\r\n\tsandwiches, etc.
\r\n\r\n\tListeria monocytogenes causes one of the most serious and life-threatening diseases (listeriosis), usually caused by eating food contaminated with Listeria monocytogenes. An estimate of 1,600 people get sick (especially at risk-groups including pregnant women, newborns, old people (65 years old and above), people with weakened immune systems, etc.) and about 260 die (Listeria is the third leading cause of death from foodborne illness in the U.S.) each year, in the U.S. from Listeriosis.
\r\n\t
\r\n\tThe main goal of the book is to provide accurate and updated information on Listeria monocytogenes so governments (decision-makers), food industry, consumers, and other stakeholders can implement appropriate preventative measures to control Listeria monocytogenes. This book will cover several topics including the prevalence of Listeria monocytogenes in developed countries, the prevalence of Listeria monocytogenes in developing countries, the prevalence of Listeria monocytogenes in ready-to-eat food, detection of Listeria monocytogenes in Food, control of Listeria monocytogenes in food-processing facilities, etc.
As one of the major health problems in the world, diabetes affects over 346 million people worldwide. In United States alone, according to the statistical fact sheet released 2011 by American Diabetes Association, 25.8 million children and adults accounting for 8.3% of the population are affected by diabetes. Unfortunately, the therapy of diabetes remains unsatisfied despite of extensive studies in the last decades. Diabetes can be categorized into two main types: type 1 and type 2. Type 1 diabetes mellitus, used to known as juvenile diabetes, is typically developed in children and juveniles. Despite the increasing rate of Type 2 diabetes in the United States, type 1 diabetes accounts for over 2/3 of new adolescent diabetes diagnoses. Although most commonly presented in childhood, type 1 diabetes also accounts for 5-10% cases of adult diabetes (1). Recent epidemiologic studies revealed that the incidence for type 1 diabetes in most regions of the world has increased by 2-5% (2).
Unlike type 2 diabetes, which is caused by the loss of insulin sensitivity, type 1 diabetes is caused by insulin deficiency following destruction of insulin-producing pancreatic β cells. Autoimmune-mediated β cell death has been considered as the major cause of β-cell loss in type 1 diabetes. However, the underlying mechanisms are not fully understood. Accumulating evidence suggests an involvement of endoplasmic reticulum (ER) stress in multiple biological processes during the development of type 1 diabetes. Pancreatic β cells exhibit exquisite sensitivity to ER stress due to their high development in order to secrete large amounts of insulin. There is also evidence supporting that ER stress regulates the immune cell functionality and cytokine production that is relevant to autoimmune processes in type 1 diabetes. Furthermore, β cell loss caused by autoimmune attack results in an increased ER burden on the rest pancreatic β cells and induces unfolded protein response (UPR) and ER stress, which further exacerbates β cell death. Here I will summarize the functional involvement of ER stress in the pathogenesis of type 1 diabetes and the potential underlying mechanisms.
The major cause of type 1 diabetes is loss of insulin-secreting pancreatic β cell and insulin inadequacy (3;4). For a better understanding of the pathogenesis of type 1 diabetes, the regulatory mechanisms of blood glucose by pancreaswill briefly introduced. Blood glucose level is closely regulated in order to provide a homeostatic microenvironment for tissues and organs. According to the American Diabetes Association, a normal fasting blood glucose level is between 70 to 100 mg/dL, and the recommended fasting level is to aim for 70 to 130 mg/dL and less than 180 mg/dL after meals (5). Blood glucose is monitored by the cells in the islets of Langerhans (6). Islets of Langerhans are clusters of pancreatic cells that execute the endocrine function of pancreas. They contain the following 4 types of cells, in order of abundance: β cells, α cells, δ cells, and γ cells. Pancreatic β cells and α cells make up about 70% and 17% of islet cells respectively, and both of them are responsible for the blood glucose regulation by producing insulin (β cells) and glucagon (α cells) (6). Pancreatic δ cells produce somatostatin which has a major inhibitory effect, including on pancreatic juice production. Pancreatic γ cells secrete pancreatic polypeptide that is responsible for reducing appetite.
Insulin and glucagon have opposite functions on glucose regulation. They keep blood glucose level in a normal range by coordinating with each other (Figure 1). After a meal, the digestive system breaks down the carbohydrates to small sugar molecules, mainly glucose. The glucose is then absorbed across the intestinal wall and travel to the circulating bloodstream. Pancreatic β cells sense increased blood glucose level by taking up glucose through GLUT2, a glucose transporter. The metabolism of glucose in β cells leads to the increase of ATP/ADP ratio, which causes the closing of ATP-sensitive potassium channels and further leads to the open of calcium channels on membrane. The resulting increase of intracellular calcium concentration promotes the secretion of insulin into circulation of blood. Circulating insulin then acts on cells in a variety of tissues including liver, muscle, and fat through interacting with insulin receptor on the cell membrane. Insulin signaling induces the translocation of glucose transporter GLUT4 to cell membrane of muscle cells and adipocytes, leading to the uptake of glucose into cells as an energy source. In addition, insulin signaling also stimulates the conversion of glucose into glycogen, a process called glycogenesis, in liver. Therefore, insulin lowers blood glucose level by promoting glycogenesis and glucose uptake by peripheral tissues (7). In contrast, a drop in blood glucose caused by starving or other situations like extreme exercise suppresses the secretion of insulin by β cells and stimulates α cells of pancreas to release glucagon. Glucagon acts on liver and promotes glucose production by the breakdown of glycogen to glucose (called glycogenolysis), resulting in the increase of blood glucose.
Homeostatic regulation of blood glucose by pancreas. Pancreas is the major organ responsible for maintaining the blood glucose homeostasis. Increase of blood glucose level can be sensed by GLUT2 on β cells, a glucose transporter. The metabolism of glucose in β cells promotes the secretion of insulin into circulation of blood. Circulating insulin then increases the glucose uptake by a variety of tissues including liver, muscle, and fat. In liver, insulin signaling also stimulates the conversion of glucose into glycogen, a process called glycogenesis. Both glycogenesis and glucose uptake by peripheral tissues can lead to a decrease of glucose level in blood stream. In contrast, a drop of blood glucose level suppresses the secretion of insulin by β cells and stimulates α cells to release glucagon. Glucagon acts on liver and promotes glucose production by the breakdown of glycogen to glucose, a process called glycogenolysis, and results in the increase of blood glucose.
Either insulin deficiency or insulin inefficiency can cause diabetes. As the only cell type producing insulin, β cell plays a critical role in the development of diabetes. In type 1 diabetes, autoimmune-mediated destruction of β cell leads to insufficient insulin production and inability of cells to take up glucose. In contrast, type 2 diabetes is caused by loss of insulin sensitivity. In response to insulin resistance, the body secretes more insulin to overcome the impaired insulin action. However, pancreatic β cells fail to secrete sufficient insulin to overcome insulin resistance in some individuals, resulting in type 2 diabetes (8;9). Therefore, dysfunction of β cell exists in both types of diabetes.
Pancreatic β cell is specialized for production of insulin to control blood glucose level. In response to hyperglycemia, insulin is secreted from a readily available pool in β cells. In the meantime, the secretion of insulin activates the biosynthesis of insulin (10). Insulin is first synthesized as preproinsulin with a signal peptide in the ribosomes of the rough endoplasmic reticulum. Preproinsulin is translocated into ER lumen by interaction of signal peptide with signal recognition particle on the ER membrane. Preproinsulin is converted to proinsulin by removing the signal peptide forming three disulfide bonds in the ER. Proinsulin is then translocated into Golgi apparatus and packaged into secretory granules that are close to the cell membrane. In the secretory granules, proinsulin is cleaved into equal amounts of insulin and C-peptide (Figure 2). Insulin is accumulated and stored in the secretory granules. When the β cell is appropriately stimulated, insulin is secreted from the cell by exocytosis (11). As the major site for protein synthesis, ER plays an important role in insulin biosynthesis. To fulfill the requirement for secreting large amount of insulin, the pancreatic β cells are equipped with highly developed ER, leading to the vulnerability of β cell to ER stress (12). In type 1 diabetes, the loss of β cell increases the burden of insulin secretion on the residual β cells. On the on hand, this compensated action is beneficial for the control of blood glucose. On the other hand, it also increases the ER burden of residual β cells, which further exacerbates β cell death.
Biosynthesis of insulin in β cell. In the ribosomes of rough endoplasmic reticulum, insulin is first synthesized as a precursor, preproinsulin. Preproinsulin has a signal peptide that directs it to translocate into ER lumen by interacting with signal recognition particle on the ER membrane. In ER lumen, preproinsulin is converted to proinsulin by removing the signal peptide and forming three disulfide bonds. Proinsulin is then translocated into Golgi apparatus and packaged into secretory granules where it is cleaved into equal amounts of insulin and C-peptide. After synthesis, insulin is stored in the secretory granules and secreted from the cell until the β cell is appropriately stimulated.
Endoplasmic Reticulum (ER) is an organelle of eukaryotic cells that is responsible for the facilitation of protein folding and assembly (13-15), manufacture of the membranes(16), biosynthesis of lipid and sterol, storage of intracellular Ca2+, and transport of synthesized proteins in cisternae.It is a membranous network of tubules, vesicles, and cisternae that are interconnected by the cytoskeleton.The ER is well developed in endocrine cells such as β cell in which large amounts of secretory proteins are synthesized.
ER is categorized into two types: rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER). As featured by its name, RER looks bumpy and rough under a microscope due to the ribosomes on the outer surfaces of the cisternae. RER is in charge for protein synthesis. The newly synthesized proteins are folded into 3-dimensional structure in RER and sent to Golgi complex or membrane via small vesicles. In contrast, SER appears to have a smooth surface under the microscope as it does not have ribosomes on its cisternae. SER is responsible for the synthesis of lipids and steroids, regulation of calcium concentration, attachment of receptors on cell membrane proteins, and detoxification of drugs. It is found commonly in places such as in the liver and muscle. It is important for the liver to detoxify poisonous substances. Sarcoplasmic reticulum is a special type of SER. It is found in smooth and striated muscle, and is important for the regulation of calcium levels. It sequesters a large store of calcium and releases them when the muscle cell is stimulated.
ER stress is defined as the cellular responses to the disturbances of normal function of ER. The most common cause of ER stress is protein mis-folding. ER is the place where newly produced proteins fold into 3-dimensional conformation which is essential for their biological function. The sensitive folding environment could be disturbed by a variety of pathological insults like environmental toxins, viral infection, and inflammation. In addition to pathological insults, it can also be induce by many physiological processes such as overloaded protein biosynthesis on ER, For example, in case of type 1 diabetes, increased insulin synthesis in residual β cell exceeds the folding capacity of ER, resulting in the accumulation of unfolded insulin. The accumulation of unfolded or mis-folded proteins in the ER leads a protective pathway to restore ER function, termed as unfolded protein response (UPR).
Protein folding requires a serial of ER-resident protein folding machinery. A special type of proteins called chaperones is used as a quality control mechanism in the ER. As the major mechanisms to promote protein folding, chaperones assist protein folding by interacting with the newly synthesized proteins.In addition,chaperones also help to break down unfolded or incorrectly folded proteins in the ER via a process called ER associated degradation.The monitoring mechanism ensures the correct protein folding in the ER. The unfolded proteins usually have a higher number of hydrophobic surface patches than that of proteins with native conformation (17). Thus, unfolded proteins are prone to aggregate with each other in a crowed environment and directed to degradative pathway (18). Molecular chaperones in the ER preferentially interact with hydrophobic surface patches on unfolded proteins and create a private folding environment by preventing unfolded proteins from interaction and aggregation with other unfolded proteins. In addition, the concentration of Ca2+ in ER also impairs protein folding by inhibiting the activity of ER-resident chaperones and foldases (19-22). ER is the major site for Ca2+ storage in mammalian cells. The concentration of Ca2+ in ER is thousands times higher than that in the cytosol (23). Most chaperones and foldases in ER are vigorous Ca2+ binding proteins. Their activity, therefore, is affected by the concentration of Ca2+ in ER.
Exhaustion of the protein folding machineries or insufficient energy supply increases the accumulation of unfolded or mis-folded proteins in ER, which is responsible for the activation of UPR. UPR is a protective mechanism by which it monitors and maintains the homeostasis of ER. Various physiological and pathological insults such as increased protein synthesis, failure of posttranslational modifications, nutrient/glucose starvation, hypoxia, and alterations in calcium homeostasis, can result in the accumulation of unfolded or mis-folded proteins in ER which further causes ER stress (24).For example, altered expression of antithrombin III (25;26) or blood coagulation factor VIII (27;28), may result in the exhaustion of protein folding machinery and thus induces UPR. Some physiological processes such as the differentiation of B lymphocytes into plasma cells along with the development of highly specialized secretory capacity can also cause unfolded protein accumulation and activate UPR (29-31). In response to those physiological and pathological insults, cells initiate UPR process to get rid of the unfolded or mis-folded proteins. For instance, UPR can increase the folding capacity by up-regulating ER chaperones and foldases, as well as attenuate the biosynthetic burden through down-regulating the expression of secreted proteins (32-34). In addition, UPR also eliminates unfolded or mis-folded proteins by activating ER associated degradation process (35-37). However, once the stress is beyond the compensatory capacity of UPR, the cells would undergo apoptosis. As such, UPR and ER stress are reported to be implicated in a variety of pathological processes, including diabetes, neurodegenerative diseases, pathogenic infections, atherosclerosis, and ischemia (24;38).
In addition to protein folding, a variety of post-translational modifications including N-linked glycosylation, disulfide bond formation, lipidation, hydroxylation, and oligomerization, occur in ER. Disruption of those post-translational modifications can also result in the accumulation of incorrectly folded proteins and thereby induce UPR or ER stress. For example, glucose deprivation impairs the process for N-linked protein glycosylation and thus leads to ER stress (39).
As a protective mechanism during ER stress, UPR initiates a variety of process to ensure the homeostasis of ER. UPR can be mediated by three major pathways, which are initiated by the three transmembrane signaling proteins located on the ER membrane. Those transmembrane proteins function as a bridge linking cytosol and ER with their C-terminal in the cytosol and N-terminal in the ER lumen. The N-terminal is usually engaged by an ER resident chaperone BiP (Grp78) to avoid aggregation. When unfolded proteins accumulate in ER, chaperons are occupied by unfolded proteins and release those transmembrane signaling proteins. There are three axes of signals that are initiated by the pancreatic endoplasmic reticulum kinase (PERK), the inositol-requiring enzyme 1 (IRE1), and the activating transcription factor 6 (ATF6) respectively. The release of these proteins from BiP triggers UPR and ER stress (Figure 3).
UPR signal pathways. Under normal condition, PERK, IRE1, and ATF6 binding to the ER chaperone BiP to remain inactive state. Upon the accumulation of unfolded proteins, BiP preferentially binds to the unfolded proteins, leading to the release of PERK, IRE1, and ATF6. PERK becomes oligomerized and activated once released from BiP, and subsequently phosphorylates eIF2α. The phosphorylation of eIF2α results in the suppression of the overall transcription of mRNAs and selectively enhanced transcription of genes implicated in UPR such as the ATF4 mRNA. Similar to PERK, IRE1 is dimerized and activated after released from BiP. Activated IRE1 induces XBP-1 by enhancing the splicing of its mRNA. XBP-1 enhances UPR by regulating the transcription of its target genes. The detachment of ATF6 from BiP results in the translocation of ATF6 to the Golgi apparatus and cleavage of ATF6. Cleaved ATF6 then translocates into the nucleus and initiates the transcription of target genes.
PERK/eIF2α/ATF4 axis: PERK is a type I transmembrane Ser/Thr protein kinase uniquely present in ER. In response to ER stress, the binding of unfolded proteins to BiP leads to the release of PERK from BiP. Once released from BiP, PERK becomes oligomerized and autophosphorylated. As a result, PERK inactivates eukaryotic initiation factor 2α (eIF2α) by the phosphorylation of Ser51 to inhibit mRNA translation and protein load on ER (34;40). In addition, phosphorylated eIF2α also promotes the expression of stress-induced genes including the transcription factors ATF4 and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) (41). Deficiency of PERK results in an abnormally elevated protein synthesis in response to the accumulation of unfolded proteins in ER.
IRE1/XBP-1 axis: IRE1 is another axis of signal involved in UPR. There are 2 isoforms of IRE1: IRE1α and IRE1β. IRE1α is expressed in most cells and tissues, while IRE1β is restricted in intestinal epithelial cells (42;43). Once disassociated with BiP, IRE1 becomes activated. Activated IRE1 possesses endoribonuclease activity and cleaves 26 nucleotides from the mRNA encoding X-box binding protein-1 (XBP-1), resulting in the increased production of XBP-1 (44). XBP-1 is a transcriptional factor belonging to basic leucine zipper transcription factorfamily. It heterodimerizes with NF-Y and enhances gene transcription by binding to the ER stress enhancer and unfolded protein response element in the promoters of targeted genes involved in ER expansion, protein maturation, folding and export from the ER, and degradation of mis-folded proteins (44-49). In addition, IRE1α also mediates the degradation of ER-targeted mRNAs, thus decreasing the ER burden (50).
ATF6 axis: The third axis of ER stress signal is mediated by ATF6. Unlike PERK and IRE1 which oligomerize upon UPR, ATF6 translocates into the Golgi apparatus after released from BiP. The transmembrane domain is then cleaved in the Golgi apparatus (51). The 50-kDa cleaved ATF6 is relocated into the nucleus where it binds to the ER stress response element CCAAT(N)9CCACG to regulate the expression of targeted genes. For example, once released from the ER membrane, ATF6 enhances the transcription of XBP-1 mRNA which is further regulated by IRE1 (44). In addition, ATF6 also increases the expression of the two major chaperon systems in the ER: calnexin/calreticulin and BiP/GRP94 (44;52;53).
The importance of innate immunity was highlighted in the pathophysiology of type 1 diabetes (54-57). Type 1 diabetes was initially considered a T-cell-mediated autoimmune disease (58), in which T-cell was believed as the major immune cell causing β cell destruction while the involvement of innate immune response has been ignored for a long time. However, recent studies suggest a critical role of innate immune responses in the development of type 1 diabetes (54;55). As the first line of defense mechanism, innate immunity is implicated in the initiation as well as the progression of autoimmune responses against pancreatic β cell.
Innate immune response is regulated by elements of the UPR pathway (59). For example, Cyclic-AMP-responsive-element-binding protein H(CREBH), an ER stress-associated transcription factor, regulates the expression of serum amyloid P-component and C-reactive protein, the two critical factors implicated in innate immune responses. Like ATF6, CREBH is an ER-membrane-bound protein. In response to ER stress, CREBH release an N-terminal fragment and transit to nucleus to regulate the expression of target genes. Innate immune response, in turn, regulates the expression of CREBH through inflammatory cytokines such as IL-1β and IL-6 (60). The development of dendritic cells, the major innate immune cells, is also regulated by ER stress response (61). High levels of mRNA splicing for XBP-1 are found in dendritic cell, and mice deficient in XBP-1 show defective differentiation of dendritic cell. Both conventional (CD11b+ CD11c+
) and plasmacytoid dendritic cells (B220+ CD11c+The association of ER stress with innate immune response is confirmed in many disease models. Richardson and coworkers reported that innate immune response induced by P. aeruginosa infection causes ER stress in C. elegans, and loss-of-function mutations of XBP-1 lead to larval lethality (63). In consistent with that, polymorphisms of XBP-1 gene were found to be associated with Crohn’s disease and ulcerative colitis in humans (64), the two autoimmune diseases share similar properties with type 1 diabetes. Lack of XBP-1 in intestinal epithelial cells may induce Paneth cell dysfunction which further results in impaired mucosal defense to Listeria monocytogenes and increased sensitivity to colitis (64).
In addition to IRE1/XBP-1 axis, PERK/eIF2α/ATF4 axis of UPR is also associated with innate response. TLR signaling, the most important innate signaling pathway, can induce selective suppression of the PERK/eIF2α/ATF-4/CHOP axis of UPR pathway (65). The activation of TLR decreases eIF2α-induced ATF4 translation. For instance, pretreatment of LPS, an agonist for TLR4, attenuated ATF4/CHOP signaling and prevented systemic ER stress-induced apoptosis in macrophages, renal tubule cells, and hepatocytes (65). In contrast, loss of Toll-IL-1R-containing adaptor inducing IFN-β (TRIF), an important adapter for TLR signaling, abrogated the protective effect of LPS on renal dysfunction and hepatosteatosis induced by ER stress, suggesting that TLR signaling suppresses ATF4/CHOP via a TRIF-dependent pathway (65).
The presence of β cell specific autoantibodies is a marker for autoimmune diabetes (66). IRE1/XBP1 axis is required for the differentiation of antibody-producing B lymphocytes. IRE1 is necessary for the Ig gene rearrangement, production of B cell receptors, and lymphopoiesis. The expression multiple UPR components including BiP, GRP94, and XBP-1 is up-regulated during the differentiation of B cells (67). Mice with a deficiency of IRE1 in hematopoietic cells have a defective differentiation of pro-B cells towards pre-B cells (68). XBP-1, an IRE1 downstream molecule, is also involved in the differentiation of B cell and antibody production by mature B cells. It was found that the engagement of B-cell receptor induces ubiquitin-mediated degradation of BCL-6, a repressor for B-lymphocyte-induced maturation protein 1 (69), while B-lymphocyte-induced maturation protein 1 negatively regulates the expression of B-cell-lineage-specific activator protein (70), a repressor for XBP-1 (71). In line with these results, B lymphocytes deficient in B-lymphocyte-induced maturation protein 1 failed to express XBP-1 in response to LPS stimulation (72). The expression of XBP-1 is rapidly up-regulated when B cells differentiate into plasma cells. Furthermore, XBP-1is able to initiate plasma cell differentiation when introduced into B-lineage cells. XBP-1-deficient lymphoid chimeras have a defective B-cell-dependent immune response due to the absence of immunoglobulin and plasma cells (30). In addition to IRE1/XBP-1 axis, ATF6 axis may also implicated in the differentiation of B cells, as increased ATF6 cleavage is found in differentiating B cells (67). However, PERK axis does not seem to be involved in the B-cell differentiation and maturation (68;73).
