First-passage dynamics of obstructed tracer particle diffusion in one-dimensional systems

The standard setup for single-file diffusion is diffusing particles in one dimension which cannot overtake each other, where the dynamics of a tracer (tagged) particle is of main interest. In this article we generalise this system and investigate first-passage properties of a tracer particle when flanked by crowder particles which may, besides diffuse, unbind (rebind) from (to) the one-dimensional lattice with rates $k_{\rm off}$ ($k_{\rm on}$). The tracer particle is restricted to diffuse with rate $k_D$ on the lattice. Such a model is relevant for the understanding of gene regulation where regulatory proteins are searching for specific binding sites ona crowded DNA. We quantify the first-passage time distribution, $f(t)$ ($t$ is time), numerically using the Gillespie algorithm, and estimate it analytically. In terms of our key parameter, the unbinding rate $k_{\rm off}$, we study the bridging of two known regimes: (i) when unbinding is frequent the particles may effectively pass each other and we recover the standard single particle result $f(t)\sim t^{-3/2}$ with a renormalized diffusion constant, (ii) when unbinding is rare we recover well-known single-file diffusion result $f(t)\sim t^{-7/4}$. The intermediate cases display rich dynamics, with the characteristic $f(t)$-peak and the long-time power-law slope both being sensitive to $k_{\rm off}$

Aging dynamics in interacting many-body systems

Low-dimensional, complex systems are often characterized by logarithmically slow dynamics. We study the generic motion of a labeled particle in an ensemble of identical diffusing particles with hardcore interactions in a strongly disordered, one-dimensional environment. Each particle in this single file is trapped for a random waiting time $\tau$ with power law distribution $\psi(\tau)\simeq\tau^{-1- \alpha}$, such that the $\tau$ values are independent, local quantities for all particles. From scaling arguments and simulations, we find that for the scale-free waiting time case $0<\alpha<1$, the tracer particle dynamics is ultra-slow with a logarithmic mean square displacement (MSD) $\langle x^2(t)\rangle\simeq(\log t)^{1/2}$. This extreme slowing down compared to regular single file motion $\langle x^2(t)\rangle\simeq t^{1/2}$ is due to the high likelihood that the labeled particle keeps encountering strongly immobilized neighbors. For the case $1<\alpha<2$ we observe the MSD scaling $\langle x^2(t)\rangle\simeq t^{\gamma}$, where $\gamma2$ we recover Harris law $\simeq t^{1/2}$.Comment: 5 pages, 4 figure

Duality in Nondifferentiable Vector Programming

AbstractIn this paper we study the saddle point optimality conditions and Lagrange duality in multiobjective optimization for generalized subconvex-like functions. We obtain results which will allow us to characterize the solutions for multiobjective programming problems from the saddle point conditions and allow us to relate them to the dual problem solutions which will be adequately defined. We also define a new dual problem for the multiobjective programming problem with the special property of being a scalar programming problem

Response to sequential treatment schedules in childhood epilepsy Risk for development of refractory epilepsy

AbstractPurposeTo investigate response to sequential treatment schedules and risk of development of refractory epilepsy in childhood.MethodsAll children younger than 14 years with two or more unprovoked seizures seen at our hospital between 1994 and 2004 were included and prospectively followed. “Seizure control” was defined as a 2-year seizure-free interval without further recurrences except those related to attempts of medication withdrawal and “refractory epilepsy” as failure of >2 drugs plus >1 seizure/month for ≥18 months.Results343 Patients were included, 191 males and 152 females. Mean age at diagnosis was 4y 10 mo (SD 3 year 10 month). Mean follow-up period was 76.2 mo (SD 35.2). The probability of achieving “seizure control” was 70% and 86% at 5 and 10 years. 59% of patients were “controlled” with the first drug used. Among patients failing the first, second and third therapeutic regimen due to lack of efficacy, 39%, 23% and 12% respectively were finally “controlled” with subsequent treatment schedules Risk of development of refractory epilepsy was 8% and 12% at 6 and 10 years.ConclusionAfter failing a first drug, a significant proportion of children can still be controlled with subsequent therapeutic schedules. Only a small proportion develops refractory epilepsy

Serum Uric Acid as a Predictor for Development of Diabetic Nephropathy in Type 1 Diabetes: An Inception Cohort Study

OBJECTIVE—Experimental and clinical studies have suggested that uric acid may contribute to the development of hypertension and kidney disease. Whether uric acid has a causal role in the development of diabetic nephropathy is not known. The objec-tive of the present study is to evaluate uric acid as a predictor of persistent micro- and macroalbuminuria. RESEARCH DESIGN AND METHODS—This prospective ob-servational follow-up study consisted of an inception cohort of 277 patients followed from onset of type 1 diabetes. Of these, 270 patients had blood samples taken at baseline. In seven cases, uric acid could not be determined; therefore, 263 patients (156 men) were available for analysis. Uric acid was measured 3 years after onset of diabetes and before any patient developed microalbuminuria. RESULTS—During a median follow-up of 18.1 years (rang

Network Physiology reveals relations between network topology and physiological function

The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.Comment: 12 pages, 9 figure

¿Pueden los programas de entrenamiento de resistencia con banda elástica mitigar el aumento de peso durante las vacaciones y mejorar la fuerza de agarre de las manos en mujeres mayores?

Este estudio evaluó el efecto del entrenamien- to con ejercicios de resistencia (EER) sobre la composición corpo- ral y la fuerza muscular en 16 mujeres adultas mayores durante las vacaciones de verano (70, 5 ± 8, 4 años; Rango 60-87). Las sesio- nes de ejercicio se llevaron a cabo durante doce semanas, dos ve- ces por semana, con 60 minutos de ejercicio por sesión. Se evaluó el índice de masa corporal (IMC), el porcentaje de masa grasa (% MG, por bioimpedancia) y la fuerza de presión con un dinamómetro manual antes y después de la intervención. Las participantes mos- traron un aumento significativo en el IMC (p< 0, 05), % de MG (p<0, 001) y un incremento significativo en la fuerza prensil (p <0, 05). El programa de EER podría ser una estrategia importante para mejorar la fuerza de mujeres adultas mayores durante el periodo estival. El EER se sugiere combinarlo con otras variables, como ejercicios aeróbicos con intensidad gradualmente creciente y una intervención nutricional, para mantener un peso constante durante los períodos de vacaciones. This study evaluated the effect of resistance exercise training (RET) on body composition and muscle strength in 16 older women during summer holidays (70.5 ± 8.4 years old; Range 60-87). Exercise sessions were carried out for twelve weeks, two sessions per week, with 60 minutes of exercise per session. We measured body mass index (BMI), fat mass percentage (FM%, by bioimpedance) and grip strength with a dynamometer before and after the intervention. The participants showed a significant increase in BMI (p<0.05), FM% (p<0.001), and a significant gain in grip strength (p<0.05). The RET program could be an important strategy for improving strength for older women, but we would suggest combining it with other interventions, such as aerobic exercises with gradually increasing intensity and nutrition interventions, in order to maintain a steady weight during holiday periods

Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug-resistant focal epilepsy.

OBJECTIVE: Although many studies have attempted to describe treatment outcomes in patients with drug-resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug-resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. METHODS: This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug-resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). RESULTS: A seizure-free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a "treatment failure" as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as "undetermined outcome" (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug-resistant by the EP. SIGNIFICANCE: This study validates the use of ILAE treatment outcome criteria in a real-life setting, providing validated estimates of seizure freedom in patients with drug-resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases

Excision of an Unstable Pathogenicity Island in Salmonella enterica Serovar Enteritidis Is Induced during Infection of Phagocytic Cells

The availability of the complete genome sequence of several Salmonella enterica serovars has revealed the presence of unstable genetic elements in these bacteria, such as pathogenicity islands and prophages. This is the case of Salmonella enterica serovar Enteritidis (S. Enteritidis), a bacterium that causes gastroenteritis in humans and systemic infection in mice. The whole genome sequence analysis for S. Enteritidis unveiled the presence of several genetic regions that are absent in other Salmonella serovars. These regions have been denominated “regions of difference” (ROD). In this study we show that ROD21, one of such regions, behaves as an unstable pathogenicity island. We observed that ROD21 undergoes spontaneous excision by two independent recombination events, either under laboratory growth conditions or during infection of murine cells. Importantly, we also found that one type of excision occurred at higher rates when S. Enteritidis was residing inside murine phagocytic cells. These data suggest that ROD21 is an unstable pathogenicity island, whose frequency of excision depends on the environmental conditions found inside phagocytic cells