bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial Cells Augment Barrier Function via Activation of the Toll-Like Receptor 2/Phosphatidylinositol 3-Kinase Pathway upon Recognition of Salmonella enterica Serovar Typhimurium Curli Fibrils in the Gut
Authors: Oppong Gertrude O. , Rapsinski Glenn J. , Newman Tiffanny N. , Nishimori Jessalyn H. , Biesecker Steven G. , Tükel Çagla 
Published: December 2012

ABSTRACTCurli fibrils, the best-characterized functional bacterial amyloids, are an important component of enterobacterial biofilms. We have previously shown that curli fibrils are recognized by the Toll-like receptor 2 (TLR2)/TLR1 heterodimer complex. Utilizing polarized T-84 cells, an intestinal epithelial cell line derived from colon carcinoma grown on semipermeable tissue culture inserts, we determined that infection with aSalmonella entericaserovar TyphimuriumcsgBAmutant, which does not express curli, resulted in an increase in intestinal barrier permeability and an increase in bacterial translocation compared to infection with curliated wild-typeS. Typhimurium. When the TLR2 downstream signaling molecule phosphatidylinositol 3-kinase (PI3K) was blocked using wortmannin or LY294002, the difference in disruption of the intestinal epithelium and bacterial translocation was no longer observed. Additionally, disruption of polarized T-84 cells treated basolaterally with the TLR5 ligand flagellin was prevented when the polarized cells were simultaneously treated with the synthetic TLR2/TLR1 ligand Pam3CSK4or with purified curli fibrils in the apical compartment. Similar toin vitroobservations, C57BL/6 mice infected with thecsgBAmutant suffered increased disruption of the intestinal epithelium and therefore greater dissemination of the bacteria to the mesenteric lymph nodes than mice infected with wild-typeS. Typhimurium. The differences in disruption of the intestinal epithelium and bacterial dissemination in the mice infected withcsgBAmutant or wild-typeS. Typhimurium were not apparent in TLR2-deficient mice. Overall, these studies report for the first time that activation of the TLR2/PI3K pathway by microbial amyloids plays a critical role in regulating the intestinal epithelial barrier as well as monitoring bacterial translocation during infection.
Tannic Acid Inhibits Staphylococcus aureus Surface Colonization in an IsaA-Dependent Manner
Authors: Payne David E. , Martin Nicholas R. , Parzych Katherine R. , Rickard Alex H. , Underwood Adam , Boles Blaise R. 
Published: December 2012

ABSTRACT

Staphylococcus aureus
is a human commensal and pathogen that is capable of forming biofilms on a variety of host tissues and implanted medical devices. Biofilm-associated infections resist antimicrobial chemotherapy and attack from the host immune system, making these infections particularly difficult to treat. In order to gain insight into environmental conditions that influence
S. aureus
biofilm development, we screened a library of small molecules for the ability to inhibit
S. aureus
biofilm formation. This led to the finding that the polyphenolic compound tannic acid inhibits
S. aureus
biofilm formation in multiple biofilm models without inhibiting bacterial growth. We present evidence that tannic acid inhibits
S. aureus
biofilm formation via a mechanism dependent upon the putative transglycosylase IsaA. Tannic acid did not inhibit biofilm formation of an
isaA
mutant. Overexpression of wild-type IsaA inhibited biofilm formation, whereas overexpression of a catalytically dead IsaA had no effect. Tannin-containing drinks like tea have been found to reduce methicillin-resistant
S. aureus
nasal colonization. We found that black tea inhibited
S. aureus
biofilm development and that an
isaA
mutant resisted this inhibition. Antibiofilm activity was eliminated from tea when milk was added to precipitate the tannic acid. Finally, we developed a rodent model for
S. aureus
throat colonization and found that tea consumption reduced
S. aureus
throat colonization via an
isaA
-dependent mechanism. These findings provide insight into a molecular mechanism by which commonly consumed polyphenolic compounds, such as tannins, influence
S. aureus
surface colonization.
Site of Isolation Determines Biofilm Formation and Virulence Phenotypes of Streptococcus pneumoniae Serotype 3 Clinical Isolates
Authors: Trappetti Claudia , van der Maten Erika , Amin Zarina , Potter Adam J. , Chen Austen Y. , van Mourik Paula M. , Lawrence Andrew J. , Paton Adrienne W. , Paton James C. 
Published: December 2012

ABSTRACT

Streptococcus pneumoniae
is a diverse species causing invasive as well as localized infections that result in massive global morbidity and mortality. Strains vary markedly in pathogenic potential, but the molecular basis is obscured by the diversity and plasticity of the pneumococcal genome. In the present study,
S. pneumoniae
serotype 3 blood (
n
= 12) or ear (
n
= 13) isolates were multilocus sequence typed (MLST) and assessed for biofilm formation and virulence phenotype. Blood and ear isolates exhibited similar MLST distributions but differed markedly in phenotype. Blood isolates formed robust biofilms only at pH 7.4, which were enhanced in Fe(III)-supplemented medium. Conversely, ear isolates formed biofilms only at pH 6.8, and Fe(III) was inhibitory. Biofilm formation paralleled
luxS
expression and genetic competence. In a mouse intranasal challenge model, blood isolates did not stably colonize the nasopharynx but spread to the blood; none spread to the ear. Ear isolates colonized the nasopharynx at higher levels and also spread to the ear compartment in a significant proportion of animals; none caused bacteremia. Thus, pneumococci of the same serotype and MLST exhibit distinct phenotypes in accordance with clinical site of isolation, indicative of stable niche adaptation within a clonal lineage.
Infection cycle ofSalmonella entericaserovar Enteritidis in latent carrier mice1The work was carried out at the Microbial Biotechnology Laboratory of Universidade Estadual de Santa Cruz, Ilhéus, Bahia State, Brazil.
Authors: Maciel Bianca Mendes , Sriranganathan Nammalwar , Romano Carla Cristina , Santos Thalis Ferreira dos , Dias João Carlos Teixeira , Gross Eduardo , Rezende Rachel Passos 
Published: December 2012

This work reports the distribution of an oral dose of Salmonella enterica serovar Enteritidis (SE) in C57Bl/6-Bcgr mice, to study its pathogenesis in a latent carrier animal. Mice orally inoculated with a high dose of SE developed a latent infection characterized by the absence of clinical symptoms in which the cecum is functioning as a “strategic site” of SE proliferation, releasing bacteria into feces intermittently over the 4-week study. A sequence of disruptions occurred in the small intestine at 1 day postinculation (PI). The microvilli exhibited different degrees of degeneration, which were reversible as the cells became vacuolated. From 2 days PI, SE was detected in the mononuclear phagocytic system, and an exponential growth of the remaining bacteria in tissues was observed until 4 days PI. The production of interferon gamma from 3 days PI is restricting the SE growth, and a plateau phase was observed from 4 to 15 days PI. A recurrence of the bacterial growth in tissue occurred from 15 to 28 days PI, especially in the cecum. Increasing our knowledge about the host–pathogen interaction of adapted pathogens with the ability to develop latency is essential for the development of an efficient strategy for Salmonella control.
Widespread erosion and mass failure from the ∼51 Ma Montagnais marine bolide impact off southwestern Nova Scotia, Canada 1This article is one of a series of papers published in this CJES Special Issue on the theme of Mesozoic–Cenozoic geology of the Scotian Basin. 2Earth Sciences Sector Contribution 20120241.
Authors: Deptuck Mark E. , Campbell D. Calvin 
Published: December 2012

The ∼51 Ma Montagnais impact crater on the outer Scotian Shelf is well known, but the potential effects from the impact event on the slope and rise seaward of the crater have, until now, remained poorly understood. Through detailed seismic stratigraphic correlation and ties to available wells, we define a threefold seismic stratigraphic subdivision for Upper Cretaceous to Eocene strata on the shelf and slope, calibrated to the most recent biostratigraphic results. Using this framework, we identify a number of depositional and erosional products that are temporally consistent with a late Ypresian impact event (within the limits of seismic and biostratigraphic resolution). We link a series of prominent failure scarps on the outer shelf and upper slope to a single widespread mass-transport deposit (MTD) on the lower continental slope, rise, and abyssal plain. Failed material amassed in a large debris field referred to here as the “Montagnais MTD”. It covers an area of ∼93 000 km2 and travelled up to 580 km from the impact site where its distal termination onlaps the New England Seamounts, making it one of the largest known debris avalanches on Earth. We interpret these deposits, and the associated pattern of erosion landward of them, as products of widespread margin collapse caused by a combination of ground shaking and ensuing tsunamis triggered by the Montagnais impact event. This study provides insight into the potential effects of outer-shelf marine impact events immediately downslope from impact sites, and their diminished effects with increasing distance along the margin.
Bringing Virtualization to the x86 Architecture with the Original VMware Workstation
Authors: Bugnion Edouard , Devine Scott , Rosenblum Mendel , Sugerman Jeremy , Wang Edward Y. 
Published: December 2012

This article describes the historical context, technical challenges, and main implementation techniques used by VMware Workstation to bring virtualization to the x86 architecture in 1999. Although virtual machine monitors (VMMs) had been around for decades, they were traditionally designed as part of monolithic, single-vendor architectures with explicit support for virtualization. In contrast, the x86 architecture lacked virtualization support, and the industry around it had disaggregated into an ecosystem, with different vendors controlling the computers, CPUs, peripherals, operating systems, and applications, none of them asking for virtualization. We chose to build our solution independently of these vendors.
As a result, VMware Workstation had to deal with new challenges associated with (i) the lack of virtualization support in the x86 architecture, (ii) the daunting complexity of the architecture itself, (iii) the need to support a broad combination of peripherals, and (iv) the need to offer a simple user experience within existing environments. These new challenges led us to a novel combination of well-known virtualization techniques, techniques from other domains, and new techniques.
VMware Workstation combined a hosted architecture with a VMM. The hosted architecture enabled a simple user experience and offered broad hardware compatibility. Rather than exposing I/O diversity to the virtual machines, VMware Workstation also relied on software emulation of I/O devices. The VMM combined a trap-and-emulate direct execution engine with a system-level dynamic binary translator to efficiently virtualize the x86 architecture and support most commodity operating systems. By relying on x86 hardware segmentation as a protection mechanism, the binary translator could execute translated code at near hardware speeds. The binary translator also relied on partial evaluation and adaptive retranslation to reduce the overall overheads of virtualization.
Written with the benefit of hindsight, this article shares the key lessons we learned from building the original system and from its later evolution.
Quantifying the Mismatch between Emerging Scale-Out Applications and Modern Processors
Authors: Ferdman Michael , Adileh Almutaz , Kocberber Onur , Volos Stavros , Alisafaee Mohammad , Jevdjic Djordje , Kaynak Cansu , Popescu Adrian Daniel , Ailamaki Anastasia , Falsafi Babak 
Published: December 2012

Emerging scale-out workloads require extensive amounts of computational resources. However, data centers using modern server hardware face physical constraints in space and power, limiting further expansion and calling for improvements in the computational density per server and in the per-operation energy. Continuing to improve the computational resources of the cloud while staying within physical constraints mandates optimizing server efficiency to ensure that server hardware closely matches the needs of scale-out workloads.
In this work, we introduce CloudSuite, a benchmark suite of emerging scale-out workloads. We use performance counters on modern servers to study scale-out workloads, finding that today’s predominant processor microarchitecture is inefficient for running these workloads. We find that inefficiency comes from the mismatch between the workload needs and modern processors, particularly in the organization of instruction and data memory systems and the processor core microarchitecture. Moreover, while today’s predominant microarchitecture is inefficient when executing scale-out workloads, we find that continuing the current trends will further exacerbate the inefficiency in the future. In this work, we identify the key microarchitectural needs of scale-out workloads, calling for a change in the trajectory of server processors that would lead to improved computational density and power efficiency in data centers.
Exploiting External Collections for Query Expansion
Authors: Weerkamp Wouter , Balog Krisztian , de Rijke Maarten 
Published: December 2012

A persisting challenge in the field of information retrieval is the vocabulary mismatch between a user’s information need and the relevant documents. One way of addressing this issue is to apply query modeling: to add terms to the original query and reweigh the terms. In social media, where documents usually contain creative and noisy language (e.g., spelling and grammatical errors), query modeling proves difficult. To address this, attempts to use external sources for query modeling have been made and seem to be successful. In this article we propose a general generative query expansion model that uses external document collections for term generation: the External Expansion Model (EEM). The main rationale behind our model is our hypothesis that each query requires its own mixture of external collections for expansion and that an expansion model should account for this. For some queries we expect, for example, a news collection to be most beneficial, while for other queries we could benefit more by selecting terms from a general encyclopedia. EEM allows for query-dependent weighing of the external collections.
We put our model to the test on the task of blog post retrieval and we use four external collections in our experiments: (i) a news collection, (ii) a Web collection, (iii) Wikipedia, and (iv) a blog post collection. Experiments show that EEM outperforms query expansion on the individual collections, as well as the Mixture of Relevance Models that was previously proposed by Diaz and Metzler [2006]. Extensive analysis of the results shows that our naive approach to estimating query-dependent collection importance works reasonably well and that, when we use “oracle” settings, we see the full potential of our model. We also find that the query-dependent collection importance has more impact on retrieval performance than the independent collection importance (i.e., a collection prior).
Prediction and Diagnosis of the Motion and Rapid Intensification of Typhoon Sinlaku during Tropical Cyclone Structure Experiment 2008 (TCS08)
Authors: Leroux Marie-Dominique , Davidson Noel E. , Ma Yimin , Kepert Jeffrey D. 
Published: December 2012

Abstract
The impact of initial structure on storm evolution is examined for the case of a tropical storm entering rapid intensification. At the onset of rapid intensification, satellite cloud signatures suggest that the structural organization of Typhoon Sinlaku (2008) was dominated by a primary band of convection present at outer radii. The development of the eyewall subsequently occurred within this band of deep convection.
Numerical forecasts of Sinlaku are initialized at 15- and 5-km resolution using a broad range of vortex scales, at a time when the storm was still weak and its structure not clearly defined. Evidence is presented that beta propagation played a key role in changing the storm’s motion under weak environmental steering. It is found that the track forecast improves over the period when beta propagation is prominent if the vortex is initialized with a large radius of maximum wind (RMW), corresponding with the primary outer cloud band. The initial vortex structure is also suggested to play a critical role in the pathway to rapid intensification, and in the formation of the eyewall for the defined environmental forcing. With an initially large RMW, the forecast captures the evolution of structure and intensity more skillfully. Eyewall formation inside the primary outer convective band for the weak storm is illustrated and some possible dynamical interpretations are discussed.
Holistic Rural Marketing
Authors: Jha Mithileshwar 
Published: December 2012

Rural Marketing has evolved in India over the years from agricultural marketing with commodity and institutional focus to a more comprehensive three-dimensional perspective of rural to urban, urban to rural and rural to rural focus, in terms of flow of goods, services and ideas. It subsequently adopted a developmental perspective with focus on the poor and vulnerable and development objectives. Marketing as a discipline also evolved over these years from production orientation, product orientation, sales orientation, market orientation, societal marketing orientation to holistic marketing orientation. This article critically examines the current state of marketing and rural marketing, traces the evolution of rural marketing from agricultural marketing orientation, to rural marketing, and further to developmental orientation and advocates moving to holistic rural marketing orientation. Though normative in approach, it can provide a useful framework for enhancing and enriching rural marketing knowledge and practice.
Adolescents with a diagnosis of anorexia nervosa: Parents’ experience of recognition and deciding to seek help
Authors: Thomson Samuel , Marriott Michael , Telford Katherine , Law Hou , McLaughlin Jo , Sayal Kapil 
Published: December 2012

