Stochastic focusing coupled with negative feedback enables robust regulation in biochemical reaction networks

Nature presents multiple intriguing examples of processes which proceed at high precision and regularity. This remarkable stability is frequently counter to modelers' experience with the inherent stochasticity of chemical reactions in the regime of low copy numbers. Moreover, the effects of noise and nonlinearities can lead to "counter-intuitive" behavior, as demonstrated for a basic enzymatic reaction scheme that can display stochastic focusing (SF). Under the assumption of rapid signal fluctuations, SF has been shown to convert a graded response into a threshold mechanism, thus attenuating the detrimental effects of signal noise. However, when the rapid fluctuation assumption is violated, this gain in sensitivity is generally obtained at the cost of very large product variance, and this unpredictable behavior may be one possible explanation of why, more than a decade after its introduction, SF has still not been observed in real biochemical systems. In this work we explore the noise properties of a simple enzymatic reaction mechanism with a small and fluctuating number of active enzymes that behaves as a high-gain, noisy amplifier due to SF caused by slow enzyme fluctuations. We then show that the inclusion of a plausible negative feedback mechanism turns the system from a noisy signal detector to a strong homeostatic mechanism by exchanging high gain with strong attenuation in output noise and robustness to parameter variations. Moreover, we observe that the discrepancy between deterministic and stochastic descriptions of stochastically focused systems in the evolution of the means almost completely disappears, despite very low molecule counts and the additional nonlinearity due to feedback. The reaction mechanism considered here can provide a possible resolution to the apparent conflict between intrinsic noise and high precision in critical intracellular processes

Redox processes as revealed by voltammetry in the surface sediments of the Gotland Basin, Baltic Sea

Sulfur cycling in marine sediments undergoes dramatic changes with changing redox conditions of the overlying waters. The upper sediments of the anoxic Gotland Basin, central Baltic Sea represent a dynamic redox environment with extensive mats of sulfide oxidizing bacteria covering the seafloor beneath the chemocline. In order to investigate sulfur redox cycling at the sediment-water interface, sediment cores were sampled over a transect covering 65 – 174 m water depth in August-September 2013. High resolution (0.25 mm minimum) vertical microprofiles of electroactive redox species including dissolved sulfide and iron were obtained with solid state Au-Hg voltammetric microelectrodes. This approach enabled a fine-scale comparison of porewater profiles across the basin. The steepest sulfide gradients (i.e. the highest sulfide consumption) occurred within the upper 10 mm in sediments covered by surficial mats (2.10 to 3.08 mmol m-2 day-1). In sediments under permanently anoxic waters (>140m), voltammetric signals for Fe(II) and aqueous FeS were detected below a subsurface maximum in dissolved sulfide, indicating a Fe flux originating from older, deeper sedimentary layers. Our results point to a unique sulfur cycling in the Gotland basin seafloor where sulfide accumulation is moderated by sulfide oxidation at the sediment surface and by FeS precipitation in deeper sediment layers. These processes may play an important role in minimizing benthic sulfide fluxes to bottom waters around the major basins of the Baltic Sea

Microbial Sulfide Filter along a Benthic Redox Gradient in the Eastern Gotland Basin, Baltic Sea

The sediment-water interface is an important site for material exchange in marine systems and harbor unique microbial habitats. The flux of nutrients, metals, and greenhouse gases at this interface may be severely dampened by the activity of microorganisms and abiotic redox processes, leading to the “benthic filter” concept. In this study, we investigate the spatial variability, mechanisms and quantitative importance of a microbially-dominated benthic filter for dissolved sulfide in the Eastern Gotland Basin (Baltic Sea) that is located along a dynamic redox gradient between 65 and 173 m water depth. In August-September 2013, high resolution (0.25 mm minimum) vertical microprofiles of redox-sensitive species were measured in surface sediments with solid-state gold-amalgam voltammetric microelectrodes. The highest sulfide consumption (2.73–3.38 mmol m−2 day−1) occurred within the top 5 mm in sediments beneath a pelagic hypoxic transition zone (HTZ, 80–120 m water depth) covered by conspicuous white bacterial mats of genus Beggiatoa. A distinct voltammetric signal for polysulfides, a transient sulfur oxidation intermediate, was consistently observed within the mats. In sediments under anoxic waters (>140 m depth), signals for Fe(II) and aqueous FeS appeared below a subsurface maximum in dissolved sulfide, indicating a Fe(II) flux originating from older sediments presumably deposited during the freshwater Ancylus Lake that preceded the modern Baltic Sea. Our results point to a dynamic benthic sulfur cycling in Gotland Basin where benthic sulfide accumulation is moderated by microbial sulfide oxidation at the sediment surface and FeS precipitation in deeper sediment layers. Upscaling our fluxes to the Baltic Proper; we find that up to 70% of the sulfide flux (2281 kton yr−1) toward the sediment-seawater interface in the entire basin can be consumed at the microbial mats under the HTZ (80–120 m water depth) while only about 30% the sulfide flux effuses to the bottom waters (>120 m depth). This newly described benthic filter for the Gotland Basin must play a major role in limiting the accumulation of sulfide in and around the deep basins of the Baltic Sea

Implementing Advanced RBAC Administration Functionality with USE

Role-based access control (RBAC) is a powerful means for laying out and developing higher-level organizational policies such as separation of duty, and for simplifying the security management process. One of the important aspects of RBAC is authorization constraints that express such organizational policies. While RBAC has generated a great interest in the security community, organizations still seek a flexible and effective approach to impose role-based authorization constraints in their security-critical applications. In particular, today often only basic RBAC concepts have found their way into commercial RBAC products; specifically, authorization constraints are not widely supported. In this paper, we present an RBAC administration tool that can enforce certain kinds of role-based authorization constraints such as separation of duty constraints. The authorization constraint functionality is based upon the OCL validation tool USE. We also describe our practical experience that we gained on integrating OCL functionality into a prototype of an RBAC administration tool that shall be extended to a product in the future

Nitrate and nitrite variability at the seafloor of an oxygen minimum zone revealed by a novel microfluidic in-situ chemical sensor

Microfluidics, or lab-on-a-chip (LOC) is a promising technology that allows the development of miniaturized chemical sensors. In contrast to the surging interest in biomedical sciences, the utilization of LOC sensors in aquatic sciences is still in infancy but a wider use of such sensors could mitigate the undersampling problem of ocean biogeochemical processes. Here we describe the first underwater test of a novel LOC sensor to obtain in situ calibrated time-series (up to 40 h) of nitrate+nitrite (ΣNOx) and nitrite on the seafloor of the Mauritanian oxygen minimum zone, offshore Western Africa. Initial tests showed that the sensor successfully reproduced water column (160 m) nutrient profiles. Lander deployments at 50, 100 and 170 m depth indicated that the biogeochemical variability was high over the Mauritanian shelf: The 50 m site had the lowest ΣNOx concentration, with 15.2 to 23.4 μM (median=18.3 μM); while at the 100 site ΣNOx varied between 21.0 and 30.1 μM over 40 hours (median = 25.1μM). The 170 m site had the highest median ΣNOx level (25.8 μM) with less variability (22.8 to 27.7 μM). At the 50 m site, nitrite concentration decreased fivefold from 1 to 0.2 μM in just 30 hours accompanied by decreasing oxygen and increasing nitrate concentrations. Taken together with the time series of oxygen, temperature, pressure and current velocities, we propose that the episodic intrusion of deeper waters via cross-shelf transport leads to intrusion of nitrate-rich, but oxygen-poor waters to shallower locations, with consequences for benthic nitrogen cycling. This first validation of an LOC sensor at elevated water depths revealed that when deployed for longer periods and as a part of a sensor network, LOC technology has the potential to contribute to the understanding of the benthic biogeochemical dynamics

Triple valve infective endocarditis - a late diagnosis

Behcet\u27s disease is a systemic vasculitis of unknown aetiology with cardiac involvement as well as damage to other organs. Whether the sterile valvular inflammation which occurs in this autoimmune disease predisposes to bacterial adhesion and infective endocarditis is not yet established. We present the case of a patient with Behcet disease in which transthoracic echocardiography showed mobile masses on the aortic, tricuspid, and mitral valves, leading to multivalvular infective endocarditis diagnosis, possibly in the context of valvular inflammation. The case presented in this article confirms observation of other studies, namely that ultrasonography plays an important role in the diagnosis and evaluation of rheumatic diseases and permits optimal management in daily practice

Continuum and kinetic simulations of Heat Transfer trough Rarefied Gas in Annular and Planar Geometries in the Slip Regime

International audienceSteady-state heat transfer through a rarefied gas confined between parallel plates or coaxial cylinders, whose surfaces are maintained at different temperatures is investigated using the non-linear Shakhov (S) model kinetic equation and DSMC technique in the slip regime. The profiles of heat flux and temperature are reported for different values of gas rarefaction parameter δ, ratios of hotter to cooler surface temperatures T , and inner to outer radii ratio R. The results of S-model kinetic equation and DSMC technique are compared to the numerical and analytical solutions of the Fourier equation subjected to the Lin & Willis temperature-jump boundary condition. The analytical expressions are derived for temperature and heat flux for both geometries with hotter and colder surfaces having different values of the thermal accommodation coefficient. The results of the comparison between the kinetic and continuum approaches showed that the Lin & Willis temperature-jump model accurately predicts heat flux and temperature profiles for small temperature ratio T = 1.1 and large radius ratios R ≥ 0.5, however, for large temperature ratio, a pronounced disagreement is observed