Schmid factors of the four slip systems for three different loading directions. Reconstructed from reference [2].
\r\n\t
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OP is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fractures with minimal trauma, known as fragility fractures. These fractures lead to disproportionally high mortality rate and a drastic decline in quality of life for those affected.
OP is diagnosed by an X-ray (typically by dual energy X-ray absorptiometry or DEXA) scan to measure bone mineral density (BMD) [3]. Two scores are returned: a Z-score and a T-score [4]. The T-score is normalized BMD by sex and age, whereas the Z-score also accounts for weight and ethnicity. Both scores report standard deviations (σ) of BMD from mean. A T-score of −1 is normal (within 1 σ of mean), whereas less than −1 to −2.5 indicates osteopenia. A patient with T-scores less than −2.5 is considered osteoporotic. Additional factors to BMD such as smoking, family history of fractures, the diagnosis of rheumatoid arthritis, alcohol consumption and glucocorticoid use many be considered to predict the probability of fracture using a fracture risk assessment tool score or FRAX score [5, 6].
The skeletal system has several physiological functions. First, it provides mechanical support that allows for locomotion. Bone is weight bearing and serves as an anchor for muscle. Osteocytes are bone matrix embedded mechanosensory cells, that promote bone loss or gain (adaptation) to loads placed on the bone (i.e., Wolff’s law). The marrow space within long bones serves as the primary site of hematopoiesis in an adult. When hematopoietic-derived cells are depleted in the periphery (due to inflammation, for instance) there is demand on the bone marrow [7, 8] to release both progenitors and differentiated cells into circulation [9, 10]. Bone also serves as the primary store for calcium and phosphate, and thus is under control of hormones produced by the parathyroid gland (parathyroid hormone or PTH and calcitonin) and kidneys (fibroblast growth factor 23 or FGF23). Vitamin D facilitate calcium absorption from the diet while PTH, calcitonin and FGF23 regulate serum calcium levels and responds to different physiological needs. In recent years, there is growing appreciation of the diverse roles the skeletal system plays in a person’s health, including whole body metabolism, immune regulation and neurocognitive functions [11], in addition to the previously recognized roles of mechanical support and mineral homeostasis. Based on the function of the skeleton, OP can result from dysregulation in one or more factors that we will discuss in detail below (Figure 1).
The multifactorial nature of osteoporosis (OP). Osteoporosis is most commonly associated both aging and estrogen loss. This figure summarizes factors that affect bone health.
Bone remodeling is a coordinated process where bone resorption and bone formation occur at the same location throughout life to repair microfractures and maintain bone homeostasis. Imbalances in bone remodeling underscore the pathophysiology of OP. There are three major cell types involved in bone remodeling: bone resorbing osteoclasts, bone forming osteoblasts, and osteocytes. Osteoclasts (OC) are multinucleated, bone-specialized macrophages, whose differentiation depends on receptor activator of nuclear factor kappa B (NF-κB) (RANK) and its ligand (RANKL). Osteoblasts (OB) differentiate from mesenchymal stem cells (MSC) and are responsible for bone formation. Many signaling pathways have been discovered that are critical for osteogenic differentiation, including Wingless and Int-1 (WNT)/β-catenin, bone morphogenic protein (BMP) and mechanistic target of rapamycin (mTOR). During bone remodeling, OC are recruited to the site of repair, where they will initiate bone resorption through two major mechanisms: 1) acidification of the microenvironment and 2) secretion of matrix metalloproteases. Towards the end of the resorption phase, OC will recruit MSC and osteoprogenitors and promote the differentiation and maturation of OB. At the same time, OB will secrete osteoprotegerin (OPG), a decoy receptor of RANKL, which will inhibit osteoclastogenesis and shut down bone resorption. OB will then begin producing extracellular matrix that will eventually calcify and become newly mineralized bone. As such, bone resorption and bone formation are tightly coupled and highly regulated. Together, OC and OB form the basic multicellular unit (BMU), the smallest functional unit during bone formation. During remodeling the OC and OB form the bone remodeling unit (BRU). Mature OB have three different fates when bone formation is complete. The majority will undergo apoptosis, a small fraction will become senescent bone lining cells, and an even smaller number become osteocytes. Osteocytes (Ocy) are stellate like cells embedded within mineralized bone that are mechanosensors within the bone. Ocy have a pivotal regulatory role in bone homeostasis, directing and coordinating fracture repair by regulating the BRU. Ocy they have recently been shown to have both osteolytic and anabolic functions and play a pivotal role during lactation [12].
Both men and women develop OP [13]. The skeletal system grows rapidly postnatally and through puberty. Peak bone mass is attained by mid-third decade (mid 20s) of life [14]. Beginning at the end of the third decade, both sexes start to lose bone mass [14] that continues with aging. The rate (or slope = change in bone mass/change in time) varies by anatomical site [15] and by additional factors discussed in this chapter. It follows that the range between normal bone mass, osteopenia and OP is determined by both the peak bone mass (baseline) and the rate of age-related bone loss. Aging leads to increased senescent stem cells that repopulate OC and OB leading to deficiency in repair of microfractures that develop with use [16, 17, 18]. A recent study has shown that ablating senescent osteoclast precursors did not improve age-related bone loss [19]. There is accelerated bone loss (called the acute phase) in menopausal women [20, 21, 22]. The sex differences in age-related bone loss in humans can be recapitulated in mice [23]. In addition to the senescence of progenitor cells, increased oxidative stress during aging have been reported to decreased osteoblastogenesis while simultaneously increase osteoclastogenesis, favoring bone resorption [24]. Further research is needed to understand the effects of aging on bone and crosstalk with other factors.
It is standard practice to advise supplementation of calcium and vitamin D to osteoporotic women. However, most studies have shown that subjects of European ancestry are replete in calcium and vitamin D [25]. A number of studies and meta-analyses prior to 2010 showed an efficacy in reducing fracture risk with vitamin D alone, calcium alone and the combination [26, 27]. The lack of efficacy in some studies was attributed to lack of compliance [28]. There is a historical precedence that links rickets/osteomalacia and OP from the 17th century. The softening of bones became rampant in industrialized countries during the 19th century but rickets/osteomalacia were not clearly distinguished from OP until 1885. It was shown that rickets was due to the lack of new bone formation whereas OP was due to increased bone resorption [29]. Nonetheless, the overlap between hyperparathyroidism, under nourishment, calcium malabsorption with vitamin D insufficiency has become a paradigm for OP leading to practice of advising supplementation [30]. However, recent studies that have indicated that high serum calcium is associated with cardiovascular events, specifically stroke and increase coronary artery calcification, have led to questioning this practice [31, 32, 33]. This increase was due to supplementary calcium and not observed with natural dietary calcium [31, 32]. More recent meta-analysis found a trend for increased risk of cardiovascular events with calcium supplementation, although it was not statistically significant [34]. Additional studies are needed to resolve this question.
Epidemiological studies have shown elderly men and postmenopausal women with low BMI have lower T-scores and are classified as osteopenic or osteoporotic. A positive correlation has been observed in postmenopausal women between high BMI and prevalence of osteoarthritis (OA) and a negative correlation with prevalence of OP [35, 36, 37]. Adipocytes produce hormones (adipokines) that have been shown to regulate bone mass [38, 39]. Adipose tissue, especially visceral adipose tissue, has also been shown to harbor proinflammatory T-cells [40, 41]. Recently, Zou et al. showed that ablation of bone marrow adipocytes in mice cause a dramatic increase in bone mass [42]. Therefore, adipose tissue and obesity forms a complex link to bone health. First, white adipose tissue directly influences OB via adipokines [43]. Second, adipose tissue activates T-cells to produce proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin (IL)-1β and IL-6. Additionally, insulin resistance is associated with obesity, thus altered glucose metabolism also affects bone metabolism, which has been shown to impede OB differentiation [44]. Further studies are needed to understand the mechanism(s) connecting inflammation, lipid and glucose metabolism to OA and OP.
Recent studies have shown that patients taking certain commonly prescribed medicines have higher incidence of OP [45]. The best understood drug-induced bone loss is with glucocorticoids [46, 47]. There are also data suggesting that anticoagulants such as warfarin and heparin, which effect Vitamin K levels, are detrimental to bone health [48, 49]. This class of drugs also alters the gut microbiome adding to the complexity of interpretation [50]. Other drugs, including antiepileptics, proton pump inhibitors, opioid analgesics and aromatase inhibitors induce osteoporosis as well [51, 52, 53, 54]. Further confounding the interpretation of data, these medications are often prescribed long-term in elderly populations who are already at risk due to age of osteoporosis. Even if the effect size of each medication is small, the combined drug–drug interactions can be more than additive [55, 56].
The human digestive tract harbors trillions of microorganisms collectively known as the gut microbiome (GMB), which contain magnitudes more genetic information than our own genome. It is well recognized that the GMB plays an important role in educating the immune system, as germfree (GF) mice have reduced T cell populations. A number of studies have shown an association between GMB and bone health in both animal models [57, 58] and in humans [50]. However, Sjögrne et.al were the first to present evidence of direct interaction between the GMB and the bone [59]. They showed that GF mice had increased bone mass compared to conventionally raised (CONV-R) mice, and that transplantation of a GMB from CONV-R normalized bone mass. Since then, a number of studies have been conducted to investigate the regulation of bone homeostasis by the GMB. Estrogen (E2) loss increases gut permeability [60, 61, 62], which leads to increased priming and activation of inflammation in the gut mucosa, leading to the generation of type 17 helper T-cells (Th17 cells). Segmented filamentous bacterium (SFB) have been shown to induce Th17 in the mice intestine and to promote decreased bone mass [63]. Th17 cells are potent inducers of osteoclastogenesis leading to increased bone resorption and bone loss. Li et al. demonstrated that bone loss in ovariectomized (OVX) mice is depended on the GMB and it can be prevented with supplementation of probiotics [64]. There is clear correlation between GMB and bone health, however the precise mechanisms remain elusive. Recent studies have suggested GMB produce microbial metabolites that have regulatory function on distal organs, including the bone. GMB derived butyrate, polyamines and short-chain fatty acids have been shown to induce regulatory T cell (TREG) generation in the colon [65, 66, 67] and to regulate bone health. Thus, GMB modulate bone mass through a number of mechanisms,
The recognition that T-cell derived cytokines affect bone has given rise to the field of osteoimmunology. The word
In women, aging leads to menopause, the cessation of ovarian function that is one of the leading causes of secondary osteoporosis. Early studies suggested that E2 directly regulates OC [88, 89, 90, 91] and OB [92, 93] and its loss at menopause results in long lived OC and impaired OB, and to uncoupled bone resorption [94]. Postmenopausal osteoporosis (PMOP) has been traditionally regarded as an endocrinal, E2 deficiency mediated disease. Over the last two decades, it has become apparent that E2-loss promotes persistent activation of T-cell that promotes acute phase of osteoporosis [80, 95, 96]. The mechanistic studies for linking E2 loss at menopause and activation of the T-cells has come from ovariectomy (OVX) of rodents and key outcomes have been validated in human studies. OVX of female rodents is a well-established and widely used model for menopause. E2 loss leads to both increased bone resorption and formation, however, this process is uncoupled where the former greatly exceeds the latter, resulting in net bone loss. Pacifici and colleagues first reported in 1990 that there is increased monocytic production of IL-1 in osteoporotic patients, indicating that in the absence of sex steroids, cytokines promote bone loss [97]. OVX of sexually mature mice that were T-cell deficient showed decreased bone loss, which provided further evidence that T-cells play a key role in promoting bone resorption [98, 99, 100, 101, 102], as did blockade of TNFα [103] and IL-17A [104]. At the same time, Takayanagi et al. showed that IFN-γ regulated osteoclastogenesis [69, 105]. In the past decade, there is mounting evidence suggesting that the immune system and inflammation play a critical pathogenic role in uncoupled bone loss [82, 106, 107, 108, 109, 110].
Recently, our lab has described a new pathway where E2 loss leads to chronic low-grade production of the proinflammatory cytokines TNFα and IL-17 by memory T-cells (TMEM) that was dependent on IL-7 and IL-15 in mice [111] (Figure 2). The increased production of IL-7 and IL-15 was mediated by bone marrow dendritic cells (BMDCs), which in the absence of E2 do not express FasL, leading to an antigen-independent activation of TMEM. These TMEM proliferate, and a subset become effector memory T-cells (TEM) to produce TNFα and IL-17A. TMEM encode a lifetime of exposures to antigens and only a subset of these could be converted to IL-17A and TNFα expressing. This notion would explain the variance at the population level in the development of PMOP. We hypothesize that the difference in the bone marrow TMEM population based on the life-time antigen exposure would result in varying sensitivity of reactivation.
Novel pathway of E2 loss induced chronic inflammations leading to bone loss.
The therapeutics prescribed most commonly for osteoporosis are anti-resorptives like bisphosphonates or denosumab. One issue with this class of medications are the adverse effects, most notably osteonecrosis of the jaw (ONJ). Although ONJ is rare (1–3%), it has been observed with anti-resorptive therapies (both bisphosphonates and denosumab) in patients with certain predisposing factors (i.e., after tooth extraction or in people with type 2 diabetes).
The second class of therapies are bone anabolics. Two examples of this class are teriparatide [112] and more recently romosozumab that targets sclerostin [113]. The bone anabolic therapies are also limited in their use because of potential adverse effects with prolonged use [114, 115, 116] and in special populations as well [117]. Furthermore, there is a limited window for the efficacy of many bone anabolic therapies due to adaptations in the bone in response to therapy. Interestingly, it has been observed in randomized control trials that the sequence of medication has substantial impacts on the long-term outcome. Patients who received teriparatide for 2 years first, followed by anti-resorptives maintained bone mass significantly longer than patient who received antiresorptives first [118].
As we discussed in this chapter, OP can arise from a combination of multiple causes. It follows that the treatment of osteoporosis should target additional mechanisms. All current therapies target the cells of the BRU, to suppress resorption of to promote bone formation. Furthermore, the current therapies have shortcomings and adverse effects with prolonged use necessitating drug holidays [119]. Therefore, additional therapies are needed, including a more precision medicine approach to treat osteoporosis. Immunomodulatory options such as anti-TNFα, anti-IL-17A and anti-RANKL have yielded inconsistent results in patients. Recently, Chong et al. [120] showed that neutralization of IL-17A induces compensatory increase of other Th17 cytokines, including IL-17F, IL-22 and GM-CSF. This has implication for the use of immunomodulatory therapies in PMOP.
Our laboratory discovered that OC are antigen presenting cells that induce Forkhead box protein 3 (FoxP3), cluster of differentiation (CD) 25, cytotoxic T-lymphocyte-associated protein (CTLA) 4 and expression of IFN-γ and IL-10 in CD8+ T-cells in vitro (Figure 3). We have validated that these CD8+ regulatory T-cell (TcREG) are induced by OC during bone resorption in vivo [121, 122]. Bone resorbing OC induce TcREG and TcREG suppress bone resorption by OC to form a negative feedback loop [123]. TcREG are also immunosuppressive like their CD4+ counter parts [124]. Both in vivo induction by low dose pulse RANKL (pRANKL) and adoptive transfer of ex vivo generated TcREG suppressed bone resorption, TNFα production and promoted bone formation to ameliorate osteoporosis in OVX mice [125]. In unpublished studies, OVX IL-10 deficient mice were unresponsive to the bone anabolic effects of pRANKL. However, TcREG retained its ability to inhibit TNFα production in TEM, suggesting that the immunosuppressive effects are IL-10 independent. Further investigation showed that IL-10 directly regulates OB at the gene expression level. Taken together, our observations indicate that the immune system plays a fundamental role in modulating bone homeostasis, able to tip the balance either in favor of uncoupled bone resorption or bone formation.
Osteoclasts induce tolerogenic TcREG. OC use three signals to induce TcREG: Antigen-loaded MHC I, CD200 (a costimulation molecule that activates NF-κB) and the notch ligand DLL4. Treatment with pRANKL leads to increased expression DLL4 and therefore increased induction of TcREG. TcREG secrete IFN-γ that suppress osteoclastogenesis by degrading TRAF6 and resorption by mature OC. TcREG also secrete IL-10, which is required for the bone anabolic activity but not resolution of inflammation. IL-10 may also target Ocy to improve cortical bone mass. Resolution of inflammation appears to be mediated by CTLA4 expressed on TcREG.
In this chapter, we highlighted the multifactorial nature of osteoporosis. Bone loss occurs with age and slope associated with this decline may be enhanced with decreased vitamin D3, calcium deficiency in diet, medicines and polypharmacy, excess secretion of phosphate by kidneys, by hyperparathyroidism, chronic inflammation by persistent infections and autoimmune disease. E2 loss also triggers a low-grade persistent inflammation in a subset of memory T-cells that promotes rapid bone erosion. Emerging evidence demonstrates significant interplay between these factors revealing the tradeoffs between organismal homeostasis and organ-specific regulation. Research in current decade is likely to provide new insights and mechanisms into the crosstalk. Revealing the mechanistic details will provide exciting new targets for therapies. Furthermore, determining the factors in each individual would allow for precision medicine approach to promoting bone health in the aging population.
We thank Daniel Goering, Yiyi Zhang and Lizzie Geerling for contributing to additional unpublished experiments referenced herein.
The authors declare no conflict of interest.
RA conceived of the manuscript. DW and RA drafted the manuscript. ACS and ES provided literature search and edits. All authors were involved in scientific discussion of the review.
DEXA | dual energy X-ray absorptiometry |
BMD | bone mineral density |
FRAX | fracture risk assessment tool |
PTH | parathyroid hormone |
FGF23 | fibroblast growth factor 23 |
OC | osteoclasts |
NF-κB | nuclear factor kappa B |
RANK | receptor activator of NF-κB |
RANKL | receptor activator of NF-κB ligand |
OB | osteoblasts |
MSC | mesenchymal stem cells |
WNT | wingless and Int-1 |
BMP | bone morphogenic protein |
mTOR | mechanistic target of rapamycin |
OPG | osteoprotegerin |
BMU | basic multicellular unit |
BRU | bone remodeling unit |
BIM | body mass index |
OA | osteoarthritis |
TNFα | tumor necrosis factor alpha |
IL | interleukin |
GMB | gut microbiome |
CONV-R | conventionally raised |
Th | helper T cell |
OVX | ovariectomy (surgery) or ovariectomized |
TREG | regulatory T cell |
IFNγ | interferon gamma |
HIV | human immunodeficiency virus |
TMEM | memory T cell |
BMDC | bone marrow dendritic cells |
TEM | effector memory T cell |
ONJ | osteonecrosis of the jaw |
FoxP3 | forkhead box P3 |
CD | cluster of differentiation |
CTLA4 | cytotoxic T-lymphocyte-associated protein 4 |
As time passes, the advancement of nanotechnology has spread to all fronts. The concept states that at least two dimensions that construct nanomaterials fall between 1 and 100 nm. Nanomaterials are classified as zero- (0D), one- (1D), two- (2D), and three-dimensional (3D) nanostructures. The nanoscale has unprecedented attributes that fundamentally alter materials’ properties. Since K. Novoselov et al. successfully mechanically exfoliated a single layer of graphene off the graphite in 2004 [1], extensive efforts and progress have been made on the synthesis and applications of graphene and various 2D nanomaterials in resemblance to graphene nanostructure, including transition metal dichalcogenides (TMDs), hexagonal boron nitride (BN), and perovskites, just to name a few. They have lateral extension but their individual layer is merely a single or few atoms thick. Hence, they have characteristics like electron confinement and anisotropy in various properties manifested in two dimensions, while they possess extended interlayer spacing for active kinetic and physicochemical events, which has attracted broad research interests on their physicochemical, electrochemical, electronic and mechanical properties. For metallic materials, metallic thin films/coatings have 2D extension but limited thickness. The 2D materials selected to represent each materials family are crystalline materials and, in general, possess crystal anisotropy in their mechanical behaviors and even functional property. The single crystal face-centered cubic (FCC) structure is taken as an example. It is well known that the FCC single crystals have crystal anisotropy determined by the Schmid factor that associates the loading direction to the load resolved on the specific slip system [2]. Because the glide of the dislocations is favored on the slip systems subjected to a larger Schmid factor, plastic anisotropy manifests in the form of different cellular substructure made of dislocation walls. As we alleged, the non-metallic 2D nanomaterials have extended interlayer spacing and metallic thin films, fabricated primarily by ultrahigh vacuum techniques and electrodeposition, feature high-density directional grain boundaries (GBs) and preferential texture. As a result, anisotropy in 2D materials is prone to deviate from that of the bulk crystals, and plays substantial roles in their mechanical applications and the reliability of the apparatuses and devices with 2D materials as components or building blocks, but has not been put emphasis on as much as their functional properties and synthesis. Prior to comprehension toward the mechanical anisotropy of 2D materials, their general microstructural features and applications are first set forth so as to better grasp the anisotropy in their mechanical response to external stimuli and its importance in their functional and engineering applications.
