Microwell evaluation of mammalian cell lines for large scale culture.

Experimentation in shaken microplate formats offers a potential platform technology for the evaluation and optimisation of cell culture conditions. Provided that the results obtained are reliable, and indicative of large scale performance, it should be possible to obtain process design data early and cost effectively. This work describes a detailed engineering characterisation of liquid mixing and gas-liquid mass transfer in microwell systems and their impact on suspension cell cultures. Furthermore, an initial attempt at scaling a microwell culture to shake flasks and a 5-L stirred-tarik reactor is made. For suspension cultures of murine hybridoma cells producing IgGl, 24-well plates have been characterised in terms of power dissipation (P/V) (via CFD). Fluid flow patterns and oxygen transfer rate as a function of shaking frequency and liquid fill volume. Predicted ka values varied between 1.3 and 29 h_1 mixing time, quantified using decolourisation of iodine, varied from 1.7 s to 3.5 h while the P/V ranged from 5 to 35 W m-3. CFD simulations of the shear rate predicted hydrodynamic forces will not be lethal to cells. High shaking speed (> 250 rpm) was shown to be detrimental to cell growth, while a combination of low shaking speed and high well fill volume (120 rpm. 2000 //l) resulted in oxygen limited conditions. Using matched average energy dissipation as a basis for scale translation, cell growth and antibody titre were found to be similar in a 24-well plate. 250 ml shake flask and 5-L stirred-tank reactor. Overall this work has demonstrated that cell culture performed in shaken microwell plates can provide data that is both reproducible and representative of larger-scale cultures. Linked with automation this provides a route towards the high throughput evaluation of robust cell lines under realistic process conditions

Cooling atoms in an optical trap by selective parametric excitation

We demonstrate the possibility of energy-selective removal of cold atoms from a tight optical trap by means of parametric excitation of the trap vibrational modes. Taking advantage of the anharmonicity of the trap potential, we selectively remove the most energetic trapped atoms or excite those at the bottom of the trap by tuning the parametric modulation frequency. This process, which had been previously identified as a possible source of heating, also appears to be a robust way for forcing evaporative cooling in anharmonic traps.Comment: 5 pages, 5 figure

Initial State Interactions for K−K^--Proton Radiative Capture

The effects of the initial state interactions on the $K^--p$ radiative capture branching ratios are examined and found to be quite sizable. A general coupled-channel formalism for both strong and electromagnetic channels using a particle basis is presented, and applied to all the low energy $K^--p$ data with the exception of the {\it 1s} atomic level shift. Satisfactory fits are obtained using vertex coupling constants for the electromagnetic channels that are close to their expected SU(3) values.Comment: 16 pages, uses revte

The effect of adherence to spectacle wear on early developing literacy: a longitudinal study based in a large multi-ethnic city, Bradford, UK

YesObjectives: To determine the impact of adherence to spectacle wear on visual acuity (VA) and developing literacy following vision screening at age 4–5 years. Design: Longitudinal study nested within the Born in Bradford birth cohort. Setting and participants: Observation of 944 children: 432 had failed vision screening and were referred (treatment group) and 512 randomly selected (comparison group) who had passed (<0.20 logarithm of the minimum angle of resolution (logMAR) in both eyes). Spectacle wear was observed in school for 2 years following screening and classified as adherent (wearing spectacles at each assessment) or non-adherent. Main outcome measures: Annual measures of VA using a crowded logMAR test. Literacy was measured by Woodcock Reading Mastery Tests-Revised subtest: letter identification. Results: The VA of all children improved with increasing age, −0.009 log units per month (95% CI −0.011 to −0.007) (worse eye). The VA of the adherent group improved significantly more than the comparison group, by an additional −0.008 log units per month (95% CI −0.009 to −0.007) (worse eye) and −0.004 log units per month (95% CI −0.005 to −0.003) in the better eye. Literacy was associated with the VA, letter identification (ID) reduced by −0.9 (95% CI −1.15 to −0.64) for every one line (0.10 logMAR) fall in VA (better eye). This association remained after adjustment for socioeconomic and demographic factors (−0.33, 95% CI −0.54 to −0.12). The adherent group consistently demonstrated higher letter-ID scores compared with the non-adherent group, with the greatest effect size (0.11) in year 3. Conclusions: Early literacy is associated with the level of VA; children who adhere to spectacle wear improve their VA and also have the potential to improve literacy. Our results suggest failure to adhere to spectacle wear has implications for the child’s vision and education.AB is funded by a National Institute for Health Research Post- Doctoral Fellowship Award (PDF-2013-06-050). The Born in Bradford study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044)

A review of Monte Carlo simulations of polymers with PERM

In this review, we describe applications of the pruned-enriched Rosenbluth method (PERM), a sequential Monte Carlo algorithm with resampling, to various problems in polymer physics. PERM produces samples according to any given prescribed weight distribution, by growing configurations step by step with controlled bias, and correcting "bad" configurations by "population control". The latter is implemented, in contrast to other population based algorithms like e.g. genetic algorithms, by depth-first recursion which avoids storing all members of the population at the same time in computer memory. The problems we discuss all concern single polymers (with one exception), but under various conditions: Homopolymers in good solvents and at the $\Theta$ point, semi-stiff polymers, polymers in confining geometries, stretched polymers undergoing a forced globule-linear transition, star polymers, bottle brushes, lattice animals as a model for randomly branched polymers, DNA melting, and finally -- as the only system at low temperatures, lattice heteropolymers as simple models for protein folding. PERM is for some of these problems the method of choice, but it can also fail. We discuss how to recognize when a result is reliable, and we discuss also some types of bias that can be crucial in guiding the growth into the right directions.Comment: 29 pages, 26 figures, to be published in J. Stat. Phys. (2011

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Evolutionary dynamics of group formation

This is an open access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0 https://creativecommons.org/licenses/by/4.0/ which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Group formation is a quite ubiquitous phenomenon across different animal species, whose individuals cluster together forming communities of diverse size. Previous investigations suggest that, in general, this phenomenon might have similar underlying reasons across the interested species, despite genetic and behavioral differences. For instance improving the individual safety (e.g. from predators), and increasing the probability to get food resources. Remarkably, the group size might strongly vary from species to species, e.g. shoals of fishes and herds of lions, and sometimes even within the same species, e.g. tribes and families in human societies. Here we build on previous theories stating that the dynamics of group formation may have evolutionary roots, and we explore this fascinating hypothesis from a purely theoretical perspective, with a model using the framework of Evolutionary Game Theory. In our model we hypothesize that homogeneity constitutes a fundamental ingredient in these dynamics. Accordingly, we study a population that tries to form homogeneous groups, i.e. composed of similar agents. The formation of a group can be interpreted as a strategy. Notably, agents can form a group (receiving a ‘group payoff’), or can act individually (receiving an ‘individual payoff’). The phase diagram of the modeled population shows a sharp transition between the ‘group phase’ and the ‘individual phase’, characterized by a critical ‘individual payoff’. Our results then support the hypothesis that the phenomenon of group formation has evolutionary roots.Peer reviewedFinal Published versio