bluuebunny/crossref_metadata_2025 huggingface dataset:
Load Power Quality Characteristics of Trains With Switch-Type Converters and the Impact to AC Electrified Traction Power Systems
Authors: Ku Bih-Yuan , Chen Yen-Chun , Chen Guan-Ru , Ko Ming-Jan
Published: June 2014

In this paper we present our study on load power quality characteristics of new trains with switch-type converters using field measurement data. We apply these data to perform power flow and harmonic power flow computations to examine the impacts of new train loads to existing ac traction power network with filters designed for old train loads. Our simulation results show that existing filters can result in over-compensation of reactive power and ineffective filtering of load current harmonic components. It is recommended that filter designs be modified to suit the load power characteristics of new-generation trains.
The Relationship Between Design, Processing and Shot Peening on Wheel Plate Failures
Authors: Dedmon Steven L.
Published: June 2014

Wheel plate failures occur rarely in North American freight car service. When they do occur, derailments are a likely result. Shot peening has been used to improve fatigue life for more than 80 years and the efficacy of the process is now undisputed in reducing fatigue failures of parts subjected to high levels of cyclic stresses. The introduction of residual compressive stresses from shot peening is acknowledged as the reason for the improvement in fatigue life; comparable processes such as cold rolling, are successful for the same reason. Since residual stresses are so important to fatigue life, then design and processing prior to shot peening should have an equally important role. This investigation demonstrates some of the variables which are important to producing wheels resistant to plate fatigue failures.
Evaluation of Single Track Timetables Using Simulation
Authors: Sipilä Hans
Published: June 2014

One way to model train operations and make predictions of future outcome is to use simulation. Many lines and networks connecting major cities have a high capacity utilization, meaning that running additional trains leads to an even more strained situation and delays are likely to increase. The mix of average train speeds is also related to capacity and delay propagation.

Considering one line or several lines connected in a network a requested train traffic can consist of different train categories and departure frequencies. There are usually several possible timetables satisfying this traffic demand. The infrastructure often implies limitations on the type and volume of traffic that can be handled. Additionally constraints introduced by requests for regular intervals, minimum headways, passenger transfers between trains etc. can reduce the number of acceptable timetables.

This paper presents an approach using combinatorial train initiations and simulation to generate conflict-free timetables. These can then be simulated with random variations in departure and dwell times. This is implemented on a fictive single track line with high speed passenger train traffic. The objective is to study outcome by varying allowance times and delays. Simulations are carried out in RailSys, a software using synchronous simulation to model train traffic operations.
Analysis of Roadway Worker Injuries and Fatalities at FRA and FTA-Regulated Railroads
Authors: Schlesinger Dave
Published: June 2014

Roadway workers perform a key role in keeping the nation’s freight, passenger, and transit rail systems operating safely and efficiently. These individuals perform a variety of critical maintenance, repairs, and inspection on all aspects of the rail system.

Despite a renewed effort by the rail industry, fatalities and injuries to roadway workers continue to occur across the nation’s freight, passenger, and transit rail systems. The causes of these accidents are all human factor related, especially in the area of adherence to rules and procedures. Other factors include rules compliance and organizational issues.

At the same time, there is no unified and cohesive source from which railroads and other concerned organizations can gain a perspective of roadway worker safety issues.

Using accident reports and information available primarily from the National Transportation Safety Board (NTSB) as well as the FRA and FTA, and the railroad industry, research was conducted, with a focus on the probable causes and contributing factors. Research was also conducted on the various industry efforts, both public and private, to curb these fatalities and injuries.

One of these efforts has been to develop a roadway worker warning system, to notify employees of an approaching train. Those railroads who have implemented this solution have reported positive results; however, this technology has not been widely accepted. This may be, in part, due to major capital requirements, such as Positive Train Control, which limits funding for other programs.

Training best practices are also outlined, with the goal of ensuring that roadway workers understand the risks they face while working on the railroad. Strategies are presented to ensure that training is conducted following best practices, including key case studies whose real life examples help trainees understand the criticality of following the rules and procedures each and every time they work on the system.
Reliable Transfer Length Assessment for Real-Time Monitoring of Railroad Crosstie Production
Authors: Zhao Weixin , Beck B. Terry , Peterman Robert J. , Wu Chih-Hang John , Bodapati Naga Narendra B. , Lee Grace
Published: June 2014

Automated in-plant diagnostic testing of prestressed concrete railroad crossties is now within reach due to recent progress in robust surface strain measurement techniques. The newly developed non-contact Laser Speckle Imaging (LSI) technique has been shown to provide rapid and accurate surface strain profile measurement, which is a key requirement for rapid transfer length assessment. Accurate determination of transfer length is critical for maintaining continuous production quality in the modern manufacture of prestressed concrete railroad crossties.

Conventional assessment of transfer length generally presumes the underlying existence of a bilinear prestressing force distribution and a corresponding bilinear surface strain profile. Furthermore, it is well-known that this bilinear profile is smoothed due to the effects of finite gauge length during the process of measuring surface strain. In addition, recent extensive crosstie measurements in concrete railroad tie plants have shown significant departures from this simple bilinear profile, which bring to question the general validity and reliability of the traditional 95% AMS (95% Average Maximum Strain) method. Deviations from the simple bilinear profile shape were shown to be partially due to the non-prismatic shape of typical concrete railroad ties. In addition, extensive comparisons between predicted and measured surface strain profiles on numerous crossties suggest that the underlying strain distribution for crossties is best represented by an exponential strain profile, with an asymptotic approach to the fully-developed compressive strain. This is in contrast with extensive testing of prisms with fixed cross-section and fixed prestressing wire eccentricity, for which the surface strain appears to be best represented by the simple bilinear strain profile.

Clearly, departures from non-prismatic behavior have added complexity to transfer length measurement. If accurate and reliable measurements of this important quality control parameter are to be realized, these issues of transfer length uncertainty need to be addressed. This paper provides an experimental comparison of several possible alternative transfer length assessment procedures, in an attempt to answer important uncertainty questions which need to be addressed if rapid real-time transfer length is to be achieved. It is shown that in spite of considerable differences in the transfer length processing methods, and significant departures from prismatic behavior, the averaged results are in many cases consistent with the simple bilinear underlying strain profile assumption. Bias in the measurement of crosstie transfer length due to non-prismatic behavior will also be investigated in this paper.
Improving the Controllability of the Infrastructure in AC-Fed Railways With Neutral Zones
Authors: Pilo Eduardo , Mazumder Sudip K.
Published: June 2014

This paper presents an enhancement to the electrical infrastructure that applies to those AC railway power supply systems which have neutral zones. The proposed upgrade allows an improved degree of controllability of the infrastructure, making it possible to perform power routing in traction electrical grids. The modified system consists on the addition of controlled power electronic devices connected in parallel to both sides of the neutral zones. The paper discusses the advantages of such a system in a real section of the high-speed Madrid-Barcelona.
Hertzian Contact Stress Modeling in Railway Bearings for Assorted Load Conditions and Geometries
Authors: Mason Michael A. , Cartin Charles P. , Shahidi Parham , Fetty Mark W. , Wilson Brent M.
Published: June 2014

Increasing freight car loads demand higher performance tapered roller bearings. As the stress state on railway bearing applications continues to increase, further advancement in the modeling tools and methods used for subsurface contact stress evaluations are needed. Heat treat specifications and contact geometries for railway bearings were originally developed for ideal load conditions. However, in railroad applications, tapered roller bearings are exposed to a vast range of load conditions that are seldom perfect. Moreover, when comparing global rail markets, there are often differences in bearing loads, railcar wear conditions, maintenance practices, and reliability versus utilization expectations. Advanced modeling techniques need to be developed by bearing designers in order to meet the specific needs of each individual rail market.

Prior research has shown that subsurface stresses, resulting from rolling contact, are the primary factor in the development of fatigue cracks in railway bearings. In addition, finite element modeling software has previously been used to analyze Hertzian contact stresses under rolling contact. Recent advancements in the technology and computational power of finite element methods can be used to numerically analyze more detailed simulations of complex geometries and biased load conditions in railway bearings. These improvements in the tapered roller bearing modeling methodology are necessary to determine the material, heat treat specifications, and geometry required to meet the demands of specific railway bearing applications. Furthermore, the specific risks associated with some common railway bearing design and modeling assumptions will be evaluated. An exploratory list of these assumptions include: line versus point contact, load deflection factor, zero contact angle, rigid body assumptions, linear material behavior, neglect for overload, and uniform loading on the bearing. Emphasis will be placed on potential improvements in the theoretical and finite element prediction of surface and subsurface stresses in railway bearings under rolling contact with a review of prior research on the subject.
Flammable Liquid Fire Consequence Modeling
Authors: Serrano Jesus Aguilar , Saat Mohd Rapik
Published: June 2014

The recent expansion in the production of shale petroleum crude oil, combined with the lack of new pipeline construction, has placed the railroads at the center stage for safe and efficient transport of very large volumes of this commodity. Petroleum crude oil poses fire risk in the event of train accidents. The consequence modeling based on the US DOT Emergency Response Guidebook (ERG) or ALOHA (Areal Locations of Hazardous Atmospheres), a popular atmospheric dispersion model used for evaluating releases of hazardous chemical vapors, may be overly simplistic and limited to estimate the risk of flammable liquid releases. This paper aims to address this gap and develop a simple model to estimate flammable liquid release consequences, focusing on petroleum crude oil. A flow model using the spatial geographic information system (GIS) and the digital elevation model (DEM) is developed. The methodology was illustrated with a case study comparing the results from the model to the area affected from the Lac-Mégantic accident. Although the model does not consider advanced flow types or fire propagation, the results accurately describe the consequences of the accident, demonstrating the potential capability of this methodology to estimate the consequences of a crude oil release.
Effect of Concrete Properties on Transfer Lengths in Concrete Rail-Road Ties
Authors: Bodapati Naga Narendra B. , Peterman Robert J. , Beck B. Terry , Wu Chih-Hang John
Published: June 2014

