P19-53 LB. Priming with recombinant BCG expressing HIV-1 Gag or RT and boosting with recombinant MVA induces an effective immune response in mice

Mycobacterium bovis BCG (BCG) has a number of characteristics that give it great potential to act as a vehicle for the delivery of recombinant vaccines. However, its success depends on overcoming the challenges of poor antigen expression levels and genetic instability. Our studies using an optimized mycobacterial shuttle vector which utilizes the Mycobacterium tuberculosis mtrA promoter, induced upon infection of macrophages, and the M. tuberculosis 19 kDa signal sequence may overcome these issues. We have used this system to generate a recombinant BCG (rBCG) expressing HIV-1 subtype C full length Gag or reverse transcriptase (RT)

Google DeepMind and healthcare in an age of algorithms

Data-driven tools and techniques, particularly machine learning methods that underpin artificial intelligence, offer promise in improving healthcare systems and services. One of the companies aspiring to pioneer these advances is DeepMind Technologies Limited, a wholly-owned subsidiary of the Google conglomerate, Alphabet Inc. In 2016, DeepMind announced its first major health project: a collaboration with the Royal Free London NHS Foundation Trust, to assist in the management of acute kidney injury. Initially received with great enthusiasm, the collaboration has suffered from a lack of clarity and openness, with issues of privacy and power emerging as potent challenges as the project has unfolded. Taking the DeepMind-Royal Free case study as its pivot, this article draws a number of lessons on the transfer of population-derived datasets to large private prospectors, identifying critical questions for policy-makers, industry and individuals as healthcare moves into an algorithmic age

Effect of herbicide resistance endowing Ile-1781-Leu and Asp-2078-Gly ACCase gene mutations on ACCase kinetics and growth traits in Lolium rigidum

4711-4718The rate of herbicide resistance evolution in plants depends on fitness traits endowed by alleles in both the presence and absence (resistance cost) of herbicide selection. The effect of two Lolium rigidum spontaneous homozygous target-site resistance-endowing mutations (Ile-1781-Leu, Asp-2078-Gly) on both ACCase activity and various plant growth traits have been investigated here. Relative growth rate (RGR) and components (net assimilation rate, leaf area ratio), resource allocation to different organs, and growth responses in competition with a wheat crop were assessed. Unlike plants carrying the Ile-1781-Leu resistance mutation, plants homozygous for the Asp-2078-Gly mutation exhibited a significantly lower RGR (30 per cent), which translated into lower allocation of biomass to roots, shoots, and leaves, and poor responses to plant competition. Both the negligible and significant growth reductions associated, respectively, with the Ile-1781-Leu and Asp-2078-Gly resistance mutations correlated with their impact on ACCase activity. Whereas the Ile-1781-Leu mutation showed no pleiotropic effects on ACCase kinetics, the Asp-2078-Gly mutation led to a significant reduction in ACCase activity. The impaired growth traits are discussed in the context of resistance costs and the effects of each resistance allele on ACCase activity. Similar effects of these two particular ACCase mutations on the ACCase activity of Alopecurus myosuroides were also confirmed

Method for Measuring the Dielectric Constant of Ferroelectric Ceramics at S-Band Frequencies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66190/1/j.1151-2916.1960.tb13658.x.pd

Evidence for a vortex-glass transition in superconducting Ba(Fe0.9_{0.9}Co0.1_{0.1})2_{2}As2_{2}

Measurements of magneto-resistivity and magnetic susceptibility were performed on single crystals of superconducting Ba(Fe$_{0.9}$Co$_{0.1}$)$_{2}$As$_{2}$ close to the conditions of optimal doping. The high quality of the investigated samples allows us to reveal a dynamic scaling behaviour associated with a vortex-glass phase transition in the limit of weak degree of quenched disorder. Accordingly, the dissipative component of the ac susceptibility is well reproduced within the framework of Havriliak-Negami relaxation, assuming a critical power-law divergence for the characteristic correlation time $\tau$ of the vortex dynamics. Remarkably, the random disorder introduced by the Fe$_{1-x}$Co$_{x}$ chemical substitution is found to act on the vortices as a much weaker quenched disorder than previously reported for cuprate superconductors such as, e.g., Y$_{1-x}$Pr$_{x}$Ba$_{2}$Cu$_{3}$O$_{7-\delta}$.Comment: 10 pages, 8 figure

Effects of disorder in location and size of fence barriers on molecular motion in cell membranes

The effect of disorder in the energetic heights and in the physical locations of fence barriers encountered by transmembrane molecules such as proteins and lipids in their motion in cell membranes is studied theoretically. The investigation takes as its starting point a recent analysis of a periodic system with constant distances between barriers and constant values of barrier heights, and employs effective medium theory to treat the disorder. The calculations make possible, in principle, the extraction of confinement parameters such as mean compartment sizes and mean intercompartmental transition rates from experimentally reported published observations. The analysis should be helpful both as an unusual application of effective medium theory and as an investigation of observed molecular movements in cell membranes.Comment: 9 pages, 5 figure

Molecular motion in cell membranes: analytic study of fence-hindered random walks

A theoretical calculation is presented to describe the confined motion of transmembrane molecules in cell membranes. The study is analytic, based on Master equations for the probability of the molecules moving as random walkers, and leads to explicit usable solutions including expressions for the molecular mean square displacement and effective diffusion constants. One outcome is a detailed understanding of the dependence of the time variation of the mean square displacement on the initial placement of the molecule within the confined region. How to use the calculations is illustrated by extracting (confinement) compartment sizes from experimentally reported published observations from single particle tracking experiments on the diffusion of gold-tagged G-protein coupled mu-opioid receptors in the normal rat kidney cell membrane, and by further comparing the analytical results to observations on the diffusion of phospholipids, also in normal rat kidney cells.Comment: 10 pages, 5 figure

Scalable and cost-effective NGS genotyping in the cloud

Background: While next-generation sequencing (NGS) costs have plummeted in recent years, cost and complexity of computation remain substantial barriers to the use of NGS in routine clinical care. The clinical potential of NGS will not be realized until robust and routine whole genome sequencing data can be accurately rendered to medically actionable reports within a time window of hours and at scales of economy in the 10’s of dollars. Results: We take a step towards addressing this challenge, by using COSMOS, a cloud-enabled workflow management system, to develop GenomeKey, an NGS whole genome analysis workflow. COSMOS implements complex workflows making optimal use of high-performance compute clusters. Here we show that the Amazon Web Service (AWS) implementation of GenomeKey via COSMOS provides a fast, scalable, and cost-effective analysis of both public benchmarking and large-scale heterogeneous clinical NGS datasets. Conclusions: Our systematic benchmarking reveals important new insights and considerations to produce clinical turn-around of whole genome analysis optimization and workflow management including strategic batching of individual genomes and efficient cluster resource configuration.Yassine Souilmi, Alex K. Lancaster, Jae-Yoon Jung, Ettore Rizzo, Jared B. Hawkins, Ryan Powles, Saaïd Amzazi, Hassan Ghazal, Peter J. Tonellato and Dennis P. Wal