Graphene is a typical 2D carbon allotrope and a monolayer of graphene, with a thickness of 0.335 nm, has a hexagonal honeycomb structure. This 2D nanomaterial is remarkably electric and thermal conductive and is equipped with the promising quantum Hall effect. Moreover, the pristine graphene possesses an elastic modulus of ∼1 TPa and a mechanical quality factor of 104 at an elevated temperature of 5 K. Despite similar sheet-like nanostructures, 2D nanomaterials made of inorganic compounds can render intriguing properties and versatility due to their more complex compositions. In contrary to chemically inert graphene with no intrinsic bandgap, MoS2 with layered structure is one transition metal dichalcogenide. MoS2 has been often synthesized using chemical vapor deposition (CVD) and its reaction principle involves first the transformation of solid-state MoO3 and sublimed surfur to gas state and then the mixed gases driven by argon caused the formation of gas-phase MoO3-x and MoS2 and eventually the formation of solid-state MoS2, the reactions of which is expressed as [3]:
MoS2 structure is comprised of two layers of closely packed S atoms layers sandwiching a layer of Mo atoms and it features strong covalent bonding as a result of the Mo-S interaction and the Van der Waals force between S layers. This leads to the comparably facile kinetic transportation of ions and even molecules through S-Mo-S layered structure [4]. Hence, it has drawn enormous attention for its potent applications in energy storage and conversion, such as photocatalysis for the pollutant degradation and biosensors, just to name a few. In addition, MoS2 has a good tunability toward its band gap, which offers high flexibility in property customization and optimization. At the same time, MoS2 manifests comparable physical attributes when compared to graphene, including high charge carrier mobility and superb wear properties. Compared to hexagonal structure, other structurally complex 2D materials, such as arsenic trisulfide (As2S3), also showed mechanical anisotropy [5]. A unit cell of As2S3 consists of two layers inverted with respect to a symmetry center and is defined by 20 atoms in contrast to two for graphene and three for MoS2.
Now, we turn our attention to a different 2D materials family, i.e. metallic coating and thin films. The protective coatings, from an engineering point of view, are essential as to apparatus maintenance and the enhanced equipment safety and lifespan. One application of metallic or their composite coating is to prevent corrosion. Coatings should render compatibility with parental materials and operate at extreme atmospheres, such as high temperature and corrosive conditions. Metallic coatings either provide passive protection by forming a barrier of oxides or offer active protection obtained through the adsorption of chemical inhibitors [6]. Metallic coatings as biomaterials are potent components in body implants and they ought to possess superb mechanical behaviors and biocompatibility, and high corrosion resistance, while they are required to release minimal metallic ions to avoid the toxicity. Ti, NiTi, Pt and 316 L austenitic stainless steel are often implemented. Furthermore, various metals with unique characteristics are used in the applications of thin film optics, such as surface plasmon generation and optoelectronics. Metallic thin films are frequently applied onto ceramic matrices, rendering high-quality broadband reflective finishing highly desired to control over the directionality of the laser beam. In addition, Cu is commonly utilized as an interconnect material and serves as thin conductive layers ensuring the adhesion to dielectrics and inhibiting diffusion into silicon or dielectrics, and provide capability of electrodeposition of Cu [7]. From the aforementioned applications of metallic coating and thin films, it is realized that their fabrication often relies on non-equilibrium routes, such as a variety of ultrahigh vacuum techniques and electrodeposition/electroplating. The energetic adatoms landing on the substrate often first form nanometric epitaxial zone and then become 3D clusters during the growth process [8]. Moreover, the sophisticated compositions or the interaction between matrix atoms and impurity atoms as dopants and alloying elements often exert pinning effects. These factors result in the formation of abundant GBs among the columnar nanograins. Many thin films have been grown homo- or heteroepitaxially on single crystal templates or locally on polycrystalline templates, giving rise to the preferential texture in the films. Both the GB directionality and the preferential texture in the coatings or thin films should lead to mechanical and crystal anisotropies which greatly affect their performance in practical applications and hint at the property optimization along each direction.
In FCC single crystals, the Schmid factors mainly explains the crystal anisotropy. For a given crystal, different loading directions result in different sets of Schmid factors on the 24 slip systems FCC structure intrinsically has, eventually tailoring dislocations on different slip systems. Along with the dislocation populations, the dislocations would self-organize into certain low energy substructures with cellular shape. For instance, [111]-loading generally leads to planar-shaped cell substructures, whereas [100] direction renders spherical-shaped ones. To be specific, the Schmid factors of the four slip planes for three different loading directions are present in Table 1. Z. Q. Wang et al. introduced an H-factor based on Schmid factors to comprehend the deformation heterogeneity and the formula is expressed as [2].
0.41, 0.41, 0.0 | 0.0, 0.0, 0.0 | 0.0, 0.0, 0.0 | |
0.41, 0.41, 0.0 | 0.27, 0.27, 0.0 | 0.41, 0.27, 0.14 | |
0.41, 0.41, 0.0 | 0.27, 0.27, 0.0 | 0.41, 0.27, 0.14 | |
0.41, 0.41, 0.0 | 0.27, 0.27, 0.0 | 0.27, 0.27, 0.0 |
Schmid factors of the four slip systems for three different loading directions. Reconstructed from reference [2].
where
For polycrystalline cubic metallic materials, the Yield strength is associated to a Taylor factor,
where
The 2D non-metallic materials display remarked structural anisotropy due to the large interlayer spacing and comparably low interlayer cohesion and interaction, which causes that a monolayer of graphene could be readily mechanically exfoliated and hexagonal MoS2 (h-MoS2) with lamellar structure can be used as a solid lubricant owing to its superlubricity causing the facile glide among MoS2 nanosheets. However, in the in-plane direction, the assumption of mechanical isotropy in 2D materials is premature just based on the six-fold symmetry in their hexagonal lattice when the isotropy has been assumed for some estimations of the elastic behaviors in carbon nanotubes. Prior researches unveiled that friction force exerted on both graphene and MoS2 along in-plane ‘zigzag’ and ‘armchair’ directions of the hexagonal lattice gave rise to different results and friction tests along armchair direction resulted in larger friction forces. M. Dienwiebel et al. found the angular interval between two friction peak force being approximate 60° upon friction tests on graphite [12]. This suggests that the 2D materials with hexagonal lattice manifest a sixfold anisotropy with a 60° periodicity. Meanwhile, studies showed that the anisotropy in both graphene and MoS2 has a thickness dependence [13]. 2D non-metallic nanomaterials have been often used as building blocks or components for micro/nano-electromechanical systems (M/NEMSs) and nanoelectronics. The anisotropy of those 2D materials have great influence on not only mechanical properties but also functional properties.
Metallic coating and thin films have been largely fabricated adopting non-equilibrium ultrahigh vacuum techniques and electrodeposition. When the nuclei heterogeneously grow and then 3D clusters collide amid the coalescence process, forming intercrystalline interface. This process generally gives rise to nanocolumnar grains whose grain size is small, even in monolithic metals, in contrast to other equilibrium processes. Figure 1 shows the structure zone diagram after energetic deposition of a thin film on a substrate, indicating that columnar grains preferentially being generated at different generalized temperature
Structure zone diagram after energetic deposition at different generalized temperature
It has been known that graphene, graphene oxide and their composites exhibit mechanical anisotropy due to their characteristic of 2D extension [17, 18]. The investigations on the superlubricity of 2D nanomaterials have been also extensively conducted. A classic example is that M. Dienwiebel et al. studied the energy dissipation of a graphite at selective sliding directions on a Tribolever setup equipped with a tungsten tip and found the ultralow friction with the incommensurability nature [12]. Another example is M. Poot and H. S. J. Van der Zant adopted atomic force microscope (AFM) to measure force-distance relations on few-layer graphene and graphite flakes and discovered that a principle direction represents a stiffer direction than the others [19]. In contrast to those studies, a molecular dynamics simulation (MD) study is particularly selected to exhibit the anisotropic mechanical behaviors of graphene monolayers under uniaxial tensile condition along the zigzag and armchair directions [11]. 4.15 × 4.15 nm2 square-shaped graphene monolayers with a thickness of 0.335 nm were fixed at one end and the tensile tests along the zigzag and armchair directions are present in Figure 2a and b. The relations between applied force and one unit cell are also present. The specific parameters of the non-equilibrium MD simulations can be found in the literature.
Molecular dynamics simulation of tensile tests on 4.15 × 4.15 nm2 square-shaped graphene monolayer along (a) zigzag and (b) armchair directions and the relations between applied force and one unit cell are present. Reprinted with permission from reference [
Regardless of the fracture patterns, the MD experiments first calculated the fracture stresses along the zigzag and armchair directions, which are 0.18 TPa at a strain of 32.48% and 0.21 TPa at 43.85%, respectively. In is worth noting that the predicted critical stresses and strains are anticipated to be higher than the empirical ones due to the idealism in the conditions of MD simulations. Prior to the crack formation, two test modes share similarity, that is, in the elastic region, the graphene monolayers regardless of testing directions could sustain large elastic deformation and upon crack formations, the crack propagated rapidly and led to the final fracture within 0.01% strain, suggestive of a brittle cleavage fracture. For the zigzag direction, within the strain from 32.484% to 32.489%, the crack propagated from one edge to the other edge, forming a zigzag-like fracture topography and the topological defects, whereas a rather smooth fracture feature was monitored as the strain varied from 43.859% to 43.866% under the test along armchair direction and the process left limited topological defects. It should be noted the five significant digits might be trivial in the real experiments but it was non-trivial in the MD simulations to capture detailed fracture process. The fracture evolutions along two directions were captured using snapshots in Figure 3. Since the C-C bonds have a critical strength, i.e.
Tensile strain-induced fracture process (a) along the zigzag direction and (b) along the armchair direction at various strain levels. Reprinted with permission from reference [
The MoS2 has similar lamellar structure as graphene and has been considered promising in the field of nanotribology, despites its various applications due to its functional properties. The inherent crystallographic characteristics of h-MoS2 equips it with friction anisotropy pertaining to the effect of the lateral sliding direction on the friction behaviors or the commensurability/incommensurability conditions between two sliding planes. In the case of incommensurability where the two sliding surfaces have crystallographic nonmatching, ultralow friction is obtained and superlubricity occurs, which has been observed in 2D materials, such as MoS2, graphene and highly oriented pyrolytic graphite to name a few. The superlubricity is related to the structural anisotropy. Figure 4 presents the debris of five-layer thick MoS2 after a wear test and the high resolution transition electron microscopic (HRTEM) image shows different mosaic lattice domains as a result of 15° and 30° relative rotations between MoS2 nanosheets [21]. Commonly, six-fold and two-fold symmetry of the friction behaviors have been captured on empirical and computational researches. Some two-fold symmetry of friction behaviors, namely 180° periodicity, have been attributed to the oriented linear wrinkles induced by the elastic deformation of the substrate and the testing conditions, one of which is the direction-dependent friction measured by an AFM tip with rotation. It was hypothesized that the tip rotation generated a variety of possible combination of the tip-specimen interfaces and the friction results might be able to reflect the genuine crystallographic pattern of the tested materials.
High resolution TEM micrograph of a five-layer thick MoS2 specimen after a wear test and the slide led to different mosaic lattice domains with 15° and 30° relative rotations. Reprinted with permission from reference [
A study involving experimental and MD simulation results on the friction property of MoS2 was present [22]. The direction-dependent friction behaviors were measured by changing the scanning direction and a 5 nm travel distance was applied to preclude the influence from the nanowrinkles. The atomic configuration and the scanning direction with respect to the lattice are illustrated in Figure 5a. Figure 5b presents the two friction loops consisting of forward and backward lateral scans, measured by AFM along zigzag and armchair directions, and it shows that the energy dissipated in each scan cycle of the tests along the armchair direction was 11 times higher than that of the tests along the zigzag direction. Figure 5c shows comparable simulation results and the quantitative discrepancy between the empirical and simulation results originates from the difference in tip conditions and the magnitude of the scanning speed and force. The Prandtl-Tomlinson model alleged that the friction at the atomic level relies on the height of the surface energy barrier and longer scanning length along the armchair direction would result in accumulated energy dissipation in comparison with the zigzag direction. Hence, the direction-dependent friction behaviors were examined using potential energy surface (PES). Figure 6a reveals a six-fold symmetry of the friction force in nN in comparison with the two-fold symmetry. To further comprehend the friction symmetry, PEC at various angular positions was observed with a 10° interval. Figure 6b reflects the cross-section energy profiles for the scans at 0°, 10° and 50°. Figure 6c-j show that PES possessed a 60° periodicity, e.g. the energy surfaces of the 0° and 60° being identical. Therefore, a friction anisotropy was explored at an atomic level, proving that the testing direction and tip-specimen contact quality greatly play significant roles in changing the energy landscape and affecting the friction behaviors. X. Cao et al. have exhibited that the friction behaviors of MoS2 had a thickness effect [13]. In brief, the decrease in MoS2 thickness down to a few nanometers could progressively weaken the anisotropy phenomenon and be more governed by the puckering effect.
(a) Atomic configuration of a MoS2 monolayer in the simulations, indicating the armchair (30°) and zigzag directions (60°). (b) the experimental friction loops consisting of the forward and backward scanning along the armchair and zigzag directions. (c) the friction traces, due to tip-specimen contacts, predicted by the MD simulations along the armchair and zigzag directions. Reprinted with permission from reference [
(a) MD simulation that monitored a 6-fold symmetry in the results of friction tests on MoS2 as a function of the rotational. (b) Cross-sectional barrier profiles along the scanning distance at a sample rotation angle of 0°, 10° and 50°. (c − j) potential energy surface (PES) calculated for the specimen rotated from 0° to 70°. Reprinted with permission from reference [
Since the early 1950’s when Hall and Petch empirically demonstrated that the Yield strength of metallic materials is inversely proportional to the square root of the microstructural features, researchers have put enormous efforts in refining the microstructure and thus developed ultrafine grained materials and nanocrystalline materials in order to lift mechanical strength for both fundamental exploration and practical applications. Non-equilibrium routes have been commonly used to shrink the grain size of the metallic materials and most of techniques, such as ultrahigh vacuum techniques and electrodeposition, produce 2D metallic materials, i.e. coatings and thin films. Researchers have found that the tensile strength collected from the tensile tests on thin film metals, especially alloys, fell short of the predicted strength translated from nanoindentation measurements according to the Taylor relation, i.e. H = C
Figure 7a shows the dark-field TEM image and HRTEM image, suggesting that the Al-Fe alloys have abundant vertical GBs, which were identified as incoherent twin boundaries (ITBs) with a diffused feature, and an average grain size of ∼5 nm. It is expected that the tiny grain size would greatly suppress the dislocation accumulation process that takes place in the plastic deformation of single crystals or polycrystalline materials with large grain size, making the deformation or fracture events more dominantly influenced by the directionality of the GBs. Figure 7b-d illustrate the micro-tension and compression experiments along in-plane and out-of-plane directions and exhibit the microsized specimens awaiting the in-situ experiments.