This paper presents findings from a current research project titled “Quantifying the Effect of Prestressing Steel and Concrete Variables on the Transfer Length in Pretensioned Concrete Crossties” that is funded by the Federal Railroad Administration (FRA). Specifically, the paper focuses on the effect of concrete properties on the resulting transfer lengths. These properties include concrete consistency (slump), compressive strength at the time of prestress transfer, the water-to-cementitious (W/C) ratio, the aggregate type, and the use of a viscosity-modifying admixture (VMA). Pre-tensioned concrete prisms were cast in the laboratory and transfer lengths were determined from surface strain measurements that were obtained prior-to and immediately after prestress transfer (de-tensioning). The concrete compressive strength at de-tensioning was determined using cylindrical concrete test specimens that were match-cured to the temperature of the pre-tensioned concrete members. The release strengths investigated were 3500 psi (24.13 Mpa), 4500 psi (31.03 Mpa), and 6000 psi (41.37 Mpa). The effect of concrete consistency on the transfer length was evaluated by varying the slump between 3″ (76.20 mm) and 9″ (228.60 mm) while maintaining release strength of 4500 psi (31.03 Mpa) and a W/C ratio of 0.32. The effect of W/C ratio on transfer length was evaluated by maintaining release strength of 4500 ±220 psi (31.03 ± 1.52 Mpa) and a slump of 6 ± 1/2″ (152.40 ± 12.7 mm) while varying the W/C between 0.27 and 0.42. These values represent the extreme values used in the North American concrete tie industry that were noted by the authors during research that was conducted in 2010–2011[15]. Results for each parameter type will be compared and discussed in this paper. Transfer length results obtained during earlier work [4] conducted by the authors at a W/C ratio of 0.32 will be compared. Finally, results will be presented from transfer length measurements that were obtained on identical-sized prisms that were manufactured with concrete mixtures that used different aggregate sources and also the use of a viscosity-modifying admixture.

Work presented in this paper was conducted on two wire samples with generic labels [WG] and [WH]. Laboratory prism specimens of size 3 ½″ (88.9 mm) × 3 ½″ (88.9 mm) each with 4 wires were cast to measure transfer lengths. These proportions were chosen to replicate the original concrete crosstie wire-to-concrete proportions. Potential usage of these prisms in estimating transfer lengths was validated in another phase [5] and is not discussed here.

Essential information obtained from results allowed researchers to discuss attributed influence of each concrete property on transfer length. The research knowledge acquired from this study will give proper insight about transfer length and will be helpful to manufacture a better product by adjusting concrete mix design.
Protecting Fittings on Tank Cars: Preliminary Evaluation of Pressure Tank Cars
Authors: Prabhakaran Anand , González Francisco
Published: June 2014

Railroad tank car top fittings are susceptible to damage and failure in rollover derailments, which might result in release of hazardous material lading. Prior research has focused on the susceptibility of fittings on non-pressure tank cars and potential mitigation strategies. This paper presents current work that extends the analysis/test methods and lessons learned to fittings on pressure tank cars. Pressure tank cars carry significantly more hazardous materials such as Chlorine and Anhydrous Ammonia, which are classified as Toxic Inhalation Hazards (TIH). In particular, this paper presents the results of analytical modeling and validation testing of top fittings on a base design Chlorine car.

In addition, the paper compares and contrasts the test methodology employed in prior full scale tests of tank car fittings against the 9 mph evaluation scenario outlined in current Federal regulations governing the design of fittings on TIH tank cars, and further explores how full scale test results may be interpreted.
Deadlock Avoidance and Detection in Railway Simulation Systems
Authors: Simon Bertrand , Jaumard Brigitte , Le Thai Hoa
Published: June 2014

Avoiding or preventing deadlocks in simulation tools for train scheduling remains a critical issue, especially when combined with the objective of minimizing, e.g., the travel times of the trains. In this paper, we revisit the deadlock avoidance and detection problem, and propose a new deadlock avoidance algorithm, called DEADAALG, based on a resource reservation mechanism. The DEADAALG algorithm is proved to be exact, i.e., either detects an unavoidable deadlock resulting from the input data or provide a train scheduling thanks to the scheduling algorithm, called SIMTRAS, which is free of deadlocks. Moreover, we show that the SIMTRAS algorithm is a polynomial time algorithm with an O(|S| × |T|2log |T|) time complexity, where T is the set of trains and S is the set of sections in the railway topology. Numerical experiments are conducted on the Vancouver-Calgary single-track corridor of Canadian Pacific. We then show that the SIMTRAS algorithm is very efficient and provides schedules of a quality that is comparable to those of an exact optimization algorithm, in tens of seconds for up to 30 trains/day over a planning period of 60 days.
On the Development and Implementation of Scalable Models of Long Tracks for the Rapid Computation of Transient Response and Dynamic Interaction of Train-Track Systems due to High Speed and Freight Train Traffic
Authors: Leon L. , Rizos D. C.
Published: June 2014

In continuation of the authors’ previous published work, this paper presents improved models of relatively long railway tracks and discusses the new studies on their development and implementation. The proposed models address the through-the-soil interaction of ties in a long track segment and capture the traveling wave effects on ties located long distances from a loaded tie. These models are very computationally efficient, since they are expressed in a closed solution form. They are also very accurate and capture all the dynamic characteristics of the physical problem (e.g. frequency content), since they represent scaled characteristics responses of a reference response that is computed through rigorous analytical procedures. It is noted that the proposed models are developed for all vibration modes of ties due to wave propagation in linear, isotropic and homogeneous media. The models are verified through comparisons with other BEM solutions, and the accuracy and efficiency are established. Implementation of the proposed modes is demonstrated through a study on the critical train velocity and the effects on the system’s vibration response are quantified and discussed.
A Sport Federation’s Attempt to Restructure a Coach Education Program Using Constructivist Principles
Authors: Paquette Kyle J. , Hussain Aman , Trudel Pierre , Camiré Martin
Published: June 2014

Building on Hussain et al.’s (2012) analysis of Triathlon Canada’s constructivist-informed coach education program from the perspective of the program designer, this case study explored the structure and initial implementation of the program, as well as coaches’ perspectives of their journey to certification. Through a series of document analyses and interviews with the inaugural group of coach participants (N = 4), strategies for the application of constructivist principles are presented and discussed in relation to the coaches’ perspectives and coach development literature. More specifically, through its innovative use of learning activities and formative evaluation and assessment strategies, the program is shown to place considerable emphasis on coaches’ biographies, refection, and representation of learning. Finally, recommendations for coach educators are presented.
The Authentic Coaching Model: A Grounded Theory of Coaching
Authors: Barnson Steven C.
Published: June 2014

The purpose of this research was to: (a) describe the coaching process using language that is meaningful for practicing coaches; (b) explain how different coaches maneuver through the process of coaching; and (c) probe the paradoxical nature of the coaching process. Data gathered over a 6-month period with eight high school team sport coaches in the United States representing six different sport contexts, revealed three foundational paradoxes. Based on the results, coaching is best viewed as the convergence of three paradoxical forces: the paradox of authenticity, the paradox of purpose, and the pendulum paradox. The paper closes with the suggested definition of sports coaching: Coaching is the process of utilizing an intentional philosophic approach to simultaneously teach, motivate, and organize an athlete to attain higher levels of success over time.
Store-Operated Calcium Entry Promotes the Degradation of the Transcription Factor Sp4 in Resting Neurons
Authors: Lalonde Jasmin , Saia Gregory , Gill Grace
Published: June 2014

Resting neurons use a specific calcium influx pathway to actively control transcription factor function.
Science Signaling
Podcast: 3 June 2014
Authors: Earley Scott , VanHook Annalisa M.
Published: June 2014

A pressure-sensitive signaling pathway maintains constant blood flow to the brain.
High-Definition View of the Synapse
Authors: Hurtley Stella M.
Published: June 2014

A model of the “average” synapse shows ~300,000 proteins and all organelles in the correct copy numbers, sizes, and positions.
Intravitreal Injection of the Chimeric Phage Endolysin Ply187 Protects Mice from Staphylococcus aureus Endophthalmitis
Authors: Singh Pawan Kumar , Donovan David M. , Kumar Ashok
Published: June 2014

The treatment of endophthalmitis is becoming very challenging due to the emergence of multidrug-resistant bacteria. Hence, the development of novel therapeutic alternatives for ocular use is essential. Here, we evaluated the therapeutic potential of Ply187AN-KSH3b, a chimeric phage endolysin derived from the Ply187 prophage, in a mouse model of
Staphylococcus aureus
endophthalmitis. Our data showed that the chimeric Ply187 endolysin exhibited strong antimicrobial activity against both methicillin-sensitive
S. aureus
and methicillin-resistant
S. aureus
(MRSA) strains, as evidenced by MIC determinations, reductions in turbidity, and disruption of biofilms. Moreover, exposure of
S. aureus
to Ply187 for up to 10 generations did not lead to resistance development. The intravitreal injection of chimeric Ply187 (at 6 or 12 h postinfection) significantly improved the outcome of endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinogram analysis. Furthermore, phage lysin treatment significantly reduced the bacterial burden and the levels of inflammatory cytokines and neutrophil infiltration in the eyes. These results indicate that the intravitreal administration of a phage lytic enzyme attenuates the development of bacterial endophthalmitis in mice. To the best of our knowledge, this is the first study demonstrating the therapeutic use of phage-based antimicrobials in ocular infections.
Population-Based Cohort Study of Anti-Infective Medication Use before and after the Onset of Type 1 Diabetes in Children and Adolescents
Authors: Fazeli Farsani Soulmaz , Souverein Patrick C. , van der Vorst Marja M. J. , Knibbe Catherijne A. J. , de Boer Anthonius , Mantel-Teeuwisse Aukje K.
Published: June 2014

A population-based cohort study was conducted in the Dutch PHARMO database to investigate prevalence and patterns of anti-infective medication use in children and adolescents with type 1 diabetes (T1D) before and after the onset of this disease. All patients <19 years with at least 2 insulin prescriptions (1999 to 2009) were identified (T1D cohort) and compared with an age- and sex-matched (ratio: 1 up to 4) diabetes-free reference group. The prevalence and average number of anti-infective use was studied from (up to) 8 years before until a maximum of 4 years after the onset of T1D. A total of 925 patients with T1D and 3,591 children and adolescents in the reference cohort (51% boys, mean age of 10.1 [standard deviation, 4.5] years) were included. The overall prevalence of anti-infective use (62.6 compared to 52.6%,
P
< 0.001) and average number of prescriptions (2.71 compared to 1.42 per child,
P
< 0.001) in the T1D cohort were significantly higher than those in the reference cohort after the onset of diabetes. This pattern was consistent across sex and age categories and already observed in the year before the onset of type 1 diabetes. Patients in the T1D cohort received more antibacterials (49.8 compared to 40%,
P
< 0.001), antimycotics (4.0 compared to 1.3%,
P
< 0.001), antivirals (2.5 compared to 0.4%,
P
< 0.001), and second-line antibiotics, such as aminoglycosides, quinolones, and third-generation cephalosporins and carbapenems. Our findings that elevated anti-infective use in the T1D cohort exists in the period before the onset of type 1 diabetes and the consumption of more second-line anti-infective compounds in this time period warrant further research.
Pyocyanin Stimulates Quorum Sensing-Mediated Tolerance to Oxidative Stress and Increases Persister Cell Populations in Acinetobacter baumannii
Authors: Bhargava Nidhi , Sharma Prince , Capalash Neena
Published: June 2014

Acinetobacter baumannii
and
Pseudomonas aeruginosa
are nosocomial pathogens with overlapping sites of infection. This work reports that the two can coexist stably in mixed-culture biofilms. In a study intended to improve our understanding of the mechanism of their coexistence, it was found that pyocyanin, produced by
P. aeruginosa
that generally eliminates competition from other pathogens, led to the generation of reactive oxygen species (ROS) in
A. baumannii
cells, which in response showed a significant (
P
≤ 0.05) increase in production of enzymes, specifically, catalase and superoxide dismutase (SOD). This work shows for the first time that the expression of catalase and SOD is under the control of a quorum-sensing system in
A. baumannii
. In support of this observation, a quorum-sensing mutant of
A. baumannii
(
abaI
::Km) was found to be sensitive to pyocyanin compared to its wild type and showed significantly (
P
≤ 0.001) lower levels of the antioxidant enzymes, which increased on addition of 5 μM
N
-(3-hydroxydodecanoyl)-
l
-homoserine lactone. Likewise, in wild-type
A. baumannii
, there was a significant (
P
< 0.01) decrease in the level of anti-oxidant enzymes in the presence of salicylic acid, a known quencher of quorum sensing. In the presence of amikacin and carbenicillin,
A. baumannii
formed 0.07 and 0.02% persister cells, which increased 4- and 3-fold, respectively, in the presence of pyocyanin. These findings show that pyocyanin induces a protective mechanism in
A. baumannii
against oxidative stress and also increases its persistence against antibiotics which could be of clinical significance in the case of coinfections with
A. baumannii
and
P. aeruginosa
.
Morphogenesis Is Not Required for Candida albicans-Staphylococcus aureus Intra-Abdominal Infection-Mediated Dissemination and Lethal Sepsis
Authors: Nash Evelyn E. , Peters Brian M. , Palmer Glen E. , Fidel Paul L. , Noverr Mairi C.
Published: June 2014

Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An established experimental mouse model of
Staphylococcus aureus
-
Candida albicans
intra-abdominal infection results in ∼60% mortality within 48 h postinoculation, concomitant with amplified local inflammatory responses, while monomicrobial infections are avirulent. The purpose of this study was to characterize early local and systemic innate responses during coinfection and determine the role of
C. albicans
morphogenesis in lethality, a trait involved in virulence and physical interaction with
S. aureus
. Local and systemic proinflammatory cytokines were significantly elevated during coinfection at early time points (4 to 12 h) compared to those in monoinfection. In contrast, microbial burdens in the organs and peritoneal lavage fluid were similar between mono- and coinfected animals through 24 h, as was peritoneal neutrophil infiltration. After optimizing the model for 100% mortality within 48 h, using 3.5 × 10
7
C. albicans
(5× increase), coinfection with
C. albicans
yeast-locked or hypha-locked mutants showed similar mortality, dissemination, and local and systemic inflammation to the isogenic control. However, coinfection with the yeast-locked
C. albicans
mutant given intravenously (i.v.) and
S. aureus
given intraperitoneally (i.p.) failed to induce mortality. These results suggest a unique intra-abdominal interaction between the host and
C. albicans-S. aureus
that results in strong inflammatory responses, dissemination, and lethal sepsis, independent of
C. albicans
morphogenesis.
A Specific Polymorphism in Mycobacterium tuberculosis H37Rv Causes Differential ESAT-6 Expression and Identifies WhiB6 as a Novel ESX-1 Component
Authors: Solans Luis , Aguiló Nacho , Samper Sofía , Pawlik Alexandre , Frigui Wafa , Martín Carlos , Brosch Roland , Gonzalo-Asensio Jesús
Published: June 2014

The ESX-1 secreted virulence factor ESAT-6 is one of the major and most well-studied virulence factors ofMycobacterium tuberculosis, given that its inactivation severely attenuates virulent mycobacteria. In this work, we show that clinical isolates ofM. tuberculosisproduce and secrete larger amounts of ESAT-6 than the widely usedM. tuberculosisH37Rv laboratory strain. A search for the genetic polymorphisms underlying this observation showed thatwhiB6(rv3862c), a gene upstream of the ESX-1 genetic locus that has not previously been found to be implicated in the regulation of the ESX-1 secretory apparatus, presents a unique single nucleotide insertion in its promoter region in strains H37Rv and H37Ra. This polymorphism is not present in any of the other publicly availableM. tuberculosiscomplex genomes or in any of the 76 clinicalM. tuberculosisisolates analyzed in our laboratory. We demonstrate that in consequence, the virulence master regulator PhoP downregulateswhiB6expression in H37Rv, while it upregulates its expression in clinical strains. Importantly, reintroduction of the wild-type (WT) copy ofwhiB6in H37Rv restored ESAT-6 production and secretion to the level of clinical strains. Hence, we provide clear evidence that inM. tuberculosis—with the exception of the H37Rv strain—ESX-1 expression is regulated by WhiB6 as part of the PhoP regulon, which adds another level of complexity to the regulation of ESAT-6 secretion with a potential role in virulence adaptation.
Exposure to Bacillus anthracis Capsule Results in Suppression of Human Monocyte-Derived Dendritic Cells
Authors: Jelacic Tanya M. , Chabot Donald J. , Bozue Joel A. , Tobery Steven A. , West Michael W. , Moody Krishna , Yang De , Oppenheim Joost J. , Friedlander Arthur M.
Published: June 2014

