Spindle cell sarcoma of sphenoid bone

Primary bone tumors involving skull are extremely rare and they constitute 0.8% of all bone tumors. The common tumors that are seen in skull base include fibrous dysplasia, giant cell tumor, chordoma, ossifying fibroma, angiosarcoma. We report a rare case of spindle cell sarcoma arising from right sphenoid bone in a 70-year-old male which presented as unilateral defective vision with mild proptosis

Postremediation dose assessment for the former Alba Craft Laboratory site, Oxford, Ohio

Potential maximum radiation dose rates were calculated for the former Alba Craft Laboratory site in Oxford, Ohio, which was involved in machining of uranium metal in the 1950s for the U.S. atomic energy program. The site is not currently being used. The residual radioactive material guidelines (RESRAD) computer code, which implements the methodology described in the US Department of Energy`s (DOE`s) manual for establishing residual radioactive material guidelines, was sued in this evaluation. Three potential land use scenarios were considered for the former Alba Craft site; the scenarios vary with regard to the type of site use, time spent at the site by the exposed individual, and sources of food consumed. Scenario A (a possible land use scenario) assumed industrial use of the site; Scenario B (a likely future land use scenario) assumed residential use of the site; and Scenario C (a possible but unlikely land use scenario) assumed the presence of a resident farmer. For scenario A, it was assumed that any water used for domestic or industrial activities would be from uncontaminated off-site municipal sources. The water used for drinking, household purposes, and irrigation was assumed to be from uncontaminated municipal sources in Scenario B; groundwater drawn from a well located at the downgradient edge of the contaminated zone would be the only source of water for drinking, irrigation, and raising livestock in Scenario C. The results of the evaluation indicated that the DOE dose limit of 100 mrem/yr would not be exceeded for any of the scenarios analyzed. The potential maximum dose rates for Scenarios A, B, and C are 0.64, 2.0, and 11 mrem/yr, respectively

Adult hematopoietic progenitors are pluripotent in chimeric mice

18 pages, 7 figures.Embryonic stem cells (ESCs) and adult somatic cells, induced to pluripotency (iPSCs) by genetic manipulation, display high self-­‐renewal potential and the capacity to differentiate into multiple cell lineages. We asked whether there are in adult mammals natural stem cells that are pluripotent. We previously reported that normal adult mammalian bone marrow contains a sub-­‐population of CD34+ cells, that naturally expresses genes characteristic of ESCs and those required to generate iPSCs, but have a limited lifespan and do not form teratomas. In addition, these CD34+ cells spontaneously express, without genetic manipulation, genes characteristic of the three embryonic germ layers: i.e., ectodermal neural, mesodermal cardiac muscle, and endodermal pancreatic and intestinal lineage genes (Pessac, B, et al. 2011. Hematopoietic progenitors express embryonic stem cell and germ layer genes. Comptes Rendus Biologies 334: 300-­‐306). This suggested that these cells may be pluripotent. Here we have transplanted these CD34+ bone marrow stem cells from adult male C56Bl/6J ROSA mice, that carry two markers: the ß-­‐galactosidase gene and the male Y chromosome, into blastocysts of wildtype C57Bl/6J mice. These blastocysts develop normally and give rise to healthy adult chimeric mice. Each female ROSA chimeric mouse had a distinct pattern of male organs expressing ß-­‐galactosidase derived from each of the three embryonic germ layers: ectodermal brain, dorsal root ganglia and skin; mesodermal heart, bone and bone marrow; and endodermal pancreas, intestine, and liver. Thus, adult mammals still carry cells that appear to exhibit a developmental potential comparable to ESCs and iPSCs suggesting that CD34+ cells from adult bone marrow could be used for cell therapy

Deciphering the relative roles of matrix metalloproteinase‐ and plasmin‐mediated matrix degradation during capillary morphogenesis using engineered hydrogels

Extracellular matrix (ECM) remodeling is essential for the process of capillary morphogenesis. Here we employed synthetic poly(ethylene glycol) (PEG) hydrogels engineered with proteolytic specificity to either matrix metalloproteinases (MMPs), plasmin, or both to investigate the relative contributions of MMP‐ and plasmin‐mediated ECM remodeling to vessel formation in a 3D‐model of capillary self‐assembly analogous to vasculogenesis. We first demonstrated a role for both MMP‐ and plasmin‐mediated mechanisms of ECM remodeling in an endothelial‐fibroblast co‐culture model of vasculogenesis in fibrin hydrogels using inhibitors of MMPs and plasmin. When this co‐culture model was employed in engineered PEG hydrogels with selective protease sensitivity, we observed robust capillary morphogenesis only in MMP‐sensitive matrices. Fibroblast spreading in plasmin‐selective hydrogels confirmed this difference was due to protease preference by endothelial cells, not due to limitations of the matrix itself. In hydrogels engineered with crosslinks that were dually susceptible to MMPs and plasmin, capillary morphogenesis was unchanged. These findings highlight the critical importance of MMP‐mediated degradation during vasculogenesis and provide strong evidence to justify the preferential selection of MMP‐degradable peptide crosslinkers in synthetic hydrogels used to study vascular morphogenesis and promote vascularization. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2507–2516, 2019.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151850/1/jbmb34341_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151850/2/jbmb34341.pd

Derivation of guidelines for uranium residual radioactive material in soil at the New Brunswick Site, Middlesex County, New Jersey

Residual radioactive material guidelines for uranium in soil were derived for the New Brunswick Site, located in Middlesex County, New Jersey. This site has been designated for remedial action under the Formerly Utilized Sites Remedial Action Program of the US Department of Energy (DOE). Residual radioactive material guidelines for individual radionuclides of concern and total uranium were derived on the basis of the requirement that the 50-year committed effective dose equivalent to a hypothetical individual who lives or works in the immediate vicinity of the New Brunswick Site should not exceed a dose of 30 mrem/yr following remedial action for the current-use and likely future-use scenarios or a dose of 100 mrem/yr for less likely future-use scenarios. The DOE residual radioactive material guideline computer code, RESRAD, was used in this evaluation; RESRAD implements the methodology described in the DOE manual for establishing residual radioactive material guidelines. The guidelines derived in this report are intended to apply to the remediation of these remaining residual radioactive materials at the site. The primary radionuclides of concern in these remaining materials are expected to be radium-226 and, to a lesser extent, natural uranium and thorium. The DOE has established generic cleanup guidelines for radium and thorium in soil; however, cleanup guidelines for other radionuclides must be derived on a site-specific basis

CPU, GPU i FPGA implementacija MALD algoritma za otkrivanje nepravilnosti na površini keramičkih pločica

This paper addresses adjustments, implementation and performance comparison of the Moving Average with Local Difference (MALD) method for ceramic tile surface defects detection. Ceramic tile production process is completely autonomous, except the final stage where human eye is required for defects detection. Recent computational platform development and advances in machine vision provides us with several options for MALD algorithm implementation. In order to exploit the shortest execution time for ceramic tile production process, the MALD method is implemented on three different platforms: CPU, GPU and FPGA, and it is implemented on each platform in at least two ways. Implementations are done in MATLAB’s MEX/C++, C++, CUDA/C++, VHDL and Assembly programming languages. Execution times are measured and compared for different algorithms and their implementations on different computational platforms.U ovom radu razmatra se prilagodba, implementacija i usporedba performansi metode pomičnog usrednjavanja s lokalnom diferencijom (MALD) s primjenom u otkrivanju površinskih nedostataka na keramičkim pločicama. Proizvodna linija keramičkih pločica je autonomna sve do zadnje faze u kojoj je potreban ljudski vid kako bi se otkrili eventualni nedostaci na keramičkim pločicama. Nedavnim razvojem računalnih platformi i razvojem metoda računalnog vida omogućena je implementacija MALD metode na nekoliko načina. U nastojanju skraćenja vremena potrebnog za proizvodnju keramičkih pločica, MALD metoda je implementirana u trima različitim platformama: CPU (central processing unit), GPU (graphic processing unit) i FPGA (field programmable gate array), te s barem dva različita algoritma. Implementacija je izvršena sa MATLAB MEX/C++, C++, CUDA/C++, VHDL te Asembler programskim jezicima. Izmjerena vremena obrade su me.usobno uspore.ena za različite algoritme i njihove implementacije na različitim računalnim platformama

Vasohibin inhibits angiogenic sprouting in vitro and supports vascular maturation processes in vivo

<p>Abstract</p> <p>Background</p> <p>The murine homologue of human vasohibin (mVASH1), a putative antiangiogenic protein, was investigated for its effects on <it>in vitro </it>and <it>in vivo </it>angiogenesis.</p> <p>Methods</p> <p>Cell growth and migration were analyzed in murine fibroblasts, smooth muscle cells and endothelial cells. Angiogenic sprouting was studied in human umbilical vein endothelial cells (HUVECs) in the spheroid sprouting assay. <it>In vivo </it>effects on blood vessel formation were investigated in the chorioallantoic membrane (CAM) assay and in the C57BL/6 melanoma xenograft model.</p> <p>Results</p> <p>Purified murine and human VASH1 protein induced apoptosis of murine fibroblasts <it>in vitro</it>, but not of vascular aortic smooth muscle cells (AoSMC) or endothelial cells. Adenoviral overexpression of murine and human VASH1 inhibited capillary sprouting of HUVECs in the spheroid assay. Administration of recombinant murine and human VASH1 inhibited growth of large vessels in the CAM assay and promoted the formation of a dense, fine vascular network. Murine VASH1-overexpressing B16F10 melanomas displayed a reduction in large vessels and vascular area. Moreover, tumors showed more microvessels that stained positive for the mural cell markers α-smooth muscle cell actin (ASMA) and proteoglycan (NG2).</p> <p>Conclusion</p> <p>Our data imply that murine VASH1 causes angiogenic remodelling by inhibiting angiogenic sprouting and large vessel growth, thereby supporting the formation of a vascular bed consisting predominantly of mature microvessels.</p

Near-infrared molecular imaging of tumors via chemokine receptors CXCR4 and CXCR7

The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye IRDye®800CW, tested their selectivity, sensitivity and biological activity in vitro and their feasibility to visualize tumors in vivo. Purified CXCL12-conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7 breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was time- and concentration-dependent, and the label could be competitively displaced by the native peptide. Control conjugates with bovine serum albumin or lactalbumin failed to label the cells. In mice, the conjugate distributed rapidly. After 1–92 h, subcutaneous tumors of human MCF-7 and A764 cells in immunodeficient mice were detected with high sensitivity. Background was observed in particular in liver within the first 24 h, but also skull and hind limbs yielded some background. Overall, fluorescent CXCL12-conjugates are sensitive and selective probes to detect solid and metastatic tumors by targeting tumor cells and tumor vasculature

Sympathetic Effects of Internal Carotid Nerve Manipulation on Choroidal Vascularity and Related Measures

Purpose: To investigate specific effects of denervation and stimulation of the internal carotid nerve (ICN) on the choroid and retina. Methods: Female Sprague Dawley rats underwent unilateral ICN transection (n = 20) or acute ICN electrical stimulation (n = 7). Rats in the denervation group were euthanized 6 weeks after nerve transection, and eyes were analyzed for changes in choroidal vascularity (via histomorphometry) or angiogenic growth factors and inflammatory markers (via ELISA). Rats in the stimulation group received acute ICN electrical stimulation with a bipolar cuff electrode over a range of stimulus amplitudes, frequencies, and pulse widths. Choroidal blood flow and pupil diameter were monitored before, during, and after stimulation. Results: Six weeks after unilateral ICN transection, sympathectomized choroids exhibited increased vascularity, defined as the percentage of choroidal surface area occupied by blood vessel lumina. Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein levels in denervated choroids were 61% and 124% higher than in contralateral choroids, respectively. TNF-α levels in denervated retinas increased by 3.3-fold relative to levels in contralateral retinas. In animals undergoing acute ICN electrical stimulation, mydriasis and reduced choroidal blood flow were observed in the ipsilateral eye. The magnitude of the reduction in blood flow correlated positively with stimulus frequency. Conclusions: Modulation of ICN activity reveals a potential role of the ocular sympathetic system in regulating endpoints related to neovascular diseases of the eye

Impact of glucocorticoid receptor density on ligand-independent dimerization, cooperative ligand-binding and basal priming of transactivation: a cell culture model

Glucocorticoid receptor (GR) levels vary between tissues and individuals and are altered by physiological and pharmacological effectors. However, the effects and implications of differences in GR concentration have not been fully elucidated. Using three statistically different GR concentrations in transiently transfected COS-1 cells, we demonstrate, using co-immunoprecipitation (CoIP) and fluorescent resonance energy transfer (FRET), that high levels of wild type GR (wtGR), but not of dimerization deficient GR (GRdim), display ligand-independent dimerization. Whole-cell saturation ligand-binding experiments furthermore establish that positive cooperative ligand-binding, with a concomitant increased ligand-binding affinity, is facilitated by ligand-independent dimerization at high concentrations of wtGR, but not GRdim. The down-stream consequences of ligand-independent dimerization at high concentrations of wtGR, but not GRdim, are shown to include basal priming of the system as witnessed by ligand-independent transactivation of both a GRE-containing promoter-reporter and the endogenous glucocorticoid (GC)-responsive gene, GILZ, as well as ligand-independent loading of GR onto the GILZ promoter. Pursuant to the basal priming of the system, addition of ligand results in a significantly greater modulation of transactivation potency than would be expected solely from the increase in ligand-binding affinity. Thus ligand-independent dimerization of the GR at high concentrations primes the system, through ligand-independent DNA loading and transactivation, which together with positive cooperative ligand-binding increases the potency of GR agonists and shifts the bio-character of partial GR agonists. Clearly GR-levels are a major factor in determining the sensitivity to GCs and a critical factor regulating transcriptional programs