Retroviral capsid recognition by Trim5 blocks productive infection. Rhesus macaques harbor three functionally distinct Trim5 alleles: Trim5 alpha Q, Trim5 alpha TFP and Trim5CypA. Despite the high ...degree of amino acid identity between Trim5 alpha Q and Trim5 alpha TFP alleles, the Q/TFP polymorphism results in the differential restriction of some primate lentiviruses, suggesting these alleles differ in how they engage these capsids. Simian immunodeficiency virus of rhesus macaques (SIVmac) evolved to resist all three alleles. Thus, SIVmac provides a unique opportunity to study a virus in the context of the Trim5 repertoire that drove its evolution in vivo. We exploited the evolved rhesus Trim5 alpha resistance of this capsid to identify gain-of-sensitivity mutations that distinguish targets between the Trim5 alpha Q and Trim5 alpha TFP alleles. While both alleles recognize the capsid surface, Trim5 alpha Q and Trim5 alpha TFP alleles differed in their ability to restrict a panel of capsid chimeras and single amino acid substitutions. When mapped onto the structure of the SIVmac239 capsid N-terminal domain, single amino acid substitutions affecting both alleles mapped to the beta -hairpin. Given that none of the substitutions affected Trim5 alpha Q alone, and the fact that the beta -hairpin is conserved among retroviral capsids, we propose that the beta -hairpin is a molecular pattern widely exploited by Trim5 alpha proteins. Mutations specifically affecting rhesus Trim5 alpha TFP (without affecting Trim5 alpha Q) surround a site of conservation unique to primate lentiviruses, overlapping the CPSF6 binding site. We believe targeting this site is an evolutionary innovation driven specifically by the emergence of primate lentiviruses in Africa during the last 12 million years. This modularity in targeting may be a general feature of Trim5 evolution, permitting different regions of the PRYSPRY domain to evolve independent interactions with capsid.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As part of the James Webb Space Telescope (JWST) Guaranteed Time Observation (GTO) program "Direct Imaging of YSOs" (program ID 1179), we use JWST NIRCam's direct imaging mode in F187N, F200W, F405N, ...and F410M to perform high contrast observations of the circumstellar structures surrounding the protostar HL Tau. The data reveal the known stellar envelope, outflow cavity, and streamers, but do not detect any companion candidates. We detect scattered light from an in-flowing spiral streamer previously detected in \(\textrm{HCO}^+\) by ALMA, and part of the structure connected to the c-shaped outflow cavity. For detection limits in planet mass we use BEX evolutionary tracks when \(M_\textrm{p}<2M_\textrm{J}\) and AMES-COND evolutionary tracks otherwise, assuming a planet age of 1 Myr (youngest available age). Inside the disk region, due to extended envelope emission, our point-source sensitivities are \(\sim5\) mJy (\(37~M_{\rm J}\)) at 40 AU in F187N, and \(\sim0.37\) mJy (\(5.2~M_{\rm J}\)) at 140 AU in F405N. Outside the disk region, the deepest limits we can reach are \(\sim0.01\) mJy (\(0.75~M_{\rm J}\)) at a projected separation of \(\sim525\) AU.
We present JWST/NIRCam F187N, F200W, F405N and F410M direct imaging data of
the disk surrounding SAO 206462. Previous images show a very structured disk,
with a pair of spiral arms thought to be ...launched by one or more external
perturbers. The spiral features are visible in three of the four filters, with
the non-detection in F410M due to the large detector saturation radius. We
detect with a signal-to-noise ratio of 4.4 a companion candidate (CC1) that, if
on a coplanar circular orbit, would orbit SAO 206462 at a separation of
$\sim300$ au, $2.25\sigma$ away from the predicted separation for the driver of
the eastern spiral. According to the BEX models, CC1 has a mass of
$M_\mathrm{CC1}=0.8\pm0.3~M_\mathrm{J}$. No other companion candidates were
detected. At the location predicted by simulations of both spirals generated by
a single massive companion, the NIRCam data exclude objects more massive than
$\sim2.2~M_\mathrm{J}$ assuming the BEX evolutionary models. In terms of
temperatures, the data are sensitive to objects with
$T_{\text{eff}}\sim650-850$ K, when assuming planets emit like blackbodies
($R_\mathrm{p}$ between 1 and $3 R_\mathrm{J}$). From these results, we
conclude that if the spirals are driven by gas giants, these must be either
cold or embedded in circumplanetary material. In addition, the NIRCam data
provide tight constraints on ongoing accretion processes. In the low extinction
scenario we are sensitive to mass accretion rates of the order
$\dot{M}\sim10^{-9} M_\mathrm{J}$ yr$^{-1}$. Thanks to the longer wavelengths
used to search for emission lines, we reach unprecedented sensitivities to
processes with $\dot{M}\sim10^{-7} M_\mathrm{J}$ yr$^{-1}$ even towards highly
extincted environments ($A_\mathrm{V}\approx50$~mag).
Spirometry is the most common pulmonary function test. It is widely used in the assessment of lung function to provide objective information used in the diagnosis of lung diseases and monitoring lung ...health. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for conducting spirometry. Improvements in instrumentation and computational capabilities, together with new research studies and enhanced quality assurance approaches, have led to the need to update the 2005 technical standards for spirometry to take full advantage of current technical capabilities.
This spirometry technical standards document was developed by an international joint task force, appointed by the American Thoracic Society and the European Respiratory Society, with expertise in conducting and analyzing pulmonary function tests, laboratory quality assurance, and developing international standards. A comprehensive review of published evidence was performed. A patient survey was developed to capture patients' experiences.
Revisions to the 2005 technical standards for spirometry were made, including the addition of factors that were not previously considered. Evidence to support the revisions was cited when applicable. The experience and expertise of task force members were used to develop recommended best practices.
Standards and consensus recommendations are presented for manufacturers, clinicians, operators, and researchers with the aims of increasing the accuracy, precision, and quality of spirometric measurements and improving the patient experience. A comprehensive guide to aid in the implementation of these standards was developed as an online supplement.
The 2018 GaN power electronics roadmap Amano, H; Baines, Y; Beam, E ...
Journal of physics. D, Applied physics,
04/2018, Letnik:
51, Številka:
16
Journal Article
Recenzirano
Odprti dostop
Gallium nitride (GaN) is a compound semiconductor that has tremendous potential to facilitate economic growth in a semiconductor industry that is silicon-based and currently faced with diminishing ...returns of performance versus cost of investment. At a material level, its high electric field strength and electron mobility have already shown tremendous potential for high frequency communications and photonic applications. Advances in growth on commercially viable large area substrates are now at the point where power conversion applications of GaN are at the cusp of commercialisation. The future for building on the work described here in ways driven by specific challenges emerging from entirely new markets and applications is very exciting. This collection of GaN technology developments is therefore not itself a road map but a valuable collection of global state-of-the-art GaN research that will inform the next phase of the technology as market driven requirements evolve. First generation production devices are igniting large new markets and applications that can only be achieved using the advantages of higher speed, low specific resistivity and low saturation switching transistors. Major investments are being made by industrial companies in a wide variety of markets exploring the use of the technology in new circuit topologies, packaging solutions and system architectures that are required to achieve and optimise the system advantages offered by GaN transistors. It is this momentum that will drive priorities for the next stages of device research gathered here.
There is limited evidence that a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) reduces gut symptoms in quiescent inflammatory bowel disease (IBD). We ...performed a randomized, controlled trial to investigate the effects of a low FODMAP diet on persistent gut symptoms, the intestinal microbiome, and circulating markers of inflammation in patients with quiescent IBD.
We performed a single-blind trial of 52 patients with quiescent Crohn’s disease or ulcerative colitis and persistent gut symptoms at 2 large gastroenterology clinics in the United Kingdom. Patients were randomly assigned to groups that followed a diet low in FODMAPs (n = 27) or a control diet (n = 25), with dietary advice, for 4 weeks. Gut symptoms and health-related quality of life were measured using validated questionnaires. Stool and blood samples were collected at baseline and end of trial. We assessed fecal microbiome composition and function using shotgun metagenomic sequencing and phenotypes of T cells in blood using flow cytometry.
A higher proportion of patients reported adequate relief of gut symptoms following the low FODMAP diet (14/27, 52%) than the control diet (4/25, 16%, P=.007). Patients had a greater reduction in irritable bowel syndrome severity scores following the low FODMAP diet (mean reduction of 67; standard error, 78) than the control diet (mean reduction of 34; standard error, 50), although this difference was not statistically significant (P = .075). Following the low FODMAP diet, patients had higher health-related quality of life scores (81.9 ± 1.2) than patients on the control diet (78.3 ± 1.2, P = .042). A targeted analysis revealed that in stool samples collected at the end of the study period, patients on the low FODMAP diet had significantly lower abundance of Bifidobacterium adolescentis, Bifidobacterium longum, and Faecalibacterium prausnitzii than patients on control diet. However, microbiome diversity and markers of inflammation did not differ significantly between groups.
In a trial of the low FODMAP diet vs a control diet in patients with quiescent IBD, we found no significant difference after 4 weeks in change in irritable bowel syndrome severity scores, but significant improvements in specific symptom scores and numbers reporting adequate symptom relief. The low FODMAP diet reduced fecal abundance of microbes believed to regulate the immune response, compared with the control diet, but had no significant effect on markers of inflammation. We conclude that a 4-week diet low in FODMAPs is safe and effective for managing persistent gut symptoms in patients with quiescent IBD. www.isrctn.com no.: ISRCTN17061468
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