Residual stress-affected diffusion during plasma nitriding of tool steels

Plasma nitriding of tool materials is common practice to improve the wear resistance and lifetime of tools. Machining-induced compressive residual stresses in shallow layers of some tenths of microns are observed accompanied by other characteristic properties of machined surfaces in these high-strength materials. After plasma nitriding of M2 high-speed steel, previously induced compressive residual stresses remain stable and the depth of diffusion layers decreases with increasing compressive residual stresses. This article reports investigations of plasma nitrided samples with different levels of residual stresses induced prior to the nitriding process. For comparison, experiments with bending load stresses during plasma nitriding have also been carried out. The plasma nitriding treatment was performed at constant temperature of 500 °C with a gas mixture of 5 vol pct N₂ in hydrogen. Nitriding time was varied from 30 to 120 minutes. All samples were characterized before and after plasma nitriding concerning microstructure, roughness, microhardness, chemical composition, and residual stress states. Experimental results are compared with analytical calculations on (residual) stress effects in diffusion and show a clear effect of residual and load stresses in the diffusion of nitrogen in a high-strength M2 tool steel.     

Modelling of Bird Strike on an Aircraft Wing Leading Edge Made from Fibre Metal Laminates – Part 2: Modelling of Impact with SPH Bird Model

Fibre Metal Laminates with layers of aluminium alloy and high strength glass fibre composite have been reported to possess excellent impact properties and be suitable for aircraft parts likely to be subjected to impacts such as runway debris or bird strikes. In a collaborative research project, aircraft wing leading edge structures with a glass-based FML skin have been designed, built, and subjected to bird strike tests that have been modelled with finite element analysis. In this second part of a two-part paper, a finite element model is developed for simulating the bird strike tests, using Smooth Particle Hydrodynamics (SPH) for modelling the bird and the material model developed in Part 1 of the paper for modelling the leading edge skin. The bird parameters are obtained from a system identification analysis of strikes on flat plates. Pre-test simulations correctly predicted that the bird did not penetrate the leading edge skin, and correctly forecast that one FML lay-up would deform more than the other. Post test simulations included a model of the structure supporting the test article, and the predicted loads transferred to the supporting structure were in good agreement with the experimental values. The SPH bird model showed no signs of instability and correctly modelled the break-up of the bird into particles. The rivets connecting the skin to the ribs were found to have a profound effect on the performance of the structure.     

Is the Context Shift Effect a Case of Retrieval Failure? The Effects of Retrieval Enhancing Treatments on Forgetting Under Altered Stimulus Conditions in Rats.

This series of experiments sought to clarify the role of retrieval failure in forgetting that results from a change in context between training and testing (the context shift effect [CSE]). Because spontaneous forgetting (SF) is generally considered to reflect a retrieval failure, the effects of three manipulations known to alleviate SF were examined on forgetting due to an explicit shift in context at a short delay (24 hr). Pretest exposure to a reminder treatment involving the reinforcer from training (Experiment 1), pretest amphetamine administration (Experiment 2), and overtraining (Experiment 3) alleviated both SF and the CSE, supporting the view that the CSE reflects a retrieval deficit. Implications for the context change account of SF are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Removal and destruction of endocrine disrupting contaminants by adsorption with molecularly imprinted polymers followed by simultaneous extraction and phototreatment

This study presents a method to regenerate molecularly imprinted polymers (MIPs) used for the selective removal of endocrine disrupting compounds from aqueous effluents. Regeneration was based on solvent extraction under UV irradiation to regenerate the polymer and the solvent while destroying the contaminants. Acetone was selected as the best solvent for irradiation of estrone (E1), 17beta-estradiol (E2) and ethinylestradiol (EE2) using either UVC (254 nm) or UV-vis. A MIP synthesized with E2 as template was then tested for the extraction of this compound from a 2 microg/L loaded aqueous solution. E2 was recovered by 73+/-11% and 46+/-13% from the MIPs and a non-imprinted control polymer synthesized under the same conditions, respectively, after a single step elution with acetone. The irradiated polymers and acetone were reused for an additional extraction-regeneration cycle and showed no capacity decrease.     

Improvement of Glycaemia and Endothelial Function by a New Low-Dose Curcuminoid in an Animal Model of Type 2 Diabetes

Curcumin has been suggested as a promising treatment for metabolic diseases, but the high doses required limit its therapeutic use. In this study, a new curcuminoid is synthesised to increase curcumin anti-inflammatory and antioxidant potential and to achieve hypoglycaemic and protective vascular effects in type 2 diabetic rats in a lower dose. In vitro, the anti-inflammatory effect was determined through the Griess reaction, and the antioxidant activity through ABTS and TBARS assays. In vivo, Goto-Kakizaki rats were treated for 2 weeks with the equimolar dose of curcumin (40 mg/kg/day) or curcuminoid (52.4 mg/kg/day). Fasting glycaemia, insulin tolerance, plasma insulin, insulin signalling, serum FFA, endothelial function and several markers of oxidative stress were evaluated. Both compounds presented a significant anti-inflammatory effect. Moreover, the curcuminoid had a marked hypoglycaemic effect, accompanied by higher GLUT4 levels in adipose tissue. Both compounds increased NO-dependent vasorelaxation, but only the curcuminoid exacerbated the response to ascorbic acid, consistent with a higher decrease in vascular oxidative and nitrosative stress. SOD1 and GLO1 levels were increased in EAT and heart, respectively. Altogether, these data suggest that the curcuminoid developed here has more pronounced effects than curcumin in low doses, improving the oxidative stress, endothelial function and glycaemic profile in type 2 diabetes.     

Insights into the Pharmacokinetics and In Vitro Cell-Based Studies of the Imidazoline I2 Receptor Ligand B06

The impact of neurodegenerative diseases (ND) is becoming unbearable for humankind due to their vast prevalence and the lack of efficacious treatments. In this scenario, we focused on imidazoline I₂ receptors (I₂-IR) that are widely distributed in the brain and are altered in patients with brain disorders. We took the challenge of modulating I₂-IR by developing structurally new molecules, in particular, a family of bicyclic α-iminophosphonates, endowed with high affinity and selectivity to these receptors. Treatment of two murine models, one for age-related cognitive decline and the other for Alzheimer’s disease (AD), with representative compound B06 ameliorated their cognitive impairment and improved their behavioural condition. Furthermore, B06 revealed beneficial in vitro ADME-Tox properties. The pharmacokinetics (PK) and metabolic profile are reported to de-risk B06 for progressing in the preclinical development. To further characterize the pharmacological properties of B06, we assessed its neuroprotective properties and beneficial effect in an in vitro model of Parkinson’s disease (PD). B06 rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine (6-OHDA) and showed a crucial anti-inflammatory effect in a cellular model of neuroinflammation. This research reveals B06 as a putative candidate for advancing in the difficult path of drug discovery and supports the modulation of I₂-IR as a fresh approach for the therapy of ND.     

Characterization of commercial double-walled carbon nanotube material: composition, structure, and heat capacity

A purified commercial double-walled carbon nanotube (DWCNT) sample was investigated by transmission electron microscopy (TEM), thermogravimetry (TG), and Raman spectroscopy. Moreover, the heat capacity of the DWCNT sample was determined by temperature-modulated differential scanning calorimetry in the range of temperature between −50 and 290 °C. The main thermo-oxidation characterized by TG occurred at 474 °C with the loss of 90 wt% of the sample. Thermo-oxidation of the sample was also investigated by high-resolution TG, which indicated that a fraction rich in carbon nanotube represents more than 80 wt% of the material. Other carbonaceous fractions rich in amorphous coating and graphitic particles were identified by the deconvolution procedure applied to the derivative of TG curve. Complementary structural data were provided by TEM and Raman studies. The information obtained allows the optimization of composites based on this nanomaterial with reliable characteristics.     

Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations

Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies.     

Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence,Severity, and Treatment Response

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea–hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.     

Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG.