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Living organisms react to external stimuli to adapt their activity to the environment for survival. Acquired information is encoded by neurons by action potentials (APs) in a series of discrete electrical events. Rapid initiation of the AP is critical for fast reactions and strongly relies on voltage-activated Na+-selective channels (NaVs), which are widely expressed by both invertebrate and vertebrate neurons. Intuitively, NaVs of higher mammals should be activated faster than those of any other species. In addition to improved NaV channel structure, central mammalian neurons also demonstrate a patterned distribution of specific types of NaV1 channels at and near the site of AP initiation within the axonal initial segment (AIS). The AIS has different types of fast Nav1 channels and is thought to provide the biological basis for efficient frequency coding of information. In the present work, we review data related to the channels underlying fast initiation of action potentials in vertebrates and invertebrates, along with their evolution, distribution, and known specific roles. Current research has established that all mammalian NaV1 (1.1–1.9) channels share a similar structure, with 4 conservative transmembrane D-domains with a highly homologous sequence, but significant differences in the length of the functional cytoplasmic linkers. Similarly, the structure of NaV1 channels in invertebrates is generally similar to that of mammals, but it shows high variability across the evolutionary tree in the length of the linkers. AP initiation in mammalian cortical neurons is mediated by NaV1.2 and NaV1.6 channels, whereas interneurons mostly rely on NaV1.1 channels in their firing. Although invertebrate NaV1 channels normally display relatively slow kinetics, their activation is fast enough to produce APs, even in simple animals such as Placozoa. Remarkably, fast sodium-based excitability is not limited to animals. Recently, a photosynthetic prokaryote has been found to show rapidly activated sodium currents provided by their independently evolved single D-domain EuKatB sodium channels.

The objective of this paper is to quantify the coupling effect on the power distribution of sodium-cooled fast reactors (SFRs), specifically the European SFR. Calculations are performed with several state-of-the-art reactor physics and Multiphysics codes (TRACE/PARCS, DYN3D, WIMS, COUNTHER, and GeN-Foam) to build confidence in the methodologies and validity of results. Standalone neutronic calculations were generally in excellent agreement with a reference Monte Carlo-calculated power distribution (from Serpent). Next, the impact of coolant density and fuel temperature Doppler feedback was calculated. Reactivity coefficients for perturbations in the inlet temperature, coolant heat up and core power was shown to be negative with values of around −0.5 pcm/°C, −0.3 pcm/°C, and −3.5 pcm/%, respectively. Fuel temperature and coolant density feedback was found to introduce a roughly −1%/+1% in/out power tilt across the core. Calculations were then extended to axial expansion for cases where fuel is linked and unlinked to the clad. Core calculations are in good agreement with each other. The impact of differential fuel expansion is found to be larger for fuel both linked and unlinked to the clad, with the in/out power tilt increasing to around −4%/+2%. Thus, while broadly confirming the known result that standalone physics calculations give good results, the expansion coupling effect is perhaps more than anticipated a priori. These results provide a useful benchmark for the further development of Multiphysics codes and methodologies in support of advanced reactor calculations.

The coupled DYN3D/ATHLET code system was recently adapted for Sodium cooled Fast Reactors (SFRs) applications. The main objective of this study is to validate further the DYN3D/ATHLET code system by performing a coupled 3D neutron kinetics/thermal-hydraulics analysis of six transient start-up tests conducted at the French Superphenix (SPX) reactor. The tests were a part of the startup test program aiming at evaluation of the core reactivity feedback characteristics. Peculiarity of these transients is the necessity of accounting for the thermal expansions of the primary system structural elements influencing the position of control rods in the core. The paper includes a brief summary on the benchmark specification, description of the neutronics and thermal-hydraulics models, and comparison of the simulation results to the available experimental data. For all six transients, a good agreement between simulations and experiments was observed confirming a reasonable performance of DYN3D/ATHLET.

В даній роботі отримані математичні моделі систем керування тиристорний перетворювач-двигун, скалярної та векторної для використання в електроприводі механізму пересування електродів печі ДСП-3. Дослідження трьох варіантів систем керування виконано з метою реалізації оптимальних перехідних процесів, що відповідають критеріям максимально можливої швидкодії та мінімізації динамічної похибки відпрацювання випадкових збурень.

The Vitis vinifera L. cultural grape includes many varieties that are highly valued in winemaking and viticulture, as raw materials for the production of fresh and dried berries, for the production of wines. The fruits of cultural grapes play an important role in medicine, where they are used as a source of substances with high antioxidant activity. Grapes are often affected by phytopathogenic fungal infections. In recent years, a large number of reports have appeared in the literature about the acquisition of resistance of microorganisms to industrial pesticide preparations, which in turn leads to an increase in drug doses, the multiplicity of treatments and the accumulation of harmful substances in the environment and in the plants themselves. In this study, we evaluate the effectiveness of the fungicidal action of industrial preparations and plant extracts in relation to two native species of fungi (V1 and V2) isolated from the leaves of cultivated Vitis vinifera L. grapes, as well as against the phytopathogen Alternaria solani K-100054. Minimal inhibitory (MIC) and fungicidal concentrations (MFC) were detected for each sample. Ethanol extracts of plants showed low antimycotic activity in relation to fungi cultures isolated from grapes. Activity started from 0.0625%. The best result among industrial fungicides was shown by the drug “Maxim”, whose MIC values was 0.097 μg/mL, and the MFC varies between 3.125-12.5 μg/mL for pathogens V1 and V2, respectively.

INTRODUCTION: Patients with chronic lymphocytic leukemia (CLL) have significantly decreased health related quality of life (HRQoL), particularly related to severe and progressive fatigue. Side effects of chemotherapies and the emotional burden of living with an often poor prognosis disease also negatively impact patient HRQoL. Venetoclax, an oral agent that targets the anti-apoptotic protein BCL2, has demonstrated high rates of deep and durable response in patients with relapsed/refractory (R/R) CLL, including those with 17p deletions, and has been shown to facilitate clinically relevant improvement in several key aspects of functioning and HRQoL. We evaluated the impact of venetoclax monotherapy on the quality of life of patients with R/R CLL. METHODS: VENICE II is an ongoing open-label, phase 3b, multicenter study (NCT02980731) that assessed patient-reported HRQoL in patients who were ≥18 years old with R/R CLL, including those with 17p deletion, TP53 mutations, and/or prior experience with B-cell receptor pathway inhibitor-containing (BCRi) therapy, treated with venetoclax monotherapy (5-week dose-titration, starting at 20mg once daily, then increased weekly to 50 mg, 100 mg, 200 mg, and 400 mg, followed by 400mg once daily). The primary endpoint was the mean change from baseline to Week 48 in the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) subscale. HRQoL subscales analyzed included: Global Health Status, Role Functioning, Emotional Functioning, Cognitive Functioning, Social Functioning, and Fatigue. The impact on QoL was also assessed on the CLL Module (EORTC QLQ-CLL16). Relevance of mean changes in HRQoL measures from baseline were analyzed based on minimum important difference (MID); a 5-10 point change was defined as MID, and >10 points was considered clinically meaningful.(Osoba, D., et al. J Clin Oncol. 1998;16:139-44. Osoba, D., et al. Qual Life Res. 1994;3:353-64.) Safety and adverse events (AEs) were also monitored. RESULTS: As of the data cutoff, April 30, 2018, the median time on study was 28 weeks (range: 1 - 73) and the median time on therapy was 23 weeks (range: 0.1 - 69) in this ongoing study. Of the 169 treated patients, 70% were male; the median age was 65 years (range: 24 - 86). Among those with available data, 17p deletions and TP53 mutations were confirmed in 34% (41/122) and 38% (19/50) of patients, respectively. Overall, 38%, 20%, and 42% of patients had one, two, and three (or more) prior lines of therapy respectively; 21% of patients had prior BCRi therapy. Clinically meaningful improvements from baseline were observed by week 12 and were sustained through week 48 in the EORTC-QLQ-C30 global health status and the role function, social function, and fatigue subscales (Table and Figure 1A) and EORTC-QLQ-CLL16 future health and disease effect subscales (Table and Figure 1B). Eighty-two percent of patients had at least 1 AE; most commonly observed AEs (≥10% of patients) were neutropenia (35%), diarrhea (17%), thrombocytopenia (15%), anemia (12%), nausea (12%), and upper respiratory infection (11%). Twenty-eight percent of patients had a serious AE, of which the most common were pneumonia (5%), febrile neutropenia (4%) and pyrexia (3%). Five percent of patients discontinued the study due to an AE. CONCLUSIONS: Preliminary data from this ongoing study suggest that patients with R/R CLL experienced improvement in several key aspects of functioning and quality of life with venetoclax monotherapy within the first 12 weeks which is sustained over time. Venetoclax monotherapy was well tolerated in R/R CLL patients. These findings are consistent with previous studies of R/R CLL patients who received venetoclax monotherapy. Disclosures Cochrane: Janssen: Membership on an entity's Board of Directors or advisory committees; Cilag: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Calgene: Honoraria; Amgen: Honoraria; Novartis: Honoraria; MSD: Honoraria. Robak:AbbVie, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy. Yeh:GNT Biotech & Medicals Crop.: Research Funding. Nikitin:AbbVie, Inc: Speakers Bureau. Breuleux:Roche: Employment, Equity Ownership; Gilead: Equity Ownership; Basilea: Patents & Royalties; Novartis: Patents & Royalties. Masud:AbbVie, Inc: Employment, Equity Ownership. Sail:AbbVie, Inc: Employment, Equity Ownership. Komlosi:AbbVie, Inc: Employment, Equity Ownership. Anderson:Walter and Eliza Hall: Employment, Patents & Royalties; AbbVie, Inc: Research Funding; Genentech: Research Funding.

The reactor dynamics code DYN3D being developed at the Helmholtz-Zentrum Dresden-Rossendorf is currently under extension for Sodium cooled Fast Reactor analyses. This paper provides an overview on the new version of DYN3D to be used for SFR core calculations. The current article shortly describes the newly implemented thermal mechanical models, which can account for thermal expansion effects of the reactor core. Furthermore, the methodology used in Sodium cooled Fast Reactor analyses to generate homogenized few-group cross sections is summarized. The conducted and planned verification and validation studies are briefly presented. Related publications containing more detailed descriptions are outlined for the completeness of this overview.

Precapillary artery--arterial (bronchial artery--pulmonay artery) anastomoses, come into play in cases where the locking artery open and alveoli washed arterialized blood. Normally, these anastomoses are closed. Intrapulmonary shunts carry blood supply acinar hinder extraordinary circumstances (chronic pulmonary embolism, surgery, occurring in cardiopulmonary bypass, when the flaw of blood through the Iungs is suspended for the duration of cardiopulmonary bypass). Patients operated on the ascending aorta with the expansion of intervention on the nortic arch during the correction of pathology carry blood supply only the central nervous system. All other organs and systems at this time were protected by mild hypothermia. However, during circulatory arrest, required for correction of pathology acinar damage as a result of hypoxia, probably because there is no blood flow in the pulmonary artery and there is no blood flow in the bronchial arteries. Last, in the ordinary course of artificial circulation, capable due to arterio-arterial pulmonary anastomoses prevent hypoxic damage to acinar, not lead to persistent hypoxemia in the immediate postoperative period in these patients, as a result of violations of lung diffusion capacity.