bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental and Numerical Investigation of BOP Shear Ram Performance
Authors: Tulimilli Bhaskar Rao , Naik Pramod , Chakraborty Arindam , Sawant Sourabh , Whooley Alan , Weiss Robert 
Published: September 2014

A Blowout Preventer (BOP) consists of several sets of shear rams stacked together out of which Blind Shear Rams (BSR) is a very critical component to achieve complete shearing of drill pipe. The current study focusses on developing a methodology to model the shearing process and validate it with the shop test. Shop tests were conducted to shear a drill pipe using a surface BOP to obtain the maximum shearing force, shape of sheared drill pipes, shearing time etc. The shear rams used in the test are laser scanned and used in FEA simulations. The FEA model is developed such that it replicates the shop test and simulations are performed using Abaqus Explicit finite element solver. The output from simulations and shop test are compared and found to be in good agreement. The developed methodology is further verified by applying it for shearing different drill pipe sizes and the output is compared with the available data and found to be comparative which proves that the methodology can be implemented for various shearing studies.
Original Equipment Manufacturer (OEM) formulas are currently being used in industry to compute the maximum shearing force required to shear the drill pipe under various scenarios. The OEM shearing force is computed for the model under consideration and compared with the shop test and simulation and is found to be conservative. The validated model can be used for conducting studies that provide information on the governing parameters in terms of loading or positioning of the drill pipe to be considered in shear ram designs. This study provides a tool for optimizing the preliminary design of new shear rams and can contribute to more reliable and efficient shear ram design. The study is conducted as part of a Technology Assessment Programs (TAP) for the Bureau of Safety and Environmental Enforcement (BSEE) in the areas of BOP stack sequencing, monitoring and kick detection.
Pharmacokinetics and Pharmacodynamics of (+)-Primaquine and (−)-Primaquine Enantiomers in Rhesus Macaques (Macaca mulatta)
Authors: Saunders David , Vanachayangkul Pattaraporn , Imerbsin Rawiwan , Khemawoot Phisit , Siripokasupkul Raveewan , Tekwani Babu L. , Sampath Aruna , Nanayakkara N. P. Dhammika , Ohrt Colin , Lanteri Charlotte , Gettyacamin Montip , Teja-Isavadharm Paktiya , Walker Larry 
Published: September 2014

ABSTRACT

Primaquine (PQ) remains the sole available drug to prevent relapse of
Plasmodium vivax
malaria more than 60 years after licensure. While this drug was administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential antirelapse activity and/or toxicities of its enantiomers. Oral primaquine enantiomers prepared using a novel, easily scalable method were given for 7 days to healthy rhesus macaques in a dose-rising fashion to evaluate their effects on the blood, liver, and kidneys. The enantiomers were then administered to
Plasmodium cynomolgi
-infected rhesus macaques at doses of 1.3 and 0.6 mg/kg of body weight/day in combination with chloroquine. The (−)-PQ enantiomer had higher clearance and apparent volume of distribution than did (+)-PQ and was more extensively converted to the carboxy metabolite. There is evidence for differential oxidative stress with a concentration-dependent rise in methemoglobin (MetHgb) with increasing doses of (+)-PQ greater than that seen for (−)-PQ. There was a marked, reversible hepatotoxicity in 2 of 3 animals dosed with (−)-PQ at 4.5 mg/kg. (−)-PQ in combination with chloroquine was successful in preventing
P. cynomolgi
disease relapse at doses of 0.6 and 1.3 mg/kg/day, while 1 of 2 animals receiving (+)-PQ at 0.6 mg/kg/day relapsed. While (−)-PQ was also associated with hepatotoxicity at higher doses as seen previously, this has not been identified as a clinical concern in humans during >60 years of use. Limited evidence for increased MetHgb generation with the (+) form in the rhesus macaque model suggests that it may be possible to improve the therapeutic window for hematologic toxicity in the clinic by separating primaquine into its enantiomers.
Inhibition of Rift Valley Fever Virus Replication and Perturbation of Nucleocapsid-RNA Interactions by Suramin
Authors: Ellenbecker Mary , Lanchy Jean-Marc , Lodmell J. Stephen 
Published: September 2014

ABSTRACT

Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. There are currently no proven safe and effective treatment options for RVFV infection. Inhibition of RNA binding to RVFV nucleocapsid protein (N) represents an attractive antiviral therapeutic strategy because several essential steps in the RVFV replication cycle involve N binding to viral RNA. In this study, we demonstrate the therapeutic potential of the drug suramin by showing that it functions well as an inhibitor of RVFV replication at multiple stages in human cell culture. Suramin has been used previously to treat trypanosomiasis in Africa. We characterize the dynamic and cooperative nature of N-RNA binding interactions and the dissociation of high-molecular-mass ribonucleoprotein complexes using suramin, which we previously identified as an N-RNA binding inhibitor in a high-throughput screen. Finally, we elucidate the molecular mechanism used by suramin
in vitro
to disrupt both specific and nonspecific binding events important for ribonucleoprotein formation.
Spectrum of Activity and Mechanisms of Resistance of Various Nucleoside Derivatives against Gammaherpesviruses
Authors: Coen Natacha , Duraffour Sophie , Topalis Dimitri , Snoeck Robert , Andrei Graciela 
Published: September 2014

ABSTRACT

The susceptibilities of gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and animal rhadinoviruses, to various nucleoside analogs was investigated in this work. Besides examining the antiviral activities and modes of action of antivirals currently marketed for the treatment of alpha- and/or betaherpesvirus infections (including acyclovir, ganciclovir, penciclovir, foscarnet, and brivudin), we also investigated the structure-activity relationship of various 5-substituted uridine and cytidine molecules. The antiviral efficacy of nucleoside derivatives bearing substitutions at the 5 position was decreased if the bromovinyl was replaced by chlorovinyl. 1-β-
d
-Arabinofuranosyl-(
E
)-5-(2-bromovinyl)uracil (BVaraU), a nucleoside with an arabinose configuration of the sugar ring, exhibited no inhibitory effect against rhadinoviruses but was active against EBV. On the other hand, the fluoroarabinose cytidine analog 2′-fluoro-5-iodo-aracytosine (FIAC) showed high selectivity indices against gammaherpesviruses that were comparable to those of brivudin. Additionally, we selected brivudin- and acyclovir-resistant rhadinoviruses
in vitro
and characterized them by phenotypic and genotypic (i.e., sequencing of the viral thymidine kinase, protein kinase, and DNA polymerase) analysis. Here, we reveal key amino acids in these enzymes that play an important role in substrate recognition. Our data on drug susceptibility profiles of the different animal gammaherpesvirus mutants highlighted cross-resistance patterns and indicated that pyrimidine nucleoside derivatives are phosphorylated by the viral thymidine kinase and purine nucleosides are preferentially activated by the gammaherpesvirus protein kinase.
New Insights into Chloramphenicol Biosynthesis in Streptomyces venezuelae ATCC 10712
Authors: Fernández-Martínez Lorena T. , Borsetto Chiara , Gomez-Escribano Juan Pablo , Bibb Maureen J. , Al-Bassam Mahmoud M. , Chandra Govind , Bibb Mervyn J. 
Published: September 2014

ABSTRACT

Comparative genome analysis revealed seven uncharacterized genes,
sven0909
to
sven0915
, adjacent to the previously identified chloramphenicol biosynthetic gene cluster (
sven0916–sven0928
) of
Streptomyces venezuelae
strain ATCC 10712 that was absent in a closely related
Streptomyces
strain that does not produce chloramphenicol. Transcriptional analysis suggested that three of these genes might be involved in chloramphenicol production, a prediction confirmed by the construction of deletion mutants. These three genes encode a cluster-associated transcriptional activator (Sven0913), a phosphopantetheinyl transferase (Sven0914), and a Na
+
/H
+
antiporter (Sven0915). Bioinformatic analysis also revealed the presence of a previously undetected gene,
sven0925
, embedded within the chloramphenicol biosynthetic gene cluster that appears to encode an acyl carrier protein, bringing the number of new genes likely to be involved in chloramphenicol production to four. Microarray experiments and synteny comparisons also suggest that
sven0929
is part of the biosynthetic gene cluster. This has allowed us to propose an updated and revised version of the chloramphenicol biosynthetic pathway.
Salmonella enterica Serovar Enteritidis Antimicrobial Peptide Resistance Genes Aid in Defense against Chicken Innate Immunity, Fecal Shedding, and Egg Deposition
Authors: McKelvey Jessica A. , Yang Ming , Jiang Yanhua , Zhang Shuping 
Published: September 2014

ABSTRACT

Salmonella enterica
serovar Enteritidis (
S
. Enteritidis) is a major etiologic agent of nontyphoid salmonellosis in the United States.
S
. Enteritidis persistently and silently colonizes the intestinal and reproductive tract of laying hens, resulting in contaminated poultry products. The consumption of contaminated poultry products has been identified as a significant risk factor for human salmonellosis. To understand the mechanisms
S
. Enteritidis utilizes to colonize and persist in laying hens, we used selective capture of transcribed sequences to identify genes overexpressed in the HD11 chicken macrophage cell line and in primary chicken oviduct epithelial cells. From the 15 genes found to be overexpressed in both cell types, we characterized the antimicrobial peptide resistance (AMPR) genes,
virK
and
ybjX
,
in vitro
and
in vivo. In vitro
, AMPR genes were required for natural morphology, motility, secretion, defense against detergents such as EDTA and bile salts, and resistance to antimicrobial peptides polymyxin B and avian β-defensins. From this, we inferred the AMPR genes play a role in outer membrane stability and/or modulation. In the intestinal tract, AMPR genes were involved in early intestinal colonization and fecal shedding. In the reproductive tract,
virK
was required in early colonization whereas a deletion of
ybjX
caused prolonged ovary colonization and egg deposition. Data from the present study indicate that AMPR genes are differentially utilized in various host environments, which may ultimately assist
S
. Enteritidis in persistent and silent colonization of chickens.
Strain-Dependent Cellular Immune Responses in Cattle following Escherichia coli O157:H7 Colonization
Authors: Corbishley Alexander , Ahmad Nur Indah , Hughes Kirsty , Hutchings Michael R. , McAteer Sean P. , Connelley Timothy K. , Brown Helen , Gally David L. , McNeilly Tom N. 
Published: September 2014

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) O157:H7 causes hemorrhagic diarrhea and potentially fatal renal failure in humans. Ruminants are considered to be the primary reservoir for human infection. Vaccines that reduce shedding in cattle are only partially protective, and their underlying protective mechanisms are unknown. Studies investigating the response of cattle to colonization generally focus on humoral immunity, leaving the role of cellular immunity unclear. To inform future vaccine development, we studied the cellular immune responses of cattle during EHEC O157:H7 colonization. Calves were challenged either with a phage type 21/28 (PT21/28) strain possessing the Shiga toxin 2a (Stx2a) and Stx2c genes or with a PT32 strain possessing the Stx2c gene only. T-helper cell-associated transcripts at the terminal rectum were analyzed by reverse transcription-quantitative PCR (RT-qPCR). Induction of gamma interferon (IFN-γ) and T-bet was observed with peak expression of both genes at 7 days in PT32-challenged calves, while upregulation was delayed, peaking at 21 days, in PT21/28-challenged calves. Cells isolated from gastrointestinal lymph nodes demonstrated antigen-specific proliferation and IFN-γ release in response to type III secreted proteins (T3SPs); however, responsiveness was suppressed in cells isolated from PT32-challenged calves. Lymph node cells showed increased expression of the proliferation marker Ki67 in CD4
+
T cells from PT21/28-challenged calves, NK cells from PT32-challenged calves, and CD8
+
and γδ T cells from both PT21/28- and PT32-challenged calves following
ex vivo
restimulation with T3SPs. This study demonstrates that cattle mount cellular immune responses during colonization with EHEC O157:H7, the temporality of which is strain dependent, with further evidence of strain-specific immunomodulation.
A Novel Transcriptional Activator,
tubX
, Is Required for the Stability of Bacillus sphaericus Mosquitocidal Plasmid pBsph
Authors: Ge Yong , Zhao Ni , Hu Xiaomin , Shi Tingyu , Cai Quanxin , Yuan Zhiming 
Published: September 2014

