Design for an 8 Meter Monolithic UV/OIR Space Telescope

ATLAST-8 is an 8-meter monolithic UV/optical/NIR space observatory to be placed in orbit at Sun-Earth L2 by NASA's planned Ares V cargo launch vehicle. The ATLAST-8 will yield fundamental astronomical breakthroughs. The mission concept utilizes two enabling technologies: planned Ares-V launch vehicle (scheduled for 2019) and autonomous rendezvous and docking (AR&D). The unprecedented Ares-V payload and mass capacity enables the use of a massive, monolithic, thin-meniscus primary mirror - similar to a VLT or Subaru. Furthermore, it enables simple robust design rules to mitigate cost, schedule and performance risk. AR&D enables on-orbit servicing, extending mission life and enhancing science return

Peptide cargo tunes a network of correlated motions in human leukocyte antigens

Most biomolecular interactions are typically thought to increase the (local) rigidity of a complex, for example, in drug‐target binding. However, detailed analysis of specific biomolecular complexes can reveal a more subtle interplay between binding and rigidity. Here, we focussed on the human leucocyte antigen (HLA), which plays a crucial role in the adaptive immune system by presenting peptides for recognition by the αβ T‐cell receptor (TCR). The role that the peptide plays in tuning HLA flexibility during TCR recognition is potentially crucial in determining the functional outcome of an immune response, with obvious relevance to the growing list of immunotherapies that target the T‐cell compartment. We have applied high‐pressure/temperature perturbation experiments, combined with molecular dynamics simulations, to explore the drivers that affect molecular flexibility for a series of different peptide–HLA complexes. We find that different peptide sequences affect peptide–HLA flexibility in different ways, with the peptide cargo tuning a network of correlated motions throughout the pHLA complex, including in areas remote from the peptide‐binding interface, in a manner that could influence T‐cell antigen discrimination

ATLAST-8 Mission Concept Study for 8-Meter Monolithic UV/Optical Space Telescope

ATLAST-8m is an 8-meter monolithic UV/optical/NIR space observatory which could be placed in orbit at Sun-Earth L2 by a heavily lift launch vehicle. Two development study cycles have resulted in a detailed concept including a dual foci optical design; several primary mirror launch support and secondary mirror support structural designs; spacecraft propulsion, power and pointing control design; and thermal design. ATLAST-8m is designed to yield never before achieved performance to obtain fundamental astronomical breakthrough

AEGIS: The Clustering of X-ray AGN Relative to Galaxies at z~1

We measure the clustering of non-quasar X-ray AGN at z=0.7-1.4 in the AEGIS field. Using the cross-correlation of 113 Chandra-selected AGN, with a median log L_X=42.8 erg s^-1, with ~5,000 DEEP2 galaxies, we find that the X-ray AGN are fit by a power law with a clustering scale length of r_0=5.95 +/-0.90 h^-1 Mpc and slope gamma=1.66 +/-0.22. X-ray AGN have a similar clustering amplitude as red, quiescent and `green' transition galaxies at z~1 and are significantly more clustered than blue, star-forming galaxies. The X-ray AGN clustering strength is primarily determined by the host galaxy color; AGN in red host galaxies are significantly more clustered than AGN in blue host galaxies, with a relative bias that is similar to that of red to blue DEEP2 galaxies. We detect no dependence of clustering on optical brightness, X-ray luminosity, or hardness ratio within the ranges probed here. We find evidence for galaxies hosting X-ray AGN to be more clustered than a sample of galaxies with matching joint optical color and magnitude distributions. This implies that galaxies hosting X-ray AGN are more likely to reside in groups and more massive dark matter halos than galaxies of the same color and luminosity without an X-ray AGN. In comparison to optically-selected quasars in the DEEP2 fields, we find that X-ray AGN at z~1 are more clustered than optically-selected quasars (with a 2.6-sigma significance) and therefore likely reside in more massive dark matter halos. Our results are consistent with galaxies undergoing a quasar phase while in the blue cloud before settling on the red sequence with a lower-luminosity X-ray AGN, if they are similar objects at different evolutionary stages.Comment: 18 pages, accepted to ApJ, minor changes made to match accepted version, Figure 1 adde