The antiphagocytic capsule ofBacillus anthracisis a major virulence factor. We hypothesized that it may also mediate virulence through inhibition of the host's immune responses. During an infection, the capsule exists attached to the bacterial surface but also free in the host tissues. We sought to examine the impact of free capsule by assessing its effects on human monocytes and immature dendritic cells (iDCs). Human monocytes were differentiated into iDCs by interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) over 7 days in the presence of capsule derived from wild-type encapsulatedB. anthracisAmes (WT) or a control preparation from an isogenicB. anthracisAmes strain that produces only 2% of the capsule of the WT (capAmutant). WT capsule consistently induced release of IL-8 and IL-6 while thecapAmutant control preparation elicited either no response or only a minimal release of IL-8. iDCs that were differentiated in the presence of WT capsule had increased side scatter (SSC), a measure of cellular complexity, when assessed by flow cytometry. iDCs differentiated in the presence of WT capsule also matured less well in response to subsequentB. anthracispeptidoglycan (Ba PGN) exposure, with reduced upregulation of the chemokine receptor CCR7, reduced CCR7-dependent chemotaxis, and reduced release of certain cytokines. Exposure of naive differentiated control iDCs to WT capsule did not alter cell surface marker expression but did elicit IL-8. These results indicate that free capsule may contribute to the pathogenesis of anthrax by suppressing the responses of immune cells and interfering with the maturation of iDCs.
Analysis of the Arabinose-5-Phosphate Isomerase of Bacteroides fragilis Provides Insight into Regulation of Single-Domain Arabinose Phosphate Isomerases
Authors: Cech David , Wang Pan Fen , Holler Tod P. , Woodard Ronald W.
Published: June 2014

Arabinose-5-phosphate isomerases (APIs) catalyze the interconversion of
d
-ribulose-5-phosphate and
d
-arabinose-5-phosphate, the first step in the biosynthesis of 3-deoxy-
d
-manno-octulosonic acid (Kdo), an essential component of the lipopolysaccharide in Gram-negative bacteria. Classical APIs, such as
Escherichia coli
KdsD, contain a sugar isomerase domain and a tandem cystathionine beta-synthase domain. Despite substantial effort, little is known about structure-function relationships in these APIs. We recently reported an API containing only a sugar isomerase domain. This protein, c3406 from
E. coli
CFT073, has no known physiological function. In this study, we investigated a putative single-domain API from the anaerobic Gram-negative bacterium
Bacteroides fragilis
. This putative API (UniProt ID
Q5LIW1
) is the only protein encoded by the
B. fragilis
genome with significant identity to any known API, suggesting that it is responsible for lipopolysaccharide biosynthesis in
B. fragilis
. We tested this hypothesis by preparing recombinant
Q5LIW1
protein (here referred to by the UniProt ID
Q5LIW1
), characterizing its API activity
in vitro
, and demonstrating that the gene encoding
Q5LIW1
(GenBank ID
YP_209877.1
) was able to complement an API-deficient
E. coli
strain. We demonstrated that
Q5LIW1
is inhibited by cytidine 5′-monophospho-3-deoxy-
d
-
manno
-2-octulosonic acid, the final product of the Kdo biosynthesis pathway, with a

K
i

of 1.91 μM. These results support the assertion that
Q5LIW1
is the API that supports lipopolysaccharide biosynthesis in
B. fragilis
and is subject to feedback regulation by CMP-Kdo. The sugar isomerase domain of
E. coli
KdsD, lacking the two cystathionine beta-synthase domains, demonstrated API activity and was further characterized. These results suggest that
Q5LIW1
may be a suitable system to study API structure-function relationships.
The first report of a Chinese family with McLeod syndrome
Authors: Man Bik Ling , Yuen Yuet Ping , Fu Yat Pang
Published: June 2014

We report the first case of a Chinese family with McLeod syndrome (MLS). The two affected brothers show significant phenotypic heterogeneity. The index case has peripheral acanthocytosis, choreoathetosis of his feet, a slowly progressive neuropathy and myopathy, and an elevated serum creatine kinase (CK) level. His elder brother has more prominent chorea of the shoulders, epilepsy, a rapidly progressive neuropathy and normal serum CK. The diagnosis of MLS was confirmed by a genetic test which showed a hemizygous frameshift mutation in theXKgene.
Refractory nausea and vomiting in the setting of well-controlled idiopathic intracranial hypertension
Authors: Barnett Dennis L , Rosenbaum Rachel A , Diaz Jonathan R
Published: June 2014

A 27-year-old woman with a history of recurrent nausea and vomiting in the setting of idiopathic intracranial hypertension (IIH) was admitted for control of unremitting nausea and vomiting. Initial antiemetic therapy included optimisation of IIH therapy by titrating acetazolamide, in addition to using ondansetron and metoclopramide as needed, with minimal relief. She was ultimately treated with palonosetron with complete resolution of her acute nausea. Nausea, often treated with 5-hydroxytryptamine (5-HT3) receptor antagonists, approved for perioperative and chemotherapy-induced nausea, are used off-label to treat nausea and vomiting outside of those settings. The efficacy of different regimens has been compared in the literature and continues to remain controversial. When choosing from different 5-HT3 antagonists there are other considerations, in addition to efficacy to consider: dosing schedule, half-life, time of onset, duration and cost-to-benefit ratio, and although one 5-HT3 antagonist may not have been effective, another one may be. In our case palonosetron, with a significantly longer half-life than other 5-HT3 antagonists, was effective in resolving nausea when compared with the more commonly used ondansetron.
Surgery and radiation therapy for brain metastases from classic biphasic pulmonary blastoma
Authors: Kawasaki Kenta , Yamamoto Kuniatsu , Suzuki Yoshio , Saito Hirohisa
Published: June 2014

Pulmonary blastoma, a rare malignant lung tumour, can metastasise to the brain. However, there is no evidence for any effective treatment. The aim of this report is to discuss the treatment options for pulmonary blastoma and confirm the necessity for a pathological diagnosis. A 75-year-old man was admitted with progressive right-sided hemiplegia and aphasia. MRI showed multiple brain tumours. A left frontal lobe lesion was surgically resected, after which he underwent whole brain radiation (30 Gy/10 fractions). He died of an acute exacerbation of interstitial pneumonia. On performing autopsy, partial responses in the brain metastases that had been irradiated were confirmed pathologically. Thus, we present pathological confirmation that surgery and radiation therapy have therapeutic effects on brain metastases from pulmonary blastoma.
Impact of lifetime opioid exposure on arterial stiffness and vascular age: cross-sectional and longitudinal studies in men and women
Authors: Reece Albert Stuart , Hulse Gary Kenneth
Published: June 2014

Objective

To characterise and compare the potentiation of arterial stiffness and vascular ageing by opioids in men and women.

Design

Cross-sectional and longitudinal studies of 576 clinical controls and 687 opioid-dependent patients (ODP) on 710 and 1305 occasions, respectively, over a total of 2382 days (6.52 years), 2006–2011. Methodology Radial pulse wave analysis with Atcor SphygmoCor system (Sydney).

Setting

Primary care.

Participants

Controls: General practice patients with non-cardiovascular disorders, and university student controls.ODP: Patients undergoing clinical management of their opioid dependence. Controls had lower chronological ages (CAs) than ODP (30.0±0.5 vs 34.5±0.3, mean±SEM, p<0.0001). 69.6% and 67.7% participants were men, and 16% and 92.3% were smokers (p<0.0001) for controls and ODP, respectively. 86.3%, 10.3% and 3.4% of ODP were treated with buprenorphine (6.98±0.21 mg), methadone (63.04±4.01 mg) or implant naltrexone, respectively. Body mass index (BMI) was depressed in ODP.

Interventions

Nil.

Primary outcome measures

Vascular Reference Age (RA) and the ratio of vascular age to chronological age (RA/CA).

Secondary outcome measures

Arterial stiffness including Augmentation Index.

Results

After BMI adjustment, RA in ODP was higher as a function of CA and of time (both p<0.05). Modelled mean RA in control and ODP was 35.6 and 36.3 years (+1.97%) in men, and 34.5 and 39.2 years (+13.43%) in women, respectively. Changes in RA and major arterial stiffness indices were worse in women both as a factor (p = 0.0036) and in interaction with CA (p = 0.0040). Quadratic, cubic and quartic functions of opioid exposure duration outperformed linear models with RA/CA over CA and over time. The opioid dose–response relationship persisted longitudinally after multiple adjustments from p=0.0013 in men and p=0.0073 in women.

Conclusions

Data show that lifetime opioid exposure, an interactive cardiovascular risk factor, particularly in women, is related to linear, quadratic, cubic and quartic functions of treatment duration and is consistent with other literature of accelerated ageing in patients with OD.
Controlled rehabilitative and supportive care intervention trials in patients with high-grade gliomas and their caregivers: a systematic review
Authors: Piil K , Juhler M , Jakobsen J , Jarden M
Published: June 2014

Background

Patients diagnosed with high-grade gliomas experience a varying and complex symptom burden, and face a high mortality rate. As a consequence, patients with high-grade gliomas and their caregivers have imminent and changing rehabilitative and supportive care needs.

Objectives

To give a detailed overview of non-pharmacological rehabilitative and supportive care interventions for patients with high-grade gliomas and/or their caregivers, and provide an appraisal of the methodological quality of these studies.

Method

PubMed, Cumulative Index of Nursing and Allied Health Literature and Embase were searched for literature published from 1995 to May 2013. Data from eight studies were reviewed for substantive methods and results. Methodological quality was described and assessed using the scoring system for appraising mixed methods research and concomitantly appraising qualitative, quantitative and mixed methods primary studies in mixed study reviews.

