bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Meteorological Development Laboratory’s Aviation Weather Prediction System
Authors: Ghirardelli Judy E. , Glahn Bob 
Published: February 2010

Abstract
The Meteorological Development Laboratory (MDL) has developed and implemented an aviation weather prediction system that runs each hour and produces forecast guidance for each hour into the future out to 25 h covering the major forecast period of the National Weather Service (NWS) Terminal Aerodrome Forecast. The Localized Aviation Model Output Statistics (MOS) Program (LAMP) consists of analyses of observations, simple advective models, and a statistical component that updates the longer-range MOS forecasts from the Global Forecast System (GFS) model. LAMP, being an update to GFS MOS, is shown to be an improvement over it, as well as improving over persistence. LAMP produces probabilistic forecasts for the aviation weather elements of ceiling height, sky cover, visibility, obstruction to vision, precipitation occurrence and type, and thunderstorms. Best-category forecasts are derived from these probabilities and their associated thresholds. The LAMP guidance of sensible weather is available for 1591 stations in the contiguous United States, Alaska, Hawaii, Puerto Rico, and the Virgin Islands. Probabilistic guidance of thunderstorms is also available on a grid. The LAMP guidance is available to the entire weather enterprise via NWS communication networks and the World Wide Web. In the future, all station guidance will be gridded and be made available in a form compatible with the NWS’s National Digital Forecast Database.
The Crisis in the U.S. and the Future of East Asian Production Sharing
Authors: Chen Lurong , Lombaerde Philippe De 
Published: February 2010

The East Asian economic zone is well known for its highly integrated manufacturing system that was initialized and is driven by the market mechanism. As participants in a common production sharing network, East Asian economies are highly interdependent. Externally, advanced economies in the West make up the main target markets for exports from East Asia. Moreover, they provide capital to feed the investments required by regional growth.This paper investigates the potential effects of the recent economic crisis on East Asian production sharing. It suggests that the high interdependency of the global economy has made it unlikely for East Asia to remain immune to the crisis. Indeed, the impacts of the crisis on the regional economy in the long run are likely to be more serious than those in the short term. The crisis could be a factor in accelerating the process of East Asian regional integration, especially in terms of financial integration.Fundamentally, the weakness of the East Asian economy comes from its rather passive position in the global industry value chains. In order to improve its core competitiveness in the global market, East Asia needs to increase the technical and knowledge based contents of production sharing. Meanwhile, East Asian countries need to develop a mature social security system to buffer temporary unemployment. By boosting the intra-regional market and strengthening inter-regional cooperation with other emerging economies, East Asia could gradually turn the current production sharing network into a multi-oriented one, allowing the regional economy to be relatively less dependent on the West, and therefore less vulnerable to a crisis originating in the West. Last but not least, it is in the region’s best interests to support the multilateral trade negotiation system in order to secure free trade and capital movement globally.
Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters
Authors: Yadav Vijayshree , Marracci Gail H , Munar Myrna Y , Cherala Ganesh , Stuber Lauren E , Alvarez Lilia , Shinto Lynne , Koop Dennis R , Bourdette Dennis N 
Published: February 2010

Lipoic acid is a natural anti-oxidant available as an oral supplement from a number of different manufacturers. Lipoic acid administered subcutaneously is an effective therapy for murine experimental autoimmune encephalomyelitis, a model of multiple sclerosis. The aim of this study was to compare serum lipoic acid levels with oral dosing in patients with multiple sclerosis with serum levels in mice receiving subcutaneous doses of lipoic acid. We performed serum pharmacokinetic studies in patients with multiple sclerosis after a single oral dose of 1200 mg lipoic acid. Patients received one of the three different racemic formulations randomly: tablet (Formulation A) and capsules (Formulations B and C). Mice pharmacokinetic studies were performed with three different subcutaneous doses (20, 50 and 100 mg/kg racemic lipoic acid). The pharmacokinetic parameters included Maximum Serum Concentrations (Cmax in μg/ml) and area under the curve 0—infinity (AUC 0—infinity in μg*min/ml). We found mean Cmax and AUC 0—infinity in patients with multiple sclerosis as follows: group A ( N = 7) 3.8 ± 2.6 and 443.1 ± 283.9; group B ( N = 8) 9.9 ± 4.5 and 745.2 ± 308.7 and group C ( N = 8) 10.3 ± 3.8 and 848.8 ± 360.5, respectively. Mean Cmax and AUC 0—infinity in the mice were: 100 mg/kg lipoic acid: 30.9 ± 2.9 and 998 ± 245; 50 mg/kg lipoic acid: 7.6 ± 1.4 and 223 ± 20; 20 mg/kg lipoic acid: 2.7 ± 0.7 and 119 ± 33. We conclude that patients taking 1200 mg of lipoic acid from two of the three oral formulations achieved serum Cmax and AUC levels comparable to that observed in mice receiving 50 mg/kg subcutaneous dose of lipoic acid, which is a highly therapeutic dose in experimental autoimmune encephalomyelitis. A dose of 1200 mg oral lipoic acid can achieve therapeutic serum levels in patients with multiple sclerosis.
Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac
Authors: Pollitt Alice Y. , Grygielska Beata , Leblond Bertrand , Désiré Laurent , Eble Johannes A. , Watson Steve P. 
Published: February 2010

Abstract
The C-type lectin-like receptor 2 (CLEC-2) activates platelets through Src and Syk tyrosine kinases via a single cytoplasmic YxxL motif known as a hem immunoreceptor tyrosine-based activation motif (hemITAM). Here, we demonstrate using sucrose gradient ultracentrifugation and methyl-β-cyclodextrin treatment that CLEC-2 translocates to lipid rafts upon ligand engagement and that translocation is essential for hemITAM phosphorylation and signal initiation. HemITAM phosphorylation, but not translocation, is also critically dependent on actin polymerization, Rac1 activation, and release of ADP and thromboxane A2 (TxA2). The role of ADP and TxA2 in mediating phosphorylation is dependent on ligand engagement and rac activation but is independent of platelet aggregation. In contrast, tyrosine phosphorylation of the GPVI-FcRγ-chain ITAM, which has 2 YxxL motifs, is independent of actin polymerization and secondary mediators. These results reveal a unique series of proximal events in CLEC-2 phosphorylation involving actin polymerization, secondary mediators, and Rac activation.
Reference equations for specific airway resistance in children: the Asthma UK initiative
Authors: Kirkby J. , Stanojevic S. , Welsh L. , Lum S. , Badier M. , Beardsmore C. , Custovic A. , Nielsen K. , Paton J. , Tomalak W. , Stocks J. 
Published: February 2010

Plethysmographic specific airway resistance (sRaw) is a useful research method for discriminating lung disease in young children. Its use in clinical management has, however, been limited by lack of consensus regarding equipment, methodology and reference data.The aim of our study was to collate reference data from healthy children (3–10 yrs), document methodological differences, explore the impact of these differences and construct reference equations from the collated dataset.Centres were approached to contribute sRawdata as part of the Asthma UK initiative. A random selection of pressure–flow plots were assessed for quality and site visits elucidated data collection and analysis protocols.Five centres contributed 2,872 measurements. Marked variation in methodology and analysis excluded two centres. sRawover-read sheets were developed for quality control. Reference equations and recommendations for recording and reporting both specific effective and total airway resistance (sReffand sRtot, respectively) were developed for White European children from 1,908 measurements made under similar conditions.Reference sRawdata collected from a single centre may be misleading, as methodological differences exist between centres. These preliminary reference equations can only be applied under similar measurement conditions. Given the potential clinical usefulness of sRaw, particularly with respect to sReff, methodological guidelines need to be established and used in prospective data collection.
Serotype-specific pneumococcal disease may be influenced by mannose-binding lectin deficiency
Authors: Vallès X. , Roca A. , Lozano F. , Morais L. , Suárez B. , Casals F. , Mandomando I. , Sigaúque B. , Nhalungo D. , Esquinas C. , Quintó L. , Alonso P.L. , Torres A. 
Published: February 2010

Previous studies of the association between the mannose-binding lectin pathway deficiencies and invasive pneumococcal disease are inconclusive. Invasiveness ofStreptococcus pneumoniaeis dependent on serotype. We aimed to determine the association between invasive pneumococcal disease andMBL2andMASP2genetic variants, regarding serotype distribution.A hospital-based case–control study was conducted in children admitted to hospital in rural Mozambique in June 2002–November 2003. The study included children admitted to hospital with invasive pneumococcal disease, in whomS. pneumoniaewas isolated from blood and subsequently serotyped. Sequence-based typing analysis of amplicons covering the polymorphic regions ofMASP2(exon 3) andMBL2(promoter and exon 1) was performed.An overall high frequency ofMBL2genotypes associated with low serum levels of MBL (43%) was found. Carriers of MBL-deficient genotypes were associated with invasive pneumococcal disease produced by low-invasive serotypes (OR 5.55, 95% CI 1.4–21.9; p = 0.01).Our data suggest that susceptibility to pneumococcal disease among MBL-deficient patients may be influenced by serotype invasiveness. Type-specific capsular serotype ofS. pneumoniaewould need to be taken into account in further genetic association studies of invasive pneumococcal disease.
Influence of pneumococcal serotype group on outcome in adults with bacteraemic pneumonia
Authors: Luján M. , Gallego M. , Belmonte Y. , Fontanals D. , Vallès J. , Lisboa T. , Rello J. 
Published: February 2010

The influence of infecting serotype group on outcome in bacteraemic pneumococcal pneumonia remains unclear.We performed a prospective, 10-yr observational study in an 800-bed teaching hospital. 299 adults diagnosed with pneumonia whose blood cultures showed growth ofStreptococcus pneumoniaewere included in the study. High invasive disease potential (H) serotypes included serotypes 1, 5 and 7F, which served as a reference category, were compared with low invasive disease potential (L) serotypes (3, 6A, 6B, 8, 19F, and 23F) and other (O) serotypes (non-H, non-L). The influence on outcome was determined for each group of serotypes after adjusting for underlying conditions and severity of illness at admission.Overall, 30-day mortality was 11%. H serotypes (n = 93) infected primarily younger people and presented a higher risk of complicated parapneumonic effusion or empyema (17.2versus5.1%; p = 0.01), with lower mortality (3.2%). The isolation of L serotypes (n = 78) was an independent risk factor for 30-day mortality (OR 7.02, 95% CI 1.72–28.61), as were Charlson score (OR 1.30, 95% CI 1.08–1.58), alcohol abuse (OR 3.99, 95% CI 1.39–11.39) and severity of illness measured by American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) criteria (OR 4.80, 95% CI 1.89–12.13).A vaccination strategy including serotypes 3, 6A, 6B, 8, 19F and 23F may improve survival in adults.
Factors influencing duration of exposure with symptoms and costs of occupational asthma
Authors: Miedinger D. , Malo J-L. , Ghezzo H. , L'Archevêque J. , Zunzunegui M-V. 
Published: February 2010

The most important factor for the prognosis of occupational asthma is the length of exposure with symptoms prior to removal from exposure. We wanted to identify factors, including socioeconomic status, that can influence the delay in submitting a claim to a medicolegal agency after the onset of asthmatic symptoms, and to confirm that this delay is associated with worse respiratory prognosis and higher direct costs.This is a cross-sectional study of subjects who claimed compensation for occupational asthma at the Workers' Compensation Board of Quebec, Canada. Data were collected at re-evaluation ∼2.5 yrs after diagnosis. Information on the number of years with symptoms and removal from exposure was obtained from the medicolegal file.60 subjects were included in the study. Being older, having a revenue of >30,000 Canadian dollars and having occupational asthma due to high molecular weight agents were all positively associated with the number of years of exposure with symptoms before removal from exposure. Subjects with persistent airway hyperresponsiveness at follow-up had a higher number of years with symptoms. Experiencing symptoms in the workplace for <1 yr generated lower direct costs.These findings might help in surveillance programmes that could be preferentially targeted for these subgroups of workers.
Comparative analyses reveal distinct sets of lineage-specific genes within Arabidopsis thaliana
Authors: Lin Haining , Moghe Gaurav , Ouyang Shu , Iezzoni Amy , Shiu Shin-Han , Gu Xun , Buell C Robin 
Published: February 2010

Abstract

Background
The availability of genome and transcriptome sequences for a number of species permits the identification and characterization of conserved as well as divergent genes such as lineage-specific genes which have no detectable sequence similarity to genes from other lineages. While genes conserved among taxa provide insight into the core processes among species, lineage-specific genes provide insights into evolutionary processes and biological functions that are likely clade or species specific.

Results
Comparative analyses using the Arabidopsis thaliana genome and sequences from 178 other species within the Plant Kingdom enabled the identification of 24,624 A. thaliana genes (91.7%) that were termed Evolutionary Conserved (EC) as defined by sequence similarity to a database entry as well as two sets of lineage-specific genes within A. thaliana. One of the A. thaliana lineage-specific gene sets share sequence similarity only to sequences from species within the Brassicaceae family and are termed Conserved Brassicaceae-Specific Genes (914, 3.4%, CBSG). The other set of A. thaliana lineage-specific genes, the Arabidopsis Lineage-Specific Genes (1,324, 4.9%, ALSG), lack sequence similarity to any sequence outside A. thaliana. While many CBSGs (76.7%) and ALSGs (52.9%) are transcribed, the majority of the CBSGs (76.1%) and ALSGs (94.4%) have no annotated function. Co-expression analysis indicated significant enrichment of the CBSGs and ALSGs in multiple functional categories suggesting their involvement in a wide range of biological functions. Subcellular localization prediction revealed that the CBSGs were significantly enriched in proteins targeted to the secretory pathway (412, 45.1%). Among the 107 putatively secreted CBSGs with known functions, 67 encode a putative pollen coat protein or cysteine-rich protein with sequence similarity to the S-locus cysteine-rich protein that is the pollen determinant controlling allele specific pollen rejection in self-incompatible Brassicaceae species. Overall, the ALSGs and CBSGs were more highly methylated in floral tissue compared to the ECs. Single Nucleotide Polymorphism (SNP) analysis showed an elevated ratio of non-synonymous to synonymous SNPs within the ALSGs (1.99) and CBSGs (1.65) relative to the EC set (0.92), mainly caused by an elevated number of non-synonymous SNPs, indicating that they are fast-evolving at the protein sequence level.

Conclusions
Our analyses suggest that while a significant fraction of the A. thaliana proteome is conserved within the Plant Kingdom, evolutionarily distinct sets of genes that may function in defining biological processes unique to these lineages have arisen within the Brassicaceae and A. thaliana.
Genomics based analysis of interactions between developing B-lymphocytes and stromal cells reveal complex interactions and two-way communication
Authors: Zetterblad Jenny , Qian Hong , Zandi Sasan , Månsson Robert , Lagergren Anna , Hansson Frida , Bryder David , Paulsson Nils , Sigvardsson Mikael 
Published: February 2010

Abstract

Background
The use of functional genomics has largely increased our understanding of cell biology and promises to help the development of systems biology needed to understand the complex order of events that regulates cellular differentiation in vivo. One model system clearly dependent on the integration of extra and intra cellular signals is the development of B-lymphocytes from hematopoietic stem cells in the bone marrow. This developmental pathway involves several defined differentiation stages associated with specific expression of genes including surface markers that can be used for the prospective isolation of the progenitor cells directly from the bone marrow to allow for ex vivo gene expression analysis. The developmental process can be simulated in vitro making it possible to dissect information about cell/cell communication as well as to address the relevance of communication pathways in a rather direct manner. Thus we believe that B-lymphocyte development represents a useful model system to take the first steps towards systems biology investigations in the bone marrow.

Results
In order to identify extra cellular signals that promote B lymphocyte development we created a database with approximately 400 receptor ligand pairs and software matching gene expression data from two cell populations to obtain information about possible communication pathways. Using this database and gene expression data from NIH3T3 cells (unable to support B cell development), OP-9 cells (strongly supportive of B cell development), pro-B and pre-B cells as well as mature peripheral B-lineage cells, we were able to identify a set of potential stage and stromal cell restricted communication pathways. Functional analysis of some of these potential ways of communication allowed us to identify BMP-4 as a potent stimulator of B-cell development in vitro. Further, the analysis suggested that there existed possibilities for progenitor B cells to send signals to the stroma. The functional consequences of this were investigated by co-culture experiments revealing that the co-incubation of stromal cells with B cell progenitors altered both the morphology and the gene expression pattern in the stromal cells.

Conclusions
We believe that this gene expression data analysis method allows for the identification of functionally relevant interactions and therefore could be applied to other data sets to unravel novel communication pathways.
Air pollution and mortality in the Canary Islands: a time-series analysis
Authors: López-Villarrubia Elena , Ballester Ferran , Iñiguez Carmen , Peral Nieves 
Published: February 2010

Abstract

Background
The island factor of the cities of Las Palmas de Gran Canaria and Santa Cruz de Tenerife, along with their proximity to Africa and their meteorology, create a particular setting that influences the air quality of these cities and provides researchers an opportunity to analyze the acute effects of air-pollutants on daily mortality.

Methods
From 2000 to 2004, the relationship between daily changes in PM10, PM2.5, SO2, NO2, CO, and ozone levels and daily total mortality and mortality due to respiratory and heart diseases were assessed using Generalized Additive Poisson models controlled for potential confounders. The lag effect (up to five days) as well as the concurrent and previous day averages and distributed lag models were all estimated. Single and two pollutant models were also constructed.

Results
Daily levels of PM10, PM2.5, NO2, and SO2 were found to be associated with an increase in respiratory mortality in Santa Cruz de Tenerife and with increased heart disease mortality in Las Palmas de Gran Canaria, thus indicating an association between daily ozone levels and mortality from heart diseases. The effects spread over five successive days. SO2 was the only air pollutant significantly related with total mortality (lag 0).

Conclusions
There is a short-term association between current exposure levels to air pollution and mortality (total as well as that due specifically to heart and respiratory diseases) in both cities. Risk coefficients were higher for respiratory and cardiovascular mortality, showing a delayed effect over several days.
NSC114792, a novel small molecule identified through structure-based computational database screening, selectively inhibits JAK3
Authors: Kim Byung-Hak , Jee Jun-Goo , Yin Chang-Hong , Sandoval Claudio , Jayabose Somasundaram , Kitamura Daisuke , Bach Erika A , Baeg Gyeong-Hun 
Published: February 2010

AbstractBackgroundHuman or animals lacking either JAK3 or the common gamma chain (γc) expression display severe combined immunodeficiency disease, indicating the crucial role of JAK3 in T-cell development and the homeostasis of the immune system. JAK3 has also been suggested to contribute to the pathogenesis of tumorigenesis. Recent studies identified activatingJAK3mutations in patients with various hematopoietic malignancies, including acute megakaryoblastic leukemia. Importantly, functional analyses of some of thoseJAK3mutations have been shown to cause lethal hematopoietic malignancies in animal models. These observations make JAK3 an ideal therapeutic target for the treatment of various human diseases. To identify novel small molecule inhibitors of JAK3, we performed structure-based virtual screen using the 3D structure of JAK3 kinase domain and the NCI diversity set of compounds.ResultsWe identified NSC114792 as a lead compound. This compound directly blocked the catalytic activity of JAK3 but not that of other JAK family membersin vitro. In addition, treatment of 32D/IL-2Rβ cells with the compound led to a block in IL-2-dependent activation of JAK3/STAT5 but not IL-3-dependent activation of JAK2/STAT5. Consistent with the specificity of NSC114792 for JAK3, it selectively inhibited persistently-activated JAK3, but failed to affect the activity of other JAK family members and other oncogenic kinases in various cancer cell lines. Finally, we showed that NSC114792 decreases cell viability by inducing apoptosis through down-regulating anti-apoptotic gene expression only in cancer cells harboring persistently-active JAK3.ConclusionsNSC114792 is a lead compound that selectively inhibits JAK3 activity. Therefore, our study suggests that this small molecule inhibitor of JAK3 can be used as a starting point to develop a new class of drugs targeting JAK3 activity, and may have therapeutic potential in various diseases that are caused by aberrant JAK3 activity.