Detection of coherent airstreams using cluster analysis: application to an extratropical cyclone

Flow in geophysical fluids is commonly summarized by coherent streams, for example conveyor belt flows in extratropical cyclones or jet streaks in the upper troposphere. Typically, parcel trajectories are calculated from the flow field and subjective thresholds are used to distinguish coherent streams of interest. This methodology contribution develops a more objective approach to distinguish coherent airstreams within extratropical cyclones. Agglomerative clustering is applied to trajectories along with a method to identify the optimal number of cluster classes. The methodology is applied to trajectories associated with the low-level jets of a well-studied extratropical cyclone. For computational efficiency, a constraint that trajectories must pass through these jet regions is applied prior to clustering; the partitioning into different airstreams is then performed by the agglomerative clustering. It is demonstrated that the methodology can identify the salient flow structures of cyclones: the warm and cold conveyor belts. A test focusing on the airstreams terminating at the tip of the bent-back front further demonstrates the success of the method in that it can distinguish fine-scale flow structure such as descending sting jet airstreams

Sting-jet windstorms over the North Atlantic: climatology and contribution to extreme wind risk

Extratropical cyclones with damaging winds can have large socio-economic impacts when they make landfall. During the last decade, studies have identified a mesoscale transient jet, the sting jet, that descends from the tip of the hooked cloud head towards the top of the boundary layer in the dry intrusion region as a cause of strong surface winds, and especially gusts, in some cyclones. While many case studies have focused on the dynamics and characteristics of these jets, there have been few studies that assess the climatology of the associated cyclones and their importance for wind risk. Here we determine the climatological characteristics of North Atlantic cyclones in terms of the possibility that they had sting jets using a previously-published sting-jet precursor diagnostic applied to ERA-Interim data over 32 extended winter seasons from 1979–2012. Of the 5447 cyclones tracked, 32% had the precursor (42% in the 22% of cyclones that developed explosively). Precursor storms have a more southerly and zonal storm track than storms without the precursor and precursor storms tend to be more intense as defined by 850-hPa relative vorticity. This study also shows that precursor storms are the dominant cause of cyclone-related resolved strong wind events over the British Isles for 850-hPa windspeeds exceeding 30 ms−1. Hence, early detection of a sting jet storm could give advance warning of enhanced wind risk. However, over continental northwestern Europe, precusor cyclone-related windstorm events occur far less often

Increased wind risk from sting-jet windstorms with climate change

Extra-tropical cyclones dominate autumn and winter weather over western Europe. The strongest cyclones, often termed windstorms, have a large socio-economic impact on landfall due to strong surface winds and coastal storm surges. Climate model integrations have predicted a future increase in the frequency of, and potential damage from, European windstorms and yet these integrations cannot properly represent localised jets, such as sting jets, that may significantly enhance damage. Here we present the first prediction of how the climatology of sting-jet-containing cyclones will change in a future warmer climate, considering the North Atlantic and Europe. A proven sting-jet precursor diagnostic is applied to 13-year present-day and future ($\sim$2100) climate integrations from the Met Office Unified Model in its Global Atmosphere 3.0 configuration. The present-day climate results are consistent with previously-published results from a reanalysis dataset (with around 32\% of cyclones exhibiting the sing-jet precursor), lending credibility to the analysis of the future-climate integration. The proportion of cyclones exhibiting the sting-jet precursor in the future-climate integration increases to 45\%. Furthermore, while the proportion of explosively-deepening storms increases only slightly in the future climate, the proportion of those storms with the sting-jet precursor increases by 60\%. The European resolved-wind risk associated with explosively-deepening storms containing a sting-jet precursor increases substantially in the future climate; in reality this wind risk is likely to be further enhanced by the release of localised moist instability, unresolved by typical climate models

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

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.

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

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

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes