KCNK18 Biallelic Variants Associated with Intellectual Disability and Neurodevelopmental Disorders Alter TRESK Channel Activity

The TWIK-related spinal cord potassium channel (TRESK) is encoded by KCNK18, and variants in this gene have previously been associated with susceptibility to familial migraine with aura (MIM #613656). A single amino acid substitution in the same protein, p.Trp101Arg, has also been associated with intellectual disability (ID), opening the possibility that variants in this gene might be involved in different disorders. Here, we report the identification of KCNK18 biallelic missense variants (p.Tyr163Asp and p.Ser252Leu) in a family characterized by three siblings affected by mild-to-moderate ID, autism spectrum disorder (ASD) and other neurodevelopment-related features. Functional characterization of the variants alone or in combination showed impaired channel activity. Interestingly, Ser252 is an important regulatory site of TRESK, suggesting that alteration of this residue could lead to additive downstream effects. The functional relevance of these mutations and the observed co-segregation in all the affected members of the family expand the clinical variability associated with altered TRESK function and provide further insight into the relationship between altered function of this ion channel and human disease.     

The Endocannabinoid System in the Mediterranean Mussel Mytilus galloprovincialis: Possible Mediators of the Immune Activity?

Anandamide (AEA) is one of the best characterized members of the endocannabinoid family and its involvement in many pathophysiological processes has been well documented in vertebrates and invertebrates. Here, we report the biochemical and functional characterization of key elements of the endocannabinoid system in hemocytes isolated from the Mediterranean mussel Mytilus galloprovincialis. We also show the effects of exogenous AEA, as well as of capsaicin, on the cell ability to migrate and to activate the respiratory burst, upon in vitro stimulation of phagocytosis. Interestingly, our findings show that both AEA and capsaicin suppress the hemocyte response and that the use of selective antagonists of CB₂ and TRPV1 receptors revert their inhibitory effects. Overall, present data support previous evidence on the presence of endocannabinoid signaling in mollusks and advance our knowledge about the evolutionary origins of this endogenous system and its role in the innate response of mollusks.     

Aluminosilicate glasses for zinc selenide tunable fiber laser cladding

A set of novel potassium-calcium-aluminosilicate glasses are developed to serve as the cladding material for a doped ZnSe core infrared fiber laser. The compositions exhibit high glass transition temperatures between 753°C and 918°C and high thermal expansion coefficients between 5.75 ppm/°C and 8.21 ppm/°C. We demonstrate successful application of these glass compositions as a cladding for a ZnSe tunable fiber laser.     

Time-resolved thermal lens and thermal mirror spectroscopy with sample-fluid heat coupling: a complete model for material characterization

This work presents a theoretical study of a heat transfer effect, taking into account the heat transfer within the heated sample and out to the surrounding medium. The analytical solution is used to model the thermal lens and thermal mirror effects and the results are compared with the finite element analysis (FEA) software solution. The FEA modeling results were found to be in excellent agreement with the analytical solutions. Our results also show that the heat transfer between the sample surface and the air coupling fluid does not introduce an important effect over the induced phase shift in the sample when compared to the solution obtained without considering axial heat flux. On the other hand, the thermal lens created in the air coupling fluid has a significant effect on the predicted time-dependent photothermal signals. When water is used as fluid, the heat coupling leads to a more significant effect in both sample and fluid phase shift. Our results could be used to obtain physical properties of low optical absorption fluids by using a reference solid sample in both thermal lens and thermal mirror experiments.     

Transport Characteristics of a Beta Sheet Breaker Peptide Across Excised Bovine Nasal Mucosa

ABSTRACT

The purpose of the present study was to investigate the permeation characteristics of the beta sheet breaker peptide AS 602704 (BSB) on excised bovine nasal mucosa using an Ussing chamber model. The influence of various absorption enhancers such as sodium cholate, sodium dodecyl sulfate (SDS), cetrimidum, sodium caprate, Na₂EDTA, polycarbophil (PCP), the thiomer conjugate polycarbophil-cysteine (PCP-Cys), and poly-l-arginine (poly-l-arg; 100 kDa) was evaluated. Additionally, the influence of temperature and pH on the transport rate as well as the stability of the peptide drug against enzymatic degradation were investigated in vitro.

The effective permeability coefficient (P_eff) of BSB in Krebs-Ringer-buffer (KRB) pH 7.4 was (1.89 ± 0.44)* 10^?5, while in the presence of sodium caprate (0.5%) a P_eff of (9.58 ± 1.82)*10^?5 was achieved. Rank order of enhancement ratio was sodium caprate > SDS > sodium cholate > Na₂EDTA > poly-l-arg = PCP-Cys. In case of cetrimidum and PCP even a decrease in the absorption of BSB was determined. Na₂EDTA reduced the enzymatic degradation of BSB when exposed to a nasal tissue homogenate by more than the half. An increased lipophilicity of BSB because of a more acidic milieu (pH 5.5) did not lead to an increased transcellular transport. Permeation studies carried out at 4°C compared to 37°C demonstrated a temperature dependent permeation behaviour suggesting an additional active carrier mediated transport.

The results obtained within these studies should facilitate the development of a nasal delivery system for AS 602704 for the treatment of Alzheimer's disease.     

Acoustic emission monitoring of activation behavior of LaNi5 hydrogen storage alloy

The acoustic emission technique is proposed for assessing the irreversible phenomena occurring during hydrogen absorption/desorption cycling in LaNi₅. In particular, we have studied, through a parametric analysis of in situ detected signals, the correlation between acoustic emission (AE) parameters and the processes occurring during the activation of an intermetallic compound. Decreases in the number and amplitude of AE signals suggest that pulverization due to hydrogen loading involves progressively smaller volumes of material as the number of cycles increases. This conclusion is confirmed by electron microscopy observations and particle size distribution measurements.     

On the thermoeconomic approach to the diagnosis of energy system malfunctions: Part 1: the TADEUS problem

This work is the first part of a wider project aiming at demonstrating the capabilities offered by the thermoeconomic approach to the diagnosis of malfunctions in energy utility systems (TADEUS problem). The final goal is to create a common basis of work for people interested in applying thermoeconomics to identify malfunctions and to evaluate their effects on the overall plant performance. The main issues to be addressed when performing a diagnosis of energy system malfunctions using a thermoeconomic approach are summarized. A combined cycle power plant is proposed to demonstrate the practical feasibility of the thermoeconomic approach. An overview of its operation characteristics, thermodynamic design properties and control strategy is given in Part 1, and a comprehensive model is described for further use as common basis to illustrate the various diagnosis approaches either by the authors or third parties. Possible component malfunctions and main theoretical aspects of the thermoeconomic approach are presented in Part 2. The paper shows at which level of detail the analysis of physical and technical characteristics of the plant should be performed, how to develop a design and off-design model suitable for malfunction analysis, how to analyse and define component malfunctions and how to interpret and use thermoeconomic variables and indexes.     

Plasmon resonance in silver nanoparticles arrays grown by atomic terrace low-angle shadowing

The plasmonic properties of aligned silver nanoparticles grown by atomic terrace low-angle shadowing (ATLAS) were studied by optical transmission spectroscopy. ATLAS is a novel nanofabrication technique that combines the advantages of self-assembly with control of the nanostructure features. The silver nanoarrays were optically characterized and distinct optical responses with strong polarization dependence were obtained indicating the existence of a strong near-field coupling between the particles. We found that different morphologies gave rise to a similar optical response due to the local contributions to the overall response. Numerical model based on discrete dipole approximation was used to give a qualitative insight into the studied phenomena.     

Initial Brazilian experience with short-duration in-center daily hemodialysis

The whole initial Brazilian experience with short-duration in-center daily hemodialysis is summarized here. The study was performed at a time when low-flux membrane and nonproportional dialysis represented the standard dialysis treatment in Brazil. Five patients were treated for 2 years. The subject is developed in a way to narrate the efforts to set the research project and summarize the findings, meeting presentations, and publications that derived from the project. At the end of the study, the main benefits observed consisted of alleviation of the end-stage renal disease anemia; reduction of the frequency of complications during dialysis sessions; a lower degree of azotemia; easier blood pressure control; and improvements in acid-base status, mineral metabolism and bone disease, nutrition, and quality of life.