bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hindcasting the January 2009 Arctic Sudden Stratospheric Warming with Unified Parameterization of Orographic Drag in NOGAPS. Part II: Short-Range Data-Assimilated Forecast and the Impacts of Calibrated Radiance Bias Correction
Authors: Kim Young-Joon , Campbell William , Ruston Benjamin 
Published: July 2011

Abstract
This study is Part II of the effort to improve the forecasting of sudden stratospheric warming (SSW) events by using a version of the Navy Operational Global Atmospheric Prediction System (NOGAPS) that covers the full stratosphere. In Part I, extended-range (3 week) hindcast experiments (without data assimilation) for the January 2009 Arctic major SSW were performed using NOGAPS with a unified orographic drag parameterization that consists of the schemes employed by Webster et al., as well as Kim and Arakawa and Kim and Doyle. Part I demonstrated that the model with upgraded middle-atmospheric orographic drag physics better forecasts the magnitude and evolution of the SSW and better simulates the trend of the Arctic Oscillation (AO) index. In this study (Part II), a series of 5-day hindcast experiments is performed with cycling data assimilation using the Naval Research Laboratory Atmospheric Variational Data Assimilation System-Accelerated Representer (NAVDAS-AR), a four-dimensional variational data assimilation (4DVAR) system. Further efforts are made to improve the hindcasting of SSW by improving the satellite radiance bias correction process that strongly affects the data assimilation. The innovation (observation minus background) limit is optimally determined to reduce the rejection of useful radiance data. It is found that when the innovation limit is properly set, both the analysis and forecast of the SSW event can be improved, and that the orographic drag helps improve the SSW forecast.
Application of the WRF Hybrid ETKF–3DVAR Data Assimilation System for Hurricane Track Forecasts
Authors: Wang Xuguang 
Published: July 2011

Abstract
A hybrid ensemble transform Kalman filter (ETKF)–three-dimensional variational data assimilation (3DVAR) system developed for the Weather Research and Forecasting Model (WRF) was studied for the forecasts of the tracks of two major hurricanes, Ike and Gustav, in 2008 over the Gulf of Mexico. The impacts of the flow-dependent ensemble covariance generated by the ETKF were revealed by comparing the forecasts, analyses, and analysis increments generated by the hybrid data assimilation method with those generated by the 3DVAR that used the static background covariance. The root-mean-square errors of the track forecasts by the hybrid data assimilation (DA) method were smaller than those by the 3DVAR for both Ike and Gustav. Experiments showed that such improvements were due to the use of the flow-dependent covariance provided by the ETKF ensemble in the hybrid DA system. Detailed diagnostics further revealed that the increments produced by the hybrid and the 3DVAR were different for both the analyses of the hurricane itself and its environment. In particular, it was found that the hybrid, using the flow-dependent covariance that gave the hurricane-specific error covariance estimates, was able to systematically adjust the position of the hurricane during the assimilation whereas the 3DVAR was not. The study served as a pilot study to explore and understand the potential of the hybrid method for hurricane data assimilation and forecasts. Caution needs to be taken to extrapolate the results to operational forecast settings.
A comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia using mouse ES cell–based assay
Authors: Biswas Kajal , Das Ranabir , Alter Blanche P. , Kuznetsov Sergey G. , Stauffer Stacey , North Susan L. , Burkett Sandra , Brody Lawrence C. , Meyer Stefan , Byrd R. Andrew , Sharan Shyam K. 
Published: July 2011

Abstract
Biallelic mutations in the human breast cancer susceptibility gene, BRCA2, are associated with Fanconi anemia, implying that some persons who inherit 2 deleterious variants of BRCA2 are able to survive even though it is well established that BRCA2 is indispensable for viability in mice. One such variant, IVS7 + 2T > G, results in premature protein truncation because of skipping of exon 7. Surprisingly, the persons who are either IVS7 + 2T > G homozygous or compound heterozygous are born alive but die of malignancy associated with Fanconi anemia. Using a mouse embryonic stem cell–based functional assay, we found that the IVS7 + 2T > G allele produces an alternatively spliced transcript lacking exons 4-7, encoding an in-frame BRCA2 protein with an internal deletion of 105 amino acids (BRCA2Δ105). We demonstrate that BRCA2Δ105 is proficient in homologous recombination-mediated DNA repair as measured by different functional assays. Evaluation of this transcript in normal and leukemia cells suggests that BRCA2Δ105 may contribute to the viability of persons inheriting this mutation. In this study, we have also characterized 5 other BRCA2 variants and found 3 of these (p.L2510P, p.R2336H, and p.W2626C) to be deleterious and 2 (p.I2490T and p.K2729N) probably neutral. Such studies are important to understand the functional significance of unclassified BRCA2 variants.
Characterization of immunologic properties of a second HLA-A2 epitope from a granule protease in CML patients and HLA-A2 transgenic mice
Authors: Lacey Simon F. , La Rosa Corinna , Kaltcheva Teodora , Srivastava Tumul , Seidel Aprille , Zhou Wendi , Rawal Ravindra , Hagen Katharine , Krishnan Aparna , Longmate Jeff , Andersson Helen A. , St. John Lisa , Bhatia Ravi , Pullarkat Vinod , Forman Stephen J. , Cooper Laurence J. N. , Molldrem Jeffrey , Diamond Don J. 
Published: July 2011

Abstract
The serine proteases, neutrophil elastase (HNE) and proteinase 3 (PR3), are aberrantly expressed in human myeloid leukemias. T-cell responses to these proteins have been correlated with remission in patients with chronic myeloid leukemia (CML). Human PR3/HNE-specific CD8+ T cells predominantly recognize a nonameric HLA-A2–restricted T-cell epitope called PR1 which is conserved in both Ags. However, CML patients have CD8+ T cells in peripheral blood recognizing an additional HLA-A2 epitope termed PR2. To assess immunologic properties of these Ags, novel recombinant vaccinia viruses (rVV) expressing PR3 and HNE were evaluated in HLA-A2 transgenic (Tg) mice (HHDII). Immunization of HHDII mice with rVV-PR3 elicited a robust PR3-specific CD8+ T-cell response dominated by recognition of PR2, with minimal recognition of the PR1 epitope. This result was unexpected, because the PR2 peptide has been reported to bind poorly to HLA. To account for these findings, we proposed that HHDII mice negatively selected PR1-specific T cells because of the presence of this epitope within murine PR3 and HNE, leading to immunodominance of PR2-specific responses. PR2-specific splenocytes are cytotoxic to targets expressing naturally processed PR3, though PR1-specific splenocytes are not. We conclude that PR2 represents a functional T-cell epitope recognized in mice and human leukemia patients. These studies are registered at www.clinicaltrials.gov as NCT00716911.
Effect of an ambulatory diagnostic and treatment programme in patients with sleep apnoea
Authors: Andreu A.L. , Chiner E. , Sancho-Chust J.N. , Pastor E. , Llombart M. , Gomez-Merino E. , Senent C. , Barbé F. 
Published: July 2011

The aim of this study to evaluate the efficacy of a home-based programme on clinical response, continuous positive airway pressure (CPAP) compliance and cost in a population of high pre-test probability of suffering obstructive sleep apnoea syndrome (OSAS).Patients were randomised into the following three groups. Group A: home respiratory polygraphy (RP) and home follow-up; group B: hospital polysomnography and hospital follow-up; and group C: home RP and hospital follow-up. Evaluation during 6 months included Epworth Sleepiness Scale (ESS), Functional Outcomes Sleep Questionnaire (FOSQ), and daily activity and symptom questionnaires. Compliance was assessed by memory cards (group A) and using an hourly counter (groups B and C).66 patients were included (22 per branch), 83% were males, aged mean±sd52±10 yrs, body mass index 34±7kg·m−2, apnoea/hypopnoea index 43±20 h−1, CPAP pressure 8±2 cmH2O, with no between-group differences. Clinical response showed an ESS of mean±sd15±3 to 6±4, a FOSQ of 16±3 to 18±2, symptoms of 43±7 to 25±7, and activity of 37±11 to 25±8. At the end of the study, compliance was: group A 73%, group B 68% and group C 57%. The cost per patient was: group A €590±43, group B €894±11 and group C €644±93 (p<0.001).In conclusion, patients with a high initial probability of having OSAS can be diagnosed and treated in a home setting, with a high level of CPAP compliance and lower cost than using either a hospital-based approach or home RP/hospital follow-up.
RNA is favourable for analysingEGFRmutations in malignant pleural effusion of lung cancer
Authors: Tsai T-H. , Su K-Y. , Wu S-G. , Chang Y-L. , Luo S-C. , Jan I-S. , Yu C-J. , Yu S-L. , Shih J-Y. , Yang P-C. 
Published: July 2011

Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation ofEGFRstatus in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive forEGFRmutation detection.To test whetherEGFRanalysis from RNA is less prone to interference from nontumour cells that have no or lowerEGFRexpression, we compared three methods (sequencing from cell-derived RNAversussequencing and mass-spectrometric analysis from genomic DNA), in parallel, forEGFRmutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs).Among these MPE samples,EGFRmutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3versus44.7 and 46.7%; for L858R or exon 19 deletions, 61.3versus41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance,EGFRsequencing from RNA provided satisfactory detection of T790M (54.2%).These results demonstrated thatEGFRsequencing using RNA as template greatly improves sensitivity forEGFRmutation detection from samples of MPE, highlighting RNA as the favourable source for analysingEGFRmutations from heterogeneous MPE specimens in NSCLC.
Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis
Authors: Kieninger E. , Vareille M. , Kopf B.S. , Blank F. , Alves M.P. , Gisler F.M. , Latzin P. , Casaulta C. , Geiser T. , Johnston S.L. , Edwards M.R. , Regamey N. 
Published: July 2011

Respiratory virus infections play an important role in cystic fibrosis (CF) exacerbations, but underlying pathophysiological mechanisms are poorly understood. We aimed to assess whether an exaggerated inflammatory response of the airway epithelium on virus infection could explain the increased susceptibility of CF patients towards respiratory viruses.We used primary bronchial and nasal epithelial cells obtained from 24 healthy control subjects and 18 CF patients. IL-6, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, RANTES/CCL5 and GRO-α/CXCL1 levels in supernatants and mRNA expression in cell lysates were measured before and after infection with rhinoviruses (RV-16 and RV-1B) and RSV. Cytotoxicity was assessed by lactate dehydrogenate assay and flow cytometry.All viruses induced strong cytokine release in both control and CF cells. The inflammatory response on virus infection was heterogeneous and depended on cell type and virus used, but was not increased in CF compared with control cells. On the contrary, there was a marked trend towards lower cytokine production associated with increased cell death in CF cells.An exaggerated inflammatory response to virus infection in bronchial epithelial cells does not explain the increased respiratory morbidity after virus infection in CF patients.
Determinants of success
Authors: Garrod R. , Malerba M. , Crisafulli E. 
Published: July 2011

In chronic obstructive pulmonary disease (COPD) patients, pulmonary rehabilitation is a nonpharmacological intervention aimed at improving physical exercise tolerance, dyspnoea and perceived quality of life. However, identifying predictors of clinical response and which patients achieve benefit remains a difficult question to answer with no conclusive data available.Baseline characteristics of COPD patients, such as degree of breathlessness, body weight and arterial partial pressure of oxygen, generally appear to be too direct to have a correlation with improvement of post-rehabilitation outcomes. Furthermore, some additional benefits of patients treated with rehabilitation are simply not detected by usual measures (social interaction, sleep quality and confidence).Although there are some data suggesting that some medical conditions frequently associated with COPD (osteoporosis, metabolic syndrome and heart diseases) may negatively influence rehabilitation outcomes, at present the evidence is contradictory.
IκBα glutathionylation and reduced histone H3 phosphorylation inhibit eotaxin and RANTES
Authors: Seidel P. , Roth M. , Ge Q. , Merfort I. , S’ng C.T. , Ammit A.J. 
Published: July 2011

Airway smooth muscle cells (ASMCs) secrete eotaxin and RANTES (regulated on activation, normal T-cell expressed and secreted) in response to tumour necrosis factor (TNF)-α, which is inhibited by the nuclear factor (NF)-κB inhibitor dimethylfumarate (DMF). NF-κB/IκB (inhibitor of NF-κB) glutathionylation and changes in chromatin remodelling can inhibit NF-κB activity. In this study, we determined whether NF-κB/IκB glutathionylation and reduced histone H3 phosphorylation might underlie the inhibitory effect of DMF on NF-κB activity, and eotaxin and RANTES secretion.Primary human ASMCs were treated with DMF, diamide and/or glutathione (GSH) ethylester (OEt) prior to TNF-α stimulation and were subsequently analysed by ELISA, electrophoretic mobility shift assay, immunofluorescence, co-immunoprecipitation or immunoblotting.DMF reduced intracellular GSH and induced IκBα glutathionylation (IκBα-SSG), which inhibited IκBα degradation, NF-κB p65 nuclear entry and NF-κB/DNA binding. In addition, DMF inhibited the phosphorylation of histone H3, which was possibly mediated by the inhibitory effect of DMF on mitogen- and stress-activated protein kinase (MSK)-1. However, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase MAPK and MAPK phosphatase-1, upstream of MSK-1, were not inhibited by DMF. Importantly, DMF-mediated effects on NF-κB, histone H3, eotaxin and RANTES were reversed by addition of GSH-OEt.Our data suggest that DMF inhibits NF-κB-dependent eotaxin and RANTES secretion by reduction of GSH with subsequent induction of IκBα-SSG and inhibition of histone H3 phosphorylation. Our findings offer new potential drug targets to reduce airway inflammation in asthma.
The burden of TB–HIV in the EU: how much do we know? A survey of surveillance practices and results
Authors: Kruijshaar M.E. , Pimpin L. , Abubakar I. , Rice B. , Delpech V. , Drumright L.N. , Hollo V. , Huitric E. , van de Laar M. , Amato-Gauci A. , Manissero D. , Ködmön C. 
Published: July 2011

Information on the burden of tuberculosis (TB)–HIV co-infection is critical for the planning and evaluation of TB–HIV control and treatment strategies. This study assessed current practices in countries of the European Union (EU) and European Economic Area (EEA) for monitoring HIV co-infection in TB surveillance systems, countries’ current co-infection burden and associated clinical practice.An online survey was distributed to all national TB surveillance nominated European Centre for Disease Prevention and Control contact points in the EU/EEA.We received 25 responses from 30 countries (83% response rate). Patients’ HIV status was collected in 18 out of the 25 TB surveillance systems, usuallyviaclinician reporting (16 out of 18 surveillance systems). Although most countries recommended routine testing of TB patients for HIV, the proportion actually tested varied from 5% to 90%. The burden of HIV co-infection was found to be elevated in countries with higher levels of HIV testing and higher prevalence of HIV.We suggest that TB–HIV co-infection be monitored in all EU/EEA countries to facilitate the planning and evaluation of TB–HIV control strategies. Strengthening collaboration between TB and HIV clinicians and surveillance departments, and consideration of patient confidentiality restraints would be advantageous. The level of HIV testing in TB patients is low despite national recommendations and testing should be further promoted and monitored.
All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl, Dvl, and serine/threonine kinases
Authors: Kivimäe Saul , Yang Xiao Yong , Cheyette Benjamin NR 
Published: July 2011

Abstract

Background
The Dact family of scaffold proteins was discovered by virtue of binding to Dvl proteins central to Wnt and Planar Cell Polarity (PCP) signaling. Subsequently Dact proteins have been linked to a growing list of potential partners implicated in β-catenin-dependent and β-catenin-independent forms of Wnt and other signaling. To clarify conserved and non-conserved roles for this protein family, we systematically compared molecular interactions of all three murine Dact paralogs by co-immunoprecipitation of proteins recombinantly expressed in cultured human embryonic kidney cells.

Results
Every Dact paralog readily formed complexes with the Vangl, Dvl, and CK1δ/ε proteins of species ranging from fruit flies to humans, as well as with PKA and PKC. Dact proteins also formed complexes with themselves and with each other; their conserved N-terminal leucine-zipper domains, which have no known binding partners, were necessary and sufficient for this interaction, suggesting that it reflects leucine-zipper-mediated homo- and hetero-dimerization. We also found weaker, though conserved, interactions of all three Dact paralogs with the catenin superfamily member p120ctn. Complex formation with other previously proposed partners including most other catenins, GSK3, LEF/TCF, HDAC1, and TGFβ receptors was paralog-specific, comparatively weak, and/or more sensitive to empirical conditions.

Conclusions
Combined with published functional evidence from targeted knock-out mice, these data support a conserved role for Dact proteins in kinase-regulated biochemistry involving Vangl and Dvl. This strongly suggests that a principal role for all Dact family members is in the PCP pathway or a molecularly related signaling cascade in vertebrates.
Effect of hosts on competition among clones and evidence of differential selection between pathogenic and saprophytic phases in experimental populations of the wheat pathogen Phaeosphaeria nodorum
Authors: Sommerhalder Rubik J , McDonald Bruce A , Mascher Fabio , Zhan Jiasui 
Published: July 2011

Abstract

Background
Monoculture, multi-cropping and wider use of highly resistant cultivars have been proposed as mechanisms to explain the elevated rate of evolution of plant pathogens in agricultural ecosystems. We used a mark-release-recapture experiment with the wheat pathogen Phaeosphaeria nodorum to evaluate the impact of two of these mechanisms on the evolution of a pathogen population. Nine P. nodorum isolates marked with ten microsatellite markers and one minisatellite were released onto five replicated host populations to initiate epidemics of Stagonospora nodorum leaf blotch. The experiment was carried out over two consecutive host growing seasons and two pathogen collections were made during each season.

Results
A total of 637 pathogen isolates matching the marked inoculants were recovered from inoculated plots over two years. Genetic diversity in the host populations affected the evolution of the corresponding P. nodorum populations. In the cultivar mixture the relative frequencies of inoculants did not change over the course of the experiment and the pathogen exhibited a low variation in selection coefficients.

Conclusions
Our results support the hypothesis that increasing genetic heterogeneity in host populations may retard the rate of evolution in associated pathogen populations. Our experiment also provides indirect evidence of fitness costs associated with host specialization in P. nodorum as indicated by differential selection during the pathogenic and saprophytic phases.
The replication origin of a repABC plasmid
Authors: Cervantes-Rivera Ramón , Pedraza-López Francisco , Pérez-Segura Gabriela , Cevallos Miguel A 
Published: July 2011

Abstract

Background

repABC operons are present on large, low copy-number plasmids and on some secondary chromosomes in at least 19 α-proteobacterial genera, and are responsible for the replication and segregation properties of these replicons. These operons consist, with some variations, of three genes: repA, repB, and repC. RepA and RepB are involved in plasmid partitioning and in the negative regulation of their own transcription, and RepC is the limiting factor for replication. An antisense RNA encoded between the repB-repC genes modulates repC expression.

Results
To identify the minimal region of the Rhizobium etli p42d plasmid that is capable of autonomous replication, we amplified different regions of the repABC operon using PCR and cloned the regions into a suicide vector. The resulting vectors were then introduced into R. etli strains that did or did not contain p42d. The minimal replicon consisted of a repC open reading frame under the control of a constitutive promoter with a Shine-Dalgarno sequence that we designed. A sequence analysis of repC revealed the presence of a large A+T-rich region but no iterons or DnaA boxes. Silent mutations that modified the A+T content of this region eliminated the replication capability of the plasmid. The minimal replicon could not be introduced into R. etli strain containing p42d, but similar constructs that carried repC from Sinorhizobium meliloti pSymA or the linear chromosome of Agrobacterium tumefaciens replicated in the presence or absence of p42d, indicating that RepC is an incompatibility factor. A hybrid gene construct expressing a RepC protein with the first 362 amino acid residues from p42d RepC and the last 39 amino acid residues of RepC from SymA was able to replicate in the presence of p42d.

Conclusions
RepC is the only element encoded in the repABC operon of the R. etli p42d plasmid that is necessary and sufficient for plasmid replication and is probably the initiator protein. The oriV of this plasmid resides within the repC gene and is located close to or inside of a large A+T region. RepC can act as an incompatibility factor, and the last 39 amino acid residues of the carboxy-terminal region of this protein are involved in promoting this phenotype.