A Novel KCNA2 Variant in a Patient with Non-Progressive Congenital Ataxia and Epilepsy: Functional Characterization and Sensitivity to 4-Aminopyridine

Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous system, where they regulate neuronal excitability. Recently, heterozygous mutations in KCNA2 have been associated with a spectrum of symptoms extending from epileptic encephalopathy, intellectual disability, and cerebellar ataxia. Patients are treated with a combination of antiepileptic drugs and 4-aminopyridine (4-AP) has been recently trialed in specific cases. We identified a novel variant in KCNA2, E236K, in a Serbian proband with non-progressive congenital ataxia and early onset epilepsy, treated with sodium valproate. To ascertain the pathogenicity of E236K mutation and to verify its sensitivity to 4-AP, we transfected HEK 293 cells with Kv1.2 WT or E236K cDNAs and recorded potassium currents through the whole-cell patch-clamp. In silico analysis supported the electrophysiological data. E236K channels showed voltage-dependent activation shifted towards negative potentials and slower kinetics of deactivation and activation compared with Kv1.2 WT. Heteromeric Kv1.2 WT+E236K channels, resembling the condition of the heterozygous patient, confirmed a mixed gain- and loss-of-function (GoF/LoF) biophysical phenotype. 4-AP inhibited both Kv1.2 and E236K channels with similar potency. Homology modeling studies of mutant channels suggested a reduced interaction between the residue K236 in the S2 segment and the gating charges at S4. Overall, the biophysical phenotype of E236K channels correlates with the mild end of the clinical spectrum reported in patients with GoF/LoF defects. The response to 4-AP corroborates existing evidence that KCNA2-disorders could benefit from variant-tailored therapeutic approaches, based on functional studies.     

Performance Analysis of Nonlinear Energy‐Harvesting DF Relay System in Interference‐Limited Nakagami‐m Fading Environment

A decode‐and‐forward system with an energy‐harvesting relay is analyzed for the case when an arbitrary number of independent interference signals affect the communication at both the relay and the destination nodes. The scenario in which the relay harvests energy from both the source and interference signals using a time switching scheme is analyzed. The analysis is performed for the interference‐limited Nakagami‐m fading environment, assuming a realistic nonlinearity for the electronic devices. The closed‐form outage probability expression for the system with a nonlinear energy harvester is derived. An asymptotic expression valid for the case of a simpler linear harvesting model is also provided. The derived analytical results are corroborated by an independent simulation model. The impacts of the saturation threshold power, the energy‐harvesting ratio, and the number and power of the interference signals on the system performance are analyzed.     

Preliminary management and optimization of a gas reservoir in central Serbia

Management of hydrocarbon reservoirs is a dynamic, continuous and complex process. It is applied from reservoir discovery to its abandonment, with the objective of achieving maximum profitability by using a recovery process with minimum capital investments and operation costs.The goals of modern system-engineer' approach to hydrocarbon reservoir management are: managing efficiency; adequate and on time decision making; increasing reserves, and oil and gas recovery factor; production increment; risk reduction; investment efficiency; minimizing costs and environmental protection.The gas reservoir “M” is the gas reservoir discovered in central part of Serbia. It was not put in production yet, so it is important to apply reservoir management concepts from the beginning of the production process.Based on production characteristics, this reservoir belongs to a group of smaller gas reservoirs that characterizes most often the Serbian exploitation area. Also, this reservoir fullfils most of criteria for using it as an underground gas storage reservoir. Thus, the analysis of possibilities for conversion into the underground gas storage after certain production period was also considered.The management of gas reservoir “M” has been analyzed by two different approaches. The first one refers to the management of the reservoir as a gas producer during the whole reservoir life. The second management approach considers gas production for a certain period of time, followed by underground gas storage (UGS). In this paper, economic and financial evaluation results are given for the presented options of gas reservoir management.A decision analysis has been applied to select an optimized gas reservoir management approach.Adequate management of this gas reservoir would contribute to further development and reform of Serbia's gas energy sector that is characterized by great dependence on natural gas imports, and a lack of underground gas storage.     

Ferroelectric Response and Induced Biaxiality in the Nematic Phase of Bent‐Core Mesogens

The still undiscovered fluid ferroelectric nematic phase is expected to exhibit a much faster and easier response to an external electric field compared to conventional ferroelectric smectic liquid crystals; therefore, the discovery of such a phase could open new avenues in electro‐optic device technology. Here, experimental evidence of a ferroelectric response to a switching electric field in a low molar mass nematic liquid crystal is reported and connected with field‐induced biaxiality. The fluid is made of bent‐core polar molecules and is nematic over a range of 120 °C. Combining repolarization current measurements, electro‐optical characterizations, X‐ray diffraction and computer simulations, ferroelectric switching is demonstrated and it is concluded that the response is due to field‐induced reorganization of polar cybotactic groups within the nematic phase. This work represents significant progress toward the realization of ferroelectric fluids that can be aligned at command with a simple electric field.     

A Sulfur–Limonene‐Based Electrode for Lithium–Sulfur Batteries: High‐Performance by Self‐Protection

The lithium–sulfur battery is considered as one of the most promising energy storage systems and has received enormous attentions due to its high energy density and low cost. However, polysulfide dissolution and the resulting shuttle effects hinder its practical application unless very costly solutions are considered. Herein, a sulfur‐rich polymer termed sulfur–limonene polysulfide is proposed as powerful electroactive material that uniquely combines decisive advantages and leads out of this dilemma. It is amenable to a large‐scale synthesis by the abundant, inexpensive, and environmentally benign raw materials sulfur and limonene (from orange and lemon peels). Moreover, owing to self‐protection and confinement of lithium sulfide and sulfur, detrimental dissolution and shuttle effects are successfully avoided. The sulfur–limonene‐based electrodes (without elaborate synthesis or surface modification) exhibit excellent electrochemical performances characterized by high discharge capacities (≈1000 mA h g^?1 at C/2) and remarkable cycle stability (average fading rate as low as 0.008% per cycle during 300 cycles).