Performance of ePix10K, a high dynamic range, gain auto-ranging pixel detector for FELs

ePix10K is a hybrid pixel detector developed at SLAC for demanding free-electron laser (FEL) applications, providing an ultrahigh dynamic range (245 eV to 88 MeV) through gain auto-ranging. It has three gain modes (high, medium and low) and two auto-ranging modes (high-to-low and medium-to-low). The first ePix10K cameras are built around modules consisting of a sensor flip-chip bonded to 4 ASICs, resulting in 352x384 pixels of 100 $\mu$m x 100 $\mu$m each. We present results from extensive testing of three ePix10K cameras with FEL beams at LCLS, resulting in a measured noise floor of 245 eV rms, or 67 e$^-$ equivalent noise charge (ENC), and a range of 11000 photons at 8 keV. We demonstrate the linearity of the response in various gain combinations: fixed high, fixed medium, fixed low, auto-ranging high to low, and auto-ranging medium-to-low, while maintaining a low noise (well within the counting statistics), a very low cross-talk, perfect saturation response at fluxes up to 900 times the maximum range, and acquisition rates of up to 480 Hz. Finally, we present examples of high dynamic range x-ray imaging spanning more than 4 orders of magnitude dynamic range (from a single photon to 11000 photons/pixel/pulse at 8 keV). Achieving this high performance with only one auto-ranging switch leads to relatively simple calibration and reconstruction procedures. The low noise levels allow usage with long integration times at non-FEL sources. ePix10K cameras leverage the advantages of hybrid pixel detectors with high production yield and good availability, minimize development complexity through sharing the hardware, software and DAQ development with all other versions of ePix cameras, while providing an upgrade path to 5 kHz, 25 kHz and 100 kHz in three steps over the next few years, matching the LCLS-II requirements.Comment: 9 pages, 5 figure

Incidence, Timing, and Correlates of Stent Thrombosis With the Polymeric Paclitaxel Drug-Eluting Stent

n/

Institutional conditions for integrated mobility services (IMS): Towards a framework for analysis

The present text is a theoretical framework that has been developed with the aim to generate knowledge of and policy recommendations for the promotion of integrated mobility services (IMS), with specific regard to institutional dimensions. Integrated mobility services are services where the passenger’s transport needs are met by a service that not only integrates a range of mobility services, both public and private, but also provides one-stop access to all services through a common interface. These types of services are currently being developed in several cities globally, and the purpose of the project is to understand and explain how institutions can enable, but also impede, their realization. Institutions are defined as a relatively stable collection of rules and practices, embedded in structures that enable action. In the project a broad theoretical approach, developed by an interdisciplinary research team, will be applied. As such, the framework includes factors at the macro, meso and micro levels, thus including extensive societal trends as well as individual\u27s needs and behaviour. The macro level includes broader social and political factors, including both formal rules and more informal social norms and perceptions. The division between formal and informal variables recur on the meso and micro levels respectively. The meso level – which includes both public and private actors at regional and local levels – consists of both formal institutional factors such as taxation and regulations, and informal factors such as organizational culture and inherited networks between regional actors. Each actor enters the collaborative processes that signify IMS with their own ideals, interests and expectations, and it is in these processes of negotiation that the framework takes it point of departure. It is also in this context that business models will be developed, another central aspect of the realisation of IMS. Finally, the framework also includes the micro level, where an individual perspective is placed at centre stage. Individuals are affected by various formal incentives and push factors, as well as more informal aspects such as self-image and social status. Through the application of the framework in a number of case studies, empirical findings will help illuminate which institutional factors enable or constrain the development of IMS. The findings will provide the empirical and analytical foundation for suggestions on how formal and informal rules and practices can be modified to enable new IMS to contribute to sustainable mobility

Identification of ER-000444793, a Cyclophilin D-independent inhibitor of mitochondrial permeability transition, using a high-throughput screen in cryopreserved mitochondria

Growing evidence suggests persistent mitochondrial permeability transition pore (mPTP) opening is a key pathophysiological event in cell death underlying a variety of diseases. While it has long been clear the mPTP is a druggable target, current agents are limited by off-target effects and low therapeutic efficacy. Therefore identification and development of novel inhibitors is necessary. To rapidly screen large compound libraries for novel mPTP modulators, a method was exploited to cryopreserve large batches of functionally active mitochondria from cells and tissues. The cryopreserved mitochondria maintained respiratory coupling and ATP synthesis, Ca(2+) uptake and transmembrane potential. A high-throughput screen (HTS), using an assay of Ca(2+)-induced mitochondrial swelling in the cryopreserved mitochondria identified ER-000444793, a potent inhibitor of mPTP opening. Further evaluation using assays of Ca(2+)-induced membrane depolarisation and Ca(2+) retention capacity also indicated that ER-000444793 acted as an inhibitor of the mPTP. ER-000444793 neither affected cyclophilin D (CypD) enzymatic activity, nor displaced of CsA from CypD protein, suggesting a mechanism independent of CypD inhibition. Here we identified a novel, CypD-independent inhibitor of the mPTP. The screening approach and compound described provides a workflow and additional tool to aid the search for novel mPTP modulators and to help understand its molecular nature

Sneutrino cold dark matter, a new analysis: relic abundance and detection rates

We perform a new and updated analysis of sneutrinos as dark matter candidates, in different classes of supersymmetric models. We extend previous analyses by studying sneutrino phenomenology for full variations of the supersymmetric parameters which define the various models. We first revisit the standard Minimal Supersymmetric Standard Model, concluding that sneutrinos are marginally compatible with existing experimental bounds, including direct detection, provided they compose a subdominant component of dark matter. We then study supersymmetric models with the inclusion of right-handed fields and lepton-number violating terms. Simple versions of the lepton-number-violating models do not lead to phenomenology different from the standard case when the neutrino mass bounds are properly included. On the contrary, models with right-handed fields are perfectly viable: they predict sneutrinos which are compatible with the current direct detection sensitivities, both as subdominant and dominant dark matter components. We also study the indirect detection signals for such successful models: predictions for antiproton, antideuteron and gamma-ray fluxes are provided and compared with existing and future experimental sensitivities. The neutrino flux from the center of the Earth is also analyzed.Comment: 72 pages, 50 figures. The version on the archive has low-resolution figures. The paper with high resolution figures may be found through http://www.to.infn.it/~arina/papers or http://www.to.infn.it/~fornengo/Research/paperlist.htm

Spatial competition in a global disturbance minimum; the seabed under an Antarctic ice shelf

The marine habitat beneath Antarctica's ice shelves spans ∼1.6 million km2, and life in this vast and extreme environment is among Earth's least accessible, least disturbed and least known, yet likely to be impacted by climate-forced warming and environmental change. Although competition among biota is a fundamental structuring force of ecological communities, hence ecosystem functions and services, nothing was known of competition for resources under ice shelves, until this study. Boreholes drilled through a ∼ 200 m thick ice shelf enabled collections of novel sub-ice-shelf seabed sediment which contained fragments of biogenic substrata rich in encrusting (lithophilic) macrobenthos, principally bryozoans – a globally-ubiquitous phylum sensitive to environmental change. Analysis of sub-glacial biogenic substrata, by stereo microscopy, provided first evidence of spatial contest competition, enabling generation of a new range of competition measures for the sub-ice-shelf benthic space. Measures were compared with those of global open-water datasets traversing polar, temperate and tropical latitudes (and encompassing both hemispheres). Spatial competition in sub-ice-shelf samples was found to be higher in intensity and severity than all other global means. The likelihood of sub-ice-shelf competition being intraspecific was three times lower than for open-sea polar continental shelf areas, and competition complexity, in terms of the number of different types of competitor pairings, was two-fold higher. As posited for an enduring disturbance minimum, a specific bryozoan clade was especially competitively dominant in sub-ice-shelf samples compared with both contemporary and fossil assemblage records. Overall, spatial competition under an Antarctic ice shelf, as characterised by bryozoan interactions, was strikingly different from that of open-sea polar continental shelf sites, and more closely resembled tropical and temperate latitudes. This study represents the first analysis of sub-ice-shelf macrobenthic spatial competition and provides a new ecological baseline for exploring, monitoring and comparing ecosystem response to environmental change in a warming world

Polymer-based paclitaxel-eluting stents reduce in-stent neointimal tissue proliferation A serial volumetric intravascular ultrasound analysis from the TAXUS-IV trial

ObjectivesThe aim of this study was to use serial volumetric intravascular ultrasound (IVUS) to evaluate the effects of polymer-based, paclitaxel-eluting stents on in-stent neointima formation and late incomplete stent apposition.BackgroundThe TAXUS-IV trial demonstrated that the slow-release, polymer-based, paclitaxel-eluting stent reduces angiographic restenosis and the need for repeat revascularization procedures. Serial IVUS studies reveal details of the pattern of vascular responses provoked by stent implantation that provide insight into device safety and efficacy.MethodsIn the TAXUS-IV trial, patients were randomized to the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or a bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). As part of a formal substudy, complete volumetric IVUS data were available in 170 patients, including 88 TAXUS patients and 82 controls, at implantation and at nine-month follow-up.ResultsNo baseline differences were present in the clinical characteristics or IVUS parameters between the control and TAXUS groups. At nine-month follow-up, IVUS lumen volumes were larger in the TAXUS group (123 ± 43 mm3vs. 104 ± 44 mm3, p = 0.005), due to a reduction in neointimal volume (18 ± 18 mm3vs. 41 ± 23 mm3, p < 0.001). Millimeter-by-millimeter analysis within the stent demonstrated uniform suppression of neointimal growth along the entire stent length. Late lumen loss was similar at the proximal edge of the stent between the two groups, and reduced with the TAXUS stent at the distal edge (p = 0.004). Incomplete stent apposition at nine months was observed in only 3.0% of control and 4.0% of TAXUS stents (p = 0.12).ConclusionsPolymer-based, paclitaxel-eluting TAXUS stents are effective in inhibiting neointimal tissue proliferation, and do not result in late incomplete stent apposition

Fluorescent Fusion Proteins of Soluble Guanylyl Cyclase Indicate Proximity of the Heme Nitric Oxide Domain and Catalytic Domain

BACKGROUND: To examine the structural organisation of heterodimeric soluble guanylyl cyclase (sGC) Förster resonance energy transfer (FRET) was measured between fluorescent proteins fused to the amino- and carboxy-terminal ends of the sGC beta1 and alpha subunits. METHODOLOGY/PRINCIPAL FINDINGS: Cyan fluorescent protein (CFP) was used as FRET donor and yellow fluorescent protein (YFP) as FRET acceptor. After generation of recombinant baculovirus, fluorescent-tagged sGC subunits were co-expressed in Sf9 cells. Fluorescent variants of sGC were analyzed in vitro in cytosolic fractions by sensitized emission FRET. Co-expression of the amino-terminally tagged alpha subunits with the carboxy-terminally tagged beta1 subunit resulted in an enzyme complex that showed a FRET efficiency of 10% similar to fluorescent proteins separated by a helix of only 48 amino acids. Because these findings indicated that the amino-terminus of the alpha subunits is close to the carboxy-terminus of the beta1 subunit we constructed fusion proteins where both subunits are connected by a fluorescent protein. The resulting constructs were not only fluorescent, they also showed preserved enzyme activity and regulation by NO. CONCLUSIONS/SIGNIFICANCE: Based on the ability of an amino-terminal fragment of the beta1 subunit to inhibit activity of an heterodimer consisting only of the catalytic domains (alphacatbetacat), Winger and Marletta (Biochemistry 2005, 44:4083-90) have proposed a direct interaction of the amino-terminal region of beta1 with the catalytic domains. In support of such a concept of "trans" regulation of sGC activity by the H-NOX domains our results indicate that the domains within sGC are organized in a way that allows for direct interaction of the amino-terminal regulatory domains with the carboxy-terminal catalytic region. In addition, we constructed "fluorescent-conjoined" sGC's by fusion of the alpha amino-terminus to the beta1 carboxy-terminus leading to a monomeric, fluorescent and functional enzyme complex. To our knowledge this represents the first example where a fluorescent protein links two different subunits of a higher ordered complex to yield a stoichometrically fixed functionally active monomer