ГЛОБАЛЬНА ЗМІНА КЛІМАТУ: ПРИЧИНИ ВИНИКНЕННЯ ТА НАСЛІДКИ ДЛЯ СІЛЬСЬКОГОСПОДАРСЬКОГО ВИРОБНИЦТВА ПІВДЕННОГО СТЕПУ

Relevance of the research. If greenhouse gases in the XXI century enter the atmosphere in the same volume as now, the increase in the average temperature on the planet will reach 2–4°C, and therefore the threat of extinction of up to 20–30% of species of animals and plants in existing biocenosis is not excluded. At the same time, the water level in the world ocean will rise, which during the XX century became higher by 17 cm, that is, more than for the previous 2000 years. Simultaneously with the increase in the average monthly air temperature in the conditions of natural moisturizing (without irrigation) of the southern Steppe subzone of Ukraine in recent years, insufficient precipitation has been recorded, especially in July, August and September that, according to various estimates, is typical for the semi-desert and desert. As a result, the aridity of the climate has increased and the frequency of droughts has risen as well. If for the period of 400 years, in the XI–XIV centuries droughts occurred only 8 times, in the XVII–XVIII – 17, in the XIX – 20, in the XX century the number of them increased to 30. The purpose of the article is to reveal the causes of global climate change on the planet and its impact on agricultural production of the southern Steppe subzone that resulted in increasing the coefficient of moisture, evaporation and moisture deficit. Research methods. The study was carried out using long-term meteorological observations of Kherson meteorological station. Scientific research was based on the complex application of statistical, monographic, abstract-logical methods and system analysis. Research results. The analysis of the main causes of global and regional climate change was conducted. Four models of the bases of climate change on the planet Earth were made. The influence of climate change on the formation of crops yield in the subzone of the southern Steppe was specified. The amount of precipitation fell during the growing period of 2011–2017 in medium dry and dry years shows that, compared to the long-term average precipitation, it was significantly lower and amounted to 47.2–63.6 mm. In average for the 65 years (1945–2010) evaporation was 722.0 mm, and the deficit of moisture, respectively 487.4 mm. In wet years, the volatility does not exceed 608.6 mm, and the deficit of moisture was made up of 243.6 mm. In average as to water supply years the evaporation increased up to 645.7–746.3 mm and the deficit of moisture increased up to 406.7–507.7 mm. In mid-dry and dry years, evaporation increased up to 769.8–934.5 mm, and the deficit of moisture – up to 580.9–791.0 mm. Conclusions. The decrease in precipitation, especially in dry years, compared to average annual indicators, was recorded in spring period as 24–27% and in autumn – as 62–65%, along with a simultaneous increase in air temperature in those periods as 2.7 and 2.8°C respectively. In general, during the vegetation period the increase in evaporation was 30–31% and the deficit of moisture was 53–55% that resulted in low yields of crops. The main way to overcome the negative impact of global climate change on the agricultural production of the southern Steppe subzone is the effective use and further extending the areas of actual irrigation, that will ensure stable high yields and food security of the state.Здійснено аналіз впливу глобальної та регіональної зміни клімату на збільшення випаровуваності, дефіциту вологозабезпеченості та зменшення кількості атмосферних опадів у підзоні південного Степу. Виявлено чотири моделі основ змін клімату на планеті. Згідно з першою моделлю підвищення температури пов’язано з антропогенними викидами в атмосферу вуглекислого газу, метану, оксиду азоту, гексафториду сірки, гідрофторвуглецю та перфторвуглецю. Другою моделлю причин зміни клімату вважаються періодичні четвертинні зледеніння, які повторюються на планеті кожні 100 тис. років. Третя модель передбачає зміну клімату через інтенсивне видобування нафти з надр нашої планети. Четвертою моделлю причин зміни клімату є діяльність гідротермальних джерел в океанах, які викидають в атмосферу вуглекислий газ і метан. Встановлена кількість атмосферних опадів, які випадали протягом 2011–2017 рр. у середньосухі та сухі за забезпеченістю опадами роки, яка, порівняно з середньою багаторічною за 1945–2010 рр. (232,7 мм), була істотно нижчою і становила 47,2–63,6 мм. Зменшення останніми роками кількості опадів навесні на 24–27% і восени на 62–65%, за одночасного підвищення температури та зниження відносної вологості повітря в зазначені пори року на 2,7–2,8°С, призводило до збільшення випаровуваності на 30–31% і дефіциту вологозабезпеченості на 53–55%. У середньому за 65 років випаровуваність складала 722,0 мм, а дефіцит вологозабезпечення – 487,4 мм. У вологі за забезпеченістю опадами роки випаровуваність не перевищувала 608,6 мм, відповідно, дефіцит вологозабезпечення знижувався до 243,6 мм. У середньовологі та середні роки випаровуваність зростає до 645,7–746,3 мм, а дефіцит вологозабезпечення підвищується до 406,7–507,7 мм. У середньосухі та сухі за забезпеченістю опадами роки випаровуваність зростає до 769,8–934,5 мм, а дефіцит вологозабезпечення – до 580,9–791,0 мм. Обґрунтовано доцільність ефективного використання та подальшого розширення площ зрошуваних земель, що забезпечить отримання стабільно високих урожаїв сільськогосподарських культур і продовольчу безпеку населення України

Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

On the utility of predictive chromatography to complement mass spectrometry based intact protein identification

The amino acid sequence determines the individual protein three-dimensional structure and its functioning in an organism. Therefore, "reading" a protein sequence and determining its changes due to mutations or post-translational modifications is one of the objectives of proteomic experiments. The commonly utilized approach is gradient high-performance liquid chromatography (HPLC) in combination with tandem mass spectrometry. While serving as a way to simplify the protein mixture, the liquid chromatography may be an additional analytical tool providing complementary information about the protein structure. Previous attempts to develop "predictive" HPLC for large biomacromolecules were limited by empirically derived equations based purely on the adsorption mechanisms of the retention and applicable to relatively small polypeptide molecules. A mechanism of the large biomacromolecule retention in reversed-phase gradient HPLC was described recently in thermodynamics terms by the analytical model of liquid chromatography at critical conditions (BioLCCC). In this work, we applied the BioLCCC model to predict retention of the intact proteins as well as their large proteolytic peptides separated under different HPLC conditions. The specific aim of these proof-of-principle studies was to demonstrate the feasibility of using "predictive" HPLC as a complementary tool to support the analysis of identified intact proteins in top-down, middle-down, and/or targeted selected reaction monitoring (SRM)-based proteomic experiments

SMC complexes differentially compact mitotic chromosomes according to genomic context

Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Shattered pellet injection experiments at JET in support of the ITER disruption mitigation system design

A series of experiments have been executed at JET to assess the efficacy of the newly installed shattered pellet injection (SPI) system in mitigating the effects of disruptions. Issues, important for the ITER disruption mitigation system, such as thermal load mitigation, avoidance of runaway electron (RE) formation, radiation asymmetries during thermal quench mitigation, electromagnetic load control and RE energy dissipation have been addressed over a large parameter range. The efficiency of the mitigation has been examined for the various SPI injection strategies. The paper summarises the results from these JET SPI experiments and discusses their implications for the ITER disruption mitigation scheme

Overview of JET results for optimising ITER operation

The JET 2019–2020 scientific and technological programme exploited the results of years of concerted scientific and engineering work, including the ITER-like wall (ILW: Be wall and W divertor) installed in 2010, improved diagnostic capabilities now fully available, a major neutral beam injection upgrade providing record power in 2019–2020, and tested the technical and procedural preparation for safe operation with tritium. Research along three complementary axes yielded a wealth of new results. Firstly, the JET plasma programme delivered scenarios suitable for high fusion power and alpha particle (α) physics in the coming D–T campaign (DTE2), with record sustained neutron rates, as well as plasmas for clarifying the impact of isotope mass on plasma core, edge and plasma-wall interactions, and for ITER pre-fusion power operation. The efficacy of the newly installed shattered pellet injector for mitigating disruption forces and runaway electrons was demonstrated. Secondly, research on the consequences of long-term exposure to JET-ILW plasma was completed, with emphasis on wall damage and fuel retention, and with analyses of wall materials and dust particles that will help validate assumptions and codes for design and operation of ITER and DEMO. Thirdly, the nuclear technology programme aiming to deliver maximum technological return from operations in D, T and D–T benefited from the highest D–D neutron yield in years, securing results for validating radiation transport and activation codes, and nuclear data for ITER