bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Topographic Variability on Initial Condition Sensitivity of Low-Level Wind Forecasts. Part I: Experiments Using Idealized Terrain
Authors: Bieringer Paul E. , Ray Peter S. , Annunzio Andrew J. 
Published: November 2012

Abstract
The concept of improving the accuracy of numerical weather forecasts by targeting additional meteorological observations in areas where the initial condition error is suspected to grow rapidly has been the topic of numerous studies and field programs. The challenge faced by this approach is that it typically requires a costly observation system that can be quickly adapted to place instrumentation where needed. The present study examines whether the underlying terrain in a mesoscale model influences model initial condition sensitivity and if knowledge of the terrain and corresponding predominant flow patterns for a region can be used to direct the placement of instrumentation. This follows the same concept on which earlier targeted observation approaches were based, but eliminates the need for an observation system that needs to be continually reconfigured. Simulations from the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) and its adjoint are used to characterize the locations, variables, and magnitudes of initial condition perturbations that have the most significant impact on the surface wind forecast. This study examines a relatively simple case where an idealized mountain surrounded by a flat plain is located upwind of the forecast verification region. The results suggest that, when elevated terrain is present upstream of the target forecast area, the largest forecast impact (defined as the difference between the simulation with perturbed initial conditions and a control simulation where the initial condition was not perturbed) occurs when the initial analysis perturbations are made in regions with complex terrain.
An Improved Method for Estimating Radar Echo-Top Height
Authors: Lakshmanan Valliappa , Hondl Kurt , Potvin Corey K. , Preignitz David 
Published: November 2012

Abstract
It is demonstrated that the traditional method, in widespread use on Next Generation Weather Radar (NEXRAD) and other radar systems, to compute echo-top heights results in both under- and overestimates. It is proposed that echo tops be computed by interpolating between elevation scans that bracket the echo-top threshold. The traditional and proposed techniques are evaluated using simulated radar samples of a modeled thunderstorm and by sampling a high-resolution range–height indicator (RHI) of a real thunderstorm. It is shown that the proposed method results in smaller errors when higher-elevation scans are available.
Direct FGF-2 Gene Transfer via Recombinant Adeno-Associated Virus Vectors Stimulates Cell Proliferation, Collagen Production, and the Repair of Experimental Lesions in the Human ACL
Authors: Madry Henning , Kohn Dieter , Cucchiarini Magali 
Published: November 2012

Background: Basic fibroblast growth factor (FGF-2) is a powerful stimulator of fibroblast proliferation and type I/III collagen production. Hypothesis: Overexpression of FGF-2 via direct recombinant adeno-associated virus (rAAV) vector–mediated gene transfer enhances the healing of experimental lesions to the human anterior cruciate ligament (ACL). Study Design: Controlled laboratory study. Methods: rAAV vectors carrying a human FGF-2 sequence or the lacZ marker gene were applied to primary human ACL fibroblasts in vitro and to intact or experimentally injured human ACL explants in situ to evaluate the efficacy and duration of transgene expression and the potential effects of FGF-2 treatment upon the proliferative, metabolic, and regenerative activities in these systems. Results: Sustained, effective dose-dependent lacZ expression was achieved in all systems tested (up to 96% ± 2% in vitro and 80%-85% in situ for at least 30 days). rAAV allowed for continuous FGF-2 production both in vitro and in the intact ACL in situ (32.7 ± 1.4 and 33.1 ± 0.8 pg/mL/24 h, respectively, ie, up to 41-fold more than in the controls at day 30; always P ≤ .001), leading to significantly and durably enhanced levels of proliferation and type I/III collagen production vis-à-vis lacZ (at least 3- and 4-fold increases at day 30, respectively; always P ≤ .001). Most notably, rAAV FGF-2 promoted a significant, long-term production of the factor in experimental ACL lesions (92.7 ± 3.9 pg/mL/24 h, ie, about 5-fold more than in the controls; P ≤ .001) associated with enhanced levels of proliferation and type I/III collagen synthesis (at least 2- and 4-fold increases at day 30, respectively; always P ≤ .001). Remarkably, the FGF-2 treatment allowed for a decrease in the amplitude of such lesions possibly because of the increased expression in contractile α–smooth muscle actin, ligament-specific transcription factor scleraxis, and nuclear factor–κB for proliferation and collagen deposition, which are all markers commonly induced in response to injury. Conclusion: Efficient, stable FGF-2 expression via rAAV enhances the healing of experimental human ACL lesions by activating key cellular and metabolic processes. Clinical Relevance: This approach has potential value for the development of novel, effective treatments for ligament reconstruction.
Obtaining surrogate consent for a minimal-risk research study in the intensive care unit setting
Authors: Larkin Mary E , Beauharnais Catherine C , Magyar Kendra , Macey Laurel , Grennan Kerry B , Boykin Emily E , Russell Steven J 
Published: November 2012

Background Obtaining surrogate consent for clinical research studies conducted in the intensive care unit (ICU) setting is logistically challenging. Purpose To determine whether differences in proportions consenting to trial enrollment existed among patients eligible to consent directly versus those requiring surrogate decision makers in a minimal-risk study to evaluate the accuracy of continuous glucose monitoring in the ICU setting. Methods Low initial enrollment rates prompted a detailed tracking of the screening and consent process. We analyzed the subset of eligible patients identified during a single year to document whether they were approached about trial enrollment, whether they consented or declined, the reasons for declining, and the method of consent (self or surrogate). The proportion of participants who consented and the reasons for declining were compared for self-consenting and surrogate-consenting participants. Results Of the 3041 patients screened, one-third (n = 982) were eligible; 119 of the 982 were approached regarding enrollment. Absence of a surrogate accounted for the majority of eligible patients (726; 84%) not approached. The most common reasons for refusal in the self versus surrogate groups included feeling overwhelmed (13% vs 24%), fear of discomfort (22% vs 12%), and fear of risk (7% vs 4%). Of the 57 eligible patients capable of consenting directly, 11 (19%) enrolled versus 12 (19%) of the 62 who required surrogate consent. When recruitment hours were expanded to include evening time, more eligible patients or their surrogates could be approached than during the day-shift hours alone. Consent was obtained for a larger proportion of potential participants with a history of diabetes (40%) than for those without a history of diabetes (14%). Limitations The findings are from a subset of the entire study sample; data were available only for participants who could be approached, who may have differed from those who could not be approached. Conclusions Surrogate and self-consent rates were similar. Surrogate unavailability was a major barrier to enrollment; overlap of staffing with usual visiting hours should be considered when planning trials in the ICU.
Role of SOX17 in hematopoietic development from human embryonic stem cells
Authors: Nakajima-Takagi Yaeko , Osawa Mitsujiro , Oshima Motohiko , Takagi Haruna , Miyagi Satoru , Endoh Mitsuhiro , Endo Takaho A. , Takayama Naoya , Eto Koji , Toyoda Tetsuro , Koseki Haruhiko , Nakauchi Hiromitsu , Iwama Atsushi 
Published: November 2012

AbstractTo search for genes that promote hematopoietic development from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), we overexpressed several known hematopoietic regulator genes in hESC/iPSC-derived CD34+CD43− endothelial cells (ECs) enriched in hemogenic endothelium (HE). Among the genes tested, only Sox17, a gene encoding a transcription factor of the SOX family, promoted cell growth and supported expansion of CD34+CD43+CD45−/low cells expressing the HE marker VE-cadherin. SOX17 was expressed at high levels in CD34+CD43− ECs compared with low levels in CD34+CD43+CD45− pre-hematopoietic progenitor cells (pre-HPCs) and CD34+CD43+CD45+ HPCs. Sox17-overexpressing cells formed semiadherent cell aggregates and generated few hematopoietic progenies. However, they retained hemogenic potential and gave rise to hematopoietic progenies on inactivation of Sox17. Global gene-expression analyses revealed that the CD34+CD43+CD45−/low cells expanded on overexpression of Sox17 are HE-like cells developmentally placed between ECs and pre-HPCs. Sox17 overexpression also reprogrammed both pre-HPCs and HPCs into HE-like cells. Genome-wide mapping of Sox17-binding sites revealed that Sox17 activates the transcription of key regulator genes for vasculogenesis, hematopoiesis, and erythrocyte differentiation directly. Depletion of SOX17 in CD34+CD43− ECs severely compromised their hemogenic activity. These findings suggest that SOX17 plays a key role in priming hemogenic potential in ECs, thereby regulating hematopoietic development from hESCs/iPSCs.
Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal pathogenesis in rats
Authors: Kau Jyh-Hwa , Shih Yung-Luen , Lien Te-Sheng , Lee Chin-Cheng , Huang Hsin-Hsien , Lin Hung-Chi , Sun Der-Shan , Chang Hsin-Hou 
Published: November 2012

Abstract

Background
Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear.

Methods
To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC) on LT-mediated pathogenesis were also evaluated.

Results
Fibrin depositions were detected in the lungs of LT-treated rats, indicating that coagulation was activated. Increased levels of plasma D-dimer and thrombomodulin, and the ameliorative effect of aPC further suggested that the activation of coagulation-fibrinolysis pathways plays a role in LT-mediated pathogenesis in rats. Reduced mortality was associated with decreased plasma levels of D-dimer and thrombomodulin following aPC treatments in rats with LT-mediated pathogenesis.

Conclusions
These findings suggest that the activation of coagulation in lung tissue contributes to mortality in LT-mediated pathogenesis in rats. In addition, anticoagulant aPC may help to develop a feasible therapeutic strategy.
SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity
Authors: Carrasquillo Robert , Tian Dequan , Krishna Sneha , Pollak Martin R , Greka Anna , Schlöndorff Johannes 
Published: November 2012

Abstract

Background
Transient receptor potential canonical (TRPC) channels are non-selective cation channels involved in receptor-mediated calcium signaling in diverse cells and tissues. The canonical transient receptor potential 6 (TRPC6) has been implicated in several pathological processes, including focal segmental glomerulosclerosis (FSGS), cardiac hypertrophy, and pulmonary hypertension. The two large cytoplasmic segments of the cation channel play a critical role in the proper regulation of channel activity, and are involved in several protein-protein interactions.

Results
Here we report that SNF8, a component of the endosomal sorting complex for transport-II (ESCRT-II) complex, interacts with TRPC6. The interaction was initially observed in a yeast two-hybrid screen using the amino-terminal cytoplasmic domain of TRPC6 as bait, and confirmed by co-immunoprecipitation from eukaryotic cell extracts. The amino-terminal 107 amino acids are necessary and sufficient for the interaction. Overexpression of SNF8 enhances both wild-type and gain-of-function mutant TRPC6-mediated whole-cell currents in HEK293T cells. Furthermore, activation of NFAT-mediated transcription by gain-of-function mutants is enhanced by overexpression of SNF8, and partially inhibited by RNAi mediated knockdown of SNF8. Although the ESCRT-II complex functions in the endocytosis and lysosomal degradation of transmembrane proteins, SNF8 overexpression does not alter the amount of TRPC6 present on the cell surface.

Conclusion
SNF8 is novel binding partner of TRPC6, binding to the amino-terminal cytoplasmic domain of the channel. Modulating SNF8 expression levels alters the TRPC6 channel current and can modulate activation of NFAT-mediated transcription downstream of gain-of-function mutant TRPC6. Taken together, these results identify SNF8 as a novel regulator of TRPC6.
Transcriptional and metabolomic analysis of Ascophyllum nodosum mediated freezing tolerance in Arabidopsis thaliana
Authors: Nair Prasanth , Kandasamy Saveetha , Zhang Junzeng , Ji Xiuhong , Kirby Chris , Benkel Bernhard , Hodges Mark D , Critchley Alan T , Hiltz David , Prithiviraj Balakrishnan 
Published: November 2012

Abstract

Background
We have previously shown that lipophilic components (LPC) of the brown seaweed Ascophyllum nodosum (ANE) improved freezing tolerance in Arabidopsis thaliana. However, the mechanism(s) of this induced freezing stress tolerance is largely unknown. Here, we investigated LPC induced changes in the transcriptome and metabolome of A. thaliana undergoing freezing stress.

Results
Gene expression studies revealed that the accumulation of proline was mediated by an increase in the expression of the proline synthesis genes P5CS1 and P5CS2 and a marginal reduction in the expression of the proline dehydrogenase (ProDH) gene. Moreover, LPC application significantly increased the concentration of total soluble sugars in the cytosol in response to freezing stress. Arabidopsis sfr4 mutant plants, defective in the accumulation of free sugars, treated with LPC, exhibited freezing sensitivity similar to that of untreated controls. The 1H NMR metabolite profile of LPC-treated Arabidopsis plants exposed to freezing stress revealed a spectrum dominated by chemical shifts (δ) representing soluble sugars, sugar alcohols, organic acids and lipophilic components like fatty acids, as compared to control plants. Additionally, 2D NMR spectra suggested an increase in the degree of unsaturation of fatty acids in LPC treated plants under freezing stress. These results were supported by global transcriptome analysis. Transcriptome analysis revealed that LPC treatment altered the expression of 1113 genes (5%) in comparison with untreated plants. A total of 463 genes (2%) were up regulated while 650 genes (3%) were down regulated.

Conclusion
Taken together, the results of the experiments presented in this paper provide evidence to support LPC mediated freezing tolerance enhancement through a combination of the priming of plants for the increased accumulation of osmoprotectants and alteration of cellular fatty acid composition.
Genome sequence of the necrotrophic fungus Penicillium digitatum, the main postharvest pathogen of citrus
Authors: Marcet-Houben Marina , Ballester Ana-Rosa , de la Fuente Beatriz , Harries Eleonora , Marcos Jose F , González-Candelas Luis , Gabaldón Toni 
Published: November 2012

Abstract

Background

Penicillium digitatum is a fungal necrotroph causing a common citrus postharvest disease known as green mold. In order to gain insight into the genetic bases of its virulence mechanisms and its high degree of host-specificity, the genomes of two P. digitatum strains that differ in their antifungal resistance traits have been sequenced and compared with those of 28 other Pezizomycotina.

Results
The two sequenced genomes are highly similar, but important differences between them include the presence of a unique gene cluster in the resistant strain, and mutations previously shown to confer fungicide resistance. The two strains, which were isolated in Spain, and another isolated in China have identical mitochondrial genome sequences suggesting a recent worldwide expansion of the species. Comparison with the closely-related but non-phytopathogenic P. chrysogenum reveals a much smaller gene content in P. digitatum, consistent with a more specialized lifestyle. We show that large regions of the P. chrysogenum genome, including entire supercontigs, are absent from P. digitatum, and that this is the result of large gene family expansions rather than acquisition through horizontal gene transfer. Our analysis of the P. digitatum genome is indicative of heterothallic sexual reproduction and reveals the molecular basis for the inability of this species to assimilate nitrate or produce the metabolites patulin and penicillin. Finally, we identify the predicted secretome, which provides a first approximation to the protein repertoire used during invasive growth.

