Методы и механизмы геттерирования кремниевых структур в производстве интегральных микросхем

Увеличение степени интеграции элементной базы предъявляет все более жесткие требования к уменьшению концентрации загрязняющих примесей и окислительных дефектов упаковки в исходных кремниевых пластинах с ее сохранением в технологическом цикле изготовления ИМС. Это обуславливает высокую актуальность применения геттерирования в современной технологии микроэлектроники. В статье рассмотрены существующие методы геттерирования кремниевых пластин и механизмы их протекания.Збільшення ступеня інтеграції елементної бази пред'являє все більш жорсткі вимоги до зменшення концентрації забруднюючих домішок та окислювальних дефектів упаковки у вихідних кремнієвих пластинах за її збереження у технологічному циклі виготовлення ІМС. Це обумовлює високу актуальність застосування гетерування в сучасній технології мікроелектроніки. Розглянуто існуючі методи гетерування кремнієвих пластин та розглянуто механізми їх перебігу.Increasing the degree of integration of hardware components imposes more stringent requirements for the reduction of the concentration of contaminants and oxidation stacking faults in the original silicon wafers with its preservation in the IC manufacturing process cycle. This causes high relevance of the application of gettering in modern microelectronic technology. The existing methods of silicon wafers gettering and the mechanisms of their occurrence are considered

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Abstract: Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Publisher Copyright: © 2019, The Author(s).Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.Peer reviewe

Production Method under Surveillance: Laboratory Pilot-Scale Simulation of CH 4 –CO 2 Exchange in a Natural Gas Hydrate Reservoir

The "guest exchange"of methane (CH4) by carbon dioxide (CO2) in naturally occurring gas hydrates is seen as a possibility to concurrently produce CH4 and sequester CO2. Presently, process evaluation is based on CH4-CO2 exchange yields of small-or medium-scale laboratory experiments, mostly neglecting mass and heat transfer processes. This work investigates process efficiencies in two large-scale experiments (210 L sample volume) using fully water-saturated, natural reservoir conditions and a gas hydrate saturation of 50%. After injecting 50 kg of heated CO2 discontinuously (E1) and continuously (E2) and a subsequent soaking period, the reservoir was depressurized discontinuously. It was monitored using electrical resistivity, temperature and pressure sensors, and fluid flow and gas composition measurements. Phase and component inventories were analyzed based on mass and volume balances. The total CH4 production during CO2 injection was only 5% of the initial CH4 inventory. Prior to CO2 breakthrough, the produced CH4 roughly equaled dissolved CH4 in the produced pore water, which balanced the volume of the injected CO2. After CO2 breakthrough, CH4 ratios in the released CO2 quickly dropped to 2.0-0.5 vol %. The total CO2 retention was the highest just before the CO2 breakthrough and higher in E1 where discontinuous injection improved the distribution of injected CO2 and subsequent mixed hydrate formation. The processes were improved by the succession of CO2 injection by controlled degassing at stability limits below that of the pure CH4 hydrate, particularly in experiment E2. Here, a more heterogeneous distribution of liquid CO2 and larger availability of free water led to smaller initial degassing of liquid CO2. This allowed for quick re-formation of mixed gas hydrates and CH4 ratios of 50% in the produced gases. The experiments demonstrate the importance of fluid migration patterns, heat transport, sample inhomogeneity, and secondary gas hydrate formation in water-saturated sediments

Development, test, and evaluation of exploitation technologies for the application of gas production from natural gas hydrate reservoirs and their potential application in the Danube Delta, Black Sea

Highlights • The SUGAR project has developed and tested various methods for gas production from marine gas hydrates from micro to field scale. • Numerical simulations improved the understanding of processes on molecular to reservoir scale. • Depressurization is a promising technology for exploiting gas hydrate deposits in the Danube Delta. • The injection of CO2 or CO2–N2 is not a suitable method for the exploitation of gas hydrate deposits in the Danube Delta. Abstract One important scientific objective of the national research project SUGAR – Submarine Gas Hydrate Reservoirs was the development, improvement, and test of innovative concepts for the production of methane from natural gas hydrate reservoirs. Therefore, different production methods, such as the thermal stimulation using in situ combustion, the chemical stimulation via injection of CO2 as a gaseous, liquid or supercritical phase and depressurization were tested alone or in combination at different scales. In the laboratory experiments these ranged from pore and hydrate grain scale to 425-L reactor volume, whereas numerical models were applied to describe the related processes from molecular to reservoir scale. In addition, the numerical simulations also evaluated the feasibility and efficiency of the application of these methods in selected areas, such as the Danube Paleodelta in the Black Sea, addressing the two dominant methane hydrate reservoir settings, buried channel-levee and turbidite systems. It turned out, that the injection of CO2 or a CO2–N2 gas mixture is not applicable for the Danube Paleodelta in the Black Sea, because the local pressure and temperature conditions are too close to the equilibrium conditions of both, the CO2 hydrate and a CO2–N2 mixed hydrate stability fields. Experiments using thermal stimulation and depressurization showed promising results but also some issues, such as sufficient heat transfer. In summary it can be said that the applicability and efficiency of each method has to be proven for each specific hydrate reservoir conditions. Based on the results obtained by numerical simulations the most promising and safe method for the production of CH4 from hydrate bearing sediments in the Danube Paleodelta would be the depressurization technique. This study summarizes the main experimental and modeling results