Positively Correlated miRNA-miRNA Regulatory Networks in Mouse Frontal Cortex During Early Stages of Alcohol Dependence

Although the study of gene regulation via the action of specific microRNAs (miRNAs) has experienced a boom in recent years, the analysis of genome-wide interaction networks among miRNAs and respective targeted mRNAs has lagged behind. MicroRNAs simultaneously target many transcripts and fine-tune the expression of genes through cooperative/combinatorial targeting. Therefore, they have a large regulatory potential that could widely impact development and progression of diseases, as well as contribute unpredicted collateral effects due to their natural, pathophysiological, or treatment-induced modulation. We support the viewpoint that whole mirnome-transcriptome interaction analysis is required to better understand the mechanisms and potential consequences of miRNA regulation and/or deregulation in relevant biological models. In this study, we tested the hypotheses that ethanol consumption induces changes in miRNA-mRNA interaction networks in the mouse frontal cortex and that some of the changes observed in the mouse are equivalent to changes in similar brain regions from human alcoholics. Results: miRNA-mRNA interaction networks responding to ethanol insult were identified by differential expression analysis and weighted gene coexpression network analysis (WGCNA). Important pathways (coexpressed modular networks detected by WGCNA) and hub genes central to the neuronal response to ethanol are highlighted, as well as key miRNAs that regulate these processes and therefore represent potential therapeutic targets for treating alcohol addiction. Importantly, we discovered a conserved signature of changing miRNAs between ethanol-treated mice and human alcoholics, which provides a valuable tool for future biomarker/diagnostic studies in humans. We report positively correlated miRNA-mRNA expression networks that suggest an adaptive, targeted miRNA response due to binge ethanol drinking. Conclusions: This study provides new evidence for the role of miRNA regulation in brain homeostasis and sheds new light on current understanding of the development of alcohol dependence. To our knowledge this is the first report that activated expression of miRNAs correlates with activated expression of mRNAs rather than with mRNA downregulation in an in vivo model. We speculate that early activation of miRNAs designed to limit the effects of alcohol-induced genes may be an essential adaptive response during disease progression.NIAAA 5R01AA012404, 5P20AA017838, 5U01AA013520, P01AA020683, 5T32AA007471-24/25Waggoner Center for Alcohol and Addiction Researc

Sample Return Systems for Extreme Environments (SaRSEE)

Sample return missions offer a greater science yield when compared to missions that only employ in situ experiments or remote sensing observations, since they allow the application of more complex technological and analytical methodologies in controlled terrestrial laboratories,that are both repeatable and can be independently verified. The successful return of extraterrestrial materials over the last four decades has contributed to our understanding of the solar system, but retrieval techniques have largely depended on the use of either soft-landing, or touch-and-go procedures that result in high V requirements, larger spacecraft mass ratios, and return yields typically limited to a few grams of surface materials that have experienced varying degrees of alteration from space weathering. Hard-landing methods using planetary penetrators offer an alternative for sample return that significantly reduce a mission's V and mass ratios,increase sample yields, and allow for the collection of subsurface materials, and lessons can be drawn from previous sample return missions. The following details progress in the design,development, and testing of penetrator/sampler technology capable of surviving subsonic and low, supersonic impact velocities (<700 m/s) that would enable the collection of geologic materials using tether technology to return the sample to a passing spacecraft. The testing of energy absorbing material for protecting the sample, design evolution and field testing of the penetrator, and dynamic modeling of tether behavior during sampling are discussed. It is shown through both modeling and field testing that penetrators at speeds between 300-600 m/s (~Mach 1-2) can penetrator into the ground to depths of 1-2 m with overall structural integrity attained.The first flight tests demonstrated the potential for survivability at these speeds. The second flight series demonstrated core sample collection with partial ejection of the sample return canister. The 3rd flight series demonstrated self-ejection of the sample return system fully intact and with the core retaining the full stratigraphy of the rock bed. The tether analysis shows that the forces on the tether during release and return of the sample to the main spacecraft are all at levels that can easily be handled by existing tether materials. The mass analysis of the requirements indicates that sample return form the asteroids could be handled with Discovery or New Frontier range of missions dependent on the number of samples to be returned to the Earth

Dissipation in nanocrystalline-diamond nanomechanical resonators

We have measured the dissipation and frequency of nanocrystalline-diamond nanomechanical resonators with resonant frequencies between 13.7 MHz and 157.3 MHz, over a temperature range of 1.4–274 K. Using both magnetomotive network analysis and a time-domain ring-down technique, we have found the dissipation in this material to have a temperature dependence roughly following T^(0.2), with Q^(–1) ≈ 10^(–4) at low temperatures. The frequency dependence of a large dissipation feature at ~35–55 K is consistent with thermal activation over a 0.02 eV barrier with an attempt frequency of 10 GHz

