An expanded multilocus sequence typing scheme for propionibacterium acnes : investigation of 'pathogenic', 'commensal' and antibiotic resistant strains

The Gram-positive bacterium Propionibacterium acnes is a member of the normal human skin microbiota and is associated with various infections and clinical conditions. There is tentative evidence to suggest that certain lineages may be associated with disease and others with health. We recently described a multilocus sequence typing scheme (MLST) for P. acnes based on seven housekeeping genes (http://pubmlst.org/pacnes). We now describe an expanded eight gene version based on six housekeeping genes and two ‘putative virulence’ genes (eMLST) that provides improved high resolution typing (91eSTs from 285 isolates), and generates phylogenies congruent with those based on whole genome analysis. When compared with the nine gene MLST scheme developed at the University of Bath, UK, and utilised by researchers at Aarhus University, Denmark, the eMLST method offers greater resolution. Using the scheme, we examined 208 isolates from disparate clinical sources, and 77 isolates from healthy skin. Acne was predominately associated with type IA1 clonal complexes CC1, CC3 and CC4; with eST1 and eST3 lineages being highly represented. In contrast, type IA2 strains were recovered at a rate similar to type IB and II organisms. Ophthalmic infections were predominately associated with type IA1 and IA2 strains, while type IB and II were more frequently recovered from soft tissue and retrieved medical devices. Strains with rRNA mutations conferring resistance to antibiotics used in acne treatment were dominated by eST3, with some evidence for intercontinental spread. In contrast, despite its high association with acne, only a small number of resistant CC1 eSTs were identified. A number of eSTs were only recovered from healthy skin, particularly eSTs representing CC72 (type II) and CC77 (type III). Collectively our data lends support to the view that pathogenic versus truly commensal lineages of P. acnes may exist. This is likely to have important therapeutic and diagnostic implications

Low Temperature District Heating for Future Energy Systems

The building sector is responsible for more than one third of the final energy consumption of societies and produces the largest amount of greenhouse gas emissions of all sectors. This is due to the utilisation of combustion processes of mainly fossil fuels to satisfy the heating demand of the building stock. Low temperature district heating (LTDH) can contribute significantly to a more efficient use of energy resources as well as better integration of renewable energy (e.g. geothermal or solar heat), and surplus heat (e.g. industrial waste heat) into the heating sector. LTDH offers prospects for both the demand side (community building structure) and the supply side (network properties or energy sources). Especially in connection with buildings that demand only low temperatures for space heating. The utilisation of lower temperatures reduces losses in pipelines and can increase the overall efficiency of the total energy chains used in district heating. To optimise the exergy efficiency of community supply systems the LowEx approach can be utilised, which entails matching the quality levels of energy supply and demand in order to optimise the utilisation of high-value resources, such as combustible fuels, and minimising energy losses and irreversible dissipation. The paper presents the international co-operative work in the framework of the International Energy Agency (IEA), the Technology Cooperation Programme on District Heating and Cooling including Combined Heat and Power (DHC|CHP) Annex TS1

Profiling the SO2 Plume from Volcan Turrialba: Ticosonde Balloon Measurements Compared with OMI and OMPS Retrievals

The summit of Volcan Turrialba (elev. 3340 m) lies less than 50 km upstream in the prevailing easterlies from the Ticosonde balloon launch site at San Jose, Costa Rica, where ECC ozone sondes have been launched regularly since 2005. In 2006 we began to see telltale notches in the ozone profiles in the altitude range between 2 and 6 km. Given the proximity of Turrialba, it seemed likely that SO2 in the volcano's plume was interfering in the chemical reaction in the ECC ozone sonde used to detect ozone. In early 2010, fumarolic activity in the Turrialba crater increased strongly, and the profile notches in our soundings increased in frequency as well, consistent with this hypothesis. In February 2012 we tested a dual ECC sonde system, where an additional sonde is flown on the same payload using a selective SO2 filter. The difference of the measurements in the dual sonde is a direct measure of the amount of SO2 encountered. This first dual sonde passed through the plume, and the data indicated a tropospheric SO2 column of 1.4 DU, comparing favorably with a total column of 1.7 DU in the OMI 3-km linear fit (LF) product at the sonde profile location and at nearly the same time. We are now launching dual sondes on a regular basis with 18 launches in the first 12 months through July 2014; 11 of these have detectable SO2 signals. These soundings have great potential for validation of the Aura OMI and the Suomi-NPP OMPS retrievals of SO2. Here we present the sonde measurements and compare them with two satellite datasets: the Aura OMI Linear Fit (LF) product and the Suomi-NPP OMPS Principal Components Analysis (PCA) boundary layer product. The PCA algorithm reduces retrieval noise and artifacts by more accurately accounting for various interferences in SO2 retrievals such as O3 absorption and rotational Raman scattering. The comparisons with the in situ observations indicate a significant improvement of the PCA algorithm in capturing relatively weak volcanic SO2 signals

Probing Hot Gas in Galaxy Groups through the Sunyaev-Zeldovich Effect

We investigate the potential of exploiting the Sunyaev-Zeldovich effect (SZE) to study the properties of hot gas in galaxy groups. It is shown that, with upcoming SZE surveys, one can stack SZE maps around galaxy groups of similar halo masses selected from large galaxy redshift surveys to study the hot gas in halos represented by galaxy groups. We use various models for the hot halo gas to study how the expected SZE signals are affected by gas fraction, equation of state, halo concentration, and cosmology. Comparing the model predictions with the sensitivities expected from the SPT, ACT and Planck surveys shows that a SPT-like survey can provide stringent constraints on the hot gas properties for halos with masses M ~> 10^{13} h^{-1}Msun. We also explore the idea of using the cross correlation between hot gas and galaxies of different luminosity to probe the hot gas in dark matter halos without identifying galaxy groups to represent dark halos. Our results show that, with a galaxy survey as large as the Sloan Digital Sky Survey and with the help of the conditional luminosity function (CLF) model, one can obtain stringent constraints on the hot gas properties in halos with masses down to 10^{13} h^{-1}Msun. Thus, the upcoming SZE surveys should provide a very promising avenue to probe the hot gas in relatively low-mass halos where the majority of L*-galaxies reside.Comment: 22 pages, 16 figures, accepted for publication on MNRA

Multiwavelength VLBI observations of Sagittarius A*

The compact radio source Sgr\,A*, associated with the super massive black hole at the center of the Galaxy, has been studied with VLBA observations at 3 frequencies (22, 43, 86\,GHz) performed on 10 consecutive days in May 2007. The total VLBI flux density of Sgr\,A* varies from day to day. The variability is correlated at the 3 observing frequencies with higher variability amplitudes appearing at the higher frequencies. For the modulation indices, we find 8.4\,% at 22\,GHz, 9.3\,% at 43\,GHz, and 15.5\,% at 86\,GHz. The radio spectrum is inverted between 22 and 86\,GHz, suggesting inhomogeneous synchrotron self-absorption with a turnover frequency at or above 86\,GHz. The radio spectral index correlates with the flux density, which is harder (more inverted spectrum) when the source is brighter. The average source size does not appear to be variable over the 10-day observing interval. However, we see a tendency for the sizes of the minor axis to increase with increasing total flux, whereas the major axis remains constant. Towards higher frequencies, the position angle of the elliptical Gaussian increases, indicative of intrinsic structure, which begins to dominate the scatter broadening. At cm-wavelength, the source size varies with wavelength as $\lambda^{2.12\pm0.12}$, which is interpreted as the result of interstellar scatter broadening. After removal of this scatter broadening, the intrinsic source size varies as $\lambda^{1.4 ... 1.5}$. The VLBI closure phases at 22, 43, and 86\,GHz are zero within a few degrees, indicating a symmetric or point-like source structure. In the context of an expanding plasmon model, we obtain an upper limit of the expansion velocity of about 0.1\,c from the non-variable VLBI structure. This agrees with the velocity range derived from the radiation transport modeling of the flares from the radio to NIR wavelengths.}Comment: 14pages, 14 Figures, Accepted for publication in A&

Accurate and exact CNV identification from targeted high-throughput sequence data

<p>Abstract</p> <p>Background</p> <p>Massively parallel sequencing of barcoded DNA samples significantly increases screening efficiency for clinically important genes. Short read aligners are well suited to single nucleotide and indel detection. However, methods for CNV detection from targeted enrichment are lacking. We present a method combining coverage with map information for the identification of deletions and duplications in targeted sequence data.</p> <p>Results</p> <p>Sequencing data is first scanned for gains and losses using a comparison of normalized coverage data between samples. CNV calls are confirmed by testing for a signature of sequences that span the CNV breakpoint. With our method, CNVs can be identified regardless of whether breakpoints are within regions targeted for sequencing. For CNVs where at least one breakpoint is within targeted sequence, exact CNV breakpoints can be identified. In a test data set of 96 subjects sequenced across ~1 Mb genomic sequence using multiplexing technology, our method detected mutations as small as 31 bp, predicted quantitative copy count, and had a low false-positive rate.</p> <p>Conclusions</p> <p>Application of this method allows for identification of gains and losses in targeted sequence data, providing comprehensive mutation screening when combined with a short read aligner.</p

The sialic acid-dependent nematocyst discharge process in relation to its physical-chemical properties is a role model for nanomedical diagnostic and therapeutic tools

Formulas derived from theoretical physics provide important insights about the nematocyst discharge process of Cnidaria (Hydra, jellyfishes, box-jellyfishes and sea-anemones). Our model description of the fastest process in living nature raises and answers questions related to the material properties of the cell- and tubule-walls of nematocysts including their polysialic acid (polySia) dependent target function. Since a number of tumor-cells, especially brain-tumor cells such as neuroblastoma tissues carry the polysaccharide chain polySia in similar concentration as fish eggs or fish skin, it makes sense to use these findings for new diagnostic and therapeutic approaches in the field of nanomedicine. Therefore, the nematocyst discharge process can be considered as a bionic blue-print for future nanomedical devices in cancer diagnostics and therapies. This approach is promising because the physical background of this process can be described in a sufficient way with formulas presented here. Additionally, we discuss biophysical and biochemical experiments which will allow us to define proper boundary conditions in order to support our theoretical model approach. PolySia glycans occur in a similar density on malignant tumor cells than on the cell surfaces of Cnidarian predators and preys. The knowledge of the polySia-dependent initiation of the nematocyst discharge process in an intact nematocyte is an essential prerequisite regarding the further development of target-directed nanomedical devices for diagnostic and therapeutic purposes. The theoretical description as well as the computationally and experimentally derived results about the biophysical and biochemical parameters can contribute to a proper design of anti-tumor drug ejecting vessels which use a stylet-tubule system. Especially, the role of nematogalectins is of interest because these bridging proteins contribute as well as special collagen fibers to the elastic band properties. The basic concepts of the nematocyst discharge process inside the tubule cell walls of nematocysts were studied in jellyfishes and in Hydra which are ideal model organisms. Hydra has already been chosen by Alan Turing in order to figure out how the chemical basis of morphogenesis can be described in a fundamental way. This encouraged us to discuss the action of nematocysts in relation to morphological aspects and material requirements. Using these insights, it is now possible to discuss natural and artificial nematocyst-like vessels with optimized properties for a diagnostic and therapeutic use, e.g., in neurooncology. We show here that crucial physical parameters such as pressure thresholds and elasticity properties during the nematocyst discharge process can be described in a consistent and satisfactory way with an impact on the construction of new nanomedical devices

CONTRA: copy number analysis for targeted resequencing

Motivation: In light of the increasing adoption of targeted resequencing (TR) as a cost-effective strategy to identify disease-causing variants, a robust method for copy number variation (CNV) analysis is needed to maximize the value of this promising technology

Star Formation in the Central 400 pc of the Milky Way: Evidence for a Population of Massive YSOs

The central kpc of the Milky Way might be expected to differ significantly from the rest of the Galaxy with regard to gas dynamics and the formation of YSOs. We probe this possibility with mid-infrared observations obtained with IRAC and MIPS on Spitzer and with MSX. We use color-color diagrams and SED fits to explore the nature of YSO candidates (including objects with 4.5 micron excesses possibly due to molecular emission). There is an asymmetry in the distribution of the candidate YSOs, which tend to be found at negative Galactic longitudes; this behavior contrasts with that of the molecular gas, approximately 2/3 of which is at positive longitudes. The small scale height of these objects suggests that they are within the Galactic center region and are dynamically young. They lie between two layers of infrared dark clouds and may have originated from these clouds. We identify new sites for this recent star formation. The methanol masers appear to be associated with young, embedded YSOs characterized by 4.5 micron excesses. We use the SEDs of these sources to estimate their physical characteristics. Within the central 400x50 pc (|l|<1.3\degr and |b|<10') the star formation rate based on the identification of Stage I evolutionary phase of YSO candidates is about 0.14 solar mass/yr. We suggest that a recent burst of star formation took place within the last 10^5 years. This suggestion is also consistent with estimates of star formation rates within the last ~10^7 years showing a peak around 10^5 years ago. Lastly, we find that the Schmidt-Kennicutt Law applies well in the central 400 pc of the Galaxy. This implies that star formation does not appear to be dramatically affected by the extreme physical conditions in the Galactic center region.Comment: 96 pages, ten tables, 35 figures, ApJ (in press), replaced by a revised versio