bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory Development and Testing of “SmartRock” for Railroad Ballast Using Discrete Element Modeling
Authors: Liu Shushu , Huang Hai , Qiu Tong 
Published: June 2015

Ballast aggregate settlement is generally a result of consolidation or rearrangment of ballast particles in the area underneath crossties. Excessive settlement negatively impacts track performance, resulting in increased risk of train derailment. The purpose of this paper is to compare two methods to evaluate ballast aggregate settlement with repeated loading in railroad: discrete element modeling and laboratory tests using “SmartRock”.
In this study, ballast aggregates are considered as uniformly graded, angular shaped with crushed faces. For the discrete element modeling, digital imaging techniques are utilized to create the ballast aggregates. Aggregate settlement in railroad ballast and the effect of aggregate shape on the dynamic response of ballast are evaluated through the discrete element simulations. A wireless device, “SmartRock” is developed to study the relationship between individual ballast particle behavior and overall ballast performance. It has a shell of a typical ballast particle shape with force cells attached on the surface and embedded with a tri-axial gyroscope, a tri-axial accelerometer, and a tri-axial magnetometer. The device can move under train traffic like a real ballast particle and record inter-particle contact forces and particle motion in real time. For the laboratory tests, a model-scale track section is constructed and subjected to repeated loading similar to train traffic. The developed “SmartRock” are embedded below rail seats and in the track shoulders.
The laboratory data using “SmartRock” can be compared with results from the discrete element modeling in the future. These comparisons will validate the discrete element modeling procedure as a means to analyze railroad ballast aggregate behavior and the potential of “SmartRock” in railroad applications.
Decreased Circulating mtDNA Levels in Professional Male Volleyball Players
Authors: Nasi Milena , Cristani Alessandro , Pinti Marcello , Lamberti Igor , Gibellini Lara , De Biasi Sara , Guazzaloca Alessandro , Trenti Tommaso , Cossarizza Andrea 
Published: June 2015

Purpose:Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance.Methods:Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed.Results:The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters.Conclusions:Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.
Pacing Behavior and Tactical Positioning in 1500-m Short-Track Speed Skating
Authors: Konings Marco J. , Noorbergen Olaf S. , Parry David , Hettinga Florentina J. 
Published: June 2015

Purpose:To gain more insight in pacing behavior and tactical positioning in 1500-m short-track speed skating, a sport in which several athletes directly compete in the same race.Methods:Lap times and intermediate rankings of elite 1500-m short-track-skating competitors were collected over the season 2012–13 (N = 510, 85 races). Two statistical approaches were used to assess pacing behavior and tactical positioning. First, lap times were analyzed using a MANOVA, and for each lap differences between sex, race type, final rankings, and stage of competition were determined. Second, Kendall tau b correlations were used to assess relationships between intermediate and final rankings. In addition, intermediate rankings of the winner of each race were examined.Results:In 1500 m (13.5 laps of 111.12 m), correlations between intermediate and final ranking gradually increased throughout the race (eg, lap 1, r = .05; lap 7, r = .26; lap 13, r = .85). Moreover, the percentage of race winners skating in the leading position was over 50% during the last 3 laps. Top finishers were faster than bottom-place finishers only during the last 5 laps, with on average 0.1- to 1.5-s faster lap times of the race winners compared with the others during the last 5 laps.Conclusions:Although a fast start led to faster finishing times, top finishers were faster than bottom-placed finishers only during the last 5 laps. Moreover, tactical positioning at 1 of the foremost positions during the latter phase of the race appeared to be a strong determinant of finishing position.
The Effectiveness of Nonoperative Rehabilitation Programs for Athletes Diagnosed With Osteitis Pubis
Authors: Cheatham Scott W. , Kolber Morey J. , Shimamura Kathryn Kumagai 
Published: June 2015

