bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Anthrax Immune Globulin on Response to BioThrax (Anthrax Vaccine Adsorbed) in New Zealand White Rabbits
Authors: Malkevich Nina V. , Basu Subhendu , Rudge Thomas L. , Clement Kristin H. , Chakrabarti Ajoy C. , Aimes Ronald T. , Nabors Gary S. , Skiadopoulos Mario H. , Ionin Boris
Published: August 2013

Development of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. Anthrax immune globulin intravenous (AIGIV) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (PA), a component of anthrax toxins. We evaluated the interaction between AIGIV and BioThrax (anthrax vaccine adsorbed) in rabbits. While pharmacokinetics of AIGIV were not altered by vaccination, the vaccine-induced immune response was abrogated in AIGIV-treated animals.
Novel Pseudo-Staphylococcal Cassette Chromosome
mec
Element (ΨSCC
mec
57395
) in Methicillin-Resistant Staphylococcus pseudintermedius CC45
Authors: Perreten Vincent , Chanchaithong Pattrarat , Prapasarakul Nuvee , Rossano Alexandra , Blum Shlomo E. , Elad Daniel , Schwendener Sybille
Published: August 2013

Genetic characterization of methicillin-resistant
Staphylococcus pseudintermedius
(MRSP) from Thailand and Israel revealed the presence of a predominant atypical clonal lineage which was not typeable by SmaI-PFGE and SCC
mec
typing. All the atypical isolates (
n
= 34) belonged to CC45 (30 ST45 and 2 ST179 isolates, 1 ST57 isolate, and 1 ST85 isolate). The isolates originated from healthy and diseased dogs and cats, as well as from the environment of one clinic. Cfr9I–pulsed-field gel electrophoresis (Cfr9I-PFGE) and
dru
typing permitted the further distinction of CC45 isolates from the two different countries. Microarray analysis identified genes that confer resistance to β-lactams (
mecA
;
blaZ
), aminoglycosides [
aac(6′)-Ie–aph(2′)-Ia
;
aph(3′)-III
;
ant(6)-Ia
], macrolides and lincosamides [
erm
(B)], tetracyclines [
tet
(M)], trimethoprim [
dfr
(G)], streptothricin (
sat4
), and chloramphenicol (
cat
pC221
). Fluoroquinolone resistance was attributed to specific amino acid substitutions, i.e., Ser84Leu in GyrA and Ser80Ile and Asp84Asn in GrlA. A novel pseudo-staphylococcal cassette chromosome (ΨSCC
mec
57395
) element was identified in MRSP strain 57395 (sequence type ST45) by whole-genome sequencing. The 12,282-bp ΨSCC
mec
57395
element contained a class C1
mec
gene complex but no
ccr
genes. In addition to the methicillin resistance gene
mecA
, ΨSCC
mec
57395
also carried determinants of resistance to heavy metals, such as arsenic, cadmium, and copper. Bsu36I restriction analysis of the ΨSCC
mec
57395
element amplified by long-range PCR revealed the presence of ΨSCC
mec
57395
in the 33 additional isolates of MRSP CC45. The ΨSCC
mec
57395
element represents a new class of SCC
mec
and has been identified in MRSP of CC45, which is a predominant clonal lineage in Israel and Thailand.
Nested Case-Control Study of the Emergence of Tigecycline Resistance in Multidrug-Resistant Klebsiella pneumoniae
Authors: Nigo Masayuki , Cevallos Catalina Salinas , Woods Krystina , Flores Vicente Maco , Francis Gweneth , Perlman David C. , Revuelta Manuel , Mildvan Donna , Waldron Mary , Gomez Tessa , Koshy Sanjana , Jodlowski Tomasz , Riley William , Ruhe Jörg J.
Published: August 2013

We performed a nested case-control study (ratio of 1:4) on the emergence of tigecycline-resistant multidrug-resistant
Klebsiella pneumoniae
(TR-MDRKP) isolates among patients who initially presented with a tigecycline-susceptible MDRKP isolate. Out of 260 patients, 24 (9%) had a subsequent clinical culture positive for a TR-MDRKP isolate within the 90-day follow-up period. On logistic regression analyses, receipt of tigecycline (adjusted odds ratio [OR], 5.06; 95% confidence interval [CI], 1.80 to 14.23;
P
= 0.002) was the only independent predictor of subsequent isolation of a TR strain.
A Novel FexA Variant from a Canine Staphylococcus pseudintermedius Isolate That Does Not Confer Florfenicol Resistance
Authors: Gómez-Sanz Elena , Kadlec Kristina , Feßler Andrea T. , Zarazaga Myriam , Torres Carmen , Schwarz Stefan
Published: August 2013

Transposon Tn
558
integrated in the chromosomal
radC
gene was detected for the first time in
Staphylococus pseudintermedius
. It carried a novel
fexA
variant (
fexAv
) that confers only chloramphenicol resistance. The exporter FexAv exhibited two amino acid substitutions, Gly33Ala and Ala37Val, both of which seem to be important for substrate recognition. Site-directed mutagenesis that reverted the mutated base pairs to those present in the original
fexA
gene restored the chloramphenicol-plus-florfenicol resistance phenotype.
Comparison between the EUCAST Procedure and the Etest for Determination of the Susceptibility of Candida Species Isolates to Micafungin
Authors: Marcos-Zambrano Laura Judith , Escribano Pilar , Rueda Cristina , Zaragoza Óscar , Bouza Emilio , Guinea Jesús
Published: August 2013

We compared the ability of the EUCAST EDef 7.2 and the Etest to detect the susceptibility to micafungin of 160
Candida
and non-
Candida
clinical isolates. Agreement was higher when Etest MICs were obtained after 24 h of incubation; essential agreement was 90%, and categorical agreement was >90%. False susceptibility was seen only for
Candida krusei
(10%), and false resistance was observed in 6% of the isolates, ranging from 2.6% (
C. glabrata
) to 13% (
C. albicans
).
Impact of Reduced Vancomycin MIC on Clinical Outcomes of Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Park So-Youn , Oh In-Hwan , Lee Hee-Joo , Ihm Chun-Gyoo , Son Jun Seong , Lee Mi Suk , Kim Mi-Na
Published: August 2013

Vancomycin has been a key antibiotic agent for the treatment of methicillin-resistant
Staphylococcus aureus
(MRSA) infections. However, little is known about the relationship between vancomycin MIC values at the higher end of the susceptibility range and clinical outcomes. The aim of this study was to determine the impact of MRSA bacteremia on clinical outcomes in patients with a vancomycin MIC near the upper limit of the susceptible range. Patients with MRSA bacteremia were divided into a high-vancomycin-MIC group (2 μg/ml) and a low-vancomycin-MIC group (≤1.0 μg/ml). We examined the relationship between MIC, genotype, primary source of bacteremia, and mortality. Ninety-four patients with MRSA bacteremia, including 31 with a high vancomycin MIC and 63 with a low MIC were analyzed. There was no significant difference between the presence of
agr
dysfunction and SCC
mec
type between the two groups. A higher vancomycin MIC was not found to be associated with mortality. In contrast, high-risk bloodstream infection sources (hazard ratio [HR], 4.63; 95% confidence interval [CI] = 1.24 to 17.33) and bacterial eradication after treatment (HR, 0.06; 95% CI = 0.02 to 0.17), irrespective of vancomycin MIC, were predictors of all-cause 30-day mortality. Our study suggests that a high-risk source of bacteremia is likely to be associated with unfavorable clinical outcomes, but a high vancomycin MIC in a susceptible range, as well as genotype characteristics, are not associated with mortality.
Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens
Authors: Sutcliffe J. A. , O'Brien W. , Fyfe C. , Grossman T. H.
Published: August 2013

Eravacycline (TP-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline) is a novel fluorocycline that was evaluated for antimicrobial activity against panels of recently isolated aerobic and anaerobic Gram-negative and Gram-positive bacteria. Eravacycline showed potent broad-spectrum activity against 90% of the isolates (MIC
90
) in each panel at concentrations ranging from ≤0.008 to 2 μg/ml for all species panels except those of
Pseudomonas aeruginosa
and
Burkholderia cenocepacia
(MIC
90
values of 32 μg/ml for both organisms). The antibacterial activity of eravacycline was minimally affected by expression of tetracycline-specific efflux and ribosomal protection mechanisms in clinical isolates. Furthermore, eravacycline was active against multidrug-resistant bacteria, including those expressing extended-spectrum β-lactamases and mechanisms conferring resistance to other classes of antibiotics, including carbapenem resistance. Eravacycline has the potential to be a promising new intravenous (i.v.)/oral antibiotic for the empirical treatment of complicated hospital/health care infections and moderate-to-severe community-acquired infections.
Plasma Concentrations of Isoniazid and Rifampin Are Decreased in Adult Pulmonary Tuberculosis Patients with Diabetes Mellitus
Authors: Babalik Aylin , Ulus Ismail Hakki , Bakirci Nadi , Kuyucu Tulin , Arpag Huseyin , Dagyildizi Lale , Capaner Esen
Published: August 2013

Plasma isoniazid and rifampin concentrations, but not pyrazinamide and ethambutol concentrations, were decreased by about 50% (
P
< 0.05) in diabetic pulmonary tuberculosis patients. The prevalences of subnormal plasma isoniazid, rifampin, pyrazinamide, and ethambutol concentrations were 49% or 100% (
P
< 0.01), 66% or 100% (
P
< 0.05), 30% or 50% (
P
= 0.198), and 32% or 21% (
P
= 0.742) in nondiabetic or diabetic tuberculosis patients, respectively. These data show that plasma concentrations of isoniazid and rifampin were greatly reduced in diabetic tuberculosis patients.
In Vivo
Emergence of Colistin Resistance in Klebsiella pneumoniae Producing KPC-Type Carbapenemases Mediated by Insertional Inactivation of the PhoQ/PhoP
mgrB
Regulator
Authors: Cannatelli Antonio , D'Andrea Marco Maria , Giani Tommaso , Di Pilato Vincenzo , Arena Fabio , Ambretti Simone , Gaibani Paolo , Rossolini Gian Maria
Published: August 2013

Colistin is one of the few agents that retain activity against extensively drug-resistant strains of
Klebsiella pneumoniae
producing KPC-type carbapenemases (KPC-KP). However, resistance to colistin is increasingly reported among KPC-KP. Comparative genomic analysis of a pair of sequential KPC-KP isolates from the same patient including a colistin-susceptible isolate (KKBO-1) and a colistin-resistant isolate (KKBO-4) selected after colistin exposure revealed that insertional inactivation of the
mgrB
gene, encoding a negative regulator of the PhoQ/PhoP signaling system, is a genetic mechanism for acquired colistin resistance. The role of
mgrB
inactivation in acquired colistin resistance was confirmed by complementation experiments with wild-type
mgrB
, which restored colistin susceptibility in KKBO-4, and by construction of an
mgrB
deletion mutant from KKBO-1, which exhibited a colistin-resistant phenotype. Insertional
mgrB
inactivation was also detected in 60% of colistin-resistant mutants selected from KKBO-1
in vitro
, following plating on colistin-containing medium, confirming the role (although not unique) of this mechanism in the emergence of acquired colistin resistance. In colistin-resistant mutants carrying insertional inactivation or deletion of the
mgrB
gene, upregulated transcription of
phoP
,
phoQ
, and
pmrK
(which is part of the
pmrHFIJKLM
operon) was detected. These findings confirmed the MgrB regulatory role in
K. pneumoniae
and were in agreement with the known association between upregulation of the PhoQ/PhoP system and activation of the
pmrHFIJKLM
operon, which eventually leads to resistance to polymyxins by modification of the lipopolysaccharide target.
A Novel C5a-Derived Immunobiotic Peptide Reduces Streptococcus agalactiae Colonization through Targeted Bacterial Killing
Authors: Cavaco Courtney K. , Patras Kathryn A. , Zlamal Jaime E. , Thoman Marilyn L. , Morgan Edward L. , Sanderson Sam D. , Doran Kelly S.
Published: August 2013

Streptococcus agalactiae(group BStreptococcus[GBS]) is a Gram-positive bacterium that colonizes the cervicovaginal tract in approximately 25% of healthy women. Although colonization is asymptomatic, GBS can be vertically transmitted to newborns peripartum, causing severe disease such as pneumonia and meningitis. Current prophylaxis, consisting of late gestation screening and intrapartum antibiotics, has failed to completely prevent transmission, and GBS remains a leading cause of neonatal sepsis and meningitis in the United States. Lack of an effective vaccine and emerging antibiotic resistance necessitate exploring novel therapeutic strategies. We have employed a host-directed immunomodulatory therapy using a novel peptide, known as EP67, derived from the C-terminal region of human complement component C5a. Previously, we have demonstratedin vivothat EP67 engagement of the C5a receptor (CD88) effectively limits staphylococcal infection by promoting cytokine release and neutrophil infiltration. Here, using our established mouse model of GBS vaginal colonization, we observed that EP67 treatment results in rapid clearance of GBS from the murine vagina. However, this was not dependent on functional neutrophil recruitment or CD88 signaling, as EP67 treatment reduced the vaginal bacterial load in mice lacking CD88 or the major neutrophil receptor CXCr2. Interestingly, we found that EP67 inhibits GBS growthin vitroandin vivoand that antibacterial activity was specific toStreptococcusspecies. Our work establishes that EP67-mediated clearance of GBS is likely due to direct bacterial killing rather than to enhanced immune stimulation. We conclude that EP67 may have potential as a therapeutic to control GBS vaginal colonization.
CD38 Controls the Innate Immune Response against Listeria monocytogenes
Authors: Lischke Timo , Heesch Kira , Schumacher Valéa , Schneider Michael , Haag Friedrich , Koch-Nolte Friedrich , Mittrücker Hans-Willi
Published: August 2013

CD38, adenosine-5′-diphosphate-ribosyl cyclase 1, is a multifunctional enzyme, expressed on a wide variety of cell types. CD38 has been assigned diverse functions, including generation of calcium-mobilizing metabolites, cell activation, and chemotaxis. Using a murine
Listeria monocytogenes
infection model, we found that CD38 knockout (KO) mice were highly susceptible to infection. Enhanced susceptibility was already evident within 3 days of infection, suggesting a function of CD38 in the innate immune response. CD38 was expressed on neutrophils and inflammatory monocytes, and especially inflammatory monocytes further upregulated CD38 during infection. Absence of CD38 caused alterations of the migration pattern of both cell types to sites of infection. We observed impaired accumulation of cells in the spleen but surprisingly similar or even higher accumulation of cells in the liver. CD38 KO and wild-type mice showed similar changes in the composition of neutrophils and inflammatory monocytes in blood and bone marrow, indicating that mobilization of these cells from the bone marrow was CD38 independent.
In vitro
, macrophages of CD38 KO mice were less efficient in uptake of listeria but still able to kill the bacteria. Dendritic cells also displayed enhanced CD38 expression following infection. However, absence of CD38 did not impair the capacity of mice to prime CD8
+
T cells against
L. monocytogenes
, and CD38 KO mice could efficiently control secondary listeria infection. In conclusion, our results demonstrate an essential role for CD38 in the innate immune response against
L. monocytogenes
.
Identification ofMycobacterium tuberculosisfrom pericardial fluid using the new Xpert MTB/RIF assay
Authors: Dhana Ashar Vijay , Howell Pauline , Sanne Ian , Spencer David
Published: August 2013

Extrapulmonary tuberculosis (EPTB) is common in HIV-infected patients, especially at lower CD4 cell counts, yet is often difficult to diagnose with certainty. A 35-year-old man presented with dyspnoea and constitutional symptoms of tuberculosis (TB). Laboratory investigations included a positive HIV test and a CD4 cell count of 138 cells/μL. Chest radiography revealed a globular-shaped heart and bilateral pleural effusions, while echocardiography confirmed a massive pericardial effusion. The new Xpert MTB/RIF (Xpert) assay detected rifampicin-sensitiveMycobacterium tuberculosisin pericardial as well as sputum samples. Smear of the pericardial sample was negative. The patient was started on anti-TB treatment and is presently well. He will initiate antiretroviral therapy after 4–6 weeks. To the best of our knowledge, this is the first case report of EPTB diagnosed on pericardial fluid using the Xpert assay in Africa. This report also summarises the use of this assay in the diagnosis of EPTB in HIV-associated TB.
Choosing a model to predict hospital admission: an observational study of new variants of predictive models for case finding
Authors: Billings John , Georghiou Theo , Blunt Ian , Bardsley Martin
Published: August 2013

Objectives

To test the performance of new variants of models to identify people at risk of an emergency hospital admission. We compared (1) the impact of using alternative data sources (hospital inpatient, A&E, outpatient and general practitioner (GP) electronic medical records) (2) the effects of local calibration on the performance of the models and (3) the choice of population denominators.

Design

Multivariate logistic regressions using person-level data adding each data set sequentially to test value of additional variables and denominators.

Setting

5 Primary Care Trusts within England.

Participants

1 836 099 people aged 18–95 registered with GPs on 31 July 2009.

Main outcome measures

Models to predict hospital admission and readmission were compared in terms of the positive predictive value and sensitivity for various risk strata and with the receiver operating curve C statistic.

Results

The addition of each data set showed moderate improvement in the number of patients identified with little or no loss of positive predictive value. However, even with inclusion of GP electronic medical record information, the algorithms identified only a small number of patients with no emergency hospital admissions in the previous 2 years. The model pooled across all sites performed almost as well as the models calibrated to local data from just one site. Using population denominators from GP registers led to better case finding.

Conclusions

These models provide a basis for wider application in the National Health Service. Each of the models examined produces reasonably robust performance and offers some predictive value. The addition of more complex data adds some value, but we were unable to conclude that pooled models performed less well than those in individual sites. Choices about model should be linked to the intervention design. Characteristics of patients identified by the algorithms provide useful information in the design/costing of intervention strategies to improve care coordination/outcomes for these patients.
Are interventions to reduce interruptions and errors during medication administration effective?: a systematic review
Authors: Raban Magdalena Z , Westbrook Johanna I
Published: August 2013

Background

Medication administration errors are frequent and lead to patient harm. Interruptions during medication administration have been implicated as a potential contributory factor.

Objective

To assess evidence of the effectiveness of interventions aimed at reducing interruptions during medication administration on interruption and medication administration error rates.

Methods

In September 2012 we searched MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Effective Practice and Organisation of Care Group reviews, Google and Google Scholar, and hand searched references of included articles. Intervention studies reporting quantitative data based on direct observations of at least one outcome (interruptions, or medication administration errors) were included.

Results

Ten studies, eight from North America and two from Europe, met the inclusion criteria. Five measured significant changes in interruption rates pre and post interventions. Four found a significant reduction and one an increase. Three studies measured changes in medication administration error rates and showed reductions, but all implemented multiple interventions beyond those targeted at reducing interruptions. No study used a controlled design pre and post. Definitions for key outcome indicators were reported in only four studies. Only one study reported κ scores for inter-rater reliability and none of the multi-ward studies accounted for clustering in their analyses.

Conclusions

There is weak evidence of the effectiveness of interventions to significantly reduce interruption rates and very limited evidence of their effectiveness to reduce medication administration errors. Policy makers should proceed with great caution in implementing such interventions until controlled trials confirm their value. Research is also required to better understand the complex relationship between interruptions and error to support intervention design.
Antimicrobial susceptibilities and distribution of sequence types of Neisseria gonorrhoeae isolates in Canada: 2010
Authors: Martin Irene , Sawatzky Pam , Liu Gary , Allen Vanessa , Lefebvre Brigitte , Hoang Linda , Lovgren Marguerite , Haldane David , Caeseele Paul Van , Horsman Greg , Garceau Richard , Ratnam Sam , Wong Tom , Gilmour Matthew
Published: August 2013

