Simplicity of Completion Time Distributions for Common Complex Biochemical Processes

Biochemical processes typically involve huge numbers of individual reversible steps, each with its own dynamical rate constants. For example, kinetic proofreading processes rely upon numerous sequential reactions in order to guarantee the precise construction of specific macromolecules. In this work, we study the transient properties of such systems and fully characterize their first passage (completion) time distributions. In particular, we provide explicit expressions for the mean and the variance of the completion time for a kinetic proofreading process and computational analyses for more complicated biochemical systems. We find that, for a wide range of parameters, as the system size grows, the completion time behavior simplifies: it becomes either deterministic or exponentially distributed, with a very narrow transition between the two regimes. In both regimes, the dynamical complexity of the full system is trivial compared to its apparent structural complexity. Similar simplicity is likely to arise in the dynamics of many complex multi-step biochemical processes. In particular, these findings suggest not only that one may not be able to understand individual elementary reactions from macroscopic observations, but also that such understanding may be unnecessary

Methods of tropical optimization in rating alternatives based on pairwise comparisons

We apply methods of tropical optimization to handle problems of rating alternatives on the basis of the log-Chebyshev approximation of pairwise comparison matrices. We derive a direct solution in a closed form, and investigate the obtained solution when it is not unique. Provided the approximation problem yields a set of score vectors, rather than a unique (up to a constant factor) one, we find those vectors in the set, which least and most differentiate between the alternatives with the highest and lowest scores, and thus can be representative of the entire solution.Comment: 9 pages, presented at the Annual Intern. Conf. of the German Operations Research Society (GOR), Helmut Schmidt University Hamburg, Germany, August 30 - September 2, 201

Designing a physical activity parenting course : parental views on recruitment, content and delivery

Background Many children do not engage in sufficient levels of physical activity (PA) and spend too much time screen-viewing (SV). High levels of SV (e.g. watching TV, playing video games and surfing the internet) and low levels of PA have been associated with adverse health outcomes. Parenting courses may hold promise as an intervention medium to change children’s PA and SV. The current study was formative work conducted to design a new parenting programme to increase children’s PA and reduce their SV. Specifically, we focussed on interest in a course, desired content and delivery style, barriers and facilitators to participation and opinions on control group provision. Methods In-depth telephone interviews were conducted with thirty two parents (29 female) of 6–8 year olds. Data were analysed thematically. An anonymous online survey was also completed by 750 parents of 6–8 year old children and descriptive statistics calculated. Results Interview participants were interested in a parenting course because they wanted general parenting advice and ideas to help their children be physically active. Parents indicated that they would benefit from knowing how to quantify their child’s PA and SV levels. Parents wanted practical ideas of alternatives to SV. Most parents would be unable to attend unless childcare was provided. Schools were perceived to be a trusted source of information about parenting courses and the optimal recruitment location. In terms of delivery style, the majority of parents stated they would prefer a group-based approach that provided opportunities for peer learning and support with professional input. Survey participants reported the timing of classes and the provision of childcare were essential factors that would affect participation. In terms of designing an intervention, the most preferred control group option was the opportunity to attend the same course at a later date. Conclusions Parents are interested in PA/SV parenting courses but the provision of child care is essential for attendance. Recruitment is likely to be facilitated via trusted sources. Parents want practical advice on how to overcome barriers and suggest advice is provided in a mutually supportive group experience with expert input

Morphometric parameters of the human pineal gland in relation to age, body weight and height

The aim of the study was to compare the size, weight, volume and density of the pineal gland in several groups divided by age, body weight and height. 80 human pineal glands were included in the study. Obtained data were statistically analysed by means of Statistica by Statsoft to check existing differences. Obtained data show some significant differences between pineal gland morphometry in weight- and height-related groups. However, these differences do not influence pineal volume significantly. Differences between the pineal gland volume in the maximal and in the minimal weight groups may suggest some relationship between the gland’s structure and body weight. No age-related changes in the morphometry of the pineal gland were observed

Final State Interactions Effects in Neutrino-Nucleus Interactions

Final State Interactions effects are discussed in the context of Monte Carlo simulations of neutrino-nucleus interactions. A role of Formation Time is explained and several models describing this effect are compared. Various observables which are sensitive to FSI effects are reviewed including pion-nucleus interaction and hadron yields in backward hemisphere. NuWro Monte Carlo neutrino event generator is described and its ability to understand neutral current $\pi^0$ production data in $\sim 1$ GeV neutrino flux experiments is demonstrated.Comment: 13 pages, 16 figure

Fast Primal-Dual Gradient Method for Strongly Convex Minimization Problems with Linear Constraints

In this paper we consider a class of optimization problems with a strongly convex objective function and the feasible set given by an intersection of a simple convex set with a set given by a number of linear equality and inequality constraints. A number of optimization problems in applications can be stated in this form, examples being the entropy-linear programming, the ridge regression, the elastic net, the regularized optimal transport, etc. We extend the Fast Gradient Method applied to the dual problem in order to make it primal-dual so that it allows not only to solve the dual problem, but also to construct nearly optimal and nearly feasible solution of the primal problem. We also prove a theorem about the convergence rate for the proposed algorithm in terms of the objective function and the linear constraints infeasibility.Comment: Submitted for DOOR 201

Magnetic-film atom chip with 10 μ\mum period lattices of microtraps for quantum information science with Rydberg atoms

We describe the fabrication and construction of a setup for creating lattices of magnetic microtraps for ultracold atoms on an atom chip. The lattice is defined by lithographic patterning of a permanent magnetic film. Patterned magnetic-film atom chips enable a large variety of trapping geometries over a wide range of length scales. We demonstrate an atom chip with a lattice constant of 10 $\mu$m, suitable for experiments in quantum information science employing the interaction between atoms in highly-excited Rydberg energy levels. The active trapping region contains lattice regions with square and hexagonal symmetry, with the two regions joined at an interface. A structure of macroscopic wires, cut out of a silver foil, was mounted under the atom chip in order to load ultracold $^{87}$Rb atoms into the microtraps. We demonstrate loading of atoms into the square and hexagonal lattice sections simultaneously and show resolved imaging of individual lattice sites. Magnetic-film lattices on atom chips provide a versatile platform for experiments with ultracold atoms, in particular for quantum information science and quantum simulation.Comment: 7 pages, 7 figure

Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer

Actividad antitumoral; Calidad de vida con cáncer; PARPActivitat antitumoral; Qualitat de vida amb càncer; PARPAntitumor activity; Quality of life with cancer; PARPBACKGROUND Patients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitor olaparib has had antitumor activity in this population. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients who had a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy. Patients were randomly assigned, in a 3:2 ratio, to receive maintenance olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival, which was assessed by blinded independent central review. RESULTS Of the 3315 patients who underwent screening, 154 underwent randomization and were assigned to a trial intervention (92 to receive olaparib and 62 to receive placebo). The median progression-free survival was significantly longer in the olaparib group than in the placebo group (7.4 months vs. 3.8 months; hazard ratio for disease progression or death, 0.53; 95% confidence interval [CI], 0.35 to 0.82; P=0.004). An interim analysis of overall survival, at a data maturity of 46%, showed no difference between the olaparib and placebo groups (median, 18.9 months vs. 18.1 months; hazard ratio for death, 0.91; 95% CI, 0.56 to 1.46; P=0.68). There was no significant between-group difference in health-related quality of life, as indicated by the overall change from baseline in the global quality-of-life score (on a 100-point scale, with higher scores indicating better quality of life) based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (between-group difference, −2.47 points; 95% CI, −7.27 to 2.33). The incidence of grade 3 or higher adverse events was 40% in the olaparib group and 23% in the placebo group (between-group difference, 16 percentage points; 95% CI, −0.02 to 31); 5% and 2% of the patients, respectively, discontinued the trial intervention because of an adverse event. CONCLUSIONS Among patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo.Supported by AstraZeneca (as part of an alliance between AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck) and by a grant (P30-17 CA008748) from the National Institutes of Health National Cancer Institute Cancer Center

Accurate Liability Estimation Improves Power in Ascertained Case Control Studies

Linear mixed models (LMMs) have emerged as the method of choice for confounded genome-wide association studies. However, the performance of LMMs in non-randomly ascertained case-control studies deteriorates with increasing sample size. We propose a framework called LEAP (Liability Estimator As a Phenotype, https://github.com/omerwe/LEAP) that tests for association with estimated latent values corresponding to severity of phenotype, and demonstrate that this can lead to a substantial power increase

On some entropy functionals derived from R\'enyi information divergence

We consider the maximum entropy problems associated with R\'enyi $Q$-entropy, subject to two kinds of constraints on expected values. The constraints considered are a constraint on the standard expectation, and a constraint on the generalized expectation as encountered in nonextensive statistics. The optimum maximum entropy probability distributions, which can exhibit a power-law behaviour, are derived and characterized. The R\'enyi entropy of the optimum distributions can be viewed as a function of the constraint. This defines two families of entropy functionals in the space of possible expected values. General properties of these functionals, including nonnegativity, minimum, convexity, are documented. Their relationships as well as numerical aspects are also discussed. Finally, we work out some specific cases for the reference measure $Q(x)$ and recover in a limit case some well-known entropies