ALMA Observations of Asteroid 3 Juno at 60 Kilometer Resolution

We present Atacama Large Millimeter/submillimeter Array (ALMA) 1.3 mm continuum images of the asteroid 3 Juno obtained with an angular resolution of 0.042 arcseconds (60 km at 1.97 AU). The data were obtained over a single 4.4 hr interval, which covers 60% of the 7.2 hr rotation period, approximately centered on local transit. A sequence of ten consecutive images reveals continuous changes in the asteroid's profile and apparent shape, in good agreement with the sky projection of the three-dimensional model of the Database of Asteroid Models from Inversion Techniques. We measure a geometric mean diameter of 259pm4 km, in good agreement with past estimates from a variety of techniques and wavelengths. Due to the viewing angle and inclination of the rotational pole, the southern hemisphere dominates all of the images. The median peak brightness temperature is 215pm13 K, while the median over the whole surface is 197pm15 K. With the unprecedented resolution of ALMA, we find that the brightness temperature varies across the surface with higher values correlated to the subsolar point and afternoon areas, and lower values beyond the evening terminator. The dominance of the subsolar point is accentuated in the final four images, suggesting a reduction in the thermal inertia of the regolith at the corresponding longitudes, which are possibly correlated to the location of the putative large impact crater. These results demonstrate ALMA's potential to resolve thermal emission from the surface of main belt asteroids, and to measure accurately their position, geometric shape, rotational period, and soil characteristics.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

First Results from High Angular Resolution ALMA Observations Toward the HL Tau Region

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations from the 2014 Long Baseline Campaign in dust continuum and spectral line emission from the HL Tau region. The continuum images at wavelengths of 2.9, 1.3, and 0.87 mm have unprecedented angular resolutions of 0.075 arcseconds (10 AU) to 0.025 arcseconds (3.5 AU), revealing an astonishing level of detail in the circumstellar disk surrounding the young solar analogue HL Tau, with a pattern of bright and dark rings observed at all wavelengths. By fitting ellipses to the most distinct rings, we measure precise values for the disk inclination (46.72pm0.05 degrees) and position angle (+138.02pm0.07 degrees). We obtain a high-fidelity image of the 1.0 mm spectral index ($\alpha$), which ranges from $\alpha\sim2.0$ in the optically-thick central peak and two brightest rings, increasing to 2.3-3.0 in the dark rings. The dark rings are not devoid of emission, we estimate a grain emissivity index of 0.8 for the innermost dark ring and lower for subsequent dark rings, consistent with some degree of grain growth and evolution. Additional clues that the rings arise from planet formation include an increase in their central offsets with radius and the presence of numerous orbital resonances. At a resolution of 35 AU, we resolve the molecular component of the disk in HCO+ (1-0) which exhibits a pattern over LSR velocities from 2-12 km/s consistent with Keplerian motion around a ~1.3 solar mass star, although complicated by absorption at low blue-shifted velocities. We also serendipitously detect and resolve the nearby protostars XZ Tau (A/B) and LkHa358 at 2.9 mm.Comment: 11 pages, 5 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma

Summary: The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma. : Using peptide phosphorylation profiling, Zomerman et al. identify two medulloblastoma phosphoprotein-signaling profiles that have prognostic value and are potentially targetable. They find that these profiles extend across transcriptome-based subgroup borders. This suggests that diverse genetic information converges on common protein-signaling pathways and highlights protein-signaling as a unique information layer. Keywords: medulloblastoma, protein-signaling, protein synthesis, MYC, TP53, proteome, phosphoproteom

An Overview of the 2014 ALMA Long Baseline Campaign

A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in the Astrophysical Journal Letters; this version with small changes to affiliation

Hemoglobin level predicts outcome for vulvar cancer patients independent of GLUT-1 and CA-IX expression in tumor tissue

Intratumoral hypoxia has been associated with poor prognosis in several solid tumors. The aim of this study was to determine whether the hypoxia-associated markers glucose transporter (GLUT)-1 and carbonic anhydrase (CA)-IX expression and preoperative hemoglobin (Hb) levels correlate with presence of inguinofemoral or distant metastases, and disease-free survival (DSS) in vulvar squamous cell carcinoma (SCC) patients. Vulvar SCC (n = 103) were reviewed for histopathological characteristics by an expert gynecopathologist and stained for GLUT-1 and CA-IX. Clinical data and preoperative Hb levels were obtained from medical records. No significant correlations were observed between GLUT-1 or CA-IX expression patterns and preoperative Hb levels, presence of inguinofemoral or distant metastases and DSS. However, anemic patients (Hb < 11.2 g/dL) had significantly more inguinofemoral metastases and lower Hb level was an independent prognostic factor for a worse DSS (p < 0.001). The number of comorbidic conditions was inversely correlated with preoperative Hb level. Preoperative Hb levels are associated with poor DSS for vulvar SCC patients, whereas tumor hypoxia reflected by GLUT-1 and CA-IX expression does not have a predictive value. Because preoperative Hb levels inversely correlated with the number of comorbidic conditions and not with GLUT-1 or CA-IX expression, it is most likely that preoperative Hb levels represent overall physical condition

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The 2014 ALMA Long Baseline Campaign: An Overview

Instrumentatio

Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study

Background: Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error. Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults aged 50 years and older. Findings: Global crude prevalence of avoidable vision impairment and blindness in adults aged 50 years and older did not change between 2010 and 2019 (percentage change −0·2% [95% UI −1·5 to 1·0]; 2019 prevalence 9·58 cases per 1000 people [95% IU 8·51 to 10·8], 2010 prevalence 96·0 cases per 1000 people [86·0 to 107·0]). Age-standardised prevalence of avoidable blindness decreased by −15·4% [–16·8 to −14·3], while avoidable MSVI showed no change (0·5% [–0·8 to 1·6]). However, the number of cases increased for both avoidable blindness (10·8% [8·9 to 12·4]) and MSVI (31·5% [30·0 to 33·1]). The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7–18·0]), followed by glaucoma (3·6 million cases [2·8–4·4]), undercorrected refractive error (2·3 million cases [1·8–2·8]), age-related macular degeneration (1·8 million cases [1·3–2·4]), and diabetic retinopathy (0·86 million cases [0·59–1·23]). Leading causes of MSVI were undercorrected refractive error (86·1 million cases [74·2–101·0]) and cataract (78·8 million cases [67·2–91·4]). Interpretation: Results suggest eye care services contributed to the observed reduction of age-standardised rates of avoidable blindness but not of MSVI, and that the target in an ageing global population was not reached. Funding: Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg

Expression map of 78 brainexpressed mouse orphan GPCRs provides a translational resource for neuropsychiatric research

Orphan G-protein-coupled receptors (oGPCRs) possess untapped potential for drug discovery. In the brain, oGPCRs are generally expressed at low abundance and their function is understudied. Expression profiling is an essential step to position oGPCRs in brain function and disease, however public databases provide only partial information. Here, we fine-map expression of 78 brain-oGPCRs in the mouse, using customized probes in both standard and supersensitive in situ hybridization. Images are available at http://ogpcr-neuromap.douglas.qc.ca. This searchable database contains over 8000 coronal brain sections across 1350 slides, providing the first public mapping resource dedicated to oGPCRs. Analysis with public mouse (60 oGPCRs) and human (56 oGPCRs) genome-wide datasets identifies 25 oGPCRs with potential to address emotional and/or cognitive dimensions of psychiatric conditions. We probe their expression in postmortem human brains using nanoString, and included data in the resource. Correlating human with mouse datasets reveals excellent suitability of mouse models for oGPCRs in neuropsychiatric research

Zugeigenschaften eines austenitischen Huellrohrstahls nach Korrosion mit Urandioxid und simulierten Spaltprodukten sowie Neutronenbestrahlung

The tensile properties of corroded and irradiated specimens were calculated using the tensile properties of only corroded, only irradiated and not exposed specimens. The corrosion medium used was hyperstoichiometric uranium dioxide with simulated fission products (Cs, I, Te). The flat tensile specimens were made from the austenitic fuel rod cladding steel type 1.4970. The model for calculation supposes the following correlation of the tensile properties Z: Z (corroded + irradiated) = Z (corroded). Z (irradiated)/Z (not exposed). The results of calculations and experiments agree well although the scattering of the experimental results caused by the corrosion is considerable. The following experimental parameters were investigated: test temperature, deformation rate, corrosion depth, simulated burnup and thermal-mechanical treatment of the material. (orig./HP)Es wurden die Zugeigenschaften von korrodierten und bestrahlten Proben aus den Zugeigenschaften von Proben im korrodierten, im bestrahlten und im Ausgangszustand berechnet. Als Korrosionsmedium wurde in Analogie zu Brueterbrennstaeben eine Mischung aus ueberstoechiometrischem Urandioxid und simulierten Spaltprodukten (Cs, I, Te) verwendet. Die Flachproben bestanden aus dem austenitischen Huellrohrstahl 1.4970. Das Rechenmodell setzt folgende Beziehung der Zugeigenschaften Z voraus: Z (korrod. + bestrahlt) = Z (korrod.). Z (bestrahlt): Z (Ausgangszustand). Die Ergebnisse der Berechnungen stimmen mit den Messergebnissen im Mittel gut ueberein, obwohl die korrosionsbedingten Steuungen der Messwerte z.T. erheblich sind. Als Parameter wurden die Verformungsgeschwindigkeit, die Prueftemperatur, die Korrosionstiefe, der simulierte Abbrand und der Werkstoffzustand variiert. (orig./HP)Available from TIB Hannover: ZA 5141(5188) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman