bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azithromycin Alters Macrophage Phenotype and Pulmonary Compartmentalization during Lung Infection withPseudomonas
Authors: Feola David J. , Garvy Beth A. , Cory Theodore J. , Birket Susan E. , Hoy Heather , Hayes Don , Murphy Brian S. 
Published: March 2010

ABSTRACTInfection with mucoid strains ofPseudomonas aeruginosain chronic inflammatory diseases of the airway is difficult to eradicate and can cause excessive inflammation. The roles of alternatively activated and regulatory subsets of macrophages in this pathophysiological process are not well characterized. We previously demonstrated that azithromycin induces an alternatively activated macrophage-like phenotypein vitro. In the present study, we tested whether azithromycin affects the macrophage activation status and migration in the lungs ofP. aeruginosa-infected mice. C57BL/6 mice received daily doses of oral azithromycin and were infected intratracheally with a mucoid strain ofP. aeruginosa. The properties of macrophage activation, immune cell infiltration, and markers of pulmonary inflammation in the lung interstitial and alveolar compartments were evaluated postinfection. Markers of alternative macrophage activation were induced by azithromycin treatment, including the surface expression of the mannose receptor, the upregulation of arginase 1, and a decrease in the production of proinflammatory cytokines. Additionally, azithromycin increased the number of CD11b+monocytes and CD4+T cells that infiltrated the alveolar compartment. A predominant subset of CD11b+cells was Gr-1 positive (Gr-1+), indicative of a subset of cells that has been shown to be immunoregulatory. These differences corresponded to decreases in neutrophil influx into the lung parenchyma and alteration of the characteristics of peribronchiolar inflammation without any change in the clearance of the organism. These results suggest that the immunomodulatory effects of azithromycin are associated with the induction of alternative and regulatory macrophage activation characteristics and alteration of cellular compartmentalization during infection.
In Vitro
Activity of a New Isothiazoloquinolone, ACH-702, against
Mycobacterium tuberculosis
and Other Mycobacteria
Authors: Molina-Torres Carmen A. , Ocampo-Candiani Jorge , Rendón Adrian , Pucci Michael J. , Vera-Cabrera Lucio 
Published: March 2010

ABSTRACT

In this work, we describe the activity of ACH-702 against clinical isolates of
Mycobacterium tuberculosis
and six different nontuberculous mycobacteria. The MIC
50
and MIC
90
of both susceptible and drug-resistant
M. tuberculosis
strains tested were 0.0625 and 0.125 μg/ml, respectively. The MIC
50
and MIC
90
values for
Mycobacterium fortuitum
isolates were 0.0625 μg/ml in both cases;
Mycobacterium avium
complex isolates showed MIC
50
and MIC
90
values of 0.25 and 4 μg/ml, respectively.
Antimicrobial Susceptibilities of Health Care-Associated and Community-Associated Strains of Methicillin-Resistant
Staphylococcus aureus
from Hospitalized Patients in Canada, 1995 to 2008
Authors: Simor Andrew E. , Louie Lisa , Watt Christine , Gravel Denise , Mulvey Michael R. , Campbell Jennifer , McGeer Allison , Bryce Elizabeth , Loeb Mark , Matlow Anne 
Published: March 2010

ABSTRACT

We determined the
in vitro
antimicrobial susceptibilities of 7,942 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates obtained from patients hospitalized in 48 Canadian hospitals from 1995 to 2008. Regional variations in susceptibilities were identified. The dissemination of community-associated strains in Canada appears to have contributed to increased susceptibility of MRSA to several non-β-lactam antimicrobial agents in the past decade. Reduced susceptibility to glycopeptides was not identified.
The Small RNA Chaperone Hfq Is Required for the Virulence of
Yersinia pseudotuberculosis
Authors: Schiano Chelsea A. , Bellows Lauren E. , Lathem Wyndham W. 
Published: March 2010

