IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\n
By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n
"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n
"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\n
In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\n
Feel free to share this news on social media and help us mark this memorable moment!
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\n
By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n
"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n
"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\n
In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\n
Feel free to share this news on social media and help us mark this memorable moment!
\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"898",leadTitle:null,fullTitle:"System of Systems",title:"System of Systems",subtitle:null,reviewType:"peer-reviewed",abstract:"The present book proposes and fosters discussion on the current applications in the field of system of systems, with emphasis on the implications of the fact that new developments and area of technical and non-technical applications are merging. 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During 1993 - 2006 he was Director with the Centre of Excellence on Risk and Safety Sciences, and Senior Scientist, with the Swiss Federal Institute of Technology, Zurich, Switzerland and Professor (Visitor) Operations Research and Decision Analysis.\nIn March 2006 he was appointed as Professor of Engineering Management and Systems Engineering, and offered the Batten Endowed Chair on System Engineering. 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\r\n\tTotal body weight is the sum of the weight of all body components. Among these components, water, adipose tissue, muscle, and bone represent relevant contributors. The physiological or pathological variations in the amount or mass of each component can lead to an increase or a decrease in total body weight. These variations are increase (retention) or decrease (dehydration) in water amount, increase (hypertrophy, hyperplasia) or decrease (lipodystrophy) in adipose tissue mass, increase (hypertrophy) or decrease (sarcopenia) in muscle mass, and increase (increased bone density) or decrease (osteopenia, osteoporosis) in bone mass. A variety of causes including genetic factors, lifestyle, environment, aging, diseases, and medications can promote these conditions. There is a risk of increased morbidity (e.g., obesity, type 2 diabetes, and fracture) and mortality associated with some body weight variations.
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\r\n\tThis book intends to provide the reader with a comprehensive overview of the current knowledge about the pathophysiology, consequences, complications, and treatment of different types of body weight changes with special emphasis on preventive measures.
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1. Introduction
The inappropriate or excessive secretion of parathyroid hormone (PTH) from one or multiple abnormal parathyroid glands typically results in hypercalcemia and the disorder of mineral metabolism called primary hyperparathyroidism (HPT) [1]. Most cases of HPT are sporadic (~95%). Among the small remaining fraction of patients with an inherited basis for HPT, most harbor germline mutation of a known parathyroid tumor susceptibility gene (listed in Table 1). In spite of their infrequency, study of the genetics of these uncommon inherited syndromes has yielded substantial insight into the etiology of both sporadic and familial parathyroid tumor development. Since the release of PTH from parathyroid cells involves close regulation by the calcium-sensing receptor (CASR), a cell surface transmembrane receptor of the G protein-coupled receptor family C [2], the germline mutation of the CASR and other genes mediating its signaling can also result in inherited syndromes characterized by hypercalcemia and circulating levels of PTH that are elevated or inappropriately normal. This chapter will summarize current knowledge of the clinical genetics and molecular pathophysiology of HPT that results from both benign and malignant parathyroid gland neoplasia.
Gene
Corresponding protein
Chromosomal location
Associated hyperparathyroid syndrome: main syndromic manifestations
Multiple endocrine neoplasia type 4 (MEN4): anterior pituitary, other involvement varies
Single to multiple glands (benign in reports to date); can be recurrent
GCM2
Glial cells missing transcription factor 2
6p24.2
Familial isolated primary hyperparathyroidism
Single to multiple glands
CASR
Calcium-sensing receptor
3q13.33-q21.1
Familial hypocalciuric hypercalcemia type 1 (FHH1) with heterozygous inactivation; neonatal severe hyperparathyroidism (NSHPT) with homozygous inactivation
FHH1: near-normal size and surgical pathology; altered serum calcium set-point for PTH release NSHPT: marked enlargement of multiple glands by polyclonal (non-neoplastic) mechanism
GNA11
G protein α11 subunit
19p13.3
Familial hypocalciuric hypercalcemia type 2 (FHH2)
ND
AP2S1
Adaptor protein-2 sigma subunit
19q13.32
Familial hypocalciuric hypercalcemia type 3 (FHH3): hypercalcemia more severe than in FHH1
NA (to date, only implicated in sporadic parathyroid tumors)
NA (to date, only implicated in sporadic parathyroid tumors)
Table 1.
Genes implicated in syndromic parathyroid neoplasia and related hypercalcemic states.
2. The evolution of calcium regulation in vertebrates
In sea water the concentration of elemental calcium is approximately 10 mM. As a result, early eukaryotes living in a marine environment had easy access to calcium. Given this abundant supply of extracellular calcium, numerous intracellular processes evolved in simple eukaryotes that depended on this divalent cation. Such calcium-dependent processes were preserved in metazoans. Thus marine chordates and early vertebrate fish depended on calcium for cellular processes such as membrane permeability, neurotransmitter release, intracellular second messenger signaling, muscular contraction, neuromuscular excitability, and the actions of multiple calcium-dependent enzymes. Calcium’s particular coordination chemistry facilitated many proteins’ ability to reversibly bind divalent calcium ions, thus enabling signaling through such binding [3].
Calcium is much scarcer on land compared to the marine environment. As lobe-finned fish, marine vertebrates believed to be the ancestors of the early amphibians, began to explore the periphery of the terrestrial environment, evolutionary pressure to develop a system of internal calcium balance mounted. A system of internal calcium homeostasis at the organismal level would ensure the continued preservation and function of numerous cellular and tissue operations that vitally depended on calcium.
Metabolically-active trabecular or cancellous bone in lobe-finned fish and associated hematopoietic bone marrow likely co-evolved [4]. These developments probably both lightened overall skeletal mass and provided a reliable internal source of calcium as a basis for calcium homeostasis. The lightening of skeletal mass was critical since lobe-finned fish and early amphibians had to come to terms with full gravitational force in their terrestrial movements, no longer buoyed by surrounding seawater in accordance with Archimedes’ principle [5]. The potential significance of the close physical apposition of hematopoietic bone marrow to spongiform bone, inferred from X-ray synchrotron microtomography of fossilized lobe-finned fish humerus [4], is suggested by the realization that osteoclasts, cells uniquely specialized to mobilize ionized calcium via resorption of bone, develop from hematopoietic stem cell precursors [6]. In contrast, osteoblasts, which lay down osteoid and mineralize bone, derive from mesenchymal stem cells which are abundant in non-hematopoietic bone marrow.
Although analogs of Gcm2, Gata3, CaSR, PTH, and other genes associated with the development and function of human parathyroid glands are expressed in the fish gills, actual parathyroid glands are first seen in amphibians [7, 8, 9]. Complete surgical excision of parathyroid gland tissue in amphibians, reptiles, birds, and mammals results in tetany and death.
3. The pathophysiology of primary hyperparathyroidism
PTH secretion from cells of the parathyroid glands is finely regulated in response to changes in the ambient ionized calcium level in order to maintain the circulating calcium concentration within a defined physiologic range. The G protein-coupled CASR is a critical regulator of PTH secretion and is located on the plasma membrane of chief cells in the parathyroid glands [10, 11]. In a classic endocrine negative feedback loop, the active form of cholecalciferol, 1,25-dihydroxyvitamin D, whose synthesis is stimulated by PTH acting on proximal renal tubular cells, inhibits PTH biosynthesis and release from parathyroid cells [12, 13, 14, 15]. The simultaneous demonstration of elevated serum calcium with an inappropriately normal or elevated PTH is a typical clinical definition of HPT [16]. The vast majority of parathyroid tumors are adenomas (i.e. benign tumors), with parathyroid cancer accounting for less than 1% of HPT in most series.
Most cases of HPT are sporadic with inherited forms of HPT representing only 2–5% of cases. As illustrated in Table 1, research into the molecular pathophysiology of this small subcategory of cases has notwithstanding yielded important understanding with respect to the genes and pathways that promote parathyroid tumorigenesis. Multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), the hyperparathyroidism-jaw tumor syndrome (HPT-JT), and familial isolated hyperparathyroidism (FIHP) are the most common inherited disorders associated with HPT [17, 18, 19, 20, 21]. Familial hypocalciuric hypercalcemia (FHH) is a related and largely benign autosomal dominant condition characterized by lifelong asymptomatic hypercalcemia. Often mis-diagnosed as HPT, in FHH the PTH-dependent hypercalcemia does not correct with partial or even subtotal parathyroidectomy [22]. The relevance of these inherited disorders to the underlying molecular pathogenetic alterations in parathyroid tumorigenesis will be discussed in more detail below.
4. Oncogenes and proto-oncogenes
Mutant genes that drive cell growth are called oncogenes and represent one potential molecular mechanism for tumor development. Oncogenes are mutationally activated versions of naturally occurring genes, called proto-oncogenes, which under normal conditions positively regulate cell division and/or cell growth [23]. Oncogenes represent gain-of-function mutants or overexpressed forms of proto-oncogenes that can induce cell growth and cell division, often in a tissue-specific fashion, resulting in tumor formation. Proto-oncogenes often encode proteins that are involved in mitogenic signal transduction. In the context of currently recognized familial cancer syndromes, germline mutational activation of proto-oncogenes is rare as an etiology compared to the inactivation of tumor suppressor genes (see below). Constitutive proliferative signaling resulting from the germline activation of most proto-oncogenes would presumably be deleterious to embryonic and fetal development.
5. The role of tumor suppressor genes in tumor development
Alfred Knudson proposed another model for tumor development based on the study of retinoblastoma disease patterns nearly 50 years ago [24]. Sporadic retinoblastoma is usually monocular. Familial retinoblastoma, though rare compared to the sporadic form, is more frequently binocular and has a much earlier age of onset. The “two-hit” hypothesis of tumor development, as proposed by Knudson, hypothesizes that two events (or “hits”) in a parental cell confer a selective growth advantage and result in that cell’s clonal expansion [25].
Newer clinical and molecular genetic insight that has emerged since his original proposal allow us to update Knudson’s concept. In many hereditary tumor syndromes, an inherited germline DNA mutation that affects one copy of a tumor suppressor gene represents the first “hit” or event and is present throughout all cells of the affected offspring. The greater likelihood of any particular cell acquiring a “second hit”, i.e. a somatic mutation in the second allele of the same tumor suppressor gene that was heretofore unaffected, accounts for the earlier age of onset and predisposition for bilateral and multifocal disease in hereditary tumor syndromes. This “second hit” in somatic DNA, that disables the remaining wild-type allele, typically results from a deletion that involves a portion or the entirety of a chromosome. In the familial tumor syndromes MEN1 and HPT-JT, inactivating mutation that involves both alleles of the MEN1 and the CDC73/HRPT2 tumor suppressor genes, respectively, can often be found in parathyroid tumor-derived DNA. In such patients, the first “hit”, namely a loss-of-function mutation of the relevant tumor suppressor gene, can frequently be demonstrated in the germline DNA.
6. Multiple endocrine neoplasia type 1 (MEN1)
MEN1 is the most common hereditary cause of primary hyperparathyroidism [26]. The syndrome of MEN1 is characterized by the predisposition to develop tumors derived from cells in the anterior pituitary, parathyroid glands, and endocrine cells present in the gut and pancreatic islets (such as gastrinomas, and pancreatic neuroendocrine tumors such as insulinomas) [27]. Tumors in several other endocrine organs and non-endocrine tumors such as lipomas, angiofibromas, and leiomyomas affecting the esophagus, uterus, and/or ureters for example, can also be associated with the syndrome [27]. HPT is the most penetrant hormonal feature of MEN1.
Familial MEN1 is characterized by autosomal dominant transmission. The predisposition to tumor development in one of the tissues characteristically involved in the MEN1 syndrome is caused by germline inactivating mutation in one copy of the MEN1 gene on chromosome 11q13 [28]. As of 2015, 576 unique germline mutations in MEN1 were reported from patients and families with MEN1 [29]. The study of DNA derived from pituitary, parathyroid, and entero-pancreatic tumors from MEN1 patients has shown that most syndromic tumors possess an acquired deletion or other inactivating mutation of the second, wild-type MEN1 allele [18, 30]. Approximately 10% of patients with MEN1 on a clinical basis are germline MEN1 mutation-negative.
Conventional DNA sequencing of tumor DNA has identified somatic MEN1 mutation in up to 35% of sporadic parathyroid adenomas [31, 32, 33, 34, 35]. In studies testing for loss-of-heterozygosity (LOH) in sporadic parathyroid adenomas, the frequency of LOH at the MEN1 locus on chromosome 11q13 ranged from 26 to 37%. Using whole exome sequencing (WES) methodology, somatic MEN1 mutation was found in some 35% of parathyroid benign tumors, comparable to results using conventional Sanger DNA sequencing [36, 37]. As mentioned above, HPT is the most penetrant feature of MEN1 and is usually the initial manifestation. As a result, true MEN1 families may sometimes be initially mis-assigned a clinical diagnosis of familial isolated hyperparathyroidism (FIHP) if only younger affected members are considered at the time that the family is ascertained (see Figure 1).
Figure 1.
The relationship among familial forms of hyperparathyroidism that may present as familial isolated hyperparathyroidism (FIHP) as a Venn diagram. The dashed circle represents the set of patients that can present with a provisional diagnosis of FIHP at the time of initial ascertainment. This includes patients with FIHP who have been evaluated for, but lack findings diagnostic of, MEN1, FHH and HPT-JT (nonsyndromic FIHP; in a solid circle). Approximately 18% of nonsyndromic FIHP kindreds harbor germline gain-of-function mutations in GCM2 (see text), whereas the remainder have currently unknown genetic etiologies. Subsets of patients with incomplete expression of MEN1, FHH and HPT-JT (the total set of patients in each syndrome represented by a solid circle) can also present with the FIHP phenotype (and thus overlap with the dashed circle). The distinction between the nonsyndromic FIHP category and the syndromic categories arbitrarily depends on the thoroughness of evaluation and the sensitivity of diagnostic tests used to detect the syndrome that can include germline gene mutational testing. MEN2A is a familial form of hyperparathyroidism that seldom if ever presents as FIHP. Within each circle representing a defined syndrome are included the genetic locus (or loci in the case of FHH; see text) of the syndromic trait and the associated gene product. The causative gene for HPT-JT encoding parafibromin is CDC73, formerly called HRPT2. The relationship among the patient sets illustrated as circles in this diagram is intended to be qualitative and neither the area of each circle nor the area of overlap between circles has any quantitative significance.
Mutation of the MEN1 gene is only rarely associated with parathyroid carcinoma. The occurrence of parathyroid carcinoma in the context of familial MEN1 is extremely uncommon. Fewer than 20 patients with HPT due to parathyroid cancer in the context of the MEN1 syndrome have been reported [38]. LOH analysis of parathyroid tumor-extracted DNA has shown that DNA loss at the location of the MEN1 gene on chromosome 11q, though frequently seen in benign parathyroid tumors, is quite uncommon in parathyroid carcinomas [39]. Recent studies that use next-generation WES of tumor-derived DNA to profile parathyroid cancers did not report any somatic mutations in MEN1 [40, 41].
7. The hyperparathyroidism-jaw tumor syndrome (HPT-JT)
HPT-JT is a familial syndrome with variable and incomplete penetrance transmitted in an autosomal dominant fashion. The key clinical features of HPT-JT include HPT, jaw tumors (fibro-osseous tumors involving the maxilla and/or mandible, formally classified as cemento-ossifying fibromas [42], and distinct from so called “brown” tumors sometimes associated with HPT), renal cysts or tumors and uterine tumors in women [43, 44, 45]. HPT is the most penetrant feature of HPT-JT and is usually the presenting manifestation. In contrast to MEN1, parathyroid cancer is frequent in HPT-JT, affecting some 20% or more of those with HPT [43, 44, 45, 46].
In the majority of HPT-JT kindreds, a germline loss-of-function mutation of the CDC73 gene (formerly called HRPT2) can be identified [19, 47]. The majority of such CDC73 mutations are predicted to inactivate gene function via frameshift or nonsense mutation, and only a minority of the mutations are missense [48]. Patients and kindreds with partial or complete deletion of the CDC73 gene in the germline have also been described [49, 50, 51, 52]. The CDC73 gene encodes a 531-residue protein named parafibromin [47]. Because germline mutation predicted to cause loss-of-function of the CDC73 gene predisposes to the neoplastic expressions of HPT-JT, parafibromin is considered to be a tumor suppressor protein. Mixed epithelial tumor of the kidney (MEST), a rare type of renal tumor (formerly classified as cystic hamartoma of the renal pelvis, leiomyomatous renal hamartoma, or adult type mesoblastic nephroma), has been associated with HPT-JT and appears to correlate with a specific CDC73 genotype, namely the Met1ILe missense mutation replacing the initiator methionine of parafibromin with isoleucine [47, 53, 54]. Somatic mutation of the CDC73 tumor suppressor gene is uncommon in sporadic parathyroid adenomas [55]. In contrast to the results of analyses in benign parathyroid tumors, mutations of CDC73 are quite frequently seen in apparently sporadic cases of parathyroid cancer [56, 57, 58]. Interestingly, recurrent somatic mutations in CDC73 have been documented by exome sequence analysis of tumor DNA from parathyroid cancers [40, 41]. Selective amplification of the mutant copy of CDC73 has been demonstrated in a subset of parathyroid carcinomas [40]. Approximately 25% of cases of seemingly sporadic parathyroid carcinoma may possess germline loss-of-function alterations in CDC73, suggesting that such patients may in fact have previously unrecognized, or formes frustes of, HPT-JT [19, 57, 58]. A minority of patients and families classified as FIHP can be shown to carry CDC73 mutation in the germline, suggesting that this inherited disorder may in some cases be phenocopied by incompletely penetrant HPT-JT (see below and Figure 1). Approximately 20% of genetically confirmed or obligate CDC73 mutation-positive family members lack HPT, fibro-osseous jaw tumors, or other manifestations of HPT-JT when their kindred is initially ascertained. Because the penetrance of the manifestations of HPT-JT increases with age among CDC73 mutation carriers, lifelong surveillance of initially asymptomatic carriers is recommended [59].
