bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of either Lethal Toxin or Edema Toxin by Bacillus anthracis Is Sufficient for Virulence in a Rabbit Model of Inhalational Anthrax
Authors: Lovchik Julie A. , Drysdale Melissa , Koehler Theresa M. , Hutt Julie A. , Lyons C. Rick 
Published: April 2012

ABSTRACT

The development of therapeutics against biothreats requires that we understand the pathogenesis of the disease in relevant animal models. The rabbit model of inhalational anthrax is an important tool in the assessment of potential therapeutics against
Bacillus anthracis
. We investigated the roles of
B. anthracis
capsule and toxins in the pathogenesis of inhalational anthrax in rabbits by comparing infection with the Ames strain versus isogenic mutants with deletions of the genes for the capsule operon (
capBCADE
), lethal factor (
lef
), edema factor (
cya
), or protective antigen (
pagA
). The absence of capsule or protective antigen (PA) resulted in complete avirulence, while the presence of either edema toxin or lethal toxin plus capsule resulted in lethality. The absence of toxin did not influence the ability of
B. anthracis
to traffic to draining lymph nodes, but systemic dissemination required the presence of at least one of the toxins. Histopathology studies demonstrated minimal differences among lethal wild-type and single toxin mutant strains. When rabbits were coinfected with the Ames strain and the PA− mutant strain, the toxin produced by the Ames strain was not able to promote dissemination of the PA− mutant, suggesting that toxigenic action occurs in close proximity to secreting bacteria. Taken together, these findings suggest that a major role for toxins in the pathogenesis of anthrax is to enable the organism to overcome innate host effector mechanisms locally and that much of the damage during the later stages of infection is due to the interactions of the host with the massive bacterial burden.
Vibrio cholerae Classical Biotype Strains Reveal Distinct Signatures in Mexico
Authors: Alam Munirul , Islam M. Tarequl , Rashed Shah Manzur , Johura Fatema-tuz , Bhuiyan Nurul A. , Delgado Gabriela , Morales Rosario , Mendez Jose Luis , Navarro Armando , Watanabe Haruo , Hasan Nur-A , Colwell Rita R. , Cravioto Alejandro 
Published: April 2012

ABSTRACT

Vibrio cholerae
O1 classical (CL) biotype caused the fifth and sixth pandemics, and probably the earlier cholera pandemics, before the El Tor (ET) biotype initiated the seventh pandemic in Asia in the 1970s by completely displacing the CL biotype. Although the CL biotype was thought to be extinct in Asia and although it had never been reported from Latin America,
V. cholerae
CL and ET biotypes, including a hybrid ET, were found associated with areas of cholera endemicity in Mexico between 1991 and 1997. In this study, CL biotype strains isolated from areas of cholera endemicity in Mexico between 1983 and 1997 were characterized in terms of major phenotypic and genetic traits and compared with CL biotype strains isolated in Bangladesh between 1962 and 1989. According to sero- and biotyping data, all
V. cholerae
strains tested had the major phenotypic and genotypic characteristics specific for the CL biotype. Antibiograms revealed the majority of the Bangladeshi strains to be resistant to trimethoprim-sulfamethoxazole, furazolidone, ampicillin, and gentamicin, while the Mexican strains were sensitive to all of these drugs, as well as to ciprofloxacin, erythromycin, and tetracycline. Pulsed-field gel electrophoresis (PFGE) of NotI-digested genomic DNA revealed characteristic banding patterns for all of the CL biotype strains although the Mexican strains differed from the Bangladeshi strains in 1 to 2 DNA bands. The difference was subtle but consistent, as confirmed by the subclustering patterns in the PFGE-based dendrogram, and can serve as a regional signature, suggesting the pre-1991 existence and evolution of the CL biotype strains in the Americas, independent from Asia.
Coccidioides Thyroiditis in an HIV-Infected Patient
Authors: Jinno Sadao , Chang Shelley , Jacobs Michael R. 
Published: April 2012

ABSTRACT

We report a case of
Coccidioides
thyroiditis in an HIV-infected patient with a history of recent
Coccidioides
pneumonia but with negative
Coccidioides
serology determined by enzyme immunoassay at presentation. Diagnosis of
Coccidioides
thyroiditis was made based on histopathologic examination and culture of thyroid abscess material obtained by fine-needle aspiration biopsy.
Comparison of the Luminex xTAG RVP Fast Assay and the Idaho Technology FilmArray RP Assay for Detection of Respiratory Viruses in Pediatric Patients at a Cancer Hospital
Authors: Babady N. Esther , Mead Peter , Stiles Jeffrey , Brennan Carrie , Li Haijing , Shuptar Susan , Stratton Charles W. , Tang Yi-Wei , Kamboj Mini 
Published: April 2012

ABSTRACTRespiratory viruses are increasingly recognized as serious causes of morbidity and mortality in immunocompromised patients. The rapid and sensitive detection of respiratory viruses is essential for the early diagnosis and administration of appropriate antiviral therapy, as well as for the effective implementation of infection control measures. We compared the performance of two commercial assays, xTAG RVP Fast (Luminex Diagnostics, Toronto, Canada) and FilmArray RVP (FA RVP; Idaho Technology, Salt Lake City, UT), in pediatric patients at Memorial Sloan-Kettering Cancer Center. These assays detect the following viruses: respiratory syncytial virus; influenza A and B viruses; parainfluenza viruses 1, 2, 3, and 4; human metapneumovirus; adenovirus; enterovirus-rhinovirus; coronaviruses NL63, HKU1, 229E, and OC43; and bocavirus. We tested a total of 358 respiratory specimens from 173 pediatric patients previously tested by direct fluorescence assay (DFA) and viral culture. The overall detection rate (number of positive specimens/total specimens) for viruses tested by all methods was 24% for DFA/culture, 45% for xTAG RVP Fast, and 51% for FA RVP. The agreement between the two multiplex assays was 84.5%, and the difference in detection rate was statistically significant (P< 0.0001). Overall, the FA RVP assay was more sensitive than the xTAG RVP Fast assay and had a turnaround time of approximately 1 h. The sensitivity, simplicity, and random-access platform make FA RVP an excellent choice for laboratory on-demand service with low to medium volume.
Antimicrobial Resistance, Toxinotype, and Genotypic Profiling of Clostridium difficile Isolates of Swine Origin
Authors: Fry Pamela R. , Thakur Siddhartha , Abley Melanie , Gebreyes Wondwossen A. 
Published: April 2012

ABSTRACT

The occurrence of
Clostridium difficile
infections in patients that do not fulfill the classical risk factors prompted us to investigate new risk factors of disease. The goal of this study was to characterize strains and associated antimicrobial resistance determinants of
C. difficile
isolated from swine raised in Ohio and North Carolina. Genotypic approaches used include PCR detection, toxinotyping, DNA sequencing, and pulsed-field gel electrophoresis (PFGE) DNA fingerprinting. Thirty-one percent (37/119) of isolates carried both
tetM
and
tetW
genes. The
ermB
gene was found in 91% of isolates that were resistant to erythromycin (68/75). Eighty-five percent (521/609) of isolates were toxin gene
tcdB
and
tcdA
positive. A total of 81% (494/609) of isolates were positive for
cdtB
and carry a
tcdC
gene (a toxin gene negative regulator) with a 39-bp deletion. Overall, 88% (196/223) of pigs carry a single
C. difficile
strain, while 12% (27/223) of pigs carried multiple strains. To the best of our knowledge, this is the first report of individual pigs found to carry more than one strain type of
C. difficile
. A significant difference in toxinotype profiles in the two geographic locations was noted, with a significantly (
P
< 0.001) higher prevalence of toxinotype V found in North Carolina (84%; 189/224) than in Ohio (55%; 99/181). Overall, the study findings indicate that significant proportions of
C. difficile
in swine are toxigenic and often are associated with antimicrobial resistance genes, although they are not resistant to drugs that are used to treat
C. difficile
infections.
Babies born at the threshold of viability: changes in survival and workload over 20 years
Authors: Seaton Sarah E , King Sophie , Manktelow Bradley N , Draper Elizabeth S , Field David J 
Published: April 2012

ObjectiveTo assess the care given to the babies born at the threshold of viability over the last 20 years using regional and national data.DesignPopulation-based retrospective study.SettingFormer ‘Trent’ health region.ParticipantsBabies born between 1 January 1991 and 31 December 2010 at 22+0to 25+6weeks gestational age.Main outcome measureSurvival and use of respiratory support.MethodsData of all babies born between 1 January 1991 and 31 December 2010 with a gestational age of 22+0to 25+6weeks and admitted to a neonatal unit were extracted from The Neonatal Survey. Use of respiratory support in terms of ventilation and continuous positive airway pressure (CPAP) for this group of babies was calculated as a proportion of the total used by the whole neonatal intensive care population within the defined study area.ResultsThe proportion of babies surviving to discharge increased significantly over time in those born at 24 and 25 weeks (p<0.01) but failed to achieve statistical significance for those at 23 weeks (p=0.08). No babies born at 22 weeks survived. The babies born at 22–25 weeks accounted for 26.3% of all ventilation and 21.5% of CPAP given.ConclusionOur work concurs with the current UK guidelines. There could be advantages in focusing the care of babies born at 23 weeks to a small number of intensive care units to allow specialist expertise to develop in all aspects of the management of these babies. However, focusing care will not necessarily improve survival or reduce morbidity.
On the Relative Strength of Pebbling and Resolution
Authors: Nordström Jakob 
Published: April 2012

The last decade has seen a revival of interest in pebble games in the context of proof complexity. Pebbling has proven to be a useful tool for studying resolution-based proof systems when comparing the strength of different subsystems, showing bounds on proof space, and establishing size-space trade-offs. The typical approach has been to encode the pebble game played on a graph as a CNF formula and then argue that proofs of this formula must inherit (various aspects of) the pebbling properties of the underlying graph. Unfortunately, the reductions used here are not tight. To simulate resolution proofs by pebblings, the full strength of nondeterministic black-white pebbling is needed, whereas resolution is only known to be able to simulate deterministic black pebbling. To obtain strong results, one therefore needs to find specific graph families which either have essentially the same properties for black and black-white pebbling (not at all true in general) or which admit simulations of black-white pebblings in resolution.
This article contributes to both these approaches. First, we design a restricted form of black-white pebbling that can be simulated in resolution and show that there are graph families for which such restricted pebblings can be asymptotically better than black pebblings. This proves that, perhaps somewhat unexpectedly, resolution can strictly beat black-only pebbling, and in particular that the space lower bounds on pebbling formulas in Ben-Sasson and Nordström [2008] are tight. Second, we present a versatile parametrized graph family with essentially the same properties for black and black-white pebbling, which gives sharp simultaneous trade-offs for black and black-white pebbling for various parameter settings. Both of our contributions have been instrumental in obtaining the time-space trade-off results for resolution-based proof systems in Ben-Sasson and Nordström [2011].
CS Unplugged and Middle-School Students’ Views, Attitudes, and Intentions Regarding CS
Authors: Taub Rivka , Armoni Michal , Ben-Ari Mordechai 
Published: April 2012

Many students hold incorrect ideas and negative attitudes about computer science (CS). In order to address these difficulties, a series of learning activities called Computer Science Unplugged was developed by Tim Bell and his colleagues. These activities expose young people to central concepts in CS in an entertaining way without requiring a computer. The CS Unplugged activities have become more and more popular among CS educators and several activities are recommended in the ACM K-12 curriculum for elementary schools. CS Unplugged is used worldwide and has been translated into many languages.
We examined the effect of the CS Unplugged activities on middle-school students’ ideas about CS and their desire to consider and study it in high school. The results indicate that following the activities the ideas of the students on what CS is about were partially improved, but their desire to study CS lessened.
In order to provide possible explanations to these results, we analyzed the CS Unplugged activities to determine to what extent the objectives of CS Unplugged were addressed in the activities. In addition, we checked whether the activities were designed according to constructivist principles and whether they were explicitly linked to central concepts in CS. We found that only some of the objectives were addressed in the activities, that the activities do not engage with the students’ prior knowledge and that most of the activities are not explicitly linked to central concepts in CS. We offer suggestions for modifying the CS Unplugged activities so that they will be more likely to achieve their objectives.
Chameleon
Authors: Panneerselvam Sankaralingam , Swift Michael M. 
Published: April 2012

