Development of rapid, automated diagnostics for infectious disease: advances and challenges

The last 2 years has seen an exponential rise in the amount of research funding made available for the development of rapid diagnostic devices for infectious agents of medical importance. This review reports on several such projects. These highlight the development of fully automated devices for rapid diagnostics, ranging from fully automated real-time PCR-based detection methods to fully automated PCR- and array-based machines for the detection and typing of influenza. This review will also highlight the importance of refocusing work on classical immunoassay techniques, showing how biosensor-based immunoassays can greatly enhance existing assays and at a much reduced cost to molecular-based methods

Population-based neuropathological studies of dementia: design, methods and areas of investigation – a systematic review

Background Prospective population-based neuropathological studies have a special place in dementia research which is under emphasised. Methods A systematic review of the methods of population-based neuropathological studies of dementia was carried out. These studies were assessed in relation to their representativeness of underlying populations and the clinical, neuropsychological and neuropathological approaches adopted. Results Six studies were found to be true population-based neuropathological studies of dementia in the older people: the Hisayama study (Japan); Vantaa 85+ study (Finland); CC75C study (Cambridge, UK); CFAS (multicentre, UK); Cache County study (Utah, USA); HAAS (Hawaï, USA). These differ in the core characteristics of their populations. The studies used standardised neuropathological methods which facilitate analyses on: clinicopathological associations and confirmation of diagnosis, assessing the validity of hierarchical models of neuropathological lesion burden; investigating the associations between neuropathological burden and risk factors including genetic factors. Examples of findings are given although there is too little overlap in the areas investigated amongst these studies to form the basis of a systematic review of the results. Conclusion Clinicopathological studies based on true population samples can provide unique insights in dementia. Individually they are limited in power and scope; together they represent a powerful source to translate findings from laboratory to populations

Irregular speech rate dissociates auditory cortical entrainment, evoked responses, and frontal alpha

The entrainment of slow rhythmic auditory cortical activity to the temporal regularities in speech is considered to be a central mechanism underlying auditory perception. Previous work has shown that entrainment is reduced when the quality of the acoustic input is degraded, but has also linked rhythmic activity at similar time scales to the encoding of temporal expectations. To understand these bottom-up and top-down contributions to rhythmic entrainment, we manipulated the temporal predictive structure of speech by parametrically altering the distribution of pauses between syllables or words, thereby rendering the local speech rate irregular while preserving intelligibility and the envelope fluctuations of the acoustic signal. Recording EEG activity in human participants, we found that this manipulation did not alter neural processes reflecting the encoding of individual sound transients, such as evoked potentials. However, the manipulation significantly reduced the fidelity of auditory delta (but not theta) band entrainment to the speech envelope. It also reduced left frontal alpha power and this alpha reduction was predictive of the reduced delta entrainment across participants. Our results show that rhythmic auditory entrainment in delta and theta bands reflect functionally distinct processes. Furthermore, they reveal that delta entrainment is under top-down control and likely reflects prefrontal processes that are sensitive to acoustical regularities rather than the bottom-up encoding of acoustic features

Integral D-Finite Functions

We propose a differential analog of the notion of integral closure of algebraic function fields. We present an algorithm for computing the integral closure of the algebra defined by a linear differential operator. Our algorithm is a direct analog of van Hoeij's algorithm for computing integral bases of algebraic function fields

Root asymptotics of spectral polynomials for the Lame operator

The study of polynomial solutions to the classical Lam\'e equation in its algebraic form, or equivalently, of double-periodic solutions of its Weierstrass form has a long history. Such solutions appear at integer values of the spectral parameter and their respective eigenvalues serve as the ends of bands in the boundary value problem for the corresponding Schr\"odinger equation with finite gap potential given by the Weierstrass $\wp$-function on the real line. In this paper we establish several natural (and equivalent) formulas in terms of hypergeometric and elliptic type integrals for the density of the appropriately scaled asymptotic distribution of these eigenvalues when the integer-valued spectral parameter tends to infinity. We also show that this density satisfies a Heun differential equation with four singularities.Comment: final version, to appear in Commun. Math. Phys.; 13 pages, 3 figures, LaTeX2

