Expression patterns of chondrocyte genes cloned by differential display in tibial dyschondroplasia

AbstractTibial dyschondroplasia (TD) appears to involve a failure of the growth plate chondrocytes within growing long bones to differentiate fully to the hypertrophic stage, resulting in a mass of prehypertrophic chondrocytes which form the avascular TD lesion. Many biochemical and molecular markers of chondrocyte hypertrophy are absent from the lesion, or show reduced expression, but the cause of the disorder remains to be identified. As differentiation to the hypertrophic state is impaired in TD, we hypothesised that chondrocyte genes that are differentially expressed in the growth plate should show altered expression in TD. Using differential display, four genes, B-cadherin, EF2, HT7 and Ex-FABP were cloned from chondrocytes stimulated to differentiate to the hypertrophic stage in vitro, and their differential expression confirmed in vivo. Using semi-quantitative RT-PCR, the expression patterns of these genes were compared in chondrocytes from normal and TD growth plates. Surprisingly, none of these genes showed the pattern of expression that might be expected in TD lesion chondrocytes, and two of them, B-cadherin and Ex-FABP, were upregulated in the lesion. This indicates that the TD phenotype does not merely reflect the absence of hypertrophic marker genes, but may be influenced by more complex developmental mechanisms/defects than previously thought

Statistical mechanics of voting

Decision procedures aggregating the preferences of multiple agents can produce cycles and hence outcomes which have been described heuristically as `chaotic'. We make this description precise by constructing an explicit dynamical system from the agents' preferences and a voting rule. The dynamics form a one dimensional statistical mechanics model; this suggests the use of the topological entropy to quantify the complexity of the system. We formulate natural political/social questions about the expected complexity of a voting rule and degree of cohesion/diversity among agents in terms of random matrix models---ensembles of statistical mechanics models---and compute quantitative answers in some representative cases.Comment: 9 pages, plain TeX, 2 PostScript figures included with epsf.tex (ignore the under/overfull \vbox error messages

Budget Processes: Theory and Experimental Evidence

This paper studies budget processes, both theoretically and experimentally. We compare the outcomes of bottom-up and top-down budget processes. It is often presumed that a top-down budget process leads to a smaller overall budget than a bottom-up budget process. Ferejohn and Krehbiel (1987) showed theoretically that this need not be the case. We test experimentally the theoretical predictions of their work. The evidence from these experiments lends strong support to their theory, both at the aggregate and the individual subject level

The Expression of PHOSPHO1, nSMase2 and TNAP is Coordinately Regulated by Continuous PTH Exposure in Mineralising Osteoblast Cultures

Sustained exposure to high levels of parathyroid hormone (PTH), as observed in hyperparathyroidism, are catabolic to bone. The increase in the RANKL/OPG ratio in response to continuous PTH, resulting in increased osteoclastogenesis is well established. However, the effects of prolonged PTH exposure on key regulators of skeletal mineralisation has yet to be investigated. This study sought to examine the temporal expression of PHOSPHO1, TNAP and nSMase2 in mineralising osteoblast-like cell cultures and to investigate the effects of continuous PTH exposure on the expression of these genes in vitro. PHOSPHO1, nSMase2 and TNAP expression in cultured MC3T3-C14 cells significantly increased from day 0 to day 10. PTH induced a rapid downregulation of Phospho1 and Smpd3 gene expression in MC3T3-C14 cells and cultured hemi-calvariae. Alpl was differentially regulated by PTH, displaying upregulation in cultured MC3T3-C14 cells and downregulation in hemi-calvariae. The effects of PTH on Phospho1 expression were mimicked with the cAMP agonist forskolin, and blocked by the PKA inhibitor PKI (5-24), highlighting a role for the cAMP/PKA pathway in this regulation. The potent down-regulation of Phospho1 and Smpd3 in osteoblasts in response to continuous PTH may provide a novel explanation for the catabolic effects on the skeleton of such an exposure. Furthermore, our findings support the hypothesis that PHOSPHO1, nSMase2 and TNAP function cooperatively in the initiation of skeletal mineralisation

Radiometric measurements of the microwave emissivity of foam

Includes bibliographical references.Radiometric measurements of the microwave emissivity of foam were conducted during May 2000 at the Naval Research Laboratory's Chesapeake Bay Detachment using radiometers operating at 10.8 and 36.5 GHz. Horizontal and vertical polarization measurements were performed at 36.5 GHz; horizontal, vertical, +45°, ­45°, left-circular, and right-circular polarization measurements were obtained at 10.8 GHz. These measurements were carried out over a range of incidence angles from 30° to 60°. Surface foam was generated by blowing compressed air through a matrix of gas-permeable tubing supported by an aluminum frame and floats. Video micrographs of the foam were used to measure bubble size distribution and foam layer thickness. A video camera was boresighted with the radiometers to determine the beam-fill fraction of the foam generator. Results show emissivities that were greater than 0.9 and approximately constant in value over the range of incidence angles for vertically polarized radiation at both 10.8 and 36.5 GHz, while emissivities of horizontally polarized radiation showed a gradual decrease in value as incidence angle increased. Emissivities at +45°, ­45°, left-circular, and right-circular polarizations were all very nearly equal to each other and were in turn approximately equal to the average values of the horizontal and vertical emissivities in each case.This work was sponsored by the Department of the Navy, Office of Naval Research under Award N0014-00-1-280 to the University of Massachusetts, Award N00014-00-0152 to the University of Washington, and Award N0001400WX21032 to the Naval Research Laboratory

NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer

Oncolytic viruses (OVs) can trigger profound innate and adaptive immune responses, which have the potential both to potentiate and reduce the activity of OVs. Natural killer (NK) cells can mediate potent anti-viral and anti-tumoral responses, but there are no data on the role of NK cells in oncolytic adenovirus activity. Here, we have used two different oncolytic adenoviruses—the Ad5 E1A CR2-deletion mutant dl922-947 (group C) and the chimeric Ad3/Ad11p mutant enadenotucirev (group B)—to investigate the effect of NK cells on overall anti-cancer efficacy in ovarian cancer. Because human adenoviruses do not replicate in murine cells, we utilized primary human NK cells from peripheral blood and ovarian cancer ascites. Our results show that dl922-947 and enadenotucirev do not infect NK cells, but induce contact-dependent activation and anti-cancer cytotoxicity against adenovirus-infected ovarian cancer cells. Moreover, manipulation of NK receptors DNAM-1 (DNAX accessory molecule-1) and TIGIT (T cell immunoreceptor with Ig and ITIM domains) significantly influences NK cytotoxicity against adenovirus-infected cells. Together, these results indicate that NK cells act to increase the activity of oncolytic adenovirus in ovarian cancer and suggest that strategies to augment NK activity further via the blockade of inhibitory NK receptor TIGIT could enhance therapeutic potential of OVs

Remote sensing-based statistical approach for defining drained lake basins in a continuous Permafrost region, North Slope of Alaska

Lake formation and drainage are pervasive phenomena in permafrost regions. Drained lake basins (DLBs) are often the most common landforms in lowland permafrost regions in the Arctic (50% to 75% of the landscape). However, detailed assessments of DLB distribution and abundance are limited. In this study, we present a novel and scalable remote sensing-based approach to identifying DLBs in lowland permafrost regions, using the North Slope of Alaska as a case study. We validated this first North Slope-wide DLB data product against several previously published sub-regional scale datasets and manually classified points. The study area covered \u3e71,000 km2, including a \u3e39,000 km2 area not previously covered in existing DLB datasets. Our approach used Landsat-8 multispectral imagery and ArcticDEM data to derive a pixel-by-pixel statistical assessment of likelihood of DLB occurrence in sub-regions with different permafrost and periglacial landscape conditions, as well as to quantify aerial coverage of DLBs on the North Slope of Alaska. The results were consistent with previously published regional DLB datasets (up to 87% agreement) and showed high agreement with manually classified random points (64.4–95.5% for DLB and 83.2– 95.4% for non-DLB areas). Validation of the remote sensing-based statistical approach on the North Slope of Alaska indicated that it may be possible to extend this methodology to conduct a comprehensive assessment of DLBs in pan-Arctic lowland permafrost regions. Better resolution of the spatial distribution of DLBs in lowland permafrost regions is important for quantitative studies on landscape diversity, wildlife habitat, permafrost, hydrology, geotechnical conditions, and high-lat-itude carbon cycling