Results

The search yielded 914 unique publications, of which 9 were classified eligible for this review. There is preliminary evidence that cognitive group therapy improves memory skills in patients with high-grade gliomas, early physical training improves functional outcome and massage therapy reduces stress. Patients and caregivers found that telephone follow-up and a specialist nurse function was an effective and useful way to achieve information and support. Finally, psycho-education increased feelings of mastery among caregivers.

Conclusions

As evidence is beginning to emerge, there is a need for well-designed longitudinal and randomised controlled trials of non-pharmacological interventions in high-grade glioma patients and their caregivers in order to develop clinical guidelines for supportive and rehabilitative approaches in this unique population.
Impact of national culture on knowledge sharing in international construction projects
Authors: Kivrak Serkan , Arslan Gokhan , Tuncan Mustafa , Birgonul M. Talat
Published: June 2014

International construction projects generally involve participants from different cultural backgrounds. In this type of projects, national culture can significantly influence knowledge sharing between individuals. This research contributes to the literature by providing a deeper understanding of cultural issues that influence knowledge sharing in international construction projects. The research was carried out in three international construction joint ventures located in Qatar, Libya, and Bulgaria. A mixed method design was used to better understand the research problem and strengthen the findings. The findings are interpreted through the cultural dimensions of Hofstede and Hall. Based on the analysis, language and communication difficulties, trust, motivation, and personal relationships were found as the critical barriers to successful knowledge sharing in multicultural project teams. Findings from this study can help managers to better understand the role of national culture in knowledge sharing in the context of improving project performance.
bta-miR-29b attenuates apoptosis by directly targeting caspase-7 and NAIF1 and suppresses bovine viral diarrhea virus replication in MDBK cells
Authors: Fu Qiang , Shi Huijun , Shi Mengting , Meng Luping , Zhang Hui , Ren Yan , Guo Fei , Jia Bin , Wang Pengyan , Ni Wei , Chen Chuangfu
Published: June 2014

MicroRNAs (miRNAs) are small, endogenous, noncoding RNA molecules that serve as powerful regulators of multiple cellular processes, including apoptosis, differentiation, growth, and proliferation. Bovine viral diarrhea virus (BVDV) contributes significantly to health-related economic losses in the beef and dairy industries. Although BVDV-induced apoptosis correlates with increased intracellular viral RNA accumulation and with bta-miR-29b (miR-29b) expression upregulation in Madin–Darby bovine kidney (MDBK) cells infected with BVDV strain NADL, the role of miR-29b in regulating BVDV-infection-related apoptosis remains unexplored. Here, we report that miR-29b serves as a new miRNA regulating apoptosis. We showed that miR-29b target sequences were present in the 3′ untranslated regions of 2 key apoptosis regulators mRNAs, cysteine aspartases-7 (caspase-7) and nuclear apoptosis-inducing factor 1 (NAIF1). Indeed, upon miRNA overexpression, both mRNA and protein levels of caspase-7 and NAIF1 were decreased. We further found that miR-29b attenuated apoptosis by directly regulating intracellular levels of caspase-7 and NAIF1. Moreover, apoptosis blockage by miR-29b was rescued upon co-infection of MDBK cells with lentiviruses expressing caspase-7 and NAIF1. Importantly, miR-29b decreased BVDV NADL envelope glycoprotein E1 mRNA levels and suppressed viral replication. These studies advance our understanding of the mechanisms of miRNAs in mediating the cells combating viral infections.
A BEST POSSIBLE ONLINE ALGORITHM FOR SCHEDULING TO MINIMIZE MAXIMUM FLOW-TIME ON BOUNDED BATCH MACHINES
Authors: JIAO CHENGWEN , LI WENHUA , YUAN JINJIANG
Published: June 2014

We consider online scheduling of unit length jobs on m identical parallel-batch machines. Jobs arrive over time. The objective is to minimize maximum flow-time, with the flow-time of a job being the difference of its completion time and its release time. A parallel-batch machine can handle up to b jobs simultaneously as a batch. Here, the batch capacity is bounded, that is b < ∞. In this paper, we provide a best possible online algorithm for the problem with a competitive ratio of [Formula: see text].
Stripe phases in a frustrated spin-1/2 dimer Heisenberg model
Authors: Guo L.-F. , Chen Q.-H. , Li P.
Published: June 2014

We use a bond-operator mean-field theory and a generalized spin-wave theory to study the frustrated spin-1/2 dimer Heisenberg model on a square lattice with frustrations in both cardinal and corner directions. We establish the ground state phase diagram with very rich phases. It has been disclosed that the frustrations in cardinal directions can induce exotic superfluid (SF) and supersolid (SS) phases. By introducing the frustrations in corner directions, we found more interesting phases, such as the striped superfluid (S-SF) and the striped supersolid (S-SS). We also investigate the excitation spectra and analyze the anisotropic spin-wave velocities of the stripe phases.
Breaking a magnetic zero locus: Asymptotic analysis
Authors: Raymond N.
Published: June 2014

This paper deals with the spectral analysis of the Laplacian in the presence of a magnetic field vanishing along a broken line. Denoting by θ the breaking angle, we prove complete asymptotic expansions of all the lowest eigenpairs when θ goes to 0. The investigation strongly uses a coherent state decomposition and a microlocal analysis of the eigenfunctions.