Temporal neural networks for downscaling climate variability and extremes.

This paper presents an application of temporal neural networks for downscaling global climate models (GCMs) output. Because of computational constraints, GCMs are usually run at coarse grid resolution (in the order of 100s of kilometres) and as a result they are inherently unable to present local sub-grid scale features and dynamics. Consequently, outputs from these models cannot be used directly in many climate change impact studies. This research explored the issues of 'downscaling' the outputs of GCMs using a temporal neural network (TNN) approach. The method is proposed for downscaling daily precipitation and temperature series for a region in northern Quebec, Canada. The downscaling models are developed and validated using large-scale predictor variables derived from the National Center for Environmental Prediction (NCEP) reanalysis data set. The performance of the temporal neural network downscaling model is also compared to a regression-based statistical downscaling model with emphasis on their ability in reproducing the observed climate variability and extremes. The downscaling results for the base period (1961-2000) suggest that the TNN is an efficient method for downscaling both daily precipitation as well as daily maximum and minimum temperature series. Furthermore, the different model test results indicate that the TNN model mostly outperforms the statistical models for the downscaling of daily precipitation extremes and variability.     

The human desmin gene: A specific regulatory programme in skeletal muscle both in vitro and in transgenic mice

Desmin synthesis is restricted to cardiac, skeletal and smooth muscles. In several familial myopathies involving fibre disorganization, filamentous aggregation of desmin has been characterized. During the development of the mouse embryo, desmin is one of the first muscle proteins detected in both the heart and the somites. To identify the DNA sequences involved in the regulation of desmin gene expression a 4.5 kb 5′-flanking region of the human desmin gene has been isolated. Different mutants were used to characterize specific enhancers in vitro and in vivo. The results obtained with transgenic mice provide evidence that the 1 kb cis-regulatory sequences, functional in skeletal muscle cells in vitro, confer specific developmental control for skeletal muscles. Furthermore, distinct programmes for cardiac and skeletal muscle-specific expression of the desmin gene are revealed.     

Characterization of intestinal invasion by Salmonella typhimurium and Salmonella dublin and effect of a mutation in the invH gene.

The relative levels of invasiveness of two bovine isolates each of Salmonella typhimurium and Salmonella dublin and of invH mutants of S. typhimurium were determined in MDCK and Int 407 cultured-cell assays and in bovine ileal loops. S. dublin was found to be significantly less invasive in cultured cells than S. typhimurium, but this difference was not observed in bovine intestines. The invH mutants exhibited a significant reduction in invasion in both cultured cells and bovine intestines. The invasive phenotypes of the strains were confirmed by fluorescent microscopy and scanning and transmission electron microscopy. The wild-type strains were observed in the laminae propriae of the intestinal villi, while in contrast the invH mutants were generally associated with the enterocyte layer. The degree of damage in the bovine ileum was related to the magnitude of the invasion. There was no difference in the amount of S. typhimurium or S. dublin recovered from the bovine ileum either with or without Peyer's patches 3 h after inoculation of the loop.     

Analysis of the floral transcriptome uncovers new regulators of organ determination and gene families related to flower organ differentiation in Gerbera hybrida (Asteraceae)

Development of composite inflorescences in the plant family Asteraceae has features that cannot be studied in the traditional model plants for flower development. In Gerbera hybrida, inflorescences are composed of morphologically different types of flowers tightly packed into a flower head (capitulum). Individual floral organs such as pappus bristles (sepals) are developmentally specialized, stamens are aborted in marginal flowers, petals and anthers are fused structures, and ovaries are located inferior to other floral organs. These specific features have made gerbera a rewarding target of comparative studies. Here we report the analysis of a gerbera EST database containing 16,994 cDNA sequences. Comparison of the sequences with all plant peptide sequences revealed 1656 unique sequences for gerbera not identified elsewhere within the plant kingdom. Based on the EST database, we constructed a cDNA microarray containing 9000 probes and have utilized it in identification of flower-specific genes and abundantly expressed marker genes for flower scape, pappus, stamen, and petal development. Our analysis revealed several regulatory genes with putative functions in flower-organ development. We were also able to associate a number of abundantly and specifically expressed genes with flower-organ differentiation. Gerbera is an outcrossing species, for which genetic approaches to gene discovery are not readily amenable. However, reverse genetics with the help of gene transfer has been very informative. We demonstrate here the usability of the gerbera microarray as a reliable new tool for identifying novel genes related to specific biological questions and for large-scale gene expression analysis.     

