bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and electronic properties of the transition layer at the SiO2/4H-SiC interface
Authors: Li Wenbo , Zhao Jijun , Wang Dejun
Published: January 2015

Using first-principles methods, we generate an amorphous SiO2/4H-SiC interface with a transition layer. Based this interface model, we investigate the structural and electronic properties of the interfacial transition layer. The calculated Si 2p core-level shifts for this interface are comparable to the experimental data, indicating that various SiCxOy species should be present in this interface transition layer. The analysis of the electronic structures reveals that the tetrahedral SiCxOy structures cannot introduce any of the defect states at the interface. Interestingly, our transition layer also includes a C-C=C trimer and SiO5 configurations, which lead to the generation of interface states. The accurate positions of Kohn-Sham energy levels associated with these defects are further calculated within the hybrid functional scheme. The Kohn-Sham energy levels of the carbon trimer and SiO5 configurations are located near the conduction and valence band of bulk 4H-SiC, respectively. The result indicates that the carbon trimer occurred in the transition layer may be a possible origin of near interface traps. These findings provide novel insight into the structural and electronic properties of the realistic SiO2/SiC interface.
Country-of-origin effects on managers' environmental scanning behaviours: evidence from the political crisis in the Eurozone
Authors: Barron Andrew , Hultén Peter , Vanyushyn Vladimir
Published: January 2015

Using original survey data, we investigate how British, French, and Swedish managers scanned their political environments during the crisis in the Eurozone. We expose instances when country of origin has a significant effect on scanning practices: British managers claimed to possess the most developed political scanning capabilities, making the most frequent use of government information sources. British and Swedish managers used business associations as intelligence sources more frequently than their French counterparts. We also found that exposure to the Euro crisis significantly affected scanning behaviours: irrespective of country of origin, managers strongly exposed to the crisis considered it strategically important to scan political events during the crisis, developed formal scanning routines, and reported frequent use of both governments and business associations as sources of political information. Combined, our findings contribute to county-specific research into executives' environmental scanning practices by suggesting a universal mindset of environmental scanning during times of crisis.
How Perception Affects Racial Categorization: On the Influence of Initial Visual Exposure on Labelling People as Diverse Individuals or Racial Subjects
Authors: Harsányi Géza , Carbon Claus-Christian
Published: January 2015

In research on racial categorization we tend to focus on socialization, on environmental influences, and on social factors. One important factor, though, is perception itself. In our experiment we let people label persons on dimensions which they could freely use. The participants were initially exposed to a full series either of black faces or of white faces. We observed a clear effect of initial exposure on explicit verbal categorizations. When initially exposed to white faces, participants used racial labels for the subsequent black faces only. In contrast, racial labels were used for black as well as white faces after initial exposure to black faces, which indicates a shift to in-group categorization after having initially inspected black faces. In conclusion, this effect documents highly adaptive categorizations caused by visual context alone, suggesting that racial thoughts are based on relatively volatile category representations.
A regional model of sheep lice management practices for predicting the impact of treatment for lice when no lice are detected
Authors: Horton Brian J. , Bailey Andrew , Carew Anna L.
Published: January 2015

A model of sheep lice management incorporating different assumed levels of lice prevalence in different regions of Australia was used to determine the conditions under which it would be cost-effective to treat sheep for lice at shearing when no lice had been detected. The probability that a flock might be infested was calculated from the probability that the previous treatment had failed to eradicate lice, purchased sheep may have introduced lice, or lice may have entered on straying sheep. The model showed that a flock should be treated if the probability of infestation is greater than 10%. It was projected that acceptance of a risk level greater than 10% would reduce treatment of flocks where no lice were present, thus reducing treatment costs. This higher risk level, however, would increase the proportion of louse-infested flocks that remained untreated, resulting in increased direct lice costs and an increase in the regional prevalence of lice, but little overall change in costs to the sheep industry. The model indicated that treatment of sheep at lower levels of risk (less than 10%) would incur unnecessary costs due to treatment of flocks where no lice were present and would not reduce the regional prevalence of lice more effectively than a 10% intervention level. The model suggested that more accurate methods of detecting lice at shearing would allow higher levels of risk, reduce the use of treatment and hence reduce overall costs associated with managing lice, without increasing the prevalence of lice.
Soluble epoxide hydrolase inhibitory activity of phenolic components from the rhizomes and roots of Gentiana scabra
Authors: Li Wei , Kim Jang Hoon , Zhou Wei , Shim Sang Hee , Ma Jin Yeul , Kim Young Ho
Published: January 2015

Two new (1 and 2) and seven known phenolic compounds were isolated from a methanol extract of the rhizomes and roots of Gentiana scabra. Their structures were identified by spectroscopic analysis and comparing with reported values. The inhibitory effects of each compound on soluble epoxide hydrolase (sEH) were evaluated. Among them, compounds 2, 6, and 9 potently inhibited sEH activity.
Chief examiners as Prophet and Priest: relations between examination boards and school subjects, and possible implications for knowledge
Authors: Puttick Steven
Published: January 2015

Evidence from an ethnographic study of three secondary school geography departments in England is drawn on to describe aspects of the relationships between examination boards and school subjects. This paper focuses on one department, in ‘Town Comprehensive’, and the argument is illustrated through a discussion of observed lessons with a teacher in this department. Ofqual (Office of Qualifications and Examinations Regulation) have recently announced that examination boards may continue to endorse commercially available teaching resources. The argument presented in this paper extends possible areas of ‘risk’ identified beyond those they currently consider. Specifically, it is argued that chief examiners play multiple roles in the recontextualisation of knowledge, holding substantial power over school subjects. The strong role of accreditation as a rationale is argued to restrict knowledge taught in school geography to horizontal discourses, limiting students’ access to powerful knowledge.
Severe Reversible Pulmonary Hypertension in Smoldering Multiple Myeloma: Two Cases and Review of the Literature
Authors: Feyereisn Wayne L. , Fenstad Eric R. , McCully Robert B. , Lacy Martha Q.
Published: January 2015

An association between pulmonary hypertension (PH) and POEMS syndrome (characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) as well as other plasma cell dyscrasias, including multiple myeloma (MM), has been shown to exist. Recent case reports have identified a reversible form of PH that occurs outside of previously identified etiologies. We report two cases of PH in the setting of smoldering MM (SMM) that resolved with chemotherapy and stem cell transplantation. Although other features were individualized among the cases (dermatomyositis, scleromyxedema), treatment of MM and SMM resulted in a normalization of right ventricular systolic pressure and improvement in right ventricular dysfunction that was previously unresponsive to PH therapies. The magnitude and sustained nature of reversibility in these four cases could offer clues about the pathophysiology and treatment of PH.
Local and global regularity of weak solutions of elliptic equations with superquadratic Hamiltonian
Authors: Dall’Aglio Andrea , Porretta Alessio
Published: January 2015

In this paper, we study the regularity of weak solutions and subsolutions of second order elliptic equations having a gradient-dependent term with superquadratic growth. We show that, under appropriate integrability conditions on the data, all weak subsolutions in a bounded and regular open set

Ω
\Omega

are Hölder-continuous up to the boundary of

Ω
\Omega

. Some local and global summability results are also presented. The main feature of this kind of problem is that the gradient term, not the principal part of the operator, is responsible for the regularity.
PDGF‑stimulated dispersal of cell clusters and disruption of fibronectin matrix on three-dimensional collagen matrices requires matrix metalloproteinase-2
Authors: da Rocha-Azevedo Bruno , Ho Chin-Han , Grinnell Frederick
Published: January 2015

Formation of cell clusters is a common morphogenic cell behavior observed during tissue and organ development and homeostasis, as well as during pathological disorders. Dynamic regulation of cell clustering depends on the balance between contraction of cells into clusters and migration of cells as dispersed individuals. Previously we reported that under procontractile culture conditions, fibronectin fibrillar matrix assembly by human fibroblasts functioned as a nucleation center for cell clustering on three-dimensional collagen matrices. Here we report that switching preformed cell clusters from procontractile to promigratory culture conditions results in cell dispersal out of clusters and disruption of FN matrix. Experiments using small interfering RNA silencing and pharmacological inhibition demonstrated that matrix metalloproteinase activity involving MMP-2 was necessary for fibronectin matrix disruption and dispersal of cell clusters.
Involvement of general control nonderepressible kinase 2 in cancer cell apoptosis by posttranslational mechanisms
Authors: Wei Chen , Lin Ma , Jinjun Bian , Su Feng , Dan Cao , Yan Chen , Jie Yang , Jin Zhang , Zi-Chun Hua , Wu Yin
Published: January 2015

General control nonderepressible kinase 2 (GCN2) is a promising target for cancer therapy. However, the role of GCN2 in cancer cell survival or death is elusive; further, small molecules targeting GCN2 signaling are not available. By using a GCN2 level-based drug screening assay, we found that GCN2 protein level critically determined the sensitivity of the cancer cells toward Na+,K+-ATPase ligand–induced apoptosis both in vitro and in vivo, and this effect was largely dependent on C/EBP homologous protein (CHOP) induction. Further analysis revealed that GCN2 is a short-lived protein. In A549 lung carcinoma cells, cellular β-arrestin1/2 associated with GCN2 and maintained the GCN2 protein level at a low level by recruiting the E3 ligase NEDD4L and facilitating consequent proteasomal degradation. However, Na+,K+-ATPase ligand treatment triggered the phosphorylation of GCN2 at threonine 899, which increased the GCN2 protein level by disrupting the formation of GCN2–β-arrestin–NEDD4L ternary complex. The enhanced GCN2 level, in turn, aggravated Na+,K+-ATPase ligand–induced cancer cell apoptosis. Our findings reveal that GCN2 can exert its proapoptotic function in cancer cell death by posttranslational mechanisms. Moreover, Na+,K+-ATPase ligands emerge as the first identified small-molecule drugs that can trigger cancer cell death by modulating GCN2 signaling.
R Wave in aVL Lead Is a Robust Index of Left Ventricular Hypertrophy: A Cardiac MRI Study
Authors: Courand Pierre-Yves , Grandjean Adrien , Charles Paul , Paget Vinciane , Khettab Fouad , Bricca Giampiero , Boussel Loïc , Lantelme Pierre , Harbaoui Brahim
Published: January 2015

BACKGROUND

In patients free from overt cardiac disease, R wave in aVL lead (RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by transthoracic echocardiography. The aim of the present study was to extend this finding to other settings (cardiomyopathy or conduction disorders), by comparing ECG criteria of left ventricular hypertrophy (LVH) to cardiac MRI (CMR).

METHODS

In 501 patients, CMR and ECG were performed within a median-period of 5 days. CMR LVH cut-offs used were 83g/m2 in men and 67g/m2 in women.

RESULTS

RaVL was independently correlated with LVMI in patients with or without myocardial infarction (MI) (N = 300 and N = 201, respectively). SV3 was independently correlated with LVMI and LV enlargement only in patients without MI. In the whole cohort, RaVL had area under receiver-operating characteristic curve of 0.729 (specificity 98.3%, sensitivity 19.6%, optimal cut-off 1.1 mV). The performance of RaVL was remarkable in women, in Caucasians, and in the presence of right bundle branch block. It decreased in case of MI. Overall, it is proposed that below 0.5 mV and above 1.0 mV, RaVL is sufficient to exclude or establish LVH. Between 0.5 and 1 mV, composite indices (Cornell voltage or product) should be used. Using this algorithm allowed classifying appropriately 85% of the patients.

CONCLUSIONS

Our results showed that RaVL is a good index of LVH with a univocal threshold of 1.0 mV in various clinical conditions. SV3 may be combined to RaVL in some conditions, namely LV enlargement to increase its performance.
The transcriptomic response of Acinetobacter baumannii to colistin and doripenem alone and in combination in an in vitro pharmacokinetics/pharmacodynamics model
Authors: Henry Rebekah , Crane Bethany , Powell David , Deveson Lucas Deanna , Li Zhifeng , Aranda Jesús , Harrison Paul , Nation Roger L. , Adler Ben , Harper Marina , Boyce John D. , Li Jian
Published: January 2015

Objectives

Colistin remains a last-line treatment for MDR Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against MDR strains. In order to understand the bacterial responses to these antibiotics, we analysed the transcriptome of A. baumannii following exposure to each.

Methods

RNA sequencing was employed to determine changes in the transcriptome following treatment with colistin and doripenem, both alone and in combination, using an in vitro pharmacokinetics (PK)/pharmacodynamics model to mimic the PK of both antibiotics in patients.

Results

After treatment with colistin (continuous infusion at 2 mg/L), >400 differentially regulated genes were identified, including many associated with outer membrane biogenesis, fatty acid metabolism and phospholipid trafficking. No genes were differentially expressed following treatment with doripenem (Cmax 25 mg/L, t1/2 1.5 h) for 15 min, but 45 genes were identified as differentially expressed after 1 h of growth under this condition. Treatment of A. baumannii with both colistin and doripenem together for 1 h resulted in >450 genes being identified as differentially expressed. More than 70% of these gene expression changes were also observed following colistin treatment alone.

Conclusions

These data suggest that colistin causes gross damage to the outer membrane, facilitates lipid exchange between the inner and outer membrane and alters the normal asymmetric outer membrane composition. The transcriptional response to colistin was highly similar to that observed for an LPS-deficient strain, indicating that many of the observed changes are responses to outer membrane instability resulting from LPS loss.
The 2015 Nucleic Acids Research Database Issue and Molecular Biology Database Collection
Authors: Galperin Michael Y. , Rigden Daniel J. , Fernández-Suárez Xosé M.
Published: January 2015

The 2015 Nucleic Acids Research Database Issue contains 172 papers that include descriptions of 56 new molecular biology databases, and updates on 115 databases whose descriptions have been previously published in NAR or other journals. Following the classification that has been introduced last year in order to simplify navigation of the entire issue, these articles are divided into eight subject categories. This year's highlights include RNAcentral, an international community portal to various databases on noncoding RNA; ValidatorDB, a validation database for protein structures and their ligands; SASBDB, a primary repository for small-angle scattering data of various macromolecular complexes; MoonProt, a database of ‘moonlighting’ proteins, and two new databases of protein–protein and other macromolecular complexes, ComPPI and the Complex Portal. This issue also includes an unusually high number of cancer-related databases and other databases dedicated to genomic basics of disease and potential drugs and drug targets. The size of NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/a/, remained approximately the same, following the addition of 74 new resources and removal of 77 obsolete web sites. The entire Database Issue is freely available online on the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).
Opposing roles of H3- and H4-acetylation in the regulation of nucleosome structure—a FRET study
Authors: Gansen Alexander , Tóth Katalin , Schwarz Nathalie , Langowski Jörg
Published: January 2015

Using FRET in bulk and on single molecules, we assessed the structural role of histone acetylation in nucleosomes reconstituted on the 170 bp long Widom 601 sequence. We followed salt-induced nucleosome disassembly, using donor–acceptor pairs on the ends or in the internal part of the nucleosomal DNA, and on H2B histone for measuring H2A/H2B dimer exchange. This allowed us to distinguish the influence of acetylation on salt-induced DNA unwrapping at the entry–exit site from its effect on nucleosome core dissociation. The effect of lysine acetylation is not simply cumulative, but showed distinct histone-specificity. Both H3- and H4-acetylation enhance DNA unwrapping above physiological ionic strength; however, while H3-acetylation renders the nucleosome core more sensitive to salt-induced dissociation and to dimer exchange, H4-acetylation counteracts these effects. Thus, our data suggest, that H3- and H4-acetylation have partially opposing roles in regulating nucleosome architecture and that distinct aspects of nucleosome dynamics might be independently controlled by individual histones.
DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes
Authors: Cohen Isadora S. , Bar Carmit , Paz-Elizur Tamar , Ainbinder Elena , Leopold Karoline , de Wind Niels , Geacintov Nicholas , Livneh Zvi
Published: January 2015

DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells.
Sequences spanning the leader-repeat junction mediate CRISPR adaptation to phage in Streptococcus thermophilus
Authors: Wei Yunzhou , Chesne Megan T. , Terns Rebecca M. , Terns Michael P.
Published: January 2015

CRISPR-Cas systems are RNA-based immune systems that protect prokaryotes from invaders such as phages and plasmids. In adaptation, the initial phase of the immune response, short foreign DNA fragments are captured and integrated into host CRISPR loci to provide heritable defense against encountered foreign nucleic acids. Each CRISPR contains a ∼100–500 bp leader element that typically includes a transcription promoter, followed by an array of captured ∼35 bp sequences (spacers) sandwiched between copies of an identical ∼35 bp direct repeat sequence. New spacers are added immediately downstream of the leader. Here, we have analyzed adaptation to phage infection in Streptococcus thermophilus at the CRISPR1 locus to identify cis-acting elements essential for the process. We show that the leader and a single repeat of the CRISPR locus are sufficient for adaptation in this system. Moreover, we identified a leader sequence element capable of stimulating adaptation at a dormant repeat. We found that sequences within 10 bp of the site of integration, in both the leader and repeat of the CRISPR, are required for the process. Our results indicate that information at the CRISPR leader-repeat junction is critical for adaptation in this Type II-A system and likely other CRISPR-Cas systems.
Antiretroviral Regimen and Suboptimal Medication Adherence Are Associated With Low-Level Human Immunodeficiency Virus Viremia
Authors: Konstantopoulos Christina , Ribaudo Heather , Ragland Kathleen , Bangsberg David R. , Li Jonathan Z.
Published: January 2015

Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification.
Impaired Autophagosome Clearance Contributes to Local Anesthetic Bupivacaine-induced Myotoxicity in Mouse Myoblasts
Authors: Li Rongrong , Ma He , Zhang Xiaojin , Li Chuanfu , Xiong Jingwei , Lu Ting , Mao Yu , Dai Juncheng , Liu Li , Ding Zhengnian
Published: January 2015

AbstractAbstract

Bupivacaine stimulates autophagosome formation as a stress response and impairs autophagosome clearance by interfering with autophagosome–lysosome fusion, resulting in muscle cell injury. Rapamycin attenuates bupivacaine myotoxicity by increasing both autophagosome formation and autophagosome–lysosome fusion.

Supplemental Digital Content is available in the text.

Background:

The current study examined the role(s) of autophagy in myotoxicity induced by bupivacaine in mouse myoblast C2c12 cells.

Methods:

C2c12 cells were treated with bupivacaine. Myotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (n = 3 to 30), live/dead assay (n = 3 to 4), and morphological alterations (n = 3). Autophagosome formation was reflected by microtubule-associated protein light chain 3 conversion (n = 4 to 12) and light chain 3 punctation (n = 4 to 5). Autophagosome clearance was evaluated by p62 protein level (n = 4) and autolysosomes generation (n = 3).

Results:

Bupivacaine induced significant cell damage. Notably, there was a significant increase in autophagosome generation as evidenced by light chain 3 puncta formation (72.7 ± 6.9 vs. 2.1 ± 1.2) and light chain 3 conversion (2.16 ± 0.15 vs. 0.33 ± 0.04) in bupivacaine-treated cells. Bupivacaine inactivated the protein kinase B/mammalian target of rapamycin/p70 ribosomal protein S6 kinase signaling. However, cellular levels of p62 protein were significantly increased upon bupivacaine treatment (1.29 ± 0.15 vs. 1.00 ± 0.15), suggesting that the drug impaired autophagosome clearance. Further examination revealed that bupivacaine interrupted autophagosome–lysosome fusion (10.87% ± 1.48% vs. 32.94% ± 4.22%). Administration of rapamycin increased autophagosome clearance and, most importantly, improved the survival in bupivacaine-treated cells. However, knockdown of autophagy-related protein 5 (atg5) exacerbated bupivacaine-induced impairment of autophagosome clearance and myotoxicity.

Conclusions:

The data suggest that autophagosome formation was induced as a stress response mechanism after bupivacaine challenge; however, autophagosome clearance was impaired due to inadequate autophagosome–lysosome fusion. Therefore, impairment of autophagosome clearance appears to be a novel mechanism underlying bupivacaine-induced myotoxicity.
Modular continuing professional development for emergency physicians – the MNSHA masterclass programme
Authors: van den Berg Eefje E.P. , Bracey Amanda , van Driel A. Pieter G. , Geijsel Femke E.C. , Manders Sander
Published: January 2015

Introduction

Emergency physician (EP) training in the Netherlands is currently a 3-year competency-based programme. Upon its completion, many Dutch EPs feel that they lack some of the skills and the knowledge necessary to be fully prepared for the challenges of emergency medicine. We perceived a need for new methods to deliver continuing professional development (CPD).

Methods

A needs analysis survey was conducted to ascertain whether our perceived need for a new CPD programme was genuine. A new course was developed, incorporating innovative learning methods. The results of the needs analysis were incorporated into the programme. Another survey was held among participants of the first two editions of the programme.

Results, discussion and conclusion

Modular CPD for Emergency Physicians (Dutch: MNSHA) is a modular programme that aims to deliver CPD to Dutch EPs. It combines innovative educational methods, such as asynchronous learning in a flipped classroom, with web-based mentoring. The aim is for participants to develop effective, individualized and sustainable methods to gain and maintain knowledge and skills as a part of their ongoing professional education. The participant survey showed encouraging results, strongly suggesting an improvement in confidence. A more robust study would be required to better assess the outcomes of our programme.
Efficacy and Safety of Adalimumab After Infliximab Failure in Pediatric Crohn Disease
Authors: Fumery Mathurin , Jacob Anne , Sarter Hélène , Michaud Laurent , Spyckerelle Claire , Mouterde Olivier , Savoye Guillaume , Colombel Jean‐Frédéric , Peyrin‐Biroulet Laurent , Gower‐Rousseau Corinne , Turck Dominique ,   EPIMAD Group
Published: January 2015

Objectives:

The objective of the present study was to evaluate the effectiveness and safety of adalimumab (ADA) in children with Crohn disease (CD) who experienced infliximab (IFX) failure at the population level.

Methods:

The present retrospective study included all of the children with CD from a pediatric‐onset population‐based cohort who received ADA before 18 years because of IFX failure or intolerance. Efficacy of ADA was evaluated using the physician's global assessment score, C‐reactive protein and orosomucoid, and nutritional and growth indicators.

Results:

A total of 27 children with CD received ADA. Median age at CD diagnosis and at ADA initiation was 11 years (Q1 = 9; Q3 = 12) and 15 years (12; 15), respectively. After a median follow‐up of 16 (8; 26) months after ADA initiation, ADA had clinical benefit as measured by the physical global assessment score in 19 patients (70%). Cumulative probability of failure to ADA treatment was 38% at 6 months and 55% at 1 year. Eight patients had a primary failure (30%) and 5 of 19 (26%) a secondary failure to ADA. Furthermore, 11 patients (40%) experienced a total of 19 adverse effects. No serious adverse effects were observed and none resulted in ADA discontinuation. There was no significant change in growth and nutritional patterns during the study period, but we found a significant decrease in median C‐reactive protein (15 mg/L [4; 44] vs 9 mg/L [3; 19]; P = 0.05) and orosomucoid (1.6 g/L [1.5; 2.6] vs 1.1 g/L [0.8; 1.9]; P = 0.001) from ADA initiation to maximal follow‐up in patients responding to ADA.

Conclusions:

In the present population‐based cohort of pediatric‐onset CD with IFX failure, treatment with ADA was safe and effective in two‐thirds of patients.
Epidemiology of Irritable Bowel Syndrome in Children and Adolescents in Asia
Authors: Devanarayana Niranga M. , Rajindrajith Shaman , Pathmeswaran Arunasalam , Abegunasekara Chithra , Gunawardena Nipul K. , Benninga Marc A.
Published: January 2015

Objectives:

Several cross‐sectional surveys have been conducted to study the prevalence of irritable bowel syndrome (IBS) in children. The aim of the present study was to conduct a systematic review and a meta‐analysis of published literature to estimate the prevalence of IBS among Asian children.

Method:

A computer‐assisted search of MEDLINE, EMBASE, PsycINFO, and regional databases of Asia was carried out. Selected articles were reviewed in depth and data were extracted. Pooled prevalence, sex differences, and 95% confidence intervals were calculated. Heterogeneity of the studies was assessed using the I2 test.

Results:

A total of 16 cross‐sectional studies that reported prevalence of IBS (in children and adolescents) and qualified to be included were taken into the final analysis containing 38,076 patients. Selected studies are from China, Korea, Japan, Iran, Sri Lanka, and Saudi Arabia. Studies showed a marked heterogeneity with I2 of 98.59 (P < 0.0001). Prevalence of IBS ranges from 2.8% to 25.7%, with a pooled prevalence of 12.41% (95% confidence interval 9.87–14.95). Prevalence risk ratio of girl:boy is 1.39. Prevalence of subtypes is diverse and varies between studies.

Conclusions:

The published data indicate that IBS is a significant problem among Asian children and adolescents. Female sex predisposes children and adolescents to develop IBS.
Many hepatitis C reinfections that spontaneously clear may be undetected: Markov-chain Monte Carlo analysis of observational study data
Authors: Sacks-Davis Rachel , McBryde Emma , Grebely Jason , Hellard Margaret , Vickerman Peter
Published: January 2015

Hepatitis C virus (HCV) reinfection rates are probably underestimated due to reinfection episodes occurring between study visits. A Markov model of HCV reinfection and spontaneous clearance was fitted to empirical data. Bayesian post-estimation was used to project reinfection rates, reinfection spontaneous clearance probability and duration of reinfection. Uniform prior probability distributions were assumed for reinfection rate (more than 0), spontaneous clearance probability (0–1) and duration (0.25–6.00 months). Model estimates were 104 per 100 person-years (95% CrI: 21–344), 0.84 (95% CrI: 0.59–0.98) and 1.3 months (95% CrI: 0.3–4.1) for reinfection rate, spontaneous clearance probability and duration, respectively. Simulation studies were used to assess model validity, demonstrating that the Bayesian model estimates provided useful information about the possible sources and magnitude of bias in epidemiological estimates of reinfection rates, probability of reinfection clearance and duration or reinfection. The quality of the Bayesian estimates improved for larger samples and shorter test intervals. Uncertainty in model estimates notwithstanding, findings suggest that HCV reinfections frequently and quickly result in spontaneous clearance, with many reinfection events going unobserved.
In vivorecording of aerodynamic force with an aerodynamic force platform: from drones to birds
Authors: Lentink David , Haselsteiner Andreas F. , Ingersoll Rivers
Published: January 2015

Flapping wings enable flying animals and biomimetic robots to generate elevated aerodynamic forces. Measurements that demonstrate this capability are based on experiments with tethered robots and animals, and indirect force calculations based on measured kinematics or airflow during free flight. Remarkably, there exists no method to measure these forces directly during free flight. Suchin vivorecordings in freely behaving animals are essential to better understand the precise aerodynamic function of their flapping wings, in particular during the downstroke versus upstroke. Here, we demonstrate a new aerodynamic force platform (AFP) for non-intrusive aerodynamic force measurement in freely flying animals and robots. The platform encloses the animal or object that generates fluid force with a physical control surface, which mechanically integrates the net aerodynamic force that is transferred to the earth. Using a straightforward analytical solution of the Navier–Stokes equation, we verified that the method is accurate. We subsequently validated the method with a quadcopter that is suspended in the AFP and generates unsteady thrust profiles. These independent measurements confirm that the AFP is indeed accurate. We demonstrate the effectiveness of the AFP by studying aerodynamic weight support of a freely flying birdin vivo. These measurements confirm earlier findings based on kinematics and flow measurements, which suggest that the avian downstroke, not the upstroke, is primarily responsible for body weight support during take-off and landing.
Stick–slip friction of gecko-mimetic flaps on smooth and rough surfaces
Authors: Das Saurabh , Cadirov Nicholas , Chary Sathya , Kaufman Yair , Hogan Jack , Turner Kimberly L. , Israelachvili Jacob N.
Published: January 2015

The discovery and understanding of gecko ‘frictional-adhesion’ adhering and climbing mechanism has allowed researchers to mimic and create gecko-inspired adhesives. A few experimental and theoretical approaches have been taken to understand the effect of surface roughness on synthetic adhesive performance, and the implications of stick–slip friction during shearing. This work extends previous studies by using a modified surface forces apparatus to quantitatively measure and model frictional forces between arrays of polydimethylsiloxane gecko footpad-mimetic tilted microflaps against smooth and rough glass surfaces. Constant attachments and detachments occur between the surfaces during shearing, as described by an
avalanche
model. These detachments ultimately result in failure of the adhesion interface and have been characterized in this study. Stick–slip friction disappears with increasing velocity when the flaps are sheared against a smooth silica surface; however, stick–slip was always present at all velocities and loads tested when shearing the flaps against rough glass surfaces. These results demonstrate the significance of pre-load, shearing velocity, shearing distances, commensurability and shearing direction of gecko-mimetic adhesives and provide us a simple model for analysing and/or designing such systems.
Bacterial genospecies that are not ecologically coherent: population genomics ofRhizobium leguminosarum
Authors: Kumar Nitin , Lad Ganesh , Giuntini Elisa , Kaye Maria E. , Udomwong Piyachat , Shamsani N. Jannah , Young J. Peter W. , Bailly Xavier
Published: January 2015

Biological species may remain distinct because of genetic isolation or ecological adaptation, but these two aspects do not always coincide. To establish the nature of the species boundary within a local bacterial population, we characterized a sympatric population of the bacteriumRhizobium leguminosarumby genomic sequencing of 72 isolates. Although all strains have 16S rRNA typical ofR. leguminosarum, they fall into five genospecies by the criterion of average nucleotide identity (ANI). Many genes, on plasmids as well as the chromosome, support this division: recombination of core genes has been largely within genospecies. Nevertheless, variation in ecological properties, including symbiotic host range and carbon-source utilization, cuts across these genospecies, so that none of these phenotypes is diagnostic of genospecies. This phenotypic variation is conferred by mobile genes. The genospecies meet the Mayr criteria for biological species in respect of their core genes, but do not correspond to coherent ecological groups, so periodic selection may not be effective in purging variation within them. The population structure is incompatible with traditional ‘polyphasic taxonomy′ that requires bacterial species to have both phylogenetic coherence and distinctive phenotypes. More generally, genomics has revealed that many bacterial species share adaptive modules by horizontal gene transfer, and we envisage a more consistent taxonomic framework that explicitly recognizes this. Significant phenotypes should be recognized as ‘biovars' within species that are defined by core gene phylogeny.
Drosophilagenetao-1encodes proteins with and without a Ste20 kinase domain that affect cytoskeletal architecture and cell migration differently
Authors: Pflanz Ralf , Voigt Aaron , Yakulov Toma , Jäckle Herbert
Published: January 2015

Tao-1, the single representative of the Sterile 20 kinase subfamily inDrosophila, is best known for destabilizing microtubules at the actin-rich cortex, regulating the cytoskeletal architecture of cells. More recently, Tao-1 was shown to act in the Salvador–Warts–Hippo pathway by phosphorylating Hippo, regulating cell growth as well as cell polarity. Here, we show thattao-1encodes two proteins, one with the Sterile 20 kinase domain (Tao-L) and one without it (Tao-S), and that they act in an antagonistic manner. Tao-L expression causes lamellipodia-like cell protrusions, whereas Tao-S expression results in filopodia-like structures that make cells stick to the surface they attach to. Ectopic Tao-1 expression in the anterior region ofDrosophilaembryos results in pole cell formation as normally observed at the posterior end. Tao-S expression causes primordial germ cells (PGCs) to adhere to the inner wall of the gut primordia and prevents proper transepithelial migration to the gonads. Conversely, RNAi knockdowns of Tao-1 cause disordered migration of PGCs out of the gut epithelium, their dispersal within the embryo and cell death. The results reveal a novel function of Tao-1 in cell migration, which is based on antagonistic activities of two proteins encoded by a single gene.
MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of
Mycoplasma hyopneumoniae
Authors: Jarocki Veronica M. , Santos Jerran , Tacchi Jessica L. , Raymond Benjamin B. A. , Deutscher Ania T. , Jenkins Cheryl , Padula Matthew P. , Djordjevic Steven P.
Published: January 2015

Aminopeptidases are part of the arsenal of virulence factors produced by bacterial pathogens that inactivate host immune peptides.
Mycoplasma hyopneumoniae
is a genome-reduced pathogen of swine that lacks the genetic repertoire to synthesize amino acids and relies on the host for availability of amino acids for growth.
M. hyopneumoniae
recruits plasmin(ogen) onto its cell surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125. Plasmin plays an important role in regulating the inflammatory response in the lungs of pigs infected with
M. hyopneumoniae
. We show that recombinant MHJ_0461 (rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate specificity for leucine, alanine, phenylalanine, methionine and arginine and that MHJ_0461 resides on the surface of
M. hyopneumoniae
. rMHJ_0461 also binds heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily converted to plasmin in the presence of tPA. Computational modelling identified putative DNA and heparin-binding motifs on solvent-exposed sites around a large pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a multifunctional adhesin on the cell surface of
M. hyopneumoniae
.
Surface drag reduction and flow separation control in pelagic vertebrates, with implications for interpreting scale morphologies in fossil taxa
Authors: Palmer Colin , Young Mark T.
Published: January 2015

Living in water imposes severe constraints on the evolution of the vertebrate body. As a result of these constraints, numerous extant and extinct aquatic vertebrate groups evolved convergent osteological and soft-tissue adaptations. However, one important suite of adaptations is still poorly understood: dermal cover morphologies and how they influence surface fluid dynamics. This is especially true for fossil aquatic vertebrates where the soft tissue of the dermis is rarely preserved. Recent studies have suggested that the keeled scales of mosasaurids (pelagic lizards that lived during the Late Cretaceous) aided in surface frictional drag reduction in a manner analogous to the riblets on shark placoid scales. However, here we demonstrate that mosasaurid scales were over an order of magnitude too large to have this effect. More likely they increased the frictional drag of the body and may have played a role in controlling flow separation by acting as surface roughness that turbulated the boundary layer. Such a role could have reduced pressure drag and enhanced manoeuvrability. We caution those studying fossil aquatic vertebrates from positing the presence of surface drag reducing morphologies, because as we show herein, to be effective such features need to have a spacing of approximately 0.1 mm or less.
Sex ratio effects on reproductive strategies in humans
Authors: Schacht Ryan , Borgerhoff Mulder Monique
Published: January 2015

Characterizations of coy females and ardent males are rooted in models of sexual selection that are increasingly outdated. Evolutionary feedbacks can strongly influence the sex roles and subsequent patterns of sex differentiated investment in mating effort, with a key component being the adult sex ratio (ASR). Using data from eight Makushi communities of southern Guyana, characterized by varying ASRs contingent on migration, we show that even within a single ethnic group, male mating effort varies in predictable ways with the ASR. At male-biased sex ratios, men's and women's investment in mating effort are indistinguishable; only when men are in the minority are they more inclined towards short-term, low investment relationships than women. Our results support the behavioural ecological tenet that reproductive strategies are predictable and contingent on varying situational factors.
How the zebra got its stripes: a problem with too many solutions
Authors: Larison Brenda , Harrigan Ryan J. , Thomassen Henri A. , Rubenstein Daniel I. , Chan-Golston Alec M. , Li Elizabeth , Smith Thomas B.
Published: January 2015

The adaptive significance of zebra stripes has thus far eluded understanding. Many explanations have been suggested, including social cohesion, thermoregulation, predation evasion and avoidance of biting flies. Identifying the associations between phenotypic and environmental factors is essential for testing these hypotheses and substantiating existing experimental evidence. Plains zebra striping pattern varies regionally, from heavy black and white striping over the entire body in some areas to reduced stripe coverage with thinner and lighter stripes in others. We examined how well 29 environmental variables predict the variation in stripe characteristics of plains zebra across their range in Africa. In contrast to recent findings, we found no evidence that striping may have evolved to escape predators or avoid biting flies. Instead, we found that temperature successfully predicts a substantial amount of the stripe pattern variation observed in plains zebra. As this association between striping and temperature may be indicative of multiple biological processes, we suggest that the selective agents driving zebra striping are probably multifarious and complex.
Boundary regularized integral equation formulation of the Helmholtz equation in acoustics
Authors: Sun Qiang , Klaseboer Evert , Khoo Boo-Cheong , Chan Derek Y. C.
Published: January 2015

A boundary integral formulation for the solution of the Helmholtz equation is developed in which all traditional singular behaviour in the boundary integrals is removed analytically. The numerical precision of this approach is illustrated with calculation of the pressure field owing to radiating bodies in acoustic wave problems. This method facilitates the use of higher order surface elements to represent boundaries, resulting in a significant reduction in the problem size with improved precision. Problems with extreme geometric aspect ratios can also be handled without diminished precision. When combined with the CHIEF method, uniqueness of the solution of the exterior acoustic problem is assured without the need to solve hypersingular integrals.
Salipiger nanhaiensis sp. nov., a bacterium isolated from deep sea water
Authors: Dai Xiaofeng , Shi Xiaochong , Gao Xin , Liang Jing , Zhang Xiao-Hua
Published: January 2015

A Gram-stain-negative, facultatively anaerobic, chemoheterotrophic, moderately halophilic, exopolysaccharide (EPS)-producing, cream, non-motile and rod-shaped bacterium, designated strain ZH114T, was isolated from deep water of the South China Sea, and was subjected to a polyphasic taxonomic study. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that this strain belongs to the genus

Salipiger

with the highest sequence similarity to

Salipiger mucescens

LMG 22090T (96.83 %), followed by

Pseudodonghicola xiamenensis

LMG 24574T (96.12 %). Growth occurred at 4–37 °C (optimum 32 °C), pH 6.0–10.0 (optimum pH 9.0–10.0) and in the presence of 0–19 % NaCl (w/v) (optimum 6 %, w/v). It did not produce poly-β-hydroxyalkanoate granules or bacteriochlorophyll a. Acid was produced from glycerol, erythrose, ribose, d-xylose, galactose, glucose, fructose, mannitol, cellobiose, maltose, lactose, melibiose, turanose, d-lyxose, d-tagatose, d-fucose, d-arabitol and l-arabitol after inoculating for 24 h and weakly positive results were also detected after 48 h in API 50CH strips with d-arabinose, l-arabinose, l-xylose, adonitol, mannose, aesculin, salicin, sucrose, mycose and l-fucose. The predominant fatty acids were C18 : 1ω7c and/or C18 : 1ω6c, C16 : 0, C18 : 0 and 11-methyl C18 : 1ω7c. The major polar lipids of ZH114T were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and two unidentified lipids. The major respiratory quinone was ubiquinone Q-10. The genomic DNA G+C content of strain ZH114T was 63.8 mol%. Based on this phenotypic, chemotaxonomic and phylogenetic analysis, strain ZH114T should be classified as a representative of a novel species of the genus

Salipiger

, for which the name Salipiger nanhaiensis sp. nov. is proposed. The type strain is ZH114T ( = JCM 19383T = KCTC 32468T).