ABSTRACT

Bacterial small, noncoding RNAs (sRNAs) participate in the posttranscriptional regulation of gene expression, often by affecting protein translation, transcript stability, and/or protein activity. For proper function, many sRNAs rely on the chaperone Hfq, which mediates the interaction of the sRNA with its target mRNA. Recent studies have demonstrated that Hfq contributes to the pathogenesis of a number of bacterial species, suggesting that sRNAs play an essential role in the regulation of virulence. The enteric pathogen
Yersinia pseudotuberculosis
causes the disease yersiniosis. Here we show that Hfq is required by
Y. pseudotuberculosis
to cause mortality in an intragastric mouse model of infection, and a strain lacking Hfq is attenuated 1,000-fold compared to the wild type. Hfq is also required for virulence through the intraperitoneal route of infection and for persistence of the bacterium in the Peyer's patches, mesenteric lymph nodes, and spleen, suggesting a role for Hfq in systemic infection. Furthermore, the Δ
hfq
mutant of
Y. pseudotuberculosis
is hypermotile and displays increased production of a biosurfactant-like substance, reduced intracellular survival in macrophages, and decreased production of type III secretion effector proteins. Together, these data demonstrate that Hfq plays a critical role in the virulence of
Y. pseudotuberculosis
by participating in the regulation of multiple steps in the pathogenic process and further highlight the unique role of Hfq in the virulence of individual pathogens.
Multiple Host Proteins That Function in Phosphatidylinositol-4-Phosphate Metabolism Are Recruited to the Chlamydial Inclusion
Authors: Moorhead Andrew M. , Jung Joo-Yong , Smirnov Asya , Kaufer Susanne , Scidmore Marci A. 
Published: March 2010

ABSTRACT

Chlamydiae replicate within a nonacidified vacuole, termed an inclusion. As obligate intracellular bacteria, chlamydiae actively modify their vacuole to exploit host signaling and trafficking pathways. Recently, we demonstrated that several Rab GTPases are actively targeted to the inclusion. To define the biological roles of inclusion localized Rab GTPases, we have begun to identify inclusion-localized Rab effectors. Here we demonstrate that oculocerebrorenal syndrome of Lowe protein 1 (OCRL1), a Golgi complex-localized phosphatidylinositol (PI)-5-phosphatase that binds to multiple Rab GTPases, localizes to chlamydial inclusions. By examining the intracellular localization of green fluorescent protein (GFP) fusion proteins that bind to unique phosphoinositide species, we also demonstrate that phosphatidylinositol-4-phosphate (PI4P), the product of OCRL1, is present at the inclusion membrane. Furthermore, two additional host proteins, Arf1, which together with PI4P mediates the recruitment of PI4P-binding proteins to the Golgi complex, and PI4KIIα, a major producer of Golgi complex-localized PI4P, also localize to chlamydial inclusions. Depletion of OCRL1, Arf1, or PI4KIIα by small interfering RNA (siRNA) decreases inclusion formation and the production of infectious progeny. Infectivity is further decreased in cells simultaneously depleted for all three host proteins, suggesting partially overlapping functions in infected cells. Collectively, these data demonstrate that
Chlamydia
species create a unique replication-competent vacuolar environment by modulating both the Rab GTPase and the PI composition of the chlamydial inclusion.
The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
Authors: Jagger Brett W. , Memoli Matthew J. , Sheng Zong-Mei , Qi Li , Hrabal Rachel J. , Allen Genevieve L. , Dugan Vivien G. , Wang Ruixue , Digard Paul , Kash John C. , Taubenberger Jeffery K. 
Published: March 2010

ABSTRACT
The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus’s recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice.

IMPORTANCE
Influenza A virus (IAV) evolution is characterized by host-specific lineages, and IAVs derived in whole or in part from animal reservoirs have caused pandemics in humans. Because IAVs are known to acquire host-adaptive genome mutations, and since the PB2 gene of the 2009 H1N1 virus is of recent avian derivation, there exists concern that the pathogenicity of the 2009 H1N1 influenza A pandemic virus could be potentiated by acquisition of the host-adaptive PB2-E627K or -D701N mutations, which have been shown to enhance the virulence of other influenza viruses. We present data from a mouse model of influenza infection showing that such mutations do not increase the virulence of viruses containing the 2009 H1N1 viral polymerase.
Routing in self-organizing nano-scale irregular networks
Authors: Liu Yang , Dwyer Chris , Lebeck Alvin R. 
Published: March 2010

The integration of novel nanotechnologies onto silicon platforms is likely to increase fabrication defects compared with traditional CMOS technologies. Furthermore, the number of nodes connected with these networks makes acquiring a global defect map impractical. As a result, on-chip networks will provide defect tolerance by self-organizing into irregular topologies. In this scenario, simple static routing algorithms based on regular physical topologies, such as meshes, will be inadequate. Additionally, previous routing approaches for irregular networks assume abundant resources and do not apply to this domain of resource-constrained self-organizing nano-scale networks. Consequently, routing algorithms that work in irregular networks with limited resources are needed.
In this article, we explore routing for self-organizing nano-scale irregular networks in the context of a Self-Organizing SIMD Architecture (SOSA). Our approach trades configuration time and a small amount of storage for reduced communication latency. We augment an Euler path-based routing technique for trees to generate static shortest paths between certain pairs of nodes while remaining deadlock free. Simulations of several applications executing on SOSA show our proposed routing algorithm can reduce execution time by 8% to 30%.
Probabilistic job symbiosis modeling for SMT processor scheduling
Authors: Eyerman Stijn , Eeckhout Lieven 
Published: March 2010

Symbiotic job scheduling boosts simultaneous multithreading (SMT) processor performance by co-scheduling jobs that have `compatible' demands on the processor's shared resources. Existing approaches however require a sampling phase, evaluate a limited number of possible co-schedules, use heuristics to gauge symbiosis, are rigid in their optimization target, and do not preserve system-level priorities/shares.
This paper proposes probabilistic job symbiosis modeling, which predicts whether jobs will create positive or negative symbiosis when co-scheduled without requiring the co-schedule to be evaluated. The model, which uses per-thread cycle stacks computed through a previously proposed cycle accounting architecture, is simple enough to be used in system software. Probabilistic job symbiosis modeling provides six key innovations over prior work in symbiotic job scheduling: (i) it does not require a sampling phase, (ii) it readjusts the job co-schedule continuously, (iii) it evaluates a large number of possible co-schedules at very low overhead, (iv) it is not driven by heuristics, (v) it can optimize a performance target of interest (e.g., system throughput or job turnaround time), and (vi) it preserves system-level priorities/shares. These innovations make symbiotic job scheduling both practical and effective.
Our experimental evaluation, which assumes a realistic scenario in which jobs come and go, reports an average 16% (and up to 35%) reduction in job turnaround time compared to the previously proposed SOS (sample, optimize, symbios) approach for a two-thread SMT processor, and an average 19% (and up to 45%) reduction in job turnaround time for a four-thread SMT processor.
Request behavior variations
Authors: Shen Kai 
Published: March 2010

A large number of user requests execute (often concurrently) within a server system. A single request may exhibit fluctuating hardware characteristics (such as instruction completion rate and on-chip resource usage) over the course of its execution, due to inherent variations in application execution semantics as well as dynamic resource competition on resource-sharing processors like multicores. Understanding such behavior variations can assist fine-grained request modeling and adaptive resource management.
This paper presents operating system management to track request behavior variations online. In addition to metric sample collection during periodic interrupts, we exploit the frequent system calls in server applications to perform low-cost in-kernel sampling. We utilize identified behavior variations to support or enhance request modeling in request classification, anomaly analysis, and online request signature construction. A foundation of our request modeling is the ability to quantify the difference between two requests' time series behaviors. We evaluate several differencing measures and enhance the classic dynamic time warping technique with additional penalties for asynchronous warp steps. Finally, motivated by fluctuating request resource usage and the resulting contention, we implement contention-easing CPU scheduling on multicore platforms and demonstrate its effectiveness in improving the worst-case request performance.
Experiments in this paper are based on five server applications -- Apache web server, TPCC, TPCH, RUBiS online auction benchmark, and a user-content-driven online teaching application called WeBWorK.
ConMem
Authors: Zhang Wei , Sun Chong , Lu Shan 
Published: March 2010

Multicore technology is making concurrent programs increasingly pervasive. Unfortunately, it is difficult to deliver reliable concurrent programs, because of the huge and non-deterministic interleaving space. In reality, without the resources to thoroughly check the interleaving space, critical concurrency bugs can slip into production runs and cause failures in the field. Approaches to making the best use of the limited resources and exposing severe concurrency bugs before software release would be desirable.
Unlike previous work that focuses on bugs caused by specific interleavings (e.g., races and atomicity-violations), this paper targets concurrency bugs that result in one type of severe effects: program crashes. Our study of the error-propagation process of realworld concurrency bugs reveals a common pattern (50% in our non-deadlock concurrency bug set) that is highly correlated with program crashes. We call this pattern concurrency-memory bugs: buggy interleavings directly cause memory bugs (NULL-pointer-dereference, dangling-pointer, buffer-overflow, uninitialized-read) on shared memory objects.
Guided by this study, we built ConMem to monitor program execution, analyze memory accesses and synchronizations, and predicatively detect these common and severe concurrency-memory bugs. We also built a validator ConMem-v to automatically prune false positives by enforcing potential bug-triggering interleavings.
We evaluated ConMem using 7 open-source programs with 9 real-world severe concurrency bugs. ConMem detects more tested bugs (8 out of 9 bugs) than a lock-set-based race detector and an unserializable-interleaving detector that detect 4 and 5 bugs respectively, with a false positive rate about one tenth of the compared tools. ConMem-v further prunes out all the false positives. ConMem has reasonable overhead suitable for development usage.
Flexible architectural support for fine-grain scheduling
Authors: Sanchez Daniel , Yoo Richard M. , Kozyrakis Christos 
Published: March 2010

To make efficient use of CMPs with tens to hundreds of cores, it is often necessary to exploit fine-grain parallelism. However, managing tasks of a few thousand instructions is particularly challenging, as the runtime must ensure load balance without compromising locality and introducing small overheads. Software-only schedulers can implement various scheduling algorithms that match the characteristics of different applications and programming models, but suffer significant overheads as they synchronize and communicate task information over the deep cache hierarchy of a large-scale CMP. To reduce these costs, hardware-only schedulers like Carbon, which implement task queuing and scheduling in hardware, have been proposed. However, a hardware-only solution fixes the scheduling algorithm and leaves no room for other uses of the custom hardware.
This paper presents a combined hardware-software approach to build fine-grain schedulers that retain the flexibility of software schedulers while being as fast and scalable as hardware ones. We propose asynchronous direct messages (ADM), a simple architectural extension that provides direct exchange of asynchronous, short messages between threads in the CMP without going through the memory hierarchy. ADM is sufficient to implement a family of novel, software-mostly schedulers that rely on low-overhead messaging to efficiently coordinate scheduling and transfer task information. These schedulers match and often exceed the performance and scalability of Carbon when using the same scheduling algorithm. When the ADM runtime tailors its scheduling algorithm to application characteristics, it outperforms Carbon by up to 70%.
Technology for developing regions
Authors: Brewer Eric A. 
Published: March 2010

The historic focus of development has rightfully been on macroeconomics and good governance, but technology has an increasingly large role to play. In this talk, I review several novel technologies that we have deployed in India and Africa, and discuss the challenges and opportunities of this new subfield of EECS research. Working with the Aravind Eye Hospital, we are currently supporting doctor / patient videoconferencing in 30+ rural villages; more than 25,000 people have had their blindness cured due to these exams.
Although Moore's Law has led to great cost reductions and thus enabled new technologies, we have reached essentially the low point for cost: the computing is essentially free compared to the rest of the system. The premium is thus on a combination of 1) deeper integration (fewer compo-nents), 2) shared usage models (even phones are shared), and 3) lower operating costs in terms of power and connectivity.
Potential Impact of the Tropical Indian Ocean–Indonesian Seas on El Niño Characteristics*
Authors: Annamalai H. , Kida Shinichiro , Hafner Jan 
Published: March 2010

Abstract
Diagnostics performed with twentieth-century (1861–2000) ensemble integrations of the Geophysical Fluid Dynamics Laboratory Climate Model, version 2.1 (CM2.1) suggest that, during the developing phase, El Niño events that co-occur with the Indian Ocean Dipole Zonal Mode (IODZM; class 1) are stronger than those without (class 2). Also, during class 1 events coherent sea surface temperature (SST) anomalies develop in the Indonesian seas that closely follow the life cycle of IODZM. This study investigates the effect of these regional SST anomalies (equatorial Indian Ocean and Indonesian seas) on the amplitude of the developing El Niño.
An examination of class 1 minus class 2 composites suggests two conditions that could lead to a strong El Niño in class 1 events: (i) during January, ocean–atmosphere conditions internal to the equatorial Pacific are favorable for the development of a stronger El Niño and (ii) during May–June, coinciding with the development of regional SST anomalies, an abrupt increase in westerly wind anomalies is noticeable over the equatorial western Pacific with a subsequent increase in thermocline and SST anomalies over the eastern equatorial Pacific. This paper posits the hypothesis that, under favorable conditions in the equatorial Pacific, regional SST anomalies may enable the development of a stronger El Niño.
Owing to a wealth of feedbacks in CM2.1, solutions from a linear atmosphere model forced with May–June anomalous precipitation and anomalous SST from selected areas over the equatorial Indo-Pacific are examined. Consistent with our earlier study, the net Kelvin wave response to contrasting tropical Indian Ocean heating anomalies cancels over the equatorial western Pacific. In contrast, Indonesian seas SST anomalies account for about 60%–80% of the westerly wind anomalies over the equatorial western Pacific and also induce anomalous precipitation over the equatorial central Pacific. It is argued that the feedback between the precipitation and circulation anomalies results in an abrupt increase in zonal wind anomalies over the equatorial western Pacific.
Encouraged by these results, the authors further examined the processes that cause cold SST anomalies over the Indonesian seas using an ocean model. Sensitivity experiments suggest that local wind anomalies, through stronger surface heat loss and evaporation, and subsurface upwelling are the primary causes. The present results imply that in coupled models, a proper representation of regional air–sea interactions over the equatorial Indo-Pacific warm pool may be important to understand and predict the amplitude of El Niño.
Understanding the Anomalously Cold European Winter of 2005/06 Using Relaxation Experiments
Authors: Jung T. , Palmer T. N. , Rodwell M. J. , Serrar S. 
Published: March 2010

Abstract
Experiments with the atmospheric component of the ECMWF Integrated Forecasting System (IFS) have been carried out to study the origin of the atmospheric circulation anomalies that led to the unusually cold European winter of 2005/06. Experiments with prescribed sea surface temperature (SST) and sea ice fields fail to reproduce the observed atmospheric circulation anomalies suggesting that the role of SST and sea ice was either not very important or the atmospheric response to SST and sea ice was not very well captured by the ECMWF model. Additional experiments are carried out in which certain regions of the atmosphere are relaxed toward analysis data thereby artificially suppressing the development of forecast error. The relaxation experiments suggest that both tropospheric circulation anomalies in the Euro–Atlantic region and the anomalously weak stratospheric polar vortex can be explained by tropical circulation anomalies. Separate relaxation experiments for the tropical stratosphere and tropical troposphere highlight the role of the easterly phase of quasi-biennial oscillation (QBO) and, most importantly, tropospheric circulation anomalies, especially over South America and the tropical Atlantic. From the results presented in this study, it is argued that the relaxation technique is a powerful diagnostic tool to understand possible remote origins of seasonal-mean anomalies.