Panfungal PCR and multiplex liquid hybridization for detection of fungi in tissue specimens

A procedure based on panfungal PCR and multiplex liquid hybridization was developed for the detection of fungi in tissue specimens. The PCR amplified the fungal internal transcribed spacer (ITS) region (ITS1-5.8S rRNA-ITS2). After capture with specific probes, eight common fungal pathogens (Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Candida krusei, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Cryptococcus neoformans) were identified according to the size of the amplification product on an automated sequencer. The nonhybridized products were identified by sequencing. The performance of the procedure was examined with 12 deep-tissue specimens and 8 polypous tissue biopsies from the paranasal sinuses. A detection level of 0.1 to 1 pg of purified DNA (2 to 20 CFU) was achieved. Of the 20 specimens, PCR was positive for 19 (95%), of which 10 (53%) were hybridization positive. In comparison, 12 (60%) of the specimens were positive by direct microscopy, but only 7 (35%) of the specimens showed fungal growth. Sequencing of the nonhybridized amplification products identified an infecting agent in six specimens, and three specimens yielded only sequences of unknown fungal origin. The procedure provides a rapid (within 2 days) detection of common fungal pathogens in tissue specimens, and it is highly versatile for the identification of other fungal pathogens.     

Reimbursement models to tackle market failures for antimicrobials: Approaches taken in France,Germany, Sweden,the United Kingdom,and the United States

IntroductionThe pipeline of new antibacterials remains limited. Reasons include low research investments, limited commercial prospects, and scientific challenges. To complement existing initiatives such as research grants, governments are exploring policy options for providing new market incentives to drug developers.Materials and methodsReimbursement interventions for antibacterials in France, Germany, Sweden, US, and UK were reviewed and analysed by the authors.ResultsIn France, Germany, and the US, implemented interventions centre on providing exceptions in cost-containment mechanisms to allow higher prices for certain antibacterials. In the US, also, certain antibacterials are granted additional years of protection from generic competition (exclusivity) and faster regulatory review. The UK is piloting a model that will negotiate contracts with manufacturers to pay a fixed annual fee for ongoing supply of as many units as needed. Sweden is piloting a model that will offer manufacturers of selected antibacterials contracts that would guarantee a minimum annual revenue. A similar model of guaranteed minimal annual revenues is under consideration in the US (PASTEUR Act).ConclusionsThe UK and Sweden are piloting entirely novel procurement and reimbursement models. Existing interventions in the US, France, and Germany represent important, but relatively minor interventions. More countries should explore the use of novel models and international coordination will be important for ‘pull’ incentives to be effective. If adopted, the PASTEUR legislation in the US would constitute a significant ‘pull’ incentive.     

The ret protooncogene is expressed in normal human parafollicular thyroid-cells

The RET proto-oncogene has been demonstrated to be expressed in medullary thyroid carcinomas and pheochromocytomas, and was mutated in patients with the multiple endocrine neoplasia type 2A (MEN 2A). The results presented herein show its expression in normal human thyroid parafollicular C cells. Since RET is predicted to encode a receptor for a still unknown ligand, these data confirm its involvement in the regulation and growth of these cells.     

Production of tgf-Beta and hgf receptor by a differentiated papillary thyroid-carcinoma cell-line (B-cpap) - implication in malignancy

The B-CPAP cell line was obtained from a human differentiated papillary thyroid carcinoma. Previous studies showed that the cells present thyroid characteristics such as thyroglobulin production, phenotypic alterations such as synthesis of human chorionic gonadotropin hormone (HCG), expression of neuron specific enolase (NSE) and protein S100, and also somatic mutations of p53 and K-rns oncogenes. The present data further characterize this cell line and show an overexpression of transforming growth factor (TGF beta 1) and c-met gene product i.e. the receptor for human growth factor (HGF). The relation between the phenotypic and somatic alterations in the process of malignancy are discussed.