bluuebunny/crossref_metadata_2025_split huggingface dataset:
Industrial Trent Development and Application
Authors: Roberts J. A. 
Published: January 2015

The industrial Trent is the largest aeroderivative gas turbine available, at 50+ MW, and the most efficient gas turbine available to industrial and marine operators, at 42%. Its Dry Low Emissions combustion system embodies the features of the similar combustor on the industrial RB211, which is enjoying very successful service experience.
Its design features and derivation from the aero engine are reviewed, together with an assessment of the maintenance aspects of the engine.
The current status of the engine validation programme is discussed, covering both component rig testing and progress on the full engine testing being carried out in Montreal, Canada.
The applications of the industrial Trent are considered by reviewing the major markets and examining its suitability, both technically and economically, for several existing and emerging sectors.
Launched as a power generation machine, the industrial Trent is shown to be well suited to those sectors which have resulted from the growing deregulation of this industry worldwide. In addition it is shown to be attractive for certain applications in the oil and gas industry and, in the marine market, for some large high speed vessel concepts.
Automated and nonbiased regional quantification of functional neuroimaging data
Authors: Parker Jason G. , Speidel Benjamin , Sherwood Matthew S. 
Published: January 2015

Purpose:In the quantification of functional neuroimaging data, region‐of‐interest (ROI) analysis can be used to assess a variety of properties of the activation signal, but taken alone these properties are susceptible to noise and may fail to accurately describe overall regional involvement. Here, the authors present and evaluate an automated method for quantification and localization of functional neuroimaging data that combines multiple properties of the activation signal to generate rank‐order lists of regional activation results.Methods:The proposed automated quantification method, referred to as neuroimaging results decomposition (NIRD), begins by decomposing an activation map into a hierarchical list of ROIs using a digital atlas. In an intermediate step, the ROIs are rank‐ordered according to extent, mean intensity, and total intensity. A final rank‐order list (NIRD average rank) is created by sorting the ROIs according to the average of their ranks from the intermediate step. The authors hypothesized that NIRD average rank would have improved regional quantification accuracy compared to all other quantitative metrics, including methods based on properties of statistical clusters. To test their hypothesis, NIRD rankings were directly compared to three common cluster‐based methods using simulated fMRI data both with and without realistic head motion.Results:For both the no‐motion and motion datasets, an analysis of variance found that significant differences between the quantification methods existed (F = 64.8, p < 0.0001 for no motion; F = 55.2, p < 0.0001 for motion), and a post‐hoc test found that NIRD average rank was the most accurate quantification method tested (p < 0.05 for both datasets). Furthermore, all variants of the NIRD method were found to be significantly more accurate than the cluster‐based methods in all cases.Conclusions:These results confirm their hypothesis and demonstrate that the proposed NIRD methodology provides improved regional quantification accuracy compared to cluster‐based methods.
In Vitro
Assessment of Dual Drug Combinations To Inhibit Growth of Neisseria gonorrhoeae
Authors: Pettus Kevin , Sharpe Samera , Papp John R. 
Published: January 2015

ABSTRACT

The development of resistance to first-line antimicrobial therapies has led to recommendations for combination therapies for the treatment of gonorrhea infection. Recent studies have shown the success of combination therapies in treating patients, but few have reported on the
in vitro
activities of these drug combinations. An
in vitro
assessment of azithromycin in combination with gentamicin demonstrated inhibition of growth and suggests that clinical trials may be warranted to assess the utility of this combination in treating gonorrhea infections.
In Vivo
Efficacy of Anuran Trypsin Inhibitory Peptides against Staphylococcal Skin Infection and the Impact of Peptide Cyclization
Authors: Malik U. , Silva O. N. , Fensterseifer I. C. M. , Chan L. Y. , Clark R. J. , Franco O. L. , Daly N. L. , Craik D. J. 
Published: January 2015

ABSTRACT

Staphylococcus aureus
is a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weak
in vitro
inhibitory activities against
S. aureus
, but several had strong antibacterial activities against
S. aureus
in an
in vivo
murine wound infection model. pYR, an immunomodulatory peptide from
Rana sevosa
, was the most potent, with complete bacterial clearance at 3 mg · kg
−1
. Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.
Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist
Authors: Wang Kaiyu , Gan Longjie , Jiang Li , Zhang Xianhui , Yang Xiangyue , Chen Min , Lan Xiaopeng 
Published: January 2015

ABSTRACT

Staphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). SEB activates a large subset of the T lymphocytic population, releasing proinflammatory cytokines. Blocking SEB-initiated toxicity may be an effective strategy for treating TSS. Using a process known as systematic evolution of ligands by exponential enrichment (SELEX), we identified an aptamer that can antagonize SEB with nanomolar binding affinity (

K
d

= 64 nM). The aptamer antagonist effectively inhibits SEB-mediated proliferation and cytokine secretion in human peripheral blood mononuclear cells. Moreover, a PEGylated aptamer antagonist significantly reduced mortality in a “double-hit” mouse model of SEB-induced TSS, established via sensitization with
d
-galactosamine followed by SEB challenge. Therefore, our novel aptamer antagonist may offer potential therapeutic efficacy against SEB-mediated TSS.
Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study
Authors: Cornely Oliver A. , Böhme Angelika , Schmitt-Hoffmann Anne , Ullmann Andrew J. 
Published: January 2015

ABSTRACT

Isavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort (
n
= 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort (
n
= 12). The mean ± standard deviation plasma isavuconazole areas under the concentration-time curves for the dosing period on day 7 were 60.1 ± 22.3 μg · h/ml and 113.1 ± 19.6 μg · h/ml for the patients in the low-dose and high-dose cohorts, respectively. The adverse events in five patients in the low-dose cohort and in eight patients in the high-dose cohort were considered to be drug related. Most were mild to moderate in severity, and the most common adverse events were headache and rash (
n
= 3 each). One patient in the high-dose cohort experienced a serious adverse event (unrelated to isavuconazole treatment), and two patients each in the low-dose and high-dose cohorts discontinued the study due to adverse events. Of the 20 patients who completed the study, 18 were classified as a treatment success. In summary, the results of this analysis support the safety and tolerability of isavuconazole administered at 200 mg and 400 mg once-daily as prophylaxis in immunosuppressed patients at high risk of fungal infections. (This study is registered at ClinicalTrials.gov under registration number NCT00413439.)
Evolutionary Adaptation of an AraC-Like Regulatory Protein in Citrobacter rodentium and Escherichia Species
Authors: Tan Aimee , Petty Nicola K. , Hocking Dianna , Bennett-Wood Vicki , Wakefield Matthew , Praszkier Judyta , Tauschek Marija , Yang Ji , Robins-Browne Roy 
Published: January 2015

ABSTRACT

The evolution of pathogenic bacteria is a multifaceted and complex process, which is strongly influenced by the horizontal acquisition of genetic elements and their subsequent expression in their new hosts. A well-studied example is the RegA regulon of the enteric pathogen
Citrobacter rodentium
. The RegA regulatory protein is a member of the AraC/XylS superfamily, which coordinates the expression of a gene repertoire that is necessary for full pathogenicity of this murine pathogen. Upon stimulation by an exogenous, gut-associated signal, namely, bicarbonate ions, RegA activates the expression of a series of genes, including virulence factors, such as autotransporters, fimbriae, a dispersin-like protein, and the
grlRA
operon on the locus of enterocyte effacement pathogenicity island. Interestingly, the genes encoding RegA homologues are distributed across the genus
Escherichia
, encompassing pathogenic and nonpathogenic subtypes. In this study, we carried out a series of bioinformatic, transcriptional, and functional analyses of the RegA regulons of these bacteria. Our results demonstrated that
regA
has been horizontally transferred to
Escherichia
spp. and
C. rodentium
. Comparative studies of two RegA homologues, namely, those from
C. rodentium
and
E. coli
SMS-3-5, a multiresistant environmental strain of
E. coli
, showed that the two regulators acted similarly
in vitro
but differed in terms of their abilities to activate the virulence of
C. rodentium
in vivo
, which evidently was due to their differential activation of
grlRA
. Our data indicate that RegA from
C. rodentium
has strain-specific adaptations that facilitate infection of its murine host. These findings shed new light on the development of virulence by
C. rodentium
and on the evolution of virulence-regulatory genes of bacterial pathogens in general.
Identification and Characterization of VpsR and VpsT Binding Sites in Vibrio cholerae
Authors: Zamorano-Sánchez David , Fong Jiunn C. N. , Kilic Sefa , Erill Ivan , Yildiz Fitnat H. 
Published: January 2015

