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Thresholded mode-switched ODEs are restricted dynamical systems that switch ODEs depending on digital input signals only, and produce a digital output signal by thresholding some internal signal. Such systems arise in recent digital circuit delay models, where the analog signals within a gate are governed by ODEs that change depending on the digital inputs. We prove the continuity of the mapping from digital input signals to digital output signals for a large class of thresholded mode-switched ODEs. This continuity property is known to be instrumental for ensuring the faithfulness of the model w.r.t. propagating short pulses. We apply our result to several instances of such digital delay models, thereby proving them to be faithful.

An implementation of training units that provide evidence for improving students’ communication skills in the dental curriculum is now more than ever of utmost importance. This study aimed to investigate how students assess their skills after communication training and whether this training also increased students’ self-efficacy expectancy. A total of 32 male and 71 female students with a mean age of 25.6 ± 3.9 years participated in the study. Self-assessment of communication skills and self-efficacy expectancies were collected at two time points using Likert scales. Our study shows that the communication training, consisting of a practical exercise with actors and an online theory module, significantly improved the students’ self-assessment of their communication skills and also improved some aspects of self-efficacy expectancy. These results indicate that, in addition to the practical and technical-theoretical training of students, communication training is essential in the dental curriculum. In summary, this study showed that a one-time practical exercise with actors together with an online theory module could improve both the self-assessment of communication competence and some aspects of self-efficacy expectancy, which demonstrates the importance of training communication skills alongside practical and technical-theoretical training.

For banks using the Advanced Internal Ratings-Based Approach in accordance with Basel III requirements, the amount of required regulatory capital relies on the banks' estimates of the probability of default, the loss given default and the conversion factor for their credit risk portfolio. Therefore, for both model development and validation, assessing the models' predictive and discriminatory abilities is of key importance in order to ensure an adequate quantification of risk. This paper compares different measures of discriminatory power suitable for multi-class target variables such as in loss given default (LGD) models, which are currently used among banks and supervisory authorities. This analysis highlights the disadvantages of using measures that solely rely on pairwise comparisons when applied in a multi-class setting. Thus, for multi-class classification problems, we suggest using a generalisation of the well-known area under the receiver operating characteristic (ROC) curve known as the volume under the ROC surface (VUS). Furthermore, we present the R-package VUROCS, which allows for a time-efficient computation of the VUS as well as associated (co)variance estimates and illustrate its usage based on real-world loss data and validation principles.

A nonsplit graph is a directed graph where each pair of nodes has a common incoming neighbor. We show that the radius of such graphs is in $O(\log \log n)$, where $n$ is the number of nodes. We then generalize the result to products of nonsplit graphs. The analysis of nonsplit graph products has direct implications in the context of distributed systems, where processes operate in rounds and communicate via message passing in each round: communication graphs in several distributed systems naturally relate to nonsplit graphs and the graph product concisely represents relaying messages in such networks. Applying our results, we obtain improved bounds on the dynamic radius of such networks, i.e., the maximum number of rounds until all processes have received a message from a common process, if all processes relay messages in each round. We finally connect the dynamic radius to lower bounds for achieving consensus in dynamic networks., Comment: 12 pages, 1 figure

Building on the weak CSR approach developed in a previous paper by Merlet, Nowak and Sergeev, we establish new bounds for the periodicity threshold of the powers of a tropical matrix. According to that approach, bounds on the ultimate periodicity threshold take the form of T=max(T_1,T_2), where T_1 is a bound on the time after which the weak CSR expansion starts to hold and T_2 is a bound on the time after which the first CSR term starts to dominate. The new bounds on T_1 and T_2 established in this paper make use of the cyclicity of the associated graph and the (tropical) factor rank of the matrix, which leads to much improved bounds in favorable cases. For T_1, in particular, we obtain new extensions of bounds of Schwarz, Kim and Gregory-Kirkland-Pullman, previously known as bounds on exponents of digraphs. For similar bounds on T_2, we introduce the novel concept of walk reduction threshold and establish bounds on it that use both cyclicity and factor rank., Comment: 37 pages

Modern electronic computing devices profit from two far-reaching design choices: the digital abstraction of a continuous signal domain into a binary domain to tolerate noise, and the use of the complementary metal-oxide-semiconductor (CMOS) technique in gates to reduce noise and power consumption. Biological circuit design in the last two decades has been greatly inspired by the digital abstraction of electronic circuits, while still using a relatively analog machinery. With the constantly growing techniques and components available in synthetic biology, the question arises if chip design choices and other lessons learned from silicon computers can be transferred to biological designs. In this context, we discuss here the similarities and differences between the two fields concerning representation of circuits, solutions to computational problems, their implementations, and challenges.

