Rhesus Monkey Rhadinovirus Uses Eph Family Receptors for Entry into B Cells and Endothelial Cells but Not Fibroblasts

Cellular Ephrin receptor tyrosine kinases (Ephrin receptors, Ephs) were found to interact efficiently with the gH/gL glycoprotein complex of the rhesus monkey rhadinovirus (RRV). Since EphA2 was recently identified as a receptor for the Kaposi's sarcoma-associated herpesvirus (KSHV) (Hahn et al., Nature Medicine 2012), we analyzed RRV and KSHV in parallel with respect to Eph-binding and Eph-dependent entry. Ten of the 14 Eph proteins, including both A- and B-type, interacted with RRV gH/gL. Two RRV strains with markedly different gH/gL sequences exhibited similar but slightly different binding patterns to Ephs. gH/gL of KSHV displayed high affinity towards EphA2 but substantially weaker binding to only a few other Ephs of the A-type. Productive entry of RRV 26-95 into B cells and into endothelial cells was essentially completely dependent upon Ephs since expression of a GFP reporter cassette from recombinant virus could be blocked to greater than 95% by soluble Eph decoys using these cells. In contrast, entry of RRV into fibroblasts and epithelial cells was independent of Ephs by these same criteria. Even high concentrations and mixtures of soluble Eph decoys were not able to reduce by any appreciable extent the number of fibroblasts and epithelial cells productively entered by RRV. Thus, RRV is similar to its close relative KSHV in the use of Eph family receptors for productive entry into B cells and endothelial cells. However, RRV uses a separate, distinct, Eph-independent pathway for productive entry into fibroblasts and epithelial cells. Whether KSHV also uses an Eph-independent pathway in some circumstances or to some extent remains to be determined

Breastfeeding woman are at higher risk of vitamin D deficiency than non-breastfeeding women - insights from the German VitaMinFemin study

Background: Despite increased awareness of the adverse health effects of vitamin D deficiency, only a few studies have evaluated the vitamin D status (25-hydroxyvitamin D [25(OHD)]) of breastfeeding women and up to now, no information exits for German breastfeeding women. Therefore, the aim of study was to determine the vitamin D status of breastfeeding women compared to non-pregnant and non-breastfeeding (NPNB) women. Methods: This cross-sectional study investigated 124 breastfeeding women and 124 age and season matched NPNB women from the German "Vitamin and mineral status among German women" study. The study participants were recruited from April 2013 to March 2015 and did not take vitamin D supplements. Serum 25(OH)D was analyzed by chemiluminescent immunoassay. Results: Vitamin D deficiency (<25.0 nmol/L) was prevalent in 26.6% of the breastfeeding women. The majority of women (49.2%) showed 25(OH)D concentration between 25.0 and 49.9 nmol/L. In multiple binary logistic regression analysis, breastfeeding women had a 4.0-fold higher odds ratio (OR) (95% confidence interval [CI] 1.8, 8.7) for vitamin D deficiency than NPNB women. For breastfeeding women, the risk of vitamin D deficiency was higher in the winter and spring months (OR: 2.6, 95% CI 1.1, 6.3) and increased with lower longitude per one unit (OR 0.7, 95% CI 0.6, 0.9). Conclusion: Breastfeeding women in Germany had a higher risk of deficient vitamin D levels than NPNB women. In further studies, the optimal vitamin D status for breastfeeding women should be investigated and also the required vitamin D doses to ensure this vitamin D status. Trial registration: German Clinical Trial Register (identification number: DRKS00004789 ).Rottapharm Madaus GmbHMeda A

Unification of Random Dynamical Decoupling and the Quantum Zeno Effect

Periodic deterministic bang-bang dynamical decoupling and the quantum Zeno effect are known to emerge from the same physical mechanism. Both concepts are based on cycles of strong and frequent kicks provoking a subdivision of the Hilbert space into independent subspaces. However, previous unification results do not capture the case of random bang-bang dynamical decoupling, which can be advantageous to the deterministic case but has an inherently acyclic structure. Here, we establish a correspondence between random dynamical decoupling and the quantum Zeno effect by investigating the average over random decoupling evolutions. This protocol is a manifestation of the quantum Zeno dynamics and leads to a unitary bath evolution. By providing a framework that we call equitability of system and bath, we show that the system dynamics under random dynamical decoupling converges to a unitary with a decoupling error that characteristically depends on the convergence speed of the Zeno limit. This reveals a unification of the random dynamical decoupling and the quantum Zeno effect.Comment: 31 pages, 4 figure

Cost-effectiveness and budget impact of the microprocessor-controlled knee C-Leg in transfemoral amputees with and without diabetes mellitus

Background: The safe use of a prosthesis in activities of daily living is key for transfemoral amputees. However, the number of falls varies significantly between different prosthetic device types. This study aims to compare medical and economic consequences of falls in transfemoral amputees who use the microprocessor-controlled knee joint C-Leg with patients who use non-microprocessor-controlled (mechanical) knee joints (NMPK). The main objectives of the analysis are to investigate the cost-effectiveness and budget impact of C-Legs in transfemoral amputees with diabetes mellitus (DM) and without DM in Germany. Methods: A decision-analytic model was developed that took into account the effects of prosthesis type on the risk of falling and fall-related medical events. Cost-effectiveness and budget impact analyses were performed separately for transfemoral amputees with and without DM. The study took the perspective of the statutory health insurance (SHI). Input parameters were derived from the published literature. Univariate and probabilistic sensitivity analyses (PSA) were performed to investigate the impact of changes in individual input parameter values on model outcomes and to explore parameter uncertainty. Results: C-Legs reduced the rate of fall-related hospitalizations from 134 to 20 per 1000 person years (PY) in amputees without DM and from 146 to 23 per 1000 PY in amputees with DM. In addition, the C-Leg prevented 15 or 14 fall-related death per 1000 PY. Over a time horizon of 25 years, the incremental cost-effectiveness ratio (ICER) was 16,123 Euro per quality-adjusted life years gained (QALY) for amputees without DM and 20,332 Euro per QALY gained for amputees with DM. For the period of 2020–2024, the model predicted an increase in SHI expenditures of 98 Mio Euro (53 Mio Euro in prosthesis users without DM and 45 Mio Euro in prosthesis users with DM) when all new prosthesis users received C-Legs instead of NMPKs and 50% of NMPK user whose prosthesis wore out switched to C-Legs. Results of the PSA showed moderate uncertainty and a probability of 97–99% that C-Legs are cost-effective at an ICER threshold of 40,000 Euro (˜ German GDP per capita in 2018) per QALY gained. Conclusion: Results of the study suggest that the C-Leg provides substantial additional health benefits compared with NMPKs and is likely to be cost-effective in transfemoral amputees with DM as well as in amputees without DM at an ICER threshold of 40,000 Euro per QALY gained. © 2020, The Author(s)

Renewal-anomalous-heterogeneous files

Renewal-anomalous-heterogeneous files are solved. A simple file is made of Brownian hard spheres that diffuse stochastically in an effective 1D channel. Generally, Brownian files are heterogeneous: the spheres' diffusion coefficients are distributed and the initial spheres' density is non-uniform. In renewal-anomalous files, the distribution of waiting times for individual jumps is exponential as in Brownian files, yet obeys: {\psi}_{\alpha} (t)~t^(-1-{\alpha}), 0<{\alpha}<1. The file is renewal as all the particles attempt to jump at the same time. It is shown that the mean square displacement (MSD) in a renewal-anomalous-heterogeneous file, , obeys, ~[_{nrml}]^{\alpha}, where _{nrml} is the MSD in the corresponding Brownian file. This scaling is an outcome of an exact relation (derived here) connecting probability density functions of Brownian files and renewal-anomalous files. It is also shown that non-renewal-anomalous files are slower than the corresponding renewal ones.Comment: Accepted for publication (August, 2010

State-dependent Trotter Limits and their approximations

The Trotter product formula is a key instrument in numerical simulations of quantum systems. However, computers cannot deal with continuous degrees of freedom, such as the position of particles in molecules, or the amplitude of electromagnetic fields. It is therefore necessary to discretize these variables to make them amenable to digital simulations. Here, we give sufficient conditions to conclude the validity of this approximate discretized physics. Essentially, it depends on the state-dependent Trotter error, for which we establish explicit bounds that are also of independent interest.Comment: 16 pages, 5 figure