Clinical Scenario:The differential diagnosis of groin pain can be very challenging due to the many causative pathologies. Osteitis pubis is a pathology that is becoming more recognized in athletes who participate in sports such as soccer, ice hockey, rugby, and football. Conservative nonoperative treatment is often prescribed first before surgical intervention. Of particular interest are the outcomes of nonoperative rehabilitation programs and their effectiveness to return athletes to preinjury levels of participation. The most recent systematic review in 2011 examined the spectrum of treatments for osteitis pubis and found only level 4 (case report or case series) evidence with varying approaches to treatment. Due to the amount of time since the last published review, there is a need to critically appraise the recent literature to see if more high-quality research has been published that measured nonoperative interventions for athletes with osteitis pubis.Focused Clinical Question:Is there evidence to suggest that nonoperative rehabilitation programs for osteitis pubis are effective at returning athletes to their preinjury levels of participation?Summary of Key Findings:Four studies met the inclusion criteria. Only level 4 evidence was found. All studies reported using a structured nonoperative rehabilitation program with a successful return to preinjury participation between 4 and 14 wk, except for 1 study reporting a successful return at 30 wk. Successful long-term follow-up was reported at 6–48 mo for all patients.Clinical Bottom Line:There is weak evidence to support the efficacy of nonoperative rehabilitation programs at returning athletes to their preinjury levels of participation.Strength of Recommendation:There is grade D evidence that a nonoperative program for osteitis pubis is effective at helping athletes return to their preinjury level of participation. The Centre of Evidence Based Medicine recommends a grade D for level 4 evidence with consistent findings.
Relative Strengths of Promoters Provided by Common Mobile Genetic Elements Associated with Resistance Gene Expression in Gram-Negative Bacteria
Authors: Kamruzzaman Muhammad , Patterson Jason D. , Shoma Shereen , Ginn Andrew N. , Partridge Sally R. , Iredell Jonathan R. 
Published: June 2015

ABSTRACT

Comparison of green fluorescent protein expression from outward-facing promoters (P
OUT
) of IS
Aba1
, IS
Ecp1
, and IS
Aba125
revealed approximate equivalence in strength, intermediate between P
C
S (strong) and P
C
W
TGN-10
(weak) class 1 integron promoter variants, >30-fold stronger than P
OUT
of IS
CR1
, and >5 times stronger than P
tac
. Consistent with its usual role, P
C
W
TGN-10
produces more mRNA from a “downstream”
gfp
gene transcriptionally linked to a “usual” P
C
W
TGN-10
-associated gene cassette than does P
OUT
of IS
Aba1
.
Antiviral Efficacy of a Respiratory Syncytial Virus (RSV) Fusion Inhibitor in a Bovine Model of RSV Infection
Authors: Jordan Robert , Shao Matt , Mackman Richard L. , Perron Michel , Cihlar Tomas , Lewis Sandy A. , Eisenberg Eugene J. , Carey Anne , Strickley Robert G. , Chien Jason W. , Anderson Mark L. , McEligot Heather A. , Behrens Nicole E. , Gershwin Laurel J. 
Published: June 2015

ABSTRACT
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Effective treatment for RSV infection is a significant unmet medical need. While new RSV therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human RSV, making it difficult to evaluate new disease interventions. Experimental infection of Holstein calves with bovine RSV (bRSV) causes a severe respiratory infection that is similar to human RSV infection, providing a relevant model for testing novel therapeutic agents. In this model, viral load is readily detected in nasal secretions by quantitative real-time PCR (qRT-PCR), and cumulative symptom scoring together with histopathology evaluations of infected tissue allow for the assessment of disease severity. The bovine RSV model was used to evaluate the antiviral activity of an RSV fusion inhibitor, GS1, which blocks virus entry by inhibiting the fusion of the viral envelope with the host cell membrane. The efficacy of GS1, a close structural analog of GS-5806 that is being developed to treat RSV infection in humans was evaluated in two randomized, blind, placebo-controlled studies in bRSV-infected calves. Intravenous administration of GS1 at 4 mg/kg of body weight/day for 7 days starting 24 h or 72 h postinoculation provided clear therapeutic benefit by reducing the viral load, disease symptom score, respiration rate, and lung pathology associated with bRSV infection. These data support the use of the bovine RSV model for evaluation of experimental therapeutics for treatment of RSV.
In Vitro
Antifungal Activity of ME1111, a New Topical Agent for Onychomycosis, against Clinical Isolates of Dermatophytes
Authors: Ghannoum M. , Isham N. , Long L. 
Published: June 2015