Computing with synthetically engineered bacteria is a vibrant and active field with numerous applications in bio-production, bio-sensing, and medicine. Motivated by the lack of robustness and by resource limitation inside single cells, distributed approaches with communication among bacteria have recently gained in interest. In this paper, we focus on the problem of population growth happening concurrently, and possibly interfering, with the desired bio-computation. Specifically, we present a fast protocol in systems with continuous population growth for the majority consensus problem and prove that it correctly identifies the initial majority among two inputs with high probability if the initial difference is Ω(√{nlog n}) where n is the total initial population. We also present a fast protocol that correctly computes the NAND of two inputs with high probability. We demonstrate that combining the NAND gate protocol with the continuous-growth majority consensus protocol, using the latter as an amplifier, it is possible to implement circuits computing arbitrary Boolean functions., LIPIcs, Vol. 179, 34th International Symposium on Distributed Computing (DISC 2020), pages 7:1-7:17

Accurate delay models are important for static and dynamic timing analysis of digital circuits, and mandatory for formal verification. However, F\"ugger et al. [IEEE TC 2016] proved that pure and inertial delays, which are employed for dynamic timing analysis in state-of-the-art tools like ModelSim, NC-Sim and VCS, do not yield faithful digital circuit models. Involution delays, which are based on delay functions that are mathematical involutions depending on the previous-output-to-input time offset, were introduced by F\"ugger et al. [DATE'15] as a faithful alternative (that can easily be used with existing tools). Although involution delays were shown to predict real signal traces reasonably accurately, any model with a deterministic delay function is naturally limited in its modeling power. In this paper, we thus extend the involution model, by adding non-deterministic delay variations (random or even adversarial), and prove analytically that faithfulness is not impaired by this generalization. Albeit the amount of non-determinism must be considerably restricted to ensure this property, the result is surprising: the involution model differs from non-faithful models mainly in handling fast glitch trains, where small delay shifts have large effects. This originally suggested that adding even small variations should break the faithfulness of the model, which turned out not to be the case. Moreover, the results of our simulations also confirm that this generalized involution model has larger modeling power and, hence, applicability., Comment: 9 pages, 9 figures, extended version of a paper which was accepted at DATE'18

BACKGROUND Careful selection and testing of plasma reduces the risk of blood-borne viruses in the starting material for plasma-derived products. Furthermore, effective measures such as pasteurization at 60°C for 10 hours have been implemented in the manufacturing process of therapeutic plasma proteins such as human albumin, coagulation factors, immunoglobulins, and enzyme inhibitors to inactivate blood-borne viruses of concern. A comprehensive compilation of the virus reduction capacity of pasteurization is presented including the effect of stabilizers used to protect the therapeutic protein from modifications during heat treatment. STUDY DESIGN AND METHODS The virus inactivation kinetics of pasteurization for a broad range of viruses were evaluated in the relevant intermediates from more than 15 different plasma manufacturing processes. Studies were carried out under the routine manufacturing target variables, such as temperature and product-specific stabilizer composition. Additional studies were also performed under robustness conditions, that is, outside production specifications. RESULTS The data demonstrate that pasteurization inactivates a wide range of enveloped and nonenveloped viruses of diverse physicochemical characteristics. After a maximum of 6 hours' incubation, no residual infectivity could be detected for the majority of enveloped viruses. Effective inactivation of a range of nonenveloped viruses, with the exception of nonhuman parvoviruses, was documented. CONCLUSION Pasteurization is a very robust and reliable virus inactivation method with a broad effectiveness against known blood-borne pathogens and emerging or potentially emerging viruses. Pasteurization has proven itself to be a highly effective step, in combination with other complementary safety measures, toward assuring the virus safety of final product.

Design and production of semiconductor devices for the automotive industry are characterized by high reliability requirements, such that the proper functioning of these devices is ensured over the whole specified lifetime. Therefore, manufacturers let their products undergo extensive testing procedures that simulate the tough requirements their products have to withstand. Such tests typically are highly accelerated, to test the behavior of the products over the whole lifetime. In case of drift of electrical parameters, manufacturers then need to find appropriate tolerance limits for their final electrical product tests, such that the proper functioning of their devices over the whole specified lifetime is ensured. In this study, we present a statistical model for the determination of tolerance limits that minimize yield loss. The model considers longitudinal measurements of continuous features, based on censored data from stress tests. The tolerance limits are derived from multivariate distributions where the dependence structure is described by different copulas. Based on extensive numerical testing, we are able to provide insights into the properties of our model for different drift behaviors of the devices.

Alpha 1 -proteinase inhibitor (A 1 PI) deficiency is a genetic condition predisposing to emphysema. Respreeza/Zemaira, a therapeutic preparation of A 1 PI, is prepared from human plasma. This article describes the purity and stability of Respreeza/Zemaira and the capacity of virus and prion reduction steps incorporated into its manufacturing process. Purity and stability of Respreeza/Zemaira were analysed using established methods. To test pathogen clearance capacity, high levels of test viruses/prions were spiked into aliquots of production intermediates and clearance studies were performed for selected manufacturing steps, under production and robustness conditions, using validated scale-down models. Respreeza/Zemaira had a purity of 99% A 1 PI and consisted of 96% monomers. It remained stable after storage for 3 years at 25 °C. Specific activity was 0.895 mg active A 1 PI/mg protein. Pasteurisation inactivated enveloped viruses and the non-enveloped hepatitis A virus. 20 N/20 N virus filtration was highly effective and robust at removing all tested viruses, including parvoviruses, to below the limit of detection. Cold ethanol fractionation provided substantial reduction of prions. The manufacturing process of Respreeza/Zemaira ensures the production of a stable and pure product. Taking into consideration the donor selection process, the testing of donations, and the highly effective virus and prion reduction, Respreeza/Zemaira has a high safety margin.

BACKGROUND Beriplex P/N/Kcentra/Coaplex/Confidex is a four-factor human prothrombin complex concentrate (PCC). Here, we describe the pathogen safety profile and biochemical characteristics of an improved manufacturing process that further enhances the virus safety of Beriplex P/N. STUDY DESIGN AND METHODS Samples of product intermediates were spiked with test viruses, and prions were evaluated under routine production and robustness conditions of the scale-down version of the commercial manufacturing process for their capacity to inactivate or remove pathogens. The PCC was characterized by determining the activity of Factor (F)II, FVII, FIX, FX, protein C, and protein S and the concentration of heparin and antithrombin III in nine product lots. RESULTS The manufacturing process had a very high virus reduction capacity for a broad variety of virus challenges (overall reduction factors ≥15.5 to ≥18.4 log for enveloped viruses and 11.5 to ≥11.9 log for nonenveloped viruses). The high virus clearance capacity was provided by two dedicated virus reduction steps (pasteurization and serial 20N virus filtration) that provided effective inactivation and removal of viruses and a purification step (ammonium sulfate precipitation and adsorption to calcium phosphate) that contributed to the overall virus removal capacity. The diethylaminoethyl (DEAE) chromatography and ammonium sulfate precipitation steps removed prions to below the limit of detection. The levels of different clotting factors in the final product were well balanced. CONCLUSION The improved manufacturing process of Beriplex P/N further enhances the margin of pathogen safety based on its capacity to remove and inactivate a wide range of virus challenges.

International audience; [Függer et al., IEEE TC 2016] proved that no existing digital circuit model, including those based on pure and inertial delay channels, faithfully captures glitch propagation: For the Short-Pulse Filtration (SPF) problem similar to that of building a one-shot inertial delay, they showed that every member of the broad class of bounded single-history channels either contradicts the unsolvability of SPF in bounded time or the solvability of SPF in unbounded time in physical circuits. In this paper, we propose binary circuit models based on novel involution channels that do not suffer from this deficiency. Namely, in sharp contrast to bounded single-history channels, SPF cannot be solved in bounded time with involution channels, whereas it is easy to provide an unbounded SPF implementation. Hence, binary-valued circuit models based on involution channels allow to solve SPF precisely when this is possible in physical circuits. Additionally, using both Spice simulations and physical measurements of an inverter chain instrumented by high-speed analog amplifiers, we demonstrate that our model provides good modeling accuracy with respect to real circuits as well. Consequently , our involution channel model is not only a promising basis for sound formal verification, but also allows to seamlessly improve existing dynamic timing analysis.

International audience; In this paper, we provide a rigorous characterization of consensus solvability in synchronous directed dynamic networks controlled by an arbitrary message adversary using point-set topology: We extend the approach introduced by Alpern and Schneider in 1985 by introducing two novel topologies on the space of infinite executions: the process-view topology, induced by a distance function that relies on the local view of a given process in an execution, and the minimum topology, which is induced by a distance function that focuses on the local view of the process that is the last to distinguish two executions. We establish some simple but powerful topological results, which not only lead to a topological explanation of bivalence arguments, but also provide necessary and sufficient topological conditions on the admissible graph sequences of a message adversary for solving consensus. In particular, we characterize consensus solvability in terms of connectivity of the set of admissible graph sequences. For non-compact message adversaries, which are not limit-closed in the sense that there is a convergent sequence of graph sequences whose limit is not permitted, this requires the exclusion of all "fair" and "unfair" limit sequences that coincide with the forever bivalent runs constructed in bivalence proofs. For both compact and non-compact message adversaries, we also provide tailored characterizations of consensus solvability, i.e., tight conditions for impossibility and existence of algorithms, based on the broadcastability of the connected components of the set of admissible graph sequences.

We consider the standard population protocol model, where (a priori) indistinguishable and anonymous agents interact in pairs according to uniformly random scheduling. The self-stabilizing leader election problem requires the protocol to converge on a single leader agent from any possible initial configuration. We initiate the study of time complexity of population protocols solving this problem in its original setting: with probability 1, in a complete communication graph. The only previously known protocol by Cai, Izumi, and Wada [Theor. Comput. Syst. 50] runs in expected parallel time $\Theta(n^2)$ and has the optimal number of $n$ states in a population of $n$ agents. The existing protocol has the additional property that it becomes silent, i.e., the agents' states eventually stop changing. Observing that any silent protocol solving self-stabilizing leader election requires $\Omega(n)$ expected parallel time, we introduce a silent protocol that uses optimal $O(n)$ parallel time and states. Without any silence constraints, we show that it is possible to solve self-stabilizing leader election in asymptotically optimal expected parallel time of $O(\log n)$, but using at least exponential states (a quasi-polynomial number of bits). All of our protocols (and also that of Cai et al.) work by solving the more difficult ranking problem: assigning agents the ranks $1,\ldots,n$., Comment: fixed typo in Figure 2

