We report the results from a haloscope search for axion dark matter in the 3.3-4.2 μeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of ..."invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.
Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on ...initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension.
Abstract
The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism genetic and genome resource for the laboratory mouse. MGD is the authoritative source for ...biological reference data sets related to mouse genes, gene functions, phenotypes, and mouse models of human disease. MGD is the primary outlet for official gene, allele and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. In this report we describe significant enhancements to MGD, including two new graphical user interfaces: (i) the Multi Genome Viewer for exploring the genomes of multiple mouse strains and (ii) the Phenotype-Gene Expression matrix which was developed in collaboration with the Gene Expression Database (GXD) and allows researchers to compare gene expression and phenotype annotations for mouse genes. Other recent improvements include enhanced efficiency of our literature curation processes and the incorporation of Transcriptional Start Site (TSS) annotations from RIKEN’s FANTOM 5 initiative.
The Morphometry of Impact Craters on Bennu Daly, R. T.; Bierhaus, E. B.; Barnouin, O. S. ...
Geophysical research letters,
28 December 2020, Letnik:
47, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Bennu is an ~500‐m‐diameter rubble‐pile asteroid that is the target of detailed study by the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS‐REx) ...mission. Here we use data from the OSIRIS‐REx Laser Altimeter to assess depth‐to‐diameter ratios (d/D) of 108 impact craters larger than 10 m in diameter. The d/D of craters on Bennu ranges from 0.02 to 0.19. The mean is 0.10 ± 0.03. The smallest craters show the broadest range in d/D, consistent with d/D measurements on other asteroids. A few craters have central mounds, which is interpreted as evidence that a more competent substrate lies a few meters beneath them. The range of d/D narrows as crater size increases, with craters larger than 80 m tending toward smaller d/D. At large scales, increases in target strength with depth, combined with target curvature, may affect crater morphometry.
Plain Language Summary
Between 2018 and 2020, National Aeronautics and Space Administration (NASA)'s Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS‐REx) spacecraft orbited a small asteroid called Bennu in preparation to collect a sample for return to Earth. Bennu is a “rubble‐pile” asteroid, meaning an aggregate of rock fragments that have coalesced together in space. OSIRIS‐REx observations showed that Bennu has many craters on its surface, which formed when other, smaller objects collided with it in the past. Crater depths and widths (diameters), in addition to relating to the size and speed of the impacting object, also reflect the physical characteristics of the impacted surface. Accordingly, we measured the depths and diameters of many of Bennu's craters to better understand the surface and interior properties of this rubble‐pile asteroid and how it compares to other asteroids. The smaller craters on Bennu have a variety of depths, even among similarly sized craters. The largest are so wide that they appear to be affected by the curvature of Bennu's surface and by the presence of stronger material at depth. We observe mounds inside some of the smaller craters, supporting the idea that a more competent substrate underlies the surface material.
Key Points
The depth‐to‐diameter ratio (d/D) of asteroid Bennu's craters >10 m in diameter ranges from 0.02 to 0.19 with a mean of 0.10 ± 0.03
Small craters show the greatest diversity in d/D, whereas larger craters (>80 m) span a narrower range in d/D and tend to be shallower
For craters >80 m, increases in target strength with depth, combined with target curvature, likely contribute to smaller d/D
The Pioneer and Voyager spacecraft made close-up measurements of Saturn's ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical interaction between the rings and ...atmosphere. Exploring this interaction provides information on ring composition and the influence on Saturn's atmosphere from infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the region between the D ring and Saturn during the spacecraft's Grand Finale phase. We used these measurements to characterize the atmospheric structure and material influx from the rings. The atmospheric He/H
ratio is 10 to 16%. Volatile compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as well as larger organic-bearing grains, are flowing inward at a rate of 4800 to 45,000 kilograms per second.