Controllable valley splitting in silicon quantum devices

Silicon has many attractive properties for quantum computing, and the quantum dot architecture is appealing because of its controllability and scalability. However, the multiple valleys in the silicon conduction band are potentially a serious source of decoherence for spin-based quantum dot qubits. Only when these valleys are split by a large energy does one obtain well-defined and long-lived spin states appropriate for quantum computing. Here we show that the small valley splittings observed in previous experiments on Si/SiGe heterostructures result from atomic steps at the quantum well interface. Lateral confinement in a quantum point contact limits the electron wavefunctions to several steps, and enhances the valley splitting substantially, up to 1.5 meV. The combination of electronic and magnetic confinement produces a valley splitting larger than the spin splitting, which is controllable over a wide range. These results improve the outlook for realizing spin qubits with long coherence times in silicon-based devices.Comment: Published version, including supplementary material

Very Shallow Water Bathymetry Retrieval from Hyperspectral Imagery at the Virginia Coast Reserve (VCR\u2707) Multi-Sensor Campaign

A number of institutions, including the Naval Research Laboratory (NRL), have developed look up tables for remote retrieval of bathymetry and in-water optical properties from hyperspectral imagery (HSI) [6]. For bathymetry retrieval, the lower limit is the very shallow water case (here defined as \u3c 2m), a depth zone which is not well resolved by many existing bathymetric LIDAR sensors, such as SHOALS [4]. The ability to rapidly model these shallow water depths from HSI directly has potential benefits for combined HSI/LIDAR systems such as the Compact Hydrographic Airborne Rapid Total Survey (CHARTS) [10]. In this study, we focused on the validation of a near infra-red feature, corresponding to a local minimum in absorption (and therefore a local peak in reflectance), which can be correlated directly to bathymetry with a high degree of confidence. Compared to other VNIR wavelengths, this particular near-IR feature corresponds to a peak in the correlation with depth in this very shallow water regime, and this is a spectral range where reflectance depends primarily on water depth (water absorption) and bottom type, with suspended constituents playing a secondary role

Linking goniometer measurements to hyperspectral and multi-sensor imagery for retrieval of beach properties and coastal characterization

In June 2011, a multi-sensor airborne remote sensing campaign was flown at the Virginia Coast Reserve Long Term Ecological Research site with coordinated ground and water calibration and validation (cal/val) measurements. Remote sensing imagery acquired during the ten day exercise included hyperspectral imagery (CASI-1500), topographic LiDAR, and thermal infra-red imagery, all simultaneously from the same aircraft. Airborne synthetic aperture radar (SAR) data acquisition for a smaller subset of sites occurred in September 2011 (VCR\u2711). Focus areas for VCR\u2711 were properties of beaches and tidal flats and barrier island vegetation and, in the water column, shallow water bathymetry. On land, cal/val emphasized tidal flat and beach grain size distributions, density, moisture content, and other geotechnical properties such as shear and bearing strength (dynamic deflection modulus), which were related to hyperspectral BRDF measurements taken with the new NRL Goniometer for Outdoor Portable Hyperspectral Earth Reflectance (GOPHER). This builds on our earlier work at this site in 2007 related to beach properties and shallow water bathymetry. A priority for VCR\u2711 was to collect and model relationships between hyperspectral imagery, acquired from the aircraft at a variety of different phase angles, and geotechnical properties of beaches and tidal flats. One aspect of this effort was a demonstration that sand density differences are observable and consistent in reflectance spectra from GOPHER data, in CASI hyperspectral imagery, as well as in hyperspectral goniometer measurements conducted in our laboratory after VCR\u2711

Constraints on the Mode and Extent of Sedimentary Rock Alteration in Hyper-Arid and Hypo-Thermal Environments

Geologic evidence suggests that the surface of Mars has been dominated by cold, dry, and relatively stable environmental conditions over the past ~3.5 Ga. These conditions differ from those pre-sumed to be present prior to ~3.5 Ga, when observa-tions indicate that the martian surface was at least in-termittently able to support the prolonged flow of liq-uid water. Despite the more than 75% of martian his-tory dominated by cold, dry, and stable conditions, few investigations have studied weathering and alteration processes that may influence the martian surface dur-ing this time. Please see attachment

Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy

The tumor microenvironment consists of stromal cells and extracellular factors that evolve in parallel with carcinoma cells. To gain insights into the activities of stromal cell populations, we developed and applied multicolor imaging techniques to analyze the behavior of these cells within different tumor microenvironments in the same live mouse. We found that regulatory T-lymphocytes (Tregs) migrated in proximity to blood vessels. Dendriticlike cells, myeloid cells and carcinoma-associated fibroblasts all exhibited higher motility in the microenvironment at the tumor periphery than within the tumor mass. Since oxygen levels differ between tumor microenvironments, we tested if acute hypoxia could account for the differences in cell migration. Direct visualization revealed that Tregs ceased migration under acute systemic hypoxia, whereas myeloid cells continued migrating. In the same mouse and microenvironment, we experimentally subdivided the myeloid cell population and revealed that uptake of fluorescent dextran defined a low-motility subpopulation expressing markers of tumor-promoting, alternatively activated macrophages. In contrast, fluorescent anti-Gr1 antibodies marked myeloid cells patrolling inside tumor vessels and in the stroma. Our techniques allow real-time combinatorial analysis of cell populations based on spatial location, gene expression, behavior and cell surface molecules within intact tumors. The techniques are not limited to investigations in cancer, but could give new insights into cell behavior more broadly in development and disease