bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Wave-Induced Skid Motions on the Launch of Free-Fall Skid Lifeboats From Floating Hosts: Experimental and Numerical Investigations
Authors: Luxcey Neil , Reinholdtsen Svein-Arne , Sauder Thomas , Fouques Sébastien , Jin Jingzhe , Kauczynski Wojciech , Hovland Geir 
Published: September 2014

The evacuation of personnel from offshore installations in severe weather conditions is generally ensured by free-fall lifeboats. Their performance can be assessed by means of numerical simulations to estimate accelerations loads on occupants, structural loads on the lifeboat hull, as well as forward speed after water-exit. These parameters strongly depend on the water entry conditions of the lifeboat, which in turn are very sensitive to the previous phases of the launch that starts on the skid. On floating production, storage and offloading (FPSO) vessels in the Norwegian Sea, lifeboats are often installed on skids at the bow so that waves may induce large skid motions with typical extreme vertical amplitude of fifteen to twenty meters in a 100-year storm condition. Moreover, wave-induced motions may also cause trim and list of the skid, which initiates more complex six degrees-of-freedom trajectories during free-fall. In such conditions, a proper modelling of the lifeboat trajectory on the moving skid is necessary in order to assess the performance of the lifeboat with numerical simulations.
This paper investigates the effects of the wave-induced skid motion on the launch of free-fall lifeboats from floating hosts. The first part of the paper describes the six-degrees-of-freedom numerical skid model used in MARINTEK’s lifeboat launch simulator VARUNA. The second part presents two model test campaigns aimed at validating the numerical skid model. The model test results are compared to those obtained from the numerical simulations. Finally, the importance of the skid motion on the lifeboat trajectory is discussed.
Fatigue Strength Assessment of Propellers by Means of Weakly Coupled CFD and FEM Analyses
Authors: Bertoglio Chiara , Gaggero Stefano , Rizzo Cesare M. , Viviani Michele 
Published: September 2014

Propeller design considerably evolved during years, continuously imposing new challenges to the designer, from usual high efficiency and avoidance of erosive cavitation up to reduction of radiated noise and pressure pulses for “high added value” ships. New more stringent limits, together with a general requirement for performances optimization, leads to the need of a continuous review of design procedures which, in some cases, still rely on rather “old-fashioned” approaches.
The aim of this paper is to analyse in detail the importance of considering fatigue phenomena in the propeller design, proposing a procedure for the evaluation in time of the stress field acting on a blade during one revolution, which is then considered for fatigue assessment.
Analysis and Probabilistic Modeling of the Stationary Ice Loads Stochastic Process With Lognormal Distribution
Authors: Zvyagin Petr , Sazonov Kirill 
Published: September 2014

Until recent times researchers who investigated ice loads stochastic processes usually stated the fact of normal distribution for them. In the paper the model of a stationary stochastic process with a lognormal distribution for ice loads is offered. This model relates to the strain gauge transducer ice loads measurements as well as to some examples considered in different papers that were published earlier.
For this model dependencies of the autocorrelation function were found that allows to simulate the ice loads process relatively easily. The procedure of such a simulation is described in details and the example of the analysis and simulation ice loads measurements is provided.
Finite Element Analysis Applied in Structural Integrity Management
Authors: Dybwad Jacob , Bryndum Mads , Hollingworth Russell 
Published: September 2014

During the periodic inspection of the Alvheim subsea system 2013 a number of cracks were observed at the Mid Water Arch (MWA) tether anchoring arrangement. The MWA and associated anchor block are critical design elements. Detailed investigations were initiated in order to determine future development of the cracks and their severity.
The application of advanced non-linear finite element analysis as part of the inspection and maintenance strategy resulted in significant cost savings compared to a solution based on immediate mitigation action.
This paper describes the background for occurrence of these cracks and the analyses used to determine their development:
• The cracks are located in non-loadbearing locking brackets. The function of the brackets is primarily to secure the pins connecting the top part of the tether hinge to the anchor block.
• During construction the locking brackets were welded to the pin and to the tether hinge. This way the non-structural element became part of the load bearing system resulting in very high stresses in the bracket and subsequent crack development. It could not immediately be excluded that the cracks observed could initiate further cracking into main bearing parts of the hinge.
• FE modeling using Abaqus [1] was used to analyze the criticality of the situation. Non-linear material properties and removal of elements were applied in order to simulate crack initiation and crack growth.
The system was analyzed by modelling the load paths from initial assembly on land, installation loads and finally the loads during operation. Removal of elements was introduced to replicate the crack growth pattern observed on ROV still photos from periodic surveys 2012 and 2013.
The analysis documented the principle mechanism behind the crack development and further demonstrated that the risk of failure of any of the load bearing elements was negligible.
The results of the analysis provided the necessary documentation for the appropriate precautions and at the same time plan for execution of mitigation measures which would have minimal economic impact.
Complex Polymorphisms in the Plasmodium falciparum Multidrug Resistance Protein 2 Gene and Its Contribution to Antimalarial Response
Authors: Veiga Maria Isabel , Osório Nuno S. , Ferreira Pedro Eduardo , Franzén Oscar , Dahlstrom Sabina , Lum J. Koji , Nosten Francois , Gil José Pedro 
Published: September 2014

ABSTRACT

Plasmodium falciparum
has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the
Apicomplexa
parasites.
P. falciparum
genome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters:
Pfmrp1
, previously associated with decreased parasite drug susceptibility, and the poorly studied
Pfmrp2
. The role of
Pfmrp2
polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of the
Pfmrp2
genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found that
Pfmrp2
harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identified
Pfmrp2
polymorphisms with altered
in vitro
susceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggested
Pfmrp2
polymorphisms modulate the parasite's
in vitro
response to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association with
in vivo
parasite clearance. In conclusion, our study reveals that the
Pfmrp2
gene is the most diverse ABC transporter known in
P. falciparum
with a potential role in antimalarial drug resistance.
Beneficial Effect of Oral Tigecycline Treatment on Clostridium difficile Infection in Gnotobiotic Piglets
Authors: Kim Hyeun Bum , Zhang Quanshun , Sun Xingmin , Beamer Gillian , Wang Yuankai , Tzipori Saul 
Published: September 2014

ABSTRACT

The efficacy of oral tigecycline treatment (2 mg/kg of body weight for 7 days) of
Clostridium difficile
infection (CDI) was evaluated in the gnotobiotic pig model, and its effect on human gut microflora transplanted into the gnotobiotic pig was determined. Tigecycline oral treatment improved survival, clinical signs, and lesion severity and markedly decreased concentrations of
Firmicutes
but did not promote CDI. Our data showed that oral tigecycline treatment has a potential beneficial effect on the treatment of CDI.
Effect of Fluorescent Dyes on
In Vitro
-Differentiated, Late-Stage Plasmodium falciparum Gametocytes
Authors: Gebru Tamirat , Mordmüller Benjamin , Held Jana 
Published: September 2014

ABSTRACT

Plasmodium falciparum
gametocytes are not associated with clinical symptoms, but they are responsible for transmitting the pathogen to mosquitoes. Therefore, gametocytocidal interventions are important for malaria control and resistance containment. Currently available drugs and vaccines are not well suited for that purpose. Several dyes have potent antimicrobial activity, but their use against gametocytes has not been investigated systematically. The gametocytocidal activity of nine synthetic dyes and four control compounds was tested against stage V gametocytes of the laboratory strain 3D7 and three clinical isolates of
P. falciparum
with a bioluminescence assay. Five of the fluorescent dyes had submicromolar 50% inhibitory concentration (IC
50
) values against mature gametocytes. Three mitochondrial dyes, MitoRed, dihexyloxacarbocyanine iodide (DiOC6), and rhodamine B, were highly active (IC
50
s < 200 nM). MitoRed showed the highest activity against gametocytes, with IC
50
s of 70 nM against 3D7 and 120 to 210 nM against clinical isolates. All compounds were more active against the laboratory strain 3D7 than against clinical isolates. In particular, the endoperoxides artesunate and dihydroartemisinin showed a 10-fold higher activity against 3D7 than against clinical isolates. In contrast to all clinically used antimalarials, several fluorescent dyes had surprisingly high
in vitro
activity against late-stage gametocytes. Since they also act against asexual blood stages, they shall be considered starting points for the development of new antimalarial lead compounds.
Genome Sequencing of an Extended Series of NDM-Producing Klebsiella pneumoniae Isolates from Neonatal Infections in a Nepali Hospital Characterizes the Extent of Community- versus Hospital-Associated Transmission in an Endemic Setting
Authors: Stoesser N. , Giess A. , Batty E. M. , Sheppard A. E. , Walker A. S. , Wilson D. J. , Didelot X. , Bashir A. , Sebra R. , Kasarskis A. , Sthapit B. , Shakya M. , Kelly D. , Pollard A. J. , Peto T. E. A. , Crook D. W. , Donnelly P. , Thorson S. , Amatya P. , Joshi S. 
Published: September 2014

ABSTRACT

NDM-producing
Klebsiella pneumoniae
strains represent major clinical and infection control challenges, particularly in resource-limited settings with high rates of antimicrobial resistance. Determining whether transmission occurs at a gene, plasmid, or bacterial strain level and within hospital and/or the community has implications for monitoring and controlling spread. Whole-genome sequencing (WGS) is the highest-resolution typing method available for transmission epidemiology. We sequenced carbapenem-resistant
K. pneumoniae
isolates from 26 individuals involved in several infection case clusters in a Nepali neonatal unit and 68 other clinical Gram-negative isolates from a similar time frame, using Illumina and PacBio technologies. Within-outbreak chromosomal and closed-plasmid structures were generated and used as data set-specific references. Three temporally separated case clusters were caused by a single NDM
K. pneumoniae
strain with a conserved set of four plasmids, one being a 304,526-bp plasmid carrying
bla
NDM-1
. The plasmids contained a large number of antimicrobial/heavy metal resistance and plasmid maintenance genes, which may have explained their persistence. No obvious environmental/human reservoir was found. There was no evidence of transmission of outbreak plasmids to other Gram-negative clinical isolates, although
bla
NDM
variants were present in other isolates in different genetic contexts. WGS can effectively define complex antimicrobial resistance epidemiology. Wider sampling frames are required to contextualize outbreaks. Infection control may be effective in terminating outbreaks caused by particular strains, even in areas with widespread resistance, although this study could not demonstrate evidence supporting specific interventions. Larger, detailed studies are needed to characterize resistance genes, vectors, and host strains involved in disease, to enable effective intervention.
Fibronectin-Degrading Activity of Trypanosoma cruzi Cysteine Proteinase Plays a Role in Host Cell Invasion
Authors: Maeda Fernando Yukio , Cortez Cristian , Izidoro Mario Augusto , Juliano Luiz , Yoshida Nobuko 
Published: September 2014

ABSTRACTTrypanosoma cruzi, the agent of Chagas disease, binds to diverse extracellular matrix proteins. Such an ability prevails in the parasite forms that circulate in the bloodstream and contributes to host cell invasion. Whether this also applies to the insect-stage metacyclic trypomastigotes, the developmental forms that initiate infection in the mammalian host, is not clear. UsingT. cruziCL strain metacyclic forms, we investigated whether fibronectin bound to the parasites and affected target cell invasion. Fibronectin present in cell culture medium bound to metacyclic forms and was digested by cruzipain, the majorT. cruzicysteine proteinase. G strain, with negligible cruzipain activity, displayed a minimal fibronectin-degrading effect. Binding to fibronectin was mediated by gp82, the metacyclic stage-specific surface molecule implicated in parasite internalization. When exogenous fibronectin was present at concentrations higher than cruzipain can properly digest, or fibronectin expression was stimulated by treatment of epithelial HeLa cells with transforming growth factor beta, the parasite invasion was reduced. Treatment of HeLa cells with purified recombinant cruzipain increased parasite internalization, whereas the treatment of parasites with cysteine proteinase inhibitor had the opposite effect. Metacyclic trypomastigote entry into HeLa cells was not affected by anti-β1 integrin antibody but was inhibited by anti-fibronectin antibody. Overall, our results have indicated that the cysteine proteinase ofT. cruzimetacyclic forms, through its fibronectin-degrading activity, is implicated in host cell invasion.
Bordetella parapertussis Survives inside Human Macrophages in Lipid Raft-Enriched Phagosomes
Authors: Gorgojo Juan , Harvill Eric T. , Rodríguez Maria Eugenia 
Published: September 2014

ABSTRACT

Bordetella parapertussis
is a human pathogen that causes whooping cough. The increasing incidence of
B. parapertussis
has been attributed to the lack of cross protection induced by pertussis vaccines. It was previously shown that
B. parapertussis
is able to avoid bacterial killing by polymorphonuclear leukocytes (PMN) if specific opsonic antibodies are not present at the site of interaction. Here, we evaluated the outcome of
B. parapertussis
innate interaction with human macrophages, a less aggressive type of cell and a known reservoir of many persistent pathogens. The results showed that in the absence of opsonins, O antigen allows
B. parapertussis
to inhibit phagolysosomal fusion and to remain alive inside macrophages. The O antigen targets
B. parapertussis
to lipid rafts that are retained in the membrane of phagosomes that do not undergo lysosomal maturation. Forty-eight hours after infection, wild-type
B. parapertussis
bacteria but not the O antigen-deficient mutants were found colocalizing with lipid rafts and alive in nonacidic compartments. Taken together, our data suggest that in the absence of opsonic antibodies,
B. parapertussis
survives inside macrophages by preventing phagolysosomal maturation in a lipid raft- and O antigen-dependent manner. Two days after infection, about 15% of macrophages were found loaded with live bacteria inside flotillin-enriched phagosomes that had access to nutrients provided by the host cell recycling pathway, suggesting the development of an intracellular infection. IgG opsonization drastically changed this interaction, inducing efficient bacterial killing. These results highlight the need for
B. parapertussis
opsonic antibodies to induce bacterial clearance and prevent the eventual establishment of cellular reservoirs of this pathogen.
The Type II Secretion System Delivers Matrix Proteins for Biofilm Formation by Vibrio cholerae
Authors: Johnson Tanya L. , Fong Jiunn C. , Rule Chelsea , Rogers Andrew , Yildiz Fitnat H. , Sandkvist Maria 
Published: September 2014

ABSTRACT

Gram-negative bacteria have evolved several highly dedicated pathways for extracellular protein secretion, including the type II secretion (T2S) system. Since substrates secreted via the T2S system include both virulence factors and degradative enzymes, this secretion system is considered a major survival mechanism for pathogenic and environmental species. Previous analyses revealed that the T2S system mediates the export of ≥20 proteins in
Vibrio cholerae
, a human pathogen that is indigenous to the marine environment. Here we demonstrate a new role in biofilm formation for the
V. cholerae
T2S system, since wild-type
V. cholerae
was found to secrete the biofilm matrix proteins RbmC, RbmA, and Bap1 into the culture supernatant, while an isogenic T2S mutant could not. In agreement with this finding, the level of biofilm formation in a static microtiter assay was diminished in T2S mutants. Moreover, inactivation of the T2S system in a rugose
V. cholerae
strain prevented the development of colony corrugation and pellicle formation at the air-liquid interface. In contrast, extracellular secretion of the exopolysaccharide VPS, an essential component of the biofilm matrix, remained unaffected in the T2S mutants. Our results indicate that the T2S system provides a mechanism for the delivery of extracellular matrix proteins known to be important for biofilm formation by
V. cholerae
. Because the T2S system contributes to the pathogenicity of
V. cholerae
by secreting proteins such as cholera toxin and biofilm matrix proteins, elucidation of the molecular mechanism of T2S has the potential to lead to the development of novel preventions and therapies.
Epigenetic DNA Methylation of Antioxidative Stress Regulator NRF2 in Human Prostate Cancer
Authors: Khor Tin Oo , Fuentes Francisco , Shu Limin , Paredes-Gonzalez Ximena , Yang Anne Yuqing , Liu Yue , Smiraglia Dominic J. , Yegnasubramanian Srinivasan , Nelson William G. , Kong Ah-Ng Tony 
Published: September 2014