(
The experiment results showed that the out-of-plane compression experiments gave rise to a ∼ 2 GPa strength and exhibited extensive deformability attributed to the grain coarsening, whereas in-plane compressions yielded a ∼ 1.6 GPa strength but an intergranular shear deformation along the GBs, leaving the formation of shear bands. This deformation mode was governed by the maximum resolved shear stress. In addition, out-of-plane tensile experiments gave a tensile strength of ∼1.8 GPa, comparable to the 2 GPa compressive strength, and a fracture mode governed by the intragranular shear propagation which were substantially deflected by vertical GBs. The apparent global engineering strain cannot be equated to the ductility of the common ductile materials with larger grain size and dislocation-dominated deformation mechanisms. In contrast, the in-plane tension experiments exhibited a relatively low strength of ∼1.1 GPa and classic brittle behaviors governed by the nominal stress-induced fracture. The premature fracture propagated along GBs. It was found that the chemical combination of binary Al-Fe alloys did not satisfy the embrittlement criteria in the Gibson-Schuh model [23], meaning that the relation between applied tensile stress and the directionality of the vertical void-free GBs, i.e. vertical ITBs, mostly rendered the premature fracture phenomenon under in-plane tension mode rather than other factors including voids and GB embrittlement. Figure 8 had summarized the major deformation or fracture mechanisms of the tension and compression tests along the in-plane and out-of-plane directions. It is noted that the anisotropy experienced in the Al-Fe thin films is different from the anisotropy in single crystals and polycrystals, governed by the Schmid factor and the Tylor factors. Moreover, the thin film alloys, including the Al-Fe, are also different from the isotropic nanocrystalline metals and alloys with textureless feature. However, dislocations were indeed captured in the differently deformed Al-Fe specimens. It was found that under compression, the ratio of the yield strength collected under out-of-plane compression mode and in-plane compression mode was ∼1.25, which was mostly governed by the Taylor factors of two testing directions. Since the Al-Fe alloys have a strong (111) out-of-plane texture, the out-of-plane Taylor factor is 3.67. Moreover, the in-plane direction has no obvious texture or a weak (112) texture and the two possibilities rendered similar Taylor factor of 3.06. This two Taylor factors led to a strength ratio of 1.2, coinciding with the 1.25 collected experimentally. This indicates that the anisotropy in the Al-Fe thin films was both influenced by the directionality of the GBs and the conventional Taylor factor. Figure 9 plots the collected strengths under tension and compression along the in-plane and out-of-plane directions as a function of extrinsic specimen dimension and intrinsic microstructural feature size and it clearly manifested the anisotropy under both tension and compression modes. The Al-Fe alloys underwent negligible extrinsic size effect and are highly competitive as to the high strength.
Schematics that illustrate the deformation or fracture mechanisms for Al-Fe specimens tested at different modes along different directions. Reprinted with permission from reference [
(a) The yield strength or fracture strength, collected from different testing conditions, of Al-Fe thin films in comparison to the ones of other Al alloys with extrinsic dimensions at similar magnitudes. (b) the comparison of the strengths
Some thin films or coatings consisting of constituent elements with low stacking fault energy might have columnar grains packed with high-density horizontal coherent TBs (CTBs). Q. H. Lu et al. found that the dislocations were confined within the twin/matrix lamellae and the testing direction, the slip systems and the horizontal CTBs of the NT Cu could result in different dislocation structures and dislocation-CTB interactions, which rendered different hardening and softening modes and thus the anisotropy in metallic thin films made of constituent elements with low stacking fault energy [24]. Furthermore, it should be noted that not all the metallic thin films prepared by non-equilibrium methods possessed the conventional columnar GBs. Li et al. recently exhibited that manipulation of electrolytic solution with certain organic additive could potentially transfer the 3D cluster growth to a flat 2D layer-by-layer growth mode to facilitate the formation of TBs and suppress the formation of the columnar GBs from the island coalescence process [8]. The anisotropy of the NT metals mainly constructed by horizontal CTBs needs further investigation. Furthermore, the mechanical anisotropy in metallic materials could be also displayed from the dynamic strain-induced phase transformation. In a Transformation induced plasticity (TRIP) steel, a strong texture after rolling was obtained in the austenite and the texture in austenite gave rise to a higher martensitic transformation rate along the rolling direction, which contributed to a more pronounced TRIP effect and a higher strain-hardening rate [25, 26].
The synthesis, microstructural controls and the functional applications of 2D materials have been top trending research topics in the past 2 decades. However, the anisotropy of the 2D materials has not been put equal but actually exerts potent influence on not only their mechanical behaviors but also the multifunctional performance of materials and devices with 2D materials as components or building blocks. The unique microstructural characteristics of 2D materials result in distinct and intriguing structural and crystal anisotropy. As to the non-metallic 2D nanomaterials, such as graphene and MoS2, the orientation of the applied stress with respect to the lattice often cause different interlayer friction, even the superlubricity, and the monolayer with the inherent crystallographic symmetry of the hexagonal honeycomb lattice also exhibited anisotropy when subjected to fracture. For the metallic thin films with 2D extension and limited thickness, the directional and abundant grain boundaries could influence the anisotropy comparison with the bulk single crystals or polycrystals whose anisotropy is primarily dominated by the Schmid factor or Taylor factor. It is anticipated that the sustainability and reliability of the materials and devices constructed by various 2D materials rely on the prominent anisotropy inside 2D materials. The in-depth comprehension toward the anisotropy of 2D materials would be also instructive to realize the orientation-dependent properties and the property optimization.
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Anti-inflammatory diet is designed to improve health and prevent the occurrence and development of chronic diseases associated with inadequate diet. Proper nutrition is based on the anti-inflammatory pyramid and changes in poor eating habits are the long-term strategy for preventing inflammation and chronic diseases. Inflammatory factors from food may play a role in the development of osteoporosis and an anti-inflammatory diet may be a way to control and reduce long-term inflammation and prevent bone loss. Pro-inflammatory cytokines from the fat tissue, through activation of the RANKL/RANK/OPG system could intervene with bone metabolism in a way of increased bone loss. Therefore the special attention need to be given to obese patients due to twofold risk, one related to pro-inflammatory cytokines release and the other related to the deprivation of the vitamin D in the fat tissue.",book:{id:"10323",slug:"osteoporosis-recent-advances-new-perspectives-and-applications",title:"Osteoporosis",fullTitle:"Osteoporosis - Recent Advances, New Perspectives and Applications"},signatures:"Olga Cvijanović Peloza, Sandra Pavičić Žeželj, Gordana Kenđel Jovanović, Ivana Pavičić, Ana Terezija Jerbić Radetić, Sanja Zoričić Cvek, Jasna Lulić Drenjak, Gordana Starčević Klasan, Ariana Fužinac Smojver and Juraj Arbanas",authors:[{id:"339281",title:"Associate Prof.",name:"Olga",middleName:null,surname:"Cvijanović Peloza",slug:"olga-cvijanovic-peloza",fullName:"Olga Cvijanović Peloza"},{id:"346420",title:"Prof.",name:"Sandra",middleName:null,surname:"Pavičić Žeželj",slug:"sandra-pavicic-zezelj",fullName:"Sandra Pavičić Žeželj"},{id:"346421",title:"BSc.",name:"Ivana",middleName:null,surname:"Pavičić",slug:"ivana-pavicic",fullName:"Ivana Pavičić"},{id:"346423",title:"Prof.",name:"Ana Terezija",middleName:null,surname:"Jerbić Radetić",slug:"ana-terezija-jerbic-radetic",fullName:"Ana Terezija Jerbić Radetić"},{id:"346424",title:"Prof.",name:"Sanja",middleName:null,surname:"Zoričić Cvek",slug:"sanja-zoricic-cvek",fullName:"Sanja Zoričić Cvek"},{id:"346426",title:"MSc.",name:"Jasna",middleName:null,surname:"Lulić Drenjak",slug:"jasna-lulic-drenjak",fullName:"Jasna Lulić Drenjak"},{id:"346427",title:"Prof.",name:"Gordana",middleName:null,surname:"Starčević Klasan",slug:"gordana-starcevic-klasan",fullName:"Gordana Starčević Klasan"},{id:"346428",title:"MSc.",name:"Ariana",middleName:null,surname:"Fužinac Smojver",slug:"ariana-fuzinac-smojver",fullName:"Ariana Fužinac Smojver"},{id:"346429",title:"Prof.",name:"Juraj",middleName:null,surname:"Arbanas",slug:"juraj-arbanas",fullName:"Juraj Arbanas"},{id:"350011",title:"Dr.",name:"Gordana",middleName:null,surname:"Kenđel Jovanović",slug:"gordana-kendjel-jovanovic",fullName:"Gordana Kenđel Jovanović"}]},{id:"76351",doi:"10.5772/intechopen.97416",title:"Glucocorticoid-Induced Osteoporosis",slug:"glucocorticoid-induced-osteoporosis",totalDownloads:254,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The use of glucocorticoids (GC) in the medium and long term, causes several considerable side effects, being one of the main ones the reduction of bone mineral density (BMD). Prolonged corticosteroid therapy reduces BMD by up to 20% in trabecular bone and approximately 2–3% in cortical bone in the first year of use. This loss rate declines and stabilizes at approximately 2% in subsequent years. Therefore, there is a considerable increase in the incidence of pathological fractures, whether clinically symptomatic or asymptomatic (detected as a radiological finding), which varies between 30 and 50% of patients who use GC for more than three months. In view of the above, it is essential to prevent fractures and treat osteoporosis in patients using glucocorticoids for long periods (in particular, greater than or equal to 3 months), which may or may not be associated with clinical risk factors or previous fractures. The guidelines for the treatment and prevention of this comorbidity are well established for postmenopausal women and men over 50 years of age. However, for patients below this range, studies are still lacking.",book:{id:"10323",slug:"osteoporosis-recent-advances-new-perspectives-and-applications",title:"Osteoporosis",fullTitle:"Osteoporosis - Recent Advances, New Perspectives and Applications"},signatures:"José Renan Vieira da Costa Júnior and Sérgio Luchini Batista",authors:[{id:"164388",title:"Prof.",name:"Sergio",middleName:null,surname:"Luchini Batista",slug:"sergio-luchini-batista",fullName:"Sergio Luchini Batista"},{id:"354032",title:"Dr.",name:"José Renan",middleName:null,surname:"Vieira Da Costa Júnior",slug:"jose-renan-vieira-da-costa-junior",fullName:"José Renan Vieira Da Costa Júnior"}]},{id:"76677",doi:"10.5772/intechopen.97760",title:"Introductory Chapter: Osteoporosis Overview",slug:"introductory-chapter-osteoporosis-overview",totalDownloads:176,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"10323",slug:"osteoporosis-recent-advances-new-perspectives-and-applications",title:"Osteoporosis",fullTitle:"Osteoporosis - Recent Advances, New Perspectives and Applications"},signatures:"Luis Rodrigo",authors:[{id:"73208",title:"Prof.",name:"Luis",middleName:null,surname:"Rodrigo",slug:"luis-rodrigo",fullName:"Luis Rodrigo"}]}],mostDownloadedChaptersLast30Days:[{id:"75660",title:"Bone Quality of the Dento-Maxillofacial Complex and Osteoporosis. Opportunistic Radiographic Interpretation",slug:"bone-quality-of-the-dento-maxillofacial-complex-and-osteoporosis-opportunistic-radiographic-interpre",totalDownloads:354,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Research suggests the use of different indexes on panoramic radiography as a way to assess BMD and to be able to detect changes in bone metabolism before fractures occur. Therefore, the objective of this chapter is to describe the use of these parameters as an auxiliary mechanism in the detection of low bone mineral density, as well as to characterize the radiographic findings of patients with osteoporosis.",book:{id:"10323",slug:"osteoporosis-recent-advances-new-perspectives-and-applications",title:"Osteoporosis",fullTitle:"Osteoporosis - Recent Advances, New Perspectives and Applications"},signatures:"Plauto Christopher Aranha Watanabe, Giovani Antonio Rodrigues, Marcelo Rodrigues Azenha, Michel Campos Ribeiro, Enéas de Almeida Souza Filho, Rafael Angelo Soares Vieira and Fabio Santos Bottacin",authors:[{id:"76171",title:"Prof.",name:"Plauto C. A.",middleName:null,surname:"Watanabe",slug:"plauto-c.-a.-watanabe",fullName:"Plauto C. A. Watanabe"},{id:"337631",title:"Dr.",name:"Giovani Antonio",middleName:null,surname:"Rodrigues",slug:"giovani-antonio-rodrigues",fullName:"Giovani Antonio Rodrigues"},{id:"350577",title:"Dr.",name:"Fabio",middleName:null,surname:"Santos Bottacin",slug:"fabio-santos-bottacin",fullName:"Fabio Santos Bottacin"},{id:"350578",title:"Dr.",name:"Rafael Angelo",middleName:null,surname:"Soares Vieira",slug:"rafael-angelo-soares-vieira",fullName:"Rafael Angelo Soares Vieira"},{id:"350579",title:"Dr.",name:"Enéas de Almeida",middleName:null,surname:"Souza Filho",slug:"eneas-de-almeida-souza-filho",fullName:"Enéas de Almeida Souza Filho"},{id:"350580",title:"Dr.",name:"Michel",middleName:null,surname:"Campos Ribeiro",slug:"michel-campos-ribeiro",fullName:"Michel Campos Ribeiro"},{id:"350581",title:"Dr.",name:"Rodrigues Azenha",middleName:null,surname:"Rodrigues Azenha",slug:"rodrigues-azenha-rodrigues-azenha",fullName:"Rodrigues Azenha Rodrigues Azenha"}]},{id:"76677",title:"Introductory Chapter: Osteoporosis Overview",slug:"introductory-chapter-osteoporosis-overview",totalDownloads:176,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"10323",slug:"osteoporosis-recent-advances-new-perspectives-and-applications",title:"Osteoporosis",fullTitle:"Osteoporosis - Recent Advances, New Perspectives and Applications"},signatures:"Luis Rodrigo",authors:[{id:"73208",title:"Prof.",name:"Luis",middleName:null,surname:"Rodrigo",slug:"luis-rodrigo",fullName:"Luis Rodrigo"}]},{id:"76507",title:"Osteoporosis: A Multifactorial Disease",slug:"osteoporosis-a-multifactorial-disease",totalDownloads:209,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"A great achievement of modern medicine is the increased lifespan of the human population. Unfortunately, the comorbidities of aging have created a large economic and health burden on society. Osteoporosis is the most prevalent age-related disease. It is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. These fractures lead to disproportionally high mortality rate and a drastic decline in quality of life for those affected. While estrogen loss is one known trigger of osteoporosis, a number of recent studies have shown that osteoporosis is a multifactorial condition in both humans and rodent models. The presence or absence of certain factors are likely to determine which subset of the population develop osteoporosis. In this chapter, we review the factors that contribute to osteoporosis with an emphasis on its multifactorial nature and the therapeutic consequences.",book:{id:"10323",slug:"osteoporosis-recent-advances-new-perspectives-and-applications",title:"Osteoporosis",fullTitle:"Osteoporosis - Recent Advances, New Perspectives and Applications"},signatures:"Di Wu, Anna Cline-Smith, Elena Shashkova and Rajeev Aurora",authors:[{id:"339667",title:"Associate Prof.",name:"Rajeev",middleName:null,surname:"Aurora",slug:"rajeev-aurora",fullName:"Rajeev Aurora"},{id:"347366",title:"Mr.",name:"Di",middleName:null,surname:"Wu",slug:"di-wu",fullName:"Di Wu"},{id:"347367",title:"Ms.",name:"Anna",middleName:null,surname:"Cline-Smith",slug:"anna-cline-smith",fullName:"Anna Cline-Smith"},{id:"347579",title:"Dr.",name:"Elena",middleName:null,surname:"Shashkova",slug:"elena-shashkova",fullName:"Elena Shashkova"}]},{id:"75742",title:"Osteoporosis and Dietary Inflammatory Index",slug:"osteoporosis-and-dietary-inflammatory-index",totalDownloads:235,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Healthy bones are constantly being renewed and proper nutrition is an important factor in this process. Anti-inflammatory diet is designed to improve health and prevent the occurrence and development of chronic diseases associated with inadequate diet. Proper nutrition is based on the anti-inflammatory pyramid and changes in poor eating habits are the long-term strategy for preventing inflammation and chronic diseases. Inflammatory factors from food may play a role in the development of osteoporosis and an anti-inflammatory diet may be a way to control and reduce long-term inflammation and prevent bone loss. Pro-inflammatory cytokines from the fat tissue, through activation of the RANKL/RANK/OPG system could intervene with bone metabolism in a way of increased bone loss. Therefore the special attention need to be given to obese patients due to twofold risk, one related to pro-inflammatory cytokines release and the other related to the deprivation of the vitamin D in the fat tissue.",book:{id:"10323",slug:"osteoporosis-recent-advances-new-perspectives-and-applications",title:"Osteoporosis",fullTitle:"Osteoporosis - Recent Advances, New Perspectives and Applications"},signatures:"Olga Cvijanović Peloza, Sandra Pavičić Žeželj, Gordana Kenđel Jovanović, Ivana Pavičić, Ana Terezija Jerbić Radetić, Sanja Zoričić Cvek, Jasna Lulić Drenjak, Gordana Starčević Klasan, Ariana Fužinac Smojver and Juraj Arbanas",authors:[{id:"339281",title:"Associate Prof.",name:"Olga",middleName:null,surname:"Cvijanović Peloza",slug:"olga-cvijanovic-peloza",fullName:"Olga Cvijanović Peloza"},{id:"346420",title:"Prof.",name:"Sandra",middleName:null,surname:"Pavičić Žeželj",slug:"sandra-pavicic-zezelj",fullName:"Sandra Pavičić Žeželj"},{id:"346421",title:"BSc.",name:"Ivana",middleName:null,surname:"Pavičić",slug:"ivana-pavicic",fullName:"Ivana Pavičić"},{id:"346423",title:"Prof.",name:"Ana Terezija",middleName:null,surname:"Jerbić Radetić",slug:"ana-terezija-jerbic-radetic",fullName:"Ana Terezija Jerbić Radetić"},{id:"346424",title:"Prof.",name:"Sanja",middleName:null,surname:"Zoričić Cvek",slug:"sanja-zoricic-cvek",fullName:"Sanja Zoričić Cvek"},{id:"346426",title:"MSc.",name:"Jasna",middleName:null,surname:"Lulić Drenjak",slug:"jasna-lulic-drenjak",fullName:"Jasna Lulić Drenjak"},{id:"346427",title:"Prof.",name:"Gordana",middleName:null,surname:"Starčević Klasan",slug:"gordana-starcevic-klasan",fullName:"Gordana Starčević Klasan"},{id:"346428",title:"MSc.",name:"Ariana",middleName:null,surname:"Fužinac Smojver",slug:"ariana-fuzinac-smojver",fullName:"Ariana Fužinac Smojver"},{id:"346429",title:"Prof.",name:"Juraj",middleName:null,surname:"Arbanas",slug:"juraj-arbanas",fullName:"Juraj Arbanas"},{id:"350011",title:"Dr.",name:"Gordana",middleName:null,surname:"Kenđel Jovanović",slug:"gordana-kendjel-jovanovic",fullName:"Gordana Kenđel Jovanović"}]},{id:"76351",title:"Glucocorticoid-Induced Osteoporosis",slug:"glucocorticoid-induced-osteoporosis",totalDownloads:254,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The use of glucocorticoids (GC) in the medium and long term, causes several considerable side effects, being one of the main ones the reduction of bone mineral density (BMD). Prolonged corticosteroid therapy reduces BMD by up to 20% in trabecular bone and approximately 2–3% in cortical bone in the first year of use. This loss rate declines and stabilizes at approximately 2% in subsequent years. Therefore, there is a considerable increase in the incidence of pathological fractures, whether clinically symptomatic or asymptomatic (detected as a radiological finding), which varies between 30 and 50% of patients who use GC for more than three months. In view of the above, it is essential to prevent fractures and treat osteoporosis in patients using glucocorticoids for long periods (in particular, greater than or equal to 3 months), which may or may not be associated with clinical risk factors or previous fractures. The guidelines for the treatment and prevention of this comorbidity are well established for postmenopausal women and men over 50 years of age. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. 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Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"10",type:"subseries",title:"Animal Physiology",keywords:"Physiology, Comparative, Evolution, Biomolecules, Organ, Homeostasis, Anatomy, Pathology, Medical, Cell Division, Cell Signaling, Cell Growth, Cell Metabolism, Endocrine, Neuroscience, Cardiovascular, Development, Aging, Development",scope:"Physiology, the scientific study of functions and mechanisms of living systems, is an essential area of research in its own right, but also in relation to medicine and health sciences. The scope of this topic will range from molecular, biochemical, cellular, and physiological processes in all animal species. Work pertaining to the whole organism, organ systems, individual organs and tissues, cells, and biomolecules will be included. Medical, animal, cell, and comparative physiology and allied fields such as anatomy, histology, and pathology with physiology links will be covered in this topic. 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