Numerical Simulation of Grain Boundary Grooving By Level Set Method

A numerical investigation of grain-boundary grooving by means of a Level Set method is carried out. An idealized polygranular interconnect which consists of grains separated by parallel grain boundaries aligned normal to the average orientation of the surface is considered. The surface diffusion is the only physical mechanism assumed. The surface diffusion is driven by surface curvature gradients, and a fixed surface slope and zero atomic flux are assumed at the groove root. The corresponding mathematical system is an initial boundary value problem for a two-dimensional Hamilton-Jacobi type equation. The results obtained are in good agreement with both Mullins' analytical "small slope" solution of the linearized problem (W.W. Mullins, 1957) (for the case of an isolated grain boundary) and with solution for the periodic array of grain boundaries (S.A. Hackney, 1988).Comment: Submitted to the Journal of Computational Physics (19 pages, 8 Postscript figures, 3 tables, 29 references

High-Frequency Nanofluidics: An Experimental Study using Nanomechanical Resonators

Here we apply nanomechanical resonators to the study of oscillatory fluid dynamics. A high-resonance-frequency nanomechanical resonator generates a rapidly oscillating flow in a surrounding gaseous environment; the nature of the flow is studied through the flow-resonator interaction. Over the broad frequency and pressure range explored, we observe signs of a transition from Newtonian to non-Newtonian flow at $\omega\tau\approx 1$, where $\tau$ is a properly defined fluid relaxation time. The obtained experimental data appears to be in close quantitative agreement with a theory that predicts purely elastic fluid response as $\omega\tau\to \infty$

Évaluation du risque toxique lié à la prévalence de trihalométhanes dans l'eau utilisée pour la dialyse

L'hémodialyse est une thérapeutique réservée aux sujets insuffisants rénaux en attente d'une greffe. Elle permet de recueillir dans un soluté aqueux les déchets que l'organisme ne peut plus évacuer par voie rénale. L'eau nécessaire à la préparation de ce dialysat représente un volume de 90 à 200 litres par séance et par sujet. Elle est obtenue en faisant subir à l'eau du réseau de distribution un traitement complémentaire. Celui-ci comporte en milieu spécialisé une chloration, un adoucissement par résines cationiques, une filtration sur colonne de charbon actif en grains et une osmose inverse.Les trihalométhanes sont probablement les sous-produits de chloration les plus répandus dans les eaux distribuées. Certains parmi eux sont cancérigènes chez l'animal et mutagènes in vitro. Chez l'homme, leurs effets à faibles doses et à long terme restent discutés. Compte tenu des importants volumes d'eau nécessaires à la pratique de l'hémodialyse, il nous a paru intéressant d'observer l'efflcacité du circuit de pré-traitement sur ces composés et d'évaluer les doses auxquelles sont exposés les patients qui bénéficient de cette thérapeutique.Des prélèvements ont été réalisés aux différentes étapes du pré-traitement, de façon hebdomadaire dans deux installations identiques, à la recherche de trihalométhanes. Ils permettent de constater que du chloroforme à une concentration moyenne de 10,5 llgA est encore présent en bout de chaîne. En tenant compte des volumes d'eau utilisés pour chaque séance, ceci signifie que les patients dialysés sont exposés, selon leur âge, à des doses pouvant atteindre jusqu'à dix fois la valeur préconisée dans l'eau potable par l'OMS. La moitié de ce chloroforme est susceptible de passer dans la circulation sanguine et d'exercer un effet toxique. Cette situation peut être corrigée par le choix d'une ressource en eau à charge organique faible, par un renouvellement fréquent du charbon actif et par l'utilisation de membranes en polyamides dans les modules d'osmose inverse. Ces résultats doivent amener à une réflexion plus générale sur la présenoe de sous-produits de la chloration et de micropolluants dans l'eau utilisée en dialyse. Ils doivent également inciter les cliniciens à rechercher, chez les dialysés les plus exposés, d'éventuels effets délétères liés à ces produits.Hemodialysis is an indispensable therapy for patients with chronic renal failure. Two or three times a week and over several years, their blood is dialyzed in an artificial kidney against a dialysis fluid called dialysate.Each time, 90 to 200 liters of this fluid will flow through the apparatus. Before being mixed with the dialysis concentrate, the water will be treated in order to eliminate harmful substances such as aluminum or endotoxins.Trihalomethanes (THM) are probably the most widespread chlorination byproducts of tap water. Most of them are known as carcinogens for animals and mutagens in vitro. Although their hepatotoxicity and nephrotoxicity are obvious after acute intoxication, their effects at low doses on human health have still not been clearly demonstrated.Considering the great amount of water required by hemodialysis patients, we found interested in determining wether the control of these substances by the hospital water treatment plant was efficient. We decided then to analyze weekly and during two months, the tap water of two hemodialysis departments for THM, before and after various forms of treatment. The treatment in both departments was the same and made up of four important stages: chlorination, softening, charcoal filtering and reverse osmosis.THM determinations were conducted using the headspace technique with a gas chromatograph equipped with a split injector and an [sup]63Ni electron capture detector.Our results show that chloroform and dichlorobromomethane were present in tap water. Their respective mean concentration in both department came to 56 µg/l and 5 µg/l. After chlorination and water softening, these figures had moderately but significantly increased. In the first department, thanks to new granular activated carbon, a large part of THM (especially dichlorobromomethane) had been removed. However after seven weeks, this treatment was no longer efficient and only 7% of the influent chloroform and 50% of the dichlorobromomethane could be removed. In the second department, the charcoal filter had already been working for more than one year at the beginning of our study. No decrease of the chloroform concentration had been observed and dichlorobromomethane had significantly increased. 80 to 90% of influent THM were removed after the double stage of reverse osmosis using polyamide membranes. With new granular activated carbon, the dialysis fluid only contains 1 µg/l of chloroform. But after seven weeks or more, it will reach an average of 10.5 g/l of chloroform and 1 µg/l of dichlorobromomethane. These figures are probably underestimated as our study was performed in winter and THM concentrations are less important during that season.These results mean that during a single session, 0.9 to 2.1 mg of chloroform will reach the artificial kidney. Depending on the weight of the patients, this exposure will be equivalent up to 10 times the value recommended by the World Health Organization (WHO) for drinking water.The last part of our study monitored the chloroform concentration in dialysate coming out the artificial kidney during an hemodialysis period. A significant decrease, reaching up to 45% of the influent amount, was observed. This result suggests that some of the chloroform must have crossed the dialysis membrane.According to all these results, we think that it would be of great interest to explore the metabolism of chloroform on hemodialysis patients and to search for eventual toxic effects. Practical advices to people in charge of water treatment plants in hemodialysis department would be to use raw water with low concentrations of humic materials, in order to restrict THM formation. The charcoal filter should be changed more often (probably after 6 or 7 weeks). Alternatively, ways could be found for rapid regeneration of charcoal for THM removal. Finally and according to previous studies, a polyamide membrane should be systematically used for reverse osmosis.Our study could eventually be completed by searching in the dialysis fluid any other chlorination by-products which are responsible to a large extent for tap water mutagenicity

Are current-induced forces conservative?

The expression for the force on an ion in the presence of current can be derived from first principles without any assumption about its conservative character. However, energy functionals have been constructed that indicate that this force can be written as the derivative of a potential function. On the other hand, there exist compelling specific arguments that strongly suggest the contrary. We propose physical mechanisms that invalidate such arguments and demonstrate their existence with first-principles calculations. While our results do not constitute a formal resolution to the fundamental question of whether current-induced forces are conservative, they represent a substantial step forward in this direction.Comment: 4 pages, 4 Figures, submitted to PR

Modeling the impact of amino acid substitution in a monoclonal antibody on cation exchange chromatography

A vital part of biopharmaceutical research is decision making around which lead candidate should be progressed in early-phase development. When multiple antibody candidates show similar biological activity, developability aspects are taken into account to ease the challenges of manufacturing the potential drug candidate. While current strategies for developability assessment mainly focus on drug product stability, only limited information is available on how antibody candidates with minimal differences in their primary structure behave during downstream processing. With increasing time-to-market pressure and an abundance of monoclonal antibodies (mAbs) in development pipelines, developability assessments should also consider the ability of mAbs to integrate into the downstream platform. This study investigates the influence of amino acid substitutions in the complementarity-determining region (CDR) of a full-length IgG1 mAb on the elution behavior in preparative cation exchange chromatography. Single amino acid substitutions within the investigated mAb resulted in an additional positive charge in the light chain (L) and heavy chain (H) CDR, respectively. The mAb variants showed an increased retention volume in linear gradient elution compared with the wild-type antibody. Furthermore, the substitution of tryptophan with lysine in the H-CDR3 increased charge heterogeneity of the product. A multiscale in silico analysis, consisting of homology modeling, protein surface analysis, and mechanistic chromatography modeling increased understanding of the adsorption mechanism. The results reveal the potential effects of lead optimization during antibody drug discovery on downstream processing

Software defined networks in industrial automation

Trends such as the Industrial Internet of Things and Industry 4.0 have increased the need to use new and innovative network technologies in industrial automation. The growth of industrial automation communications is an outcome of the shift to harness the productivity and efficiency of manufacturing and process automation with a minimum of human intervention. Due to the ongoing evolution of industrial networks from Fieldbus technologies to Ethernet, a new opportunity has emerged to harness the benefits of Software Defined Networking (SDN). In this paper, we provide a brief overview of SDN in the industrial automation domain and propose a network architecture called the Software Defined Industrial Automation Network (SDIAN), with the objective of improving network scalability and efficiency. To match the specific considerations and requirements of having a deterministic system in an industrial network, we propose two solutions for flow creation: the Pro-active Flow Installation Scheme and the Hybrid Flow Installation Scheme. We analytically quantify the proposed solutions that alleviate the overhead incurred from the flow setup. The analytical model is verified using Monte Carlo simulations. We also evaluate the SDIAN architecture and analyze the network performance of the modified topology using the Mininet emulator. We further list and motivate SDIAN features and report on an experimental food processing plant demonstration featuring Raspberry Pi as a software-defined controller instead of traditional proprietary Programmable Logic Controllers. Our demonstration exemplifies the characteristics of SDIAN

Gene-Gene Interactions Lead to Higher Risk for Development of Type 2 Diabetes in an Ashkenazi Jewish Population

Evidence has accumulated that multiple genetic and environmental factors play important roles in determining susceptibility to type 2 diabetes (T2D). Although variants from candidate genes have become prime targets for genetic analysis, few studies have considered their interplay. Our goal was to evaluate interactions among SNPs within genes frequently identified as associated with T2D.Logistic regression was used to study interactions among 4 SNPs, one each from HNF4A[rs1884613], TCF7L2[rs12255372], WFS1[rs10010131], and KCNJ11[rs5219] in a case-control Ashkenazi sample of 974 diabetic subjects and 896 controls. Nonparametric multifactor dimensionality reduction (MDR) and generalized MDR (GMDR) were used to confirm findings from the logistic regression analysis. HNF4A and WFS1 SNPs were associated with T2D in logistic regression analyses [P<0.0001, P<0.0002, respectively]. Interaction between these SNPs were also strong using parametric or nonparametric methods: the unadjusted odds of being affected with T2D was 3 times greater in subjects with the HNF4A and WFS1 risk alleles than those without either (95% CI = [1.7-5.3]; P<or=0.0001). Although the univariate association between the TCF7L2 SNP and T2D was relatively modest [P = 0.02], when paired with the HNF4A SNP, the OR for subjects with risk alleles in both SNPs was 2.4 [95% CI = 1.7-3.4; P<or=0.0001]. The KCNJ11 variant reached significance only when paired with either the HNF4A or WFSI SNPs: unadjusted ORs were 2.0 [95% CI = 1.4-2.8; P<or=0.0001] and 2.3 [95% CI = 1.2-4.4; P<or=0.0001], respectively. MDR and GMDR results were consistent with the parametric findings.These results provide evidence of strong independent associations between T2D and SNPs in HNF4A and WFS1 and their interaction in our Ashkenazi sample. We also observed an interaction in the nonparametric analysis between the HNF4A and KCNJ11 SNPs (P<or=0.001), demonstrating that an independently non-significant variant may interact with another variant resulting in an increased disease risk

Phase protection of Fano-Feshbach resonances

Decay of bound states due to coupling with free particle states is a general phenomenon occurring at energy scales from MeV in nuclear physics to peV in ultracold atomic gases. Such a coupling gives rise to Fano-Feshbach resonances (FFR) that have become key to understanding and controlling interactions—in ultracold atomic gases, but also between quasiparticles, such as microcavity polaritons. Their energy positions were shown to follow quantum chaotic statistics. In contrast, their lifetimes have so far escaped a similarly comprehensive understanding. Here, we show that bound states, despite being resonantly coupled to a scattering state, become protected from decay whenever the relative phase is a multiple of π. We observe this phenomenon by measuring lifetimes spanning four orders of magnitude for FFR of spin–orbit excited molecular ions with merged beam and electrostatic trap experiments. Our results provide a blueprint for identifying naturally long-lived states in a decaying quantum system