Salivary biomarker development using genomic, proteomic and metabolomic approaches.

The use of saliva as a diagnostic sample provides a non-invasive, cost-efficient method of sample collection for disease screening without the need for highly trained professionals. Saliva collection is far more practical and safe compared with invasive methods of sample collection, because of the infection risk from contaminated needles during, for example, blood sampling. Furthermore, the use of saliva could increase the availability of accurate diagnostics for remote and impoverished regions. However, the development of salivary diagnostics has required technical innovation to allow stabilization and detection of analytes in the complex molecular mixture that is saliva. The recent development of cost-effective room temperature analyte stabilization methods, nucleic acid pre-amplification techniques and direct saliva transcriptomic analysis have allowed accurate detection and quantification of transcripts found in saliva. Novel protein stabilization methods have also facilitated improved proteomic analyses. Although candidate biomarkers have been discovered using epigenetic, transcriptomic, proteomic and metabolomic approaches, transcriptomic analyses have so far achieved the most progress in terms of sensitivity and specificity, and progress towards clinical implementation. Here, we review recent developments in salivary diagnostics that have been accomplished using genomic, transcriptomic, proteomic and metabolomic approaches

What is the nature of morality? A response to Casebeer, Railton and Ruse

A response to comments by William Casebeer, Peter Railton, and Michael Ruse on "Naturalizing Ethics" (2007)

Inference and Optimization of Real Edges on Sparse Graphs - A Statistical Physics Perspective

Inference and optimization of real-value edge variables in sparse graphs are studied using the Bethe approximation and replica method of statistical physics. Equilibrium states of general energy functions involving a large set of real edge-variables that interact at the network nodes are obtained in various cases. When applied to the representative problem of network resource allocation, efficient distributed algorithms are also devised. Scaling properties with respect to the network connectivity and the resource availability are found, and links to probabilistic Bayesian approximation methods are established. Different cost measures are considered and algorithmic solutions in the various cases are devised and examined numerically. Simulation results are in full agreement with the theory.Comment: 21 pages, 10 figures, major changes: Sections IV to VII updated, Figs. 1 to 3 replace

Grain Physics and Rosseland Mean Opacities

Tables of mean opacities are often used to compute the transfer of radiation in a variety of astrophysical simulations from stellar evolution models to proto-planetary disks. Often tables, such as Ferguson et al. (2005), are computed with a predetermined set of physical assumptions that may or may not be valid for a specific application. This paper explores the effects of several assumptions of grain physics on the Rosseland mean opacity in an oxygen rich environment. We find that changing the distribution of grain sizes, either the power-law exponent or the shape of the distribution, has a marginal effect on the total mean opacity. We also explore the difference in the mean opacity between solid homogenous grains and grains that are porous or conglomorations of several species. Changing the amount of grain opacity included in the mean by assuming a grain-to-gas ratio significantly affects the mean opacity, but in a predictable way.Comment: 19 pages, 6 figures, accepted for publication in Ap

Colloidal transport through optical tweezer arrays

Viscously damped particles driven past an evenly spaced array of potential energy wells or barriers may become kinetically locked in to the array, or else may escape from the array. The transition between locked-in and free-running states has been predicted to depend sensitively on the ratio between the particles' size and the separation between wells. This prediction is confirmed by measurements on monodisperse colloidal spheres driven through arrays of holographic optical traps.Comment: 4 pages, 4 figure

Microorganisms in the Stratosphere (MIST): In-flight Sterilization with UVC Leds

The stratosphere (10 km to 50 km above sea level) is a unique place on Earth for astrobiological studies of microbes in extreme environments due to the combination of harsh conditions (high ultraviolet radiation, low pressure, desiccation, and low temperatures). Microorganisms in the Stratosphere (MIST) will attempt to characterize the diversity of microbes at these altitudes using a balloon collection device on a meteorological weather balloon. A major challenge of such an aerobiology study is the potential for ground contamination that makes it difficult to distinguish between collected microbes and contaminants. One solution is to use germicidal ultraviolet light emitting diodes (UV LEDs) to sterilize the collection strip. To use this solution, an optimal spatial arrangement of the lights had to be determined to ensure the greatest chance of complete sterilization within the 30 to 60 minute time of balloon ascent. A novel, 3D-printed test stand was developed to experimentally determine viable Bacillus pumilus SAFR-032 spore reduction after exposure to ultraviolet radiation at various times, angles, and distances. Taken together, the experimental simulations suggested that the UV LEDs on the MIST flight hardware should be active for at least 15 minutes and mounted within 4 cm of the illuminated surface at any angle to achieve optimal sterilization. These findings will aid in the production of the balloon collection device to ensure pristine stratospheric microbial samples are collected. Flight hardware capable of in-flight self-sterilization will enable future life detection missions to minimize both forward contamination and false positives

An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.

Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease