromosomes can be pre-treated and stained according to different protocols to induce specific banding patterns. By karyotyping, the specifically banded chromosomes can be arranged into seven groups (A to G) based on descending order of size and of the position of the centromere. According to the type of induced banding pattern, two subtypes can be defined: a) those resulting in bands distributed along the length of the whole chromosome, such as G-, Q- and R-bands, and b) those that stain specific chromosome structures (e.g. C-bands, nucleolus organizing regions, telomeric bands)(Shaffer et al., 2009).
The advantage of classical cytogenetics is that both unbalanced as well as balanced chromosomal aberrations are detectable. However, the technique is limited by the microscopic solution. Therefore, imbalances <5 Mb are not analysable by routine cytogenetics. Another disadvantage is that the majority of cell types has to be cultured in vitro either as a short-term or long-term culture. The long culture times bear the risk of
Chromosome analyses are mainly done after lymphocyte culture from peripheral blood samples. The cells are easily obtained and stimulated to mitosis, and the time of cultivation is only 48-72h.
The chromosomes are arranged in a formal karyotype, according to their size, centromere position, and banding pattern (Figure 2a) following the International System for Human Cytogenetic Nomenclature (ISCN; Shaffer et al. 2009).
FISH is a widely used method to analyse different target DNA sequences by supplying specific DNA - probes. It combines cytogenetic and molecular genetic techniques. The principle of FISH is the interaction of a labelled single-stranded DNA with a denatured metaphase or interphase.
Since a much higher resolution than chromosome analysis, FISH is used to identify and characterise small structural chromosome aberrations in clinical cytogenetics, including microdeletions and microduplications. A precise and detailed breakpoint analysis is possible. However, a FISH investigation is only applicable if the aberration in question is suspected.
At first this technique was restricted to metaphase analysis, meanwhile, it has gained importance in interphase diagnostics as well. In particular the latter procedure is extremely helpful to detect low-level mosaicism. Furthermore, it has enabled rapid prenatal testing for the frequent aneuploidies in the fetus, including trisomy 21 (for review: Caine et al., 2005).
Short tandem repeat markers (STRs, microsatellites) are highly informative molecular markers which are easy to handle. STRs have been described as an abundant class of DNA - polymorphisms in the human genome, consisting of highly repetitive short DNA - sequences. They can be typed by using PCR and single-copy primers flanking the repeats, followed by denaturing on a high resolution gel or by capillary electrophoresis. In 1991, Petersen and co-workers were the first to describe the application of these markers in order to determine the parental origin of the extra chromosome in families with a trisomy 21 patient. Meanwhile, numerous studies on the origin of unbalanced chromosomal aberrations have been published.
It is the advantage of microsatellite analysis that it needs only minimal amounts of genomic DNA. Furthermore, it is a fast and simple method which is widely established. It is therefore not amazing that this technique is one of the most frequently used methods for rapid prenatal aneuploidy testing (Mann et al., 2004). It circumvents time-consuming cell cultivation and needs approximately 6-8 h from taking the sample to final report. In addition, the comparison of the allelic distribution of a fetus and his parents allows the exclusion of a maternal contamination in fetal DNA - samples.
However, the technique does not allow the detection of balanced rearrangements. Furthermore, a reduced informativity of microsatellite markers might hamper the interpretation. In particular in case of parental consanguinity, the informativity might be reduced.
Multiplex Ligation-dependent Probe Amplification (MLPA) is a simple, high throughput method that allows detection of DNA copy number changes of up to 40 sequences in a single reaction. It is based on the semi-quantitative polymerase chain reaction principle and can be applied for detecting copy number changes and has been developed by MRC Holland (
The advantage of MLPA is indeed the low amount of genomic DNA needed for genotyping and the fact that that parental samples are not necessary for comparison. However, the procedure is time-consuming and needs at least two days.
Molecular karyotyping is meanwhile a well established method to identify genomic imbalances. In particular the resolution is much better than that of conventional cytogenetics. While chromosome analysis detects imbalances (deletions and duplications) >5 Mb, array typing has a resolution of <100 kb (figure 4). Microarray analysis allows the identification of any type of segmental imbalance by virtue of its design, but it does not allow the identification of balanced rearrangements or small mosaics.
Example of Micro-array based characterisation of a partial trisomy 21 in a patient affected by Silver-Russell syndrome (
As a large number of strategies and platforms are commercially available and cannot be covered here, we strongly emphasize checking the updated literature. Dependent on the array type, molecular karyotyping allows the detection of imbalances with a size of a few kb. And thus the detection rate for chromosomal aberrations in patients with mental retardation could be increased impressively (for review: Shaffer and Bejjani, 2010). However, the interpretation of microarray data is currently hampered by the large genomic instability mainly in non-coding regions, resulting in the analysis of a growing number of copy number variations (CNVs).
Nevertheless, first guidelines for molecular karyotyping have recently been published (Vermeesch et al., 2010).
Due to the development of genome-wide sequencing (next generation sequencing) the cheap and accurate characterisation of whole genomes in a short time has become possible. Indeed, the methods and applications are extremely manifold and can be merely covered in this short paragraph (for review: Metzker, 2010). Of course, it is too early to apply this complex technology for characterisation of whole chromosome aberrations like trisomy 21. However, target assays will be developed, and it has to be considered that next generation sequencing will allow to rapidly identify and reliably characterise genomic disturbances – balanced as well as unbalanced – and breakpoints in cases of structural rearrangements.
As the clinical symptoms of a child with the phenotype of DS cannot be considered as a reliable classification, the diagnosis must always be accompanied by a chromosome analysis.
The occurrence of trisomy 21 in young mothers lead to screening investigations to ascertain whether exogeneous factors might play a role in the aetiology of trisomy 21 besides the well-known genetic risk factors.
Different substances known as mutagens, co-mutagens, and teratogens have been investigated in detail.
The atomic bomb blasts in Japan at the end of the World War Two and the explosion of the atomic reactor in Chernobyl in 1986 are well-known examples of exposures and have been thoroughly explored. However, they did not lead to an increased birth of children with DS (Dean et al., 2000).
Furthermore, neither contact with different organic substances or heavy metals nor an increased consumption of caffeine, alcohol, or nicotine could be shown to increase the number of births of children with trisomy 21 or other chromosome aberrations.
This group encloses carriers of balanced and unbalanced chromosome 21 aberrations and includes the risk of advanced maternal age at pregnancy as well.
Adequate therapy has increased the life expectancy of carriers of trisomy 21 significantly within the last decades. Furthermore, a largerly normal life by a specific support of motor and mental abilities has become possible for many DS individuals. This leads to pregnancies in DS women and makes adequate genetic counselling necessary. The theoretical risk for a woman with trisomy 21 to have a child with trisomy 21 is 50%, but it is reduced by the high amount of abortions in early pregnancy. An empirical risk of 30-40% can therefore be delineated.
However, genetic counselling has also to take into account the risks of a pregnancy in a DS woman suffering from malformations such as heart defects or kidney anomalies. Males with a trisomy 21 are usually sterile.
In mosaic cases, the risk of a female or male in rare cases carrier to have a child with full trisomy 21 cannot be estimated precisely, because only the amount of trisomic cells in the somatic tissues can be analysed but not the one in the gonads. The ratio of trisomic cells may even be 100% in the ovaries and testes, leading to the same risk factor as in carriers with a full trisomy.
A special situation is given if the carrier has a normal karyotype in all somatic cells investigated, and the trisomic cells are restricted to the gonads (parental germline mosaicism). In these cases the empiric recurrence risk is delineated as 1-2%, but in two cases of two or more pregnancies with trisomy 21 it is estimated to be much higher (empirical value of more than 10%) (Warburton et al., 2001).
Mosaics are usually found in free trisomy 21 but mosaicism of translocation trisomy 21 has also been observed.
Significant differences concerning risk factors have been observed for female and male carriers of heterologous translocations. In female carriers, the empiric risk of having a child with an unbalanced translocation is about 10%, and in males it is only 1-2% (Ferguson-Smith, 1983; Daniel et al., 1989). In both sexes, the translocations rob(14q21q) and rob(15q21q) harbour the additional risk of uniparental disomy 14 or 15 as a consequence of trisomic rescue (Kotzot and Utermann, 2005) which is associated with specific clinical syndromes.
Balanced carriers of these two types of rearrangements have a risk of 100% that the offspring will inherit a translocation trisomy 21, regardless of the sex.
