GPI-anchor signal sequence influences PrPC sorting, shedding and signalling, and impacts on different pathomechanistic aspects of prion disease in mice

The cellular prion protein (PrPC) is a cell surface glycoprotein attached to the membrane by a glycosylphosphatidylinositol (GPI)-anchor and plays a critical role in transmissible, neurodegenerative and fatal prion diseases. Alterations in membrane attachment influence PrPC-associated signaling, and the development of prion disease, yet our knowledge of the role of the GPI-anchor in localization, processing, and function of PrPC in vivo is limited We exchanged the PrPC GPI-anchor signal sequence of for that of Thy-1 (PrPCGPIThy-1) in cells and mice. We show that this modifies the GPI-anchor composition, which then lacks sialic acid, and that PrPCGPIThy-1 is preferentially localized in axons and is less prone to proteolytic shedding when compared to PrPC. Interestingly, after prion infection, mice expressing PrPCGPIThy-1 show a significant delay to terminal disease, a decrease of microglia/astrocyte activation, and altered MAPK signaling when compared to wild-type mice. Our results are the first to demonstrate in vivo, that the GPI-anchor signal sequence plays a fundamental role in the GPI-anchor composition, dictating the subcellular localization of a given protein and, in the case of PrPC, influencing the development of prion disease

A distributed multiscale computation of a tightly coupled model using the Multiscale Modeling Language

AbstractNature is observed at all scales; with multiscale modeling, scientists bring together several scales for a holistic analysis of a phenomenon. The models on these different scales may require significant but also heterogeneous computational resources, creating the need for distributed multiscale computing. A particularly demanding type of multiscale models, tightly coupled, brings with it a number of theoretical and practical issues. In this contribution, a tightly coupled model of in-stent restenosis is first theoretically examined for its multiscale merits using the Multiscale Modeling Language (MML); this is aided by a toolchain consisting of MAPPER Memory (MaMe), the Multiscale Application Designer (MAD), and Gridspace Experiment Workbench. It is implemented and executed with the general Multiscale Coupling Library and Environment (MUSCLE). Finally, it is scheduled amongst heterogeneous infrastructures using the QCG-Broker. This marks the first occasion that a tightly coupled application uses distributed multiscale computing in such a general way

MaGICC discs: matching observed galaxy relationships over a wide stellar mass range

We use the same physical model to simulate four galaxies that match the relation between stellar and total mass, over a mass range that includes the vast majority of disc galaxies. The resultant galaxies, part of the Making Galaxies in a Cosmological Context (MaGICC) program, also match observed relations between luminosity, rotation velocity, size, colour, star formation rate, HI mass, baryonic mass, and metallicity. Radiation from massive stars and supernova energy regulate star formation and drive outflows, balancing the complex interplay between cooling gas, star formation, large scale outflows, and recycling of gas in a manner which correctly scales with the mass of the galaxy. Outflows also play a key role in simulating galaxies with exponential surface brightness profiles, flat rotation curves and dark matter cores. Our study implies that large scale outflows are the primary driver of the dependence of disc galaxy properties on mass. We show that the amount of outflows invoked in our model is required to meet the constraints provided by observations of OVI absorption lines in the circum-galactic-media of local galaxies

"LUDO" - Kids playing Distributed Denial of Service

Distributed denial of service attacks pose a serious threat to the availability of the network infrastructures and services. GE̿ANT, the pan-European network with terabit capacities witnesses close to hundreds of DDoS attacks on a daily basis. The reason is that DDoS attacks are getting larger, more sophisticated and frequent. At the same time, it has never been easier to execute DDoS attacks, e.g., Booter services offer paying customers without any technical knowledge the possibility to perform DDoS attacks as a service. Given the increasing size, frequency and complexity of DDoS attacks, there is a need to perform a collaborative mitigation. Therefore, we developed (i) a DDoSDB to share real attack data and allow collaborators to query, compare, and download attacks, (ii) the Security attack experimentation framework to test mitigation and response capabilities and (iii) a collaborative mitigation and response process among trusted partners to disseminate security event information. In addition to these developments, we present and would like to discuss our latest research results with experienced networking operators and bridging the gap between academic research and operational business

The {\eta}'-carbon potential at low meson momenta

The production of $\eta^\prime$ mesons in coincidence with forward-going protons has been studied in photon-induced reactions on $^{12}$C and on a liquid hydrogen (LH$_2$) target for incoming photon energies of 1.3-2.6 GeV at the electron accelerator ELSA. The $\eta^\prime$ mesons have been identified via the $\eta^\prime\rightarrow \pi^0 \pi^0\eta \rightarrow 6 \gamma$ decay registered with the CBELSA/TAPS detector system. Coincident protons have been identified in the MiniTAPS BaF$_2$ array at polar angles of $2^{\circ} \le \theta _{p} \le 11^{\circ}$. Under these kinematic constraints the $\eta^\prime$ mesons are produced with relatively low kinetic energy ($\approx$ 150 MeV) since the coincident protons take over most of the momentum of the incident-photon beam. For the C-target this allows the determination of the real part of the $\eta^\prime$-carbon potential at low meson momenta by comparing with collision model calculations of the $\eta^\prime$ kinetic energy distribution and excitation function. Fitting the latter data for $\eta^\prime$ mesons going backwards in the center-of-mass system yields a potential depth of V = $-$(44 $\pm$ 16(stat)$\pm$15(syst)) MeV, consistent with earlier determinations of the potential depth in inclusive measurements for average $\eta^\prime$ momenta of $\approx$ 1.1 GeV/$c$. Within the experimental uncertainties, there is no indication of a momentum dependence of the $\eta^\prime$-carbon potential. The LH$_2$ data, taken as a reference to check the data analysis and the model calculations, provide differential and integral cross sections in good agreement with previous results for $\eta^\prime$ photoproduction off the free proton.Comment: 9 pages, 13 figures. arXiv admin note: text overlap with arXiv:1608.0607

Thin disc, Thick Disc and Halo in a Simulated Galaxy

Within a cosmological hydrodynamical simulation, we form a disc galaxy with sub- components which can be assigned to a thin stellar disc, thick disk, and a low mass stellar halo via a chemical decomposition. The thin and thick disc populations so selected are distinct in their ages, kinematics, and metallicities. Thin disc stars are young (<6.6 Gyr), possess low velocity dispersion ({\sigma}U,V,W = 41, 31, 25 km/s), high [Fe/H], and low [O/Fe]. The thick disc stars are old (6.6<age<9.8 Gyrs), lag the thin disc by \sim21 km/s, possess higher velocity dispersion ({\sigma}U,V,W = 49, 44, 35 km/s), relatively low [Fe/H] and high [O/Fe]. The halo component comprises less than 4% of stars in the "solar annulus" of the simulation, has low metallicity, a velocity ellipsoid defined by ({\sigma}U,V,W = 62, 46, 45 km/s) and is formed primarily in-situ during an early merger epoch. Gas-rich mergers during this epoch play a major role in fuelling the formation of the old disc stars (the thick disc). This is consistent with studies which show that cold accretion is the main source of a disc galaxy's baryons. Our simulation initially forms a relatively short (scalelength \sim1.7 kpc at z=1) and kinematically hot disc, primarily from gas accreted during the galaxy's merger epoch. Far from being a competing formation scenario, migration is crucial for reconciling the short, hot, discs which form at high redshift in {\Lambda}CDM, with the properties of the thick disc at z=0. The thick disc, as defined by its abundances maintains its relatively short scale-length at z = 0 (2.31 kpc) compared with the total disc scale-length of 2.73 kpc. The inside-out nature of disc growth is imprinted the evolution of abundances such that the metal poor {\alpha}-young population has a larger scale-length (4.07 kpc) than the more chemically evolved metal rich {\alpha}-young population (2.74 kpc).Comment: Submitted to MNRAS. This version after helpful referee comments. Comments welcome to [email protected]

Photoproduction of eta mesons from the neutron: cross sections and double polarization observable E

Photoproduction of $\eta$ mesons from neutrons} \abstract{Results from measurements of the photoproduction of $\eta$ mesons from quasifree protons and neutrons are summarized. The experiments were performed with the CBELSA/TAPS detector at the electron accelerator ELSA in Bonn using the $\eta\to3\pi^{0}\to6\gamma$ decay. A liquid deuterium target was used for the measurement of total cross sections and angular distributions. The results confirm earlier measurements from Bonn and the MAMI facility in Mainz about the existence of a narrow structure in the excitation function of $\gamma n\rightarrow n\eta$. The current angular distributions show a forward-backward asymmetry, which was previously not seen, but was predicted by model calculations including an additional narrow $P_{11}$ state. Furthermore, data obtained with a longitudinally polarized, deuterated butanol target and a circularly polarized photon beam were analyzed to determine the double polarization observable $E$. Both data sets together were also used to extract the helicity dependent cross sections $\sigma_{1/2}$ and $\sigma_{3/2}$. The narrow structure in the excitation function of $\gamma n\rightarrow n\eta$ appears associated with the helicity-1/2 component of the reaction

Experimental constraints on the ω\omega-nucleus real potential

In a search for $\omega$ mesic states, the production of $\omega$-mesons in coincidence with forward going protons has been studied in photon induced reactions on $^{12}$C for incident photon energies of 1250 - 3100 MeV. The $\pi^0 \gamma$ pairs from decays of bound or quasi-free $\omega$-mesons have been measured with the CBELSA/TAPS detector system in coincidence with protons registered in the MiniTAPS forward array. Structures in the total energy distribution of the $\pi^0 \gamma$ pairs, which would indicate the population and decay of bound $\omega~^{11}$B states, are not observed. The $\pi^0 \gamma$ cross section of 0.3 nb/MeV/sr observed in the bound state energy regime between -100 and 0 MeV may be accounted for by yield leaking into the bound state regime because of the large in-medium width of the $\omega$-meson. A comparison of the measured total energy distribution with calculations suggests the real part $V_0$ of the $\omega~^{11}$B potential to be small and only weakly attractive with $V_0(\rho=\rho_0) = -15\pm$ 35(stat) $\pm$20(syst) MeV in contrast to some theoretical predictions of attractive potentials with a depth of 100 - 150 MeV.Comment: 13 pages, 8 figure

Radiation Sterilization of Anthracycline Antibiotics in Solid State

The impact of ionizing radiation generated by a beam of electrons of 25–400 kGy on the stability of such analogs of anthracycline antibiotics as daunorubicin (DAU), doxorubicin (DOX), and epidoxorubicin (EPI) was studied. Based on EPR results, it was established that unstable free radicals decay exponentially with the half-time of 4 days in DAU and DOX and 7 days in EPI after irradiation. Radiation-induced structural changes were analyzed with the use of spectrophotometric methods (UV-Vis and IR) and electron microscope imaging (SEM). A chromatographic method (HPLC-DAD) was applied to assess changes in the contents of the analogs in the presence of their impurities. The study showed that the structures of the analogs did not demonstrate any significant alterations at the end of the period necessary for the elimination of unstable free radicals. The separation of main substances and related substances (impurities and potential degradation products) allowed determining that no statistically significant changes in the content of particular active substances occurred and that their conversion due to the presence of free radicals resulting from exposure to an irradiation of 25 kGy (prescribed to ensure sterility) was not observed