8. Multiple endocrine neoplasia type 4 (MEN4)
MEN4 is a syndrome originally described by Pellegata and coworkers in a multi-generational family with features resembling MEN1, including a proband with a growth hormone-secreting pituitary adenoma and HPT, but lacking germline MEN1 mutation [60, 61]. A germline heterozygous truncation mutation in CDKN1B was identified in the proband and several members of this kindred [60]. CDKN1B encodes the cyclin dependent-kinase inhibitor p27 (Kip1). Attention to the CDKN1B locus was a consequence of a previous genetic analysis of rats with the MenX phenotype, a recessively inherited condition caused by a frameshift mutation in Cdkn1b [60, 62]. The MenX phenotype in rats was manifest by the development of bilateral pheochromocytomas, paragangliomas, parathyroid adenomas and thyroid C cell hyperplasia [60, 62]. In the study by Pellegata et al., the proband was the only member of the MEN4/MENX kindred described who manifested HPT [60].
Following the original report by Pellegata et al. [60], several groups have investigated a possible role for CDKN1B mutation in parathyroid tumorigenesis. None of the earlier reports of MEN1 mutation-negative families harboring germline mutation in CDKN1B, and expressing MEN1-like tumors and thus classified as MEN4, had included families with more than one member with HPT proven to track with the CDKN1B mutation [60, 63, 64, 65, 66, 67, 68, 69, 70, 71], apart from the demonstration of HPT linked to CDKN1B mutation in monozygotic twins [64]. That was true until a more recent report by Frederiksen et al. describing a large Danish family in which HPT occurred in 13 members, spanning two generations, who carried a germline frameshift CDKN1B mutation [72].
Recent evidence supports the characterization of CDKN1B as a susceptibility gene for the development of primary parathyroid tumors [69, 72, 73]. This evidence validates the inclusion of germline CDKN1B mutation in the differential diagnosis of familial HPT, particularly in the evaluation of germline MEN1 mutation-negative families who yet have MEN1-like features. The strongest justification for this follows from consideration of the Danish kindred in which 13 unique family members manifest HPT linked to germline inactivating mutation of CDKN1B, described by Frederiksen and co-workers [72].
9. Familial isolated hyperparathyroidism (FIHP)
By definition, FIHP is a non-syndromic category of familial HPT describing families that contain two or more members with HPT but which lack the specific features of MEN1, MEN2A, HPT-JT or FHH (Figure 1) [74]. FIHP is genetically heterogeneous and is a diagnosis of exclusion. While at the time of initial ascertainment germline mutation of MEN1, CDC73, or CASR may account for a fraction of kindreds with the FIHP phenotype [20, 34, 75, 76, 77], the majority of FIHP families lack mutations in these established HPT-susceptibility genes (Figure 1) [20, 75, 78].
Missense variants in GCM2, a transcription factor homologous to the Drosophila “glial cells missing” (gcm) gene and required for parathyroid gland development, were recently described in the germline DNA of eight unrelated families with FIHP [21]. Previous studies showed that germline dominant-negative and loss-of-function mutations in GCM2 were associated with autosomal dominant and autosomal recessive familial isolated hypoparathyroidism, respectively [79, 80]. The two rare germline GCM2 genetic variants associated with FIHP act as gain-of-function mutations [21]. These missense mutations map to the C-terminal conserved inhibitory domain (CCID) of GCM2 and increase its transcriptional activity when measured in vitro, suggesting that GCM2 in the context of FIHP is a parathyroid proto-oncogene. It has been estimated that approximately 18% of FIHP families harbor germline activating GCM2 mutations [21], leaving ~80% of FIHP families without a currently-identified genetic etiology [74]. Other clinical investigators have identified rare germline GCM2 variants in a subset of FIHP kindreds [81]. Activating GCM2 variants mapping to the CCID region have been found among patients with sporadic parathyroid tumors in low frequency and appear to be of low penetrance [82].
10. Familial hypocalciuric hypercalcemia (FHH)
FHH is a condition of PTH-dependent hypercalcemia, often resembling HPT, that is clinically benign and genetically heterogeneous (Table 1) [22]. Following partial or subtotal parathyroidectomy, affected patients from FHH kindreds almost always remain hypercalcemic. FHH is transmitted in an autosomal dominant fashion and usually causes mild hypercalcemia with relative hypocalciuria. The hypercalcemia seen in FHH is highly penetrant across all ages, including in infants [22, 83]. The majority of cases of FHH result from heterozygous germline inactivating mutation of the CASR gene on the long arm of chromosome 3 that encodes the calcium-sensing receptor [10, 84], and is classified as type 1 FHH (FHH1). Neonatal severe hyperparathyroidism (NSHPT), a rare autosomal recessive disorder typically presenting with severe hypercalcemia occurring in the first 6 months of life, most often results from the compound heterozygous or homozygous inheritance of two loss-of-function mutant CASR alleles [85]. Rather than the cellular monoclonality that would be expected in true parathyroid tumors, molecular genetic analysis of the hyperfunctioning parathyroid glands removed from a patient with NSHPT demonstrated generalized polyclonal hyperplasia, underscoring the non-neoplastic nature of the abnormal parathyroid glands associated with CASR inactivating mutation [86].
Loss of surface expression of the CASR protein has been documented in parathyroid adenomas and may contribute to the altered calcium set point and impaired calcium-mediated negative feedback on the release of PTH typical of such adenomas. Decreased CASR mRNA expression, but not LOH at the CASR locus, has been documented in parathyroid adenomas [87]. In sporadic parathyroid tumors studied to date, somatic inactivation of the CASR gene has not been reported [88, 89].
Type 2 FHH (FHH2) resulting from germline loss-of-function mutation of GNA11, encoding the G protein α11 subunit [90, 91], and type 3 FHH (FHH3) resulting from germline inactivating mutation in AP2S1, the gene that encodes an adaptor protein involved in endocytosis mediated by clathrin [92, 93, 94, 95], have also been described. In studies of sporadic parathyroid tumors, somatic inactivating mutations of GNA11 and AP2S1 have so far not been reported.
11. Multiple endocrine neoplasia type 2A (MEN2A)
MEN2A is a familial cancer syndrome characterized by a predisposition to the development of medullary thyroid cancer (MTC), pheochromocytoma (typically benign and often bilateral), and primary HPT. In the context of MEN2A, HPT is usually mild and resembles sporadic HPT. HPT in MEN2A is almost always results from benign parathyroid disease. MEN2A is an autosomal dominant disorder that results from germline gain-of-function mutation in the RET proto-oncogene at chromosomal location 10q11. RET encodes a receptor tyrosine kinase that binds the ligand glial derived neurotrophic factor, together with a glycosylphosphatidylinositol-anchored protein co-receptor Gfra1 [96].
Germline oncogenic mutations of RET are associated with three distinct familial endocrine neoplasia syndromes, all associated with MTC: MEN2A, multiple endocrine neoplasia type 2B (MEN2B), and familial medullary thyroid cancer (FMTC). The disease spectrum of typical MEN2B or FMTC does not include parathyroid tumors and HPT. Genotype–phenotype correlations based on particular RET mutations are apparent and account for the distinct patterns of disease. Some 95% of MEN2A cases are due to the presence in the germline of nonsynonymous variants affecting the RET receptor’s extracellular cysteine-rich domain, namely missense mutations of RET codons 609, 611, 618, 620, or 634 [97]. In fact, germline missense alteration of RET residue cysteine-634 accounts for approximately 85% of cases of MEN2A [98].
12. Parathyroid tumorigenesis involving the CCND1 oncogene
The discovery of the CCND1 (or PRAD1, for parathyroid adenomatosis 1) oncogene resulted from the analysis of several large, non-familial, parathyroid adenomas that harbored DNA re-arrangements that involved the PTH gene locus [99, 100, 101]. A breakpoint resulting from the pericentromeric inversion of chromosome 11 DNA was identified just upstream of the CCND1/PRAD1 oncogene [101]. The inversion positioned the PTH gene regulatory region, that is normally located on the short arm of chromosome 11, just upstream of the CCND1/PRAD1 proto-oncogene located on 11q [99, 100, 101]. The product encoded by the proto-oncogene was subsequently recognized by DNA sequence analysis to be a member of the cyclin protein family [101]. The gene was therefore re-named cyclin D1 (CCND1). Overexpression of CCND1 in the parathyroid cells of transgenic mice induces cell proliferation and gives rise to the metabolic abnormalities that characterize HPT in humans [102].
While activating CCND1 missense mutations have not been observed in sporadic parathyroid tumors [103], overexpression of CCND1 has been demonstrated in 20–40% of sporadic benign parathyroid tumors and in an even larger percentage of parathyroid carcinomas [104, 105, 106, 107]. In parathyroid carcinoma, no somatic chromosomal rearrangements on chromosome 11 involving CCND1 have been reported. Neither germline activating missense mutations of CCND1 nor chromosomal translocations or rearrangements involving the CCND1 locus have been reported in any familial form of HPT.
13. Other genes involved in parathyroid tumorigenesis
Recurrent mutations in a subset of genes likely relevant to parathyroid tumorigenesis have been identified by WES analysis of DNA derived from sporadic parathyroid tumors. Eight out of 193 sporadic parathyroid tumors analyzed by WES demonstrated the Y641N missense mutation in the EZH2 gene on chromosome 7 that encodes the enhancer of zeste 2 polycomb repressive complex 2 subunit [36]. Analysis by WES of 22 parathyroid tumors derived from a Chinese patient population identified a distinct somatic missense mutation, Y646N, in EZH2 [108]. Acquired mutations of Y641 and Y646 in EZH2 were described previously in lymphoid malignancy [109, 110]. Molecular genetic profiling of 80 sporadic parathyroid neoplasms by separate investigators failed to uncover any pathogenic EZH2 mutations however, suggesting acquired EZH2 mutation may be uncommon in parathyroid tumors [111]. In the context of lymphoma, EZH2 is thought to function as a proto-oncogene [109]. To date, no transgenic mouse models restricting EZH2 mutation or overexpression to parathyroid cells have been reported.
Soong and Arnold used WES analysis of DNA extracted from 19 parathyroid adenomas and matching germline DNA to identify somatic mutations in ZFX, a putative parathyroid proto-oncogene and member of the Krüppel associated box domain-containing family of zinc finger protein transcription factors [112]. Their observations in the discovery cohort were confirmed by direct sequencing of tumor DNA from an additional validation set comprised of 111 parathyroid adenomas [112]. The mutant ZFX alleles detected in parathyroid tumors likely act as oncogenes [113]. Such somatically acquired ZFX mutations in parathyroid tumors may be uncommon, however, since an independent mutational analysis of 23 sporadic parathyroid carcinomas and 57 adenomas failed to identify any pathogenic ZFX variants [111]. The development of a transgenic mouse model and/or better characterization of the functional properties of the mutant ZFX protein may clarify the potential significance of ZFX as a parathyroid proto-oncogene.
WES analysis of 22 blood-sporadic parathyroid adenoma tumor pairs from a Chinese patient cohort identified recurrent mutations of ASXL3 [108]. ASXL3 belongs to a family of vertebrate Additional sex combs (Asx)-like proteins that may function as regulators of transcription. It remains unclear if the somatic missense ASXL3 mutations identified in the parathyroid adenomas, mutations that affected highly conserved residues, would result in gain- or loss of ASXL3 function [108]. Further studies will be required to confirm this initial observation and to clarify the mechanism by which ASXL3 mutation might drive parathyroid tumor development.
14. Conclusions
While inherited forms of HPT represent only a small fraction of cases (<5%), study of the molecular pathophysiology of these uncommon familial syndromes has yielded substantial insight into the genetic etiology of both sporadic and familial parathyroid disease and resulted in the identification of genes such as MEN1, CDC73, CASR, GNA11, AP2S1, CDKN1B, CCND1, and GCM2. It is highly likely that the mutational gain- or loss-of-function of other, yet unrecognized, genes is able to drive parathyroid neoplasia. For example, the risk in the majority of FIHP kindreds predisposing to the development of parathyroid tumors seems to result from the germline mutation of genes not presently recognized as having a role in parathyroid disease. This follows from the observation that nearly 70% of families initially considered as FIHP in multiple studies that examined for germline MEN1, CASR and CDC73/HRPT2 gene mutation, had no recognized syndromic etiology (Figure 1) [20, 75, 76, 77]. From among those FIHP kindreds who are MEN1, CASR and CDC73 mutation-negative, only about 20% are estimated to harbor germline activating mutations in the GCM2 proto-oncogene [21], which leaves nearly 80% of FIHP kindreds with a currently-undefined genetic basis for their disease (Figure 1).
The existence of currently unidentified parathyroid tumor suppressors and oncogenes is also suggested by analysis of parathyroid tumors using techniques such as comparative genomic hybridization (CGH) to identify specific chromosomal regions harboring loss or gain of DNA. Several investigators have documented recurrent loss of DNA at the 1p, 6q, 9p, and 13q chromosomal loci in parathyroid tumors, indicating the potential presence there of novel parathyroid tumor suppressor genes [114, 115, 116, 117]. The potential presence of novel oncogenes at chromosomal loci 9q, 16p, 19p, and Xq is suggested by results demonstrating specific chromosomal gain at these loci in benign or malignant parathyroid tumors [114, 116, 117, 118].
Next-generation sequencing analysis including WES of parathyroid neoplasms is an auspicious approach for the identification of novel acquired and germline gene variations that predispose to the development of HPT and parathyroid neoplasia. The apparent validation of this line of investigation by the identification of EXH2 [36], ZFX [112], and potentially ASXL3 [108], as candidate driver genes for parathyroid neoplasia was previously discussed. WES analysis of parathyroid cancer-derived DNA has similarly underscored the possible significance of recurrent somatic and germline inactivating mutations of PRUNE2 in the etiology of parathyroid malignancy [40]. The comprehensive quality and great sensitivity of WES and related next-generation sequencing methodologies should further advance our insight into the genetic basis and endocrine pathophysiology of inherited and sporadic parathyroid neoplasia in the decades ahead.
Acknowledgments
The author wishes to thank the members of the Metabolic Diseases Branch, NIDDK for many helpful discussions and suggestions. The Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (ZIA DK043012-18) supported this research. The author declares no competing financial interests.
Conflict of interest
The author declares no conflict of interest.
\n',keywords:"multiple endocrine neoplasia, MEN1, MEN2A, jaw tumor syndrome, CDC73, HRPT2, GCM2, CCND1, RET, CASR, CDKN1B, tumor suppressor, oncogene",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/72573.pdf",chapterXML:"https://mts.intechopen.com/source/xml/72573.xml",downloadPdfUrl:"/chapter/pdf-download/72573",previewPdfUrl:"/chapter/pdf-preview/72573",totalDownloads:353,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:26,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"May 18th 2020",dateReviewed:"May 26th 2020",datePrePublished:"July 7th 2020",datePublished:"June 30th 2021",dateFinished:"June 22nd 2020",readingETA:"0",abstract:"Regulation of serum calcium in vertebrates is maintained by the actions of the parathyroid glands working in concert with vitamin D and critical target tissues that include the renal tubules, the small intestine, and bone cells. The parathyroid glands release parathyroid hormone (PTH) into the systemic circulation as is required in order to maintain the serum calcium concentration within a narrow physiologic range. Excessive secretion of PTH from one or more abnormal parathyroid glands however results in primary hyperparathyroidism (HPT), a metabolic disease typically associated with abnormally elevated serum calcium. Although HPT is typically a sporadic disease, it can represent a manifestation of an inherited syndrome. Many sporadic parathyroid tumors result from inactivating mutations in tumor suppressor genes that were first discovered by the analysis of genomic DNA from patients with HPT as part of an inherited syndrome. Somatic and inherited alterations in DNA encoding proto-oncogenes can also cause parathyroid neoplasia. Two promising future approaches for the discovery of novel genes pertinent to parathyroid tumor development are the analysis of acquired genetic alterations in DNA isolated from parathyroid tumors and the investigation of familial HPT in kindreds lacking germline mutation in the known genes predisposing to HPT.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/72573",risUrl:"/chapter/ris/72573",book:{id:"8935",slug:"mineral-deficiencies-electrolyte-disturbances-genes-diet-and-disease-interface"},signatures:"William F. Simonds",authors:[{id:"320057",title:"Dr.",name:"William F.",middleName:null,surname:"Simonds",fullName:"William F. Simonds",slug:"william-f.-simonds",email:"bills@niddk.nih.gov",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The evolution of calcium regulation in vertebrates",level:"1"},{id:"sec_3",title:"3. The pathophysiology of primary hyperparathyroidism",level:"1"},{id:"sec_4",title:"4. Oncogenes and proto-oncogenes",level:"1"},{id:"sec_5",title:"5. The role of tumor suppressor genes in tumor development",level:"1"},{id:"sec_6",title:"6. Multiple endocrine neoplasia type 1 (MEN1)",level:"1"},{id:"sec_7",title:"7. The hyperparathyroidism-jaw tumor syndrome (HPT-JT)",level:"1"},{id:"sec_8",title:"8. Multiple endocrine neoplasia type 4 (MEN4)",level:"1"},{id:"sec_9",title:"9. Familial isolated hyperparathyroidism (FIHP)",level:"1"},{id:"sec_10",title:"10. Familial hypocalciuric hypercalcemia (FHH)",level:"1"},{id:"sec_11",title:"11. Multiple endocrine neoplasia type 2A (MEN2A)",level:"1"},{id:"sec_12",title:"12. Parathyroid tumorigenesis involving the CCND1 oncogene",level:"1"},{id:"sec_13",title:"13. Other genes involved in parathyroid tumorigenesis",level:"1"},{id:"sec_14",title:"14. 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Journal of Endocrinological Investigation. 2004;27(11):1015-1021'},{id:"B34",body:'Vierimaa O, Villablanca A, Alimov A, Georgitsi M, Raitila A, Vahteristo P, et al. Mutation analysis of MEN1, HRPT2, CASR, CDKN1B, and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition. Journal of Endocrinological Investigation. 2009;32(6):512-518'},{id:"B35",body:'Heppner C, Kester MB, Agarwal SK, Debelenko LV, Emmert-Buck MR, Guru SC, et al. Somatic mutation of the MEN1 gene in parathyroid tumours. Nature Genetics. 1997;16:375-378'},{id:"B36",body:'Cromer MK, Starker LF, Choi M, Udelsman R, Nelson-Williams C, Lifton RP, et al. Identification of somatic mutations in parathyroid tumors using whole-exome sequencing. The Journal of Clinical Endocrinology and Metabolism. 2012;97(9):E1774-E1781'},{id:"B37",body:'Newey PJ, Nesbit MA, Rimmer AJ, Attar M, Head RT, Christie PT, et al. Whole-exome sequencing studies of nonhereditary (sporadic) parathyroid adenomas. 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A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome. European Journal of Endocrinology. 2014;171(2):K7-K17'},{id:"B69",body:'Costa-Guda J, Marinoni I, Molatore S, Pellegata NS, Arnold A. Somatic mutation and germline sequence abnormalities in CDKN1B, encoding p27Kip1, in sporadic parathyroid adenomas. The Journal of Clinical Endocrinology and Metabolism. 2011;96(4):E701-E706'},{id:"B70",body:'Belar O, De La Hoz C, Perez-Nanclares G, Castano L, Gaztambide S, Spanish MENG. Novel mutations in MEN1, CDKN1B and AIP genes in patients with multiple endocrine neoplasia type 1 syndrome in Spain. Clinical Endocrinology. 2012;76(5):719-724'},{id:"B71",body:'Elston MS, Meyer-Rochow GY, Dray M, Swarbrick M, Conaglen JV. Early onset primary hyperparathyroidism associated with a novel Germline mutation in CDKN1B. Case Reports in Endocrinology. 2015;2015:510985'},{id:"B72",body:'Frederiksen A, Rossing M, Hermann P, Ejersted C, Thakker RV, Nielsen MF. Clinical features of multiple endocrine neoplasia type 4—Novel pathogenic variant and review of published cases. The Journal of Clinical Endocrinology and Metabolism. 2019;104:3637-3646'},{id:"B73",body:'Costa-Guda J, Arnold A. Genetic and epigenetic changes in sporadic endocrine tumors: Parathyroid tumors. Molecular and Cellular Endocrinology. 2014;386(1-2):46-54'},{id:"B74",body:'Marx SJ. New concepts about familial isolated hyperparathyroidism. The Journal of Clinical Endocrinology and Metabolism. 2019;104:4058-4066'},{id:"B75",body:'Simonds WF, Robbins CM, Agarwal SK, Hendy GN, Carpten JD, Marx SJ. Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. The Journal of Clinical Endocrinology and Metabolism. 2004;89(1):96-102'},{id:"B76",body:'Warner J, Epstein M, Sweet A, Singh D, Burgess J, Stranks S, et al. Genetic testing in familial isolated hyperparathyroidism: Unexpected results and their implications. Journal of Medical Genetics. 2004;41(3):155-160'},{id:"B77",body:'Cetani F, Pardi E, Ambrogini E, Lemmi M, Borsari S, Cianferotti L, et al. Genetic analyses in familial isolated hyperparathyroidism: Implication for clinical assessment and surgical management. Clinical Endocrinology. 2006;64(2):146-152'},{id:"B78",body:'Pontikides N, Karras S, Kaprara A, Anagnostis P, Mintziori G, Goulis DG, et al. Genetic basis of familial isolated hyperparathyroidism: A case series and a narrative review of the literature. Journal of Bone and Mineral Metabolism. 2014;32(4):351-366'},{id:"B79",body:'Baumber L, Tufarelli C, Patel S, King P, Johnson CA, Maher ER, et al. Identification of a novel mutation disrupting the DNA binding activity of GCM2 in autosomal recessive familial isolated hypoparathyroidism. Journal of Medical Genetics. 2005;42(5):443-448'},{id:"B80",body:'Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN. Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: Effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism. Human Mutation. 2009;30(1):85-92'},{id:"B81",body:'Cetani F, Pardi E, Aretini P, Saponaro F, Borsari S, Mazoni L, et al. Whole exome sequencing in familial isolated primary hyperparathyroidism. Journal of Endocrinological Investigation. 2020;43(2):231-245'},{id:"B82",body:'Riccardi A, Aspir T, Shen L, Kuo CL, Brown TC, Korah R, et al. Analysis of activating GCM2 sequence variants in sporadic parathyroid adenomas. The Journal of Clinical Endocrinology and Metabolism. 2019;104(6):1948-1952'},{id:"B83",body:'Papadopoulou A, Gole E, Melachroinou K, Meristoudis C, Siahanidou T, Papadimitriou A. Identification and functional characterization of a calcium-sensing receptor mutation in an infant with familial hypocalciuric hypercalcemia. Journal of Clinical Research in Pediatric Endocrinology. 2016;8(3):341-346'},{id:"B84",body:'Brown EM. Familial hypocalciuric hypercalcemia and other disorders with resistance to extracellular calcium. Endocrinology and Metabolism Clinics of North America. 2000;29(3):503-522'},{id:"B85",body:'Brown EM. Mutations in the calcium-sensing receptor and their clinical implications. Hormone Research. 1997;48:199-208'},{id:"B86",body:'Corrado KR, Andrade SC, Bellizzi J, D’Souza-Li L, Arnold A. Polyclonality of parathyroid tumors in neonatal severe hyperparathyroidism. Journal of Bone and Mineral Research. 2015;30(10):1797-1802'},{id:"B87",body:'Farnebo F, Enberg U, Grimelius L, Backdahl M, Schalling M, Larsson C, et al. Tumor-specific decreased expression of calcium sensing receptor messenger ribonucleic acid in sporadic primary hyperparathyroidism. The Journal of Clinical Endocrinology and Metabolism. 1997;82(10):3481-3486'},{id:"B88",body:'Hosokawa Y, Pollak MR, Brown EM, Arnold A. Mutational analysis of the extracellular Ca(2+)-sensing receptor gene in human parathyroid tumors. The Journal of Clinical Endocrinology and Metabolism. 1995;80(11):3107-3110'},{id:"B89",body:'Cetani F, Pinchera A, Pardi E, Cianferotti L, Vignali E, Picone A, et al. No evidence for mutations in the calcium-sensing receptor gene in sporadic parathyroid adenomas. Journal of Bone and Mineral Research. 1999;14(6):878-882'},{id:"B90",body:'Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, Cranston T, et al. Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia. The New England Journal of Medicine. 2013;368(26):2476-2486'},{id:"B91",body:'Gorvin CM, Cranston T, Hannan FM, Rust N, Qureshi A, Nesbit MA, et al. A G-protein subunit-alpha11 loss-of-function mutation, Thr54Met, causes familial hypocalciuric hypercalcemia type 2 (FHH2). Journal of Bone and Mineral Research. 2016;31(6):1200-1206'},{id:"B92",body:'Nesbit MA, Hannan FM, Howles SA, Reed AA, Cranston T, Thakker CE, et al. Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. Nature Genetics. 2013;45(1):93-97'},{id:"B93",body:'Hendy GN, Canaff L, Newfield RS, Tripto-Shkolnik L, Wong BY, Lee BS, et al. Codon Arg15 mutations of the AP2S1 gene: Common occurrence in familial hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR) mutations. The Journal of Clinical Endocrinology and Metabolism. 2014;99(7):E1311-E1315'},{id:"B94",body:'Hannan FM, Howles SA, Rogers A, Cranston T, Gorvin CM, Babinsky VN, et al. Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects. 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Journal of the American Medical Association. 1996;276(19):1575-1579'},{id:"B99",body:'Arnold A, Kim HG, Gaz RD, Eddy RL, Fukushima Y, Byers MG, et al. Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma. The Journal of Clinical Investigation. 1989;83(6):2034-2040'},{id:"B100",body:'Rosenberg CL, Kim HG, Shows TB, Kronenberg HM, Arnold A. Rearrangement and overexpression of D11S287E, a candidate oncogene on chromosome 11q13 in benign parathyroid tumors. Oncogene. 1991;6(3):449-453'},{id:"B101",body:'Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, et al. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991;350(6318):512-515'},{id:"B102",body:'Imanishi Y, Hosokawa Y, Yoshimoto K, Schipani E, Mallya S, Papanikolaou A, et al. Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice. The Journal of Clinical Investigation. 2001;107(9):1093-1102'},{id:"B103",body:'Hosokawa Y, Tu T, Tahara H, Smith AP, Arnold A. Absence of cyclin D1/PRAD1 point mutations in human breast cancers and parathyroid adenomas and identification of a new cyclin D1 gene polymorphism. Cancer Letters. 1995;93(2):165-170'},{id:"B104",body:'Hsi ED, Zukerberg LR, Yang WI, Arnold A. Cyclin D1/PRAD1 expression in parathyroid adenomas: An immunohistochemical study. The Journal of Clinical Endocrinology and Metabolism. 1996;81(5):1736-1739'},{id:"B105",body:'Hemmer S, Wasenius VM, Haglund C, Zhu Y, Knuutila S, Franssila K, et al. Deletion of 11q23 and cyclin D1 overexpression are frequent aberrations in parathyroid adenomas. The American Journal of Pathology. 2001;158(4):1355-1362'},{id:"B106",body:'Tominaga Y, Tsuzuki T, Uchida K, Haba T, Otsuka S, Ichimori T, et al. Expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma. Kidney International. 1999;55(4):1375-1383'},{id:"B107",body:'Vasef MA, Brynes RK, Sturm M, Bromley C, Robinson RA. Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: A paraffin immunohistochemical study. Modern Pathology. 1999;12(4):412-416'},{id:"B108",body:'Wei Z, Sun B, Wang ZP, He JW, Fu WZ, Fan YB, et al. Whole-exome sequencing identifies novel recurrent somatic mutations in sporadic parathyroid adenomas. Endocrinology. 2018;159(8):3061-3068'},{id:"B109",body:'Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood. 2011;117(8):2451-2459'},{id:"B110",body:'Li Y, Cui W, Woodroof JM, Zhang D. Extranodal B cell lymphoma with prominent spindle cell features arising in uterus and in maxillary sinus: Report of two cases and literature review. Annals of Clinical and Laboratory Science. 2016;46(2):213-218'},{id:"B111",body:'Sanpaolo E, Miroballo M, Corbetta S, Verdelli C, Baorda F, Balsamo T, et al. EZH2 and ZFX oncogenes in malignant behaviour of parathyroid neoplasms. Endocrine. 2016;54:55-59'},{id:"B112",body:'Soong CP, Arnold A. Recurrent ZFX mutations in human sporadic parathyroid adenomas. Oncoscience. 2014;1(5):360-366'},{id:"B113",body:'Arnold A, Soong CP. New role for ZFX in oncogenesis. Cell Cycle. 2014;13(22):3465-3466'},{id:"B114",body:'Palanisamy N, Imanishi Y, Rao PH, Tahara H, Chaganti RS, Arnold A. Novel chromosomal abnormalities identified by comparative genomic hybridization in parathyroid adenomas. The Journal of Clinical Endocrinology and Metabolism. 1998;83(5):1766-1770'},{id:"B115",body:'Agarwal SK, Schrock E, Kester MB, Burns AL, Heffess CS, Ried T, et al. Comparative genomic hybridization analysis of human parathyroid tumors. Cancer Genetics and Cytogenetics. 1998;106:30-36'},{id:"B116",body:'Farnebo F, Kytölä S, Teh BT, Dwight T, Wong FK, Höög A, et al. Alternative genetic pathways in parathyroid tumorigenesis. The Journal of Clinical Endocrinology & Metabolism. 1999;84:3775-3780'},{id:"B117",body:'Kytölä S, Farnebo F, Obara T, Isola J, Grimelius L, Farnebo LO, et al. Patterns of chromosomal imbalances in parathyroid carcinomas. The American Journal of Pathology. 2000;157:579-586'},{id:"B118",body:'Garcia JL, Tardio JC, Gutierrez NC, Gonzalez MB, Polo JR, Hernandez JM, et al. Chromosomal imbalances identified by comparative genomic hybridization in sporadic parathyroid adenomas. European Journal of Endocrinology. 2002;146(2):209-213'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"William F. Simonds",address:"bills@niddk.nih.gov",affiliation:'
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA
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1. Introduction
The phenomena of transport properties in ionic liquids are of great important in the industrial science and technology, as well as in physics and chemistry. In connection with these, a number of experimental and theoretical studies have been published until the present time [1, 2, 3]. Ionic liquids are mainly classified into two categories; one is a group of molten salts and the other is a large number of electrolytic solutions, in particular, aqueous solutions of electrolytes.
In the case of molten salts, Sundheim discovered that the ratio of the partial conductivities of cation and anion were always equal to their inverse mass ratio, namely, σ+(DC)/σ−(DC) = m−/m+ [4].
Later on, this golden rule or a unified rule was theoretically explained by our group [5, 6, 7, 8, 9]. Detailed procedure will be shown in what follows.
Paralleling to above discovery, a number of scientific studies in molten salts have been developed from 1960s by several researchers [10, 11].
In order to study the structural and transport properties in molten salts, experimental investigations and molecular dynamics simulations have also been carried out from mid-70s of the last century [12, 13, 14, 15, 16].
Following to these, we have been engaged in the study of transport properties in molten salts [6, 7, 8, 9, 17]. We have carried out a theoretical study on the electrical conductivity of molten salts, starting from the Langevin equation and the velocity correlation functions for the constituent ions. Subsequently this treatment was successful to obtain the golden rule σ+/σ− = m−/m+ in a microscopic view point.
It remains, however, unclear how the adopted Langevin equation can be effectively solved within a short time region, under an appropriate memory function, because our former theory was only successful to get the partial conductivities.
We like to discuss more generally the correlation between the velocity correlation functions incorporated with the partial DC conductivities and some of useful memory functions which are closely related to the friction constants acting on cations and anions in molten salts.
Preceding the investigation for molten salts, on the other hand, there have been a number of studies for ionic solutions since the discovery of Faraday, in which a typical example is electrolytic solution. During such long-termed history of electrochemistry, it was well established by Kohlrausch that the experimental results on the ionic conductivities in dilute electrolytic solutions indicated the law of independent migration of ions, Λc = Λ0 − kc1/2, where Λ0 being the conductivity in the dilute limit and c the concentration and k the constant specified by the electrolyte dissolved in water.
The beginning of the modern aspect, in particular, on the thermodynamic and transport properties in electrolytic solutions might be originated from Debye-Hückel theory [18].
In order to explain the ionic conductivity in electrolytic solution, successful works following to Debye-Hückel theory have been reported by Onsager [19], Prigogine [20], and Fuoss and his co-worker [21]. In these theories, Λ0 is treated by the Stokes law and the concentration dependence is mainly explained by the electrophoretic effect and relaxation one. Therefore, these treatments are based on a kind of mixing of the microscopic and partially macroscopic view point.
Starting from the Liouville equation, statistical mechanics of irreversible process for the ionic conductivity in electrolytic solution have been developed by Davis and Résibois [22] and Friedman [23], although they did not derive any explicit expressions for the friction constant in terms of inter-particle interactions.
It has been required to investigate the static and dynamic properties of dissolved ions in aqueous solutions from the microscopic view point. Along this requirement, the technique of molecular dynamic simulation has been applied, using some qualified inter-particle potentials. Various theoretical attempts have been recently tried to establish the dynamical behaviors of dissolved ions in these solutions, which is able to discuss parallel with results obtained by MD simulation [24, 25, 26].
Chandra and Bagchi [27] have developed a new theoretical approach to study the ionic conduction in electrolytic solutions, based on the combination of the mode coupling theory and the generalized Langevin equation, and they were successful to obtain the Onsager equation. However, there still remains the task to obtain how to derive the theoretical formula for Λ0 in terms of inter-particle potentials and corresponding pair distribution functions.
We will apply the linear response theory for the electrolytic solution and to obtain Λ0 and the concentration dependence of the conductivity in terms of pair-wise potentials and pair distribution functions among ions and water molecules, which can compare parallel with dynamical properties of MD simulation [28].
In addition, we will also clarify how the electrophoretic and relaxation effects treated by many researchers are explained in a microscopic view point.
From these, we will see what is similar and what is different for the case of molten salts and that of electrolytic solutions.
2. Generalized Langevin equations for the cation and anion in a molten salt
Let us consider a molten salt composed of the density n+ = n− = n0 (= N/V0), of the constituent ion’s masses m+ and m−, and of the charge z+ = − z− = z = 1, where N being the total number of cation and/or anion in the volume V0.
A golden rule, σ+(DC)/σ−(DC) = m−/m+, can be obtainable from a generalized Drude theory, as a law of motion under an electric field [5].
As an extension, the generalized Langevin equation for an arbitrary cation or anion in the system under an external field E is written as follows:
m±dvi±t/dt=−m±∫−∞tξ±t−t′vi±t′dt′+Ri±t+z±eEE1
where ξ±(t) and Ri±(t) are the retarded friction function in relation to the friction force and the random fluctuating force, acting on the cation or anion i, respectively.
After taking the ensemble average, equations of time evolution based on Eq. (1) in respect to the partial ionic conductivities are then written as follows:
And the equation of time evolution in relation to the diffusion constants of constituent ions is written as follows:
m±d<vi±tvi±0>/dt=−m±∫−∞t<ξ±t−t′vi±t′vi±0>dt′E4
As was previously illustrated [9], the retarded friction function ξ±(t) cannot be independent for the averaging procedure and we have to define new memory functions as follows:
<ξ±t−t′vi±t′vj±0>=γσ±t<vi±t′vj±0>fori=jandi≠jE5
and
<ξ±t−t′vi±t′vk∓0>=γσ±t<vi±t′vk∓0>fori≠kE6
While, in the case of diffusion constants of constituent ions, that is, E = 0, we can define
<ξ±t−t′vi±t′vi±0>=γD±t<vi±t′vi±0>E7
It is emphasized that the memory functions γσ±(t) is not equal to γD±(t) as shown in previous paper [9]. In other words, the retarded friction function, ξ±(t − t′), is a kind of vector function and is varied with the environment such as the existence of electric field E. Therefore, the memory function is varied in accordance with what sort of evolution is considered in the time-dependent correlation function [29].
Assuming that the ensemble average for the fluctuating force is zero and if we apply the following electric field,
Et=ReE0expiωtE8
where Re means the real part and ω is the angular frequency, then the averaged ion’s velocity induced by this external filed is equal to
<vi±t>=Reμ±ωz±eEtE9
where μ±(ω) is the mobility of cation or anion.