Activation of T lymphocyte, another important adaptive immune cell, seems also involves UPR. TCR engagement, the first T cell activation signal, induces the expression of ER chaperons including BiP and GRP94. Inhibition of protein kinase C, a serine/threonine protein kinase downstream of TCR signaling, suppresses the activation of ER stress response induced by T cell activation (74). IRE1/XBP-1 axis regulates the differentiation of effector CD8+ T cell. IRE1/XBP-1 pathway is activated in effector CD8+ T cell during acute infection. IL-2 promotes XBP-1 mRNA transcription, while TCR ligation induces the splicing of XBP-1 mRNA. The differentiation of CD8+ T cell is reduced by suppression of XBP-1 (75). Other than IRE1/XBP-1, CHOP is also involved in the functionality of T cells. A recent report suggests GTPase of the immunity-associated protein 5 (Gimap5) mutation in BioBreeding diabetes-prone rat, a model for type 1 diabetes, leads to ER stress and thus induces spontaneous apoptosis of T cells. Inhibition of CHOP protects Gimap5-/- T cells from ER stress-induced apoptosis (76).
Cytokine production is an important inflammatory process in response to insults of pathogens, mutated self-antigens or tissue damage. ER stress is interconnected with the induction of inflammatory cytokines through multiple mechanisms including reactive oxygen species (ROS), NFκB and JNK (Figure 4). ROS are defined as highly reactive small molecules with unpaired electrons. They are important mediators of inflammatory response., Oxidative stress, caused by the accumulation of ROS, was confirmed to be associated with ER stress (77). For example, the disulphide bond formation during the process of protein folding requires oxidizing condition (78). Therefore, increased protein folding load may lead to oxidative stress. The PERK axis of UPR is able to activate antioxidant pathway by promoting ATF4 and nuclear factor-erythroid-derived 2-related factor 2 (NRF2) (79;80). Therefore, deficiency of PERK markedly increases ROS accumulation in response to toxic chemicals (79;81). The IRE1 axis of UPR can activate NFκB, a key regulator in inflammation, by recruiting IκB kinase (82). As a result, loss of IRE1 reduces the activation of NFκB activation and production of TNF-α (82). In addition, the IRE1 axis can also activate JNK, and subsequently induce the expression of inflammatory genes by activating activator protein 1 (AP1) (83). ATF6, the third axis of UPR signaling, can also activate NFκB pathway and induce inflammatory response. Therefore, suppression of ATF6 reduces NFκB activation caused by BiP degradation (84).
UPR-mediated inflammatory signaling. UPR regulates inflammation through a variety of mechanisms involving ROS, JNK, and NFκB. PERK promotes ATF4 and NRF2, which then suppress ROS production by activating antioxidant pathway. Upon activation, IRE1/TRAF2 complex recruits IKK (IκB Kinase), leading to the phosphorylation of IκBα and subsequent activation of NFκB. IRE1/TRAF2 can also activate JNK, followed by the activation of AP1. XBP-1 induced by IRE1 can also induce the expression of various genes implicated inflammation. Furthermore, cleaved ATF6 can promote inflammation via activating NFκB.
ER stress regulates the expression of cytokines, while cytokines in turn may also induce ER stress via pathways including inducible nitric oxide synthase (iNOS) and JNK. JNK pathway is activated by IL-1β. Suppression of JNK by its inhibitor SP600125 can protectβ cells from IL-1β-induced apoptosis (85). Inflammatory cytokines induce iNOS expression in β cells and produce copious amount of nitric oxygen (86).Nitric oxygen is an important mediator of β-cell death in type 1 diabetes. Excessive nitric oxygencan induce DNA damage, which leads to β cell apoptosis through p53 pathway or necrosis through poly (ADP-ribose) polymerase pathway (87). In addition, nitric oxygencan also deplete ER Ca2+ stores by activating Ca2+ channels or inhibiting Ca2+ pumps (88-90). Depletion of Ca2+ then leads to the activation of CHOP and induces ER stress and apoptosis of β cells (91;92).
Given the involvement of ER stress in both innate and adaptive immune systems, pathways of ER stress play a role in the autoimmune process of type 1 diabetes. For example, mice deficient in PERK, a molecule responsible for regulating UPR, are extremely susceptible to diabetes. Although the exocrine and endocrine pancreas developed normally, the null mice display a progressive loss of β mass and insulin insufficiency postnatally (93) (93). A severe defect of β cell proliferation and differentiation was also found in PERK null mice, resulting in low pancreatic β mass and proinsulin trafficking defects (94). Consistent with those observations in mice, some infant-onset diabetic cases in humans are confirmed to be associated with the mutations in PERK. For example, loss of EIF2AK3 (the gene encodes PERK) develops Wolcott-Rallison syndrome, an autosomal recessive disorder featured by early infancy insulin-dependency and multiple systemic manifestations including growth retardation, hepatic/renal dysfunction, mental retardation, and cardiovascular abnormalities (86;95). Similarly, disruption of UPR by mutating eIF2α, the downstream molecule of PERK signaling, enhances the sensitivity to ER stress-induced apoptosis and results in defective gluconeogenesis. Mice carrying a homozygous Ser51Ala mutation for eIF2α show multiple defects in pancreatic β cells including the smaller core of insulin-secreting β cells and attenuated insulin secretion (41). Altogether, defects in PERK/eIF2α signaling render β cells highly vulnerable to ER stress in both humans and mice (87;96). In addition to PERK/eIF2α signaling, the other two pathways of ER stress, IRE1 and ATF6, are also implicated in the functionality of β cells. The activation of IRE1 signaling is involved in the insulin biosynthesis induced by hyperglycemia. Transient exposure to high glucose enhances IRE1α phosphorylation without activation of XBP-1 and BiP dissociation. IRE1α activation induced by transient exposure to high glucose induces insulin biosynthesis by up-regulating WFS1, a component involved in UPR and maintaining ER homeostasis (10;97). However, chronic exposure of β cells to high glucose may cause activation of IRE1 but with a different downstream signaling, leading to the suppression of insulin biosynthesis (10). The activation of ATF6 induced by ER stress also suppressed the expression of insulin by up-regulating orphan nuclear receptor small heterodimer partner (98).
Increasing evidence suggests an important role of ER stress in autoimmune-mediated β cell destruction (99;100). It was noted that β cell loss is the direct causing factor for insufficient insulin secretion in type 1 diabetes patients. Pancreatic β cells have a very well-developed ER to fulfill their biological function for secreting insulin and other glycoproteins, causing the high sensitivity of β cells to ER stress and the subsequent UPR. Severe or long-term ER stress would direct β cells undergoing apoptosis (99). As described earlier, all the three pathways of ER stress are important in the execution of β cell function and involved in the autoimmune responses during the process of type 1 diabetes.
Pro-inflammatory cytokines are believed as the major mediators contributing to ER stress in β cell mediated by autoimmune response. Autoreactive immune cells infiltrated in pancreas produce pro-inflammatory cytokines, the primary causing factor for β cell death in type 1 diabetes(101). Autoreactive macrophages and T-lymphocytes present in the pancreatic islets in the early stage of type 1 diabetes and secrete massive pro-inflammatory cytokines including IL-1β, IFN-γ and TNF-α. Pro-inflammatory cytokines have been confirmed as strong inducers of ER stress in pancreatic β cells. Insult of β cells with IL-1β and IFN-γ was reported to induce the expression of death protein 5, a protein involved in the cytokine-induced ER stress and β cell death (102). Suppression of death protein 5 by siRNA provides protection for β cells against pro-inflammatory cytokine-induced ER stress (102). In addition, stimulation of β cells with IL-1β and IFN-γ can decrease the expression of sarcoendoplasmic reticulum pump Ca2+ ATPase 2b, leading to subsequent depletion of Ca2+ in the ER (103). It has been well demonstrated that altered ER Ca2+ concentration induces the accumulation of unfolded proteins in ER associated with the induction of UPR and ER stress in β cells (104). Reactive oxygen species such as nitric oxygen produced during inflammation are believed to play a critical role in ER stress-induced β cell death. Excessive nitric oxygen production during insulitis induces β cell apoptosis in a CHOP-dependent manner (91).
In addition to cytokine-induced ER stress, defective protein processing and trafficking are also a direct cause of ER stress in β cell. For instance, mis-folding of insulin in β cells directly induces chronic ER stress as evidenced by the observations in Akita mice. The mutation of Ins2 gene in Akita mouse disrupts a disulfide bond betweenα and β chain of proinsulin, leading to the mis-folding of the mutated insulin. This mutation therefore induces chronic ER stress in β cells and finally causes diabetes in Akita mouse (105). The inefficiency of protein trafficking from ER to Golgi apparatus also causes ER stress in β cells (106).
Hyperglycemia occurs only when β cells fail to compensate the increased demand for insulin. Therefore, β cells are usually “exhausted” in diabetic patients (87). The increased insulin demandrequires the remaining functional β cellsto increase insulin synthesis to compensate the decrease of β mass. The altered insulin synthesis causes ER stress in the β cells of patients with type 1 diabetes. In later case, this compensation is beneficial for control of blood glucose homeostasisin a short term.However, the long term alterations of insulin synthesis in the β cells also induce ER stress which in turn exacerbates β cell dysfunction and promotes disease progression. Collectively, there is convincing evidence that ER stress plays an essential role in β cell destruction during the course of type 1 diabetes.
The primary purpose of ER stress response is to compensate the damage caused by the disturbances of normal ER function. However, persistence of ER dysfunction would eventually render cells undergoing apoptosis. The mechanisms underlying ER stress induced cell death are not fully elucidated, due to the fact that multiple potential participants involved but little clarity on the dominant death effectors in a particular cellular context. Generally, the process of cell death by ER stress can be illustrated in three phases: adaptation, alarm, and apoptosis (39).
The adaptation response phase is to protect cells from damage induced by the disturbances of ER function and restore the homeostasis of ER. As described earlier, UPR signaling involves three axes of responses: IRE1, PERK, and ATF6. These axes interact between each other and form a feedback regulatory mechanism to control the activity of UPR. The accumulation of unfolded proteins in ER results in the engagement of ER resident chaperon BiP, and as a consequence, IRE1, PERK, and ATF6 are released from BiP. Therefore, over-expression of BiP can prevent cell death induced by oxidative stress, Ca2+ disturbances, and hypoxia (107). Upon ER stress, the transcription of BiP is enhanced by ATF6p50, the cleaved form of ATF6 (108). PERK is oligomerized and phosphorylated upon the release from BiP. Activated PERK inactivates eIF2α to reduce mRNA translation and protein load on ER. Therefore, PERK deficiency results in an abnormally elevated protein synthesis in response to ER stress, and renders cells highly sensitive to ER stress-induced apoptosis (109). Consistently, as a downstream molecule of PERK, eIF2α is required for cell survival upon the insult of ER stress. A mutation at the phosphorylation site of eIF2α (Ser51Ala) abolishes the translational suppression in response to ER stress (41). When released from BiP, IRE1 becomes dimerized and activated. Activated IRE1 then induces XBP-1 by promoting the splicing of its mRNA (44). XBP-1 is responsible for the transcription of many adaptation genes implicated in UPR. Unlike PERK and IRE1, ATF6 translocates into the Golgi apparatus once released from BiP. The transmembrane domain of ATF6 is cleaved in the Golgi apparatus and is then relocated into the nucleus, by which it regulates gene expression (51).
During the alarm phase, many signal pathways are activated to alert the system. For instance, the cytoplasmic part of IRE1 can bind to TNF receptor-associated factor 2 (TRAF2), a key adaptor mediating TNF-induced innate immune response. TRAF2 then activates NFκB pathway via activating IKK and activates the signaling for c-Jun N-terminal kinases (JNK) by apoptosis signal-regulating kinase 1 (Ask1). It is reported that dominant negative TRAF2 suppresses the activation of JNK in response to ER stress (110). In addition, TRAF2 is also a critical component for E3 ubiquitin-protein ligase complex (111). E3 ubiquitin-protein ligase complex binds to Ubc13 and mediates the noncanonical ubiquitination of substrates, which is suggested to be required for the activation of JNK (112). Furthermore, IRE1 can also activate JNK signaling by interacting with c-Jun N-terminal inhibitory kinase (JIK) (113).
Although the purpose of UPR is to maintain the homeostasis of ER, apoptosis could occur when the insult of ER stress exceeds the cellular regulatory capacity. Apoptosis is initiated by the activation of several proteases including caspase-12, caspase-4, caspase-2, and caspase-9. Studies in rodents suggest that caspase-12 is activated by IRE1 and is involved in ER stress-induced apoptosis. Mice deficient for caspase-12 are resistant to ER stress-induced apoptosis, but remain susceptible to apoptosis induced by other stimuli (114). Caspase-12 can also be activated by TRAF2, a downstream molecule of IRE1 (113). In response to ER stress, caspase-7 is translocated from the cytosol to the ER surface, and then activates procaspase-12 (115). Human caspase-4, the closest paralog of rodent caspase-12, can only be activated by ER stress-inducing reagents not by the other apoptotic reagents. Knockdown of caspase-4 by siRNA reduces ER stress-induced apoptosis in neuroblastoma cells, suggesting the involvement of human caspase-4 in ER stress-induced cell death (116). Similarly, caspase-2 and caspase-9 are also activated in the early phase of ER stress. Inhibition of their activation either by inhibitors or siRNA reduces ER stress-induced apoptosis (117). Other than caspase proteins, Ask1 kinase and CHOP are also critical mediators for ER stress-induced cell death. IRE1/TRAF2 complex recruits Ask1 and activates subsequent JNK signaling. The activation of JNK then induces apoptosis by inhibiting anti-apoptotic protein BCL-2 (118) and inducing pro-apoptotic protein Bim (119;120). Deficiency of Ask1 suppresses ER stress-induced JNK activation and protects cells against ER stress-induced apoptosis (121). CHOP, a transcription factor belonging to basic leucine zipper transcription factor family, can be activated by many inducers of UPR including ATF4, ATF6, and XBP-1. Upon activation, CHOP induces cells undergoing apoptosis through suppressing anti-apoptotic protein BCL-2 (122-124).
Although exogenous insulin therapy partly compensates the function of β cells, it cannot regulate blood glucose as accurately as the action of endogenous insulin. As a result, long-term improperly control of blood glucose homeostasis predisposes patients with type 1 diabetes to the development of diverse complications such as diabetic retinopathy (125-127), nephropathy (128;129), neuropathy (130-132), foot ulcers (133-135), and cardiovascular diseases (136-138). Due to the long-term health consequences of diabetes, impact of insulin dependence on life quality, and increasing appearance in both young and old populations, understanding the pathophysiology of diabetes and finding a better way to treat diabetes has become a high priority. Although the underlying mechanisms leading to type 1 diabetes have yet to be fully addressed, accumulating evidence suggests that ER stress plays a critical role in autoimmune-mediated β cell destruction during the course of type 1 diabetes. ER stress in β cells can be triggered by either autoimmune responses against β-cell self-antigens or the increase of compensated insulin synthesis. During the course of type 1 diabetes, autoreactive immune cells secrete copious amount of inflammatory cytokines, leading to excessive production of nitric oxygenand β cell destruction in an ER stress-dependent pathway. ER stress also regulates the functionality of immune cells with implications in autoimmune progression. The inadequate insulin secretion in patients with type 1 diabetes renders the residual β cells for compensated insulin secretion to maintain blood glucose homeostasis. This increase in insulin biosynthesis could overwhelm the folding capacity of ER, and exacerbate β cell dysfunction by inducing ER stress in β cells.
Although ER stress is a critical factor involved in the pathogenesis of type 1 diabetes, it should be kept in mind that the mechanisms underlying autoimmune-mediated β cell destruction in type 1 diabetes are complex, and ER stress is unlikely the exclusive mechanism implicated in disease process. Despite recent significant progress in this area, there are still many questions yet to be addressed. Are there additional factors inducing ER stress in β cells during type 1 diabetes development? Can ER stress be served as a biomarker for β cell destruction and autoimmune progression in the clinic setting? Does blockade of ER stress in immune cells attenuate autoimmune progression and protect β cells? Future studies aimed to dissect these questions would provide a deep insight for type 1 diabetes pathogenesis and would have great potential for developing novel therapeutic strategies against this devastating disorder.
This work is supported by a grant from the National Natural Science Foundation of China (81101553/H1604) to JZ. The author declares no competing financial interest.
AP1, activator protein 1; Ask1, apoptosis signal-regulating kinase 1; ATF6, Activating Transcription Factor 6; C/EBP, CCAAT/enhancer binding protein; CHOP, C/EBP homologous protein; CREBH, Cyclic-AMP-responsive-element-binding protein H; eIF2α, eukaryotic initiation factor 2α; ER, Endoplasmic Reticulum; ER stress, Endoplasmic Reticulum stress; iNOS, inducible nitric oxide synthase; IRE1, inositol-requiring enzyme 1; IRS-1, insulin receptor substrate-1; JIK, c-Jun N-terminal inhibitory kinase; JNK, c-Jun N-terminal kinases; NRF2, nuclear factor-erythroid-derived 2-related factor 2; PERK, pancreatic endoplasmic reticulum kinase; RER, rough endoplasmic reticulum; ROS, reactive oxygen species; SER, smooth endoplasmic reticulum; TLR, Toll-like receptor; TRAF2, TNF receptor-associated factor 2; TRIF, Toll-IL-1R-containing adaptor inducing IFN-β; UPR, unfolded protein response; XBP-1, X box protein-1.
Topology optimization (TO) is carried out to obtain an optimal structural layout [1]. It is one of the branches of optimization methods differing from size and shape optimization. As expected, as a type of optimization method, it has constant parameters, like applied loads, material type, etc., objective function and constraints which change for every problem, and lastly variable which are the parameters of the material layout. In shape optimization, it aimed to find the position of the member of the structure, while in size optimization, only finding the size of the members is enough. In both cases, there will be no change in the number of members. On the other hand, in topology optimization some part or member of the structure will be deleted and a new layout will be prepared [2]. It is generally preferred to use finite element method (FEM) as meshing eases to find the places to be deleted. But as an optimization algorithm, several kinds are used including both gradient-based such as optimality criteria methods and non-gradient-based algorithms such as genetic algorithm [3].
The topology optimization of structures has proven to be a valuable tool for the identification of the best concepts in early phases of the design process. It is widely used in lightweight design of structures in automotive and aerospace industry, as well as in civil engineering, material science, and biomechanics [1, 4, 5].
This chapter will give brief introduction on topology optimization and later give related studies under several classifications. There are several well-prepared and intensely examined review studies in literature, but some of them are on specific application area (vibration problems [6], continuum structures [7]) or are on a specific methodology (evolutionary algorithms [8, 9], level-set methods [10]), or recent studies are not included [11, 12]. This study mostly aims to present recent studies while giving brief description on previous ones.
During the twentieth century, architects and engineers have used innovative and novel methods to develop optimum forms of structures and sculptures. While the techniques employed by these innovators generated efficient and aesthetic forms, they shared a common limitation: reaching optimum structure. Although the purpose of applying topology optimization has never been a standard procedure, developments in finding optimum structure form let the researchers and designers be free to constructing better designs [13, 14].
Topology optimization offers conceptual design for lighter and stiffer structures. It helps to reach to efficient and aesthetic designs within a small time interval (Figure 1). The benefits are:
Building weight-saving and complete designs.
Decrease needed time to present and test product.
By the help of FEM software, you are able to check your design from the perspective of:
Determining feasible design range.
Accurate checking for different loads and conditions.
Considering design and manufacturing constraints [15].
Optimized unit by using topology optimization approach (Dassault) [15].
By the time, TO has shown its power and efficiency in the design of structures by the increase in advances on computational speed and power. Changes in computer hardware and software technology have also changed the approach to topology formation of structures. Nowadays, you could use a drawing software in forming different topologies as if it is a standard task, and so, you are able to alter old designs and produce new alternative designs in virtual environment. Designers and engineers are pleased to have such a powerful tool in their work [16].
A topology optimization problem can be written in the general form of an optimization problem as [3, 17]:
The problem statement includes the following:
An objective function
Main design variable: material distribution. Here material density at each point of the members
The design space
m constraints is a characteristic that the solution must satisfy
Evaluating
The topology of a structure is defined as a spatial arrangement of structural members and joints or internal boundaries. For both discrete and continuum structures, topology optimization helps to arrange association form of members as can be realized in Figure 2 [18].
Variation of topology [18].
The conceptual process is shown in Figure 3.
Conceptual process [18].
Structural optimization is concerned with maximizing the utility of a fixed quantity of resources to fulfill a given objective. In structural optimization the best “structural” design is selected regarding three categories: size optimization, shape optimization, and topology optimization [19]. The application of topology optimization to structures to reveal the best position and size of the parts in a continuum is the most favorite one. Michell presented the first solutions as seen in Figure 4. Today much more advanced techniques are used, and by the help of finite element method, it could be applied to complex problems. Weight savings are managed by engineers in several structures as a consequence of utilization of these methods. There are many examples in literature on the application of these methods [13, 20, 21]. Today, many commercial finite element software has an optimization module (Altair OptiStruct, Simulia Tosca, OPTISHAPE-TS, etc.) to obtain lighter structure, but several researchers have generated their codes [22, 23] or developed scripts [24] using these software’s programming languages.
One of the first proposed solutions to a structural topology optimization problem [13].
Structural optimization concerns on getting the required task of the mechanical system and maximizing its efficiency by an ordered procedure. At the beginning the design variables should be selected carefully. Then, limitations of these variables and system performance factors will be defined. By changing variable values, it is possible to see the change in these factors so we are able to determine the best combination among the design space. As design variables, the size of the members or mechanical properties of materials could be selected similar to size optimization, and the configuration of members is also another possible parameter as in shape optimization. Material distribution and layout are the parameter that is concerned in topology optimization. As the objective function, the most used one is cost function (related to total weight) to be minimized. Stress and buckling conditions are mostly used constraints in literature [18]. The aim is to optimize parts or units for specific load cases and extreme situations.
Figure 5 shows a sample application of topology optimization in finding the best material distribution. Minimizing objective function is acquired by checking different structure forms step by step. Each time design is narrowed down by selecting the best form among feasible sets.
Initial and optimized unit structure of a short cantilever.
Topology optimization methods are mathematical techniques/approaches, and they can be programmed using different algorithms. These algorithms could be classified as follows: the criterion algorithm, the mathematical programming algorithm, and the intelligent algorithm.
The criterion algorithm obtains the optimality condition by the perceptual knowledge or the rational derivation. Result geometry will be gained by checking constraint violations and objective function value in an iterative way.
The perceptual criterion is usually the extension of the optimality condition of the full stress criterion of the size optimization. The rational criterion is derived usually by the Lagrange multiplier method of equality constraint. The ESO method is the typical criterion method.
Common mathematical programming algorithms like linear programming (LP) and nonlinear programming methods are also used in topology optimization of structures. The first attempts begin with using LP and successive LP methods later continued with sequential quadratic programming methods. Similar too criterion algorithm, mathematical programming algorithms are solved iteratively. Both stability and sensitivity of the structure are checked in each iteration. Of course it means that more calculation should be done for large-scale systems, and consequently low performance is observed for these cases. Fleury discussed the relationship between the criteria method and the mathematical programming method of size optimization. Fleury found that they both have given approximate results. This study refers still to the basics of the topology optimization [25, 26].
Genetic algorithm, simulated annealing algorithms, and particle swarm are the frequently used algorithms for topology optimization as the intelligent algorithm. The advantage of these algorithms is to keep it from too much calculations. The main idea is to search the optimum topology by checking only the objective function and constraints without calculating any gradients. On the contrary, solution speed can be slow, especially for large-scale system; finding optimum could take longer times [27, 28]. Several algorithms are also developed to combine topology optimization with additive manufacturing [29].
Two classes of approaches, the so-called material or micro-approaches and the geometrical or macro-approaches, are available [30, 31]. For the areas such as MEMS or biomaterial applications, classical continuum mechanics theories sometimes could not give accurate results. So, there are essential conceptual differences between these two types of approaches because of size effect.
Furthermore, another most commonly used classification merit of methodologies is if its discrete elements are used or not. The mainly used methods using discrete elements can be regarded, such as [18] ground structure approach (GSA) [21, 32], solid isotropic material with penalization (SIMP) method [33], homogenization method (HM) [34], evolutionary structural optimization (ESO) [35], and level-set method (LSM) [35]. On the other hand, the mainly used meshless methods are element-free Galerkin (EFG) [36], moving particle [37], and peridynamics [38]. Here, some of the studies post 2010 using these methodologies and their hybrids will be given under different headings.
Sokol and Rozvany [39] applied a hybrid method of linear programming and GSA to multi-load truss systems. Zhang et al. [40] combined GSA with simulated annealing to apply truss systems. Xu et al. [41] combined GSA with mixed integer linear programming for topology optimization of tensegrity structures. Zhang et al. [42] compared two different ground structure approach (macroelement and macropatch) on a skyscraper and arch bridge. Chun et al. [43] used a discrete filtering scheme in which thin bars are eliminated during reliability-based topology optimization. Gao et al. [44] considered principal stress trajectories to find the suitable nodal points to decrease the computational cost in building ground structure. Ha and Guest [45] applied the method to find the optimum 3D woven material structure and, in a later study, with their colleagues tested this structure [46]. Kosaka et al. [47] applied hybrid method of GSA and ESO to frame structures. Ramos and Paulino [48] considered the materials’ nonlinear behavior to solve several topology optimization benchmarking problems. Shakya et al. [49] combined particle swarm optimization (PSO) algorithm with GSA in order to detect and remove useless elements of truss systems. Sokol [50] used GSA in the optimization of large-scale pin-jointed frames considering a new member adding strategy. Wang and Zhang [51] proposed a new approach, parallel optimization tactic, in topology optimization of multi-material compliant mechanism. Zegard and Paulino provided a code for 2D [52] and 3D [53] domains to prevent creating members not intersecting with others. Zhang et al. [54] worked on arranging optimum structure of multi-material composite material using Zhang-Paulino-Ramos design variable update scheme with Karush-Kuhn-Tucker conditions. Zhang et al. [21] used a different filtering scheme for the optimization of multi-materials (hyperelastic Ogden-based and bilinear materials).
Shao [55] has combined BESO with SIMP considering 3D printing applications. Lógó [56] has solved a continuum-type topology optimization problem considering uncertainties in load positions. Garcia-Lopez et al. [57] combined simulated annealing with SIMP to eliminate gray areas resulted by SIMP. Gebremedhen et al. [58] used SIMP to solve 3D stress-constrained topology optimization problems. Jantos et al. [59] used a new approach based on thermodynamics material modeling and not containing any filter and compared the results with SIMPs’. Jiao et al. [60] combined ESO with SIMP and used strain energy in their filtering function as sensitivity number. Kandemir et al. [61] proposed a new approach to define intermediate densities (gray areas) with new penalization factor. Marck et al. [62] applied SIMP to solve a multiobjective conductivity problem while using finite volume method (FVM) to solve the energy equation. Ospald and Herzog [63] used projected gradient method with SIMP to solve the structure problem of mold where short-fiber-reinforced polymer material is used in injection molding. Qiao et al. [64] applied the hybrid method of SIMP and BESO to a MBB beam and a cantilever beam and compared the results with literature. Schlinquer et al. [65] applied SIMP to design a mechanism used to amplify the displacement of a piezoelectric actuators. Tsai and Cheng [66] employed SIMP to design flywheel rotor having maximum stiffness. Wang et al. [67] combined topology and size optimization for a folding wing structural design. Yang et al. [68] accomplished topology optimization of an electric vehicle body by SIMP. Yang et al. [69] used SIMP for topology optimization of a hard disk drive. Yunfei et al. [70] applied SIMP to design a robot’s upper arm. Zhang and Ren [71] proposed a new optimality criterion method concerning minimum compliance. Zhang et al. [72] presented a new approach to control the length scale of structural members. Zhang et al. [73] presented a method for cellular structures with multiple types of microstructures. Zuo and Saitou [74] introduced power functions with scaling and translation coefficients and the cost properties for multiple materials.
Allaire et al. applied HM to structures made of periodically perforated material in 2D [75] and 3D [76]. Zhang and Khandelwal [77] presented a nonlinear homogenization method to be able to design metamaterials. Lee et al. [78] proposed asymptotic homogenization method to solve topology optimization problem of magnetic composite materials. El-Kahlout and Kiziltas [79] used together MATLAB code to integrate material model derived using homogenization theory with COMSOL and solved several design problems where periodic dielectric materials with desired properties are aimed. Noguchi et al. [80] proposed a level-set-based topology optimization method for the design of hyperbolic acoustic metamaterials using a high-frequency homogenization method. Larsen et al. [81] proposed a new approach based on HM extracting discrete structure from the continuum model. Milani and Bruggi [82] used an adaptive meshing algorithm with HM to optimize multistory masonry wall loaded up to failure. Groen and Sigmund [83] presented a projection method to get better meshes during topology optimization. Xia and Breitkopf [84] implemented a MATLAB code which uses energy-based homogenization approach rather than the asymptotic approach. Bruggi and Milani [85] arranged strut-and-tie models in reinforced concrete structures. Kaminakis et al. [86] used hybrid algorithm based on evolutionary algorithms in the design of microstructures having auxetic behavior.
Martínez-Frutos and Herrero-Pérez [87] used evolutionary algorithm to increase the efficiency of GPU and enable to solve with smaller amount of device memory. Daróczy and Jármai [88] proposed a new bidirectional evolutionary structural optimization (BESO) algorithm based on fluid dynamics analogy. Tomšič and Duhovnik [89] discussed simultaneous topology and size optimization of trusses. Abdi et al. [90] used a combination of ESO with XFEM which uses isoline design approach. Ansola et al. [91] used ESO to optimize compliant mechanism under concentrated and thermal loads. Aulig and Olhofer [92] combined a neuro-evolution algorithm with a gradient-based optimizer and later proposed another algorithm considering state-based representation [93]. Azamirad and Arezoo [94] combined programming environment with Abaqus FEM software to optimize die components. Bureerat and Sriworamas [95] proposed multiobjective real-code population-based incremental learning (RPBIL) and a hybrid algorithm of RPBIL with differential evolution (DE) (termed RPBIL-DE) to solve water distribution network. Chen et al. [96] used ESO to optimize the rotary lobe of root vacuum pumps. Chen [97] used modified ESO algorithm for the optimization of plate structure under harmonic loading. Cho et al. [98] obtained optimum topology for the inner reinforcement of a vehicle’s hood having uncertainties in variables. Finotto et al. [99] used an algorithm combination of ground structure approach, nonlinear finite element analysis, and quantum-inspired evolutionary algorithms. Garcia-Lopez et al. [100] used multiobjective evolutionary algorithm handling uncertainties and also giving the Pareto frontier solutions to let user select the best solution. Greiner and Hajela [101] used multiobjective evolutionary algorithm using reunification criterion to increase search efficiency. Huang and Xie [102] used BESO utilizing an alternative material interpolation scheme. Huang et al. [103] used BESO to optimize the topology of PBC made of two-phase composites. Zuo and Xie [104] used ESO letting limiting displacement. Jantos et al. [105] added a control mechanism for growth factor where at each step Lagrange multiplier is used to find optimum. Jia et al. [106] used hybrid of ESO with LSM. Kaminakis et al. [107] proposed hybrid method of Particle Swarm Optimization and differential evolution in the design of microstructures. Kunakote and Bureerat [108] compared Pareto archive evolution strategy (PAES), population-based incremental learning (PBIL), non-dominated sorting genetic algorithm (NSGA), strength Pareto evolutionary algorithm (SPEA), and multiobjective particle swarm optimization (MPSO). Li et al. [109] used a combination of SIMP and ESO. Li et al. [110] used BESO method in the design of hinge-free compliant mechanisms. Maleki Jebeli and Shariat Panahi [111] used GA as evolutionary algorithm to optimize the material property distribution in FG structures. Okamoto et al. [112] enhanced genetic algorithm, immune algorithm, additional search in the restricted design space with enabling island, and void distribution during FEM analysis to solve a typical magnetic circuit problem. Picelli et al. [113] used BESO to free vibration problems of acoustic-structure systems. Riehl and Steinmann [114] employed the traction method to define descent directions for shape variation. Shi et al. [115] used APDL and UIDL to implement BESO in ANSYS to improve results. Sun et al. [116] applied BESO a cantilever composite laminate under uniform in-plane pressure. Tominaga et al. [117] used GA algorithms for magnetostatic shielding to minimize the magnetic flux intensity in a specified region. Wang et al. [118] used to optimize constrained damping layer structure. Fritzen et al. [119] taken nonlinear elastoviscoplastic microscopic RVE into account at all points of the macroscopic design domain by using BESO. Later, Xia et al. [120] introduced a damping scheme on sensitivity numbers to the same approach. Zhu et al. [121] used bidirectional evolutionary level-set method allowing automatic hole generation. Zuo et al. [27] enhanced the BESO method to multiple constraints of displacement and frequency in addition to the amount of material usage.
Allaire et al. [122] applied LSM with enabling local mesh modifications. Chen and Chen [123] considered geometric uncertainty and related problems. Van Dijk et al. [124] used uses a direct steepest-descent update of the design variables in a LSM. Dunning and Alicia Kim [125] developed a third dimension for 2D problems to adjust new hole positions and to prevent violations with boundaries. Emmendoerfer and Fancello [126] minimized mass under stress constraints using an augmented Lagrangian approach. Gomes et al. [127] interested in the reduction of the design space dimension by the help of a GUI. Guo et al. [128] used LSM in stress-related topology optimization problems. Otomori et al. applied LSM to the design of electromagnetic cloaks using a ferrite material [129] and a light-scattering layer for solar cell applications [130]. Guo et al. [131] developed a local and explicit feature control scheme. James et al. [132] used isoparametric finite element, and James and Martins [133] used a body-fitted, nonuniform finite element mesh to overcome irregular shape problems. Jang et al. [134] considered geometric uncertainties in the production of microsystems. Lim et al. [135] applied to magnetic actuator design problems. Liu et al. [136] adopted extended finite element method (XFEM) with unified structural optimization model help to cover the topology, shape, and sizing optimization at the same time. Luo et al. [137] combined meshless Galerkin method with LSM. Makhija and Maute [138] applied a generalized Heaviside enrichment strategy with XFEM formulation. Mohamadian and Shojaee [139] combined binary level-set method and Merriman-Bence-Osher scheme. Otomori et al. [140] used LSM in the design of negative permeability dielectric metamaterials. Shojaee and Mohammadian [141] combined piecewise constant level-set (PCLS) method with a MBO scheme. Shu et al. [142] used LSM to minimize frequency response which results in the reduction in the vibration of structure. Shu et al. [143] used LSM in the design of coupled structural-acoustic system with a focus on interior noise reduction. Suresh and Takalloozadeh [144] used LSM considering stress constraints. Xia et al. [145] used LSM to maximize the simple or repeated first eigenvalue of structure vibration. Xia et al. [146] built a strict 0–1 model considering stress to be minimized. Xia et al. [147] optimized both structure and support using traction free and Dirichlet boundaries separately. Yamasaki et al. [148] proposed a method combined application of boundary element mesh with LSM. Zhu and Zhang [149] used LSM without re-initialization for the optimization of compliant mechanisms. Zhu et al. [150] combined projection Lagrangian method with piecewise constant level-set functions to manage the optimization for elliptic boundary value problems. Zhu et al. [151] used LSM to optimize hinge-free compliant mechanisms with multiple outputs. Zhu and Zhang [152] developed an accelerated level-set evolution algorithm by adding an extra energy function to be able to optimize the distributed compliant mechanisms. Zhu et al. [153] developed a new LSM to manage multiobjective optimization of hinge-free compliant mechanisms.
Lin et al. [154] generated a method mimicking leaf venation and using element-free Galerkin method to design heat conduction channels. Wang and Luo [155] proposed a meshless Galerkin level-set method using compactly supported radial basis functions to construct the meshless shape functions. Cui et al. [156] proposed a new method based on SIMP and using EFG method for multi-material optimization problems. Zhao [157] developed a new approach based on Pareto frontier solutions using EFG method. He et al. [158] combined density variable approach with EFG to optimize geometrically nonlinear structures. Evgrafov [159] proposed a method based on SIMP combined with Petrov-Galerkin methods based on minimizing the squared residual. Khan et al. [160] used EFG with LSM and also implemented sensitivity analysis. Gong et al. [161] developed a new method, particle moving, based on EFG considering density gradient and combined it with SIMP. Hur et al. [162] used a Spline-based meshfree method where nonuniform rational B-spline functions are used to smooth trimmed boundaries. Ren et al. [163] used a method combination of EFG and SIMP to design a two-material micro-compliant mechanism under stress constraints. Zhang et al. [164] applied a combined method of SIMP and direct coupling method of FE and EFG methods to decrease computational cost of meshless methods. Ai and Gao [165] integrated a parametric level-set method with a meshless method based on compactly supported radial basis functions. Wang et al. [166] applied EFG to the design of large displacement compliant mechanisms having geometrical nonlinearity. Yang et al. [167] applied EFG to the design of continuum structures under displacement constraints. Kefal et al. [38] combined BESO with a new meshless method peridynamics. Zheng et al. [168] used a combination of SIMP and EFG to optimize free vibrating continuum structures. Zhang et al. [169] used a directly coupled FE and EFG to optimize nonlinear hyperelastic structures. Luo et al. [36] used dual-level point-wise density approximation with EFG. Wu et al. [170] improved EFG by adding moving least squares approximation. Zheng et al. [171] used EFG to optimize geometrically nonlinear continuum structures. Zhao [172] combined BESO with EFG.
Sigmund and Maute [11] drawn a good framework on the classification of methodologies, and they pointed an important spot that differences between topology optimization approaches become small and an approach evolves into the other by the time such as evolutionary methods are converging towards discrete SIMP schemes. However, this trend has gone forward using hybrid approaches rather than becoming similar techniques to keep all the approaches having their advantages and limitations. There are many studies using hybrid methodologies given before under different headings, but there is still room for new applications. Especially from evolutionary algorithms perspective, using new optimization algorithms will enable to improve methodologies advanced up to now.
Another important area to work on is how uncertainties are handled. Topology optimization of small sized systems brings researchers to the position where small changes should be taken into account as todays’ technology is covering nano-sized systems beyond MEMS. In any case when changes are formed either because of manufacturing errors or that applied loads has caused comparatively large deformations on members, it will not be possible to use precise geometry and crisp size values in the optimization stage. So, handling uncertainties such as using fuzzy systems is still an open field to study.
Lastly, another rapidly growing area at the last decade is rapid prototyping. Even though there are abundant studies in literature (over a hundred studies could be easily found [173]), new algorithms on the application of BESO, handling composite/functionally graded materials, and considering support and structure in the meantime are the promising areas to study.
In addition to the aforementioned emerging areas, researchers are encouraged to study (1) to develop the efficiency of standard methods; (2) to construct new benchmarking problems; (3) to consider several constraints rather than buckling, stress, or displacement of such natural frequency; (4) to adapt meshes to nonlinear geometries with a more accurate way; (5) to develop GUIs to help researcher to observe/interfere the optimization stage; and (6) to implement new meshless methods rather than EFG such as peridynamics.
At IntechOpen, we not only specialize in the publication of Book Chapters as part of our Edited Volumes, but also the publication and dissemination of longer manuscripts, known as Long Form Monographs. Monographs allow Authors to focus on presenting a single subject or a specific aspect of that subject and publish their research in detail.
\n\nEven if you have an area of research that does not at first sight fit within a previously defined IntechOpen project, we can still offer support and help you in publishing your individual research. Publishing your IntechOpen book in the form of a Long Form Monograph is a viable alternative.
",metaTitle:"Publish a Whole Book",metaDescription:"At IntechOpen, we not only specialize in the publication of book chapters as part of our Edited Volumes, but also the publication and dissemination of long form manuscripts, known as monographs. Monographs allow authors to focus on presenting a single subject or a specific aspect of that subject and publish their research at length.\n\nPerhaps you have an area of research that does not fit within a previously defined IntechOpen project, but rather need help in publishing your individual research? Publishing your IntechOpen book in the form of a long form monograph is a great alternative.",metaKeywords:null,canonicalURL:"/page/publish-a-whole-book",contentRaw:'[{"type":"htmlEditorComponent","content":"MONOGRAPH - LONG FORM MANUSCRIPT
\\n\\nFORMATS
\\n\\nCOST
\\n\\n10,000 GBP Monograph - Long Form
\\n\\nThe final price includes project management, editorial and peer-review services, technical editing, language copyediting, cover design, book layout, book promotion and ISBN assignment.
\\n\\n*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate applied in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
\\n\\nOptional Services
\\n\\nIntechOpen has collaborated with Enago, through its sister brand, Ulatus, which is one of the world’s leading providers of book translation services. The services are designed to convey the essence of your work to readers from across the globe in a language they understand. Enago’s expert translators incorporate cultural nuances in translations to make the content relevant for local audiences while retaining the original meaning and style. Enago translators are equipped to handle all complex and multiple overlapping themes encompassed in a single book and their high degree of linguistic and subject expertise enables them to deliver a superior quality output.
\\n\\nIntechOpen Authors that wish to use this service will receive a 20% discount on all translation services. To find out more information or obtain a quote, please visit: https://www.enago.com/intech.
\\n\\nFUNDING
\\n\\nWe feel that financial barriers should never prevent researchers from publishing their work. Please consult our Open Access Funding page to explore funding opportunities and learn more about how you can finance your IntechOpen publication.
\\n\\nBENEFITS
\\n\\nPUBLISHING PROCESS STEPS
\\n\\nFor a complete overview of all publishing process steps and descriptions, go to How Open Access Publishing Works.
\\n\\nSEND YOUR PROPOSAL
\\n\\nIf you are interested in publishing your book with IntechOpen, please submit your book proposal by completing the Publishing Proposal Form.
\\n\\nNot sure if this is the right option for you? Please refer back to the main Publish with IntechOpen page or feel free to contact us directly at book.department@intechopen.com.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'MONOGRAPH - LONG FORM MANUSCRIPT
\n\nFORMATS
\n\nCOST
\n\n10,000 GBP Monograph - Long Form
\n\nThe final price includes project management, editorial and peer-review services, technical editing, language copyediting, cover design, book layout, book promotion and ISBN assignment.
\n\n*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate applied in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
\n\nOptional Services
\n\nIntechOpen has collaborated with Enago, through its sister brand, Ulatus, which is one of the world’s leading providers of book translation services. The services are designed to convey the essence of your work to readers from across the globe in a language they understand. Enago’s expert translators incorporate cultural nuances in translations to make the content relevant for local audiences while retaining the original meaning and style. Enago translators are equipped to handle all complex and multiple overlapping themes encompassed in a single book and their high degree of linguistic and subject expertise enables them to deliver a superior quality output.
\n\nIntechOpen Authors that wish to use this service will receive a 20% discount on all translation services. To find out more information or obtain a quote, please visit: https://www.enago.com/intech.
\n\nFUNDING
\n\nWe feel that financial barriers should never prevent researchers from publishing their work. Please consult our Open Access Funding page to explore funding opportunities and learn more about how you can finance your IntechOpen publication.
\n\nBENEFITS
\n\nPUBLISHING PROCESS STEPS
\n\nFor a complete overview of all publishing process steps and descriptions, go to How Open Access Publishing Works.
\n\nSEND YOUR PROPOSAL
\n\nIf you are interested in publishing your book with IntechOpen, please submit your book proposal by completing the Publishing Proposal Form.
\n\nNot sure if this is the right option for you? Please refer back to the main Publish with IntechOpen page or feel free to contact us directly at book.department@intechopen.com.
