Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular disease (CVD)—the leading cause of death in the United States. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed toward treating conventional risk factors have failed to significantly reduce this residual risk in T2DM patients. Thus newer targets and markers are needed for the development and testing of novel therapies. Herein we review two complementary MS-based approaches—mass spectrometric immunoassay (MSIA) and MS/MS as MRM—for the analysis of plasma proteins and PTMs of relevance to T2DM and CVD. Together, these complementary approaches allow for high-throughput monitoring of many PTMs and the absolute quantification of proteins near the low picomolar range. In this review article, we discuss the clinical relevance of the high density lipoprotein (HDL) proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on HDL proteins from T2DM patients to provide examples of how these MS approaches can be applied to gain new insight regarding cardiovascular risk factors. Also discussed are the reproducibility, interpretation, and limitations of each technique with an emphasis on their capacities to facilitate the translation of new biomarkers into clinical practice. 相似文献
This review documents the uses of quantitative MS applied to colorectal cancer (CRC) proteomics for biomarker discovery and molecular pathway profiling. Investigators are adopting various labeling and label-free MS approaches to quantitate differential protein levels in cells, tumors, and plasma/serum. We comprehensively review recent uses of this technology to examine mouse models of CRC, CRC cell lines, their secretomes and subcellular fractions, CRC tumors, CRC patient plasma/serum, and stool samples. For biomarker discovery these approaches are uncovering proteins with potential diagnostic and prognostic utility, while in vitro cell culture experiments are characterizing proteomic and phosphoproteomic responses to disrupted signaling pathways due to mutations or to inhibition of drugable enzymes. 相似文献
The development of flexible organic light emitting diode displays and flexible thin film photovoltaic devices is dependent on the use of flexible, low-cost, optically transparent and durable barriers to moisture and/or oxygen. It is estimated that this will require high moisture barriers with water vapor transmission rates (WVTR) between 10(-4) and 10(-6) g/m(2)/day. Thus there is a need to develop a relatively fast, low-cost, and quantitative method to evaluate such low permeation rates. Here, we demonstrate a method where the resistance changes of patterned Ca films, upon reaction with moisture, enable one to calculate a WVTR between 10 and 10(-6) g/m(2)/day or better. Samples are configured with variable aperture size such that the sensitivity and/or measurement time of the experiment can be controlled. The samples are connected to a data acquisition system by means of individual signal cables permitting samples to be tested under a variety of conditions in multiple environmental chambers. An edge card connector is used to connect samples to the measurement wires enabling easy switching of samples in and out of test. This measurement method can be conducted with as little as 1 h of labor time per sample. Furthermore, multiple samples can be measured in parallel, making this an inexpensive and high volume method for measuring high moisture barriers. 相似文献
This paper outlines the major motivating factors concerning a novel collaborative project between Edinburgh College of Art and Edinburgh Virtual Environment Centre. The Tacitus project will investigate the use of multi-modal virtual environments, specifically, the haptic (touch) modality, with regards to the creative processes employed by designers working within the field of applied arts. The salient areas of research are described, and the methods by which information regarding these areas will be obtained are considered. Initial investigations have revealed a strong need to mimic the traditional applied artists' workspaces, with co-location of visual and haptic cues a priority. 相似文献
We present the development and evaluation of a realtime indoor localisation system for tracking people. Our aim was to track a person’s indoor position using dead-reckoning, while limiting position error without depending on extensive wireless network infrastructure. The Indoor People Tracker used wearable motion sensors, a floor-plan map and a limited wireless sensor network for proximity ranging. We evaluated how the position accuracy of the Indoor People Tracker was affected by floor-plan map features, wireless proximity range and motion information. The advantage of the Indoor People Tracker was found; it was able to achieve accurate position resolution with minimal error, while not depending on wireless proximity. 相似文献
Remote sensing of invasive species is a critical component of conservation and management efforts, but reliable methods for the detection of invaders have not been widely established. In Hawaiian forests, we recently found that invasive trees often have hyperspectral signatures unique from that of native trees, but mapping based on spectral reflectance properties alone is confounded by issues of canopy senescence and mortality, intra- and inter-canopy gaps and shadowing, and terrain variability. We deployed a new hybrid airborne system combining the Carnegie Airborne Observatory (CAO) small-footprint light detection and ranging (LiDAR) system with the Airborne Visible and Infrared Imaging Spectrometer (AVIRIS) to map the three-dimensional spectral and structural properties of Hawaiian forests. The CAO-AVIRIS systems and data were fully integrated using in-flight and post-flight fusion techniques, facilitating an analysis of forest canopy properties to determine the presence and abundance of three highly invasive tree species in Hawaiian rainforests.