ABSTRACT

The treatment of onychomycosis has improved considerably over the past several decades following the introduction of the oral antifungals terbinafine and itraconazole. However, these oral agents suffer from certain disadvantages, including drug interactions and potential liver toxicity. Thus, there is a need for new topical agents that are effective against onychomycosis. ME1111 is a novel selective inhibitor of succinate dehydrogenase (complex II) of dermatophyte species, whose small molecular weight enhances its ability to penetrate the nail plate. In this study, we determined the antifungal activity of ME1111 against dermatophyte strains, most of which are known to cause nail infections, as measured by the MIC (
n
= 400) and the minimum fungicidal concentration (MFC) (
n
= 300). Additionally, we examined the potential for resistance development in dermatophytes (
n
= 4) following repeated exposure to ME1111. Our data show that the MIC
90
of ME1111 against dermatophyte strains was 0.25 μg/ml, which was equivalent to that of the comparators amorolfine and ciclopirox (0.25 and 0.5 μg/ml, respectively). ME1111 was fungicidal at clinically achievable concentrations against dermatophytes, and its MFC
90
s against
Trichophyton rubrum
and
Trichophyton mentagrophytes
were 8 μg/ml, comparable to those of ciclopirox. Furthermore, ME1111, as well as ciclopirox, did not induce resistance in 4 dermatophytes tested. Our studies show that ME1111 possesses potent antifungal activity and suggest that it has low potential for the development of resistance in dermatophytes.
Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity
Authors: D'Alessandro Sarah , Corbett Yolanda , Ilboudo Denise P. , Misiano Paola , Dahiya Nisha , Abay Solomon M. , Habluetzel Annette , Grande Romualdo , Gismondo Maria R. , Dechering Koen J. , Koolen Karin M. J. , Sauerwein Robert W. , Taramelli Donatella , Basilico Nicoletta , Parapini Silvia 
Published: June 2015

ABSTRACT

The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of
Plasmodium
, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on
Plasmodium falciparum
asexual and sexual erythrocytic stages and on the development of the
Plasmodium berghei
and
P. falciparum
mosquito stages is reported here. Gametocytogenesis of the
P. falciparum
strain 3D7 was induced
in vitro
, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC
50
). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads.
NDM-1-Producing Citrobacter freundii, Escherichia coli, and Acinetobacter baumannii Identified from a Single Patient in China
Authors: Huang Ying-Min , Zhong Lan-lan , Zhang Xue-Fei , Hu Hang-tong , Li Yu-qi , Yang Xiao-rong , Feng Lian-Qiang , Huang Xi , Tian Guo-Bao 
Published: June 2015

ABSTRACT

We identified New Delhi metallo-β-lactamase (NDM-1)-producing
Citrobacter freundii
GB032,
Escherichia coli
GB102, and
Acinetobacter baumannii
GB661 in urine and stool samples from a single patient in China. Plasmid profiling and Southern blotting indicated that
bla
NDM-1
from GB032 and that from GB102 were likely located on the same plasmid, while
bla
NDM-1
from GB661 was located on a very large (>400-kb) plasmid. This case underscores the broad host range of
bla
NDM-1
and its potential to spread between members of the family
Enterobacteriaceae
and
A. baumannii
.
TREM-1 Signaling Promotes Host Defense during the Early Stage of Infection with Highly Pathogenic Streptococcus suis
Authors: Yang Chao , Chen Bo , Zhao Jianqing , Lin Lan , Han Li , Pan Shan , Fu Lei , Jin Meilin , Chen Huanchun , Zhang Anding 
Published: June 2015

ABSTRACT

Infection with highly pathogenic
Streptococcus suis
can cause septic shock, which is characterized by high levels of inflammatory cytokines and a high mortality rate. Our previous study indicated that TREM-1 (triggering receptor expressed on myeloid cells 1) was upregulated in swine spleen cells in response to
S. suis
infection. The role of TREM-1 signaling in enhancement of the proinflammatory response promoted us to examine its effect on the outcome of
S. suis
infection. In the present study, the recombinant extracellular domain of TREM-1 (rTREM-1) and an agonistic TREM-1 antibody were used to inhibit and activate TREM-1 signaling to evaluate its role in neutrophil activation, pathogen clearance, proinflammatory cytokine response, and the outcome of highly pathogenic
S. suis
infection in a mouse model. Blockage of TREM-1 signaling caused a more severe proinflammatory response to
S. suis
infection and increased the mortality rate, while its activation had the opposite effect. Blockage or activation of TREM-1 signaling lowered or raised the number of neutrophils in the blood, which correlated well with host clearance of
S. suis
. In conclusion, the TREM-1-mediated innate immune response played an essential role in the activation of neutrophils and
S. suis
clearance, which further reduced severe inflammation and finally benefited the outcome of the infection.
Members of the PpaA/AerR Antirepressor Family Bind Cobalamin
Authors: Vermeulen Arjan J. , Bauer Carl E. 
Published: June 2015

ABSTRACT

PpaA from
Rhodobacter sphaeroides
is a member of a family of proteins that are thought to function as antirepressors of PpsR, a widely disseminated repressor of photosystem genes in purple photosynthetic bacteria. PpaA family members exhibit sequence similarity to a previously defined SCHIC (
s
ensor
c
ontaining
h
eme
i
nstead of
c
obalamin) domain; however, the tetrapyrrole-binding specificity of PpaA family members has been unclear, as
R. sphaeroides
PpaA has been reported to bind heme while the
Rhodobacter capsulatus
homolog has been reported to bind cobalamin. In this study, we reinvestigated tetrapyrrole binding of PpaA from
R. sphaeroides
and show that it is not a heme-binding protein but is instead a cobalamin-binding protein. We also use bacterial two-hybrid analysis to show that PpaA is able to interact with PpsR and activate the expression of photosynthesis genes
in vivo
. Mutations in PpaA that cause loss of cobalamin binding also disrupt PpaA antirepressor activity
in vivo
. We also tested a number of PpaA homologs from other purple bacterial species and found that cobalamin binding is a conserved feature among members of this family of proteins.

IMPORTANCE
Cobalamin (vitamin B
12
) has only recently been recognized as a cofactor that affects gene expression by interacting in a light-dependent manner with transcription factors. A group of related antirepressors known as the AppA/PpaA/AerR family are known to control the expression of photosynthesis genes in part by interacting with either heme or cobalamin. The specificity of which tetrapyrroles that members of this family interact with has, however, remained cloudy. In this study, we address the tetrapyrrole-binding specificity of the PpaA/AerR subgroup and establish that it preferentially binds cobalamin over heme.
Cathepsin W Is Required for Escape of Influenza A Virus from Late Endosomes
Authors: Edinger Thomas O. , Pohl Marie O. , Yángüez Emilio , Stertz Silke 
Published: June 2015