In the rare group of parents carrying a balanced chromosome rearrangement affecting whole or partial 21q, the risk of having a child with a complete or partial trisomy 21 is relatively high, with about 20% in females and 10% in males. If the translocation chromosomes and their normal homologous show pairing difficulties in meiosis I, the additional risk of a 3:1 segregation has to be taken into account, leading to a recurrence risk of up to 30%. Offspring with an unbalanced translocation show monosomy of the heterologous chromosomal segment, in addition to the complete or partial trisomy 21. As a result, the phenotype will be complex and heterogeneous, depending on the origin of the second translocation chromosome.
This is the main group of consultants. The maternal age at pregnancy is significantly elevated in the majority of cases, and therefore, an increased risk for elder women can be delineated (risk of 1:1667 at 20 years and 1:32 at 45 years (Morris et al., 2002). There is a second slight increase of risk in very young mothers (1:1000 at 15 years). The probability for a child with DS is not correlated with paternal age.
However, in a small cohort of families an age independent high risk for pregnancies with different trisomies has been observed (Munné et al., 2004; Baart et al., 2006).
Molecular investigations made it probable that in these cases the increased aneuploidy rate is caused by an autosomal recessive mutation. To identify this group of carriers a thorough pedigree analysis is necessary, cytogenetic karyotyping is indicated for the consultants and their offspring – children and miscarriages. Failures from pregnancy induction by IVF (in-vitro fertilisation) have to be included in the risk estimation. These couples are usually recommended to a special IVF program for a further pregnancy, and preimplantation-testing procedures might be considered (Stumm et al., 2006).
Healthy relatives of a patient with a free trisomy 21 have no increased risk for the birth of a child with trisomy 21 when compared to the average population of the same age.
Relatives of a proband with DS caused by an unbalanced structural rearrangement have an increased risk if they are balanced carriers of the translocation (see above). The risk factor depends on the type of rearrangement and on the sex of the carrier.
At the end of the first trimester of pregnancy (10th to 12th week,) ultrasound investigations are routinely recommended. At that age, the majority of fetuses with trisomy 21 show a number of characteristic features. These include nuchal translucency, absence of nasal bone, heart defect and growth retardation. In the second trimester, the main symptoms detectable by ultrasonography are a flat occiput, a flat profile of the face, small nose, dysmorphic and deep seated ears, receding chin and short neck, malformations of the internal organs, and growth retardation.
These observations by ultrasound are an indication for prenatal chromosome analysis either by chorionic villi sampling (CVS) or by amniocentesis (AC).
The main technique in prenatal diagnostics is ultrasound. In Germany, it is usually applied three times during pregnancy. Ultrasound can meanwhile be regarded as a prerequisite for CVS, AC, or fetal blood sampling (FBS) since morphologic abnormalities are caused by a pathologic karyotype in 20-50% of the cases (personal observation).
A second group of non-invasive parameters are specific biochemical factors (AFP, β-HCG, estriol) analysed from maternal blood. They are combined with the risk delineated from the given maternal age. If the result differs from expectation and corresponds to an increased risk for DS, invasive methods to determine the karyotype are applied.
A third possibility for non-invasive investigations in pregnancy is the analysis of fetal cells and fetal DNA in the maternal blood. By special procedures, fetal DNA can be isolated and enriched from maternal blood, however, this method is still under development and is currently not applied in routine prenatal testing.
Invasive prenatal investigationsThree different methods are usually applied: CVS in the first trimester, AC in the second, and AC, FBS, and placenta biopsy in the third.
All three methods generally include an investigation risk of about 1%. Therefore, these methods should only be applied if the genetic risk is higher than the risk of investigation.
Sometimes different methods have to be combined to receive a diagnosis. However, this increases the time of investigation and prolongs the psychological stress of the parents (Gekas et al., 2011).
Usually, a reliable, final diagnosis can only be achieved by invasive investigations but the non-invasive methods enable the investigator to get information of an increased or decreased extent of the pre-existing risk in the individual pregnancy.
As a full monosomy 21 is lethal in life-born children and also exceedingly rare in spontaneous abortions, the phenotype of carriers of this aberration is delineated from mosaic cases and partial deletions. The clinical findings revealed a number of symptoms, especially facial dysmorphic features that can be defined as opposite type or “contretype” to patients with trisomy 21 (Table 1).
