bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical Downscaling of Extreme Precipitation Events Using Censored Quantile Regression
Authors: Friederichs P. , Hense A. 
Published: June 2007

Abstract
A statistical downscaling approach for extremes using censored quantile regression is presented. Conditional quantiles of station data (e.g., daily precipitation sums) in Germany are estimated by means of the large-scale circulation as represented by the NCEP reanalysis data. It is shown that a mixed discrete–continuous response variable, such as a daily precipitation sum, can be statistically modeled by a censored variable. Furthermore, a conditional quantile skill score is formulated to assess the relative gain of a quantile forecast compared with a reference forecast. Just like multiple regression for expectation values, quantile regression provides a tool to formulate a model output statistics system for extremal quantiles.
Impact of the Different Components of 4DVAR on the Global Forecast System of the Meteorological Service of Canada
Authors: Laroche Stéphane , Gauthier Pierre , Tanguay Monique , Pellerin Simon , Morneau Josée 
Published: June 2007

Abstract
A four-dimensional variational data assimilation (4DVAR) scheme has recently been implemented in the medium-range weather forecast system of the Meteorological Service of Canada (MSC). The new scheme is now composed of several additional and improved features as compared with the three-dimensional variational data assimilation (3DVAR): the first guess at the appropriate time from the full-resolution model trajectory is used to calculate the misfit to the observations; the tangent linear of the forecast model and its adjoint are employed to propagate the analysis increment and the gradient of the cost function over the 6-h assimilation window; a comprehensive set of simplified physical parameterizations is used during the final minimization process; and the number of frequently reported data, in particular satellite data, has substantially increased. The impact of these 4DVAR components on the forecast skill is reported in this article. This is achieved by comparing data assimilation configurations that range in complexity from the former 3DVAR with the implemented 4DVAR over a 1-month period. It is shown that the implementation of the tangent-linear model and its adjoint as well as the increased number of observations are the two features of the new 4DVAR that contribute the most to the forecast improvement. All the other components provide marginal though positive impact. 4DVAR does not improve the medium-range forecast of tropical storms in general and tends to amplify the existing, too early extratropical transition often observed in the MSC global forecast system with 3DVAR. It is shown that this recurrent problem is, however, more sensitive to the forecast model than the data assimilation scheme employed in this system. Finally, the impact of using a shorter cutoff time for the reception of observations, as the one used in the operational context for the 0000 and 1200 UTC forecasts, is more detrimental with 4DVAR. This result indicates that 4DVAR is more sensitive to observations at the end of the assimilation window than 3DVAR.
Is Blocking a Circulation Regime?
Authors: Stan Cristiana , Straus David M. 
Published: June 2007

Abstract
The relationship between Pacific blocking and large-scale circulation regimes is investigated. The large-scale circulation regimes are obtained by cluster analysis using the k-means method and tested against significance and reproducibility. Pacific blocking is described using two different methods. In a direct approach, blocking is described by a recently developed blocking index, which is defined in terms of potential temperature anomaly on a surface of constant potential vorticity. In an indirect approach, the occurrence of extreme events is used as a proxy for blockings. Between the two methods there is a causal relationship; the direct one is an indication of the occurrence of the blocking, while the indirect one is a measure of some of the effects caused by the blocking. The results indicate that large-scale circulation regimes are related to but not necessarily tightly coupled to blocking and weather extremes in the Pacific–North America region.
Molecular determinants of caste differentiation in the highly eusocial honeybee Apis mellifera
Authors: Barchuk Angel R , Cristino Alexandre S , Kucharski Robert , Costa Luciano F , Simões Zilá LP , Maleszka Ryszard 
Published: June 2007

Abstract
Background
In honeybees, differential feeding of female larvae promotes the occurrence of two different phenotypes, a queen and a worker, from identical genotypes, through incremental alterations, which affect general growth, and character state alterations that result in the presence or absence of specific structures. Although previous studies revealed a link between incremental alterations and differential expression of physiometabolic genes, the molecular changes accompanying character state alterations remain unknown.