Conclusions
The complete genome of P. digitatum, the first of a phytopathogenic Penicillium species, is a valuable tool for understanding the virulence mechanisms and host-specificity of this economically important pest.
De novo characterization of the Chinese fir (Cunninghamia lanceolata) transcriptome and analysis of candidate genes involved in cellulose and lignin biosynthesis
Authors: Huang Hua-Hong , Xu Li-Li , Tong Zai-Kang , Lin Er-Pei , Liu Qing-Po , Cheng Long-Jun , Zhu Mu-Yuan 
Published: November 2012

Abstract

Background
Chinese fir (Cunninghamia lanceolata) is an important timber species that accounts for 20–30% of the total commercial timber production in China. However, the available genomic information of Chinese fir is limited, and this severely encumbers functional genomic analysis and molecular breeding in Chinese fir. Recently, major advances in transcriptome sequencing have provided fast and cost-effective approaches to generate large expression datasets that have proven to be powerful tools to profile the transcriptomes of non-model organisms with undetermined genomes.

Results
In this study, the transcriptomes of nine tissues from Chinese fir were analyzed using the Illumina HiSeq™ 2000 sequencing platform. Approximately 40 million paired-end reads were obtained, generating 3.62 gigabase pairs of sequencing data. These reads were assembled into 83,248 unique sequences (i.e. Unigenes) with an average length of 449 bp, amounting to 37.40 Mb. A total of 73,779 Unigenes were supported by more than 5 reads, 42,663 (57.83%) had homologs in the NCBI non-redundant and Swiss-Prot protein databases, corresponding to 27,224 unique protein entries. Of these Unigenes, 16,750 were assigned to Gene Ontology classes, and 14,877 were clustered into orthologous groups. A total of 21,689 (29.40%) were mapped to 119 pathways by BLAST comparison against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The majority of the genes encoding the enzymes in the biosynthetic pathways of cellulose and lignin were identified in the Unigene dataset by targeted searches of their annotations. And a number of candidate Chinese fir genes in the two metabolic pathways were discovered firstly. Eighteen genes related to cellulose and lignin biosynthesis were cloned for experimental validating of transcriptome data. Overall 49 Unigenes, covering different regions of these selected genes, were found by alignment. Their expression patterns in different tissues were analyzed by qRT-PCR to explore their putative functions.

Conclusions
A substantial fraction of transcript sequences was obtained from the deep sequencing of Chinese fir. The assembled Unigene dataset was used to discover candidate genes of cellulose and lignin biosynthesis. This transcriptome dataset will provide a comprehensive sequence resource for molecular genetics research of C. lanceolata.
Population and sex differences in Drosophila melanogaster brain gene expression
Authors: Catalán Ana , Hutter Stephan , Parsch John 
Published: November 2012

AbstractBackgroundChanges in gene regulation are thought to be crucial for the adaptation of organisms to their environment. Transcriptome analyses can be used to identify candidate genes for ecological adaptation, but can be complicated by variation in gene expression between tissues, sexes, or individuals. Here we use high-throughput RNA sequencing of a singleDrosophila melanogastertissue to detect brain-specific differences in gene expression between the sexes and between two populations, one from the ancestral species range in sub-Saharan Africa and one from the recently colonized species range in Europe.ResultsRelatively few genes (<100) displayed sexually dimorphic expression in the brain, but there was an enrichment of sex-biased genes, especially male-biased genes, on the X chromosome. Over 340 genes differed in brain expression between flies from the African and European populations, with the inter-population divergence being highly correlated between males and females. The differentially expressed genes included those involved in stress response, olfaction, and detoxification. Expression differences were associated with transposable element insertions at two genes implicated in insecticide resistance (Cyp6g1andCHKov1).ConclusionsAnalysis of the brain transcriptome revealed many genes differing in expression between populations that were not detected in previous studies using whole flies. There was little evidence for sex-specific regulatory adaptation in the brain, as most expression differences between populations were observed in both males and females. The enrichment of genes with sexually dimorphic expression on the X chromosome is consistent with dosage compensation mechanisms affecting sex-biased expression in somatic tissues.