Oligosaccharide model of the vascular endothelial glycocalyx in physiological flow

Experiments have consistently revealed the pivotal role of the endothelial glycocalyx layer in vasoregulation and the layer’s contribution to mechanotransduction pathways. However, the exact mechanism by which the glycocalyx mediates fluid shear stress remains elusive. This study employs atomic-scale molecular simulations with the aim of investigating the conformational and orientation properties of highly flexible oligosaccharide components of the glycocalyx and their suitability as transduction molecules under hydrodynamic loading. Fluid flow was shown to have nearly no effect on the conformation populations explored by the oligosaccharide, in comparison with static (diffusion) conditions. However, the glycan exhibited a significant orientation change, when compared to simple diffusion, aligning itself with the flow direction. It is the tethered end of the glycan, an asparagine amino acid, which experienced conformational changes as a result of this flow-induced bias. Our results suggest that shear flow through the layer can have an impact on the conformational properties of saccharide-decorated transmembrane proteins, thus acting as a mechanosensor

Nonlinear Volatility of River Flux Fluctuations

We study the spectral properties of the magnitudes of river flux increments, the volatility. The volatility series exhibits (i) strong seasonal periodicity and (ii) strongly power-law correlations for time scales less than one year. We test the nonlinear properties of the river flux increment series by randomizing its Fourier phases and find that the surrogate volatility series (i) has almost no seasonal periodicity and (ii) is weakly correlated for time scales less than one year. We quantify the degree of nonlinearity by measuring (i) the amplitude of the power spectrum at the seasonal peak and (ii) the correlation power-law exponent of the volatility series.Comment: 5 revtex pages, 6 page

Troubles musculo-squelettiques : rôles des médecins-conseils et relations interprofessionnelles

INTRODUCTION: Musculoskeletal disorders (MSD) were responsible for 9.7 million days of sick leave in 2010 in France. They are also a leading cause of occupational exclusion. The objective was to study the role of medical advisers (Mas) in the care of patients with MSD and their interactions with general practitioners (GPs) and occupational health physicians (OPs). METHODS: We performed a qualitative study with semi-structured interviews with medical advisers from the Brittany region. Semistructured interviews were double-coded and were submitted to thematic analysis. RESULTS: Nine interviews were conducted with MAs from the general regime, agricultural regime, and independent workers regime. MAs described an increase in MSD, especially with complex forms. They explained that their activity was not limited to control, but that they also had an important role in limiting occupational exclusion. It is important to anticipate difficulties related to return to work in this setting. They reported contrasted but necessary relations with GPs who are at the centre of care. Return to work may require negotiation with OPs. CONCLUSION: Relations between MAs and GPs are partly based on control of prescriptions, which can create a climate of suspicion. Emphasizing the fight against occupational exclusion can provide new light on the role of MAs. Improving relations between MAs and GPs can be achieved by a better understanding of their respective roles

Labyrinthine Turing Pattern Formation in the Cerebral Cortex

I propose that the labyrinthine patterns of the cortices of mammalian brains may be formed by a Turing instability of interacting axonal guidance species acting together with the mechanical strain imposed by the interconnecting axons.Comment: See home page http://lec.ugr.es/~julya

Computing prime factors with a Josephson phase qubit quantum processor

A quantum processor (QuP) can be used to exploit quantum mechanics to find the prime factors of composite numbers[1]. Compiled versions of Shor's algorithm have been demonstrated on ensemble quantum systems[2] and photonic systems[3-5], however this has yet to be shown using solid state quantum bits (qubits). Two advantages of superconducting qubit architectures are the use of conventional microfabrication techniques, which allow straightforward scaling to large numbers of qubits, and a toolkit of circuit elements that can be used to engineer a variety of qubit types and interactions[6, 7]. Using a number of recent qubit control and hardware advances [7-13], here we demonstrate a nine-quantum-element solid-state QuP and show three experiments to highlight its capabilities. We begin by characterizing the device with spectroscopy. Next, we produces coherent interactions between five qubits and verify bi- and tripartite entanglement via quantum state tomography (QST) [8, 12, 14, 15]. In the final experiment, we run a three-qubit compiled version of Shor's algorithm to factor the number 15, and successfully find the prime factors 48% of the time. Improvements in the superconducting qubit coherence times and more complex circuits should provide the resources necessary to factor larger composite numbers and run more intricate quantum algorithms.Comment: 5 pages, 3 figure

Multifractal stationary random measures and multifractal random walks with log-infinitely divisible scaling laws

We define a large class of continuous time multifractal random measures and processes with arbitrary log-infinitely divisible exact or asymptotic scaling law. These processes generalize within a unified framework both the recently defined log-normal Multifractal Random Walk (MRW) [Bacry-Delour-Muzy] and the log-Poisson "product of cynlindrical pulses" [Barral-Mandelbrot]. Our construction is based on some ``continuous stochastic multiplication'' from coarse to fine scales that can be seen as a continuous interpolation of discrete multiplicative cascades. We prove the stochastic convergence of the defined processes and study their main statistical properties. The question of genericity (universality) of limit multifractal processes is addressed within this new framework. We finally provide some methods for numerical simulations and discuss some specific examples.Comment: 24 pages, 4 figure

Theory and simulation of short-range models of globular protein solutions

We report theoretical and simulation studies of phase coexistence in model globular protein solutions, based on short-range, central, pair potential representations of the interaction among macro-particles. After reviewing our previous investigations of hard-core Yukawa and generalised Lennard-Jones potentials, we report more recent results obtained within a DLVO-like description of lysozyme solutions in water and added salt. We show that a one-parameter fit of this model based on Static Light Scattering and Self-Interaction Chromatography data in the dilute protein regime, yields demixing and crystallization curves in good agreement with experimental protein-rich/protein-poor and solubility envelopes. The dependence of cloud and solubility points temperature of the model on the ionic strength is also investigated. Our findings highlight the minimal assumptions on the properties of the microscopic interaction sufficient for a satisfactory reproduction of the phase diagram topology of globular protein solutions.Comment: 17 pages, 8 figures, Proc. of Conference "Structural Arrest Transitions in Colloidal Systems with Short-Range Attractions", Messina (ITALY) 17-20 December 200

Perspectives for a mixed two-qubit system with binomial quantum states

The problem of the relationship between entanglement and two-qubit systems in which it is embedded is central to the quantum information theory. This paper suggests that the concurrence hierarchy as an entanglement measure provides an alternative view of how to think about this problem. We consider mixed states of two qubits and obtain an exact solution of the time-dependent master equation that describes the evolution of two two-level qubits (or atoms) within a perfect cavity for the case of multiphoton transition. We consider the situation for which the field may start from a binomial state. Employing this solution, the significant features of the entanglement when a second qubit is weakly coupled to the field and becomes entangled with the first qubit, is investigated. We also describe the response of the atomic system as it varies between the Rabi oscillations and the collapse-revival mode and investigate the atomic inversion and the Q-function. We identify and numerically demonstrate the region of parameters where significantly large entanglement can be obtained. Most interestingly, it is shown that features of the entanglement is influenced significantly when the multi-photon process is involved. Finally, we obtain illustrative examples of some novel aspects of this system and show how the off-resonant case can sensitize entanglement to the role of initial state setting.Comment: 18 pages, 9 figure

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases