377 research outputs found

    Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition

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    <p>Abstract</p> <p>Background</p> <p>Epithelial to mesenchymal transition (EMT), implicated as a mechanism for tumor dissemination, is marked by loss of E-cadherin, disruption of cell adhesion, and induction of cell motility and invasion. In most intraductal breast carcinomas E-cadherin is regulated epigenetically via methylation of the promoter. E-cadherin expression is therefore dynamic and open to modulation by the microenvironment. In addition, it has been observed that metastatic foci commonly appear more differentiated than the primary tumor, suggesting that cancer cells may further undergo a mesenchymal to epithelial reverting transition (MErT) in the secondary organ environment following the EMT that allows for escape.</p> <p>Results</p> <p>We first examined E-cadherin expression in primary breast tumors and their corresponding metastases to liver, lung and brain and discovered that 62% (10/16) of cases showed increased E-cadherin expression in the metastases compared to the primaries. These observations led to the question of whether the positive metastatic foci arose from expansion of E-cadherin-positive cells or from MErT of originally E-cadherin-negative disseminated cells. Thus, we aimed to determine whether it was possible for the mesenchymal-like MDA-MB-231 breast cancer cells to undergo an MErT through the re-expression of E-cadherin, either through exogenous introduction or induction by the microenvironment. Ectopic expression of full-length E-cadherin in MDA-MB-231 cells resulted in a morphological and functional reversion of the epithelial phenotype, with even just the cytosolic domain of E-cadherin yielding a partial phenotype. Introduction of MDA-MB-231 cells or primary explants into a secondary organ environment simulated by a hepatocyte coculture system induced E-cadherin re-expression through passive loss of methylation of the promoter. Furthermore, detection of E-cadherin-positive metastatic foci following the spontaneous metastasis of MDA-MB-231 cells injected into the mammary fat pad of mice suggests that this re-expression is functional.</p> <p>Conclusions</p> <p>Our clinical observations and experimental data indicate that the secondary organ microenvironment can induce the re-expression of E-cadherin and consequently MErT. This phenotypic change is reflected in altered cell behavior and thus may be a critical step in cell survival at metastatic sites.</p

    Averting HIV Infections in New York City: A Modeling Approach Estimating the Future Impact of Additional Behavioral and Biomedical HIV Prevention Strategies

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    Background:New York City (NYC) remains an epicenter of the HIV epidemic in the United States. Given the variety of evidence-based HIV prevention strategies available and the significant resources required to implement each of them, comparative studies are needed to identify how to maximize the number of HIV cases prevented most economically.Methods:A new model of HIV disease transmission was developed integrating information from a previously validated micro-simulation HIV disease progression model. Specification and parameterization of the model and its inputs, including the intervention portfolio, intervention effects and costs were conducted through a collaborative process between the academic modeling team and the NYC Department of Health and Mental Hygiene. The model projects the impact of different prevention strategies, or portfolios of prevention strategies, on the HIV epidemic in NYC.Results:Ten unique interventions were able to provide a prevention benefit at an annual program cost of less than 360,000,thethresholdforconsiderationasacost−savingintervention(becauseofoffsetsbyfutureHIVtreatmentcostsaverted).Anoptimizedportfolioofthesespecificinterventionscouldresultinuptoa34360,000, the threshold for consideration as a cost-saving intervention (because of offsets by future HIV treatment costs averted). An optimized portfolio of these specific interventions could result in up to a 34% reduction in new HIV infections over the next 20 years. The cost-per-infection averted of the portfolio was estimated to be 106,378; the total cost was in excess of 2billion(overthe20yearperiod,orapproximately2 billion (over the 20 year period, or approximately 100 million per year, on average). The cost-savings of prevented infections was estimated at more than 5billion(orapproximately5 billion (or approximately 250 million per year, on average).Conclusions:Optimal implementation of a portfolio of evidence-based interventions can have a substantial, favorable impact on the ongoing HIV epidemic in NYC and provide future cost-saving despite significant initial costs. © 2013 Kessler et al

