bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncogenic Transcription Factors: Target Genes
Authors: Paccez Juliano D , Zerbini Luiz F
Published: September 2017

Transcription factors (TFs) are a class of proteins that are essential for the regulation of gene expression and for the control of protein expression in normal physiological conditions. On the other hand, de‐regulated expression of TFs plays a critical role in different diseases, including cancer. An elevated percentage of oncogenes and tumour suppressor genes encode TFs. In fact, the majority of oncogenic signalling pathways converge on sets of TFs that ultimately control gene expression patterns, resulting in aggressive phenotype, disease progression and increased resistance to drug therapy. Since the expression and activities of these TFs are tightly regulated, they represent a highly desirable entry point for the development and validation of new therapeutic drugs against cancer.

Key Concepts

TFs are essential for controlling gene expression during normal physiological conditions and disease.

High proportion of oncogenes and tumour suppressors encode TFs.

Hallmarks of cancer, such as control of cell cycle, protection from apoptosis, induction of angiogenesis, proliferation, migration and invasion are controlled by gene expression patterns and signalling pathways that are regulated by TFs.

Upregulation of TFs is related to increased resistance to drugs used in cancer treatment.

TFs may represent an important target for the treatment of several types of cancers.
Oncogenic Kinases in Cancer
Authors: Tsintarakis Antonis , Zafiropoulos Alexandros
Published: September 2017

Oncogenesis involves the generation and transmission of signals that result in de‐regulation of cell proliferation, inhibition of apoptosis and morphological changes. Transmembrane or cytoplasmic tyrosine and serine/threonine kinases participate both directly and indirectly in cell transformation and tumorigenesis. Such kinases transfer phosphates to tyrosine residues or serine and threonine residues of other kinases or proteins that participate in various signalling pathways in the cell. Up to 20% of the 32 000 human genes sequenced by the Human Genome Project encode proteins that are involved in cellular signalling, and among these, more than 520 are protein kinases. Many of these kinases have been implicated in tumorigenesis involving transmembrane, cytoplasmic and nuclear signalling, cell‐cycle control and regulation of apoptosis. Screening and targeting oncogenic kinases are becoming rapidly part of a personalised strategy for the treatment of cancer.

Key Concepts

Oncogenic receptor kinases.

Cytoplasmic and nuclear signalling oncogenic kinases.

Oncogenic kinases involved in cell‐cycle control.

Kinases contribute to oncogenesis by regulating apoptosis.

Targeting kinases is a viable strategy for cancer therapy.
Male Sex Determination: Genetics
Authors: Ostrer Harry
Published: September 2017

The basic dichotomy of life is sexual. Sex is important not only for reproductive role but also for physical attributes, personal identity and disease susceptibility. The determination of sex, that is, whether one is male or female, is controlled genetically. The key genetic event in male sex determination is transmission of a Y chromosome from father to offspring. In the developing gonad, the sex‐determining gene on this chromosome,
SRY
, triggers the expression of a repertoire of other genes. These genes cause the gonad to develop as a testis. Hormones secreted by the developing testis influence the differentiation of male internal and external genitalia and other somatic features.

Key Concepts

Testes are important not only for mediating male reproduction but also for producing hormones that masculinise other organs, including internal and external genitalia.

Male and female embryos share a common gonadal ridge that has the potential to differentiate either as a testis or as an ovary.

The
SRY
gene acts as the master switch for testis differentiation.

Once a testis has developed, the
DRMT1
gene acts to prevent the testis from transdifferentiating into an ovary.

The other reproductive organs are derived from a common set of internal and external genital structures.

The differentiation of the prostate, seminal vesicles and epididymis from the Wolffian ducts is mediated by the hormone testosterone.

The formation of the penis and scrotum is mediated by the hormone dihydrotestosterone.

Disorders of sex development (DSDs) arise when mutated genes prevent the normal gonadal and genital development.

Germ cell tumours are common among individuals with 46,XY DSDs.

Individuals who develop testicular cancer may have a mild form of DSDs.
Molecular Genetics of Familial Mediterranean Fever
Authors: Manukyan Gayane , Aminov Rustam , Khachatryan Zaruhi , Yepiskoposyan Levon
Published: September 2017

Familial Mediterranean fever (FMF) is an autoinflammatory disease, which is prevalent in populations of the Mediterranean ancestry. Traditionally, FMF was considered as an autosomal recessive genetic disorder; however, several studies showed that a heterozygote state might also result in disease. Mutations responsible for the disease are located in theMEFVgene encoding a protein called pyrin/marenostrin/TRIM20. FMF is characterised by seemingly unprovoked periodic activation of innate immunity, with fever and serosal inflammation. Among more than 300 mutations in theMEFVgene, five mutations (M694V, V726A, M680I, M694I and E148Q) are the most common in classically affected populations (Armenians, Arabs, Jews and Turks). Disease severity depends on specificMEFVmutations and also on a number of other genetic or environmental modifiers. Certain evolutionary aspects of the disease were intensively investigated including the origin of majorMEFVmutations, structure‐and‐function and evolution of pyrin and potential selective advantage of heterozygous carriage.

Key Concepts

Familial Mediterranean fever (FMF, MIM 249100) is an autoinflammatory genetic disease, and it is prevalent in populations of Mediterranean origin.

The highest incidence of the disorder is documented in four ethnic groups Armenians, Arabs, Jews and Turks, which are considered as ‘classically affected populations’.

Clinical manifestations of FMF include periodic occurrence of fever and inflammation in the peritoneum, synovium or pleura. Renal amyloidosis is the most serious complication of the disease.

The disease is caused by mutations in theMEFV(MEditerraneanFeVer) gene, which is composed of 10 exons and located on chromosome 16 (16p13.3).

MEFVencodes a protein named pyrin or marenostrin or TRIM20, which is a key component of innate immunity.

Presently, more than 300MEFVmutations have been identified. Five mutations (M694V, V726A, M680I and M694I in exon 10 and E148Q in exon 2) are most frequent in classically affected populations.

Severity of FMF depends on specificMEFVmutations as well as on a number of other genetic and environmental modifiers.

The most commonMEFVmutations display a relatively ancient origin, with the subsequent penetration to other populations following migratory and interbreeding processes.

The high carriage rate ofMEFVmutations in classically affected populations may be explained by a potential selection for the heterozygote genotype, which may have conferred some sort of selective advantage for populations in the area but currently there is no proof for this.
Hsp60andHsp70Chaperones: Guardians of Mitochondrial Proteostasis
Authors: Jebara Fady , Weiss Celeste , Azem Abdussalam
Published: September 2017

Most protein molecules are dynamic and marginally stable and therefore constantly at risk for acquiring misfolded conformations. Constant surveillance is required to preserve proteostasis. Maintenance of the mitochondrial proteome relies on a diverse set of molecular chaperones and proteases, which together form an interconnected network. An imbalance in mitochondrial proteostasis will result in the accumulation of damaged polypeptides, potentially leading to collapse of mitochondrial integrity. The Hsp60 and Hsp70 chaperone systems play a central role in the folding of matrix‐localised proteins. In this article, we summarise major aspects of the molecular function of these nano‐machines and their interplay with other matrix chaperones and proteases.

Key Concepts

Hsp60 and Hsp70 chaperone systems play a crucial role in the maintenance of mitochondrial proteostasis.

Hsp60 and Hsp70 carry out various functions via interaction with a large number of extra‐mitochondrial complexes.

In addition to its critical role in protein import into the mitochondria, Hsp70 plays an important role in protein folding, disaggregation and degradation in the mitochondrial matrix.

Hsp60 is an essential protein that plays a central role in protein‐folding within the mitochondrial matrix.

The Hsp60 reaction cycle differs from that of GroEL in its incorporation of a single‐ring intermediate in the reaction cycle.
The Genetics of Facial Morphology
Authors: Cole Joanne B , Spritz Richard A
Published: September 2017

Human facial morphology broadly encompasses several distinct facial structures that alone and together contain enormous variations which contribute to our physical identities as both individuals and members of families and populations. The human face comprises an assemblage of multifactorial complex traits, with clear genetic components and known environmental factors playing key roles in its development and maturation throughout life. Current understanding of the genes and pathways pertaining to normal facial development and morphology comes largely from research on craniofacial malformations in both humans and animal models. Recent advances in methodology for deriving accurate and precise facial traits have allowed for several large genomic studies that have provided new insights into the heritability and genes involved in normal facial variation. Continued research on the genetics of facial morphology will improve quantitative diagnosis, treatment and management of craniofacial syndromes, perhaps enabling us to one day model the human face from deoxyribonucleic acid (DNA).

Key Concepts

Understanding the genetics of normal human facial morphology and development provides insights relevant to the fields of both medicine and forensics.

The known genes and signalling pathways that are involved in craniofacial development have mostly been identified through studies of craniofacial malformations and typically relate to the embryonic development of cranial neural crest cells.

Quantifying normal human facial traits that are both accurate and precise is exceedingly important to understanding the genetic architecture of those traits.

There exist numerous diverse quantitation methods for studying both the underlying facial skeleton and the overlying soft facial tissues.

Overall, the human face is highly heritable. However, large differences in the study design and population attributes pertaining to age, ethnicity and environmental background have led to limited consistency in heritability estimates and genetic conclusions.

Five genome‐wide association studies to date have identified largely non‐overlapping genome‐wide significant loci for normal facial morphology, with some of these located in or near genes previously implicated in rare craniofacial syndromes and/or facial development.

Animal studies of facial development are a powerful tool both for identifying candidate genes and for functional analyses of candidate genes from human studies.
Evolution of Culture
Authors: Bradie Michael
Published: September 2017

Theories of cultural evolution are attempts to model cultural change as an evolutionary process. Drawing inspiration from Darwin's theory of evolution, there are four major contemporary approaches to the evolution of culture which differ from one another in the extent to which they see the engine of cultural evolution as analogous to Darwinian natural selection. One of the major motivations for ‘Darwinising’ culture is to incorporate the study of human behaviour into the modern synthesis and to provide a framework for the unification of the social sciences. It remains an open question how successful this project can be.

Key Concepts

The concept of culture is a social construction.

Theories of the emergence of culture as a biological adaptation need to be distinguished from theories of the transmission of culture.

Constructed cultural niches are an important environmental influence on genetic and cultural evolution.

The integration of the social sciences into the Modern Synthesis has been only partially successful.

Theories of cultural evolution are attempts to model change as an evolutionary process.
Recent Advances in Acid–Base and Solvation Properties of Metal Phenolates
Authors: Bastos Erick L. , Machado Caroline O.
Published: September 2017

This chapter is an update of a recent review on the acid–base chemistry and solvation properties of metal phenolates. After a brief introduction on the physicochemical properties of metal phenolates, the interaction between phenolate ligands and metal Lewis acids is discussed. Examples of solvent effects on the acid–base properties, structure, and chemical reactivity are presented. Furthermore, the interaction of multidentate phenolic ligands and metal cations is highlighted because of their relevance in transition‐metal coordination chemistry, catalyst development, metalloenzyme mimicry, cytotoxicity, and magnetic properties.
Asymmetric Synthesis of Quaternary Stereocenters via Metal Enolates
Authors: Korch Katerina M. , Loskot Steven A. , Stoltz Brian M.
Published: September 2017

The strategy of using chiral metal enolate intermediates in a diverse variety of asymmetric transformations has allowed the generation of quaternary stereocenter‐bearing products that are otherwise difficult to access. Many classic transformations including aldol, Mannich, conjugate addition, alkylation, and pericyclic‐type reactions, as well as allylic alkylation and α‐arylation/alkenylation, have been adapted to proceed through chiral metal enolate intermediates, allowing the asymmetric synthesis of many complex products in both an intermolecular and intramolecular manner. These transformations have proven useful in the synthesis of natural products and may also be applied to the synthesis of novel pharmaceuticals and other compounds of interest in the future. This review includes work done up to and including the year 2014.
Base‐Free Selective O‐Arylation and Sequential [3,3]‐Rearrangement of Amidoximes with Diaryliodonium Salts: Synthesis of 2‐Substituted Benzoxazoles
Authors: Shi Wei‐Min , Li Xiao‐Hua , Liang Cui , Mo Dong‐Liang
Published: September 2017

A variety of functionalized 2‐substituted benzoxazoles can be prepared in good yields from amidoximes and diaryliodonium salts by selective O‐arylation and sequential [3,3]‐rearrangement under metal‐free conditions. O‐arylation of amidoximes was promoted by 3 Å molecule sieves in the absence of a base and a sequential TFA‐mediated [3,3]‐rearrangement was used to synthesize 2‐substituted benzoxazoles. Both of the O‐aryl products and rearrangement products were compatible with a broad range of sensitive functional groups such as ester, aldehyde, nitro, vinyl, amine, and amide groups in addition to halides. A bidentate N‐ligand with double benzoxazoles was prepared at gram‐scale in two steps.

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Clinical implication of surgical resection for recurrent biliary tract cancer: Does it work or not?
Authors: Miyazaki Masaru , Shimizu Hiroaki , Yoshitomi Hideyuki , Kato Atsushi , Furukawa Katsunori , Takayashiki Tsukasa , Kuboki Satoshi , Takano Shigetsugu , Ohtsuka Masayuki
Published: September 2017

Although recent advances in imaging diagnosis, surgical techniques, and perioperative management can result in increased resectability and improved surgical outcomes, most resected patients still develop cancer recurrence. If patients develop cancer recurrence, their prognosis is very ominous. However, there have been some recent reports to show promising outcomes by aggressive surgical strategy in selected patients who developed cancer recurrence. Because there are various surgical procedures being selected at initial surgery in patients with biliary tract cancers, recurrent patterns after resection are very variable in each patient. However, surgical procedures might usually be very complicated and difficult if re‐surgical resection is considered in patients with recurrent biliary tract cancer, Therefore, surgical re‐resection could bring about high surgical morbidity and mortality rates in most previously reported series. Although re‐surgical resection might offer a chance of favorable outcome in selected patients with biliary tract cancers, these aggressive surgical approaches should be carried out in strictly selected patients by expert surgeons at high‐volume centers.
Neighborhood Predictors of Intimate Partner Violence: A Theory‐Informed Analysis Using Hierarchical Linear Modeling
Authors: Voith Laura A. , Brondino Michael J.
Published: September 2017

Highlights

Understanding men's experiences related to IPV perpetration has promise to improve IPV intervention.

Combining prevailing theories provides a promising framework for ecological IPV research.

Female‐to‐male partner violence puts women at significantly greater risk for IPV victimization.

Neighborhoods of higher concentrated disadvantage enhance women's risk of IPV victimization.
Solid‐State Thermochromic Luminescence through Twisted Intramolecular Charge Transfer and Excimer Formation of a Carborane−Pyrene Dyad with an Ethynyl Spacer
Authors: Nishino Kenta , Yamamoto Hideki , Tanaka Kazuo , Chujo Yoshiki
Published: September 2017

The pyrene‐tethered carborane CBEP, which exhibited rapid and dramatic luminochromism, was synthesized. Based on optical measurements, we found that CBEP exhibited orange emission at room temperature, which was caused by intramolecular charge transfer in the solid state, and green excimer emission at 77 K. We proposed that excimer formation could be encouraged by introducing a small amount of steric hindrance with an ethynyl spacer group. We found that o‐carborane could suppress aggregation‐caused quenching without the inhibition of excimer formation because of this steric hindrance.
Silver Thiolate Nano‐sized Molecular Clusters and Their Supramolecular Covalent Frameworks: An Approach Toward Pre‐templated Synthesis
Authors: Chen Zi‐Yi , Tam Dennis Y. S. , Zhang Leon Li‐Min , Mak Thomas C. W.
Published: September 2017

A series of seven new complexes including silver‐thiolate molecular clusters and their covalent supramolecular frameworks have been assembled from the silver carbide precursor Ag2C2 using a C22− pre‐templated approach. Herein, two prototype clusters Ag14(SR)6 and CO3@Agm(SR)10 (R=isopropyl, cyclohexyl or tert‐butyl; m=18 or 20) are employed to construct cluster‐based metal–organic frameworks of different dimensions. In particular, both new ellipsoidal tetradecanuclear molecular cluster compounds, namely, Ag14(S‐iPr)6(CO2CF3)8⋅(DMSO)6 (two polymorphic forms 1, 2) and [Ag14(S‐Cy)6(CO2CF3)8(DMSO)4]⋅(DMSO)3 (3), and a cluster‐based metal–organic framework {Ag3[Ag14(S‐iPr)6(CO2CF3)11(H2O)3CH3OH]⋅(H2O)2.5}n (4) have been isolated and structurally characterized. Furthermore, increased acidity of the reaction mixture afforded three carboxylate‐templated cluster based frameworks: a chain‐like compound {[HN(CH3)2CO]⋅[CO3@Ag18(S‐tBu)10(NO3)7(DMF)4]⋅DMF}n (5), as well as two layer‐type compounds, namely, {Ag[CO3@Ag20(S‐iPr)10(CO2CF3)9(CO2HCF3)(CH3OH)2]}n (6) and {Ag2[CO3@Ag20(S‐Cy)10(CO2CF3)10(CO2HCF3)2(H2O)2]⋅(H2O)3⋅(CH3OH)3}n (7) exhibiting sql‐net characteristics. It is demonstrated that the C≡C2− pre‐template, which draws several Ag+ ions together to form the C2@Agn entity, plays an indispensable role in the syntheses of these compounds. Furthermore, covalent linkage of these nano‐sized silver thiolate clusters from one‐ to three‐dimensions revealed enormous potential for the future development of silver cluster‐based frameworks.
Design of Optimal Petri Net Supervisors for Flexible Manufacturing Systems via Weighted Inhibitor Arcs
Authors: Cong XuYa , Gu Chao , Uzam Murat , Chen YuFeng , Al‐Ahmari Abdulrahman M. , Wu NaiQi , Zhou MengChu , Li ZhiWu
Published: September 2017

This paper develops an approach to the design of an optimal Petri net supervisor that enforces liveness to flexible manufacturing systems. The supervisor contains a set of observer places with weighted inhibitor arcs. An observer place with a weighted inhibitor arc is used to forbid a net from yielding an illegal marking by inhibiting the firing of a transition at a marking while ensuring that all legal markings are preserved. A marking reduction technique is presented to decrease the number of considered markings, which can dramatically lower the computational burden of the proposed approach. An integer linear program is presented to simplify the supervisory structure by minimizing the number of observer places. Finally, several examples are used to shed light on the proposed approach which can lead to an optimal supervisor for the net models that cannot be optimally controlled via pure Petri net supervisors.
Complete remission of chemo‐refractory multiple‐metastatic upper tract urothelial carcinoma by autologous formalin‐fixed tumor vaccine
Authors: Miyoshi Tatsu , Kashiwabara Takeshi , Asahi Atsuko , Kataoka Tatsuji , Maruyama Takashi , Okada Rika , Uemae Yoji , Ohno Tadao
Published: September 2017

Key Clinical Message

A patient with chemo‐refractory multiple‐metastatic upper tract urothelial carcinoma (UTUC) treated by monotherapy with autologous formalin‐fixed tumor vaccine (AFTV) resulted in complete remission of the lung and para‐aortic lymph node metastases (ongoing >3 years after AFTV). The tumor was immunohistologically negative for PD‐L1. AFTV will be an attractive treatment option.
Contraction of π‐Conjugated Rings upon Oxidation from Cyclooctatetraene to Benzene via the Tropylium Cation
Authors: Tamoto Akira , Aratani Naoki , Yamada Hiroko
Published: September 2017

We have serendipitously discovered a unique transformation of a cyclooctatetraene derivative 1 into a cycloheptatriene spirolactone 3 upon oxidation, which is the first such transformation reported in 60 years. Product 3 could be reversibly interconverted into the aromatic tropylium cation 3H+ by acid/base treatment, which was accompanied by drastic spectroscopic changes. The resultant cycloheptatriene could be further converted into benzene upon oxidation. We characterized all the key structures by X‐ray studies. Eventually, the π‐conjugated ring size shrinks from 8 to 7, then finally to 6 upon oxidation, in the direction of the stronger aromatization.
Modeling Tolerance Development for the Effect on Heart Rate of the Selective S1P1 Receptor Modulator Ponesimod
Authors: Lott Dominik , Lehr Thorsten , Dingemanse Jasper , Krause Andreas
Published: September 2017

Ponesimod is a selective sphingosine‐1‐phosphate‐1 (S1P1) receptor modulator currently under investigation for the treatment of multiple sclerosis. S1P receptor modulators reduce heart rate following treatment initiation. This effect disappears with repeated dosing, enabling development of innovative uptitration regimens to optimize patient safety. There are currently no published pharmacokinetic/pharmacodynamic models describing the heart rate reduction of S1P receptor modulators in humans. The model developed here provides quantification of this effect for ponesimod. A direct‐effect Imax model with estimated maximum reduction of 45%, tolerance development, and circadian variation best described this effect. The pooled data from nine clinical studies enabled characterization of interindividual variability. The model was used to simulate different treatment regimens to compare the effect of high initial doses vs. gradual uptitration with respect to the occurrence of bradycardia. The results indicate a better safety profile when using gradual uptitration. The model allows studying dosing regimens not clinically tested in silico.
Clopidogrel in Critically Ill Patients
Authors: Schoergenhofer Christian , Hobl Eva‐Luise , Schellongowski Peter , Heinz Gottfried , Speidl Walter S. , Siller‐Matula Jolanta M. , Schmid Monika , Sunder‐Plaßmann Raute , Stimpfl Thomas , Hackl Matthias , Jilma Bernd
Published: September 2017

Only limited data are available regarding the treatment of critically ill patients with clopidogrel. This trial investigated the effects and the drug concentrations of the cytochrome P450 (CYP450) activated prodrug clopidogrel (n = 43) and the half‐life of the similarly metabolized pantoprazole (n = 16) in critically ill patients. ADP‐induced aggregometry in whole blood classified 74% (95% confidence intervals 59–87%) of critically ill patients as poor responders (n = 43), and 65% (49–79%) responded poorly according to the vasodilator‐stimulated phosphoprotein phosphorylation (VASP‐P) assay. Although the plasma levels of clopidogrel active metabolite normally exceed the inactive prodrug ∼30‐fold, the parent drug levels even exceeded those of the metabolite 2‐fold in critically ill patients. The half‐life of pantoprazole was several‐fold longer in these patients compared with reference populations. The inverse ratio of prodrug/active metabolite indicates insufficient metabolization of clopidogrel, which is independently confirmed by the ∼5‐fold increase in half‐life of pantoprazole. Thus, high‐risk patients may benefit from treatment with alternative platelet inhibitors.
Italian Mediators in Action: The Impact of Style and Attitude
Authors: Cominelli Luigi , Lucchiari Claudio
Published: September 2017

We analyzed a questionnaire sent to Italian mediators. We sought to investigate three areas: style of mediation, personal attitude toward the conflict, and effectiveness in leading the parties to a negotiated agreement in mediation. We found no significant correlations between the style of mediation and the attitude of the respondents to the conflict. Respondents with postgraduate training in economics or accounting achieved higher rates of settlement. The style of the mediator may be of some use as a paradigm of orientation, but has no sufficient predictive value to be confirmed as a key to the functioning of the mediation.
Chemoselective and Catalyst‐Free O‐Borylation of Silanols: A Facile Access to Borasiloxanes
Authors: Kuciński K. , Hreczycho G.
Published: September 2017

This paper demonstrates the first highly chemoselective syntheses of various borasiloxanes from hydroboranes and silanols, achieved through catalyst‐free dehydrogenative coupling at room temperature. This green protocol, which uses easily accessible reagents, allows for the obtaining of borasiloxanes under air atmosphere and solvent‐free conditions.
Age‐dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats
Authors: Gawlak Maciej , Szulczyk Bartłomiej , Berłowski Adam , Grzelka Katarzyna , Stachurska Anna , Pełka Justyna , Czarzasta Katarzyna , Małecki Maciej , Kurowski Przemysław , Nurowska Ewa , Szulczyk Paweł
Published: September 2017

Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.9 sodium channels conduct a Na+current that is TTX resistant with a low threshold and noninactivating over time. The purpose of this study was to assess the presence of Nav1.9 channels in medial prefrontal cortex (mPFC) layer II and V pyramidal neurons in young (20‐day old), late adolescent (60‐day old), and adult (6‐ to 7‐month old) rats. First, we demonstrated that layer II and V mPFC pyramidal neurons in slices obtained from young rats exhibited a TTX‐resistant, low‐threshold, noninactivating, and voltage‐dependent Na+current. The mRNA expression of the SCN11a gene (which encodes the Nav1.9 channel) in mPFC tissue was significantly higher in young rats than in late adolescent and adult rats. Nav1.9 protein was immunofluorescently labeled in mPFC cells in slices and analyzed via confocal microscopy. Nav1.9 immunolabeling was present in layer II and V mPFC pyramidal neurons and was more prominent in the neurons of young rats than in the neurons of late adolescent and adult rats. We conclude that Nav1.9 channels are expressed in layer II and V mPFC pyramidal neurons and that Nav1.9 protein expression in the mPFC pyramidal neurons of late adolescent and adult rats is lower than that in the neurons of young rats. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1371–1384, 2017
Multivariable Controller Design Achieving Diagonal Dominance Using Frequency Response Data
Authors: SHINODA SHOGO , YUBAI KAZUHIRO , YASHIRO DAISUKE , HIRAI JUNJI
Published: September 2017

A model‐based controller design method is widely used in the industrial field. However, in this method, a modeling error deteriorates the control performance. This article proposes a multivariable controller design method using only frequency response data sets. This method omits the time‐consuming model identification and designs a controller directly from raw data sets of the controlled plant. The proposed method provides the parameters of a PID controller using convex optimization subject to stability constrains. The optimization problem is formulated in terms of the diagonal dominance of the system. The designed controller suppresses an interaction and achieves high gain of the system in the case of highly diagonal dominance. The stability of MIMO systems can be evaluated by eigenvalue loci without overestimation of eigenvalue loci. The formulated optimization problem involving nonconvex functions and/or constraints is solved using concave–convex procedure that solves a problem written as a difference between two convex functions. The experimental results show the effectiveness of the proposed method in comparison with the conventional method.
Invading oysters and native mussels: from hostile takeover to compatible bedfellows
Authors: Reise Karsten , Buschbaum Christian , Büttger Heike , Wegner K. Mathias
Published: September 2017

Unintended species introductions may offer valuable insights into the functioning of species assemblages. A spectacular invasion of introduced Pacific oysters Magallana (formerly Crassostrea) gigas in the northern Wadden Sea (eastern North Sea, NE Atlantic) has relegated resident mussels Mytilus edulis on their beds to subtenant status. At the beginning of feral oyster establishment, mussel beds offered suitable sites with ample substrate to settle upon. After larval attachment to mussels, the fast‐growing M. gigas overtopped and smothered their basibionts. With increasing Pacific oyster abundance and size, oyster larvae preferentially settled upon oysters, and the ecological impact of the invaders on the residents changed from competitive displacement to accommodation of mussels underneath a canopy of oysters. Oysters took the best feeding positions while mussels received shelter from predation and detrimental epibionts. The resident's mono‐dominance has turned into co‐dominance with an alien, persisting in novel, multi‐layered mixed reefs of oysters with mussels, which we term “oyssel reefs.” The first 26 yr of the Pacific oyster's conquest of mussel beds in the northern Wadden Sea may question the overcome notions of natural balance, superiority of pristine over novel species combinations, and of introduced alien species threatening biodiversity and ecosystem stability in general.
Courts Reviewing, Finally, FERC's Appeal Process for Enforcement
Authors: Mansholt Tyler E. , White Brett K.
Published: September 2017

Twelve years after Congress vested the Federal Energy Regulatory Commission (FERC) with authority to assess civil penalties for manipulation of energy markets through the Energy Policy Act of 2005 (EPAct 2005), federal courts finally have begun shedding light on the scope of FERC's prohibition of market manipulation authority and the legality of its enforcement processes.
EPA's Rollercoaster of Repealing Methane Rule for Oil and Gas
Authors: Pepper Richard L.
Published: September 2017

Over the past two months, a daily battle has been raging between oil and gas interests, states, and environmentalists in the DC Circuit over the methane new source performance standards (NSPS) for oil and gas operations.
States Assuming Momentum in Energy Policy Formerly Led by Feds
Authors: DeCotis Paul A.
Published: September 2017

One does not have to look far to see how US energy policy is being advanced. While the federal government has led many major energy and environmental policy initiatives over the past several decades, and Congress passed and presidents signed several pieces of major energy legislation, energy policy leadership has now nearly fully transitioned to the states. At each of the last half‐dozen or so energy‐related conferences attended in the last six months, there was little or no representation by the federal government. A federal employee was present and did speak at one of the conferences attended, but as a career industry professional sharing a personal interest and point of view rather than a representative of the federal government.
Autocrine and Paracrine Regulation of the Murine Skeleton by Osteocyte-Derived Parathyroid Hormone-Related Protein
Authors: Ansari Niloufar , Ho Patricia WM , Crimeen-Irwin Blessing , Poulton Ingrid J , Brunt Athena R , Forwood Mark R , Divieti Pajevic Paola , Gooi Jonathan H , Martin T John , Sims Natalie A
Published: September 2017

Parathyroid hormone–related protein (PTHrP) and parathyroid hormone (PTH) have N-terminal domains that bind a common receptor, PTHR1. N-terminal PTH (teriparatide) and now a modified N-terminal PTHrP (abaloparatide) are US Food and Drug Administration (FDA)-approved therapies for osteoporosis. In physiology, PTHrP does not normally circulate at significant levels, but acts locally, and osteocytes, cells residing within the bone matrix, express both PTHrP and the PTHR1. Because PTHR1 in osteocytes is required for normal bone resorption, we determined how osteocyte-derived PTHrP influences the skeleton. We observed that adult mice with low PTHrP in osteocytes (targeted with the Dmp1(10kb)-Cre) have low trabecular bone volume and osteoblast numbers, but osteoclast numbers were unaffected. In addition, bone size was normal, but cortical bone strength was impaired. Osteocyte-derived PTHrP therefore stimulates bone formation and bone matrix strength, but is not required for normal osteoclastogenesis. PTHrP knockdown and overexpression studies in cultured osteocytes indicate that osteocyte-secreted PTHrP regulates their expression of genes involved in matrix mineralization. We determined that osteocytes secrete full-length PTHrP with no evidence for secretion of lower molecular weight forms containing the N-terminus. We conclude that osteocyte-derived full-length PTHrP acts through both PTHR1 receptor-mediated and receptor-independent actions in a paracrine/autocrine manner to stimulate bone formation and to modify adult cortical bone strength. © 2017 American Society for Bone and Mineral Research.
Cherubism Mice Also Deficient in c-Fos Exhibit Inflammatory Bone Destruction Executed by Macrophages That Express MMP14 Despite the Absence of TRAP+ Osteoclasts
Authors: Kittaka Mizuho , Mayahara Kotoe , Mukai Tomoyuki , Yoshimoto Tetsuya , Yoshitaka Teruhito , Gorski Jeffrey P , Ueki Yasuyoshi
Published: September 2017