We show that no existing continuous-time, binary value-domain model for digital circuits is able to correctly capture glitch propagation. Prominent examples of such models are based on pure delay channels (P), inertial delay channels (I), or the elaborate PID channels proposed by Bellido-D\'iaz et al. We accomplish our goal by considering the solvability/non-solvability border of a simple problem called Short-Pulse Filtration (SPF), which is closely related to arbitration and synchronization. On one hand, we prove that SPF is solvable in bounded time in any such model that provides channels with non-constant delay, like I and PID. This is in opposition to the impossibility of solving bounded SPF in real (physical) circuit models. On the other hand, for binary circuit models with constant-delay channels, we prove that SPF cannot be solved even in unbounded time; again in opposition to physical circuit models. Consequently, indeed none of the binary value-domain models proposed so far (and that we are aware of) faithfully captures glitch propagation of real circuits. We finally show that these modeling mismatches do not hold for the weaker eventual SPF problem., Comment: 23 pages, 15 figures

Different parvoviruses are used interchangeably as models in validation studies to demonstrate effective clearance of small viruses by filtration in the manufacturing of biotherapeutics. The aim of these experiments was to determine if filtration of different parvoviruses (canine parvovirus [CPV], minute virus of mice [MVM], and porcine parvovirus [PPV]) results in similar virus retention. While filtration with a Planova™ 20 N filter (mean pore size: 19 ± 2 nm) completely removed PPV and MVM from the filtrate (mean log reduction factors [LRFs] ≥5.8 to ≥7.3 log10), CPV was only partly retained (3.6 log10) in a series of single and co-spike experiments. Additional co-spike experiments in 2 different feedstreams using 10 commercially available small pore filters confirmed these results; the LRF for CPV was around 2 log10 lower than for MVM and PPV. A sizing study using filters with mean pore sizes between 16.5 and 19 nm resulted in complete removal of CPV only with smaller pore sizes (17 and 16.5 nm). CPV behaves differently to MVM and PPV in viral filtration due to its apparent smaller size, suggesting CPV represents a worst-case model for other parvoviruses. Interpretation of efficacy and robustness of virus filtration thus depends on the choice of model virus.

International audience; This paper improves pulse-coupled synchronization for highly dynamic wireless networks, where vehicles may move unpredictably, causing topological changes of the network. For pulse-coupled methods, vehicles broadcast zero-bit pulses to estimate the clock differences to their neighbors. Vehicles then update local clocks according to the average of difference of pulses from its neighbors. The proposed algorithm further introduces (1) a time wheel to improve the robustness of the synchronization protocol and (2) an additional drift compensation mechanism to reduce clock skew. We compare our new algorithm to previous works via simulation. Both static and dynamic networks are simulated and compared. Different frequencies and clock drifts are analyzed. The proposed algorithm adapts to highly dynamic vehicle networks more quickly and more robustly than previous algorithms.

We study the transients of matrices in max-plus algebra. Our approach is based on the weak CSR expansion. Using this expansion, the transient can be expressed by $\max\{T_1,T_2\}$, where $T_1$ is the weak CSR threshold and $T_2$ is the time after which the purely pseudoperiodic CSR terms start to dominate in the expansion. Various bounds have been derived for $T_1$ and $T_2$, naturally leading to the question which matrices, if any, attain these bounds. In the present paper we characterize the matrices attaining two particular bounds on $T_1$, which are generalizations of the bounds of Wielandt and Dulmage-Mendelsohn on the indices of non-weighted digraphs. This also leads to a characterization of tightness for the same bounds on the transients of critical rows and columns. The characterizations themselves are generalizations of those for the non-weighted case., 42 pages, 9 figures

Agreeing on a common value among a set of agents is a fundamental problem in distributed computing, which occurs in several variants: In contrast to exact consensus, approximate variants are studied in systems where exact agreement is not possible or required, e.g., in human-made distributed control systems and in the analysis of natural distributed systems, such as bird flocking and opinion dynamics. We study the time complexity of two classical agreement problems: non-terminating asymptotic consensus and terminating approximate consensus. Asymptotic consensus, requires agents to repeatedly set their outputs such that the outputs converge to a common value within the convex hull of initial values; approximate consensus requires agents to eventually stop setting their outputs, which must then lie within a predefined distance of each other. We prove tight lower bounds on the contraction ratios of asymptotic consensus algorithms subject to oblivious message adversaries, from which we deduce bounds on the time complexity of approximate consensus algorithms. In particular, the obtained bounds show optimality of asymptotic and approximate consensus algorithms presented by Charron-Bost et al. (ICALP’16) for certain systems, including the strongest oblivious message adversary in which asymptotic and approximate consensus are solvable. As a corollary we also obtain asymptotically tight bounds for asymptotic consensus in the classical asynchronous model with crashes. Central to the lower-bound proofs is an extended notion of valency, the set of reachable limits of an asymptotic consensus algorithm starting from a given configuration. We further relate topological properties of valencies to the solvability of exact consensus, shedding some light on the relation of these three fundamental problems in dynamic networks.

Electrical and electronic equipment waste (e-waste) is growing fast. Due to its potential economic value as well as its possible negative impacts on the environment, tracing e-waste flow is a major concern for stakeholders of e-waste management. Especially, whether or not adequate amounts of electrical and electronic equipment waste (WEEE) flow into the designed recycling systems is a fundamental issue for sustainable operations. In this paper, we analyze how technical, market, and legislative factors influence the total amount of e-waste that is collected, recycled, exported and (legally and illegally) disposed off. We formulate the e-waste network flow model as a variational inequality problem. The results of the numerical examples highlight the importance of considering the interaction between the supply and the demand side for precious materials in policy-decisions. Low collection rates of e-waste lead to low profits for stakeholders and make it difficult to establish sustainable recycling operations. Increasing WEEE collection rates increases recyclers' profits; however, it only increases smelters' profits up to a certain limit, after which smelters cannot benefit further due to limited demand for precious materials. Furthermore, the results emphasize the importance of establishing international control regimes for WEEE flows and reveal possible negative consequences of the recent trend of dematerialization. More precisely, product dematerialization tends to decrease recyles' and smelters' profits as well as to increase the outflow of e-waste from the designated recycling system. (authors' abstract)

As input ows of secondary raw materials show high volatility and tend to behave in a chaotic way, the identification of the main drivers of the dynamic behavior of returns plays a crucial role. Based on a stylized productionrecycling system consisting of a set of nonlinear difference equations, we explicitly derive parameter constellations where the system will or will not converge to its equilibrium. Using a constant elasticity of substitution production function, the model is then extended to enable coverage of real world situations. Using waste paper as a reference raw material, we empirically estimate the parameters of the system. By using these regression results, we are able to show that the equilibrium solution is a Lyapunov unstable saddle point. This implies that the system is sensitive on initial conditions that will hence impede the predictability of product returns. Small variations of production input proportions could however stabilize the whole system. (authors' abstract)

Retrograde ascending aortic dissections usually complicate endovascular reconstructions of Stanford B dissections. Although rare, with an incidence of 1.3% to 6.8%, they are catastrophic, with a high mortality rate of up to 42%. The exact mechanism is not known, but all indications point to a mechanical interaction between the tips of the proximal bare stent and a fragile aortic wall. Practically all reported cases involve dissections of the thoracic aorta. We report a patient with an asymptomatic retrograde ascending aortic dissection that originated at the level of a damaged suprarenal stent during capture tip retrieval during a routine endovascular aneurysm repair to treat an infrarenal aortic aneurysm.

Geological storage of CO2 is receiving growing attention by industry as an option to reduce CO2 emissions. For this, it is indispensable to develop geochemical models for the interaction of CO2 and incidental components like SO2 with formation rocks and brines. To establish such whole-rock models it is essential to have a good understanding of the chemical reactions, thermodynamic properties, and kinetic data of mono-mineral systems. In the German project “CO2 Purity for Capture and Storage (COORAL)” several institutes are working on the requirements for the purity of the CO2 stream during capture, transport, injection, and storage. Geochemical modeling and laboratory experiments on water-rock-gas interactions are carried out to improve understanding of mineral alteration processes. In whole- rock models of a generic Buntsandstein (sandstone), short-term precipitation of anhydrite occurred when SO2 was present. Furthermore, increasing feldspar dissolution and related illitisation reactions for the system CO 2 -SO2 in comparison to pure CO2 are of importance.

Background: As a minimally invasive technique endovascular aneurysm repair (EVAR) reduces the risk of mortality and should be the preferred technique used in older patients. We analysed trends in endovascular and open surgical procedures in patients hospitalized for abdominal aortic aneurysm (AAA) in Germany. Patients and methods: We used national statistics (DRG statistics) published by the Federal Office of Statistics in Germany to calculate the incidence of patients hospitalised with ruptured (rAAA) and elective (eAAA) AAA. In addition, annual procedure rates of endovascular (EVAR) procedures were calculated. Results: Incidence rates of eAAA per 100,000 males (females) showed a small increase from 2006 to 2007 but remained almost unchanged with 74.8 (8.8) in 2007 and 74.5 (9.8) in 2009. Incidence rates of rAAA per 100 000 males remained unchanged but showed a decreasing trend in females. The rate of people treated by EVAR increased form 2006 to 2009: in males from 24.0 % to 40.3 % and in females from 17.3 % to 31.0 %. In younger males (55 - 60 years) the increase in those who received EVAR was smaller (from 22.1 % to 33.9 %) than in older males (85 - 90 years) (from 20.4 to 41.6 %). Despite a clear increase in the use of EVAR from 2006 to 2009 there is only a small trend in reduction of the death rates which is more pronounced in rAAA. Conclusions: There has been a relevant increase in EVAR procedures for the treatment of AAA in Germany in recent years. Parallel to this increase of EVAR, aneurysm-related in-hospital deaths seem be declining slightly. A causal relationship between these trends remains to be proven.

Modelling fluid–rock interactions induced by CO2 is a key issue when evaluating the technical feasibility and long-term safety assessment of CO2 storage projects in deep formations. The German R&D programme CLEAN (CO2 Large-Scale Enhanced Gas Recovery in the Altmark Natural Gas Field) investigated the almost depleted onshore gas reservoir located in the Rotliegend sandstone at over 3,000-m depth. The high salinity of the formation fluids and the elevated temperature in the reservoir exceed the validity limits of commonly available thermodynamic databases needed for predictive geochemical modelling. In particular, it is shown that the activity model of Pitzer has to be applied, even if necessary input data for this model are incomplete or inconsistent for complex systems and for the considered temperatures. Simulations based on Debye- Hu¨ckel activity model lead to severe, systematic discrepancies already in the simple proposed reference case where experimental data could be used for comparison. A simplified geochemical model, consistent with the average measured composition of formation fluids and the prevailing mineralogical assemblage of the host rock, identifies the mineral phases most likely to be considered at equilibrium with the formation fluid. The simulated reactions due to CO2 injection, under the hypothesis of local thermodynamical equilibrium, result in a moderate reactivity of the system, with the dissolution of anhydrite cementation and haematite being the most relevant expected mineral reactions. This is compensated, at equilibrium, by the precipitation of new carbonates, like calcite and siderite, for an overall very small loss of porous space. The simulated rather small effect of mineral alteration is also due to the scarce amount of water available for reactions in the reservoir. The results of the model are qualitatively in line with observations from batch experiments and from natural analogues.

The present work discusses the numerical modelling of thermo-hydro-mechanical coupled processes for two in situ experiments on engineered barrier systems, which were performed at a real test site in the geological underground. Based on the phase related balance equations for mass, linear momentum and energy, a classical continuum approach for multiphysics analyses in porous media is presented. Within this context, the non-isothermal Richards' approximation is used for flow simulations in a partially saturated deformable solid skeleton. Regarding the constitutive modelling, basically relations typically discussed in literature for the applications under consideration are applied, and are calibrated on experimental data. Some specific problem-related modifications are presented. An incremental staggered finite element scheme is preferred to solve the coupled nonlinear initial-boundary value problem. Due to the process complexity of the combined simulation of both of the in situ experiments, a 3-D model is required. Additionally, the realisation of parallel algorithms in conjunction with high performance computing facilities essentially improves the efficiency of the numerical simulations. The presented models and algorithms are implemented into the scientific finite element code OpenGeoSys. Based on the analysis of the in situ experiments under consideration, the capabilities of OpenGeoSys to model application-oriented problems are shown.

This consensus statement from the members of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine recommends a standardized method for measuring gastric emptying (GE) by scintigraphy. A low-fat, egg-white meal with imaging at 0, 1, 2, and 4 h after meal ingestion, as described by a published multicenter protocol, provides standardized information about normal and delayed GE. Adoption of this standardized protocol will resolve the lack of uniformity of testing, add reliability and credibility to the results, and improve the clinical utility of the GE test.

This paper studies asymptotic consensus in systems in which agents do not necessarily have self-confidence, i.e., may disregard their own value during execution of the update rule. We show that the prevalent hypothesis of self-confidence in many convergence results can be replaced by the existence of aperiodic cores. These are stable aperiodic subgraphs, which allow to virtually store information about an agent's value distributedly in the network. Our results are applicable to systems with message delays and memory loss., 13 pages

International audience; Fast digital timing simulations based on continuous-time, digital-value circuit models are an attractive and heavily used alternative to analog simulations. Models based on analytic delay formulas are particularly interesting here, as they also facilitate formal verification and delay bound synthesis of complex circuits. Recently, Függer et al. (arXiv:1406.2544 [cs.OH]) proposed a circuit model based on so-called involution channels. It is the first binary circuit model that realistically captures solvability of short-pulse filtration, a non-trivial glitch propagation problem related to building one-shot inertial delays. In this work, we address the question of whether involu-tion channels also accurately model the delay of real circuits. Using both Spice simulations and physical measurements, we confirm that modeling an inverter chain by involution channels accurately describes reality. We also demonstrate that transitions in vanishing pulse trains are accurately predicted by the involution model. For our Spice simulations, we used both UMC-90 and UMC-65 technology, with varying supply voltages from nominal down to near sub-threshold range. The measurements were performed on a special-purpose UMC-90 ASIC that combines an inverter chain with low-intrusive high-speed on-chip analog amplifiers.

International audience; This paper studies the clock synchronization problem in highly dynamic networks. We show that diffusive synchronization algorithms are well adapted to environments in which the network topology may change unpredictably. In a diffusive algorithm, each node repeatedly (i) estimates the clock difference to its neighbors via broadcast of zero-bit messages, and (ii) updates its local clock according to a weighted average of the estimated differences. The system model allows for drifting local clocks, running at possibly different frequencies. We show that having a rooted spanning tree in the network at every time instance suffices to solve clock synchronization. We do not require any stability of the spanning tree, nor do we impose that the links of the spanning tree be known to the nodes. Explicit bounds on the convergence speed are obtained. In particular, our results settle an open question posed by Simeone and Spagnolini to reach clock synchronization in dynamic networks in the presence of nonzero clock drift. We also identify certain reasonable assumptions that allow for a significant higher convergence speed, e.g., bidirectional networks or random graph models.

International audience; We study variants of the α-synchronizer by Awerbuch (J. ACM, 1985) within a distributed message passing system with probabilistic message loss. The purpose of a synchronizer is to maintain a virtual (lock-step) round structure, which simplifies the design of higher-level distributed algorithms. The underlying idea of an α-synchronizer is to let processes continuously exchange round numbers and to allow a process to proceed to the next round only after it has witnessed that all processes have already started the current round. In this work, we study the performance of several synchronizers in an environment with probabilistic message loss. In particular, we analyze how different strategies of forgetting affect the round durations. The synchronizer variants considered differ in the times when processes discard part of their accumulated knowledge during the execution. Possible applications can be found, e.g., in sensor fusion, where sensor data become outdated and thus invalid after a certain amount of time. For all synchronizer variants considered, we develop corresponding Markov chain models and quantify the performance degradation using both analytic approaches and Monte-Carlo simulations. Our results allow to explicitly calculate the asymptotic behavior of the round durations: While in systems with very reliable communication the effect of forgetting is negligible, the effect is more profound in systems with less reliable communication. Our study thus provides compu-tationally efficient bounds on the performance of the (non-forgetting) α-synchronizer and allows to quantitatively assess the effect accumulated knowledge has on the performance.

International audience; Computing deterministic performance guarantees is a defining issue for systems with hard real-time constraints , like reactive embedded systems. In this paper, we use burst-rate constrained arrivals and rate-latency servers to deduce tight worst-case delay bounds in tandem networks under arbitrary multiplexing. We present a constructive method for computing the exact worst-case delay, which we prove to be a linear function of the burstiness and latencies; our bounds are hence symbolic in these parameters. Our algorithm runs in quadratic time in the number of servers. We also present an application of our algorithm to the case of stochastic arrivals and server capacities. For a generalization of the exponentially bounded burstiness (EBB) model, we deduce a polynomial-time algorithm for stochastic delay bounds that strictly improve the state-of-the-art separated flow analysis (SFA) type bounds.

Saccharomyces cerevisiae phosphoenolpyruvate (PEP) carboxykinase catalyses the reversible metal-dependent formation of oxaloacetate and ATP from PEP, ADP, and CO2 and plays a key role in gluconeogenesis. This enzyme also has oxaloacetate decarboxylase and pyruvate kinase-like activities. Mutations of PEP carboxykinase have been constructed where the residues Lys213 and His233, two residues of the putative Mn2+ binding site of the enzyme, were altered. Replacement of these residues by Arg and by Gln, respectively, generated enzymes with 1.9 and 2.8 kcal/mol lower Mn2+ binding affinity. Lower PEP binding affinity was inferred for the mutated enzymes from the protection effect of PEP against urea denaturation. Kinetic studies of the altered enzymes show at least a 5000-fold reduction in V(max) for the primary reaction relative to that for the wild-type enzyme. V(max) values for the oxaloacetate decarboxylase and pyruvate kinase-like activities of PEP carboxykinase were affected to a much lesser extent in the mutated enzymes. The mutated enzymes show a decreased steady-state affinity for Mn2+ and PEP. The results are consistent with Lys213 and His233 being at the Mn2+ binding site of S. cerevisiae PEP carboxykinase and the Mn2+ affecting the PEP interaction. The different effects of mutations in V(max) for the main reaction and the secondary activities suggest different rate-limiting steps for these reactions.

In this paper, we investigate the approximate consensus problem in highly dynamic networks in which topology may change continually and unpredictably. We prove that in both synchronous and partially synchronous systems, approximate consensus is solvable if and only if the communication graph in each round has a rooted spanning tree, i.e., there is a coordinator at each time. The striking point in this result is that the coordinator is not required to be unique and can change arbitrarily from round to round. Interestingly, the class of averaging algorithms, which are memoryless and require no process identifiers, entirely captures the solvability issue of approximate consensus in that the problem is solvable if and only if it can be solved using any averaging algorithm. Concerning the time complexity of averaging algorithms, we show that approximate consensus can be achieved with precision of $\varepsilon$ in a coordinated network model in $O(n^{n+1} \log\frac{1}{\varepsilon})$ synchronous rounds, and in $O(\Delta n^{n\Delta+1} \log\frac{1}{\varepsilon})$ rounds when the maximum round delay for a message to be delivered is $\Delta$. While in general, an upper bound on the time complexity of averaging algorithms has to be exponential, we investigate various network models in which this exponential bound in the number of nodes reduces to a polynomial bound. We apply our results to networked systems with a fixed topology and classical benign fault models, and deduce both known and new results for approximate consensus in these systems. In particular, we show that for solving approximate consensus, a complete network can tolerate up to 2n-3 arbitrarily located link faults at every round, in contrast with the impossibility result established by Santoro and Widmayer (STACS '89) showing that exact consensus is not solvable with n-1 link faults per round originating from the same node.