Climate effects on hydrology impart high variability to water-quality properties, including nutrient loadings, concentrations, and phytoplankton biomass as chlorophyll-a (chl-a), in estuarine and ...coastal ecosystems. Resolving long-term trends of these properties requires that we distinguish climate effects from secular changes reflecting anthropogenic eutrophication. Here, we test the hypothesis that strong climatic contrasts leading to irregular dry and wet periods contribute significantly to interannual variability of mean annual values of water-quality properties using in situ data for Chesapeake Bay. Climate effects are quantified using annual freshwater discharge from the Susquehanna River together with a synoptic climatology for the Chesapeake Bay region based on predominant sea-level pressure patterns. Time series of water-quality properties are analyzed using historical (1945–1983) and recent (1984–2012) data for the bay adjusted for climate effects on hydrology. Contemporary monitoring by the Chesapeake Bay Program (CBP) provides data for a period since mid-1984 that is significantly impacted by anthropogenic eutrophication, while historical data back to 1945 serve as historical context for a period prior to severe impairments. The generalized additive model (GAM) and the generalized additive mixed model (GAMM) are developed for nutrient loadings and concentrations (total nitrogen—TN, nitrate + nitrate—NO₂ + NO₃) at the Susquehanna River and water-quality properties in the bay proper, including dissolved nutrients (NO₂ + NO₃, orthophosphate—PO₄), chl-a, diffuse light attenuation coefficient (K D (PAR)), and chl-a/TN. Each statistical model consists of a sum of nonlinear functions to generate flow-adjusted time series and compute long-term trends accounting for climate effects on hydrology. We present results identifying successive periods of (1) eutrophication ca. 1945–1980 characterized by approximately doubled TN and NO₂ + NO₃ loadings, leading to increased chl-a and associated ecosystem impairments, and (2) modest decreases of TN and NO₂ + NO₃ loadings from 1981 to 2012, signaling a partial reversal of nutrient over-enrichment. Comparison of our findings with long-term trends of water-quality properties for a variety of estuarine and coastal ecosystems around the world reveals that trends for Chesapeake Bay are weaker than for other systems subject to strenuous management efforts, suggesting that more aggressive actions than those undertaken to date will be required to counter anthropogenic eutrophication of this valuable resource.
Searching for axion dark matter, the ADMX Collaboration acquired data from January to October 2018, over the mass range 2.81–3.31 μeV, corresponding to the frequency range 680–790 MHz. Using an ...axion haloscope consisting of a microwave cavity in a strong magnetic field, the ADMX experiment excluded Dine-Fischler-Srednicki-Zhitnisky (DFSZ) axions at 90% confidence level and 100% dark matter density over this entire frequency range, except for a few gaps due to mode crossings. This paper explains the full ADMX analysis for run 1B, motivating analysis choices informed by details specific to this run.
The conduction electrons in a metal experience competing interactions with each other and the atomic nuclei. This competition can lead to many types of magnetic order in metals. For example, in ...chromium the electrons order to form a spin-density-wave (SDW) antiferromagnetic state. A magnetic field may be used to perturb or tune materials with delicately balanced electronic interactions. Here, we show that the application of a magnetic field can induce SDW magnetic order in a quasi-2D metamagnetic metal, where none exists in the absence of the field. We use magnetic neutron scattering to show that the application of a large (B ≈ 8 T) magnetic field to the perovskite metal Sr3Ru2O7 (refs 3-7) can be used to tune the material through two magnetically ordered SDW states. The ordered states exist over relatively small ranges in field (≲0.4 T), suggesting that their origin is due to a new mechanism related to the electronic fine structure near the Fermi energy, possibly combined with the stabilizing effect of magnetic fluctuations. The magnetic field direction is shown to control the SDW domain populations, which naturally explains the strong resistivity anisotropy or 'electronic nematic' behaviour observed in this material.
Lentiviral Vector Bioprocessing Perry, Christopher; Rayat, Andrea C M E
Viruses,
02/2021, Letnik:
13, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Lentiviral vectors (LVs) are potent tools for the delivery of genes of interest into mammalian cells and are now commonly utilised within the growing field of cell and gene therapy for the treatment ...of monogenic diseases and adoptive therapies such as chimeric antigen T-cell (CAR-T) therapy. This is a comprehensive review of the individual bioprocess operations employed in LV production. We highlight the role of envelope proteins in vector design as well as their impact on the bioprocessing of lentiviral vectors. An overview of the current state of these operations provides opportunities for bioprocess discovery and improvement with emphasis on the considerations for optimal and scalable processing of LV during development and clinical production. Upstream culture for LV generation is described with comparisons on the different transfection methods and various bioreactors for suspension and adherent producer cell cultivation. The purification of LV is examined, evaluating different sequences of downstream process operations for both small- and large-scale production requirements. For scalable operations, a key focus is the development in chromatographic purification in addition to an in-depth examination of the application of tangential flow filtration. A summary of vector quantification and characterisation assays is also presented. Finally, the assessment of the whole bioprocess for LV production is discussed to benefit from the broader understanding of potential interactions of the different process options. This review is aimed to assist in the achievement of high quality, high concentration lentiviral vectors from robust and scalable processes.
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