Agent-Based Modeling of Intracellular Transport

We develop an agent-based model of the motion and pattern formation of vesicles. These intracellular particles can be found in four different modes of (undirected and directed) motion and can fuse with other vesicles. While the size of vesicles follows a log-normal distribution that changes over time due to fusion processes, their spatial distribution gives rise to distinct patterns. Their occurrence depends on the concentration of proteins which are synthesized based on the transcriptional activities of some genes. Hence, differences in these spatio-temporal vesicle patterns allow indirect conclusions about the (unknown) impact of these genes. By means of agent-based computer simulations we are able to reproduce such patterns on real temporal and spatial scales. Our modeling approach is based on Brownian agents with an internal degree of freedom, $\theta$, that represents the different modes of motion. Conditions inside the cell are modeled by an effective potential that differs for agents dependent on their value $\theta$. Agent's motion in this effective potential is modeled by an overdampted Langevin equation, changes of $\theta$ are modeled as stochastic transitions with values obtained from experiments, and fusion events are modeled as space-dependent stochastic transitions. Our results for the spatio-temporal vesicle patterns can be used for a statistical comparison with experiments. We also derive hypotheses of how the silencing of some genes may affect the intracellular transport, and point to generalizations of the model

Weak capture of protons by protons

The cross section for the proton weak capture reaction $^1H(p,e^+\nu_e)^2H$ is calculated with wave functions obtained from a number of modern, realistic high-precision interactions. To minimize the uncertainty in the axial two-body current operator, its matrix element has been adjusted to reproduce the measured Gamow-Teller matrix element of tritium $\beta$ decay in model calculations using trinucleon wave functions from these interactions. A thorough analysis of the ambiguities that this procedure introduces in evaluating the two-body current contribution to the pp capture is given. Its inherent model dependence is in fact found to be very weak. The overlap integral $\Lambda^2(E=0)$ for the pp capture is predicted to be in the range 7.05--7.06, including the axial two-body current contribution, for all interactions considered.Comment: 17 pages RevTeX (twocolumn), 5 postscript figure

Muon capture by 3He nuclei followed by proton and deuteron production

The paper describes an experiment aimed at studying muon capture by ${}^{3}\mathrm{He}$ nuclei in pure ${}^{3}\mathrm{He}$ and $\mathrm{D}_2 + {}^{3}\mathrm{He}$ mixtures at various densities. Energy distributions of protons and deuterons produced via $\mu^-+{}^{3}\mathrm{He}\to p+n+n + \nu_{\mu }$ and $\mu^-+{}^{3} \mathrm{He} \to d+n + \nu_{\mu}$ are measured for the energy intervals $10 - 49$ MeV and $13 - 31$ MeV, respectively. Muon capture rates, $\lambda_\mathrm{cap}^p (\Delta E_p)$ and $\lambda_\mathrm{cap}^d (\Delta E_d)$ are obtained using two different analysis methods. The least--squares methods gives $\lambda_\mathrm{cap}^p = (36.7\pm 1.2) {s}^{- 1}$, $\lambda_\mathrm{cap}^d = (21.3 \pm 1.6) {s}^{- 1}$. The Bayes theorem gives $\lambda_\mathrm{cap}^p = (36.8 \pm 0.8) {s}^{- 1}$, $\lambda_\mathrm{cap}^d = (21.9 \pm 0.6) {s}^{- 1}$. The experimental differential capture rates, $d\lambda_\mathrm{cap}^p (E_p) / dE_p$ and $d\lambda_\mathrm{cap}^d (E_d) / dE_d$, are compared with theoretical calculations performed using the plane--wave impulse approximation (PWIA) with the realistic NN interaction Bonn B potential. Extrapolation to the full energy range yields total proton and deuteron capture rates in good agreement with former results.Comment: 17 pages, 13 figures, accepted for publication in PR

On derivation of Euler-Lagrange Equations for incompressible energy-minimizers

We prove that any distribution $q$ satisfying the equation $\nabla q=\div{\bf f}$ for some tensor ${\bf f}=(f^i_j), f^i_j\in h^r(U)$ ($1\leq r<\infty$) -the {\it local Hardy space}, $q$ is in $h^r$, and is locally represented by the sum of singular integrals of $f^i_j$ with Calder\'on-Zygmund kernel. As a consequence, we prove the existence and the local representation of the hydrostatic pressure $p$ (modulo constant) associated with incompressible elastic energy-minimizing deformation ${\bf u}$ satisfying $|\nabla {\bf u}|^2, |{\rm cof}\nabla{\bf u}|^2\in h^1$. We also derive the system of Euler-Lagrange equations for incompressible local minimizers ${\bf u}$ that are in the space $K^{1,3}_{\rm loc}$; partially resolving a long standing problem. For H\"older continuous pressure $p$, we obtain partial regularity of area-preserving minimizers.Comment: 23 page

Modern theories of low-energy astrophysical reactions

We summarize recent ab initio studies of low-energy electroweak reactions of astrophysical interest, relevant for both big bang nucleosynthesis and solar neutrino production. The calculational methods include direct integration for np radiative and pp weak capture, correlated hyperspherical harmonics for reactions of A=3,4 nuclei, and variational Monte Carlo for A=6,7 nuclei. Realistic nucleon-nucleon and three-nucleon interactions and consistent current operators are used as input.Comment: 29 pages, 4 figure

Correlation of MRI T2 mapping sequence with knee pain location in young patients with normal standard MRI

'Objective: 'To assess the correlation of T2 mapping abnormalities to knee pain location, in young adults with normal standard knee MRI at 3.0 Tesla. 'Subjects and methods: 'Twenty-three consecutive patients were included prospectively from September 2011 to April 2012. Inclusion criteria were age under 50 years old, knee pain without surgical history, and normal knee MRI at 3.0 Tesla (sagittal T1-weighted images, and sagittal, axial and coronal proton-density-weighted images with saturation of fat signal). Ten asymptomatic volunteers were also included as a control group. Patients and controls had a cartilage T2 mapping MRI sequence in addition to the standard MRI protocol. Two musculoskeletal radiologists, blinded to the patient/control condition and pain location, independently reviewed the T2 mapping images. T2 values below 40 ms were considered normal. They rated the number of hyaline cartilage lesions and their grade according to an ICRS-like score (inspired by the International Cartilage Research Society score) in each anatomical compartment (medial and lateral femoro-tibial and anterior patello-femoral joints). In addition, the T2 value of the largest lesion was measured. Patient’s pain location was classified in the following categories: anterior, lateral, medial and global. T2 mapping findings were compared to pain location, and retrospectively to the initial standard sequences. Sensitivity and specificity were calculated for MRI with T2 mapping according to pain location for each reader. Kappa coefficient was calculated for inter-reader agreement. We used variance analysis in a linear regression to compare T2 values and ICRS-like classification in each compartment. 'Results: 'Sensitivity of MRI with T2 mapping, according to the symptomatic compartment, was respectively: 78% and 87% for Reader 1 and Reader 2 and specificity was 70% for both readers. Kappa coefficient for T2 mapping abnormalities location and pain location was good, with a calculated value of 0.64. There was no significant correlation between ICRS-like classification and T2 values of lesions (p = 0.18). 'Conclusion: 'Our results suggest that T2 mapping is an interesting MRI sequence for the exploration of young patients knee pain in case of normal MRI with a standard protocol, with a good correlation between pain location and focal prolongations of the cartilage T2 relaxation time

Induced pseudoscalar coupling of the proton weak interaction

The induced pseudoscalar coupling $g_p$ is the least well known of the weak coupling constants of the proton's charged--current interaction. Its size is dictated by chiral symmetry arguments, and its measurement represents an important test of quantum chromodynamics at low energies. During the past decade a large body of new data relevant to the coupling $g_p$ has been accumulated. This data includes measurements of radiative and non radiative muon capture on targets ranging from hydrogen and few--nucleon systems to complex nuclei. Herein the authors review the theoretical underpinnings of $g_p$, the experimental studies of $g_p$, and the procedures and uncertainties in extracting the coupling from data. Current puzzles are highlighted and future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic

Formulating 'principles of procedure' for the foreign language classroom: A framework for process model language curricula

This article aims to apply Stenhouse's process model of curriculum to foreign language (FL) education, a model which is characterized by enacting principles of procedure which are specific to the discipline which the school subject belongs to. Rather than to replace or dissolve current approaches to FL teaching and curriculum development, this article seeks to improve and enrich communicative and task-based orientations with an additional criterion for assessing the educational worth of the tasks through which these orientations are developed. Unlike the objectives and competences models, principles of procedure provide an intrinsic justification of school curriculum by enacting the epistemological structure of any given area of knowledge in the educational process. Accordingly, the article will first justify the need to come up with a process model of curriculum for FL education which is built around such principles; then, it will formulate a basic framework that reflects the logical structure, concepts and epistemological perspectives of the language studies, as a first step to allowing these to enter the FL classroom and orient the teaching conducted in it; finally, it will present three tasks whose design was inspired by the abovementioned framework, and which were put into practice with Primary education English as a Foreign Language learners during the 2013 2014 and 2014 2015 academic years

Rabies, Still Neglected after 125 Years of Vaccination

International audienceno abstrac

A Novel Mechanism Is Involved in Cationic Lipid-Mediated Functional siRNA Delivery

A key challenge for therapeutic application of RNA interference is to efficiently deliver synthetic small interfering RNAs (siRNAs) into target cells that will lead to the knockdown of the target transcript (functional siRNA delivery). To facilitate rational development of nonviral carriers, we have investigated by imaging, pharmacological and genetic approaches the mechanisms by which a cationic lipid carrier mediates siRNA delivery into mammalian cells. We show that 95% of siRNA lipoplexes enter the cells through endocytosis and persist in endolysosomes for a prolonged period of time. However, inhibition of clathrin-, caveolin-, or lipid-raft-mediated endocytosis or macropinocytosis fails to inhibit the knockdown of the target transcript. In contrast, depletion of cholesterol from the plasma membrane has little effect on the cellular uptake of siRNA lipoplexes, but it abolishes the target transcript knockdown. Furthermore, functional siRNA delivery occurs within a few hours and is gradually inhibited by lowering temperatures. These results demonstrate that although endocytosis is responsible for the majority of cellular uptake of siRNA lipoplexes, a minor pathway, probably mediated by fusion between siRNA lipoplexes and the plasma membrane, is responsible for the functional siRNA delivery. Our findings suggest possible directions for improving functional siRNA delivery by cationic lipids.National Institutes of Health (U.S.) (NIH Grant AI56267)National Institutes of Health (U.S.) (NIH Grant CA112967)National Institutes of Health (U.S.) (NIH Grant CA119349)Natural Sciences and Engineering Research Council of Canada (NSERC) (Post-doctoral fellowship