ABSTRACT

Stable maintenance of the low-copy-number plasmid pBsph in
Bacillus sphaericus
requires a partitioning (
par
) system that consists of a filament-forming protein,
B. sphaericus
TubZ (TubZ-Bs); a centromere-binding protein, TubR-Bs; and a centromere-like DNA site,
tubC
, composed of three blocks (I, II, and III) of 12-bp degenerate repeats. Previous studies have shown that mini-pBsph replicons encoding the TubZ system are segregationally highly unstable, whereas the native pBsph is stably maintained. However, the mechanism underlying the stability discrepancy between pBsph and its minireplicon is poorly understood. Here
orf187
(encoding TubX), a gene downstream of
tubZ
-Bs, was found to play a role in plasmid stabilization. Null mutation or overexpression of
tubX
resulted in a defect in pBsph stability and a significant decrease in the level of
tubRZ
-Bs expression, and the TubX-null phenotype was suppressed by ectopic expression of a wild-type copy of
tubX
and additional
tubRZ
-Bs. An electrophoresis mobility shift assay (EMSA) and a DNase I footprinting assay revealed that the TubX protein bound directly to five 8-bp degenerate repeats located in the
par
promoter region and that TubX competed with TubR-Bs for binding to the
par
promoter. Further studies demonstrated that TubX significantly stimulated the transcription of the
par
operon in the absence of
tubR
-Bs, and a higher level of gene activation was observed when
tubR
-Bs was present. These results suggested that TubX positively regulates
tubRZ
-Bs transcription by interfering with TubR-Bs-mediated repression and binding directly to the
tubRZ
-Bs promoter region.
New tools and approaches in carbonate reservoir quality prediction: a case history from the Shu'aiba Formation, Saudi Arabia
Authors: Cantrell D. L. , Griffiths C. M. , Hughes G. W. 
Published: September 2014

Abstract
Reservoir quality prediction has historically been the ‘holy grail’ of reservoir geologists, yet few have succeeded at achieving this in a quantitative fashion. This study presents a new approach to pre-drill reservoir quality prediction that involves the integration of a variety of modelling techniques to understand, quantify and predict the geological processes that control reservoir quality. Since the initial reservoir quality framework is established at the time of deposition by a variety of depositional controls, this approach uses numerical process models to predict initial reservoir quality; results from these depositional models are then modified via a series of process modelling technologies to quantify and predict post-depositional modifications that have significantly affected reservoir quality in the interval of interest. This approach is illustrated using an example from the Early Cretaceous Shu'aiba Formation in eastern Saudi Arabia, where depositional facies, diagenesis and resulting reservoir quality are predicted and tested against well and seismic data, with generally positive results. Model-predicted sediment thicknesses match thicknesses measured in wells to within ±0.5%; depositional facies and diagenetic trends seen in key wells from the Shaybah field matched model-predicted facies and diagenesis; and model-predicted porosity matched observed porosity within ±1.8 porosity units.
Direct Chemosensitivity Monitoring Ex Vivo on Undissociated Melanoma Tumor Tissue by Impedance Spectroscopy
Authors: Jahnke Heinz-Georg , Poenick Sarah , Maschke Jan , Kendler Michael , Simon Jan C. , Robitzki Andrea A. 
Published: September 2014

