Integrating heterogeneous knowledges for understanding biological behaviors: a probabilistic approach

Despite recent molecular technique improvements, biological knowledge remains incomplete. Reasoning on living systems hence implies to integrate heterogeneous and partial informations. Although current investigations successfully focus on qualitative behaviors of macromolecular networks, others approaches show partial quantitative informations like protein concentration variations over times. We consider that both informations, qualitative and quantitative, have to be combined into a modeling method to provide a better understanding of the biological system. We propose here such a method using a probabilistic-like approach. After its exhaustive description, we illustrate its advantages by modeling the carbon starvation response in Escherichia coli. In this purpose, we build an original qualitative model based on available observations. After the formal verification of its qualitative properties, the probabilistic model shows quantitative results corresponding to biological expectations which confirm the interest of our probabilistic approach.Comment: 10 page

Electrical conductivity in granular media and Branly's coherer: A simple experiment

accepted for publication in American Journal of Physics (to be published between February 2005 and June 2005)We show how a simple laboratory experiment can illustrate certain electrical transport properties of metallic granular media. At a low critical imposed voltage, a transition from an insulating to a conductive state is observed. This transition comes from an electro-thermal coupling in the vicinity of the microcontacts between grains where microwelding occurs. Our apparatus allows us to obtain an implicit determination of the microcontact temperature, which is analogous to the use of a resistive thermometer. The experiment also illustrates an old problem, the explanation of Branly's coherer effect - a radio wave detector used for the first wireless radio transmission, and based on the sensitivity of the metal fillings conductivity to an electromagnetic wave

Some aspects of electrical conduction in granular systems of various dimensions

We report on measurements of the electrical conductivity in both a 2D triangular lattice of metallic beads and in a chain of beads. The voltage/current characteristics are qualitatively similar in both experiments. At low applied current, the voltage is found to increase logarithmically in a good agreement with a model of widely distributed resistances in series. At high enough current, the voltage saturates due to the local welding of microcontacts between beads. The frequency dependence of the saturation voltage gives an estimate of the size of these welded microcontacts. The DC value of the saturation voltage (~ 0.4 V per contact) gives an indirect measure of the number of welded contact carrying the current within the 2D lattice. Also, a new measurement technique provides a map of the current paths within the 2D lattice of beads. For an isotropic compression of the 2D granular medium, the current paths are localized in few discrete linear paths. This quasi-onedimensional nature of the electrical conductivity thus explains the similarity between the characteristics in the 1D and 2D systems.Comment: To be published in The European Physical Journal

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial

Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. Methods For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. Findings Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3–5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9–5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1–9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39–0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. Interpretation In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART

Ціноутворення земель техногенного походження як чинник формування рівня їх споживчих властивостей

Визначено засади ціноутворення як головного чинника обгрунтування рівня відтворення екологічної та господарської цінності земель техногенного походження, встановлено вплив грошової оцінки на формування їх цільового споживчого ринку, представлено принципи поєднання екологічних та економічних складових оцінки рекультивованого ґрунту.Определены основы ценообразования как главного фактора обоснования уровня восстановления экологической и хозяйственной ценности земель техногенного происхождения, определено влияние денежной оценки на формирование их целевого потребительского рынка, представлены принципы объединения экологических и экономических составляющих оценки рекультивированного грунта.Defined pricing principles as the main factor of level playing ground environmental and economic values of land anthropogenic origin, the effect of monetary valuation of forming their target consumer market, representing a combination of ecological principles and economic evaluation of reclaimed soil constituents

Spatiotemporal-MIMO channel estimator and beamformer for 5G

With requirements of spiraling data rates and limited spectrum availability, there is an increased interest in mm-wave beamformer-based communications for 5G. For upcoming cellular networks, the critical point is to exploit the increased number of employable antennas at both Tx and Rx to: 1) combat increased path loss; 2) tackle higher interference due to higher user density; and 3) handle multipath effects in frequency selective channels. Toward this, a multi-beam spatiotemporal superresolution beamforming framework is proposed in this paper as a promising candidate to design beampatterns that mitigate/suppress co-channel interference and deliver massive gain in the desired directions. Initially, channel and signal models suitable for the mm-wave MIMO system are presented using the manifold vectors of both Tx and Rx antenna arrays. Based on these models, a novel subspace-based channel estimator is employed, which estimates delays, directions, velocities, and fading coefficients of the desired signal paths. This information is then exploited by the proposed spatiotemporal beamformer to provide a massive array gain that combats path loss without increasing the number of antenna array elements and to be tolerant to the near-far problem in a high interference environment. The performance of the proposed channel estimator and beamformer is examined using computer simulation studies

The production of fluorescent transgenic trout to study in vitro myogenic cell differentiation

<p>Abstract</p> <p>Background</p> <p>Fish skeletal muscle growth involves the activation of a resident myogenic stem cell population, referred to as satellite cells, that can fuse with pre-existing muscle fibers or among themselves to generate a new fiber. In order to monitor the regulation of myogenic cell differentiation and fusion by various extrinsic factors, we generated transgenic trout (<it>Oncorhynchus mykiss</it>) carrying a construct containing the green fluorescent protein reporter gene driven by a fast myosin light chain 2 (MlC2f) promoter, and cultivated genetically modified myogenic cells derived from these fish.</p> <p>Results</p> <p>In transgenic trout, green fluorescence appeared in fast muscle fibers as early as the somitogenesis stage and persisted throughout life. Using an <it>in vitro </it>myogenesis system we observed that satellite cells isolated from the myotomal muscle of transgenic trout expressed GFP about 5 days post-plating as they started to fuse. GFP fluorescence persisted subsequently in myosatellite cell-derived myotubes. Using this <it>in vitro </it>myogenesis system, we showed that the rate of muscle cell differentiation was strongly dependent on temperature, one of the most important environmental factors in the muscle growth of poikilotherms.</p> <p>Conclusions</p> <p>We produced MLC2f-gfp transgenic trout that exhibited fluorescence in their fast muscle fibers. The culture of muscle cells extracted from these trout enabled the real-time monitoring of myogenic differentiation. This <it>in vitro </it>myogenesis system could have numerous applications in fish physiology to evaluate the myogenic activity of circulating growth factors, to test interfering RNA and to assess the myogenic potential of fish mesenchymal stem cells. In ecotoxicology, this system could be useful to assess the impact of environmental factors and marine pollutants on fish muscle growth.</p

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)