Background: Adolescents with anorexia nervosa rarely present themselves as having a problem and are usually reliant on parents to recognise the problem and facilitate help-seeking. This study aimed to investigate parents’ experiences of recognising that their child had an eating problem and deciding to seek help. Methods: A qualitative study with interpretative phenomenological analysis applied to semi-structured interviews with eight parents of adolescents with a diagnosis of anorexia nervosa. Results: Parents commonly attributed early signs of anorexia nervosa to normal adolescent development and they expected weight loss to be short-lived. As parents’ suspicions grew, close monitoring exposing their child’s secretive attempts to lose weight and the use of internet searches aided parental recognition of the problem. They avoided using the term anorexia as it made the problem seem ‘real’. Following serial unsuccessful attempts to effect change, parental fear for their child’s life triggered a desire for professional help. Conclusions: Parents require early advice and support to confirm their suspicions that their child might have anorexia nervosa. Since parents commonly approach the internet for guidance, improving awareness of useful and accurate websites could reduce delays in help-seeking.
Phosphatase Wip1 negatively regulates neutrophil development through p38 MAPK-STAT1
Authors: Liu Guangwei , Hu Xuelian , Sun Bo , Yang Tao , Shi Jianfeng , Zhang Lianfeng , Zhao Yong 
Published: December 2012

Abstract
Neutrophils are critically involved in host defense and tissue damage. Intrinsic molecular mechanisms controlling neutrophil differentiation and activities are poorly defined. Herein we found that p53-induced phosphatase 1(Wip1) is preferentially expressed in neutrophils among immune cells. The Wip1 expression is gradually up-regulated during the differentiation of myeloid precursors into mature neutrophils. Wip1-deficient mice and chimera mice with Wip1−/− hematopoietic cells had an expanded pool of neutrophils with hypermature phenotypes in the periphery. The in vivo and in vitro studies showed that Wip1 deficiency mainly impaired the developing process of myeloid progenitors to neutrophils in an intrinsic manner. Mechanism studies showed that the enhanced development and maturation of neutrophils caused by Wip1 deficiency were mediated by p38 MAPK-STAT1 but not p53-dependent pathways. Thus, our findings identify a previously unrecognized p53-independent function of Wip1 as a cell type-specific negative regulator of neutrophil generation and homeostasis through limiting the p38 MAPK-STAT1 pathway.
Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore
Authors: Soh Shu E , Cook Alex R , Chen Mark IC , Lee Vernon J , Cutter Jeffery L , Chow Vincent TK , Tee Nancy WS , Lin Raymond TP , Lim Wei-Yen , Barr Ian G , Lin Cui , Phoon Meng Chee , Ang Li Wei , Sethi Sunil K , Chong Chia Yin , Goh Lee Gan , Goh Denise LM , Tambyah Paul A , Thoon Koh Cheng , Leo Yee Sin , Saw Seang Mei 
Published: December 2012

AbstractBackgroundSchools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools.MethodsDuring the initial wave of pandemic H1N1 (pdmH1N1) infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC) and daily temperature monitoring (Sch-DTM), and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI). Comparisons were made against age-stratified clinic-based influenza-like illness (ILI) data from 23 primary care clinics (GP-ILI) and proportions of ILI testing positive for pdmH1N1 (Lab-ILI) by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked); and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ≥ 40 between pre-epidemic and post-epidemic sera). Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model.ResultsBy week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9) in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9%) of primary and 43.2% (95% CI: 28.2% to 60.8%) of secondary school-aged children were infected. Sch-FRI rates were similar across the 6 schools (23 to 34 episodes per 100 children), but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit.ConclusionsEpidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission.