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Abstract Poly(arylene ether ketones) with preset molecular weights (reduced viscosity from 0. 2 to 0.82 dL g-1) containing terminal phenolic groups were synthesized by the reactions of 4,4'-difluorobenzophenone with bisphenol A or phenolphthalein in the presence of K2CO3 in N,N-dimethylacetamide. The influence of an excess of bisphenols on the molecular weights of the polymers obtained was studied. The structures of the polymers were confirmed by 1H NMR spectroscopy. The molecular weight distributions of the polymers were determined. [ABSTRACT FROM AUTHOR]

Fast ions in fusion plasmas often leave characteristic signatures in the neutron emission from the plasma. In this paper, we show how neutron measurements can be used to study fast ions and give examples of physics results obtained on present day tokamaks. The focus is on measurements with dedicated neutron spectrometers and with compact neutron detectors used in each channel of neutron profile monitors. A measured neutron spectrum can be analyzed in several different ways, depending on the physics scenario under consideration. Gross features of a fast ion energy distribution can be studied by applying suitably chosen thresholds to the measured spectrum, thus probing ions with different energies. With this technique it is possible to study the interaction between fast ions and MHD activity, such as toroidal Alfvén eigenmodes (TAEs) and sawtooth instabilities. Quantitative comparisons with modeling can be performed by a direct computation of the neutron emission expected from a given fast ion distribution. Within this framework it is also possible to determine physics parameters, such as the supra-thermal fraction of the neutron emission, by fitting model parameters to the data. A detailed, model-independent estimate of the fast ion distribution can be obtained by analyzing the data in terms of velocity space weight functions. Using this method, fast ion distributions can be resolved in both energy and pitch by combining neutron and gamma-ray measurements obtained along several different sightlines. Fast ion measurements of the type described in this paper will also be possible at ITER, provided that the spectrometers have the dynamic range required to resolve the fast ion spectral features in the presence of the dominating thermonuclear neutron emission. A dedicated high-resolution neutron spectrometer has been designed for this purpose. [ABSTRACT FROM AUTHOR]

One of the promising methods for determining physical and mechanical properties and structure of wood is the method based on the measurement of drilling resistance. Limitations of application of the method of measuring drilling resistance in dendrochronological studies are related to a number of factors that have a significant impact on the accuracy of determining the variation of physical and mechanical properties of wood within annual layers: the depth of drilling, its direction relative to the fibers, and the speed parameters of the drilling process. In order to assess the accuracy of measuring the radial growth of pine wood (Pinus sylvestris L.) with moisture content of 6–8 %, the ResistYX device and standard thin drill bits were used. On the basis of comparative analysis of radial wood growth determined by the optical method and the method of measuring resistance to drilling, it was found that in order to obtain accurate data on growth with a correlation coefficient greater than 0.7, it is recommended to measure no more than 17 annual layers on one sample, which corresponds to an average total width of annual layers of 36.6 mm. The influence of the main reasons for the decrease in the accuracy of radial growth determination by the drilling resistance measurement method was studied: geometrical parameters of the cutting part of a thin drill bit, deviation of the drilling direction from the specified one, impossibility of precise determination of the strictly radial drilling direction, wood flaws, as well as friction of the drill shank when the drilling depth increases. To increase the accuracy of the method of measuring drilling resistance in dendrochronological studies it is proposed to develop a method including the use of a special or newly developed tool for more accurate determination of the core and radial drilling of wood or round timber; to increase the rigidity of the thin drill bit; to provide the required fixation of the thin drill bit during its initial contact with wood and inside the device. Further studies in this direction will be associated with the assessment of measuring accuracy for the radial growth of coniferous wood by the feeding force for drill bit penetration. Acknowledgements: The research was supported by the Ministry of Science and Higher Education of the Russian Federation (Grant № 075-15-2021-674/3) and Core Facility Centre «Ecology, biotechnologies and processes for obtaining environmentally friendly energy carriers» of the Volga State University of Technology, Yoshkar-Ola and by the Russian Science Foundation grant No. 22-79-00098, https://rscf.ru/project/22-79-00098/. For citation: Chernov V.Yu., Sharapov E.S., Gaisin I.G. Evaluation of the Accuracy of Wood Drilling Resistance Measurement Method in Dendrochronological Studies. Lesnoy Zhurnal = Russian Forestry Journal, 2023, no. 5, pp. 135–150. (In Russ.). https://doi.org/10.37482/0536-1036-2023-5-135-150

Introduction. The adhesion properties and factors influencing the formation of the composition of thermally modified timber (TMT) and cement are investigated. The results were focused on the creation of a new material with improved service properties, which is named thermo-wood concrete (TWC).Materials and methods. Adapted standard methods to assess the adhesion of sand-cement mortar with TMT and compressive strength of sand-cement mortar obtained on waters infused with different types of wood and TMT were applied. The influence of the following factors was considered: the intensity (classes) of wood thermal modification, wood species, mortar formation method, cement binder content, wood surface conditions and moisture content of TMT, the presence of final steam curing of specimens.Results. The sand-cement mortar with a high content of cement binder had the highest adhesion with TMT. PVA-emulsion solution resulted in additional slight improvement of the sand-cement mortar and TMT adhesion. In general, unmodified (natural) wood had higher adhesion in comparison with TMT under the same conditions. Negative factors included premoistening of thermally modified timber surface, cleaning and leveling of its surface and the use of coniferous species for TMT specimens. The strength of sand-cement mortar was the lowest for specimens with addition of PVA-emulsion. Factor of water purification after infusion with TMT and unmodified wood had insignificant effect on strength of sand-cement mortar.Conclusions. TMT-cement composition had a lower adhesive force in comparison with unmodified wood. This is due to the combined effect of low hygroscopicity and wettability of the TMT surface. Water washing of the TMT is inappropriate due to deterioration of adhesion properties of the filler in TWC. To increase the adhesion of the components, it is recommended to use mortars with a high content of cement binder.

Observations made in a JET experiment aimed at accelerating deuterons to the MeV range by third harmonic radio-frequency (RF) heating coupled into a deuterium beam are reported. Measurements are based on a set of advanced neutron and gamma-ray spectrometers that, for the first time, observe the plasma simultaneously along vertical and oblique lines of sight. Parameters of the fast ion energy distribution, such as the high energy cut-off of the deuteron distribution function and the RF coupling constant, are determined from data within a uniform analysis framework for neutron and gamma-ray spectroscopy based on a one-dimensional model and by a consistency check among the individual measurement techniques. A systematic difference is seen between the two lines of sight and is interpreted to originate from the sensitivity of the oblique detectors to the pitch-angle structure of the distribution around the resonance, which is not correctly portrayed within the adopted one dimensional model. A framework to calculate neutron and gamma-ray emission from a spatially resolved, two-dimensional deuteron distribution specified by energy/pitch is thus developed and used for a first comparison with predictions from ab initio models of RF heating at multiple harmonics.The results presented in this paper are of relevance for the development of advanced diagnostic techniques for MeV range ions in high performance fusion plasmas, with applications to the experimental validation of RF heating codes and, more generally, to studies of the energy distribution of ions in the MeV range in high performance deuterium and deuterium-tritium plasmas. [ABSTRACT FROM AUTHOR]

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets., Competing Interests: Competing interests P.R.H.J.T. is a salaried employee of BioAge Labs, Inc. R.E.M. has received a speaker fee from Illumina, is an advisor to the Epigenetic Clock Development Foundation and is a scientific consultant for Optima Partners. E.W. is now an employee of AstraZeneca. Y.S.A. is now an employee of GSK. A.S.B. has received grants from AstraZeneca, Bayer, Biogen, BioMarin and Sanofi. A.M. is an employee of Pfizer. X.S. is the founder of Quantix BioSciences and has received a speaker fee from Olink Proteomics. The remaining authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Providing stable and clean energy sources is a necessity for the increasing demands of humanity. Energy produced by Deuterium (D) and Tritium (T) fusion reactions, in particular in tokamaks, is a promising path towards that goal. However, there is little experience with plasmas formed by D-T mixtures, since most of the experiments are currently performed in pure D. After more than 20 years, the Joint European Torus (JET) has carried out new D-T experiments with the aim of exploring some of the unique characteristics expected in future fusion reactors, such as the presence of highly energetic ions in low plasma rotation conditions. A new stable, high confinement and impurity-free D-T regime, with reduction of energy losses with respect to D, has been found. Multiscale physics mechanisms critically determine the thermal confinement. These crucial achievements importantly contribute to the establishment of fusion energy generation as an alternative to fossil fuels., (© 2024. The Author(s).)

Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification., (© 2023. The Author(s).)

Background: This article presents the results of a long-term study of the impact of rotavirus vaccination in Uzbekistan. Uzbekistan is the first country in the Central Asian region to introduce rotavirus vaccination into the national compulsory vaccination calendar. The study aimed to evaluate the impact of rotavirus vaccination on hospitalizations due to all-cause AGE and RVGE in children < 5 years of age in Uzbekistan., Methods: Detection of rotavirus antigen was performed using Rotavirus-Antigen-IFA-BEST "Vector Best" kit (Novosibirsk, Russia)., Results: The total of 20,128 children under 5 years of age were hospitalized in sentinel hospitals with a diagnosis of acute gastroenteritis during the study period (2019-2020). Of this number of children, 4481 children (22.2%) were included in the study. Of 4481 children, 367 (8.2%) children tested positive for rotavirus. In our study, decrease in the rotavirus rate was noted in all age groups. The peak of rotavirus positivity occurred in the months of January and February., Conclusion: The average rotavirus-positive rate in the period (2019-2020) was 8.2% and the absolute percentage decrease was 18.1% compared to the pre-vaccination period (2005-2009) where the rotavirus-positive rate was 26.3%. The percentage of prevented cases averaged 68.8%., (© 2023. The Author(s).)

A new deuterium-tritium experimental, DTE2, campaign has been conducted at the Joint European Torus (JET) between August 2021 and late December 2021. Motivated by significant enhancements in the past decade at JET, such as the ITER-like wall and enhanced auxiliary heating power, the campaign achieved a new fusion energy world record and performed a broad range of fundamental experiments to inform ITER physics scenarios and operations. New capabilities in the area of fusion product measurements by nuclear diagnostics were available as a result of a decade long enhancement program. These have been tested for the first time in DTE2 and a concise overview is provided here. Confined alpha particle measurements by gamma-ray spectroscopy were successfully demonstrated, albeit with limitations at neutron rates higher than some 10 17 n/s. High resolution neutron spectroscopy measurements with the magnetic proton recoil instrument were complemented by novel data from a set of synthetic diamond detectors, which enabled studies of the supra-thermal contributions to the neutron emission. In the area of escaping fast ion diagnostics, a lost fast ion detector and a set of Faraday cups made it possible to determine information on the velocity space and poloidal distribution of the lost alpha particles for the first time. This extensive set of data provides unique information for fundamental physics studies and validation of the numerical models, which are key to inform the physics and scenarios of ITER.

Background: Previous studies suggest a potential link between glycosylation and prostate cancer. To better characterize the relationship between the two, we performed a study to comprehensively evaluate the associations between genetically predicted blood plasma N-glycan levels and prostate cancer risk., Methods: Using genetic variants associated with N-glycan levels as instruments, we evaluated the associations between levels of 138 plasma N-glycans and prostate cancer risk. We analyzed data of 79,194 cases and 61,112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL., Results: We identified three N-glycans with genetically predicted levels in plasma to be associated with prostate cancer risk after Bonferroni correction. The estimated odds ratios (95% confidence intervals) were 1.29 (1.20-1.40), 0.80 (0.74-0.88), and 0.79 (0.72-0.87) for PGP18, PGP33, and PGP109, respectively, per every one standard deviation increase in genetically predicted levels of N-glycan. However, the instruments for these N-glycans only involved one to two variants. The proportions of variations that can be explained by the instruments range from 1.58% to 2.95% for these three N-glycans., Conclusion: We observed associations between genetically predicted levels of three N-glycans PGP18, PGP33, and PGP109 and prostate cancer risk. Given the correlated nature of the N-glycans and that many N-glycans share genetic loci, pleiotropy is a major concern. Future work is warranted to better characterize the relationship between N-glycans and prostate cancer., Competing Interests: The authors declare no potential conflicts of interest., (© 2021 Liu et al.)

Uzbekistan, the most populous country in central Asia, was the first in the region to introduce rotavirus vaccine into its national immunization program. Rotarix (GlaxoSmithKline Biologicals, RV1) was introduced in June 2014, with doses recommended at age 2 and 3 months. To evaluate vaccine impact, active surveillance for rotavirus diarrhea was reestablished in 2014 at 2 hospitals in Tashkent and Bukhara which had also performed surveillance during the pre-vaccine period 2005-2009. Children aged <5 y admitted with acute diarrhea had stool specimens collected and tested for rotavirus by enzyme immunoassay. Proportions testing rotavirus-positive in post-vaccine years were compared with the pre-vaccine period. Vaccine records were obtained and effectiveness of 2 RV1 doses vs 0 doses was estimated using rotavirus-case and test-negative design among children enrolled from Bukhara city. In 2015 and 2016, 8%-15% of infants and 10%-16% of children aged<5 y hospitalized with acute diarrhea at the sites tested rotavirus-positive, compared with 26% of infants and 27% of children aged<5 y in pre-vaccine period (reductions in proportion positive of 42%-68%, p <.001). Vaccine effectiveness of 2 RV1 doses vs 0 doses in protecting against hospitalization for rotavirus disease among those aged ≥6 months was 51% (95% CI 2-75) and is based on cases predominantly of genotype G2P[4]. Vaccine effectiveness point estimates tended to be higher against cases with higher illness severity (e.g., clinical severity based on modified Vesikari score ≥11). Our data demonstrate that the monovalent rotavirus vaccine is effective in reducing the likelihood of hospitalization for rotavirus disease in young children in Uzbekistan.

ZIP8 is a metal transporter with a role in manganese (Mn) homeostasis. A common genetic variant in ZIP8 (rs13107325; A391T) ranks in the top 10 of pleiotropic SNPs identified in GWAS; A391T has associations with an increased risk of schizophrenia, obesity, Crohn's disease, and reduced blood Mn. Here, we used CRISPR/Cas9-mediated knockin (KI) to generate a mouse model of ZIP8 A391T (Zip8 393T-KI mice). Recapitulating the SNP association with blood Mn, blood Mn was reduced in Zip8 393T-KI mice. There was restricted abnormal tissue Mn homeostasis, with decreases in liver and kidney Mn and a reciprocal increase in biliary Mn, providing in vivo evidence of hypomorphic Zip8 function. Upon challenge in a chemically induced colitis model, male Zip8 393T-KI mice exhibited enhanced disease susceptibility. ZIP8 391-Thr associated with reduced triantennary plasma N-glycan species in a population-based cohort to define a genotype-specific glycophenotype hypothesized to be linked to Mn-dependent glycosyltransferase activity. This glycophenotype was maintained in a cohort of patients with Crohn's disease. These data and the pleiotropic disease associations with ZIP8 391-Thr suggest underappreciated roles of Mn homeostasis in complex human disease.

Aging populations face diminishing quality of life due to increased disease and morbidity. These challenges call for longevity research to focus on understanding the pathways controlling healthspan. We use the data from the UK Biobank (UKB) cohort and observe that the risks of major chronic diseases increased exponentially and double every eight years, i.e., at a rate compatible with the Gompertz mortality law. Assuming that aging drives the acceleration in morbidity rates, we build a risk model to predict the age at the end of healthspan depending on age, gender, and genetic background. Using the sub-population of 300,447 British individuals as a discovery cohort, we identify 12 loci associated with healthspan at the whole-genome significance level. We find strong genetic correlations between healthspan and all-cause mortality, life-history, and lifestyle traits. We thereby conclude that the healthspan offers a promising new way to interrogate the genetics of human longevity., Competing Interests: P.F. is a shareholder of Gero LLC. Y.A. is a founder and co-owner of PolyOmica, a private research organization that specializes in computational and statistical (gen)omics, and a shareholder of PolyKnomics BV. A.Z., L.M., E.G., and P.F. are employees of Gero LLC. A patent application submitted by Gero LLC on the described methods and tools for evaluating genetic risks factors in association with diseases is pending. The remaining authors declare no competing interests.

Joint modeling of a number of phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication has not been sought. Modern omics technologies allow characterization of functional phenomena using a large number of related phenotype measures, which can benefit from such joint analysis. Here, we report a multivariate genome-wide association studies of 23 immunoglobulin G (IgG) N-glycosylation phenotypes. In the discovery cohort, our multi-phenotype method uncovers ten genome-wide significant loci, of which five are novel (IGH, ELL2, HLA-B-C, AZI1, FUT6-FUT3). We convincingly replicate all novel loci via multivariate tests. We show that IgG N-glycosylation loci are strongly enriched for genes expressed in the immune system, in particular antibody-producing cells and B lymphocytes. We empirically demonstrate the efficacy of multivariate methods to discover novel, reproducible pleiotropic effects.Multivariate analysis methods can uncover the relationship between phenotypic measures characterised by modern omic techniques. Here the authors conduct a multivariate GWAS on IgG N-glycosylation phenotypes and identify 5 novel loci enriched in immune system genes.

The Joint European Torus (JET) neutron profile monitor ensures 2D coverage of the gamma and neutron emissive region that enables tomographic reconstruction. Due to the availability of only two projection angles and to the coarse sampling, tomographic inversion is a limited data set problem. Several techniques have been developed for tomographic reconstruction of the 2-D gamma and neutron emissivity on JET, but the problem of evaluating the errors associated with the reconstructed emissivity profile is still open. The reconstruction technique based on the maximum likelihood principle, that proved already to be a powerful tool for JET tomography, has been used to develop a method for the numerical evaluation of the statistical properties of the uncertainties in gamma and neutron emissivity reconstructions. The image covariance calculation takes into account the additional techniques introduced in the reconstruction process for tackling with the limited data set (projection resampling, smoothness regularization depending on magnetic field). The method has been validated by numerically simulations and applied to JET data. Different sources of artefacts that may significantly influence the quality of reconstructions and the accuracy of variance calculation have been identified.

Neutron spectroscopy measurements with a single crystal diamond detector have been carried out at JET, for the first time in an experiment aimed at accelerating deuterons to MeV energies with radio frequency heating at the third harmonic. Data are interpreted by means of the expected response function of the detector and are used to extract parameters of the highly non-Maxwellian distribution function generated in this scenario. A comparison with observations using a time of flight and liquid scintillator neutron spectrometers is also presented. The results demonstrate the capability of diamond detectors to contribute to fast ion physics studies at JET and are of more general relevance in view of the application of such detectors for spectroscopy measurements in the neutron camera of next step tokamak devices.

Aims: Genome-wide association studies highlighted single nucleotide polymorphisms (SNPs) within the IFNL3/IL28B locus predict the treatment outcome for patients with HCV. Furthermore, SNPs in newly discovered IFNL4 are shown to have population-specific correlation with spontaneous clearance of HCV. The aim of this study was to examine the prevalence and clinical significance of the outlined SNPs in a population from Central Asia, a multi-ethnic region with a developing economy and a high prevalence of HCV infection., Methods: One hundred and thirty-five chronic HCV patients from Uzbekistan were enrolled. DNA specimens were extracted from peripheral blood mononuclear cells and the IFNL3 SNPs (rs8099917, rs12979860) were genotyped by the Invader Plus assay, the TaqMan assay, and by direct sequence analysis. The IFL4 region (ss469415590) was sequenced., Results: Of the 135 patients that completed 24 or 48 weeks of treatment with Peg-IFN-α plus RBV, 87.4% were of Central Asian (CA) ancestry and 12.6% were of Eastern European (EE) ancestry. A non-virological response was observed in 21.2% of CA and in 35.3% of EE, respectively (p<0.32). The rs12979860 was strongly associated with treatment response (OR, 5.2; 95% CI, 1.9-14.6; p<0.004) in the overall sample; however, SNP rs8099917 was the most predictive of outcome for CA group (OR, 6.9; 95% CI, 2.6-18.0; p<0.002). The allele frequency of IFNL4 SNP, ss469415590, was identical with that of rs12979860 in all samples., Conclusions: SNPs in IFNL3 and IFNL4 can be used to predict HCV treatment outcome in a population of Central Asian ancestry.

Experiments were carried out in the JET tokamak to determine the critical ion temperature inverse gradient length (R/LTi=R|nablaTi|/Ti) for the onset of ion temperature gradient modes and the stiffness of Ti profiles with respect to deviations from the critical value. Threshold and stiffness have been compared with linear and nonlinear predictions of the gyrokinetic code GS2. Plasmas with higher values of toroidal rotation show a significant increase in R/LTi, which is found to be mainly due to a decrease of the stiffness level. This finding has implications on the extrapolation to future machines of present day results on the role of rotation on confinement.

The first electron temperature modulation experiments in plasmas characterized by strong and long-lasting electron and ion internal transport barriers (ITB) have been performed in JET using ion cyclotron resonance heating in mode conversion scheme. The ITB is shown to be a well localized narrow layer with low heat diffusivity, characterized by subcritical transport and loss of stiffness. In addition, results from cold pulse propagation experiments suggest a second order transition process for ITB formation.