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He has edited four books and collaborated on ten others as well as seventeen patents and in the organization of three international conferences. He is a\nreviewer for ninety-eight journals.",institutionString:"Nanjing Medical University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Nanjing Medical University",institutionURL:null,country:{name:"China"}}}],coeditorOne:{id:"184798",title:"Ms.",name:"Qiuqin",middleName:null,surname:"Tang",slug:"qiuqin-tang",fullName:"Qiuqin Tang",profilePictureURL:"https://mts.intechopen.com/storage/users/184798/images/13334_n.jpg",biography:"Qiuqin Tang is an attending doctor of The Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital). Her research interests include genetic and epigenetic risk factors of reproductive and developmental health. 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He is also the headmaster of the Family Planning Centre and Gynecological Cytology\nLaboratory at the same university. Dr. Tsikouras is a fellow of the\nInternational Academy of Clinical and Applied Thrombosis/Hemostasis. His scientific activities focus on paediatric and adolescence medicine, gynecological oncology, high-risk pregnancies. He is a reviewer for several international journals and has numerous scientific publications to his credit, including papers and book chapters. 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He\nis currently a professor in the Gynecology and Obstetrics Faculty\nof Medicine, University of Kiel, Germany, and honorary doctor\nat the Democritus University of Thrace, Alexandroupoli University Hospital He previously served as chief of the Department\nof Gynecology and Obstetrics at University Hospital RWTH Aachen,\nGermany. Dr. Rath is a reviewer for numerous journals and chief editor of Geburtshilfe und Frauenheilkunde (GebFra). 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1. Introduction
Induced pluripotent stem cells (iPSC) are generated by reprogramming differentiated somatic cells to a pluripotent cell state that highly resembles embryonic stem cells (ESC) [1]. Fully reprogrammed iPSC can differentiate into any adult cell type [2-6]. Takahashi and Yamanaka generated the first iPSC in 2006 by transfecting fibroblasts with four defined factors: SOX2, OCT4, KLF4, c-MYC (SOKM; also referred to as Yamanaka factors) [7]. The clinical use of iPSC offers great potential for regenerative medicine as any cell type can be generated from true pluripotent cells [8-10]. However, human clinical iPSC applications are currently limited by inefficient methods of reprogramming that often generate incompletely reprogrammed pluripotent states that harbor potentially cancerous epigenetic signatures, and possess limited or skewed differentiation capacities [11-13]. Many standard iPSC lines do not fully resemble pluripotent ESC, and often retain an epigenetic memory of their cell of origin [14, 15]. Such incompletely reprogrammed iPSC also display limited differentiation potential to all three germ layers (e.g., endoderm, ectoderm, mesoderm) [16, 17].
To avoid integrating retroviral constructs that may carry mutagenic risks, many non-viral methods have been described for hiPSC derivation [18, 19]. For example, one successful approach is to transiently express reprogramming factors with EBNA1-based episomal vectors [20-22]. It was initially intuitive to reprogram skin fibroblasts due to their easy accessibility. However, standard episomal reprogramming in fibroblasts occurs at even lower efficiencies (< 0.001-0.1%) than reprogramming with retroviral vectors (0.1%–1%) [23-25]. Subsequent studies revealed that various cell types possess differential receptiveness for being reprogrammed to pluripotency [26-30]. One highly accessible human donor source is blood, which has been demonstrated to reprogram with significantly greater efficiency than fibroblasts [4, 20, 31-33].
The innate immune system possesses highly flexible cell types that are able to adapt quickly to various pathogens by eliciting defense responses that protect the host [34-36]. Innate immune cells derived from the myeloid lineage (eg, monocyte-macrophage, dendritic cells, neutrophils) are able to reactivate some unique features of pluripotent stem cells that may give them greater flexibility for being reprogrammed to a pluripotent cell state than other differentiated cells [37]. Additionally, the differentiation state of the cell seems to be of critical importance for its reprogramming efficiency [38].
Our group established a reprogramming method that solves many of the technical caveats cited above (Figure 1). We have generated high-fidelity human iPSC (hiPSC) from stromal-primed (sp) myeloid progenitors [20]. This system can reprogram >50% of episome-expressing myeloid cells to high-quality hiPSC characterized by minimal retention of hematopoietic-specific epigenetic memory and a molecular signature that is indistinguishable from bona fide human ESC (hESC). The use of bone marrow-, peripheral-or cord blood (CB)-derived myeloid progenitor cells instead of fibroblasts, and a brief priming step on human bone marrow stromal cells / mesenchymal stem cells (MSC) appeared to be critical for this augmented reprogramming efficiency. In this system, CD34+ - enriched cord blood cells (CB) are expanded with the growth factors (GF) FLT3L (FMS-like tyrosine kinase 3 ligand), SCF (stem cell factor) and TPO (thrombopoietin) for 3 days, subsequently nucleofected with non-integrating episomes expressing the Yamanaka factors (4F, SOX2, OCT4, KLF4, c-MYC), and then co-cultured on irradiated MSC for an additional 3 days. Cells are then harvested, and passaged onto MEF (mouse embryonic fibroblasts), and hiPSC are generated via standard methods and culture medium. The initial population of enriched CD34+ CB progenitors quickly differentiates to myeloid and monocytic cells in this system, and reprogrammed cells arise from CD34- myeloid cells. The first iPSC colonies appear around day 10, and stable mature iPSC colonies can be established after ~21-25 days. The episomal constructs are partitioned after relatively few cell divisions (e.g., 2-9 passages) to generate high quality non-integrated hiPSC.
Figure 1.
Schema of the stromal-primed myeloid reprogramming protocol for the generation of high quality human iPSC. 4F: four Yamanaka factors, GF: hematopoietic growth factors.
A proteomics and bioinformatics analysis of this reprogramming system implicated significant activation of MSC-induced inflammatory TLR-NFκB and STAT3 signaling [20]. A combination of cell contact-dependent and soluble factors mediate these effects. A recent study similarly implicated inflammatory TLR3 signaling as a novel trigger for enhanced fibroblast reprogramming, albeit at much lesser efficiencies than observed in our myeloid reprogramming system. TLR3 signaling leads to epigenetic modifications that favor an open chromatin state, which increases cell plasticity and the induction of pluripotency [39]. Lee et al. termed this novel link between inflammatory pathways and cell reprogramming ‘Transflammation’ [40].
In this chapter we will discuss hypotheses why inflammation-activated myeloid cells may be highly receptive to factor-mediated reprogramming. Specifically, we will explore the role of the NFκB-STAT3 signaling axis in mediating the unique susceptibility of myeloid cells to high-quality human iPSC derivation.
2. Overview of the canonical and non-canonical NFκB pathway
Multipotent myeloid progenitors are derived from hematopoietic stem cells and differentiate to monocytes macrophages, dendritic cells, and granulocytes, which elicit the initial innate immune response toward pathogens [41]. NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a central transcription factor that regulates these innate immune responses during microbial infections [42-44]. The NFκB system belongs to a group of early-acting transcription factors that are present in the cytoplasm in an inactive state but can be quickly activated by multiple inflammatory stimuli [45, 46].
2.1. The canonical NFκB signaling pathway
The NFκB family consists of 5 members; p65 (RelA), p50 and c-Rel are involved in canonical signaling, and p52 and RelB are involved in non-canonical signaling. Canonical NFκB signaling is characterized by activation of the IκB kinase complex (IKK), which contains two kinases, IKK1/α and IKK2/β along with a non-catalytic subunit called IKKγ (NEMO) [47, 48]. Unstimulated NFκB is sequestered in the cytoplasm by IκBα protein. In contrast, activation of the IKK complex (e.g., by TLRs) leads to IKKβ-mediated serine phosphorylation of IκBα triggering its proteasome-mediated degradation and its dissociation from NFκB [49, 50]. This activates the p65:p50 dimer through p65 phosphorylation and leads to NFκB translocation into the nucleus where it induces target gene expression. Subsequent acetylation keeps p65 in the nucleus [51]. This can be reverted by HDAC3 (histone deacetylase 3)-induced deacetylation of p65, which increases the affinity of NFκB proteins for IκBα and nuclear export [52, 53]. Canonical NFκB signaling is a fast and transient process that regulates complex inflammatory processes that includes the initial pro-inflammatory phase, the induction of apoptosis, and even tumorigenesis [54]. It can be activated by toll-like receptors (TLR), which recognize characteristic pathogenic molecules to activate innate immune responses [55-57].
2.2. The non-canonical NFκB signaling pathway
Non-canonical NFκB signaling is stimulated via the NFκB-inducing kinase (NIK), which leads to phosphorylation of the p100 precursor protein and generation of the p52:RelB dimer that translocates to the nucleus to activate gene transcription. This pathway is uniquely dependent on steady state levels of NIK expression, which are controlled under normal conditions through TRAF3-directed ubiquitination and proteasomal degradation. Non-canonical NFκB signaling is slow but persistent and requires de novo NIK protein synthesis and NIK stabilization [58]. It is activated by receptors that belong to the TNFR (tumor necrosis factor receptor) superfamily like BAFF (B-cell-activating factor), CD40 or lymphotoxin β-receptor (LTβR) [59-62].
The common feature of these receptors is the possession of a TRAF-binding motif, which recruits TRAF members (e.g., TRAF2 and TRAF3) during ligand ligation [63, 64]. Receptor recruitment of TRAF members triggers their degradation, and leads to NIK activation and p100 processing [65]. Additionally, BAFF is an important component of pluripotency-supporting growth media for the culture of ESC and a regulator of B-cell maturation [66]. It predominantly activates non-canonical NFκB signaling due to its possession of an atypical TRAF-binding sequence, which interacts only with TRAF3 but not with TRAF2 [67]. TRAF3 degradation is sufficient to trigger non-canonical NFκB signaling, whereby activation of the canonical NFκB pathway requires TRAF2 recruitment [68].
2.3. CD40 stimulates both NFκB pathway components
Another receptor associated with NFκB signaling is CD40, which is expressed on various cell types including B cells and monocytes. The CD40 receptor interacts with its ligand CD40L, which is primarily expressed on activated T cells. This signaling is majorly involved in B-cell activation, dendritic cell maturation, antigen presentation and acts as a co-stimulatory pathway of T-cells [69]. Upon ligation by CD40L, CD40 targets both the canonical and non-canonical NFκB pathways via proteolysis of TRAF2 and TRAF3 [70-72]. Non-canonical NFκB signaling regulates hematopoietic stem cell self-renewal via regulating their interactions with the microenvironment [73]. The deregulation of non-canonical hematopoietic NFκB signaling is associated with auto-immunity, inflammation and lymphoid malignancies [58, 74].
2.4. NFκB subunit functions
A third NFκB signaling pathway is activated following response to DNA damage that results in IκB degradation independent of IKK. This results in dimerization of free NFκB subunits that are mobilized similarly to canonical NFκB signaling [47]. Unlike RelA, RelB, and c-Rel, the p50 and p52 NFκB subunits do not contain transactivation domains in their C-terminus. Nevertheless, the p50 and p52 NFκB members play critical roles in modulating the specificity of NFκB functions and form heterodimers with RelA, RelB, or c-Rel [75]. Cell contact-dependent signals are crucial during immune responses and can be mediated through NFκB signaling [76]. This can be augmented by co-stimulatory signals like CD40 or CD28 that directly bind to NFκB proteins like p65 [77-81].
3. Functional role of NFκB signaling in stem cells
3.1. Differential roles of canonical and non-canonical NFκB signaling in embryonic stem cells
TLR activation is not only important for mediating innate immune responses, but also for stem cell differentiation. For example, hESC are characterized by the expression of pluripotency genes and markers such as OCT4, NANOG, alkaline phosphatase (AP) and telomerase [82-86]. NFκB signaling has been demonstrated to be crucial for maintaining ESC pluripotency and viability, and drives lineage-specific differentiation [87, 88]. A balance of canonical and non-canonical NFκB signaling regulates these opposing functions; non-canonical pathway signaling maintains hESC pluripotency, and canonical pathway signaling regulates hESC viability and differentiation [89, 90]. For example, non-canonical NFκB signaling has to be silenced during cell differentiation, which allows this pathway to act like a switch between hESC self-renewal and differentiation. RelB positively regulates several key pluripotency markers and represses lineage markers by direct binding to their regulatory units. RelB down-regulation reduces the expression of pluripotency genes like SOX2 and induces differentiation-associated genes like BRACHYURY (mesodermal marker), CDX2 (trophoectodermal marker) and GATA6 (endodermal marker) [89].
3.2. Canonical NFκB signaling in hematopoietic stem cells
RelB/p52 signaling also positively regulates hematopoietic stem-progenitor cell (HSPC) self-renewal in response to cytokines (e.g., TPO and SCF) and maintains osteoblast niches and the bone marrow stromal cell population. It negatively regulates HSPC lineage commitment through cytokine down-regulation in the bone marrow microenvironment, although it is able to direct early HSC commitment to the myeloid lineage [73, 91].
Canonical p65 signaling also regulates hematopoietic stem cell functions and lineage commitment by controlling key factors involved in hematopoietic cell fate [92-94]. Canonical NFκB signaling is positively regulated by Notch1, which facilitates nuclear retention of NFκB proteins and promotes self-renewal [95-98]. FGF2 (fibroblast growth factor 2) is important for hESC self-renewal and preserves the long-term repopulating ability of HSPC through NFκB activation [99-102]. Deletion of p65, p52 and RelB dramatically decreases HSC differentiation, function and leads to extramedullary hematopoiesis [103]. NFκB pathway components and FGF4 are highly expressed in CD34+HSPC from cord blood, where they regulate clonogenicity. Nuclear p65 can be detected in 90% CB-derived CD34+ cells but only in 50% BM-derived CD34+ cells [104]. The important role of NFκB in regulating myeloid cell lineage development has been most potently revealed via genetic deletion of IKKβ, IκBα, and RelB, which resulted in granulocytosis, splenomegaly and impaired immune responses [73, 103].
3.3. Canonical NFκB signaling during ESC differentiation
Canonical NFκB signaling is very low in the undifferentiated pluripotent state, where it maintains hESC viability. However, it strongly increases during lineage-specific differentiation of pluripotent stem cells. p65 binds to the regulatory regions of similar differentiation genes as RelB with opposing effects on their activation or silencing. It regulates cell proliferation by direct binding to the CYCLIN D1 promoter [89]. There are different levels of inhibiting canonical NFκB signaling: first, p65 translational repression by the microRNA cluster miR-290 to maintain low p65 protein amounts and second, the inhibition of translated p65 by physical interaction with NANOG. Similarly, OCT4 expression is reversely correlated with canonical NFκB signaling [105]. In contrast to most observations in mouse ESC, NFκB probably plays a more important role in the maintenance of human ESC pluripotency [106]. Finally, active TLRs are expressed on embryonic, hematopoietic and mesenchymal stem cells (MSC), thus implicating their roles in a variety of stem cell types [107-110].
4. Role of NFκB signaling during reprogramming to pluripotency
Undifferentiated human iPSC have elevated NFκB activities, which play important roles in maintaining OCT4 and NANOG expression in pluripotent hiPSC [111]. Innate immune TLR signaling was recently shown to enhance nuclear reprogramming probably through the induction of an open chromatin state, and global changes of epigenetic modifiers [39]. This normally increases cell plasticity in response to a pathogen, but may also enhance the induction of pluripotency, transdifferentiation and even malignant transformation [112-116].
