Importance of localized skin infection in tick-borne encephalitis virus transmission

Arboviruses 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 uninfected Ixodes ricinus ticks 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 > or = 2.0 log10 ic 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.     

Flexible Hardware Acceleration for Instruction-Grain Lifeguards

Instruction-grain lifeguards monitor executing programs at the granularity of individual instructions to quickly detect bugs and security attacks, but their fine-grain nature incurs high monitoring overheads. This article identifies three common sources of these overheads and proposes three techniques that together constitute a general-purpose hardware acceleration framework for lifeguards.     

Pervasive Personal Computing in an Internet Suspend/Resume System

The Internet suspend/resume model of mobile computing cuts the tight binding between PC state and PC hardware. By layering a virtual machine on distributed storage, ISR lets the VM encapsulate execution and user customization state; distributed storage then transports that state across space and time. This article explores the implications of ISR for an infrastructure-based approach to mobile computing. It reports on experiences with three versions of ISR and describes work in progress toward the OpenISR version     

Recombination in Tula hantavirus evolution: analysis of genetic lineages from Slovakia

To examine the evolution of Tula hantavirus (TUL), carried by the European common vole (Microtus arvalis and M. rossiaemeridionalis), we have analyzed genetic variants from Slovakia, the country where the virus is endemic. Phylogenetic analysis (PHYLIP) based on either partial (nucleotides [nt] 441 to 898) or complete N-protein-encoding sequences divided Slovakian TUL variants into two main lineages: (i) strains from eastern Slovakia, which clustered with Russian strains, and (ii) strains from western Slovakia situated closer to those from the Czech Republic. We found genetic diversity of 19% between the two groups and 4% within the western Slovakian TUL strains. Phylogenetic analysis of the 3' noncoding region (3'-NCR), however, placed the eastern Slovakian strains closer to those from western Slovakia and the Czech Republic, with a greater distance to the Russian strains, suggesting a recombinant nature of the S segment in the eastern Slovakian TUL lineage. A bootscan search of the S-segment sequences of TUL strains revealed at least two recombination points in the S sequences of eastern Slovakian TUL strains (nt 400 to 415 and around 1200) which agreed well with the pattern of amino acid substitutions in the N protein and deletions/insertions in the 3'-NCR of the S segment. These data suggest that homologous recombination events occurred in the evolution of hantaviruses.     

Carbon doped GaAs and AlGaAs grown by OMVPE: doping properties, oxygen incorporation, and hydrogen passivation

The carbon-doping behavior of GaAs and AlGaAs grown by organometallic vapor phase epitaxy was examined using AsH₃ or tertiarybutylarisine (TBAs) as the arsenic precursors. Carbon tetrachloride was utilized as the carbon dopant precursor for GaAs and AlGaAs. In addition, the intrinsic carbon doping of AlGaAs was also examined for these two As sources. The use of TBAs led to a significant reduction in carbon incorporation, by approximately a factor of 5–10 per mole of As precursor, both with respect to extrinsic and intrinsic carbon incorporation. For the GaAs:C layers grown at temperatures 550°C, significant concentrations (10−6 × 10¹⁹ cm⁻³) of hydrogen were detected. Approximately 25–55% of the carbon acceptors were passivated by the hydrogen, based on Hall measurements and infrared absorption measurements. The CCl₄ source introduced oxygen into the AlGaAs layers. TBAs was more effective in reducing oxygen incorporation compared to AsH₃ and the concentration of oxygen was reduced with either increasing TBAs or AsH₃ flow rate.     

Potential‐Dependent Surface‐Enhanced Resonance Raman Spectroscopy at Nanostructured TiO2: A Case Study on Cytochrome b5

Nanostructured titanium dioxide (TiO₂) electrodes, prepared by anodization of titanium, are employed to probe the electron‐transfer process of cytochrome b₅ (cyt b₅) by surface‐enhanced resonance Raman (SERR) spectroscopy. Concomitant with the increased nanoscopic surface roughness of TiO₂, achieved by raising the anodization voltage from 10 to 20 V, the enhancement factor increases from 2.4 to 8.6, which is rationalized by calculations of the electric field enhancement. Cyt b₅ is immobilized on TiO₂ under preservation of its native structure but it displays a non‐ideal redox behavior due to the limited conductivity of the electrode material. The electron‐transfer efficiency which depends on the crystalline phase of TiO₂ has to be improved by appropriate doping for applications in bioelectrochemistry.     

How to conceptualize catalytic cycles? The energetic span model

A computational study of a catalytic cycle generates state energies (the E-representation), whereas experiments lead to rate constants (the k-representation). Based on transition state theory (TST), these are equivalent representations. Nevertheless, until recently, there has been no simple way to calculate the efficiency of a catalytic cycle, that is, its turnover frequency (TOF), from a theoretically obtained energy profile. In this Account, we introduce the energetic span model that enables one to evaluate TOFs in a straightforward manner and in affinity with the Curtin-Hammett principle. As shown herein, the model implies a change in our kinetic concepts. Analogous to Ohm's law, the catalytic chemical current (the TOF) can be defined by a chemical potential (independent of the mechanism) divided by a chemical resistance (dependent on the mechanism and the nature of the catalyst). This formulation is based on Eyring's TST and corresponds to a steady-state regime. In many catalytic cycles, only one transition state and one intermediate determine the TOF. We call them the TOF-determining transition state (TDTS) and the TOF-determining intermediate (TDI). These key states can be located, from among the many states available to a catalytic cycle, by assessing the degree of TOF control (X(TOF)); this last term resembles the structure-reactivity coefficient in classical physical organic chemistry. The TDTS-TDI energy difference and the reaction driving force define the energetic span (δE) of the cycle. Whenever the TDTS appears after the TDI, δE is the energy difference between these two states; when the opposite is true, we must also add the driving force to this difference. Having δE, the TOF is expressed simply in the Arrhenius-Eyring fashion, wherein δE serves as the apparent activation energy of the cycle. An important lesson from this model is that neither one transition state nor one reaction step possess all the kinetic information that determines the efficiency of a catalyst. Additionally, the TDI and TDTS are not necessarily the highest and lowest states, nor do they have to be adjoined as a single step. As such, we can conclude that a change in the conceptualization of catalytic cycles is in order: in catalysis, there are no rate-determining steps, but rather rate-determining states. We also include a study on the effect of reactant and product concentrations. In the energetic span approximation, only the reactants or products that are located between the TDI and TDTS accelerate or inhibit the reaction. In this manner, the energetic span model creates a direct link between experimental quantities and theoretical results. The versatility of the energetic span model is demonstrated with several catalytic cycles of organometallic reactions.     

Seamless mobile computing on fixed infrastructure

The term mobile computing typically evokes images of a laptop, handheld, or wearable computer. However, the plummeting cost of hardware suggests that pervasive computing infrastructure could minimize the need to carry such devices in the near future. Personal computing will be available anywhere on demand, like light at the flip of a switch. Only when a user starts to use a computer will it acquire unique customization and state. When the user finishes using the computer, this customization and state will disappear from it. Thus, a user could travel hands-free yet be confident of making productive use of slivers of free time anywhere. For this to be a compelling vision from a user's viewpoint, the customization and state acquisition process must be accurate and nearly instantaneous. For it to be a viable business model, the management and system administration costs of pervasive deployments of machines must be low. Internet Suspend/Resume is a thick-client approach to mobility in which hardware virtualization and file caching are the keys to rapid personalization of anonymous hardware for transient use.     

Left ventricular morphology and function in diabetic and nondiabetic hemodialyzed patients

Morbidity in end-stage renal disease (ESRD) diabetic patients is worse than in patients without diabetes mellitus (DM). This study aims to compare clinical, laboratory, and echocardiographic features between the ESRD patients with and without DM. Fifty-eight ESRD patients on dialysis were prospectively divided into two groups according to the presence of DM. Demographic, clinical, laboratory, and echocardiographic features (ejection fraction and wall motion score index) were compared between the two groups. Overall, 20 out of 58 patients (37.8%) with ESRD had DM. There were no significant differences between the patients with DM and those without DM when it comes to age (60.6 ± 10.6 vs. 59.0 ± 10.6 years, P = 0.665), ejection fraction (52.6% ± 12.8% vs. 54.2% ± 12.8%, P = 0.59), and wall motion score index (1.21 ± 0.3 vs.1.15 ± 0.3, P = 0.37). In multivariant analysis of the interventricular septum, posterior wall thickness and left atrium size correlated positively with DM. There was also no statistical difference in myocardial perfusion disturbances on real-time contrast echocardiography between the groups with and without DM (12 (60%) patients vs. 14 patients (36.8%), P = 0.079). Among diabetics 77.8% had significant atherosclerotic changes, while in the group without DM, only 38.1%, P = 0.01. From the laboratory parameters ferritin and high-sensitivity C-reactive protein levels were significantly higher in the group with DM, P = 0.014 and P = 0.026, respectively. Patients with ESRD and DM have significantly bigger left atrial size, thicker left ventricular walls, and higher serum ferritin and high-sensitivity C-reactive protein levels than the patients without DM. The aforementioned features may be possible risk factors for the development of adverse cardiac events in patients on hemodialysis.