Eicosapentaenoic acid and oxypurinol in the treatment of muscle wasting in a mouse model of cancer cachexia

Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P&lt;0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P&lt;0.05). EPA (18.2&plusmn;3.2 pg/ml) and combination (18.4&plusmn;3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9&plusmn;1.4 pg/ml, P&le;0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P&le;0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P&le;0.05). Activity of total SOD was higher in the oxypurinol group (32.2&plusmn;1.5 U/ml) compared to control (27.0&plusmn;1.3 U/ml, P&lt;0.01), GPx activity was lower in the EPA group (8.76&plusmn;2.0 U/ml) compared to control (14.0&plusmn;1.9 U/ml, P&lt;0.05), and catalase activity was lower in the combination group (14.4&plusmn;2.8 U/ml) compared to control (20.9&plusmn;2.0 U/ml, P&lt;0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.<br /

An Investigation into the Effects of Variable Lake Ice Properties on Passive and Active Microwave Measurements Over Tundra Lakes Near Inuvik, N.W.T.

The accurate estimation of snow water equivalent (SWE) in the Canadian sub-arctic is integral to climate variability studies and water availability forecasts for economic considerations (drinking water, hydroelectric power generation). Common passive microwave (PM) snow water equivalent (SWE) algorithms that utilize the differences in brightness temperature (Tb) at 37 GHz – 19 GHz falter in lake-rich tundra environments because of the inclusion of lakes within PM pixels. The overarching goal of this research was to investigate the use of multiple platforms and methodologies to observe and quantify the effects of lake ice and sub-ice water on passive microwave emission for the purpose of improving snow water equivalent (SWE) retrieval algorithms. Using in situ snow and ice measurements as input, the Helsinki University of Technology (HUT) multi-layer snow emission model was modified to include an ice layer below the snow layer. Emission for 6.9, 19, 37 and 89 GHz were simulated at horizontal and vertical polarizations, and were validated by high resolution airborne passive microwave measurements coincident with in situ sampling sites over two lakes near Inuvik, Northwest Territories (NWT). Overall, the general magnitude of brightness temperatures were estimated by the HUT model for 6.9 and 19 GHz H/V, however the variability was not. Simulations produced at 37 GHz exhibited the best agreement relative to observed temperatures. However, emission at 37 GHz does not interact with the radiometrically cold water, indicating that ice properties controlling microwave emission are not fully captured by the HUT model. Alternatively, active microwave synthetic aperture radar (SAR) measurements can be used to identify ice properties that affect passive microwave emission. Dual polarized X-band SAR backscatter was utilized to identify ice types by the segmentation program MAGIC (MAp Guided Ice Classification). Airborne passive microwave transects were grouped by ice type classes and compared to backscatter measurements. In freshwater, where there were few areas of high bubble concentration at the ice/water interface Tbs exhibited positive correlations with cross-polarized backscatter, corresponding to ice types (from low to high emission/backscatter: clear ice, transition zone between clear and grey ice, grey ice and rafted ice). SWE algorithms were applied to emission within each ice type producing negative or near zero values in areas of low 19 GHz Tbs (clear ice, transition zone), but also produced positive values that were closer to the range of in situ measurements in areas of high 19 GHz Tbs (grey and rafted ice). Therefore, cross-polarized X-band SAR measurements can be used as a priori ice type information for spaceborne PM algorithms, providing information on ice types and ice characteristics (floating, frozen to bed), integral to future tundra-specific SWE retrieval algorithms

Re-evaluating Scattering Mechanisms in Snow-Covered Freshwater Lake Ice Containing Bubbles Using Polarimetric Ground-based and Spaceborne Radar Data

Lakes are a prominent feature of the sub-Arctic and Arctic regions of North America, covering up to 40% of the landscape. Seasonal ice cover on northern lakes afford habitat for several flora and fauna species, and provide drinking water and overwintering fishing areas for local communities. The presence of lake ice influences lake-atmosphere exchanges by modifying the radiative properties of the lake surface and moderating the transfer of heat to the atmosphere. The thermodynamic aspects of lakes exhibit a pronounced effect on weather and regional climate, but are also sensitive to variability in climate forcings such as air temperature and snow fall, acting as proxy indicators of climate variability and change. To refine the understanding of lake-climate interactions, improved methods of monitoring lake ice properties are needed. Manual lake ice monitoring stations have dropped significantly since the 1990s and existing stations are restricted to populated and coastal regions. Recently, studies have indicated the use of radar remote sensing as a viable option for the monitoring of small lakes in remote regions due to its high spatial resolution and imaging capability independent of solar radiation or cloud cover. Active microwave radar in the frequency range of 5 – 10 GHz have successfully retrieved lake ice information pertaining to the physical status of the ice cover and areas that are frozen to bed, but have not been demonstrated as effective for the derivation of on-ice snow depth. In the 10 – 20 GHz range, radar has been shown to be sensitive to terrestrial snow cover, but has not been investigated over lakes. Utilizing a combination of spaceborne and ground-based radar systems spanning a range of 5 – 17 GHz, simulations from the Canadian Lake Ice Model (CLIMo), and ice thickness information from a shallow water ice profiler (SWIP), this research aimed to further our understanding of lake ice scattering sources and mechanisms for small freshwater lakes in the sub-Arctic. Increased comprehension of scattering mechanisms in ice advances the potential for the derivation of lake ice properties, including on-ice snow depth, lake ice thickness and identification of surface ice types. Field observations of snow-covered lake ice were undertaken during the winter seasons of 2009-2010 and 2010-2011 on Malcolm Ramsay Lake, near Churchill Manitoba. In-situ snow and ice observations were coincident with ground-based scatterometer (UW-Scat) and spaceborne synthetic aperture radar (SAR) acquisitions. UW-Scat was comprised of two fully polarimetric frequency modulated continuous wave (FMCW) radars with centre frequencies of 9.6 and 17.2 GHz (X- and Ku-bands, respectively). SAR observations included fine-beam fully polarimetric RADARSAT-2 acquisitions, obtained coincident to UW-Scat observations during 2009-2010. Three experiments were conducted to characterize and evaluate the backscatter signatures from snow-covered freshwater ice coincident to in-situ snow and ice observations. To better understand the winter backscatter (σ°) evolution of snow covered ice, three unique ice cover scenarios were observed and simulated using a bubbled ice σ° model. The range resolution of UW-SCAT provided separation of microwave interaction at the snow/ice interface (P1), and within the ice volume (P2). Ice cores extracted at the end of the observation period indicated that a considerable σ° increase at P2 of approximately 10 – 12 decibels (dB) HH/VV at X- and Ku-band occurred coincident to the timing of tubular bubble development in the ice. Similarly, complexity of the ice surface (high density micro-bubbles and snow ice) resulted in increased P1 σ° at X- and Ku-band at a magnitude of approximately 7 dB. P1 observations also indicated that Ku-band was sensitive to snowpack overlying lake ice, with σ° exhibiting a 5 (6) dB drop for VV (HH) when ~ 60 mm SWE is removed from the scatterometer field of view. Observations indicate that X-band was insensitive to changes in overlying snowpack within the field of view. A bubbled ice σ° model was developed using the dense medium radiative transfer theory under the Quasi-Crystalline Approximation (DMRT-QCA), which treated bubbles as spherical inclusions within the ice volume. Results obtained from the simulations demonstrated the capability of the DMRT model to simulate the overall magnitude of observed σ° using in-situ snow and ice measurements as input. This study improved understanding of microwave interaction with bubble inclusions incorporated at the ice surface or within the volume. The UW-Scat winter time series was then used to derive ice thickness under the assumption of interactions in range occurring at the ice-snow and ice-water interface. Once adjusted for the refractive index of ice and slant range, the distance between peak returns agreed with in-situ ice thickness observations. Ice thicknesses were derived from the distance of peak returns in range acquired in off-nadir incidence angle range 21 - 60°. Derived ice thicknesses were compared to in-situ measurements provided by the SWIP and CLIMo. Median ice thicknesses derived using UW-Scat X- and Ku-band observations agreed well with in-situ measurements (RMSE = 0.053 and 0.045 m), SWIP (RMSE = 0.082 and 0.088 m) and Canadian Lake Ice Model (CLIMo) simulations using 25% of terrestrial snowpack scenario (RMSE = 0.082 and 0.079), respectively. With the launch of fully polarimetric active microwave satellites and upcoming RADARSAT Constellation Mission (RCM), the utility of polarimetric measurements was observed for freshwater bubbled ice to further investigate scattering mechanisms identified by UW-Scat. The 2009-2010 time series of UW-Scat and RADARSAT-2 (C-band) fully polarimetric observations coincident to in-situ snow and ice measurements were acquired to identify the dominant scattering mechanism in bubbled freshwater lake ice. Backscatter time series at all frequencies show increases from the ice-water interface prior to the inclusion of tubular bubbles in the ice column based on in-situ observations, indicating scattering mechanisms independent of double-bounce scatter, contrary to the longstanding hypothesis of double-bounce scatter off tubular bubbles and the ice-water interface. The co-polarized phase difference of interactions at the ice-water interface from both UW-Scat and SAR observations were centred at 0°, indicating a scattering regime other than double bounce. A Yamaguchi three-component decomposition of the time series suggested the dominant scattering mechanism to be single-bounce off the ice-water interface with appreciable surface roughness or preferentially oriented facets. Overall, this work provided new insight into the scattering sources and mechanisms within snow-covered freshwater lake ice containing spherical and tubular bubbles

Geophysical-geotechnical sensor networks for landslide monitoring

Landslides are often the result of complex, multi-phase processes where gradual deterioration of shear strength within the sub-surface precedes the appearance of surface features and slope failure. Moisture content increases and the build-up of associated pore water pressures are invariably associated with a loss of strength, and thus are a precursor to failure. Consequently, hydraulic processes typically play a major role in the development of landslides. Geoelectrical techniques, such as resistivity and self-potential are being increasingly applied to study landslide structure and the hydraulics of landslide processes. The great strengths of these techniques are that they provide spatial or volumetric information at the site scale, which, when calibrated with appropriate geotechnical and hydrogeological data, can be used to characterise lithological variability and monitor hydraulic changes in the subsurface. In this study we describe the development of an automated time-lapse electrical resistivity tomography (ALERT) and geotechnical monitoring system on an active inland landslide near Malton, North Yorkshire, UK. The overarching objective of the research is to develop a 4D landslide monitoring system that can characterise the subsurface structure of the landslide, and reveal the hydraulic precursors to movement. The site is a particularly import research facility as it is representative of many lowland UK situations in which weak mudrocks have failed on valley sides. Significant research efforts have already been expended at the site, and a number of baseline data sets have been collected, including ground and airborne LIDAR, geomorphologic and geological maps, and geophysical models. The monitoring network comprises an ALERT monitoring station connected to a 3D monitoring electrode array installed across an area of 5,500 m2, extending from above the back scarp to beyond the toe of the landslide. The ALERT instrument uses wireless telemetry (in this case GPRS) to communicate with an office based server, which runs control software and a database management system. The control software is used to schedule data acquisition, whilst the database management system stores, processes and inverts the remotely streamed ERT data. Once installed and configured, the system operates autonomously without manual intervention. Modifications to the ALERT system at this site have included the addition of environmental and geotechnical sensors to monitor rainfall, ground movement, ground and air temperature, and pore pressure changes within the landslide. The system is housed in a weatherproof enclosure and is powered by batteries charged by a wind turbine & solar panels. 3D ERT images generated from the landslide have been calibrated against resistivity information derived from laboratory testing of borehole core recovered from the landslide. The calibrated images revealed key aspects of the 3D landslide structure, including the lateral extent of slipped material and zones of depletion and accumulation; the surface of separation and the thickness of individual earth flow lobes; and the dipping in situ geological boundary between the bedrock formations. Time-lapse analysis of resistivity signatures has revealed artefacts within the images that are diagnostic of electrode movement. Analytical models have been developed to simulate the observed artefacts, from which predictions of electrode movement have been derived. This information has been used to correct the ERT data sets, and has provided a means of using ERT to monitor landslide movement across the entire ALERT imaging area. Initial assessment of seasonal changes in the resistivity signature has indicated that the system is sensitive to moisture content changes in the body of the landslide, thereby providing a basis for further development of the system with the aim of monitoring hydraulic precursors to failure

Combining Slaughterhouse Surveillance Data with Cattle Tracing Scheme and Environmental Data to Quantify Environmental Risk Factors for Liver Fluke in Cattle.

Liver fluke infection causes serious disease (fasciolosis) in cattle and sheep in many regions of the world, resulting in production losses and additional economic consequences due to condemnation of the liver at slaughter. Liver fluke depends on mud snails as an intermediate host and infect livestock when ingested through grazing. Therefore, environmental factors play important roles in infection risk and climate change is likely to modify this. Here, we demonstrate how slaughterhouse data can be integrated with other data, including animal movement and climate variables to identify environmental risk factors for liver fluke in cattle in Scotland. We fitted a generalized linear mixed model to the data, with exposure-weighted random and fixed effects, an approach which takes into account the amount of time cattle spent at different locations, exposed to different levels of risk. This enabled us to identify an increased risk of liver fluke with increased animal age, rainfall, and temperature and for farms located further to the West, in excess of the risk associated with a warmer, wetter climate. This model explained 45% of the variability in liver fluke between farms, suggesting that the unexplained 55% was due to factors not included in the model, such as differences in on-farm management and presence of wet habitats. This approach demonstrates the value of statistically integrating routinely recorded slaughterhouse data with other pre-existing data, creating a powerful approach to quantify disease risks in production animals. Furthermore, this approach can be used to better quantify the impact of projected climate change on liver fluke risk for future studies

The Blue Tip of the Stellar Locus: Measuring Reddening with the SDSS

We present measurements of reddening due to dust using the colors of stars in the Sloan Digital Sky Survey (SDSS). We measure the color of main sequence turn-off stars by finding the "blue tip" of the stellar locus: the prominent blue edge in the distribution of stellar colors. The method is sensitive to color changes of order 18, 12, 7, and 8 mmag of reddening in the colors u-g, g-r, r-i, and i-z, respectively, in regions measuring 90' by 14'. We present maps of the blue tip colors in each of these bands over the entire SDSS footprint, including the new dusty southern Galactic cap data provided by the SDSS-III. The results disfavor the best fit O'Donnell (1994) and Cardelli et al. (1989) reddening laws, but are well described by a Fitzpatrick (1999) reddening law with R_V = 3.1. The SFD dust map is found to trace the dust well, but overestimates reddening by factors of 1.4, 1.0, 1.2, and 1.4 in u-g, g-r, r-i, and i-z, largely due to the adopted reddening law. In select dusty regions of the sky, we find evidence for problems in the SFD temperature correction. A dust map normalization difference of 15% between the Galactic north and south sky may be due to these dust temperature errors.Comment: 18 pages, 22 figure

Searching for stellar mass black holes in the solar neighborhood

We propose a strategy for searching for isolated stellar mass black holes in the solar neighborhood with the Sloan Digital Sky Survey. Due to spherical accretion of the inter-stellar medium and the ambient magnetic field, an isolated black hole is expected to emit a blended, thermal synchrotron spectrum with a roughly flat peak from the optical down to the far infra-red. We find that the Sloan Survey will be able to detect isolated black holes, in the considered mass range of 1--100$M_{\odot}$, out to a few hundred parsecs, depending on the local conditions of the ISM. We also find that the black holes are photmetrically distinguishable from field stars and they have a photometry similar to QSOs. They can be further singled out from QSO searches because they have a featureless spectrum with no emission lines. The Sloan Survey will likely find hundreds of objects that meet these criteria, and to further reduce the number of candidates, we suggest other selection criteria such as infra-red searches and proper motion measurements. Estimates indicate that dozens of black holes may exist out to a few hundred parsecs. If no black hole candidates are found in this survey, important limits can be placed on the local density of black holes and the halo fraction in black holes, especially for masses greater than about $20 M_{\odot}$.Comment: Latex, 7 pages, 3 postscript figures, submitted to ApJ Letters. Also available at http://fnas08.fnal.gov

Mapping the Galactic Halo I. The `Spaghetti' Survey

We describe a major survey of the Milky Way halo designed to test for kinematic substructure caused by destruction of accreted satellites. We use the Washington photometric system to identify halo stars efficiently for spectroscopic followup. Tracers include halo giants (detectable out to more than 100 kpc), blue horizontal branch stars, halo stars near the main sequence turnoff, and the ``blue metal-poor stars'' of Preston et al (1994). We demonstrate the success of our survey by showing spectra of stars we have identified in all these categories, including giants as distant as 75 kpc. We discuss the problem of identifying the most distant halo giants. In particular, extremely metal-poor halo K dwarfs are present in approximately equal numbers to the distant giants for V fainter than 18, and we show that our method will distinguish reliably between these two groups of metal-poor stars. We plan to survey 100 square degrees at high galactic latitude, and expect to increase the numbers of known halo giants, BHB stars and turnoff stars by more than an order of magnitude. In addition to the strong test that this large sample will provide for the question `was the Milky Way halo accreted from satellite galaxies?', we will improve the accuracy of mass measurements of the Milky Way beyond 50 kpc via the kinematics of the many distant giants and BHB stars we will find. We show that one of our first datasets constrains the halo density law over galactocentric radii of 5-20 kpc and z heights of 2-15 kpc. The data support a flattened power-law halo with b/a of 0.6 and exponent -3.0. More complex models with a varying axial ratio may be needed with a larger dataset.Comment: 55 pages, 22 figures, to appear in the Astronomical Journa

Observing Scattering Mechanisms of Bubbled Freshwater Lake Ice Using Polarimetric RADARSAT-2 (C-Band) and UW-Scat (X- and Ku-Bands)

A winter time series of ground-based (X- and Ku-bands) scatterometer and spaceborne synthetic aperture radar (SAR) (C-band) fully polarimetric observations coincident with in situ snow and ice measurements are used to identify the dominant scattering mechanism in bubbled freshwater lake ice in the Hudson Bay Lowlands near Churchill, Manitoba. Scatterometer observations identify two physical sources of backscatter from the ice cover: the snow-ice and ice-water interfaces. Backscatter time series at all frequencies show increases from the ice-water interface prior to the inclusion of tubular bubbles in the ice column based on in situ observations, indicating scattering mechanisms independent of double-bounce scatter. The co-polarized phase difference of interactions at the ice-water interface from both scatterometer and SAR observations is centered at 0° during the time series, also indicating a scattering regime other than double bounce. A Yamaguchi three-component decomposition of the RADARSAT-2 C-band time series is presented, which suggests the dominant scattering mechanism to be single-bounce off the ice-water interface with appreciable surface roughness or preferentially oriented facets, regardless of the presence, absence, or density of tubular bubble inclusions. This paper builds on newly established evidence of single-bounce scattering mechanism for freshwater lake ice and is the first to present a winter time series of ground-based and spaceborne fully polarimetric active microwave observations with polarimetric decompositions for bubbled freshwater lake ice.European Space Agency (ESTEC): 10.13039/501100000844 Natural Sciences and Engineering Research Council of Canada: 10.13039/50110000003