Search

The composite materials (CM) based on Co, Ti-Cu, and Pt and reinforced with diamond-like carbon particles and diamonds with different component ratios have been obtained by high-pressure high-temperature synthesis (5–9 GPa, 800–1800 °C). The methods of optical microscopy, dynamic indentation, and tribological tests were used to establish the correlation between the structure and properties of the reinforcing phase and CM and to define the limits of the applicability of the CM as tribotechnical materials. Low friction coefficients (0.08–0.06) were demonstrated by the CM reinforced with a superhard (35–40 GPa) diamond-like phase obtained from ball-milled fullerites with a cobalt binder as well as by the CM with diamonds regardless of the binder type and particle size. The wear resistance of the cobalt-based CM increases with increasing hardness of the reinforcing diamond-like particles. The condition for obtaining super wear-resistant CM from metal-fullerene mixtures is the synthesis at a temperature of about 800 °C, which ensures the collapse of fullerene molecules, but limits the graphitization of the diamond-like structure. [ABSTRACT FROM AUTHOR]

This paper examined the problem of noise in the aircraft cabin and ways to solve it. Through observations, the following causes of noise were identified: the power plant (acoustic and mechanical vibrations, turbulent boundary layer and others), the location of the engine relative to the airframe, the noise of the propeller (if it is a propeller power plant), the propeller of the power plant itself, the air conditioning system, and so on the same operating device in the cabin. There is a comprehensive way to solve the problem of noise in the aircraft cabin: for aircraft with turbojet engines, measures aimed at changing the design and use of sound- absorbing materials can be effective. For a turboprop aircraft, it is necessary to create low-noise propellers and synchronize the rotation of the propellers. For air conditioning elements, reducing duct and exhaust velocities allows for satisfactory acoustic performance of these sources. The reduction in “cabin noise” is achieved by changing the manufacturing technology of various noisy units. It should be emphasized that the possibility of reduction in the cabin and the aircraft is, in principle, laid down when designing the units and the aircraft as a whole. It is worth noting sound insulation, vibration insulation, as well as the rational location of noisy units, including the power plant, relative to the passenger cabin of the aircraft. From the study on sound insulation, we conclude that it is best to use 2 sound insulation options. Reducing noise is a feasible task and its greatest progress is achieved even at the design stage itself

The made research results of the dependence of the film photovoltaic converter efficiency on their operating temperature and their comparison are considered in the paper. The physical mechanisms of temperature influence analysis on output, diode and electronic parameters of photovoltaic converters were conducted. The output parameters determination of the flexible photovoltaic converters was carried out by measurement of light current-voltage characteristics by using illuminator based on powerful semiconductor LEDs with different colors for simulated radiation which is close to the standard ground and ultraviolet solar spectrum. For ensuring effective non-destructive switching of the test specimens of the flexible PVC based on cadmium telluride to the measurement circle, the special contact device was developed and used. The main feature of contact device is four separate vertically moving metal probes in form of semi spheres with polished surfaces, which makes it impossible to puncture the PVC electrodes. These probes have possibility of individual positioning of each probe that is carried out with the help of a hard rotary console of variable length attached to the body and can be pressed with a given effort without impact on the frontal and any rear electrodes of the PVC experiments. The efficiency temperature coefficients of the photovoltaic converter, which make up for devices with a CdTe of 0.14 %/C, CuInSe2 – 0.36 %/C, amorphous silicon -0.21 %/C were obtained. The analytical processing and analysis of the light diode characteristic effect on the PVC efficiency based on the CdTe showed that the temperature stability of their efficiency is ensured by the diode current density, the incision of which increases by 50 % from 1.9·10-9 A to 2.7·10-9 A with the temperature rise from 20 °С to 50 °С. At the same time, it has been established for PVC on the CuInSe and amorphous silicon base that the decrease of short circuit current density, open circuit voltage and fill factor of current-voltage characteristics plays the main role in efficiency reduction with rising temperature. [ABSTRACT FROM AUTHOR]

Experimentally established, the influence of the working temperature and solar radiation power on the efficiency of industrial production silicon solar cells. Based on the experimental results designed the concept of a hybrid solar generating module equipped with a mirror concentrator of solar radiation and solar cells cooling system for using in high-performance solar energy station. Concentrator of solar radiation provides in 1.5-time increase of electrical power generating by such module, and water-cooling system can reduce the equilibrium temperature of the module up to 10 degrees and twice reduce efficiency losses from solar cells overheating. The proposed concept will reduce the number of modules needed to build solar energy station. [ABSTRACT FROM AUTHOR]

While studying at a higher educational institution, a student is immersed in a unique world with its own rules and laws. Training in various forms of specialization lasts from 4 to 5.5 years. During this time, the student manages to replenish his knowledge base with unique competencies and qualities that will later help to achieve successful career growth. It is obvious that getting a higher education plays a significant role in the formation of a personality, higher schools have everything necessary to test the acquired knowledge and skills. The flexibility of the curricula allows students to choose which disciplines they want to study. But before starting to function comfortably in an educational environment, students must go through adaptation. In the entire history of the existence of educational organizations, there was no higher educational institution where the student felt comfortable and cozy from the first days. This article pays special attention to the methods and forms of undergoing the adaptation period for first-year students on the example of the implementation of a number of activities taking place at the Institute No. 1 “Aviation Technology” of the Moscow Aviation Institute (National Research University).

p50 protein is a member of the Y-box binding transcription factor family and is a counterpart of YB-1 protein. The generic microchip was used to analyze the sequence specificity of p50 binding to single (ss) and double-stranded (ds) oligodeoxyribonucleotides. The generic microchip contained 4096 single-stranded octadeoxyribonucleotides in which all possible core 6-mers (46=4096) were flanked at their 3′ and 5′-ends with degenerated nucleotides. The oligonucleotides were chemically immobilized within polyacrylamide gel pads fixed on a glass slide. The binding of p50 to the generic microchip was shown to be the most specific to ss GGGG motif and then to ss CACC and CATC motifs. GC-rich ds oligonucleotides of the generic microchip, and particularly those containing GGTG/CACC, GATG/CATC, and GTGG/CCAC heterogeneous motifs, were most efficiently destabilized due to interaction with p50. Gel-shift electrophoresis has shown that the protein exhibits much higher binding specificity to 24-mer oligoA-TGGGGG-oligoA containing G-rich 6-mer, in comparison with 24-mer oligoA-AAATAT-oligoA carrying A,T-rich 6-mer in full correspondence with the data obtained with the microchip. Studies of DNA-binding proteins using gel-immobilized ss and ds DNA fragments provide a unique possibility to detect low-affinity complexes of these proteins with short sequence motifs and assess the role of these motifs in sequence-specific interactions with long recognition sites. [Copyright &y& Elsevier]

Introduction: Alzheimer's disease (AD) is the most common form of dementia in the elderly. Given that AD neuropathology begins decades before symptoms, there is a dire need for effective screening tools for early detection of AD to facilitate early intervention., Methods: Here, we used tree-based and deep learning methods to train polyomic prediction models for AD affection status and age at onset, employing genomic, proteomic, metabolomic, and drug use data from UK Biobank. We used SHAP to determine the feature's importance., Results: Our best-performing polyomic model achieved an area under the receiver operating characteristics curve (AUROC) of 0.87. We identified GFAP and CXCL17 proteins to be the strongest predictors of AD, besides apolipoprotein E (APOE) alleles. Increasing the number of cases by including "AD-by-proxy" cases did not improve AD prediction., Discussion: Among the four modalities, genomics, and proteomics were the most informative modality based on AUROC (area under the receiver operating characteristic curve). Our data suggest that two blood-based biomarkers (glial fibrillary acidic protein [GFAP] and CXCL17) may be effective for early presymptomatic prediction of AD., Highlights: We developed a polyomic model to predict AD and age-at-onset using omics and medication use data from EHR. We identified GFAP and CXCL17 proteins to be the strongest predictors of AD, besides APOE alleles. "AD-by-proxy" cases, if used in training, do not improve AD prediction. Proteomics was the most informative modality overall for affection status and AAO prediction., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Alzheimer's disease (AD) is the most prevalent form of dementia. While many AD-associated genetic determinants have been previously identified, few studies have analyzed individuals of non-European ancestry. Here, we describe a multi-ancestry genome-wide association study of clinically-diagnosed AD and AD-by-proxy using whole genome sequencing data from NIAGADS, NIMH, UKB, and All of Us (AoU) consisting of 49,149 cases (12,074 clinically-diagnosed and 37,075 AD-by-proxy) and 383,225 controls. Nearly half of NIAGADS and AoU participants are of non-European ancestry. For clinically-diagnosed AD, we identified 14 new loci - five common (FBN2,/SCL27A6, AC090115.1, DYM, KCNG1/AL121785.1, TIAM1) and nine rare (VWA5B1, RNU6-755P/LMX1A, MOB1A, MORC1-AS1, LINC00989, PDE4D, RNU2-49P/CDO1, NEO1, and SLC35G3/AC022916.1). Meta-analysis of UKB and AoU AD-by-proxy cases yielded two new rare loci (RPL23/LASP1 and CEBPA/ AC008738.6) which were also nominally significant in NIAGADS. In summary, we provide evidence for 16 novel AD loci and advocate for more studies using WGS-based GWAS of diverse cohorts.

Alzheimer's disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood 1-3 . Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer's disease. We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses. We identify vulnerable populations of excitatory and inhibitory neurons that are depleted in specific brain regions in Alzheimer's disease, and provide evidence that the Reelin signalling pathway is involved in modulating the vulnerability of these neurons. We develop a scalable method for discovering gene modules, which we use to identify cell-type-specific and region-specific modules that are altered in Alzheimer's disease and to annotate transcriptomic differences associated with diverse pathological variables. We identify an astrocyte program that is associated with cognitive resilience to Alzheimer's disease pathology, tying choline metabolism and polyamine biosynthesis in astrocytes to preserved cognitive function late in life. Together, our study develops a regional atlas of the ageing human brain and provides insights into cellular vulnerability, response and resilience to Alzheimer's disease pathology., (© 2024. The Author(s).)

The prediction of the susceptibility of an individual to a certain disease is an important and timely research area. An established technique is to estimate the risk of an individual with the help of an integrated risk model, that is, a polygenic risk score with added epidemiological covariates. However, integrated risk models do not capture any time dependence, and may provide a point estimate of the relative risk with respect to a reference population. The aim of this work is twofold. First, we explore and advocate the idea of predicting the time-dependent hazard and survival (defined as disease-free time) of an individual for the onset of a disease. This provides a practitioner with a much more differentiated view of absolute survival as a function of time. Second, to compute the time-dependent risk of an individual, we use published methodology to fit a Cox's proportional hazard model to data from a genetic SNP study of time to Alzheimer's disease (AD) onset, using the lasso to incorporate further epidemiological variables such as sex, APOE (apolipoprotein E, a genetic risk factor for AD) status, 10 leading principal components, and selected genomic loci. We apply the lasso for Cox's proportional hazards to a data set of 6792 AD patients (composed of 4102 cases and 2690 controls) and 87 covariates. We demonstrate that fitting a lasso model for Cox's proportional hazards allows one to obtain more accurate survival curves than with state-of-the-art (likelihood-based) methods. Moreover, the methodology allows one to obtain personalized survival curves for a patient, thus giving a much more differentiated view of the expected progression of a disease than the view offered by integrated risk models. The runtime to compute personalized survival curves is under a minute for the entire data set of AD patients, thus enabling it to handle datasets with 60,000-100,000 subjects in less than 1 h., (© 2024 Wiley Periodicals LLC.)

Background: Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking. Methods: We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by sex in the COPDGene study ( n = 6144 participants of European ancestry and n = 2589 participants of African ancestry) with replication in the Diabetes Heart Study (DHS). We adjusted for age, sex, current smoking status, BMI, diabetes, self-reported high blood pressure, self-reported high cholesterol, and genetic ancestry (as summarized by principal components computed within each racial group). For the significant signals from the GWA analyses, we examined the single nucleotide polymorphism (SNP) by sex interactions, stratified by smoking status (current vs. former), and tested for a SNP by smoking status interaction on CAC. Results: We identified genome-wide significant associations for CAC in the chromosome 9p21 region [ CDKN2B-AS1 ] among all COPDGene participants ( p = 7.1 × 10 -14 ) and among males ( p = 1.0 × 10 -9 ), but the signal was not genome-wide significant among females ( p = 6.4 × 10 -6 ). For the sex stratified GWA analyses among females, the chromosome 6p24 region [ PHACTR1 ] had a genome-wide significant association ( p = 4.4 × 10 -8 ) with CAC, but this signal was not genome-wide significant among all COPDGene participants ( p = 1.7 × 10 -7 ) or males ( p = 0.03). There was a significant interaction for the SNP rs9349379 in PHACTR1 with sex ( p = 0.02), but the interaction was not significant for the SNP rs10757272 in CDKN2B-AS1 with sex ( p = 0.21). In addition, PHACTR1 had a stronger association with CAC among current smokers ( p = 6.2 × 10 -7 ) than former smokers ( p = 7.5 × 10 -3 ) and the SNP by smoking status interaction was marginally significant ( p = 0.03). CDKN2B-AS1 had a strong association with CAC among both former ( p = 7.7 × 10 -8 ) and current smokers ( p = 1.7 × 10 -7 ) and the SNP by smoking status interaction was not significant ( p = 0.40). Conclusions: Among current and former smokers of European ancestry in the COPDGene study, we identified a genome-wide significant association in the chromosome 6p24 region [ PHACTR1 ] with CAC among females, but not among males. This region had a significant SNP by sex and SNP by smoking interaction on CAC.

