bluuebunny/crossref_metadata_2025 huggingface dataset:
Variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma POLG1 are not associated with increased risk for valproate‐induced hepatotoxicity or pancreatic toxicity: A retrospective cohort study of patients with epilepsy
Authors: Hynynen Johanna , Pokka Tytti , Komulainen‐Ebrahim Jonna , Myllynen Päivi , Kärppä Mikko , Pylvänen Laura , Kälviäinen Reetta , Sokka Arja , Jyrkilä Aino , Lähdetie Jaana , Haataja Leena , Mäkitalo Anna , Ylikotila Pauli , Eriksson Kai , Haapala Piia , Ansakorpi Hanna , Hinttala Reetta , Vieira Päivi , Majamaa Kari , Rantala Heikki , Uusimaa Johanna
Published: September 2018

Objective

Previous studies have suggested that heterozygous variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma (POLG1) increase the risk for liver injury for patients on valproate (VPA) therapy. We assessed the prevalence of these common variants and seven other pathogenic mutations in POLG1 and determined the occurrence of VPA‐induced hepatotoxicity (VHT) or pancreatic toxicity in a cohort of patients with epilepsy.

Methods

Patients with epilepsy (N = 367) were retrospectively identified from medical record files and screened for mutations in POLG1. Patients who had received VPA monotherapy and carried either of the two variants, p.Q1236H or p.E1143G, without other pathogenic mutations in POLG1 (n = 33, variant group) and patients without these variants (n = 28, nonvariant group) were included in the study. Clinical data on epilepsy, characteristics of VPA treatment, risk factors for VHT, laboratory data on liver and pancreas functions, and adverse effects were collected.

Results

A total of 122 patients had either the POLG1 p.Q1236H (n = 99) or p.E1143G (n = 24) variant in the heterozygous or homozygous state. Transient liver dysfunction was identified in three (n = 33, 9.1%) variant group patients and in one (n = 28, 3.6%) nonvariant group patient (P = 0.62). Mild to moderate elevations in liver enzymes were encountered in both groups. Furthermore, two patients on VPA polytherapy developed acute pancreatitis, and two pediatric patients with heterozygous p.Q1236H variants and mutations in IQSEC2 and GLDC, respectively, had elevated levels of VPA metabolites in urine, elevated plasma glycine, and/or increased acylglycine excretion.

Significance

POLG1 p.Q1236H and p.E1143G variants could not be identified as statistically significant risk factors for VHT or pancreatic toxicity. We suggest that VPA treatment could be suitable for patients who harbor these common variants in the absence of other pathogenic mutations in POLG1.
Pharmacokinetics and ex vivo anti‐inflammatory effects of oral misoprostol in horses
Authors: Martin E. M. , Schirmer J. M. , Jones S. L. , Davis J. L.
Published: September 2018

Background

Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and preventNSAID‐inducedGIinjury in horses. Misoprostol elicits anti‐inflammatory effects in vivo in men and rodents, and inhibitsTNFα production in equine leucocytes in vitro.

Objective

Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyteTNFα production in an ex vivo inflammation model.

Study design

Pharmacokinetic study, ex vivo experimental study.

Methods

Six healthy adult horses of mixed breeds were used. In phase one, horses were given 5 μg/kg misoprostol orally, and blood was collected at predetermined times for determination of misoprostol free acid (MFA) byUHPLC‐MS/MS. Pharmacokinetic parameters were calculated. In phase two, horses were dosed as in phase one, and blood was collected at T0, 0.5, 1 and 4 h following misoprostol administration for leucocyte isolation. Leucocytes were stimulated with 100 ng/mLLPS, andTNFαmRNAconcentrations were determined via quantitative real‐time PCR.

Results

About 5 μg/kg oral misoprostol produced a rapid time to maximum concentration (Tmax) of 23.4 ± 2.4 min, with a maximum concentration (Cmax) of 0.29 ± 0.07 ng/mL and area under the curve (AUC0−∞) of 0.4 ± 0.12 h ng/mL.LPSstimulation of equine leucocytes ex vivo significantly increasedTNFαmRNAconcentrations, and there was no significant effect of misoprostol even at the Tmax.

Main limitations

Only a single dose was used, and sample size was small.

Conclusions

Misoprostol is rapidly absorbed following oral administration in horses, and a single 5 μg/kg dose had no significant inhibitory effect on ex vivoLPS‐stimulatedTNFαmRNAproduction in leucocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti‐inflammatory drugs, are warranted.
Effect of calcination temperature on friction and wear behavior of α–alumina (α‐Al2O3) for biomedical applications
Authors: Fellah Mamoun , Aissani Linda , Abdul Samad Mohammed , Prakasam Mythili , Purnama Agung , Montagne Alex , IOST Alain , Mejias Alberto , Kossman Stephania
Published: September 2018

In this study, structural evolution, sliding friction, and wear behavior of the nano‐sized alpha‐alumina (α‐Al2O3), synthesized by calcination of gibbsite (Al2(OH)6) at different temperatures (273‐1473 K) are reported using X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), Scanning electron microscopy (SEM), and ball‐on‐disk wear tests. The effect of calcination temperature and the correlation between grain size, mechanical properties, and tribological behavior of the compounds are investigated. After calcination at 1473 K, the crystallite size of calcined and sintered alumina (α‐Al2O3) compacts is as small as 10 nm. Also, it is observed that the average particle and grain size significantly affect the tribological properties of the compounds. At all the applied loads of 2, 8, and 16 N, respectively, the sliding wear rate and coefficient of friction were lower in the alumina compacts calcined at 1473 K. The improved tribological properties are attributed to the finer microstructure resulting in enhanced hardness of the sintered compacts calcined at 1473 K.
Do fine feathers make a fine bird? The influence of attractiveness on fraud‐risk judgments by internal auditors
Authors: Eulerich Marc , Theis Jochen C. , Lao Junpeng , Ramon Meike
Published: September 2018

Independence and objectivity are key principles assumed to underlie internal auditors' fraud‐risk judgments. However, a substantial body of evidence suggests that physical attractiveness of suspects may influence internal auditors' fraud‐risk judgments. In this experimental study we investigated whether internal auditors are susceptible to appearance‐related biases, or whether they correct for them due to their expertise and motivation. A total of 193 internal auditors were presented a misappropriation‐of‐assets scenario in which the attractiveness of a suspect was manipulated. To determine whether professional expertise is associated with increased resilience to appearance‐related biases, their fraud‐risk judgments were contrasted with those acquired from 240 subjects without auditing experience (“naive subjects”). In line with our predictions, attractiveness modulated naive subjects' fraud‐risk judgments, whereas internal auditors did not show any indication for appearance‐related biases. Our findings suggest that internal auditors' experience and motivation may immunize them to the phenomena of physical attractiveness stereotyping and the attractiveness halo effect.
Antineutrophil cytoplasmic antibodies negative levamisole‐induced leukocytoclastic vasculitis: a presumed case and literature review
Authors: Kunzler Daniel , Lagrimas Lauren , Vo Thiennga , DeCrescenzo Andrew , Kaltwasser Kyle , Wilson Janice
Published: September 2018

Levamisole‐contaminated cocaine toxicity is a serious emerging public health concern, and providers should be aware of its presentation and management. Most cases of levamisole‐induced vasculitis/vasculopathy (LIV) are associated with high antineutrophil cytoplasmic antibodies (ANCA). We describe a unique case of a cocaine user who presented with an acute purpuric eruption and negative ANCA laboratory findings. A brief clinical overview of LIV, spanning from patient presentation to treatment, is provided. In addition, we present a summary of all cases of ANCA‐negative vasculitis identified via a PubMed literature review.
Hypothesis: Caco‐2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts
Authors: Zheng Gen , Kalinin Alexandr A. , Dinov Ivo D. , Meixner Walter , Zhu Shengtao , Wiley John W.
Published: September 2018

Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco‐2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco‐2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single‐ to multi‐cell ring/torus‐shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well‐described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders.
Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy
Authors: Sai Buqing , Xiang Juanjuan
Published: September 2018

Accumulating evidence indicates that cancer cells spread much earlier than was previously believed. Recent technological advances have greatly improved the detection methods of circulating tumour cells (CTCs), suggesting that the dissemination of cancer cells into the circulation occurs randomly. Most CTCs die in circulation as a result of shear stress and/or anoikis. However, the persistence of disseminated tumour cells (DTCs) in the bone marrow is the result of interaction of DTCs with bone marrow microenvironment. DTCs in the bone marrow undergo successive clonal expansions and a parallel progression that leads to new variants. Compared to the CTCs, DTCs in the bone marrow have a unique signature, which displayed dormant, mesenchymal phenotype and osteoblast‐like or osteoclast‐like phenotype. The persistence of DTCs in the bone marrow is always related to minimal residual diseases (MRDs). This review outlines the difference between CTCs and DTCs in the bone marrow and describes how this difference affects the clinical values of CTCs and DTCs, such as metastasis and recurrence. We suggest that DTCs remaining in the bone marrow after therapy can be used as a superior marker in comparison with CTCs to define patients with an unfavourable prognosis and may therefore be a potential prognostic factor and therapeutic target for cancer therapy.
Increase of PRPP enhances chemosensitivity of PRPS1 mutant acute lymphoblastic leukemia cells to 5‐Fluorouracil
Authors: Wang Dan , Chen Yao , Fang Houshun , Zheng Liang , Li Ying , Yang Fan , Xu Yan , Du Lijuan , Zhou Bin‐Bing S. , Li Hui
Published: September 2018

Relapse‐specific mutations in phosphoribosyl pyrophosphate synthetase 1 (PRPS1), a rate‐limiting purine biosynthesis enzyme, confer significant drug resistances to combination chemotherapy in acute lymphoblastic leukemia (ALL). It is of particular interest to identify drugs to overcome these resistances. In this study, we found that PRPS1 mutant ALL cells specifically showed more chemosensitivity to 5‐Fluorouracil (5‐FU) than control cells, attributed to increased apoptosis of PRPS1 mutant cells by 5‐FU. Mechanistically, PRPS1 mutants increase the level of intracellular phosphoribosyl pyrophosphate (PRPP), which causes the apt conversion of 5‐FU to FUMP and FUTP in Reh cells, to promote 5‐FU‐induced DNA damage and apoptosis. Our study not only provides mechanistic rationale for re‐targeting drug resistant cells in ALL, but also implicates that ALL patients who harbor relapse‐specific mutations of PRPS1 might benefit from 5‐FU‐based chemotherapy in clinical settings.
Longitudinal structural brain development and externalizing behavior in adolescence
Authors: Bos Marieke G.N. , Wierenga Lara M. , Blankenstein Neeltje E. , Schreuders Elisabeth , Tamnes Christian K. , Crone Eveline A.
Published: September 2018

Background

Cross‐sectional studies report relations between externalizing behavior and structural abnormalities in cortical thickness of prefrontal regions and volume reductions in subcortical regions. To understand how these associations emerge and develop, longitudinal designs are pivotal.

Method

In the current longitudinal study, a community sample of children, adolescents and young adults (N = 271) underwent magnetic resonance imaging (MRI) in three biennial waves (680 scans). At each wave, aspects of externalizing behavior were assessed with parent‐reported aggression and rule‐breaking scores (Child Behavior Checklist), and self‐reported aggression scores (Buss‐Perry Aggression Questionnaire). Regions of interest (ROIs) were selected based on prior research: dorsolateral prefrontal (dlPFC), orbitofrontal (OFC), anterior cingulate cortex (ACC), insula, and parahippocampal cortex, as well as subcortical regions. Linear mixed models were used to assess the longitudinal relation between externalizing behavior and structural brain development. Structural covariance analyses were employed to identify whether longitudinal relations between ROIs (maturational coupling) were associated with externalizing behavior.

Results

Linear mixed model analyses showed a negative relation between parent‐reported aggression and right hippocampal volume. Moreover, this longitudinal relation was driven by change in hippocampal volume and not initial volume of hippocampus at time point 1. Exploratory analyses showed that stronger maturational coupling between prefrontal regions, the limbic system, and striatum was associated with both low and high externalizing behavior.

Conclusions

Together, these findings reinforce the hypothesis that altered structural brain development coincides with development of more externalizing behavior. These findings may guide future research on normative and deviant development of externalizing behavior.
Wholesale price discrimination: Innovation incentives and upstream competition
Authors: Akgün Uğur , Chioveanu Ioana
Published: September 2018

In intermediate good markets where there are alternative supply sources, wholesale price discrimination may enhance innovation incentives downstream. We consider a vertical chain where a dominant firm and a competitive fringe supply imperfect substitutes to duopoly retailers which carry both varieties. We show that a ban on price discrimination by the dominant supplier makes uniform pricing credible and reduces retailers’ incentives to decrease the cost of acquiring the competitively supplied variety, leading to higher upstream profits and lower downstream welfare. Our analysis complements existing results by identifying a novel channel through which wholesale price discrimination can improve dynamic market efficiency.
Ultrasound assisted enzymolysis of sunflower meal protein: Kinetics and thermodynamics modeling
Authors: Dabbour Mokhtar , He Ronghai , Mintah Benjamin , Tang Yingxiu , Ma Haile
Published: September 2018

This study examined the effect of dual‐frequency ultrasound (DFU) pretreatment on thermodynamics and kinetics of sunflower‐meal protein (SMP) using alcalase to improve efficiency in enzymolysis process. The concentration of hydrolyzed protein and kinetic parameters after traditional pretreatment (control) were investigated and compared with DFU‐assisted enzymolysis. The results indicated that DFU‐pretreatment enhanced SMP‐enzymolysis efficiency at different substrate and enzyme concentrations, temperature, and pH. Kinetics analysis showed DFU‐pretreatment reduced the Michaelis constant by 11.29%, while the apparent breakdown rate constant increased by 1.96%, indicating DFU‐pretreatment improved the affinity among substrate and enzyme. The rate constants for DFU‐pretreatment were increased by 45.96, 26.92, 21.14, and 27.89% at 293, 303, 313, and 323 K, respectively (p < .05). On Arrhenius kinetics, DFU reduced the activation energy, enthalpy and entropy by 24.28, 26.13, and 9.10%, respectively (p < .05). DFU had slight influence on Gibbs‐free energy when temperature increased from 293 to 323 K.

Practical applications

The positive impact of DFU pretreatment of sunflower meal protein on enzymatic hydrolysis kinetics makes this method suitable for use in the pharmaceutical and food process industries to yield peptides from residues of oil industry.
An assessment of the optimum timing of coastal flood adaptation given sea‐level rise using real options analysis
Authors: Kim Myung‐Jin , Nicholls Robert J. , Preston John M. , de Almeida Gustavo A. M.
Published: September 2018

There is large uncertainty about the changing magnitude and occurrence of coastal flood events with sea‐level rise; which poses significant challenges to adaptation planning. Recent decision‐making employs flexible options that can be modified/adjusted over time to address uncertainty. This research analyses a real option based method for assessing adaptation investment timing under coastal flooding and sea‐level rise. This method recognises and values the flexibility of waiting as an additional adaptation option under an uncertain future, that is, the key question concerns when the option is best implemented? Real options are applied using a test‐case in Lymington (UK), a floodprone coastal town. Our findings show that the option value (i.e., the net value of the overall benefit minus cost) grows with rising sea level to a maximum, which is the optimal time for the adaptation investment. The optimum investment time tends to occur at the same magnitude of sea‐level rise (relative to 1990) across most sea‐level rise scenarios for the same socio‐economic scenario. Hence, monitoring sea‐level rise provides important information to plan adaptation. The analysis provides an analytical framework on how and when to implement the adaptation option given the various future scenarios which can be developed further.
Nonthermal pasteurization of onion juice by continuous UV‐C reactor
Authors: Demir Hande , Oral Mehmet Onur
Published: September 2018

The objective of this study is to investigate the continuous pasteurization of onion (Allium cepa L.) juice by ultraviolet (UV‐C) irradiation by a designed coiled‐tube type UV‐C reactor. System is composed of four vertical low‐pressure mercury lamps (20 W/lamp, 254 nm) coiled using a PTFE tube. A secondary eddy flow effect was achieved with a Dean number of 0.073. The Escherichia coli K‐12 count in onion juice was reduced by 4.83 log after exposure to UV‐C light for 8.13 min at an estimated UV‐C dosage of 38.1 J/mL with the flow rate of 1.26 L/min. After UV‐C treatment, the total color change (ΔE) of the onion juice was recorded as 1.15 which can be referred as slightly noticeable. Total aerobic mesophilic count of UV‐C irradiated samples was below acceptable limits after 6 weeks of storage. Meat marination in UV‐C‐treated onion juice reduced the hardness of meat by 78%.

Practical applications

Currently, many of the large‐scale processed meat producers prefer to marinate the meat directly in the onion juice or in a sauce formulation including onion juice. Therefore, they are the major end‐users of this product. In addition, onion juice has a large potential to be used by the catering industry providing food service for relatively large number of people. If the storage space for onions, the preparation, and service time for the meals are taken into consideration, catering services may highly benefit from the pasteurized onion juice products. Conventional heat treatment is the most common method to extend shelf‐life of vegetable juices. The results of this study indicated that continuous UV‐C irradiation can successfully be used to pasteurize onion juice. The outcomes will also serve the basis to technical knowledge for designing the pilot‐scale production of onion juice processed by nonthermal treatments.
Nociceptin/orphanin FQ opioid peptide‐receptor expression in pachyonychia congenita
Authors: Pan Baohan , Schröder Wolfgang , Jostock Ruth , Schwartz Mary , Rosson Gedge , Polydefkis Michael
Published: September 2018

Nociceptin/orphanin FQ opioid peptide (NOP)‐receptor (NOP‐R) is a member of the opioid receptor family. NOP‐R activation has demonstrated analgesic effects in preclinical pain models without the addiction risks associated with other opiate targets. Pachyonychia congenita (PC) is a palmoplantar keratoderma characterized by neuropathic pain in affected skin. A cohort of KRT6A gene mutation PC patients with no other explanation for their neuropathic pain offered a unique opportunity to assess potential of NOP‐R as a therapeutic target. Plantar biopsies from 10 PC patients and 10 age/gender matched controls were performed at the ball (PC‐affected) and the arch (PC‐unaffected) of the foot. NOP‐R expression was assessed by immunohistochemistry. Localization of NOP‐R in subsets of epidermal nerve fibers was investigated using the pan‐neuronal marker PGP9.5, markers for unmyelinated peptidergic fibers (calcitonin gene‐related peptide [CGRP] and substance P [SP]), as well as for myelinated Aδ and Aβ fibers (neurofilament H [NFH]). Robust NOP‐R expression was detected in epidermal keratinocytes and in a subset of PGP9.5+ fibers in both epidermis and dermis, confirmed by western blot and absorption experiments with NOP‐R peptide. NOP‐R expression in keratinocytes was significantly reduced in PC‐affected plantar skin compared with PC‐unaffected skin. In addition, NOP‐R expression occurred in dermal NFH+ myelinated fibers in all groups, although few CGRP+ fibers co‐expressed NOP‐R. Furthermore, most SP+ fibers also co‐expressed NOP‐R. These findings indicate that NOP‐R is expressed on epidermal keratinocytes, as well as on epidermal and dermal nerve fibers and has potential as a promising target to treat neuropathic pain in PC.
Unspanned stochastic volatility in the multifactor CIR model
Authors: Filipović Damir , Larsson Martin , Statti Francesco
Published: September 2018

Empirical evidence suggests that fixed‐income markets exhibit unspanned stochastic volatility (USV), that is, that one cannot fully hedge volatility risk solely using a portfolio of bonds. While Collin‐Dufresne and Goldstein (2002, Journal of Finance, 57, 1685–1730) showed that no two‐factor Cox–Ingersoll–Ross (CIR) model can exhibit USV, it has been unknown to date whether CIR models with more than two factors can exhibit USV or not. We formally review USV and relate it to bond market incompleteness. We provide necessary and sufficient conditions for a multifactor CIR model to exhibit USV. We then construct a class of three‐factor CIR models that exhibit USV. This answers in the affirmative the above previously open question. We also show that multifactor CIR models with diagonal drift matrix cannot exhibit USV.
A Multivariate Computational Framework to Characterize and Rate Virtual Portland Cements
Authors: Tao Chengcheng , Watts Benjamin , Ferraro Christopher C. , Masters Forrest J.
Published: September 2018

This article presents a novel application of metaheuristic optimization and rating techniques to virtual test results for cement and mortar, and presents objective computational methods for the evaluation and selection of cementitious materials based on simulated material testing. A scalable approach based on particle swarm optimization of the National Institute of Standards and Technology Virtual Cement and Concrete Testing Laboratory (VCCTL) is successfully demonstrated using ∼150,000 combinations of cement phase distributions and water‐to‐cement ratios, with as few as 10% of the VCCTL runs required to obtain the optimal solutions. The application of Pareto front analysis reveals an inherent trade‐off between the modulus of elasticity, time of set, and kiln temperature (using alite:belite as a proxy) at the performance limits. This study also provides a means to objectively characterize cements in these contexts using a maximum likelihood estimator to calculate a score from the cumulative distribution function, using a random subset of the 150,000 simulated cement pastes. The proposed approach provides a new pathway to optimally proportion raw materials (and eventually waste by‐products) to reduce production costs, extend the life of a quarry, or reduce the carbon footprint of cement plants.
Influences of immunostimulants on phagocytes in cultured fish: a mini review
Authors: Abarike Emmanuel D. , Kuebutornye Felix K.A. , Jian Jichang , Tang Jufen , Lu Yishan , Cai Jia
Published: September 2018

Lower vertebrates like fish mostly depend on innate immunity as the first line of defence against invading pathogens. One of the defence mechanisms in innate immunity for fish is the use of phagocytic cells such as monocytes, macrophages, neutrophils, mast cells and dendritic cells in fighting pathogens. These cellular cells employ a variety of mechanisms in protecting fish including but not limited to; the use of pattern recognition receptors and antigen presenting cells to detect the presence of pathogens in host, neutralising them using measures including; inflammation, production of lysosomal enzymes released into the phagosome to neutralising pathogens and prevention of systemic autoimmunity by apoptosis. Some phagocytic cells play the extra role of serving as a bridge between innate and adaptive immunity in fish. Recent accumulating data showed that phagocyte cell activity in fish could be enhanced by a natural or chemical substance (immunostimulants) that stimulates the immune system in fish principally meant to enhance the immune response mechanisms. In this review, the main focus is on elucidating the distinct phagocytic mechanisms played by monocytes, macrophages, neutrophils, mast cells and dendritic cells as principal phagocytes in immune defence and how their activities are influenced by immunostimulants in cultured fish.
Numbers in regulatory intermediation: Exploring the role of performance measurement between legitimacy and compliance
Authors: Mehrpouya Afshin , Samiolo Rita
Published: September 2018

Much regulatory intermediation has come to entail forms of calculation and performance measurement. In this paper we analyze the role of performance measurement in regulatory intermediation in a transnational multistakeholder setting where intermediation lacks an official mandate. We do this through a study of the Access to Medicine Index, which ranks pharmaceutical companies in terms of their access to medicine policies and practices in developing countries. We conceptualize multistakeholder intermediaries as “second order rulemakers” reconciling diverse and often competing implicit and explicit rules across the governance field. We then detail various intermediation roles of performance measurement between attaining input and output legitimacy and enticing compliance among targets. Our case demonstrates how the selective formalization of measurement processes and the related ability to move back and forth from the role of intermediary to that of “ad hoc rulemaker” are important conditions for achieving and maintaining legitimacy. Furthermore, it shows that for multistakeholder intermediaries that rely on performance measurement, compliance by targets depends on the uptake of performance information by powerful constituencies. This illustrates how addressing legitimacy concerns and enticing compliance through performance measurement should be examined as co‐emerging processes.
Residential segregation and educational attainment of children from regional migrant families in China
Authors: Ma Xiangjun , Zhou Yean
Published: September 2018

This paper studies the residential segregation effects on educational attainment of children from regional migrant families in China. We find that if migrant families live in segregated communities with fewer local residents, the school dropout rate of the children living with their parents in the host cities is higher and their high school enrollment rate is lower. We employ a unique set of nationwide survey data of regional migrants in China in 2012 and 2013 that comprises more than 150,000 individuals in each year. We first use the ratio of migrants over the total population residing in a community to measure segregation. When the ratio increases by 10%, the school dropout rate of migrant children increases by 4.7% from the mean value. Secondly, we identify segregation from the housing type of the migrant family. When they reside in the dorms provided by their employers or in the workplace, they will also be surrounded by many migrant colleagues. We find that living in such places increases the “not‐going‐to‐high‐school rate” of migrant children by 35% from the mean value. Our subsample analysis indicates that the segregation effects only exist in the samples of male migrant children and rural hukou families.
Assessment of the common carotid artery wall stiffness by Shear Wave Elastography in Behcet’s disease
Authors: Alis Deniz , Durmaz Emine Sebnem Memis , Civcik Ceren , Tutuncu Melih , Saip Sabahattin , Kocer Naci , Islak Civan , Kizilkilic Osman
Published: September 2018

Aim: To evaluate endothelial dysfunction and subclinical atherosclerosis in Behcet’s disease (BD) by measuring the common carotid artery (CCA) wall stiffness and carotid intima-media thickness (CIMT).Materials and methods: We prospectively evaluated CIMT and the CCA wall stiffness of 34 BD patients and 28 age/sex-matched controls. CIMT measurements were performed from the posterior wall of the carotid artery approximately 10 mm proximal to the initiation of the carotid bulb using B-mode ultrasound. The stiffness of the CCA was measured from the superficial wall of the CCA using shear wave elastography (SWE). SWE measurements were recorded as shear wave velocity (SWV) using m/s as a unit.Results: The mean right (0.5±0.11 mm) and left (0.5±0.14 mm) CIMT of the patients were significantly higher compared to the mean right (0.41±0.07 mm) and left (0.41±0.11 mm) CIMT of the healthy controls (p=0.001 and p= 0.003 respectively). The mean right (3.72±0.94 m/s) and left (3.57±0.72 m/s) CCA wall stiffness of the patients were significantly higher compared to the mean right (2.42±0.49 m/s) and left (2.56±0.49 m/s) CCA wall stiffness of the controls (p<0.001 for both).Conclusions: SWE seems to be a promising modality to evaluate endothelial dysfunction in BD by interpreting the arterial stiffness, and SWE might be an important adjunct to clinical and laboratory findings, and imaging modalities to assess cardiovascular risk in BD. Moreover, SWE evaluation of the arterial stiffness might assist us to understand pathophysiological aspects of BD.
Evaluating biological activity of compounds by transcription factor activity profiling
Authors: Medvedev Alexander , Moeser Matt , Medvedeva Liubov , Martsen Elena , Granick Alexander , Raines Lydia , Zeng Ming , Makarov Sergei , Houck Keith A. , Makarov Sergei S.
Published: September 2018

Transcription factor activity profiling reveals invariant signatures of perturbed biological pathways and cell systems.
Flagellar number governs bacterial spreading and transport efficiency
Authors: Najafi Javad , Shaebani Mohammad Reza , John Thomas , Altegoer Florian , Bange Gert , Wagner Christian
Published: September 2018

We show that the flagellar number affects the intrinsic dynamics of swimming bacteria and governs their transport efficiency.
A new fossil assemblage shows that large angiosperm trees grew in North America by the Turonian (Late Cretaceous)
Authors: Jud Nathan A. , D’Emic Michael D. , Williams Scott A. , Mathews Josh C. , Tremaine Katie M. , Bhattacharya Janok
Published: September 2018

Fossils from Utah show large flowering trees evolved at least 15 million years earlier than previously thought.
Large regional shortwave forcing by anthropogenic methane informed by Jovian observations
Authors: Collins William D. , Feldman Daniel R. , Kuo Chaincy , Nguyen Newton H.
Published: September 2018

Methane also heats the climate system by absorbing sunlight, and the absorption is maximized over bright clouds and deserts.
Evidence for precision grasping in Neandertal daily activities
Authors: Karakostis Fotios Alexandros , Hotz Gerhard , Tourloukis Vangelis , Harvati Katerina
Published: September 2018

Contrary to common assumptions, Neandertal habitual behavior relied mainly on manual precision rather than brute grip force.
Facile profiling of molecular heterogeneity by microfluidic digital melt
Authors: O’Keefe Christine M. , Pisanic Thomas R. , Zec Helena , Overman Michael J. , Herman James G. , Wang Tza-Huei
Published: September 2018

Digital microfluidic technology enables profiling of genetic and epigenetic differences within tumors or cells.
Manta rays feed using ricochet separation, a novel nonclogging filtration mechanism
Authors: Divi Raj V. , Strother James A. , Paig-Tran E. W. Misty
Published: September 2018

Experimental and computational fluid dynamics indicate that manta rays use a novel filtration mechanism for feeding.
A unique role for DNA (hydroxy)methylation in epigenetic regulation of human inhibitory neurons
Authors: Kozlenkov Alexey , Li Junhao , Apontes Pasha , Hurd Yasmin L. , Byne William M. , Koonin Eugene V. , Wegner Michael , Mukamel Eran A. , Dracheva Stella
Published: September 2018

DNA hydroxymethylation is a distinctive epigenetic regulator of human inhibitory neurons, potentially affecting brain diseases.
Survival of Extremophilic Yeasts in the Stratospheric Environment during Balloon Flights and in Laboratory Simulations
Authors: Pulschen André Arashiro , de Araujo Gabriel Guarany , de Carvalho Ana Carolina Souza Ramos , Cerini Maria Fernanda , Fonseca Lucas de Mendonça , Galante Douglas , Rodrigues Fabio
Published: September 2018

Studies of eukaryotic microorganisms under conditions of astrobiological relevance, as well as the aerial dispersion potential of extremophilic yeasts, are still lacking in the literature compared to works with bacteria. Using stratospheric balloon flights and a simulation chamber, we demonstrate that yeasts isolated from an extreme environment are capable of surviving all stressors found in the stratosphere, including intense UV irradiation, scoring an even higher survival than
B. subtilis
spores. Notably, the yeast
N. friedmannii
, which displayed one of the highest tolerances to the stratospheric environment in the experiments, was recently proposed to be adapted to airborne transportation, although such a hypothesis had not yet been tested. Our results strengthen such an assumption and can help explain the observed distribution and ecology of this particular yeast species.
Coassembly of SecYEG and SecA Fully Restores the Properties of the Native Translocon
Authors: Bariya Priya , Randall Linda L.
Published: September 2018

This work presents a comprehensive quantification of the parameters of transport by the Sec general secretory system in the three
in vitro
systems. The standard reconstitution used by most investigators can be enhanced to yield six times as many active translocons simply by adding SecA to SecYEG during reconstitution. This robust system faithfully reflects the properties of translocation in native membrane vesicles. We have expanded the number of precursors studied to nine. This has allowed us to conclude that the rate constant for translocation varies with precursor species.
Expression of Human Cytomegalovirus IE1 Leads to Accumulation of Mono-SUMOylated PML That Is Protected from Degradation by Herpes Simplex Virus 1 ICP0
Authors: Hou Wangheng , Cruz-Cosme Ruth , Wen Fayuan , Ahn Jin-Hyun , Reeves Inez , Luo Min-Hua , Tang Qiyi
Published: September 2018

Our finding that HCMV IE1 protected hPML from degradation by HSV ICP0 is important, because the PML body (aka ND10) is believed to be the first line of host intrinsic defense against herpesviral infection. How the infected viruses overcome the nuclear defensive structure (PML body) has not been fully understood. Herpesviral proteins, ICP0 of HSV and IE1 of CMV, have been identified to interact with PML. Here, we report that HCMV IE1 incompletely deSUMOylated PML, resulting in the mono-SUMOylated PML, which is consistent with the report of Schilling et al. (J Virol 91:e02049-16, 2017,
https://doi.org/10.1128/JVI.02049-16
). The mono-SUMOylated PML was subjected to degradation by HSV ICP0. However, it was protected by IE1 from degradation by ICP0 or HSV-1 infection. In contrast, IE1 with L174P mutation lost the function of deSUMOylating PML and failed to protect the degradation of the mono-SUMOylated PML. Whether the mono-SUMOylated PML has any defensive function against viral infection will be further investigated.
Complete Genome Sequences of Historic Clostridioides difficile Food-Dwelling Ribotype 078 Strains in Canada Identical to That of the Historic Human Clinical Strain M120 in the United Kingdom
Authors: Kumar Anand , Davenport Karen Walston , Vuyisich Grace , Kunde Yuliya A. , Johnson Shannon Lyn , Chain Patrick Sam Guy , Dichosa Armand Earl Ko , Rodriguez-Palacios Alex
Published: September 2018

Clostridioides
(
Clostridium
)
difficile
is a spore-forming anaerobic bacterium that causes severe intestinal diseases in humans. Here, we report the complete genome sequence of the first
C. difficile
foodborne type strain (PCR ribotype 078) isolated from food animals in Canada in 2004, which has 100% similarity to the genome sequence of the historic human clinical strain M120.
Genome Sequence of Chiqui Virus, a Novel Reovirus Isolated from Mosquitoes Collected in Colombia
Authors: Contreras-Gutiérrez María Angélica , Guzman Hilda , Cardoso Jedson F. , Popov Vsevolod L. , Nunes Marcio R. T. , Uribe Sandra , Widen Steven G. , Wood Thomas G. , Vasilakis Nikos , Tesh Robert B.
Published: September 2018

We report here the complete genome sequence of a novel reovirus, designated Chiqui virus (CHQV) strain CoB38d, that was isolated from a pool of unidentified mosquitoes collected in northern Colombia in 2013. CHQV has nine double-stranded DNA (dsRNA) genome segments and has similarity to viruses belonging to the family
Reoviridae
, subfamily
Spinareovirinae
.
Complete Genome Sequence of Avian Pathogenic Escherichia coli Strain APEC O2-211
Authors: Nielsen Daniel W. , Mangiamele Paul , Ricker Nicole , Barbieri Nicolle L. , Allen Heather K. , Nolan Lisa K. , Logue Catherine M.
Published: September 2018

Avian pathogenic
Escherichia coli
(APEC) is the causative agent of colibacillosis, a disease that affects poultry production worldwide and leads to multimillion-dollar losses annually. Here, we report the genome sequence of APEC O2-211, a sequence type 117 (ST117) strain isolated from a diseased chicken.
First Reported Complete Genome Sequence of a Dengue Virus Serotype 4 Strain from Papua New Guinea
Authors: Pyke Alyssa T. , Moore Peter R. , Hewitson Glen , Burtonclay Peter
Published: September 2018

A male patient in his 50s who traveled from Papua New Guinea (PNG) to Australia in 2016 was diagnosed with a dengue virus serotype 4 (DENV-4) infection, and the virus was isolated from his acute-phase serum. Here, we describe the first complete genome sequence of a DENV-4 strain from PNG.
Complete Genome Sequence of an Efficient Vitamin D
3
-Hydroxylating Bacterium, Pseudonocardia autotrophica NBRC 12743
Authors: Yoshida Keitaro , Yasutake Yoshiaki , Tamura Tomohiro
Published: September 2018

Pseudonocardia autotrophica
NBRC 12743 contains a cytochrome P450 vitamin D
3
hydroxylase, and it is used as a biocatalyst for the commercial production of hydroxyvitamin D
3
, a valuable compound for medication. Here, we report the complete genome sequence of
P. autotrophica
NBRC 12743, which could be useful for improving the productivity of hydroxyvitamin D
3
.
Draft Genome Sequence of Taylorella equigenitalis Strain 210217RC10635, Isolated from a Pony Stallion in Germany
Authors: Melzer Falk , Raßbach Astrid , Köenig-Mozes Astrid , Elschner Mandy Carolina , Tomaso Herbert , Busch Anne
Published: September 2018

Here, we report the draft genome sequence of
Taylorella equigenitalis
strain 210217RC10635, a Gram-negative bacterium belonging to the genus
Taylorella
and the order
Burkholderiales
.
Taylorella equigenitalis
is the causative agent of contagious equine metritis (CEM).
Draft Genome Sequences of Violacein-Producing Duganella sp. Isolates from a Waterway in Eastern Pennsylvania
Authors: Lamendella Regina , Jude Brooke A.
Published: September 2018

Five
Duganella
sp. bacterial isolates that synthesize violacein were cultured from a central Pennsylvania waterway.
Electroacupuncture Ameliorates Cognitive Impairment through Inhibition of Ca2+-Mediated Neurotoxicity in a Rat Model of Cerebral Ischaemia–reperfusion Injury
Authors: Zhang Yun , Mao Xiang , Lin Ruhui , Li Zuanfang , Lin Jing
Published: September 2018

Background

The hippocampus is vulnerable to severe damage after cerebral ischaemia–reperfusion (I/R) injury. This study aimed to explore the effect of electroacupuncture (EA) on cognitive impairment and its relationship with Ca2+neurotoxicity in a rat model of I/R injury induced by middle cerebral artery occlusion (MCAO).

Methods

60 adult male Sprague-Dawley rats were randomly divided into three groups: control (sham surgery) group, untreated MCAO group and EA-treated MCAO+EA group. Rats in the MCAO and MCAO+EA groups underwent modelling of poststroke cognitive impairment by MCAO surgery. EA was performed for 30 min daily at GV20 and GV24 (1–20 Hz) for 1 week. The Morris water maze experiment was used to assess cognitive function. 2,3,5-triphenyl tetrazolium chloride staining was used to measure infarct volume. The intracellular Ca2+content in the Cornu Ammonis (CA)1 area of the hippocampus was assessed by laser confocal scanning microscopy. ELISA was performed to evaluate the concentration of glutamate (Glu) in the hippocampus, and the protein expression of two Glu receptors (N-methyl-D-aspartic acid receptor (NMDAR) 2A and NMDAR2B) were analysed by Western blotting.

Results

Compared with the untreated MCAO group, EA effectively ameliorated cognitive impairment (P=0.01) and shrunk the infarct volume (P=0.032). The content of intracellular Ca2+, Glu and NMDAR2B in the hippocampus was significantly raised by MCAO (P=0.031-0.043), while EA abrogated these effects. NMDAR2A was decreased by MCAO (P=0.015) but increased by EA (P=0.033).

Conclusions

EA had a beneficial effect on cognitive repair after cerebral I/R, and its mechanism of action likely involves a reduction of Ca2+influx via inhibition of Glu neurotoxicity and downregulation of NMDAR2B expression.
Drug-susceptible tuberculosis treatment success and associated factors in Ethiopia from 2005 to 2017: a systematic review and meta-analysis
Authors: Seid Mohammed Assen , Ayalew Mohammed Biset , Muche Esileman Abdela , Gebreyohannes Eyob Alemayehu , Abegaz Tadesse Melaku
Published: September 2018

Objectives

The main aim of this study was to assess the overall tuberculosis (TB) treatment success in Ethiopia and to identify potential factors for poor TB treatment outcome.

Design

A systematic review and meta-analysis of published literature was conducted. Original studies were identified through a computerised systematic search using PubMed, Google Scholar and Science Direct databases. Heterogeneity across studies was assessed using Cochran’s Q test and I2statistic. Pooled estimates of treatment success were computed using the random-effects model with 95% CI using Stata V.14 software.

Results

A total of 230 articles were identified in the systematic search. Of these 34 observational studies were eligible for systematic review and meta-analysis. It was found that 117 750 patients reported treatment outcomes. Treatment outcomes were assessed by World Health Organization (WHO) standard definitions of TB treatment outcome. The overall pooled TB treatment success rate in Ethiopia was 86% (with 95% CI 83%_88%). TB treatment success rate for each region showed that, Addis Ababa (93%), Oromia (84%), Amhara (86%), Southern Nations (83%), Tigray (85%) and Afar (86%). Mainly old age, HIV co-infection, retreatment cases and rural residence were the most frequently identified factors associated with poor TB treatment outcome.

Conclusion

The result of this study revealed that the overall TB treatment success rate in Ethiopia was below the threshold suggested by WHO (90%). There was also a discrepancy in TB treatment success rate among different regions of Ethiopia. In addition to these, HIV co-infection, older age, retreatment cases and rural residence were associated with poor treatment outcome. In order to further improve the treatment success rate, it is strategic to give special consideration for regions which had low TB treatment success and patients with TB with HIV co-infection, older age, rural residence and retreatment cases.
Expedited assessment of terrestrial arthropod diversity by coupling Malaise traps with DNA barcoding
Authors: deWaard Jeremy R. , Levesque-Beaudin Valerie , deWaard Stephanie L. , Ivanova Natalia V. , McKeown Jaclyn T.A. , Miskie Renee , Naik Suresh , Perez Kate H.J. , Ratnasingham Sujeevan , Sobel Crystal N. , Sones Jayme E. , Steinke Claudia , Telfer Angela C. , Young Andrew D. , Young Monica R. , Zakharov Evgeny V. , Hebert Paul D.N.
Published: September 2018

Monitoring changes in terrestrial arthropod communities over space and time requires a dramatic increase in the speed and accuracy of processing samples that cannot be achieved with morphological approaches. The combination of DNA barcoding and Malaise traps allows expedited, comprehensive inventories of species abundance whose cost will rapidly decline as high-throughput sequencing technologies advance. Aside from detailing protocols from specimen sorting to data release, this paper describes their use in a survey of arthropod diversity in a national park that examined 21 194 specimens representing 2255 species. These protocols can support arthropod monitoring programs at regional, national, and continental scales.
Odd dimensional manifolds with highly connected covers
Authors: Johnson F. E. A.
Published: September 2018

We show that for each integer [Formula: see text] any finite group [Formula: see text] acts smoothly and freely on a connected sum [Formula: see text] for some [Formula: see text]. Moreover, as a module over [Formula: see text], the middle dimensional homotopy group can be specified in advance to belong to the stable syzygy [Formula: see text].
Influence of distributed roughness elements on boundary layer transition for NACA0012 airfoil
Authors: Dong Hao , Liu Shicheng , Geng Xi , Zhang Kun , Cheng Keming
Published: September 2018

The influence of distributed cylinder roughness elements on boundary layer transition for NACA0012 airfoil at Ma = 0.6 has been investigated by subsonic/transonic/supersonic wind tunnel experiment with oil-film interferometry. Three different heights and two different distances of cylinder roughness elements on the airfoil model were used, and the skin friction coefficient was measured by the oil-film interferometry. The experimental results show that higher roughness elements promote the transition earlier. In addition, narrower distance of roughness elements can delay the transition compared with the case of wider distance.