The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony

A role for the Plasmodium falciparum cyclic GMP (cGMP)-dependent protein kinase (PfPKG) in gametogenesis in the malaria parasite was elucidated previously. In the present study we examined the role of PfPKG in the asexual blood-stage of the parasite life cycle, the stage that causes malaria pathology. A specific PKG inhibitor (compound 1, a trisubstituted pyrrole) prevented the progression of P. falciparum schizonts through to ring stages in erythrocyte invasion assays. Addition of compound 1 to ring-stage parasites allowed normal development up to 30 h postinvasion, and segmented schizonts were able to form. However, synchronized schizonts treated with compound 1 for ≥6 h became large and dysmorphic and were unable to rupture or liberate merozoites. To conclusively demonstrate that the effect of compound 1 on schizogony was due to its selective action on PfPKG, we utilized genetically manipulated P. falciparum parasites expressing a compound 1-insensitive PfPKG. The mutant parasites were able to complete schizogony in the presence of compound 1 but not in the presence of the broad-spectrum protein kinase inhibitor staurosporine. This shows that PfPKG is the primary target of compound 1 during schizogony and provides direct evidence of a role for PfPKG in this process. Discovery of essential roles for the P. falciparum PKG in both asexual and sexual development demonstrates that cGMP signaling is a key regulator of both of these crucial life cycle phases and defines this molecule as an exciting potential drug target for both therapeutic and transmission blocking action against malaria

The transfer of fibres in the carding machine

The problem of understanding the transfer of fibres between carding-machine surfaces is addressed by considering the movement of a single fibre in an airflow. The structure of the aerodynamic flow field predicts how and when fibres migrate between the different process surfaces. In the case of a revolving-flats carding machine the theory predicts a “strong” aerodynamic mechanism between taker-in and cylinder and a “weak” mechanism between cylinder and removal cylinder resulting in effective transfer in the first case and a more limited transfer in the second

On the global hydration kinetics of tricalcium silicate cement

We reconsider a number of measurements for the overall hydration kinetics of tricalcium silicate pastes having an initial water to cement weight ratio close to 0.5. We find that the time dependent ratio of hydrated and unhydrated silica mole numbers can be well characterized by two power-laws in time, $x/(1-x)\sim (t/t_x)^\psi$. For early times $t < t_x$ we find an `accelerated' hydration ($\psi = 5/2$) and for later times $t > t_x$ a `deaccelerated' behavior ($\psi = 1/2$). The crossover time is estimated as $t_x \approx 16 hours$. We interpret these results in terms of a global second order rate equation indicating that (a) hydrates catalyse the hydration process for $t<t_x$, (b) they inhibit further hydration for $t > t_x$ and (c) the value of the associated second order rate constant is of magnitude 6x10^{-7} - 7x10^{-6} liter mol^{-1} s^{-1}. We argue, by considering the hydration process actually being furnished as a diffusion limited precipitation that the exponents $\psi = 5/2$ and $\psi = 1/2$ directly indicate a preferentially `plate' like hydrate microstructure. This is essentially in agreement with experimental observations of cellular hydrate microstructures for this class of materials.Comment: RevTeX macros, 6 pages, 4 postscript figure

Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis

Background: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. Methods: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatmentresistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/ 3.7 mmHg, respectively (P &lt; 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P 0.01) and 0.86/0.42 mmHg (P 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P ¼ 0.0006), ARV (P ¼ 0.01), and VIM (P ¼ 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. Conclusion: RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN

A variational formulation of anisotropic geometric evolution equations in higher dimensions

Accepted versio

Green function techniques in the treatment of quantum transport at the molecular scale

The theoretical investigation of charge (and spin) transport at nanometer length scales requires the use of advanced and powerful techniques able to deal with the dynamical properties of the relevant physical systems, to explicitly include out-of-equilibrium situations typical for electrical/heat transport as well as to take into account interaction effects in a systematic way. Equilibrium Green function techniques and their extension to non-equilibrium situations via the Keldysh formalism build one of the pillars of current state-of-the-art approaches to quantum transport which have been implemented in both model Hamiltonian formulations and first-principle methodologies. We offer a tutorial overview of the applications of Green functions to deal with some fundamental aspects of charge transport at the nanoscale, mainly focusing on applications to model Hamiltonian formulations.Comment: Tutorial review, LaTeX, 129 pages, 41 figures, 300 references, submitted to Springer series "Lecture Notes in Physics

Infrared Behavior of Three-Point Functions in Landau Gauge Yang-Mills Theory

Analytic solutions for the three-gluon and ghost-gluon vertices in Landau gauge Yang-Mills theory at low momenta are presented in terms of hypergeometric series. They do not only show the expected scaling behavior but also additional kinematic divergences when only one momentum goes to zero. These singularities, which have also been proposed previously, induce a strong dependence on the kinematics in many dressing functions. The results are generalized to two and three dimensions and a range of values for the ghost propagator's infrared exponent kappa.Comment: 21 pages, 29 figures; numerical data of the infrared dressing functions can be obtained from the authors v2: a few minor changes, corresponds to version appearing in EPJ

Low Complexity Regularization of Linear Inverse Problems

Inverse problems and regularization theory is a central theme in contemporary signal processing, where the goal is to reconstruct an unknown signal from partial indirect, and possibly noisy, measurements of it. A now standard method for recovering the unknown signal is to solve a convex optimization problem that enforces some prior knowledge about its structure. This has proved efficient in many problems routinely encountered in imaging sciences, statistics and machine learning. This chapter delivers a review of recent advances in the field where the regularization prior promotes solutions conforming to some notion of simplicity/low-complexity. These priors encompass as popular examples sparsity and group sparsity (to capture the compressibility of natural signals and images), total variation and analysis sparsity (to promote piecewise regularity), and low-rank (as natural extension of sparsity to matrix-valued data). Our aim is to provide a unified treatment of all these regularizations under a single umbrella, namely the theory of partial smoothness. This framework is very general and accommodates all low-complexity regularizers just mentioned, as well as many others. Partial smoothness turns out to be the canonical way to encode low-dimensional models that can be linear spaces or more general smooth manifolds. This review is intended to serve as a one stop shop toward the understanding of the theoretical properties of the so-regularized solutions. It covers a large spectrum including: (i) recovery guarantees and stability to noise, both in terms of $\ell^2$-stability and model (manifold) identification; (ii) sensitivity analysis to perturbations of the parameters involved (in particular the observations), with applications to unbiased risk estimation ; (iii) convergence properties of the forward-backward proximal splitting scheme, that is particularly well suited to solve the corresponding large-scale regularized optimization problem

«Desvoyé de la droitte voye ...» : Gadifer de La Salle, Jean de Béthencourt et "Le Canarien"

Résumé Le livre nommé Le Canarien est la chronique de la conquête, en 1402, des Îles Canaries par deux aventuriers normands, Jean de Béthencourt et Gadifer de La Salle : expédition qui sombra très tôt dans la mauvaise foi et dans la discorde. Deux clercs au service de chacun des chevaliers ont, paraît-il, rédigé ensemble l?histoire de l?expédition. Leur ?uvre a disparu, mais deux manuscrits remaniés ultérieurement conservent actuellement l?histoire, avec des points de vue différents : Rouen, BM, MS MM 129 celui de Jean ; Londres, British Library, MS Egerton 2709 celui de Gadifer. Ces récits permettent de peindre les deux protagonistes : Gadifer, révolté, estimant que son compatriote l?a trahi en assumant la souveraineté des îles et en abrogeant les recettes fiscales ; Jean, se montrant inflexible, dédaigneux et rigide. Chaque texte veut faire prévaloir sa version des événements : leurs réécritures respectives, leurs lexiques, et jusqu?à la mise en page de leurs manuscrits nous laissent percevoir la triste dynamique de l?expédition, et nous révèlent des man?uvres qu?on pourrait à bon droit appeler propagandistes. Abstract The book known as Le Canarien is the chronicle of the 1402 conquest of the Canary Islands by two Norman adventurers, Jean de Béthencourt and Gadifer de La Salle: an expedition which soon foundered into discord and betrayal. Our two heroes? chaplains, it seems, put together an account of the expedition; their work is lost, but two manuscripts, each considerably emended, each from the point of view of one of the protagonists, have survived: Rouen, BM MS MM129 preserves Jean?s angle, London, British Library MS Egerton 2709 that of Gadifer. This remarkable circumstance enables us to glimpse the point of view of each of the knights: Gadifer angry and resentful, convinced that his compatriot has betrayed him by assuming the sovereignty of the islands, and seizing their tax revenues; Jean always dismissive, unrelenting. Each text insists on its own version of events: their writers? rewritings, emendations, their choice of words, the very lay-out of the manuscript page, allow us to glimpse the bleak dynamics of the expedition, and each version shows evidence of manoeuvres which one might legitimately call propagandist

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results