bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crude Oil Network Modeling, Simulation and Optimization: Novel Approach and Operational Benefits
Authors: Rizwan Mohamed , Al-Otaibi Mohammed F. , Al-Khaledi Sadoun 
Published: October 2013

This technical paper presents the approach adopted by Kuwait Oil Company to establish an integrated Crude Oil Export Pipeline simulation model in South & East Kuwait area to achieve increase in overall asset-wide production and to improve future Pipeline & Facilities Design.
The simulation used As-Built pipeline data along with field data to achieve the objectives of the study.
The study had the following objectives:
• Identify additional capacity/ deficiency within the system.
• Perform Hydraulic Calculations (Pressure losses, Temperature Changes & Estimation of Pumping requirements from Gathering Centers).
• Determination of operating constraints/bottlenecks due to non-availability of any critical pipe segments.
• Optimization of Network.
Accuracy of the pipeline model was verified by comparing simulation results of the existing pipelines & Manifolds with the operating data to confirm that model results duplicated field measurements. The model developed in this study has the characteristics and the ability to predict the flows and pressures under wide range of conditions — including various operational modes and constraints.
The model accurately predicted the capacities and also raised few flags which were solved within short time and subsequently the network was optimized. Hydraulics study revealed that no additional capacity or looping were required. Model was studied for reliability of supply under wide range of conditions subject to potential bottlenecks and constraints which were identified in the study.
Nitrate Reductase Assay for Rapid Detection of Isoniazid, Rifampin, Ethambutol, and Streptomycin Resistance in Mycobacterium tuberculosis: a Systematic Review and Meta-Analysis
Authors: Coban Ahmet Yilmaz , Deveci Aydin , Sunter Ahmet Tevfik , Martin Anandi 
Published: October 2013

ABSTRACT

Colorimetric phenotypic tests recently gained interest because traditional primary drug susceptibility testing of
Mycobacterium tuberculosis
isolates takes a long time. We used meta-analysis techniques to review the reliability and accuracy of the nitrate reductase assay (NRA), which is one of the most popular colorimetric methods to detect resistance to first-line drugs. Medline, PubMed, ISI Web, Web of Science, and Google Scholar were used to search for studies enrolled in the meta-analysis. The analysis included 35 studies for isoniazid (INH), 38 for rifampin (RIF), and 22 for ethambutol (EMB) and streptomycin (STR). Summary receiver operating characteristic (SROC) curves were applied to summarize diagnostic accuracy. The meta-analyses were performed by the use of Meta-DiSc software (version 1.4) and were focused on sensitivity and specificity values for measurements of accuracy. The pooled sensitivities were 96% for INH, 97% for RIF, 90% for EMB, and 82% for STR. The pooled specificities for INH, RIF, EMB, and STR were 99%, 100%, 98%, and 96%, respectively. The times required to obtain results were between 5 and 28 days by the direct NRA and between 5 and 14 days by the indirect test. In conclusion, the present meta-analysis showed that the NRA is a reliable low-cost rapid colorimetric susceptibility test that can be used for the detection of multidrug-resistant (MDR) tuberculosis, including detection of EMB resistance. However, the test appears to have a relatively low sensitivity for STR and needs further improvement.
Homology Analysis of Pathogenic Yersinia Species Yersinia enterocolitica, Yersinia pseudotuberculosis, and Yersinia pestis Based on Multilocus Sequence Typing
Authors: Duan Ran , Liang Junrong , Shi Guoxiang , Cui Zhigang , Hai Rong , Wang Peng , Xiao Yuchun , Li Kewei , Qiu Haiyan , Gu Wenpeng , Du Xiaoli , Jing Huaiqi , Wang Xin 
Published: October 2013

ABSTRACT

We developed a multilocus sequence typing (MLST) scheme and used it to study the population structure and evolutionary relationships of three pathogenic
Yersinia
species. MLST of these three
Yersinia
species showed a complex of two clusters, one composed of
Yersinia pseudotuberculosis
and
Yersinia pestis
and the other composed of
Yersinia enterocolitica
. Within the first cluster, the predominant
Y. pestis
sequence type 90 (ST90) was linked to
Y. pseudotuberculosis
ST43 by one locus difference, and 81.25% of the ST43 strains were from serotype O:1b, supporting the hypothesis that
Y. pestis
descended from the O:1b serotype of
Y. pseudotuberculosis
. We also found that the worldwide-prevalent serotypes O:1a, O:1b, and O:3 were predominated by specific STs. The second cluster consisted of pathogenic and nonpathogenic
Y. enterocolitica
strains, two of which may not have identical STs. The pathogenic
Y. enterocolitica
strains formed a relatively conserved group; most strains clustered within ST186 and ST187. Serotypes O:3, O:8, and O:9 were separated into three distinct blocks. Nonpathogenic
Y. enterocolitica
STs were more heterogeneous, reflecting genetic diversity through evolution. By providing a better and effective MLST procedure for use with the
Yersinia
community, valuable information and insights into the genetic evolutionary differences of these pathogens were obtained.
Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough
Authors: Monroy-Vaca Ernesto X. , de Armas Yaxsier , Illnait-Zaragozí María T. , Toraño Gilda , Diaz Raúl , Vega Dania , Alvarez-Lam Ileana , Calderón Enrique J. , Stensvold Christen R. 
Published: October 2013

ABSTRACT

This study describes the prevalence and genotype distribution of
Pneumocystis jirovecii
obtained from nasopharyngeal (NP) swabs from immunocompetent Cuban infants and toddlers with whooping cough (WC). A total of 163 NP swabs from 163 young Cuban children with WC who were admitted to the respiratory care units at two pediatric centers were studied. The prevalence of the organism was determined by a quantitative PCR (qPCR) assay targeting the
P. jirovecii
mitochondrial large subunit (mtLSU) rRNA gene. Genotypes were identified by direct sequencing of mtLSU ribosomal DNA (rDNA) and restriction fragment length polymorphism (RFLP) analysis of the dihydropteroate synthase (DHPS) gene amplicons. qPCR detected
P. jirovecii
DNA in 48/163 (29.4%) samples. mtLSU rDNA sequence analysis revealed the presence of three different genotypes in the population. Genotype 2 was most common (48%), followed in prevalence by genotypes 1 (23%) and 3 (19%); mixed-genotype infections were seen in 10% of the cases. RFLP analysis of DHPS PCR products revealed four genotypes, 18% of which were associated with resistance to sulfa drugs. Only contact with coughers (prevalence ratio [PR], 3.51 [95% confidence interval {CI}, 1.79 to 6.87];
P
= 0.000) and exposure to tobacco smoke (PR, 1.82 [95% CI, 1.14 to 2.92];
P
= 0.009) were statistically associated with being colonized by
P. jirovecii
. The prevalence of
P. jirovecii
in infants and toddlers with WC and the genotyping results provide evidence that this population represents a potential reservoir and transmission source of
P. jirovecii
.
Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host
Authors: Conway Michael J. , Watson Alan M. , Colpitts Tonya M. , Dragovic Srdjan M. , Li Zhiyong , Wang Penghua , Feitosa Fabiana , Shepherd Denueve T. , Ryman Kate D. , Klimstra William B. , Anderson John F. , Fikrig Erol 
Published: October 2013

ABSTRACT

Dengue virus (DENV), a flavivirus of global importance, is transmitted to humans by mosquitoes. In this study, we developed
in vitro
and
in vivo
models of saliva-mediated enhancement of DENV infectivity. Serine protease activity in
Aedes aegypti
saliva augmented virus infectivity
in vitro
by proteolyzing extracellular matrix proteins, thereby increasing viral attachment to heparan sulfate proteoglycans and inducing cell migration. A serine protease inhibitor reduced saliva-mediated enhancement of DENV
in vitro
and
in vivo
, marked by a 100-fold reduction in DENV load in murine lymph nodes. A saliva-mediated infectivity enhancement screen of fractionated salivary gland extracts identified serine protease CLIPA3 as a putative cofactor, and short interfering RNA knockdown of CLIPA3 in mosquitoes demonstrated its role in influencing DENV infectivity. Molecules in mosquito saliva that facilitate viral infectivity in the vertebrate host provide novel targets that may aid in the prevention of disease.
Characterization of the Envelope Glycoprotein of a Novel Filovirus, Lloviu Virus
Authors: Maruyama Junki , Miyamoto Hiroko , Kajihara Masahiro , Ogawa Hirohito , Maeda Ken , Sakoda Yoshihiro , Yoshida Reiko , Takada Ayato 
Published: October 2013

ABSTRACTLloviu virus (LLOV), a novel filovirus detected in bats, is phylogenetically distinct from viruses in the generaEbolavirusandMarburgvirusin the familyFiloviridae. While filoviruses are known to cause severe hemorrhagic fever in humans and/or nonhuman primates, LLOV is biologically uncharacterized, since infectious LLOV has never been isolated. To examine the properties of LLOV, we characterized its envelope glycoprotein (GP), which likely plays a key role in viral tropism and pathogenicity. We first found that LLOV GP principally has the same primary structure as the other filovirus GPs. Similar to the other filoviruses, virus-like particles (VLPs) produced by transient expression of LLOV GP, matrix protein, and nucleoprotein in 293T cells had densely arrayed GP spikes on a filamentous particle. Mouse antiserum to LLOV VLP was barely cross-reactive to viruses of the other genera, indicating that LLOV is serologically distinct from the other known filoviruses. For functional study of LLOV GP, we utilized a vesicular stomatitis virus (VSV) pseudotype system and found that LLOV GP requires low endosomal pH and cathepsin L, and that human C-type lectins act as attachment factors for LLOV entry into cells. Interestingly, LLOV GP-pseudotyped VSV infected particular bat cell lines more efficiently than viruses bearing other filovirus GPs. These results suggest that LLOV GP mediates cellular entry in a manner similar to that of the other filoviruses while showing preferential tropism for some bat cells.
Chronic Joint Disease Caused by Persistent Chikungunya Virus Infection Is Controlled by the Adaptive Immune Response
Authors: Hawman David W. , Stoermer Kristina A. , Montgomery Stephanie A. , Pal Pankaj , Oko Lauren , Diamond Michael S. , Morrison Thomas E. 
Published: October 2013

ABSTRACTChikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that causes incapacitating disease in humans characterized by intense joint pain that can persist for weeks, months, or even years. Although there is some evidence of persistent CHIKV infection in humans suffering from chronic rheumatologic disease symptoms, little is known about chronic disease pathogenesis, and no specific therapies exist for acute or chronic CHIKV disease. To investigate mechanisms of chronic CHIKV-induced disease, we utilized a mouse model and defined the duration of CHIKV infection in tissues and the associated histopathological changes. Although CHIKV RNA was readily detectable in a variety of tissues very early after infection, CHIKV RNA persisted specifically in joint-associated tissues for at least 16 weeks. Inoculation ofRag1−/−mice, which lack T and B cells, resulted in higher viral levels in a variety of tissues, suggesting that adaptive immunity controls the tissue specificity and persistence of CHIKV infection. The presence of CHIKV RNA in tissues of wild-type andRag1−/−mice was associated with histopathological evidence of synovitis, arthritis, and tendonitis; thus, CHIKV-induced persistent arthritis is not mediated primarily by adaptive immune responses. Finally, we show that prophylactic administration of CHIKV-specific monoclonal antibodies prevented the establishment of CHIKV persistence, whereas therapeutic administration had tissue-specific efficacy. These findings suggest that chronic musculoskeletal tissue pathology is caused by persistent CHIKV infection and controlled by adaptive immune responses. Our results have significant implications for the development of strategies to mitigate the disease burden associated with CHIKV infection in humans.
Alternative Reassortment Events Leading to Transmissible H9N1 Influenza Viruses in the Ferret Model
Authors: Kimble J. Brian , Angel Matthew , Wan Hongquan , Sutton Troy C. , Finch Courtney , Perez Daniel R. 
Published: October 2013

ABSTRACT

Influenza A H9N2 viruses are common poultry pathogens that occasionally infect swine and humans. It has been shown previously with H9N2 viruses that reassortment can generate novel viruses with increased transmissibility. Here, we demonstrate the modeling power of a novel transfection-based inoculation system to select reassortant viruses under
in vivo
selective pressure. Plasmids containing the genes from an H9N2 virus and a pandemic H1N1 (pH1N1) virus were transfected into HEK 293T cells to potentially generate the full panel of possible H9 reassortants. These cells were then used to inoculate ferrets, and the population dynamics were studied. Two respiratory-droplet-transmissible H9N1 viruses were selected by this method, indicating a selective pressure in ferrets for the novel combination of surface genes. These results show that a transfection-based inoculation system is a fast and efficient method to model reassortment and highlight the risk of reassortment between H9N2 and pH1N1 viruses.
Transcription of True Late (γ2) Cytomegalovirus Genes Requires UL92 Function That Is Conserved among Beta- and Gammaherpesviruses
Authors: Omoto Shinya , Mocarski Edward S. 
Published: October 2013

ABSTRACT

Human cytomegalovirus-encoded UL92 plays an essential role in viral replication that has not been resolved. We show here that this gene controls the accumulation of true late (γ
2
) viral transcripts, a property shared with several other recently evaluated genes (UL79, UL87, UL91, and UL95) conserved among beta- and gammaherpesviruses. When the UL92 mutant virus was evaluated, function was fully complemented by either the natural protein or the homologous Rh127 protein from rhesus cytomegalovirus. N-terminal epitope-tagged UL92 protein is functional, follows complex early-late expression kinetics, and localizes in the nucleus within viral replication compartments. UL92 severely impacts the late (72-h postinfection) expression of nine genes encoding virion proteins (UL32, UL55, UL73, UL75, UL80, UL86, UL99, and UL115), as well as UL91 and itself, but does not influence the levels of UL44, UL82, or UL83 accumulation. Although viral DNA is made at normal levels, viral capsid accumulation in the nucleus is severely compromised in UL92 mutant virus-infected cells, and mature virions are not observed in the cytoplasm. Taken together, UL92 is a key regulator of late viral gene expression, apparently functioning with four other beta- or gammaherpesvirus gene products in a pattern that appears reminiscent of gene regulation in T4 DNA bacteriophage.
Exception handlers for healing component-based systems
Authors: Chang Hervé , Mariani Leonardo , Pezzè Mauro 
Published: October 2013

To design effective exception handlers, developers must predict at design time the exceptional events that may occur at runtime, and must implement the corresponding handlers on the basis of their predictions. Designing exception handlers for component-based software systems is particularly difficult because the information required to build handlers is distributed between component and application developers. Component developers know the internal details of the components but ignore the applications, while application developers own the applications but cannot access the details required to implement handlers in components.
This article addresses the problem of automatically healing the infield failures that are caused by faulty integration of OTS components. In the article, we propose a technique and a methodology to decouple the tasks of component and application developers, who will be able to share information asynchronously and independently, and communicate implicitly by developing and deploying what we call healing connectors. Component developers implement healing connectors on the basis of information about the integration problems frequently experienced by application developers. Application developers easily and safely install healing connectors in their applications without knowing the internal details of the connectors. Healing connectors heal failures activated by exceptions raised in the OTS components actually deployed in the system.
The article defines healing connectors, introduces a methodology to develop and deploy healing connectors, and presents several case studies that indicate that healing connectors are effective, reusable and efficient.
HAb18G/CD147 Promotes pSTAT3-Mediated Pancreatic Cancer Development via CD44s
Authors: Li Ling , Tang Wenhua , Wu Xiaoqing , Karnak David , Meng Xiaojie , Thompson Rachel , Hao Xinbao , Li Yongmin , Qiao Xiaotan T. , Lin Jiayuh , Fuchs James , Simeone Diane M. , Chen Zhi-Nan , Lawrence Theodore S. , Xu Liang 
Published: October 2013

Abstract
Purpose: Signal transducer and activator of transcription 3 (STAT3) plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 has failed clinically. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate the potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo.
Experimental Design: The expression of HAb18G/CD147, pSTAT3, and CD44s was determined in tissue microarrays. The tumorigenic function and molecular signaling mechanism of HAb18G/CD147 were assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot assay, immunofluorescence staining, immunoprecipitation, and in vivo tumor formation using loss or gain-of-function strategies.
Results: Highly expressed HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity in vivo. Cyclophilin A (CyPA), a ligand of CD147, stimulated STAT3 phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147-dependent mechanisms. HAb18G/CD147 was associated and colocalized with cancer stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell growth. High HAb18G/CD147 expression in pancreatic cancer was significantly correlated with the poor tumor differentiation, and the high coexpression of HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with pancreatic cancer.
Conclusions: We identified HAb18G/CD147 as a novel upstream activator of STAT3, which interacts with CD44s and plays a critical role in the development of pancreatic cancer. The data suggest that HAb18G/CD147 could be a promising therapeutic target for highly aggressive pancreatic cancer and a surrogate marker in the STAT3-targeted molecular therapies. Clin Cancer Res; 19(24); 6703–15. ©2013 AACR.
Darexaban (YM150) versus enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a randomised phase IIb dose confirmation study (ONYX-3)
Authors: Agnelli Giancarlo , Gallus Alexander S. , Lassen Michael R. , Prins Martin H. , Renfurm Ronny W. , Kashiwa Makoto , Turpie Alexander G. G. , Eriksson Bengt I. 
Published: October 2013

SummaryThis double-blind, double-dummy, randomised, phase IIb study (NCT00902928) evaluated different dosing regimens of darexaban compared with enoxaparin (randomised 1:1:1:1:1 to 15 mg twice daily [bid], 30 mg once daily [qd], 30 mg bid or 60 mg qd or enoxaparin 40 mg qd) in patients undergoing elective total hip arthroplasty. Patients, investigators, pharmacists and sponsor were all blinded to treatment allocation. Darexaban administration started 6-10 hours (h) post-surgery. Enoxaparin 40 mg qd administration started 12 ± 2 h before surgery. Treatment continued for 35 days. Bilateral venography was performed on Day 10 ± 2. The primary efficacy outcome was total VTEs (composite of proximal/distal deep-vein thrombosis, pulmonary embolism) or death, at Day 12. Total VTE rates were similar across all groups. There was no apparent difference in efficacy between onceand twice-daily darexaban (odds ratio [OR] 1.00; 95% confidence interval [CI] 0.71–1.42; p=0.988), or total daily dose (30 mg/day vs 60 mg/day; OR 0.81; 95% CI 0.57–1.15; p=0.244). There was no significant difference in major and/or clinically relevant non-major bleeding between darexaban qd or bid, or between total daily doses of 30 mg or 60 mg, and also for any dosing regimen of darexaban vs enoxaparin. Darexaban was well tolerated, without signs of liver toxicity. In conclusion, darexaban, administered qd or bid, and at total daily doses of 30 mg or 60 mg, appears to be effective for VTE prevention and was well tolerated. Data suggest no significant differences between a once- or twice-daily dosing regimen.
Universal versus platelet reactivity assay-driven use of P2Y12 inhibitors in acute coronary syndrome patients
Authors: Limone Brendan L. , Coleman Craig I. 
Published: October 2013

SummaryPlatelet reactivity assays (PRAs) can predict patients’ likely response to clopidogrel. As ticagrelor and prasugrel are typically considered first-line agents for acute coronary syndrome in Europe, we assessed the cost-effectiveness of universal compared to PRA-driven selection of these agents. A Markov model was used to calculate five-year costs (2013£/€), quality-adjusted life-years and incremental cost-effectiveness ratios (ICERs) for one-year of universal ticagrelor or prasugrel (given to all) compared to each agents’ corresponding PRA-driven strategy (ticagrelor/prasugrel in those with high platelet reactivity [HPR, >208 on the VerifyNow P2Y12 assay], others given generic clopidogrel). We assumed patients had their index event at 65–70 years of age and had a 42.7% incidence of HPR 24–48 hours post-revascularisation. The analysis was conducted from the perspective of six countries (France, Germany, Italy, Spain, the Netherlands and United Kingdom) and used a one-year cycle length. Event data for P2Y12 inhibitors were taken from multinational randomised trials and adjusted using country-specific epidemiologic data. Neither universal ticagrelor nor prasugrel were found to be cost-effective (all ICERs >40,250€ or £36,600/QALY) compared to their corresponding PRA-driven strategies in any of the countries evaluated. Results were sensitive to differences in P2Y12 Inhibitors costs and drug-specific relative risks of major adverse cardiac events. Monte Carlo simulation suggested universal ticagrelor or prasugrel were cost-effective in only 25–44% and 11–17% of 10,000 iterations compared to their respective PRA-driven strategies, when applying a willingness-to-pay threshold = €30,000 or £20,000/QALY. In conclusion, the universal use of newer P2Y12 inhibitors is not likely cost-effective compared to PRA-driven strategies.