The EBNA (Epstein-Barr virus nuclear antigen) is a virus-derived protein that is not only a critical component of episomal reprogramming vectors, where it mediates extra-chromosomal self-replication, but it is also known to activate several TLRs [117-119]. These include TLR3, which is known to augment reprogramming efficiencies through the activation of inflammatory pathways [39, 120]. TLR3 recognizes double-stranded RNA from retroviruses and signals through TRAF6 and NFκB [121-123]. The TLR3 agonist poly I:C was shown to have the same effect as retroviral particles in enhancing Yamanaka factor-induced iPSC production. TLR3 causes widespread changes in the expression of epigenetic modifiers and facilitates nuclear reprogramming by inducing an open chromatin state through down-regulation of histone deacetylases (HDACs) and H3K4 (histone H3 at lysine 4) trimethylations [38, 39, 124]. These epigenetic modifications mark transcriptionally active genes, whereas the H3K9me3 (Histone H3 at lysine 9) modification marks transcriptionally silenced genes [125, 126]. Histone deacetylation is generally associated with a closed chromatin state and HDAC inhibitors were shown to enhance nuclear reprogramming [127, 128]. Histone acetylation favors an open chromatin state, and is maintained by proteins containing histone acetyltransferase (HAT) domains, such as p300 and CBP [129, 130]. Interestingly, p300/CBP is able to interact with NFκB [131, 132]. RelB directly interacts with the methyltransferase G9a to mediate gene silencing of differentiation genes [133]. Epigenetic changes that allow an open chromatin state are crucial for giving the Yamanaka factors access to promoter regions necessary for the induction of pluripotency. Epigenetic chromatin modifications by TLRs are normally involved in the expression of host defense genes during infections [134-136]. This capability can be deployed to enable nuclear reprogramming as TLR3 was shown to change the methylation status of the Oct4 and Sox2 promoters. Interestingly, changes in these methylation marks were not observed with TLR3 activation alone but only in the presence of the reprogramming factors. Although TLR3 by itself promotes an open chromatin configuration, the reprogramming proteins are likely necessary to direct the epigenetic modifiers to the appropriate promoter sequences [137]. Lee et al. described the potential of inflammatory pathways to facilitate the induction of pluripotency as ‘transflammation’ [40, 138].
5. Overview of the JAK/STAT pathway
The JAK/STAT pathway (Janus kinase/signal transducer and activator of transcription) integrates a complex network of exterior signals into the cell, and can be activated by a variety of ligands and their receptors [139]. These receptors are associated with a JAK tyrosine kinase at their cytoplasmic domain. The JAK family consists of the four members JAK1, JAK2, JAK3 and TYK2 [140, 141]. Many cytokines and growth factors signal through this pathway to regulate immune responses, cell proliferation, differentiation and apoptosis [142-146]. Ligand binding induces the multimerization of gp130 receptor subunits, which brings two JAKs close to each other inducing trans-phosphorylation. Such activated JAKs phosphorylate their receptor at the C-terminus and the transcription factor STAT at tyrosine residues. This allows STAT dimerization and their nuclear translocation to induce target gene transcription. [147, 148] STAT3 acetylation is critical for stable dimer formation and DNA binding [149]. From the 7 mammalian STATs, STAT3 and STAT5 are expressed in many cell types, are activated by a plethora of cytokines and growth factors, and integrate complex biological signals [150, 151]. The other STAT proteins mainly play specific roles in the immune response to bacterial and viral infections. STAT3 is an acute phase protein with important functions during immediate immune reactions [152-154]. STAT3 can be recruited by receptor tyrosine kinases that harbor a common STAT3 binding motif in their cytoplasmic domain (e.g., GCSF (granulocyte colony-stimulating factor), LIF (leukemia inhibitory factor), EGF (epidermal growth factor), PDGF (platelet-derived growth factor), interferons (IFNγ) and interleukins (IL-6, IL-10)) [155-158]. Many cytokines signal through IL-10/STAT3 to achieve an immunosuppressive function or anti-apoptotic effect [159, 160]. IL-10 is also required during terminal differentiation of immunoglobulins [161]. STAT3 can be phosphorylated at tyrosine or serine residues. The phosphorylation site can play distinct roles in the regulation of downstream gene transcription [162]. Stat3-deficient mice die during early embryogenesis due to Stat3 requirement for the self-renewal of ESC [163].
Negative feedback regulation of the JAK/STAT circuitry is mediated by the SOCS family of target genes (suppressors of cytokine signaling) in a way that activated STAT induces SOCS transcription [164, 165]. SOCS proteins can bind to phosphorylated JAKs as a pseudo-substrate to inhibit JAK kinase activity and turn off the pathway [166, 167]. SOCS are negative regulators of the immune response [168, 169]. A small peptide antagonist of SOCS1 was shown to bind to the activation loop of JAK2 leading to constitutive STAT activation and TLR3 induction. This boosts the immune system to exert broad antiviral activities [170]. The JAK/STAT pathway also interacts with many other signaling pathways in a complex manner to regulate cell homeostasis and immune reactions [149, 171].
6. Functional role of the JAK/STAT pathway in stem cells
6.1. Stat3 maintains naïve pluripotency in mouse embryonic stem cells
ESC pluripotency is regulated by transcriptional networks that maintain self-renewal and inhibit differentiation [172-174]. Stat3 and Myc are necessary to maintain mouse ESC (mESC) self-renewal and bind to many ESC-enriched genes [175]. Their target genes include pluripotency-related transcription factors, polycomb group repressive proteins, and histone modifiers [176, 177]. The transcription factor Stat3 is a key pluripotency factor required for ESC self-renewal [178, 179]. Mouse ESC require LIF-Stat3 (leukemia inhibitory factor) and Bmp4 (bone morphogenic protein 4) to remain pluripotent in in vitro cultures, whereas human ESC require FGF2/MAPK (fibroblast growth factor / mitogen-activated protein kinase) and TGFβ/Activin/Nodal (transforming growth factor β) [180-183]. Nevertheless, the core circuitry of pluripotency is conserved among species and includes OCT4, SOX2 and NANOG [174].
6.2. The LIF-IL6-STAT3 circuitry
LIF belongs to the IL-6 family of cytokines and acts in parallel through the Jak/Stat3 and PI3K/Akt (Phosphatidylinositide 3-kinase) pathways to maintain Oct4, Sox2 and Nanog expression via Kruppel-like factor 4 (Klf4) and T-box factor 3 [184, 185]. Lif and IL-6 are necessary for STAT3 phosphorylation mediated by Jak1 [186]. Stat3 phosphorylation positively regulates Klf4 and Nanog transcripts and facilitates Lif-dependent maintenance of pluripotency in a signaling loop [106]. Stat3 directly binds to genomic sites of Oct4 and Nanog, regulates the Oct4-Nanog circuitry and is necessary to maintain the self-renewal and pluripotency of mESC [187-189]. Overexpression of Stat3 maintains mESC self-renewal even in the absence of Lif [190]. Withdrawal of LIF up-regulates the NFκB pathway and results in ESC differentiation as well as STAT3 disruption [191-193]. The interleukin 6 (IL-6) response element (IRE) is activated by STAT3, vice versa IL-6 stimulation leads to STAT3 phosphorylation and transactivation of IRE- containing promoters providing a positively regulated STAT3-IL6 loop. STAT3 directly associates with c-Jun and c-Fos in response to IL-6 [194]. c-Jun and c-Fos are DNA binding proteins and components of the AP-1 (activation protein-1) transcription factor complex [195]. AP-1 can be activated by TLR2/4, IL-10 or STAT3 to regulate inflammatory responses or drive keratinocyte differentiation in interplay with STAT3 and c-MYC [196]. Tlr2 also plays an important role in the maintenance of mESC [107]. STAT3 is important to tune appropriate amounts of AP-1 proteins required for proper differentiation. DNA binding sites for both AP-1 and STAT3 have been found in many gene promoters [194, 197]. It is important to note that c-Jun is able to capture or release the NuRD (nucleosome remodeling and deacetylation) repressor complex, an important epigenetic modulator of gene silencing [198, 199]. STAT3 is able to bind to bivalent histone modifications enabling a quick switch between the activation of pluripotency genes during ESC maintenance and their inhibition during cell differentiation [193].
6.3. STAT3 signaling in immune cells
STAT3 also has complex functions during hematopoietic development, immune regulation, cell growth, and leukemic transformation [200-202]. It is critically important for the survival and differentiation of lymphocytes and myeloid progenitors [171]. STAT3 signaling can be activated in a cell contact-dependent way, which is distinct from its cytokine activation. Co-cultures of MSC (human mesenchymal stem cells) and APC (antigen-presenting cell) increase STAT3 signaling in both cell types in a cell contact-dependent way, which mediates the immune-modulatory effects of MSC to block APC maturation and induce T-cell tolerance [203]. MSC are high-proliferative non-hematopoietic stem cells with the ability to differentiate into multiple mesenchymal lineages [204-206]. They accumulate in tumor environments in response to NFκB signaling and produce cytokines [207]. MSCs are FDA-approved for the treatment of severe acute GVHD, due to their immunomodulatory properties [208]. STAT3 phosphorylation is induced by cell-cell contacts and inhibited in postconfluent cells that consequently become apoptotic. Therefore, STAT3 may represent a molecular junction that allows cell proliferation or growth arrest depending on the state of the cell. Increased STAT3 activity may promote cell survival during cell confluency [209].
6.4. Cell contact-dependent STAT3 signaling during cell transformation
Constitutive STAT3 activation can by itself result in cellular transformation [210-214]. For example, contact-dependent STAT3 activation is known to play a promoting role in the interactions between tumor cells and their environment [215-218]. Cell transformation and the induction of pluripotency may share very similar signaling processes, and it is possible that STAT3 may represent a common axis [219, 220]. During early tumor development, certain cells have to acquire stem cell-like features that allow them to self-renew (tumor-initiating cells) and to produce cell progeny (tumor bulk) [221-224]. These tumor-initiating cells are very difficult to eradicate during chemotherapies and often re-establish the tumor seen as clinical relapse [225-227]. Tumor-initiating cells display strong inflammatory gene signatures with elevated IL6-STAT3-NFκB signaling to sustain their self-renewal [228-231]. A better understanding of the mechanism by which STAT3 and NFκB regulates the acquisition of pluripotency and self-renewal might also give us crucial insight about tumor development, and may lead to future novel therapies [171, 232].
7. The role of STAT3 signaling during reprogramming
7.1. STAT3 is a master reprogramming factor
Activation of Stat3 is a limiting factor for the induction of pluripotency, and its over-expression eliminates the requirement for additional factors to establish pluripotency [233]. These key properties have positioned Stat3 signaling as one of the master reprogramming factors that dominantly instructs naïve pluripotency [175]. Elevated Stat3 activity overcomes the pre-iPSC reprogramming block and enhances the establishment of pluripotency induced by SOKM [234]. Stat3 and Klf4 co-occupy genomic sites of Oct4, Sox2 and Nanog. Klf4 and c-Myc are downstream targets of Stat3 signaling and part of the transcriptional network governing pluripotency. The Stat3 effect is combinatorial with other reprogramming factors, which implies that additional targets of Stat3 play a pivotal role [235].
7.2. STAT3 is an epigenetic regulator
Stat3 activation regulates major epigenetic events that induce an open-chromatin state during late-stage reprogramming to establish pluripotency [236-238]. For example, Stat3 signaling stimulates DNA methylations to silence lineage commitment genes and facilitates DNA demethylations to activate pluripotency-related genes [106, 239, 240]. Other chromatin modifications include histone acetylation and deacetylation, which are catalyzed by enzymes with histone acetyltransferase (HAT) or histone deacetylase (HDAC) activities. Histone acetylation is associated with an open chromatin state that allows active gene transcription. HDAC inhibitors are known to significantly improve the efficiency of iPSC generation by allowing promoter accessibility [128, 241, 242]. STAT3 suppresses HDAC expression and repressive chromatin regulators to establish an open-chromatin structure giving full access to transcriptional machineries. The key pluripotency factor Nanog cooperates with Stat3 to maintain ESC pluripotency [173]. Interestingly, HDAC inhibitors but not NANOG over-expression rescues complete reprogramming in the presence of STAT3 inhibition.
Finally, DNA demethylation is regulated in mammalian cells by Tet proteins (tet methylcytosine dioxygenase), which convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Tet1 suppresses ESC differentiation and Tet1 knockdown leads to defects in ESC self-renewal. Tet1 up-regulation is positively regulated by Stat3 during the late-reprogramming stage [243-246].
8. Interactions between NFκB and STAT3 signaling
8.1. Synergistic NFκB and STAT3 signaling
The NFκB and STAT3 pathways are closely interconnected in regulating immune responses [247, 248]. STAT3 activation itself induces further STAT3 phosphorylation. Un-phosphorylated STAT3 that accumulates in the cell can bind to un-phosphorylated NFκB in competition with IκB. The resulting STAT3/NFκB dimer localizes to the nucleus to induce NFκB-dependent gene expression [249]. STAT3 associates with the p300/CBP (CREB-binding protein) co-activator enabling its histone acetyltranferase activity to open chromatin structures, which allows chromatin-modifying proteins to bind the DNA and activate gene transcription. [250, 251] Tyrosine-phosphorylated and acetylated STAT3 additionally binds to the NFκB precursor protein p100 and induces its processing to p52 by activation of IKKα. STAT3 then binds to the DNA-binding p52 complex to assist in the activation of target genes [252]. Both, the NFκB and STAT3 pathway synergize during terminal B-cell differentiation [253]. Phosho-p65/STAT3 dimers and phospho-STAT3/NFκB dimer complexes can bind to κB motifs. Also, phospho-STAT3 and phosho-p50 interact with each other. Soluble CD40L rapidly activates NFκB p65 and up-regulates IL10 receptors on the cell surface. This renders STAT3 more susceptible to IL-10 induced phosphorylation [161]. Macrophage activation is regulated by Toll-like receptors, JAK/STAT signaling and immunoreceptors that signal via ITAM motifs [254, 255]. These pathways have low activity levels under homeostatic conditions but are strongly activated during innate immune responses. ITAM-coupled receptors cooperate with TLRs in driving NFκB signaling and inflammation during infections, whereas extensive ITAM activation inhibits JAK/STAT signaling to limit the immune reaction [256, 257]. Pleiotropic cytokines like interferons and IL-6 regulate the balance of pro-and anti-inflammatory functions by activating variable levels of STAT1 and STAT3 [258].
8.2. NFκB and STAT3 synergies in stem cells
NFκB and STAT3 are also part of an important stem cell pathway axis [259, 260]. A functional link between NANOG, NFκB and LIF/STAT3 signaling was shown in the maintenance of pluripotency [228]. Non-canonical NFκB signaling is activated by STAT3 through activation of IKKα and p100 processing [58]. Conversely, STAT3 inhibits TLR-induced canonical NFκB activity probably through up-regulated SOCS3. C-terminal binding of NANOG inhibits the pro-differentiation activities of canonical NFκB signaling and directly cooperates with STAT3 to maintain ESC pluripotency. NANOG and STAT3 bind to each other and synergistically activate STAT3-dependent promoters [106, 261].
The STAT3 pathway also interacts with many signaling pathways that are critically involved in the reprogramming process. For example, STAT3 signaling activates the MYC transcriptome and signals in loop with LIN28 [229]. LIN28 is expressed in undifferentiated hESC and is able to enhance the reprogramming efficiency of fibroblasts. It is down-regulated upon ESC differentiation [262-265]. Proto-oncogene tyrosine-protein kinase Src activation triggers an inflammatory response mediated by NFκB that directly activates IL6 and Lin28B expression through a binding site in the first intron. IL6-mediated activation of STAT3 transcription is necessary for monocyte activation and tumorigenesis. IL6 itself further activates NFκB, thereby completing a positive NFκB-STAT3-IL6 feedback loop that links inflammation to cell transformation [229]. Constitutive STAT3 signaling maintains constitutive NFκB activity in tumors by inhibiting its nuclear export through p65 acetylation, although STAT3 signaling inhibits NFκB activation during normal immune responses [52].
9. The role of epigenetic regulators during the induction of pluripotency
9.1. The NuRD complex
A panoply of chromatin remodelers play active, regulatory roles during the reprogramming process [266, 267]. For example, the Mbd3/NuRD complex is an important epigenetic regulator that restricts the expression of key pluripotency genes [268]. MBD3 (Methyl-CpG-binding domain protein 3) is part of the NuRD (nucleosome remodeling and deacetylation) repressor complex, which mediates chromatin remodeling through histone deacetylation via HDAC1/2 and ATPase activities [269-271]. The NuRD complex interacts with methylated DNA to mediate heterochromatin formation and transcriptional silencing of ESC-specific genes. Whereas MBD2 recruits NuRD to methylated DNA, MBD3 fails to bind methylated DNA as it evolved from a methyl-CpG-binding domain to a protein–protein interaction module [272]. Mbd3 antagonizes the establishment of pluripotency and facilitates differentiation [273].
9.2. MBD3 suppression is a rate-limiting step in factor-mediated reprogramming
Recent evidence suggested that efficient reprogramming may require NuRD complex down-regulation [274]. The reprogramming factors OCT4, SOX2, KLF4 and MYC bind to MBD3, a critical component of the NURD complex. In the absence of MBD3, SOKM over-expression induces pluripotency with almost 100% efficiency [275]. Such reprogramming occurs within seven days in mouse cells. Once pluripotency is established, MBD3 does not appear to compromise its maintenance. The MBD3/NuRD repressor complex is probably the predominant molecular block that prevents the induction of ground-state pluripotency. Several reprogramming factors directly interact with the MBD3/NuRD complex to form a potent negative regulatory complex that restrains pluripotency gene reactivation. Thus, chromatin de-repression is of critical importance for the conversion of somatic cells into iPSC.
9.3. Bivalent histone modifications
Embryonic stem cells are not only able to maintain their undifferentiated state indefinitely, but also need to retain their ability to differentiate into various cell types [276]. The co-existence of these two features requires the combined action of signal transduction pathways, transcription factor networks, and epigenetic regulators [277]. Pluripotent gene expression has to be maintained in a way that it can be rapidly silenced upon receiving differentiation signals. The NuRD complex maintains this ESC flexibility by inducing variability in pluripotency factor expression that results in a low-expressing subpopulation of ESCs primed for differentiation [268, 278]. The control of gene expression by juxtaposition of antagonistic chromatin regulators is a common regulatory strategy in ESC, called bivalent histone modification [279, 280]. Individual promoters exhibit trimethylation of two different residues of histone H3: lysine 4 (H3K4me3) and lysine 27 (H3K27me3) [281, 282]. H3K27me3 is a repressive histone modification, whereas H3K4me3 is an activation-associated mark [283]. Both epigenetic markers have opposing effects and allow quick adjustments between ESC self-renewal and differentiation. Bivalent genes are generally transcriptionally silent in ESCs but are prone for rapid activation. MBD3 binding is enriched at bivalent genes characterized by 5hmC modifications. STAT3 binds to bivalent histone modifications and is able to switch between cellular pluripotency and differentiation [236, 284, 285].
9.4. MBD3 may prevent completion of the reprogramming process
MBD3 plays key roles in the biology of 5-hydroxy-methylcytosine (5hmC) [286]. 5hMC is an oxidation product of 5-methylcytosine (5mC) [287, 288]. MBD3 silences pluripotency genes like Oct4 and Nanog through 5-hydroxy-methylation of their promoters. MBD3 binds to 5hmC in cooperation with Tet1 to regulate 5hmC-marked genes, but does not interact with 5mC. Mbd3 interaction with 5hmC recruits NuRD to its targets resulting in gene repression. Knockdown of the MBD3/NuRD complex affects the expression of 5hmC-marked genes [289]. Mbd3 acts upstream of Nanog and may block the transition from partially to fully reprogrammed iPSC by silencing Nanog. Nanog overexpression was dominant over Mbd3 knockdown in the induction of efficient reprogramming and is in general sufficient to maintain mESC pluripotency. Mbd3 depletion facilitates the transcription of Oct4 and Nanog and leads to the generation of iPSC and chimeric mice even in the absence of Sox2 or c-Myc [290]. The depletion of Mbd3/NuRD does not replace Oct4 during iPSC formation as reprogramming did not occur with Klf4 and c-Myc alone. Mbd3-dependent silencing of pluripotency factors occurs during ESC differentiation. This involves NuRD-dependent deacetylation of H3K27 required for the binding of the polycomb repressive complex two. NuRD-dependent silencing of pluripotency genes prevents the de-differentiation of somatic cells. In the absence of Mbd3, NuRD disassembles, which lowers this epigenetic barrier and allows the activation of pluripotency genes. Drug-induced down-regulation of Mbd3/NuRD may greatly improve the efficiency and fidelity of reprogramming [291].
9.5. STAT3-MBD3 counteractions
Figure 2.
The master reprogramming factor STAT3 may overcome an unknown reprogramming block by inducing an open chromatin formation that facilitates the pluripotency factors SOKM to bind to ESC gene promoters. We hypothesize that upstream inflammatory signals mediated by NFκB signaling may facilitate STAT3 to de-repress the NuRD complex via c-Jun.
Stat3 promotes the expression of self-renewal transcription factors and opposes NURD-mediated repression of several hundred target genes in ESCs. The opposing functions of Stat3 and NuRD maintain variability in the levels of key self-renewal transcription factors. Stat3, but not NuRD, is the rate-limiting factor for pluripotency gene expression. Self-renewing ESC face a barrier that prohibits differentiation. NuRD constrains this barrier within a range that can be overcome when self-renewal signals are withdrawn [268, 278, 292]. Mbd3/NuRD-mediated gene silencing is a critical determinant of lineage commitment in embryonic stem cells and allows cells to exhibit pluripotency and self-renewal. Mbd3-deficient ESC show persistent self-renewal even in the absence of Lif. They are able to undergo the initial steps of differentiation, but their ability for lineage commitment is severely compromised. They fail to downregulate undifferentiated cell markers as well as upregulate differentiation markers [293]. Stat3 has many downstream effectors like the proto-oncogene c-Jun that is part of the AP-1 complex [194]. The transactivation domain of un-phosphorylated c-Jun recruits Mbd3/NuRD to AP-1 target genes to mediate gene repression. This repression is relieved by c-Jun N-terminal phosphorylation or Mbd3 depletion. Upon JNK activation, NuRD dissociates from c-Jun, which results in de-repression of target gene transcription. Termination of the JNK signal induces Mbd3/NuRD re-binding to un-phosphorylated c-Jun and cessation of target gene expression (Figure 2) [199].
10. Conclusions
In this review, we have discussed a potentially novel link between inflammatory pathways and efficient cell reprogramming. In this context, our group reported that bone marrow stromal-primed human myeloid cell progenitors are significantly more receptive to reprogramming stimuli than other cell types [20]. Myeloid cells harbor a unique epigenetic plasticity that allows them to quickly respond to a plethora of pathogens. They are innately equipped to transcriptionally and epigenetically activate key inflammatory pathways via an interconnected NFκB and STAT3 signaling machinery [294]. Both pathways act as epigenetic modifiers during normal inflammation stimulation, and both are also known to promote ESC pluripotency by inducing an open chromatin state that allows other transcription factors to regulate cell fates [236]. This epigenetic remodeling may prove crucial for efficient reprogramming, as well as the generation of high quality iPSC that resemble ESC without excessive epigenetic memory of their cell of origin [295].
Moreover, Stat3 is a master reprogramming factor that is able to dominantly instruct pluripotency, yet is also inherently interconnected with inflammatory signaling cascades (Figure 2). It binds to bivalent histone modifications, and allows rapid transitions between pluripotency and differentiation [193]. The NFκB pathway acts in synergy with downstream STAT3 signaling, whereby non-canonical NFκB signaling maintains pluripotency through epigenetic silencing of differentiation genes and canonical NFκB signaling promotes cell differentiation [296]. Finally, recent evidence suggests that strong chromatin repression by the NuRD complex is a key rate-limiting factor during reprogramming to pluripotency. This important complex may normally function to ensure that differentiated cells do not reactivate pluripotency genes, which might enable tumorigenesis [268]. We propose the hypothesis that NuRD complex silencing might be more easily achieved through the activation of inflammatory pathways in receptive cells such as those from the myeloid lineage.
It remains to be elucidated how all these processes are inter-regulated. It will be especially important to link reprogramming efficiency with the resulting quality of the pluripotent state achieved in hiPSC. We hypothesize that epigenetic plasticity in inflammatory cells that normally allows chromatin accessibility to the transcriptional machinery, could be manipulated to facilitate a complete erasure of the donor epigenetic memory during factor-mediated reprogramming. Additionally, preventing cancerous epigenetic patterns in iPSC via more accurate high-fidelity reprogramming methods will be the foundation for future clinical applications [13]. Finally, the basic understanding of pluripotency induction may also give us a better understanding of how tumor-initiating cells arise and how they can be eradicated to prevent tumor relapse, thus potentially opening a new era of cancer treatments.
Acknowledgments
JRA was supported by a fellowship from the German Research Foundation (DFG, DJ 71/1-1). ETZ was supported by grants from the NIH/NHLBI U01HL099775 and the Maryland Stem Cell Research Fund (2011-MSCRF-II-0008-00; 2007-MSCRF-II-0379-00). We would like to thank Dr. Alan Friedman for assistance in reading and editing the manuscript.
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Zambidis",authors:[{id:"169311",title:"Dr.",name:"Elias",middleName:null,surname:"Zambidis",fullName:"Elias Zambidis",slug:"elias-zambidis",email:"ezambid1@jhmi.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"169984",title:"Dr.",name:"Jasmin",middleName:null,surname:"Agarwal",fullName:"Jasmin Agarwal",slug:"jasmin-agarwal",email:"jasminroya@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Overview of the canonical and non-canonical NFκB pathway",level:"1"},{id:"sec_2_2",title:"2.1. The canonical NFκB signaling pathway",level:"2"},{id:"sec_3_2",title:"2.2. The non-canonical NFκB signaling pathway",level:"2"},{id:"sec_4_2",title:"2.3. CD40 stimulates both NFκB pathway components",level:"2"},{id:"sec_5_2",title:"2.4. NFκB subunit functions",level:"2"},{id:"sec_7",title:"3. Functional role of NFκB signaling in stem cells",level:"1"},{id:"sec_7_2",title:"3.1. Differential roles of canonical and non-canonical NFκB signaling in embryonic stem cells",level:"2"},{id:"sec_8_2",title:"3.2. Canonical NFκB signaling in hematopoietic stem cells",level:"2"},{id:"sec_9_2",title:"3.3. Canonical NFκB signaling during ESC differentiation",level:"2"},{id:"sec_11",title:"4. Role of NFκB signaling during reprogramming to pluripotency",level:"1"},{id:"sec_12",title:"5. Overview of the JAK/STAT pathway",level:"1"},{id:"sec_13",title:"6. Functional role of the JAK/STAT pathway in stem cells",level:"1"},{id:"sec_13_2",title:"6.1. Stat3 maintains naïve pluripotency in mouse embryonic stem cells",level:"2"},{id:"sec_14_2",title:"6.2. The LIF-IL6-STAT3 circuitry",level:"2"},{id:"sec_15_2",title:"6.3. STAT3 signaling in immune cells",level:"2"},{id:"sec_16_2",title:"6.4. Cell contact-dependent STAT3 signaling during cell transformation",level:"2"},{id:"sec_18",title:"7. The role of STAT3 signaling during reprogramming",level:"1"},{id:"sec_18_2",title:"7.1. STAT3 is a master reprogramming factor",level:"2"},{id:"sec_19_2",title:"7.2. STAT3 is an epigenetic regulator",level:"2"},{id:"sec_21",title:"8. Interactions between NFκB and STAT3 signaling",level:"1"},{id:"sec_21_2",title:"8.1. Synergistic NFκB and STAT3 signaling",level:"2"},{id:"sec_22_2",title:"8.2. NFκB and STAT3 synergies in stem cells",level:"2"},{id:"sec_24",title:"9. The role of epigenetic regulators during the induction of pluripotency",level:"1"},{id:"sec_24_2",title:"9.1. The NuRD complex",level:"2"},{id:"sec_25_2",title:"9.2. MBD3 suppression is a rate-limiting step in factor-mediated reprogramming",level:"2"},{id:"sec_26_2",title:"9.3. Bivalent histone modifications",level:"2"},{id:"sec_27_2",title:"9.4. MBD3 may prevent completion of the reprogramming process",level:"2"},{id:"sec_28_2",title:"9.5. STAT3-MBD3 counteractions",level:"2"},{id:"sec_30",title:"10. 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The Journal of Biological Chemistry. 2009;284(41):27857–65.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Jasmin Roya Agarwal",address:null,affiliation:'
Institute for Cell Engineering and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, USA
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1. Introduction
Although 80% of mergers and acquisitions (M&As) results are reported as failures based on the desired profitability [1, 2], M&A is still one of the most essential methods for an organisation to quickly attain corporate growth in order to gain market share or achieve synergies and innovation [3]. As M&A activities continue to rise, ‘human factors’ are often blamed for disappointing M&A outcomes. A substantial body of literature has examined various facts of the integration models and HR issues [4, 5]. In particular, HR is recognised as one of the critical factors after the M&A period (post-M&As) for success or failure outcomes [6, 7, 8, 9]. However, research in this area is more focused on emotive moments in the initiation of M&As [10], little research literature has looked at post-integration from a human resource (HR) process perspective [11].
Chinese overseas mergers and acquisitions (M&As) have a relatively short history [12], beginning with the Go Global policy in 1999 [13]. The golden age for Chinese-Western M&A deals was made between 2005 and 2017 [14], after which the Chinese government changed its policies on overseas investments, and M&A activity dropped dramatically. There was significant interest among Chinese companies to acquire the advanced technology used by Western companies [15], along with their more modern management systems [16, 17], market resources, and innovation capacity [13]. High-income countries, particularly those of North America and Europe, attracted 65.6% of Chinese foreign direct investment outflows during this period [18]. However, only a small amount of these outward-bound investments by Chinese firms has shown successful performance after the M&As. [19, 20, 21, 22].
