A Decade of SN1993J: Discovery of Wavelength Effects in the Expansion Rate

We have studied the growth of the shell-like radio structure of supernova SN1993J in M81 from September 1993 through October 2003 with very-long-baseline interferometry (VLBI) observations at the wavelengths of 3.6, 6, and 18cm. For this purpose, we have developed a method to accurately determine the outer radius (R) of any circularly symmetric compact radio structure like SN1993J. The source structure of SN1993J remains circularly symmetric (with deviations from circularity under 2%) over almost 4000 days. We characterize the decelerated expansion of SN 1993J through approximately day 1500 after explosion with an expansion parameter $m= 0.845\pm0.005$ ($R \propto t^{m}$). However, from that day onwards the expansion is different when observed at 6 and 18cm. Indeed, at 18cm, the expansion can be well characterized by the same $m$ as before day 1500, while at 6cm the expansion appears more decelerated, and is characterized by another expansion parameter, $m_{6}= 0.788\pm0.015$. Therefore, since about day 1500 on, the radio source size has been progressively smaller at 6cm than at 18cm. These findings are in stark contrast to previous reports by other authors on the details of the expansion. In our interpretation the supernova expands with a single expansion parameter, $m= 0.845\pm0.005$, and the 6cm results beyond day 1500 are due to physical effects, perhaps also coupled to instrumental limitations. Two physical effects may be involved: (a) a changing opacity of the ejecta to the 6cm radiation, and (b) a radial decrease of the magnetic field in the emitting region. (Long abstract cut. Please, read full abstract in manuscript).Comment: 21 pages, 19 figures, accepted in A&

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Extreme infrared variables from UKIDSS-I. A concentration in star-forming regions

We present initial results of the first panoramic search for high-amplitude near-infrared variability in theGalactic plane.We analyse the widely separated two-epoch K-band photometry in the fifth and seventh data releases of the UKIDSS Galactic plane survey.We find 45 stars with δK > 1 mag, including two previously known OH/IR stars and a Nova. Even though the midplane is not yet included in the data set, we find the majority (66 per cent) of our sample to be within known star-forming regions (SFRs), with two large concentrations in the Serpens OB2 association (11 stars) and the Cygnus-X complex (12 stars). Sources in SFRs show spectral energy distributions that support classification as young stellar objects (YSOs). This indicates that YSOs dominate the Galactic population of high-amplitude infrared variable stars at low luminosities and therefore likely dominate the total high-amplitude population. Spectroscopic follow up of the DR5 sample shows at least four stars with clear characteristics of eruptive premain- sequence variables, two of which are deeply embedded. Our results support the recent concept of eruptive variability comprising a continuum of outburst events with different timescales and luminosities, but triggered by a similar physical mechanism involving unsteady accretion. Also, we find what appears to be one of the most variable classical Be stars. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society

Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys

Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian–human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56 days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans.National Institutes of Health (U.S.) (AI055332)National Institutes of Health (U.S.) (AI060354)National Institutes of Health (U.S.) (AI078526)National Institutes of Health (U.S.) (AI084794)National Institutes of Health (U.S.) (AI095985)National Institutes of Health (U.S.) (AI096040)National Institutes of Health (U.S.) (AI100148)National Institutes of Health (U.S.) (AI10063)Bill & Melinda Gates Foundation (OPP1033091)Bill & Melinda Gates Foundation (OPP1033115)Bill & Melinda Gates Foundation (OPP1040741)Bill & Melinda Gates Foundation (OPP1040753)Ragon Institute of MGH, MIT, and HarvardStavros S. Niarchos FoundationHoward Hughes Medical Institute (Investigator

Copy number variant discrepancy resolution using the ClinGen dosage sensitivity map results in updated clinical interpretations in ClinVar

Conflict resolution in genomic variant interpretation is a critical step toward improving patient care. Evaluating interpretation discrepancies in copy number variants (CNVs) typically involves assessing overlapping genomic content with focus on genes/regions that may be subject to dosage sensitivity (haploinsufficiency (HI) and/or triplosensitivity (TS)). CNVs containing dosage sensitive genes/regions are generally interpreted as â likely pathogenicâ (LP) or â pathogenicâ (P), and CNVs involving the same known dosage sensitive gene(s) should receive the same clinical interpretation. We compared the Clinical Genome Resource (ClinGen) Dosage Map, a publicly available resource documenting known HI and TS genes/regions, against germline, clinical CNV interpretations within the ClinVar database. We identified 251 CNVs overlapping known dosage sensitive genes/regions but not classified as LP or P; these were sent back to their original submitting laboratories for reâ evaluation. Of 246 CNVs reâ evaluated, an updated clinical classification was warranted in 157 cases (63.8%); no change was made to the current classification in 79 cases (32.1%); and 10 cases (4.1%) resulted in other types of updates to ClinVar records. This effort will add curated interpretation data into the public domain and allow laboratories to focus attention on more complex discrepancies.The ClinGen Dosage Sensitivity (DS) Map provides evidenceâ based assessments of the haploinsufficiency and triplosensitivity of genes/genomic regions. We identified 251 clinical copy number variants (CNVs) in ClinVar that overlapped known DS genes/regions but were not interpreted as â likely pathogenicâ or â pathogenic;â these were sent back to their original laboratories for reâ evaluation. Of the 246 that were reâ evaluated, 63.0% resulted in updated classifications, showing that the ClinGen DS Map can be an effective initial step in CNV classification discrepancy resolution.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146425/1/humu23610_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146425/2/humu23610.pd

Ocean acidification reduces demersal zooplankton that reside in tropical coral reefs

The in situ effects of ocean acidification on zooplankton communities remain largely unexplored. Using natural volcanic CO2 seep sites around tropical coral communities, we show a threefold reduction in the biomass of demersal zooplankton in high-CO2 sites compared with sites with ambient CO2. Differences were consistent across two reefs and three expeditions. Abundances were reduced in most taxonomic groups. There were no regime shifts in zooplankton community composition and no differences in fatty acid composition between CO2 levels, suggesting that ocean acidification affects the food quantity but not the quality for nocturnal plankton feeders. Emergence trap data show that the observed reduction in demersal plankton may be partly attributable to altered habitat. Ocean acidification changes coral community composition from branching to massive bouldering coral species, and our data suggest that bouldering corals represent inferior daytime shelter for demersal zooplankton. Since zooplankton represent a major source of nutrients for corals, fish and other planktivores, this ecological feedback may represent an additional mechanism of how coral reefs will be affected by ocean acidification

The Knee Clinical Assessment Study – CAS(K). A prospective study of knee pain and knee osteoarthritis in the general population

BACKGROUND: Knee pain affects an estimated 25% of the adult population aged 50 years and over. Osteoarthritis is the most common diagnosis made in older adults consulting with knee pain in primary care. However, the relationship between this diagnosis and both the current disease-based definition of osteoarthritis and the regional pain syndrome of knee pain and disability is unclear. Expert consensus, based on current evidence, views the disease and the syndrome as distinct entities but the clinical usefulness of these two approaches to classifying knee pain in older adults has not been established. We plan to conduct a prospective, population-based, observational cohort study to investigate the relative merits of disease-based and regional pain syndrome-based approaches to classification and prognosis of knee pain in older adults. METHODS: All patients aged 50 years and over registered with three general practices in North Staffordshire will be invited to take part in a two-stage postal survey. Respondents to this survey phase who indicate that they have experienced knee pain within the previous 12 months will be invited to attend a research clinic for a detailed assessment. This will consist of clinical interview, physical examination, digital photography, plain x-rays, anthropometric measurement and a brief self-complete questionnaire. All consenting clinic attenders will be followed up by (i) general practice medical record review, (ii) repeat postal questionnaire at 18-months

Deciphering Normal Blood Gene Expression Variation—The NOWAC Postgenome Study

There is growing evidence that gene expression profiling of peripheral blood cells is a valuable tool for assessing gene signatures related to exposure, drug-response, or disease. However, the true promise of this approach can not be estimated until the scientific community has robust baseline data describing variation in gene expression patterns in normal individuals. Using a large representative sample set of postmenopausal women (N = 286) in the Norwegian Women and Cancer (NOWAC) postgenome study, we investigated variability of whole blood gene expression in the general population. In particular, we examined changes in blood gene expression caused by technical variability, normal inter-individual differences, and exposure variables at proportions and levels relevant to real-life situations. We observe that the overall changes in gene expression are subtle, implying the need for careful analytic approaches of the data. In particular, technical variability may not be ignored and subsequent adjustments must be considered in any analysis. Many new candidate genes were identified that are differentially expressed according to inter-individual (i.e. fasting, BMI) and exposure (i.e. smoking) factors, thus establishing that these effects are mirrored in blood. By focusing on the biological implications instead of directly comparing gene lists from several related studies in the literature, our analytic approach was able to identify significant similarities and effects consistent across these reports. This establishes the feasibility of blood gene expression profiling, if they are predicated upon careful experimental design and analysis in order to minimize confounding signals, artifacts of sample preparation and processing, and inter-individual differences