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Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
Parkinson's disease (PD) shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF). Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (<= 1.5 kDa) in the plasma and CSF from early PD patients (disease duration 0-4 years; n = 80 and 40, respectively), and sex-and age-matched controls (n = 76 and 38, respectively). We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. The semetabolites differentiated the test set with an AUC of 0.8 (plasma) and 0.9 (CSF). Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD
We combine HST imaging from the GEMS ( Galaxy Evolution from Morphologies and SEDs) survey with photometric redshifts from COMBO-17 to explore the evolution of disk-dominated galaxies since z less than or similar to 1.1. The sample is composed of all GEMS galaxies with Sersic indices n < 2.5, derived from fits to the galaxy images. We account fully for selection effects through careful analysis of image simulations; we are limited by the depth of the redshift and HST data to the study of galaxies with M-V less than or similar to -20, or equivalently, log (M/M-circle dot) greater than or similar to 10. We find strong evolution in the magnitude-size scaling relation for galaxies with M-V less than or similar to -20, corresponding to a brightening of similar to 1 mag arcsec(-2) in rest-frame V band by z similar to 1. Yet disks at a given absolute magnitude are bluer and have lower stellar mass-to-light ratios at z similar to 1 than at the present day. As a result, our findings indicate weak or no evolution in the relation between stellar mass and effective disk size for galaxies with log (M/M-circle dot) greater than or similar to 10 over the same time interval. This is strongly inconsistent with the most naive theoretical expectation, in which disk size scales in proportion to the halo virial radius, which would predict that disks are a factor of 2 denser at fixed mass at z similar to 1. The lack of evolution in the stellar mass-size relation is consistent with an "inside-out'' growth of galaxy disks on average (galaxies increasing in size as they grow more massive), although we cannot rule out more complex evolutionary scenarios
Computational methods for the design of effective therapies against drug resistant HIV strains
(2005)
The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure exerted by the human immune system and by combination drug therapy. We have developed several computational methods whose combined use can support the design of optimal antiretroviral therapies based on viral genomic data
We have performed Hubble Space Telescope imaging of a sample of 23 high-redshift (1.8<z<2.75) active galactic nuclei (AGNs), drawn from the COMBO-17 survey. The sample contains moderately luminous quasars (M(B)similar to-23). The data are part of the Galaxy Evolution from Morphologies and SEDs imaging survey that provides high-resolution optical images obtained with the Advanced Camera for Surveys in two bands (F606W and F850LP), sampling the rest-frame UV flux of the targets. To deblend the AGN images into nuclear and resolved (host galaxy) components, we use a point-spread function subtraction technique that is strictly conservative with respect to the flux of the host galaxy. We resolve the host galaxies in both filter bands in nine of the 23 AGNs, whereas the remaining 14 objects are considered nondetections, with upper limits of less than 5% of the nuclear flux. However, when we co-add the unresolved AGN images into a single high signal-to-noise ratio composite image, we find again an unambiguously resolved host galaxy. The recovered host galaxies have apparent magnitudes of 23.0<F606W<26.0 and 22.5<F850LP<24.5, with rest-frame UV colors in the range -0.2<(F606W-F850LP)(obs)<2.3. The rest-frame absolute magnitudes at 200 nm are -20.0<M-200 nm<-22.2. The photometric properties of the composite host are consistent with the individual resolved host galaxies. We find that the UV colors of all host galaxies are substantially bluer than expected from an old population of stars with formation redshift z<=5, independent of the assumed metallicities. These UV colors and luminosities range up to the values found for Lyman break galaxies (LBGs) at z=3. Our results suggest either a recent starburst of, e. g., a few percent of the total stellar mass at 100 Myr before observation, with mass fraction and age strongly degenerate, or the possibility that the detected UV emission may be due to young stars forming continuously. For the latter case we estimate star formation rates of typically &SIM;6 M&ODOT; yr(-1) (uncorrected for internal dust attenuation), which again lies in the range of rates implied from the UV flux of LBGs. Our results agree with the recent discovery of enhanced blue stellar light in AGN hosts at lower redshifts
We present the results from a study of the host galaxies of 15 optically selected active galactic nuclei (AGNs) with 0.5<z<1.1 from the Galaxy Evolution from Morphology and SEDs project (GEMS). GEMS is a Hubble Space Telescope imaging survey of a similar to28' x 28' contiguous field centered on the Chandra Deep Field-South in the F606W and F850LP filter bands. It incorporates the spectral energy distributions and redshifts of similar to10,000 objects, obtained by the COMBO-17 project. We have detected the host galaxies of all 15 AGNs in the F850LP band (and 13 of 15 in the F606W band), recovering their fluxes, morphologies, and structural parameters. We find that 80% of the host galaxies have early-type (bulge-dominated) morphologies, while the rest have structures characteristic of late-type (disk-dominated) galaxies. We find that 25% of the early types and 30% of the late types exhibit disturbances consistent with galaxy interactions. The hosts show a wide range of colors, from those of red-sequence galaxies to blue colors consistent with ongoing star formation. Roughly 70% of the morphologically early-type hosts have rest-frame blue colors, a much larger fraction than those typical of nonactive morphologically early-type galaxies in this redshift and luminosity range. Yet, we find that the early-type hosts are structurally similar to red-sequence elliptical galaxies, inasmuch as they follow an absolute magnitude versus half-light size correlation that is consistent with the mean relation for early-type galaxies at similar redshifts
Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis of PPMS and its differentiation from the relapsing remitting subtype (RRMS), primary neurodegenerative disease (Parkinson’s disease, PD), and healthy controls (HCs) and that significantly change during the disease course and could serve as surrogate markers of multiple sclerosis (MS)-associated neurodegeneration over time. We applied untargeted high-resolution metabolomics to plasma samples to identify PPMS-specific signatures, validated our findings in independent sex- and age-matched PPMS and HC cohorts and built discriminatory models by partial least square discriminant analysis (PLS-DA). This signature was compared to sex- and age-matched RRMS patients, to patients with PD and HC. Finally, we investigated these metabolites in a longitudinal cohort of PPMS patients over a 24-month period. PLS-DA yielded predictive models for classification along with a set of 20 PPMS-specific informative metabolite markers. These metabolites suggest disease-specific alterations in glycerophospholipid and linoleic acid pathways. Notably, the glycerophospholipid LysoPC(20:0) significantly decreased during the observation period. These findings show potential for diagnosis and disease course monitoring, and might serve as biomarkers to assess treatment efficacy in future clinical trials for neuroprotective MS therapies.
Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/MuteSwan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.
Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/MuteSwan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.