Muscular hypotonia | Muscular hypertonia |
Overextension of joints | Spasticity |
Hyperflexible fingers | Camptodactyly |
Flat occiput | Protuberant occiput |
Upslanting palpebral fissures | Downslanting palpebral fissures |
Small round ears | Large ears |
Aplastic nasal bridge | Protuberant nasal bridge |
Phenotypes of trisomy and (partial or mosaic) monosomy 21. (Schinzel, 2001)
As trisomic rescue is the most frequent way of uniparental disomy formation, this type of cytogenetic aberration has to be discussed in context with trisomy 21. Uniparental disomy (UPD) is the inheritance of both homologous of a chromosome pair from only one parent. The concept of UPD was first postulated to cause specific phenotypes in the eighties (Engel, 1980). This hypothesis was then confirmed by UPD of different chromosomes in association with typical syndromes. The best examples of this type of aberration are maternal UPD15 (upd(15)mat) in Prader-Willi and paternal UPD15 (upd(15)pat) in Angelman syndrome.
Different mechanisms may lead to UPD (Spence et al., 1988): each of them includes at least two errors either during meiosis or in postzygotic mitoses. During meiosis, a nondisjunction of two homologous chromosomes occurs, which leads to a trisomy in the zygote. In most cases, this zygote will not be viable, unless a correction or a “trisomic rescue” happens. Statistically, in one third of cases, the chromosome of the parent who did not contribute to the trisomy is lost, thus resulting in UPD.
A cytogenetic hint for a trisomy rescue is the confined placental mosaicism (CPM), which describes the presence of a partial chromosomal aberration (usually a trisomy mosaic) in the placenta but not in the fetus. This constitution can be diagnosed in approximately 1-2% of chorionic villous samples (Kalousek et al., 1989). CPM can have relevant clinical consequences since it may lead to placental insufficiency and then induces intrauterine growth retardation.
Clinical features in context with UPD can be caused by:
hidden chromosomal mosaicism originating by the UPD formation via trisomy rescue;
by the imbalanced expression of imprinted genes in the respective chromosomal region resulting in a specific imprinting disorder;
homozygosity for recessive mutations. Interestingly, this phenomenon led to the detection of the first case of UPD. Spence et al. (1988) reported a patient suffering from cystic fibrosis who was homozygous for the mutation F508del in the CFTR gene. Only his mother was a heterozygous carrier for F508del transmitting the mutant gene copy twice to her child. Therefore, UPD always involves the usually unpredictable risk for homozygosity of mutant genes in addition to imprinted gene effects.
Due to the frequency of trisomy 21, UPD of this chromosome should be a well-known aberration. Indeed, maternal as well as paternal UPD21 (upd(21)mat, upd(21)pat) have been reported for several times (for review: Kotzot and Utermann, 2005), including healthy carriers. Based on the latter finding, it can be decided that the clinical course of upd(21)mat or upd(21)pat carriers is rather caused by a hidden chromosomal mosaicism which can be delineated from the UPD formation mechanism or by homozygosity of a recessive allele than by the UPD itself. Imprinted genes involved in the aetiology of imprinting disorders are not localised on chromosome 21. A different epigenetic effect was shown by recent investigations.
It could be demonstrated that trisomy 21 affects the methylation pattern of different heterologous chromosomes by decreasing their extent of methylation (Weinhaeusel et al., 2011) and thus leas to clinical abnormalitiesof the carrier.
This group of combined aberrations comprises numerical and structural abnormalities which present as pathologic karyotype in all cells of an organism or as different types of mosaicism.
Investigations usually rely on conventional chromosome analyses of spontaneous abortions as in this group the frequency among conceptus with pathological karyotype is about 25% compared to life-born children with 0.2% (own investigations and findings from the literature).
Trisomy 21 can be combined with aneuploidies of different heterologous chromosomes (Micale et al., 2010). The maternal age of a pregnancy with a conceptus showing a double aneuploidy is on average higher than that with a single trisomy. The life expectance of the carrier is lower in prenatal and postnatal period than in single trisomies. Double trisomies of autosomes show a higher lethality than combinations of autosomes and gonosomes.
Gonosomal aneuploidies in patients with an additional trisomy 21 were diagnosed in the four possible combinations with monosomy X, XXY, XYY and XXX. The most frequent gonosome aberration in this context is XXY. Monosomy X often presents as mosaic.
The phenotype of the patients usually corresponds to that of trisomy 21. The reason might be the inactivation of more than one X chromsome and the low number of genes on the Y chromosome. The combinations of these double aneuploidies are more frequent than the total amount of the two single trisomies, or the trisomy combined with that of monosomy X.
In life-born children, only three combinations of trisomy 21 with additional heterologous chromosomes have been observed: +8, +13, +18, and trisomy 8 is always occurring as mosaic. The double trisomy 21 and 18 seems to be the most frequent combination with an average of 1:1000 among trisomy 21 carriers. The frequency of this combination is much higher in spontaneous abortions with about 2.5 in 100 trisomies. This is explained by the high and early lethality of conceptus with a double autosomal trisomy.
Clinical investigations reveal a heterogenous picture: The carrier can show the phenotype of one of the 2 trisomies or a combination of both. The majority of double trisomies presents as a mosaic with one or two trisomic cell lines.
The most frequent aberration is a trisomy 21 in combination with a balanced Robertsonian translocation rob(13q14q). It has been hypothesized that a familial translocation rob(13q14q) induces frequently errors of pairing of heterologous chromosomes in the prophase of meiosis I leading to an aneuploid gamete (interchromosomal effect). Recent investigations could not prove this hypothesis. It is nowadays assumed that the reduced fertility of the translocation carriers is the reason for pregnancies at increased maternal age, which leads to an elevated risk for pregnancies with trisomy 21.
Further single cases of trisomy 21 combined with structural aberrations comprise unbalanced and balanced reciprocal translocations, deletions, and sub-microscopic aberrations.
Carriers of trisomy 21 are characterised by a number of clinical symptoms caused by disturbances during early embryonic development. This abnormal course of differentiation can also occur in other syndromes based on an aberrant embryogenesis.
These syndromes can be caused by other chromosome abnormalities, by monogenic mutations, and by exogeneous factors or teratogenic agents.
Chromosome syndromes with a phenotype that, especially in early childhood, resembles that of children with trisomy 21 are the two poly-X syndromes, penta-X syndrome in the female, and XXXXY in the male.
A monogenic disease with a phenotype similar to that of trisomy 21 is hypothyroidism.
The best-known differential diagnosis to trisomy 21 though, is fetal alcohol syndrome.
The similarity between them is so high and the facial dysmorphic features are so characteristic for both that even in the general population the typical phenotype is well-known but often misinterpreted. Therefore, it may happen that a child with DS is wrongly mistaken as one with fetal alcohol syndrome and which can lead to discrimination of the family.
The possibility that the phenotype of DS may be caused by other diseases than trisomy 21 makes it necessary for all patients with the clinical diagnosis of DS to be investigated cytogenetically because otherwise prognosis, therapy, and estimation of recurrence risk might not be correct.
We thank U. Mau-Holzmann for providing us with Figure 2a and J.R. Korenberg for the kind permission to use the data included in Figure 3.
In 1954 C. N. Yang and R. Mills proposed a classical field theory that incorporates Lie groups at a fundamental level [1]. Since then, great progress has been made in the area of subatomic physics by realizing that physics which is described by non-abelian Lie groups can display many novel features and play a major role in the kinds of physical theories they describe [2, 3, 4, 5, 6, 7]. These features are alluded to having no classical analogu. When formulated using rigorous mathematics, Yang-Mills theories as well as gauge theories make elegant use of complicated structures called fiber bundles and associated vector bundles. These are indispensable in physics where spacetime, the base manifold has a non-trivial topology. This occurs in string theory for example spacetime is usually assumed to be a product
The Lagrangian and action of a field theory should be invariant under the action of certain symmetry groups such as the Lorentz group, gauge symmetry, and conformal symmetry [21, 22, 23, 24, 25, 26]. This means the Lagrangian for the fields, hence the laws of physics, are invariant under symmetry transformations. For spontaneously broken gauge theories, the Lagrangian is invariant under gauge transformations that originate in a Lie group. The Higgs condensate yields a vacuum configuration invariant only under a subgroup of
In mathematical terms, suppose
Using a bundle chart,
Principal fiber bundles are a combination of the concepts of fiber bundle and group action; that is, fiber bundles have a Lie group action such that both structures can be made compatible. Let
A fiber bundle
If we denote by
Similarly, suppose that
for
The fundamental vector field will also be denoted
It is shown here that a physical theory can be constructed based on the idea of a differentiable manifold along with many other associated mathematical structures that can be defined on it. The result is a theory which can be used to describe fundamental interactions of elementary particles at the classical level. This also permits the introduction of other ideas which can have a physical influence such as topological invariants. There is no discussion with regard to quantization of gauge theories. These interactions include the strong and weak forces. Physically, Yang-Mills fields represent forces or carriers of force. The first half of the paper introduces most of the mathematical concepts needed to describe particles of both fermionic and bosonic nature. The last part specializes to Yang-Mills in four dimensions. It is discussed how the field equations can be obtained from a variational principle and how the theory of partial differential equations plays a role in their study.
Lie groups appear in principal bundles in gauge theories. These are associated to vector bundles which describe particles and where representations on vector spaces are built into gauge theories. Connections are associated with gauge fields and give rise to covariant derivatives representing interactions.
At
Under composition of diffeomorphisms, the set of all gauge transformations forms a group
Let
If
Suppose we have a manifold chart on
The corresponding real-valued fields
A principal bundle can have many gauges and it is of interest to determine how the local connection one-forms transform as we change the local gauge. Let
In (8),
on
where
with group action
By the defining properties of the connection form
The second claim follows by recalling that for a matrix Lie group
Let
is called the curvature two form of
where the commutators on the right are the commutator in the Lie algebra
It is useful to recall that if
The differential of a one-form
where vectors
If both
If
Thus since
Connections define an important idea in geometry: that of parallel transport in principal and associated vector bundles and leads to the concept of covariant derivative on an associated vector bundle. An interesting result is that if
is called parallel transport in the principal bundle
Similarly for a curve
The restriction of the curve
Let
For
Consequently,
To finish,
Since the curve
and so the claim.
In fact, the theorem implies that
where
The fact that
The map
Suppose
The map
It is useful to show the covariant derivative can be extended similarly to an exterior covariant derivative
This exterior covariant derivative, however, in general does not satisfy
with uniquely defined
It should be stated that the definition of forms can be extended by defining
with Hodge star operator
If
Then
The last term is zero since
The derivative
as well as the Leibnitz formula for exterior covariant derivative. Unlike the case of the standard exterior derivative
In physics, the Lagrangians that are used are restricted out of an infinite set of possible Lagrangians by various principles. The Lagrangian or action of a field theory should be invariant under certain transformations of the fields by symmetry groups. The laws of physics have to be invariant as well, a second meaning of symmetry is invariance of the actual field configurations. In spontaneously broken gauge theories, the Lagrangian is invariant under gauge transformations with values in a given Lie group
The scalar product of forms is given as
To write the Yang-Mills equations, the Hodge star operator written as
The
To obtain a finite integral, it is usual to work with forms of compact support. The codifferential
Therefore, we have
Stokes’ Theorem applied here implies the result.
This knowledge allows us to define the covariant codifferential
To define the Yang-Mills Lagrangian and the associated Yang-Mills equations, procced as follows. To do so, we use an
Let
For a fixed connection
and
where
Suppose
A connection
for all such variations on
Differentiating this and using the adjoint property on
The scalar product on the Lie algebra is non-degenerate, the
Any connection
When the group
Fields of different types can be introduced into the picture. These include matter fields that couple to the gauge field
A complex scalar field is a smooth map
For given fields
The associated action
In a local gauge
As with the Yang-Mills Lagrangian, the Klein-Gordon Lagrangian of a multiplet of complex scalar fields coupled to a gauge field is gauge invariant.
To describe fermion fields classically using spinor fields on spacetime, a Lagrangian for fermions is defined. The setting for doing this is an
where
Based on the fundamental Lagrangians which couple the fields to the gauge field, the Lagrangian of the Standard Model can be built up as the sum of all the individual Lagrangians that are to be accounted for and required to describe all the observed fields. It could be referred to as the Yang-Mills-Dirac-Higgs-Yukawa Lagrangian
Experiment informs us that a realistic theory of particle physics has to involve chiral fermions with a nonzero mass because the weak interaction is not invariant under parity inversion.
The general overview of Yang-Mills theory is now restricted to four-dimensional compact Riemannian manifolds. This will emphasize how Yang-Mills relates to manifolds which are the natural context for Yang-Mills theory for more than one reason. First the four-dimensional action is bounded below by the characteristic number of the bundle so the field is constrained by the topology. By invariant theory, this is linked to the conformal invariance of the action occuring just in dimension four. The base manifold conformal structure leads to the relevant geometry. The curvature is given in terms of the connection form
Riemannian geometry in dimension four is distinguished by the fact that the universal cover
Suppose
Choosing a local basis of sections
Let
on
Given a connection
There are also two second order operators. They are the trace Laplacian
on
The curvature of a connection
Alternatively,
The formula descends to the base
For the Riemannian connection,
On a four-dimensional Riemannian manifold, the metric covariant derivative on the spin bundle
The Dirac operator is elliptic and is formally self-adjoint on the total spin bundle
In four dimensions, the Riemannian curvature tensor
The components of this tensor under this decomposition are
Suppose
This can be summarized as
Since
Compact four-dimensional manifolds
Topological invariants arise in the consideration of four-dimensional manifolds
More generally, if
For functions on a bounded domain in
These spaces are related by the Sobolev embedding theorems: for
It is the case that once the geometrical setting for a gauge theory has been set out, the requirement of naturality then determines the theory. Let
where the Lagrangian is a
Then
These properties of the Lagrangian are required
where
Let us be concerned with the action which depends on the bundle curvature which is called the Yang-Mills action
The action is evidently regular and
A gauge transformation
where
where
Both Lagrangians are regular
Let us calculate the first variation of the action for a spinor field. Introduce two real parameters
Expanding the action, it is given by
In (83),
Recall that
In (85),
The boson action is defined on
The first variation of this action is computed as follows. Choose a one-parameter family of connections
Hence, the action is
Differentiating with respect to
Equating the results, (90) to zero yields the coupled fermion and boson equations of motion taking
In physics, one says
When the structure group is abelian, the equation
The field Eqs. (91) simplify considerably when we take
Thus
Thus upon solving the second in (94) for
Consequently,
and apply Kato’s inequality gives
By Hölder’s inequality, followed by Sobolev’s inequality, the last term is bounded by
This is dominated by the first two terms whenever
(ii) If
Whenever
Therefore,
Solutions of the coupled field equations have the properties expected of elliptic equations, specifically, for
The tangent space to the orbit of the gauge group through
We can choose a
In the new metric, Hölder’s inequality gives,
where
Uhlenbeck has proved the much more difficult fact that the rescaling used here depends only on
where
An extensive theory of Yang-Mills fields coupled to scalar and spinor fields on finite dimensional manifolds has been established. As well as differential geometric ideas, the appearence and systematic use of non-abelian Lie groups is also crucial and as such play a deep role in the study of elementary particles. The Yang-Mills fields represent forces or more accurately, they can be thought of as carriers of those fundamental forces. The presentation has been innovative and proofs have been given for all of the theorems that were introduced. It can also be looked at as a starting point for the study of other topics such as the existence of singularities or isolated singularities.
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\n\nThe University of Massachusetts, Amherst is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\n\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\n\nThe University of Surrey is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\n\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\n\nMonographs Only
\n\n\n\nImportant: You must be a member or grantee of the above listed institutions in order to apply for their Open Access publication funds.
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The toxic and allergic reactions of synthetic dyes are compelling the people to think about natural dyes. Natural dyes are renewable source of colouring materials. Besides textiles it has application in colouration of foods, medicine and in handicraft items. Though natural dyes are ecofriendly, protective to skin and pleasing colour to eyes, they are having very poor bonding with textile fibre materials, which necessitate mordanting with metallic mordants, some of which are not eco friendly, for fixation of natural dyes on textile fibres. So the supremacy of natural dyes is somewhat subdued. This necessitates newer research on application of natural dyes on different natural fibres for completely eco friendly textiles. The fundamentals of natural dyes chemistry and some of the important research work are therefore discussed in this review article.",book:{id:"9203",slug:"chemistry-and-technology-of-natural-and-synthetic-dyes-and-pigments",title:"Chemistry and Technology of Natural and Synthetic Dyes and Pigments",fullTitle:"Chemistry and Technology of Natural and Synthetic Dyes and Pigments"},signatures:"Virendra Kumar Gupta",authors:[{id:"305259",title:"Dr.",name:"Virendra",middleName:null,surname:"Kumar Gupta",slug:"virendra-kumar-gupta",fullName:"Virendra Kumar Gupta"}]},{id:"49647",title:"Fiber Selection for the Production of Nonwovens",slug:"fiber-selection-for-the-production-of-nonwovens",totalDownloads:10512,totalCrossrefCites:9,totalDimensionsCites:17,abstract:"The most significant feature of nonwoven fabric is made directly from fibers in a continuous production line. While manufacturing nonwovens, some conventional textile operations, such as carding, drawing, roving, spinning, weaving or knitting, are partially or completely eliminated. For this reason the choice of fiber is very important for nonwoven manufacturers. The commonly used fibers include natural fibers (cotton, jute, flax, wool), synthetic fibers (polyester (PES), polypropylene (PP), polyamide, rayon), special fibers (glass, carbon, nanofiber, bi-component, superabsorbent fibers). Raw materials have not only delivered significant product improvements but also benefited people using these products by providing hygiene and comfort.",book:{id:"5062",slug:"non-woven-fabrics",title:"Non-woven Fabrics",fullTitle:"Non-woven Fabrics"},signatures:"Nazan Avcioglu Kalebek and Osman Babaarslan",authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",slug:"osman-babaarslan",fullName:"Osman Babaarslan"},{id:"175829",title:"Dr.",name:"Nazan",middleName:null,surname:"Kalebek",slug:"nazan-kalebek",fullName:"Nazan Kalebek"}]},{id:"41409",title:"Surface Modification Methods for Improving the Dyeability of Textile Fabrics",slug:"surface-modification-methods-for-improving-the-dyeability-of-textile-fabrics",totalDownloads:7038,totalCrossrefCites:13,totalDimensionsCites:36,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Sheila Shahidi, Jakub Wiener and Mahmood Ghoranneviss",authors:[{id:"58854",title:"Dr.",name:null,middleName:null,surname:"Shahidi",slug:"shahidi",fullName:"Shahidi"}]}],onlineFirstChaptersFilter:{topicId:"296",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:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:320,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:16,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). 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He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"19",type:"subseries",title:"Animal Science",keywords:"Animal Science, Animal Biology, Wildlife Species, Domesticated Animals",scope:"The Animal Science topic welcomes research on captive and wildlife species, including domesticated animals. 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A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null,series:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517"},editorialBoard:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",institutionString:null,institution:{name:"Universidade Paulista",institutionURL:null,country:{name:"Brazil"}}},{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",slug:"juan-jose-valdez-alarcon",fullName:"Juan José Valdez-Alarcón",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBfcQAG/Profile_Picture_1631354558068",institutionString:"Universidad Michoacana de San Nicolás de Hidalgo",institution:{name:"Universidad Michoacana de San Nicolás de Hidalgo",institutionURL:null,country:{name:"Mexico"}}},{id:"161556",title:"Dr.",name:"Maria Dos Anjos",middleName:null,surname:"Pires",slug:"maria-dos-anjos-pires",fullName:"Maria Dos Anjos Pires",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS8q2QAC/Profile_Picture_1633432838418",institutionString:null,institution:{name:"University of Trás-os-Montes and Alto Douro",institutionURL:null,country:{name:"Portugal"}}},{id:"209839",title:"Dr.",name:"Marina",middleName:null,surname:"Spinu",slug:"marina-spinu",fullName:"Marina Spinu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLXpQAO/Profile_Picture_1630044895475",institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"92185",title:"Dr.",name:"Sara",middleName:null,surname:"Savic",slug:"sara-savic",fullName:"Sara Savic",profilePictureURL:"https://mts.intechopen.com/storage/users/92185/images/system/92185.jfif",institutionString:'Scientific Veterinary Institute "Novi Sad"',institution:{name:'Scientific Veterinary Institute "Novi Sad"',institutionURL:null,country:{name:"Serbia"}}}]},onlineFirstChapters:{paginationCount:14,paginationItems:[{id:"82457",title:"Canine Hearing Management",doi:"10.5772/intechopen.105515",signatures:"Peter M. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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