Genetic and Epigenomic Modifiers of Diabetic Neuropathy

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.     

The Tumor Proteolytic Landscape: A Challenging Frontier in Cancer Diagnosis and Therapy

In recent decades, dysregulation of proteases and atypical proteolysis have become increasingly recognized as important hallmarks of cancer, driving community-wide efforts to explore the proteolytic landscape of oncologic disease. With more than 100 proteases currently associated with different aspects of cancer development and progression, there is a clear impetus to harness their potential in the context of oncology. Advances in the protease field have yielded technologies enabling sensitive protease detection in various settings, paving the way towards diagnostic profiling of disease-related protease activity patterns. Methods including activity-based probes and substrates, antibodies, and various nanosystems that generate reporter signals, i.e., for PET or MRI, after interaction with the target protease have shown potential for clinical translation. Nevertheless, these technologies are costly, not easily multiplexed, and require advanced imaging technologies. While the current clinical applications of protease-responsive technologies in oncologic settings are still limited, emerging technologies and protease sensors are poised to enable comprehensive exploration of the tumor proteolytic landscape as a diagnostic and therapeutic frontier. This review aims to give an overview of the most relevant classes of proteases as indicators for tumor diagnosis, current approaches to detect and monitor their activity in vivo, and associated therapeutic applications.     

A comparative study of photocatalytically active nanocrystalline tetragonal zyrcon-type and monoclinic scheelite-type bismuth vanadate

Monoclinic scheelite-type BiVO₄ is currently considered as one of the most promising non-titania photocatalysts, wheras tetragonal zircon-type BiVO₄ is still poorly understood. Herein, a new and simple synthetic approach was applied and nanostructured single-phase zircon-type BiVO₄ was successfully prepared by a controllable ethylene-glycol colloidal route. In addition, nanostructured monoclinic scheelite-type BiVO₄ powders were also fabricated through annealing of the as-prepared samples. A comparative study of the two BiVO₄ polymorphs was conducted and it turned out that the novel synthetic approach had a significant impact on porosity and photocatalytic performance of zircon-structured BiVO₄. All the prepared materials, as-prepared and annealed, were mesoporous, while measured values of specific surface area of some zircon-structured samples (～34?m²/g) were ～7 times higher than those reported thus far for this phase. Interestingly, for the first time, zircon-type BiVO₄, previously considered to be a poor photocatalyst, exhibited a better overall performance in degradation of methyl orange compared to monoclinic scheelite-type BiVO₄. Hence, it could be expected that the here-presented synthesis and observations will both arouse interest in scarcely studied tetragonal zircon-type BiVO₄ and facilitate as well as speed up further research of its properties.     

Contribution of marine and continental aerosols to the content of major ions in the precipitation of the central Mediterranean

The region of the investigated receptor is situated in the southern part of the Adriatic Sea in the Mediterranean. The measuring station is located on the seashore, which, being considered as a border area, is representative for the qualitative and quantitative estimation of the influence of marine and continental aerosols on the content of major ions in precipitation. In the sampling period, precipitation in the region of the investigated receptor was more abundant during the summer and autumn than during the winter and spring. The most frequent precipitation heights were up to 20 mm, while high precipitation came exclusively from the continental region. The results of the measurements of ions readily soluble in water were used for the differentiation of marine from continental contributions of primary and secondary aerosols to their content in the precipitation. Using PCA, it was shown that main contribution of Cl(-), Na(+) and Mg(2+) came from primary marine aerosols, while the contribution from continental sources was dominant for the content of SO(4)(2-), NO(3)(-), NH(4)(+) and Ca(2+) in the precipitation. The continental origin of Ca(2+) was from a primary source, while SO(4)(2-), NO(3)(-) and NH(4)(+) were representatives of secondary aerosols produced by reactions between acid oxides and alkaline species in the atmosphere, but SO(4)(2-) and NO(3)(-) also exist in the precipitation as free acids. The origin of the trace elements Cd, Cu, Pb and Zn in the precipitation came from anthropogenic emission sources. The results obtained in this work are based on experimental data from 609 samples collected during the period 1995-2000.     

Analysis of medications change in Parkinson’s disease progression data

Parkinson’s disease is a neurodegenerative disorder that affects people worldwide. Careful management of patient’s condition is crucial to ensure the patient’s independence and quality of life. This is achieved by personalized treatment based on individual patient’s symptoms and medical history. The aim of this study is to determine patient groups with similar disease progression patterns coupled with patterns of medications change that lead to the improvement or decline of patients’ quality of life symptoms. To this end, this paper proposes a new methodology for clustering of short time series of patients’ symptoms and prescribed medications data, and time sequence data analysis using skip-grams to monitor disease progression. The results demonstrate that motor and autonomic symptoms are the most informative for evaluating the quality of life of Parkinson’s disease patients. We show that Parkinson’s disease patients can be divided into clusters ordered in accordance with the severity of their symptoms. By following the evolution of symptoms for each patient separately, we were able to determine patterns of medications change which can lead to the improvement or worsening of the patients’ quality of life.     

Determination of 200 °C Isothermal Section of Al-Ag-Ga Phase Diagram by Microanalysis,X-ray Diffraction,Hardness and Electrical Conductivity Measurements

Ternary Al-Ag-Ga system at 200 °C was experimentally and thermodynamically assessed. Isothermal section was extrapolated using optimized thermodynamic parameters for constitutive binary systems. Microstructure and phase composition of the selected alloy samples were analyzed using light microscopy, scanning electron microscopy combined with energy-dispersive spectrometry and x-ray powder diffraction technique. The obtained experimental results were found to be in a close agreement with the predicted phase equilibria. Hardness and electrical conductivity of the alloy samples from four vertical sections Al-Ag₈₀Ga₂₀, Al-Ag₆₀Ga₄₀, Ag-Al₈₀Ga₂₀ and Ag-Al₆₀Ga₄₀ of the ternary Al-Ag-Ga system at 200 °C were experimentally determined using Brinell method and eddy current measurements. Additionally, hardness of the individual phases present in the microstructure of the studied alloy samples was determined using Vickers microhardness test. Based on experimentally obtained results, isolines of Brinell hardness and electrical conductivity were calculated for the alloys from isothermal section of the ternary Al-Ag-Ga system at 200 °C.     

Influence of electrodeposition parameters of Ni–W on Ni cathode for alkaline water electrolyser

In this study, different Ni–W coatings, obtained by cheap and technologically simple electrodeposition method, were examined as potential electrocatalysts for the hydrogen evolution reaction (HER). All electrodepositions were done on a Ni mesh substrate from ammoniacal-citrate bath containing different concentrations of Na₂WO₄. The influence of deposition parameters, such as deposition current density, pH and composition of ammoniacal-citrate bath on electrocatalytic activity of obtained Ni–W coatings toward HER was examined by polarization curve measurements in 6 M KOH at room temperature. The morphology and tungsten content of the Ni–W coatings were investigated by means of SEM and EDS analysis. All investigated electrodes have shown high electrocatalytic activity for the HER. The samples obtained at higher deposition current densities had the lowest overvoltage for the HER. It has been shown that the plating bath pH value is very important parameter in obtaining active coatings. Results of the analysis of polarization curves, morphology of deposited Ni–W coatings and the content of tungsten in the coatings, indicate that the surface roughness of the coatings is responsible for their catalytic activity towards HER.     

Project finance risk evaluation of the Electric power industry of Serbia

From the aspect of the development of a country, the energy sector represents a domain of strategic interest. Generation and use of energy resources most often belongs to the public sector, and are most often under the influence of the government in most countries. This paper analyzes the risks that are characteristic to the business of the public enterprise, Electric Power Industry of Serbia (EPS). EPS has started its restructuring and is adjusting to changes and challenges imposed by the launched reforms in the energy sector. However, due to certain limitations, it is still not possible to implement its complete restructuring and modernization. The paper aims to point at the risks a potential strategic partner faces. The risks have been identified as commercial, financial and political, classification immanent for project finance, and their evaluation was done using Failure Mode and Effects Analysis (FMEA). Risk analysis was performed based on current conditions for two potential scenarios that predict different types of changes in the analyzed period. The results of the analysis show that the potential strategic partner should pay special attention to price risks, estimation, investments, project activity neglect, quasi-risks and debt collection.