Replication in the Mononuclear Phagocyte System (MPS) as a Determinant of Hantavirus Pathogenicity

Members of different virus families including Hantaviridae cause viral hemorrhagic fevers (VHFs). The decisive determinants of hantavirus-associated pathogenicity are still enigmatic. Pathogenic hantavirus species, such as Puumala virus (PUUV), Hantaan virus (HTNV), Dobrava-Belgrade virus (DOBV), and Sin Nombre virus (SNV), are associated with significant case fatality rates. In contrast, Tula virus (TULV) only sporadically causes mild disease in immunocompetent humans and Prospect Hill virus (PHV) so far has not been associated with any symptoms. They are thus defined here as low pathogenic/apathogenic hantavirus species. We found that productive infection of cells of the mononuclear phagocyte system (MPS), such as monocytes and dendritic cells (DCs), correlated well with the pathogenicity of hantavirus species tested. HTNV (intermediate case fatality rates) replicated more efficiently than PUUV (low case fatality rates) in myeloid cells, whereas low pathogenic/apathogenic hantavirus species did not produce any detectable virus titers. Analysis of PHPUV, a reassortant hantavirus derived from a pathogenic (PUUV) and an apathogenic (PHV) hantavirus species, indicated that the viral glycoproteins are not decisive for replication in MPS cells. Moreover, blocking acidification of endosomes with chloroquine decreased the number of TULV genomes in myeloid cells suggesting a post-entry block for low pathogenic/apathogenic hantavirus species in myeloid cells. Intriguingly, pathogenic but not low pathogenic/apathogenic hantavirus species induced conversion of monocytes into inflammatory DCs. The proinflammatory programming of MPS cells by pathogenic hantavirus species required integrin signaling and viral replication. Our findings indicate that the capacity to replicate in MPS cells is a prominent feature of hantaviral pathogenicity

Clinical trial for the effectiveness of Unilateral Paravertebral Block Versus Unilateral Subarachnoid Block in Unilateral inguinal hernia for Herniorrhaphy

Background: Inguinal Herniorrhaphy is most commonly performed surgical procedurein male. Till now inguinal hernia repair was performed under general, regional, and peripheral nerve blocks. So the concept of paravertebral blocks which provided an excellent alternative anaesthesia technique for hernia repair. Aim: To study the effectiveness of unilateral paravertebral block versus unilateral subarachnoid block in unilateral inguinal hernias repair. Materials and Methods: 100 patients of unilateral inguinal hernia where enrolled in the study and randomized into two groups each of 50 patients. Group S (50) receiving subarachnoid block, group P (50) receiving paravertebral block. Time for procedure and onset of action, intraoperative hemodynamics, post-operative analgesia, and ambulation time were compared. Results: Significant difference was observed in time to perform and onset of action with group P (13.08± 1.31) & (15.94± 1.21) and group S (1.35±0.61) & (5.14±0.76) respectively. No significant difference in hemodynamic parameters and post op analgesia lasted for (324.00±52.84min) in group P and (182.67±40.13min) in group S. Conclusion: Paravertebral block provides excellent anesthesia with unilateral motor, sympathetic, and prolonged sensory blockade, provide excellent postoperative analgesia, and encourages early ambulation

Steady computations of ingress through gas turbine rim seals

In gas turbines, rim seals are fitted at the periphery of the wheel-space between the turbine disc and its adjacent casing; their purpose is to reduce the ingress of hot mainstream gases. This paper describes the use of a three-dimensional, steady-state model to investigate ingress through engine-representative single and double radial-clearance seals. The three-dimensional Reynolds-averaged Navier–Stokes computations of a simplified turbine stage are carried out using the commercial computational fluid dynamics code ANSYS CFX v13, and the model is based on the geometry of an experimental test rig at the University of Bath. The measured variation of the peak-to-trough pressure difference in the annulus, which is the main driving mechanism for ingress, is reproduced well qualitatively by the computations; quantitatively, the maximum local differences between computation and experiment are less than 20% of the measured peak-to-trough circumferential variation. The radial variation of swirl ratio in the rotor–stator wheel-space is well predicted over the range of flow rates and rim seal geometries studied. The radial distribution of sealing effectiveness determined from experiments is reproduced inward of the mixing region near the seal clearance over a range of sealing flow rates; some over-prediction of the effectiveness was found for both seals at high radius, probably due to limitations in the turbulent mixing modelling. The three-dimensional steady-state approach may be a practical tool for the engine designer where there is a lack of experimental data, providing quantitative predictions of the flow structure within the rotor–stator wheel-space and qualitative predictions of the sealing effectiveness for a given rim seal geometry. </jats:p

Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-beta and Runx2 in bone is required for hearing

Publisher version: http://www.nature.com/embor/journal/v11/n10/full/embor2010135.htmlDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEPhysical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-beta (TGFbeta)-responsive pathway that controls osteoblast differentiation. Deregulated TGFbeta or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2(+/-) mice, inhibition of TGFbeta signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue functio

Design optimization of pixel sensors using device simulations for the phase-II CMS tracker upgrade

In order to address the problems caused by the harsh radiation environment during the high luminosity phase of the LHC (HL-LHC), all silicon tracking detectors (pixels and strips) in the CMS experiment will undergo an upgrade. And so to develop radiation hard pixel sensors, simulations have been performed using the 2D TCAD device simulator, SILVACO, to obtain design parameters. The effect of various design parameters like pixel size, pixel depth, implant width, metal overhang, p-stop concentration, p-stop depth and bulk doping density on the leakage current and critical electric field are studied for both non-irradiated as well as irradiated pixel sensors. These 2D simulation results of planar pixels are useful for providing insight into the behaviour of non-irradiated and irradiated silicon pixel sensors and further work on 3D simulation is underway. © 2015 Elsevier B.V

Search for eta-mesic 4He in the dd->3He n pi0 and dd->3He p pi- reactions with the WASA-at-COSY facility

The search for 4He-eta bound states was performed with the WASA-at-COSY facility via the measurement of the excitation function for the dd->3He n pi0 and dd->3He p pi- processes. The beam momentum was varied continuously between 2.127 GeV/c and 2.422 GeV/c, corresponding to the excess energy for the dd->4He eta reaction ranging from Q=-70 MeV to Q=30 MeV. The luminosity was determined based on the dd->3He n reaction and quasi-free proton-proton scattering via dd->pp n_spectator n_spectator reactions. The excitation functions determined independently for the measured reactions do not reveal a structure which could be interpreted as a narrow mesic nucleus. Therefore, the upper limits of the total cross sections for the bound state production and decay in dd->(4He-eta)_bound->3He n pi0 and dd->(4He-eta)_bound->3He p pi- processes were determined taking into account the isospin relation between both the channels considered. The results of the analysis depend on the assumptions of the N* momentum distribution in the anticipated mesic-4He. Assuming as in the previous works, that this is identical with the distribution of nucleons bound with 20 MeV in 4He, we determined that (for the mesic bound state width in the range from 5 MeV to 50 MeV) the upper limits at 90% confidence level are about 3 nb and about 6 nb for npi0 and ppi- channels, respectively. However, based on the recent theoretical findings of the N*(1535) momentum distribution in the N*-3He nucleus bound by 3.6 MeV, we find that the WASA-at-COSY detector acceptance decreases and hence the corresponding upper limits are 5 nb and 10 nb for npi0 and ppi- channels respectively.Comment: This article will be submitted to JHE

Evidence for a vector charmonium-like state in e+e−→Ds+Ds2∗(2573)−+c.c.e^+e^- \to D^+_sD^*_{s2}(2573)^-+c.c.

We report the measurement of $e^+e^- \to D^+_sD^*_{s2}(2573)^-+c.c.$ via initial-state radiation using a data sample of an integrated luminosity of 921.9 fb$^{-1}$ collected with the Belle detector at the $\Upsilon(4S)$ and nearby. We find evidence for an enhancement with a 3.4$\sigma$ significance in the invariant mass of $D^+_sD^*_{s2}(2573)^- +c.c.$ The measured mass and width are $(4619.8^{+8.9}_{-8.0}({\rm stat.})\pm2.3({\rm syst.}))~{\rm MeV}/c^{2}$ and $(47.0^{+31.3}_{-14.8}({\rm stat.})\pm4.6({\rm syst.}))~{\rm MeV}$, respectively. The mass, width, and quantum numbers of this enhancement are consistent with the charmonium-like state at 4626 MeV/$c^2$ recently reported by Belle in $e^+e^-\to D^+_sD_{s1}(2536)^-+c.c.$ The product of the $e^+e^-\to D^+_sD^*_{s2}(2573)^-+c.c.$ cross section and the branching fraction of $D^*_{s2}(2573)^-\to{\bar D}^0K^-$ is measured from $D^+_sD^*_{s2}(2573)^-$ threshold to 5.6 GeV.Comment: 9 pages, 4 figure

Measurement of the Branching Fraction of the Decay B+→π+π−ℓ+νℓ\boldsymbol{B^{+}\to\pi^{+}\pi^{-}\ell^{+}\nu_\ell} in Fully Reconstructed Events at Belle

We present an analysis of the exclusive $B^{+}\to\pi^{+}\pi^{-}\ell^{+}\nu_{\ell}$ decay, where $\ell$ represents an electron or a muon, with the assumption of charge-conjugation symmetry and lepton universality. The analysis uses the full $\Upsilon(4S)$ data sample collected by the Belle detector, corresponding to 711 fb$^{-1}$ of integrated luminosity. We select the events by fully reconstructing one $B$ meson in hadronic decay modes, subsequently determining the properties of the other $B$ meson. We extract the signal yields using a binned maximum-likelihood fit to the missing-mass squared distribution in bins of the invariant mass of the two pions or the momentum transfer squared. We measure a total branching fraction of ${{\cal B}(B^{+}\to \pi^{+}\pi^{-}\ell^{+}\nu_{\ell})= [22.7 ^{+1.9}_{-1.6} (\mathrm{stat}) \pm 3.5(\mathrm{syst}) ]\times 10^{-5}}$, where the uncertainties are statistical and systematic, respectively. This result is the first reported measurement of this decay.Comment: 23 pages, 19 figure

ABC Effect and Resonance Structure in the Double-Pionic Fusion to 3^3He

Exclusive and kinematically complete measurements of the double pionic fusion to $^3$He have been performed in the energy region of the so-called ABC effect, which denotes a pronounced low-mass enhancement in the $\pi\pi$-invariant mass spectrum. The experiments were carried out with the WASA detector setup at COSY. Similar to the observations in the basic $pn \to d \pi^0\pi^0$ reaction and in the $dd \to ^4$He$\pi^0\pi^0$ reaction, the data reveal a correlation between the ABC effect and a resonance-like energy dependence in the total cross section. Differential cross sections are well described by the hypothesis of $d^*$ resonance formation during the reaction process in addition to the conventional $t$-channel $\Delta\Delta$ mechanism. The deduced $d^*$ resonance width can be understood from collision broadening due to Fermi motion of the nucleons in initial and final nuclei