Currently, it is believed that osteoclasts positive for tartrate-resistant acid phosphatase (TRAP+) are the exclusive bone-resorbing cells responsible for focal bone destruction in inflammatory arthritis. Recently, a mouse model of cherubism (Sh3bp2KI/KI) with a homozygous gain-of-function mutation in the SH3-domain binding protein 2 (SH3BP2) was shown to develop auto-inflammatory joint destruction. Here, we demonstrate that Sh3bp2KI/KI mice also deficient in the FBJ osteosarcoma oncogene (c-Fos) still exhibit noticeable bone erosion at the distal tibia even in the absence of osteoclasts at 12 weeks old. Levels of serum collagen I C-terminal telopeptide (ICTP), a marker of bone resorption generated by matrix metalloproteinases (MMPs), were elevated, whereas levels of serum cross-linked C-telopeptide (CTX), another resorption marker produced by cathepsin K, were not increased. Collagenolytic MMP levels were increased in the inflamed joints of the Sh3bp2KI/KI mice deficient in c-Fos. Resorption pits contained a large number of F4/80+ macrophages and genetic depletion of macrophages rescued these erosive changes. Importantly, administration of NSC405020, an MMP14 inhibitor targeted to the hemopexin (PEX) domain, suppressed bone erosion in c-Fos-deficient Sh3bp2KI/KI mice. After activation of the NF-κB pathway, macrophage colony-stimulating factor (M-CSF)-dependent macrophages from c-Fos-deficient Sh3bp2KI/KI mice expressed increased amounts of MMP14 compared with wild-type macrophages. Interestingly, receptor activator of NF-κB ligand (RANKL)-deficient Sh3bp2KI/KI mice failed to show notable bone erosion, whereas c-Fos deletion did restore bone erosion to the RANKL-deficient Sh3bp2KI/KI mice, suggesting that osteolytic transformation of macrophages requires both loss-of-function of c-Fos and gain-of-function of SH3BP2 in this model. These data provide the first genetic evidence that cells other than osteoclasts can cause focal bone destruction in inflammatory bone disease and suggest that MMP14 is a key mediator conferring pathological bone-resorbing capacity on c-Fos-deficient Sh3bp2KI/KI macrophages. In summary, the paradigm that osteoclasts are the exclusive cells executing inflammatory bone destruction may need to be reevaluated based on our findings with c-Fos-deficient cherubism mice lacking osteoclasts. © 2017 American Society for Bone and Mineral Research.
Hypercalcemic Disorders in Children
Authors: Stokes Victoria J , Nielsen Morten F , Hannan Fadil M , Thakker Rajesh V
Published: September 2017

Hypercalcemia is defined as a serum calcium concentration that is greater than two standard deviations above the normal mean, which in children may vary with age and sex, reflecting changes in the normal physiology at each developmental stage. Hypercalcemic disorders in children may present with hypotonia, poor feeding, vomiting, constipation, abdominal pain, lethargy, polyuria, dehydration, failure to thrive, and seizures. In severe cases renal failure, pancreatitis and reduced consciousness may also occur and older children and adolescents may present with psychiatric symptoms. The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)-dependent or PTH-independent, and may be congenital or acquired. PTH-independent hypercalcemia, ie, hypercalcemia associated with a suppressed PTH, is commoner in children than PTH-dependent hypercalcemia. Acquired causes of PTH-independent hypercalcemia in children include hypervitaminosis; granulomatous disorders, and endocrinopathies. Congenital syndromes associated with PTH-independent hypercalcemia include idiopathic infantile hypercalcemia (IIH), William's syndrome, and inborn errors of metabolism. PTH-dependent hypercalcemia is usually caused by parathyroid tumors, which may give rise to primary hyperparathyroidism (PHPT) or tertiary hyperparathyroidism, which usually arises in association with chronic renal failure and in the treatment of hypophosphatemic rickets. Acquired causes of PTH-dependent hypercalcemia in neonates include maternal hypocalcemia and extracorporeal membrane oxygenation. PHPT usually occurs as an isolated nonsyndromic and nonhereditary endocrinopathy, but may also occur as a hereditary hypercalcemic disorder such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated primary hyperparathyroidism, and less commonly, as part of inherited complex syndromic disorders such as multiple endocrine neoplasia (MEN). Advances in identifying the genetic causes have resulted in increased understanding of the underlying biological pathways and improvements in diagnosis. The management of symptomatic hypercalcemia includes interventions such as fluids, antiresorptive medications, and parathyroid surgery. This article presents a clinical, biochemical, and genetic approach to investigating the causes of pediatric hypercalcemia. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Parental Apologies, Empathy, Shame, Guilt, and Attachment: A Path Analysis
Authors: Ruckstaetter Jeremy , Sells James , Newmeyer Mark D. , Zink Daniel
Published: September 2017

The authors investigated the complex relationships of parental attitudes toward apologies, empathy, shame, guilt, and the parent's attachment orientation. Survey responses were obtained from 327 parents. A path analysis of the developed model demonstrated a close model fit (root‐mean‐square error of approximation = .07; comparative fit index = .93; incremental fit index = .94; χ2 = 30.71, p < .001), supporting previous research on apologies as beneficial to relationships. A parent's proclivity toward apologies, positively influenced by empathy and guilt and negatively influenced by shame‐withdraw behaviors, produced a more secure parent–child attachment.
Effects of Attachment on Coping Efficacy, Career Decision Self‐Efficacy, and Life Satisfaction
Authors: Wright Stephen L. , Firsick Dylan M. , Kacmarski Jason A. , Jenkins‐Guarnieri Michael A.
Published: September 2017

This study examined attachment, self‐efficacy variables, and life satisfaction of 583 undergraduate students. The type of analysis used was structural equation modeling. Findings indicated that students with greater avoidant and anxious attachment patterns reported lower levels of career decision self‐efficacy and coping efficacy, which then had a positive relationship with life satisfaction. Implications for theory, research, and practice were provided.
Characterization of Titanium Dioxide Doped with Nitrogen and Sulfur and its Photocatalytic Appraisal for Degradation of Phenol and Methylene Blue
Authors: Syafiuddin Achmad , Hadibarata Tony , Zon Nur Farhan , Salmiati
Published: September 2017

The degradation of organic dyes in the presence of modified TiO2 is still under intensive investigation. We report here an evaluation of the photocatalytic activity of nitrogen‐ (N‐) and sulfur‐ (S‐) doped TiO2 for the degradation of phenol and methylene blue (MB). N‐doped TiO2 (N–TiO2), S‐doped TiO2 (S–TiO2), and N–S‐doped TiO2 (N–S–TiO2) were prepared using the sol–gel method. The photocatalytic activity was evaluated in a batch reactor using phenol and MB as models of pollutants. In addition, this investigation was performed using a household lamp as the visible light source. Properties of the synthesized materials in terms of Brunauer–Emmett–Teller (BET) surface analysis, field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), and photocatalytic ability were examined. Our study shows that N–S–TiO2 exhibits better photocatalytic degradation ability for all the considered dyes compared to the other doped TiO2 materials. In conclusion, we have successfully prepared and evaluated the photocatalytic activity of N‐ and S‐doped TiO2 for the degradation of phenol and MB using an ordinary household lamp.
Optimization of protein recovery from bovine lung by pH shift process using response surface methodology
Authors: Lynch Sarah A , Álvarez Carlos , O'Neill Eileen E , Keenan Derek F , Mullen Anne Maria
Published: September 2017

BACKGROUND

Response surface methodology (RSM) was used in a sequential manner to optimize solubilization and precipitation conditions in the recovery of protein from bovine lung using pH shift.

RESULTS

Separate D‐optimal designs were employed for protein solubilization and precipitation. Independent variables investigated for protein solubilization were time (10–120 min), temperature (4–20 °C), pH (8.0–11.0) and solvent/sample ratio (2.5–10). Variables for protein precipitation were time (0–60 min) and pH (4.25–6.00). Soluble protein yields ranged from 323 to 649 g kg−1 and the quadratic model for protein solubilization revealed a coefficient of determination R2 of 0.9958. Optimal conditions for maximum protein solubility were extraction time 140 min, temperature 19 °C, pH 10.8 and solvent/sample ratio 13.02. Protein precipitation yields varied from 407 to 667 g kg−1, giving a coefficient of determination R2 of 0.9335. Optimal conditions for maximum protein precipitation were pH 5.03 and 60 min. Based on the RSM model, solubilization conditions were manipulated to maximize protein solubilization under reduced water and alkaline usage. These conditions were also validated.

CONCLUSION

Models for solubilization and precipitation using bovine and porcine lung were validated; predicted and actual yields were in good agreement, showing cross‐species applicability of the results. © 2017 Society of Chemical Industry
The Incredible Additive Manufacturing Creates Movement
Authors: Hanreich Klaus
Published: September 2017

At first glance, additive manufacturing seems to be a very simple manufacturing process. Nevertheless, many companies are not happy with their adaption of this new technology or are even overburdened by it. Often, we have to undisputedly agree with these companies. However, we can change their opinions straight away. The fascinating metal 3D printing nowadays even manages to print moving objects without needing assembly afterwards. Even though it seems hard to believe, it surely is possible with suitable handling and application. But has that always been this way?
Determining RUSLE P‐ and C‐factors for stone bunds and trenches in rangeland and cropland, North Ethiopia
Authors: Taye Gebeyehu , Vanmaercke Matthias , Poesen Jean , Van Wesemael Bas , Tesfaye Samuale , Teka Daniel , Nyssen Jan , Deckers Jozef , Haregeweyn Nigussie
Published: September 2017

The implementation of soil and water conservation (SWC) measures in the Ethiopian Highlands is a top priority to reduce soil erosion rates. However, the effectiveness of these measures for different hillslope gradients and land use conditions remains poorly understood. This study addresses this knowledge gap by determining support practice (P) and cover‐management (C) factors of the Revised Universal Soil Loss Equation for commonly used SWC structures in semi‐arid environments. The factor values were calculated on the basis of soil loss data collected with 21 large runoff plots installed in rangeland and cropland sites. The P‐ and C‐factors were calculated following the recommended procedures. Results show P‐factors ranging from 0.32 to 0.74 for stone bunds, from 0.07 to 0.65 for trenches, and from 0.03 to 0.22 for stone bunds with trenches. Reduced storage capacities due to sediment deposition resulted in significant declines of the effectiveness of SWC structures over time. For example, the average P‐factor value for trenches increased from 0.1 in the first year after installation to 0.51 after 3 years. C‐factor values ranged from 0.23 to 0.82 in rangeland and from 0.03 to 0.35 in cropland. For rangeland, this large variability is due to vegetation cover changes caused by grazing. In cropland, C‐factors vary with crop types and tillage practices. The results of this study not only aid in modelling and quantifying the short‐term impacts of SWC structures on soil erosion rates but also highlight the importance of considering temporal variations of the effectiveness of SWC measures.