131 research outputs found
Role of Excited State Photoionization in the 852.1 nm Cs Laser Pumped by Cs-Ar Photoassociation
Photoionization of Cs (6pâ2P3/2) atoms during the operation of a Cs D2 line (852.1ânm: 6pâ2P3/2â6sâ2S1/2) laser, pumped by freeâfree transitions of thermal Cs-Ar ground state pairs, has been investigated experimentally and computationally. Photoexcitation of Cs vapor/Ar mixtures through the blue satellite of the D2 transition (peaking at 836.7ânm) selectively populates the 2P3/2 upper laser level by the dissociation of the CsAr excited complex. Comparison of laser output energy data, for instantaneous pump powers up to 3âMW, with the predictions of a numerical model sets an upper bound of 8âĂâ10â26 cm4 Wâ1 on the Cs (6pâ2P3/2) two photon ionization cross-section at 836.7ânm which corresponds to a single photon cross-section of 2.4âĂâ10â19 cm2 for a peak pump intensity of 3âMW cmâ2
Estimation of genetic parameters for feed efficiency traits using random regression models in dairy cattle.
Feed efficiency has become an increasingly important research topic in recent years. As feed costs rise and the environmental impacts of agriculture become more apparent, improving the efficiency with which dairy cows convert feed to milk is increasingly important. However, feed intake is expensive to measure accurately on large populations, making the inclusion of this trait in breeding programs difficult. Understanding how the genetic parameters of feed efficiency and traits related to feed efficiency vary throughout the lactation period is valuable to gain understanding into the genetic nature of feed efficiency. This study used 121,226 dry matter intake (DMI) records, 120,500 energy corrected milk (ECM) records, and 98,975 metabolic body weight (MBW) records, collected on 7,440 first lactation Holstein cows from 6 countries (Canada, Denmark, Germany, Spain, Switzerland, and United States of America), from January 2003 to February 2022. Genetic parameters were estimated using a multiple-trait random regression model with a fourth order Legendre polynomial for all traits. Weekly phenotypes for DMI were re-parameterized using linear regressions of DMI on ECM and MBW, creating a measure of feed efficiency that was genetically corrected for ECM and MBW, referred to as genomic residual feed intake (gRFI). Heritability (SE) estimates varied from 0.15 (0.03) to 0.29 (0.02) for DMI, 0.24 (0.01) to 0.29 (0.03) for ECM, 0.55 (0.03) to 0.83 (0.05) for MBW, and 0.12 (0.03) to 0.22 (0.06) for gRFI. In general, heritability estimates were lower in the first stage of lactation compared with the later stages of lactation. Additive genetic correlations between weeks of lactation varied, with stronger correlations between weeks of lactation that were close together. The results of this study contribute to a better understanding of the change in genetic parameters across the first lactation, providing insight into potential selection strategies to include feed efficiency in breeding programs
Deterministic evolution and stringent selection during preneoplasia
The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over 2âyears. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single-cell sequencing of TP53-deficient gastric organoids similarly indicates progression towards malignant transcriptional programmes. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programmes repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference and a marked degree of phenotypic convergence in premalignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and show evolutionary constraints and barriers to malignant transformation, with implications for earlier detection and interception of aggressive, genome-instable tumours
Interstellar MHD Turbulence and Star Formation
This chapter reviews the nature of turbulence in the Galactic interstellar
medium (ISM) and its connections to the star formation (SF) process. The ISM is
turbulent, magnetized, self-gravitating, and is subject to heating and cooling
processes that control its thermodynamic behavior. The turbulence in the warm
and hot ionized components of the ISM appears to be trans- or subsonic, and
thus to behave nearly incompressibly. However, the neutral warm and cold
components are highly compressible, as a consequence of both thermal
instability in the atomic gas and of moderately-to-strongly supersonic motions
in the roughly isothermal cold atomic and molecular components. Within this
context, we discuss: i) the production and statistical distribution of
turbulent density fluctuations in both isothermal and polytropic media; ii) the
nature of the clumps produced by thermal instability, noting that, contrary to
classical ideas, they in general accrete mass from their environment; iii) the
density-magnetic field correlation (or lack thereof) in turbulent density
fluctuations, as a consequence of the superposition of the different wave modes
in the turbulent flow; iv) the evolution of the mass-to-magnetic flux ratio
(MFR) in density fluctuations as they are built up by dynamic compressions; v)
the formation of cold, dense clouds aided by thermal instability; vi) the
expectation that star-forming molecular clouds are likely to be undergoing
global gravitational contraction, rather than being near equilibrium, and vii)
the regulation of the star formation rate (SFR) in such gravitationally
contracting clouds by stellar feedback which, rather than keeping the clouds
from collapsing, evaporates and diperses them while they collapse.Comment: 43 pages. Invited chapter for the book "Magnetic Fields in Diffuse
Media", edited by Elisabete de Gouveia dal Pino and Alex Lazarian. Revised as
per referee's recommendation
Setting an Optimal α That Minimizes Errors in Null Hypothesis Significance Tests
Null hypothesis significance testing has been under attack in recent years, partly owing to the arbitrary nature of setting α (the decision-making threshold and probability of Type I error) at a constant value, usually 0.05. If the goal of null hypothesis testing is to present conclusions in which we have the highest possible confidence, then the only logical decision-making threshold is the value that minimizes the probability (or occasionally, cost) of making errors. Setting α to minimize the combination of Type I and Type II error at a critical effect size can easily be accomplished for traditional statistical tests by calculating the α associated with the minimum average of α and ÎČ at the critical effect size. This technique also has the flexibility to incorporate prior probabilities of null and alternate hypotheses and/or relative costs of Type I and Type II errors, if known. Using an optimal α results in stronger scientific inferences because it estimates and minimizes both Type I errors and relevant Type II errors for a test. It also results in greater transparency concerning assumptions about relevant effect size(s) and the relative costs of Type I and II errors. By contrast, the use of αâ=â0.05 results in arbitrary decisions about what effect sizes will likely be considered significant, if real, and results in arbitrary amounts of Type II error for meaningful potential effect sizes. We cannot identify a rationale for continuing to arbitrarily use αâ=â0.05 for null hypothesis significance tests in any field, when it is possible to determine an optimal α
Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease. We therefore compiled a collection of transcriptomic datasets that can be used to aid the scientific community in better understanding the transcriptional effects of ligand-activated AHR.Peer reviewe
Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer
Few patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors with complete and durable remissions being quite rare. Oncogenes can regulate tumor immune infiltration, however whether oncogenes dictate diminished response to immunotherapy and whether these effects are reversible remains poorly understood. Here, we report that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy. Using mouse models and patient data, we show that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, mice experience tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and when strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors. The oncoprotein c-Myc is often overexpressed in triple negative breast cancer and has a role in tumor progression and resistance to therapy. Here the authors show that elevated MYC expression is correlated with low immune infiltration, diminished MHC-I pathway expression and that CpG/aOX40 treatment could overcome resistance to PD-L1 blockade in MYC-high breast tumors.Peer reviewe
Tiny-Scale Molecular Structures in the Magellanic Clouds (Part 1)
We report on the {\small FUSE} detections of the HD and CO molecules {\bf on
the lines of sight towards three Large Magellanic stars}: Sk 67D05, Sk
68D135, and Sk 69D246. HD is also detected for the first time {\bf on the
lines of sight towards two Small Magellanic Cloud stars}: AV 95 and Sk 159.
While the HD and CO abundances are expected to be lower in the Large Magellanic
Cloud where molecular fractions are a third of the Galactic value and where the
photodissociation flux is up to thousands times larger, we report an average
HD/H ratio of 1.40.5 ppm and CO/H ratio ranging from 0.8 to 2.7
ppm similar to the Galactic ones. We tentatively identify a deuterium reservoir
(hereafter D--reservoir) towards the Small Magellanic Cloud, along the light
path to AV 95. We derive a D/H ratio ranging from 1. 10 to 1.1
10.Comment: 34 pages, 10 tables, 12 figures, accepted for publication in A&
Motion for a Resolution tabled by Mr Richard Balfe for entry in the register pursuant to Rule 49 of the Rules of Procedure on supply of military equipment to states where basic human rights are not respected. Working Documents 1982-83, Document 1-265/82, 19 May 1982
Abstract Background The clinical sequencing of cancer genomes to personalize therapy is becoming routine across the world. However, concerns over patient re-identification from these data lead to questions about how tightly access should be controlled. It is not thought to be possible to re-identify patients from somatic variant data. However, somatic variant detection pipelines can mistakenly identify germline variants as somatic ones, a process called âgermline leakageâ. The rate of germline leakage across different somatic variant detection pipelines is not well-understood, and it is uncertain whether or not somatic variant calls should be considered re-identifiable. To fill this gap, we quantified germline leakage across 259 sets of whole-genome somatic single nucleotide variant (SNVs) predictions made by 21 teams as part of the ICGC-TCGA DREAM Somatic Mutation Calling Challenge. Results The median somatic SNV prediction set contained 4325 somatic SNVs and leaked one germline polymorphism. The level of germline leakage was inversely correlated with somatic SNV prediction accuracy and positively correlated with the amount of infiltrating normal cells. The specific germline variants leaked differed by tumour and algorithm. To aid in quantitation and correction of leakage, we created a tool, called GermlineFilter, for use in public-facing somatic SNV databases. Conclusions The potential for patient re-identification from leaked germline variants in somatic SNV predictions has led to divergent open data access policies, based on different assessments of the risks. Indeed, a single, well-publicized re-identification event could reshape public perceptions of the values of genomic data sharing. We find that modern somatic SNV prediction pipelines have low germline-leakage rates, which can be further reduced, especially for cloud-sharing, using pre-filtering software
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In the last years many populations of anurans have declined and extinctions have been recorded. They were related to environmental pollution, changes of land use and emerging diseases. The main objective of this study was to determine copper sensitivity of the anuran of the Amazon Rhinella granulosa and Scinax ruber tadpoles at stage 25 and Scinax ruber eggs exposed for 96 h to copper concentrations ranging from 15 ”g Cu L-1 to 94 ”g Cu L-1. LC50 at 96 h of Rhinella granulosa Gosner 25, Scinax ruber Gosner 25 and Scinax ruber eggs in black water of the Amazon were 23.48, 36.37 and 50.02 ”g Cu L-1, respectively. The Biotic Ligand Model was used to predict the LC50 values for these species and it can be considered a promising tool for these tropical species and water conditions. Copper toxicity depends on water physical-chemical composition and on the larval stage of the tadpoles. The Gosner stage 19-21 (related to the appearance of external gills) is the most vulnerable and the egg stage is the most resistant. In case of contamination by copper, the natural streams must have special attention, since copper is more bioavailable.Nos Ășltimos anos foram registrados muitas extinçÔes e declĂnios de populaçÔes de anuros. Eles estavam relacionados com a poluição do ambiente, a mudanças no uso da terra e ao surgimento de doenças. O principal objetivo deste estudo foi determinar a sensibilidade dos anuros amazĂŽnicos ao cobre. Os girinos de Scinax ruber e Rhinella granulosa no estadio 25 e os ovos de Scinax ruber foram expostos por 96 horas a concentraçÔes de cobre entre 15 ”g Cu L-1 a 94 ”g Cu L-1. A CL50 -96 h dos girinos de Rhinella granulosa, dos girinos de Scinax ruber e dos ovos de Scinax ruber em ĂĄguas pretas da AmazĂŽnia foram 23,48; 36,37 e 50,02 ”g Cu L-1, respectivamente. O modelo do ligante biĂłtico foi usado para prever os valores de CL50 para essas duas espĂ©cies e pode ser considerado uma ferramenta promissora para essas espĂ©cies tropicais e para essas condiçÔes de ĂĄgua. A Toxicidade de cobre depende da composição fĂsico-quĂmica da ĂĄgua e do estagio larval dos girinos. O estadio 19-21 de Gosner (relacionados ao aparecimento das brĂąnquias externas) sĂŁo os mais vulnerĂĄvel e o estagio de ovo Ă© o mais resistente. Em caso de contaminação por cobre, os igarapĂ©s naturais devem ter uma atenção especial, uma vez que o cobre Ă© mais biodisponĂvel nesse ambiente
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