bluuebunny/crossref_metadata_2025_split huggingface dataset:
Root infection of potato by Spongospora subterranea: knowledge review and evidence for decreased plant productivity
Authors: Falloon R. E. , Merz U. , Butler R. C. , Curtin D. , Lister R. A. , Thomas S. M. 
Published: June 2015

Information is reviewed on root infection of potato by the plasmodiophorid Spongospora subterranea f. sp. subterranea. This pathogen has long been recognized as the cause of root galls (hyperplasia) and the economically important disease powdery scab on tubers (modified stolons). The significance for plant productivity of the zoosporangium stages of the pathogen in potato roots has only recently begun to be documented. Two experiments are described that assessed effects of S. subterranea root infection on potato plant root function and productivity. A greenhouse experiment measured root function and plant parameters for eight potato cultivars with markedly different susceptibilities to tuber powdery scab. Water uptake and plant growth were reduced by S. subterranea inoculation in all eight cultivars. The magnitudes of these negative effects, and intensities of root hyperplasia, differed among the cultivars, but were not related to respective susceptibilities to tuber powdery scab. A field trial assessed root function and plant productivity for a cultivar (Iwa) that is very susceptible to Spongospora tuber and root diseases. Soil water content beneath uninoculated plants was consistently less than for inoculated plants, indicating that inoculation reduced water uptake (root function). Inoculation reduced shoot and root dry weights, and reduced weight of tubers per plant by 42%. Spongospora subterranea causes three diseases of potato: root membrane dysfunction, root hyperplasia and tuber powdery scab. The root diseases caused by the pathogen are likely to be important both for powdery scab management and for deleterious effects on potato crop yields.
MicroRNAs in cardiovascular ageing
Authors: Seeger Timon , Boon Reinier A. 
Published: June 2015

AbstractMicroRNAs (miRs) have emerged as potent regulators of pathways in physiological and disease contexts. This review focuses on the role of miRs in ageing of the cardiovascular system. Several miRs have been described to be regulated during ageing and some of these miRs are involved in the regulation of ageing‐related processes. We discuss the roles of miR‐34, miR‐217 and miR‐29, which are induced during ageing in the vasculature. The roles of miR‐34, miR‐29 (age‐induced) and miR‐18/19, which are decreased during ageing in the heart, are discussed as well. Furthermore, numerous miRs that play a role in diseases associated with ageing, like diabetes, atherosclerosis, hypertension, cardiac hypertrophy and atrial fibrillation, are also briefly discussed. miRs also serve as circulating biomarkers for cardiovascular ageing or ageing‐associated diseases. Finally, pharmacological modulation of ageing‐related miRs might become a promising strategy to combat cardiovascular ageing in a clinical setting.
Heavy Axle Load Revenue Service Bridge Approach Problems and Remedies
Authors: Li Dingqing , Maal Luis 
Published: June 2015

Two different remedies to reduce track stiffness and increase track damping for the track on the bridges were implemented for two separate ballast deck bridges with standard concrete ties located on a high tonnage heavy haul revenue service route. One remedy used concrete ties fitted with rubber pads on the bottom surface and the other used ballast mats between the ballast layer and bridge deck. The ballast sections were increased to a minimum depth of 12 inches below the bottom of the ties, and drainage improvement was made to ensure that water would not accumulate on the bridges or in the approaches.
The two bridge locations were selected in September 2007 and June 2009, for remediation and long-term monitoring of performance as part of the heavy axle load revenue service mega site testing program conducted by Transportation Technology Center, Inc. and Union Pacific Railroad.
Before remediation, these two locations experienced excessive track geometry degradation, mud pumping, and track component failure that required localized maintenance work on a quarterly basis (approximately 63 MGT).
After remediation, no localized maintenance (except yearly surfacing operations for the entire line) has been required for more than 1,000 MGT.
The main root causes of these problems were determined to be high track stiffness and low track damping for the track on the bridges, which adversely affected dynamic vehicle-track interaction when differential track settlement started to occur at the bridge approaches. Some of these ballast deck bridges with concrete ties had track modulus measured at 12,000 lb/in/in, which is considered too high to accommodate dynamic vehicle-track interaction.
Long-term performance of these remedies has been excellent, resulting in significant benefits from reduction of slow orders, train delays, and major track maintenance activities.
A Review of Past Geotechnical Performance of the Hudson Bay Rail Embankment and Its Comparison to the Current Condition
Authors: Addison Priscilla E. , Oommen Thomas , Lautala Pasi 
Published: June 2015

The Hudson Bay Railway (HBR) is a 510 mile railway completed in 1929 in northern Manitoba, Canada. It connects domestic locations in North America with international destinations through the Port of Churchill.
Permafrost was encountered during construction at milepost 136 in isolated peat bogs which continued in a gradual northward transition from discontinuous to continuous permafrost. Over the past 80 years, warming climate combined with poor engineering properties of the railway embankment material has resulted in further thawing of the discontinuous permafrost leading to differential settlement along the rail embankment and high annual maintenance costs.
In a bid to understand the geothermal regime of the embankment, underlying subsurface condition, and to seek for solutions to stabilize the embankment, extensive work has been done from 1977 to the present time. This paper seeks to review reports of the past projects and compare the results against current conditions at selected test locations.
Identifying Electrically Infeasible Traffic Scenarios on the Iron Ore Line; Applied on the Present-Day System, Converter Station Outages, and Optimal Locomotive Reactive Power Strategies
Authors: Abrahamsson Lars , Skogberg Ronny , Östlund Stefan , Lagos Mario , Söder Lennart 
Published: June 2015

This paper presents the main findings of a Master’s Thesis project carried out in cooperation between Transrail and Royal Institute of Technology (KTH). The main objective was to create a plugin for checking the electric power system feasibility of a train traffic plan with an associated driving strategy created by TRAINS — a Transrail software product. Secondary aims with the project was to study power system feasibilities during converter station outages, and to which extent optimal operation of the locomotive converters’ reactive power assure power system feasibilities.
In the developed optimal reactive power strategies, the main priority was to fulfill the desired traffic plans, whereas the secondary priority was to minimize railway power system power consumption.
The case studies are applied on representative traffic scenarios and power system models representing the northern part of the Iron Ore line in Northern Sweden. The focus of the study is set on the IORE locomotives and the iron ore trains they haul. The optimized locomotive reactive power regards IORE, so also the investigated power system feasibilities of the traffic plans.
A new automated quantification algorithm for the detection and evaluation of focal liver lesions with contrast‐enhanced ultrasound
Authors: Gatos Ilias , Tsantis Stavros , Spiliopoulos Stavros , Skouroliakou Aikaterini , Theotokas Ioannis , Zoumpoulis Pavlos , Hazle John D. , Kagadis George C. 
Published: June 2015

Purpose:Detect and classify focal liver lesions (FLLs) from contrast‐enhanced ultrasound (CEUS) imaging by means of an automated quantification algorithm.Methods:The proposed algorithm employs a sophisticated segmentation method to detect and contour focal lesions from 52 CEUS video sequences (30 benign and 22 malignant). Lesion detection involves wavelet transform zero crossings utilization as an initialization step to the Markov random field model toward the lesion contour extraction. After FLL detection across frames, time intensity curve (TIC) is computed which provides the contrast agents’ behavior at all vascular phases with respect to adjacent parenchyma for each patient. From each TIC, eight features were automatically calculated and employed into the support vector machines (SVMs) classification algorithm in the design of the image analysis model.Results:With regard to FLLs detection accuracy, all lesions detected had an average overlap value of 0.89 ± 0.16 with manual segmentations for all CEUS frame‐subsets included in the study. Highest classification accuracy from the SVM model was 90.3%, misdiagnosing three benign and two malignant FLLs with sensitivity and specificity values of 93.1% and 86.9%, respectively.Conclusions:The proposed quantification system that employs FLLs detection and classification algorithms may be of value to physicians as a second opinion tool for avoiding unnecessary invasive procedures.
Reduced Radial Displacement of the Gastrocnemius Medialis Muscle After Electrically Elicited Fatigue
Authors: Macgregor Lewis J. , Ditroilo Massimiliano , Smith Iain J. , Fairweather Malcolm M. , Hunter Angus M. 
Published: June 2015

Context:Assessments of skeletal-muscle functional capacity often necessitate maximal contractile effort, which exacerbates muscle fatigue or injury. Tensiomyography (TMG) has been investigated as a means to assess muscle contractile function after fatigue; however, observations have not been contextualized by concurrent physiological measures.Objective:To measure peripheral-fatigue-induced alterations in mechanical and contractile properties of the plantar-flexor muscles through noninvasive TMG concurrently with maximal voluntary contraction (MVC) and passive muscle tension (PMT) to validate TMG as a gauge of peripheral fatigue.Design:Pre- and posttest intervention with control.Setting:University laboratory.Participants:21 healthy male volunteers.Interventions:Subjects’ plantar flexors were tested for TMG parameters, along with MVC and PMT, before and after either a 5-min rest period (control) or a 5-min electrical-stimulation intervention (fatigue).Main Outcome Measures:Temporal (contraction velocity) and spatial (radial displacement) contractile parameters of the gastrocnemius medialis were recorded through TMG. MVC was measured as an indicator of muscle fatigue, and PMT was measured to assess muscle stiffness.Results:Radial displacement demonstrated a fatigue-associated reduction (3.3 ± 1.2 vs 4.0 ± 1.4 mm, P = .031), while contraction velocity remained unaltered. In addition, MVC significantly declined by 122.6 ± 104 N (P < .001) after stimulation (fatigue). PMT was significantly increased after fatigue (139.8 ± 54.3 vs 111.3 ± 44.6 N, P = .007).Conclusions:TMG successfully detected fatigue, evident from reduced MVC, by displaying impaired muscle displacement accompanied by elevated PMT. TMG could be useful in establishing skeletalmuscle fatigue status without exacerbating the functional decrement of the muscle.
Incomplete APOBEC3G/F Neutralization by HIV-1 Vif Mutants Facilitates the Genetic Evolution from CCR5 to CXCR4 Usage
Authors: Alteri Claudia , Surdo Matteo , Bellocchi Maria Concetta , Saccomandi Patrizia , Continenza Fabio , Armenia Daniele , Parrotta Lucia , Carioti Luca , Costa Giosuè , Fourati Slim , Di Santo Fabiola , Scutari Rossana , Barbaliscia Silvia , Fedele Valentina , Carta Stefania , Balestra Emanuela , Alcaro Stefano , Marcelin Anne Genevieve , Calvez Vincent , Ceccherini-Silberstein Francesca , Artese Anna , Perno Carlo Federico , Svicher Valentina 
Published: June 2015

ABSTRACTIncomplete APOBEC3G/F neutralization by a defective HIV-1Vif protein can promote genetic diversification by inducing G-to-A mutations in the HIV-1 genome. The HIV-1 Env V3 loop, critical for coreceptor usage, contains several putative APOBEC3G/F target sites. Here, we determined if APOBEC3G/F, in the presence of Vif-defective HIV-1 virus, can induce G-to-A mutations at V3 positions critical to modulation of CXCR4 usage. Peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM) from 2 HIV-1-negative donors were infected with CCR5-using 81.A-VifWTvirus (i.e., with wild-type [WT] Vif protein), 81.A-VifE45G, or 81.A-VifK22E(known to incompletely/partially neutralize APOBEC3G/F). The rate of G-toA mutations was zero or extremely low in 81.A-VifWT- and 81.A-VifE45G-infected PBMC from both donors. Conversely, G-to-A enrichment was detected in 81.A-VifK22E-infected PBMC (prevalence ranging from 2.18% at 7 days postinfection [dpi] to 3.07% at 21 dpi in donor 1 and from 10.49% at 7 dpi to 8.69% at 21 dpi in donor 2). A similar scenario was found in MDM. G-to-A mutations occurred at 8 V3 positions, resulting in nonsynonymous amino acid substitutions. Of them, G24E and E25K strongly correlated with phenotypically/genotypically defined CXCR4-using viruses (P= 0.04 and 5.5e−7, respectively) and increased the CXCR4 N-terminal binding affinity for V3 (WT, −40.1 kcal/mol; G24E, −510 kcal/mol; E25K, −522 kcal/mol). The analysis of paired V3 and Vif DNA sequences from 84 HIV-1-infected patients showed that the presence of a Vif-defective virus correlated with CXCR4 usage in proviral DNA (P= 0.04). In conclusion, incomplete APOBEC3G/F neutralization by a single Vif amino acid substitution seeds a CXCR4-using proviral reservoir. This can have implications for the success of CCR5 antagonist-based therapy, as well as for the risk of disease progression.
Characterization of BKC-1 Class A Carbapenemase from Klebsiella pneumoniae Clinical Isolates in Brazil
Authors: Nicoletti Adriana Giannini , Marcondes Marcelo F. M. , Martins Willames M. B. S. , Almeida Luiz G. P. , Nicolás Marisa F. , Vasconcelos Ana T. R. , Oliveira Vitor , Gales Ana Cristina 
Published: June 2015

