Investigating the role of the experimental protocol in phenylhydrazine-induced anemia on mice recovery

Producción CientíficaProduction of red blood cells involves growth-factor mediated regulation of erythroid progenitor apoptosis and self-renewal. During severe anemia, characterized by a strong fall of the hematocrit followed by a recovery phase, these controls allow a fast recovery of the hematocrit and survival of the organism. Using a mathematical model of stress erythropoiesis and an ad hoc numerical method, we investigate the respective roles of anemia-inducing phenylhydrazine injections and physiological regulation on the organism’s recovery. By explicitly modeling the experimental protocol, we show that it mostly characterizes the fall of the hematocrit following the anemia and its severeness, while physiological process regulation mainly controls the recovery. We confront our model and our conclusions to similar experiments inducing anemia and show the model’s ability to reproduce several protocols of phenylhydrazine-induced anemia. In particular, we establish a link between phenylhydrazine effect and the severeness of the anemia.Ministerio de Economía, Industria y Competitividad (project MTM2014-56022-C2-2-P

Destruction of superconductivity in disordered materials : a dimensional crossover

The disorder-induced Superconductor-to-Insulator Transition in amorphous Nb$_{x}$Si$_{1-x}$ two-dimensional thin films is studied for different niobium compositions $x$ through a variation of the sample thickness $d$. We show that the critical thickness $d_c$, separating a superconducting regime from an insulating one, increases strongly with diminishing $x$, thus attaining values of over 100 {\AA}. The corresponding phase diagram in the $(d, x)$ plane is inferred and related to the three-dimensional situation. The two-dimensional Superconductor-to-Insulator Transition well connects with the three-dimensional Superconductor-to-Metal Transition

Effect of annealing on the superconducting properties of a-Nb(x)Si(1-x) thin films

a-Nb(x)Si(1-x) thin films with thicknesses down to 25 {\AA} have been structurally characterized by TEM (Transmission Electron Microscopy) measurements. As-deposited or annealed films are shown to be continuous and homogeneous in composition and thickness, up to an annealing temperature of 500{\deg}C. We have carried out low temperature transport measurements on these films close to the superconductor-to-insulator transition (SIT), and shown a qualitative difference between the effect of annealing or composition, and a reduction of the film thickness on the superconducting properties of a-NbSi. These results question the pertinence of the sheet resistance R_square as the relevant parameter to describe the SIT.Comment: 9 pages, 12 figure

Muon-induced background in the EDELWEISS dark matter search

A dedicated analysis of the muon-induced background in the EDELWEISS dark matter search has been performed on a data set acquired in 2009 and 2010. The total muon flux underground in the Laboratoire Souterrain de Modane (LSM) was measured to be $\Phi_{\mu}=(5.4\pm 0.2 ^{+0.5}_{-0.9})$\,muons/m$^2$/d. The modular design of the muon-veto system allows the reconstruction of the muon trajectory and hence the determination of the angular dependent muon flux in LSM. The results are in good agreement with both MC simulations and earlier measurements. Synchronization of the muon-veto system with the phonon and ionization signals of the Ge detector array allowed identification of muon-induced events. Rates for all muon-induced events $\Gamma^{\mu}=(0.172 \pm 0.012)\, \rm{evts}/(\rm{kg \cdot d})$ and of WIMP-like events $\Gamma^{\mu-n} = 0.008^{+0.005}_{-0.004}\, \rm{evts}/(\rm{kg \cdot d})$ were extracted. After vetoing, the remaining rate of accepted muon-induced neutrons in the EDELWEISS-II dark matter search was determined to be $\Gamma^{\mu-n}_{\rm irred} < 6\cdot 10^{-4} \, \rm{evts}/(\rm{kg \cdot d})$ at 90%\,C.L. Based on these results, the muon-induced background expectation for an anticipated exposure of 3000\,\kgd\ for EDELWEISS-3 is $N^{\mu-n}_{3000 kg\cdot d} < 0.6$ events.Comment: 21 pages, 16 figures, Accepted for publication in Astropart. Phy

A new high-background-rejection dark matter Ge cryogenic detector

A new design of a cryogenic germanium detector for dark matter search is presented, taking advantage of the coplanar grid technique of event localisation for improved background discrimination. Experiments performed with prototype devices in the EDELWEISS II setup at the Modane underground facility demonstrate the remarkably high efficiency of these devices for the rejection of low-energy $\beta$, approaching 10$^5$ . This opens the road to investigate the range beyond 10$^{-8}$ pb in the WIMP-nucleon collision cross-sections, as proposed in the EURECA project of a one-ton cryogenic detector mass.Comment: submitted to Physical Review Letter

Ribavirin-Induced Anemia in Hepatitis C Virus Patients Undergoing Combination Therapy

The current standard of care for hepatitis C virus (HCV) infection – combination therapy with pegylated interferon and ribavirin – elicits sustained responses in only ∼50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in conjunction with models of viral kinetics, the rational identification of treatment protocols that maximize treatment response while curtailing side effects