ABSTRACT
Human cathepsin W (CtsW) is a cysteine protease, which was identified in a genome-wide RNA interference (RNAi) screen to be required for influenza A virus (IAV) replication. In this study, we show that reducing the levels of expression of CtsW reduces viral titers for different subtypes of IAV, and we map the target step of CtsW requirement to viral entry. Using a set of small interfering RNAs (siRNAs) targeting CtsW, we demonstrate that knockdown of CtsW results in a decrease of IAV nucleoprotein accumulation in the nuclei of infected cells at 3 h postinfection. Assays specific for the individual stages of IAV entry further show that attachment, internalization, and early endosomal trafficking are not affected by CtsW knockdown. However, we detected impaired escape of viral particles from late endosomes in CtsW knockdown cells. Moreover, fusion analysis with a dual-labeled influenza virus revealed a significant reduction in fusion events, with no detectable impact on endosomal pH, suggesting that CtsW is required at the stage of viral fusion. The defect in IAV entry upon CtsW knockdown could be rescued by ectopic expression of wild-type CtsW but not by the expression of a catalytically inactive mutant of CtsW, suggesting that the proteolytic activity of CtsW is required for successful entry of IAV. Our results establish CtsW as an important host factor for entry of IAV into target cells and suggest that CtsW could be a promising target for the development of future antiviral drugs.

IMPORTANCE
Increasing levels of resistance of influenza viruses to available antiviral drugs have been observed. Development of novel treatment options is therefore of high priority. In parallel to the classical approach of targeting viral enzymes, a novel strategy is pursued: cell-dependent factors of the virus are identified with the aim of developing small-molecule inhibitors against a cellular target that the virus relies on. For influenza A virus, several genome-wide RNA interference (RNAi) screens revealed hundreds of potential cellular targets. However, we have only limited knowledge on how these factors support virus replication, which would be required for drug development. We have characterized cathepsin W, one of the candidate factors, and found that cathepsin W is required for escape of influenza virus from the late endosome. Importantly, this required the proteolytic activity of cathepsin W. We therefore suggest that cathepsin W could be a target for future host cell-directed antiviral therapies.
Acetic Acid Acts as a Volatile Signal To Stimulate Bacterial Biofilm Formation
Authors: Chen Yun , Gozzi Kevin , Yan Fang , Chai Yunrong 
Published: June 2015

ABSTRACT

Volatiles are small air-transmittable chemicals with diverse biological activities. In this study, we showed that volatiles produced by the bacterium
Bacillus subtilis
had a profound effect on biofilm formation of neighboring
B. subtilis
cells that grew in proximity but were physically separated. We further demonstrated that one such volatile, acetic acid, is particularly potent in stimulating biofilm formation. Multiple lines of genetic evidence based on
B. subtilis
mutants that are defective in either acetic acid production or transportation suggest that
B. subtilis
uses acetic acid as a metabolic signal to coordinate the timing of biofilm formation. Lastly, we investigated how
B. subtilis
cells sense and respond to acetic acid in regulating biofilm formation. We showed the possible involvement of three sets of genes (
ywbHG
,
ysbAB
, and
yxaKC
), all encoding putative holin-antiholin-like proteins, in cells responding to acetic acid and stimulating biofilm formation. All three sets of genes were induced by acetate. A mutant with a triple mutation of those genes showed a severe delay in biofilm formation, whereas a strain overexpressing
ywbHG
showed early and robust biofilm formation. Results of our studies suggest that
B. subtilis
and possibly other bacteria use acetic acid as a metabolic signal to regulate biofilm formation as well as a quorum-sensing-like airborne signal to coordinate the timing of biofilm formation by physically separated cells in the community.

IMPORTANCE
Volatiles are small, air-transmittable molecules produced by all kingdoms of organisms including bacteria. Volatiles possess diverse biological activities and play important roles in bacteria-bacteria and bacteria-host interactions. Although volatiles can be used as a novel and important way of cell-cell communication due to their air-transmittable nature, little is known about how the volatile-mediated signaling mechanism works. In this study, we demonstrate that the bacterium
Bacillus subtilis
uses one such volatile, acetic acid, as a quorum-sensing-like signal to coordinate the timing of the formation of structurally complex cell communities, also known as biofilms. We further characterized the molecular mechanisms of how
B. subtilis
responds to acetic acid in stimulating biofilm formation. Our study also suggests that acetic acid may be used as a volatile signal for cross-species communication.