bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay between predicted inner‐rod and gatekeeper in controlling substrate specificity of the type III secretion system
Authors: Cherradi Youness , Schiavolin Lionel , Moussa Simon , Meghraoui Alaeddine , Meksem Ahmed , Biskri Latéfa , Azarkan Mohamed , Allaoui Abdelmounaaïm , Botteaux Anne 
Published: January 2013

SummaryThe type III secretion apparatus (T3SA) is a multi‐protein complex central to the virulence of many Gram‐negative pathogens. Currently, the mechanisms controlling the hierarchical addressing of needle subunits, translocators and effectors to the T3SA are still poorly understood. In Shigella, MxiC is known to sequester effectors within the cytoplasm prior to receiving the activation signal from the needle. However, molecules involved in linking the needle and MxiC are unknown. Here, we demonstrate a molecular interaction between MxiC and the predicted inner‐rod component MxiI suggesting that this complex plugs the T3SA entry gate. Our results suggest that MxiI–MxiC complex dissociation facilitates the switch in secretion from translocators to effectors. We identified MxiCF206S variant, unable to interact with MxiI, which exhibits a constitutive secretion phenotype although it remains responsive to induction. Moreover, we identified the mxiIQ67A mutant that only secretes translocators, a phenotype that was suppressed by coexpression of the MxiCF206S variant. We demonstrated the interaction between MxiI and MxiC homologues in Yersinia and Salmonella. Lastly, we identified an interaction between MxiC and chaperone IpgC which contributes to understanding how translocators secretion is regulated. In summary, this study suggests the existence of a widely conserved T3S mechanism that regulates effectors secretion.
Characteristics and outcomes in community‐acquired versus hospital‐acquired acute kidney injury
Authors: Schissler Michael M , Zaidi Syed , Kumar Haresh , Deo Datinder , Brier Michael E , McLeish Kenneth R. 
Published: January 2013

AbstractAimRelatively little is known about the prevalence of acute kidney injury developing outside a hospital setting (CA‐AKI) or the impact of CA‐AKI on short‐term or long‐term clinical outcomes. The objective of this study was to compare the prevalence, causes, severity and outcomes of patients with CA‐AKI and hospital‐acquired (HA)‐AKI.MethodsA retrospective cohort study of patients with AKI identified by ICD‐9 code at a single VA (Veterans Affairs) hospital from September 1999 to May 2007 was performed. AKI was verified by applying the RIFLE criteria, and patients were categorized as CA‐AKI if RIFLE criteria were met at admission. Demographic, clinical, and outcome variables were extracted by chart review.ResultsFour hundred twenty‐two patients met inclusion criteria, of which 335 (79.4%) developed CA‐AKI. Patients with CA‐AKI were more likely to have volume depletion as the aetiology, had fewer chronic illnesses and hospital complications, had a shorter length of stay, and had a reduced mortality, compared with HA‐AKI. Distribution among the three RIFLE classes did not differ between groups, and recovery of renal function was incomplete in both groups.ConclusionWe conclude that CA‐AKI is a common cause of AKI that is as severe as that seen in HA‐AKI. CA‐AKI has a significant impact on length of hospital stay, mortality, and the development and/or progression of chronic kidney disease. Strategies to limit the risk of CA‐AKI are likely to have a significant impact on healthcare costs and patient care.
Inflammatory bowel disease: perspectives from cingulate cortex in the first brain
Authors: Vogt B. A. 
Published: January 2013

AbstractThe article by Agostiniet al.(2013) in this issue ofNeurogastroenterology and Motilityevaluated patients with Crohn’s disease (CD) for volumetric changes throughout the brain. They observed decreased gray matter volumes in dorsolateral prefrontal cortex and anterior midcingulate cortex (aMCC) and disease duration was negatively correlated with volumes in subgenual anterior cingulate (sACC), posterior MCC (pMCC), ventral posterior cingulate (vPCC), and parahippocampal cortices. As all patients were in remission and suffered from ongoing abdominal pain, this study provides a critical link between forebrain changes and abdominal pain experience independent of active disease and drug treatment. The aMCC has a role in feedback‐mediated decision making and there are specific cognitive tasks that differentiate aMCC and pMCC that can be used to evaluate defects in CD. The sACC is an important area as it has impaired functions in major depression. As depressive symptoms are a feature in a subset of patients with active inflammatory diseases including IBD, treatment targeting this subregion should prove efficacious. Finally, vPCC has a role in ongoing self‐monitoring of the personal relevance of sensory stimuli including visceral signals via sACC. This pathway may be interrupted by vPCC atrophy in CD. Cingulate atrophy in CD leads to targeting chronic pain and psychiatric symptoms via cingulate‐mediated therapies. These include psychotherapy, guided imagery and relaxation training, analgesic dosages of morphine or antidepressants, and hypnosis. Thus, a new generation of novel treatments may emerge from drug and non‐traditional therapies for CD in this formative area of research.
Evaluation of esophageal motor function in clinical practice
Authors: Gyawali C. P. , Bredenoord A. J. , Conklin J. L. , Fox M. , Pandolfino J. E. , Peters J. H. , Roman S. , Staiano A. , Vaezi M. F. 
Published: January 2013

AbstractEsophageal motor function is highly coordinated between central and enteric nervous systems and the esophageal musculature, which consists of proximal skeletal and distal smooth muscle in three functional regions, the upper and lower esophageal sphincters, and the esophageal body. While upper endoscopy is useful in evaluating for structural disorders of the esophagus, barium esophagography, radionuclide transit studies, and esophageal intraluminal impedance evaluate esophageal transit and partially assess motor function. However, esophageal manometry is the test of choice for the evaluation of esophageal motor function. In recent years, high‐resolution manometry (HRM) has streamlined the process of acquisition and display of esophageal pressure data, while uncovering hitherto unrecognized esophageal physiologic mechanisms and pathophysiologic patterns. New algorithms have been devised for analysis and reporting of esophageal pressure topography from HRM. The clinical value of HRM extends to the pediatric population, and complements preoperative evaluation prior to foregut surgery. Provocative maneuvers during HRM may add to the assessment of esophageal motor function. The addition of impedance to HRM provides bolus transit data, but impact on clinical management remains unclear. Emerging techniques such as 3‐D HRM and impedance planimetry show promise in the assessment of esophageal sphincter function and esophageal biomechanics.
Assessment of a condition‐specific quality‐of‐life measure for patients with developmentally absent teeth: validity and reliability testing
Authors: Akram A. J. , Ireland A. J. , Postlethwaite K. C. , Sandy J. R. , Jerreat A. S. 
Published: January 2013

Structured AbstractObjectivesThis article describes the process of validity and reliability testing of a condition‐specific quality‐of‐life measure for patients with hypodontia presenting for orthodontic treatment. The development of the instrument is described in a previous article.Setting and Sample populationRoyal Devon and Exeter NHS Foundation Trust & Musgrove Park Hospital, Taunton.Materials and MethodsThe child perception questionnaire was used as a standard against which to test criterion validity. The Bland and Altman method was used to check agreement between the two questionnaires. Construct validity was tested using principal component analysis on the four sections of the questionnaire. Test–retest reliability was tested using intraclass correlation coefficient and Bland and Altman method. Cronbach's alpha was used to test internal consistency reliability.ResultsOverall the questionnaire showed good reliability, criterion and construct validity. This together with previous evidence of good face and content validity suggests that the instrument may prove useful in clinical practice and further research.ConclusionsThis study has demonstrated that the newly developed condition‐specific quality‐of‐life questionnaire is both valid and reliable for use in young patients with hypodontia.
Extended Likelihood Approach to Large-Scale Multiple Testing
Authors: Lee Youngjo , Bjørnstad Jan F. 
Published: January 2013

SummaryTo date, only frequentist, Bayesian and empirical Bayes approaches have been studied for the large-scale inference problem of testing simultaneously hundreds or thousands of hypotheses. Their derivations start with some summarizing statistics without modelling the basic responses. As a consequence testing procedures have been developed without necessarily checking model assumptions, and empirical null distributions are needed to avoid the problem of rejecting all null hypotheses when the sample sizes are large. Nevertheless these procedures may not be statistically efficient. We present the multiple-testing problem as a multiple-prediction problem of whether a null hypothesis is true or not. We introduce hierarchical random-effect models for basic responses and show how the extended likelihood is built. It is shown that the likelihood prediction has a certain oracle property. The extended likelihood leads to new testing procedures, which are optimal for the usual loss function in hypothesis testing. The new tests are based on certain shrinkage t-statistics and control the local probability of false discovery for individual tests to maintain the global frequentist false discovery rate and have no need to consider an empirical null distribution for the shrinkage t-statistics. Conditions are given when these false rates vanish. Three examples illustrate how to use the likelihood method in practice. A numerical study shows that the likelihood approach can greatly improve existing methods and finding the best fitting model is crucial for the behaviour of test procedures.
Internal architecture and evolution of bioclastic beach ridges in a megatidal chenier plain: Field data and wave flume experiment
Authors: Weill Pierre , Mouazé Dominique , Tessier Bernadette 
Published: January 2013

AbstractBeach ridges in macrotidal environments experience strong multi‐annual to multi‐decennial fluctuations of tidal inundation. The duration of tide flooding directly controls the duration of sediment reworking by waves, and thus the ridge dynamics. Flume modelling was used to investigate the impact of low‐frequency tidal cycles on beach ridge evolution and internal architecture. The experiment was performed using natural bioclastic sediment, constant wave parameters and low‐frequency variations of the mean water level. The morphological response of the beach ridge to water level fluctuations and the preservation of sedimentary structures were monitored by using side‐view and plan‐view photographs. Results were compared with the internal architecture of modern bioclastic beach ridges in a macrotidal chenier plain (Mont St. Michel Bay, France) surveyed with ground‐penetrating radar. The experimentally obtained morphologies and internal structures matched those observed in the field, and the three ridge development stages identified in ground‐penetrating radar profiles (early transgressive, late transgressive and progradational) were modelled successfully. Flume experiments indicate that flat bioclastic shapes play a key role in sediment sorting in the breaker zone, and in sediment layering in the beach and washover fans. Water level controls washover geometry, beach ridge evolution and internal structure. Low water levels allow beach ridge stabilization and sediment accumulation lower on tidal flats. During subsequent water level rise, accumulated sediment becomes available for deposition of new washover units and for bayward extension of the beach ridges. In the field, low‐frequency water level fluctuations are related to the 4·4 year and 18·6 year tidal cycles. Experimental results suggest that these cycles may represent the underlying factor in the evolution of the macrotidal chenier coast at the multi‐decadal to centennial time scale.
Arsenic in framboidal pyrite from recent sediments of a shallow water lagoon of the Baltic Sea
Authors: Neumann Thomas , Scholz Florian , Kramar Utz , Ostermaier Michael , Rausch Nicole , Berner Zsolt 
Published: January 2013

AbstractArsenic is a redox‐sensitive element of environmental relevance and often enriched in iron sulphides. Because sediments from the Achterwasser lagoon, a part of the estuarine system of the river Oder, south‐west Baltic Sea, show unexpectedly high pyrite concentrations of up to 7·5 wt% they were used to investigate the influence of authigenic pyrite on the mobility and burial of As in the coastal environment. Micro‐X‐ray‐fluorescence measurements of 106 micrometre‐sized pyrite framboids from the anoxic sediments show highly variable As concentrations ranging from 6 to 1142 μg g−1. Even within a 1 cm thick layer, the As concentration of different framboids varies greatly and no clear depth trend is visible throughout the 50 cm long sediment core. Pyrite can account for 9 to 55% (average 22%) of the total As budget of the sediments and the degree of trace metalloid pyritization for As ranges from 26 to 61%, indicating that authigenic pyrite formation is an important process in the geochemical cycling of As in coastal sediments. High‐resolution micro‐X‐ray fluorescence mapping of single pyrite grains shows that As is distributed inhomogeneously within larger framboids, suggesting changing pore water composition during pyrite growth. X‐ray absorption near edge structure spectra indicate that As is usually present as As(‐I) substituting S in the pyrite lattice. However, in samples close to the sediment/water interface a considerable part of As is in higher valence states (+III/+V). This can be explained by frequent re‐suspension of the surficial sediments to the oxic water column due to wave action and subsequent re‐deposition, leading to the adsorption of As oxyanions onto pyrite. Although reduced As(‐I) becomes more important in the deeper samples, reflecting decreasing redox potential and a longer time since deposition, the occurrence of oxidized As species (AsIII/AsV) in pyrite in the anoxic part of the sediment suggests formation under dysoxic conditions.
Trade Liberalisation, Product Complexity and Productivity Improvement: Evidence from Chinese Firms
Authors: Yu Miaojie , Ye Guangliang , Qu Baozhi 
Published: January 2013

AbstractThis paper investigates the impact of trade liberalisation on firm productivity by using both Chinese manufacturing firm‐level data and highly disaggregated Chinese import data from 1998 to 2002. We construct a measure of firms’ total factor productivity by adopting an augmented Olley–Pakes semi‐parametric methodology to correct the simultaneity bias from reverse causality and selection bias from firms’ exits. Even when controlling for the endogeneity, trade liberalisation increases productivity for firms that produce complex goods (highly differentiated products). In contrast, we found that trade liberalisation has an opposite effect on the productivity of the producers of simple goods. Moreover, the effect of trade liberalisation on exporting firms is found to be smaller than that on non‐exporting firms. Our main results are robust to the use of different econometric methods.
Functional role of vasoactive intestinal polypeptide in inhibitory motor innervation in the mouse internal anal sphincter
Authors: Keef K. D. , Saxton S. N. , McDowall R. A. , Kaminski R. E. , Duffy A. M. , Cobine C. A. 
Published: January 2013

Key points
Vasoactive intestinal polypeptide (VIP)‐ergic neuromuscular transmission (NMT) was examined in the internal anal sphincter of wild‐type mice and compared with that of VIP−/− mice.
Relaxation and hyperpolarization during brief trains of electrical field stimulation (EFS; 4 s) were mediated by purinergic and nitrergic NMT.
During longer stimulus trains, a non‐purinergic, non‐nitrergic (NNNP) relaxation and hyperpolarization slowly developed and persisted for several minutes beyond the end of the stimulus train.
The NNNP NMT was abolished by VIP receptor antagonists, absent in the VIP−/− mouse internal anal sphincter and mimicked by exogenous VIP.
These data suggest that NNNP NMT gives rise to ultraslow relaxation and hyperpolarization that is mediated by VIP. In vivo, this pathway may be activated with larger rectal distensions, leading to a more prolonged anal relaxation.
Abstract  There is evidence that vasoactive intestinal polypeptide (VIP) participates in inhibitory neuromuscular transmission (NMT) in the internal anal sphincter (IAS). However, specific details concerning VIP‐ergic NMT are limited, largely because of difficulties in selectively blocking other inhibitory neural pathways. The present study used the selective P2Y1 receptor antagonist MRS2500 (1 μm) and the nitric oxide synthase inhibitor NG‐nitro‐l‐arginine (l‐NNA; 100 μm) to block purinergic and nitrergic NMT to characterize non‐purinergic, non‐nitrergic (NNNP) inhibitory NMT and the role of VIP in this response. Nerves were stimulated with electrical field stimulation (0.1–20 Hz, 4–60 s) and the associated changes in contractile and electrical activity measured in non‐adrenergic, non‐cholinergic conditions in the IAS of wild‐type and VIP−/− mice. Electrical field stimulation gave rise to frequency‐dependent relaxation and hyperpolarization that was blocked by tetrodotoxin. Responses during brief trains of stimuli (4 s) were mediated by purinergic and nitrergic NMT. During longer stimulus trains, an NNNP relaxation and hyperpolarization developed slowly and persisted for several minutes beyond the end of the stimulus train. The NNNP NMT was abolished by VIP6–28 (30 μm), absent in the VIP−/− mouse and mimicked by exogenous VIP (1–100 nm). Immunoreactivity for VIP was co‐localized with neuronal nitric oxide synthase in varicose intramuscular fibres but was not detected in the VIP−/− mouse IAS. In conclusion, this study identified an ultraslow component of inhibitory NMT in the IAS mediated by VIP. In vivo, this pathway may be activated with larger rectal distensions, leading to a more prolonged period of anal relaxation.
Republished: Failure of reflux inhibitors in clinical trials: bad drugs or wrong patients?
Authors: Kahrilas Peter J , Boeckxstaens Guy 
Published: January 2013

Abstract
Treatment modalities for gastro-oesophageal reflux disease (GORD) mirror the pathophysiology of the disease. Since acid plays a key role in GORD-associated mucosal lesions, proton pump inhibitors (PPIs) are the dominant GORD treatment, being the most potent inhibitors of acid secretion available. However, the clinical effectiveness of PPIs varies with the specific symptoms being treated; they are more effective for heartburn than for regurgitation than for extra-oesophageal symptoms. An alternative therapeutic approach to GORD is to prevent the most fundamental cause of reflux symptoms, reflux itself, which most commonly occurs by transient lower oesophageal sphincter relaxation (TLOSR). Among potential pharmaceutical agents developed to target TLOSRs, the most advanced are GABAB (γ-aminobutyric acid) agonists, which experimentally reduce the occurrence of TLOSRs by about 40% in both animal and human studies. However, the effectiveness of GABAB agonists in clinical trials of patients with GORD with an incomplete response to PPI treatment has been modest. In part, this is probably attributable to the difficult problem of patient selection in these trials. Identifying patients by partial response to PPI treatment results in a heterogeneous population, including those with persistent weakly acidic reflux, patients with visceral hypersensitivity and those with functional heartburn, dyspepsia, or chest pain. From the clinical data available, the best treatment results and, hence, the patients most likely to benefit from reflux inhibitors, are those with persistent reflux, most commonly manifest as persistent regurgitation despite PPI treatment.
Optimal DPM and DVFS for frame-based real-time systems
Authors: Gerards Marco E. T. , Kuper Jan 
Published: January 2013

Dynamic Power Management (DPM) and Dynamic Voltage and Frequency Scaling (DVFS) are popular techniques for reducing energy consumption. Algorithms for optimal DVFS exist, but optimal DPM and the optimal combination of DVFS and DPM are not yet solved.
In this article we use well-established models of DPM and DVFS for frame-based systems. We show that it is not sufficient—as some authors argue—to consider only individual invocations of a task. We define a schedule that also takes interactions between invocations into account and prove—in a theoretical fashion—that this schedule is optimal.
Lock-contention-aware scheduler
Authors: Cui Yan , Wang Yingxin , Chen Yu , Shi Yuanchun 
Published: January 2013

In response to the increasing ubiquity of multicore processors, there has been widespread development of multithreaded applications that strive to realize their full potential. Unfortunately, lock contention within operating systems can limit the scalability of multicore systems so severely that an increase in the number of cores can actually lead to reduced performance (i.e., scalability collapse).
Existing efforts of solving scalability collapse mainly focus on making critical sections of kernel code fine-grained or designing new synchronization primitives. However, these methods have disadvantages in scalability or energy efficiency. In this article, we observe that the percentage of lock-waiting time over the total execution time for a lock intensive task has a significant correlation with the occurrence of scalability collapse. Based on this observation, a lock-contention-aware scheduler is proposed. Specifically, each task in the scheduler monitors its percentage of lock waiting time continuously. If the percentage exceeds a predefined threshold, this task is considered as lock intensive and migrated to a Special Set of Cores (i.e., SSC). In this way, the number of concurrently running lock-intensive tasks is limited to the number of cores in the SSC, and therefore, the degree of lock contention is controlled. A central challenge of using this scheme is how many cores should be allocated in the SSC to handle lock-intensive tasks. In our scheduler, the optimal number of cores is determined online by the model-driven search.
The proposed scheduler is implemented in the recent Linux kernel and evaluated using micro- and macrobenchmarks on AMD and Intel 32-core systems. Experimental results suggest that our proposal is able to remove scalability collapse completely and sustains the maximal throughput of the spin-lock-based system for most applications. Furthermore, the percentage of lock-waiting time can be reduced by up to 84%. When compared with scalability collapse reduction methods such as requester-based locking scheme and sleeping-based synchronization primitives, our scheme exhibits significant advantages in scalability, power consumption, and energy efficiency.