bluuebunny/crossref_metadata_2025 huggingface dataset:
KIAA1199: A novel regulator of MEK/ERK‐induced Schwann cell dedifferentiation
Authors: Boerboom Angélique , Reusch Céline , Pieltain Alexandra , Chariot Alain , Franzen Rachelle
Published: July 2017

The molecular mechanisms that regulate Schwann cell (SC) plasticity and the role of the Nrg1/ErbB‐induced MEK1/ERK1/2 signalling pathway in SC dedifferentiation or in myelination remain unclear. It is currently believed that different levels of MEK1/ERK1/2 activation define the state of SC differentiation. Thus, the identification of new regulators of MEK1/ERK1/2 signalling could help to decipher the context‐specific aspects driving the effects of this pathway on SC plasticity. In this perspective, we have investigated the potential role of KIAA1199, a protein that promotes ErbB and MEK1/ERK1/2 signalling in cancer cells, in SC plasticity. We depleted KIAA1199 in the SC‐derived MSC80 cell line with RNA‐interference‐based strategy and also generated Tamoxifen‐inducible and conditional mouse models in which KIAA1199 is inactivated through homologous recombination, using the Cre‐lox technology. We show that the invalidation of KIAA1199 in SC decreases the expression of cJun and other negative regulators of myelination and elevates Krox20, driving them towards a pro‐myelinating phenotype. We further show that in dedifferentiation conditions, SC invalidated for KIAA1199 exhibit lower myelin clearance as well as increased myelination capacity. Finally, the Nrg1‐induced activation of the MEK/ERK/1/2 pathway is severely reduced when KIAA1199 is absent, indicating that KIAA1199 promotes Nrg1‐dependent MEK1 and ERK1/2 activation in SCs. In conclusion, this work identifies KIAA1199 as a novel regulator of MEK/ERK‐induced SC dedifferentiation and contributes to a better understanding of the molecular control of SC dedifferentiation.
Spatial distribution of EGFR and KRAS mutation frequencies correlates with histological growth patterns of lung adenocarcinomas
Authors: Dietz Steffen , Harms Alexander , Endris Volker , Eichhorn Florian , Kriegsmann Mark , Longuespée Rémi , Stenzinger Albrecht , Sültmann Holger , Warth Arne , Kazdal Daniel
Published: July 2017

Multiregional analysis provided first indications for morphological and molecular heterogeneity in lung adenocarcinomas (ADCs), but comprehensive morpho‐molecular comparisons are still lacking. The purpose of our study was to investigate the spatial distribution of EGFR and KRAS alterations systematically throughout whole tumor cross‐sections in correlation with the tumor cell content and the histopathological patterns. Central sections of 19 ADCs were subdivided into 467 segments of 5 mm × 5 mm. We determined the predominant histological growth pattern and the allele frequencies of driver gene mutations by digital PCR in every segment. We further quantified the absolute cell counts and proportions of tumor and non‐neoplastic cells in all segments to normalize the mutant allele frequencies. Driver gene mutations could be detected in >99% of the tumor containing segments, with high levels of inter‐ and intratumor heterogeneity regarding the mutant allele frequency (range: 0.04–19.36). Different patterns for the distribution of the variant allele frequency within a tumor were recognizable. While some cases showed ubiquitously low or high levels, others revealed regions with focally elevated frequencies. Differences between KRAS and EGFR alterations were not significant. The great majority of the analyzed tumor sections (16/19) exhibited two or more morphological growth patterns. Mutant allele frequencies were significantly higher in segments with a predominant solid pattern compared to all other histologies (p < 0.01). Our data indicate that driver gene mutations are present with high levels of inter‐ and intratumor heterogeneity throughout the whole tumor, with a correlation between the allele frequencies and histological growth patterns.
Postnatal risk factors for testicular cancer: The EPSAM case–control study
Authors: Moirano Giovenale , Zugna Daniela , Grasso Chiara , Mirabelli Dario , Lista Patrizia , Ciuffreda Libero , Segnan Nereo , Merletti Franco , Richiardi Lorenzo
Published: July 2017

Testicular cancer is considered to originate from an impaired differentiation of fetal germ cells, but puberty could represent another time window of susceptibility. Our study aimed at investigating the association between environmental exposures acting during puberty/adolescence (13–19 years of age) and the risk of testicular cancer. We used data of the EPSAM study, a case–control study on germ‐cell testicular cancer conducted in the province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Histologically confirmed cases (n = 255) and controls (n = 459) completed a postal questionnaire focusing in particular on the pubertal period (namely age 13 years) with questions on physical activity (competitive sports, gardening), lifestyle (alcohol consumption, smoking), occupational history and medical conditions. All analyses were adjusted for the matching variables, cryptorchidism and educational level. Having done at least one competitive sport during puberty (odds ratio [OR]: 0.72, 95% confidence interval: 0.52–1.00), gardening activities during puberty (OR: 0.62, 0.42–0.94) and having a lower weight than peers during puberty (OR: 0.64, 0.42–0.97) were all inversely associated with the risk of testicular cancer. No evidence of association between smoking or alcohol consumption during puberty and the risk of testicular cancer was observed. Regarding agriculture‐related occupations, we found an association with the risk of testicular cancer both for occasional jobs during puberty (OR: 2.40, 95% CI: 1.08–5.29) and ever employment in adolescence (OR: 2.59, 95% CI: 0.83–8.10). Our results suggest that postnatal exposures could play a role in testicular cancer aetiology, at least when acting in puberty or adolescence.
Standardizing bimanual vaginal examination using cognitive task analysis
Authors: Plumptre Isabella , Mulki Omar , Granados Alejandro , Gayle Claudine , Ahmed Shahla , Low‐Beer Naomi , Higham Jenny , Bello Fernando
Published: July 2017

Objective

To create a standardized universal list of procedural steps for bimanual vaginal examination (BVE) for teaching, assessment, and simulator development.

Methods

This observational study, conducted from June–July 2012 and July–December 2014, collected video data of 10 expert clinicians performing BVE in a nonclinical environment. Video data were analyzed to produce a cognitive task analysis (CTA) of the examination steps performed. The CTA was further refined through structured interviews to make it suitable for teaching or assessment. It was validated through its use as a procedural examination checklist to rate expert clinician performance.

Results

BVE was deconstructed into 88 detailed steps outlining the complete examination process. These initial 88 steps were reduced to 35 by focusing on the unseen internal examination, then further refined through interviews with five experts into 30 essential procedural steps, five of which are additional steps if pathology is suspected. Using the CTA as a procedural checklist, the mean number of steps performed and/or verbalized was 21.6 ± 3.12 (72% ± 10.4%; range, 15.9–27.9, 53%–93%).

Conclusion

This approach identified 30 essential steps for performing BVE, producing a new technique and standardized tool for teaching, assessment, and simulator development.
Biological responses in Balb/c mice after long‐term parenteral administration of the light subunit of mushroom tyrosinase
Authors: Ismaya Wangsa T. , Efthyani Alida , Tjandrawinata Raymond R. , Rachmawati Heni
Published: July 2017

Light subunit of mushroom tyrosinase (LSMT) is a protein of unknown function from mushroom Agaricus bisporus that has been demonstrated to permeate through rat intestine ex vivo. Thus, it can be absorbed in the intestine, thereby holding a promise as a drug carrier for oral administration, similar to HA‐33 protein from botulinum, one of the closest structural homologs of LSMT. However, the safety of LSMT should be ensured prior to its use. Here, we described biological response of LSMT upon weekly intraperitoneal administration of 50 μg/day to the Balb/c mice for 12 weeks. Motoric and behavior profiles, as well as the index of main organs (liver, spleen, lung, heart, and kidney), and body weight, were not significantly changed as compared with the control group. Also, no IgG was detected in the serum. The results suggest that LSMT is safe for further development.
Aversive functions of response effort: Fact or artifact?
Authors: Pinkston Jonathan W. , Libman Benjamin M.
Published: July 2017

Historically, effort has been viewed as aversive. Most supporting evidence comes from studies demonstrating increased force/effort requirements reduce operant responding. Changes in force/effort requirements, however, are often accompanied by changes in response definition when mechanical devices are used to define the response. As a consequence, responses measured at one point in a study may go unmeasured at other points. In an alternative approach, we used a continuous measurement strategy that provided a means to fix the threshold force defining the response class and simultaneously allowed independent manipulation of the force criteria required to produce reinforcement. Rats pressed a force transducer according to a fixed‐ratio 5 schedule of food delivery. The criterion force was systematically increased and decreased; the threshold for response detection was constant. When response rates included only criterion responses, overall rate decreased when force requirements increased. By contrast, when all responses, both those meeting force criteria and those that did not (above the threshold but below the criteria for reinforcement) were included in the rate calculation, increases in force increased response rate. Increases in force criteria also increased the maximum force (g) and time‐integral of force (g‐s) of operant behavior. Control conditions showed increases in responding could be explained by the emergence of subcriterion responses, irrespective of force. We conclude that prior results showing effort decreases response rates are due to an artifact arising from inadvertent changes in response definitions. Increases in effort may better be understood as changes in the response:reinforcer payoff owing to the emergence of a subcriterion response class.
Scanning electron and light microscopy of foliar epidermal characters: A tool for plant taxonomists in the identification of grasses
Authors: Khan Raees , Ahmad Mushtaq , Zafar Muhammad , Ullah Asad
Published: July 2017

SEM and light microscopy are of special interest for biologist to observe various features of the living bodies. In the current study we observed the foliar epidermal micro‐morphological characters of 44 grass species using SEM and Light microscopy to assess their taxonomic utility for taxonomists in the identification process. The aim of this study is to use the foliar epidermal structural variations in both upper and lower surfaces for identification of grasses. Significant diversity was observed in both qualitative and quantitative characters using SEM and Light microscopy. Variations were observed in stomatal number, size, guard cells shape, silica bodies, macro‐hairs, micro‐hairs, epidermal cell number, subsidiary cells, prickles, hooks, papillae, and short and long cells. A taxonomic key is prepared using these variations for the identification of grass species. Based on these findings, SEM and Light microscopy of foliar epidermal features can be of special interest for taxonomists in the identification of complex grass taxa.
Anal HPV 16 and 18 viral load: A comparison between HIV‐negative and ‐positive MSM and association with persistence
Authors: Marra Elske , King Audrey , van Logchem Elske , van der Weele Pascal , Mooij Sofie H. , Heijman Titia , Meijer Chris J.L.M. , Verhagen Dominique W.M. , van der Sande Marianne A. B. , Schim van der Loeff Maarten F.
Published: July 2017

Does anal HPV viral load explain the difference in anal HPV persistence between HIV‐negative and ‐positive men who have sex with men (MSM)? MSM ≥18 years were recruited in Amsterdam, the Netherlands, in 2010‐2011. Anal self‐swabs were collected every 6 months and genotyped (SPF10‐PCR‐DEIA‐LIPA25‐system). HPV16 and HPV18 load was determined with a type specific quantitative (q)PCR, and compared between HIV‐negative and ‐positive men using ranksum test. Persistence was defined as ≥3 positive samples for the same HPV‐type. Determinants of persistent HPV16/18 infection and its association with HPV16/18 load were assessed with logistic regression. Of 777 recruited MSM, 54 and 22 HIV negative men were HPV16 and HPV18 positive at baseline, and 64 and 39 HIV‐positive MSM. The geometric mean titer (GMT) of HPV16 was 19.6 (95%CI 10.1‐38.0) and of HPV18 8.6 (95%CI 2.7‐27.5) DNA copies/human cell. HPV16 and HPV18 load did not differ significantly between HIV‐negative and ‐positive MSM (P = 0.7; P = 0.8, respectively). In multivariable analyses HPV16 load was an independent determinant of HPV16 persistence (OR 1.8, 95%CI 1.3‐2.4). No difference in anal HPV viral load was found between HIV‐positive and HIV‐negative MSM. HPV 16/18 viral load is an independent determinant of type‐specific persistence.
Modeling and simulation of 2DEG density and intrinsic capacitances in AlInN/GaN MOSHEMT
Authors: Amarnath G. , Swain R. , Lenka T.R.
Published: July 2017

In this paper, an analytical model for intrinsic capacitance is developed by estimating 2‐dimensional electron gas density inside the triangular quantum well in AlInN/GaN metal oxide semiconductor high‐electron mobility transistors by considering gate charge and through self‐consistent solution of Poisson and Schrödinger equations. The charge separation method is applied to develop the intrinsic terminal charges and then the intrinsic capacitances accordingly. In order to validate the developed model, the results are compared with TCAD device simulation results.
Different characteristics of cell volume and intracellular calcium ion concentration dynamics between the hippocampal CA1 and lateral cerebral cortex of male mouse brain slices during exposure to hypotonic stress
Authors: Takahashi Nanae , Omi Akibumi , Uchino Hiroyuki , Kudo Yoshihisa
Published: July 2017

The mechanism of brain edema is complex and still remains unclear. Our aim was to investigate the regional differences of cell volume and intracellular Ca2+ concentration ([Ca2+]i) dynamics during hypotonic stress in male mouse hemi‐brain slices. Brain slices were loaded with the fluorescence Ca2+ indicator fura‐2, and cell volume and [Ca2+]i in the lateral cerebral cortex (LCC) and hippocampal CA1 (CA1) region were measured simultaneously during exposure to hypotonic stress using Ca2+ insensitive (F360) and Ca2+ sensitive fluorescence (F380), respectively. Brain cell swelling induced by hypotonic stress was followed by a regulatory volume change that coincided with an increase in [Ca2+]i. The degrees of change in cell volume and [Ca2+]i were significantly different between the LCC and CA1. The increase in cell volume and [Ca2+]i in the LCC, but not in the CA1, was decreased by the transient receptor potential channel blockers LaCl3 and GdCl3. The increase in [Ca2+]i in both the LCC and CA1, was significantly decreased by the intracellular Ca2+ modulators thapsigargin and xestospongin C. The K+ channel activator isoflurane and Cl‐ channel blocker NPPB significantly decreased [Ca2+]i in the LCC. This study demonstrated that, between cells located in the LCC and in the CA1, the characteristics of brain edema induced by hypotonic stress are different. This can be ascribed to the different contribution of volume sensitive G‐protein coupled receptor and stretch sensitive Ca2+ channels.
Calcium dependence of spontaneous neurotransmitter release
Authors: Williams Courtney L. , Smith Stephen M.
Published: July 2017

Spontaneous release of neurotransmitters is regulated by extracellular [Ca2+] and intracellular [Ca2+]. Curiously, some of the mechanisms of Ca2+signaling at central synapses are different at excitatory and inhibitory synapses. While the stochastic activity of voltage‐activated Ca2+channels triggers a majority of spontaneous release at inhibitory synapses, this is not the case at excitatory nerve terminals. Ca2+release from intracellular stores regulates spontaneous release at excitatory and inhibitory terminals, as do agonists of the Ca2+‐sensing receptor. Molecular machinery triggering spontaneous vesicle fusion may differ from that underlying evoked release and may be one of the sources of heterogeneity in release mechanisms.
A seasonal prediction for the wet–cold spells leading to winter crop damage in northwestern Taiwan with a combined empirical–dynamical approach
Authors: Promchote Parichart , Wang S.‐Y. Simon , Shen Yuan , Johnson Paul G. , Yao Ming‐Hwi
Published: July 2017

Winter crop losses from extreme weather in Taiwan have increased in the recent decade, with those losses associated with pronounced wet‐and‐cold events (temperature < 10 °C and precipitation >5 mm day−1). The regional and global patterns of atmospheric circulation and the sea surface temperature (SST) related to the extreme cold that damages fruits, vegetables, and paddy rice in northwest Taiwan were investigated. Cool SST anomalies in the western North Pacific (WNP) and warm SST in the central‐eastern Pacific associated with the Pacific meridional mode (PMM) shared a significant role in the occurrence of wet‐and‐cold events in northwest Taiwan. The interactions of the WNP/PMM with the North Pacific Oscillation (NPO) and the Central Pacific type of El Niño led to a pronounced lead–lag relationship with the occurrence of wet‐and‐cold events. An empirical model was subsequently developed to predict the wet‐and‐cold event frequency using observed values of WNP, Niño‐3.4, and Arctic Oscillation from year‐1 and predicted indices of WNP and PMM derived from the Climate Forecast System Version 2 (CFSv2) outputs. The predictive skill of this hybrid empirical–dynamical model was statistically significant throughout the 6 months leading up to the occurrence of wet‐and‐cold events.
Analyzing the inner product of 2 circles with Gaalop
Authors: Hildenbrand Dietmar , Benger Werner , Zhaoyuan Yu
Published: July 2017

This paper describes the geometric meaning of the inner product of 2 circles based on Compass Ruler Algebra, the Conformal Geometric Algebra in 2D. It analyzes in detail the cases of intersecting and tangent circles as well as when one circle is completely inside or completely outside the other circle. The paper reflects the systematic way of deriving the results based on the Geometric Algebra software tool Gaalop. The results are easily conferrable to arbitrary dimensions.
Monotonicity, uniqueness, and stability of traveling waves in a nonlocal reaction‐diffusion system with delay
Authors: Zhao Hai‐Qin
Published: July 2017

The purpose of this paper is to study the traveling wave solutions of a nonlocal reaction‐diffusion system with delay arising from the spread of an epidemic by oral‐faecal transmission. Under monostable and quasimonotone it is well known that the system has a minimal wave speed c* of traveling wave fronts. In this paper, we first prove the monotonicity and uniqueness of traveling waves with speed c⩾c∗. Then we show that the traveling wave fronts with speed c>c∗ are exponentially asymptotically stable.
Global solution of the 3‐D incompressible Navier‐Stokes equations in the Besov spaces B˙r1,r2,r3σ,1
Authors: Ru Shaolei , Chen Jiecheng
Published: July 2017

In this paper, we construct a more general Besov spaces
and consider the global well‐posedness of incompressible Navier‐Stokes equations with small data in
for
. In particular, we show that for any
and
, the solution with initial data in
belong to
, which, as far as we know, has not been discussed in other papers. Moreover, the smoothing effect of the solution to Navier‐Stokes equations is proved, which may have its own interest.
Partial affine system–based frames and dual frames
Authors: Li Yun‐Zhang , Tian Yu
Published: July 2017

In this paper, we introduce the notion of partial affine system that is a subset of an affine system. It has potential applications in signal analysis. A general affine system has been extensively studied; however, the partial one has not. The main focus of this paper is on partial affine system–based frames and dual frames. We obtain a necessary condition and a sufficient condition for a partial affine system to be a frame and present a characterization of partial affine system–based dual frames. Some examples are also provided.
Recent developments in elastomeric heat shielding materials for solid rocket motor casing application for future perspective
Authors: George Kesiya , Panda Bishnu P. , Mohanty Smita , Nayak Sanjay K.
Published: July 2017

Catastrophic breakdown that occurs during the flight of supersonic vehicles demands more focused research in the insulation of rocket engines. At present, optimization of polymeric ablatives as viable insulation for solid rocket motor casing has a prominent role in the successful mission of rockets. Among polymers, elastomer serves an imperative part. Comprehensive investigations were disclosed, especially in the elastomeric heat shielding materials with various reinforcing agents. In this paper, research progress of mostly used elastomers is reviewed, and a circumstantial understanding about the features of ablation and insulation has been validated.
IMP‐6 Carbapenemase‐Producing Enterobacteriaceae Bacteremia Successfully Treated with Amikacin‐Meropenem in Two Patients
Authors: Nakakura Ichiro , Ogawa Yoshihiko , Sakakura Kota , Imanishi Kaori , Hirota Kazuyuki , Shimatani Yasuaki , Uehira Tomoko , Nakamori Shoji , Sako Rumi , Doi Toshiyuki , Yamazaki Kunio
Published: July 2017

Infections caused by carbapenemase‐producing Enterobacteriaceae (CPE) are becoming increasingly common worldwide. Although CPE infections can be fatal, few reports in the literature have described effective and successful treatments for infectious diseases caused by several types of IMP CPE, and, to our knowledge, no reports have described the successful treatment of IMP‐6 CPE infections. We describe two patients who developed bacteremia caused by IMP‐6 CPE after surgery for cancer who were successfully treated with amikacin plus high‐dose prolonged‐infusion meropenem. Both patients were treated over a 2‐week period using amikacin 15 mg/kg at various intervals based on therapeutic drug monitoring and meropenem 2000 mg infused over 3 hours every 12 hours. The dosages of amikacin and meropenem were determined based on the creatinine clearance of each patient. Both patients were cured of their bacteremia and did not experience any antibiotic‐related adverse effects. Based on the outcomes of these patients, it appears that amikacin plus high‐dose prolonged‐infusion meropenem may be safe and effective for the treatment of bacteremia caused by IMP‐6 CPE.
Dynamic effects in the didehydro‐Diels‐Alder (DDDA) reaction of enyne‐ketoenes: 50% stepwise bond formation in spite of concerted transition state
Authors: Rana Anup , Paul Indrajit , Schmittel Michael
Published: July 2017

The C2─C6/Diels‐Alder cyclization of enyne‐ketoene 1 was studied by experiments, theoretical calculations, and dynamic trajectory computations. The failure to trap possible intermediate(s), indicates a concerted reaction mechanism. A detailed search for stationary points revealed a concerted mechanism and surprisingly a diradical intermediate with no direct connection to the enyne‐ketoene 1. To probe the accessibility of this intermediate quasiclassical trajectories were initiated from the concerted transition state structure. Notably, 36% of the trajectories reach the product zone directly and 5% arrive at the product via the intermediate diradical. Additionally, 31% of the trajectories go to the intermediate zone and stay there within the simulation time limit.
Ductal adenocarcinoma of the prostate: Clinical and biological profiles
Authors: Vinceneux Armelle , Bruyère Franck , Haillot Olivier , Charles Thomas , de la Taille Alexandre , Salomon Laurent , Allory Yves , Ouzaid Idir , Choudat Laurence , Rouprêt Morgan , Comperat Eva , Houede Nadine , Beauval Jean‐Baptiste , Vourc'h Patrick , Fromont Gaëlle
Published: July 2017

Background

Ductal adenocarcinoma (DAC) is a rare and aggressive subtype of prostate cancer (PCa). In the present study, we analyzed the clinical and biological characteristics of DAC, in comparison with high grade conventional acinar PCa.

Methods

Samples and data were retrospectively collected from seven institutions and centrally reviewed. Immunohistochemistry was performed on tissue microarrays to assess the expression of candidate proteins, based on the molecular classification of PCa, including ERG, PTEN, and SPINK1. SPOP mutations were investigated from tumor DNA by Sanger sequencing. Relationships with outcome were analyzed using log‐rank analysis and multivariable Cox regression.

Results

Among 56 reviewed prostatectomy specimens, 45 cases of DAC were finally confirmed. The pathological stage was pT3 in more than 66% of cases. ERG was expressed in 42% of DAC, SPINK1 in 9% (all ERG‐negative), and two cases (ERG‐negative) harbored a SPOP mutation. Compared to high grade conventional PCa matched for the pathological stage, cell proliferation was higher (P = 0.04) in DAC, and complete PTEN loss more frequent (P = 0.023). In multivariate analysis, SPINK1 overexpression (P = 0.017) and loss of PSA immunostaining (P = 0.02) were significantly associated with biochemical recurrence.

Conclusion

these results suggest that, despite biological differences that highlighted DAC aggressiveness, the molecular classification recently proposed in conventional PCa could also be applied in DAC.
Cytotoxic peptides with insulin‐releasing activities from skin secretions of the Italian stream frog Rana italica (Ranidae)
Authors: Conlon J. Michael , Musale Vishal , Attoub Samir , Mangoni Maria Luisa , Leprince Jérôme , Coquet Laurent , Jouenne Thierry , Abdel‐Wahab Yasser H. A. , Flatt Peter R. , Rinaldi Andrea C.
Published: July 2017

Peptidomic analysis of norepinephrine‐stimulated skin secretions from Italian stream frog Rana italica led to the purification and characterization of two host‐defense peptides differing by a single amino acid residue belonging to the brevinin‐1 family (brevinin‐1ITa and ‐1ITb), a peptide belonging to the temporin family (temporin‐ITa) and a component identified as prokineticin Bv8. The secretions contained relatively high concentrations of the methionine‐sulphoxide forms of brevinin‐1ITa and ‐1ITb suggesting that these peptides may have a role as antioxidants in the skin of this montane frog. Brevinin‐1ITa (IVPFLLGMVPKLVCLITKKC) displayed potent cytotoxicity against non‐small cell lung adenocarcinoma A549 cells (LC50 = 18 μM), breast adenocarcinoma MDA‐MB‐231 cells (LC50 = 8 μM) and colorectal adenocarcinoma HT‐29 cells (LC50 = 18 μM), but the peptide was also strongly hemolytic against mouse erythrocytes (LC50 = 7 μM). Temporin‐ITa (VFLGAIAQALTSLLGKL.NH2) was between three and fivefold less potent against these cells. Brevinin‐1ITa inhibited growth of both Gram‐positive Staphylococcus epidermidis and Gram‐negative Escherichia coli as well as a strain of the opportunist yeast pathogen Candida parapsilosis, whereas temporin‐ITa was active only against S. epidermidis and C. parapsilosis. Both peptides stimulated the release of insulin from BRIN‐BD11 clonal β‐cells at concentrations ≥1 nM, but brevinin‐1ITa was cytotoxic to the cells at concentrations ≥3 μM. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
Model‐based Meta‐Analysis on the Efficacy of Pharmacological Treatments for Idiopathic Pulmonary Fibrosis
Authors: Chan Phyllis , Bax Leon , Chen Chunlin , Zhang Nancy , Huang Shu‐Pang , Soares Holly , Rosen Glenn , AbuTarif Malaz
Published: July 2017

Recently, the US Food and Drug Administration (FDA) approved the first two drugs (pirfenidone and nintedanib) indicated for the treatment of idiopathic pulmonary fibrosis (IPF). The purpose of this analysis was to leverage publicly available data to quantify comparative efficacy of compounds that are approved or in development. An analysis‐ready database was developed, and the analysis dataset is composed of summary‐level data from 43 arms in 20 trials, with treatment durations ranging from 8–104 weeks. A hierarchical multivariable regression model with nonparametric placebo estimation was used to fit the longitudinal profile of change from baseline of percent predicted forced vital capacity (%predicted FVC) data. Pirfenidone and nintedanib were the only drugs identified to have significant estimated positive treatment effects. Model simulations were performed to further evaluate the covariate and time course of treatment effects on longitudinal change from baseline %predicted FVC to inform future trial designs and support decision making.
Isotopic homogeneity throughout the skin in small cetaceans
Authors: Arregui Marina , Josa Marta , Aguilar Alex , Borrell Asunción
Published: July 2017

Rationale

Isotope ratios from skin samples have been widely used to study cetacean trophic ecology. Usually, isotopic skin uniformity has been assumed, despite the heterogeneity of this tissue. This study aims to investigate (1) regional isotopic variation within the skin in cetaceans, and (2) isotopic variation among internal tissues.

Methods

Stable carbon (δ13C values) and nitrogen (δ15N values) isotope ratios were measured in 11 skin positions in 10 common dolphins (Delphinus delphis) and 9 striped dolphins (Stenella coeruleoalba). In addition, the isotope ratios in the muscle, liver and kidney of both species were determined and compared with those from the skin and from all tissues combined. The signatures were determined by means of elemental analyser/isotope ratio mass spectrometry (EA/IRMS).

Results

In both species, no differences between isotope ratios of the skin positions were found. Moreover, the isotope ratios of skin were similar to those of muscle. In contrast, liver and kidney showed higher isotope ratios than muscle and skin.

Conclusions

Isotopic homogeneity within the skin suggests that the isotope ratios of a sample from a specific skin position can be considered representative of the ratios from the entire skin tissue in dolphins. This conclusion validates the results of previous stable isotope analyses in dolphins that used skin samples as representative of the whole skin tissue. Isotopic similarities or dissimilarities among tissues should be considered when analysing different tissues and comparing results from the same or different species.
Dynamic modeling and nonlinear tracking control of a novel modified quadrotor
Authors: Tofigh Mohamad Ali , Mahjoob Mohamad J. , Ayati Moosa
Published: July 2017

In this article, a nonlinear tracking controller is designed based on Lyapunov stability for a novel aerial robot. The proposed 6‐rotor configuration improves stability and payload lifting capacity of the robot compared with conventional quadrotors while avoiding further complexities in the robot dynamics and steering principles. The dynamical model of the robot is derived using Newton‐Euler method. The model represents a nonlinear, coupled, and underactuated system. The proposed control strategy includes 2 main parts: an attitude controller and a position controller. Both the attitude and position controls are Lyapunov‐based nonlinear tracking controllers that guarantee the asymptotic convergence of the states' tracking errors to zero. Simulation results are presented to illustrate appropriate performance of the closed‐loop system in terms of position/attitude tracking even in the presence of wind disturbance.
Driving in search of analyses
Authors: Simons‐Morton Bruce
Published: July 2017

Although transportation safety has greatly improved over the past 2 decades, motor vehicle crash injuries remain a leading cause of morbidity and mortality, particularly among young drivers. Driver errors and behaviors such as speeding and distraction contribute disproportionately to crashes among inexperienced novices, who develop safe driving judgment only with substantial driving experience, commonly described as the “young driver problem.” Research on young drivers has applied a range of research methods, including analyses of national archival data (mainly from police reports), crash analyses, observation of driver behavior, surveys of driver behavior and dispositions, and experimental research on driver behavior and vehicle crash worthiness. Prominent research questions regarding young driver safety include what and how do novices learn to drive safely, what are the predictors of young driver crashes, what is the variability and overtime trajectories of young driver performance and outcomes, and to what extent is the young driver problem due mainly to average population risk or high‐risk groups? Current research on young drivers is complicated by small sample sizes, relatively rare events, high within and between group variability, missing data, the need to estimate exposure, and the lack of longitudinal and experimental designs, problems that require complex analytic methods. In this paper, we provide an overview of driving research methods, examples of research addressing the young driver problem, and examples of statistical collaboration on young driver research, focusing particularly on estimating prediction of crash risk and estimating variability in young driver performance and outcomes.
Acetylated Signal Transducer and Activator of Transcription 3 Functions as Molecular Adaptor Independent of Transcriptional Activity During Human Cardiogenesis
Authors: Mehta Ashish , Ramachandra Chrishan J. A. , Chitre Anuja , Singh Pritpal , Lua Chong Hui , Shim Winston
Published: July 2017

Activation of signal transducer and activator of transcription 3 (STAT3) is imperative for mammalian development, specifically cardiogenesis. STAT3 phosphorylation and acetylation are key post-translational modifications that regulate its transcriptional activity. Significance of such modifications during human cardiogenesis remains elusive. Using human pluripotent stem cells to recapitulate cardiogenesis, two independently modified STAT3α (92 kDa) isoforms (phosphorylated and acetylated), which perform divergent functions were identified during cardiomyocyte (CM) formation. Phosphorylated STAT3α functioned as the canonical transcriptional activator, while acetylated STAT3α underwent caspase-3-mediated cleavage to generate a novel STAT3ζ fragment (∼45 kDa), which acted as a molecular adaptor integral to the ErbB4-p38γ signaling cascade in driving CM formation. While STAT3α knockdown perturbed cardiogenesis by eliminating both post-translationally modified STAT3α isoforms, caspase-3 knockdown specifically abrogates the function of acetylated STAT3α, resulting in limited STAT3ζ formation thereby preventing nuclear translocation of key cardiac transcription factor Nkx2-5 that disrupted CM formation. Our findings show the coexistence of two post-translationally modified STAT3α isoforms with distinct functions and define a new role for STAT3 as a molecular adaptor that functions independently of its canonical transcriptional activity during human cardiogenesis.
The energy dispersive scheme of X‐ray fluorescence analysis with a crystal polarizer and polycapillary optics
Authors: Turyanskiy A.G. , Gizha S.S. , Senkov V.M. , Stanishevskiy Ya.M.
Published: July 2017

The efficiency of the polarization scheme based on polycapillary optics and a diamond crystal polarizer was demonstrated. The scheme provides suppression of the background of scattered radiation in measuring X‐ray fluorescence spectra. A quasi‐parallel X‐ray beam with an angular divergence of 4.2 mrad was formed by a microfocus source with a copper anode and polycapillary half‐lens. Simultaneous polarization and monochromatization of radiation was obtained with a crystal of natural diamond, which was set at the diffraction reflection (113). The degree of polarization of CuKα1 spectral line and the maximum radiation flux were respectively equal to 99.86% and 5 · 106 photon/s. In the direction orthogonal to the plane of diffraction, the maximum attenuation of the background was up to 19 dB.
The Moral Person of the State
Authors: Holland Ben
Published: July 2017

This is the first detailed study in any language of the single most influential theory of the modern state: Samuel von Pufendorf's account of the state as a 'moral person'. Ben Holland reconstructs the theological and political contexts in and for which Pufendorf conceived of the state as being a person. Pufendorf took up an early Christian conception of personality and a medieval conception of freedom in order to fashion a theory of the state appropriate to continental Europe, and which could head off some of the absolutist implications of a rival theory of state personality, that of Hobbes. The book traces the fate of the concept in the hands of others - international lawyers, moral philosophers and revolutionaries - until the early twentieth century. It will be essential reading for historians of political thought and for those interested in the development of key ideas in theology, international law and international relations.
The Neuroscience of Expertise
Authors: Bilalić Merim
Published: July 2017

The Neuroscience of Expertise examines the ways in which the brain accommodates the incredible feats of experts. It builds on a tradition of cognitive research to explain how the processes of perception, attention, and memory come together to enable experts' outstanding performance. The text explains how the brain adapts to enable the complex cognitive machinery behind expertise, and provides a unifying framework to illuminate the seemingly unconnected performance of experts in different domains. Whether it is a radiologist who must spot a pathology in a split second, a chess grandmaster who finds the right path in a jungle of possible continuations, or a tennis professional who reacts impossibly quickly to return a serve, The Neuroscience of Expertise offers insight into the universal cognitive and neural mechanisms behind these achievements.
National Security Secrecy
Authors: Setty Sudha
Published: July 2017

Excessive government secrecy in the name of counterterrorism has had a corrosive effect on democracy and the rule of law. In the United States, when controversial national security programs were run by the Bush and Obama administrations - including in areas of targeted killings, torture, extraordinary rendition, and surveillance - excessive secrecy often prevented discovery of those actions. Both administrations insisted they acted legally, but often refused to explain how they interpreted the governing law to justify their actions. They also fought to keep Congress from exercising oversight, to keep courts from questioning the legality of these programs, and to keep the public in the dark. Similar patterns have arisen in other democracies around the world. In National Security Secrecy, Sudha Setty takes a critical and comparative look at these problems and demonstrates how government transparency, privacy, and accountability should provide the basis for reform.
The Archaeology of Death in Roman Syria
Authors: de Jong Lidewijde
Published: July 2017

In the first centuries of the Common Era, an eclectic collection of plain and embellished underground and aboveground tombs filled the cemeteries of the Roman province of Syria. Its inhabitants used rituals of commemoration to express messages about their local identity, family, and social position, while simultaneously ensuring that the deceased was given proper burial rites. In this book, Lidewijde de Jong investigates these customs and the belief systems that governed the choices made in the commemoration of Syrian men, women and children. Presenting the first all-inclusive overview of the archaeology of death in Roman Syria, this book combines spatial analysis of cemeteries with the study of funerary architecture, decoration, and grave goods, as well as information about the deceased provided by sculptural, epigraphic, and osteological sources. It sheds a new light on life and death in Syria and offers a novel way of understanding provincial culture in the Roman Empire.
Genes, Determinism and God
Authors: Alexander Denis
Published: July 2017

Over the past centuries the pendulum has constantly swung between an emphasis on the role of either nature or nurture in shaping human destiny, a pendulum often energised by ideological considerations. In recent decades the flourishing of developmental biology, genomics, epigenetics and our increased understanding of neuronal plasticity have all helped to subvert such dichotomous notions. Nevertheless, the media still report the discovery of a gene 'for' this or that behaviour, and the field of behavioural genetics continues to extend its reach into the social sciences, reporting the heritability of such human traits as religiosity and political affiliation. There are many continuing challenges to notions of human freedom and moral responsibility, with consequent implications for social flourishing, the legal system and religious beliefs. In this book, Denis Alexander critically examines these challenges, concluding that genuine free will, often influenced by genetic variation, emerges from an integrated view of human personhood derived from contemporary biology.
Theatre and Governance in Britain, 1500–1900
Authors: Fisher Tony
Published: July 2017

This book begins with a simple observation - that just as the theatre resurfaced during the late Renaissance, so too government as we understand it today also began to appear. Their mutually entwining history was to have a profound influence on the development of the modern British stage. This volume proposes a new reading of theatre's relation to the public sphere. Employing a series of historical case studies drawn from the London theatre, Tony Fisher shows why the stage was of such great concern to government by offering close readings of well-known religious, moral, political, economic and legal disputes over the role, purpose and function of the stage in the 'well-ordered society'. In framing these disputes in relation to what Michel Foucault called the emerging 'art of government', this book draws out - for the first time - a full genealogy of the governmental 'discourse on the theatre'.
Electing Peace
Authors: Matanock Aila M.
Published: July 2017

Settlements to civil conflict, which are notably difficult to secure, sometimes contain clauses enabling the combatant sides to participate as political parties in post-conflict elections. In Electing Peace, Aila M. Matanock presents a theory that explains both the causes and the consequences of these provisions. Matanock draws on new worldwide cross-national data on electoral participation provisions, case studies in Central America, and interviews with representatives of all sides of the conflicts. She shows that electoral participation provisions, non-existent during the Cold War, are now in almost half of all peace agreements. Moreover, she demonstrates that these provisions are associated with an increase in the chance that peace will endure, potentially contributing to a global decline in civil conflict, a result which challenges prevailing pessimism about post-conflict elections. Matanock's theory and evidence also suggest a broader conception of international intervention than currently exists, identifying how these inclusive elections can enable external enforcement mechanisms and provide an alternative to military coercion by peacekeeping troops in many cases.
Carbohydrase enzymes improve performance of broilers fed both nutritionally adequate and marginal wheat-based diets
Authors: Wu D. , Choct M. , Wu S. B. , Liu Y. G. , Swick R. A.
Published: July 2017

A study was conducted to examine the effects of a multi-carbohydrase enzyme complex on the nutritive value of wheat in diets differing in nutrient density. It was hypothesised that response to enzyme inclusion would be greater in diets with lower nutrient density. The study was conducted using 1008 Ross 308 male broiler chicks (four treatments with seven replicate pens of 36 chicks). A 2 × 2 factorial arrangement of treatments was employed. Factors were adequate or low nutrient density with or without enzyme supplementation. The wheat-soybean meal based positive control (PC) diet was formulated to be nutritionally adequate in energy and digestible amino acids according to local industry recommendations. A negative control (NC) was formulated to have 80 kcal/kg less ME and 1.5% less digestible amino acids as compared to the PC. A multi-carbohydrase complex containing 19 carbohydrase activities derived from Penicillium funiculosum was added in both the PC and NC diets (Rovabio® Excel LC, Adisseo Asia Pacific Pte Ltd., Singapore). Birds fed the NC had 3.7 points (P < 0.05) poorer FCR than the PC. Across the diet type, enzyme supplementation increased body weight by 3.2% (P < 0.05) and improved FCR by 5.2 points (P < 0.01). There was no nutrient density x enzyme interaction (P > 0.05), indicating that performance improvement was independent of nutrient density. Apparent ileal digestibility of crude protein followed a similar trend, showing a 4.9% enhancement (P < 0.01) with the inclusion of the enzyme product in either diet. Enzyme supplementation reduced ileal viscosity by 39.0% (P < 0.05). It was concluded that multi-carbohydrase could overcome the negative effect in broiler performance brought by nutrient reduction, however, there was no indication that nutrient density affected bird response to supplementation of multi-carbohydrase.
ONE STEP FORWARD AND TWO STEPS BACK IN PRODUCT LIABILITY: THE SEARCH FOR CLARITY IN THE IDENTIFICATION OF DEFECTS
Authors: Eisler Jacob
Published: July 2017

PRODUCT liability law has struggled to develop a test for identifying when products are defective under the Consumer Protection Act 1987 (“CPA”). In Wilkes v Depuy International Ltd. [2016] EWHC 3096 (QB), Hickinbottom J. offered the most prolonged reflection on product defect since A v National Blood Authority [2001] EWHC 446 (QB), and rejected much of the framework of NBA. However, Wilkes provides little guidance regarding when products should be identified as being defective, reinforcing the need for a more deeply grounded approach.
Tianjin Mandarin
Authors: Li Qian , Chen Yiya , Xiong Ziyu
Published: July 2017

Tianjin Mandarin is a member of the northern Mandarin Chinese family (ISO 693-3: [cmn]). It is spoken in the urban areas of the Tianjin Municipality (CN-12) in the People's Republic of China, which is about 120 kilometers to the southeast of Beijing. Existing studies on Tianjin Mandarin have focused mainly on its tonal aspects, especially its intriguing tone sandhi system, with few studies examining the segmental aspects (on tone, see e.g. Li & Liu 1985, Shi 1986, Liu 1993, Lu 1997, Wang & Jiang 1997, Chen 2000, Liu & Gao 2003, Ma 2005, Ma & Jia 2006, Zhang & Liu 2011, Li & Chen 2016; on segmental aspects, see e.g. Han 1993a, b; Wee, Yan & Chen 2005). As also noted in Wee et al. (2005), this is probably due to the similarity in segmental structures between Tianjin Mandarin and Standard Chinese, especially among speakers of the younger generation, and what differentiates the two Mandarin varieties is most notably their tonal systems. The aim of the present description is therefore to provide a systematic phonetic description of both segmental and tonal aspects of Tianjin Mandarin, with main focus on the tonal aspects.