Results
By using cDNA microarray analyses of >6,000 Apis mellifera ESTs, we found 240 differentially expressed genes (DEGs) between developing queens and workers. Many genes recorded as up-regulated in prospective workers appear to be unique to A. mellifera, suggesting that the workers' developmental pathway involves the participation of novel genes. Workers up-regulate more developmental genes than queens, whereas queens up-regulate a greater proportion of physiometabolic genes, including genes coding for metabolic enzymes and genes whose products are known to regulate the rate of mass-transforming processes and the general growth of the organism (e.g., tor). Many DEGs are likely to be involved in processes favoring the development of caste-biased structures, like brain, legs and ovaries, as well as genes that code for cytoskeleton constituents. Treatment of developing worker larvae with juvenile hormone (JH) revealed 52 JH responsive genes, specifically during the critical period of caste development. Using Gibbs sampling and Expectation Maximization algorithms, we discovered eight overrepresented cis-elements from four gene groups. Graph theory and complex networks concepts were adopted to attain powerful graphical representations of the interrelation between cis-elements and genes and objectively quantify the degree of relationship between these entities.

Conclusion
We suggest that clusters of functionally related DEGs are co-regulated during caste development in honeybees. This network of interactions is activated by nutrition-driven stimuli in early larval stages. Our data are consistent with the hypothesis that JH is a key component of the developmental determination of queen-like characters. Finally, we propose a conceptual model of caste differentiation in A. mellifera based on gene-regulatory networks.
Monitoring of transcriptional regulation in Pichia pastoris under protein production conditions
Authors: Gasser Brigitte , Maurer Michael , Rautio Jari , Sauer Michael , Bhattacharyya Anamitra , Saloheimo Markku , Penttilä Merja , Mattanovich Diethard 
Published: June 2007

Abstract

Background
It has become evident that host cells react to recombinant protein production with a variety of metabolic and intrinsic stresses such as the unfolded protein response (UPR) pathway. Additionally, environmental conditions such as growth temperature may have a strong impact on cell physiology and specific productivity. However, there is little information about the molecular reactions of the host cells on a genomic level, especially in context to recombinant protein secretion. For the first time, we monitored transcriptional regulation of a subset of marker genes in the common production host Pichia pastoris to gain insights into the general physiological status of the cells under protein production conditions, with the main focus on secretion stress related genes.

Results
Overexpression of the UPR activating transcription factor Hac1p was employed to identify UPR target genes in P. pastoris and the responses were compared to those known for Saccharomyces cerevisiae. Most of the folding/secretion related genes showed similar regulation patterns in both yeasts, whereas genes associated with the general stress response were differentially regulated. Secretion of an antibody Fab fragment led to induction of UPR target genes in P. pastoris, however not to the same magnitude as Hac1p overproduction. Overexpression of S. cerevisiae protein disulfide isomerase (PDI1) enhances Fab secretion rates 1.9 fold, but did not relief UPR stress. Reduction of cultivation temperature from 25°C to 20°C led to a 1.4-fold increase of specific product secretion rate in chemostat cultivations, although the transcriptional levels of the product genes (Fab light and heavy chain) were significantly reduced at the lower temperature. A subset of folding related genes appeared to be down-regulated at the reduced temperature, whereas transcription of components of the ER associated degradation and the secretory transport was enhanced.

Conclusion
Monitoring of genomic regulation of marker genes with the transcriptional profiling method TRAC in P. pastoris revealed similarities and discrepancies of the responses compared to S. cerevisiae. Thus our results emphasize the importance to analyse the individual hosts under real production conditions instead of drawing conclusions from model organisms. Cultivation temperature has a significant influence on specific productivity that cannot be related just to thermodynamic effects, but strongly impacts the regulation of specific genes.
A predictive model relating daily fluctuations in summer temperatures and mortality rates
Authors: Fouillet Anne , Rey Grégoire , Jougla Eric , Frayssinet Philippe , Bessemoulin Pierre , Hémon Denis 
Published: June 2007

Abstract

Background
In the context of climate change, an efficient alert system to prevent the risk associated with summer heat is necessary. The authors' objective was to describe the temperature-mortality relationship in France over a 29-year period and to define and validate a combination of temperature factors enabling optimum prediction of the daily fluctuations in summer mortality.

Methods
The study addressed the daily mortality rates of subjects aged over 55 years, in France as a whole, from 1975 to 2003. The daily minimum and maximum temperatures consisted in the average values recorded by 97 meteorological stations. For each day, a cumulative variable for the maximum temperature over the preceding 10 days was defined.
The mortality rate was modelled using a Poisson regression with over-dispersion and a first-order autoregressive structure and with control for long-term and within-summer seasonal trends. The lag effects of temperature were accounted for by including the preceding 5 days. A "backward" method was used to select the most significant climatic variables. The predictive performance of the model was assessed by comparing the observed and predicted daily mortality rates on a validation period (summer 2003), which was distinct from the calibration period (1975–2002) used to estimate the model.

Results
The temperature indicators explained 76% of the total over-dispersion. The greater part of the daily fluctuations in mortality was explained by the interaction between minimum and maximum temperatures, for a day t and the day preceding it. The prediction of mortality during extreme events was greatly improved by including the cumulative variables for maximum temperature, in interaction with the maximum temperatures. The correlation between the observed and estimated mortality ratios was 0.88 in the final model.

Conclusion
Although France is a large country with geographic heterogeneity in both mortality and temperatures, a strong correlation between the daily fluctuations in mortality and the temperatures in summer on a national scale was observed. The model provided a satisfactory quantitative prediction of the daily mortality both for the days with usual temperatures and for the days during intense heat episodes. The results may contribute to enhancing the alert system for intense heat waves.
Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer
Authors: King Michael , Chatelain Kourt , Farris Dustin , Jensen Dayne , Pickup Jason , Swapp Aaron , O'Malley Susan , Kingsley Karl 
Published: June 2007

AbstractBackgroundDespite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC) to proanthocyanidin (PAC), a plant-derived compound that may inhibit the progression of several other cancers.MethodsUsing a series ofin vitroassays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV) may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation.ResultsOur results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control.ConclusionThese results signify that PAC may be a compelling candidate for testing in both animal and human models. Furthermore, these data provide adequate justification for elucidating the divergent mechanisms of PAC-induced proliferation, inhibition, and apoptosis among these and other cell lines.
Involving deprived communities in improving the quality of primary care services: does participatory action research work?
Authors: Cawston Peter G , Mercer Stewart W , Barbour Rosaline S 
Published: June 2007

Abstract

Background
Participation by communities in improving the quality of health services has become a feature of government policy in the United Kingdom. The aim of the study was to involve a deprived community in the UK in shaping quality improvements of local primary care services. The specific objectives were firstly to create participation by local people in evaluating the primary care services available in the area and secondly to bring about change as a result of this process.

Methods
The methods of participatory action research was used. The study was set in an area of high socio-economic deprivation served by a 'Local Health Care Co-operative' in a peripheral housing estate in Glasgow, Scotland. 72 local residents took part in 11 focus groups: eight of these were with community groups and three with other residents. 372 local residents completed questionnaires either by brief face-to-face interviews (114) or by self or carer completion (258).

Results
The study group produced recommendations on physical access to the health centre, time constraints in accessing services and problems encountered in individual relationships with health staff. They also highlighted the social gap between health service providers and the daily life of community residents. Action was taken to bring these recommendations to the attention of the Primary Care Organisation.

Conclusion
Participatory action research was used to involve a deprived community in the UK in a 'bottom-up' approach aimed at improving quality of local primary care services. Although successful in creating a partnership between academic researchers and lay researchers and participation by local people in evaluating the primary care services available in the area, the impact of the study in terms of immediate action taken over specific issues has been modest. The possible reasons for this are discussed.
Comparative analysis of structured RNAs in S. cerevisiaeindicates a multitude of different functions
Authors: Steigele Stephan , Huber Wolfgang , Stocsits Claudia , Stadler Peter F , Nieselt Kay 
Published: June 2007

Abstract

Background

Non-coding RNAs (ncRNAs) are an emerging focus for both computational analysis and experimental research, resulting in a growing number of novel, non-protein coding transcripts with often unknown functions. Whole genome screens in higher eukaryotes, for example, provided evidence for a surprisingly large number of ncRNAs. To supplement these searches, we performed a computational analysis of seven yeast species and searched for new ncRNAs and RNA motifs.

