Tolerating diabetes: an alternative therapeutic approach for diabetic neuropathy

It is becoming apparent that a number of pathogenic mechanisms contribute to diabetic neuropathy, so that therapeutic interventions that target one particular mechanism may have limited success. A recently published preclinical study has adopted an alternative approach by using a novel small molecule to induce heat-shock protein 70. This confers upon neurons, and perhaps other cells of the nervous system, the ability to better tolerate the diverse stresses associated with diabetes rather than intervening in their production

Enhancing Practice and Achievement in Introductory Programming With a Robot Olympics

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SnO₂ nanoparticles in silica: nanosized tools for femtosecond-laser machining of refractive index patterns

We show that SnO2 nanoclusters in silica interact with ultrashort infrared laser pulses focused inside the material generating a hydrostatic compression and photoelastic response of the surrounding glass. This effect, together with the laser-induced nanocluster amorphization, gives rise to positive or negative refractive-index changes, up to 10–2, depending on the beam-power density. This result points out a wide tuning of the refractive index patterns obtainable in silica-based optical technology

Flow Pressure Behavior Downstream of Ski Jumps

Ski jump spillways are frequently implemented to dissipate energy from high-speed flows. The general feature of this structure is to transform the spillway flow into a free jet up to a location where the impact of the jet creates a plunge pool, representing an area for potential erosion phenomena. In the present investigation, several tests with di erent ski jump bucket angles are executed numerically by means of the OpenFOAM® digital library, taking advantage of the Reynolds-averaged Navier–Stokes equations (RANS) approach. The results are compared to those obtained experimentally by other authors as related to the jet length and shape, obtaining physical insights into the jet characteristics. Particular attention is given to the maximum pressure head at the tailwater. Simple equations are proposed to predict the maximum dynamic pressure head acting on the tailwater, as dependent upon the Froude number, and the maximum pressure head on the bucket. Results of this study provide useful suggestions for the design of ski jump spillways in dam construction

Quinoline-based molecules targeting c-Met, EGF, and VEGF receptors and the proteins involved in related carcinogenic pathways

The quinoline ring system has long been known as a versatile nucleus in the design and synthesis of biologically active compounds. Currently, more than one hundred quinoline compounds have been approved in therapy as antimicrobial, local anaesthetic, antipsychotic, and anticancer drugs. In drug discovery, indeed, over the last few years, an increase in the publication of papers and patents about quinoline derivatives possessing antiproliferative properties has been observed. This trend can be justified by the versatility and accessibility of the quinoline scaffold, from which new derivatives can be easily designed and synthesized. Within the numerous quinoline small molecules developed as antiproliferative drugs, this review is focused on compounds effective on c-Met, VEGF (vascular endothelial growth factor), and EGF (epidermal growth factor) receptors, pivotal targets for the activation of important carcinogenic pathways (Ras/Raf/MEK and PI3K/AkT/mTOR). These signalling cascades are closely connected and regulate the survival processes in the cell, such as proliferation, apoptosis, differentiation, and angiogenesis. The antiproliferative biological data of remarkable quinoline compounds have been analysed, confirming the pivotal importance of this ring system in the efficacy of several approved drugs. Furthermore, in view of an SAR (structure-activity relationship) study, the most recurrent ligand–protein interactions of the reviewed molecules are summarized

Discharge coefficients for sluice gates set in weirs at different ustream wall inclination

Laboratory experiments and numerical simulations are performed to measure discharge coecients in the case of a gate located on the upstream wall of a weir for flood storage. The eect of the gate slope and the side contraction have been taken into account. The study was first performed experimentally, when three series of tests were carried out with (and without) a broad crested weir located under the gate, at dierent values of the inclination angle of the weir upstream wall, and at dierent values of the shape ratio and the relative opening. In order to provide useful suggestions for those involved in sluice gate construction and management, three equations were obtained based on multiple regression, relating the discharge coecient to dierent parameters that characterize the phenomenon at hand, separating the case when the broad-crested weir was present. Then numerical simulations were executed by means of the Reynolds-averaged Navier–Stokes (RANS) equations with the k-" turbulence closure model and in conjunction with the volume of fluid (VOF) method, to validate the numerical results against the experimental and to possibly investigate phenomena not caught by the experimental measurements. Simulated discharges were very close to the observed ones showing that the proposed three-dimensional numerical procedure is a favorable option to correctly reproduce the phenomenon

Flow Resistance in Open Channel Due to Vegetation at Reach Scale: A Review

Vegetation on the banks and flooding areas of watercourses significantly affects energy losses. To take the latter into account, computational models make use of resistance coefficients based on the evaluation of bed and walls roughness besides the resistance to flow offered by vegetation. This paper, after summarizing the classical approaches based on descriptions and pictures, considers the recent advancements related to the analytical methods relative both to rigid and flexible vegetation. In particular, emergent rigid vegetation is first analyzed by focusing on the methods for determining the drag coefficient, then submerged rigid vegetation is analyzed, highlighting briefly the principles on which the different models are based and recalling the comparisons made in the literature. Then, the models used in the case of both emergent and submerged rigid vegetation are highlighted. As to flexible vegetation, the paper reminds first the flow conditions that cause the vegetation to lay on the channel bed, and then the classical resistance laws that were developed for the design of irrigation canals. The most recent developments in the case of submerged and emergent flexible vegetation are then presented. Since turbulence studies should be considered as the basis of flow resistance, even though the path toward practical use is still long, the new developments in the field of 3D numerical methods are briefly reviewed, presently used to assess the characteristics of turbulence and the transport of sediments and pollutants. The use of remote sensing to map riparian vegetation and estimating biomechanical parameters is briefly analyzed. Finally, some applications are presented, aimed at highlighting, in real cases, the influence exerted by vegetation on water depth and maintenance interventions

The increasing temperature as driving force for spatial distribution patterns of Parapenaeus longirostris (Lucas 1846) in the Strait of Sicily (Central Mediterranean Sea)

The deep-water rose shrimp Parapenaeus longirostris (DPS), a demersal decapod representing the most important component of crustacean landings in the Mediterranean Sea, has been suggested as a species that may exhibit temperature-driven changes in the spatio-temporal dynamics. Considering that Mediterranean waters are warming up faster than oceans, understanding the relationships of DPS populations with temperature variations and the related changes in spatial patterns is absolutely key for its management. Using a long-term dataset covering 13-years from scientific surveys (International Bottom Trawl-Surveys in the Mediterranean, MEDITS; Italian national trawl surveys, GRUND) in the Strait of Sicily (central Mediterranean Sea), the annual DPS spatial patches and the depth distribution were investigated using geostatistical and quotient analyses. The patches dimension and depth range occupation were then related to sea temperature by using linear regression analysis. Results showed that both the dimension of DPS spatial patches and the depth distribution range occupied increased concurrently with temperature. Our findings corroborate that the ongoing sea warming widen areas suitable for this species and in which it can expand its spatial distribution

The double face of metals: The intriguing case of chromium

Chromium (Cr) is a common element in the Earth’s crust. It may exist in different oxidation states, Cr(0), Cr(III) and Cr(VI), with Cr(III) and Cr(VI) being relatively stable and largely predominant. Chromium’s peculiarity is that its behavior relies on its valence state. Cr(III) is a trace element in humans and plays a major role in glucose and fat metabolism. The beneficial effects of Cr(III) in obesity and types 2 diabetes are known. It has been long considered an essential element, but now it has been reclassified as a nutritional supplement. On the other hand, Cr(VI) is a human carcinogen and exposure to it occurs both in occupational and environmental contexts. It induces also epigenetic effects on DNA, histone tails and microRNA; its toxicity seems to be related to its higher mobility in soil and swifter penetration through cell membranes than Cr(III). The microorganisms Acinetobacter sp. Cr1 and Pseudomonas sp. Cr13 have been suggested as a promising agent for bioremediation of Cr(VI). This review intends to underline the important role of Cr(III) for human health and the dangerousness of Cr(VI) as a toxic element. The dual and opposing roles of this metal make it particularly interesting. An overview of the recent literature is reported in support