bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endovascular Infections Caused by Methicillin-Resistant Staphylococcus aureus Are Linked to Clonal Complex-Specific Alterations in Binding and Invasion Domains of Fibronectin-Binding Protein A as Well as the Occurrence of
fnbB
Authors: Xiong Yan Q. , Sharma-Kuinkel Batu K. , Casillas-Ituarte Nadia N. , Fowler Vance G. , Rude Thomas , DiBartola Alex C. , Lins Roberto D. , Abdel-Hady Wessam , Lower Steven K. , Bayer Arnold S. 
Published: September 2015

ABSTRACT

Endovascular infections caused by
Staphylococcus aureus
involve interactions with fibronectin present as extracellular matrix or surface ligand on host cells. We examined the expression, structure, and binding activity of the two major
S. aureus
fibronectin-binding proteins (FnBPA, FnBPB) in 10 distinct, methicillin-resistant clinical isolates from patients with either persistent or resolving bacteremia. The persistent bacteremia isolates (
n
= 5) formed significantly stronger bonds with immobilized fibronectin as determined by dynamic binding measurements performed with atomic force microscopy. Several notable differences were also observed when the results were grouped by clonal complex 5 (CC5) strains (
n
= 5) versus CC45 strains (
n
= 5). Fibronectin-binding receptors on CC5 formed stronger bonds with immobilized fibronectin (
P
< 0.001). The
fnbA
gene was expressed at higher levels in CC45, whereas
fnbB
was found in only CC5 isolates. The
fnbB
gene was not sequenced because all CC45 isolates lacked this gene. Instead, comparisons were made for
fnbA
, which was present in all 10 isolates. Sequencing of
fnbA
revealed discrete differences within high-affinity, fibronectin-binding repeats (FnBRs) of FnBPA that included (i) 5-amino-acid polymorphisms in FnBR-9, FnBR-10, and FnBR-11 involving charged or polar side chains, (ii) an extra, 38-amino-acid repeat inserted between FnBR-9 and FnBR-10 exclusively seen in CC45 isolates, and (iii) CC5 isolates had the SVDFEED epitope in FnBR-11 (a sequence shown to be essential for fibronectin binding), while this sequence was replaced in all CC45 isolates with GIDFVED (a motif known to favor host cell invasion at the cost of reduced fibronectin binding). These complementary sequence and binding data suggest that differences in
fnbA
and
fnbB
, particularly polymorphisms and duplications in FnBPA, give
S. aureus
two distinct advantages in human endovascular infections: (i) FnBPs similar to that of CC5 enhance ligand binding and foster initiation of disease, and (ii) CC45-like FnBPs promote cell invasion, a key attribute in persistent endovascular infections.
Response of Vibrio cholerae to the Catecholamine Hormones Epinephrine and Norepinephrine
Authors: Halang Petra , Toulouse Charlotte , Geißel Bernadette , Michel Bernd , Flauger Birgit , Müller Manuel , Voegele Ralf T. , Stefanski Volker , Steuber Julia 
Published: September 2015

ABSTRACT

In
Escherichia coli
or
Salmonella enterica
, the stress-associated mammalian hormones epinephrine (E) and norepinephrine (NE) trigger a signaling cascade by interacting with the QseC sensor protein. Here we show that
Vibrio cholerae
, the causative agent of cholera, exhibits a specific response to E and NE. These catecholates (0.1 mM) enhanced the growth and swimming motility of
V. cholerae
strain O395 on soft agar in a medium containing calf serum, which simulated the environment within the host. During growth, the hormones were converted to degradation products, including adrenochrome formed by autooxidation with O
2
or superoxide. In
E. coli
, the QseC sensor kinase, which detects the autoinducer AI-3, also senses E or NE. The genome of
V. cholerae
O395 comprises an open reading frame coding for a putative protein with 29% identity to
E. coli
QseC. Quantitative reverse transcriptase PCR (qRT-PCR) experiments revealed increased transcript levels of the
qseC
-like gene and of
pomB
, a gene encoding a structural component of the flagellar motor complex, under the influence of E or NE. Phentolamine blocks the response of
E. coli
QseC to E or NE. A
V. cholerae
mutant devoid of the
qseC
-like gene retained the phentolamine-sensitive motility in the presence of E, whereas NE-stimulated motility was no longer inhibited by phentolamine. Our study demonstrates that
V. cholerae
senses the stress hormones E and NE. A sensor related to the histidine kinase QseC from
E. coli
is identified and is proposed to participate in the sensing of NE.

IMPORTANCE
Vibrio cholerae
is a Gram-negative bacterium that may cause cholera, a severe illness with high mortality due to acute dehydration caused by diarrhea and vomiting. Pathogenic
V. cholerae
strains possess virulence factors like the cholera toxin (CTX) and the toxin-coregulated pilus (TCP) produced in response to signals provided by the host. In pathogenic enterobacteria, the stress-associated hormones epinephrine (E) and norepinephrine (NE) of the human host act as signal molecules for the production of virulence factors and promote bacterial growth by the sequestration of iron from the host. Here we show that
V. cholerae
, like some enterobacteria, benefits from these stress hormones and possesses a sensor to recognize them.
The Sugar Kinase That Is Necessary for the Catabolism of Rhamnose in Rhizobium leguminosarum Directly Interacts with the ABC Transporter Necessary for Rhamnose Transport
Authors: Rivers Damien M. R. , Oresnik Ivan J. 
Published: September 2015

ABSTRACT

Rhamnose catabolism in
Rhizobium leguminosarum
was found to be necessary for the ability of the organism to compete for nodule occupancy. Characterization of the locus necessary for the catabolism of rhamnose showed that the transport of rhamnose was dependent upon a carbohydrate uptake transporter 2 (CUT2) ABC transporter encoded by
rhaSTPQ
and on the presence of RhaK, a protein known to have sugar kinase activity. A linker-scanning mutagenesis analysis of
rhaK
showed that the kinase and transport activities of RhaK could be separated genetically. More specifically, two pentapeptide insertions defined by the alleles
rhaK72
and
rhaK73
were able to uncouple the transport and kinase activities of RhaK, such that the kinase activity was retained, but cells carrying these alleles did not have measurable rhamnose transport rates. These linker-scanning alleles were localized to the C terminus and N terminus of RhaK, respectively. Taken together, the data led to the hypothesis that RhaK might interact either directly or indirectly with the ABC transporter defined by
rhaSTPQ
. In this work, we show that both N- and C-terminal fragments of RhaK are capable of interacting with the N-terminal fragment of the ABC protein RhaT using a 2-hybrid system. Moreover, if RhaK fragments carrying either the
rhaK72
or
rhaK73
allele were used, this interaction was abolished. Phylogenetic and bioinformatic analysis of the RhaK fragments suggested that a conserved region in the N terminus of RhaK may represent a putative binding domain. Alanine-scanning mutagenesis of this region followed by 2-hybrid analysis revealed that a substitution of any of the conserved residues greatly affected the interaction between RhaT and RhaK fragments, suggesting that the sugar kinase RhaK and the ABC protein RhaT interact directly.

IMPORTANCE
ABC transporters involved in the transport of carbohydrates help define the overall physiological fitness of bacteria. The two largest groups of transporters are the
c
arbohydrate
u
ptake
t
ransporter classes 1 and 2 (CUT1 and CUT2, respectively). This work provides the first evidence that a kinase that is necessary for the catabolism of a sugar can directly interact with a domain from the ABC protein that is necessary for its transport.
In Silico
Discovery and
In Vitro
Validation of Catechol-Containing Sulfonohydrazide Compounds as Potent Inhibitors of the Diguanylate Cyclase PleD
Authors: Fernicola Silvia , Paiardini Alessandro , Giardina Giorgio , Rampioni Giordano , Leoni Livia , Cutruzzolà Francesca , Rinaldo Serena 
Published: September 2015

ABSTRACT

Biofilm formation is responsible for increased antibiotic tolerance in pathogenic bacteria. Cyclic di-GMP (c-di-GMP) is a widely used second-messenger signal that plays a key role in bacterial biofilm formation. c-di-GMP is synthesized by diguanylate cyclases (DGCs), a conserved class of enzymes absent in mammals and hence considered attractive molecular targets for the development of antibiofilm agents. Here, the results of a virtual screening approach aimed at identifying small-molecule inhibitors of the DGC PleD from
Caulobacter crescentus
are described. A three-dimensional (3D) pharmacophore model, derived from the mode of binding of GTP to the active site of PleD, was exploited to screen the ZINC database of compounds. Seven virtual hits were tested
in vitro
for their ability to inhibit the activity of purified PleD by using circular dichroism spectroscopy. Two drug-like molecules with a catechol moiety and a sulfonohydrazide scaffold were shown to competitively inhibit PleD at the low-micromolar range (50% inhibitory concentration [IC
50
] of ∼11 μM). Their predicted binding mode highlighted key structural features presumably responsible for the efficient inhibition of PleD by both hits. These molecules represent the most potent
in vitro
inhibitors of PleD identified so far and could therefore result in useful leads for the development of novel classes of antimicrobials able to hamper biofilm formation.

