bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory Mechanism for Exfoliative Toxin Production in
Staphylococcus aureus
Authors: Kato Fuminori , Kadomoto Noriko , Iwamoto Yuko , Bunai Katsuaki , Komatsuzawa Hitoshi , Sugai Motoyuki 
Published: February 2011

ABSTRACT

The exfoliative toxin (ET) is a major virulence factor of
Staphylococcus aureus
that causes bullous impetigo and its disseminated form, staphylococcal scalded-skin syndrome (SSSS). ET selectively digests one of the intracellular adhesion molecules, desmoglein 1, of epidermal keratinocytes and causes blisters due to intraepidermal cell-cell dissociation. Most
S. aureus
strains that cause blistering disease produce either ETA or ETB. They are serologically distinct molecules, where ETA is encoded on a phage genome and ETB is enocded on a large plasmid. ETA-producing
S. aureus
strains are frequently isolated from impetigo patients, and ETB-producing
S. aureus
strains are isolated from SSSS. ET-induced blister formation can be reproduced with the neonatal mouse. To determine the regulatory mechanism of ET production, we investigated the role of the two-component systems and global regulators for
eta
or
etb
expression
in vitro
and
in vivo
with the mouse model. Western blot and transcription analyses using a series of mutants demonstrate ETA production was downregulated by
sigB
,
sarS
, and
sarA
, while ETB production was downregulated by
sigB
and
sarA
but not by
sarS
. Production of both toxins is upregulated by
saeRS
,
arlRS
, and
agrCA
. Furthermore, by the
in vivo
neonatal mouse model,
sigB
and
sarS
but not
sarA
negatively regulate the exfoliation activity of the ETA-producing strain, while
sarA
negatively regulates the ETB-producing strain. In both strains,
saeRS
,
arlRS
, and
agrCA
positively regulate the exfoliation activity
in vivo
. The data illustrate similar but distinct regulatory mechanisms for ETA and ETB production
in S. aureus in vitro
as well as
in vivo
.
CD4+T Cells Are Not Essential for Control of Early AcuteCryptosporidium parvumInfection in Neonatal Mice
Authors: Korbel Daniel S. , Barakat Farah M. , Di Santo James P. , McDonald Vincent 
Published: February 2011

ABSTRACTCryptosporidiosis is an important diarrheal disease of humans and neonatal livestock caused byCryptosporidiumspp. that infect epithelial cells. Recovery fromCryptosporidiumparvuminfection in adult hosts involves CD4+T cells with a strong Th1 component, but mechanisms of immunity in neonates are not well characterized. In the present investigation with newborn mice, similar acute patterns of infection were obtained in C57BL/6 wild-type (WT) and T and B cell-deficient Rag2−/−mice. In comparison with uninfected controls, the proportion of intestinal CD4+or CD8+T cells did not increase in infected WT mice during recovery from infection. Furthermore, infection in neonatal WT mice depleted of CD4+T cells was not exacerbated. Ten weeks after WT and Rag2−/−mice had been infected as neonates, no patent infections could be detected. Treatment at this stage with the immunosuppressive drug dexamethasone produced patent infections in Rag2−/−mice but not WT mice. Expression of inflammatory markers, including gamma interferon (IFN-γ) and interleukin-12p40 (IL-12p40), was higher in neonatal WT mice than in Rag2−/−mice around the peak of infection, but IL-10 expression was also higher in WT mice. These results suggest that although CD4+T cells may be important for elimination ofC. parvum, these cells are dispensable for controlling the early acute phase of infection in neonates.
Differential Requirements for NAIP5 in Activation of the NLRC4 Inflammasome
Authors: Lightfield Karla L. , Persson Jenny , Trinidad Norver J. , Brubaker Sky W. , Kofoed Eric M. , Sauer John-Demian , Dunipace Eric A. , Warren Sarah E. , Miao Edward A. , Vance Russell E. 
Published: February 2011

ABSTRACT

Inflammasomes are cytosolic multiprotein complexes that assemble in response to infectious or noxious stimuli and activate the CASPASE-1 protease. The inflammasome containing the nucleotide binding domain-leucine-rich repeat (NBD-LRR) protein NLRC4 (interleukin-converting enzyme protease-activating factor [IPAF]) responds to the cytosolic presence of bacterial proteins such as flagellin or the inner rod component of bacterial type III secretion systems (e.g.,
Salmonella
PrgJ). In some instances, such as infection with
Legionella pneumophila
, the activation of the NLRC4 inflammasome requires the presence of a second NBD-LRR protein, NAIP5. NAIP5 also is required for NLRC4 activation by the minimal C-terminal flagellin peptide, which is sufficient to activate NLRC4. However, NLRC4 activation is not always dependent upon NAIP5. In this report, we define the molecular requirements for NAIP5 in the activation of the NLRC4 inflammasome. We demonstrate that the N terminus of flagellin can relieve the requirement for NAIP5 during the activation of the NLRC4 inflammasome. We also demonstrate that NLRC4 responds to the
Salmonella
protein PrgJ independently of NAIP5. Our results indicate that NAIP5 regulates the apparent specificity of the NLRC4 inflammasome for distinct bacterial ligands.
In Vivo
Leukocyte Changes Induced by
Escherichia coli
Subtilase Cytotoxin
Authors: Wang Hui , Paton Adrienne W. , McColl Shaun R. , Paton James C. 
Published: February 2011

ABSTRACT

Subtilase cytotoxin (SubAB) is the prototype of a new family of AB
5
cytotoxins produced by Shiga-toxigenic
Escherichia coli
. Its cytotoxicity is due to its capacity to enter cells and specifically cleave the essential endoplasmic reticulum chaperone BiP. Previous studies have shown that intraperitoneal injection of mice with purified SubAB causes a pathology that overlaps with that seen in human cases of hemolytic-uremic syndrome, as well as dramatic splenic atrophy, suggesting that leukocytes are targeted. Here we investigated SubAB-induced leukocyte changes in the peritoneal cavity, blood, and spleen. After intraperitoneal injection, SubAB bound peritoneal leukocytes (including T and B lymphocytes, neutrophils, and macrophages). SubAB elicited marked leukocytosis, which peaked at 24 h, and increased neutrophil activation in the blood and peritoneal cavity. It also induced a marked redistribution of leukocytes among the three compartments: increases in leukocyte subpopulations in the blood and peritoneal cavity coincided with a significant decline in splenic cells. SubAB treatment also elicited significant increases in the apoptosis rates of CD4
+
T cells, B lymphocytes, and macrophages. These findings indicate that apart from direct cytotoxic effects, SubAB interacts with cellular components of both the innate and the adaptive arm of the immune system, with potential consequences for disease pathogenesis.
The OspE-Related Proteins Inhibit Complement Deposition and Enhance Serum Resistance of
Borrelia burgdorferi
, the Lyme Disease Spirochete
Authors: Kenedy Melisha R. , Akins Darrin R. 
Published: February 2011

ABSTRACT

Borrelia burgdorferi
, the Lyme disease spirochete, binds the host complement inhibitors factor H (FH) and FH-like protein 1 (FHL-1). Binding of FH/FHL-1 by the
B. burgdorferi
proteins CspA and the OspE-related proteins is thought to enhance resistance to serum-mediated killing. While previous reports have shown that CspA confers serum resistance in
B. burgdorferi
, it is unclear whether the OspE-related proteins are relevant in
B. burgdorferi
serum resistance when OspE is expressed on the borrelial surface. To assess the role of the OspE-related proteins, we overexpressed them in a serum-sensitive CspA mutant strain. OspE overexpression enhanced serum resistance of the CspA-deficient organisms. Furthermore, FH was more efficiently bound to the
B. burgdorferi
surface when OspE was overexpressed. Deposition of complement components C3 and C5b-9 (the membrane attack complex), however, was reduced on the surface of the OspE-overexpressing strain compared to that on the CspA mutant strain. These data demonstrate that OspE proteins expressed on the surface of
B. burgdorferi
bind FH and protect the organism from complement deposition and subsequent serum-mediated destruction.
Murine Immune Response to a Chronic
Staphylococcus aureus
Biofilm Infection
Authors: Prabhakara Ranjani , Harro Janette M. , Leid Jeff G. , Harris Megan , Shirtliff Mark E. 
Published: February 2011

ABSTRACT

Staphylococcus aureus
has reemerged as an important human pathogen in recent decades. Although many infections caused by this microbial species persist through a biofilm mode of growth, little is known about how the host's adaptive immune system responds to these biofilm infections. In this study,
S. aureus
cells adhered to pins in culture and were subsequently inserted into the tibiae of C57BL/6 mice, with an infecting dose of 2 × 10
5
CFU. This model was utilized to determine local cytokine levels, antibody (Ab) function, and T cell populations at multiple time points throughout infection. Like human hosts,
S. aureus
implant infection was chronic and remained localized in 100% of C57BL/6 mice at a consistent level of approximately 10
7
CFU/gram bone tissue after day 7. This infection persisted locally for >49 days and was recalcitrant to clearance by the host immune response and antimicrobial therapy. Local inflammatory cytokines of the Th1 (interleukin-2 [IL-2], IL-12 p70, tumor necrosis factor alpha [TNF-α], and IL-1β) and Th17 (IL-6 and IL-17) responses were upregulated throughout the infection, except IL-12 p70, which dwindled late in the infection. In addition, Th1 Ab subtypes against a biofilm antigen (SA0486) were upregulated early in the infection, while Th2 Abs and anti-inflammatory regulatory T cells (Tregs) were not upregulated until later. These results indicate that early Th1 and Th17 inflammatory responses and downregulated Th2 and Treg responses occur during the development of a chronic biofilm implant infection. This unrestrained inflammatory response may cause tissue damage, thereby enabling
S. aureus
to attach and thrive in a biofilm mode of growth.
Physicians promoting physical activity using pedometers and community partnerships: a real world trial
Authors: Trinh Linda , Wilson Ron , Williams Heather MacLeod , Sum Alison J , Naylor Patti-Jean 
Published: February 2011

BackgroundHealthcare providers are a primary source of information on preventive health issues for patients. Further research related to physical activity (PA) promotion in the primary care setting is needed.ObjectiveTo explore the feasibility of a physician and community PA intervention using a pedometer for: increasing PA levels among inactive patients; enhancing relationships between physicians and community PA partners; and influencing the PA promotion habits of physicians.MethodsA 6-week PA intervention was delivered to 152 inactive patients who were recruited in physician waiting rooms, counselled by their physicians, provided with a pedometer and referred to a community action site (CAS) at their local recreation centre for further support. PA was measured at baseline and follow-up using the International Physical Activity Questionnaire. Follow-up interviews were conducted with physicians and recreation representatives on the challenges and benefits associated with the intervention.ResultsStudy patients significantly increased their PA (103% change in MET min/week). Physicians and recreation professionals were highly satisfied with the intervention and partnership. There were challenges to ongoing communication. Physicians reported increased awareness of the pedometer and community resources as supports for PA.ConclusionA pedometer-based PA intervention delivered by physicians in partnership with a community PA stakeholder is feasible and warrants further research. Long-term maintenance of this intervention would require resources for pedometers, and ongoing contact and communication between the physicians and CAS to ensure availability of community supports.
Long-term safety and effectiveness of inferior vena cava filters in patients with stroke
Authors: Somarouthu Bhanusupriya , Yeddula Kalpana , Wicky Stephan , Hirsch Joshua A , Kalva Sanjeeva P 
Published: February 2011

PurposeTo assess the long-term safety and clinical effectiveness of inferior vena cava (IVC) filters in patients with stroke.Method and materialsIn this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, we reviewed the clinical data of patients who had stroke and were treated with an IVC filter from 2002 to 2009. The demographics, clinical data, indications for IVC filter, procedural complications, symptomatic post-filter pulmonary embolism (PE) and deep vein thrombosis (DVT), caval occlusion and incidental, imaging-evident filter-related complications were recorded. Safety was assessed through occurrence of filter-related complications during placement and follow-up. Effectiveness was assessed through occurrence of post-filter fatal and non-fatal PE.ResultsDuring this period, 371 patients (224 male; mean age 67.5 years) with stroke received an IVC filter. The stroke was hemorrhagic in 28%, ischemic in 20%, associated with intracranial malignancy in 21% and trauma in 31%. 235 (63%) patients (PE in 159) had venous thromboembolism on imaging. The indications for IVC filter included contraindication to anticoagulation in 251 (68%), prophylaxis in 83 (22%), added protection in 22 (6%) and complication or failure of anticoagulation in 15 (4%). There was one procedural complication. During a follow-up of 1.74±2.36 years, 180 (49%) patients died, three due to post-filter PE and the remainder all due to primary disease. Symptomatic post-filter PE and DVT occurred at a frequency of 15% (54/371) and 16% (60/371), respectively. Of these, 15 (4%) had imaging-proven PE. Three (0.8%) succumbed to post-filter PE. Imaging-proven new or recurrent DVT occurred in 6% and 8%, respectively. Symptomatic caval occlusion was seen in five (5/371, 1.3%).ConclusionIVC filters have an acceptable safety profile in stroke patients. In our cohort, they were effective in preventing life-threatening PE.
Transnational tobacco industry promotion of the cigarette gifting custom in China
Authors: Chu Alexandria , Jiang Nan , Glantz Stanton A 
Published: February 2011

ObjectiveTo understand how British American Tobacco (BAT) and Philip Morris (PM) researched the role and popularity of cigarette gifting in forming relationships among Chinese customs and how they exploited the practice to promote their brands State Express 555 and Marlboro.MethodsSearches and analysis of industry documents from the Legacy Tobacco Documents Library complemented by searches on LexisNexis Academic news, online search engines and information from the tobacco industry trade press.ResultsFrom 1980–1999, BAT and PM employed Chinese market research firms to gather consumer information about perceptions of foreign cigarettes and the companies discovered that cigarettes, especially prestigious ones, were gifted and smoked purposely for building relationships and social status in China. BAT and PM promoted their brands as gifts by enhancing cigarette cartons and promoting culturally themed packages, particularly during the gifting festivals of Chinese New Year and Mid-Autumn Festival to tie their brands in to festival values such as warmth, friendship and celebration. They used similar marketing in Chinese communities outside China.ConclusionsBAT and PM tied their brands to Chinese cigarette gifting customs by appealing to social and cultural values of respect and personal honour. Decoupling cigarettes from their social significance in China and removing their appeal would probably reduce cigarette gifting and promote a decline in smoking. Tobacco control efforts in countermarketing, large graphic warnings and plain packaging to make cigarette packages less attractive as gifts could contribute to denormalising cigarette gifting.
QUANTUM PROPERTIES IN TRANSPORT THROUGH NANOSCOPIC RINGS: CHARGE-SPIN SEPARATION AND INTERFERENCE EFFECTS
Authors: HALLBERG K. , RINCON JULIAN , RAMASESHA S. 
Published: February 2011

Many of the most intriguing quantum effects are observed or could be measured in transport experiments through nanoscopic systems such as quantum dots, wires and rings formed by large molecules or arrays of quantum dots. In particular, the separation of charge and spin degrees of freedom and interference effects have important consequences in the conductivity through these systems. Charge-spin separation was predicted theoretically in one-dimensional strongly interacting systems (Luttinger liquids) and, although observed indirectly in several materials formed by chains of correlated electrons, it still lacks direct observation. We present results on transport properties through Aharonov-Bohm rings (pierced by a magnetic flux) with one or more channels represented by paradigmatic strongly-correlated models. For a wide range of parameters we observe characteristic dips in the conductance as a function of magnetic flux which are a signature of spin and charge separation. Interference effects could also be controlled in certain molecules and interesting properties could be observed. We analyze transport properties of conjugated molecules, benzene in particular, and find that the conductance depends on the lead configuration. In molecules with translational symmetry, the conductance can be controlled by breaking or restoring this symmetry, e.g. by the application of a local external potential. These results open the possibility of observing these peculiar physical properties in anisotropic ladder systems and in real nanoscopic and molecular devices.
DRAM errors in the wild
Authors: Schroeder Bianca , Pinheiro Eduardo , Weber Wolf-Dietrich 
Published: February 2011

Errors in dynamic random access memory (DRAM) are a common form of hardware failure in modern compute clusters. Failures are costly both in terms of hardware replacement costs and service disruption. While a large body of work exists on DRAM in laboratory conditions, little has been reported on real DRAM failures in large production clusters. In this paper, we analyze measurements of memory errors in a large fleet of commodity servers over a period of 2.5 years. The collected data covers multiple vendors, DRAM capacities and technologies, and comprises many millions of dual in-line memory module (DIMM) days.
The goal of this paper is to answer questions such as the following: How common are memory errors in practice? What are their statistical properties? How are they affected by external factors, such as temperature and utilization, and by chip-specific factors, such as chip density, memory technology, and DIMM age?
We find that DRAM error behavior in the field differs in many key aspects from commonly held assumptions. For example, we observe DRAM error rates that are orders of magnitude higher than previously reported, with 25,000--70,000 errors per billion device hours per Mb and more than 8% of DIMMs affected by errors per year. We provide strong evidence that memory errors are dominated by hard errors, rather than soft errors, which previous work suspects to be the dominant error mode. We find that temperature, known to strongly impact DIMM error rates in lab conditions, has a surprisingly small effect on error behavior in the field, when taking all other factors into account. Finally, unlike commonly feared, we do not observe any indication that newer generations of DIMMs have worse error behavior.
A play on regular expressions
Authors: Fischer Sebastian , Huch Frank , Wilke Thomas 
Published: February 2011

Cody, Hazel, and Theo, two experienced Haskell programmers and an expert in automata theory, develop an elegant Haskell program for matching regular expressions: (i) the program is purely functional; (ii) it is overloaded over arbitrary semirings, which not only allows to solve the ordinary matching problem but also supports other applications like computing leftmost longest matchings or the number of matchings, all with a single algorithm; (iii) it is more powerful than other matchers, as it can be used for parsing every context-free language by taking advantage of laziness.
The developed program is based on an old technique to turn regular expressions into finite automata which makes it efficient both in terms of worst-case time and space bounds and actual performance: despite its simplicity, the Haskell implementation can compete with a recently published professional C++ program for the same problem.
A simple inductive synthesis methodology and its applications
Authors: Itzhaky Shachar , Gulwani Sumit , Immerman Neil , Sagiv Mooly 
Published: February 2011

Given a high-level specification and a low-level programming language, our goal is to automatically synthesize an efficient program that meets the specification. In this paper, we present a new algorithmic methodology for inductive synthesis that allows us to do this.
We use Second Order logic as our generic high level specification logic. For our low-level languages we choose small application-specific logics that can be immediately translated into code that runs in expected linear time in the worst case.
We explain our methodology and provide examples of the synthesis of several graph classifiers, e.g, linear-time tests of whether the input graph is connected, acyclic, etc. In another set of applications we automatically derive many finite differencing expressions equivalent to ones that Paige built by hand in his thesis [Pai81]. Finally we describe directions for automatically combining such automatically generated building blocks to synthesize efficient code implementing more complicated specifications.
The methods in this paper have been implemented in Python using the SMT solver Z3 [dMB].
Lime
Authors: Auerbach Joshua , Bacon David F. , Cheng Perry , Rabbah Rodric 
Published: February 2011

The halt in clock frequency scaling has forced architects and language designers to look elsewhere for continued improvements in performance. We believe that extracting maximum performance will require compilation to highly heterogeneous architectures that include reconfigurable hardware.
We present a new language, Lime, which is designed to be executable across a broad range of architectures, from FPGAs to conventional CPUs. We present the language as a whole, focusing on its novel features for limiting side-effects and integration of the streaming paradigm into an object- oriented language. We conclude with some initial results demonstrating applications running either on a CPU or co- executing on a CPU and an FPGA.
A graph-based approach to API usage adaptation
Authors: Nguyen Hoan Anh , Nguyen Tung Thanh , Wilson Gary , Nguyen Anh Tuan , Kim Miryung , Nguyen Tien N. 
Published: February 2011

Reusing existing library components is essential for reducing the cost of software development and maintenance. When library components evolve to accommodate new feature requests, to fix bugs, or to meet new standards, the clients of software libraries often need to make corresponding changes to correctly use the updated libraries. Existing API usage adaptation techniques support simple adaptation such as replacing the target of calls to a deprecated API, however, cannot handle complex adaptations such as creating a new object to be passed to a different API method, or adding an exception handling logic that surrounds the updated API method calls.
This paper presents LIBSYNC that guides developers in adapting API usage code by learning complex API usage adaptation patterns from other clients that already migrated to a new library version (and also from the API usages within the library's test code). LIBSYNC uses several graph-based techniques (1) to identify changes to API declarations by comparing two library versions, (2) to extract associated API usage skeletons before and after library migration, and (3) to compare the extracted API usage skeletons to recover API usage adaptation patterns. Using the learned adaptation patterns, LIBSYNC recommends the locations and edit operations for adapting API usages. The evaluation of LIBSYNC on real-world software systems shows that it is highly correct and useful with a precision of 100% and a recall of 91%.