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Age-related telomere attrition causes aberrant gene expression in sub-telomeric regions
Telomere attrition has been proposed as a biomarker and causal factor in aging. In addition to causing cellular senescence and apoptosis, telomere shortening has been found to affect gene expression in subtelomeric regions. Here, we analyzed the distribution of age-related differentially expressed genes from the GTEx RNA sequencing database of 54 tissue types from 979 human subjects and found significantly more upregulated than downregulated genes in subtelomeric regions as compared to the genome-wide average. Our data demonstrate spatial relationships between telomeres and gene expression in aging.
A Method of Image-Based Aberration Metrology for EUVL Tools
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Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants
Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species ( A. flavus , A. fumigatus and A. nidulans ) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10 −11 ( A. flavus ), 1.1 × 10 −11 ( A. fumigatus ) and 4.1 × 10 −11 ( A. nidulans ) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus . In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10 −11 ( A. flavus ), 2.2 × 10 −11 ( A. fumigatus ) and 4.5 × 10 −11 ( A. nidulans ) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans , we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus , which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified.
Wavefront aberration function in terms of R V Shack’s vector product and Zernike polynomial vectors
Not Available
Submicron focusing of high-energy X-rays with silicon saw-tooth refractive lenses: fabrication and aberrations
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Submicron focusing of high-energy X-rays with silicon saw-tooth refractive lenses – fabrication and aberrations: errata
Three (3) items of errata are submitted for our recently published paper [ Opt. Express 28 , 36505 ( 2020 ) 10.1364/OE.405566 ]. One is a clarifying extension to the Fig. 3 caption. Two are typographical corrections. The scientific results and conclusions are unaffected.
Disentangling multidimensional spatio-temporal data into their common and aberrant responses
With the advent of high-throughput measurement techniques, scientists and engineers are starting to grapple with massive data sets and encountering challenges with how to organize, process and extract information into meaningful structures. Multidimensional spatio-temporal biological data sets such as time series gene expression with various perturbations over different cell lines, or neural spike trains across many experimental trials, have the potential to acquire insight about the dynamic behavior of the system. For this potential to be realized, we need a suitable representation to understand the data. A general question is how to organize the observed data into meaningful structures and how to find an appropriate similarity measure. A natural way of viewing these complex high dimensional data sets is to examine and analyze the large-scale features and then to focus on the interesting details. Since the wide range of experiments and unknown complexity of the underlying system contribute to the heterogeneity of biological data, we develop a new method by proposing an extension of Robust Principal Component Analysis (RPCA), which models common variations across multiple experiments as the lowrank component and anomalies across these experiments as the sparse component. We show that the proposed method is able to find distinct subtypes and classify data sets in a robust way without any prior knowledge by separating these common responses and abnormal responses. Thus, the proposed method provides us a new representation of these data sets which has the potential to help users acquire new insight from data.
Aberrations and Emittance Growth in the DARHT 2nd Axis Downstream Transport
The emittance of the DARHT 2 nd Axis has been inferred from solenoid scans performed in the downstream transport (DST) region using a short kicked pulse. The beam spot size is measured by viewing optical transition radiation (OTR) in the near field as a function of the field (current) of a solenoid magnet (S4). The imaging station containing the OTR target is located about 100 cm downstream of the solenoid magnet. The emittance is then inferred using a beam optics code such as LAMDA or XTR by fitting the data to initial conditions upstream of the S4 solenoid magnet. The initial conditions are the beam size, beam convergence and emittance. The beam energy and current are measured. In preparation for a solenoid scan, the magnets upstream of the solenoid are adjusted to produce a round beam with no beam losses due to scraping in the beam tube. This is different from the standard tune in which the beam tune is adjusted to suppress the effects of ions and rf in the septum dump. In this standard tune, approximately 10% of the beam is lost due to scraping as the beam enters the small 3.75” ID beam tube after the septum. The normalized emittance inferred from recent solenoid scans typically ranges from 600 to 800 π(mm-mrad). This larger beam size increases the sensitivity to any non-linear fields in the Collins quadrupoles that are mounted along the small diameter beam tube. The primary magnet used to adjust the beam size in this region is the S3 solenoid magnet. Measurements made of the beam shape as the beam size was decreased showed significant structure consistent with non-linear fields. Using the measured magnetic fields in the Collins quadrupoles including higher order multipoles, the beam transport through the Collins quadrupoles is simulated and compared to the observed OTR images. The simulations are performed using the beam optics codes TRANSPORT [1] and TURTLE [2]. Estimates of the emittance growth and beam losses are made as a function of the S3 magnet setting. The increase in the spot size on the x-ray production target resulting from this emittance growth is examined for different DST tunes.
Measuring Electronic and Structural Transformations in Solar Thermochemical Water Splitting Materials with Aberration-Corrected STEM-EELS.
Abstract not provided.
PIE of Cycle 13 316SS Cladding Using Aberration Corrected STEM Image and Analys
Optical, SEM and TEM analysis confirmed the presence of moderate sensitization in the 20% cold worked 316SS after the iron aluminide coating was applied. The Cr depletion occurs on the grain boundaries between the closely spaced carbides, and at the interface between the carbides and matrix. Cr depletion varied from locally along the grain boundaries, in many cases showing levels down to 15 wt%, but a few isolated regions had depletion levels down to 12.5 wt%. Optical and SEM images taken from a weld heat affected zone revealed the recrystallization occurred after an end plug cap had been welded to the coated cladding. Irradiation did not affect the carbides in a noticeable manner, but radiation-induced segregation/depletion altered the Cr depletion profiles by removing the wide Cr depletion profile, and replacing it with a much deeper, more narrow profile. Cr levels were depleted to 8-10 wt%, Ni and Si were enriched to levels of 40 wt% and 12 wt% respectively. Substantial precipitation formed in the matrix, and on line dislocations in the matrix and on grain boundary dislocations. Voids were observed in the upper region of the TPBAR where the irradiation temperature exceeds 320C. The levels of Cr depletion and Ni/Si enrichment indicate a material in a state susceptible to irradiation assisted stress corrosion cracking.
MassIVE MSV000100641 - Multilayered regulation by RNA thermometers enables precise control of Cas9 expression in E. coli: Cas9-based genome editing technologies can rapidly generate mutations to probe a diverse array of mutant genotypes. However, aberrant Cas9 nuclease translation and activity can occur despite the use of inducible promoters to control expression, leading to extensive cell death. This background killing caused by promoter leakiness severely limits the application of Cas9 for generating mutant libraries because of the potential for population skew. We demonstrate the utility of temperature sensitive RNA elements as a layer of post-transcriptional regulation to reduce the impact of promoter leak. We observe significant temperature-dependent increases in cell survival when certain RNA thermometers (RNATs) are placed upstream of the cas9 coding sequence. We also show that the most highly repressing RNAT, hsp17rep, significantly reduces population skew with a library of characterized guide RNAs in Escherichia coli. This strategy should be applicable to all bacterial Cas9-based methods and technologies.
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Astronauts Plasma-Derived Exosomes Induced Aberrant EZH2-Mediated H3K27me3 Epigenetic Regulation of the Vitamin D Receptor
There are unique stressors in the spaceflight environment. Exposure to such stressors may be associated with adverse effects on astronauts' health, including increased cancer and cardiovascular disease risks. Small extracellular vesicles (sEVs, i.e., exosomes) play a vital role in intercellular communication and regulate various biological processes contributing to their role in disease pathogenesis. To assess whether spaceflight alters sEVs transcriptome profile, sEVs were isolated from the blood plasma of 3 astronauts at two different time points: 10 days before launch (L-10) and 3 days after return (R+3) from the Shuttle mission. AC16 cells (human cardiomyocyte cell line) were treated with L-10 and R+3 astronauts-derived exosomes for 24 h. Total RNA was isolated and analyzed for gene expression profiling using Affymetrix microarrays. Enrichment analysis was performed using Enrichr. Furthermore, transcription factor (TF) enrichment analysis using the ENCODE/ChEA Consensus TF database identified gene sets related to the polycomb repressive complex 2 (PRC2) and Vitamin D receptor (VDR) in AC16 cells treated with R+3 compared to cells treated with L-10 astronauts-derived exosomes. Further analysis of the histone modifications using datasets from the Roadmap Epigenomics Project confirmed enrichment in gene sets related to the H3K27me3 repressive mark. Interestingly, analysis of previously published H3K27me3–chromatin immunoprecipitation sequencing (ChIP-Seq) ENCODE datasets showed enrichment of H3K27me3 in the VDR promoter. Collectively, our results suggest that astronaut-derived sEVs may epigenetically repress the expression of the VDR in human adult cardiomyocytes by promoting the activation of the PRC2 complex and H3K27me3 levels.
High Performance DNA Probes for Perinatal Detection of Numerical Chromosome Aberrations
Human reproduction is a tightly controlled process of stepwise evolution with multiple, mostly yet unknown milestones and checkpoints. Healthy halpoid gametes have to be produced by the parents, which will fuse to form the diploid zygote that implants in the female uterus and grows to become first an embryo, then a fetus and finally matures into a newborn. There are several known risk factors that interfere with normal production of gametes, spermatocytes or oocytes, and often cause embryonic mortality and fetal demise at an early stage. Yet some embryos with chomosomal abnormalities can develop beyond the critical first trimester of pregnancy and, while those with supernumary chromosomes in their hyperdiploid cells will be spontaneously aborted, a small fraction of fetuses with an extra chromosome continues to grow to term and will be delivered as a liveborn baby. While minor clinical symptoms displayed by children with trisomies are manageable for many parents, the burden of caring for a child with numerical chromosome abnormalities can be overwhelming to partners or individual families. It also poses a significant financial burden to the society and poses ethical dilemma. In this communication, we will review the progress that has been made in the development of molecular techniques to test individual fetal cells for chromosomal imbalances. We will focus our discussion on the direct visualization of chromosome-specific DNA sequences in live or fixed specimens using fluorescence in situ hybridization (FISH) and, more specifically, talk about the groundbreaking progress that in recent years has been achieved towards an improved diagnosis with novel, chromosome-specific DNA probes.
Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness
To achieve maximal growth, cells must manage a massive economy of ribosomal proteins (r-proteins) and RNAs (rRNAs) to produce thousands of ribosomes every minute. Although ribosomes are essential in all cells, natural disruptions to ribosome biogenesis lead to heterogeneous phenotypes. Here, we model these perturbations in Saccharomyces cerevisiae and show that challenges to ribosome biogenesis result in acute loss of proteostasis. Imbalances in the synthesis of r-proteins and rRNAs lead to the rapid aggregation of newly synthesized orphan r-proteins and compromise essential cellular processes, which cells alleviate by activating proteostasis genes. Exogenously bolstering the proteostasis network increases cellular fitness in the face of challenges to ribosome assembly, demonstrating the direct contribution of orphan r-proteins to cellular phenotypes. With this being said, we propose that ribosome assembly is a key vulnerability of proteostasis maintenance in proliferating cells that may be compromised by diverse genetic, environmental, and xenobiotic perturbations that generate orphan r-proteins.
Aberrations of radio signals traversing the auroral ionosphere interim report no. 1, 1 aug. 1964 - 31 jan. 1965
Radio star signal measurement beneath auroral ionosphere for satellite tracking
Aberrations of radio signals transversing the auroral ionosphere interim report no. 2, 1 feb. - 31 jul. 1965
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Normally Expected Aberrations in the 8-hour Dynamic EKG
The establishment of norms for interpreting long term dynamic electrocardiograms is attempted by correlating a completely disease symptom and cardiac risk factor free sample with a non-pure sample in the direction of normality on various variables. Out of a population of 362 subjects exposed to dynamic electrocardiogram testing, a discrimination between normals and abnormals in terms of traditional risk factors was observed. The two groups differed significantly on the following variables: cholesterol, smoking, systolic blood pressure, white blood count, fasting blood sugar, uric acid, resting EKG, year of birth, and coronary insufficiency.