ABSTRACT

Three
Klebsiella pneumoniae
clinical isolates demonstrating carbapenem resistance were recovered from different patients hospitalized at two medical centers in São Paulo, Brazil. Resistance to all β-lactams, quinolones, and some aminoglycosides was observed for these isolates that were susceptible to polymyxin B. Carbapenem hydrolysis, which was inhibited by clavulanic acid, was observed for all
K. pneumoniae
isolates that belonged to the same pulsed-field gel electrophoresis (PFGE) type and a novel sequence type (ST), ST1781 (clonal complex 442 [CC442]). A 10-kb nonconjugative incompatibility group Q (IncQ) plasmid, denominated p60136, was transferred to
Escherichia coli
strain TOP10 cells by electroporation. The full sequencing of p60136 showed that it was composed of a mobilization system, IS
Kpn23
, the phosphotransferase aph3A-VI, and a 941-bp open reading frame (ORF) that codified a 313-amino acid protein. This ORF was named
bla
BKC-1
. Brazilian
Klebsiella
carbapenemase-1 (BKC-1) showed a pI of 6.0 and possessed the highest identity (63%) with a β-lactamase of
Sinorhizobium meliloti
, an environmental bacterium. Hydrolysis studies demonstrated that purified BKC-1 not only hydrolyzed carbapenems but also penicillins, cephalosporins, and monobactams. However, the carbapenems were less efficiently hydrolyzed due to their very low

k
cat

values (0.0016 to 0.031 s
−1
). In fact, oxacillin was the best substrate for BKC-1 (

k
cat

/

K
m

, 53,522.6 mM
−1
s
−1
). Here, we report a new class A carbapenemase, confirming the diversity and rapid evolution of β-lactamases in
K. pneumoniae
clinical isolates.
Calcium-Mediated Induction of Paradoxical Growth following Caspofungin Treatment Is Associated with Calcineurin Activation and Phosphorylation in Aspergillus fumigatus
Authors: Juvvadi Praveen R. , Muñoz Alberto , Lamoth Frédéric , Soderblom Erik J. , Moseley M. Arthur , Read Nick D. , Steinbach William J. 
Published: June 2015

ABSTRACT

The echinocandin antifungal drug caspofungin at high concentrations reverses the growth inhibition of
Aspergillus fumigatus
, a phenomenon known as the “paradoxical effect,” which is not consistently observed with other echinocandins (micafungin and anidulafungin). Previous studies of
A. fumigatus
revealed the loss of the paradoxical effect following pharmacological or genetic inhibition of calcineurin, yet the underlying mechanism is poorly understood. Here, we utilized a codon-optimized bioluminescent Ca
2+
reporter aequorin expression system in
A. fumigatus
and showed that caspofungin elicits a transient increase in cytosolic free Ca
2+
([Ca
2+
]
c
) in the fungus that acts as the initial trigger of the paradoxical effect by activating calmodulin-calcineurin signaling. While the increase in [Ca
2+
]
c
was also observed upon treatment with micafungin, another echinocandin without the paradoxical effect, a higher [Ca
2+
]
c
increase was noted with the paradoxical-growth concentration of caspofungin. Treatments with a Ca
2+
-selective chelator, BAPTA [1,2-bis(
o
-aminophenoxy)ethane-
N
,
N
,
N
′,
N
′-tetraacetic acid], or the L-type Ca
2+
channel blocker verapamil abolished caspofungin-mediated paradoxical growth in both the wild-type and the echinocandin-resistant (EMFR-S678P) strains. Concomitant with increased [Ca
2+
]
c
levels at higher concentrations of caspofungin, calmodulin and calcineurin gene expression was enhanced. Phosphoproteomic analysis revealed that calcineurin is activated through phosphorylation at its serine-proline-rich region (SPRR), a domain previously shown to be essential for regulation of hyphal growth, only at a paradoxical-growth concentration of caspofungin. Our results indicate that as opposed to micafungin, the increased [Ca
2+
]
c
at high concentrations of caspofungin activates calmodulin-calcineurin signaling at both a transcriptional and a posttranslational level and ultimately leads to paradoxical fungal growth.
Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults
Authors: Ishida Julie H. , Burgess Tracy , Derby Michael A. , Brown Pearline A. , Maia Mauricio , Deng Rong , Emu Brinda , Feierbach Becket , Fouts Ashley E. , Liao X. Charlene , Tavel Jorge A. 
Published: June 2015

ABSTRACT

Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected
in utero
and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry into host cells. A phase 1 first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study of RG7667 given intravenously was conducted in 181 healthy adults. The study involved a single ascending dose stage (1, 3, 5, and 10 mg/kg each antibody;
n
= 21), a multiple ascending dose stage (5 and 10 mg/kg each antibody monthly for 3 doses;
n
= 10), and a multiple dose expansion stage (10 mg/kg each antibody monthly for 3 doses;
n
= 150). Subjects were followed for 85 to 141 days to evaluate safety, tolerability, pharmacokinetics, and immunogenicity. Most adverse events were mild, and the incidence of adverse events was similar among the RG7667 and placebo groups. RG7667 had dose-proportional pharmacokinetics in all three dosing stages, a mean terminal half-life of 20 to 30 days, and an overall pharmacokinetic profile consistent with that of a human monoclonal antibody that lacks endogenous host targets. The proportion of subjects developing an antitherapeutic antibody response was not higher in the RG7667 group than in the placebo group. In summary, single and multiple doses of RG7667 were found to be safe and well-tolerated in healthy adults and had a favorable pharmacokinetic and immunogenicity profile. This study supports further development of RG7667 as a therapy for the prevention and treatment of cytomegalovirus infection in susceptible populations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01496755.)
Effect of Qnr on Plasmid Gyrase Toxins CcdB and ParE
Authors: Kwak Yee Gyung , Jacoby George A. , Hooper David C. 
Published: June 2015

ABSTRACT

Plasmid toxins CcdB and ParE are part of addiction systems promoting plasmid maintenance. Both target host DNA gyrase, as do quinolones and plasmid-determined Qnr proteins that protect gyrase from quinolone inhibition. We cloned
qnrB4
,
qnrS1
,
ccdB
,
parE
, and the antitoxin-encoding genes
ccdA
and
parD
on compatible plasmids and tested them in combination. CcdB and ParE had no specific effect on quinolone susceptibility or Qnr protection, and Qnr did not act as a CcdB or ParE antitoxin.
Pharmacodynamic Profile of GSK2140944 against Methicillin-Resistant Staphylococcus aureus in a Murine Lung Infection Model
Authors: So Wonhee , Crandon Jared L. , Nicolau David P. 
Published: June 2015

ABSTRACT

GSK2140944 is a novel bacterial type II topoisomerase inhibitor with
in vitro
activity against key causative respiratory pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA). We described the pharmacodynamics of GSK2140944 against MRSA in the neutropenic murine lung infection model. MICs of GSK2140944 were determined by broth microdilution. Plasma and epithelial lining fluid (ELF) pharmacokinetics were evaluated to allow determination of pulmonary distribution. Six MRSA isolates were tested. GSK2140944 doses of 1.56 to 400 mg/kg of body weight every 6 h (q6h) were utilized. Efficacy as the change in log
10
CFU at 24 h compared with 0 h controls and the area under the concentration-time curve for the free, unbound fraction of a drug (
f
AUC)/MIC required for various efficacy endpoints were determined. GSK2140944 MICs were 0.125 to 0.5 mg/liter against the six MRSA isolates. ELF penetration ratios ranged from 1.1 to 1.4. Observed maximal decreases were 1.1 to 3.1 log
10
CFU in neutropenic mice. The mean
f
AUC/MIC ratios required for stasis and 1-log-unit decreases were 59.3 ± 34.6 and 148.4 ± 83.3, respectively. GSK2140944 displayed
in vitro
and
in vivo
activity against MRSA. The pharmacodynamic profile of GSK2140944, as determined, supports its further development as a potential treatment option for pulmonary infections, including those caused by MRSA.
Mode of Action and Bactericidal Properties of Surotomycin against Growing and Nongrowing Clostridium difficile
Authors: Alam Mohammed Zahidul , Wu Xiaoqian , Mascio Carmela , Chesnel Laurent , Hurdle Julian G. 
Published: June 2015

ABSTRACT

Surotomycin (CB-183,315), a cyclic lipopeptide, is in phase 3 clinical development for the treatment of
Clostridium difficile
infection. We report here the further characterization of the
in vitro
mode of action of surotomycin, including its activity against growing and nongrowing
C. difficile
. This was assessed through time-kill kinetics, allowing a determination of the effects on the membrane potential and permeability and macromolecular synthesis in
C. difficile
. Against representative strains of
C. difficile
, surotomycin displayed concentration-dependent killing of both logarithmic-phase and stationary-phase cultures at a concentration that was ≤16× the MIC. Exposure resulted in the inhibition of macromolecular synthesis (in DNA, RNA, proteins, and cell wall). At bactericidal concentrations, surotomycin dissipated the membrane potential of
C. difficile
without changes to the permeability of propidium iodide. These observations are consistent with surotomycin acting as a membrane-active antibiotic, exhibiting rapid bactericidal activities against growing and nongrowing
C. difficile
.