1,220 research outputs found

    The added value of using convective-permitting regional climate model simulations to represent cloud band events over South America

    Get PDF
    Climate science has long explored whether higher resolution regional climate models (RCMs) provide improved simulation of regional climates over global climate models (GCMs). The advent of convective-permitting RCMs (CPRCMs), where sufficiently fine-scale grids allow explicitly resolving rather than parametrising convection, has created a clear distinction between RCM and GCM formulations. This study investigates the simulation of tropical-extratropical (TE) cloud bands in a suite of pan-South America convective-permitting Met Office Unified Model (UM) and Weather Research and Forecasting (WRF) climate simulations. All simulations produce annual cycles in TE cloud band frequency within 10–30% of observed climatology. However, too few cloud band days are simulated during the early summer (Nov–Dec) and too many during the core summer (Jan–Feb). Compared with their parent forcing, CPRCMs simulate more dry days but systematically higher daily rainfall rates, keeping the total rain biases low. During cloud band systems, the CPRCMs correctly reproduced the observed changes in tropical rain rates and their importance to climatology. Circulation analysis suggests that simulated lower subtropical rain rates during cloud bands systems, in contrast to the higher rates in the tropics, are associated with weaker northwesterly moisture flux from the Amazon towards southeast South America, more evident in the CPRCMs. Taken together, the results suggest that CPRCMs tend to be more effective at producing heavy daily rainfall rates than parametrised simulations for a given level of near-surface moist energy. The extent to which this improves or degrades biases present in the parent simulations is strongly region-dependent

    Variation in the plasma membrane monoamine transporter (PMAT) (encoded by SLC29A4) and organic cation transporter 1 (OCT1) (encoded by SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes:An IMI direct study

    Get PDF
    OBJECTIVE Gastrointestinal adverse effects occur in 20–30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5–10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. RESEARCH DESIGN AND METHODS The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance. RESULTS Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01). CONCLUSIONS These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin

    Growth control of the eukaryote cell: a systems biology study in yeast.

    Get PDF
    BACKGROUND: Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. RESULTS: Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. CONCLUSION: This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Climate variability affects water-energy-food infrastructure performance in East Africa

    Get PDF
    The need to assess major infrastructure performance under a changing climate is widely recognized yet rarely practiced, particularly in rapidly growing African economies. Here, we consider high-stakes investments across the water, energy, and food sectors for two major river basins in a climate transition zone in Africa. We integrate detailed interpretation of observed and modeled climate-system behavior with hydrological modeling and decision-relevant performance metrics. For the Rufiji River in Tanzania, projected risks for the mid-21st century are similar to those of the present day, but for the Lake Malawi-Shire River, future risk exceeds that experienced during the 20th century. In both basins a repeat of an early-20th century multi-year drought would challenge the viability of proposed infrastructure. A long view, which emphasizes past and future changes in variability, set within a broader context of climate-information interpretation and decision making, is crucial for screening the risk to infrastructure
    • …
    corecore