Importance of Localized Skin Infection in Tick-Borne Encephalitis Virus Transmission

AbstractArboviruses are transmitted to vertebrates by the ”bite“ of infected arthropods. Events at the site of virus deposition are largely unknown despite increasing evidence that blood-sucking arthropods immunomodulate their skin site of feeding. This question is particularly relevant for ixodid ticks that feed for several days. To examine events under conditions mimicking tick-borne encephalitis (TBE) virus transmission in nature (i.e., infected and uninfectedIxodes ricinusticks feeding on the same animal), infected adult and uninfected nymphal ticks were placed in one retaining chamber (skin site A) and uninfected nymphs were placed within a second chamber posteriorly (skin site B) on two natural host species, yellow-necked field mice (Apodemus flavicollis) and bank voles (Clethrionomys glareolus). Virus transmission from infected to uninfected cofeeding ticks was correlated with infection in the skin site of tick feeding. Furthermore, virus was recruited preferentially to the site in which ticks were feeding compared with uninfested skin sites. Viremia did not correspond with a generalized infection of the skin; virus was not detected in an uninfested skin site (C) of 12/13 natural hosts that had viremia levels ≥2.0 log10ic mouse LD50/0.02 ml blood. To characterize infected cells, laboratory mouse strains were infested with infected ticks and then explants were removed from selected skin sites and floated on culture medium. Numerous leukocytes were found to migrate from the skin explants of tick feeding sites. Two-color immunocytochemistry revealed viral antigen in both migratory Langerhans cells and neutrophils; in addition, the migratory monocyte/macrophages were shown to produce infectious virus. The results indicate that the local skin site of tick feeding is an important focus of viral replication early after TBE virus transmission by ticks. Cellular infiltration of tick feeding sites, and the migration of cells from such sites, may provide a vehicle for transmission between infected and uninfected cofeeding ticks that is independent of a patent viremia. The data support the hypothesis that viremia is a product, rather than a prerequisite, of tick-borne virus transmission

Resolve: Enabling Accurate Parallel Monitoring under Relaxed Memory Models

Hardware-assisted instruction-grain monitoring frameworks provide high-coverage, low overhead debugging support for parallel programs. Unfortunately, existing frameworks are ill-suited for the relaxed memory models employed by nearly all modern processor architectures—e.g., TSO (x86, SPARC), RMO (SPARC), and Weak Consistency (ARMv7). For TSO, prior proposals hint at a solution, but provide no implementation or evaluation, and fail to correctly handle important corner cases such as byte-level dependences. For more relaxed memory models such as RMO and Weak Consistency, prior frameworks deadlock, rendering them unable to detect any bugs past the first deadlock! This paper presents Resolve, the first hardware-assisted instruction-grain monitoring framework that is complete, correct and deadlock-free under relaxed memory models. Resolve is based on the observation that while relaxed memory models can produce cycles of dependences that deadlock prior approaches, these cycles can be overcome by consulting the dataflow graph of the application threads being monitored, instead of their program order. Resolve handles all possible cycles arising in relaxed memory models, through a careful approach that uses both dataflow-based processing and versioning of monitoring state, as appropriate. Moreover, we provide the first quantitative characterization of the cycles arising under RMO, demonstrating that such cycles are prevalent and persistent, and hence deadlock is a real problem that must be addressed. Yet they are not so frequent or complex, so that Resolve’s overheads are negligible. Finally, we present a simple and novel hardware mechanism for properly synchronizing updates to monitoring state under relaxed memory models, improving performance by up to 35% over the judicious use of memory fences

Boron tunneling in the "weak" bond-stretch isomerization of N-B Lewis adducts

Some nitrile-boron halide adducts exhibit a double-well potential energy surface with two distinct minima: a "long bond" geometry (LB, a van der Waals interaction mostly based on electrostatics, but including a residual charge transfer component) and a "short bond" structure (SB, a covalent dative bond). This behavior can be considered as a "weak" form of bond stretch isomerism. Our computations reveal that complexes RCN-BX3 (R=CH3, FCH2, BrCH2, and X=Cl, Br) exhibit a fast interconversion from LB to SB geometries even close to the absolute zero thanks to a boron atom tunneling mechanism. The computed half-lives of the meta-stable LB compounds vary between minutes to nanoseconds at cryogenic conditions. Accordingly, we predict that the long bond structures are practically impossible to isolate or characterize, which agrees with previous matrix-isolation experiments.Theoretical Chemistr

Inclusive dielectron production in proton-proton collisions at 2.2 GeV beam energy

Data on inclusive dielectron production are presented for the reaction p+p at 2.2 GeV measured with the High Acceptance DiElectron Spectrometer (HADES). Our results supplement data obtained earlier in this bombarding energy regime by DLS and HADES. The comparison with the 2.09 GeV DLS data is discussed. The reconstructed e+e- distributions are confronted with simulated pair cocktails, revealing an excess yield at invariant masses around 0.5 GeV/c2. Inclusive cross sections of neutral pion and eta production are obtained

Inclusive Dielectron Production in Ar+KCl Collisions at 1.76 AGeV studied with HADES

Results of the HADES measurement of inclusive dielectron production in Ar+KCl collisions at a kinetic beam energy of 1.76 AGeV are presented. For the first time, high mass resolution spectroscopy was performed. The invariant mass spectrum of dielectrons is compared with predictions of UrQMD and HSD transport codes.Comment: 4 pages, 3 figures - To appear in the conference proceedings for Quark Matter 2009, March 30 - April 4, Knoxville, Tennesse

Meson and di-electron production with HADES

The HADES experiment, installed at GSI, Darmstadt, measures di-electron production in A+A, p/pi+N and p/pi+A collisions. Here, the pi0 and eta Dalitz decays have been reconstructed in the exclusive p+p reaction at 2.2 GeV to form a reference cocktail for long-lived di-electron sources. In the C+C reaction at 1 and 2 GeV/u, these long-lived sources have been subtracted from the measured inclusive e+e- yield to exhibit the signal from the early phase of the collision. The results suggest that resonances play an important role in dense nuclear matter.Comment: Invited plenary talk at the 10th International Workshop On Meson Production, Properties And Interaction (MESON 2008) 6-10 Jun 2008, Cracow, Polan

Future perspectives at SIS-100 with HADES-at-FAIR

Currently, the HADES spectrometer undergoes un upgrade program to be prepared for measurements at the upcoming SIS-100 synchrotron at FAIR. We describe the current status of the HADES di-electron measurements at the SIS-18 and our future plans for SIS-100.Comment: Invited contribution presented at the XLVII International Winter Meeting on Nuclear Physics, Bormio (Italy), Jan. 26-30, 200

Dilepton production in pp and CC collisions with HADES

Dilepton production has been measured with HADES, the "High Acceptance DiElectron Spectrometer". In pp collisions at 2.2GeV kinetic beam energy, exclusive eta production and the Dalitz decay eta -> gamma e+e- has been reconstructed. The electromagnetic form factor is well in agreement with existing data. In addition, an inclusive e+e- spectrum from the C+C reaction at 2AGeV is presented and compared with a thermal model.Comment: 11 pages, 3 figures, proceedings of the IVth International Conference on Quarks and Nuclear Physics, Madrid, June 5th-10th, submitted to Eur.Phys.J.

Study of dielectron production in C+C collisions at 1 AGeV

The emission of e+e- pairs from C+C collisions at an incident energy of 1 GeV per nucleon has been investigated. The measured production probabilities, spanning from the pi0-Dalitz to the rho/omega! invariant-mass region, display a strong excess above the cocktail of standard hadronic sources. The bombarding-energy dependence of this excess is found to scale like pion production, rather than like eta production. The data are in good agreement with results obtained in the former DLS experiment.Comment: submitted to Physics Letters