Epidemics on contact networks: a general stochastic approach

Dynamics on networks is considered from the perspective of Markov stochastic processes. We partially describe the state of the system through network motifs and infer any missing data using the available information. This versatile approach is especially well adapted for modelling spreading processes and/or population dynamics. In particular, the generality of our systematic framework and the fact that its assumptions are explicitly stated suggests that it could be used as a common ground for comparing existing epidemics models too complex for direct comparison, such as agent-based computer simulations. We provide many examples for the special cases of susceptible-infectious-susceptible (SIS) and susceptible-infectious-removed (SIR) dynamics (e.g., epidemics propagation) and we observe multiple situations where accurate results may be obtained at low computational cost. Our perspective reveals a subtle balance between the complex requirements of a realistic model and its basic assumptions.Comment: Main document: 16 pages, 7 figures. Electronic Supplementary Material (included): 6 pages, 1 tabl

Closed-loop separation control over a sharp edge ramp using Genetic Programming

We experimentally perform open and closed-loop control of a separating turbulent boundary layer downstream from a sharp edge ramp. The turbulent boundary layer just above the separation point has a Reynolds number $Re_{\theta}\approx 3\,500$ based on momentum thickness. The goal of the control is to mitigate separation and early re-attachment. The forcing employs a spanwise array of active vortex generators. The flow state is monitored with skin-friction sensors downstream of the actuators. The feedback control law is obtained using model-free genetic programming control (GPC) (Gautier et al. 2015). The resulting flow is assessed using the momentum coefficient, pressure distribution and skin friction over the ramp and stereo PIV. The PIV yields vector field statistics, e.g. shear layer growth, the backflow area and vortex region. GPC is benchmarked against the best periodic forcing. While open-loop control achieves separation reduction by locking-on the shedding mode, GPC gives rise to similar benefits by accelerating the shear layer growth. Moreover, GPC uses less actuation energy.Comment: 24 pages, 24 figures, submitted to Experiments in Fluid

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Artificial boundary conditions for the linearized Benjamin-Bona-Mahony equation

International audienceWe consider various approximations of artificial boundary conditions for linearized Benjamin-Bona-Mahoney equation. Continuous (respectively discrete) artificial boundary conditions involve non local operators in time which in turn requires to compute time convolutions and invert the Laplace transform of an analytic function (respectively the Z-transform of an holomorphic function). In this paper, we derive explicit transparent boundary conditions both continuous and discrete for the linearized BBM equation. The equation is discretized with the Crank Nicolson time discretization scheme and we focus on the difference between the upwind and the centered discretization of the convection term. We use these boundary conditions to compute solutions with compact support in the computational domain and also in the case of an incoming plane wave which is an exact solution of the linearized BBM equation. We prove consistency, stability and convergence of the numerical scheme and provide many numerical experiments to show the efficiency of our tranparent boundary conditions

Znf202 Affects High Density Lipoprotein Cholesterol Levels and Promotes Hepatosteatosis in Hyperlipidemic Mice

Background: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. Methodology and Principal Findings: We generated mouse Znf202 expression vectors, the functionality of which was established in several in vitro systems. Next, effects of adenoviral znf202 overexpression in vivo were determined in normo- as well as hyperlipidemic mouse models. Znf202 overexpression in mouse hepatoma cells mhAT3F2 resulted in downregulation of members of the Apoe/c1/c2 and Apoa1/c3/a4 gene cluster. The repressive activity of Znf202 was firmly confirmed in an apoE reporter assay and Znf202 responsive elements within the ApoE promoter were identified. Adenoviral Znf202 transfer to Ldlr-/- mice resulted in downregulation of apoe, apoc1, apoa1, and apoc3 within 24 h after gene transfer. Interestingly, key genes in bile flux (abcg5/8 and bsep) and in bile acid synthesis (cyp7a1) were also downregulated. At 5 days post-infection, the expression of the aforementioned genes was normalized, but mice had developed severe hepatosteatosis accompanied by hypercholesterolemia and hypoalphalipoproteinemia. A much milder phenotype was observed in wildtype mice after 5 days of hepatic Znf202 overexpression. Interestingly and similar to Ldl-/- mice, HDL-cholesterol levels in wildtype mice were lowered after hepatic Znf202 overexpression. Conclusion/Significance: Znf202 overexpression in vivo reveals an important role of this transcriptional regulator in liver lipid homeostasis, while firmly establishing the proposed key role in the control of HDL levels

Using a Non-Image-Based Medium-Throughput Assay for Screening Compounds Targeting N-myristoylation in Intracellular Leishmania Amastigotes

We have refined a medium-throughput assay to screen hit compounds for activity against N-myristoylation in intracellular amastigotes of Leishmania donovani. Using clinically-relevant stages of wild type parasites and an Alamar blue-based detection method, parasite survival following drug treatment of infected macrophages is monitored after macrophage lysis and transformation of freed amastigotes into replicative extracellular promastigotes. The latter transformation step is essential to amplify the signal for determination of parasite burden, a factor dependent on equivalent proliferation rate between samples. Validation of the assay has been achieved using the anti-leishmanial gold standard drugs, amphotericin B and miltefosine, with EC50 values correlating well with published values. This assay has been used, in parallel with enzyme activity data and direct assay on isolated extracellular amastigotes, to test lead-like and hit-like inhibitors of Leishmania Nmyristoyl transferase (NMT). These were derived both from validated in vivo inhibitors of Trypanosoma brucei NMT and a recent high-throughput screen against L. donovani NMT. Despite being a potent inhibitor of L. donovani NMT, the activity of the lead T. brucei NMT inhibitor (DDD85646) against L. donovani amastigotes is relatively poor. Encouragingly, analogues of DDD85646 show improved translation of enzyme to cellular activity. In testing the high-throughput L. donovani hits, we observed macrophage cytotoxicity with compounds from two of the four NMT-selective series identified, while all four series displayed low enzyme to cellular translation, also seen here with the T. brucei NMT inhibitors. Improvements in potency and physicochemical properties will be required to deliver attractive lead-like Leishmania NMT inhibitors