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5699},{group:"region",caption:"Middle and South America",value:2,count:5172},{group:"region",caption:"Africa",value:3,count:1689},{group:"region",caption:"Asia",value:4,count:10244},{group:"region",caption:"Australia and Oceania",value:5,count:888},{group:"region",caption:"Europe",value:6,count:15650}],offset:12,limit:12,total:117315},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"12"},books:[{type:"book",id:"10590",title:"Humic Substance",subtitle:null,isOpenForSubmission:!0,hash:"85786eb36b3e13979aae664a4e046625",slug:null,bookSignature:"Prof. Abdelhadi Makan",coverURL:"https://cdn.intechopen.com/books/images_new/10590.jpg",editedByType:null,editors:[{id:"247727",title:"Prof.",name:"Abdelhadi",surname:"Makan",slug:"abdelhadi-makan",fullName:"Abdelhadi Makan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10758",title:"Sustainable Development of Lakes and Reservoirs",subtitle:null,isOpenForSubmission:!0,hash:"478fd03f02a98452a4a56ed2a6c85dbd",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10758.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10760",title:"Steppe Biome",subtitle:null,isOpenForSubmission:!0,hash:"982f06cee6ee2f27339f3c263b3e6560",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10760.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10765",title:"Environmental Management",subtitle:null,isOpenForSubmission:!0,hash:"e5ba02fedd7c87f0ab66414f3b07de0c",slug:null,bookSignature:" John P. Tiefenbacher",coverURL:"https://cdn.intechopen.com/books/images_new/10765.jpg",editedByType:null,editors:[{id:"73876",title:"Dr.",name:"John P.",surname:"Tiefenbacher",slug:"john-p.-tiefenbacher",fullName:"John P. Tiefenbacher"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10766",title:"Landscape Architecture",subtitle:null,isOpenForSubmission:!0,hash:"a0a54a9ab661e4765fee76ce580cd121",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10766.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10844",title:"Protected Areas Management",subtitle:null,isOpenForSubmission:!0,hash:"5b85cf581ee89c6c1457aefdb0bc495a",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10844.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10845",title:"Marine Ecosystems",subtitle:null,isOpenForSubmission:!0,hash:"b369ac809068d2ebf1f8c26418cc6bec",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10845.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10846",title:"Stormwater",subtitle:null,isOpenForSubmission:!0,hash:"9bfae8caba192ce3ab6744c9cbefa210",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10846.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:15},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:6},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:4},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:4},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:56},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:5},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:8},popularBooks:{featuredBooks:[{type:"book",id:"7802",title:"Modern Slavery and Human Trafficking",subtitle:null,isOpenForSubmission:!1,hash:"587a0b7fb765f31cc98de33c6c07c2e0",slug:"modern-slavery-and-human-trafficking",bookSignature:"Jane Reeves",coverURL:"https://cdn.intechopen.com/books/images_new/7802.jpg",editors:[{id:"211328",title:"Prof.",name:"Jane",middleName:null,surname:"Reeves",slug:"jane-reeves",fullName:"Jane Reeves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,isOpenForSubmission:!1,hash:"13aaddf5fdbbc78387e77a7da2388bf6",slug:"animal-reproduction-in-veterinary-medicine",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9961",title:"Data Mining",subtitle:"Methods, Applications and Systems",isOpenForSubmission:!1,hash:"ed79fb6364f2caf464079f94a0387146",slug:"data-mining-methods-applications-and-systems",bookSignature:"Derya Birant",coverURL:"https://cdn.intechopen.com/books/images_new/9961.jpg",editors:[{id:"15609",title:"Dr.",name:"Derya",middleName:null,surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8686",title:"Direct Torque Control Strategies of Electrical Machines",subtitle:null,isOpenForSubmission:!1,hash:"b6ad22b14db2b8450228545d3d4f6b1a",slug:"direct-torque-control-strategies-of-electrical-machines",bookSignature:"Fatma Ben Salem",coverURL:"https://cdn.intechopen.com/books/images_new/8686.jpg",editors:[{id:"295623",title:"Associate Prof.",name:"Fatma",middleName:null,surname:"Ben Salem",slug:"fatma-ben-salem",fullName:"Fatma Ben Salem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7434",title:"Molecular Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"eceede809920e1ec7ecadd4691ede2ec",slug:"molecular-biotechnology",bookSignature:"Sergey Sedykh",coverURL:"https://cdn.intechopen.com/books/images_new/7434.jpg",editors:[{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5145},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"7434",title:"Molecular Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"eceede809920e1ec7ecadd4691ede2ec",slug:"molecular-biotechnology",bookSignature:"Sergey Sedykh",coverURL:"https://cdn.intechopen.com/books/images_new/7434.jpg",editedByType:"Edited by",editors:[{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,isOpenForSubmission:!1,hash:"13aaddf5fdbbc78387e77a7da2388bf6",slug:"animal-reproduction-in-veterinary-medicine",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",editedByType:"Edited by",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9569",title:"Methods in Molecular Medicine",subtitle:null,isOpenForSubmission:!1,hash:"691d3f3c4ac25a8093414e9b270d2843",slug:"methods-in-molecular-medicine",bookSignature:"Yusuf Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/9569.jpg",editedByType:"Edited by",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editedByType:"Edited by",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7802",title:"Modern Slavery and Human Trafficking",subtitle:null,isOpenForSubmission:!1,hash:"587a0b7fb765f31cc98de33c6c07c2e0",slug:"modern-slavery-and-human-trafficking",bookSignature:"Jane Reeves",coverURL:"https://cdn.intechopen.com/books/images_new/7802.jpg",editedByType:"Edited by",editors:[{id:"211328",title:"Prof.",name:"Jane",middleName:null,surname:"Reeves",slug:"jane-reeves",fullName:"Jane Reeves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8063",title:"Food Security in Africa",subtitle:null,isOpenForSubmission:!1,hash:"8cbf3d662b104d19db2efc9d59249efc",slug:"food-security-in-africa",bookSignature:"Barakat Mahmoud",coverURL:"https://cdn.intechopen.com/books/images_new/8063.jpg",editedByType:"Edited by",editors:[{id:"92016",title:"Dr.",name:"Barakat",middleName:null,surname:"Mahmoud",slug:"barakat-mahmoud",fullName:"Barakat Mahmoud"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10118",title:"Plant Stress Physiology",subtitle:null,isOpenForSubmission:!1,hash:"c68b09d2d2634fc719ae3b9a64a27839",slug:"plant-stress-physiology",bookSignature:"Akbar Hossain",coverURL:"https://cdn.intechopen.com/books/images_new/10118.jpg",editedByType:"Edited by",editors:[{id:"280755",title:"Dr.",name:"Akbar",middleName:null,surname:"Hossain",slug:"akbar-hossain",fullName:"Akbar Hossain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editedByType:"Edited by",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9961",title:"Data Mining",subtitle:"Methods, Applications and Systems",isOpenForSubmission:!1,hash:"ed79fb6364f2caf464079f94a0387146",slug:"data-mining-methods-applications-and-systems",bookSignature:"Derya Birant",coverURL:"https://cdn.intechopen.com/books/images_new/9961.jpg",editedByType:"Edited by",editors:[{id:"15609",title:"Dr.",name:"Derya",middleName:null,surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8686",title:"Direct Torque Control Strategies of Electrical Machines",subtitle:null,isOpenForSubmission:!1,hash:"b6ad22b14db2b8450228545d3d4f6b1a",slug:"direct-torque-control-strategies-of-electrical-machines",bookSignature:"Fatma Ben Salem",coverURL:"https://cdn.intechopen.com/books/images_new/8686.jpg",editedByType:"Edited by",editors:[{id:"295623",title:"Associate Prof.",name:"Fatma",middleName:null,surname:"Ben Salem",slug:"fatma-ben-salem",fullName:"Fatma Ben Salem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"177",title:"Emergency Medicine",slug:"emergency-medicine",parent:{title:"Medicine",slug:"medicine"},numberOfBooks:14,numberOfAuthorsAndEditors:352,numberOfWosCitations:87,numberOfCrossrefCitations:105,numberOfDimensionsCitations:237,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"emergency-medicine",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7908",title:"Emergency Medicine and Trauma",subtitle:null,isOpenForSubmission:!1,hash:"4d0e9d0c91eff59a61e29cd67cbb036b",slug:"emergency-medicine-and-trauma",bookSignature:"Ozgur Karcioglu and Müge Günalp Eneyli",coverURL:"https://cdn.intechopen.com/books/images_new/7908.jpg",editedByType:"Edited by",editors:[{id:"221195",title:"Dr.",name:"Ozgur",middleName:null,surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6151",title:"Noninvasive Ventilation in Medicine",subtitle:"Recent Updates",isOpenForSubmission:!1,hash:"77e2fc8d909ac2458e0087490ea02a6d",slug:"noninvasive-ventilation-in-medicine-recent-updates",bookSignature:"Mayank Vats",coverURL:"https://cdn.intechopen.com/books/images_new/6151.jpg",editedByType:"Edited by",editors:[{id:"148941",title:"Dr.",name:"Mayank",middleName:"Gyan",surname:"Vats",slug:"mayank-vats",fullName:"Mayank Vats"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6616",title:"Essentials of Accident and Emergency Medicine",subtitle:null,isOpenForSubmission:!1,hash:"29c2ae810900eab0267a8fdb29646d24",slug:"essentials-of-accident-and-emergency-medicine",bookSignature:"Ahmed Subhy Alsheikhly",coverURL:"https://cdn.intechopen.com/books/images_new/6616.jpg",editedByType:"Edited by",editors:[{id:"144628",title:"Prof.",name:"Ahmad Subhy",middleName:"Humadi",surname:"Alsheikhly",slug:"ahmad-subhy-alsheikhly",fullName:"Ahmad Subhy Alsheikhly"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7290",title:"Special Topics in Resuscitation",subtitle:null,isOpenForSubmission:!1,hash:"5cc25d9b8a8bec2e374939f147f4e007",slug:"special-topics-in-resuscitation",bookSignature:"Theodoros K. Aslanidis",coverURL:"https://cdn.intechopen.com/books/images_new/7290.jpg",editedByType:"Edited by",editors:[{id:"200252",title:"Dr.",name:"Theodoros",middleName:null,surname:"Aslanidis",slug:"theodoros-aslanidis",fullName:"Theodoros Aslanidis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6432",title:"Hyperbaric Oxygen Treatment in Research and Clinical Practice",subtitle:"Mechanisms of Action in Focus",isOpenForSubmission:!1,hash:"574f9e3775c072d689ca7cab789dd590",slug:"hyperbaric-oxygen-treatment-in-research-and-clinical-practice-mechanisms-of-action-in-focus",bookSignature:"Ines Drenjančević",coverURL:"https://cdn.intechopen.com/books/images_new/6432.jpg",editedByType:"Edited by",editors:[{id:"186048",title:"Prof.",name:"Ines",middleName:null,surname:"Drenjančević",slug:"ines-drenjancevic",fullName:"Ines Drenjančević"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6288",title:"Hot Topics in Burn Injuries",subtitle:null,isOpenForSubmission:!1,hash:"c13b370b0d6dd78067ad3761613cefdf",slug:"hot-topics-in-burn-injuries",bookSignature:"Selda Pelin Kartal and Dilek Bayramgürler",coverURL:"https://cdn.intechopen.com/books/images_new/6288.jpg",editedByType:"Edited by",editors:[{id:"72686",title:"Prof.",name:"Selda Pelin",middleName:null,surname:"Kartal",slug:"selda-pelin-kartal",fullName:"Selda Pelin Kartal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5873",title:"Poisoning",subtitle:"From Specific Toxic Agents to Novel Rapid and Simplified Techniques for Analysis",isOpenForSubmission:!1,hash:"42ddd66c136bcb87140fa1f5b60f9726",slug:"poisoning-from-specific-toxic-agents-to-novel-rapid-and-simplified-techniques-for-analysis",bookSignature:"Ntambwe Malangu",coverURL:"https://cdn.intechopen.com/books/images_new/5873.jpg",editedByType:"Edited by",editors:[{id:"84773",title:"Prof.",name:"Ntambwe",middleName:null,surname:"Malangu",slug:"ntambwe-malangu",fullName:"Ntambwe Malangu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5949",title:"Resuscitation Aspects",subtitle:null,isOpenForSubmission:!1,hash:"876e8435664e85af78acd71c44e3e0a4",slug:"resuscitation-aspects",bookSignature:"Theodoros Aslanidis",coverURL:"https://cdn.intechopen.com/books/images_new/5949.jpg",editedByType:"Edited by",editors:[{id:"200252",title:"Dr.",name:"Theodoros",middleName:null,surname:"Aslanidis",slug:"theodoros-aslanidis",fullName:"Theodoros Aslanidis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5851",title:"Sepsis",subtitle:null,isOpenForSubmission:!1,hash:"140438644d49079e214fd82e9fe5e5ac",slug:"sepsis",bookSignature:"Vijay Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/5851.jpg",editedByType:"Edited by",editors:[{id:"63844",title:"Dr.",name:"Vijay",middleName:null,surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5202",title:"Extracorporeal Membrane Oxygenation",subtitle:"Advances in Therapy",isOpenForSubmission:!1,hash:"f7c8f9c0cf1cf50455fba7e2607e9268",slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",bookSignature:"Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/5202.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2621",title:"Hyperthermia",subtitle:null,isOpenForSubmission:!1,hash:"e3557de8bc852fa2c1a8b17e026cd37c",slug:"hyperthermia",bookSignature:"Nagraj Huilgol",coverURL:"https://cdn.intechopen.com/books/images_new/2621.jpg",editedByType:"Edited by",editors:[{id:"146901",title:"Dr.",name:"Nagraj",middleName:"G",surname:"Huilgol",slug:"nagraj-huilgol",fullName:"Nagraj Huilgol"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2583",title:"Sepsis",subtitle:"An Ongoing and Significant Challenge",isOpenForSubmission:!1,hash:"85121c8c358a97497c254ca2832be903",slug:"sepsis-an-ongoing-and-significant-challenge",bookSignature:"Luciano Azevedo",coverURL:"https://cdn.intechopen.com/books/images_new/2583.jpg",editedByType:"Edited by",editors:[{id:"72846",title:"Prof.",name:"Luciano",middleName:null,surname:"Azevedo",slug:"luciano-azevedo",fullName:"Luciano Azevedo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:14,mostCitedChapters:[{id:"44713",doi:"10.5772/52208",title:"Local Hyperthermia in Oncology – To Choose or not to Choose?",slug:"local-hyperthermia-in-oncology-to-choose-or-not-to-choose-",totalDownloads:3248,totalCrossrefCites:14,totalDimensionsCites:19,book:{slug:"hyperthermia",title:"Hyperthermia",fullTitle:"Hyperthermia"},signatures:"Andras Szasz, Nora Iluri and Oliver Szasz",authors:[{id:"141192",title:"Prof.",name:"Andras",middleName:null,surname:"Szasz",slug:"andras-szasz",fullName:"Andras Szasz"}]},{id:"39638",doi:"10.5772/51484",title:"The History of Sepsis from Ancient Egypt to the XIX Century",slug:"the-history-of-sepsis-from-ancient-egypt-to-the-xix-century",totalDownloads:9765,totalCrossrefCites:5,totalDimensionsCites:12,book:{slug:"sepsis-an-ongoing-and-significant-challenge",title:"Sepsis",fullTitle:"Sepsis - An Ongoing and Significant Challenge"},signatures:"Johan Sebastián Hernández Botero and María Cristina Florián Pérez",authors:[{id:"141171",title:"Dr.",name:"Johan",middleName:"Sebastian",surname:"Hernandez Botero",slug:"johan-hernandez-botero",fullName:"Johan Hernandez Botero"},{id:"141520",title:"Dr.",name:"Maria Cristina",middleName:null,surname:"Florian Perez",slug:"maria-cristina-florian-perez",fullName:"Maria Cristina Florian Perez"}]},{id:"27970",doi:"10.5772/27889",title:"Anti-Inflammatory Role of Natural Polyphenols and Their Degradation Products",slug:"anti-inflammatory-role-of-natural-polyphenolic-compounds",totalDownloads:4532,totalCrossrefCites:5,totalDimensionsCites:10,book:{slug:"severe-sepsis-and-septic-shock-understanding-a-serious-killer",title:"Severe Sepsis and Septic Shock",fullTitle:"Severe Sepsis and Septic Shock - Understanding a Serious Killer"},signatures:"Balázs Veres",authors:[{id:"71968",title:"Dr.",name:"Balazs",middleName:null,surname:"Veres",slug:"balazs-veres",fullName:"Balazs Veres"}]}],mostDownloadedChaptersLast30Days:[{id:"56521",title:"Food Poisoning Caused by Bacteria (Food Toxins)",slug:"food-poisoning-caused-by-bacteria-food-toxins-",totalDownloads:3823,totalCrossrefCites:3,totalDimensionsCites:8,book:{slug:"poisoning-from-specific-toxic-agents-to-novel-rapid-and-simplified-techniques-for-analysis",title:"Poisoning",fullTitle:"Poisoning - From Specific Toxic Agents to Novel Rapid and Simplified Techniques for Analysis"},signatures:"Cecilia Hernández-Cortez, Ingrid Palma-Martínez, Luis Uriel\nGonzalez-Avila, Andrea Guerrero-Mandujano, Raúl Colmenero Solís\nand Graciela Castro-Escarpulli",authors:[{id:"204160",title:"Prof.",name:"Graciela",middleName:null,surname:"Castro-Escarpulli",slug:"graciela-castro-escarpulli",fullName:"Graciela Castro-Escarpulli"},{id:"204162",title:"Dr.",name:"Cecilia",middleName:null,surname:"Hernández-Cortez",slug:"cecilia-hernandez-cortez",fullName:"Cecilia Hernández-Cortez"},{id:"204163",title:"MSc.",name:"Ingrid",middleName:null,surname:"Palma-Martinez",slug:"ingrid-palma-martinez",fullName:"Ingrid Palma-Martinez"},{id:"204164",title:"MSc.",name:"Luis Uriel",middleName:null,surname:"González-Avila",slug:"luis-uriel-gonzalez-avila",fullName:"Luis Uriel González-Avila"},{id:"204165",title:"MSc.",name:"Andrea",middleName:null,surname:"Guerrero-Mandujano",slug:"andrea-guerrero-mandujano",fullName:"Andrea Guerrero-Mandujano"}]},{id:"51211",title:"Triple Cannulation ECMO",slug:"triple-cannulation-ecmo",totalDownloads:3508,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"L. Christian Napp and Johann Bauersachs",authors:[{id:"180959",title:"Dr.",name:"L. Christian",middleName:null,surname:"Napp",slug:"l.-christian-napp",fullName:"L. Christian Napp"},{id:"181634",title:"Prof.",name:"Johann",middleName:null,surname:"Bauersachs",slug:"johann-bauersachs",fullName:"Johann Bauersachs"}]},{id:"51795",title:"ECMO Cannulation Techniques",slug:"ecmo-cannulation-techniques",totalDownloads:3354,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"Chand Ramaiah and Ashok Babu",authors:[{id:"183646",title:"Dr.",name:"Chand",middleName:null,surname:"Ramaiah",slug:"chand-ramaiah",fullName:"Chand Ramaiah"},{id:"189073",title:"Dr.",name:"Ashok",middleName:null,surname:"Babu",slug:"ashok-babu",fullName:"Ashok Babu"}]},{id:"51450",title:"ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring",slug:"ecmo-biocompatibility-surface-coatings-anticoagulation-and-coagulation-monitoring",totalDownloads:3440,totalCrossrefCites:5,totalDimensionsCites:9,book:{slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"Timothy M. Maul, M Patricia Massicotte and Peter D. Wearden",authors:[{id:"182691",title:"Dr.",name:"Timothy",middleName:"Michael",surname:"Maul",slug:"timothy-maul",fullName:"Timothy Maul"},{id:"187110",title:"Dr.",name:"Peter",middleName:null,surname:"Wearden",slug:"peter-wearden",fullName:"Peter Wearden"},{id:"187112",title:"Dr.",name:"Patti",middleName:null,surname:"Massicotte",slug:"patti-massicotte",fullName:"Patti Massicotte"}]},{id:"61274",title:"The Evolving Role of Ultrasound in Emergency Medicine",slug:"the-evolving-role-of-ultrasound-in-emergency-medicine",totalDownloads:667,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"essentials-of-accident-and-emergency-medicine",title:"Essentials of Accident and Emergency Medicine",fullTitle:"Essentials of Accident and Emergency Medicine"},signatures:"Laura Ann Galdamez",authors:[{id:"221942",title:"Dr.",name:"Laura",middleName:null,surname:"Galdamez",slug:"laura-galdamez",fullName:"Laura Galdamez"}]},{id:"56058",title:"Sepsis-associated Acute Kidney Injury",slug:"sepsis-associated-acute-kidney-injury",totalDownloads:1820,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"sepsis",title:"Sepsis",fullTitle:"Sepsis"},signatures:"Wiwat Chancharoenthana, Asada Leelahavanichkul and Somchai\nEiam-Ong",authors:[{id:"49591",title:"Dr.",name:"Somchai",middleName:null,surname:"Eiam-Ong",slug:"somchai-eiam-ong",fullName:"Somchai Eiam-Ong"},{id:"200624",title:"Dr.",name:"Wiwat",middleName:null,surname:"Chancharoenthana",slug:"wiwat-chancharoenthana",fullName:"Wiwat Chancharoenthana"},{id:"200625",title:"Dr.",name:"Asada",middleName:null,surname:"Leelahavanichkul",slug:"asada-leelahavanichkul",fullName:"Asada Leelahavanichkul"}]},{id:"56577",title:"Extraterrestrial CPR and Its Applications in Terrestrial Medicine",slug:"extraterrestrial-cpr-and-its-applications-in-terrestrial-medicine",totalDownloads:1282,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"resuscitation-aspects",title:"Resuscitation Aspects",fullTitle:"Resuscitation Aspects"},signatures:"Thais Russomano and Lucas Rehnberg",authors:[{id:"13838",title:"Dr.",name:"Thais",middleName:null,surname:"Russomano",slug:"thais-russomano",fullName:"Thais Russomano"},{id:"203825",title:"Dr.",name:"Lucas",middleName:null,surname:"Rehnberg",slug:"lucas-rehnberg",fullName:"Lucas Rehnberg"}]},{id:"51673",title:"Sedation, Analgesia Delirium in the ECMO Patient",slug:"sedation-analgesia-delirium-in-the-ecmo-patient",totalDownloads:2537,totalCrossrefCites:2,totalDimensionsCites:3,book:{slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"SV Satyapriya, ML Lyaker, AJ Rozycki and Papadimos",authors:[{id:"183288",title:"Dr.",name:"S. Veena",middleName:null,surname:"Satyapriya",slug:"s.-veena-satyapriya",fullName:"S. Veena Satyapriya"}]},{id:"64561",title:"Musculoskeletal Injuries: Types and Management Protocols for Emergency Care",slug:"musculoskeletal-injuries-types-and-management-protocols-for-emergency-care",totalDownloads:1454,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"essentials-of-accident-and-emergency-medicine",title:"Essentials of Accident and Emergency Medicine",fullTitle:"Essentials of Accident and Emergency Medicine"},signatures:"Ahmad Subhy Alsheikhly and Mazin Subhy Alsheikhly",authors:[{id:"144628",title:"Prof.",name:"Ahmad Subhy",middleName:"Humadi",surname:"Alsheikhly",slug:"ahmad-subhy-alsheikhly",fullName:"Ahmad Subhy Alsheikhly"}]},{id:"57336",title:"Burn Etiology and Pathogenesis",slug:"burn-etiology-and-pathogenesis",totalDownloads:1903,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"hot-topics-in-burn-injuries",title:"Hot Topics in Burn Injuries",fullTitle:"Hot Topics in Burn Injuries"},signatures:"Yesim Akpinar Kara",authors:[{id:"213746",title:"M.D.",name:"Yeşim",middleName:null,surname:"Akpınar Kara",slug:"yesim-akpinar-kara",fullName:"Yeşim Akpınar Kara"}]}],onlineFirstChaptersFilter:{topicSlug:"emergency-medicine",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/172548/simon-young",hash:"",query:{},params:{id:"172548",slug:"simon-young"},fullPath:"/profiles/172548/simon-young",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)}()