Putting (9) into the equation of motion (1) after taking the ensemble average, we have
μ±ω=1/m±1/iω+γ∼±ωE10
where
γ∼±ω=∫0∞γ±texp−iωtdtE11
Therefore, the current density is written as follows:
j±t=nz±2e2<vi±t>=Renz±2e2μ±ωEtE12
The partial conductivity is, then, equal to
σ±ω=nz±2e2μ±ω=nz±2e2/m±1/iω+γ∼±ωE13
and in the limit of ω = 0,
σ±DC=nz±2e2μ±0=nz±2e2/m±γ∼±0E14
Therefore, γ∼±0 is equal to the effective friction constant acting on each ion.
According to our previous studies [7, 8, 9], the following relation was recognized:
γ∼+0=γ∼−0≡γ∼0E15
where γ∼0 is expressed as follows:
γ∼0=α0/3μ1/2,1/μ=1/m++1/m−E16
and
α0=n∫0∞∂2ϕ+−r/∂r2+2/r∂ϕ+−r/∂rɡ+−r·4πr2drE17
ϕ+−(r) and ɡ+−(r) in this equation are the inter-ionic potential between cation and anion and the corresponding pair distribution function, respectively.
Therefore, we have a golden rule for the partial conductivities in a microscopic scale as follows:
σ+DC/σ−DC=m−/m+E18
In the following sections, as a numerical example, the MD simulation on molten NaCl at 1100 K is often utilized, for which the interionic potential functions suggested by Tosi and Fumi [30] for a study of solid alkali halides are applied. In order to make sure that the Tosi-Fumi potential for NaCl can be valid in the liquid state, we have estimated the partial pair distribution functions of molten NaCl liquid, ɡij(r) (i,j = Na+, Cl−) as shown in Figure 1, which agree with those of experimental results obtained by Edwards et al. [31].
Figure 1.
Pair distribution functions, gij(r), for molten NaCl at 1148 K, obtained by MD simulation.
Using these ɡij(r), we have also estimated the total neighboring numbers around arbitrary ions located at the distance r, which describe as nij = 4πʃ0rr2dr, as shown in Figure 2a–c.
Figure 2.
(a) gNa-Cl(r) and nNa-Cl(r) for molten NaCl at 1148 K, obtained by MD simulation. (b) gNa-Na(r) and nNa-Na(r) for molten NaCl at 1148 K, obtained by MD simulation. (c) gCl-Cl(r) and nCl-Cl(r) for molten NaCl at 1148 K, obtained by MD simulation.
The nearest neighbor number is defined as nij(r1), where r1 is the position of the first minimum of ɡij(r).
Then, the nearest neighbors around a Na+ are nearly equal to 5.0, since the distance r1 is taken at the minimum position of ɡNa-Cl(r) as shown in Figure 2a.
The application of Tosi-Fumi potentials in the MD simulations for viscosity and electrical conductivity is also valid to reproduce their experimental results [5].
Therefore, the following MD simulations for molten NaCl must be reliable to see their microscopic view.
3. Linear response theory for the partial conductivities
On the other hand, according to our previous investigations [6, 7, 8, 9, 17, 29], the partial DC conductivities σ+(DC) and σ+(DC) are expressed as follows,
σ+DC=σ+++σ+−=1/3kBT∫0∞<j+tj0>dtE19
σ−DC=σ−−+σ+−=1/3kBT∫0∞<j−tj0>dtE20
where
σ±±=1/3kBT∫0∞<j±tj±0>dtE21
σ+−=1/3kBT∫0∞<j+tj−0>dtE22
and
jt=j+t+j−tE23
where
j+t=∑i=1nz+evi+t,j−t=∑k=1nz−evk−tE24
Considering the ensemble averages of (19) and (20), it is convenient to define the velocity correlation functions Zσ+(t) and Zσ−(t) as follows:
Zσ+t≡<vi+tvj+0>−<vi+tvk−0>E25
and
Zσ−t≡<vk−tvl−0>−<vi+tvk−0>E26
where < > means the ensemble average.
Using (25) and (26), the partial DC conductivities (19) and (20) are written, respectively, as follows:
If an appropriate memory function γ(t), which is valid for both cation and anion in the system, is considered and its Laplace transformation is inserted into either (36) or (37), then we can get the partial AC conductivities.
4. Microscopic representation for the Zσ+(t) and Zσ−(t) in a molten salt
We have already shown the microscopic expressions for Zσ+(t) and Zσ−(t) as Taylor expansion forms in a molten salt in which the inter-ionic potential between cation and anion and the corresponding pair distribution function are concerned by Koishi et al. [7]. In these combined velocity correlation functions, it can be shown that the odd power terms of the time t have vanishing coefficients which, it turns out, is related to the fact that any positions and their differentiations with time are uncorrelated in an ensemble average. In facts, the velocity auto-correlation function can be expressed in terms of even powers of the time t [32, 33].
The short-time expansion forms of Zσ+(t) and Zσ−(t) are actually shown in the following forms:
Zσ+t=3kBT/m+1−t2/2α0/3μ+overt4E38
and
Zσ−t=3kBT/m−1−t2/2α0/3μ+overt4E39
Thus, the partial conductivities for cation and anion in a molten salt are written as in the following Kubo-formulae:
σ+DC=n0e2/m+∫0∞1−t2/2α0/3μ+overt4dtE40
and
σ−DC=n0e2/m−∫0∞1−t2/2α0/3μ+overt4dtE41
Using (14), (16), (40) and (41), we have a very interesting relation written in the following form:
1/γ∼0=∫0∞1−t2/2γ∼02+overt4dtE42
However, it is generally difficult to obtain Zσ±(t) from appropriate memory functions, by using the well-known method in statistical mechanics [33].
Under these circumstances, we explore a new method to solve Langevin Eqs. (29) and (30), in order to clarify a detailed correlation between γ(t) and Zσ±(t) within the short time region, which will be shown in later section.
5. Method of continued-fraction based on Mori formulae
Many years ago, Mori [34, 35] had generalized the Langevin equation starting from the Hamilton’s canonical equation of motion in a system of a monatomic liquid with the component’s mass as m. Along his theory, Copley and Lovesey [36] have concluded that the memory function in the generalized Langevin equation could be expressed as follows:
∂γnt/∂t=−∫0tγn+1t−sγnsdsn=1,2,3,…E43
where γn(t) is the n-th stage memory function and the first stage memory function is equal to γ(t) in Eqs. (29) and (30). The Fourier-Laplace transform of the above equation provides the following continued-fraction representation,
γ∼nω=−δn/ω+γ∼n+1ωE44
where the Mori coefficient δn is equal to γn(0).
The method of Copley and Lovesey [36] was able to express the short time expansion for the velocity correlation function Z(t) (= < vi(t) vj(0)>) described as in the following form:
Zt=Z01−t2/2!Z2+t4/4!Z4−t6/6!Z6+…E45
Thus, they provided the following relations if several δn’s are known:
Therefore, the problem is ascribed to the derivation of δn’s. Because of a hard task in such repeating calculations, it is difficult to obtain a number of δn’s. However, several applications along these procedures have been carried out [37, 38].
Instead of the method of continued-fraction described in the above, we will provide a simple but new method to obtain the mutual relation between the combined velocity correlation function Zσ±(t) and γ(t) in a short time region, in the following section.
6. Recursion formulae for Zσ±(t) and γ(t)
Here, we provide a new and useful method to solve the Langevin equation based on recursion process [29]. Its detail is shown below.
Let us consider a Langevin equation for an evolution function being equivalent to (29) and (30), as follows:
dyt/dt=∫0tqt−sysdsE47
The power expansion for q(t) is defined as follows:
qt=∑n=0∞qn/n!tnqn=qn0E48
and the corresponding expansion formula for y(t) is written as follows:
yt=∑m=0∞ym/m!tmym=ym0E49
Putting (48) and (49) into the right hand side of Eq. (47), we have
This method can be immediately applicable in the following way, comparing with Eqs. (38) and (39).
q0=−γ∼02E56
yt=y01−t2/2!γ∼02+…E57
where
y0=3kBT/m±=Zσ±0≡Z0±E58
7. Fluctuation dissipation theorem on the Laplace transformation of γ(t)
Considering Eqs. (56) and (57), the memory function γ(t) can be taken as the following form:
γt=γ∼02ftE59
where f(0) = 1.
The Laplace transformation of (59) in the long wavelength limit is then written as follows:
γ∼0=γ∼02∫0∞ftdtE60
Therefore, we have immediately,
∫0∞ftdt=1/γ∼0E61
On the other hand, the memory function and its Laplace transformation are described as in the following forms, by using the fluctuation dissipation theorem [6, 7, 8, 9],
γt=1/3μkBT<RitRj0>E62
and
γ∼ω=1/3μkBT∫0∞exp−iωt<RitRj0>dtE63
The most simplest expression for < Ri(t) Rj(0) > can be taken as in the following form:
This equation gives h(t) ∝ f(t), and if we take both functions are identical, then
<Rij2>=1/3μkBTγ∼02E66
Putting this relation into (62), we obtain again the relation (59), which indicates that the assumption, h(t) = f(t), is exactly justified.
Therefore, the general form for the memory function γ(t) is always written in the form of Eq. (59).
8. Former theories of velocity correlation functions in molten salts
Various analytic forms for memory functions were proposed [7, 8, 12, 39, 40, 41, 42, 43] and all these functions are qualitatively useful to obtain the combined velocity correlation functions, although some of these theories cannot predict the result obtained by MD simulation.
For example, if we use an approximate form for the memory function as
As shown in our previous results [29], the calculated Zσ+(t) for cation by using Eq. (67) agrees with that of MD simulation [7] qualitatively and semi-quantitatively.
However, the time expansion forms of Zσ±(t) are essentially equal to the even powers expansion forms, which contradicts to the expression of (67). It is, therefore, necessary to seek an appropriate memory function which can be expanded as the even powers of the time t, even though the obtained result is numerically very close to the expression of γ(t) = γ∼(0)2 exp{−γ∼(0)t}.
9. Application of recursion method for the derivation of γ(t) from Zσ±(t)
So far, we are successful to obtain the mutual relation between γ(t) and Zσ±(t) within a short time region to satisfy the Langevin equations in molten salts.
There are several works to obtain the auto-velocity correlation functions in monatomic liquids from appropriate memory functions γ(t) [39, 41, 42].
However, it is not known what sorts of model functions are suitable for the combined velocity correlation function Zσ±(t) until the present time. In order to elucidate this question, we will try to calculate the coefficients ym’s of simulated Zσ±(t) of molten NaCl in a short time region, and from these the corresponding γ(t) will be obtained.
Previously we have already carried out the MD simulation for the combined velocity correlation functions Zσ±(t) [7].
We try two types of power expansion forms in order to fit the combined correlation functions Zσ±(t) by MD simulation. One is an arbitrary expansion form given by the even power series of the time t, which is theoretically exact for the combined correlation function. Another one is the series of even and odd powers for higher order terms over t2 one. Practical reason for the use of latter case will be given below.
In the case of the utilization of only even powers, it was quite difficult to get to the simulated Zσ±(t) even if the power’s number is taken up to 36th order of time t.
On the other hand, we can get an agreement if we use even and odd serial powers over t2 up to t9. This fact encourages us that the combined velocity correlation functions Zσ±(t) in molten systems must be practically analyzed in terms of even and odd powers of the time over t2.
Therefore, the method utilizing the odd and even power series has a more rapid convergence for obtaining Zσ±(t), in comparison with the method utilizing only even power series.
The fitting parameters, which are equal to ym’s, are obtained by the non-linear least mean square method as so-called Levenberg-Marquart method [44].
The primary value in this non-linear least mean square method is inferred by utilization of simplex method.
It is inevitable that the coefficients of ym’s (m = 3, 4, …) are slightly variable because of the termination effect in the expansion form. But we have no difficulty to elucidate γ(t) in an appropriate short time range.
By using these obtained ym’s, it is immediately possible to obtain qn’s. And thereafter we can get a fitted curve indicating the curve of γ(t) within a short time region. In this figure, the fitting curve of γ(t) is obtained for the time range of 0 < t < 5.0 × 10−14 seconds, from the expansion form of Zσ±(t) up to t15.
It is therefore emphasized that the utilization of odd terms within the short time region is necessary for the derivation of qn’s from the ym’s obtained by MD simulation.
For references, several analytic functional forms describing γ(t) can also be given. The following two-types of functional forms are known as model functions being suitable for the auto-velocity correlation functions in liquids.
a−1γt=γ∼02sechπ/2γ∼0tE68
a−2γt=γ∼02exp−π/4γ∼02t2}E69
The γ(t) is expressed by the form of γ∼(0)2exp{−γ∼(0)t} agrees, at least within the short time region, with that of MD simulation.
However, an inevitable fact is that the theoretical memory function must be an expansion form of only even powers of the time, even though it is numerically close to the exponentially decaying function which includes the odd powers.
Is it possible to get a model function to fit the obtained curve of γ(t) by MD simulation? To answer this question, we have carried out the fitting procedure by using a combination of poly-Gaussian functions [29]. Practically, the following form composed of three kinds of Gaussian functions is good enough to reproduce the obtained curve of γ(t) under the condition of Eq. (61) for molten NaCl at 1100 K,
Using (70) and (71), we could reproduce the obtained curve of γ(t) by MD simulation in molten NaCl at 1100 K. And these are approximated to as {a1 = 0.2, a2 = 0.3 and a3 = 0.5}, which values correspond to the existing fractions of each short range configuration i = 1, i = 2, and i = 3, respectively. And values of {b1 = 97.50, b2 = 6.52, and b3 = 0.38} correspond to their structural decaying speeds, respectively.
According to Figure 2a, the averaged nearest neighbor’s number around the Na+ ion is equal to 5.0. Any local coordination numbers around a Na+ are possible to be 4, 5, and 6 under the condition of density fluctuation in the liquid state.
It is possible to consider that stable short range configurations seem to be two types. One is the case of cubic structure-type configuration having with the coordination of 6 chlorine ions around the centered sodium ion as shown in Figure 3a, which is similar to the solid type configuration with a sort of lengthen fluctuation of the interionic distance.
Figure 3.
(a) A stable short range configuration of 6 Cl− ions around a Na+ ion. (b) Another stable short range configuration of 4 Cl− ions around a Na+ ion.
The other is close to a tetrahedral coordination of chlorine ions around the centered sodium ion as shown in Figure 3b.
For simplicity, here we assume that the decaying or releasing of these two types of rather stable short range configurations is nearly the same, then the combined configurational decaying is given by i = 3 and b3.
On the other hand, there exist two types of rather unstable short range configurations as shown in Figure 4a and b, respectively, in which the surrounded Cl− ions around a Na+ ion are spatially asymmetric.
Figure 4.
(a) A rather unstable short range configuration of 5 Cl− ions around a Na+ ion. (b) Another unstable short range configuration of 4 Cl− ions around a Na+ ion.
Totally, the local configuration types of Cl− ions around a centered Na+ ion are listed in Table 1.
Degree of stability
Configuration type
Coordination of 4 Cl− ions
Coordination of 5 Cl− ions
Coordination of 6 Cl− ions
Existing probability, ai
i = 1
0.2
0.2
i = 2
0.3
0.3
i = 3
0.15
0.35
0.5
Table 1.
Local configuration types of Cl− ions around a centered Na+ ion.
10. Discussion and conclusions in the case of molten salts
As shown in the previous section, the combined velocity correlation functions Zσ±(t) can be analyzed in terms of odd and even powers over t2 in their expansion forms and the corresponding memory function includes the terms of odd and even powers in its expansion form.
In addition, it is emphasized that the γ(t) obtained from the simulated Zσ+(t) agrees completely with that from Zσ−(t). This fact means that the memory functions for cation and anion are identical and Eq. (15) is automatically justified by the present new type of experiment such as computer simulation.
In conclusion, we have newly obtained the mutual relation between the memory function γ(t) and the combined velocity correlation function Zσ±(t), by using a recursion method to solve the Langevin equation and it may be applicable for finding a suitable memory function in all liquid matters.
11. Generalized Langevin equation in electrolytic solution
Hereafter, we will consider the strong electrolytic solution composed of N+ cations, N− anions and X water molecules in a volume VM. For simplicity, we take that N+ = N− = N and ions charges are equal to z+ = − z− = z. Then the number densities of ions and water molecules are equal to n+ = n− = n = N/VM and x = X/VM, respectively. And furthermore we assume that the dissociation of electrolyte is complete under the condition of N ≪ X.
In the present system, a generalized Langevin equation for the cation (or anion) i under an external field E is written as follows:
m±dvi±t/dt=−m±∫0tγ±t−t′vi±t’dt′+z±eE+F+z±eεitE72
where γ±(t) is the memory function incorporating with the friction force acting on its cation (or anion). F is the induced internal field yielded by the change of ion’s distribution which is resulted from the applying external field E, and εi(t) is the random fluctuating force acting on the ion i.
According to Berne and Rice [16], the internal field F induced by the asymmetric ion’s distribution in an ionic melt is expressed as follows:
F=−δ·E=−4πn/3kBT∫d∞dϕ+−r/drɡ+−rr3dr·EE73
where ɡ+−(r) is the pair distribution function between cation and anion, and d is the hard-core contact distance between cation and anion. Hereafter, we will use this result.
If we take E = E0 e−iωt, then the ensemble average for vi±(t) is written in the following form:
<vi±t>=Reμ±ωz±eE0e−iωtE74
Inserting (74) into (72) and taking ensemble average under the assumption of <εi(t) > = 0, we have
m±<dvi±t>/dt=−m±∫0tγ±t−t′vi±t′dt′+z±e1–δEE75
Therefore,
μ±ω=1–δ/m±−iω+γ∼±ωE76
where
γ∼±ω=∫0∞γ±teiωtdtE77
The dc current density j± is then written as follows:
j±=nz±e<vi±t>ω=0=nz2e2μ±0E0=nz2e21–δE0/m±γ∼±0E78
On the other hand, j± is expressed as j± = σ±E0, where σ± being equal to the partial conductivity for cation or anion. Therefore, σ± is written as follows:
σ±=nz2e21–δ/m±γ∼±0E79
The Laplace transformation of the memory function in the long wavelength limit γ∼±(0) in Eq. (79) will be obtained in later section.