In precision medicine, both predicting the disease susceptibility of an individual and forecasting its disease-free survival are areas of key research. Besides the classical epidemiological predictor variables, data from multiple (omic) platforms are increasingly available. To integrate this wealth of information, we propose new methodology to combine both cooperative learning, a recent approach to leverage the predictive power of several datasets, and polygenic hazard score models. Polygenic hazard score models provide a practitioner with a more differentiated view of the predicted disease-free survival than the one given by merely a point estimate, for instance computed with a polygenic risk score. Our aim is to leverage the advantages of cooperative learning for the computation of polygenic hazard score models via Cox's proportional hazard model, thereby improving the prediction of the disease-free survival. In our experimental study, we apply our methodology to forecast the disease-free survival for Alzheimer's disease (AD) using three layers of data. One layer contains epidemiological variables such as sex, APOE (apolipoprotein E, a genetic risk factor for AD) status and 10 leading principal components. Another layer contains selected genomic loci, and the last layer contains methylation data for selected CpG sites. We demonstrate that the survival curves computed via cooperative learning yield an AUC of around $0.7$, above the state-of-the-art performance of its competitors. Importantly, the proposed methodology returns (1) a linear score that can be easily interpreted (in contrast to machine learning approaches), and (2) a weighting of the predictive power of the involved data layers, allowing for an assessment of the importance of each omic (or other) platform. Similarly to polygenic hazard score models, our methodology also allows one to compute individual survival curves for each patient., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Genome-wide association studies have identified numerous disease susceptibility loci (DSLs) for Alzheimer's disease (AD). However, only a limited number of studies have investigated the dependence of the genetic effect size of established DSLs on genetic ancestry., Methods: We utilized the whole genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP) including 35,569 participants. A total of 25,459 subjects in four distinct populations (African ancestry, non-Hispanic White, admixed Hispanic, and Asian) were analyzed., Results: We found that nine DSLs showed significant heterogeneity across populations. Single nucleotide polymorphism (SNP) rs2075650 in translocase of outer mitochondrial membrane 40 (TOMM40) showed the largest heterogeneity (Cochran's Q = 0.00, I 2  = 90.08), followed by other SNPs in apolipoprotein C1 (APOC1) and apolipoprotein E (APOE). Two additional loci, signal-induced proliferation-associated 1 like 2 (SIPA1L2) and solute carrier 24 member 4 (SLC24A4), showed significant heterogeneity across populations., Discussion: We observed substantial heterogeneity for the APOE-harboring 19q13.32 region with TOMM40/APOE/APOC1 genes. The largest risk effect was seen among African Americans, while Asians showed a surprisingly small risk effect., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted for age, sex, current smoking status, genetic ancestry (via principal components), income, education, and living status (urban vs. rural). In addition, we examined sex-stratified mediation models and sex-moderated mediation models. For both analyses, we adjusted for age, current smoking status, and genetic ancestry (via principal components). In the UK Biobank, rs6424532 [ LOC105378800 ] had a statistically significant indirect effect on broad depression through the log of pack-years of cigarette smoking ( p = 4.0 × 10 -4 ) among all participants and a marginally significant indirect effect among females ( p = 0.02) and males ( p = 4.0 × 10 -3 ). Moreover, rs10501696 [ GRM5 ] had a marginally significant indirect effect on broad depression through the log of pack-years of cigarette smoking ( p = 0.01) among all participants and a significant indirect effect among females ( p = 2.2 × 10 -3 ). In the secondary analyses, the sex-moderated indirect effect was marginally significant for rs10501696 [ GRM5 ] on broad depression through the log of pack-years of cigarette smoking ( p = 0.01). In the COPDGene study, the effect of an SNP (rs10501696) in GRM5 on depressive symptoms and medication was mediated by log of pack-years ( p = 0.02); however, no SNPs had a sex-moderated mediated effect on depressive symptoms. In the UK Biobank, we found SNPs in two genes [ LOC105378800 , GRM5 ] with an indirect effect on broad depression through the log of pack-years of cigarette smoking. In addition, the indirect effect for GRM5 on broad depression through smoking may be moderated by sex. These results suggest that genetic regions associated with broad depression may be mediated by cigarette smoking and this relationship may be moderated by sex.