The monitoring of antimicrobial susceptibilities in Neisseria gonorrhoeae isolates and characterization of N. gonorrhoeae multiantigen sequence types (NG-MAST, ST) provide important surveillance data as resistance rates continue to rise. A total of 2970 N. gonorrhoeae isolates were collected by Canadian provincial public health laboratories in 2010, and 1233 were submitted to the National Microbiology Laboratory for testing. The NG-MAST and minimum inhibitory concentration (MIC) by agar dilution were determined for each isolate. Of the 2970 isolates, 25.1% were resistant to penicillin, 34.6% resistant to tetracycline, 31.5% resistant to erythromycin, 35.9% resistant to ciprofloxacin, and 1.2% resistant to azithromycin. Decreased susceptibility to cefixime (MIC ≥ 0.25 mg/L) and ceftriaxone (MIC ≥ 0.125 mg/L) was identified in 3.2% and 7.3% of the isolates, respectively. The most common STs found in Canada were ST1407 (13.3%), ST3150 (11.3%), and ST3158 (9.0%), with 249 different STs identified among the isolates. Within the ST1407 group, 19.5% and 43.3% isolates have decreased susceptibility to cefixime and ceftriaxone, respectively. ST1407, the most prevalent NG-MAST in Canada in 2010, has been associated with high-level ceftriaxone MICs and with cefixime treatment failure cases worldwide. Identification and monitoring of STs and corresponding antimicrobial resistance profiles may be useful in surveillance programs and be used to inform public health actions.
The state of peer-to-peer network simulators
Authors: Basu Anirban , Fleming Simon , Stanier James , Naicken Stephen , Wakeman Ian , Gurbani Vijay K.
Published: August 2013

Networking research often relies on simulation in order to test and evaluate new ideas. An important requirement of this process is that results must be reproducible so that other researchers can replicate, validate, and extend existing work. We look at the landscape of simulators for research in peer-to-peer (P2P) networks by conducting a survey of a combined total of over 280 papers from before and after 2007 (the year of the last survey in this area), and comment on the large quantity of research using bespoke, closed-source simulators. We propose a set of criteria that P2P simulators should meet, and poll the P2P research community for their agreement. We aim to drive the community towards performing their experiments on simulators that allow for others to validate their results.
A survey of checker architectures
Authors: Kalayappan Rajshekar , Sarangi Smruti R.
Published: August 2013

Reliability is quickly becoming a primary design constraint for high-end processors because of the inherent limits of manufacturability, extreme miniaturization of transistors, and the growing complexity of large multicore chips. To achieve a high degree of fault tolerance, we need to detect faults quickly and try to rectify them. In this article, we focus on the former aspect. We present a survey of different kinds of fault detection mechanisms for processors at circuit, architecture, and software level. We collectively refer to such mechanisms as
checker architectures
. First, we propose a novel two-level taxonomy for different classes of checkers based on their structure and functionality. Subsequently, for each class we present the ideas in some of the seminal papers that have defined the direction of the area along with important extensions published in later work.
A survey of pipelined workflow scheduling
Authors: Benoit Anne , Çatalyürek Ümit V. , Robert Yves , Saule Erik
Published: August 2013

A large class of applications need to execute the same workflow on different datasets of identical size. Efficient execution of such applications necessitates intelligent distribution of the application components and tasks on a parallel machine, and the execution can be orchestrated by utilizing task, data, pipelined, and/or replicated parallelism. The scheduling problem that encompasses all of these techniques is calledpipelined workflow scheduling, and it has been widely studied in the last decade. Multiple models and algorithms have flourished to tackle various programming paradigms, constraints, machine behaviors, or optimization goals. This article surveys the field by summing up and structuring known results and approaches.
Introspection-based memory de-duplication and migration
Authors: Chiang Jui-Hao , Li Han-Lin , Chiueh Tzi-cker
Published: August 2013

Memory virtualization abstracts a physical machine's memory resource and presents to the virtual machines running on it a piece of physical memory that could be shared, compressed and moved. To optimize the memory resource utilization by fully leveraging the flexibility afforded by memory virtualization, it is essential that the hypervisor have some sense of how the guest VMs use their allocated physical memory. One way to do this is virtual machine introspection (VMI), which interprets byte values in a guest memory space into semantically meaningful data structures. However, identifying a guest VM's memory usage information such as free memory pool is non-trivial. This paper describes a bootstrapping VM introspection technique that could accurately extract free memory pool information from multiple versions of Windows and Linux without kernel version-specific hard-coding, how to apply this technique to improve the efficiency of memory de-duplication and memory state migration, and the resulting improvement in memory de-duplication speed, gain in additional memory pages de-duplicated, and reduction in traffic loads associated with memory state migration.
EXTERIOR
Authors: Fu Yangchun , Lin Zhiqiang
Published: August 2013

This paper presents EXTERIOR, a dual-VM architecture based external shell that can be used for trusted, timely out-of-VM management of guest-OS such as introspection, configuration, and recovery. Inspired by recent advances in virtual machine introspection (VMI), EXTERIOR leverages an isolated, secure virtual machine (SVM) to introspect the kernel state of a guest virtual machine (GVM). However, it goes far beyond the read-only capability of the traditional VMI, and can perform automatic, fine-grained guest-OS writable operations. The key idea of EXTERIOR is to use a dual-VM architecture in which a SVM runs a kernel identical to that of the GVM to create the necessary environment for a running process (e.g., rmmod, kill), and dynamically and transparently redirect and update the memory state at the VMM layer from SVM to GVM, thereby achieving the same effect in terms of kernel state updates of running the same trusted in-VM program inside the shell of GVM. A proof-of-concept EXTERIOR has been implemented. The experimental results show that EXTERIOR can be used for a timely administration of guest-OS, including introspection and (re)configuration of the guest-OS state and timely response of kernel malware intrusions, without any user account in the guest-OS.
A framework for application guidance in virtual memory systems
Authors: Jantz Michael R. , Strickland Carl , Kumar Karthik , Dimitrov Martin , Doshi Kshitij A.
Published: August 2013

This paper proposes a collaborative approach in which applications can provide guidance to the operating system regarding allocation and recycling of physical memory. The operating system incorporates this guidance to decide which physical page should be used to back a particular virtual page. The key intuition behind this approach is that application software, as a generator of memory accesses, is best equipped to inform the operating system about the relative access rates and overlapping patterns of usage of its own address space. It is also capable of steering its own algorithms in order to keep its dynamic memory footprint under check when there is a need to reduce power or to contain the spillover effects from bursts in demand. Application software, working cooperatively with the operating system, can therefore help the latter schedule memory more effectively and efficiently than when the operating system is forced to act alone without such guidance. It is particularly difficult to achieve power efficiency without application guidance since power expended in memory is a function not merely of the intensity with which memory is accessed in time but also how many physical ranks are affected by an application's memory usage.

Our framework introduces an abstraction called "colors" for the application to communicate its intent to the operating system. We modify the operating system to receive this communication in an efficient way, and to organize physical memory pages into intermediate level grouping structures called "trays" which capture the physically independent access channels and self-refresh domains, so that it can apply this guidance without entangling the application in lower level details of power or bandwidth management.

This paper describes how we re-architect the memory management of a recent Linux kernel to realize a three way collaboration between hardware, supervisory software, and application tasks.
A peta-scalable CPU-GPU algorithm for global atmospheric simulations
Authors: Yang Chao , Xue Wei , Fu Haohuan , Gan Lin , Li Linfeng , Xu Yangtong , Lu Yutong , Sun Jiachang , Yang Guangwen , Zheng Weimin
Published: August 2013

Developing highly scalable algorithms for global atmospheric modeling is becoming increasingly important as scientists inquire to understand behaviors of the global atmosphere at extreme scales. Nowadays, heterogeneous architecture based on both processors and accelerators is becoming an important solution for large-scale computing. However, large-scale simulation of the global atmosphere brings a severe challenge to the development of highly scalable algorithms that fit well into state-of-the-art heterogeneous systems. Although successes have been made on GPU-accelerated computing in some top-level applications, studies on fully exploiting heterogeneous architectures in global atmospheric modeling are still very less to be seen, due in large part to both the computational difficulties of the mathematical models and the requirement of high accuracy for long term simulations.

In this paper, we propose a peta-scalable hybrid algorithm that is successfully applied in a cubed-sphere shallow-water model in global atmospheric simulations. We employ an adjustable partition between CPUs and GPUs to achieve a balanced utilization of the entire hybrid system, and present a pipe-flow scheme to conduct conflict-free inter-node communication on the cubed-sphere geometry and to maximize communication-computation overlap. Systematic optimizations for multithreading on both GPU and CPU sides are performed to enhance computing throughput and improve memory efficiency. Our experiments demonstrate nearly ideal strong and weak scalabilities on up to 3,750 nodes of the Tianhe-1A. The largest run sustains a performance of 0.8 Pflops in double precision (32% of the peak performance), using 45,000 CPU cores and 3,750 GPUs.
Adoption protocols for fanout-optimal fault-tolerant termination detection
Authors: Lifflander Jonathan , Miller Phil , Kale Laxmikant
Published: August 2013

Termination detection is relevant for signaling completion (all processors are idle and no messages are in flight) of many operations in distributed systems, including work stealing algorithms, dynamic data exchange, and dynamically structured computations. In the face of growing supercomputers with increasing likelihood that each job may encounter faults, it is important for high-performance computing applications that rely on termination detection that such an algorithm be able to tolerate the inevitable faults. We provide a trio of new practical fault tolerance schemes for a standard approach to termination detection that are easy to implement, present low overhead in both theory and practice, and have scalable costs when recovering from faults. These schemes tolerate all single-process faults, and are probabilistically tolerant of faults affecting multiple processes. We combine the theoretical failure probabilities we can calculate for each algorithm with historical fault records from real machines to show that these algorithms have excellent overall survivability.
Array dataflow analysis for polyhedral X10 programs
Authors: Yuki Tomofumi , Feautrier Paul , Rajopadhye Sanjay , Saraswat Vijay
Published: August 2013

This paper addresses the static analysis of an important class of X10 programs, namely those with finish/async parallelism, and affine loops and array reference structure as in the polyhedral model. For such programs our analysis can certify whenever a program is deterministic or flags races.

Our key contributions are (i) adaptation of array dataflow analysis from the polyhedral model to programs with finish/async parallelism, and (ii) use of the array dataflow analysis result to certify determinacy. We distinguish our work from previous approaches by combining the precise statement instance-wise and array element-wise analysis capability of the polyhedral model with finish/async programs that are more expressive than doall parallelism commonly considered in the polyhedral literature. We show that our approach is exact (no false negative/positives) and more precise than previous approaches, but is limited to programs that fit the polyhedral model.
Compiler aided manual speculation for high performance concurrent data structures
Authors: Xiang Lingxiang , Scott Michael Lee
Published: August 2013

Speculation is a well-known means of increasing parallelism among concurrent methods that are usually but not always independent. Traditional nonblocking data structures employ a particularly restrictive form of speculation. Software transactional memory (STM) systems employ a much more general---though typically blocking---form, and there is a wealth of options in between.

Using several different concurrent data structures as examples, we show that manual addition of speculation to traditional lock-based code can lead to significant performance improvements. Successful speculation requires careful consideration of profitability, and of how and when to validate consistency. Unfortunately, it also requires substantial modifications to code structure and a deep understanding of the memory model. These latter requirements make it difficult to use in its purely manual form, even for expert programmers. To simplify the process, we present a compiler tool, CSpec, that automatically generates speculative code from baseline lock-based code with user annotations. Compiler-aided manual speculation keeps the original code structure for better readability and maintenance, while providing the flexibility to chose speculation and validation strategies. Experiments on UltraSPARC and x86 platforms demonstrate that with a small number annotations added to lock-based code, CSpec can generate speculative code that matches the performance of best-effort hand-written versions.
TigerQuoll
Authors: Bonetta Daniele , Binder Walter , Pautasso Cesare
Published: August 2013

JavaScript, the most popular language on the Web, is rapidly moving to the server-side, becoming even more pervasive. Still, JavaScript lacks support for shared memory parallelism, making it challenging for developers to exploit multicores present in both servers and clients. In this paper we present TigerQuoll, a novel API and runtime for parallel programming in JavaScript. TigerQuoll features an event-based API and a parallel runtime allowing applications to exploit a mutable shared memory space. The programming model of TigerQuoll features automatic consistency and concurrency management, such that developers do not have to deal with shared-data synchronization. TigerQuoll supports an innovative transaction model that allows for eventual consistency to speed up high-contention workloads. Experiments show that TigerQuoll applications scale well, allowing one to implement common parallelism patterns in JavaScript.
Data layout optimization for GPGPU architectures
Authors: Liu Jun , Ding Wei , Jang Ohyoung , Kandemir Mahmut
Published: August 2013

GPUs are being widely used in accelerating general-purpose applications, leading to the emergence of GPGPU architectures. New programming models, e.g., Compute Unified Device Architecture (CUDA), have been proposed to facilitate programming general-purpose computations in GPGPUs. However, writing high-performance CUDA codes manually is still tedious and difficult. In particular, the organization of the data in the memory space can greatly affect the performance due to the unique features of a custom GPGPU memory hierarchy. In this work, we propose an automatic data layout transformation framework to solve the key issues associated with a GPGPU memory hierarchy (i.e.,
channel skewing, data coalescing,
and
bank conflicts)
. Our approach employs a widely applicable strategy based on a novel concept called
data localization
. Specifically, we try to optimize the layout of the arrays accessed in affine loop nests, for
both
the device memory and shared memory, at
both
coarse grain and fine grain parallelization levels. We performed an experimental evaluation of our data layout optimization strategy using 15 benchmarks on an NVIDIA CUDA GPU device. The results show that the proposed data transformation approach brings around 4.3X speedup on average.
Programming with hardware lock elision
Authors: Afek Yehuda , Levy Amir , Morrison Adam
Published: August 2013

We present a simple yet effective technique for improving performance of lock-based code using the
hardware lock elision
(HLE) feature in Intel's upcoming Haswell processor.

We also describe how to extend Haswell's HLE mechanism to achieve a similar effect to our lock elision scheme entirely in hardware.
RaceFree
Authors: Lu Kai , Zhou Xu , Wang Xiaoping , Zhang Wenzhe , Li Gen
Published: August 2013

Current deterministic systems generally incur large overhead due to the difficulty of detecting and eliminating data races. This paper presents RaceFree, a novel multi-threading runtime that adopts a
relaxed deterministic model
to provide a data-race-free environment for parallel programs. This model cuts off unnecessary shared-memory communication by isolating threads in separated memories, which eliminates direct data races. Meanwhile, we leverage the happen-before relation defined by applications themselves as one-way communication pipes to perform necessary thread communication. Shared-memory communication is transparently converted to message-passing style communication by our Memory Modification Propagation (MMP) mechanism, which propagates local memory modifications to other threads through the happen-before relation pipes. The overhead of RaceFree is 67.2% according to our tests on parallel benchmarks.
Scalable data race detection for partitioned global address space programs
Authors: Park Chang-Seo , Sen Koushik , Iancu Costin
Published: August 2013

Contemporary and future programming languages for HPC promote hybrid parallelism and shared memory abstractions using a global address space. In this programming style, data races occur easily and are notoriously hard to find. Previous work on data race detection for shared memory programs reports 10X-100X slowdowns for non-scientific programs. Previous work on distributed memory programs instruments only communication operations. In this paper we present the first complete implementation of data race detection at scale for UPC programs. Our implementation tracks local and global memory references in the program and it uses two techniques to reduce the overhead: 1) hierarchical function and instruction level sampling; and 2) exploiting the runtime persistence of aliasing and locality specific to Partitioned Global Address Space applications. The results indicate that both techniques are required in practice: well optimized instruction sampling introduces overheads as high as 6500% (65X slowdown), while each technique in separation is able to reduce it to 1000% (10X slowdown). When applying the optimizations in conjunction our tool finds all previously known data races in our benchmark programs with at most 50% overhead. Furthermore, while previous results illustrate the benefits of function level sampling, our experiences show that this technique does not work for scientific programs: instruction sampling or a hybrid approach is required.
Scalable statistics counters
Authors: Dice Dave , Lev Yossi , Moir Mark
Published: August 2013

Naive statistics counters that are commonly used to monitor system events and performance become a scalability bottleneck as systems become larger and more NUMA; furthermore some are so inaccurate that they are not useful. We present a number of techniques to address these problems, evaluating solutions in terms of performance, scalability, space overhead, and accuracy.
Swift/T
Authors: Wozniak Justin M. , Armstrong Timothy G. , Wilde Michael , Katz Daniel S. , Lusk Ewing , Foster Ian T.
Published: August 2013

Swift/T, a novel programming language implementation for highly scalable data flow programs, is presented.
Work-stealing with configurable scheduling strategies
Authors: Wimmer Martin , Cederman Daniel , Träff Jesper Larsson , Tsigas Philippas
Published: August 2013

Work-stealing systems are typically oblivious to the nature of the tasks they are scheduling. They do not know or take into account how long a task will take to execute or how many subtasks it will spawn. Moreover, task execution order is typically determined by an underlying task storage data structure, and cannot be changed. There are thus possibilities for optimizing task parallel executions by providing information on specific tasks and their preferred execution order to the scheduling system.

We investigate generalizations of work-stealing and introduce a framework enabling applications to dynamically provide hints on the nature of specific tasks using
scheduling strategies
. Strategies can be used to independently control both local task execution and steal order. Strategies allow optimizations on specific tasks, in contrast to more conventional
scheduling policies
that are typically global in scope. Strategies are
composable
and allow different, specific scheduling choices for different parts of an application simultaneously. We have implemented a work-stealing system based on our strategy framework. A series of benchmarks demonstrates beneficial effects that can be achieved with scheduling strategies.
WuKong
Authors: Zhou Bowen , Kulkarni Milind , Bagchi Saurabh
Published: August 2013

A key challenge in developing large scale applications (both in system size and in input size) is finding bugs that are latent at the small scales of testing, only manifesting when a program is deployed at large scales. Traditional statistical techniques fail because no error-free run is available at deployment scales for training purposes. Prior work used
scaling models
to detect anomalous behavior at large scales without being trained on correct behavior at that scale. However, that work cannot localize bugs automatically. In this paper, we extend that work in three ways: (i) we develop an automatic diagnosis technique, based on
feature reconstruction
; (ii) we design a heuristic to effectively prune the feature space; and (iii) we validate our design through one fault-injection study, finding that our system can effectively localize bugs in a majority of cases.
Power and Agency in Precolonial African States
Authors: Monroe J. Cameron
Published: August 2013

Precolonial African polities have emerged in recent years as fertile ground for the comparative archaeological study of social complexity and the state. For much of the twentieth century, precolonial African states were misinterpreted as the product of outside stimuli. Recent archaeological research on such polities, however, has revealed the autochthonous origins of social complexity and the state in Africa, providing valuable new insights for the comparative study of state formation in the past. This review outlines how archaeologists have tackled the precolonial state in Africa, beginning with an outline of colonial-era discourse on the nature of the state and civilization in Africa, followed by a discussion of how archaeological perspectives on power provide insights into political processes across the continent. Key examples are examined within four broadly defined subregions. Throughout this review, I highlight (a) the agency of indigenous political entrepreneurs in driving state formation across the continent, and (b) how alternative modes of power shaped the political contours of these precolonial African states.
Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets
Authors: Bielohuby Maximilian , Sisley Stephanie , Sandoval Darleen , Herbach Nadja , Zengin Ayse , Fischereder Michael , Menhofer Dominik , Stoehr Barbara J. M. , Stemmer Kerstin , Wanke Rüdiger , Tschöp Matthias H. , Seeley Randy J. , Bidlingmaier Martin
Published: August 2013

Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein “Atkins-style” LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.