IMPORTANCE
Biofilm-mediated infections are difficult to eradicate, posing a threatening health issue worldwide. The capability of bacteria to form biofilms is almost universally stimulated by the second messenger c-di-GMP. This evidence has boosted research in the last decade for the development of new antibiofilm strategies interfering with c-di-GMP metabolism. Here, two potent inhibitors of c-di-GMP synthesis have been identified
in silico
and characterized
in vitro
by using the well-characterized DGC enzyme PleD from
C. crescentus
as a structural template and molecular target. Given that the protein residues implied as crucial for enzyme inhibition are found to be highly conserved among DGCs, the outcome of this study could pave the way for the future development of broad-spectrum antibiofilm compounds.
A systematic review of reliable and valid tools for the measurement of patient participation in healthcare
Authors: Phillips Nicole Margaret , Street Maryann , Haesler Emily 
Published: September 2015

IntroductionPatient participation in healthcare is recognised internationally as essential for consumer-centric, high-quality healthcare delivery. Its measurement as part of continuous quality improvement requires development of agreed standards and measurable indicators.AimThis systematic review sought to identify strategies to measure patient participation in healthcare and to report their reliability and validity. In the context of this review, patient participation was constructed as shared decision-making, acknowledging the patient as having critical knowledge regarding their own health and care needs and promoting self-care/autonomy.MethodsFollowing a comprehensive search, studies reporting reliability or validity of an instrument used in a healthcare setting to measure patient participation, published in English between January 2004 and March 2014 were eligible for inclusion.ResultsFrom an initial search, which identified 1582 studies, 156 studies were retrieved and screened against inclusion criteria. Thirty-three studies reporting 24 patient participation measurement tools met inclusion criteria, and were critically appraised. The majority of studies were descriptive psychometric studies using prospective, cross-sectional designs. Almost all the tools completed by patients, family caregivers, observers or more than one stakeholder focused on aspects of patient–professional communication. Few tools designed for completion by patients or family caregivers provided valid and reliable measures of patient participation. There was low correlation between many of the tools and other measures of patient satisfaction.ConclusionFew reliable and valid tools for measurement of patient participation in healthcare have been recently developed. Of those reported in this review, the dyadic Observing Patient Involvement in Decision Making (dyadic-OPTION) tool presents the most promise for measuring core components of patient participation. There remains a need for further study into valid, reliable and feasible strategies for measuring patient participation as part of continuous quality improvement.
Learning to Rank from Noisy Data
Authors: Ding Wenkui , Geng Xiubo , Zhang Xu-Dong 
Published: September 2015

Learning to rank, which learns the ranking function from training data, has become an emerging research area in information retrieval and machine learning. Most existing work on learning to rank assumes that the training data is clean, which is not always true, however. The ambiguity of query intent, the lack of domain knowledge, and the vague definition of relevance levels all make it difficult for common annotators to give reliable relevance labels to some documents. As a result, the relevance labels in the training data of learning to rank usually contain noise. If we ignore this fact, the performance of learning-to-rank algorithms will be damaged.In this article, we propose considering the labeling noise in the process of learning to rank and using a two-step approach to extend existing algorithms to handle noisy training data. In the first step, we estimate the degree of labeling noise for a training document. To this end, we assume that the majority of the relevance labels in the training data are reliable and we use a graphical model to describe the generative process of a training query, the feature vectors of its associated documents, and the relevance labels of these documents. The parameters in the graphical model are learned by means of maximum likelihood estimation. Then the conditional probability of the relevance label given the feature vector of a document is computed. If the probability is large, we regard the degree of labeling noise for this document as small; otherwise, we regard the degree as large. In the second step, we extend existing learning-to-rank algorithms by incorporating the estimated degree of labeling noise into their loss functions. Specifically, we give larger weights to those training documents with smaller degrees of labeling noise and smaller weights to those with larger degrees of labeling noise. As examples, we demonstrate the extensions for McRank, RankSVM, RankBoost, and RankNet. Empirical results on benchmark datasets show that the proposed approach can effectively distinguish noisy documents from clean ones, and the extended learning-to-rank algorithms can achieve better performances than baselines.
Constructing Large and Fast On-Chip Cache for Mobile Processors with Multilevel Cell STT-MRAM Technology
Authors: Jiang Lei , Zhao Bo , Yang Jun , Zhang Youtao 
Published: September 2015

Modern mobile processors integrating an increasing number of cores into one single chip demand large-capacity, on-chip, last-level caches (LLCs) in order to achieve scalable performance improvements. However, adopting traditional memory technologies such as SRAM and embedded DRAM (eDRAM) leakage and scalability problems. Spin-transfer torque magnetic RAM (STT-MRAM) is a novel nonvolatile memory technology that has emerged as a promising alternative for constructing on-chip caches in high-end mobile processors. STT-MRAM has many advantages, such as short read latency, zero leakage from the memory cell, and better scalability than eDRAM and SRAM. Multilevel cell (MLC) STT-MRAM further enlarges capacity and reduces per-bit cost by storing more bits in one cell.
However, MLC STT-MRAM has long write latency which limits the effectiveness of MLC STT-MRAM-based LLCs. In this article, we address this limitation with three novel designs: line pairing (LP), line swapping (LS), and dynamic LP/LS enabler (DLE). LP forms fast cache lines by reorganizing MLC soft bits which are faster to write. LS dynamically stores frequently-written data into these fast cache lines. We then propose a dynamic LP/LS enabler (DLE) to enable LP and LS only if they help to improve the overall cache performance. Our experimental results show that the proposed designs improve system performance by 9--15% and reduce energy consumption by 14--21% for various types of mobile processors.
Location-Free Detection of Network Boundaries
Authors: Schieferdecker Dennis 
Published: September 2015

A novel algorithm is proposed for the distributed and location-free detection of boundaries in sensor networks. The approach allows a node to decide autonomously, based solely on connectivity information of a small 2-hop neighborhood, whether it is in the interior of the network or on its fringes. This makes the presented algorithm well suited for scenarios that include mobility or dynamic changes to the network topology.
The algorithm is compared qualitatively and quantitatively to multiple previous approaches. Various models and network settings are considered in extensive simulations. Even though the algorithm uses less information than most other approaches, it yields significantly better results. It is very robust against variations in node degree and does not rely on simplified assumptions of the communication model. Moreover, the approach is easy to implement on real sensor nodes, as it requires little computational power.
The morality of online war; the fates of data analytics, HPC
Authors: Arquilla John , Reed Daniel A. 
Published: September 2015

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we will publish selected posts or excerpts.

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http://cacm.acm.org/blogs/blog-cacm
John Arquilla considers justifications for warfare in the cyber realm, while Daniel Reed looks ahead at big data and exascale computing.
VALOR DE MERCADO E FUNDAMENTOS CONTÁBEIS: uma avaliação a partir de modelos uni e multivariados de previsão.
Authors: Campos Octávio Valente , Lamounier Wagner Moura , Bressan Aureliano Angel 
Published: September 2015

<p class="ListParagraph1">O objetivo desta pesquisa foi <span class="hps">comparar a rentabilidade de carteiras formadas a partir dos melhores modelos de previsão univariados e multivariados, identificando a relevância da informação contábil. </span>Tal comparação foi feita por meio do uso de previsões com os modelos ARIMA (univariados) e os modelos VAR (multivariados). Os indicadores contábeis e os retornos das ações foram utilizados como dados de entrada para a geração das previsões e consequente formação de carteiras de investimentos – a série temporal de análise inicia-se em 30/03/1994, findando-se em 30/09/2011, com dados trimestrais. Dentro de uma amostra de 20 empresas, as carteiras de investimento foram composta pelas 5 empresas com maior rentabilidade prevista, comparando-se posteriormente as rentabilidades das carteiras formadas pelos modelos univariados contra as carteiras formadas pelos modelos multivariados. Os resultados apontaram que, de forma geral, que as previsões baseadas em modelos multivariados tendem a fornecer aos investidores retornos superiores em investimentos de longo prazo (1 ano). Já os modelos univariados tendem a fornecer aos investidores retornos superiores em investimentos de custo prazo (1 trimestre). Assim, pode-se concluir que as informações contábeis em modelos de previsão apresentam maior relevância em estratégias de longo prazo. </p>
Susceptibility Loci for Clinical Coronary Artery Disease and Subclinical Coronary Atherosclerosis Throughout the Life-Course
Authors: Salfati Elias , Nandkeolyar Shuktika , Fortmann Stephen P. , Sidney Stephen , Hlatky Mark A. , Quertermous Thomas , Go Alan S. , Iribarren Carlos , Herrington David M. , Goldstein Benjamin A. , Assimes Themistocles L. 
Published: September 2015

Background—
Recent genome-wide association studies have identified 49 single nucleotide polymorphisms associated with clinical coronary artery disease. The mechanism by which these loci influence risk remains largely unclear.

Methods and Results—

We examined the association between a genetic risk score composed of high-risk alleles at the 49 single nucleotide polymorphisms and the degree of subclinical coronary atherosclerosis in 7798 participants from 6 studies stratified into 4 age groups at the time of assessment (15–34, 35–54, 55–74, and >75 years). Atherosclerosis was quantified by staining and direct visual inspection of the right coronary artery in the youngest group and by scanning for coronary artery calcification in the remaining groups. We defined cases as subjects within the top quartile of degree of atherosclerosis in 3 groups and as subjects with a coronary artery calcium score >0 in the fourth (35–54 years) where less than one quarter had any coronary artery calcium. In our meta-analysis of all strata, we found 1-SD increase in the genetic risk score increased the risk of advanced subclinical coronary atherosclerosis by 36% (
P
=8.3×10
−25
). This increase in risk was significant in all 4 age groups including the youngest group where atherosclerosis consisted primarily of raised lesions without macroscopic evidence of plaque rupture or thrombosis. Results were similar when we restricted the genetic risk score to 32 single nucleotide polymorphisms not associated with traditional risk factors or when we adjusted for traditional risk factors.

Conclusions—
A genetic risk score for clinical coronary artery disease is associated with advanced subclinical coronary atherosclerosis throughout the life-course. This association is apparent even at the earliest, uncomplicated stages of atherosclerosis.
Fixed and Modifiable Correlates of Drug-Eluting Stent Thrombosis From a Large All-Comers Registry
Authors: Brodie Bruce R. , Garg Ankit , Stuckey Thomas D. , Kirtane Ajay J. , Witzenbichler Bernhard , Maehara Akiko , Weisz Giora , Rinaldi Michael J. , Neumann Franz-Josef , Metzger D. Christopher , Mehran Roxana , Parvataneni Rupa , Stone Gregg W. 
Published: September 2015

Background—
Previous studies evaluating correlates of stent thrombosis (ST) have included mostly patients with bare metal stents and early-generation drug-eluting stents (DES) and have not systematically evaluated the role of intravascular ultrasound–guided stenting and high platelet reactivity on clopidogrel. The purpose of this study was to evaluate the frequency and correlates of ST in patients receiving DES, specifically examining the impact of risk factors modifiable by physician and patient behavior.

Methods and Results—

Assessment of Dual Anti-platelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a multicenter, prospective study in patients undergoing successful coronary intervention with DES in whom routine platelet reactivity testing was performed. Definite or probable ST occurred in 92 (1.1%) of 8582 patients within 2 years. Independent baseline correlates of ST included presentation with an acute coronary syndrome (hazard ratio [HR]=1.81,
P
=0.01), insulin-treated diabetes mellitus (HR=1.91,
P
=0.02), previous myocardial infarction (HR=1.75,
P
=0.02), and peripheral arterial disease (HR=2.01,
P
=0.01). Independent treatment-related correlates included use of early generation DES (HR=1.75,
P
=0.02), no procedural intravascular ultrasound guidance (HR=1.75,
P
=0.04), and premature discontinuation of dual antiplatelet therapy (HR=2.67,
P
=0.003); high platelet reactivity on clopidogrel trended as a correlate of ST (HR=1.49,
P
=0.08). The 2-year risk of ST ranged from 0.3% to 10.0% when 0 to 3 modifiable risk factors were present.

Conclusions—
After successful DES implantation, ST occurred within 2 years in 1.1% of patients and was strongly associated with fixed and modifiable risk factors. The frequency of ST may be reduced with intravascular ultrasound –guided stenting, assiduous adherence to dual antiplatelet therapy, and adequate P2Y12 platelet receptor inhibition.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00638794.