bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site-Specific Mutation of the Sensor Kinase GraS in Staphylococcus aureus Alters the Adaptive Response to Distinct Cationic Antimicrobial Peptides
Authors: Cheung Ambrose L. , Bayer Arnold S. , Yeaman Michael R. , Xiong Yan Q. , Waring Alan J. , Memmi Guido , Donegan Niles , Chaili Siyang , Yang Soo-Jin 
Published: October 2014

ABSTRACT

The
Staphylococcus aureus
two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as
mprF
and
dltABCD
to modify the
S. aureus
surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant
S. aureus
(MRSA) strain (MW2), its isogenic
graS
deletion mutant (Δ
graS
strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The Δ
graS
and ΔEL strains were unable to induce
mprF
and
dltA
expression and, in turn, demonstrated significantly increased susceptibilities to daptomycin, polymyxin B, and two prototypical HD-CAPs (hNP-1 and RP-1). Further, P39A, P39S, and D35G-D37G-D41G ΔEL mutations correlated with moderate increases in HD-CAP susceptibility. Reductions of
mprF
and
dltA
induction by PMB were also found in the ΔEL mutants, suggesting these residues are pivotal to appropriate activation of the GraS sensor kinase. Importantly, a synthetic exogenous soluble EL mimic of GraS protected the parental MW2 strain against hNP-1- and RP-1-mediated killing, suggesting a direct interaction of the EL with HD-CAPs in GraS activation.
In vivo
, the Δ
graS
and ΔEL strains displayed dramatic reductions in achieved target tissue MRSA counts in an endocarditis model. Taken together, our results provide new insights into potential roles of GraS in
S. aureus
sensing of HD-CAPs to induce adaptive survival responses to these molecules.
The Esophageal Pressure-Guided Ventilation 2 (EPVent2) trial protocol: a multicentre, randomised clinical trial of mechanical ventilation guided by transpulmonary pressure
Authors: Fish Emily , Novack Victor , Banner-Goodspeed Valerie M , Sarge Todd , Loring Stephen , Talmor Daniel 
Published: October 2014

IntroductionOptimal ventilator management for patients with acute respiratory distress syndrome (ARDS) remains uncertain. Lower tidal volume ventilation appears to be beneficial, but optimal management of positive end-expiratory pressure (PEEP) remains unclear. The Esophageal Pressure-Guided Ventilation 2 Trial (EPVent2) aims to examine the impact of mechanical ventilation directed at maintaining a positive transpulmonary pressure (PTP) in patients with moderate-to-severe ARDS.Methods and analysisEPVent2 is a multicentre, prospective, randomised, phase II clinical trial testing the hypothesis that the use of a PTP-guided ventilation strategy will lead to improvement in composite outcomes of mortality and time off the ventilator at 28 days as compared with a high-PEEP control. This study will enrol 200 study participants from 11 hospitals across North America. The trial will utilise a primary composite end point that incorporates death and days off the ventilator at 28 days to test the primary hypothesis that adjusting ventilator pressure to achieve positive PTPvalues will result in improved mortality and ventilator-free days.Ethics and disseminationSafety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approvals of the protocol as well as informed consent documents were also obtained from the Institutional Review Board of each participating institution prior to enrolling study participants at each respective site. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to PubMed Central in accordance with the National Institute of Health Public Access Policy.Trial registration numberClinicalTrials.gov under numberNCT01681225.
Disparities in cancer incidence and mortality by area-level socioeconomic status: a multilevel analysis
Authors: Hastert Theresa A , Beresford Shirley A A , Sheppard Lianne , White Emily 
Published: October 2014

BackgroundDisparities in cancer incidence and mortality have been observed by measures of area-level socioeconomic status (SES); however, the extent to which these disparities are explained by individual SES is unclear.MethodsParticipants included 60 756 men and women in the VITamins And Lifestyle (VITAL) study cohort, aged 50–76 years at baseline (2000–2002) and followed through 2010. We constructed a block group SES index using the 2000 US Census and fit Cox proportional hazards models to estimate the association between area-level SES (by quintile) and total and site-specific cancer incidence and total cancer mortality, with and without household income and individual education in the models.ResultsLower area-level SES was weakly associated with higher total cancer incidence and lower prostate cancer risk, but was not associated with risk of breast cancer. Compared with the highest-SES areas, living in the lowest-SES areas was associated with higher lung (HR: 2.21, 95% CI 1.69 to 2.90) and colorectal cancer incidence (HR: 1.52, 95% CI 1.11 to 2.09) and total cancer mortality (HR: 1.68, 95% CI 1.47 to 1.93). Controlling for individual education and household income weakened the observed associations, but did not eliminate them (lung cancer HR: 1.43, 95% CI 1.07 to 1.91; colorectal cancer HR: 1.35, 95% CI 0.97 to 1.88; cancer mortality HR: 1.28, 95% CI 1.11 to 1.48).ConclusionsArea-level socioeconomic disparities exist for several cancer outcomes. These differences are not fully explained by individual SES, suggesting area-level factors may play a role.
PROSPECTIVE STUDY ON THE MANAGEMENT OF TRIGGER FINGER
Authors: Choudhury Muntasir Mannan , Tay Shian Chao 
Published: October 2014

Trigger finger is one of the very common conditions encountered in hand surgery. Currently, the treatment modes we offer in our clinics are combination therapy of topical NSAIDS, occupational therapy and splinting or invasive modes involving corticosteroid injections and trigger finger release. This is a prospective review looking at the outcomes of the various initial treatment modules currently used for treating trigger fingers and the rate of surgery following non-surgical treatment. From our study we have noted that 26% of the digits which were subjected to combination therapy eventually underwent surgery whereas 60% of digits which received corticosteroid injections underwent surgery. Even though our results comparing operation rates are not statistically significant, they appear to show that combination therapy was more effective in avoiding surgery than corticosteroid injection in lower grades of trigger.
Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion
Authors: Mierke Claudia T. 
Published: October 2014

There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present current cancer research in a different light from a physical point of view with respect to cancer cell mechanics and the special and unique role of the endothelium on cancer cell invasion. The physical view on cancer disease may lead to novel insights into cancer disease and will help to overcome the classical views on cancer. In addition, in this review it will be discussed how physics of cancer can help to reveal and propose the functional mechanism which cancer cells use to invade connective tissue and transmigrate through the endothelium to finally metastasize. Finally, in this review it will be demonstrated how biophysical measurements can be combined with classical analysis approaches of tumor biology. The insights into physical interactions between cancer cells, the endothelium and the microenvironment may help to answer some "old," but still important questions in cancer disease progression.
QLib
Authors: Lin Chia-Chun , Chakrabarti Amlan , Jha Niraj K. 
Published: October 2014

Quantum algorithms are known for their ability to solve some problems much faster than classical algorithms. They are executed on quantum circuits, which consist of a cascade of quantum gates. However, synthesis of quantum circuits is not straightforward because of the complexity of quantum algorithms.
Generally, quantum algorithms contain two parts: classical and quantum. Thus, synthesizing circuits for the two parts separately reduces overall synthesis complexity. In addition, many quantum algorithms use similar subroutines that can be implemented with similar circuit modules. Because of their frequent use, it is important to use automated scripts to generate such modules efficiently. These modules can then be subjected to further synthesis optimizations.
This article proposes QLib, a quantum module library, which contains scripts to generate quantum modules of different sizes and specifications for well-known quantum algorithms. Thus, QLib can also serve as a suite of benchmarks for quantum logic and physical synthesis.
Privacy-Preserving Ad-Hoc Equi-Join on Outsourced Data
Authors: Pang Hweehwa , Ding Xuhua 
Published: October 2014

In IT outsourcing, a user may delegate the data storage and query processing functions to a third-party server that is not completely trusted. This gives rise to the need to safeguard the privacy of the database as well as the user queries over it. In this article, we address the problem of running ad hoc equi-join queries directly on encrypted data in such a setting. Our contribution is the first solution that achieves constant complexity per pair of records that are evaluated for the join. After formalizing the privacy requirements pertaining to the database and user queries, we introduce a cryptographic construct for securely joining records across relations. The construct protects the database with a strong encryption scheme. Moreover, information disclosure after executing an equi-join is kept to the minimum—that two input records combine to form an output record if and only if they share common join attribute values. There is no disclosure on records that are not part of the join result.
Building on this construct, we then present join algorithms that optimize the join execution by eliminating the need to match every record pair from the input relations. We provide a detailed analysis of the cost of the algorithms and confirm the analysis through extensive experiments with both synthetic and benchmark workloads. Through this evaluation, we tease out useful insights on how to configure the join algorithms to deliver acceptable execution time in practice.
Targeting the MYC and PI3K Pathways Eliminates Leukemia-Initiating Cells in T-cell Acute Lymphoblastic Leukemia
Authors: Schubbert Suzanne , Cardenas Anjelica , Chen Harrison , Garcia Consuelo , Guo Wei , Bradner James , Wu Hong 
Published: October 2014

Abstract
Disease relapse remains the major clinical challenge in treating T-cell acute lymphoblastic leukemia (T-ALL), particularly those with PTEN loss. We hypothesized that leukemia-initiating cells (LIC) are responsible for T-ALL development and treatment relapse. In this study, we used a genetically engineered mouse model of Pten−/− T-ALL with defined blast and LIC-enriched cell populations to demonstrate that LICs are responsible for therapeutic resistance. Unlike acute and chronic myelogenous leukemia, LICs in T-ALL were actively cycling, were distinct biologically, and responded differently to targeted therapies in comparison with their differentiated blast cell progeny. Notably, we found that T-ALL LICs could be eliminated by cotargeting the deregulated pathways driven by PI3K and Myc, which are altered commonly in human T-ALL and are associated with LIC formation. Our findings define critical events that may be targeted to eliminate LICs in T-ALL as a new strategy to treat the most aggressive relapsed forms of this disease. Cancer Res; 74(23); 7048–59. ©2014 AACR.
Mean and Turbulent Flow Downstream of a Low-Intensity Fire: Influence of Canopy and Background Atmospheric Conditions
Authors: Kiefer Michael T. , Heilman Warren E. , Zhong Shiyuan , Charney Joseph J. , Bian Xindi 
Published: October 2014

AbstractThis study examines the sensitivity of mean and turbulent flow in the planetary boundary layer and roughness sublayer to a low-intensity fire and evaluates whether the sensitivity is dependent on canopy and background atmospheric properties. The ARPS-CANOPY model, a modified version of the Advanced Regional Prediction System (ARPS) model with a canopy parameterization, is utilized for this purpose. A series of numerical experiments are conducted to evaluate whether the ability of the fire to alter downstream wind, temperature, turbulent kinetic energy (TKE), and vertical heat flux differs between forested and open areas, sparse and dense forests, weak and strong background flow, and neutral and convective background stability. Analysis of all experiments shows that, in general, mean and turbulent flow both prior to and during a low-intensity fire is damped in the presence of a canopy. Greater sensitivity to the fire is found in cases with strong ambient wind speed than in cases with quiescent or weak wind speed. Furthermore, sensitivity of downstream atmospheric conditions to the fire is shown to be strongest with a neutrally stratified background. An analysis of the TKE budget reveals that both buoyancy and wind shear contribute to TKE production during the period of time in which the fire conditions are applied to the model. On the basis of the results of the ARPS simulations, caution is advised when applying ARPS-simulation results to predictions of smoke transport and dispersion: smoke-model users should consider whether canopy impacts on the atmosphere are accounted for and whether neutral stratification is assumed.
The Surface Diurnal Warm Layer in the Indian Ocean during CINDY/DYNAMO
Authors: Matthews Adrian J. , Baranowski Dariusz B. , Heywood Karen J. , Flatau Piotr J. , Schmidtko Sunke 
Published: October 2014

Abstract
A surface diurnal warm layer is diagnosed from Seaglider observations and develops on half of the days in the Cooperative Indian Ocean Experiment on Intraseasonal Variability/Dynamics of the Madden–Julian Oscillation (CINDY/DYNAMO) Indian Ocean experiment. The diurnal warm layer occurs on days of high solar radiation flux (&gt;80 W m−2) and low wind speed (&lt;6 m s−1) and preferentially in the inactive stage of the Madden–Julian oscillation. Its diurnal harmonic has an exponential vertical structure with a depth scale of 4–5 m (dependent on chlorophyll concentration), consistent with forcing by absorption of solar radiation. The effective sea surface temperature (SST) anomaly due to the diurnal warm layer often reaches 0.8°C in the afternoon, with a daily mean of 0.2°C, rectifying the diurnal cycle onto longer time scales. This SST anomaly drives an anomalous flux of 4 W m−2 that cools the ocean. Alternatively, in a climate model where this process is unresolved, this represents an erroneous flux that warms the ocean. A simple model predicts a diurnal warm layer to occur on 30%–50% of days across the tropical warm pool. On the remaining days, with low solar radiation and high wind speeds, a residual diurnal cycle is observed by the Seaglider, with a diurnal harmonic of temperature that decreases linearly with depth. As wind speed increases, this already weak temperature gradient decreases further, tending toward isothermal conditions.
How Does Drifter Position Uncertainty Affect Ocean Dispersion Estimates?
Authors: Haza Angelique C. , Özgökmen Tamay M. , Griffa Annalisa , Poje Andrew C. , Lelong M.-Pascale 
Published: October 2014

AbstractTo develop methodologies to maximize the information content of Lagrangian data subject to position errors, synthetic trajectories produced by both a large-eddy simulation (LES) of an idealized submesoscale flow field and a high-resolution Hybrid Coordinate Ocean Model simulation of the North Atlantic circulation are analyzed. Scale-dependent Lagrangian measures of two-particle dispersion, mainly the finite-scale Lyapunov exponent [FSLE; λ(δ)], are used as metrics to determine the effects of position uncertainty on the observed dispersion regimes. It is found that the cumulative effect of position uncertainty on λ(δ) may extend to scales 20–60 times larger than the position uncertainty. The range of separation scales affected by a given level of position uncertainty depends upon the slope of the true FSLE distribution at the scale of the uncertainty. Low-pass filtering or temporal subsampling of the trajectories reduces the effective noise amplitudes at the smallest spatial scales at the expense of limiting the maximum computable value of λ. An adaptive time-filtering approach is proposed as a means of extracting the true FSLE signal from data with uncertain position measurements. Application of this filtering process to the drifters with the Argos positioning system released during the LatMix: Studies of Submesoscale Stirring and Mixing (2011) indicates that the measurement noise dominates the dispersion regime in λ for separation scales δ < 3 km. An expression is provided to estimate position errors that can be afforded depending on the expected maximum λ in the submesoscale regime.
Comparison of Hybrid-4DEnVar and Hybrid-4DVar Data Assimilation Methods for Global NWP
Authors: Lorenc Andrew C. , Bowler Neill E. , Clayton Adam M. , Pring Stephen R. , Fairbairn David 
Published: October 2014

Abstract
The Met Office has developed an ensemble-variational data assimilation method (hybrid-4DEnVar) as a potential replacement for the hybrid four-dimensional variational data assimilation (hybrid-4DVar), which is the current operational method for global NWP. Both are four-dimensional variational methods, using a hybrid combination of a fixed climatological model of background error covariances with localized covariances from an ensemble of current forecasts designed to describe the structure of “errors of the day.” The fundamental difference between the methods is their modeling of the time evolution of errors within each data assimilation window: 4DVar uses a linear model and its adjoint and 4DEnVar uses a localized linear combination of nonlinear forecasts. Both hybrid-4DVar and hybrid-4DEnVar beat their three-dimensional versions, which are equivalent, in NWP trials. With settings based on the current operational system, hybrid-4DVar performs better than hybrid-4DEnVar. Idealized experiments designed to compare the time evolution of covariances in the methods are described: the basic 4DEnVar represents the evolution of ensemble errors as well as 4DVar. However, 4DVar also represents the evolution of errors from the climatological covariances, whereas 4DEnVar does not. This difference is the main cause of the superiority of hybrid-4DVar. Another difference is that the authors’ 4DVar explicitly penalizes rapid variations in the analysis increment trajectory, while the authors’ 4DEnVar contains no dynamical constaints on imbalance. The authors describe a four-dimensional incremental analysis update (4DIAU) method that filters out the high-frequency oscillations introduced by the poorly balanced 4DEnVar increments. Possible methods for improving hybrid-4DEnVar are discussed.
Twelve-year follow-up of a randomized controlled trial of comprehensive physiotherapy following disc herniation operation
Authors: Ebenbichler Gerold R , Inschlag Silke , Pflüger Verena , Stemberger Regina , Wiesinger Günther , Novak Klaus , Krall Christoph , Resch Karl L 
Published: October 2014

Objective: To evaluate the long-term effects of postoperative comprehensive physiotherapy starting one week after lumbar disc surgery. Design: Twelve-year follow-up of a three-armed, randomized, controlled, single-blinded clinical trial. Setting: Department of Physical Medicine & Rehabilitation. Participants: Of 111 patients following first-time, uncomplicated lumbar disc surgery who participated in the original study and completed the treatment originally allocated, 74 ((67%; 29 (73%) physiotherapy, 22 (58%) sham therapy, 23 (68%) no therapy) completed a 12-year follow-up examination. Interventions: In the original study, patients had been randomly assigned to comprehensive physiotherapy, sham intervention (neck massage), or no therapy. Measures: Low Back Pain Rating Scale; best score 0, worst score 130 points). Results: At 12 years after surgery, the group participating in comprehensive physiotherapy had significantly better functional outcomes, as rated on the Low Back Pain Rating Score, than the untreated group (mean difference: −13.2 (95% CI: (−25.4; −1.0)). Equally, there was a clinically relevant, non-significant difference between the sham therapy and no therapy (mean difference: −12.5 (95%CI: −26.1; 1.1)). Consequently, the Low Back Pain Rating Score outcome did not differ between physiotherapy and sham therapy (mean difference: −0.7 (95%CI: −14.2; 12.8)). Conclusions: Participating in a comprehensive physiotherapy program following lumbar disc surgery may be associated with better long-term health benefits over no intervention, but may not be superior to sham therapy.