bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variable Directivity Acoustical Warning Device (AWD) as an Optimized Locomotive Horn
Authors: Nash Grant S. , Ross Jason C. , Parida Basant K. , Zaouk Abdullatif K. , Punwani Swamidas K. (John) 
Published: July 2013

It is estimated that up to 9.3 million people may be impacted by locomotive horn noise and up to 4.6 million of those may be severely impacted.1 In 2009, there were over 1,900 incidents, over 700 injuries, and over 240 fatalities at highway-rail grade crossings.2 Approximately 4,000 times per year, a train and highway vehicle collide at one of over 262,000 public and private highway-rail grade crossings in the United States. Compared to a collision between two highway vehicles, a collision with a train is eleven times more likely to result in a fatality, and five and a half times more likely to result in a disabling injury. Approximately half of all collisions occur at grade crossings that are not fully equipped with warning devices. Some of the drivers involved in these collisions may have been unaware of the approaching train.3 The National Academy of Engineering Committee on Technology for a Quieter America has indicated that the public would benefit if a train horn was more directional and has recommended that research and development be undertaken to better understand the effects on safety, with benefits to the public.4
As a part of an ongoing Federal Railroad Administration (FRA)-sponsored research and development effort, the authors have developed an Acoustical Warning Device (AWD) prototype with an overall goal of maximizing safety at a grade crossing and minimizing environmental noise pollution (at the wayside and in the cabin of a locomotive in reducing railroad worker occupational hazard noise exposure). An initial prototype was created that consisted of one acoustical element. An advanced prototype is currently being developed with three acoustical elements to provide variable directivity and steering capabilities through beamforming. A digitized horn signal has been created based on characteristics from an analog air-pressure locomotive horn. The initial AWD prototype has been analyzed for detectability and noise impact area and the directivity pattern of its sound emissions have been tested. The expected performance of the advanced three-unit prototype has been evaluated based on the test results of the initial prototype and acoustic simulation modeling.
During development of the initial AW D prototype, spectrograms, polar directivity plots, frequency response plots, 1/3-octave band plots, and LAeq measurements of the AWD propagation were analyzed to ensure proper functionality of the AWD, in accordance with FRA and QinetiQ North America’s (QNA) specifications. Based on acoustic simulation modeling, the advanced AWD prototype is expected to generate sound up to 110 dBA at 100 feet forward of the locomotive. The AWD prototype is expected to improve detectability and reduced environmental noise exposure to the community and locomotive cabin.
Variation of the Virus-Related Elements within Syntenic Genomes of the Hyperthermophilic Archaeon Aeropyrum
Authors: Daifuku Takashi , Yoshida Takashi , Kitamura Takayuki , Kawaichi Satoshi , Inoue Takahiro , Nomura Keigo , Yoshida Yui , Kuno Sotaro , Sako Yoshihiko 
Published: July 2013

ABSTRACT

The increasing number of genome sequences of archaea and bacteria show their adaptation to different environmental conditions at the genomic level.
Aeropyrum
spp. are aerobic and hyperthermophilic archaea.
Aeropyrum camini
was isolated from a deep-sea hydrothermal vent, and
Aeropyrum pernix
was isolated from a coastal solfataric vent. To investigate the adaptation strategy in each habitat, we compared the genomes of the two species. Shared genome features were a small genome size, a high GC content, and a large portion of orthologous genes (86 to 88%). The genomes also showed high synteny. These shared features may have been derived from the small number of mobile genetic elements and the lack of a RecBCD system, a recombinational enzyme complex. In addition, the specialized physiology (aerobic and hyperthermophilic) of
Aeropyrum
spp. may also contribute to the entire-genome similarity. Despite having stable genomes, interference of synteny occurred with two proviruses,
A. pernix
spindle-shaped virus 1 (APSV1) and
A. pernix
ovoid virus 1 (APOV1), and clustered regularly interspaced short palindromic repeat (CRISPR) elements. Spacer sequences derived from the
A. camini
CRISPR showed significant matches with protospacers of the two proviruses infecting
A. pernix
, indicating that
A. camini
interacted with viruses closely related to APSV1 and APOV1. Furthermore, a significant fraction of the nonorthologous genes (41 to 45%) were proviral genes or ORFans probably originating from viruses. Although the genomes of
A. camini
and
A. pernix
were conserved, we observed nonsynteny that was attributed primarily to virus-related elements. Our findings indicated that the genomic diversification of
Aeropyrum
spp. is substantially caused by viruses.
Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator
Authors: Zhang Anda , Liu Zhongle , Myers Lawrence C. 
Published: July 2013

ABSTRACT

The multisubunit eukaryotic Mediator complex integrates diverse positive and negative gene regulatory signals and transmits them to the core transcription machinery. Mutations in individual subunits within the complex can lead to decreased or increased transcription of certain subsets of genes, which are highly specific to the mutated subunit. Recent studies suggest a role for Mediator in epigenetic silencing. Using white-opaque morphological switching in
Candida albicans
as a model, we have shown that Mediator is required for the stability of both the epigenetic silenced (white) and active (opaque) states of the bistable transcription circuit driven by the master regulator Wor1. Individual deletions of eight
C. albicans
Mediator subunits have shown that different Mediator subunits have dramatically diverse effects on the directionality, frequency, and environmental induction of epigenetic switching. Among the Mediator deletion mutants analyzed, only Med12 has a steady-state transcriptional effect on the components of the Wor1 circuit that clearly corresponds to its effect on switching. The
MED16
and
MED9
genes have been found to be among a small subset of genes that are required for the stability of both the white and opaque states. Deletion of the Med3 subunit completely destabilizes the opaque state, even though the Wor1 transcription circuit is intact and can be driven by ectopic expression of Wor1. The highly impaired ability of the
med3
deletion mutant to mate, even when Wor1 expression is ectopically induced, reveals that the activation of the Wor1 circuit can be decoupled from the opaque state and one of its primary biological consequences.
Effects of Low PBP2b Levels on Cell Morphology and Peptidoglycan Composition in Streptococcus pneumoniae R6
Authors: Berg Kari Helene , Stamsås Gro Anita , Straume Daniel , Håvarstein Leiv Sigve 
Published: July 2013

ABSTRACT

Streptococcus pneumoniae
produces two class B penicillin-binding proteins, PBP2x and PBP2b, both of which are essential. It is generally assumed that PBP2x is specifically involved in septum formation, while PBP2b is dedicated to peripheral cell wall synthesis. However, little experimental evidence exists to substantiate this belief. In the present study, we obtained evidence that strongly supports the view that PBP2b is essential for peripheral peptidoglycan synthesis. Depletion of PBP2b expression gave rise to long chains of cells in which individual cells were compressed in the direction of the long axis and looked lentil shaped. This morphological change is consistent with a role for pneumococcal PBP2b in the synthesis of the lateral cell wall. Depletion of PBP2x, on the other hand, resulted in lemon-shaped and some elongated cells with a thickened midcell region. Low PBP2b levels gave rise to changes in the peptidoglycan layer that made pneumococci sensitive to exogenously added LytA during logarithmic growth and refractory to chain dispersion upon addition of LytB. Interestingly, analysis of the cell wall composition of PBP2b-depleted pneumococci revealed that they had a larger proportion of branched stem peptides in their peptidoglycan than the corresponding undepleted cells. Furthermore, MurM-deficient mutants, i.e., mutants lacking the ability to synthesize branched muropeptides, were found to require much higher levels of PBP2b to sustain growth than those required by MurM-proficient strains. These findings might help to explain why increased incorporation of branched muropeptides is required for high-level beta-lactam resistance in
S. pneumoniae
.
Evaluation of the Alfred 60/AST Device as a Screening Test for Urinary Tract Infections
Authors: Lahanas Sophie , Stathopoulos George , Chan Raymond C. , van Hal Sebastiaan J. 
Published: July 2013

ABSTRACT
The performance of the Alfred 60/AST device, an automated bacterial culture device which uses laser nephelometry to detect and quantify bacterial growth, was evaluated. The instrument is effective at screening negative samples and is more reliable at detecting bacteria than yeasts. Microscopy can be used to reduce the false-negative numbers.
Activation of Human Herpesvirus Replication by Apoptosis
Authors: Prasad Alka , Remick Jill , Zeichner Steven L. 
Published: July 2013

ABSTRACTA central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.
Detection of Proton Movement Directly across Viral Membranes To Identify Novel Influenza Virus M2 Inhibitors
Authors: Sulli Chidananda , Banik Soma S. R. , Schilling Justin , Moser Allan , Xiang Xiaoxiao , Payne Riley , Wanless Antony , Willis Sharon H. , Paes Cheryl , Rucker Joseph B. , Doranz Benjamin J. 
Published: July 2013

ABSTRACT
The influenza virus M2 protein is a well-validated yet underexploited proton-selective ion channel essential for influenza virus infectivity. Because M2 is a toxic viral ion channel, existing M2 inhibitors have been discovered through live virus inhibition or medicinal chemistry rather than M2-targeted high-throughput screening (HTS), and direct measurement of its activity has been limited to live cells or reconstituted lipid bilayers. Here, we describe a cell-free ion channel assay in which M2 ion channels are incorporated into virus-like particles (VLPs) and proton conductance is measured directly across the viral lipid bilayer, detecting changes in membrane potential, ion permeability, and ion channel function. Using this approach in high-throughput screening of over 100,000 compounds, we identified 19 M2-specific inhibitors, including two novel chemical scaffolds that inhibit both M2 function and influenza virus infectivity. Counterscreening for nonspecific disruption of viral bilayer ion permeability also identified a broad-spectrum antiviral compound that acts by disrupting the integrity of the viral membrane. In addition to its application to M2 and potentially other ion channels, this technology enables direct measurement of the electrochemical and biophysical characteristics of viral membranes.
Interactions of the Vaccinia Virus A19 Protein
Authors: Satheshkumar P. S. , Olano L. Renee , Hammer Carl H. , Zhao Ming , Moss Bernard 
Published: July 2013

ABSTRACT

The A19 protein of vaccinia virus (VACV) is conserved among chordopoxviruses, expressed late in infection, packaged in the virus core, and required for a late step in morphogenesis. Multiple-sequence alignments of A19 homologs indicated conservation of a series of lysines and arginines, which could represent a nuclear localization or nucleic acid binding motif, and a pair of CXXC motifs that suggested a zinc finger or redox active sites. The importance of the CXXC motif was confirmed by cysteine-to-serine substitutions, which rendered the altered protein unable to
trans
-complement infectivity of a null mutant. Nevertheless, the cysteines were not required for function of the poxvirus-specific redox pathway. Epitope-tagged A19 proteins were detected in the nucleus and cytoplasm in both infected and uninfected cells, but this distribution was unaffected by alanine substitutions of the arginine residues, which only partially reduced the ability of the mutated protein to
trans
-complement infectivity. Viral proteins specifically associated with affinity-purified A19 were identified by mass spectrometry as components of the transcription complex, including RNA polymerase subunits, RAP94 (RNA polymerase-associated protein 94), early transcription factors, capping enzyme, and nucleoside triphosphate phosphohydrolase I, and two core proteins required for morphogenesis. Further studies suggested that the interaction of A19 with the RNA polymerase did not require RAP94 or other intermediate or late viral proteins but was reduced by mutation of cysteines in the putative zinc finger domain. Although A19 was not required for incorporation of the transcription complex in virus particles, the transcriptional activity of A19-deficient virus particles was severely reduced.
Construction of a
Sonchus Yellow Net Virus
Minireplicon: a Step toward Reverse Genetic Analysis of Plant Negative-Strand RNA Viruses
Authors: Ganesan Uma , Bragg Jennifer N. , Deng Min , Marr Sharon , Lee Mi Yeon , Qian ShaSha , Shi Manling , Kappel Justin , Peters Cole , Lee Yeon , Goodin Michael M. , Dietzgen Ralf G. , Li Zhenghe , Jackson Andrew O. 
Published: July 2013

ABSTRACT

Reverse genetic analyses of negative-strand RNA (NSR) viruses have provided enormous advances in our understanding of animal viruses over the past 20 years, but technical difficulties have hampered application to plant NSR viruses. To develop a reverse genetic approach for analysis of plant NSR viruses, we have engineered
Sonchus yellow net nucleorhabdovirus
(SYNV) minireplicon (MR) reporter cassettes for
Agrobacterium tumefaciens
expression in
Nicotiana benthamiana
leaves. Fluorescent reporter genes substituted for the SYNV N and P protein open reading frames (ORFs) exhibited intense single-cell foci throughout regions of infiltrated leaves expressing the SYNV MR derivatives and the SYNV nucleocapsid (N), phosphoprotein (P), and polymerase (L) proteins. Genomic RNA and mRNA transcription was detected for reporter genes substituted for both the SYNV N and P ORFs. These activities required expression of the N, P, and L core proteins in
trans
and were enhanced by codelivery of viral suppressor proteins that interfere with host RNA silencing. As is the case with other members of the
Mononegavirales
, we detected polar expression of fluorescent proteins and chloramphenicol acetyltransferase substitutions for the N and P protein ORFs. We also demonstrated the utility of the SYNV MR system for functional analysis of SYNV core proteins in
trans
and the
cis
-acting leader and trailer sequence requirements for transcription and replication. This work provides a platform for construction of more complex SYNV reverse genetic derivatives and presents a general strategy for reverse genetic applications with other plant NSR viruses.
Circulating Dendritic Cells Isolated from Healthy Seropositive Donors Are Sites of Human Cytomegalovirus Reactivation
In Vivo
Authors: Reeves Matthew B. , Sinclair John H. 
Published: July 2013

ABSTRACT

Primary infection with human cytomegalovirus (HCMV) is generally asymptomatic in healthy individuals and results in a lifelong infection of the host. In contrast, in immunosuppressed transplant recipients and late-stage AIDS patients, HCMV infection and reactivation can result in severe disease or death.
In vivo
, latency is established in bone marrow CD34
+
progenitor cells with reactivation linked with their differentiation to macrophages and dendritic cells (DCs). However, previous analyses have relied on
ex vivo
differentiation of myeloid progenitor cells to DCs in culture. Here, we now report on the isolation and analysis of circulating blood myeloid DCs, resulting from natural differentiation
in vivo
, from healthy HCMV-seropositive carriers. We show that these
in vivo
-differentiated circulating DCs are fully permissive for HCMV and exhibit a phenotype similar to that of monocyte-derived DCs routinely used for
in vitro
studies of HCMV. Importantly, we also show that these DCs from healthy HCMV-seropositive donors carry HCMV genomes and, significantly, are typically positive for viral immediate-early (IE) gene expression, in contrast to circulating monocytes, which carry genomes with an absence of IE expression. Finally, we show that HCMV reactivation from these circulating DCs is enhanced by inflammatory stimuli. Overall, these data argue that the differentiation
in vivo
of myeloid progenitors to circulating DCs promotes the reactivation of HCMV lytic gene expression in healthy individuals, thereby providing valuable confirmation of studies performed using
in vitro
generation of DCs from myeloid precursors to study HCMV reactivation.
Proximity to terror and post-traumatic stress: a follow-up survey of governmental employees after the 2011 Oslo bombing attack
Authors: Hansen Marianne B , Nissen Alexander , Heir Trond 
Published: July 2013

ObjectiveTo assess the prevalence of post-traumatic stress disorder (PTSD) symptoms among governmental employees after the 2011 Oslo bombing attack targeted towards the Norwegian Ministries, and to explore the importance of proximity to the bomb explosion as a predictor of PTSD.DesignA cross-sectional study.SettingData were collected from a survey 10 months after the Oslo bombing on 22 July 2011.ParticipantsA total of 3520 employees were invited to the study. Net samples comprised 1927 employees in 14 of the 17 Norwegian Ministries.Outcome measuresThe employees reported where they were at the time of the explosion. PTSD was assessed with the Norwegian version of the PTSD checklist (PCL).ResultsA total of 207 of the 1881 (11%) ministerial employees who completed the survey were present at work when the bomb exploded. Of these, a quarter (24%, 95% CI 18.4 to 30.0) had symptom levels equivalent to PTSD, while the prevalence was approximately 4% among those not present at work. In the latter group the prevalence was similar irrespective of whether their location was in Oslo, other places in Norway or abroad. Leadership responsibility was associated with lower risk for PTSD.ConclusionsThe risk of PTSD is mainly associated with being present at work at the time of a terror attack. For those not present at work, the risk of PTSD is low and independent of proximity to the terror scene. The findings may have implications for planning and priority of healthcare services after a work place terror attack.
High blood pressure during pregnancy is associated with future cardiovascular disease: an observational cohort study
Authors: Tooher Jane , Chiu Christine L , Yeung Kristen , Lupton Samantha J , Thornton Charlene , Makris Angela , O'Loughlin Aiden , Hennessy Annemarie , Lind Joanne M 
Published: July 2013

ObjectivesThe study aimed to determine if having a hypertensive disorder of pregnancy (HDP) is a risk factor for future cardiovascular disease (CVD), independent of age and body mass index (BMI).DesignData were sourced from the baseline questionnaire of the45 and Up Study, Australia, an observational cohort study.SettingParticipants were randomly selected from the Australian Medicare Database within New South Wales.ParticipantsA total of 84 619 women were eligible for this study, of which 71 819 were included. These women had given birth between the ages of 18 and 45 years, had an intact uterus and ovaries, and had not been diagnosed with high blood pressure prior to their first pregnancy.ResultsHDP was associated with higher odds of having high blood pressure (<58 years: adjusted OR 3.79, 99% CI 3.38 to 4.24; p<0.001 and ≥58 years: 2.83, 2.58 to 3.12; p<0.001) and stroke (<58 years: 1.69, 1.02 to 2.82; p=0.008 and ≥58 years: 1.46, 1.13 to 1.88; p<0.001) in later life. Women with HDP had a younger age of onset of high blood pressure (45.6 vs 54.8 years, p<0.001) and stroke (58 vs 62.5 years, p<0.001). Women who had HDP and whose present day BMI was <25 had significantly higher odds of having high blood pressure, compared with women who were normotensive during pregnancy (<58 years: 4.55, 3.63 to 5.71; p<0.001 and ≥58 years, 2.94, 2.49 to 3.47; p<0.001). Women who had HDP and a present day BMI≥25 had significantly increased odds of high blood pressure (<58 years: 12.48, 10.63 to 14.66; p<0.001 and ≥58 years, 5.16, 4.54 to 5.86; p<0.001), compared with healthy weight women with a normotensive pregnancy.ConclusionsHDP is an independent risk factor for future CVD, and this risk is further exacerbated by the presence of overweight or obesity in later life.