Very few studies have examined integration during and following Chinese overseas M&As [23], and they lack a clearly defined process or an overview of content involved in this important phenomenon [24]. Further, a consistent perspective regarding the human resource integration process (HRIP) is absent as are the interaction steps. While most studies on M&As consider the human factor critical for integration [24], few scholars have considered HRIP as a dual process that is undertaken simultaneously with integration as a whole. This study focused on the Chinese -Western overseas M&As, posits that complete integration is necessary for practitioners to realise more successful merger outcomes [25]. It propose to answer the critical question: What is the HRIP and what factors should be incorporated into the HRIP after cross-border M&As?
In order to perform the investigation over post-M&A integrations, where one firm has a dominant position over the other, and simplify the interactions and process [26]. Thirty interviews were conducted using the critical incident (CI) approach [27], with representatives of 13 Western firms acquired by Chinese companies during the period from 2010 to 2016 (including the Netherlands, Germany, United Kingdom, Canada, and Australia), to understand the process. Secondary data from newspaper articles, internal HR policies, and managerial documentation were also reviewed.
This study makes two main contributions to the field of interests. The first is to analyse with preliminary information from selected companies the HR integration process through integration leadership, change and restructuring, personnel resistance, and valuable personnel retention factors. This process influences the success or failure of the M&A integration stage. The second contribution is to present a framework that can determine the success or failure factors, the actions, and some examples of HR management and behaviour during the M&A process. This study focuses entirely on Chinese overseas M&As, where a business from an Eastern culture enters a Western culture environment. Therefore, the scope is limited to predefined national characters, and does not exhaust all possible types. A discussion of the validity of the proposed framework in other contexts is also presented in this paper.
2. Literature review and selection
Following Pablo’s [28] definition of integration, HR integration can be defined as the post-M&A change in an organisation’s technical, administrative, and cultural configuration [11]. Many studies have addressed the causes and outcomes of HRIP, and some studies have also focussed on the integration of HR management practices [11, 25]. For instance, the failure to find consistent relationships may stem from an over-emphasis on either the pre-M&A stage (characteristic of early research in strategic management) [29], the post-M&A stage (a focus of early cultural studies) [30], and strategic management research at the expense of the interconnection between the pre- and post-M&A stages [31, 32].
The integration of organisations is the process by which two companies are combined after an M&A is announced. Often, the degree of interaction and strategy between the two companies is defined before the integration begins [33]. Therefore, the decision-making process for HR factors in the pre-M&A stage is critical in understanding the integration process [34]. Following the literary traditions on human factors in post-M&As, four central themes have been studied: leadership [33] and the integration team [35]; change [36] and the restructuring process [37]; personnel resistance [3]; and valuable personnel retention [38].
There are few systemic or structured methodological frameworks available for the study of integration itself [25]. Although several researchers have focused on a process approach [39, 40, 41, 42], this perspective has not been widely taken up as anticipated. For example, Caiazza and Volpe [43] proposed a three-staged integration process: a multi-level due diligence negotiation, an organisational culture integration, and atmospheric competences [43]. Steigenberger [38] presented an integrative framework of the general process of business integration in an M&A, which underlines the interactions between the conditions and interventions that are critical for understanding M&A outcomes. Advocates of a process approach have focused on post-acquisition management rather than examining linkages throughout the entire M&A process [39, 44]. A multidisciplinary review is needed to examine all of the critical variables that appear throughout the M&A process. While some resources are considered prerequisites for the development of a firm, such as absorptive capability [45] and integration capability [35], two critical dimensions identified by Haspeslagh and Jemison [39] are essential: the need for strategic interdependence and the need for structural autonomy [46]. Gomes and Angwin [47] summarised the critical success factors for the pre- and post-M&A phases and their inter-relationships. Furthermore, no clear linkage between the steps of the post-M&A processes and human factors has been established [48].
Most studies have investigated the human side of M&As by focusing on influential human factors within organisations [45]. These include cultural fit, the relationship between management styles, cultural tolerance, and stress-related emotions experienced by employees during and after an M&A [49, 50, 51, 52]). Other works have investigated the importance of managerial practices, such as cultural learning interventions and communication initiatives [53, 54]; openness and willingness in leadership [55]; and transparency to trust between the acquirer and the employee [56]. Although integration of human resources is important, there is a dearth of studies on HRIP practices during M&As [32, 57, 58]. Further, the current understanding of when and how human resource integration leads to cross-border acquisition success is limited and extant literature does not investigate remedies for conflicts in cross-border acquisitions.
In this study, the link between the structural, processual, and strategic dimensions of integration is also expressed through the use in the strategy literature [59, 60, 61, 62]. Integration’s strategic dimension influences its structural dimension and specifies the direction for its processual dimension. Granlund [63] also suggests that structure and action are inseparable in post-merger integration (PMI). Table 1 presents an overview of leading theories related to post-M&A HR integration taken into consideration during this study.
Overview of main theories related to post-M&A HR integration.
Despite the diverse methodologies used by the studies reviewed, elements related to integration were identified in relation to the three stages of the M&A: the pre-integration stage, the integration stage, and the evaluation stage [39]. A conceptual framework for post-M&A HR integration was proposed by Chang-Howe [99], which categorises the HRIP from pre-integration (HR due diligence and determining the factors of an integration strategy) to HR integration (system integration, personnel integration, and change management) and integration outcome (success and failure indicators). It offers a clear overview of all tasks and discusses HR functions in an M&A, however, the interactional relationship between the stages remains unclear.
This study posits that a more integrative approach is required. Therefore, introducing a design management control system [97] to design a human resource intergration process (HRIP). The post-M&A HRIP can be understood as a performance management control system for the combination of two existing HR systems and two organisational cultures. This management control system incorporates a combination of competitive advantages [30] to maximise outcomes. The methodology used provides a logical workflow for organising and guiding the development of an HRIP [100]. The most important considerations for an HR management system in M&As are the level and speed of integration [41], and HRIP should be assessed with the post-merger concepts of integration strategies [50], integration planning [18], resource-based theory, and institutional theory [71, 72]. These key elements provide the content for the framework that will be used to develop the HRIP in the sections below. Previous studies on M&A integration do not differentiate between post-merger and post-acquisition integration, therefore, we employ the neutral term post-M&A integration [48].
3. Methodology
3.1 Research design and qualitative method
Three primary interviews were conducted at random with specialists from Chinese M&A consulting firms and investment banking firms. Using the data from these interviews, the potential M&A cases were selected and designed in the interview questions. The samples chose from commercially oriented companies since their segmentation toward business activities would have considerable similarities. These organisations feature a diverse collection of occupations and functions that show differences in the nature of work and the social context in which it is done [101]. To keep the sample concentrated and absolute, mergers and joint ventures were excluded from the study.
Companies were selected from five Western countries, the Netherlands, Germany, United Kingdom, Canada, and Australia. The Critical Incident (CI) approach [102] was used to collect primary data on the levels and patterns of post-M&A HRIPs. The interviewee’s experience during the M&A was used to identify critical events and the processes and challenges met within the course of the M&As [103].
Contact was made with managers through professional and personal networks, and the sample was populated using a snowball approach. The sample was limited to those to whom the best access was possible and 30 interviews were conducted with representatives of 13 privately owned companies during the period from 2017 to 2020. The companies represented sectors such as manufacturing, entertainment, energy, finance, mining, and insurance. Interviews were concentrated on individuals in top management roles or who were critical to the M&A integration.
3.2 Data collection and analysis
3.2.1 Sample and context
HR integration is usually quite time-consuming, ranging from three months to two years. To collect relevant information and follow the development of cases, multiple interviews were conducted with the interviewees over the period 2017–2020. Six interviewees were transferred back to China after the integration, and four of them transferred to another location. The interviews were conducted in China, the Netherlands, United Kingdom, France, and Germany. In ten cases, interviews were conducted over the telephone, and the others were through face-to-face meetings in the country where the interviewees were located.
The interview questions were drawn from the literature on PMI, using the definitions of HRIP and patterns of HRIP from Yan [11]. The interview questions were developed in greater depth to identify and illustrate processes and critical factors in PMI. The questions covered the following topics:
The general process of HRIP in the company and the parties involved.
Exceptional events that occurred during the HRIP, as recalled by the interviewee.
Emotions and personal experiences related to these events, in particular, the reasons for the emotions.
Comparison of those experiences with other aspects of the interviewee’s professional life and knowledge.
The participants were approached with carefully designed, open-ended questions. The interviews began by asking them to describe their work, responsibilities, and duties within the organisation, to examine their self-awareness in relation to their work and to confirm their rank. We then enquired about their knowledge of post-M&A management. Further, we explored the interviewees’ emotions regarding post-M&A integration and their experience in the HRIP by using backtrack questions that explored sections of time. This sample and context provided an excellent opportunity to examine key events and integration challenges in acquired Western organisations.
3.2.2 Data
This study followed the grounded theory approach [104] to collect the data in stages. The primary data were gathered using semi-structured interviews. Then, by adopting content analysis, we structurally analysed the interview records to discover the specific HRIP used during the post-M&A activities. Three additional interviews were held with management consultants specialising in M&As, in the early and later stages of the research to determine whether management behaviour patterns were unique or common.
Table 2 presents the characteristics of the positions held by the participants, industry sector, interview years, and other information. The final 30 candidates were selected using the criteria of position and management experience. Interviews were performed within and outside the company and lasted approximately 1 hour on average [105]. Personal information was kept confidential, and the data were stored anonymously [106]. Although we modified the interview protocols during each interview to take advantage of emerging themes [107], each set of protocols included questions on each member’s perception of his responsibility, management experience, leadership style, the experience of the HRIP, and experience in managing conflicts and difficult emotions in the M&A process. This set of questions allowed the similarities and differences among members’ perspectives to be observed.
Interview taken year
Deal Country
Company No.
Integration strategy
Integration result
Acquired firm industry
Deal Year
Participant No.
Job Title Acquires side
Job Title Acquired side
2017
2018
2019
2020
1
HR Manager of the acquired company
1st
A
Fully integrate
Failure
Heavy vehicle Manufacture
2012
2
Chairman of the Acquired company
1st
2nd
3
COO of the Acquired company
1st
B
Fully integrate
Failure
Entertainment
2015
4
Head of Youth Academy
1st
Partly integrate
Success
General manager of the Acquired company
C
Energy
2013
5
1st
6
HR Director of Acquirer company
1st
2nd
7
Director of Business Development
1st
8
Director of Technical Department
1st
9
Board member of the Acquirer company
1st
The Netherland
D
Fully integrate
Success
Electric product wholesale
2005
10
Director of Business development
1st
11
General manager of the Acquired company
1st
12
Head of Business development
1st
E
Fully integrate
Failure
Electric product wholesale
2011
13
Operational manager
1st
14
HRD of the Acquired Company
1st
2nd
3rd
F
Fully integrate
Success with re-intergration
Insurance
2015
15
CEO of the Acquired Company
1st
16
Secretary of the Board
1st
2nd
Chemical Manufacturer
2016
17
CFO of the Acquired Company
1st
2nd
3rd
G
Fully integrated
On going
18
Sales director
1st
Energy
2009
19
GM of the Acquired Company
1st
H
Fully integrate
Success
20
Office manager
1st
I
Entertainment
2016
21
HRD of the Acquired Company
1st
2nd
Germany
Fully integrate
Success with re-intergration
22
Director
1st
23
M&A manager
1st
J
Fully integrate
Failure
Electric product
2017
24
Project manager
1st
K
On going
Payment
2019
25
HRD of the Acquirer Company
1st
2nd
UK
Fully integrate
26
Project manager
1st
Canada
L
Partly integrate
Success with re-intergration
Energy
2012
27
M&A
1st
28
HRD of the Acquire Company
1st
Australia
M
Success with re-intergration
Mining
2016
29
HRD of the Acquire Company
1st
Fully integrate
30
HR manager of the Acquire company
1st
Table 2.
Participant sample.
3.2.3 Data analysis
Iterative analysis was performed on the qualitative data, by moving back and forth between the raw data and an emerging theoretical structure [108, 109, 110]. Three significant steps are followed in this iteration: creating provisional categories and first-order codes, integrating first-order codes and creating theoretical categories, and delimiting theory by aggregating theoretical dimensions [101].
The date employed in the qualitative research software ATLAS.ti, which facilitated the analysis of qualitative data. Interview transcripts were entered as text files into ATLAS.ti and coded. These included phrases, terms, or descriptions offered by the participants, in response to the semi-structured interviews. Open coding (initial coding) [111] was used in the first set of the coding process. Each coder began by reading the transcripts to identify the answers to the given questions, then joint statements were drawn on to form provisional categories. First-order codes and exit interviews were broken into sets of themes, using a strategy called focused coding [111] (e.g. post-M&A HRIP). This stage of analysis allowed a comparison to be made to establish differences between answers on the same topic. Measurements and extensions of critical incidents toward the change from the old to the new employer and the difference in organisational cultures and personal leadership representations were also deciphered. Once these theoretical categories were generated, we looked for the underlying dimensions to understand how different categories fit together into a coherent picture [112]. We formed different conceptual frameworks or models that described the relationship between the themes and available organisational theories. Once we identified a possible framework, we re-examined the fit or misfit of the data with a tentative theoretical understanding (e.g. [104, 108]).
Figure 1 summarises the process, using Corley and Gioia’s [10, 113] data structure, which presents first-order categories, theoretical categories, and aggregate theoretical dimensions. The aggregate theoretical dimensions shown are the ones that best explain the critical indicators that influence successful outcomes and employee emotions in HRIPs.
Figure 1.
Overview of data structure.
The rest of the manuscript discusses the findings, followed by a discussion on the process and constraints identified in the HRIP. We also propose a general theoretical model of HRIP as well as culturally specified values and attitudes that influence successful outcomes during post-M&A integrations. This research concludes with the discussion of the implications of the model, both in theory, related to HRIP and critical factors [114].
4. Findings
Following the fundamental argument of Jemison and Sitkin [40], M&A should be seen as a process with distinctive characteristics, which can affect important organisational activities and outcomes [100]. The results in the qualitative phase were divided into three significant steps: pre-integration (i.e. HR due diligence, choice of HRIP, and integration strategy), integration (i.e. systems integration, personnel integration, and change management), and evaluation (i.e. designed outcome and inconsistencies). As expressed by one interviewee ‘Each company has its own story, but overall, the problems are the same. First, you need to analyse what is there and what the priority is, and then what can be done’ (Participant 13). The combination of results of the current research with existing literature led to the development of the post-acquisition HRIP framework (Figure 2), which incorporates the HR integration strategy, HR system integration, personnel integration, and change management (Table 3).
Figure 2.
HR integration process (HRIP).
4.1 Pre-integration (HR due diligence, choice of HRIP, integration strategy)
Chinese firms tend to invest overseas, in countries with higher incomes, better technology, and advanced management methods [18]. In particular, Chinese companies that pursue M&As with Western companies seek to acquire knowledge, skills, and capabilities to enhance their competitive advantage, to enter Western markets. Therefore, the level of integration can be determined, depending on the absorptive capability of the acquiring company.
The pre-integration phase, took place in three steps, based on the findings: due diligence, HR analysis derived from broader business analysis, and HRIP strategy and planning.
“For mergers, there are two important issues. First, due diligence, and second, how to deal with current employees. Normally, business negotiations around the merger include personnel issues. Therefore, before integration starts, HR should already be involved. The moment of involvement should be before the merger. Involvement after the merger is dependent on the strategy before the merger.” (Participant 6)
According to Jansen and Groot [97], the management control cycle begins as soon as a control problem occurs and continues where there is a mismatch between performance and results. This identifies the nature of the poor fit between the acquired and acquiring companies. This may be caused by several factors, such as organisational constraints, cultural distance, and institutional constraints. Factors of this type should be identified during the due diligence process, in the pre-M&A phase, for later use as terminators for the integration strategy (level of integration, integration cost, and integration phase).
During due diligence, risks that may occur in the M&A should also be identified. Once a risk is identified, methods of control should be chosen. Such methods should answer two questions: Should human resource management be integrated? and to what level should it be integrated? If integration is not necessary, an autonomy-based style of integration strategy should be chosen (i.e. preservation or holding).
“HR planning [for this] is quite simple, requiring only an organisational chart and a match between headcount and positions. Organisational chart depends on business needs. Another important matter is what kind of business strategy should be adopted and what HR arrangement should be used. ”(Participant 6)
The business strategy determines the HR strategy, which leads to an integration strategy. Therefore, the question of whether the company will merge or continue to operate as a separate company is determined by the overall business strategy. HR planning covers the previously identified risks from due diligence.
Once the integration strategy is determined, preparation begins. Often, the preparation will run in parallel with business negotiations and signed deals. ‘If you wait until the deal is signed off and then begin to prepare the integration, it will be too late’ (Participant 27). ‘We need to prepare the plan for the key personnel, who will stay and who need to leave, which will influence the organisational structures and later authorisations’ (Participant 14).
Communication plans will only be drawn up after the integration strategy and all other preparatory plans are fixed. ‘The preparatory plan is often aided by external consultants, but once the deal is closed, they will leave. You are, after all, left on your own to carry out the integration’ (Participant 27).
4.2 Integration (system integration, personnel integration, and change management)
4.2.1 System integration
The acquisition process is so complex that managers often spend most of their time solving issues that were overlooked during the pre-M&A stage. Hence, the integration strategy and day-to-day management could be neglected. ‘HR integration begins the day after the deal is signed, and it sometimes lasts two to three years’ (Participant 27). Therefore, it is essential to offer a clear assessment of overall integration contents and steps. In this study, data were gathered on three aspects of the redefining processes utilised by acquired companies. Birkinshaw et al. [115] divided the post-acquisition process into task integration and human integration. During the integration phase, HR integration is implemented through three categories: HR system integration, personnel integration, and change management.
Systems integration concentrates on providing updated definitions for performance control and appraisal. When two existing management control systems need to be combined, or one needs to be replaced, system integration is a necessary step. System integration refers to task integration, which includes redefining organisational structures to fit the new business strategy; compliance checks of the acquirer’s internal and external requirements; and integration of two information technology (IT) systems. The findings revealed that for each M&A, the language barrier created a significant challenge between the Chinese acquirer and the acquired company. This includes language clashes in the vital areas of the IT system, internal control systems, and spoken language in the workplace. These language barriers aggravated the challenge of communication, both internally and externally. Participant 3 elaborated on this topic as:
“Because the Chinese manager’s English skills are poor, I have to hire local assistants to support the work. Additionally, all reports to the HQ are written in Chinese, and communication with external parties has to be translated. Therefore, I have two Dutch financial assistants and two Chinese assistants, and I report every month, where normally I do it only twice a year”(Participant 3).
4.2.2 Personnel integration
Personnel integration includes changes to personnel in a post-M&A organisation that relates to key personnel allocation; the international transfer of key Chinese staff overseas, trilingual talent recruitment, and redundancy and reorganisation (layoffs). Control problems differ on two axes: the source of the problems may be on the individual or the organisational level, and it might manifest itself in behaviours or ideas [97]. Therefore, to promote integration, the focus should be on behaviours that are related to functional factors, namely, human resource systems and personnel allocation, as well as on ideas related to personal factors, such as emotions and cultures. ‘There is still a relationship between a boss and an employee. In fact, the transactional relationship in Western society is the same; only the Chinese understanding hides it more deeply’ (Participant 9).
The issues that most often arise from system and personnel integration revolve around the following two considerations: the organisational chart, the design of the organisation’s reporting line and the human resource needs based on the chart. ‘This analysis includes HR planning, including budgets, headcounts, layoff plans, and so on. If a layoff plan is included, a payoff plan should also be made’ (Participant 6). ‘The reorganisation of all manager positions merges between departments. If it is a complete company merge, the switch of the employment agreement should be taken into consideration’ (Participant 14).
Previous studies have devoted significant attention to the allocation of top management and the shift in organisational culture linked to the CEO’s identity, during post-M&A integration [116]. Further, studies have also focused on the impact of succession on organisational outcomes (Miller, 1993; Shen & Cannella, 2002; Zhang and Rajagopalan, 2004). This study found that the stability of new management is essential for the HRIP. Top management, including the CEO, CFO, and board of directors in acquired companies, are often replaced after the acquisition, by expatriates sent from the China-based headquarters, or recruited locally. Sometimes, due to multiple reasons (including change in organisational strategy, relocation delay, personal reasons, cultural misfit, and expectations mismatch), new management do not remain longer than one or two years. Frequent changes in top management (CEO, CFO, or critical positions within the company) creates management divisions within an organisation. Departments and stakeholders become disengaged because they lose interest in management decisions, and daily operations can progress without consulting them. Divisions between top management and operations limit the rollout of strategic decisions or new policies from the management level to the operational level. Hence, changes in strategy or new management policies are not implemented throughout the organisation. ‘Three CEOs remained within two years. Many policies were changed or were not implemented before they were changed again’ (Participant 21).
4.2.3 Change management
Management control produces a never-ending loop. Any unexpected incident can, and will, alter the process chosen to achieve the desired outcome. Therefore, change management is the greatest challenge in the post-M&A environment, and requires experienced and qualified human capital to manage the risk and process [117]. ‘The challenge for Chinese overseas M&A is how to develop the acquired company in the long term. The sustainability of the company is the most challenging for the Chinese owner’ (Chinese corporate owner and roundtable participant in response to the question, ‘What is the biggest challenge to managing a Chinese-owned Western company’?)
This research suggests that change management include the following elements: emotional influence, language barrier, cultural conflict, financial change, strategic change, unexpected legal constraint, and unexpected delays in the international transfer of key personnel [118].
“In people management, there was not that much influence due to the change. The structure was changed, the structure was implemented in one way, and then I changed it to another way, then I quickly changed back to the first structure because it worked better”(Participant 1).
Critical events, even if challenging, do not necessarily entail negative outcomes, as such events are recalled as disagreements over practices. Surprisingly, criticism is not usually perceived as having negative effects, but rather, as a motivating factor. The role of HR is to facilitate change and influence its direction, hence, attention should be paid to the linkages and interrelations among the three integration processes running in parallel, and their influence on each other. For instance, process redefinition in the category of systems integration, linked with international personnel transfer and reorganisation (personnel integration), will be influenced by legal constraints and the availability of expert talents in the market. This uncertainty is usually unforeseen before the integration process and, therefore, change management is both a challenge and a major part of HRIP tasks.
An important part of managing a control system is the feedback loop, controlling the designed outcome (i.e. integrated HR systems, cost efficiency, successful transfer of knowledge, combined advantage for both companies, and effective control and feedback) and influencing the failures (high cost, ineffective systems, negative emotions, loss of key personnel, lack of resources, and prolonged integration).
All control functions are linked to cost, therefore, the method of control directly influences outcomes and costs. The tighter the control, the higher the likelihood of designed outcome; however, the related cost is high. A typical profit-oriented organisation maintains a balance between functional behaviours and cost, however, maintaining control of other dysfunctional outcomes is challenging.
To achieve long-term success and ensure the continued development of the company, a few important HR management characteristics may be excluded, such as employee training, rewards, and compensation. The findings of this study have important implications for managers seeking to better manage post-M&A integration. Generally, in Chinese companies, less effort is made in training related to creativity, management skills, and culture. Moreover, mid- to long-term incentive plans are seen as weak areas for Chinese overseas human resource management. Findings from interviews and category coding show that the perceptions of critical events during integration among employees are primarily related to their emotional states. These events, even where they are challenging, do not entail negative outcomes. Conflict or difficulties due to changes caused by the acquisition should not be seen as challenges but as positive occurrences.
The challenges of integration are perceived as drivers of motivation and success. The high-performance orientation of a work team is the key driver of a successful integration outcome. Employees in the acquired company are more concerned with the opportunities for multi-cultural experiences. In particular, when action taken to solve the dilemma is justified, these employees’ discourses feature a performance orientation (even if the integration is not ultimately ideal).
Theoretical categories
Codes and interviewee numbers
Pre - Integration
HR due diligence
Internal capabilities and resources Organisational constraints Institutional constraints Cultural distance synergy potential The golden parachute of critical executives
To define the internal capabilities of the acquired company well and understand what available resources you have within your own company. (Nos. 15, 19, 27) The key points for HR due diligence are to determine what structures and risks the acquired company has and whether there are any compliance issues. (Nos. 27, 28, 29, 23, 17, 14) We overlooked the legal and government policies that impacted our deals. (No. 4) For Chinese companies, especially state-owned ones, government policies have a great impact on decision making. (Nos. 2, 27, 28, 15) We assess the acquired company to seek synergy potential. (Nos. 28, 24, 23, 21, 19, 15, 9) Cultural assessment and determination of cultural distance is critical during the HRDD process. (Nos. 14, 27, 21, 25, 23, 27, 29) The directors in the target company have already signed off on highly paid and well-protected exit clauses before the sale, or golden parachutes. (Nos. 27, 23)
Integration strategy
Level of integration Integration cost Speed of integration
Integration can last from three months to two years. (Nos. 27, 23, 29) Determine how much effort you would like to put in and how much time you have. (Nos. 14, 21, 23, 27) How deep do you need to go and how many people need to be integrated? (Nos. 28, 29, 21, 14)
Preparation
Run in parallel Executive replacement plan Design of the organisational structure Authorisation table design Communication plan
For HR, the work begins before the deal is made, and we run in parallel with the acquired company to prepare the transition. (Nos. 28, 25) Many plans have to be made in a limited time frame, including those for the organisational structure, the talent map, the authorisation table, and the communication plan. (Nos. 6, 14, 21, 23, 25, 27, 28)
Integration
Systems integration
Organisational structure Language barrier and communication channels Compliance/non-compliance Usability of IT systems
The organisational structure was redefined. (Nos. 21, 19, 25, 28, 29) Language (English or Chinese) often caused difficulties. (No. 7) There was no English version available in the internal system of the acquired company. No one expected that. (No. 15) The two ERP systems were just not comparable. (No. 3) I did not think compliance would be such a big issue. (No. 17) Performance control, resetting target and goals. (Nos. 21, 28)
Personnel integration
Key personnel allocation International transfer (work permits) Reorganisation (layoff and recruitment)
People from the HQ were sent to the acquired company for key positions, for example: CFO, CEO, HR, and technical positions. (Nos. 2, 3, 4, 7, 8, 12, 16) Work permits are often difficult to arrange for overseas Chinese managers. (Nos. 20, 30, 16, 6). Layoffs were the number one task after the M&A, we had to let people go. (No. 28) Key positions need hiring, and we need fresh minds and talent for the new organisation. (Nos. 14,15, 21)
Change management
Cultural conflict Strategy change Unexpected legal & external constraints Unexpected delay of international transfer of key personnel
If one phrase is used to describe HR integration, it would be change management. (No. 28) The English of some Chinese colleagues is really not good. I cannot understand them. (No. 4) If all internal communication between Chinese colleagues is written in Chinese, we may feel left out. (Nos. 7, 12, 18, 22, 26) The decision-making process is quite one-way, and there are often significant cultural conflicts between Chinese and Western workers in relation to decision making and trust building. (Nos. 3, 1, 7, 12, 18, 22, 24, 26) The strategy of the company has changed over time. (No. 28) To survive, you will need for the company to become accustomed to the Chinese way of doing things. (No. 30) No one expected that the union would say no. (No. 4) We waited four months for the new CEO to arrive, but his visa was delayed. (No. 30) The HQ must decide whom to send over, and the key contact person changed a few times over three years. (No. 21) The person who was needed is pregnant. (No. 25)
Evaluation
Designed outcome
Integrated HR systems Cost efficiency Successfully transfer of knowledge. Combined both companies advantage Effective control and feedback
It took us two years to integrate the two HR systems into one, it but functions pretty well now. (No. 14) The cost is much lower, and overhead costs are much more efficient. (No. 21) We set up a sharing platform and internal transfer systems for people to transfer between the China HQ and overseas locations. (Nos. 17, 11, 2, 21) Resources and talents are shared with HQ and worldwide, and we integrate the acquired company into our global scope. (Nos. 25) The internal system is linked, and the dates and results, as well as performance, can now be easily seen. (Nos. 18) We set up a clear communication and control channel to allow the employees to talk to us and get feedback, and the engagement is much higher than before. (No. 21)
Dysfunction
High cost Ineffective systems Negative emotions Loss of key personnel Lack of resources Prolonged integration
Money was an issue; we needed have to wait until the Chinese manager made a decision. This is difficult sometimes for a Dutch company. (No. 4) Do we have qualified people or not? The financial manager they sent should be able to take responsibility. (No. 3) Chinese HR managers think trust issues during the HR integration process are not much of a problem. (Nos. 2, 6, 22, 29) We had three CEOs in two years. (No. 21) Almost all directors have left the company. (No. 28) Due to the current situation, we need to let the company run on its own for the time being. (No. 25)
Table 3.
Coding results: Contents and processes of HR integration.
5. Discussion and conclusion
There has been a growing body of research on the variables and processes that affect the success of cross-border acquisitions. However, the critical success factors and the reasons why acquisitions integration often fail are inadequately understood [119]. According to Gunkel et al. [51], mechanisms involved during the PMI process are still unclear to scholars, and practitioners may prevent exploitation of the potential synergy that can arise from sharing or transferring resources and skills. Secondly, cross-cultural conflicts and differences between the two companies may cause problems such as stress and negative attitudes toward the acquiring company and its management, including high turnover of the acquired top executives [120].
This research responds to these calls by providing insights into the process of integrating operating synergies. It empirically investigated the human resource integration processes (HRIP) to understand the dynamics of the post-M&A phase in a cross-cultural context. The HRIP presented in this research provide a clear overview of the primary human resources that are relevant to the post-phase of a cross-border M&A. However, the interactions among the constituents of the system and the interaction between the system and its environment are complex. Thus, focusing on the critical success factors facilitating the integration of tasks and the dissemination of skills of the acquired firms, is important. This study’s intent was to develop a better understanding of the parameters that make the post M&A HR integration process successful, in the context of cross-border acquisitions, thus contributing to a better understanding of the value-added creation process and synergy realisation in international M&As.
This study contributes to international management research and provides managerial implications regarding cross-border M&As in several ways. First, a framework for HRIP is proposed. This framework will assist both managers and policymakers to understand the integration approach dominantly used in Chinese cross-border M&As and benefit from the potential synergy in the wake of Chinese cross-border M&As [121].
The proposed framework (Figure 2) incorporates three theoretical perspectives, into an integrative model and addresses post-acquisition factors and issues. It is offered as a descriptive and analytical device rather than a prescriptive model, to highlight the management of the post-acquisition integration process illuminated in this study. Secondly, the framework presented can assist consultants and executives in conducting better assessments at all stages of the M&A, including screening, planning, and negotiation. Thus, it enhance the effectiveness of interventions carried out during a post-M&A HRIP. As such, this study emphasises the role of corporate HR integration analysis as an essential and influential milestone for the exploration of the international business environment [24]. Most importantly, an approach that centres on human resource integration could drive the development of organisational integration in a positive direction. Therefore, the framework proposed in this research has implications that extend beyond the limitations of the field of HR management.
5.1 Limitations and directions for future research
Perhaps the most straightforward implications are those derived from a logical interpretation of a researcher’s findings. ([122], p. 257) This study develops insights into the HRIP in the post-M&A period of a Chinese-acquired Western company [123]. There are both theoretical and managerial implications to the finding.
The knowledge produced should not be taken to be general, but instead specific to two sets of societies in a certain context. This knowledge is local, in that, it may be true and useful for Chinese managers who seek to work in Western environments. It is difficult to evaluate the consequences that flow from the choice of the HRIP in the relatively short history of Chinese cross-border M&As [20], Company D was more willing to cooperate during the research process than the others and we took advantage of this by interviewing more candidates within the company compared with the other companie, it may created a bias to the findings and study. However, it is valuable to monitor the further developments of these M&As and measure organisational performance over time. ‘I think our top management underestimated the challenge of HR integration and overestimated the value of human capital when the deal was made’ (Participant 21). Hence, further studies on these companies in the course of time, will be beneficial.
The evidence collected in this research supports the conclusions of recent studies, which have shown that connecting the pre- and post-M&A stages may yield improved M&A performance in general [124]. These studies report that if both strategic fit (synergy potential) and organisational fit (cultural differences and the national culture of the acquiring company) factors are known, pre-mergers can be taken into account in the choice of the post-acquisition integration approach. M&A performance is superior in deals that did not take pre-acquisition factors into account in post-acquisition decisions.
This study identifies theoretical aspects that may provide direction for future research in the field of post-M&A integration:
On the macro-level, from a strategic perspective, a focus on the interactions and interrelations between the steps during the human resource integration process (HRIP) could be fruitful.
At the micro-level, the individual process that often are barriers to synergistic integration, has been overlooked, (e.g. management divisions) and is worth further study.
It should be noted that the conceptual framework was developed through qualitative research and would require further validation with quantitative research to test the theory on a broader scale. As more cases from other industries and countries become available, it suggests using quantitative methods to test the framework.
It is the hope that the theoretical integration and review in this paper can provide a clear organising framework for future work, and that the conceptual framework proposed in this research will benefit the creation of a future focus in this field.
\n',keywords:"Post-M&As, Human resource integration process, Critical incident approach, HR Integration",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/76190.pdf",chapterXML:"https://mts.intechopen.com/source/xml/76190.xml",downloadPdfUrl:"/chapter/pdf-download/76190",previewPdfUrl:"/chapter/pdf-preview/76190",totalDownloads:188,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 23rd 2020",dateReviewed:"March 9th 2021",datePrePublished:"April 8th 2021",datePublished:"April 28th 2022",dateFinished:"April 8th 2021",readingETA:"0",abstract:"This research focuses on integration during and after mergers and acquisitions where one firm (Chinese) has a dominant position in comparison with another (Western firm). Using the critical incident approach, 30 interviews were conducted with representatives of 13 firms that have undergone Chinese-Western mergers and acquisitions (M&As) during the period from 2005 to 2019. This study aims to analyse the HR integration process in pre-and post-acquisition to determine the critical success factors, and present a framework that determines the success or failure factors and the actions required. The findings have important implications for an organisation post-acquisition phenomenon from a human resource point of view. As a result, it presents an overview of this critical post-HR integration phenomenon and posits that using an integrated approach from the human resources perspective is essential to ultimately enhance the acquisition integration success rate.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/76190",risUrl:"/chapter/ris/76190",signatures:"Wenjia Chang-Howe",book:{id:"9544",type:"book",title:"Global Trade in the Emerging Business Environment",subtitle:null,fullTitle:"Global Trade in the Emerging Business Environment",slug:"global-trade-in-the-emerging-business-environment",publishedDate:"April 28th 2022",bookSignature:"Muhammad Mohiuddin, Jingbin Wang , Md. Samim Al Azad and Selim Ahmed",coverURL:"https://cdn.intechopen.com/books/images_new/9544.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-147-8",printIsbn:"978-1-83969-146-1",pdfIsbn:"978-1-83969-148-5",isAvailableForWebshopOrdering:!0,editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"341176",title:"Dr.",name:"Wenjia",middleName:null,surname:"Chang-Howe",fullName:"Wenjia Chang-Howe",slug:"wenjia-chang-howe",email:"jasmine.chang@maxhrm.nl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Literature review and selection",level:"1"},{id:"sec_3",title:"3. Methodology",level:"1"},{id:"sec_3_2",title:"3.1 Research design and qualitative method",level:"2"},{id:"sec_4_2",title:"3.2 Data collection and analysis",level:"2"},{id:"sec_4_3",title:"3.2.1 Sample and context",level:"3"},{id:"sec_5_3",title:"Table 2.",level:"3"},{id:"sec_6_3",title:"3.2.3 Data analysis",level:"3"},{id:"sec_9",title:"4. Findings",level:"1"},{id:"sec_9_2",title:"4.1 Pre-integration (HR due diligence, choice of HRIP, integration strategy)",level:"2"},{id:"sec_10_2",title:"4.2 Integration (system integration, personnel integration, and change management)",level:"2"},{id:"sec_10_3",title:"4.2.1 System integration",level:"3"},{id:"sec_11_3",title:"4.2.2 Personnel integration",level:"3"},{id:"sec_12_3",title:"4.2.3 Change management",level:"3"},{id:"sec_14_2",title:"4.3 Evaluation (designed outcome and/or dysfunction)",level:"2"},{id:"sec_16",title:"5. 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European Journal of International Relations, 3, 319-363. https://doi.org/10.1177/1354066197003003003'},{id:"B67",body:'Chakrabarti, R.G., Gupta-Mukherjee, S., Jayaraman, N. (2009). Mars–Venus marriages: Culture and cross-border M&A. Journal of International Business Studies, 40, 216–236'},{id:"B68",body:'Glover, J., Friedman, H. (2014). Cultural dilemmas and sociocultural encounters: A transcultural approach for understanding, assessing, and changing culture. Organization Development Journal, 79–92'},{id:"B69",body:'Graebner, M.E., Eisenhardt, K.M. (2004). The other side of the story: Acquisition as courtship and governance as syndicate in entrepreneurial firms. Administrative Science Quarterly, 49, 366–403'},{id:"B70",body:'Puranam, P., Singh, H., Zollo, M. (2006). Organising for innovation: Managing the coordination- autonomy dilemma in technology acquisitions. Academy of Management Journal, 49, 263–280'},{id:"B71",body:'Cording, M., Christmann, P., & King, D. (2008). 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(2009), “Cultural differences, convergence, and crossvergence as explanations of knowledge transfer in international acquisitions”, Journal of International Business Studies, Vol. 41 No. 8, pp. 1365-1390'},{id:"B76",body:'Stahl, G.K. and Voigt, A. (2008), “Do cultural differences matter in mergers and acquisitions? A tentative model and examination”, Organization Science, Vol. 19 No. 1, pp. 160-176'},{id:"B77",body:'Teerikangas, S., & Very, P. 2006. The culture-performance relationship in M&A: From yes/no to how. British Journal of Management, 17(S1): S31–S48'},{id:"B78",body:'Brannen, Mary & Peterson, Mark. (2009). Merging Without Alienating: Interventions Promoting Cross-Cultural Organizational Integration and Their Limitations. Journal of International Business Studies. 40. 468-489. 10.1057/jibs.2008.80'},{id:"B79",body:'Scott D. Culture In Political Theory. Political Theory. 2003;31(1):92-115. doi:10.1177/0090591702239440'},{id:"B80",body:'Kostova, Tatiana, and Srilata Zaheer. “Organizational Legitimacy under Conditions of Complexity: The Case of the Multinational Enterprise.” The Academy of Management Review, vol. 24, no. 1, 1999, pp. 64–81. JSTOR, www.jstor.org/stable/259037. Accessed 5 Apr. 2021'},{id:"B81",body:'S Zaheer - Academy of Management journal, 1995'},{id:"B82",body:'Kostova, Tatiana & Roth, Kendall. (2002). Adoption of an organizational practice by subsidiaries of multinational corporations: Institutional and relational effects. Academy of Management Journal. 45. 215-233. 10.2307/3069293'},{id:"B83",body:'La Porta, Rafael and Lopez de Silanes, Florencio and Shleifer, Andrei, Corporate Ownership Around the World (August 1998). Available at SSRN: https://ssrn.com/abstract=103130 or http://dx.doi.org/10.2139/ssrn.103130'},{id:"B84",body:'Whitley, R. (1999). Divergent capitalisms. Oxford, UK: Oxford University Press'},{id:"B85",body:'Nahavandi, Afsaneh & Malekzadeh, Ali. (1988). Acculturation in Mergers and Acquisitions. The International Executive. 30. 10-12. 10.1002/tie.5060300103'},{id:"B86",body:'Elsass, P. M., & Veiga, J. F. (1994). Acculturation in acquired organizations: A force-field perspective. Human Relations, 47(4), 431–453. https://doi.org/10.1177/001872679404700404'},{id:"B87",body:'Cartwright, S. and Cooper, C.L. (1995), "Organizational marriage: “hard” versus “soft” issues?", Personnel Review, Vol. 24 No. 3, pp. 32-42. https://doi.org/10.1108/00483489510089632'},{id:"B88",body:'Shrivastaya P(1986). Post-merger Integration. Journal of Business Strategy, 7(1): 65–76'},{id:"B89",body:'Schweiger D M, Walsh J P(1990). Merger and acquisitions: An interdisciplinary view. Rowland K M, Ferris G R(ed): Research in Personnel and Human Resource Management. Greenwich, CT: JAI Press, (8): 41–107'},{id:"B90",body:'Shanley, M.T., Correa, M.A. (1992). Agreement with top management teams and expectations for post acquisition performance. Strategic Management Journal, 13, 245–266'},{id:"B91",body:'Chung, G.H., Jing, D., Jin, N.C. (2014). How do employees adapt to organisational change driven by cross-border M&As? A case in China. Journal of World Business, 78–86'},{id:"B92",body:'Chatterjee, S., Lubatkin, M.H., Schweiger, D.M., Weber, Y. (1992). Cultural differences and shareholder value in related mergers: Linking equity and human capital. Strategic Management Journal, 13, 319–334'},{id:"B93",body:'Dupuis, J.P. (2014). New approaches in cross-cultural management research: The importance of context and meaning in the perception of management styles. International Journal of Cross Cultural Management, 14, 67–84'},{id:"B94",body:'Walsh, J. P. \'Top management turnover following mergers and acquisitions\', Strategic Management Journal, 9, 1988. pp. 173-183'},{id:"B95",body:'Krug, Jeffrey & Hegarty, W.. (2001). Predicting Who Stays and Leaves After An Acquisition: A Study of Top Managers in Multinational Firms. Strategic Management Journal. 22. 185 - 196. 10.1002/1097-0266(200101)22:2<185::AID-SMJ149>3.0.CO;2-M'},{id:"B96",body:'Rao-Nicholson, R., Khan, Z., Akhtar, P., & Tarba, S. Y. (2020). The contingent role of distributed leadership in the relationship between HR practices and organizational ambidexterity in the cross-border M&As of emerging market multinationals. International Journal of Human Resource Management, 31(2), 232-253. https://doi.org/10.1080/09585192.2016.1216882'},{id:"B97",body:'Jansen, P.G.W., Groot, T.L.M.C. (2015). Performance management and control. Administration. Amsterdam: VU University Amsterdam, Faculty of Economics and Business'},{id:"B98",body:'Altendorf, D. (1986). When Cultures Clash: A case study of the Texaco takeover of Getty oil and the impact of acculturation on the acquired firm. Unplublished doctoral dissertation, University of Southern California'},{id:"B99",body:'Chang-Howe, W. (2019). The challenge of HR integration: A review of the M&A HR integration literature. Journal of Chinese Human Resource Management, 10, 19–34. doi:10.1108/JCHRM-03-2019-0009'},{id:"B100",body:'Friedman, Yair & Carmeli, Abraham & Tishler, Asher & Shimizu, Katsuhiko. (2015). Untangling micro-behavioral sources of failure in mergers and acquisitions: a theoretical integration and extension. The International Journal of Human Resource Management. 27. 1-31. 10.1080/09585192.2015.1042003'},{id:"B101",body:'Pratt, M.G., Rockmann, K.W., Kaufmann, J.B. (2006). Constructing professional identity: The role of work and identity learning cycles in the customization of identity Amon medical residents. Academy of Management Journal, 49, 235–262'},{id:"B102",body:'Flanagan, J.C. (1954). The critical incident technique. Psychological Bulletin, 51, 327–358'},{id:"B103",body:'Durand, M. (2016). employing critical incident technique as one way to display the hidden aspects of post-merger integration. International Business Review, 87–102'},{id:"B104",body:'Glaser, N.G., Strauss, A.L. (1967). The discovery of grounded theory: Strategies for qualitative research. New York:Aldine de Gruyter.'},{id:"B105",body:'Legard (2003). In-depth interviews'},{id:"B106",body:'Alvesson, M. (2003). Beyond neopositivists, romantics, and localists: A reflexive approach to interviews in organisational research. Academy of Management Review, 28, 13–33'},{id:"B107",body:'Johnson, B., Turner, L.A. (2003). Data collection strategies in mixed methods research. In: A. Tashakkori and C. Teddlie (eds.) Handbook of mixed methods in social and behavioral research. Thousand Oaks:Sage Publications. 297–319'},{id:"B108",body:'Locke, K. (2001). Grounded theory in management re- search. Thousand Oaks, CA:Sage'},{id:"B109",body:'Miles, M.B., Huberman, A.M. (1994). Qualitative data analysis. Beverly Hills, CA: Sage'},{id:"B110",body:'Strauss, A., Corbin, J. (1990). Basics of qualitative research: Grounded theory procedures and techniques. Newbury Park, CA: Sage'},{id:"B111",body:'Saunders, M., Kale, P., Corsten, D. (2009). Research methods for business students. Pearson Education Limited.'},{id:"B112",body:'Creswell (2007). Five qualitative approaches to inquiry. Sage Publications'},{id:"B113",body:'Gioia, D.A., Corley, K.G., Hamilton, A.L. (2013). Seeking qualitative rigor in inductive research: Notes on the Gioia methodology. Organizational Research Methods, 16, 15–31'},{id:"B114",body:'Eisenhardt, K.M., Graebner, M.E. (2007). Theory building from cases; challenges and opportunities. Academy of Management Journal, 50, 25–32'},{id:"B115",body:'Birkinshaw, J.M., Bresman, H., Håkanson, L. (2000). Managing the post-acquisition integration process: How the human integration and task integration processes interact to foster value creation. Journal of Management Studies, 37, 395.426'},{id:"B116",body:'Ma, L.K., Zihui, C. (2010). China’s outward foreign direct investment, China’s growing role in world trade. University of Chicago Press, 545–578'},{id:"B117",body:'Widener S.K. (2007). An empirical analysis of the levers of the control framework. Accounting, Organizations, and Society, 32, 757–788'},{id:"B118",body:'Clark, S.M., Gioia, D.A., Ketchen, D.J.T., Thomas, J.B. (2010). Transitional identity as a facilitator of organisational identity change during a merger. Administrative Science Quarterly, 55, 397–438'},{id:"B119",body:'Stahl, G.K., Angwin, D. N., Very, P., Gomes, E., Weber, Y., Tarba, S.Y., Noorderhaven, N., Benyamini, H., Bouckenooghe, D., Chreim, S., Durand, M., Hassett, M.E., Kokk, G., Mendenhall, M.E., Mirc, N., Miska, C., Park, K.M., Reynolds, N., Rouzies, A., Sarala, R.M., Seloti, S.L., Søndergaard, M., Yildiz, H.E. (2013). Sociocultural integration in mergers and acquisitions: Unresolved paradoxes and directions for future research. Thunderbird International Business Review, 55, 333–356'},{id:"B120",body:'Rodríguez-Sánchez, J.L., Ortiz-de-Urbina-Criado, M., Mora-Valentín, E.M. (2019). Thinking about people in mergers and acquisitions processes. International Journal of Manpower, 40, 643–657. doi:10.1108/IJM-05-2018-0143'},{id:"B121",body:'Spigarelli, F., Alon, I., Mucelli, A., 2013. Chinese overseas M&A: Overcoming cultural and organisational divides. International Journal of Technological Learning, Innovation and Development, 6, 190. doi:10.1504/IJTLID.2013.051703'},{id:"B122",body:'Tepper, G., Tepper, B.J. & (2012). Publishing in AMJ – Part 6: Discuss the implications. Academy of Management Journal, 55, 256–260'},{id:"B123",body:'Hanemann, T. Huotari, Mikko, A (2016). A new record year for Chinese outbound investment in Europe. MERICS, http://www.merics.org/en/merics-analysis/merics-reports/a-new-record-year-for-chinese-outbound-investment-in-europe/#c11166'},{id:"B124",body:'Weber, Y., Tarba, S. Y., & Rozen-Bachar, Z. (2011). Mergers and acquisitions performance paradox: The mediating role of integration approach. European Journal of International Management, 5 (4), 373-393'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Wenjia Chang-Howe",address:"jasmine.chang@maxhrm.nl",affiliation:'
Vrije Universtiteit Amsterdam, School of Business and Economics/MAX HRM B.V, The Netherlands
'}],corrections:null},book:{id:"9544",type:"book",title:"Global Trade in the Emerging Business Environment",subtitle:null,fullTitle:"Global Trade in the Emerging Business Environment",slug:"global-trade-in-the-emerging-business-environment",publishedDate:"April 28th 2022",bookSignature:"Muhammad Mohiuddin, Jingbin Wang , Md. Samim Al Azad and Selim Ahmed",coverURL:"https://cdn.intechopen.com/books/images_new/9544.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-147-8",printIsbn:"978-1-83969-146-1",pdfIsbn:"978-1-83969-148-5",isAvailableForWebshopOrdering:!0,editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"418628",title:"Dr.",name:"Lesya",middleName:null,surname:"Sas",email:"sas@tdmu.edu.ua",fullName:"Lesya Sas",slug:"lesya-sas",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"Ternopil State Medical University",institutionURL:null,country:{name:"Ukraine"}}},booksEdited:[],chaptersAuthored:[{id:"77590",title:"Aplication Arterial Oscilography to Study the Adaptive Capacity of Subject with COVID-19 in Primary Care",slug:"aplication-arterial-oscilography-to-study-the-adaptive-capacity-of-subject-with-covid-19-in-primary-",abstract:"The aim of study is finding complex pathological process markers occurred in COVID-19. Adaptive capacity, cardiovascular features, autonomic, central nervous systems in 67 patients with severe COVID-19 were studied and evaluated using (suggested by authors) temporal, spectral, correlation analysis of arterial oscillograms (AOG). The method is based on mathematical analysis adaptation of electrocardiographic signal heart rate variability to arterial pulsation variability analysis recorded during blood pressure measurement using an electronic tonometer VAT 41–2. Received results were compared with AOG 480 healthy (including 68 people after exercising) and 26 patients in a closed ward at psychoneurological hospital. Study results showed patients with severe COVID-19 have disorders at (four) cardiovascular system (CVS) regulation levels. It’s confirmed by lack of adequate sympathetic-adrenal response to a stressful situation due to severe COVID-19; higher than in healthy, parasympathetic part activity of autonomic nervous system. AOG spectral analysis revealed violation of management centralization, communication and coordination between CVS regulation levels. This leads to functional reserves decrease, low stress resistance of body and finally to a disease severe course and recovery processes. Arterial oscillography can be used to search markers of complex pathological processes occurred in COVID-19 and to improve methods of diagnosis, treatment, control of long-term results in clinical and family medicine.",signatures:"Dmytro Vakulenko, Liudmyla Vakulenko, Leonid Hryshchuk and Lesya Sas",authors:[{id:"418269",title:"Prof.",name:"Dmytro",surname:"Vakulenko",fullName:"Dmytro Vakulenko",slug:"dmytro-vakulenko",email:"dmitro_v@ukr.net"},{id:"418564",title:"Dr.",name:"Liudmyla",surname:"Vakulenko",fullName:"Liudmyla Vakulenko",slug:"liudmyla-vakulenko",email:"Vakulenko3@ukr.net"},{id:"418627",title:"Prof.",name:"Leonid",surname:"Hryshchuk",fullName:"Leonid Hryshchuk",slug:"leonid-hryshchuk",email:"gryshchuk@tdmu.edu.ua"},{id:"418628",title:"Dr.",name:"Lesya",surname:"Sas",fullName:"Lesya Sas",slug:"lesya-sas",email:"sas@tdmu.edu.ua"}],book:{id:"10707",title:"Primary Health Care",slug:"primary-health-care",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"343361",title:"Ph.D.",name:"Dimitra",surname:"Metallinou",slug:"dimitra-metallinou",fullName:"Dimitra Metallinou",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of West Attica",institutionURL:null,country:{name:"Greece"}}},{id:"346832",title:"Prof.",name:"Christina",surname:"Nanou",slug:"christina-nanou",fullName:"Christina Nanou",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of West Attica",institutionURL:null,country:{name:"Greece"}}},{id:"346833",title:"Prof.",name:"Antigoni",surname:"Sarantaki",slug:"antigoni-sarantaki",fullName:"Antigoni Sarantaki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of West Attica",institutionURL:null,country:{name:"Greece"}}},{id:"346835",title:"M.Sc.",name:"Eleftheria",surname:"Lazarou",slug:"eleftheria-lazarou",fullName:"Eleftheria Lazarou",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"346836",title:"MSc.",name:"Anastasia",surname:"Liagkou",slug:"anastasia-liagkou",fullName:"Anastasia Liagkou",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"346837",title:"Prof.",name:"Katerina",surname:"Lykeridou",slug:"katerina-lykeridou",fullName:"Katerina Lykeridou",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of West Attica",institutionURL:null,country:{name:"Greece"}}},{id:"417658",title:"Emeritus Prof.",name:"John",surname:"Geyman",slug:"john-geyman",fullName:"John Geyman",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"418229",title:"M.Sc.",name:"Michael",surname:"Willie",slug:"michael-willie",fullName:"Michael Willie",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"418233",title:"Dr.",name:"Sipho",surname:"Kabane",slug:"sipho-kabane",fullName:"Sipho Kabane",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"418240",title:"Mr.",name:"Neo",surname:"Nonyana",slug:"neo-nonyana",fullName:"Neo Nonyana",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"terms-and-conditions",title:"Terms and Conditions",intro:'
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By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
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The following terminology applies to these Terms and Conditions, Privacy Statement, Disclaimer Notice, and any or all Agreements:
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Any use of the above terminology, or other words in the singular, plural, capitalization and/or he/she or they, are taken as interchangeable.
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The hydration processes of biopolymers have been extensively studied in the past 20 years with reference to a considerable variety of models and concepts. In all recent works, a distinction is made between intracellular water that maintains the ordinary liquid state (bulk water) and water ordered in extended hydrogen‐bonded lattices at the surface and structured in the internal grooves of macromolecules (hydration water) in dependence on the chemical properties of the macromolecule surface. FTIR spectroscopy has been implemented in this field both for the sensitivity in the conformational analysis of biological macromolecules and the reliability in the investigation of the water network. A perturbation technique such as dehydration‐rehydration treatment modifies the macromolecule structure and water distribution. It was applied to two structurally different proteins: lysozyme, a globular (α + β) protein and collagen, a fibrous protein characterized by the triple helix structure. Submitted to the treatment both of them display irreversible conformational changes.",book:{id:"5411",slug:"fourier-transforms-high-tech-application-and-current-trends",title:"Fourier Transforms",fullTitle:"Fourier Transforms - High-tech Application and Current Trends"},signatures:"Maria Grazia Bridelli",authors:[{id:"108760",title:"Dr.",name:"Maria Grazia",middleName:null,surname:"Bridelli",slug:"maria-grazia-bridelli",fullName:"Maria Grazia Bridelli"}]},{id:"74096",doi:"10.5772/intechopen.94521",title:"Time Frequency Analysis of Wavelet and Fourier Transform",slug:"time-frequency-analysis-of-wavelet-and-fourier-transform",totalDownloads:1162,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"Signal processing has long been dominated by the Fourier transform. However, there is an alternate transform that has gained popularity recently and that is the wavelet transform. The wavelet transform has a long history starting in 1910 when Alfred Haar created it as an alternative to the Fourier transform. In 1940 Norman Ricker created the first continuous wavelet and proposed the term wavelet. Work in the field has proceeded in fits and starts across many different disciplines, until the 1990’s when the discrete wavelet transform was developed by Ingrid Daubechies. While the Fourier transform creates a representation of the signal in the frequency domain, the wavelet transform creates a representation of the signal in both the time and frequency domain, thereby allowing efficient access of localized information about the signal.",book:{id:"10065",slug:"wavelet-theory",title:"Wavelet Theory",fullTitle:"Wavelet Theory"},signatures:"Karlton Wirsing",authors:[{id:"325178",title:"Dr.",name:"Karlton",middleName:null,surname:"Wirsing",slug:"karlton-wirsing",fullName:"Karlton Wirsing"}]},{id:"52810",doi:"10.5772/65776",title:"Study of Green Nanoparticles and Biocomplexes Based on Exopolysaccharide by Modern Fourier Transform Spectroscopy",slug:"study-of-green-nanoparticles-and-biocomplexes-based-on-exopolysaccharide-by-modern-fourier-transform",totalDownloads:2e3,totalCrossrefCites:2,totalDimensionsCites:6,abstract:"The intention of this chapter is to contribute in clarification of nanoparticle synthesis and biocomplexes based on exopolysaccharide, green synthetic method development, their physico‐chemical characterization by modern spectroscopy, as well as testing of their antimicrobial activity. Silver nanoparticles of polysaccharide type have scientific interest, but practical importance too, because of their application in pharmaceutical and cosmetic product development due to proven antimicrobial and antioxidant activities. On the other hand, the biocomplexes based on exopolysaccharides are important in treatment of biometal deficiency in human and veterinary medicine, as well as in metal ion transporting in organism. Despite a number of studies of this kind of complexes, the investigations of effect of their structure to pharmaco‐biological activity are still interesting. It is important that question of interaction between reducing and stabilizing agents with metal ions is still opened. In this respect, the presented chapter offers further progress in the examination of silver nanoparticles and cobalt biocomplex synthesis with dextran oligosaccharides and its derivatives (such as dextran sulfate and carboxymethyl dextran). The complex structure, spectroscopic characterization, and the spectra‐structure correlation have been analyzed by different Fourier transform infrared (FTIR) spectroscopic techniques combined with energy‐dispersive X‐ray (EDX), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and surface plasmon resonance UV‐Vis methods.",book:{id:"5411",slug:"fourier-transforms-high-tech-application-and-current-trends",title:"Fourier Transforms",fullTitle:"Fourier Transforms - High-tech Application and Current Trends"},signatures:"Goran S. Nikolić, Milorad D. Cakić, Slobodan Glišić, Dragan J.\nCvetković, Žarko J. Mitić and Dragana Z. Marković",authors:[{id:"23261",title:"Prof.",name:"Goran",middleName:"S.",surname:"Nikolic",slug:"goran-nikolic",fullName:"Goran Nikolic"},{id:"195519",title:"Dr.",name:"Milorad",middleName:null,surname:"Cakic",slug:"milorad-cakic",fullName:"Milorad Cakic"},{id:"195520",title:"MSc.",name:"Slobodan",middleName:null,surname:"Glišić",slug:"slobodan-glisic",fullName:"Slobodan Glišić"},{id:"195521",title:"Prof.",name:"Dragan",middleName:"J.",surname:"Cvetkovic",slug:"dragan-cvetkovic",fullName:"Dragan Cvetkovic"},{id:"195522",title:"Dr.",name:"Žarko",middleName:null,surname:"Mitić",slug:"zarko-mitic",fullName:"Žarko Mitić"},{id:"195523",title:"MSc.",name:"Dragana",middleName:null,surname:"Marković-Nikolić",slug:"dragana-markovic-nikolic",fullName:"Dragana Marković-Nikolić"}]},{id:"53388",doi:"10.5772/66107",title:"Fourier Transform Hyperspectral Imaging for Cultural Heritage",slug:"fourier-transform-hyperspectral-imaging-for-cultural-heritage",totalDownloads:1772,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"Hyperspectral imaging is a technique of analysis that associates to each pixel of the image the spectral content of the radiation coming from the scene. This content can be helpful to recognize the chemical nature of the materials within the scene or to calculate their colours under particular conditions. Different solutions of hyperspectral imager have been realized with different spatial resolution, spectral resolution and range in the electromagnetic spectrum. In particular, improving the spectral resolution allows discriminating smaller features in the spectrum and the unambiguous detection of the absorption bands characteristic of superficial materials. Hyperspectral imagers based on interferometers have the advantage of having a spectral resolution that can be varied according to the needs by changing the optical path delay of the interferometer. A spectrum for each pixel is obtained with an algorithm based on the Fourier transform of the calibrated interferogram. We present the results of the application of a hyperspectral imager based on Fabry‐Perot interferometers to the field of cultural heritage. On different artworks, the hyperspectral imager has been used for pigment recognition, for colour rendering elaborations of the image with different light sources or standard illuminants and for calculating the chromatic coordinates useful for specific purposes.",book:{id:"5411",slug:"fourier-transforms-high-tech-application-and-current-trends",title:"Fourier Transforms",fullTitle:"Fourier Transforms - High-tech Application and Current Trends"},signatures:"Massimo Zucco, Marco Pisani and Tiziana Cavaleri",authors:[{id:"20909",title:"Dr.",name:"Marco Q.",middleName:null,surname:"Pisani",slug:"marco-q.-pisani",fullName:"Marco Q. Pisani"},{id:"20910",title:"Dr.",name:"Massimo E.",middleName:null,surname:"Zucco",slug:"massimo-e.-zucco",fullName:"Massimo E. Zucco"},{id:"194761",title:"Dr.",name:"Tiziana",middleName:null,surname:"Cavaleri",slug:"tiziana-cavaleri",fullName:"Tiziana Cavaleri"}]},{id:"53524",doi:"10.5772/66733",title:"Fourier Analysis for Harmonic Signals in Electrical Power Systems",slug:"fourier-analysis-for-harmonic-signals-in-electrical-power-systems",totalDownloads:4493,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"The harmonic content in electrical power systems is an increasingly worrying issue since the proliferation of nonlinear loads results in power quality problems as the harmonics is more apparent. In this paper, we analyze the behavior of the harmonics in the electrical power systems such as cables, transmission lines, capacitors, transformers, and rotating machines, the induction machine being the object of our study when it is excited to nonsinusoidal operating conditions in the stator winding. For this, a model is proposed for the harmonic analysis of the induction machine in steady‐state regimen applying the Fourier transform. The results of the proposed model are validated by experimental tests which gave good results for each case study concluding in a model proper for harmonic and nonharmonic analysis of the induction machine and for “harmonic” analysis in an electrical power system.",book:{id:"5411",slug:"fourier-transforms-high-tech-application-and-current-trends",title:"Fourier Transforms",fullTitle:"Fourier Transforms - High-tech Application and Current Trends"},signatures:"Emmanuel Hernández Mayoral, Miguel Angel Hernández López,\nEdwin Román Hernández, Hugo Jorge Cortina Marrero, José\nRafael Dorrego Portela and Victor Ivan Moreno Oliva",authors:[{id:"187793",title:"Dr.",name:"Emmanuel",middleName:null,surname:"Hernández",slug:"emmanuel-hernandez",fullName:"Emmanuel Hernández"},{id:"202757",title:"Dr.",name:"Miguel Angel",middleName:null,surname:"Hernández López",slug:"miguel-angel-hernandez-lopez",fullName:"Miguel Angel Hernández López"},{id:"202758",title:"Dr.",name:"Hugo Jorge",middleName:null,surname:"Cortina Marrero",slug:"hugo-jorge-cortina-marrero",fullName:"Hugo Jorge Cortina Marrero"},{id:"202759",title:"Dr.",name:"Edwin Román",middleName:null,surname:"Hernández",slug:"edwin-roman-hernandez",fullName:"Edwin Román Hernández"},{id:"202760",title:"Dr.",name:"Victor Iván Moreno",middleName:null,surname:"Oliva",slug:"victor-ivan-moreno-oliva",fullName:"Victor Iván Moreno Oliva"},{id:"202761",title:"Dr.",name:"José Rafael Dorrego",middleName:null,surname:"Portela",slug:"jose-rafael-dorrego-portela",fullName:"José Rafael Dorrego Portela"}]}],mostDownloadedChaptersLast30Days:[{id:"74096",title:"Time Frequency Analysis of Wavelet and Fourier Transform",slug:"time-frequency-analysis-of-wavelet-and-fourier-transform",totalDownloads:1162,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"Signal processing has long been dominated by the Fourier transform. However, there is an alternate transform that has gained popularity recently and that is the wavelet transform. The wavelet transform has a long history starting in 1910 when Alfred Haar created it as an alternative to the Fourier transform. In 1940 Norman Ricker created the first continuous wavelet and proposed the term wavelet. Work in the field has proceeded in fits and starts across many different disciplines, until the 1990’s when the discrete wavelet transform was developed by Ingrid Daubechies. While the Fourier transform creates a representation of the signal in the frequency domain, the wavelet transform creates a representation of the signal in both the time and frequency domain, thereby allowing efficient access of localized information about the signal.",book:{id:"10065",slug:"wavelet-theory",title:"Wavelet Theory",fullTitle:"Wavelet Theory"},signatures:"Karlton Wirsing",authors:[{id:"325178",title:"Dr.",name:"Karlton",middleName:null,surname:"Wirsing",slug:"karlton-wirsing",fullName:"Karlton Wirsing"}]},{id:"74032",title:"Wavelets for EEG Analysis",slug:"wavelets-for-eeg-analysis",totalDownloads:1157,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"This chapter introduces the applications of wavelet for Electroencephalogram (EEG) signal analysis. First, the overview of EEG signal is discussed to the recording of raw EEG and widely used frequency bands in EEG studies. The chapter then progresses to discuss the common artefacts that contaminate EEG signal while recording. With a short overview of wavelet analysis techniques, namely; Continues Wavelet Transform (CWT), Discrete Wavelet Transform (DWT), and Wavelet Packet Decomposition (WPD), the chapter demonstrates the richness of CWT over conventional time-frequency analysis technique e.g. Short-Time Fourier Transform. Lastly, artefact removal algorithms based on Independent Component Analysis (ICA) and wavelet are discussed and a comparative analysis is demonstrated. The techniques covered in this chapter show that wavelet analysis is well-suited for EEG signals for describing time-localised event. Due to similar nature, wavelet analysis is also suitable for other biomedical signals such as Electrocardiogram and Electromyogram.",book:{id:"10065",slug:"wavelet-theory",title:"Wavelet Theory",fullTitle:"Wavelet Theory"},signatures:"Nikesh Bajaj",authors:[{id:"326400",title:"Dr.",name:"Nikesh",middleName:null,surname:"Bajaj",slug:"nikesh-bajaj",fullName:"Nikesh Bajaj"}]},{id:"53524",title:"Fourier Analysis for Harmonic Signals in Electrical Power Systems",slug:"fourier-analysis-for-harmonic-signals-in-electrical-power-systems",totalDownloads:4493,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"The harmonic content in electrical power systems is an increasingly worrying issue since the proliferation of nonlinear loads results in power quality problems as the harmonics is more apparent. In this paper, we analyze the behavior of the harmonics in the electrical power systems such as cables, transmission lines, capacitors, transformers, and rotating machines, the induction machine being the object of our study when it is excited to nonsinusoidal operating conditions in the stator winding. For this, a model is proposed for the harmonic analysis of the induction machine in steady‐state regimen applying the Fourier transform. The results of the proposed model are validated by experimental tests which gave good results for each case study concluding in a model proper for harmonic and nonharmonic analysis of the induction machine and for “harmonic” analysis in an electrical power system.",book:{id:"5411",slug:"fourier-transforms-high-tech-application-and-current-trends",title:"Fourier Transforms",fullTitle:"Fourier Transforms - High-tech Application and Current Trends"},signatures:"Emmanuel Hernández Mayoral, Miguel Angel Hernández López,\nEdwin Román Hernández, Hugo Jorge Cortina Marrero, José\nRafael Dorrego Portela and Victor Ivan Moreno Oliva",authors:[{id:"187793",title:"Dr.",name:"Emmanuel",middleName:null,surname:"Hernández",slug:"emmanuel-hernandez",fullName:"Emmanuel Hernández"},{id:"202757",title:"Dr.",name:"Miguel Angel",middleName:null,surname:"Hernández López",slug:"miguel-angel-hernandez-lopez",fullName:"Miguel Angel Hernández López"},{id:"202758",title:"Dr.",name:"Hugo Jorge",middleName:null,surname:"Cortina Marrero",slug:"hugo-jorge-cortina-marrero",fullName:"Hugo Jorge Cortina Marrero"},{id:"202759",title:"Dr.",name:"Edwin Román",middleName:null,surname:"Hernández",slug:"edwin-roman-hernandez",fullName:"Edwin Román Hernández"},{id:"202760",title:"Dr.",name:"Victor Iván Moreno",middleName:null,surname:"Oliva",slug:"victor-ivan-moreno-oliva",fullName:"Victor Iván Moreno Oliva"},{id:"202761",title:"Dr.",name:"José Rafael Dorrego",middleName:null,surname:"Portela",slug:"jose-rafael-dorrego-portela",fullName:"José Rafael Dorrego Portela"}]},{id:"53366",title:"New Spectral Applications of the Fourier Transforms in Medicine, Biological and Biomedical Fields",slug:"new-spectral-applications-of-the-fourier-transforms-in-medicine-biological-and-biomedical-fields",totalDownloads:2340,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter reviews some recent spectral applications of the Fourier transform techniques as they are applied in spectroscopy. An overview about Fourier transform spectroscopy (FTS) used like a powerful and sensitive tool in medical, biological, and biomedical analysis is provided. The advanced spectroscopic techniques of FTS, such as Fourier transform visible spectroscopy (FTVS), Fourier transform infrared-attenuated total reflectance (FTIR-ATR), Fourier transform infrared-photoacoustic spectroscopy (FTIR-PAS), Fourier transform infrared imaging spectroscopy (FTIR imaging), and their biomedical applications are described. A special attention has been paid to the description of the FTVS method of commercial quantum dots like an innovative and reliable technique used in the field of nanobiotechnology.",book:{id:"5411",slug:"fourier-transforms-high-tech-application-and-current-trends",title:"Fourier Transforms",fullTitle:"Fourier Transforms - High-tech Application and Current Trends"},signatures:"Anca Armăşelu",authors:[{id:"189080",title:"Dr.",name:"Anca",middleName:null,surname:"Armăşelu",slug:"anca-armaselu",fullName:"Anca Armăşelu"}]},{id:"53419",title:"Fourier Transform Infrared Spectroscopy in the Study of Hydrated Biological Macromolecules",slug:"fourier-transform-infrared-spectroscopy-in-the-study-of-hydrated-biological-macromolecules",totalDownloads:2442,totalCrossrefCites:3,totalDimensionsCites:15,abstract:"The interaction between biological macromolecules (proteins, nucleic acids, lipids and other biomolecules in the cell) and environmental water is an important determining factor in their conformational properties, stability and function. The hydration processes of biopolymers have been extensively studied in the past 20 years with reference to a considerable variety of models and concepts. In all recent works, a distinction is made between intracellular water that maintains the ordinary liquid state (bulk water) and water ordered in extended hydrogen‐bonded lattices at the surface and structured in the internal grooves of macromolecules (hydration water) in dependence on the chemical properties of the macromolecule surface. FTIR spectroscopy has been implemented in this field both for the sensitivity in the conformational analysis of biological macromolecules and the reliability in the investigation of the water network. A perturbation technique such as dehydration‐rehydration treatment modifies the macromolecule structure and water distribution. It was applied to two structurally different proteins: lysozyme, a globular (α + β) protein and collagen, a fibrous protein characterized by the triple helix structure. Submitted to the treatment both of them display irreversible conformational changes.",book:{id:"5411",slug:"fourier-transforms-high-tech-application-and-current-trends",title:"Fourier Transforms",fullTitle:"Fourier Transforms - High-tech Application and Current Trends"},signatures:"Maria Grazia Bridelli",authors:[{id:"108760",title:"Dr.",name:"Maria Grazia",middleName:null,surname:"Bridelli",slug:"maria-grazia-bridelli",fullName:"Maria Grazia Bridelli"}]}],onlineFirstChaptersFilter:{topicId:"974",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:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,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:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems. \r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
",coverUrl:"https://cdn.intechopen.com/series/covers/25.jpg",latestPublicationDate:"April 13th, 2022",hasOnlineFirst:!1,numberOfPublishedBooks:1,editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",slug:"j.-kevin-summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. Dr. Summers holds a BA in Zoology and Psychology, an MA in Ecology, and Ph.D. in Systems Ecology/Biology.",institutionString:null,institution:{name:"Environmental Protection Agency",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"38",title:"Pollution",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",isOpenForSubmission:!0,annualVolume:11966,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"39",title:"Environmental Resilience and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",isOpenForSubmission:!0,annualVolume:11967,editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",slug:"jose-navarro-pedreno",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",biography:"Full professor at University Miguel Hernández of Elche, Spain, previously working at the University of Alicante, Autonomous University of Madrid and Polytechnic University of Valencia. Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. Prof. Navarro-Pedreño is also a director of the Ph.D. Program Environment and Sustainability (2012-present) and a member of several societies among which are the Spanish Society of Soil Science, International Union of Soil Sciences, European Society for Soil Conservation, DessertNet and the Spanish Royal Society of Chemistry.",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null},{id:"40",title:"Ecosystems and Biodiversity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/40.jpg",isOpenForSubmission:!0,annualVolume:11968,editor:{id:"209149",title:"Prof.",name:"Salustiano",middleName:null,surname:"Mato",slug:"salustiano-mato",fullName:"Salustiano Mato",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLREQA4/Profile_Picture_2022-03-31T10:23:50.png",biography:"Salustiano Mato de la Iglesia (Santiago de Compostela, 1960) is a doctor in biology from the University of Santiago and a Professor of zoology at the Department of Ecology and Animal Biology at the University of Vigo. He has developed his research activity in the fields of fauna and soil ecology, and in the treatment of organic waste, having been the founder and principal investigator of the Environmental Biotechnology Group of the University of Vigo.\r\nHis research activity in the field of Environmental Biotechnology has been focused on the development of novel organic waste treatment systems through composting. The result of this line of work are three invention patents and various scientific and technical publications in prestigious international journals.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorTwo:{id:"60498",title:"Prof.",name:"Josefina",middleName:null,surname:"Garrido",slug:"josefina-garrido",fullName:"Josefina Garrido",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRj1VQAS/Profile_Picture_2022-03-31T10:06:51.jpg",biography:"Josefina Garrido González (Paradela de Abeleda, Ourense 1959), is a doctor in biology from the University of León and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. She has focused her research activity on the taxonomy, fauna and ecology of aquatic beetles, in addition to other lines of research such as the conservation of biodiversity in freshwater ecosystems; conservation of protected areas (Red Natura 2000) and assessment of the effectiveness of wetlands as priority areas for the conservation of aquatic invertebrates; studies of water quality in freshwater ecosystems through biological indicators and physicochemical parameters; surveillance and research of vector arthropods and invasive alien species.",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorThree:{id:"464288",title:"Dr.",name:"Francisco",middleName:null,surname:"Ramil",slug:"francisco-ramil",fullName:"Francisco Ramil",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003RI7lHQAT/Profile_Picture_2022-03-31T10:15:35.png",biography:"Fran Ramil Blanco (Porto de Espasante, A Coruña, 1960), is a doctor in biology from the University of Santiago de Compostela and a Professor of Zoology at the Department of Ecology and Animal Biology at the University of Vigo. His research activity is linked to the taxonomy, fauna and ecology of marine benthic invertebrates and especially the Cnidarian group. Since 2004, he has been part of the EcoAfrik project, aimed at the study, protection and conservation of biodiversity and benthic habitats in West Africa. 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Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/418628",hash:"",query:{},params:{id:"418628"},fullPath:"/profiles/418628",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()