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

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

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

Thallium use, toxicity, and detoxification therapy: An overview

Thallium (Tl) is released into the environment, where is present at very low levels, from both natural and anthropogenic sources. Tl is considered as one of the most toxic heavy metals; it is a non‐essential metal, present in low concentrations in humans. Tl toxicity causes dermatological and gastrointestinal diseases and disorders of the nervous system, and may even result in death. Many isotopes of Tl exist, with different uses. One of the isotopes of this metal (201Tl) is used in cardiovascular scintigraphy and for the diagnosis of malignant tumors such as breast or lung cancer and osteosarcoma bone cancer. Many Tl compounds are tasteless, colorless, and odorless. Due to these characteristics and their high toxicity, they have been used as poisons in suicides and murders for criminal purposes, as well as instances of accidental poisoning. Impaired glutathione metabolism, oxidative stress, and disruption of potassium‐regulated homeostasis may play a role in the mechanism of Tl toxicity. Solanum nigrum L. and Callitriche cophocarpa have been suggested as promising agents for the phytoremediation of Tl. In addition, macrocyclic compounds such as crown ethers (18‐crown‐6) are good candidates to absorb Tl from wastewater. Through this review, we present an update to general information about the uses and toxicity of Tl. Furthermore, the attention is focused on detoxification therapies