Histone deacetylase inhibitors strongly sensitise neuroblastoma cells to TRAIL-induced apoptosis by a caspases-dependent increase of the pro- to anti-apoptotic proteins ratio

BACKGROUND: Neuroblastoma (NB) is the second most common solid childhood tumour, an aggressive disease for which new therapeutic strategies are strongly needed. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in most tumour cells, but not in normal tissues and therefore represents a valuable candidate in apoptosis-inducing therapies. Caspase-8 is silenced in a subset of highly malignant NB cells, which results in full TRAIL resistance. In addition, despite constitutive caspase-8 expression, or its possible restoration by different strategies, NB cells remain weakly sensitive to TRAIL indicating a need to develop strategies to sensitise NB cells to TRAIL. Histone deacetylase inhibitors (HDACIs) are a new class of anti-cancer agent inducing apoptosis or cell cycle arrest in tumour cells with very low toxicity toward normal cells. Although HDACIs were recently shown to increase death induced by TRAIL in weakly TRAIL-sensitive tumour cells, the precise involved sensitisation mechanisms have not been fully identified. METHODS: NB cell lines were treated with various doses of HDACIs and TRAIL, then cytotoxicity was analysed by MTS/PMS proliferation assays, apoptosis was measured by the Propidium staining method, caspases activity by colorimetric protease assays, and (in)activation of apoptotic proteins by immunoblotting. RESULTS: Sub-toxic doses of HDACIs strongly sensitised caspase-8 positive NB cell lines to TRAIL induced apoptosis in a caspases dependent manner. Combined treatments increased the activation of caspases and Bid, and the inactivation of the anti-apoptotic proteins XIAP, Bcl-x, RIP, and survivin, thereby increasing the pro- to anti-apoptotic protein ratio. It also enhanced the activation of the mitochondrial pathway. Interestingly, the kinetics of caspases activation and inactivation of anti-apoptotic proteins is accelerated by combined treatment with TRAIL and HDACIs compared to TRAIL alone. In contrast, cell surface expression of TRAIL-receptors or TRAIL is not affected by sub-toxic doses of HDACIs. CONCLUSION: HDACIs were shown to activate the mitochondrial pathway and to sensitise NB cells to TRAIL by enhancing the amplitude of the apoptotic cascade and by restoring an apoptosis-prone ratio of pro- to anti-apoptotic proteins. Combining HDACIs and TRAIL could therefore represent a weakly toxic and promising strategy to target TRAIL-resistant tumours such as neuroblastomas

Evolution of Intrinsic Scatter in the SFR-Stellar Mass Correlation at 0.5 < z < 3

We present estimates of intrinsic scatter in the star formation rate (SFR)–stellar mass (M_*) correlation in the redshift range 0.5 < z < 3.0 and in the mass range 10^7 < M_*<10^(11)M_⊙. We utilize photometry in the Hubble Ultradeep Field (HUDF12) and Ultraviolet Ultra Deep Field (UVUDF) campaigns and CANDELS/GOODS-S and estimate SFR, M_* from broadband spectral energy distributions and the best-available redshifts. The maximum depth of the UDF photometry (F160W 29.9 AB, 5σ depth) probes the SFR–M_* correlation down to M_* ~ 10^7M_⊙, a factor of 10–100× lower in M_* than previous studies, and comparable to dwarf galaxies in the local universe. We find the slope of the SFR–M_* relationship to be near unity at all redshifts and the normalization to decrease with cosmic time. We find a moderate increase in intrinsic scatter with cosmic time from 0.2 to 0.4 dex across the epoch of peak cosmic star formation. None of our redshift bins show a statistically significant increase in intrinsic scatter at low mass. However, it remains possible that intrinsic scatter increases at low mass on timescales shorter than ~100 Myr. Our results are consistent with a picture of gradual and self-similar assembly of galaxies across more than three orders of magnitude in stellar mass from as low as 10^7M_⊙

The Baryon Oscillation Spectroscopic Survey of SDSS-III

The Baryon Oscillation Spectroscopic Survey (BOSS) is designed to measure the scale of baryon acoustic oscillations (BAO) in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large scale structure. BOSS uses 1.5 million luminous galaxies as faint as i=19.9 over 10,000 square degrees to measure BAO to redshifts z<0.7. Observations of neutral hydrogen in the Lyman alpha forest in more than 150,000 quasar spectra (g<22) will constrain BAO over the redshift range 2.15<z<3.5. Early results from BOSS include the first detection of the large-scale three-dimensional clustering of the Lyman alpha forest and a strong detection from the Data Release 9 data set of the BAO in the clustering of massive galaxies at an effective redshift z = 0.57. We project that BOSS will yield measurements of the angular diameter distance D_A to an accuracy of 1.0% at redshifts z=0.3 and z=0.57 and measurements of H(z) to 1.8% and 1.7% at the same redshifts. Forecasts for Lyman alpha forest constraints predict a measurement of an overall dilation factor that scales the highly degenerate D_A(z) and H^{-1}(z) parameters to an accuracy of 1.9% at z~2.5 when the survey is complete. Here, we provide an overview of the selection of spectroscopic targets, planning of observations, and analysis of data and data quality of BOSS.Comment: 49 pages, 16 figures, accepted by A

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

Optical gain in 1.3-μm electrically driven dilute nitride VCSOAs

We report the observation of room-temperature optical gain at 1.3 μm in electrically driven dilute nitride vertical cavity semiconductor optical amplifiers. The gain is calculated with respect to injected power for samples with and without a confinement aperture. At lower injected powers, a gain of almost 10 dB is observed in both samples. At injection powers over 5 nW, the gain is observed to decrease. For nearly all investigated power levels, the sample with confinement aperture gives slightly higher gain

Identification of New Genes Involved in Human Adipogenesis and Fat Storage

Since the worldwide increase in obesity represents a growing challenge for health care systems, new approaches are needed to effectively treat obesity and its associated diseases. One prerequisite for advances in this field is the identification of genes involved in adipogenesis and/or lipid storage. To provide a systematic analysis of genes that regulate adipose tissue biology and to establish a target-oriented compound screening, we performed a high throughput siRNA screen with primary (pre)adipocytes, using a druggable siRNA library targeting 7,784 human genes. The primary screen showed that 459 genes affected adipogenesis and/or lipid accumulation after knock-down. Out of these hits, 333 could be validated in a secondary screen using independent siRNAs and 110 genes were further regulated on the gene expression level during adipogenesis. Assuming that these genes are involved in neutral lipid storage and/or adipocyte differentiation, we performed InCell-Western analysis for the most striking hits to distinguish between the two phenotypes. Beside well known regulators of adipogenesis and neutral lipid storage (i.e. PPARγ, RXR, Perilipin A) the screening revealed a large number of genes which have not been previously described in the context of fatty tissue biology such as axonemal dyneins. Five out of ten axonemal dyneins were identified in our screen and quantitative RT-PCR-analysis revealed that these genes are expressed in preadipocytes and/or maturing adipocytes. Finally, to show that the genes identified in our screen are per se druggable we performed a proof of principle experiment using an antagonist for HTR2B. The results showed a very similar phenotype compared to knock-down experiments proofing the “druggability”. Thus, we identified new adipogenesis-associated genes and those involved in neutral lipid storage. Moreover, by using a druggable siRNA library the screen data provides a very attractive starting point to identify anti-obesity compounds targeting the adipose tissue