We survey and discuss upper bounds on the length of the transient phase of max-plus linear systems and sequences of max-plus matrix powers. In particular, we explain how to extend a result by Nachtigall to yield a new approach for proving such bounds and we state an asymptotic tightness result by using an example given by Hartmann and Arguelles., Comment: 13 pages, 2 figures

Pyruvate kinase requires K+ for maximal activity; the enzyme exhibits 0.02% of maximal activity in its absence [Kayne, F. J. (1971) Arch. Biochem. Biophys. 143, 232–239]. However, pyruvate kinase entrapped in reverse micelles exhibits an important K+-independent activity [Ramirez-Silva, L., Tuena de Gomez-Puyou, M., & Gomez-Puyou, A. (1993) Biochemistry32, 5332–5338]. It is possible that the amount of water, as well as interactions of the protein with the micelles, can account for this behavior. We therefore explored the solvent effects on the catalytic properties of muscle pyruvate kinase. The enzyme exhibited an activity of 19.4 µmol·min−1·mg−1 in 40% dimethylsulfoxide, compared with 280 and 0.023 µmol· min1·mg−1 observed with and without K+ in water, respectively. pH activity profiles and kinetic constants for the substrates of pyruvate kinase in dimethylsulfoxide without K+ were similar to those in 100% water with K+, and differed from those in water without K+. The spectral center of mass of the emission spectrum of pyruvate kinase in 100% water exhibited a blue shift of 3.5 nm in the presence of Mg2+, phosphenolpyruvate, and K+, ligands that induce the active conformation of the enzyme. The spectral center of mass of the apoenzyme in 30–40% dimethylsulfoxide coincided with that of the enzyme–Mg2+–phosphenolpyruvate–K+ complex in 100% water. The water relaxation rate enhancement factor and binding of phosphenolpyruvate to the pyruvate kinase–Mn2+–(CH3)4N+ complex in 30–40% dimethylsulfoxide were similar to those of the pyruvate kinase–Mn2+–K+ complex in water. The aforementioned results indicate that when muscle pyruvate kinase is without K+, 30–40% dimethylsulfoxide induces its active conformation.

The nature of bonding and energetics in trivalent rare earth π-donor ligand complexes [NdC13–πL] and [NdCp2–πL]+ have been investigated theoretically by employing Hartree–Fock (HF) and density functional theory (DFT) based methods. Acetylene, ethylene, butadiene, and benzene served as model π-ligands. Geometries and binding energies are reported. The analysis presented in this study clearly indicates the essentially electrostatic character of that binding interaction in terms of a cation–π-ligand interaction. The lanthanide to π-ligand bonding was predicted to be weak, accompanied with a slight distortion of the ligand's geometry upon coordination. The role of electron correlation does not appear to be crucial in correctly predicting the metal–ligand interaction energy and the ligand distortion.

Background: Yeast pyruvate kinase (PK) catalyzes the final step in glycolysis. The enzyme therefore represents an important control point and is allosterically activated by fructose-1,6-bisphosphate (FBP). In mammals the enzyme is found as four different isozymes with different regulatory properties: two of these isozymes are produced by alternate splicing. The allosteric regulation of PK is directly related to proliferation of certain cell types, as demonstrated by the expression of an allosterically regulated isozyme in tumor cells. A model for the allosteric transition from the inactive (T) state to the active (R) state has been proposed previously, but until now the FBP-binding site had not been identified. Results: We report here the structures of PK from yeast complexed with a substrate analog and catalytic metal ions in the presence and absence of bound FBP. The allosteric site is located 40 a from the active site and is entirely located in the enzyme regulatory (C) domain. A phosphate-binding site for the allosteric activator is created by residues encoded by a region of the gene corresponding to the alternately spliced exon of mammalian isozymes. FBP activation appears to induce several conformational changes among active-site sidechains through a mechanism that is most likely to involve significant domain motions, as previously hypothesized. Conclusions: The structure and location of the allosteric activator site agrees with the pattern of alternate genetic splicing of the PK gene in multicellular eukaryotes that distinguishes between a non-regulated isozyme and the regulated fetal isozymes. The conformational differences observed between the active sites of inactive and fully active PK enzymes is in agreement with the recently determined thermodynamic mechanism of allosteric activation through a ‘metal relay' that increases the affinity of the enzyme for its natural phosphoenolpyruvate substrate.

We study sequences of optimal walks of a growing length, in weighted digraphs, or equivalently, sequences of entries of max-algebraic matrix powers with growing exponents. It is known that these sequences are eventually periodic when the digraphs are strongly connected. The transient of such periodicity depends, in general, both on the size of digraph and on the magnitude of the weights. In this paper, we show that some bounds on the indices of periodicity of (unweighted) digraphs, such as the bounds of Wielandt, Dulmage-Mendelsohn, Schwarz, Kim and Gregory-Kirkland-Pullman, apply to the weights of optimal walks when one of their ends is a critical node., 17 pages, 3 figures

International audience; We consider the sequence of maximal weights of walks of lengt n between two fixed nodes in a weighted digraph. It is known that these sequences show a periodic behavior after an initial transient. We identify relevant graph parameters and propose a modular strategy to derive new upper bounds on the transient. To the best of our knowledge, our bounds are the first that are both asymptotically tight and potentially subquadratic. In particular, the new bounds show that the transient is linear in the number of nodes in bi-directional trees. Besides, our results enable a fine-grained performance analysis and give guidelines for the design of distributed systems based on max-plus recursions.