    Sub-pixel Layout for Super-Resolution with Images in the Octic Group

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    13th European Conference, Zurich, Switzerland, September 6-12, 2014, Proceedings, Part IThis paper presents a novel super-resolution framework by exploring the properties of non-conventional pixel layouts and shapes. We show that recording multiple images, transformed in the octic group, with a sensor of asymmetric sub-pixel layout increases the spatial sampling compared to a conventional sensor with a rectilinear grid of pixels and hence increases the image resolution. We further prove a theoretical bound for achieving well-posed super-resolution with a designated magnification factor w.r.t. the number and distribution of sub-pixels. We also propose strategies for selecting good sub-pixel layouts and effective super-resolution algorithms for our setup. The experimental results validate the proposed theory and solution, which have the potential to guide the future CCD layout design with super-resolution functionality.United States. Air Force (Assistant Secretary of Defense for Research & Engineering Contract #FA8721-05-C-0002)SUTD-MIT International Design Centre (Joint Postdoctoral Programme)Singapore University of Technology and Design (SUTD StartUp Grant ISTD 2011 016)Singapore. Ministry of Education (MOE Academic Research Fund MOE2013-T2-1-159

    Chemical Beam Epitaxy of Compound Semiconductors

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    Contains reports on three research projects and a list of publications.3M Company Faculty Development GrantAT&T Research Foundation Special Purpose GrantDefense Advanced Research Projects Agency Subcontract 216-25013Defense Advanced Research Projects Agency Subcontract 542383Joint Services Electronics Program Contract DAAL03-89-C-0001National Science Foundation Grant ECS 88-46919National Science Foundation Grant ECS 89-05909U.S. Navy - Office of Naval Research Contract N00014-88-K-0564Charles Stark Draper Laboratories Contract DL-H-418484Defense Advanced Research Projects Agency Subcontract 530-0716-0

    Averting HIV Infections in New York City: A Modeling Approach Estimating the Future Impact of Additional Behavioral and Biomedical HIV Prevention Strategies

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    Background: New York City (NYC) remains an epicenter of the HIV epidemic in the United States. Given the variety of evidence-based HIV prevention strategies available and the significant resources required to implement each of them, comparative studies are needed to identify how to maximize the number of HIV cases prevented most economically. Methods: A new model of HIV disease transmission was developed integrating information from a previously validated micro-simulation HIV disease progression model. Specification and parameterization of the model and its inputs, including the intervention portfolio, intervention effects and costs were conducted through a collaborative process between the academic modeling team and the NYC Department of Health and Mental Hygiene. The model projects the impact of different prevention strategies, or portfolios of prevention strategies, on the HIV epidemic in NYC. Results: Ten unique interventions were able to provide a prevention benefit at an annual program cost of less than360,000,thethresholdforconsiderationasacost−savingintervention(becauseofoffsetsbyfutureHIVtreatmentcostsaverted).Anoptimizedportfolioofthesespecificinterventionscouldresultinuptoa34360,000, the threshold for consideration as a cost-saving intervention (because of offsets by future HIV treatment costs averted). An optimized portfolio of these specific interventions could result in up to a 34% reduction in new HIV infections over the next 20 years. The cost-per-infection averted of the portfolio was estimated to be 106,378; the total cost was in excess of 2billion(overthe20yearperiod,orapproximately2 billion (over the 20 year period, or approximately 100 million per year, on average). The cost-savings of prevented infections was estimated at more than 5billion(orapproximately5 billion (or approximately 250 million per year, on average). Conclusions: Optimal implementation of a portfolio of evidence-based interventions can have a substantial, favorable impact on the ongoing HIV epidemic in NYC and provide future cost-saving despite significant initial costs

    Multivariate Cutoff Level Analysis (MultiCoLA) of large community data sets

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    High-throughput sequencing techniques are becoming attractive to molecular biologists and ecologists as they provide a time- and cost-effective way to explore diversity patterns in environmental samples at an unprecedented resolution. An issue common to many studies is the definition of what fractions of a data set should be considered as rare or dominant. Yet this question has neither been satisfactorily addressed, nor is the impact of such definition on data set structure and interpretation been fully evaluated. Here we propose a strategy, MultiCoLA (Multivariate Cutoff Level Analysis), to systematically assess the impact of various abundance or rarity cutoff levels on the resulting data set structure and on the consistency of the further ecological interpretation. We applied MultiCoLA to a 454 massively parallel tag sequencing data set of V6 ribosomal sequences from marine microbes in temperate coastal sands. Consistent ecological patterns were maintained after removing up to 35–40% rare sequences and similar patterns of beta diversity were observed after denoising the data set by using a preclustering algorithm of 454 flowgrams. This example validates the importance of exploring the impact of the definition of rarity in large community data sets. Future applications can be foreseen for data sets from different types of habitats, e.g. other marine environments, soil and human microbiota

    Global importance of Indigenous Peoples, their lands, and knowledge systems for saving the world’s primates from extinction

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    Primates, represented by 521 species, are distributed across 91 countries primarily in the Neotropic, Afrotropic, and Indo-Malayan realms. Primates inhabit a wide range of habitats and play critical roles in sustaining healthy ecosystems that benefit human and nonhuman communities. Approximately 68% of primate species are threatened with extinction because of global pressures to convert their habitats for agricultural production and the extraction of natural resources. Here, we review the scientific literature and conduct a spatial analysis to assess the significance of Indigenous Peoples’ lands in safeguarding primate biodiversity. We found that Indigenous Peoples’ lands account for 30% of the primate range, and 71% of primate species inhabit these lands. As their range on these lands increases, primate species are less likely to be classified as threatened or have declining populations. Safeguarding Indigenous Peoples’ lands, languages, and cultures represents our greatest chance to prevent the extinction of the world’s primates.info:eu-repo/semantics/publishedVersio

    Global importance of Indigenous Peoples, their lands, and knowledge systems for saving the world's primates from extinction

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    Publisher Copyright: Copyright © 2022 The Authors, some rights reserved.Primates, represented by 521 species, are distributed across 91 countries primarily in the Neotropic, Afrotropic, and Indo-Malayan realms. Primates inhabit a wide range of habitats and play critical roles in sustaining healthy ecosystems that benefit human and nonhuman communities. Approximately 68% of primate species are threatened with extinction because of global pressures to convert their habitats for agricultural production and the extraction of natural resources. Here, we review the scientific literature and conduct a spatial analysis to assess the significance of Indigenous Peoples' lands in safeguarding primate biodiversity. We found that Indigenous Peoples' lands account for 30% of the primate range, and 71% of primate species inhabit these lands. As their range on these lands increases, primate species are less likely to be classified as threatened or have declining populations. Safeguarding Indigenous Peoples' lands, languages, and cultures represents our greatest chance to prevent the extinction of the world's primates.Peer reviewe

    Optical Propagation and Communication

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    Contains an introduction and reports on four research project.Maryland Procurement Office Contract MDA 904-90-C-5070Charles S. Draper Laboratories Contract DL-H-441698National Institute of Standards and Technology Grant 60-NANBOD-1052U.S. Army Research Office Grant DAAL03-90-G-0128U.S. Navy - Office of Naval Research Grant N00014-89-J-1163U.S. Air Force - Office of Scientific Research Contract F49620-90-C-003

    Optical Propagation and Communication

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    Contains an introduction and reports on five research projects.Maryland Procurement Office Contract MDA 904-90-C-5070National Science Foundation Grant ECS 87-18970National Institute of Standards and Technology Grant 60-NANBOD-1052U.S. Army Research Office Grant DAAL03-90-G-0128U.S. Army Research Office Contract DAAL03-87-K-0117U.S. Navy - Office of Naval Research Grant N00014-89-J-1163U.S. Air Force - Office of Scientific Research Contract F49620-87-C-0043U.S. Air Force - Office of Scientific Research Contract F49620-90-C-003
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