In the next section, we will discuss velocity correlation functions.
12. Linear response theory for electrolytic solutions
Eq. (79) is also obtainable from the following simplified Langevin equation:
m±dvi±t/dt=−m±γ∼±0vi±t+z±eE+F+z±eεitE80
Its derivation can be easily seen in a standard book of statistical physics.
Starting from Eq. (80) with an infinitesimal external field E, it is also easily obtainable the following Kubo-Green formulae for the partial conductivities σ+ and σ− [6, 7, 28]:
σ+=1/3kBT∫0∞<j+t·j0>dtE81
and
σ−=1/3kBT∫0∞<j−t·j0>dtE82
where the current densities j±(t) and j(t) are defined by the following expressions:
j±t=z±e∑nvi±tandjt=j+t+j−tE83
In order to obtain the partial conductivities based on Eqs. (81) and (82), it is necessary to study the velocity correlation functions, < vi+(t) vj+(0)>, < vk−(t) vl−(0) > and < vi+(t) vk−(0)>.
In the next section, we will discuss velocity correlation functions described in terms of inter-molecular (or ionic) potentials and pair distribution functions in order to obtain the γ∼±(0).
13. Short time expansion of velocity correlation functions in electrolytic solutions
The short time expansion of velocity correlation function, < vi+(t) vj+(0) > for cation is written as
<vi+tvj+0>=<vi+0vj+0>+t2/2!<vi+0v¨j+0>+higher order overt4E84
In the present aqueous solution of electrolyte, the total Hamiltonian of the system is written as follows:
Since the water molecule is not spherical in its molecular configuration, it is difficult to define the position of rqw. However, we tentatively assume that its position is located at the center of oxygen atom in the H2O molecule.
Since the second derivative of the potential term V is independent for the product of momenta, all other terms other than i = j in (87) must vanish on averaging. And in a similar way, the meaningful terms of (88) for averaging must be also equal to the case i ≠ i’ = j. Therefore, taking the ensemble averages for (87) and (88), we have
In this equation, ɡ+w(r) is the pair distribution function between cation and water molecule.
It is emphasized that there is no contribution from ϕ++(r) in Eq. (89) because of the cancelation by the terms of i = j and i ≠ j in < pi+p¨j+> [7].
Insertion of (89) into (84) gives us the following form:
Z+t≡<vi+tvj+0>=<vi+0vj+0>−t2/2!kBTn<ϕ+−>+x<ϕ+w>/m+m++higher order overt4E92
In a similar way, the term < pi+p¨k−> can be described as follows:
<pi+p¨k−>=kBTn<ϕ+−>E93
Using this relation, the distinct velocity correlation function is written as follows:
<vi+tvk−0>=<vi+0vk−0>+t2/2!<vi+0v¨k−0>+higher order overt4=<vi+0vk−0>+t2/2!kBTn<ϕ+−>/m+m−+higher order overt4E94
Using (92) and (94), the combined velocity correlation function Zσ+(t)(= < j+(t)j(0)>/n2z2e2) incorporation with the partial conductivity σ+ is therefore expressed as follows:
Zσ+t≡<vi+tvj+0>−<vi+tvk−0>=3kBT/m+1–t2/2!n<ϕ+−>/3μ+x<ϕ+w>/3m++higher order overt4E95
where μ is equal to the reduced mass of m+ and m−. In deriving (95), we have assumed the initial conditions as follows:
<vi+0vj+0>=<vi+0vi+0>=3kBT/m+and<vi+0vk−0>=0E96
These initial conditions are confirmed by our own molecular dynamic simulation, which will be shown in the later section. In a similar way, we have
Zσ−t≡<vi−tvj−0>−<vi+0vj−0>=3kBT/m−1–t2/2!n<ϕ+−>/3μ+x<ϕ−w>/3m−+higher order overt4E97
where
<ϕ−w>=∫0∞∂2ϕ−wr∂r2+2/r∂ϕ−wr∂rɡ−wr4πr2drE98
ɡ−w(r) of this equation means the pair distribution function between anion and water molecule. And it is also emphasized that the contribution from ϕ−−(r) to < vi−(t) vj−(0) > is also vanished to be zero.
It is impossible to obtain the partial conductivities by the insertion of (95) and (97) into (81) and (82), because we knew only the terms up to t2 in their explicit forms. However, these equations can be utilized for the derivation of γ∼±(0) as shown in the next section.
14. Derivation of γ∼±(0) in electrolytic solutions
According to the fluctuation dissipation theorem applied for the present system with the condition of no external field or of infinitesimal external field, the Laplace transformation of the memory function γ±(t) and that of the ensemble average of time correlation function for the fluctuating random force <εi(t)εi(0) > have the following relation [25, 28]:
The fluctuation dissipation theorem tells us the following relation:
γ∼±ω=1/3m±kBTz2e2∫0∞<εitεi0>eiωtdtE100
In the long wavelength limit, this relation is expressed by
γ∼±0=1/3m±kBTz2e2∫0∞<εitεi0>dtE101
Let us go back to the memory function γ±(t) and assume a combined exponential decay functions for it as follows, although this assumption is not exactly consistent with Eq. (84), but technically acceptable one as discussed in the case of molten salt [29],
γ±t=γ0±t(=γ00±exp−β0±t+γ1±t=γ01±exp−β1±tE102
In this equation, the pre-exponential factor γ00± is subject to the interactions between the central ion and surrounding water molecules. The decaying constants are related to the time dependence of its configuration change. The pre-exponential factor, γ01±, is equal to the magnitude of memory function at t = 0 in respect to the friction force acting on the central cation or anion caused by interactions between its central ion and neighboring ions. In other words, the first term on the right hand side of this equation means the case of dilute limit of electrolytic solution and the second one is equal to the effective friction caused by the addition of a moderate amount of electrolyte. Therefore, the first term is related to either <ϕ+w > or < ϕ−w >, while the second one is related to the term <ϕ+− > .
Using (94) and (96), γ00± and γ01± are expressed as follows:
γ00±+γ01±=−Z¨σ±0/Zσ±0=x<ϕ±w>/3m±+n<ϕ+−>/3μE103
In the dilute limit of n ≪ x, we have
γ00±=x<ϕ±w>/3m±E104
And then we have
γ01±=n<ϕ+−>/3μE105
At the dilution limit of electrolyte where the contribution of γ1±(t) can be neglected, the Laplace transformation of γ0±(t) in the long wavelength limit is then described as follows:
where the auto-correlation function of random fluctuating force <εi0(t)εi0(0) > is only related to either <ϕ+w > or < ϕ−w >.
As seen in Eq. (79), the Laplace transformation of memory function in the long wavelength limit, γ∼0±(0), corresponds to effective friction constants for cation and anion, which means that the auto-correlation function of random fluctuating force.
<εi0(t) εi0(0) > may be represented by an exponential decaying function with the time constant of γ∼0±(0) as follows:
And the Laplace transformation of this equation in the long wavelength limit is equal to
γ∼±0=x<ϕ±w>/3m±1/2+n<ϕ+−>/3μ1/2E113
15. Partial conductivities σ+ and σ−
Putting Eq. (113) into (79), we obtain the formulae of the partial conductivities, σ+ and σ−, which are expressed in terms of the pair distribution functions and pair potentials as follows [28],
If the concentration c is defined as the number of moles of electrolyte in the unit volume (actually taken as 1 cc), then the number density n is equal to cNA, where NA being the Avogadro’s number. Then, the partial conductivities, σ+ and σ−, are written as follows:
From Eqs. (119) and (120), we have a form of Λc = (Λ+ + Λ−) ≃ Λ0 + Λ1– kc1/2. Λ0 and k are written as follows:
Λ0=NAz2e23/xm+<ϕ+w>1/2+3/xm−<ϕ−w>1/2E121
Λ1=NAδz2e23/xm+<ϕ+w>1/2+3/xm−<ϕ−w>1/2E122
and
k=NAz2e21–δ3NA<ϕ+−>/μ1/2{(1/x<ϕ+w>+1/x<ϕ−w>}E123
As seen in these expressions, Λ0 means the conductance in the dilution limit of electrolyte and Λ1 is the correction term appeared by the so-called relaxation effect. The last term kc1/2 is composed of the so-called electrophoretic effect and the combined term of both effects.
In the case of a moderate concentration of electrolyte, in particular, of relatively weak electrolyte, we have to take account of the degree of association between the opposite ions into the expression for the partial conductivities.
16. Pair potentials in electrolytic solution
A number of research works to obtain the model potentials in electrolytic solutions have been presented since the Debye-Hückel theory [18]. In particular, various qualified model potentials, which satisfy the experimental data such as the hydration free energy and the enthalpies in condensed and gas phases, have recently been proposed in order to carry out the molecular dynamic simulation. It is not our intension to compare or evaluate these potentials and therefore we like to refer only some of these for our interests [24, 25, 26, 27, 45]. It may be possible to estimate these potentials by using wave mechanical approach. In fact the ion-water molecule interactions were obtained by such an elaborating method [46, 47, 48].
The essential point for these model potentials in electrolytic solutions is that the dielectric character should be concerned. According to Sack [49], the water-molecules around the constituent ion are strongly oriented and the ion’s orientating ability to neighboring water-molecules decreases with increasing of the distance between the ion and those water-molecules. Oka [50] also estimated the change of effective dielectric constant as a function of distance between the ion and water-molecule.
We propose the following model function to satisfy these results as follows:
εr=1+ε0−11−exp−r−r0/κE124
where ε0 (=78.35) is the dielectric constant of water. Other parameters are numerically equal to r0 = 5 A and κ = 3.44 A−1, respectively.
The insertion of this dielectric function ε(r) for the long range part of inter-particle potential is not necessary in molecular dynamic simulations. The dynamics produces automatically the configuration of constituents to satisfy the dielectric behavior.
On the analogy of the inter-ionic potentials in molten salts, ϕ+−(r) in aqueous solution, where the dipole-dipole and dipole-quadrupole dispersion forces are neglected, may be given as follows:
ϕ+−r=z+z−e2/rεr+A+−expB+−di++dj−−rE125
where A+− is a constant in relation to the magnitude of repulsive force between cation i and anion j. B+− the softness parameter and (di+ + dj−) is the hard core contact between cation i and anion j. A+− and B+− are also given in the literature [27]. The difference between this expression and that of ionic crystal or of molten salt is only ascribed to whether the introduction of the dielectric function ε(r) is necessary or not.
For simplicity, the pair potentials ϕ+ w(r) and ϕ− w(r) are assumed to be a combined form of the repulsive potential and the charge-dipole potential. Then the pair potential between cation and water molecule centered at the oxygen atom, ϕ+ w(r), is written as follows:
ϕ+wr=ϕrep+wr−z+eμcosθ1–3l2/8r2/r2εrE126
where ϕrep+w(r) is repulsive potential and its explicit form will be given be later. μ is the dipole of water molecule and l its length. θ is the dipole’s angle in the direction of cation.
It is well-known that the above expression is converted to the following form according to Boltzmann law,
ϕ+wr=ϕrep+wr−z+2e2μ21–3l2/8r2/3kBTr2εrE127
On the other hand, a modified Lennard-Jones potential for water molecule, ϕww(r), is useful and is written as follows [45]:
ϕwwr=4Cdw/r12−dw/r6−2μ2/r3E128
In this equation, the term 4C(dw/r)12 is equal to the repulsive part and the parameters C and dw for water molecule in the gaseous state are equal to 230.9 kB and 2.824 Å, respectively.
The repulsive part of inter-ionic potential for ϕ++(r) may be approximately described as the form of A++exp[B++(d+ + d+ − r)] similar to the repulsive one in Eq. (125), since its interaction occurs around the distance of close contact where the dielectric behavior of neighboring water molecules must be neglected.
Now let us assume that the repulsive potential ϕrep+w(r) is represented by the root mean square of 4C(dw/r)12 and A++exp[B++ (d+ + d+- r)] as follows:
ϕrep+wr=4Cdw/r12A++expB++d++d+−r1/2E129
Insertion of (129) into Eq. (127) gives us the following expression,
The dipole moment of water molecule is known to be μ = 0.38 (in the unit of e times 1 Å = 1.6 × 10−29 C·m) and l ≒0.5 Å. Therefore, all parameters in (130) and (131) are known. According to Bopp et al. [51], the repulsive parts in (130) and (131) are converted to the exponential decaying functions similar to the repulsive part in (125) [46, 47].
Under these circumstances, it is possible to use either our empirical expressions (130) and (131), or to apply the inter-particle potentials derived by Bopp et al. [51]. It is also possible to estimate the repulsion terms in (130) and (131) by using wave mechanical approach. In fact, the ion-water molecule interactions were obtained by such an elaborating method [33, 52]. However, we will use the above empirical potentials for numerical application, for simplicity.
17. Momentum conservation and the tag of water molecules by ion’s movement
We will investigate the tag of water molecules by ion’s moving in the electrolytic solutions from the view point of equation of motion under an applied field E [28].
Under this situation, the second law of motion for the cation i can be written as follows:
m+dvi+t/dt=∑j≠iN+andN−fij+∑q≠iXFiq+z+eEE132
fij is the force acting on the ion i from the ion j and Fiq is that from the water molecule q.
At the time of steady state, τ, after applying the external field E, we have
where nw is the number density of water molecules.
The summation of last three terms on the right hand side of this equation is equal to zero, because there is no external force at t = 0. All other terms on the right hand side of this equation are equal to zero by considering the law of action and reaction and charge neutrality condition.
Therefore, we have
n<m+vi+τ>+n<m−vk−τ>+nw<mwvqwτ>=0E137
This equation indicates that the partial conductivity ratio < vi+(τ)>/< vk−(τ) > is not equal to the inverse mass ratio m−/m+, which is essentially different from the case of molten salts.
Some of water molecules may be simultaneously pulled by the dissolved ions under an external field E. Here, we neglect the relative time-relaxation for velocities of particles undergoing the co-operative motion. Taking the numbers of pulled water-molecules by each cation and anion, as x+ and x−, we have
nx++nx−+xr=nwE138
Here, xr is equal to the number density of un-pulled water molecules.
Since, the movements of remainder water molecules under the external field must be isotropic, we have xr < mwvw(τ) > = 0. Then nw < mwvqw(τ) > is expressed as follows:
nw<mwvqwτ>=x+<mwvi+τ>+x−<mwvk−τ>E139
Insertion of this equation into (66) gives us the following relation:
<m++x+mwv+τ>+<m−+x−mwv−τ>=0E140
Hereafter, we omit the suffix of ion i or k.
Therefore, we have
∣<v+τ>∣/∣<v−τ>∣=m−+x−mw/m++x+mwE141
We cannot apply the above treatment for H+ and OH− ions, because their conduction mechanisms differ from that of all other dissolved ions. Their mechanisms are known as the Grotthus-type conduction which is a kind of hopping conduction of electrons or holes [3].
It is, however, straightforward to obtain the following relation for all dissolved ions in their dilute limits except for H+ and OH− ones,
∣<v+τ>∣m++x+mw=∣<v−τ>∣m−+x−mwE142
This relation seems to be valid for all aqueous solutions of equivalent electrolytes in the dilution limit.
Using Eqs. (114) and (115), Eq. (142) for the dilution limit of electrolytic solution is expressed as follows:
σ+/σ−=mass of an anion plus masses of water molecules pulledbyitsanion/mass ofacation plus masses of water molecules pulledbyitscation=m−+x−mw/m++x+mw=m−<ϕ−w>1/2/m+<ϕ+w>1/2E143
This equation may correspond to the inverse mass ratio for the partial conductivities of molten salt [6].
18. Numerical results in electrolytic solutions
According to the theoretical results we have discussed so far, the pair distribution functions appear in the essential equations [28]. Therefore, how to obtain the pair distribution functions is one of the matters of vital importance.
There are several standard theoretical methods to obtain the pair distribution functions in molecular liquids from the knowledge of inter-particle potentials [33]. In the calculation of site-site distribution function for such a molecular liquid, the reference interaction-site model (RISM) approximation proposed by Chandler and Anderson [52] seems to be useful. Until the present time, the extension of RISM approximation, in order to obtain the potentials of mean force and also the site-site pair distribution functions ɡμν(r)‘s in electrolytic solutions, has been carried out by several authors [53, 54, 55]. These attempts cover the insufficient experimental knowledge for pair distribution functions ɡ+−(r), ɡ+ w(r) and ɡ− w (r).
However, we will use the ɡμν(r)‘s in aqueous solution of sodium chloride obtained by our own MD simulation. The essential numerical procedure of MD simulation in this study is same as our previous works of molten salts [56]. The procedure of MD simulation of electrolyte aqueous solution will be briefly described as follows for reader’s benefit. In MD for the electrolyte aqueous solution, the rigid body models (TIP4P) [57] are used for water molecules. The interactions between constituent TIP4P water molecules are expressed as the charged L-J type potentials, as,
ijr=zizje2r+Ar12−Br6E144
The interactions between alkali metal cation and halide anion, TIP4P- alkali metal anion, and TIP4P – halide anion are expressed as [58]:
ijr=zizje2r+Cr9−Dr6E145
In (144) and (145), i and j stand for the constituent atoms; e is the elementary charge. The used charges for the constituent species zi and the interaction parameters are taken from the literature; TIP4P – TIP4P [57]; TIP4P – alkali metal cation, TIP4P – halide anon, between alkali metal cation, between halide anion, and between alkali metal cation and halide anion [58]. The Ewald method is used for the calculation of the Coulomb interaction. For the structure calculation, MD is performed in NTP constant condition [59, 60, 61] under the pressure of 1 atm at 283 K. MD is performed for 50,000 steps with 0.1 fs one time step in 1.1% NaCl aqueous solution. MD cell contains about 10,000 molecules (i.e. 30,000 atoms) for the calculation of the structure and the velocity autocorrelation function for alkali halide aqueous solution. The numbers of the constituent ions in the MD cell are listed in Table 2.
Solute
Water (TIP4P)
Cation
Anion
Li+ Cl−
10,000
112
112
Na+ Cl−
10,000
112
112
K+ Cl−
10,000
112
112
Table 2.
The numbers of ions in MD cell.
The main part of MD is performed using SIGRESS ME package (Fujitsu) at the supercomputing facilities in Kyushu University.
The obtained figures of ɡij(r) are shown in Figures 5–8. And using these data, we have estimated the numbers of water molecules involved within a sphere of radius r from the centered ion, nij(r) (i = Li+, Na+, K+ and Cl−; j = oxygen of water molecule) = 4πʃ0r ɡij(r)r2 dr, which are also figured in them.
Figure 5.
Pair distribution function of water molecules around a Li + ion, gLi-w(r) in the electrolyte solution of LiCl. And numbers of locating water molecules around a Li + ion within the sphere of the length r centered at its Li + ion, nLi-w(r), in its solution obtained by MD simulation.
Figure 6.
Pair distribution function of water molecules around a Na + ion, gNa-w(r) in the electrolyte solution of NaCl. And numbers of locating water molecules around a Na + ion within the sphere of the length r centered at its Na + ion, nNa-w(r), in its solution obtained by MD simulation.
Figure 7.
Pair distribution function of water molecules around a K+ ion, gK-w(r) in the electrolyte solution of KCl. And numbers of locating water molecules around a K+ ion within the sphere of the length r centered at its K+ ion, nK-w(r), in its solution obtained by MD simulation.
Figure 8.
Pair distribution function of water molecules around a Cl− ion, gCl-w(r) in the electrolyte solution of MCl (M = Li, Na and K). And numbers of locating water molecules around a Cl− ion within the sphere of the length r centered at its Cl− ion, nCl-w(r), in its solution obtained by MD simulation.
Using Eq. (143), that is, σ+/σ− = (m− + x−mw)/(m+ + x+mw), and taking an assumption that the pulling water molecules for Na+ ion is equal to 6.0 although its plausible justification seems to be difficult, then we obtain the pulling water molecules for other ions as shown in Table 3, in which the hydration numbers seen in a text book [62] and our results obtained by MD simulation, for reference.
Numbers of pulling water molecules, x+ or x− and hydration numbers.
Assumption that the pulling number x+ of Na+ ion is equal to be 6.0 and also that the pulling numbers of water molecules for Cl− are not changed even for that the pairing positive ions are different.
Using these pulling numbers for the constituent ions, we can estimate the term, (m− + x−mw)/(m+ + x+mw) as shown in Table 4. As seen in this table, agreements for both terms are satisfactory, which is a kind of proof for the assumption x+ is equal to 6.0.
Electrolyte
σ+/σ−
(m− + x−mw)/(m++ x+mw)
Li+ Cl−
0.595
0.598
Na+ Cl−
0.659
0.655
K+ Cl−
0.963
0.960
Table 4.
The ratio of ionic conductivity and the calculation results by using Table 3.
It is emphasized that the pulling number of water molecules by moving ion has no relation to the hydration number of water molecules as seen in Table 3. The hydration of water molecules around electrolytic ions is originated essentially by the thermodynamic stability which is related not only to the interaction energies among ions and water molecules but also to the configuration entropy terms. This is because that the pulling number is not always related to the hydration one.
19. Discussion on the electrical conductivities in electrolytic solutions
The present theory seems essentially comparable to the treatments developed by Onsager [19], Fuoss et al. [21], Prigogine [20], Friedman [23], Chandra and Bagchi [27], and Matsunaga and Tamaki [28].
Friedman [23] used a technique of diagram expansion starting from Kubo-Green formula for the conductivity of electrolytic solution and the obtained expression was also written in the form of Λc = (Λ+ + Λ−) = Λ0 + Λ1 – kc1/2. However, his theory is very much sophisticated and too mathematical to understand with a physical insight.
Recent theoretical work carried out by Chandra and Bagchi [27] is basically started from a Kubo-Green type theory, that is, the partial conductivities are derived from velocity correlation functions. Their treatment seems to be a modernized and beautiful and therefore it is very much appreciable. However, the friction force of their theory involves various terms which make it difficult to calculate practically the partial conductivities. In fact, there still remains the task to represent a microscopic formula for Λ0.
The present treatment is easily to understand in view of physical insight and is successful for deriving the formula of Λ0.
The short-time expansion forms for < vi+(t) vi+(0)>, < vk−(t) vk−(0) > and < vi+(t) vk−(0) > are expressed in terms inter-particle potentials and corresponding pair distribution functions as seen in (95) and (97). In the case of molten salts, all these velocity correlation functions yield some physical quantities in relation to a part of partial conductivities [6]. In the present case, however, Zσ+(t) and Zσ−(t) play its role. Such an essential difference between the case of molten salt and the electrolytic solution may be ascribed to the difference in the momentum conservation of the system.
\n',keywords:"conductivity of molten salts, conductivity of electrolytic solution, Langevin equation, MD simulation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/71299.pdf",chapterXML:"https://mts.intechopen.com/source/xml/71299.xml",downloadPdfUrl:"/chapter/pdf-download/71299",previewPdfUrl:"/chapter/pdf-preview/71299",totalDownloads:744,totalViews:0,totalCrossrefCites:0,dateSubmitted:"August 29th 2019",dateReviewed:"January 27th 2020",datePrePublished:"March 2nd 2020",datePublished:"September 16th 2020",dateFinished:"March 2nd 2020",readingETA:"0",abstract:"A microscopic description for the partial DC conductivities in molten salts has been discussed by using a Langevin equation for the constituent ions. The memory function γ(t) can be written as in the form of a decaying function with time. In order to solve the mutual relation between the combined-velocity correlation functions Zσ±(t) and the memory function γ(t) in a short time region, a new recursion method is proposed. Practical application is carried out for molten NaCl by using MD simulation. The fitted function is described by three kinds of Gaussian functions and their physical backgrounds are discussed. Also the electrical conductivity in aqueous solution of electrolyte has been obtained, based on a generalized Langevin equation for cation and anion in it. This treatment can connect and compare with the work of computer simulation. The obtained results for concentration dependence of electrical conductivity are given by a function of the square root of concentration. The electrophoretic effect and the relaxation one are also discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/71299",risUrl:"/chapter/ris/71299",signatures:"Shigeru Tamaki, Shigeki Matsunaga and Masanobu Kusakabe",book:{id:"9257",type:"book",title:"Electromagnetic Field Radiation in Matter",subtitle:null,fullTitle:"Electromagnetic Field Radiation in Matter",slug:"electromagnetic-field-radiation-in-matter",publishedDate:"September 16th 2020",bookSignature:"Walter Gustavo Fano, Adrian Razzitte and Patricia Larocca",coverURL:"https://cdn.intechopen.com/books/images_new/9257.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78984-519-8",printIsbn:"978-1-78984-518-1",pdfIsbn:"978-1-83968-568-2",isAvailableForWebshopOrdering:!0,editors:[{id:"215741",title:"Prof.",name:"Walter Gustavo",middleName:null,surname:"Fano",slug:"walter-gustavo-fano",fullName:"Walter Gustavo Fano"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"101922",title:"Prof.",name:"Shigeki",middleName:null,surname:"Matsunaga",fullName:"Shigeki Matsunaga",slug:"shigeki-matsunaga",email:"matsu@nagaoka-ct.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Nagaoka National College of Technology",institutionURL:null,country:{name:"Japan"}}},{id:"104566",title:"Prof.",name:"Shigeru",middleName:null,surname:"Tamaki",fullName:"Shigeru Tamaki",slug:"shigeru-tamaki",email:"tamakis@cocoa.ocn.ne.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Niigata University",institutionURL:null,country:{name:"Japan"}}},{id:"311340",title:"Prof.",name:"Masanobu",middleName:null,surname:"Kusakabe",fullName:"Masanobu Kusakabe",slug:"masanobu-kusakabe",email:"kusakabe@acb.niit.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Generalized Langevin equations for the cation and anion in a molten salt",level:"1"},{id:"sec_3",title:"3. Linear response theory for the partial conductivities",level:"1"},{id:"sec_4",title:"4. Microscopic representation for the Zσ+(t) and Zσ−(t) in a molten salt",level:"1"},{id:"sec_5",title:"5. Method of continued-fraction based on Mori formulae",level:"1"},{id:"sec_6",title:"6. Recursion formulae for Zσ±(t) and γ(t)",level:"1"},{id:"sec_7",title:"7. Fluctuation dissipation theorem on the Laplace transformation of γ(t)",level:"1"},{id:"sec_8",title:"8. Former theories of velocity correlation functions in molten salts",level:"1"},{id:"sec_9",title:"9. Application of recursion method for the derivation of γ(t) from Zσ±(t)",level:"1"},{id:"sec_10",title:"10. Discussion and conclusions in the case of molten salts",level:"1"},{id:"sec_11",title:"11. Generalized Langevin equation in electrolytic solution",level:"1"},{id:"sec_12",title:"12. Linear response theory for electrolytic solutions",level:"1"},{id:"sec_13",title:"13. Short time expansion of velocity correlation functions in electrolytic solutions",level:"1"},{id:"sec_14",title:"14. Derivation of γ∼±(0) in electrolytic solutions",level:"1"},{id:"sec_15",title:"15. Partial conductivities σ+ and σ−",level:"1"},{id:"sec_16",title:"16. Pair potentials in electrolytic solution",level:"1"},{id:"sec_17",title:"17. Momentum conservation and the tag of water molecules by ion’s movement",level:"1"},{id:"sec_18",title:"18. Numerical results in electrolytic solutions",level:"1"},{id:"sec_19",title:"19. Discussion on the electrical conductivities in electrolytic solutions",level:"1"}],chapterReferences:[{id:"B1",body:'Janz GJ. Molten Salts Handbook. New York: Academic Press; 1967'},{id:"B2",body:'Smedley SI. The Interpretation of Ionic Conductivity in Liquids. New York: Plenum Press; 1980'},{id:"B3",body:'Conway BE. In: Eyring H, editor. 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On the relaxation effect in the electrical conductivity of plasmas and electrolytes. The Journal of Chemical Physics. 1964;40:3276'},{id:"B23",body:'Friedman HL. A cluster expansion for the electrical conductance of solutions. Physica. 1964;30:509. On the limiting law for electrical conductance in ionic Solutions, 537; 1964'},{id:"B24",body:'Chandra A, Wei D, Patey GN. The frequency dependent conductivity of electrolyte solutions. The Journal of Chemical Physics. 1993;99:2083'},{id:"B25",body:'Smith DE, Dang LX. Computer simulations of NaCl association in polarizable water. The Journal of Chemical Physics. 1994;100:3757'},{id:"B26",body:'Koneshan S, Rasaiaha JC. Computer simulation studies of aqueous sodium chloride solutions of 298 K and 683 K. The Journal of Chemical Physics. 2000;113:8125'},{id:"B27",body:'Chandra A, Bagchi B. Ion conductance in electrolyte solutions. The Journal of Chemical Physics. 1999;110:10024'},{id:"B28",body:'Matsunaga S, Tamaki S. Ionic conduction in electrolyte solution. Journal of Solution Chemistry. 2014;43:1771'},{id:"B29",body:'Kusakabe M, Takeno S, Koishi T, Matsunga S, Tamaki S. A theoretical extension for the electrical conductivities of molten salts. Molecular Simulation. 2012;38:45-56'},{id:"B30",body:'Tosi MP, Fumi FG. Ionic sizes and born repulsive parameters in the NaCl-type alkali halides—II: The generalized Huggins-Mayer form. Journal of Physics and Chemistry of Solids. 1964;25:45'},{id:"B31",body:'Edwards FG, Enderby JE, How RA, Page DI. The structure of molten sodium chloride. Journal of Physics C. 1975;8:3483'},{id:"B32",body:'March NH, Tosi MP. Atomic Dynamics in Liquids. London: The MacMillan Press Ltd; 1976'},{id:"B33",body:'Hansen JP, McDonald IR. Theory of Simple Liquids. 2nd ed. New York: Academic; 1986'},{id:"B34",body:'Mori H. Transport, collective motion, and Brownian motion. Progress in Theoretical Physics. 1965;33:423-455'},{id:"B35",body:'Mori H. A continued-fraction representation of the time-correlation functions. Progress of Theoretical Physics. 1965;34:399-416'},{id:"B36",body:'Copley JRD, Lovesey SW. The dynamic properties of monatomic liquids. Reports on Progress in Physics. 1975;38:461-563'},{id:"B37",body:'Tankeshwar K, Pathak KN, Ranganathan S. Self-diffusion coefficients of Lennard-Jones fluids. Journal of Physics C: Solid State Physics. 1987;20:5749'},{id:"B38",body:'Joslin CG, Gray CG. Calculation of transport coefficients using a modified Mori formalism. Molecular Physics. 1986;58:789'},{id:"B39",body:'Douglass DC. Self Difusion and velocity correlation. The Journal of Chemical Physics. 1961;35(1):81'},{id:"B40",body:'Levesque D, Verlet L. Computer “experiment” on classical fluids III. Physics Review. 1970;A2(1970):2514'},{id:"B41",body:'Tankeshwar K, Pathak K, Ranganathan S. Theory of transport coefficients of simple liquids. Journal of Physics: Condensed Matter. 1990;2(1990):5891-5905'},{id:"B42",body:'Balucani U, Zoppi M. Dynamics of the Liquid State. Clarendon: Oxford; 1994'},{id:"B43",body:'Hoshino K, Shimojo F, Munejiri S. Mode-coupling analysis of atomic dynamics for liquid Ge, Sn and Na. Journal of the Physical Society of Japan. 2002;71(1):119-124'},{id:"B44",body:'Levenberg K. A method for the solution of certain non-linear problem in least squares. Quarterly of Applied Mathematics. 1944;2:164'},{id:"B45",body:'Berendsen HJC, Griegera JR, Straatsma TP. The missing term in effective pair potentials. The Journal of Chemical Physics. 1987;9:6269'},{id:"B46",body:'Clementi E, Popkie H. Study of the structure of molecular complexes. I. Energy surface of a water molecule in the field of a lithium positive ion. The Journal of Chemical Physics. 1972;57:1077'},{id:"B47",body:'McGlynn SP et al. Introduction to Applied Quantum Chemistry. New York: Rinehart and Winston Inc.; 1972, 1972'},{id:"B48",body:'Kistenmacher H, Popkie H, Clemnti E. Study of the structure of molecular complexes. V., heat of formation for the Li+, Na+, K+, F−, and Cl− ion complexes with a single water molecule. The Journal of Chemical Physics. 1974;59:5842'},{id:"B49",body:'Sack H. The dielectric constants of solutions of electrolytes at small concentrations. Physikalishce Zeitschrift. 1927;28:199'},{id:"B50",body:'Oka S. Über den Sattigungszustand einen Dipolflussigkeit in der Umgebung eines Ions. Proceedings of the Physico-Mathematical Society of Japan. 1932;14:441'},{id:"B51",body:'Bopp P, Dietz W, Heinzinger K. A molecular dynamics study of aqueous solutions X.: First results for a NaCl solution with a central force model for water. Zeitschrift für Naturforschung. 1979;34a:1424-1435'},{id:"B52",body:'Chandler D, Anderson HC. Optimized expansions for classical fluids. II. Theory of molecular liquids. The Journal of Chemical Physics. 1972;57:1930'},{id:"B53",body:'Hirata F, Rossky PJ, Pettitt BM. The interionic potential of mean force in a molecular polar solvent from an extended RISM equation. The Journal of Chemical Physics. 1983;78:4133'},{id:"B54",body:'Pettitt BM, Rossky PJ. Alkali halides in water: Ion-solvent correlations and ion-ion potentials of mean force at infinite dilution. The Journal of Chemical Physics. 1986;84:5836'},{id:"B55",body:'Kovalenko A, Hirata F. Potentials of mean force of simple ions in anbient aqueous solution. I: Three dimensional reference interaction site model approach. The Journal of Chemical Physics. 2000;112:10391. II: Solvation structure from the three-dimensional reference interaction site model approach, and comparison with simulation. 10403(2000)'},{id:"B56",body:'Matsunaga S. Structural features in molten RbAg4I5 by molecular dynamics simulation. Molecular Simulation. 2013;39:119'},{id:"B57",body:'Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple partial functions for simulating liquid water. The Journal of Chemical Physics. 1983;79:926'},{id:"B58",body:'Zhengwei P, Ewig CS, Hwang M-J, Waldman M, Hagler AT. Derivation of class II force field. 4. Van der Waals parameters of alkali metal Cations and halide anions. The Journal of Physical Chemistry. A. 1997;101:7243'},{id:"B59",body:'Andersen HC. Molecular-dynamics simulations at constant pressure and/or temperature. The Journal of Chemical Physics. 1980;72:2384'},{id:"B60",body:'Nosé S. A molecular dynamics method for simulations in the canonical ensemble. Molecular Physics. 1984;52:255'},{id:"B61",body:'Nosé S. A unified formulation of the constant temperature molecular dynamics methods. The Journal of Chemical Physics. 1984;81:511'},{id:"B62",body:'Conway BE. Ionic Hydration in Chemistry and Biophysics. Amsterdam: Elsevier; 1981'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Shigeru Tamaki",address:null,affiliation:'
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Our journals are currently in their launching issue. They will be applied to all relevant indexes as soon as they are eligible. These include (but are not limited to): Web of Science, Scopus, PubMed, MEDLINE, Database of Open Access Journals (DOAJ), Google Scholar and Inspec.
\n\n
IntechOpen books are indexed by the following abstracting and indexing services:
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BKCI is a part of Web of Science Core Collection (WoSCC) and the world’s leading citation index with multidisciplinary content from the top tier international and regional journals, conference proceedings, and books. The Book Citation Index includes over 104,500 editorially selected books, with 10,000 new books added each year. Containing more than 53.2 million cited references, coverage dates back from 2005 to present. The Book Citation Index is multidisciplinary, covering disciplines across the sciences, social sciences, and arts & humanities.
Produced by the Web Of Science group, BIOSIS Previews research database provides researchers with the most current sources of life sciences information, including journals, conferences, patents, books, review articles, and more. Researchers can also access multidisciplinary coverage via specialized indexing such as MeSH disease terms, CAS registry numbers, Sequence Databank Numbers and Major Concepts.
Produced by the Web Of Science group, Zoological Record is the world’s oldest continuing database of animal biology. It is considered the world’s leading taxonomic reference, and with coverage back to 1864, has long acted as the world’s unofficial register of animal names. The broad scope of coverage ranges from biodiversity and the environment to taxonomy and veterinary sciences.
Provides a simple way to search broadly for scholarly literature. Includes peer-reviewed papers, theses, books, abstracts and articles, from academic publishers, professsional societies, preprint repositories, universities and other scholarly organizations. Google Scholar sorts articles by weighing the full text of each article, the author, the publication in which the article appears, and how often the article has been cited in other scholarly literature, so that the most relevant results are returned on the first page.
Microsoft Academic is a project exploring how to assist human conducting scientific research by leveraging machine’s cognitive power in memory, computation, sensing, attention, and endurance. Re-launched in 2016, the tool features an entirely new data structure and search engine using semantic search technologies. The Academic Knowledge API offers information retrieval from the underlying database using REST endpoints for advanced research purposes.
The national library of the United Kingdom includes 150 million manuscripts, maps, newspapers, magazines, prints and drawings, music scores, and patents. Online catalogues, information and exhibitions can be found on its website. The library operates the world's largest document delivery service, providing millions of items a year to national and international customers.
The digital NSK portal is the central gathering place for the digital collections of the National and University Library (NSK) in Croatia. It was established in 2016 to provide access to the Library’s digital and digitized material collections regardless of storage location. The digital NSK portal enables a unified search of digitized material from the NSK Special Collections - books, visual material, maps and music material. From the end of 2019, all thematic portals are available independently: Digital Books, Digitized Manuscripts, Digitized Visual Materials, Digital Music Materials and Digitized Cartographic Materials (established in 2017). Currently available only in Croatian.
The official DOI (digital object identifier) link registration agency for scholarly and professional publications. Crossref operates a cross-publisher citation linking system that allows a researcher to click on a reference citation on one publisher’s platform and link directly to the cited content on another publisher’s platform, subject to the target publisher’s access control practices. This citation-linking network covers millions of articles and other content items from several hundred scholarly and professional publishers.
Dimensions is a next-generation linked research information system that makes it easier to find and access the most relevant information, analyze the academic and broader outcomes of research, and gather insights to inform future strategy. Dimensions delivers an array of search and discovery, analytical, and research management tools, all in a single platform. Developed in collaboration with over 100 leading research organizations around the world, it brings together over 128 million publications, grants, policy, data and metrics for the first time, enabling users to explore over 4 billion connections between them.
The primary aim of DOAB (Directory of Open Access Books) is to increase discoverability of Open Access books. Metadata will be harvestable in order to maximize dissemination, visibility and impact. Aggregators can integrate the records in their commercial services and libraries can integrate the directory into their online catalogues, helping scholars and students to discover the books.
OAPEN is dedicated to open access, peer-reviewed books. OAPEN operates two platforms, the OAPEN Library (www.oapen.org), a central repository for hosting and disseminating OA books, and the Directory of Open Access Books (DOAB, www.doabooks.org), a discovery service for OA books.
OpenAIRE aims at promoting and implementing the directives of the European Commission (EC) and the European Research Council on the promotion and funding of science and research. OpenAIRE supports the Open Access Mandate and the Open Research Data Pilot developed as part of the Horizon 2020 projects.
An integrated information service combining reference databases, subscription management, online journals, books and linking services. Widely used by libraries, schools, government institutions, medical institutions, corporations and others.
SFX® link resolver gives patrons and librarians a wealth of features that optimize management of and access to resources. It provides patrons with a direct route to electronic full-text records through OpenURL linking, delivers alternative links for further resource discovery, access to journals, and more. Released in 2001 as the first OpenURL resolver, SFX is continuously enhanced to support the newest industry developments and meet the evolving needs of customers. The records include a mix of scholarly material – primarily articles and e-books – but also conference proceedings, newspaper articles, and more.
A non-profit, membership, computer library service and research organization dedicated to the public purposes of furthering access to the world's information and reducing information costs. More than 41,555 libraries in 112 countries and territories around the world use OCLC services to locate, acquire, catalogue, lend and preserve library materials.
The world’s largest collection of open access research papers. CORE's mission is to aggregate all open access research outputs from repositories and journals worldwide and make them available to the public. In this way CORE facilitates free unrestricted access to research for all.
Since 2002, Research4Life has provided researchers at more than 10,500 institutions in over 125 lower and middle-income countries with free or low-cost online access to up 151,000 leading journals and books in the fields of health, agriculture, environment, applied sciences and legal information. There are five programs through which users can access content: Research for Health (Hinari), Research in Agriculture (AGORA), Research in the Environment (OARE), Research for Development and Innovation (ARDI) and Research for Global Justice (GOALI).
Perlego is a digital online library focusing on the delivery of academic, professional and non-fiction eBooks. It is a subscription-based service that offers users unlimited access to these texts for the duration of their subscription, however IntechOpen content integrated on the platform will always be available for free. They have been billed as “the Spotify for Textbooks” by the Evening Standard. Perlego is based in London but is available to users worldwide.
MyScienceWork provides a suite of data-driven solutions for research institutions, scientific publishers and private-sector R&D companies. MyScienceWork's comprehensive database includes more than 90 million scientific publications and 12 million patents.
CNKI (China National Knowledge Infrastructure) is a key national information construction project under the lead of Tsinghua University, and supported by PRC Ministry of Education, PRC Ministry of Science, Propaganda Department of the Communist Party of China and PRC General Administration of Press and Publication. CNKI has built a comprehensive China Integrated Knowledge Resources System, including journals, doctoral dissertations, masters' theses, proceedings, newspapers, yearbooks, statistical yearbooks, ebooks, patents, standards and so on. CNKI keeps integrating new contents and developing new products in 2 aspects: full-text academic resources, software on digitization and knowledge management. Began with academic journals, CNKI has become the largest and mostly-used academic online library in China.
As one of the largest digital content platform in China,independently developed by CNPIEC, CNPeReading positions herself as “One Platform,Vast Content, Global Services”. Through their new cooperation model and service philosophy, CNPeReading provides integrated promotion and marketing solutionsfor upstream publishers, one-stop, triune, recommendation, online reading and management servicesfor downstream institutions & libraries.
ERIC (Education Resources Information Center), sponsored by the Institute of Education Sciences (IES) of the U.S. Department of Education, provides access to education literature to support the use of educational research and information to improve practice in learning, teaching, educational decision-making, and research. The ERIC website is available to the public for searching more than one million citations going back to 1966.
The ACM Digital Library is a research, discovery and networking platform containing: The Full-Text Collection of all ACM publications, including journals, conference proceedings, technical magazines, newsletters and books. A collection of curated and hosted full-text publications from select publishers.
BASE (Bielefeld Academic Search Engine) is one of the world's most voluminous search sengines especially for academic web resources, e.g. journal articles, preprints, digital collections, images / videos or research data. BASE facilitates effective and targeted searches and retrieves high quality, academically relevant results. Other than search engines like Google or Bing BASE searches the deep web as well. The sources which are included in BASE are intellectually selected (by people from the BASE team) and reviewed. That's why data garbage and spam do not occur.
Zentralblatt MATH (zbMATH) is the world’s most comprehensive and longest-running abstracting and reviewing service in pure and applied mathematics. It is edited by the European Mathematical Society (EMS), the Heidelberg Academy of Sciences and Humanities and FIZ Karlsruhe. zbMATH provides easy access to bibliographic data, reviews and abstracts from all areas of pure mathematics as well as applications, in particular to natural sciences, computer science, economics and engineering. It also covers history and philosophy of mathematics and university education. All entries are classified according to the Mathematics Subject Classification Scheme (MSC 2020) and are equipped with keywords in order to characterize their particular content.
IDEAS is the largest bibliographic database dedicated to Economics and available freely on the Internet. Based on RePEc, it indexes over 3,100,000 items of research, including over 2,900,000 that can be downloaded in full text. RePEc (Research Papers in Economics) is a large volunteer effort to enhance the free dissemination of research in Economics which includes bibliographic metadata from over 2,000 participating archives, including all the major publishers and research outlets. IDEAS is just one of several services that use RePEc data.
As the authoritative source for chemical names, structures and CAS Registry Numbers®, the CAS substance collection, CAS REGISTRY®, serves as a universal standard for chemists worldwide. Covering advances in chemistry and related sciences over the last 150 years, the CAS content collection empowers researchers, business leaders, and information professionals around the world with immediate access to the reliable information they need to fuel innovation.
BKCI is a part of Web of Science Core Collection (WoSCC) and the world’s leading citation index with multidisciplinary content from the top tier international and regional journals, conference proceedings, and books. The Book Citation Index includes over 104,500 editorially selected books, with 10,000 new books added each year. Containing more than 53.2 million cited references, coverage dates back from 2005 to present. The Book Citation Index is multidisciplinary, covering disciplines across the sciences, social sciences, and arts & humanities.
Produced by the Web Of Science group, BIOSIS Previews research database provides researchers with the most current sources of life sciences information, including journals, conferences, patents, books, review articles, and more. Researchers can also access multidisciplinary coverage via specialized indexing such as MeSH disease terms, CAS registry numbers, Sequence Databank Numbers and Major Concepts.
Produced by the Web Of Science group, Zoological Record is the world’s oldest continuing database of animal biology. It is considered the world’s leading taxonomic reference, and with coverage back to 1864, has long acted as the world’s unofficial register of animal names. The broad scope of coverage ranges from biodiversity and the environment to taxonomy and veterinary sciences.
Provides a simple way to search broadly for scholarly literature. Includes peer-reviewed papers, theses, books, abstracts and articles, from academic publishers, professsional societies, preprint repositories, universities and other scholarly organizations. Google Scholar sorts articles by weighing the full text of each article, the author, the publication in which the article appears, and how often the article has been cited in other scholarly literature, so that the most relevant results are returned on the first page.
Microsoft Academic is a project exploring how to assist human conducting scientific research by leveraging machine’s cognitive power in memory, computation, sensing, attention, and endurance. Re-launched in 2016, the tool features an entirely new data structure and search engine using semantic search technologies. The Academic Knowledge API offers information retrieval from the underlying database using REST endpoints for advanced research purposes.
The national library of the United Kingdom includes 150 million manuscripts, maps, newspapers, magazines, prints and drawings, music scores, and patents. Online catalogues, information and exhibitions can be found on its website. The library operates the world's largest document delivery service, providing millions of items a year to national and international customers.
The digital NSK portal is the central gathering place for the digital collections of the National and University Library (NSK) in Croatia. It was established in 2016 to provide access to the Library’s digital and digitized material collections regardless of storage location. The digital NSK portal enables a unified search of digitized material from the NSK Special Collections - books, visual material, maps and music material. From the end of 2019, all thematic portals are available independently: Digital Books, Digitized Manuscripts, Digitized Visual Materials, Digital Music Materials and Digitized Cartographic Materials (established in 2017). Currently available only in Croatian.
The official DOI (digital object identifier) link registration agency for scholarly and professional publications. Crossref operates a cross-publisher citation linking system that allows a researcher to click on a reference citation on one publisher’s platform and link directly to the cited content on another publisher’s platform, subject to the target publisher’s access control practices. This citation-linking network covers millions of articles and other content items from several hundred scholarly and professional publishers.
Dimensions is a next-generation linked research information system that makes it easier to find and access the most relevant information, analyze the academic and broader outcomes of research, and gather insights to inform future strategy. Dimensions delivers an array of search and discovery, analytical, and research management tools, all in a single platform. Developed in collaboration with over 100 leading research organizations around the world, it brings together over 128 million publications, grants, policy, data and metrics for the first time, enabling users to explore over 4 billion connections between them.
The primary aim of DOAB (Directory of Open Access Books) is to increase discoverability of Open Access books. Metadata will be harvestable in order to maximize dissemination, visibility and impact. Aggregators can integrate the records in their commercial services and libraries can integrate the directory into their online catalogues, helping scholars and students to discover the books.
OAPEN is dedicated to open access, peer-reviewed books. OAPEN operates two platforms, the OAPEN Library (www.oapen.org), a central repository for hosting and disseminating OA books, and the Directory of Open Access Books (DOAB, www.doabooks.org), a discovery service for OA books.
OpenAIRE aims at promoting and implementing the directives of the European Commission (EC) and the European Research Council on the promotion and funding of science and research. OpenAIRE supports the Open Access Mandate and the Open Research Data Pilot developed as part of the Horizon 2020 projects.
An integrated information service combining reference databases, subscription management, online journals, books and linking services. Widely used by libraries, schools, government institutions, medical institutions, corporations and others.
SFX® link resolver gives patrons and librarians a wealth of features that optimize management of and access to resources. It provides patrons with a direct route to electronic full-text records through OpenURL linking, delivers alternative links for further resource discovery, access to journals, and more. Released in 2001 as the first OpenURL resolver, SFX is continuously enhanced to support the newest industry developments and meet the evolving needs of customers. The records include a mix of scholarly material – primarily articles and e-books – but also conference proceedings, newspaper articles, and more.
A non-profit, membership, computer library service and research organization dedicated to the public purposes of furthering access to the world's information and reducing information costs. More than 41,555 libraries in 112 countries and territories around the world use OCLC services to locate, acquire, catalogue, lend and preserve library materials.
The world’s largest collection of open access research papers. CORE's mission is to aggregate all open access research outputs from repositories and journals worldwide and make them available to the public. In this way CORE facilitates free unrestricted access to research for all.
Since 2002, Research4Life has provided researchers at more than 10,500 institutions in over 125 lower and middle-income countries with free or low-cost online access to up 151,000 leading journals and books in the fields of health, agriculture, environment, applied sciences and legal information. There are five programs through which users can access content: Research for Health (Hinari), Research in Agriculture (AGORA), Research in the Environment (OARE), Research for Development and Innovation (ARDI) and Research for Global Justice (GOALI).
Perlego is a digital online library focusing on the delivery of academic, professional and non-fiction eBooks. It is a subscription-based service that offers users unlimited access to these texts for the duration of their subscription, however IntechOpen content integrated on the platform will always be available for free. They have been billed as “the Spotify for Textbooks” by the Evening Standard. Perlego is based in London but is available to users worldwide.
MyScienceWork provides a suite of data-driven solutions for research institutions, scientific publishers and private-sector R&D companies. MyScienceWork's comprehensive database includes more than 90 million scientific publications and 12 million patents.
CNKI (China National Knowledge Infrastructure) is a key national information construction project under the lead of Tsinghua University, and supported by PRC Ministry of Education, PRC Ministry of Science, Propaganda Department of the Communist Party of China and PRC General Administration of Press and Publication. CNKI has built a comprehensive China Integrated Knowledge Resources System, including journals, doctoral dissertations, masters' theses, proceedings, newspapers, yearbooks, statistical yearbooks, ebooks, patents, standards and so on. CNKI keeps integrating new contents and developing new products in 2 aspects: full-text academic resources, software on digitization and knowledge management. Began with academic journals, CNKI has become the largest and mostly-used academic online library in China.
As one of the largest digital content platform in China,independently developed by CNPIEC, CNPeReading positions herself as “One Platform,Vast Content, Global Services”. Through their new cooperation model and service philosophy, CNPeReading provides integrated promotion and marketing solutionsfor upstream publishers, one-stop, triune, recommendation, online reading and management servicesfor downstream institutions & libraries.
ERIC (Education Resources Information Center), sponsored by the Institute of Education Sciences (IES) of the U.S. Department of Education, provides access to education literature to support the use of educational research and information to improve practice in learning, teaching, educational decision-making, and research. The ERIC website is available to the public for searching more than one million citations going back to 1966.
The ACM Digital Library is a research, discovery and networking platform containing: The Full-Text Collection of all ACM publications, including journals, conference proceedings, technical magazines, newsletters and books. A collection of curated and hosted full-text publications from select publishers.
BASE (Bielefeld Academic Search Engine) is one of the world's most voluminous search sengines especially for academic web resources, e.g. journal articles, preprints, digital collections, images / videos or research data. BASE facilitates effective and targeted searches and retrieves high quality, academically relevant results. Other than search engines like Google or Bing BASE searches the deep web as well. The sources which are included in BASE are intellectually selected (by people from the BASE team) and reviewed. That's why data garbage and spam do not occur.
Zentralblatt MATH (zbMATH) is the world’s most comprehensive and longest-running abstracting and reviewing service in pure and applied mathematics. It is edited by the European Mathematical Society (EMS), the Heidelberg Academy of Sciences and Humanities and FIZ Karlsruhe. zbMATH provides easy access to bibliographic data, reviews and abstracts from all areas of pure mathematics as well as applications, in particular to natural sciences, computer science, economics and engineering. It also covers history and philosophy of mathematics and university education. All entries are classified according to the Mathematics Subject Classification Scheme (MSC 2020) and are equipped with keywords in order to characterize their particular content.
IDEAS is the largest bibliographic database dedicated to Economics and available freely on the Internet. Based on RePEc, it indexes over 3,100,000 items of research, including over 2,900,000 that can be downloaded in full text. RePEc (Research Papers in Economics) is a large volunteer effort to enhance the free dissemination of research in Economics which includes bibliographic metadata from over 2,000 participating archives, including all the major publishers and research outlets. IDEAS is just one of several services that use RePEc data.
As the authoritative source for chemical names, structures and CAS Registry Numbers®, the CAS substance collection, CAS REGISTRY®, serves as a universal standard for chemists worldwide. Covering advances in chemistry and related sciences over the last 150 years, the CAS content collection empowers researchers, business leaders, and information professionals around the world with immediate access to the reliable information they need to fuel innovation.
