9,075,522 research outputs found

    Hannah Arendt's Ghosts:Reflections on the Disputable Path from Windhoek to Auschwitz

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    Historians on both sides of the Atlantic are currently engaged in a controversy about the allegedly genocidal nature of western colonialism and its connections with the mass violence unleashed by Nazi Germany between 1939 and 1945. The debate touches upon some of the most “sensitive” issues of twentieth-century history: the violent “dark side” of modern western civilization, the impact of colonial massacres on the European societies that generated this violence and, perhaps most controversially, the origins and uniqueness of the Holocaust

    Comparative Analysis of Nuclear Transfer Embryo Derived Mouse Embryonic Stem Cells. Part I: Cellular characterization

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    Embryonic stem cells derived from nuclear transfer embryos (ntESCs) are particularly valuable for regenerative medicine, as they are a patient-specific and histocompatible cell source for the treatment of varying diseases. However, currently, little is known about their cellular and molecular profile. In the present study, in a mouse model different donor cell-derived ntESCs from various genetic backgrounds were compared with reference ESCs and analyzed comprehensively at the cellular level. A number of pluripotency marker genes were compared by flow cytometry and immunocytochemistry analysis. Significant differences at the protein level were observed for POU5F1, SOX2, FGF4, NANOG, and SSEA-1. However, such differences had no effect on in vitro cell differentiation and cell fate: derivatives of the three germ layers were detected in all ntESC lines. The neural and cardiac in vitro differentiation revealed minor differences between the cell lines, both at the mRNA and protein level. Karyotype analyses and cell growth studies did not reveal any significant variations. Despite some differences observed, the present study revealed that ntESC lines had similar differentiation competences compared to other ESCs. The results indicate that the observed differences may be related to the genotype rather than to the nuclear transfer technology

    Cell

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    A key finding of the ENCODE project is that the enhancer landscape of mammalian cells undergoes marked alterations during ontogeny. However, the nature and extent of these changes are unclear. As\uc2\ua0part of the NIH Mouse Regulome Project, we here combined DNaseI hypersensitivity, ChIP-seq, and ChIA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during development correlates with promoter activity. We propose that organisms rely on a dynamic enhancer landscape to control basic cellular functions in a tissue-specific manner.DP1 GM105378/DP/NCCDPHP CDC HHS/United StatesDP1 GM105378/GM/NIGMS NIH HHS/United StatesP50 HG005550/HG/NHGRI NIH HHS/United StatesZ01 AR041148-04/Intramural NIH HHS/United StatesZ01 AR041149-04/Intramural NIH HHS/United States2014-12-19T00:00:00Z24360274PMC390544

    Moduli space actions on the Hochschild Co-Chains of a Frobenius algebra I: Cell Operads

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    This is the first of two papers in which we prove that a cell model of the moduli space of curves with marked points and tangent vectors at the marked points acts on the Hochschild co--chains of a Frobenius algebra. We also prove that a there is dg--PROP action of a version of Sullivan Chord diagrams which acts on the normalized Hochschild co-chains of a Frobenius algebra. These actions lift to operadic correlation functions on the co--cycles. In particular, the PROP action gives an action on the homology of a loop space of a compact simply--connected manifold. In this first part, we set up the topological operads/PROPs and their cell models. The main theorems of this part are that there is a cell model operad for the moduli space of genus gg curves with nn punctures and a tangent vector at each of these punctures and that there exists a CW complex whose chains are isomorphic to a certain type of Sullivan Chord diagrams and that they form a PROP. Furthermore there exist weak versions of these structures on the topological level which all lie inside an all encompassing cyclic (rational) operad.Comment: 50 pages, 7 figures. Newer version has minor changes. Some material shifted. Typos and small things correcte

    Blood Cell Classification Using the Hough Transform and Convolutional Neural Networks

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    https://doi.org/10.1007/978-3-319-77712-2_62The detection of red blood cells in blood samples can be crucial for the disease detection in its early stages. The use of image processing techniques can accelerate and improve the effectiveness and efficiency of this detection. In this work, the use of the Circle Hough transform for cell detection and artificial neural networks for their identification as a red blood cell is proposed. Specifically, the application of neural networks (MLP) as a standard classification technique with (MLP) is compared with new proposals related to deep learning such as convolutional neural networks (CNNs). The different experiments carried out reveal the high classification ratio and show promising results after the application of the CNNs.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    Memory NK cell features exploitable in anticancer immunotherapy

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    Besides their innate ability to rapidly produce effector cytokines and kill virus-infected or transformed cells, natural killer (NK) cells display a strong capability to adapt to environmental modifications and to differentiate into long-lived, hyperfunctional populations, dubbed memory or memory-like NK cells. Despite significant progress in the field of NK cell-based immunotherapies, some factors including their short life span and the occurrence of a tumor-dependent functional exhaustion have limited their clinical efficacy so that strategies aimed at overcoming these limitations represent one of the main current challenges in the field. In this scenario, the exploitation of NK cell memory may have a considerable potential. This article summarizes recent evidence in the literature on the peculiar features that render memory NK cells an attractive tool for antitumor immunotherapy, including their long-term survival and in vivo persistence, the resistance to tumor-dependent immunosuppressive microenvironment, the amplified functional responses to IgG-opsonized tumor cells, and in vitro expansion capability. Along with highlighting these issues, we speculate that memory NK cell-based adoptive immunotherapy settings would greatly take advantage from the combination with tumor-targeting therapeutic antibodies (mAbs), as a strategy to fully unleash their clinical efficacy

    Specifying sickle cell disease interventions: A study protocol of the Sickle Cell Disease Implementation Consortium (SCDIC)

