Runoff modelling in glacierized Central Asian catchments for present-day and future climate

A conceptual precipitation–runoff model was applied in five glacierized catchments in Central Asia. The model, which was first developed and applied in the Alps, works on a daily time step and yields good results in the more continental climate of the Tien Shan mountains for present-day climate conditions. Runoff scenarios for different climates (doubling of CO2) and glacierization conditions predict an increased flood risk as a first stage and a more complex picture after a complete glacier loss: a higher discharge during spring due to an earlier and more intense snowmelt is followed by a water deficiency in hot and dry summer periods. This unfavourable seasonal redistribution of the water supply has dramatic consequences for the Central Asian lowlands, which depend to a high degree on the glacier melt water for irrigation and already nowadays suffer from water shortages

Modelling of hydrological response to climate change in glacierized Central Asian catchments

The arid lowlands of Central Asia are highly dependent on the water supplied by the Tien Shan mountains. Snow and ice storage make large contributions to current runoff, particularly in summer. Two runoff models with different temporal resolutions, HBV-ETH and OEZ, were applied in three glaciated catchments of the Tien Shan mountains. Scenario runs were produced for a climate change caused by the doubling of atmospheric CO2 as predicted by the GISS global circulation model and assuming a 50% reduction of glaciation extent, as well as a complete loss of glaciation. Agreement of the results was best for runs based on 50% glaciation loss, where both models predict an increase in spring and summer runoff compared to current levels. Scenarios for complete loss of glaciation predict an increase in spring runoff levels, followed by lower runoff levels for July and August. Model predictions differ concerning the degree of reduction of late summer runoff. These scenarios are sensitive to model simulation of basin precipitation, as well as to reduction of glaciation extent

Efficient Quality Diversity Optimization of 3D Buildings through 2D Pre-optimization

Quality diversity algorithms can be used to efficiently create a diverse set of solutions to inform engineers' intuition. But quality diversity is not efficient in very expensive problems, needing 100.000s of evaluations. Even with the assistance of surrogate models, quality diversity needs 100s or even 1000s of evaluations, which can make it use infeasible. In this study we try to tackle this problem by using a pre-optimization strategy on a lower-dimensional optimization problem and then map the solutions to a higher-dimensional case. For a use case to design buildings that minimize wind nuisance, we show that we can predict flow features around 3D buildings from 2D flow features around building footprints. For a diverse set of building designs, by sampling the space of 2D footprints with a quality diversity algorithm, a predictive model can be trained that is more accurate than when trained on a set of footprints that were selected with a space-filling algorithm like the Sobol sequence. Simulating only 16 buildings in 3D, a set of 1024 building designs with low predicted wind nuisance is created. We show that we can produce better machine learning models by producing training data with quality diversity instead of using common sampling techniques. The method can bootstrap generative design in a computationally expensive 3D domain and allow engineers to sweep the design space, understanding wind nuisance in early design phases.Comment: This is the final version and has been accepted for publication in Evolutionary Computation (MIT Press

Erratum: Integrin-FAK Signaling Rapidly and Potently Promotes Mitochondrial Function Through STAT3 (Cell Communication and Signaling (2016) 14 (32) DOI: 10.1186/s12964-016-0157-7)

Reference. Unfortunately, after publication of this article [1], it was noticed that the Acknowledgements and Funding sections were incomplete. The Acknowledgements section currently reads, “We are grateful for the technical support by Aruna Visavadiya, Ying Li, and Rhesa Dykes” and the Funding section currently reads, “This work was supported by NIH grant NS45734 and ETSU medical school funds”. The full, corrected sections can be seen below. Acknowledgements We are grateful for the technical support by Aruna Visavadiya, Ying Li, and Rhesa Dykes. Dr. Britta Engelhardt (Theodor Kocher institute) is thanked for providing the bEnd5 cells. Funding This work was supported by NIH grant NS45734 and in part by NIH grant C06RR0306551 and the ETSU College of Medicine. Further to this, a duplicate image in Fig. 4e was reported. The correct image is presented in this correction article. (Figure Presented)

A genome-wide association study of the frailty index highlights brain pathways in ageing

Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) meta-analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60–70 years) and Swedish TwinGene participants (n = 10,616, 41–87 years). FI calculation was based on 49 or 44 self-reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p < 5*10−8). Many FI-associated loci have established associations with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, one appears to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes expressed in the frontal cortex and hippocampus were significantly downregulated (adjusted p < 0.05). We also used Mendelian randomization to identify modifiable traits and exposures that may affect frailty risk, with a higher educational attainment genetic risk score being associated with a lower degree of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on pathways in the brain

Transcriptional activation of endothelial cells by TGFβ coincides with acute microvascular plasticity following focal spinal cord ischaemia/reperfusion injury

Microvascular dysfunction, loss of vascular support, ischaemia and sub-acute vascular instability in surviving blood vessels contribute to secondary injury following SCI (spinal cord injury). Neither the precise temporal profile of the cellular dynamics of spinal microvasculature nor the potential molecular effectors regulating this plasticity are well understood. TGFβ (transforming growth factor β) isoforms have been shown to be rapidly increased in response to SCI and CNS (central nervous system) ischaemia, but no data exist regarding their contribution to microvascular dysfunction following SCI. To examine these issues, in the present study we used a model of focal spinal cord ischaemia/reperfusion SCI to examine the cellular response(s) of affected microvessels from 30 min to 14 days post-ischaemia. Spinal endothelial cells were isolated from affected tissue and subjected to focused microarray analysis of TGFβ-responsive/related mRNAs 6 and 24 h post-SCI. Immunohistochemical analyses of histopathology show neuronal disruption/loss and astroglial regression from spinal microvessels by 3 h post-ischaemia, with complete dissolution of functional endfeet (loss of aquaporin-4) by 12 h post-ischaemia. Coincident with this microvascular plasticity, results from microarray analyses show 9 out of 22 TGFβ-responsive mRNAs significantly up-regulated by 6 h post-ischaemia. Of these, serpine 1/PAI-1 (plasminogen-activator inhibitor 1) demonstrated the greatest increase (>40-fold). Furthermore, uPA (urokinase-type plasminogen activator), another member of the PAS (plasminogen activator system), was also significantly increased (>7.5-fold). These results, along with other select up-regulated mRNAs, were confirmed biochemically or immunohistochemically. Taken together, these results implicate TGFβ as a potential molecular effector of the anatomical and functional plasticity of microvessels following SCI

Preventing Prostate Biopsy Complications: to Augment or to Swab?

Aims for Improvement The aim of this study was to determine the antibiotic prophylaxis associated with the fewest infectious complications following prostate biopsy Determining the safest method allows the Jefferson Department of Urology to modify its biopsy protocol and improve the rate of post-biopsy complication

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients