bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-Terminally Modified Linear and Branched Spermine Backbone Dipeptidomimetics against Planktonic and Sessile Methicillin-Resistant Staphylococcus aureus
Authors: Dewangan Rikeshwer Prasad , Joshi Seema , Kumari Shalini , Gautam Hemlata , Yar Mohammed Shahar , Pasha Santosh 
Published: July 2014

ABSTRACT

Toward the discovery of useful therapeutic molecules, we report the design and synthesis of a focused library of new ultrashort N-terminally modified dipeptidomimetics, with or without modifications in the spermine backbone leading to linear (series 1) or branched (series 2) tryptophans, as antimicrobial agents. Eight peptidomimetics in the library showed good antibacterial activity (MICs of 1.77 to 14.2 μg/ml) against methicillin-resistant
Staphylococcus aureus
(MRSA) and methicillin-resistant
Staphylococcus epidermidis
bacterial strains. Tryptophan fluorescence measurements on artificial bacterial or mammalian mimic membranes and assessment of the MRSA potential depolarization ability of the designed compounds revealed membrane interactions dependent on tryptophan positioning and N-terminal tagging. Among active peptidomimetics, compounds 1c and 1d were found to be nonhemolytic, displaying rapid bactericidal activity (at 4× MIC) against exponentially growing MRSA. Further, scanning electron microscopy of peptidomimetic 1c- and 1d-treated MRSA showed morphological changes with damage to cell walls, defining a membrane-active mode of action. Moreover, peptidomimetics 1c and 1d did not induce significant drug resistance in MRSA even after 17 passages. We also investigated the activity of these molecules against MRSA biofilms. At sub-MIC levels (∼2 to 4 μg/ml), both peptidomimetics inhibited biofilm formation. At concentrations higher than the MIC (35 to 140 μg/ml), peptidomimetics 1c and 1d significantly reduced the metabolic activity and biomass of mature (24-h) MRSA biofilms. These results were corroborated by confocal laser scanning microscopy (live/dead assay). The
in vitro
protease stability and lower cytotoxicity of peptidomimetics against peripheral blood mononuclear cells (PBMCs) support them being novel staphylocidal peptidomimetics. In conclusion, this study provides two peptidomimetics as potential leads for treatment of staphylococcal infections under planktonic and sessile conditions.
Pleiotropic Role of the RNA Chaperone Protein Hfq in the Human Pathogen Clostridium difficile
Authors: Boudry P. , Gracia C. , Monot M. , Caillet J. , Saujet L. , Hajnsdorf E. , Dupuy B. , Martin-Verstraete I. , Soutourina O. 
Published: July 2014

ABSTRACT

Clostridium difficile
is an emergent human pathogen and the most common cause of nosocomial diarrhea. Our recent data strongly suggest the importance of RNA-based mechanisms for the control of gene expression in
C. difficile
. In an effort to understand the function of the RNA chaperone protein Hfq, we constructed and characterized an Hfq-depleted strain in
C. difficile
. Hfq depletion led to a growth defect, morphological changes, an increased sensitivity to stresses, and a better ability to sporulate and to form biofilms. The transcriptome analysis revealed pleiotropic effects of Hfq depletion on gene expression in
C. difficile
, including genes encoding proteins involved in sporulation, stress response, metabolic pathways, cell wall-associated proteins, transporters, and transcriptional regulators and genes of unknown function. Remarkably, a great number of genes of the regulon dependent on sporulation-specific sigma factor, SigK, were upregulated in the Hfq-depleted strain. The altered accumulation of several sRNAs and interaction of Hfq with selected sRNAs suggest potential involvement of Hfq in these regulatory RNA functions. Altogether, these results suggest the pleiotropic role of Hfq protein in
C. difficile
physiology, including processes important for the
C. difficile
infection cycle, and expand our knowledge of Hfq-dependent regulation in Gram-positive bacteria.
More than 50% of players sustained a time-loss injury (>1 day of lost training or playing time) during the 2012 Super Rugby Union Tournament: a prospective cohort study of 17 340 player-hours
Authors: Schwellnus Martin P , Thomson Alan , Derman Wayne , Jordaan Esme , Readhead Clint , Collins Rob , Morris Ian , Strauss Org , Van der Linde Ewoudt , Williams Arthur 
Published: July 2014

BackgroundProfessional Rugby Union is a contact sport with a high risk of injury.ObjectiveTo document the incidence and nature of time-loss injuries during the 2012 Super Rugby tournament.DesignProspective cohort study.Setting2012 Super Rugby tournament (Australia, New Zealand, South Africa).Participants152 players from 5 South African teams.MethodsTeam physicians collected daily injury data through a secure, web-based electronic platform. Data included size of the squad, type of day, main player position, training or match injury, hours of play (training and matches), time of the match injury, mechanism of injury, main anatomical location of the injury, specific anatomical structure of the injury, the type of injury, the severity of the injury (days lost).ResultsThe proportion (%) of players sustaining a time-loss injury during the tournament was 55%, and 25% of all players sustained >1 injury. The overall incidence rate (IR/1000 player-hours) of injuries was 9.2. The IR for matches (83.3) was significantly higher than for training (2.1) and the IR was similar for forwards and backs. Muscle/tendon (50%) and joint/ligament (32.7%) injuries accounted for >80% of injuries. Most injuries occurred in the lower (48.1%) and upper limb (25.6%). 42% of all injuries were moderate (27.5%) or severe (14.8%), and tackling (26.3%) and being tackled (23.1%) were the most common mechanisms of injury. The IR of injuries was unrelated to playing at home compared with away (locations ≥6 h time difference).Conclusions55% of all players were injured during the 4-month Super Rugby tournament (1.67 injuries/match). Most injuries occurred in the lower (knee, thigh) or upper limb (shoulder, clavicle). 42% of injuries were severe enough for players to not play for >1 week.
Epidemiological investigation and antimicrobial susceptibility analysis of ureaplasma species andMycoplasmahominis in outpatients with genital manifestations
Authors: Song Tiejun , Ye Aiqing , Xie Xinyou , Huang Jun , Ruan Zhi , Kong Yingying , Song Jingjuan , Wang Yue , Chen Jianzhong , Zhang Jun 
Published: July 2014

AimsThe aim of this study was to assess the prevalence and drug resistance ofUreaplasmaspecies andMycoplasma hominisin outpatients with genital manifestation from 2005 to 2013 in Hangzhou, China.MethodsA total of 2689 female and 2336 male patients with various genital symptoms were included in this study. Species identification and antimicrobial susceptibility test were performed by using the mycoplasma IST-2 kit.ResultsThe prevalence rate ofUreaplasmaspecies was 39.9%,M hominiswas 1.2% in female patients, and the coinfection rate was 13.4%; while in males, the prevalence rate ofUreaplasmaspecies was 18.8%,M hominiswas 0.4%, and the coinfection rate was 2.9%. Moreover, significantly high positive rates for mycoplasmas (UreaplasmaspeciesM hominis) and were found in 16–20-year-old females (65.2%) and males (27.3%).Ureaplasmaspecies andM hominisdisplayed relatively lower resistance rates (<5.0%) to doxycycline, josamycin, tetracycline and pristinamycin, and the resistance rates did not change during the study period, while the resistance rates ofUreaplasmaspecies to quinolones (ofloxacin and ciprofloxacin) were much higher (>50%) and increased significantly from 2005 to 2013.ConclusionsOur study indicates that high positive rates ofUreaplasmaspecies andM hominiswere found in young outpatients with genital symptoms, and monitoring the local drug resistance is critical for prevention of the occurrence of resistant strains.
Wheat-dependent exercise-induced anaphylaxis: a retrospective case review from a tertiary hospital
Authors: Thalayasingam Meera , Allameen Nur Azizah , Soh Jian Yi , Bigliardi Paul , Van Bever Hugo , Shek Lynette Pei-Chi 
Published: July 2014

Abstract

Background
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy caused by the combination of wheat ingestion and physical exercise and has been reported in other parts of Asia. At present, there are no published reports of WDEIA in Singapore. The objective of this study is to characterise the common local clinical and laboratory manifestations of WDEIA.

Methods
This was a retrospective descriptive study of all WDEIA who presented to a tertiary Singaporean Hospital over a 5-year-period from 1 January 2009 to 30 June 2013.

Results
Eight patients aged 9–41 years old were characterised. Six were males and the majority (5) was of Chinese ethnicity. An atopic history was found in four patients. The symptoms of anaphylaxis included cutaneous manifestations such as urticaria (n=7), angioedema (n=6), respiratory symptoms of dyspnoea and wheezing (n=5) and hypotension (n=5). The symptoms occurred 20–75 min after consumption of wheat-based products, often upon cessation of exercise [running (n=3), walking (n=4) and swimming (n=1)]. The WDEIA was recurrent in seven patients. The skin prick tests were positive to wheat in seven patients, and ω-5 gliadin test to wheat was positive in five patients.

Conclusions
With the emergence of wheat allergy in East Asian countries, WDEIA has become an important condition for physicians and Singapore is no exception. Under-recognition combined with life-threatening symptoms warrants better public awareness measures. In addition, further studies are necessary to identify possible unique genetic and environmental exposures that could explain the inter-regional differences of WDEIA.
GemDroid
Authors: Chidambaram Nachiappan Nachiappan , Yedlapalli Praveen , Soundararajan Niranjan , Kandemir Mahmut Taylan , Sivasubramaniam Anand , Das Chita R. 
Published: July 2014

As the demand for feature-rich mobile systems such as smartphones and tablets has outpaced other computing systems and is expected to continue at a faster rate, it is projected that SoCs with tens of cores and hundreds of IPs (or accelerator) will be designed to provide unprecedented level of features and functionality in future. Design of such mobile systems with required QoS and power budgets along with other design constraints will be a daunting task for computer architects since any ad hoc, piece-meal solution is unlikely to result in an optimal design. This requires early exploration of the complete design space to understand the system-level design trade-offs. To the best of our knowledge, there is no such publicly available tool to conduct a holistic evaluation of mobile platforms consisting of cores, IPs and system software.
This paper presents GemDroid, a comprehensive simulation infrastructure to address these concerns. GemDroid has been designed by integrating the Android open-source emulator for facilitating execution of mobile applications, the GEM5 core simulator for analyzing the CPU and memory centric designs, and models for several IPs to collectively study their impact on system-level performance and power. Analyzing a spectrum of applications with GemDroid, we observed that the memory subsystem is a vital cog in the mobile platform because, it needs to handle both core and IP traffic, which have very different characteristics. Consequently, we present a heterogeneous memory controller (HMC) design, where we divide the memory physically into two address regions, where the first region with one memory controller (MC) handles core-specific application data and the second region with another MC handles all IP related data. The proposed modifications to the memory controller design results in an average 25% reduction in execution time for CPU bound applications, up to 11% reduction in frame drops, and on average 17% reduction in CPU busy time for on-screen (IP bound) applications.
Balanced resource allocations across multiple dynamic MapReduce clusters
Authors: Ghit Bogdan , Yigitbasi Nezih , Iosup Alexandru , Epema Dick 
Published: July 2014

Running multiple instances of the MapReduce framework concurrently in a multicluster system or datacenter enables data, failure, and version isolation, which is attractive for many organizations. It may also provide some form of performance isolation, but in order to achieve this in the face of time-varying workloads submitted to the MapReduce instances, a mechanism for dynamic resource (re-)allocations to those instances is required. In this paper, we present such a mechanism called Fawkes that attempts to balance the allocations to MapReduce instances so that they experience similar service levels. Fawkes proposes a new abstraction for deploying MapReduce instances on physical resources, the MR-cluster, which represents a set of resources that can grow and shrink, and that has a core on which MapReduce is installed with the usual data locality assumptions but that relaxes those assumptions for nodes outside the core. Fawkes dynamically grows and shrinks the active MR-clusters based on a family of weighting policies with weights derived from monitoring their operation.
We empirically evaluate Fawkes on a multicluster system and show that it can deliver good performance and balanced resource allocations, even when the workloads of the MR-clusters are very uneven and bursty, with workloads composed from both synthetic and real-world benchmarks.
Non-work-conserving effects in MapReduce
Authors: Tan Jian , Wang Yandong , Yu Weikuan , Zhang Li 
Published: July 2014

Sequentially arriving jobs share a MapReduce cluster, each desiring a fair allocation of computing resources to serve its associated map and reduce tasks. The model of such a system consists of a processor sharing queue for the MapTasks and a multi-server queue for the ReduceTasks. These two queues are dependent through a constraint that the input data of each ReduceTask are fetched from the intermediate data generated by the MapTasks belonging to the same job. A more generalized form of MapReduce queueing model can capture the essence of other distributed data processing systems that contain interdependent processor sharing queues and multi-server queues.
Through theoretical modeling and extensive experiments, we show that, this dependence, if not carefully dealt with, can cause non-work-conserving effects that negatively impact system performance and scalability. First, we characterize the heavy-traffic approximation. Depending on how tasks are scheduled, the number of jobs in the system can even exhibit jumps in diffusion limits, resulting in prolonged job execution times. This problem can be mitigated through carefully applying a tie-breaking rule for ReduceTasks, which as a theoretical finding has direct engineering implications. Second, we empirically validate a criticality phenomenon using experiments. MapReduce systems experience an undesirable performance degradation when they have reached certain critical points, another finding that offers fundamental guidance on managing MapReduce systems.
IL15RA Drives Antagonistic Mechanisms of Cancer Development and Immune Control in Lymphocyte-Enriched Triple-Negative Breast Cancers
Authors: Marra Pierfrancesco , Mathew Sumi , Grigoriadis Anita , Wu Yin , Kyle-Cezar Fernanda , Watkins Johnathan , Rashid Mamunur , De Rinaldis Emanuele , Hessey Sonya , Gazinska Patrycja , Hayday Adrian , Tutt Andrew 
Published: July 2014

Abstract
Despite its aggressive nature, triple-negative breast cancer (TNBC) often exhibits leucocyte infiltrations that correlate with favorable prognosis. In this study, we offer an explanation for this apparent conundrum by defining TNBC cell subsets that overexpress the IL15 immune receptor IL15RA. This receptor usually forms a heterotrimer with the IL2 receptors IL2RB and IL2RG, which regulates the proliferation and differentiation of cytotoxic T cells and NK cells. However, unlike IL15RA, the IL2RB and IL2RG receptors are not upregulated in basal-like TNBC breast cancer cells that express IL15RA. Mechanistic investigations indicated that IL15RA signaling activated JAK1, STAT1, STAT2, AKT, PRAS40, and ERK1/2 in the absence of IL2RB and IL2RG, whereas neither STAT5 nor JAK2 were activated. RNAi-mediated attenuation of IL15RA established its role in cell growth, apoptosis, and migration, whereas expression of the IL15 cytokine in IL15RA-expressing cells stimulated an autocrine signaling cascade that promoted cell proliferation and migration and blocked apoptosis. Notably, coexpression of IL15RA and IL15 was also sufficient to activate peripheral blood mononuclear cells upon coculture in a paracrine signaling manner. Overall, our findings offer a mechanistic explanation for the paradoxical association of some high-grade breast tumors with better survival outcomes, due to engagement of the immune stroma. Cancer Res; 74(17); 4908–21. ©2014 AACR.
Infusions of Allogeneic Natural Killer Cells as Cancer Therapy
Authors: Leung Wing 
Published: July 2014

AbstractNatural killer (NK) cells are normal white blood cells capable of killing malignant cells without prior sensitization. Allogeneic NK cell infusions are attractive for cancer therapy because of non–cross-resistant mechanisms of action and minimal overlapping toxicities with standard cancer treatments. Although NK therapy is promising, many obstacles will need to be overcome, including insufficient cell numbers, failure of homing to tumor sites, effector dysfunction, exhaustion, and tumor cell evasion. Capitalizing on the wealth of knowledge generated by recent NK cell biology studies and the advancements in biotechnology, substantial progress has been made recently in improving therapeutic efficiency and reducing side effects. A multipronged strategy is essential, including immunogenetic-based donor selection, refined NK cell bioprocessing, and novel augmentation techniques, to improve NK function and to reduce tumor resistance. Although data from clinical trials are currently limited primarily to hematologic malignancies, broader applications to a wide spectrum of adult and pediatric cancers are under way. The unique properties of human NK cells open up a new arena of novel cell-based immunotherapy against cancers that are resistant to contemporary therapies. Clin Cancer Res; 20(13); 3390–400. ©2014 AACR.
GSK-3β–Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion
Authors: Zhang Hong , Hou Wei , Wang Hua-Li , Liu Hai-Jing , Jia Xin-Ying , Zheng Xing-Zheng , Zou Yong-Xin , Li Xin , Hou Lin , McNutt Michael A. , Zhang Bo 
Published: July 2014

AbstractPurpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution.Experimental Design: The expression and subcellular redistribution of NAT10, β-catenin, E-cadherin, and GSK-3β were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3β, transfection of wild-type or kinase-inactivated GSK-3β, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays.Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive “leading edge” of the tumor. This correlated well with nuclear accumulation of β-catenin (P &lt; 0.001; χ2 = 68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values &lt; 0.001), and was associated with a poorer prognosis (P = 0.023; χ2 = 5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3β. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility.Conclusion: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3β activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma. Clin Cancer Res; 20(17); 4717–29. ©2014 AACR.
Introduction
Authors: van den Heever Gerhard 
Published: July 2014

In this introductory essay to the theme issue “Intersections of Discourses – Pliable Body, the Making of Religion, and Social Definition,” we sketch the main contours of thinking about human bodiliness in religion. This relates both to the way in which bodies and ways of bodiliness feature in religious discourse and practice but also to the way in which scholarly theorising deal with human bodies in religion. Our argument is based on two main points of departure, namely that bodies are constructed products of discourse and that “religion” is a set of somaticising practices. After a long neglect, the body was rediscovered as a core topic for religious studies in the wake of four intersecting force fields, namely the interest in human bodies in anthropology and sociology, the intellectual legacy of Michel Foucault, the emergence of spirituality as lived religion, and interest in religious experience as study field. In sum, it is argued that the essays presented here constitute a reminder that religious discourses are not languages “out of this world”, but are very much human languages effecting human intentional (and unintentional) outcomes in interactional social and cultural settings.
The complete larval development of the mud shrimp Upogebia vasquezi (Gebiidea: Upogebiidae) reared in the laboratory
Authors: DE OLIVEIRA DANIELLY BRITO , MARTINELLI-LEMOS JUSSARA MORETTO , ABRUNHOSA FERNANDO ARAÚJO 
Published: July 2014

The larval development of Upogebia vasquezi consists of four zoeal stages and a megalopa. In the present study, each larval stage was described and illustrated in detail. The first two stages are re-described in order to provide a detailed comparison with the data available for this species recorded in a previous study. The morphological features of all the stages are compared with those of the larvae of other Upogebia species reported previously in the literature. Broad morphological similarities and distinctions were found among most Upogebia species. The main interspecific variations in the morphology of the zoeal stages are the segmentation pattern of the antennular endopod and number of aesthetascs, the number of setae on the scaphognathite and the presence or absence of a mandibular palp.
Three new species of Baeoentedon Girault (Hymenoptera: Eulophidae) from China, with the first record of whitefly host association (Hemiptera: Aleyrodidae)
Authors: WANG ZHU-HONG , HUANG JIAN , POLASZEK ANDREW 
Published: July 2014

Three new species of Baeoentedon Girault (Hymenoptera: Eulophidae) are described from China, Baeoentedon balios Wang, Huang & Polaszek sp. nov., Baeoentedon bouceki Wang, Huang & Polaszek sp. nov. and Baeoentedon virgatus Wang, Huang & Polaszek sp. nov. Both female and male of Baeoentedon balios were reared from the whitefly Pealius spina (Singh) (Hemiptera: Aleyrodidae) on the bodhi tree Ficus religiosa L. (Urticales: Moraceae). The male and the whitefly host association of Baeoentedon are recorded for the first time. A key is also provided to females of the world species of the genus.