The LiDAR sub-system was used to model forest canopy height and top-of-canopy surfaces; these structural data allowed for automated masking of forest gaps, intra- and inter-canopy shadows, and minimum vegetation height in the AVIRIS images. The remaining sunlit canopy spectra were analyzed using spatially-constrained spectral mixture analysis. The results of the combined LiDAR-spectroscopic analysis highlighted the location and fractional abundance of each invasive tree species throughout the rainforest sites. Field validation studies demonstrated < 6.8% and < 18.6% error rates in the detection of invasive tree species at 7 m2 and 2 m2 minimum canopy cover thresholds. Our results show that full integration of imaging spectroscopy and LiDAR measurements provides enormous flexibility and analytical potential for studies of terrestrial ecosystems and the species contained within them. 相似文献
Estimation of forest cover change is important for boreal forests, one of the most extensive forested biomes, due to its unique role in global timber stock, carbon sequestration and deposition, and high vulnerability to the effects of global climate change. We used time-series data from the MODerate Resolution Imaging Spectroradiometer (MODIS) to produce annual forest cover loss hotspot maps. These maps were used to assign all blocks (18.5 by 18.5 km) partitioning the boreal biome into strata of high, medium and low likelihood of forest cover loss. A stratified random sample of 118 blocks was interpreted for forest cover and forest cover loss using high spatial resolution Landsat imagery from 2000 and 2005. Area of forest cover gross loss from 2000 to 2005 within the boreal biome is estimated to be 1.63% (standard error 0.10%) of the total biome area, and represents a 4.02% reduction in year 2000 forest cover. The proportion of identified forest cover loss relative to regional forest area is much higher in North America than in Eurasia (5.63% to 3.00%). Of the total forest cover loss identified, 58.9% is attributable to wildfires. The MODIS pan-boreal change hotspot estimates reveal significant increases in forest cover loss due to wildfires in 2002 and 2003, with 2003 being the peak year of loss within the 5-year study period. Overall, the precision of the aggregate forest cover loss estimates derived from the Landsat data and the value of the MODIS-derived map displaying the spatial and temporal patterns of forest loss demonstrate the efficacy of this protocol for operational, cost-effective, and timely biome-wide monitoring of gross forest cover loss. 相似文献
High fidelity finite element modeling of continuum mechanics problems often requires using all quadrilateral or all hexahedral
meshes. The efficiency of such models is often dependent upon the ability to adapt a mesh to the physics of the phenomena.
Adapting a mesh requires the ability to both refine and/or coarsen the mesh. The algorithms available to refine and coarsen
triangular and tetrahedral meshes are very robust and efficient. However, the ability to locally and conformally refine or
coarsen all quadrilateral and all hexahedral meshes presents many difficulties. Some research has been done on localized conformal
refinement of quadrilateral and hexahedral meshes. However, little work has been done on localized conformal coarsening of
quadrilateral and hexahedral meshes. A general method which provides both localized conformal coarsening and refinement for
quadrilateral meshes is presented in this paper. This method is based on restructuring the mesh with simplex manipulations
to the dual of the mesh. In addition, this method appears to be extensible to hexahedral meshes in three dimensions.
Sandia National Laboratories is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the
United States Department of Energy under Contract DE-AC04-94AL85000. 相似文献