ABSTRACTThe ability to form biofilms is critical for environmental survival and transmission ofVibrio cholerae, a facultative human pathogen responsible for the disease cholera. Biofilm formation is controlled by several transcriptional regulators and alternative sigma factors. In this study, we report that the two main positive regulators of biofilm formation, VpsR and VpsT, bind to nonoverlapping target sequences in the regulatory region ofvpsL in vitro. VpsR binds to a proximal site (the R1 box) as well as a distal site (the R2 box) with respect to the transcriptional start site identified upstream ofvpsL. The VpsT binding site (the T box) is located between the R1 and R2 boxes. While mutations in the T and R boxes resulted in a decrease invpsLexpression, deletion of the T and R2 boxes resulted in an increase invpsLexpression. Analysis of the role of H-NS invpsLexpression revealed that deletion ofhnsresulted in enhancedvpsLexpression. The level ofvpsLexpression was higher in anhns vpsTdouble mutant than in the parental strain but lower than that in anhnsmutant.In silicoanalysis of the regulatory regions of the VpsR and VpsT targets resulted in the identification of conserved recognition motifs for VpsR and VpsT and revealed that operons involved in biofilm formation andvpsTare coregulated by VpsR and VpsT. Furthermore, a comparative genomics analysis revealed substantial variability in the promoter region of thevpsTandvpsLgenes among extantV. choleraeisolates, suggesting that regulation of biofilm formation is under active selection.IMPORTANCEVibrio choleraecauses cholera and is a natural inhabitant of aquatic environments. One critical factor that is important for environmental survival and transmission ofV. choleraeis the microbe's ability to form biofilms, which are surface-associated communities encased in a matrix composed of the exopolysaccharide VPS (Vibriopolysaccharide), proteins, and nucleic acids. Two proteins, VpsR and VpsT, positively regulate VPS production and biofilm formation. We characterized the structural features of the promoter of thevpsLgene, determined the target sequences recognized by VpsT and VpsR, and analyzed their distribution and conservation patterns in multipleV. choleraeisolates. This work fills a fundamental gap in our understanding of the regulatory mechanisms employed by the master regulators VpsR and VpsT in controlling biofilm matrix production.
Connecting Point-Level and Gridded Moments in the Analysis of Climate Data*
Authors: Director Hannah , Bornn Luke 
Published: January 2015

Abstract
The need to draw climate-related inferences from historical data makes understanding the biases and errors in these data critical. While climate data are collected at point-level monitoring sites, they are often postprocessed by averaging sites within a geographic area to align the data to a grid, easing analysis and visualization. Although this aggregation generally provides reasonable estimates of the mean, its use can be problematic for characterizing the full distribution of climate measures. Specifically, the process of averaging point-level data up to grid level can lead to inconsistencies, particularly when the grid box is heterogeneous and extremes are of interest. Point-level data are measured at individual points, while gridded data are the averaged product of many measurements within a larger spatial area. Because of this aggregation, point-level and grid-level distributions differ in many fundamental properties, such as their shape, skew, and tail behavior. This paper highlights these differences and their effects on analyses pertaining to current climatological questions. Mathematical relationships are derived to link the distributions of grid-level climate measures to the distributions of point-level climate measures using the notion of effective sample size. Then, these relationships are leveraged to propose a correction factor to use when modeling higher moments and extreme events.
Processes Leading to Double Intertropical Convergence Zone Bias in CESM1/CAM5
Authors: Wang Chia-Chi , Lee Wei-Liang , Chen Yu-Luen , Hsu Huang-Hsiung 
Published: January 2015

Abstract
The double intertropical convergence zone (ITCZ) bias in the eastern Pacific in the Community Earth System Model version 1 with Community Atmosphere Model version 5 (CESM1/CAM5) is diagnosed. In CAM5 standalone, the northern ITCZ is associated with inertial instability and the southern ITCZ is thermally forced. After air–sea coupling, the processes on both hemispheres are switched because the spatial pattern of sea surface temperature (SST) is changed.
Biases occur during boreal spring in both CAM5 and the ocean model. In CAM5 alone, weaker-than-observed equatorial easterly in the tropical eastern South Pacific leads to weaker evaporation and an increase in local SST. The shallow meridional circulation overly converges in the same region in the CAM5 standalone simulation, the planetary boundary layer and middle troposphere are too humid, and the large-scale subsidence is too weak at the middle levels. These biases may result from excessive shallow convection behavior in CAM5. The extra moisture would then fuel stronger convection and a higher precipitation rate in the southeastern Pacific.
In the ocean model, the South Equatorial Current is underestimated and the North Equatorial Countercurrent is located too close to the equator, causing a warm SST bias in the southeastern Pacific and a cold bias in the northeastern Pacific. These SST biases feed back to the atmosphere and further influence convection and the surface wind biases in the coupled simulation. When the convection in the tropical northeastern Pacific becomes thermally forced after coupling, the northern ITCZ is diminished due to colder SST, forming the so-called alternating ITCZ bias.
Political Turmoil in Egypt: Its Implications for the Region and India
Authors: Siddiqui Fazzur Rahman 
Published: January 2015

The self-immolation of a vendor in December 2010 in a Tunisian town spurred a massive scale of uprising, inspiring the Arab youth to carve out a new Arab for them which was marred by decades-old political and cultural stagnation. The sentiments emerging on the streets following the chain of revolutions in different parts of the Arab world had promised not only a different Arab but had hoped for foundation of new democratic Arab which until now was a mirage. But what followed later dashed all the hopes on the Arab streets and each country opted for a different trajectory which promised everything but the democracy. Except Tunisia, other revolution-infested countries veered to neo- authoritarianism like Egypt, while Libya and Yemen have been witnessing highest order of faction fighting and Syria is in midst of full-scale civil war. In the backdrop of present scenario, today’s Arab land is marred by complete instability, chaos and political anarchy. The cause of the present instability may be attributed to the different political and strategic context of each respective country. Egypt has taken a complete U-turn after army again came at the helm of the affairs after ousting a democratically elected Islamist government. This article aims to explore the lineage of the Arab Spring in Egypt and how it unfolded in the span of two-three years. The study would also explore the lurching security scenario in Egypt and how it would impact the regional security architecture in the near future. This article also aims to highlight the long term implications of unfolding political developments in Egypt on the entire region and India as well.
The high cost of spasticity in multiple sclerosis to individuals and society
Authors: Stevenson VL , Gras A , Bárdos JI , Broughton J 
Published: January 2015

Background: Spasticity is an extremely common, distressing and disabling symptom of multiple sclerosis. Limited data suggest the associated health care costs correlate with increasing severity and place a high economic burden on individuals, health care systems and society. Objective: The aim of this study was to quantify the impact of multiple sclerosis spasticity on health care resources and the associated costs at different levels of severity in people with multiple sclerosis in the United Kingdom. Methods: An online survey was carried out to understand the resources used in the management of spasticity in multiple sclerosis. The questionnaire asked health care specialists to estimate their involvement and the resource use associated with different levels of spasticity, and the survey outputs were used to derive the resource costs. Results: The level and cost of care substantially increased with the degree of spasticity. Key factors contributing to high annual costs per patient were home care, hospital admissions and high-cost items, such as hospital beds. Conclusions: Based on the survey results, it can be assumed that managing spasticity early and effectively could result in substantial cost savings, in addition to the improvements in health-related quality of life.
Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study
Authors: Aldenhoven Mieke , Wynn Robert F. , Orchard Paul J. , O’Meara Anne , Veys Paul , Fischer Alain , Valayannopoulos Vassili , Neven Benedicte , Rovelli Attilio , Prasad Vinod K. , Tolar Jakub , Allewelt Heather , Jones Simon A. , Parini Rossella , Renard Marleen , Bordon Victoria , Wulffraat Nico M. , de Koning Tom J. , Shapiro Elsa G. , Kurtzberg Joanne , Boelens Jaap Jan 
Published: January 2015

Key Points
Patients with Hurler syndrome show significant residual disease burden despite HCT. Early referral for HCT, using noncarrier donors and regimens designed to achieve full-donor chimerism, offers the best long-term prognosis.
Reduction of breakdown threshold by metal nanoparticle seeding in a DC microdischarge
Authors: Sawyer Jordan , Abboud Jacques , Zhang Zhili , Adams Steven F 
Published: January 2015

Abstract
Significant reduction of the breakdown threshold in a DC microdischarge via seeding metal nanoparticles has been demonstrated. Compared to standard Paschen curves in dry air, reductions in the breakdown voltage of 5% to 25% were obtained for PD values (the product of pressure and electrode gap distance) ranging from 20 to 40 Torr-cm by seeding aluminum and iron nanoparticles with mean sizes of 75 nm and 80 nm, respectively. No secondary energy source was required to achieve this breakdown threshold reduction. From high-speed chemiluminescence imaging of the discharge evolution, breakdown was shown to be initiated at reduced voltages. Following breakdown, the increase in temperature ignited some of the nanoparticles near the cathode. Results suggest that possible charging of the nanoparticles within the gap may reduce the effective transient distance, leading to the threshold reduction.