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    Abstract Background Sickle cell disease (SCD) is an inherited blood disorder that results in a lifetime of anemia, severe pain, and end-organ damage that can lead to premature mortality. While the SCD field has made major medical advances, much needs to be done to improve the quality of care for people with SCD. This study capitalizes on the Sickle Cell Disease Implementation Consortium (SCDIC), a consortium of eight academic sites aiming to test implementation strategies that could lead to more accelerated application of the NHLBI guidelines for treating SCD. This report documents the process to support the consortium by specifying the interventions being developed. Methods This study consists of three steps. The Principal Investigator of each site and two site representatives who are knowledgeable of the intervention (e.g., study coordinator or the person delivering the intervention) will answer an online survey aiming to capture components of the interventions. This survey will be completed by the site representatives three times during the study: during the development of the interventions, after one year of the interventions being implemented, and at the end of this study (after 2 years). A site visit and semi-structured interview (Step 2) in the first year of the process will capture the context of the sites. Step 3 comprises of the development of a framework with the details of the multi-component SCDIC interventions at the sites. Discussion The outcome of this study, a framework of the SCDIC, will enable accurate replication and extension of published research, facilitating the translation of SCD studies to diverse populations and settings and allowing for theory testing of the effects of the intervention components across studies in different contexts and for different populations. Trial registration ClinicalTrial.Gov (#NCT03380351). Registered December 21, 2017

    Cell

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    Increasing evidence has shown that population dynamics are qualitatively different from single-cell behaviors. Reporters to probe dynamic, single-cell behaviors are desirable yet relatively scarce. Here, we describe an easy-to-implement and generalizable technology to generate reporters of kinase activity for individual cells. Our technology converts phosphorylation into a nucleocytoplasmic shuttling event that can be measured by epifluorescence microscopy. Our reporters reproduce kinase activity for multiple types of kinases and allow for calculation of active kinase concentrations via a mathematical model. Using this technology, we made several experimental observations that had previously been technicallyunfeasible, including stimulus-dependent patterns of c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-\uce\ubaB) activation. We also measured JNK, p38, and ERK activities simultaneously, finding that p38 regulates the peak number, but not the intensity, of ERK fluctuations. Our approach opens the possibility of analyzing a wide range of kinase-mediated processes in individual cells.5DP1LM01150-05/DP/NCCDPHP CDC HHS/United StatesDP1 LM011510/LM/NLM NIH HHS/United StatesDP1 OD006413/OD/NIH HHS/United StatesP50 GM107615/GM/NIGMS NIH HHS/United StatesP50GM107615/GM/NIGMS NIH HHS/United StatesR21 5R21AI104305-02/AI/NIAID NIH HHS/United StatesR21 AI104305/AI/NIAID NIH HHS/United States2015-06-19T00:00:00Z24949979PMC409731

    Cell

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    Sexual dimorphisms in the brain underlie behavioral sex differences, but the function of individual sexually dimorphic neuronal populations is poorly understood. Neuronal sexual dimorphisms typically represent quantitative differences in cell number, gene expression, or other features, and it is unknown whether these dimorphisms control sex-typical behavior exclusively in one sex or in both sexes. The progesterone receptor (PR) controls female sexual behavior, and we find many sex differences in number, distribution, or projections of PR-expressing neurons in the adult mouse brain. Using a genetic strategy we developed, we have ablated one such dimorphic PR-expressing neuronal population located in the ventromedial hypothalamus (VMH). Ablation of these neurons in females greatly diminishes sexual receptivity. Strikingly, the corresponding ablation in males reduces mating and aggression. Our findings reveal the functions of a molecularly defined, sexually dimorphic neuronal population in the brain. Moreover, we show that sexually dimorphic neurons can control distinct sex-typical behaviors in both sexes.DP1 MH099900/MH/NIMH NIH HHS/United StatesDP1MH099900/DP/NCCDPHP CDC HHS/United StatesF31 NS078959/NS/NINDS NIH HHS/United StatesF31NS078959/NS/NINDS NIH HHS/United StatesR01 NS049488/NS/NINDS NIH HHS/United StatesR01 NS083872/NS/NINDS NIH HHS/United StatesR01NS049488/NS/NINDS NIH HHS/United States2014-05-09T00:00:00Z23663785PMC376776

    Identification and quantification of cell gas evolution in rigid polyurethane foams by novel GCMS methodology

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    Producción CientíficaThis paper presents a new methodology based on gas chromatography-mass spectrometry (GCMS) in order to separate and quantify the gases presented inside the cells of rigid polyurethane (RPU) foams. To demonstrate this novel methodology, the gas composition along more than three years of aging is herein determined for two samples: a reference foam and foam with 1.5 wt% of talc. The GCMS method was applied, on one hand, for the accurate determination of C5H10 and CO2 cell gases used as blowing agents and, on the other hand, for N2 and O2 air gases that diffuse rapidly from the surrounding environment into foam cells. GCMS results showed that CO2 leaves foam after 2.5 month (from 21% to 0.03% for reference foam and from 17% to 0.03% for foam with 1.5% talc). C5H10 deviates during 3.5 months (from 28% up to 39% for reference foam and from 29% up to 36% for foam with talc), then it starts to leave the foam and after 3.5 year its content is 13% for reference and 10% for foam with talc. Air diffuses inside the cells faster for one year (from 51% up to 79% for reference and from 54% up to 81% for foam with talc) and then more slowly for 3.5 years (reaching 86% for reference and 90% for foam with talc). Thus, the fast and simple presented methodology provides valuable information to understand the long-term thermal conductivity of the RPU foams.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (grants MAT2015-69234-R and RTC-2016-5285-5)Junta de Castilla y Leon (grant VA275P18)Agencia austriaca para la promoción de la investigación (grant 850697
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