Terrestrial implications for the maritime geoarchaeological resource: A view from the Lower Palaeolithic

Stone tools and faunal remains have been recovered from the English Channel and the North Sea through trawling, dredging for aggregates, channel clearance, and coring. These finds highlight the potential for a maritime Lower Palaeolithic archaeological resource. It is proposed here that any Lower Palaeolithic artefacts, faunal remains, and sediments deposited in the maritime zone during dry, low-stand phases were once (and may still be) contextually similar to their counterparts in the terrestrial Lower Palaeolithic records of north-western Europe. Given these similarities, can interpretive models and analytical frameworks developed for terrestrial archaeology be profitably applied to an assessment of the potential value of any maritime resource? The terrestrial geoarchaeological resource for the Lower Palaeolithic is dominated by artefacts and ecofacts that have been fluvially reworked. The spatio-temporal resolution of these data varies from entire river valleys and marine isotope stages to river channel gravel bar surfaces and decadal timescales, thus supporting a variety of questions and approaches. However, the structure of the terrestrial resource also highlights two fundamental limitations in current maritime knowledge that can restrict the application of terrestrial approaches to any potential maritime resource: (i) how have the repetitive transgressions and regressions of the Middle and Late Pleistocene modified the terrace landforms and sediments associated with the river systems of the English Channel and southern North Sea basins?; and (ii) do the surviving submerged terrace landforms and fluvial sedimentary deposits support robust geochronological models, as is the case with the classical terrestrial terrace sequences? This paper highlights potential approaches to these questions, and concludes that the fluvial palaeogeography, Pleistocene fossils, and potential Lower Palaeolithic artefacts of the maritime geoarchaeological resource can be profitably investigated in future as derived, low-resolution data sets, facilitating questions of colonisation, occupation, demography, and material culture

A novel miniature in-line load-cell to measure in-situ tensile forces in the tibialis anterior tendon of rats.

Direct measurements of muscular forces usually require a substantial rearrangement of the biomechanical system. To circumvent this problem, various indirect techniques have been used in the past. We introduce a novel direct method, using a lightweight (~0.5 g) miniature (3 x 3 x 7 mm) in-line load-cell to measure tension in the tibialis anterior tendon of rats. A linear motor was used to produce force-profiles to assess linearity, step-response, hysteresis and frequency behavior under controlled conditions. Sensor responses to a series of rectangular force-pulses correlated linearly (R2 = 0.999) within the range of 0-20 N. The maximal relative error at full scale (20 N) was 0.07% of the average measured signal. The standard deviation of the mean response to repeated 20 N force pulses was ± 0.04% of the mean response. The step-response of the load-cell showed the behavior of a PD2T2-element in control-engineering terminology. The maximal hysteretic error was 5.4% of the full-scale signal. Sinusoidal signals were attenuated maximally (-4 dB) at 200 Hz, within a measured range of 0.01-200 Hz. When measuring muscular forces this should be of minor concern as the fusion-frequency of muscles is generally much lower. The newly developed load-cell measured tensile forces of up to 20 N, without inelastic deformation of the sensor. It qualifies for various applications in which it is of interest directly to measure forces within a particular tendon causing only minimal disturbance to the biomechanical system

High Levels of Diversity Uncovered in a Widespread Nominal Taxon: Continental Phylogeography of the Neotropical Tree Frog

Species distributed across vast continental areas and across major biomes provide unique model systems for studies of biotic diversification, yet also constitute daunting financial, logistic and political challenges for data collection across such regions. The tree frog Dendropsophus minutus (Anura: Hylidae) is a nominal species, continentally distributed in South America, that may represent a complex of multiple species, each with a more limited distribution. To understand the spatial pattern of molecular diversity throughout the range of this species complex, we obtained DNA sequence data from two mitochondrial genes, cytochrome oxidase I (COI) and the 16S rhibosomal gene (16S) for 407 samples of D. minutus and closely related species distributed across eleven countries, effectively comprising the entire range of the group. We performed phylogenetic and spatially explicit phylogeographic analyses to assess the genetic structure of lineages and infer ancestral areas. We found 43 statistically supported, deep mitochondrial lineages, several of which may represent currently unrecognized distinct species. One major clade, containing 25 divergent lineages, includes samples from the type locality of D. minutus. We defined that clade as the D. minutus complex. The remaining lineages together with the D. minutus complex constitute the D. minutus species group. Historical analyses support an Amazonian origin for the D. minutus species group with a subsequent dispersal to eastern Brazil where the D. minutus complex originated. According to our dataset, a total of eight mtDNA lineages have ranges >100,000 km2. One of them occupies an area of almost one million km2 encompassing multiple biomes. Our results, at a spatial scale and resolution unprecedented for a Neotropical vertebrate, confirm that widespread amphibian species occur in lowland South America, yet at the same time a large proportion of cryptic diversity still remains to be discovered