bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-translational regulation enables robust p53 regulation
Authors: Shin Yong-Jun , Chen Kai-Yuan , Sayed Ali H , Hencey Brandon , Shen Xiling 
Published: August 2013

AbstractBackgroundThe tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism.ResultsWe analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise.ConclusionsOur analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.
Genomic characterization of remission in juvenile idiopathic arthritis
Authors: Jiang Kaiyu , Frank Mark Barton , Chen Yanmin , Osban Jeanette , Jarvis James N 
Published: August 2013

Abstract
Introduction
The attainment of remission has become an important end point for clinical trials in juvenile idiopathic arthritis (JIA), although we do not yet have a full understanding of what remission is at the cell and molecular level.

Methods
Two independent cohorts of patients with JIA and healthy child controls were studied. RNA was prepared separately from peripheral blood mononuclear cells (PBMC) and granulocytes to identify differentially expressed genes using whole genome microarrays. Expression profiling results for selected genes were confirmed by quantitative, real-time polymerase chain reaction (RT-PCR).

Results
We found that remission in JIA induced by either methotrexate (MTX) or MTX plus a TNF inhibitor (etanercept, Et) (MTX + Et) is characterized by numerous differences in gene expression in peripheral blood mononuclear cells and in granulocytes compared with healthy control children; that is, remission is not a restoration of immunologic normalcy. Network analysis of the differentially expressed genes demonstrated that the steroid hormone receptor superfamily member hepatocyte nuclear factor 4 alpha (HNF4α) is a hub in several of the gene networks that distinguished children with arthritis from controls. Confocal microscopy revealed that HNF4a is present in both T lymphocytes and granulocytes, suggesting a previously unsuspected role for this transcription factor in regulating leukocyte function and therapeutic response in JIA.

Conclusions
These findings provide a framework from which to understand therapeutic response in JIA and, furthermore, may be used to develop strategies to increase the frequency with which remission is achieved in adult forms of rheumatoid arthritis.
Increased plasmacytoid dendritic cells and RORγt-expressing immune effectors in cutaneous acute graft-versus-host disease
Authors: Malard Florent , Bossard Céline , Brissot Eolia , Chevallier Patrice , Guillaume Thierry , Delaunay Jacques , Mosnier Jean-François , Moreau Philippe , Grégoire Marc , Gaugler Béatrice , Mohty Mohamad 
Published: August 2013

ABSTRACTThe role of PDCs and Th17 cells is not well understood in the pathogenesis of aGVHD. We evaluated PDC and Th17 cells in skin biopsies of 38 patients at diagnosis of aGVHD. The biopsies were tested by immunohistochemistry for the expression of BDCA2, a typical marker of PDCs. We found an increase of BDCA2+ cells in the skin of the patients with aGVHD. Moreover, we observed a strong expression of the type I IFN-inducible protein Mx1 in the skin of the patients with aGVHD, compared with that of those without it, suggesting that PDCs produce type I IFN. We also analyzed the expression of two Th17 surface markers—CD161 and CCR6—and RORγt, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of RORγt+, CD161+, and CCR6+ cells were counted in the skin of the patients with aGVHD than in the skin of those who underwent allo-SCT and in whom aGVHD did not develop. This study provides evidence for a role of Th17-mediated responses and a potential new pathophysiological link between PDCs and Th17 in human cutaneous aGVHD.
Sestrin-2, a repressor of PDGFRβ signalling, promotes cigarette-smoke-induced pulmonary emphysema in mice and is upregulated in individuals with COPD
Authors: Heidler Juliana , Fysikopoulos Athanasios , Wempe Frank , Seimetz Michael , Bangsow Thorsten , Tomasovic Ana , Veit Florian , Scheibe Susan , Pichl Alexandra , Weisel Friederike , Lloyd K. C. Kent , Jaksch Peter , Klepetko Walter , Weissmann Norbert , von Melchner Harald 
Published: August 2013

Summary
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD is caused by chronic exposure to cigarette smoke and/or other environmental pollutants that are believed to induce reactive oxygen species (ROS) that gradually disrupt signalling pathways responsible for maintaining lung integrity. Here we identify the antioxidant protein sestrin-2 (SESN2) as a repressor of PDGFRβ signalling, and PDGFRβ signalling as an upstream regulator of alveolar maintenance programmes. In mice, the mutational inactivation of Sesn2 prevents the development of cigarette-smoke-induced pulmonary emphysema by upregulating PDGFRβ expression via a selective accumulation of intracellular superoxide anions (O2-). We also show that SESN2 is overexpressed and PDGFRβ downregulated in the emphysematous lungs of individuals with COPD and to a lesser extent in human lungs of habitual smokers without COPD, implicating a negative SESN2-PDGFRβ interrelationship in the pathogenesis of COPD. Taken together, our results imply that SESN2 could serve as both a biomarker and as a drug target in the clinical management of COPD.
Facile and Rapid Green Route for the Synthesis of Privileged Peptidotriazoles Based on Oxazolonic Acids by Click Fragment Assembly
Authors: Balan Biny , Bahulayan Damodaran 
Published: August 2013

Abstract
A convenient synthetic pathway to triazole-functionalized oxazolone peptidomimetics by click fragment assembly is described. The target molecules were obtained by the ligation of oxazolone-based peptides with azidopeptides via Cu(I)-catalyzed Huisgen cycloaddition reaction (“Click Chemistry”).
Lateral epicondylitis
Authors: Ahmad Z. , Siddiqui N. , Malik S. S. , Abdus-Samee M. , Tytherleigh-Strong G. , Rushton N. 
Published: August 2013

Lateral epicondylitis, or ’tennis elbow’, is a common condition that usually affects patients between 35 and 55 years of age. It is generally self-limiting, but in some patients it may continue to cause persistent symptoms, which can be refractory to treatment. This review discusses the mechanism of disease, symptoms and signs, investigations, current management protocols and potential new treatments. Cite this article: Bone Joint J 2013;95-B:1158–64.
When ‘minimalist’ conceptions of citizenship reveal their complexity
Authors: Williams Dierdre 
Published: August 2013

Abstract
This study explores the ways in which a group of secondary teachers in Jamaica think about and understand citizenship and considers how these understandings are informed by the social, economic and political context. The study utilizes an analytic framework of minimal versus critical conceptions of citizenship to highlight the calls by scholars and academics for conceptions of citizenship to reflect concern for issues of fairness, justice and democracy. The findings highlight that while the views of citizenship held by these teachers may be regarded by some as not sufficiently robust, an interpretation of these conceptions in light of the economic, social and political context reveals great complexity.
New distributional record of the rare endemic Peruvian Tomopeas ravus Miller, 1900 (Chiroptera, Molossidae, Tomopeatinae)
Authors: Zamora Hugo , Medina Cesar , Escobar Alain , Arteaga Yamileth , Cadenillas Richard , Velazco Paúl M. 
Published: August 2013

AbstractThe present study reports the southernmost record of
Effect of stacking sequence and geometric scaling on the brittleness number of glass fiber composite laminate with stress raiser
Authors: Mohammed Y. , Hassan Mohamed K. , El-Ainin H Abu , Hashem A.M. 
Published: August 2013

AbstractThe fracture behavior of quasi-brittle material exhibits commonly brittle behavior with some ductility in the fracture processing zone. Therefore, a matrix of experimental works is performed to investigate the failure behaviors based on a parameter known as brittleness number, which is a measure of brittle behaviors. Glass fiber-reinforced epoxy laminates of three stacking sequences, cross-ply [0/90]2s and two quasi-isotropic [0/45/90]2s and [0/45/90/-45]s, are manufactured using hand lay-up technique. A matrix of different specimen geometric scaling with open hole of the same material is used. The fracture energy GIC and nominal strength of these composite laminates are measured experimentally using compact tension test, center crack specimen, and tension test, respectively. The results showed that the increase of homogeneity of composite laminates, which is introduced by inserting a certain angle ply for the laminate structure, enhanced the material ductility as the brittle number increased. The larger size of specimen leads to the increase of brittleness for the same stacking sequences due to the increase of stress concentration factor.
Novel Paradigms for Dialysis Vascular Access
Authors: Remuzzi Andrea , Ene-Iordache Bogdan 
Published: August 2013

Summary
Failure of hemodialysis access is caused mostly by venous intimal hyperplasia, a fibro-muscular thickening of the vessel wall. The pathogenesis of venous neointimal hyperplasia in primary arteriovenous fistulae consists of processes that have been identified as upstream and downstream events. Upstream events are the initial events producing injury of the endothelial layer (surgical trauma, hemodynamic shear stress, vessel wall injury due to needle punctures, etc.). Downstream events are the responses of the vascular wall at the endothelial injury that consist of a cascade of processes including leukocyte adhesion, migration of smooth muscle cells from the media to the intimal layer, and proliferation. In arteriovenous fistulae, the stenoses occur in specific sites, consistently related to the local hemodynamics determined by the vessel geometry and blood flow pattern. Recent findings that the localization of these sites matches areas of disturbed flow may add new insights into the pathogenesis of neointimal hyperplasia in the venous side of vascular access after the creation of the anastomosis. The detailed study of fluid flow motion acting on the vascular wall in anastomosed vessels and in the arm vasculature at the patient-specific level may help to elucidate the role of hemodynamics in vascular remodeling and neointimal hyperplasia formation. These computational approaches may also help in surgical planning for the amelioration of clinical outcome. This review aims to discuss the role of the disturbed flow condition in acting as upstream event in the pathogenesis of venous intimal hyperplasia and in producing subsequent local vascular remodeling in autogenous arteriovenous fistulae used for hemodialysis access. The potential use of blood flow analysis in the management of vascular access is also discussed.
Novel Paradigms for Dialysis Vascular Access
Authors: Lee Timmy 
Published: August 2013

Summary
Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development.
Efficacy of monepantel against lower developmental stages of a multi-resistant and susceptible Haemonchus contortus isolates: an in vitro study
Authors: Lecová L. , Stuchlíková L. , Lamka J. , Špulák M. , Várady M. , Skálová L. 
Published: August 2013

Abstract
Monepantel (MOP) belongs to a new class of anthelmintic compounds, the amino-acetonitrile derivates, which have a different mode of action as the currently used anthelmintics. Many present studies confirmed the high efficacy of MOP against fourth larval and adult stages of Haemonchus contortus. The objective of this study was to determine in vitro efficacy of MOP against lower development stages (eggs, L1–L3 larvae) and to compare it between resistant and susceptible isolates of H. contortus. For this purpose, two in vitro tests - egg hatch test and micro-agar larval development test were used. Results were quantified as 50 % lethal concentration (LC50), 99 % lethal concentration (LC99) and resistance factor (RF). This study revealed the high efficacy against lower larval stages (L1–L3) of both resistant and susceptible strains of this parasite. Larval susceptibility was not dependent of the sensitivity status of the nematode isolate. On the other hand, ovicidal effect of MOP was very low.
First report about the trapping activity of Stropharia rugosoannulata acanthocytes for Northern Root Knot Nematode
Authors: Zouhar M. , Douda O. , Nováková J. , Doudová E. , Mazáková J. , Wenzlová J. , Ryšánek P. , Renčo M. 
Published: August 2013

Abstract
This study summarises the results of in vitro screening of the nematophagous activity of Stropharia rugosoannulata and Arthrobotrys oligospora. The tests were conducted with Meloidogyne hapla plant parasitic nematode juveniles placed into Petri dishes containing cultures of the tested fungal species. Immobilisation of the nematodes was observed after 4 and 24 hours. Both species of fungi showed nematophagous activity, however it was much stronger and faster in the case of S. rugosoannulata.
Unusual clinical course of trichinellosis with relapse
Authors: Paraličová Z. , Dubinský P. , Kristian P. , Jarčuška P. 
Published: August 2013

Abstract
During an outbreak of trichinellosis in Eastern Slovakia in 2008, 16 people were hospitalized, including 10 patients having specific anti-Trichinella antibodies. The disease relapse was seen in a 68-year-old woman two weeks after her discharge from hospital, where she was treated with albendazole and prednisone for 10 days. Clinical symptoms of trichinellosis, eosinophilia, elevated CRP and LDH levels were observed again with recorded elevation of aminotransferase levels during the relapse. Herein we discuss a potential cause of unusual relapse of trichinellosis with liver damage in a female patient with type II diabetes mellitus.
Les mottes castrales du Roussillon
Authors: Castellvi Georges 
Published: August 2013

Avec la Provence et le Lauragais il s'avère que le Roussillon a également été touché par la diffusion des mottes castrales. Leur datation demeure imprécise à établir notamment en raison de leur disparition pour les besoins de l'agriculture. Cependant les textes permettent d'en dresser un inventaire et amènent des éléments de réponse quant à leurs fonctions possibles.
Dans l'hypothèse la plus vraisemblable, la plupart des mottes auraient eu une vocation de contrôle, implantées à proximité d'une voie, d'un gué ou d'un croisement. Malgré le silence des textes sur cette question, les mottes auraient donc pu être subordonnées aux véritables châteaux-forts. Ainsi s'expliquerait l'absence d'hommages rendus aux souverains (comte du Roussillon, roi d'Aragon).
Fundamentals of Pyrosequencing
Authors: Harrington Colleen T. , Lin Elaine I. , Olson Matthew T. , Eshleman James R. 
Published: August 2013

Context.—DNA sequencing is critical to identifying many human genetic disorders caused by DNA mutations, including cancer. Pyrosequencing is less complex, involves fewer steps, and has a superior limit of detection compared with Sanger sequencing. The fundamental basis of pyrosequencing is that pyrophosphate is released when a deoxyribonucleotide triphosphate is added to the end of a nascent strand of DNA. Because deoxyribonucleotide triphosphates are sequentially added to the reaction and because the pyrophosphate concentration is continuously monitored, the DNA sequence can be determined.
Objective.—To demonstrate the fundamental principles of pyrosequencing.
Data Sources.—Salient features of pyrosequencing are demonstrated using the free software program Pyromaker (http://pyromaker.pathology.jhmi.edu), through which users can input DNA sequences and other pyrosequencing parameters to generate the expected pyrosequencing results.
Conclusions.—We demonstrate how mutant and wild-type DNA sequences result in different pyrograms. Using pyrograms of established mutations in tumors, we explain how to analyze the pyrogram peaks generated by different dispensation sequences. Further, we demonstrate some limitations of pyrosequencing, including how some complex mutations can be indistinguishable from single base mutations. Pyrosequencing is the basis of the Roche 454 next-generation sequencer and many of the same principles also apply to the Ion Torrent hydrogen ion-based next-generation sequencers.
High frequency of intermediate alleles on huntington disease‐associated haplotypes in British Columbia's general population
Authors: Semaka Alicia , Kay Chris , Doty Crystal N. , Collins Jennifer A. , Tam Natalie , Hayden Michael R. 
Published: August 2013

ABSTRACTIntermediate alleles (27–35 CAG, IAs) for Huntington disease (HD) usually do not confer the disease phenotype but are prone to CAG repeat instability. Consequently, offspring are at‐risk of inheriting an expanded allele in the HD range (≥36 CAG). IAs that expand into a new mutation have been hypothesized to be more susceptible to instability compared to IAs identified on the non‐HD side of a family from the general population. Frequency estimates for IAs are limited and have largely been determined using clinical samples of HD or related disorders, which may result in an ascertainment bias. This study aimed to establish the frequency of IAs in a sample of a British Columbia's (B.C.) general population with no known association to HD and examine the haplotype of new mutation and general population IAs. CAG sizing was performed on 1,600 DNA samples from B.C.'s general population. Haplotypes were determined using 22 tagging SNPs across the HTT gene. 5.8% of individuals were found to have an IA, of which 60% were on HD‐associated haplotypes. There was no difference in the haplotype distribution of new mutation and general population IAs. These findings suggest that IAs are relatively frequent in the general population and are often found on haplotypes associated with expanded CAG lengths. There is likely no difference in the propensity of new mutation and general population IAs to expand into the disease range given that they are both found on disease‐associated haplotypes. These findings have important implications for clinical practice. © 2013 Wiley Periodicals, Inc.
Optimization‐based group performance deducing
Authors: Lv Lei , Mao Tianlu , Liu Xuecheng , Wang Zhaoqi 
Published: August 2013

ABSTRACTLarge‐scale group performance animation has been an important research topic because of its diverse range of applications including virtual rehearsal and film production. Animating hundreds of virtual actors as what the director wishes is a tough task. In this paper, we address this challenge by introducing an optimization method that generates large‐scale group performance by deducing a small‐scale one with fewer actors. We introduced group motion bigraph technique and transformed the motion‐deducing problem into a constrained optimization problem. A solving process is then presented to automatically obtain the motion of the large group with velocity constraints. Moreover, an interactive system of constructing the group motion bigraph has been implemented, which provides flexible edit and control on deducing group motion. The animation results show that our method is competent for deducing large‐scale group performance from only several motion clips performed by small groups. Copyright © 2013 John Wiley & Sons, Ltd.
Change and continuity in the advancement of (scholarly) knowledge and its dissemination
Authors: Hodgkinson Gerard P. , Ford J. Kevin 
Published: August 2013

SummaryThis issue comprises the inaugural IRIOP Annual Review Issue, following the incorporation of the International Review of Industrial and Organizational Psychology (IRIOP) into the Journal of Organizational Behavior (JOB). In this editorial, we explain our rationale for transforming the IRIOP series from a long‐established, highly successful invitation‐only edited volume to a double‐blind, peer reviewed issue of the JOB, and outline our vision for its continuing development as the leading outlet for the publication of critical, state‐of‐the‐art overviews and commentary on established knowledge and developments at the forefront of the field. In so doing, we clarify the sorts of contributions we are looking to publish, exemplified by the seven papers appearing in this first issue. Copyright © 2013 John Wiley & Sons, Ltd.
Microbial and chemical properties of Cambodian traditional fermented fish products
Authors: Chuon Mony R , Shiomoto Mimoe , Koyanagi Takashi , Sasaki Tetsuya , Michihata Toshihide , Chan Sarun , Mao Sopheareth , Enomoto Toshiki 
Published: August 2013

AbstractBACKGROUNDFermented fish products, commonly consumed in south‐east Asia, are used as condiments that contribute to people's nutritional sources and as seasonings to improve food taste and flavour. Among these, the Cambodian products prahok (fish paste), kapi (shrimp paste) and toeuk trey (fish sauce) have not been examined in detail. This is the first study to investigate their chemical and microbial properties.RESULTSAcetic acid was the most common organic acid with the highest concentration in 10/13 samples (1.9–26.6 g kg−1). Lactic acid was also found at high concentrations (0.4–12.9 g kg−1). 16S ribosomal RNA gene‐dependent phylogenetic analyses indicated that Gram‐positive cocci and rods, such as Bacillus, Clostridium, Staphylococcus and Tetragenococcus, were the major microbial populations. High sodium chloride concentrations detected in these products (170–270 g kg−1) could be responsible for inhibition of the growth of Gram‐negative putrefactive microorganisms.CONCLUSIONThis study established a relationship between the chemical and microbial compositions of Cambodian fermented fish products, which provides a basis for preservation and maturation. These data could be beneficial in the manufacturing of these products in terms of microbial control and quality stabilisation. © 2013 Society of Chemical Industry