Penrose Limit and String Theories on Various Brane Backgrounds

We investigate the Penrose limit of various brane solutions including Dp-branes, NS5-branes, fundamental strings, (p,q) fivebranes and (p,q) strings. We obtain special null geodesics with the fixed radial coordinate (critical radius), along which the Penrose limit gives string theories with constant mass. We also study string theories with time-dependent mass, which arise from the Penrose limit of the brane backgrounds. We examine equations of motion of the strings in the asymptotic flat region and around the critical radius. In particular, for (p,q) fivebranes, we find that the string equations of motion in the directions with the B field are explicitly solved by the spheroidal wave functions.Comment: 41 pages, Latex, minor correction

Engineering multiple levels of specificity in an RNA viral vector

Synthetic molecular circuits could provide powerful therapeutic capabilities, but delivering them to specific cell types and controlling them remains challenging. An ideal "smart" viral delivery system would enable controlled release of viral vectors from "sender" cells, conditional entry into target cells based on cell-surface proteins, conditional replication specifically in target cells based on their intracellular protein content, and an evolutionarily robust system that allows viral elimination with drugs. Here, combining diverse technologies and components, including pseudotyping, engineered bridge proteins, degrons, and proteases, we demonstrate each of these control modes in a model system based on the rabies virus. This work shows how viral and protein engineering can enable delivery systems with multiple levels of control to maximize therapeutic specificity

MHD Memes

The celebration of Allan Kaufman's 80th birthday was an occasion to reflect on a career that has stimulated the mutual exchange of ideas (or memes in the terminology of Richard Dawkins) between many researchers. This paper will revisit a meme Allan encountered in his early career in magnetohydrodynamics, the continuation of a magnetohydrodynamic mode through a singularity, and will also mention other problems where Allan's work has had a powerful cross-fertilizing effect in plasma physics and other areas of physics and mathematics.Comment: Submitted for publication in IOP Journal of Physics: Conference Series for publication in "Plasma Theory, Wave Kinetics, and Nonlinear Dynamics", Proceedings of KaufmanFest, 5-7 October 2007, University of California, Berkeley, US

Forest Carbon Sequestration under the U.S. Biofuel Energy Policies

This paper analyzes impacts of the U.S. biofuel energy policies on the carbon sequestration by forest products, which is expressed as Harvested Wood Products (HWP) Contribution under the United Nations Framework Convention on Climate Change. Estimation for HWP Contribution is based on tracking carbon stock stored in wood and paper products in use and in solid-waste disposal sites (SWDS) from domestic consumption, harvests, imports, and exports. For this analysis, we hypothesize four alternative scenarios using the existing and pending U.S. energy policies by requirements for the share of biofuel to total energy consumption, and solve partial equilibrium for the U.S. timber market by 2030 for each scenario. The U.S. Forest Products Module (USFPM), created by USDA Forest Service Lab, operating within the Global Forest Products Model (GFPM) is utilized for projecting productions, supplies, and trade quantities for the U.S. timber market equilibrium. Based on those timber market components, we estimate scenario-specific HWP Contributions under the Production, the Stock Change, and the Atmospheric Approach suggested by Intergovernmental Panel on Climate Change (IPCC) Guidelines for National Greenhouse Gas Inventories using WOODCARB II created by VTT Technical Research Centre of Finland and modified by USDA Forest Service Lab. Lastly, we compare estimated results across alternative scenarios. Results show that HWP Contributions for the baseline scenario in 2009 for all approaches are estimated higher than estimates reported by U.S. Environmental Protection Agency in 2011, (e.g., 22.64 Tg C/ year vs 14.80 Tg C/ year under the Production Approach), which is due to the economic recovery, especially in housing construction, assumed in USFPM/GFPM. Projected HWP Contribution estimates show that the Stock Change Approach, which used to provide the highest estimates before 2009, estimate HWP Contribution lowest after 2009 due to the declining annual net imports. Though fuel wood consumption is projected to be expanded as an alternative scenario requires higher wood fuel share to total energy consumption, the overall impacts on the expansion in other timber products are very modest across scenarios in USFPM/GFPM. Those negligible impacts lead to small differences of HWP Contribution estimates under all approaches across alternative scenarios. This is explained by the points that increasing logging residues are more crucial for expansion in fuel wood projections rather than the expansion of forest sector itself, and that the current HWP Contribution does not include carbon held in fuel wood products by its definition.Forest Products, Carbon Sequestration, Biofuel Policies, HWP Contribution, Resource /Energy Economics and Policy,