bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of
sil
in Invasive Group A and G Streptococci: Antibodies against Bacterial Pheromone Peptide SilCR Result in Severe Infection
Authors: Michael-Gayego Ayelet , Dan-Goor Mary , Jaffe Joseph , Hidalgo-Grass Carlos , Moses Allon E. 
Published: August 2013

ABSTRACT

Group G beta-hemolytic streptococcus (GGS) strains cause severe invasive infections, mostly in patients with comorbidities. GGS is known to possess virulence factors similar to those of its more virulent counterpart group A streptococcus (GAS). A streptococcal invasion locus,
sil
, was identified in GAS.
sil
encodes a competence-stimulating peptide named SilCR that activates bacterial quorum sensing and has the ability to attenuate virulence in GAS infections. We found that
sil
is present in most GGS strains (82%) but in only 25% of GAS strains, with a similar gene arrangement. GGS strains that contained
sil
expressed the SilCR peptide and secreted it into the growth medium. In a modified murine model of GGS soft tissue infection, GGS grown in the presence of SilCR caused a milder disease than GGS grown in the absence of SilCR. To further study the role of the peptide in bacterial virulence attenuation, we vaccinated mice with SilCR to produce specific anti-SilCR antibodies. Vaccinated mice developed a significantly more severe illness than nonvaccinated mice. Our results indicate that the
sil
locus is much more prevalent among the less virulent GGS strains than among GAS strains. GGS strains express and secrete SilCR, which has a role in attenuation of virulence in a murine model. We show that the SilCR peptide can protect mice from infection caused by GGS. Furthermore, vaccinated mice that produce specific anti-SilCR antibodies develop a significantly more severe infection. To our knowledge, this is a novel report demonstrating that specific antibodies against a bacterial component cause more severe infection by those bacteria.
Natural Variation in the Promoter of the Gene Encoding the Mga Regulator Alters Host-Pathogen Interactions in Group A Streptococcus Carrier Strains
Authors: Flores Anthony R. , Olsen Randall J. , Wunsche Andrea , Kumaraswami Muthiah , Shelburne Samuel A. , Carroll Ronan K. , Musser James M. 
Published: August 2013

ABSTRACTHumans commonly carry pathogenic bacteria asymptomatically, but the molecular factors underlying microbial asymptomatic carriage are poorly understood. We previously reported that two epidemiologically unassociated serotype M3 group AStreptococcus(GAS) carrier strains had an identical 12-bp deletion in the promoter of the gene encoding Mga, a global positive gene regulator. Herein, we report on studies designed to test the hypothesis that the identified 12-bp deletion in themgapromoter alters GAS virulence, thereby potentially contributing to the asymptomatic carrier phenotype. Using allelic exchange, we introduced the variant promoter into a serotype M3 invasive strain and the wild-type promoter into an asymptomatic carrier strain. Compared to strains with the wild-typemgapromoter, we discovered that strains containing the promoter with the 12-bp deletion produced significantly fewermgaand Mga-regulated gene transcripts. Consistent with decreasedmgatranscripts, strains containing the variantmgapromoter were also significantly less virulent inin vivoandex vivomodels of GAS disease. Further, we provide evidence that the pleiotropic regulator protein CodY binds to themgapromoter and that the 12-bp deletion in themgapromoter reduces CodY-mediatedmgatranscription. We conclude that the naturally occurring 12-bp deletion in themgapromoter significantly alters the pathogen-host interaction of these asymptomatic carrier strains. Our findings provide new insight into the molecular basis of the carrier state of an important human pathogen.
Investigating well-being, work limitations and preferences for self-management education and peer support among younger people with hip and knee osteoarthritis: protocol for a cross-sectional study
Authors: Ackerman Ilana N , Page Richard S , Schoch Peter , Brand Caroline A 
Published: August 2013

IntroductionOsteoarthritis (OA) has traditionally been considered a condition of older age. However, younger people are also affected by hip and knee OA, often as a result of sporting and work-related injuries. As OA studies have generally focused on older individuals, little is known about the experience of younger adults with hip or knee OA who can face a distinct set of pressures including work responsibilities and parenting roles. This study aims to investigate well-being and work participation among younger people with hip or knee OA, as well as preferences for OA education and support.Methods and analysis200 people aged 20–55 years with a diagnosis of hip and/or knee OA will be recruited for this cross-sectional study. Participants will be recruited from three major public hospitals in the state of Victoria, Australia following screening of orthopaedic outpatient clinic lists and referrals, and through community-based advertisements. A study questionnaire will be mailed to all participants and written informed consent obtained. Validated measures of Health-Related Quality of Life (HRQoL), health status, psychological distress and work limitations will be used. Information on health services use will be collected, in addition to information on the perceived utility and accessibility of a range of existing and proposed education and peer support models. HRQoL data will be compared with Australian population norms using independent t tests, and associations between HRQoL, health status, psychological distress, work limitations and demographic factors will be evaluated using univariate and multivariate analyses. Data on the perceived utility and accessibility of education and peer support models will be analysed descriptively.Ethics and disseminationEthics approval for the study has been obtained. The study findings will be submitted to peer-reviewed journals and arthritis consumer organisations for broader dissemination, and presented at national and international scientific meetings.
An analysis of the door-to-balloon time in STEMI patients in an underdeveloped area of China: a single-centre analysis
Authors: Yu Zi-Xiang , Shen Xin , Ma Yi-Tong , Yang Yi-Ning , Ma Xiang , Xie Xiang 
Published: August 2013

ObjectivesThis study was conducted to break the door-to-balloon time (DTBT) into constituent elements, and compared which components prolonged markedly. We identified the factors that significantly prolonged the DTBT in an underdeveloped area of China.MethodsThe patients were included from January 2008 to December 2010 in 301 consecutive patients presenting with STEMI in our hospital. We analysed the components of total DTB times, such as ‘Diagnosis time’, ‘Cardiologist consultation time’, ‘Explain the patient's condition time’, ‘Transferring time’, ‘Preparation of the catheterisation laboratory (CL) time’, and determined which factors significantly prolonged the DTBT potentially.ResultsThe median DTBT of all patients was 134 (98–186) min. The group was divided by the DTBT into two: ≤120 min and >120 min. In the ≤120 min group, more patients (68.1%) presented to our hospital during working hours (p=0.000), whereas in the >120 min group, more patients (63.2%) presented out of hours (p=0.000). More patients (49.3%) presented when the interventionist was on site (p=0.000) in the ≤120 min group. In the >120 min group, the times for consultation by the cardiologist and explaining the patient's condition to the family prolonged markedly, as compared to the ≤120 min group (p=0.000) when the interventionist was off-duty (OR=4.050, p=0.000) and presentation during non-working hours (OR=3.334, p=0.000) were significant predictors of >120 min DTB times.ConclusionsIn our centre, the time of consultation by the cardiologists and explaining the patient's condition to the family accounted for most of the delay in reperfusion. A lack of interventionists usually resulted in a delay during non-working hours in the CL. Several measures should be taken involving asking emergency department physicians to awake CL directly, sending the patients’ information to the cardiologists, popularising medical knowledge to the citizens, and increasing the numbers of interventionists qualified to carry out primary percutaneous coronary intervention, should be developed to shorten the DTBT.
FAST ION BEAM MICROSCOPY OF WHOLE CELLS
Authors: WATT FRANK , CHEN XIAO , CHEN CE-BELLE , UDALAGAMA CHAMMIKA NB , REN MINQIN , PASTORIN G , BETTIOL ANDREW 
Published: August 2013

The way in which biological cells function is of prime importance, and the determination of such knowledge is highly dependent on probes that can extract information from within the cell. Probing deep inside the cell at high resolutions however is not easy: optical microscopy is limited by fundamental diffraction limits, electron microscopy is not able to maintain spatial resolutions inside a whole cell without slicing the cell into thin sections, and many other new and novel high resolution techniques such as atomic force microscopy (AFM) and near field scanning optical microscopy (NSOM) are essentially surface probes. In this paper we show that microscopy using fast ions has the potential to extract information from inside whole cells in a unique way. This novel fast ion probe utilises the unique characteristic of MeV ion beams, which is the ability to pass through a whole cell while maintaining high spatial resolutions. This paper first addresses the fundamental difference between several types of charged particle probes, more specifically focused beams of electrons and fast ions, as they penetrate organic material. Simulations show that whereas electrons scatter as they penetrate the sample, ions travel in a straight path and therefore maintain spatial resolutions. Also described is a preliminary experiment in which a whole cell is scanned using a low energy (45 keV) helium ion microscope, and the results compared to images obtained using a focused beam of fast (1.2 MeV) helium ions. The results demonstrate the complementarity between imaging using low energy ions, which essentially produce a high resolution image of the cell surface, and high energy ions, which produce an image of the cell interior. The characteristics of the fast ion probe appear to be ideally suited for imaging gold nanoparticles in whole cells. Using scanning transmission ion microscopy (STIM) to image the cell interior, forward scattering transmission ion microscopy (FSTIM) to improve the contrast of the gold nanoparticles, and Rutherford Backscattering Spectrometry (RBS) to determine the depth of the gold nanoparticles in the cell, a 3D visualization of the nanoparticles within the cell can be constructed. Finally a new technique, proton induced fluorescence (PIF), is tested on a cell stained with DAPI, a cell-nucleic acid stain that exhibits a 20-fold increase in fluorescence when binding to DNA. The results indicate that the technique of PIF, although still at an early stage of development, has high potential since there does not seem to be any physical barrier to develop simultaneous structural and fluorescence imaging at sub 10 nm resolutions.
A lightweight VMM on many core for high performance computing
Authors: Dai Yuehua , Qi Yong , Ren Jianbao , Shi Yi , Wang Xiaoguang , Yu Xuan 
Published: August 2013

Traditional Virtual Machine Monitor (VMM) virtualizes some devices and instructions, which induces performance overhead to guest operating systems. Furthermore, the virtualization contributes a large amount of codes to VMM, which makes a VMM prone to bugs and vulnerabilities.
On the other hand, in cloud computing, cloud service provider configures virtual machines based on requirements which are specified by customers in advance. As resources in a multi-core server increase to more than adequate in the future, virtualization is not necessary although it provides convenience for cloud computing. Based on the above observations, this paper presents an alternative way for constructing a VMM: configuring a booting interface instead of virtualization technology. A lightweight virtual machine monitor - OSV is proposed based on this idea. OSV can host multiple full functional Linux kernels with little performance overhead. There are only 6 hyper-calls in OSV. The Linux running on top of OSV is intercepted only for the inter-processor interrupts. The resource isolation is implemented with hardware-assist virtualization. The resource sharing is controlled by distributed protocols embedded in current operating systems.
We implement a prototype of OSV on AMD Opteron processor based 32-core servers with SVM and cache-coherent NUMA architectures. OSV can host up to 8 Linux kernels on the server with less than 10 lines of code modifications to Linux kernel. OSV has about 8000 lines of code which can be easily tuned and debugged. The experiment results show that OSV VMM has 23.7% performance improvement compared with Xen VMM.
FastLane
Authors: Wamhoff Jons-Tobias , Fetzer Christof , Felber Pascal , Rivière Etienne , Muller Gilles 
Published: August 2013

Software transactional memory (STM) can lead to scalable implementations of concurrent programs, as the
relative
performance of an application increases with the number of threads that support it. However, the
absolute
performance is typically impaired by the overheads of transaction management and instrumented accesses to shared memory. This often leads STM-based programs with low thread counts to perform worse than a sequential, non-instrumented version of the same application.

In this paper, we propose FastLane, a new STM algorithm that bridges the performance gap between sequential execution and classical STM algorithms when running on few cores. FastLane seeks to reduce instrumentation costs and thus performance degradation in its target operation range. We introduce a novel algorithm that differentiates between two types of threads: One thread (the master) executes transactions pessimistically without ever aborting, thus with minimal instrumentation and management costs, while other threads (the helpers) can commit speculative transactions only when they do not conflict with the master. Helpers thus contribute to the application progress without impairing on the performance of the master.
We implement FastLane as an extension of a state-of-the-art STM runtime system and compiler. Multiple code paths are produced for execution on a single, few, and many cores. The runtime system selects the code path providing the best throughput, depending on the number of cores available on the target machine. Evaluation results indicate that our approach provides promising performance at low thread counts: FastLane almost systematically wins over a classical STM in the 1-6 threads range, and often performs better than sequential execution of the non-instrumented version of the same application starting with 2 threads.
Scalable deterministic replay in a parallel full-system emulator
Authors: Chen Yufei , Chen Haibo 
Published: August 2013

Full-system emulation has been an extremely useful tool in developing and debugging systems software like operating systems and hypervisors. However, current full-system emulators lack the support for deterministic replay, which limits the reproducibility of concurrency bugs that is indispensable for analyzing and debugging the essentially multi-threaded systems software.
This paper analyzes the challenges in supporting deterministic replay in parallel full-system emulators and makes a comprehensive study on the sources of non-determinism. Unlike application-level replay systems, our system, called ReEmu, needs to log sources of non-determinism in both the guest software stack and the dynamic binary translator for faithful replay. To provide scalable and efficient record and replay on multicore machines, ReEmu makes several notable refinements to the CREW protocol that replays shared memory systems. First, being aware of the performance bottlenecks in frequent lock operations in the CREW protocol, ReEmu refines the CREW protocol with a seqlock-like design, to avoid serious contention and possible starvation in instrumentation code tracking dependence of racy accesses on a shared memory object. Second, to minimize the required log files, ReEmu only logs minimal local information regarding accesses to a shared memory location, but instead relies on an offline log processing tool to derive precise shared memory dependence for faithful replay. Third, ReEmu adopts an automatic lock clustering mechanism that clusters a set of uncontended memory objects to a bulk to reduce the frequencies of lock operations, which noticeably boost performance.
Our prototype ReEmu is based on our open-source COREMU system and supports scalable and efficient record and replay of full-system environments (both x64 and ARM). Performance evaluation shows that ReEmu has very good performance scalability on an Intel multicore machine. It incurs only 68.9% performance overhead on average (ranging from 51.8% to 94.7%) over vanilla COREMU to record five PARSEC benchmarks running on a 16-core emulated system.
Attenuation of Argininosuccinate Lyase Inhibits Cancer Growth via Cyclin A2 and Nitric Oxide
Authors: Huang Hau-Lun , Hsu Hui-Ping , Shieh Shu-Chu , Chang Yung-Sheng , Chen Wei-Ching , Cho Chien-Yu , Teng Chiao-Fang , Su Ih-Jen , Hung Wen-Chun , Lai Ming-Derg 
Published: August 2013

AbstractArginine biosynthesis and nitric oxide (NO) production are important for cancer homeostasis. Degradation of arginine may be used to inhibit liver tumors with low argininosuccinate synthetase (ASS) expression. In this report, we investigated an alternative therapeutic approach by targeting argininosuccinate lyase (ASL). ASL is transcriptionally induced by endoplasmic reticulum stress and is overexpressed in some human liver tumors. Knockdown of ASL expression by short hairpin RNA (shRNA) in three liver cancer cell lines, ML-1, HuH-7, and HepG2, decreased colony formation in vitro and tumor growth in vivo. Furthermore, lentiviral infection of ASL shRNA inhibited tumor growth in a therapeutic animal tumor model. Analysis of ASL shRNA on the cell-cycle progression revealed a G2–M delay. Among cell-cycle regulatory molecules, cyclin A2 expression was reduced. Reintroduction of exogenous cyclin A2 restored the cell growth in ASL-knockdown cells. Autophagy was observed in the cells treated with ASL shRNA, as shown by an increase in LC3-II levels and autophagosome formation. The total cellular arginine level was not altered significantly. Inhibition of autophagy further attenuated cell growth, suggesting that autophagy induced by ASL shRNA plays a feedback prosurvival function. Knockdown of ASL reduced NO content, and addition of NO donor partially recovered the growth inhibition by ASL shRNA. In summary, downregulation of ASL attenuated tumor growth and the inhibition was mainly mediated by a decrease of cyclin A2 and NO. Mol Cancer Ther; 12(11); 2505–16. ©2013 AACR.
The Ubiquity of Divinity According to Iamblichus and Syrianus
Authors: Dillon John 
Published: August 2013

Abstract
In two passages in particular of his Commentary on the Timaeus, Proclus attributes to his master Syrianus a series of arguments in favour of not confining gods or daemons to any particular level of the universe, either hypercosmic or encosmic, as had been the more or less universal practice of earlier Platonists, but asserting the ubiquity of all classes of ‘higher being’ at every level, and criticising earlier doctrine as in effect cutting the gods off from contact with man, thus undermining the power of theurgy. This interesting development was in fact initiated (as in so many other details of Syrianus’ doctrine) by his Syrian forerunner Iamblichus of Chalkis, and it is this doctrine that this essay seeks to explore.
Warm Conveyor Belts in the ERA-Interim Dataset (1979–2010). Part I: Climatology and Potential Vorticity Evolution
Authors: Madonna Erica , Wernli Heini , Joos Hanna , Martius Olivia 
Published: August 2013

Abstract
A global climatology of warm conveyor belts (WCBs) is presented for the years 1979–2010, based on trajectories calculated with Interim ECMWF Re-Analysis (ERA-Interim) data. WCB trajectories are identified as strongly ascending air parcels (600 hPa in 2 days) near extratropical cyclones. Corroborating earlier studies, WCBs are more frequent during winter than summer and they ascend preferentially in the western ocean basins between 25° and 50° latitude. Before ascending, WCB trajectories typically approach from the subtropics in summer and from more midlatitude regions in winter. Considering humidity, cloud water, and potential temperature along WCBs confirms that they experience strong condensation and integrated latent heating during the ascent (typically &gt;20 K). Liquid and ice water contents along WCBs peak at about 700 and 550 hPa, respectively. The mean potential vorticity (PV) evolution shows typical tropospheric values near 900 hPa, followed by an increase to almost 1 potential vorticity unit (PVU) at 700 hPa, and a decrease to less than 0.5 PVU at 300 hPa. These low PV values in the upper troposphere constitute significant negative anomalies with amplitudes of 1–3 PVU, which can strongly influence the downstream flow. Considering the low-level diabatic PV production, (i) WCBs starting at low latitudes (&lt;40°) are unlikely to attain high PV (due to weak planetary vorticity) although they exhibit the strongest latent heating, and (ii) for those ascending at higher latitudes, a strong vertical heating gradient and high absolute vorticity are both important. This study therefore provides climatological insight into the cloud diabatic formation of significant positive and negative PV anomalies in the extratropical lower and upper troposphere, respectively.
Long-Term Observations of Turbulent Reynolds Stresses over the Inner Continental Shelf
Authors: Kirincich Anthony R. 
Published: August 2013

AbstractIn situ observations of turbulent momentum flux, or Reynolds stresses, were estimated from a 10-yr acoustic Doppler current profiler (ADCP) record of inner-shelf velocities at the Martha’s Vineyard Coastal Observatory (MVCO) using recently developed analysis techniques that account for wave-induced biases. These observations were used to examine the vertical structure of stress and turbulent mixing in the coastal ocean during tidal-, wave-, and wind-driven circulation by conditionally averaging the dataset by the level of forcing or stratification present. Bottom-intensified stresses were found during tidally driven flow, having estimated eddy viscosities as high as 1 × 10−2 m−2 s−1 during slack water. An assessment of the mean, low-wave, low-wind stress results quantified the magnitude of an unmeasured body force responsible for the mean circulation present in the absence of wind and wave forcing. During weak stratification and isolated wind forcing, downwind stresses matched the observed wind stress near the surface and generally decreased with depth linearly for both along- and across-shelf wind forcing. While consistent with simple models of circulation during across-shelf wind forcing, the linear slope of the stress profile present during along-shelf wind forcing requires the existence of an along-shelf pressure gradient that scales with the wind forcing. At increased levels of stratification, the observed downwind stresses generally weakened and shifted to the across-wind direction during across-shelf and mixed-direction (i.e., onshore and along shelf) wind forcing consistent with Ekman spiral modification, but were more variable during along-shelf wind forcing. No measurable stresses were found due to wave-forced conditions, confirming previous theoretical results.