Abstract
Stage III/IV melanoma remains incurable in most cases due to chemotherapeutic resistance. Thus, predicting and monitoring chemotherapeutic responses in this setting offer great interest. To overcome limitations of existing assays in evaluating the chemosensitivity of dissociated tumor cells, we developed a label-free monitoring system to directly analyze the chemosensitivity of undissociated tumor tissue. Using a preparation of tumor micro-fragments (TMF) established from melanoma biopsies, we characterized the tissue organization and biomarker expression by immunocytochemistry. Robust generation of TMF was established successfully and demonstrated on a broad range of primary melanoma tumors and tumor metastases. Organization and biomarker expression within the TMF were highly comparable with tumor tissue, in contrast to dissociated, cultivated tumor cells. Using isolated TMF, sensitivity to six clinically relevant chemotherapeutic drugs (dacarbazine, doxorubicin, paclitaxel, cisplatin, gemcitabine, and treosulfan) was determined by impedance spectroscopy in combination with a unique microcavity array technology we developed. In parallel, comparative analyses were performed on monolayer tumor cell cultures. Lastly, we determined the efficacy of chemotherapeutic agents on TMF by impedance spectroscopy to obtain individual chemosensitivity patterns. Our results demonstrated nonpredictable differences in the reaction of tumor cells to chemotherapy in TMF by comparison with dissociated, cultivated tumor cells. Our direct impedimetric analysis of melanoma biopsies offers a direct ex vivo system to more reliably predict patient-specific chemosensitivity patterns and to monitor antitumor efficacy. Cancer Res; 74(22); 6408–18. ©2014 AACR.
STAT1 Drives Tumor Progression in Serous Papillary Endometrial Cancer
Authors: Kharma Budiman , Baba Tsukasa , Matsumura Noriomi , Kang Hyun Sook , Hamanishi Junzo , Murakami Ryusuke , McConechy Melissa M. , Leung Samuel , Yamaguchi Ken , Hosoe Yuko , Yoshioka Yumiko , Murphy Susan K. , Mandai Masaki , Hunstman David G. , Konishi Ikuo 
Published: September 2014

Abstract
Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a “SPEC signature” as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease. Cancer Res; 74(22); 6519–30. ©2014 AACR.
Semantic Advantage for Learning New Phonological Form Representations
Authors: Hawkins Erin , Astle Duncan E. , Rastle Kathleen 
Published: September 2014

Abstract
Learning a new word requires discrimination between a novel sequence of sounds and similar known words. We investigated whether semantic information facilitates the acquisition of new phonological representations in adults and whether this learning enhancement is modulated by overnight consolidation. Participants learned novel spoken words either consistently associated with a visual referent or with no consistent meaning. An auditory oddball task tested discrimination of these newly learned phonological forms from known words. The MMN, an electrophysiological measure of auditory discrimination, was only elicited for words learned with a consistent semantic association. Immediately after training, this semantic benefit on auditory discrimination was linked to explicit learning of the associations, where participants with greater semantic learning exhibited a larger MMN. However, although the semantic-associated words continued to show greater auditory discrimination than nonassociated words after consolidation, the MMN was no longer related to performance in learning the semantic associations. We suggest that the provision of semantic systematicity directly impacts upon the development of new phonological representations and that a period of offline consolidation may promote the abstraction of these representations.
Brain Responses to World Knowledge Violations: A Comparison of Stimulus- and Fixation-triggered Event-related Potentials and Neural Oscillations
Authors: Metzner Paul , von der Malsburg Titus , Vasishth Shravan , Rösler Frank 
Published: September 2014

AbstractRecent research has shown that brain potentials time-locked to fixations in natural reading can be similar to brain potentials recorded during rapid serial visual presentation (RSVP). We attempted two replications of Hagoort, Hald, Bastiaansen, and Petersson [Hagoort, P., Hald, L., Bastiaansen, M., & Petersson, K. M. Integration of word meaning and world knowledge in language comprehension. Science, 304, 438–441, 2004] to determine whether this correspondence also holds for oscillatory brain responses. Hagoort et al. reported an N400 effect and synchronization in the theta and gamma range following world knowledge violations. Our first experiment (n = 32) used RSVP and replicated both the N400 effect in the ERPs and the power increase in the theta range in the time–frequency domain. In the second experiment (n = 49), participants read the same materials freely while their eye movements and their EEG were monitored. First fixation durations, gaze durations, and regression rates were increased, and the ERP showed an N400 effect. An analysis of time–frequency representations showed synchronization in the delta range (1–3 Hz) and desynchronization in the upper alpha range (11–13 Hz) but no theta or gamma effects. The results suggest that oscillatory EEG changes elicited by world knowledge violations are different in natural reading and RSVP. This may reflect differences in how representations are constructed and retrieved from memory in the two presentation modes.