bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Levels of Chronic Immune Activation in the T-Cell Compartments of Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1 and on Highly Active Antiretroviral Therapy Are Reverted by Alpha Interferon and Ribavirin Treatment
Authors: Gonzalez Veronica D. , Falconer Karolin , Blom Kim G. , Reichard Olle , Mørn Birgitte , Laursen Alex Lund , Weis Nina , Alaeus Annette , Sandberg Johan K. 
Published: August 2009

ABSTRACT
Chronic immune activation is a driver of human immunodeficiency virus type 1 (HIV-1) disease progression. Here, we describe that subjects with chronic hepatitis C virus (HCV)/HIV-1 coinfection display sharply elevated immune activation as determined by CD38 expression in T cells. This occurs, despite effective antiretroviral therapy, in both CD8 and CD4 T cells and is more pronounced than in the appropriate monoinfected control groups. Interestingly, the suppression of HCV by pegylated alpha interferon and ribavirin treatment reduces activation. High HCV loads and elevated levels of chronic immune activation may contribute to the high rates of viral disease progression observed in HCV/HIV-1-coinfected patients.
Mammalian Orthoreovirus Particles Induce and Are Recruited into Stress Granules at Early Times Postinfection
Authors: Qin Qingsong , Hastings Craig , Miller Cathy L. 
Published: August 2009

ABSTRACT
Infection with many mammalian orthoreovirus (MRV) strains results in shutoff of host, but not viral, protein synthesis via protein kinase R (PKR) activation and phosphorylation of translation initiation factor eIF2α. Following inhibition of protein synthesis, cellular mRNAs localize to discrete structures in the cytoplasm called stress granules (SGs), where they are held in a translationally inactive state. We examined MRV-infected cells to characterize SG formation in response to MRV infection. We found that SGs formed at early times following infection (2 to 6 h postinfection) in a manner dependent on phosphorylation of eIF2α. MRV induced SG formation in all four eIF2α kinase knockout cell lines, suggesting that at least two kinases are involved in induction of SGs. Inhibitors of MRV disassembly prevented MRV-induced SG formation, indicating that viral uncoating is a required step for SG formation. Neither inactivation of MRV virions by UV light nor treatment of MRV-infected cells with the translational inhibitor puromycin prevented SG formation, suggesting that viral transcription and translation are not required for SG formation. Viral cores were found to colocalize with SGs; however, cores from UV-inactivated virions did not associate with SGs, suggesting that viral core particles are recruited into SGs in a process that requires the synthesis of viral mRNA. These results demonstrate that MRV particles induce SGs in a step following viral disassembly but preceding viral mRNA transcription and that core particles are themselves recruited to SGs, suggesting that the cellular stress response may play a role in the MRV replication cycle.
Ribose 2′-O Methylation of the Vesicular Stomatitis Virus mRNA Cap Precedes and Facilitates Subsequent Guanine-N-7 Methylation by the Large Polymerase Protein
Authors: Rahmeh Amal A. , Li Jianrong , Kranzusch Philip J. , Whelan Sean P. J. 
Published: August 2009

ABSTRACT

During conventional mRNA cap formation, two separate methyltransferases sequentially modify the cap structure, first at the guanine-N-7 (G-N-7) position and subsequently at the ribose 2′-O position. For vesicular stomatitis virus (VSV), a prototype of the nonsegmented negative-strand RNA viruses, the two methylase activities share a binding site for the methyl donor
S
-adenosyl-
l
-methionine and are inhibited by individual amino acid substitutions within the C-terminal domain of the large (L) polymerase protein. This led to the suggestion that a single methylase domain functions for both 2′-O and G-N-7 methylations. Here we report a
trans
-methylation assay that recapitulates both ribose 2′-O and G-N-7 modifications by using purified recombinant L and in vitro-synthesized RNA. Using this assay, we demonstrate that VSV L typically modifies the 2′-O position of the cap prior to the G-N-7 position and that G-N-7 methylation is diminished by pre-2′-O methylation of the substrate RNA. Amino acid substitutions in the C terminus of L that prevent all cap methylation in recombinant VSV (rVSV) partially retain the ability to G-N-7 methylate a pre-2′-O-methylated RNA, therefore uncoupling the effect of substitutions in the C terminus of the L protein on the two methylations. In addition, we show that the 2′-O and G-N-7 methylase activities act specifically on RNA substrates that contain the conserved elements of a VSV mRNA start at the 5′ terminus. This study provides new mechanistic insights into the mRNA cap methylase activities of VSV L, demonstrates that 2′-O methylation precedes and facilitates subsequent G-N-7 methylation, and reveals an RNA sequence and length requirement for the two methylase activities. We propose a model of regulation of the activity of the C terminus of L protein in 2′-O and G-N-7 methylation of the cap structure.
Operational Monitoring of Weather Radar Receiving Chain Using the Sun
Authors: Holleman Iwan , Huuskonen Asko , Kurri Mikko , Beekhuis Hans 
Published: August 2009

Abstract
A method for operational monitoring of a weather radar receiving chain, including the antenna gain and the receiver, is presented. The “online” method is entirely based on the analysis of sun signals in the polar volume data produced during operational scanning of weather radars. The method is an extension of that for determining the weather radar antenna pointing at low elevations using sun signals, and it is suited for routine application.
The solar flux from the online method agrees very well with that obtained from “offline” sun tracking experiments at two weather radar sites. Furthermore, the retrieved sun flux is compared with data from the Dominion Radio Astrophysical Observatory (DRAO) in Canada. Small biases in the sun flux data from the Dutch and Finnish radars (between −0.93 and +0.47 dB) are found. The low standard deviations of these sun flux data against those from DRAO (0.14–0.20 dB) demonstrate the stability of the weather radar receiving chains and of the sun-based online monitoring.
Results from a daily analysis of the sun signals in online radar data can be used for monitoring the alignment of the radar antenna and the stability of the radar receiver system. By comparison with the observations from a sun flux monitoring station, even the calibration of the receiving chain can be checked. The method presented in this paper has great potential for routine monitoring of weather radars in national and international networks.
A Modeling Case Study of Mixed-Phase Clouds over the Southern Ocean and Tasmania
Authors: Morrison Anthony E. , Siems Steven T. , Manton Michael J. , Nazarov Alex 
Published: August 2009

Abstract
The cloud structure associated with two frontal passages over the Southern Ocean and Tasmania is investigated. The first event, during August 2006, is characterized by large quantities of supercooled liquid water and little ice. The second case, during October 2007, is more mixed phase. The Weather Research and Forecasting model (WRFV2.2.1) is evaluated using remote sensed and in situ observations within the post frontal air mass. The Thompson microphysics module is used to describe in-cloud processes, where ice is initiated using the Cooper parameterization at temperatures lower than −8°C or at ice supersaturations greater than 8%. The evaluated cases are then used to numerically investigate the prevalence of supercooled and mixed-phase clouds over Tasmania and the ocean to the west. The simulations produce marine stratocumulus-like clouds with maximum heights of between 3 and 5 km. These are capped by weak temperature and strong moisture inversions. When the inversion is at temperatures warmer than −10°C, WRF produces widespread supercooled cloud fields with little glaciation. This is consistent with the limited in situ observations. When the inversion is at higher altitudes, allowing cooler cloud tops, glaciated (and to a lesser extent mixed phase) clouds are more common. The simulations are further explored to evaluate any orographic signature within the cloud structure over Tasmania. No consistent signature is found between the two cases.
Simulation of an Orographic Precipitation Event during IMPROVE-2. Part II: Sensitivity to the Number of Moments in the Bulk Microphysics Scheme
Authors: Milbrandt J. A. , Yau M. K. , Mailhot J. , Bélair S. , McTaggart-Cowan R. 
Published: August 2009

Abstract
This is the second in a series of papers examining the behavior of the Milbrandt–Yau multimoment bulk microphysics scheme for the simulation of the 13–14 December 2001 case of orographically enhanced precipitation observed during the second Improvement of Microphysical Parameterization through Observational Verification Experiment (IMPROVE-2) experiment. The sensitivity to the number of predicted moments of the hydrometeor size spectra in the bulk scheme was investigated. The triple-moment control simulations presented in Part I were rerun using double- and single-moment configurations of the multimoment scheme as well the single-moment Kong–Yau scheme. Comparisons of total precipitation and in-cloud hydrometeor mass contents were made between the simulations and observations, with the focus on a 2-h quasi-steady period of heavy stratiform precipitation. The double- and triple-moment simulations were similar; both had realistic precipitation fields, though generally overpredicted in quantity, and had overprediction of snow mass and an underprediction of cloud water aloft. Switching from the triple- to single-moment configuration resulted in a simulation with a precipitation pattern shifted upwind and with a larger positive bias, but with hydrometeor mass fields that corresponded more closely to the observations. Changing the particular single-moment scheme used had a greater impact than changing the number of moments predicted in the same scheme, with the Kong–Yau simulations greatly overpredicting the total precipitation in the lee side of the mountain crest and producing too much snow aloft. Further sensitivity tests indicated that the leeside overprediction in the Kong–Yau runs was most likely due to the combination of the absence of the latent heat effect term in the diffusional growth rate for snow combined with the assumption of instantaneous snow melting in the scheme.
Association of angiotensin-converting enzyme gene promoter single nucleotide polymorphisms and haplotype with major depression in a northeastern Thai population
Authors: Angunsri Rudee , Sritharathikhun Thapanut , Suttirat Sarawut , Tencomnao Tewin 
Published: August 2009

Introduction. Angiotensin-converting enzyme (ACE) is thought to influence the activity of the hypothalamic-pituitary-adrenocortical system, which shows hyperactivity in the majority of patients with major depressive disorder (MDD). This study aimed at determining an association between two single nucleotide polymorphisms (SNPs) (rs4291;−240A/T and rs4292;−93T/C) of the ACE gene promoter and MDD in northeastern Thais. Subjects and methods. In the present case-control study, genotyping of 187 unrelated patients with MDD (44.89±12.92 years) and 207 unrelated healthy controls (41.34±9.76 years) from the northeastern part of Thailand was performed using polymerase chain reaction-restriction fragment length polymorphism technique. Results. Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the −93T/C SNP of ACE. For the −240A/T SNP, a significant difference in genotype distributions was found (χ2=6.65, d f=2, p=0.036).The presence of the −240A allele of ACE was associated with a decreased risk for MDD compared with the −240T allele (χ2=4.24, d f=1, p=0.040, odds ratio=0.702 [95% confidence interval=0.508—0.971]). Moreover, haplotype frequency analysis revealed that the −240T/—93T combination was significantly over-represented in patients with MDD in comparison with controls (13.6% and 6.8%, p=0.002 on χ2 test, empirical p=0.004). Conclusions. In the present investigation, an association between the −240A allele and a reduced risk for MDD was observed, but the genotype distributions of controls were only just in marginal agreement with Hardy-Weinberg equilibrium.The T-T haplotype in the ACE gene was significantly associated with an increased risk for MDD.
A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis
Authors: Doebele Robert C. , Schulze-Hoepfner Frank T. , Hong Jia , Chlenski Alexandre , Zeitlin Benjamin D. , Goel Kushboo , Gomes Suzana , Liu Yuru , Abe Mark K. , Nor Jacques E. , Lingen Mark W. , Rosner Marsha Rich 
Published: August 2009

AbstractTumors depend upon angiogenesis for growth and metastasis. It is therefore critical to understand the inhibitory signaling mechanisms in endothelial cells that control angiogenesis. Epac is a cyclic adenosine 5′-monophosphate–activated guanine nucleotide exchange factor for Rap1. In this study, we show that activation of Epac or Rap1 leads to potent inhibition of angiogenesis in vivo. Epac/Rap1 activation down-regulates inhibitor of differentiation 1 (Id1), which negatively regulates thrombospondin-1 (TSP1), an inhibitor of angiogenesis. Consistent with this mechanism, activation of Epac/Rap 1 induces expression of TSP1; conversely, depletion of Epac reduces TSP1 levels in endothelial cells. Blockade of TSP1 binding to its receptor, CD36, rescues inhibition of chemotaxis or angiogenesis by activated Epac/Rap1. Mitogen-activated protein kinase kinase 5, a downstream mediator of vascular endothelial growth factor, antagonizes the effects of Epac/Rap1 by inducing Id1 and suppressing TSP1 expression. Finally, TSP1 is also secreted by fibroblasts in response to Epac/Rap1 activation. These results identify Epac and Rap1 as inhibitory regulators of the angiogenic process, implicate Id1 and TSP1 as downstream mediators of Epac/Rap1, and highlight a novel interplay between pro- and antiangiogenic signaling cascades involving multiple cell types within the angiogenic microenvironment.
CD20-targeted tetrameric interferon-α, a novel and potent immunocytokine for the therapy of B-cell lymphomas
Authors: Rossi Edmund A. , Goldenberg David M. , Cardillo Thomas M. , Stein Rhona , Chang Chien-Hsing 
Published: August 2009

AbstractInterferon-α (IFN-α) has direct inhibitory effects on some tumors and is a potent stimulator of both the innate and adaptive immune systems. A tumor-targeting antibody-IFN-α conjugate (mAb-IFN-α) could kill by direct actions of the monoclonal antibody (mAb) and IFN-α on tumor cells and also potentiate a tumor-directed immune response. The modular Dock-and-Lock method (DNL) was used to generate 20-2b, the first immunocytokine having 4 cytokine (IFN-α2b) groups that are fused to the humanized anti-CD20 mAb, veltuzumab. Additional mAb-IFN-α constructs, each retaining potent IFN-α2b biologic activity, also were produced by DNL. The 20-2b shows enhanced antibody-dependent cellular cytotoxicity compared with veltuzumab but lacks complement-dependent cytotoxicity. The 20-2b inhibits in vitro proliferation of lymphoma cells and depletes them from whole human blood more potently than the combination of veltuzumab and a nontargeting, irrelevant, mAb-IFN-α. The 20-2b demonstrated superior therapeutic efficacy compared with veltuzumab or nontargeting mAb-IFN-α in 3 human lymphoma xenograft models, even though mouse immune cells respond poorly to human IFN-α2b. Targeting IFN-α with an anti-CD20 mAb makes the immunocytokine more potent than either agent alone. These findings suggest that 20-2b merits clinical evaluation as a new candidate antilymphoma therapeutic.
Objectives of iron chelation therapy in myelodysplastic syndromes: more than meets the eye?
Authors: Pullarkat Vinod 
Published: August 2009

AbstractThe role of iron chelation therapy in myelodysplastic syndrome (MDS) remains controversial. Averting cardiac dysfunction in low-grade MDS patients who have sufficient longevity to experience deleterious cardiac effects of iron overload has been the major argument in favor of iron chelation. Although there is significant evidence showing the adverse impact of transfusion dependency on survival in MDS, direct evidence linking tissue iron overload to poor survival or in particular to cardiac dysfunction is lacking. Given the heterogeneity of MDS, it is likely that the pathophysiology of iron overload is equally heterogeneous and complex in these patients. In this article, I argue that prevention of cardiac dysfunction in patients with lower grades of MDS may not be the major benefit of iron chelation therapy, and present evidence suggesting a potential benefit of iron chelation on 3 other outcomes, namely (1) lowering infection risk, (2) improving the outcome of allogeneic hematopoietic stem cell transplantation, and (3) delaying leukemic transformation. These outcomes have particular relevance for patients with higher grades of MDS and should be evaluated in future prospective clinical trials that include patients with all grades of MDS to fully evaluate the benefit of iron chelation therapy.
QPCR: Application for real-time PCR data management and analysis
Authors: Pabinger Stephan , Thallinger Gerhard G , Snajder René , Eichhorn Heiko , Rader Robert , Trajanoski Zlatko 
Published: August 2009

Abstract

Background
Since its introduction quantitative real-time polymerase chain reaction (qPCR) has become the standard method for quantification of gene expression. Its high sensitivity, large dynamic range, and accuracy led to the development of numerous applications with an increasing number of samples to be analyzed. Data analysis consists of a number of steps, which have to be carried out in several different applications. Currently, no single tool is available which incorporates storage, management, and multiple methods covering the complete analysis pipeline.

Results
QPCR is a versatile web-based Java application that allows to store, manage, and analyze data from relative quantification qPCR experiments. It comprises a parser to import generated data from qPCR instruments and includes a variety of analysis methods to calculate cycle-threshold and amplification efficiency values. The analysis pipeline includes technical and biological replicate handling, incorporation of sample or gene specific efficiency, normalization using single or multiple reference genes, inter-run calibration, and fold change calculation. Moreover, the application supports assessment of error propagation throughout all analysis steps and allows conducting statistical tests on biological replicates. Results can be visualized in customizable charts and exported for further investigation.

Conclusion
We have developed a web-based system designed to enhance and facilitate the analysis of qPCR experiments. It covers the complete analysis workflow combining parsing, analysis, and generation of charts into one single application. The system is freely available at http://genome.tugraz.at/QPCR
Pairwise and higher-order correlations among drug-resistance mutations in HIV-1 subtype B protease
Authors: Haq Omar , Levy Ronald M , Morozov Alexandre V , Andrec Michael 
Published: August 2009

Abstract

Background
The reaction of HIV protease to inhibitor therapy is characterized by the emergence of complex mutational patterns which confer drug resistance. The response of HIV protease to drugs often involves both primary mutations that directly inhibit the action of the drug, and a host of accessory resistance mutations that may occur far from the active site but may contribute to restoring the fitness or stability of the enzyme. Here we develop a probabilistic approach based on connected information that allows us to study residue, pair level and higher-order correlations within the same framework.

Results
We apply our methodology to a database of approximately 13,000 sequences which have been annotated by the treatment history of the patients from which the samples were obtained. We show that including pair interactions is essential for agreement with the mutational data, since neglect of these interactions results in order-of-magnitude errors in the probabilities of the simultaneous occurence of many mutations. The magnitude of these pair correlations changes dramatically between sequences obtained from patients that were or were not exposed to drugs. Higher-order effects make a contribution of as much as 10% for residues taken three at a time, but increase to more than twice that for 10 to 15-residue groups. The sequence data is insufficient to determine the higher-order effects for larger groups. We find that higher-order interactions have a significant effect on the predicted frequencies of sequences with large numbers of mutations. While relatively rare, such sequences are more prevalent after multi-drug therapy. The relative importance of these higher-order interactions increases with the number of drugs the patient had been exposed to.

Conclusion
Correlations are critical for the understanding of mutation patterns in HIV protease. Pair interactions have substantial qualitative effects, while higher-order interactions are individually smaller but may have a collective effect. Together they lead to correlations which could have an important impact on the dynamics of the evolution of cross-resistance, by allowing the virus to pass through otherwise unlikely mutational states. These findings also indicate that pairwise and possibly higher-order effects should be included in the models of protein evolution, instead of assuming that all residues mutate independently of one another.
Improved mutation tagging with gene identifiers applied to membrane protein stability prediction
Authors: Winnenburg Rainer , Plake Conrad , Schroeder Michael 
Published: August 2009

Abstract

Background
The automated retrieval and integration of information about protein point mutations in combination with structure, domain and interaction data from literature and databases promises to be a valuable approach to study structure-function relationships in biomedical data sets.

Results
We developed a rule- and regular expression-based protein point mutation retrieval pipeline for PubMed abstracts, which shows an F-measure of 87% for the mutation retrieval task on a benchmark dataset. In order to link mutations to their proteins, we utilize a named entity recognition algorithm for the identification of gene names co-occurring in the abstract, and establish links based on sequence checks. Vice versa, we could show that gene recognition improved from 77% to 91% F-measure when considering mutation information given in the text. To demonstrate practical relevance, we utilize mutation information from text to evaluate a novel solvation energy based model for the prediction of stabilizing regions in membrane proteins. For five G protein-coupled receptors we identified 35 relevant single mutations and associated phenotypes, of which none had been annotated in the UniProt or PDB database. In 71% reported phenotypes were in compliance with the model predictions, supporting a relation between mutations and stability issues in membrane proteins.

Conclusion
We present a reliable approach for the retrieval of protein mutations from PubMed abstracts for any set of genes or proteins of interest. We further demonstrate how amino acid substitution information from text can be utilized for protein structure stability studies on the basis of a novel energy model.