bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empirical Modeling of a Rail Tank Car for Struck Coupler Force Estimation
Authors: Hopkins Brad M. , Maraini Dan , Seidel Andrew , Shahidi Parham 
Published: June 2014

Freight rail cars may experience high input forces during a coupling event, which could potentially cause damage to the car body and/or lading. The AAR recommended practice states that cars should not be coupled at speeds greater than 4 mph. However, this recommendation is not always followed and cars are often coupled at much higher speeds. As a result, accelerometers on the car body are sometimes used to monitor impact events. Threshold levels may be set to determine if an over-speed or high-force impact event has occurred. However, a single acceleration value can be difficult to interpret because its relationship to impact force is dependent on many factors, including car type, end-of-car device type, lading type, and loading condition. Dynamic modeling and parametric studies may be used to determine these relationships which can be applied in practice.
This paper presents a study on the relationship between struck coupler force and car body acceleration for a series of impacts on a tank car in both loaded and unloaded states. For the loaded condition, the tank was filled with water. The simplest change from an unloaded tank to a loaded tank is the decrease in acceleration for a given force due to the added mass. However, there is additional complexity added to the system due to the sloshing liquid inside the tank. When attempting to model this dynamic system there is added uncertainty in struck coupler force estimation because of the non-linearity in low frequency car body oscillations. Several example data sets are presented in the time and frequency domains to illustrate this point. The data is then used to generate an empirical model using system identification techniques. The results show that the proposed model offers improved characterization of the system as compared to conventional techniques by accounting for the uncertainties introduced by the sloshing liquid in the tank. The proposed technique is computationally efficient and can potentially be implemented in real time. The model is used to estimate struck coupler force and is validated with real data.
Rail Highway Grade Crossing Roughness Quantitative Measurement Using 3D Technology
Authors: Wang Teng (Alex) , Souleyrette Reginald R. , Lau Daniel , Xu Peng 
Published: June 2014

Quality of surface is an important aspect affecting both the safety and the performance of at-grade rail-highway crossings. Roughness may increase the risk of crashes for both trains and automobiles. Varying grades in crossing profiles increase the likelihood of high-centered crossing collisions between train and truck [1]. The US DOT Railroad Highway Grade Crossing Handbook [2] suggests that rough surfaces could distract a driver’s attention from oncoming trains and that the unevenness of the crossing could result in a driver losing control of their vehicle resulting in a crash.
No quantitative method currently exists to quickly and economically assess the condition of rail crossings in order to evaluate the long term performance of crossings and set a quantitative trigger for their rehabilitation. The conventional method to measure the surface of quality of crossings is based on expert judgment, whereby crossing surfaces are classified as poor, fair or good after an inspector visits and drives over the crossing. However, actual condition of the crossing could be different from the subjective rating. Poor condition rating crossings may not always present the most cost-effective locations for preventive maintenance to lower overall life-cycle costs. Conventional ratings may derive from driving a passenger car of pickup once over the crossing. Effects of various speed, on various vehicles (suspension), and at various places (laterally) cannot be determined or even estimated except at the smoothest of crossings. A quantifiable and extensible procedure is desired.
With rapid advances in computer science, 3D sensing and imaging technologies, it seems logical that a cost-effective quantitative method could be developed to determine the need to rehabilitate rail crossings and assess long term performance. Fundamental to the quantification of crossing condition is the acquisition of an accurate 3D surface model of the crossing in its present state. This paper reports on the development of an accurate, low cost and readily deployable sensor capable of rapid collection of this 3D surface. The research is seen as a first step towards automating the crossing inspection process, ultimately leading to the quantification and estimation of future performance of rail crossing.
A Variable No-Load Voltage Scheme for Improving Energy Efficiency in DC-Electrified Mass Transit Systems
Authors: López-López Álvaro J. , Abrahamsson Lars , Pecharromán Ramón R. , Fernández-Cardador Antonio , Cucala Paloma , Östlund Stefan , Söder Lennart 
Published: June 2014

Railway mass transit systems like subways play a fundamental role in the concept of sustainable cities. In these systems, the amount of passengers strongly fluctuates along the day. Hence, in order to provide a proper service without incurring disproportionate energy consumption, operation at different traffic densities is required.
The majority of underground systems are DC-electrified. Standard DC voltages in railway systems are low for historical and safety reasons. In the rush hours, the large number of trains demanding power of the system may lead to overloaded substations and voltage dips. This problem is partially mitigated by means of substation-transformer tap regulation, which allows operators to increase the no-load voltage.
High no-load voltage has a beneficial effect at all traffic-density scenarios in terms of transmission losses. However, at the same time it effectively reduces the system’s capacity to absorb regenerated energy, which may lead to inefficient energy consumption figures during off-peak hours.
In this paper, the sensitivity of system energy consumption to no-load voltage has been analyzed. Several traffic-density scenarios in a case-study system are explored. As a result, a scheduled no-load voltage scheme is proposed for the operation of the system. This operation strategy improves energy efficiency without incurring a high investment cost. The only costs related to this proposed method are the costs of wear-and-tear in tap-changers. In case there are devices such as energy storage systems installed in the system, there would be additional operation costs related to a simultaneous update of the voltage limits for their operation.
Techniques for Evaluating and Improving the Operational Efficiency of Positive Train Control Braking Enforcement Algorithms
Authors: Brosseau Joe 
Published: June 2014

Software algorithms are used in Positive Train Control (PTC) systems to predict train stopping distance and to enforce a penalty brake application. These algorithms have been shown to be overly conservative, leading to operational inefficiencies by interfering with normal train operations. A braking enforcement algorithm that can safely stop trains to prevent authority and speed limit violations without impacting existing railroad operations is critical to successful widespread implementation of PTC.
Due to operational issues observed with early PTC braking enforcement algorithms, a number of techniques are proposed and evaluated to improve the operational efficiency of these algorithms, with emphasis on applicability to PTC systems currently being implemented. Transportation Technology Center, Inc. (TTCI) is employing a new methodology for evaluation of braking algorithms that uses Monte Carlo simulation techniques to statistically evaluate the performance of the algorithm, with limited need for field testing to verify the simulation results. In the Monte Carlo process, computer simulations are run repeatedly using randomly selected input values to predict the resulting probability distribution of stopping locations. The method provides a higher level of confidence in algorithm performance with reduced time and cost compared to traditional methods, which rely heavily on field testing. For freight trains, the method utilizes a detailed train dynamics simulation model previously developed and validated by the Association of American Railroads (AAR). For passenger trains, TTCI is developing and validating a new model capable of simulating brake systems and components specific to passenger and commuter equipment.
New methods for addressing operational efficiency of braking algorithms focus on improving the accuracy of stopping distance prediction and reducing the potential variation from the prediction. Techniques investigated by TTCI include adaptive functions, which measure train braking performance en route and adapt the algorithm to these characteristics; emergency brake backup, which uses feedback following a penalty application to determine if additional emergency braking is required to stop the train short of the target; an improved target offset function, which relies on statistical multi-variable regression of thousands of stopping distance simulations; and including information about dynamic braking effort in the stopping distance prediction. Results from TTCI’s investigations show potential to reduce the operational impact, by demonstrating the probability of stopping excessively short of the target is significantly less than that of previous algorithms. The techniques are already being adopted by PTC onboard suppliers for the largest North American railroads, and many are applicable to railways worldwide.
Studies on the Antileishmanial Mechanism of Action of the Arylimidamide DB766: Azole Interactions and Role of CYP5122A1
Authors: Pandharkar Trupti , Zhu Xiaohua , Mathur Radhika , Jiang Jinmai , Schmittgen Thomas D. , Shaha Chandrima , Werbovetz Karl A. 
Published: June 2014

