bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Measurement of Human Papillomavirus Type 16 E5 Oncoprotein Levels in Epithelial Cell Lines by Mass Spectrometry
Authors: Sahab Ziad , Sudarshan Sawali R. , Liu Xuefeng , Zhang YiYu , Kirilyuk Alexander , Kamonjoh Christopher M. , Simic Vera , Dai Yuhai , Byers Stephen W. , Doorbar John , Suprynowicz Frank A. , Schlegel Richard 
Published: June 2012

ABSTRACT
The high-risk human papillomavirus type 16 (HPV-16) E5 protein (16E5) induces tumors in a transgenic mouse model and may contribute to early stages of cervical carcinogenesis. Although high-risk E5 expression is generally thought to be lost during the progression to cervical carcinoma following integration of HPV DNA into the host genome, episomal viral DNA has been documented in a subset of HPV-16-positive malignant lesions. Numerous studies have shown that transcripts that could potentially encode 16E5 are present in cervical biopsy specimens and cervical cancer cell lines, but the presence of E5 protein has been demonstrated in only two reports that have not been corroborated. In the present study, we show that trypsin cleavage of 16E5 generates a unique four-amino-acid C-terminal peptide (FLIT) that serves as a marker for E5 expression in transfected cells and epithelial cell lines containing integrated and episomal HPV-16 DNA. Following trypsin cleavage, reversed-phase chromatography and mass spectrometry (MS) were used to detect FLIT. Immunoprecipitation assays using a newly generated anti-16E5 antibody confirmed that 16E5 was solely responsible for the FLIT signal, and deuterated FLIT peptide provided an internal standard that enabled us to quantify the number of 16E5 molecules per cell. We show that 16E5 is expressed in the Caski but not in the SiHa cervical cancer cell line, suggesting that 16E5 may contribute to the malignant phenotype of some cervical cancers, even in cells exclusively containing an integrated HPV genome.
Restricted Varicella-Zoster Virus Transcription in Human Trigeminal Ganglia Obtained Soon after Death
Authors: Ouwendijk Werner J. D. , Choe Alexander , Nagel Maria A. , Gilden Don , Osterhaus Albert D. M. E. , Cohrs Randall J. , Verjans Georges M. G. M. 
Published: June 2012

ABSTRACT

We analyzed the varicella-zoster virus (VZV) transcriptome in 43 latently infected human trigeminal ganglia (TG) with postmortem intervals (PMIs) ranging from 3.7 to 24 h. Multiplex reverse transcriptase PCR (RT-PCR) revealed no VZV transcripts with a PMI of <9 h. Real-time PCR indicated a significant increase (
P
= 0.02) in VZV ORF63 transcript levels but not the virus DNA burden with longer PMI. Overall, both the breadth of the VZV transcriptome and the VZV ORF63 transcript levels in human cadaver TG increased with longer PMI.
Reverse Genetics Analysis of Poxvirus Intermediate Transcription Factors
Authors: Warren Robin D. , Cotter Catherine A. , Moss Bernard 
Published: June 2012

ABSTRACT

Vaccinia virus transcription is regulated in three stages. An intermediate transcription factor, comprised of virus-encoded polypeptides A8 and A23, was previously identified by
in vitro
analyses. To investigate its role, we engineered cells that stably expressed both subunits and complemented the replication of A8 and A23 deletion mutant viruses. Without A8 or A23, viral early gene expression and DNA replication occurred but intermediate and late gene expression and resolution of genome concatemers were not detected.
Biostratigraphic, strontium isotopic, and geologic constraints on the landward movement and fragmentation of terranes within the Tofino Basin, British Columbia
Authors: Johns Marjorie J. , Trotter Julie A. , Barnes Christopher R. , Narayan Y. Roshni 
Published: June 2012

Significant advancements in understanding the complex evolution of the Tofino Basin at a convergent accretionary margin are enabled by combining contextual geologic information with new isotopic and paleontological data. A high-resolution Cenozoic chronostratigraphy of the basin is constrained by strontium isotope ages (36.9–1.3 Ma) of Late Eocene to Pleistocene foraminifers together with a revised biostratigraphy (foraminifers and ichthyoliths) from six offshore wells and outcrop samples, new specimen thermal alteration values, and existing well log data. These data are integrated with archival multichannel seismic and magnetic data to interpret offshore well positions with relation to sub-basins and structural highs of the Pacific Rim and Crescent terranes, and other accreted strata. Six regions of the Tofino Basin are defined based on structure and depositional differences during the Eocene to Holocene history of accretion and fragmentation of the Crescent terrane and it underthrusting the Pacific Rim terrane. Subsequent oceanic sediment accretions and deposition of overlying sediments up to about 4000 m thick resulted as the Juan de Fuca plate subducted beneath Vancouver Island. Observations include different fragmentations and landward movements of the Crescent and Pacific Rim terranes in the regions and two fault styles in the Ucluelet and Carmanah regions where six new sub-basins are defined. Results, especially for the Ucluelet and Carmanah sub-basins, indicate periods of deformation during the Late Eocene, Late Oligocene, Middle–Late Miocene, and post middle Pliocene, whereas the Early Oligocene and Early Miocene had periods of relatively slow and less disturbed deposition.
Seismic force demand on ductile reinforced concrete shear walls subjected to western North American ground motions: Part 1 — parametric study
Authors: Boivin Yannick , Paultre Patrick 
Published: June 2012

A parametric study of regular ductile reinforced concrete (RC) cantilever walls designed with the 2010 National building code of Canada and the 2004 Canadian Standards Association (CSA) standard A23.3 for Vancouver is performed to investigate the influence of the following parameters on the higher mode amplification effects, and hence on the seismic force demand: number of storeys, fundamental lateral period (T), site class, wall aspect ratio, wall cross-section, and wall base flexural overstrength (γw). The study is based on inelastic time-history analyses performed with a multilayer beam model and a smeared membrane model accounting for inelastic shear–flexure–axial interaction. The main conclusions are that (i) T and γware the studied parameters affecting the most dynamic shear amplification and seismic force demand, (ii) the 2004 CSA standard A23.3 capacity design methods are inadequate, and (iii) a single plastic hinge design may be inadequate and unsafe for regular ductile RC walls with γw < 2.0.
Random mutagenesis suggests that sequence errors are not a major cause of variation in the activity of individual molecules of β-galactosidase
Authors: Craig Douglas B. , Schwab Thomas , Sterner Reinhard 
Published: June 2012

Wild-type Escherichia coli lacZ was subjected to error-prone PCR to generate two plasmid-encoded gene libraries containing approximately 2.6 (SD 1.9) nucleotide exchanges resulting in 1.8 (SD 1.4) amino-acid substitutions. The libraries were used, along with a plasmid containing wild-type lacZ, to transform E. coli lacking genomic lacZ. Cells expressing functional β-galactosidase were identified by blue/white screening. Cell lysates containing the populations of heterogeneously mutagenized β-galactosidase were subjected to single molecule assays using a capillary electrophoresis laser-induced fluorescence-based protocol. There was no significant difference in the average catalytic rate between the random mutagenized and wild-type enzyme populations. Furthermore, there was no clear pattern between error rates and the variances in the population catalytic rates. This suggests that random sequence errors are not a substantial source of the catalytic heterogeneity of this enzyme.
Domain specific overexpression of TIMP-2 and TIMP-3 reveals MMP-independent functions of TIMPs duringXenopus laevisdevelopment
Authors: Nieuwesteeg M.A. , Walsh L.A. , Fox M.A. , Damjanovski S. 
Published: June 2012

Extracellular matrix remodelling mediates many processes including cell migration and differentiation and is regulated through the enzymatic action of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). TIMPs are secreted proteins, consisting of structurally and functionally distinct N- and C-terminal domains. TIMP N-terminal domains inhibit MMP activity, whereas their C-terminal domains may have cell signalling activity. The in vivo role of TIMP N- and C-terminal domains in regulating developmental events has not previously been demonstrated. Here we investigated the roles of TIMP-2 and TIMP-3 N- and C-terminal domains in Xenopus laevis embryos. We show that overexpression of TIMP-2 N- and C-terminal domains results in severe developmental defects and death, as well as unique changes in MMP-2 and -9 expression, indicating that the individual domains may regulate MMPs through distinct mechanisms. In contrast, we show that only the N-terminal, but not the C-terminal domain of TIMP-3, results in developmental defects.
Reservoir characteristics of fault-controlled hydrothermal dolomite bodies: Ramales Platform case study
Authors: Dewit J. , Huysmans M. , Muchez Ph. , Hunt D. W. , Thurmond J. B. , Verges J. , Saura E. , Fernandez N. , Romaire I. , Esestime P. , Swennen R. 
Published: June 2012

Abstract
Hydrothermal dolomite (HTD) bodies are known as high-quality hydrocarbon reservoirs; however few studies focus on the geometry and distribution of reservoir characteristics. Across the platform-to-basin transition of the Ramales Platform, fault-controlled HTD bodies are present. Three kinds of bodies can be distinguished based on their morphology, that is, elongated HTD corridors, a massive HTD body (Pozalagua body) and an HTD-cemented breccia body. The differences in size and shape of the HTD bodies can be attributed to differences in local structural setting. For the Pozalagua body, an additional sedimentological control is invoked to explain the difference in HTD geometry.
A (geo)-statistical investigation of the reservoir characteristics in the Pozalagua body revealed that the HTD types (defined based on their texture) show spatial clustering controlled by the orientation of faults, joints and the platform edge. Porosity and permeability values are distributed in clusters of high and low values; however, they are not significantly different for the three HTD types. Two dolomitization phases (i.e. ferroan and non-ferroan) can be observed in all HTD bodies. In general, the HTDs resulting from the second non-ferroan dolomitization phase have lower porosity values. No difference in permeability is found for the ferroan and non-ferroan dolomites.
Lacustrine carbonates in rift settings: the interaction of volcanic and microbial processes on carbonate deposition
Authors: Wright V. Paul 
Published: June 2012

Abstract
The relatively simplistic facies models for lacustrine carbonates do not currently incorporate either the diversity of microbialite carbonate development or the influence of volcanic-related processes found in rift settings. The basic nature of the carbonate factories in these systems, whether microbial, macrophytic, skeletal or abiogenic, is not resolved. Lacustrine microbialites can develop in shallow lakes as concentrations of microbialite mounds covering many hundreds of square kilometres, or as bathymetrically controlled facies belts, but in many rift settings vent-related thermal and non-thermal carbonates (travertines and tufas) are a major component. Subaqueous vent-related carbonates, with evidence of microbial activity, can produce seismic-scale carbonate build-ups in deeper lakes or apparently more stratiform accumulations in shallow lakes. In lakes with only volcanic catchments, Mg and silica activity, coupled with high carbonate alkalinity and microbial influences, can potentially generate a complex set of mineral–microbe interactions and products, creating a unique set of challenges for predicting and understanding reservoirs in such settings.
Effects of diagenesis (cement precipitation) during fracture opening on fracture aperture-size scaling in carbonate rocks
Authors: Hooker J. N. , Gomez L. A. , Laubach S. E. , Gale J. F. W. , Marrett R. 
Published: June 2012

Abstract
A correlation is demonstrated between the presence of crack-seal texture and power-law kinematic aperture-size (width) distributions among opening-mode fractures in rocks of dominantly carbonate mineralogy. Crack-seal opening increments (opening-displacement increment sizes or ‘gaps’) within individual fractures follow narrow normal or log-normal size distributions, suggesting that fracture widening accumulates in characteristic (usually micrometre-scale) size increments. The scale invariance in overall fracture width distributions present in some fracture sets most likely arises from grouping of these increments (localization) to form larger fractures (millimetre- to centimetre-scale widths). Such localization could be a consequence of the tendency for larger, less cemented fractures to break preferentially during subsequent deformation. Cement accumulation patterns thus provide a mechanism for positive feedback whereby large-fracture growth exceeds small-fracture growth. Using characteristically sized growth increments, a fracture growth model accurately simulates fracture arrays having power-law fracture-width distributions. Model parameters can be altered to produce characteristic-width fracture size distributions. The results have implications for how fracture porosity and permeability evolve in carbonate reservoirs.
The MET Oncogene Is a Functional Marker of a Glioblastoma Stem Cell Subtype
Authors: De Bacco Francesca , Casanova Elena , Medico Enzo , Pellegatta Serena , Orzan Francesca , Albano Raffaella , Luraghi Paolo , Reato Gigliola , D'Ambrosio Antonio , Porrati Paola , Patanè Monica , Maderna Emanuela , Pollo Bianca , Comoglio Paolo M. , Finocchiaro Gaetano , Boccaccio Carla 
Published: June 2012

Abstract
The existence of treatment-resistant cancer stem cells contributes to the aggressive phenotype of glioblastoma. However, the molecular alterations that drive stem cell proliferation in these tumors remain unknown. In this study, we found that expression of the MET oncogene was associated with neurospheres expressing the gene signature of mesenchymal and proneural subtypes of glioblastoma. Met expression was almost absent from neurospheres expressing the signature of the classical subtype and was mutually exclusive with amplification and expression of the EGF receptor (EGFR) gene. Met-positive and Met-negative neurospheres displayed distinct growth factor requirements, differentiated along divergent pathways, and generated tumors with distinctive features. The Methigh subpopulation within Met-pos neurospheres displayed clonogenic potential and long-term self-renewal ability in vitro and enhanced growth kinetics in vivo. In Methigh cells, the Met ligand HGF further sustained proliferation, clonogenicity, expression of self-renewal markers, migration, and invasion in vitro. Together, our findings suggest that Met is a functional marker of glioblastoma stem cells and a candidate target for identification and therapy of a subset of glioblastomas. Cancer Res; 72(17); 4537–50. ©2012 AACR.
Transcription Factor NFATc2 Controls the Emergence of Colon Cancer Associated with IL-6–Dependent Colitis
Authors: Gerlach Katharina , Daniel Carolin , Lehr Hans A. , Nikolaev Alexei , Gerlach Thomas , Atreya Raja , Rose-John Stefan , Neurath Markus F. , Weigmann Benno 
Published: June 2012

AbstractNFAT transcription factors control T-cell activation and function. Specifically, the transcription factor NFATc2 affects the regulation of cell differentiation and growth and plays a critical role in the development of colonic inflammation. Here, we used an experimental model of colitis-associated colorectal carcinoma to investigate the contribution of NFATc2 to the promotion of colonic tumors. Compared with wild-type animals that readily presented with multiple colon tumors, NFATc2-deficient mice were protected from tumor development. This observed decrease in colonic tumor progression was associated with reduced endoscopic inflammation, increased apoptosis of lamina propria T lymphocytes, and significantly reduced levels of the critical proinflammatory cytokines interleukin (IL)-21 and IL-6. Administration of hyper IL-6 abrogated protection from tumor progression in NFATc2-knockout mice and restored tumor incidence to control levels. Taken together, our findings highlight a pivotal role for NFATc2 in the establishment of inflammation-associated colorectal tumors mediated by control of IL-6 expression. Cancer Res; 72(17); 4340–50. ©2012 AACR.
Stimulated in vivo synthesis of plasminogen activator inhibitor-1 in human adipose tissue
Authors: Liska Jan , Eriksson Per , Sverremark-Ekström Eva , Tornvall Per , Ekström Mattias 
Published: June 2012

SummaryPlasminogen activator inhibitor type-1 (PAI-1) is one of the most important inhibitors of endogenous fibrinolysis. Adipose tissue is a suggested source of the elevated plasma levels of PAI-1 in obesity. The relation between PAI-1 and inflammation is of particular interest, but current knowledge regarding regulation of PAI-1 in adipose tissue is mainly based on animal studies or ex vivo experiments on human cultured adipocytes. So far, no study has described stimulated gene expression and protein synthesis of PAI-1 in vivo in human adipose tissue. We used open heart surgery as a model of acute systemic inflammation. Twenty-two male patients underwent blood sampling and omental and subcutaneous adipose tissue biopsies for gene expression studies before and after surgery. Expression and localisation of PAI-1 antigen was evaluated by immunohistochemistry. After surgery gene expression of PAI-1 increased 27-fold in omental adipose tissue and three-fold in subcutaneous adipose tissue, but no differences were found in tissue-type plasminogen activator (t-PA) mRNA. PAI-1 antigen was localised within endothelial cells and in the adipose tissue interstitium close to vessels. The upregulated gene expression and protein synthesis in adipose tissue was followed by increased concentrations of PAI-1 antigen in plasma. In conclusion, we present for the first time that an acute systemic inflammation in humans increased gene expression and protein synthesis of PAI-1 in adipose tissue and that this increase was most prominent in omental adipose tissue. PAI-1 synthesis in adipose tissue due to acute systemic inflammation may be a link between inflammation and impaired endogenous fibrinolysis.
Comparative Effectiveness of Preventative Therapy for Venous Thromboembolism After Coronary Artery Bypass Graft Surgery
Authors: Kulik Alexander , Rassen Jeremy A. , Myers Jessica , Schneeweiss Sebastian , Gagne Joshua , Polinski Jennifer M. , Liu Jun , Fischer Michael A. , Choudhry Niteesh K. 
Published: June 2012

Background—
Controversy exists regarding the optimal preventative therapy for venous thromboembolism (VTE) after coronary artery bypass graft (CABG) surgery. We sought to compare the effectiveness and safety of the most commonly used regimens.

