bluuebunny/crossref_metadata_2025_split huggingface dataset:
An approach to comprehensive genome and proteome expression analyses in Schwann cells and neurons during peripheral nerve myelin formation
Authors: Kangas Salla M. , Ohlmeier Steffen , Sormunen Raija , Jouhilahti Eeva‐Mari , Peltonen Sirkku , Peltonen Juha , Heape Anthony M. 
Published: July 2016

AbstractPeripheral nerve myelination is a complex event resulting from spatially and temporally regulated reciprocal interactions between the neuron and myelin‐forming Schwann cells. The dynamic process and the protein functional modules and networks that operate throughout the myelination process are poorly understood because of a lack of methodologies suitable for observing specific changes in the Schwann cell/neuron‐unit. The identification of the precise roles for the proteins participating in the functional modules and networks that participate in the myelination process is hindered by the cellular and molecular complexity of the nervous tissue itself. We have developed an approach based on a myelinating dorsal root ganglion explant model that allows distinguishing clear, reproducible and predictable differences between the biochemical properties and the genomic and proteomic expression profiles of both cellular components of the Schwann cell/neuron unit at different stages of the myelination process. This model, derived from E13.5 C57BL/6J mouse embryos, is sufficiently robust for use in identifying the protein functional networks and modules related to peripheral nerve myelin formation. The genomic expression profiles of the selected neuronal, Schwann cell and myelin‐specific proteins in the cultures reflect in vivo profiles reported in the literature, and the structural and ultrastructural properties of the myelin, as well as the myelination schedule of the cultures, closely resemble those observed in peripheral nerves in situ. The RNA expression data set is available through NCBI gene expression omnibus accession GSE60345.
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We have developed a reproducible and robust cell culture‐based approach, accompanied by a genome‐wide expression data set, which allows studying myelination in the peripheral nervous system at the proteomic and transcriptomic levels in Schwann cells and neurons. Myelinating dorsal root explant cultures, prepared from C57BL/6J mouse embryos, present distinct developmental stages comparable to those observed in a peripheral nerve in situ. This model can be used for identifying the protein functional networks and modules related to peripheral nerve myelin formation.
Photodynamic therapy versus surgical excision to basal cell carcinoma: meta‐analysis
Authors: Zou Yurui , Zhao Yunxiang , Yu Jia , Luo Xue , Han Jiangbo , Ye Zhijia , Li Jintao , Lin Hui 
Published: July 2016

SummaryBackgroundSurgical excision (SE) is a first‐line treatment for basal cell carcinoma (BCC). Topical photodynamic therapy (PDT) has also been used and has cosmetic advantages over surgery. The latest European guidelines for topical PDT recommended that it be used to treat nodular basal cell carcinoma (nBCC) but a consensus has not been reached. Our study was to evaluate the efficacy of PDT versus SE for the treatment for nBCC by a meta‐analysis.Materials and methodsWe searched PubMed, EMBASE, the Cochrane Library, CKNI, VIP, and relevant references up to October 2014 including randomized controlled trials (RCTs) that compared PDT with SE for treatment of nBCC patients. A meta‐analysis was conducted by using the Cochrane Collaboration's revman 5.0 software.ResultsWe selected five studies that covered 596 of pathologically confirmed nBCC. We compared complete response rate (RR) of PDT and SE at 3 months and 1, 2, 3, 4, and 5 years. We found that the RR was 0.95 (0.90, 1.00), 0.89 (0.80, 0.99), 0.83 (0.69, 1.00), 0.73 (0.63, 0.85), 0.84 (0.65, 1.08), and 0.79 (0.61, 1.03), respectively, for those time points, the cumulative probability of recurrence for the time points post‐treatment, with an estimate at RR 5.28 (1.85, 15.12), 6.48 (2.46, 17.09), 9.67 (3.02, 30.99), 7.73 (2.81, 21.28), and 8.25 (3.01–22.62), respectively.ConclusionWe observed no significant differences between PDT and SE for the complete RR, but there was an increased cumulative probability of recurrence. More large‐scale RCTs are required to verify our findings.
The Influence of Agreeableness and Ego Depletion on Emotional Responding
Authors: Finley Anna J. , Crowell Adrienne L. , Harmon‐Jones Eddie , Schmeichel Brandon J. 
Published: July 2016

AbstractObjectiveAgreeable individuals report more intense withdrawal‐oriented negative emotions across aversive situations. Two studies tested the hypothesis that self‐regulatory depletion (i.e., ego depletion) moderates the relationship between trait Agreeableness and negative emotional responding.MethodEgo depletion was manipulated using a writing task. Emotional responding was measured with startle eye‐blink responses (Study 1, N = 71) and self‐reported valence, arousal, and empathic concern (Study 2, N = 256) during emotional picture viewing. Trait Agreeableness was measured using a questionnaire.ResultsIn Study 1, Agreeableness predicted especially large startle responses during aversive images and especially small startles during appetitive images. After exercising self‐control, the relationship between startle magnitudes and Agreeableness decreased. In Study 2, Agreeableness predicted more empathic concern for aversive images, which in turn predicted heightened self‐reported negative emotions. After exercising self‐control, the relationship between Agreeableness and empathic concern decreased.ConclusionsAgreeable individuals exhibit heightened negative emotional responding. Ego depletion reduced the link between Agreeableness and negative emotional responding in Study 1 and moderated the indirect effect of Agreeableness on negative emotional responding via empathic concern in Study 2. Empathic concern appears to be a resource‐intensive process underlying heightened responding to aversive stimuli among agreeable persons.
Influence of particle shedding from silicone tubing on antibody stability
Authors: Saller Verena , Hediger Constanze , Matilainen Julia , Grauschopf Ulla , Bechtold-Peters Karoline , Mahler Hanns-Christian , Friess Wolfgang 
Published: July 2016

Abstract

Objectives
Peristaltic pumps are increasingly employed during fill & finish operations of a biopharmaceutical drug, due to sensitivity of many biological products to rotary piston pump-related stresses. Yet, possibly also unit operations using peristaltic pumps may shed particulates into the final product due to abrasion from the employed tubing. It was the aim of this study to elucidate the potential influence of particles shed from peristaltic pump tubing on the stability of a drug product.

Methods
Spiking solutions containing shed silicone particles were prepared via peristaltic pumping of placebo under recirculating conditions and subsequently characterized. Two formulated antibodies were spiked with two realistic, but worst-case levels of particles and a 6-month accelerated stability study with storage at 2–8, 25 and 40°C were conducted.

Key findings
Regarding the formation of aggregates and fragments, both mAbs degraded at their typically expected rates and no additional impact of spiked particles was observed. No changes were discerned however in turbidity, subvisible and visible particle assessments. Flow imaging data for one of the mAb formulations with spiked particles suggested limited colloidal stability of shed particles as indicated by a similar increase in spiked placebo.

Conclusions
Shed silicone particles from peristaltic pump tubing are assumed to not impair drug product stability.
Genomic variation at the tips of the adaptive radiation of Darwin's finches
Authors: Chaves Jaime A. , Cooper Elizabeth A. , Hendry Andrew P. , Podos Jeffrey , De León Luis F. , Raeymaekers Joost A. M. , MacMillan W.Owen , Uy J. Albert C. 
Published: July 2016

AbstractAdaptive radiation unfolds as selection acts on the genetic variation underlying functional traits. The nature of this variation can be revealed by studying the tips of an ongoing adaptive radiation. We studied genomic variation at the tips of the Darwin's finch radiation; specifically focusing on polymorphism within, and variation among, three sympatric species of the genus Geospiza. Using restriction site‐associated DNA (RAD‐seq), we characterized 32 569 single‐nucleotide polymorphisms (SNPs), from which 11 outlier SNPs for beak and body size were uncovered by a genomewide association study (GWAS). Principal component analysis revealed that these 11 SNPs formed four statistically linked groups. Stepwise regression then revealed that the first PC score, which included 6 of the 11 top SNPs, explained over 80% of the variation in beak size, suggesting that selection on these traits influences multiple correlated loci. The two SNPs most strongly associated with beak size were near genes associated with beak morphology across deeper branches of the radiation: delta‐like 1 homologue (DLK1) and high‐mobility group AT‐hook 2 (HMGA2). Our results suggest that (i) key adaptive traits are associated with a small fraction of the genome (11 of 32 569 SNPs), (ii) SNPs linked to the candidate genes are dispersed throughout the genome (on several chromosomes), and (iii) micro‐ and macro‐evolutionary variation (roots and tips of the radiation) involve some shared and some unique genomic regions.
McCabe and Aquinas on Love and Natural Law
Authors: Heron Jason A. 
Published: July 2016

AbstractThis article investigates the relationship between love, law, and human nature in the thought of McCabe and Aquinas. The article puts McCabe and Aquinas into conversation in order to illuminate McCabe's estimation of the natural law as an “insufficient ethic” and a feature of ethics that sheds a “great deal of light” on the matter of human morality. The article seeks to articulate the integrity of natural morality as a feature of the Divine Wisdom that ultimately perfects natural morality via the incarnation of the Son.
Managing in the Regulatory Thicket: Regulation Legitimacy and Expertise
Authors: Amirkhanyan Anna A. , Meier Kenneth J. , O'Toole Laurence J. 
Published: July 2016

AbstractAlthough the influence of government regulation on organizations is undeniable, empirical research in this field is scarce. This article investigates how the understanding of and attitudes toward government regulation among public, nonprofit, and for‐profit managers affect organizational performance, using U.S. nursing homes as the empirical setting. Findings suggest that managers’ perceptions of regulation legitimacy—views of regulation fairness, inspectors’ effectiveness, and internal utility of the mandates—positively affect service quality. Subgroup analysis suggests that managers’ views of regulation matter in nonprofit and for‐profit organizations but not in public organizations. In nonprofit homes, performance declines when managers report higher regulatory expertise—better knowledge of the regulatory standards. In for‐profit facilities, frequent communication with regulators lowers quality. These findings suggest that the regulated entities’ views of government regulation are central to their success, which necessitates improvements in the regulatory process.
Does a Regional Trade Agreement Lessen or Worsen Growth Volatility? An Empirical Investigation
Authors: Kpodar Kangni , Imam Patrick 
Published: July 2016

AbstractThis paper assesses how regional trade agreements (RTAs) impact on growth volatility for a sample of 170 countries over the period 1978–2012. Notwithstanding concerns that trade openness through RTAs might heighten exposure to shocks, RTAs through enhanced policy credibility, improved policy coordination and reduced risk of conflicts can also ease growth volatility. Empirical estimations suggest the benefits outweigh the costs as RTAs are consistently associated with lower growth volatility. In addition, smaller economies benefit more from the reduced growth volatility associated with RTAs than larger ones. The nature of the RTA also matters as shallow agreements such as partial‐scope preferential trade agreements do not appear to have a significant effect on growth volatility, whereas free trade areas and customs unions do. Finally, in investigating the drivers of RTAs, the regression results confirm that countries that are more prone to shocks are more likely to join an RTA, in particular with countries with relatively less volatile growth.
What does normal tendon structure look like? New insights into tissue characterization in the Achilles tendon
Authors: Wezenbeek E. , Mahieu N. , Willems T. M. , Van Tiggelen D. , De Muynck M. , De Clercq D. , Witvrouw E. 
Published: July 2016

Recently, ultrasound tissue characterization (UTC) was introduced as a reliable method for quantification of tendon structure. Despite increasing publications on the use of UTC, it is striking that there is a lack of normative data in active adolescents. Therefore, the aim of this study was to provide normative values of the Achilles tendon as quantified by UTC. Seventy physiotherapy students (26 male and 44 female students) with no history of Achilles tendon injuries were recruited. The Achilles tendons were scanned with UTC to characterize tendon structure. This study demonstrated that Achilles tendons of active, healthy adolescents contained 54.6% echo type I, 42.8% echo type II, 2.2% echo type III, and 0.3% echo type IV at midportion. The comparison between insertion and midportion of the tendon showed more echo type II at insertion (P < 0.001). Furthermore, female tendons contained significantly more echo type II, in both insertion and midportion compared with male tendons (P = 0.004 and P = 0.003, respectively). The results of this study, with respect to the MDC (minimum detectable change), highlight differences in the UTC echopattern in the normal population (sex and regional location), which are important considerations for future studies.
A
Genderless Coupling Mechanism With Six-Degrees-of-Freedom Misalignment Capability for Modular
Self-Reconfigurable Robots
Authors: Saab Wael , Ben-Tzvi Pinhas 
Published: July 2016

Abstract
This paper presents the design and integration of a genderless coupling mechanism for modular self-reconfigurable mobile robots. Modular self-reconfigurable mobile robotic systems consist of a number of self-sufficient modules that interconnect via coupling mechanisms and adopt different configurations to modify locomotion and/or manipulation capabilities. Coupling mechanisms are a critical element of these robotic systems. This paper focuses on a docking mechanism called GHEFT: a Genderless, High-strength, Efficient, Fail-safe, and high misalignment Tolerant coupling mechanism that aids self-reconfiguration. GHEFT provides a high strength and energy efficient connection using nonback drivable actuation with optimized clamping profiles that tolerate translational and angular misalignments. It also enables engagement/disengagement without gender restrictions in the presence of one-sided malfunction. The detailed design of the proposed mechanism is presented, including optimization of the clamping profile geometries. Experimental validation of misalignment tolerances and achievable clamping forces and torques is performed to demonstrate the strength, efficiency, and fail-safe capabilities of the proposed mechanism, and these results are compared to reported results of some of the existing coupling mechanisms.
Draft Genome Sequence of 16SrIII-J Phytoplasma, a Plant Pathogenic Bacterium with a Broad Spectrum of Hosts
Authors: Zamorano Alan , Fiore Nicola 
Published: July 2016

ABSTRACT
Phytoplasmas are bacterial plant pathogens that can affect different vegetal hosts. In South America, a phytoplasma belonging to ribosomal subgroup 16SrIII-J has been reported in many crops. Here we report its genomic draft sequence, showing a total length of 687,253 bp and a G+C content of 27.72%.
Complete Genome Sequences of Four Isolates of
Plutella xylostella
Granulovirus
Authors: Spence Robert J. , Noune Christopher , Hauxwell Caroline 
Published: July 2016

ABSTRACT

Granuloviruses are widespread pathogens of
Plutella xylostella
L. (diamondback moth) and potential biopesticides for control of this global insect pest. We report the complete genomes of four
Plutella xylostella
granulovirus isolates from China, Malaysia, and Taiwan exhibiting pairs of noncoding, homologous repeat regions with significant sequence variation but equivalent length.
Genome Sequence of the Historical Clinical Isolate Burkholderia pseudomallei PHLS 6
Authors: D'haeseleer Patrik , Johnson Shannon L. , Davenport Karen W. , Chain Patrick S. , Schoeniger Joe , Ray Debjit , Sinha Anupama , Williams Kelly P. , Peña José , Branda Steven S. , El-Etr Sahar 
Published: July 2016

ABSTRACT

Here, we present the draft genome sequence of
Burkholderia pseudomallei
PHLS 6, a virulent clinical strain isolated from a melioidosis patient in Bangladesh in 1960. The draft genome consists of 39 contigs and is 7,322,181 bp long.
Regulatory approval of pharmaceuticals without a randomised controlled study: analysis of EMA and FDA approvals 1999–2014
Authors: Hatswell Anthony J , Baio Gianluca , Berlin Jesse A , Irs Alar , Freemantle Nick 
Published: July 2016

IntroductionThe efficacy of pharmaceuticals is most often demonstrated by randomised controlled trials (RCTs); however, in some cases, regulatory applications lack RCT evidence.ObjectiveTo investigate the number and type of these approvals over the past 15 years by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).MethodsDrug approval data were downloaded from the EMA website and the ‘Drugs@FDA’ database for all decisions on pharmaceuticals published from 1 January 1999 to 8 May 2014. The details of eligible applications were extracted, including the therapeutic area, type of approval and review period.ResultsOver the period of the study, 76 unique indications were granted without RCT results (44 by the EMA and 60 by the FDA), demonstrating that a substantial number of treatments reach the market without undergoing an RCT. The majority was for haematological malignancies (34), with the next most common areas being oncology (15) and metabolic conditions (15). Of the applications made to both agencies with a comparable data package, the FDA granted more approvals (43/44 vs 35/44) and took less time to review products (8.7 vs 15.5 months). Products reached the market first in the USA in 30 of 34 cases (mean 13.1 months) due to companies making FDA submission before EMA submissions and faster FDA review time.DiscussionDespite the frequency with which approvals are granted without RCT results, there is no systematic monitoring of such treatments to confirm their effectiveness or consistency regarding when this form of evidence is appropriate. We recommend a more open debate on the role of marketing authorisations granted without RCT results, and the development of guidelines on what constitutes an acceptable data package for regulators.
Activation of the c-Met Pathway Mobilizes an Inflammatory Network in the Brain Microenvironment to Promote Brain Metastasis of Breast Cancer
Authors: Xing Fei , Liu Yin , Sharma Sambad , Wu Kerui , Chan Michael D. , Lo Hui-Wen , Carpenter Richard L. , Metheny-Barlow Linda J. , Zhou Xiaobo , Qasem Shadi A. , Pasche Boris , Watabe Kounosuke 
Published: July 2016

Abstract
Brain metastasis is one of the chief causes of mortality in breast cancer patients, but the mechanisms that drive this process remain poorly understood. Here, we report that brain metastatic cells expressing high levels of c-Met promote the metastatic process via inflammatory cytokine upregulation and vascular reprogramming. Activated c-Met signaling promoted adhesion of tumor cells to brain endothelial cells and enhanced neovascularization by inducing the secretion of IL8 and CXCL1. Additionally, stimulation of IL1β secretion by activation of c-Met induced tumor-associated astrocytes to secrete the c-Met ligand HGF. Thus, a feed-forward mechanism of cytokine release initiated and sustained by c-Met fed a vicious cycle that generated a favorable microenvironment for metastatic cells. Reinforcing our results, we found that pterostilbene, a compound that penetrates the blood–brain barrier, could suppress brain metastasis by targeting c-Met signaling. These findings suggest a potential utility of this natural compound for chemoprevention. Cancer Res; 76(17); 4970–80. ©2016 AACR.
MEF2D Transduces Microenvironment Stimuli to ZEB1 to Promote Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer
Authors: Su Li , Luo Yongli , Yang Zhi , Yang Jing , Yao Chao , Cheng Feifei , Shan Juanjuan , Chen Jun , Li Fangfang , Liu Limei , Liu Chungang , Xu Yanmin , Jiang Lupin , Guo Deyu , Prieto Jesus , Ávila Matías A. , Shen Junjie , Qian Cheng 
Published: July 2016

Abstract
Epithelial–mesenchymal transition (EMT) is an essential mechanism of metastasis, including in colorectal cancer. Although EMT processes are often triggered in cancer cells by their surrounding microenvironment, how EMT-relevant genes control these processes is not well understood. In multiple types of cancers, the transcription factor MEF2D has been implicated in cell proliferation, but its contributions to metastasis have not been addressed. Here, we show MEF2D is overexpressed in clinical colorectal cancer tissues where its high expression correlates with metastatic process. Functional investigations showed that MEF2D promoted cancer cell invasion and EMT and that it was essential for certain microenvironment signals to induce EMT and metastasis in vivo. Mechanistically, MEF2D directly regulated transcription of the EMT driver gene ZEB1 and facilitated histone acetylation at the ZEB1 promoter. More importantly, MEF2D responded to various tumor microenvironment signals and acted as a central integrator transducing multiple signals to activate ZEB1 transcription. Overall, our results define a critical function for MEF2D in upregulating EMT and the metastatic capacity of colorectal cancer cells. Further, they offer new insights into how microenvironment signals activate EMT-relevant genes and deepen the pathophysiologic significance of MEF2D, with potential implications for the prevention and treatment of metastatic colorectal cancer. Cancer Res; 76(17); 5054–67. ©2016 AACR.
Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib
Authors: Miller Rowan E. , Brough Rachel , Bajrami Ilirjana , Williamson Chris T. , McDade Simon , Campbell James , Kigozi Asha , Rafiq Rumana , Pemberton Helen , Natrajan Rachel , Joel Josephine , Astley Holly , Mahoney Claire , Moore Jonathan D. , Torrance Chris , Gordan John D. , Webber James T. , Levin Rebecca S. , Shokat Kevan M. , Bandyopadhyay Sourav , Lord Christopher J. , Ashworth Alan 
Published: July 2016

Abstract
New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G1–S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. Mol Cancer Ther; 15(7); 1472–84. ©2016 AACR.