Results

A comparative analysis of the genomes of seven yeast species yielded roughly 2800 genomic loci that showed the hallmarks of evolutionary conserved RNA secondary structures. A total of 74% of these regions overlapped with annotated non-coding or coding genes in yeast. Coding sequences that carry predicted structured RNA elements belong to a limited number of groups with common functions, suggesting that these RNA elements are involved in post-transcriptional regulation and/or cellular localization. About 700 conserved RNA structures were found outside annotated coding sequences and known ncRNA genes. Many of these predicted elements overlapped with UTR regions of particular classes of protein coding genes. In addition, a number of RNA elements overlapped with previously characterized antisense transcripts. Transcription of about 120 predicted elements located in promoter regions and other, previously un-annotated, intergenic regions was supported by tiling array experiments, ESTs, or SAGE data.

Conclusion

Our computational predictions strongly suggest that yeasts harbor a substantial pool of several hundred novel ncRNAs. In addition, we describe a large number of RNA structures in coding sequences and also within antisense transcripts that were previously characterized using tiling arrays.
GC- and AT-rich chromatin domains differ in conformation and histone modification status and are differentially modulated by Rpd3p
Authors: Dekker Job 
Published: June 2007

Abstract
Background
Base-composition varies throughout the genome and is related to organization of chromosomes in distinct domains (isochores). Isochore domains differ in gene expression levels, replication timing, levels of meiotic recombination and chromatin structure. The molecular basis for these differences is poorly understood.

Results
We have compared GC- and AT-rich isochores of yeast with respect to chromatin conformation, histone modification status and transcription. Using 3C analysis we show that, along chromosome III, GC-rich isochores have a chromatin structure that is characterized by lower chromatin interaction frequencies compared to AT-rich isochores, which may point to a more extended chromatin conformation. In addition, we find that throughout the genome, GC-rich and AT-rich genes display distinct levels of histone modifications. Interestingly, elimination of the histone deacetylase Rpd3p differentially affects conformation of GC- and AT-rich domains. Further, deletion of RPD3 activates expression of GC-rich genes more strongly than AT-rich genes. Analyses of effects of the histone deacetylase inhibitor trichostatin A, global patterns of Rpd3p binding and effects of deletion of RPD3 on histone H4 acetylation confirmed that conformation and activity of GC-rich chromatin are more sensitive to Rpd3p-mediated deacetylation than AT-rich chromatin.

Conclusion
We find that GC-rich and AT-rich chromatin domains display distinct chromatin conformations and are marked by distinct patterns of histone modifications. We identified the histone deacetylase Rpd3p as an attenuator of these base composition-dependent differences in chromatin status. We propose that GC-rich chromatin domains tend to occur in a more active conformation and that Rpd3p activity represses this propensity throughout the genome.
Fast-evolving noncoding sequences in the human genome
Authors: Bird Christine P , Stranger Barbara E , Liu Maureen , Thomas Daryl J , Ingle Catherine E , Beazley Claude , Miller Webb , Hurles Matthew E , Dermitzakis Emmanouil T 
Published: June 2007

Abstract
Background
Gene regulation is considered one of the driving forces of evolution. Although protein-coding DNA sequences and RNA genes have been subject to recent evolutionary events in the human lineage, it has been hypothesized that the large phenotypic divergence between humans and chimpanzees has been driven mainly by changes in gene regulation rather than altered protein-coding gene sequences. Comparative analysis of vertebrate genomes has revealed an abundance of evolutionarily conserved but noncoding sequences. These conserved noncoding (CNC) sequences may well harbor critical regulatory variants that have driven recent human evolution.

Results
Here we identify 1,356 CNC sequences that appear to have undergone dramatic human-specific changes in selective pressures, at least 15% of which have substitution rates significantly above that expected under neutrality. The 1,356 'accelerated CNC' (ANC) sequences are enriched in recent segmental duplications, suggesting a recent change in selective constraint following duplication. In addition, single nucleotide polymorphisms within ANC sequences have a significant excess of high frequency derived alleles and high F
ST
values relative to controls, indicating that acceleration and positive selection are recent in human populations. Finally, a significant number of single nucleotide polymorphisms within ANC sequences are associated with changes in gene expression. The probability of variation in an ANC sequence being associated with a gene expression phenotype is fivefold higher than variation in a control CNC sequence.

Conclusion
Our analysis suggests that ANC sequences have until very recently played a role in human evolution, potentially through lineage-specific changes in gene regulation.