Abstract
Epigenetic control of NRF2, a master regulator of many critical antioxidative stress defense genes in human prostate cancer (CaP), is unknown. Our previous animal study found decreased Nrf2 expression through promoter CpG methylation/histone modifications during prostate cancer progression in TRAMP mice. In this study, we evaluated CpG methylation of human NRF2 promoter in 27 clinical prostate cancer samples and in LNCaP cells using MAQMA analysis and bisulfite genomic DNA sequencing. Prostate cancer tissue microarray (TMA) containing normal and prostate cancer tissues was studied by immunohistochemistry. Luciferase reporter assay using specific human NRF2 DNA promoter segments and chromatin immunoprecipitation (ChIP) assay against histone modifying proteins were performed in LNCaP cells. Three specific CpG sites in the NRF2 promoter were found to be hypermethylated in clinical prostate cancer samples (BPH&lt;ADT-RCaP&lt;AS-CaP). NRF2 staining in human prostate cancer TMA showed a decreasing trend for both intensity and percentage of positive cells from normal tissues to advanced-stage prostate cancer (Gleason score from 3–9). Reporter assays in the LNCaP cells containing these three CpG sites showed methylation-inhibited transcriptional activity of the NRF2 promoter. LNCaP cells treated with 5-aza/TSA restored the expression of NRF2 and NRF2 downstream target genes, decreased expression levels of DNMT and HDAC proteins, and ChIP assays showed increased RNA Pol II and H3Ac with a concomitant decrease in H3K9me3, MBD2, and MeCP2 at CpG sites of human NRF2 promoter. Taken together, these findings suggest that epigenetic modification may contribute to the regulation of transcription activity of NRF2, which could be used as prevention and treatment target of human prostate cancer. Cancer Prev Res; 7(12); 1186–97. ©2014 AACR.
Dietary Fat Supply to Failing Hearts Determines Dynamic Lipid Signaling for Nuclear Receptor Activation and Oxidation of Stored Triglyceride
Authors: Lahey Ryan , Wang Xuerong , Carley Andrew N. , Lewandowski E. Douglas 
Published: September 2014

Background—
Intramyocardial triglyceride (TG) turnover is reduced in pressure-overloaded, failing hearts, limiting the availability of this rich source of long-chain fatty acids for mitochondrial β-oxidation and nuclear receptor activation. This study explored 2 major dietary fats, palmitate and oleate, in supporting endogenous TG dynamics and peroxisome proliferator–activated receptor-α activation in sham-operated (SHAM) and hypertrophied (transverse aortic constriction [TAC]) rat hearts.

Methods and Results—

Isolated SHAM and TAC hearts were provided media containing carbohydrate with either
13
C-palmitate or
13
C-oleate for dynamic
13
C nuclear magnetic resonance spectroscopy and end point liquid chromatography/mass spectrometry of TG dynamics. With palmitate, TAC hearts contained 48% less TG versus SHAM (
P
=0.0003), whereas oleate maintained elevated TG in TAC, similar to SHAM. TG turnover in TAC was greatly reduced with palmitate (TAC, 46.7±12.2 nmol/g dry weight per min; SHAM, 84.3±4.9;
P
=0.0212), as was β-oxidation of TG. Oleate elevated TG turnover in both TAC (140.4±11.2) and SHAM (143.9±15.6), restoring TG oxidation in TAC. Peroxisome proliferator–activated receptor-α target gene transcripts were reduced by 70% in TAC with palmitate, whereas oleate induced normal transcript levels. Additionally, mRNA levels for peroxisome proliferator–activated receptor-γ-coactivator-1α and peroxisome proliferator–activated receptor-γ-coactivator-1β in TAC hearts were maintained by oleate. With these metabolic effects, oleate also supported a 25% improvement in contractility over palmitate with TAC (
P
=0.0202).

Conclusions—
The findings link reduced intracellular lipid storage dynamics to impaired peroxisome proliferator–activated receptor-α signaling and contractility in diseased hearts, consistent with a rate-dependent lipolytic activation of peroxisome proliferator–activated receptor-α. In decompensated hearts, oleate may serve as a beneficial energy substrate versus palmitate by upregulating TG dynamics and nuclear receptor signaling.