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Here, we discuss two mechanisms to explain the deviation of the lunar COM to the East from the mean direction to Earth. The first mechanism considers the secular evolution of the Moon’s orbit, using the effect of the preferred orientation of the satellite with synchronous rotation to the second (empty) orbital focus. It is established that only the scenario with an increase in the orbital eccentricity e leads to the required displacement of the lunar COM to the East. It is important that high-precision calculations confirm an increase e in our era. In order to fully explain the shift of the lunar COM to the East, a second mechanism was developed that takes into account the influence of tidal changes in the shape of the Moon at its gradual removal from the Earth. The second mechanism predicts that the elongation of the lunar figure in the early era was significant. As a result, it was found that the Moon could have been formed in the annular zone at a distance of 3–4 radii of the modern Earth.",book:{id:"8444",slug:"lunar-science",title:"Lunar Science",fullTitle:"Lunar Science"},signatures:"Boris P. Kondratyev",authors:[{id:"277909",title:"Prof.",name:"Boris",middleName:"Petrovich",surname:"Kondratyev",slug:"boris-kondratyev",fullName:"Boris Kondratyev"}]},{id:"68357",title:"Solar System Exploration Augmented by In Situ Resource Utilization: System Analyses, Vehicles, and Moon Bases for Saturn Exploration",slug:"solar-system-exploration-augmented-by-in-situ-resource-utilization-system-analyses-vehicles-and-moon",totalDownloads:824,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Human and robotic missions to Saturn are presented and analyzed with a range of propulsion options. Historical studies of space exploration, planetary spacecraft and astronomy, in situ resource utilization (ISRU), and industrialization all point to the vastness of natural resources in the solar system. Advanced propulsion is benefitted from these resources in many ways. While advanced propulsion systems were proposed in these historical studies, further investigation of nuclear options using high-power nuclear electric and nuclear pulse propulsion as well as advanced chemical propulsion can significantly enhance these scenarios. Updated analyses based on these historical visions are presented. At Saturn, nuclear pulse propulsion with alternate propellant feed systems and Saturn moon exploration with chemical propulsion and nuclear electric propulsion options are discussed. Issues with using in situ resource utilization on Saturn’s moons are discussed. At Saturn, the best locations for exploration and the use of the moons as central locations for Saturn moon exploration are assessed. Environmental issues on Titan’s surface may present extreme challenges for some ISRU processes. In-space bases for moon-orbiting propellant processing and ground-based processing will be assessed.",book:{id:"7338",slug:"planetology-future-explorations",title:"Planetology",fullTitle:"Planetology - Future Explorations"},signatures:"Bryan Palaszewski",authors:[{id:"279275",title:"M.Sc.",name:"Bryan",middleName:null,surname:"Palaszewski",slug:"bryan-palaszewski",fullName:"Bryan Palaszewski"}]},{id:"65534",title:"Solar System Exploration Augmented by In Situ Resource Utilization: Lunar Base Issues",slug:"solar-system-exploration-augmented-by-in-situ-resource-utilization-lunar-base-issues",totalDownloads:1108,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Creating a presence and an industrial capability on the Moon is essential for the development of humankind. There are many historical study results that have identified and quantified the lunar resources and analyzed the methods of obtaining and employing those resources. The idea of finding, obtaining, and using these materials is called in situ resource utilization (ISRU). The ISRU research and development efforts have led to new ideas in rocket propulsion. Applications in chemical propulsion, nuclear electric propulsion, and many other propulsion systems will be critical in making the initial lunar base and future lunar industries more sustainable and will lead to brilliant futures for humanity.",book:{id:"8444",slug:"lunar-science",title:"Lunar Science",fullTitle:"Lunar Science"},signatures:"Bryan Palaszewski",authors:[{id:"279275",title:"M.Sc.",name:"Bryan",middleName:null,surname:"Palaszewski",slug:"bryan-palaszewski",fullName:"Bryan Palaszewski"}]},{id:"32533",title:"Measuring the Isotopic Composition of Solar Wind Noble Gases",slug:"measuring-the-isotopic-composition-of-solar-wind-noble-gases",totalDownloads:2770,totalCrossrefCites:6,totalDimensionsCites:9,abstract:null,book:{id:"1617",slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"Alex Meshik, Charles Hohenberg, Olga Pravdivtseva and Donald Burnett",authors:[{id:"114740",title:"Prof.",name:"Alexander",middleName:null,surname:"Meshik",slug:"alexander-meshik",fullName:"Alexander Meshik"},{id:"115300",title:"Prof.",name:"Donald",middleName:null,surname:"Burnett",slug:"donald-burnett",fullName:"Donald Burnett"},{id:"115301",title:"Prof.",name:"Charles",middleName:null,surname:"Hohenberg",slug:"charles-hohenberg",fullName:"Charles Hohenberg"},{id:"115302",title:"Dr.",name:"Olga",middleName:null,surname:"Pravdivtseva",slug:"olga-pravdivtseva",fullName:"Olga Pravdivtseva"}]}],onlineFirstChaptersFilter:{topicId:"98",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82332",title:"Introductory Chapter: Access to Space, Access to the Moon: Two Sides of the Same Coin?",slug:"introductory-chapter-access-to-space-access-to-the-moon-two-sides-of-the-same-coin",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.105175",abstract:null,book:{id:"10955",title:"Lunar Science - Habitat and Humans",coverURL:"https://cdn.intechopen.com/books/images_new/10955.jpg"},signatures:"Yann-Henri Chemin"},{id:"81141",title:"Modeling Radiation Damage in Materials Relevant for Exploration and Settlement on the Moon",slug:"modeling-radiation-damage-in-materials-relevant-for-exploration-and-settlement-on-the-moon",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.102808",abstract:"Understanding the effect of radiation on materials is fundamental for space exploration. Energetic charged particles impacting materials create electronic excitations, atomic displacements, and nuclear fragmentation. Monte Carlo particle transport simulations are the most common approach for modeling radiation damage in materials. However, radiation damage is a multiscale problem, both in time and in length, an aspect treated by the Monte Carlo simulations only to a limited extent. In this chapter, after introducing the Monte Carlo particle transport method, we present a multiscale approach to study different stages of radiation damage which allows for the synergy between the electronic and nuclear effects induced in materials. We focus on cumulative displacement effects induced by radiation below the regime of hadronic interactions. We then discuss selected studies of radiation damage in materials of importance and potential use for the exploration and settlement on the Moon, ranging from semiconductors to alloys and from polymers to the natural regolith. Additionally, we overview some of the novel materials with outstanding properties, such as low weight, increased radiation resistance, and self-healing capabilities with a potential to reduce mission costs and improve prospects for extended human exploration of extraterrestrial bodies.",book:{id:"10955",title:"Lunar Science - Habitat and Humans",coverURL:"https://cdn.intechopen.com/books/images_new/10955.jpg"},signatures:"Natalia E. Koval, Bin Gu, Daniel Muñoz-Santiburcio and Fabiana Da Pieve"},{id:"80241",title:"The Evolution of the Moon’s Orbit Over 100 Million Years and Prospects for the Research in the Moon",slug:"the-evolution-of-the-moon-s-orbit-over-100-million-years-and-prospects-for-the-research-in-the-moon",totalDownloads:57,totalDimensionsCites:0,doi:"10.5772/intechopen.102392",abstract:"As a result of solving the problem of interaction of Solar-system bodies, data on the evolution of the Moon’s orbit were obtained. These data were used as the basis for the development of a mathematical model for the Moon representing its motion over an interval of 100 million years. A program of exploration of the Moon with the aim of creating a permanent base on it is outlined. Such a base is intended for exploring the Earth, the Sun, and outer space.",book:{id:"10955",title:"Lunar Science - Habitat and Humans",coverURL:"https://cdn.intechopen.com/books/images_new/10955.jpg"},signatures:"Joseph J. Smulsky"},{id:"80217",title:"Educational and Scientific Analog Space Missions",slug:"educational-and-scientific-analog-space-missions",totalDownloads:78,totalDimensionsCites:0,doi:"10.5772/intechopen.101392",abstract:"Analog space missions in Poland include international scientific, technological, and business projects designed and realized by a private research company Analog Astronaut Training Center Ltd. (AATC) devoted to the future Moon and Mars exploration. Growing experience in educational aspect of the training as well as continuous development of the habitat and its professional space science laboratory equipment correspond to increased interest of educational organizations, universities, and individual students. We serve unique practical platform for space engineering, space master, and even space doctoral theses. In addition to a wide range of training courses offered for future astronauts, for example, diving, skydiving, rocket workshops, and stratospheric missions, AATC provides a private laboratory to simulate the space environment. It carries out scientific experiments focused on biology and space medicine, as well as addressing several multidisciplinary issues related to the Moon and Mars exploration, including space mining. The main goal of each our analog simulation is to get publishable results, what means that our analog astronauts obtain not only certification of completion of the training but also ability to continue studies and to perform it individually. This chapter summarizes methodology used by us, didactic tools, and obtained results for both educational and scientific analog simulations.",book:{id:"10955",title:"Lunar Science - Habitat and Humans",coverURL:"https://cdn.intechopen.com/books/images_new/10955.jpg"},signatures:"Agata Maria Kołodziejczyk and M. Harasymczuk"},{id:"79544",title:"Regolith and Radiation: The Cosmic Battle",slug:"regolith-and-radiation-the-cosmic-battle",totalDownloads:113,totalDimensionsCites:0,doi:"10.5772/intechopen.101437",abstract:"This chapter discusses regolith utilization in habitat construction mainly from the point of view of radiation protection of humans on missions of long duration. It also considers other key properties such as structural robustness, thermal insulation, and micrometeoroid protection that all have to be considered in parallel when proposing regolith-based solutions. The biological hazards of radiation exposure on the Moon are presented and put in the context of lunar exploration-type missions and current astronaut career dose limits. These factors guide the research in radiation protection done with lunar regolith simulants, which are used in research and development activities on Earth due to the reduced accessibility of returned lunar samples. The ways in which regolith can be used in construction influence its protective properties. Areal density, which plays a key role in the radiation shielding capacity of a given material, can be optimized through different regolith processing techniques. At the same time, density will also affect other important properties of the construction, e.g. thermal insulation. A comprehensive picture of regolith utilization in habitat walls is drawn for the reader to understand the main aspects that are considered in habitat design and construction while maintaining the main focus on radiation protection.",book:{id:"10955",title:"Lunar Science - Habitat and Humans",coverURL:"https://cdn.intechopen.com/books/images_new/10955.jpg"},signatures:"Yulia Akisheva, Yves Gourinat, Nicolas Foray and Aidan Cowley"}],onlineFirstChaptersTotal:5},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"June 28th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. Her publications cover a wide range of scientific and technical research publications that include edited books, book chapters, refereed journals, refereed conference papers and reports for local, state and federal government clients. She has also produced podcasts for various organisations and participated in media interviews. She has received state, national and international funding worth over USD $25 million. Usha has been awarded the Quarterly Franklin Membership by London Journals Press (UK). Her biography has been included in the Marquis Who's Who in the World® 2018, 2016 (33rd Edition), along with approximately 55,000 of the most accomplished men and women from around the world, including luminaries as U.N. Secretary-General Ban Ki-moon. In 2017, Usha was awarded the Marquis Who’s Who Lifetime Achiever Award.",institutionString:null,institution:{name:"RMIT University",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo is a Professor at the Department of Engineering of the University of Naples “Parthenope”, Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino. Her research interests include multi-criteria decision analysis, industrial plant, logistics, manufacturing and safety. She serves as an Associate Editor for the International Journal of the Analytic Hierarchy Process. She is a member of AHP Academy and a member of several editorial boards. She has over 160 Scientific Publications in International Journals and Conferences and she is the author of 5 books on Innovation and Decision Making in Industrial Applications and Engineering.",institutionString:null,institution:{name:"Parthenope University of Naples",institutionURL:null,country:{name:"Italy"}}},editorTwo:null,editorThree:null},{id:"92",title:"Health and Wellbeing",coverUrl:"https://cdn.intechopen.com/series_topics/covers/92.jpg",isOpenForSubmission:!0,editor:{id:"348225",title:"Prof.",name:"Ann",middleName:null,surname:"Hemingway",slug:"ann-hemingway",fullName:"Ann Hemingway",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035LZFoQAO/Profile_Picture_2022-04-11T14:55:40.jpg",biography:"Professor Hemingway is a public health researcher, Bournemouth University, undertaking international and UK research focused on reducing inequalities in health outcomes for marginalised and excluded populations and more recently focused on equine assisted interventions.",institutionString:null,institution:{name:"Bournemouth University",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"93",title:"Inclusivity and Social Equity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/93.jpg",isOpenForSubmission:!0,editor:{id:"210060",title:"Prof. Dr.",name:"Ebba",middleName:null,surname:"Ossiannilsson",slug:"ebba-ossiannilsson",fullName:"Ebba Ossiannilsson",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6LkBQAU/Profile_Picture_2022-02-28T13:31:48.png",biography:"Professor Dr. Ebba Ossiannilsson is an independent researcher, expert, consultant, quality auditor and influencer in the fields of open, flexible online and distance learning (OFDL) and the 'new normal'. Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. She holds a Ph.D. from the University of Oulu, Finland.",institutionString:"Swedish Association for Distance Education, Sweden",institution:null},editorTwo:null,editorThree:null},{id:"94",title:"Climate Change and Environmental Sustainability",coverUrl:"https://cdn.intechopen.com/series_topics/covers/94.jpg",isOpenForSubmission:!0,editor:{id:"61855",title:"Dr.",name:"Yixin",middleName:null,surname:"Zhang",slug:"yixin-zhang",fullName:"Yixin Zhang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYWJgQAO/Profile_Picture_2022-06-09T11:36:35.jpg",biography:"Professor Yixin Zhang is an aquatic ecologist with over 30 years of research and teaching experience in three continents (Asia, Europe, and North America) in Stream Ecology, Riparian Ecology, Urban Ecology, and Ecosystem Restoration and Aquatic Conservation, Human-Nature Interactions and Sustainability, Urbanization Impact on Aquatic Ecosystems. He got his Ph.D. in Animal Ecology at Umeå University in Sweden in 1998. He conducted postdoc research in stream ecology at the University of California at Santa Barbara in the USA. After that, he was a postdoc research fellow at the University of British Columbia in Canada to do research on large-scale stream experimental manipulation and watershed ecological survey in temperate rainforests of BC. He was a faculty member at the University of Hong Kong to run ecological research projects on aquatic insects, fishes, and newts in Tropical Asian streams. He also conducted research in streams, rivers, and caves in Texas, USA, to study the ecology of macroinvertebrates, big-claw river shrimp, fish, turtles, and bats. 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Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}}]}},subseries:{item:{id:"2",type:"subseries",title:"Prosthodontics and Implant Dentistry",keywords:"Osseointegration, Hard tissue, Peri-implant soft tissue, Restorative materials, Prosthesis design, Prosthesis, Patient satisfaction, Rehabilitation",scope:"
\r\n\tThe success of dental implant treatment is not solely dependent on the osseointegration around the implant. Aside from the criteria used to describe the hard tissue response at the implant level, the success criteria in implant dentistry include three additional aspects: peri-implant soft tissue, prosthesis, and patient’s satisfaction.
\r\n
\r\n\tThe Prosthodontics and Implant Dentistry topic will provide readers with up-to-date resources on the prosthodontics factors such as aesthetics, restorative materials, the design of prosthesis, case selection, occlusion, oral rehabilitation, among others, all of which play an important role in determining the success of a well osseointegrated implant. With the help of digital dental technology, these can now be accomplished more predictably.
\r\n
\r\n\tThe end goal of prosthesis is always considered when planning successful implant placement. The readers in this field will be able to learn more about taking a holistic approach when treating their dental implant cases.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/2.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11398,editor:{id:"179568",title:"Associate Prof.",name:"Wen Lin",middleName:null,surname:"Chai",slug:"wen-lin-chai",fullName:"Wen Lin Chai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHGAQA4/Profile_Picture_2022-05-23T14:31:12.png",biography:"Professor Dr. Chai Wen Lin is currently a lecturer at the Department of Restorative Dentistry, Faculty of Dentistry of the University of Malaya. She obtained a Master of Dental Science in 2006 and a Ph.D. in 2011. Her Ph.D. research work on the soft tissue-implant interface at the University of Sheffield has yielded several important publications in the key implant journals. She was awarded an Excellent Exchange Award by the University of Sheffield which gave her the opportunity to work at the famous Faculty of Dentistry of the University of Gothenburg, Sweden, under the tutelage of Prof. Peter Thomsen. In 2016, she was appointed as a visiting scholar at UCLA, USA, with attachment in Hospital Dentistry, and involvement in research work related to zirconia implant. In 2016, her contribution to dentistry was recognized by the Royal College of Surgeon of Edinburgh with her being awarded a Fellowship in Dental Surgery. She has authored numerous papers published both in local and international journals. She was the Editor of the Malaysian Dental Journal for several years. Her main research interests are implant-soft tissue interface, zirconia implant, photofunctionalization, 3D-oral mucosal model and pulpal regeneration.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorTwo:{id:"479686",title:"Dr.",name:"Ghee Seong",middleName:null,surname:"Lim",slug:"ghee-seong-lim",fullName:"Ghee Seong Lim",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003ScjLZQAZ/Profile_Picture_2022-06-08T14:17:06.png",biography:"Assoc. Prof Dr. Lim Ghee Seong graduated with a Bachelor of Dental Surgery from University of Malaya, Kuala Lumpur in 2008. He then pursued his Master in Clinical Dentistry, specializing in Restorative Dentistry at Newcastle University, Newcastle, UK, where he graduated with distinction. He has also been awarded the International Training Fellowship (Restorative Dentistry) from the Royal College of Surgeons. His passion for teaching then led him to join the faculty of dentistry at University Malaya and he has since became a valuable lecturer and clinical specialist in the Department of Restorative Dentistry. He is currently the removable prosthodontic undergraduate year 3 coordinator, head of the undergraduate module on occlusion and a member of the multidisciplinary team for the TMD clinic. He has previous membership in the British Society for Restorative Dentistry, the Malaysian Association of Aesthetic Dentistry and he is currently a lifetime member of the Malaysian Association for Prosthodontics. Currently, he is also the examiner for the Restorative Specialty Membership Examinations, Royal College of Surgeons, England. He has authored and co-authored handful of both local and international journal articles. His main interest is in prosthodontics, dental material, TMD and regenerative dentistry.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorThree:null,series:{id:"3",title:"Dentistry",doi:"10.5772/intechopen.71199",issn:"2631-6218"},editorialBoard:null},onlineFirstChapters:{paginationCount:1,paginationItems:[{id:"82124",title:"Assessment of Diversity, Growth Characteristics and Aboveground Biomass of Tree Species in Selected Urban Green Areas of Osogbo, Osun State",doi:"10.5772/intechopen.104982",signatures:"Omolara Aremu, Olusola O. 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