Methods and Results—

We assembled a cohort of 92 699 patients who underwent CABG between 2004 and 2008, using the Premier database. Patients were categorized by method of VTE prevention initiated within 48 hours of surgery, including no preventative therapy (n=55 400), mechanical preventative therapy (n=21 162), subcutaneous unfractio-­nated or low-molecular-weight heparin (n=10 718), subcutaneous fondaparinux (n=88), and concurrent mechanical-chemical therapy (n=5331). The incidence of VTE and major bleeding events within 6 weeks of CABG were compared, using multivariable and propensity score adjustment. The overall incidence of VTE for the entire cohort was 0.74%, and the incidence of major bleeding was 1.43%. VTE and bleeding events occurred with similar incidence in each of the patient categories (VTE: 0.70%, 0.79%, 0.81%, 1.14%, and 0.73%; major bleeding: 1.36%, 1.45%, 1.69%, 3.41%, 1.50%; no prevention, mechanical prevention, subcutaneous heparin, subcutaneous fondaparinux, concurrent mechanical-chemical prevention, respectively). Compared with receiving no prevention, the use of mechanical prevention or subcutaneous heparin did not significantly reduce the risk of VTE or change the risk of major bleeding (
P
=NS).

Conclusion—
Venous thromboembolism occurs infrequently after CABG. Compared with the use of no prevention, the administration of chemical or mechanical preventative therapies to CABG patients does not appreciably lower the risk of VTE. These data provide support for the common practice of administering no VTE preventative therapy after CABG, used for nearly 60% of patients within this cohort.
Cost-Effectiveness of Apixaban Compared With Aspirin for Stroke Prevention in Atrial Fibrillation Among Patients Unsuitable for Warfarin
Authors: Lee Soyon , Anglade Moise W. , Meng Joy , Hagstrom Kelly , Kluger Jeffrey , Coleman Craig I. 
Published: June 2012

Background—
Compared with aspirin, apixaban reduces stroke risk in atrial fibrillation (AF) patients unsuitable for warfarin by 63% but does not increase major bleeding. We sought to determine the cost-effectiveness of apixaban versus aspirin.

Methods and Results—

Using the Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin-K Antagonist Treatment (AVERROES) trial and other studies, we constructed a Markov model to evaluate the costs (2011US$), quality-adjusted life-years (QALYs), and incremental cost-effectiveness of apixaban versus aspirin from the Medicare perspective. Our base-case assumed a 70-year-old AF patient cohort with a CHADS
2
score=2 and a lower-risk of bleeding. We used a 1-month cycle-length and ran separate base-case analyses assuming a trial-length (1-year) and a longer-term (10-year) follow-up. Total costs/patient were $3454 and $1805 for apixaban and aspirin in the trial-length and $44 232 and $50 066 in the 10-year model. Corresponding QALYs were 0.96 and 0.96 in the trial-length and 6.87 and 6.51 in the 10-year model, making apixaban inferior in the first model but dominant in the latter. Conclusions were sensitive to baseline stroke rate in both models, and the monthly cost of major stroke, relative risk of stroke, and prior vitamin-K antagonist use in the life-time model. Probabilistic sensitivity analysis suggested apixaban would only be a cost-effective alternative (<$50 000/QALY) to aspirin 11% of the time in the trial-length model, but cost-effective or dominant 96.7% and 87.5% of iterations in the 10-year model.

Conclusions—
In our trial-length model, apixaban was more costly and no more effective than aspirin; however, as follow-up was extended, apixaban became cost-effective and eventually dominant.
Analysis of heavy metals concentration in water and sediment in the Hara biosphere reserve, southern Iran
Authors: Nowrouzi Mohsen , Mansouri Borhan , Nabizadeh Sahar , Pourkhabbaz Alireza 
Published: June 2012

This study determined the concentration of heavy metals (Al, Cr, Cu, and Zn) in water and sediments at nine sites in the Hara biosphere reserve of southern Iran during the summer and winter 2010. Determination of Al, Cr, Cu, and Zn in water was carried out by graphite furnace atomic absorption spectrometer (Shimadzu, AA 610s) and in sediment by flame atomic absorption spectrometer (Perkin Elmer, AA3030). Results showed that the heavy metal concentrations in the water samples decreased in the sequence of Zn > Al > Cu > Cr, while in sediment samples were Cr > Zn > Cu > Al. Data analysis indicated that with the exception of Al, there was a Pearson’s correlation coefficient between pH and Cu, Zn, and Cr at α = 0.01, 0.05, and 0.001 in sediment (in winter), respectively. There were also significant differences between heavy metals of Cr, Cu, and Zn during the two seasons ( p < 0.001) in the water and sediment.