ABSTRACT

Arylimidamides (AIAs) are inspired by diamidine antimicrobials but show superior activity against intracellular parasites. The AIA DB766 {2,5-bis[2-(2-
i
-propoxy)-4-(2-pyridylimino)aminophenyl]furan hydrochloride} displays outstanding potency against intracellular
Leishmania
parasites and is effective in murine and hamster models of visceral leishmaniasis when given orally, but its mechanism of action is unknown. In this study, through the use of continuous DB766 pressure, we raised
Leishmania donovani
axenic amastigotes that displayed 12-fold resistance to this compound. These DB766-resistant (DB766R) parasites were 2-fold more sensitive to miltefosine than wild-type organisms and were hypersensitive to the sterol 14α-demethylase (CYP51) inhibitors ketoconazole and posaconazole (2,000-fold more sensitive and over 12,000-fold more sensitive than the wild type, respectively). Western blot analysis of DB766R parasites indicated that while expression of CYP51 is slightly increased in these organisms, expression of CYP5122A1, a recently identified cytochrome P450 associated with ergosterol metabolism in
Leishmania
, is dramatically reduced in DB766R parasites.
In vitro
susceptibility assays demonstrated that CYP5122A1 half-knockout
L. donovani
promastigotes were significantly less susceptible to DB766 and more susceptible to ketoconazole than their wild-type counterparts, consistent with observations in DB766R parasites. Further, DB766-posaconazole combinations displayed synergistic activity in both axenic and intracellular
L. donovani
amastigotes. Taken together, these studies implicate CYP5122A1 in the antileishmanial action of the AIAs and suggest that DB766-azole combinations are potential candidates for the development of synergistic antileishmanial therapy.
Complete Sequencing of IncI1 Sequence Type 2 Plasmid pJIE512b Indicates Mobilization of
bla
CMY-2
from an IncA/C Plasmid
Authors: Tagg Kaitlin A. , Iredell Jonathan R. , Partridge Sally R. 
Published: June 2014

ABSTRACT

Sequencing of pJIE512b, a 92.3-kb IncI1 sequence type 2 (ST2) plasmid carrying
bla
CMY-2
, revealed a
bla
CMY-2
context that appeared to have been mobilized from an IncA/C plasmid by the insertion sequence IS
1294
. A comparison with published plasmids suggests that
bla
CMY-2
has been mobilized from IncA/C to IncI1 plasmids more than once by IS
1294
-like elements. Alignment of pJIE512b with the only other available IncI1 ST2 plasmid revealed differences across the backbones, indicating variability within this sequence type.
Preclinical Studies of Amixicile, a Systemic Therapeutic Developed for Treatment of Clostridium difficile Infections That Also Shows Efficacy against Helicobacter pylori
Authors: Hoffman Paul S. , Bruce Alexandra M. , Olekhnovich Igor , Warren Cirle A. , Burgess Stacey L. , Hontecillas Raquel , Viladomiu Monica , Bassaganya-Riera Josep , Guerrant Richard L. , Macdonald Timothy L. 
Published: June 2014

ABSTRACT

Amixicile shows efficacy in the treatment of
Clostridium difficile
infections (CDI) in a mouse model, with no recurrence of CDI. Since amixicile selectively inhibits the action of a B vitamin (thiamine pyrophosphate) cofactor of pyruvate:ferredoxin oxidoreductase (PFOR), it may both escape mutation-based drug resistance and spare beneficial probiotic gut bacteria that do not express this enzyme. Amixicile is a water-soluble derivative of nitazoxanide (NTZ), an antiparasitic therapeutic that also shows efficacy against CDI in humans. In comparative studies, amixicile showed no toxicity to hepatocytes at 200 μM (NTZ was toxic above 10 μM); was not metabolized by human, dog, or rat liver microsomes; showed equivalence or superiority to NTZ in cytochrome P450 assays; and did not activate efflux pumps (breast cancer resistance protein, P glycoprotein). A maximum dose (300 mg/kg) of amixicile given by the oral or intraperitoneal route was well tolerated by mice and rats. Plasma exposure (rats) based on the area under the plasma concentration-time curve was 79.3 h · μg/ml (30 mg/kg dose) to 328 h · μg/ml (100 mg/kg dose), the maximum concentration of the drug in serum was 20 μg/ml, the time to the maximum concentration of the drug in serum was 0.5 to 1 h, and the half-life was 5.6 h. Amixicile did not concentrate in mouse feces or adversely affect gut populations of
Bacteroides
species,
Firmicutes
, segmented filamentous bacteria, or
Lactobacillus
species. Systemic bioavailability was demonstrated through eradication of
Helicobacter pylori
in a mouse infection model. In summary, the efficacy of amixicile in treating CDI and other infections, together with low toxicity, an absence of mutation-based drug resistance, and excellent drug metabolism and pharmacokinetic metrics, suggests a potential for broad application in the treatment of infections caused by PFOR-expressing microbial pathogens in addition to CDI.
Improved Detection of Emerging Drug-Resistant Mutant Cytomegalovirus Subpopulations by Deep Sequencing
Authors: Chou Sunwen , Ercolani Ronald J. , Sahoo Malaya K. , Lefterova Martina I. , Strasfeld Lynne M. , Pinsky Benjamin A. 
Published: June 2014