The rise of multi-core processors has shifted performance efforts towards parallel programs. However, single-threaded code, whether from legacy programs or ones difficult to parallelize, remains important. Proposed asymmetric multicore processors statically dedicate hardware to improve sequential performance, but at the cost of reduced parallel performance. However, several proposed mechanisms provide the best-of-both-worlds by combining multiple cores into a single, more powerful processor for sequential code. For example, Core Fusion merges multiple cores to pool caches and functional units, and Intel's Turbo Boost raises the clock speed of a core if the other cores on a chip are powered down.
These reconfiguration mechanisms have two important properties. First the set of available cores and their capabilities can vary over short time scales. Current operating systems are not designed for rapidly changing hardware: the existing hotplug mechanisms for reconfiguring processors require global operations and hundreds of milliseconds to complete. Second, configurations may be mutually exclusive: using power to speed one core means it cannot be used to speed another. Current schedulers cannot manage this requirement.
We present Chameleon, an extension to Linux to support dynamic processors that can reconfigure their cores at runtime. Chameleon provides processor proxies to enable rapid reconfiguration, execution objects to abstract the processing capabilities of physical CPUs, and a cluster scheduler to balance the needs of sequential and parallel programs. In experiments that emulate a dynamic processor, we find that Chameleon can reconfigure processors 100,000 times faster than Linux and allows applications full access to hardware capabilities: sequential code runs at full speed on a powerful execution context, while parallel code runs on as many cores as possible.
Execution migration in a heterogeneous-ISA chip multiprocessor
Authors: DeVuyst Matthew , Venkat Ashish , Tullsen Dean M. 
Published: April 2012

Prior research has shown that single-ISA heterogeneous chip multiprocessors have the potential for greater performance and energy efficiency than homogeneous CMPs. However, restricting the cores to a single ISA removes an important opportunity for greater heterogeneity. To take full advantage of a heterogeneous-ISA CMP, however, we must be able to migrate execution among heterogeneous cores in order to adapt to program phase changes and changing external conditions (e.g., system power state).
This paper explores migration on heterogeneous-ISA CMPs. This is non-trivial because program state is kept in an architecture-specific form; therefore, state transformation is necessary for migration. To keep migration cost low, the amount of state that requires transformation must be minimized. This work identifies large portions of program state whose form is not critical for performance; the compiler is modified to produce programs that keep most of their state in an architecture-neutral form so that only a small number of data items must be repositioned and no pointers need to be changed. The result is low migration cost with minimal sacrifice of non-migration performance.
Additionally, this work leverages binary translation to enable instantaneous migration. When migration is requested, the program is immediately migrated to a different core where binary translation runs for a short time until a function call is reached, at which point program state is transformed and execution continues natively on the new core.
This system can tolerate migrations as often as every 100 ms and still retain 95% of the performance of a system that does not do, or support, migration.
Novel Aspects of Mevalonate Pathway Inhibitors as Antitumor Agents
Authors: Thurnher Martin , Nussbaumer Oliver , Gruenbacher Georg 
Published: April 2012

Abstract
The mevalonate pathway for cholesterol biosynthesis and protein prenylation has been implicated in various aspects of tumor development and progression. Certain classes of drugs, such as statins and bisphosphonates, inhibit mevalonate metabolism and therefore have also been tested as antitumor agents. This concept is strongly supported by the recent finding that mutant p53, which is present in more than half of all human cancers, can significantly upregulate mevalonate metabolism and protein prenylation in carcinoma cells. The first evidence that mevalonate pathway inhibitors may have the potential to reverse the malignant phenotype has already been obtained. Moreover, recently discovered immunomodulatory properties of statins and bisphosphonates may also contribute to their known anticancer effects. Drug-induced inhibition of protein prenylation may induce sequential cellular stress responses, including the unfolded protein response and autophagy, that eventually translate into inflammasome-dependent and caspase-1-mediated activation of innate immunity. This review focuses on these novel capabilities of mevalonate pathway inhibitors to beneficially affect tumor biology and contribute to tumor immune surveillance. Clin Cancer Res; 18(13); 3524–31. ©2012 AACR.
Somatic Mutations in CCK2R Alter Receptor Activity that Promote Oncogenic Phenotypes
Authors: Willard Melinda D. , Lajiness Mary E. , Wulur Isabella H. , Feng Bo , Swearingen Michelle L. , Uhlik Mark T. , Kinzler Kenneth W. , Velculescu Victor E. , Sjöblom Tobias , Markowitz Sanford D. , Powell Steven M. , Vogelstein Bert , Barber Thomas D. 
Published: April 2012

AbstractThe roles of cholecystokinin 2 receptor (CCK2R) in numerous physiologic processes in the gastrointestinal tract and central nervous system are well documented. There has been some evidence that CCK2R alterations play a role in cancers, but the functional significance of these alterations for tumorigenesis is unknown. We have identified six mutations in CCK2R among a panel of 140 colorectal cancers and 44 gastric cancers. We show that these mutations increase receptor activity, activate multiple downstream signaling pathways, increase cell migration, and promote angiogenesis. Our findings suggest that somatic mutations in CCK2R may promote tumorigenesis through deregulated receptor activity and highlight the importance of evaluating CCK2R inhibitors to block both the normal and mutant forms of the receptor. Mol Cancer Res; 10(6); 739–49. ©2012 AACR.
Eddy-Resolving Model Estimate of the Cabbeling Effect on the Water Mass Transformation in the Southern Ocean
Authors: Urakawa L. Shogo , Hasumi Hiroyasu 
Published: April 2012

Abstract
Cabbeling effect on the water mass transformation in the Southern Ocean is investigated with the use of an eddy-resolving Southern Ocean model. A significant amount of water is densified by cabbeling: water mass transformation rates are about 4 Sv (1 Sv ≡ 106 m3 s−1) for transformation from surface/thermocline water to Subantarctic Mode Water (SAMW), about 7 Sv for transformation from SAMW to Antarctic Intermediate Water (AAIW), and about 5 Sv for transformation from AAIW to Upper Circumpolar Deep Water. These diapycnal volume transports occur around the Antarctic Circumpolar Current (ACC), where mesoscale eddies are active. The water mass transformation by cabbeling in this study is also characterized by a large amount of densification of Lower Circumpolar Deep Water (LCDW) into Antarctic Bottom Water (AABW) (about 9 Sv). Large diapycnal velocity is found not only along the ACC but also along the coast of Antarctica at the boundary between LCDW and AABW. It is found that about 3 Sv of LCDW is densified into AABW by cabbeling on the continental slopes of Antarctica in this study. This densification is not small compared with observational and numerical estimates on the AABW formation rate, which ranges from 10 to 20 Sv.
A nonlinear, data-driven model applied in the design process of disc-spring valve systems used in hydraulic dampers
Authors: Wszołek Grzegorz , Czop Piotr , Skrobol Antoni , Sławik Damian 
Published: April 2012

This paper proposes an analytical tool that supports the design process of a disc-spring valve system used in hydraulic dampers. Such a valve is representative of a broader family of valve systems used in many industrial applications. The tool will speed up the valve-system design process. The paper considers a valve system that combines a number of circular metal plates, referred to further in the paper as ‘a stack of plates’. The proposed analytical tool obtains a key design characteristic of a valve, the flow rate, and the corresponding maximum stress level in the stack of plates as a function of pressure load. The stress level enables the ranking of valve settings in terms of durability. The calculation process is based on the response of a nonlinear, data-driven model that approximates the a priori simulated cases to cover the complete range of input design parameters, namely the number of plates, their thickness and their diameter. The cases are produced by a first-principle model using a Finite Element (FE) approach. The model was calibrated based on experimental results to provide accurate results in the entire range of input parameters. The advantage of the analytical tool is its ability to immediately provide the pressure-stress-flow characteristic of a valve instead of repeating time-consuming calculations for each new setting of input parameters. The objectives of the paper are as follows: to (a) adapt the model to a three-plate stack by applying large strain theory, (b) select and rank the Artificial Neural Networks used in order to approximate simulation data, and (c) demonstrate validation and application results obtained with the Approximation Tool.