ABSTRACT
In immunosuppressed hosts, the development of multidrug resistance complicates the treatment of cytomegalovirus (CMV) infection. Improved genotypic detection of impending drug resistance may follow from recent technical advances. A severely T-cell-depleted patient with chronic lymphocytic leukemia developed CMV pneumonia and high plasma viral loads that were poorly responsive to antiviral therapy. Serial plasma specimens were analyzed for mutant viral populations by conventional and high-throughput deep-sequencing methods. Uncharacterized mutations were phenotyped for drug resistance using recombinant viruses. Conventional genotyping detected viruses with the UL97 kinase substitution C607Y after ganciclovir treatment, a transient subpopulation of UL54 polymerase L773V mutants first detected 8 weeks after foscarnet was started, and a subpopulation of a mutant with deletion of UL54 codons 981 and 982 2 months after the addition of cidofovir. Deep sequencing of the same serial specimens revealed the same UL54 mutants sooner, along with a more complex evolution of known and newly recognized mutant subpopulations missed by conventional sequencing. The UL54 exonuclease substitutions D413N, K513R, and C539G were newly shown to confer ganciclovir-cidofovir resistance, while L773V was shown to confer foscarnet resistance and add to the ganciclovir resistance conferred by UL97 C607Y. Increased sequencing depth provided a more timely and detailed diagnosis of mutant viral subpopulations that evolved with changing anti-CMV therapy.
Posaconazole Concentrations in Human Tissues after Allogeneic Stem Cell Transplantation
Authors: Blennow Ola , Eliasson Erik , Pettersson Tommy , Pohanka Anton , Szakos Attila , El-Serafi Ibrahim , Hassan Moustapha , Ringdén Olle , Mattsson Jonas 
Published: June 2014

ABSTRACT
Few data have been published regarding posaconazole tissue concentrations in humans. We analyzed tissue concentrations in biopsy specimens taken at autopsy from seven patients who received posaconazole prophylaxis because of graft-versus-host disease. The results were compared to plasma concentrations collected before death. Tissue concentrations suggestive of an accumulation of posaconazole were found in the heart, lung, liver, and kidney but not in the brain.
Role of FKS Mutations in Candida glabrata: MIC Values, Echinocandin Resistance, and Multidrug Resistance
Authors: Pham Cau D. , Iqbal Naureen , Bolden Carol B. , Kuykendall Randall J. , Harrison Lee H. , Farley Monica M. , Schaffner William , Beldavs Zintars G. , Chiller Tom M. , Park Benjamin J. , Cleveland Angela A. , Lockhart Shawn R. 
Published: June 2014

ABSTRACT

Candida glabrata
is the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of
C. glabrata
disease due to the high rate of resistance to fluconazole. Recent case reports indicate that
C. glabrata
resistance to echinocandins may be increasing. We performed susceptibility testing on 1,380 isolates of
C. glabrata
collected between 2008 and 2013 from four U.S. cities, Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and micafungin, respectively. We screened 1,032 of these isolates, including all 77 that had either a resistant or intermediate MIC value with respect to at least one echinocandin, for mutations in the hot spot regions of
FKS1
and
FKS2
, the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hot spot mutations, 16 in
FKS1
and 35 in
FKS2
. All of the isolates with an
FKS
mutation except one were resistant to at least one echinocandin by susceptibility testing. Of the isolates resistant to at least one echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among U.S.
C. glabrata
isolates is a concern, especially in light of the fact that one-third of those isolates may be multidrug resistant. Further monitoring of U.S.
C. glabrata
isolates for echinocandin resistance is warranted.
The Pseudomonas aeruginosa Diguanylate Cyclase GcbA, a Homolog of P. fluorescens GcbA, Promotes Initial Attachment to Surfaces, but Not Biofilm Formation, via Regulation of Motility
Authors: Petrova Olga E. , Cherny Kathryn E. , Sauer Karin 
Published: June 2014

ABSTRACT

Cyclic di-GMP is a conserved signaling molecule regulating the transitions between motile and sessile modes of growth in a variety of bacterial species. Recent evidence suggests that
Pseudomonas
species harbor separate intracellular pools of c-di-GMP to control different phenotypic outputs associated with motility, attachment, and biofilm formation, with multiple diguanylate cyclases (DGCs) playing distinct roles in these processes, yet little is known about the potential conservation of functional DGCs across
Pseudomonas
species. In the present study, we demonstrate that the
P. aeruginosa
homolog of the
P. fluorescens
DGC GcbA involved in promoting biofilm formation via regulation of swimming motility likewise synthesizes c-di-GMP to regulate surface attachment via modulation of motility, however, without affecting subsequent biofilm formation.
P. aeruginosa
GcbA was found to regulate flagellum-driven motility by suppressing flagellar reversal rates in a manner independent of viscosity, surface hardness, and polysaccharide production.
P. fluorescens
GcbA was found to be functional in
P. aeruginosa
and was capable of restoring phenotypes associated with inactivation of
gcbA
in
P. aeruginosa
to wild-type levels. Motility and attachment of a
gcbA
mutant strain could be restored to wild-type levels via overexpression of the small regulatory RNA RsmZ. Furthermore, epistasis analysis revealed that while both contribute to the regulation of initial surface attachment and flagellum-driven motility, GcbA and the phosphodiesterase DipA act within different signaling networks to regulate these processes. Our findings expand the complexity of c-di-GMP signaling in the regulation of the motile-sessile switch by providing yet another potential link to the Gac/Rsm network and suggesting that distinct c-di-GMP-modulating signaling pathways can regulate a single phenotypic output.
Transcription Start Site Sequence and Spacing between the −10 Region and the Start Site Affect Reiterative Transcription-Mediated Regulation of Gene Expression in Escherichia coli
Authors: Han Xiaosi , Turnbough Charles L. 
Published: June 2014

ABSTRACT

Reiterative transcription is a reaction catalyzed by RNA polymerase, in which nucleotides are repetitively added to the 3′ end of a nascent transcript due to upstream slippage of the transcript without movement of the DNA template. In
Escherichia coli
, the expression of several operons is regulated through mechanisms in which high intracellular levels of UTP promote reiterative transcription that adds extra U residues to the 3′ end of a nascent transcript during transcription initiation. Immediately following the addition of one or more extra U residues, the nascent transcripts are released from the transcription initiation complex, thereby reducing the level of gene expression. Therefore, gene expression can be regulated by internal UTP levels, which reflect the availability of external pyrimidine sources. The magnitude of gene regulation by these mechanisms varies considerably, even when control mechanisms are analogous. These variations apparently are due to differences in promoter sequences. One of the operons regulated (in part) by UTP-sensitive reiterative transcription in
E. coli
is the
carAB
operon, which encodes the first enzyme in the pyrimidine nucleotide biosynthetic pathway. In this study, we used the
carAB
operon to examine the effects of nucleotide sequence at and near the transcription start site and spacing between the start site and −10 region of the promoter on reiterative transcription and gene regulation. Our results indicate that these variables are important determinants in establishing the extent of reiterative transcription, levels of productive transcription, and range of gene regulation.