389 research outputs found

    Telepresence and the Role of the Senses

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    The telepresence experience can be evoked in a number of ways. A well-known example is a player of videogames who reports about a telepresence experience, a subjective experience of being in one place or environment, even when physically situated in another place. In this paper we set the phenomenon of telepresence into a theoretical framework. As people react subjectively to stimuli from telepresence, empirical studies can give more evidence about the phenomenon. Thus, our contribution is to bridge the theoretical with the empirical. We discuss theories of perception with an emphasis on Heidegger, Merleau-Ponty and Gibson, the role of the senses and the Spinozian belief procedure. The aim is to contribute to our understanding of this phenomenon. A telepresence-study that included the affordance concept is used to empirically study how players report sense-reactions to virtual sightseeing in two cities. We investigate and explore the interplay of the philosophical and the empirical. The findings indicate that it is not only the visual sense that plays a role in this experience, but all senses

    Increased Number of Cerebellar Granule Cells and Astrocytes in the Internal Granule Layer in Sheep Following Prenatal Intra-amniotic Injection of Lipopolysaccharide

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    Chorioamnionitis is an important problem in perinatology today, leading to brain injury and neurological handicaps. However, there are almost no data available regarding chorioamnionitis and a specific damage of the cerebellum. Therefore, this study aimed at determining if chorioamnionitis causes cerebellar morphological alterations. Chorioamnionitis was induced in sheep by the intra-amniotic injection of lipopolysaccharide (LPS) at a gestational age (GA) of 110Β days. At a GA of 140Β days, we assessed the mean total and layer-specific volume and the mean total granule cell (GCs) and Purkinje cell (PC) number in the cerebelli of LPS-exposed and control animals using high-precision design-based stereology. Astrogliosis was assessed in the gray and white matter (WM) using a glial fibrillary acidic protein staining combined with gray value image analysis. The present study showed an unchanged volume of the total cerebellum as well as the molecular layer, outer and inner granular cell layers (OGL and IGL, respectively), and WM. Interestingly, compared with controls, the LPS-exposed brains showed a statistically significant increase (+20.4%) in the mean total number of GCs, whereas the number of PCs did not show any difference between the two groups. In addition, LPS-exposed animals showed signs of astrogliosis specifically affecting the IGL. Intra-amniotic injection of LPS causes morphological changes in the cerebellum of fetal sheep still detectable at full-term birth. In this study, changes were restricted to the inner granule layer. These cerebellar changes might correspond to some of the motor or non-motor deficits seen in neonates from compromised pregnancies

    Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

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    In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

    Therapeutic Effects of Autologous Tumor-Derived Nanovesicles on Melanoma Growth and Metastasis

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    Cancer vaccines with optimal tumor-associated antigens show promise for anti-tumor immunotherapy. Recently, nano-sized vesicles, such as exosomes derived from tumors, were suggested as potential antigen candidates, although the total yield of exosomes is not sufficient for clinical applications. In the present study, we developed a new vaccine strategy based on nano-sized vesicles derived from primary autologous tumors. Through homogenization and sonication of tumor tissues, we achieved high yields of vesicle-bound antigens. These nanovesicles were enriched with antigenic membrane targets but lacked nuclear autoantigens. Furthermore, these nanovesicles together with adjuvant activated dendritic cells in vitro, and induced effective anti-tumor immune responses in both primary and metastatic melanoma mouse models. Therefore, autologous tumor-derived nanovesicles may represent a novel source of antigens with high-level immunogenicity for use in acellular vaccines without compromising safety. Our strategy is cost-effective and can be applied to patient-specific cancer therapeutic vaccination

    The Formation of the First Massive Black Holes

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    Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

    Antagonism between DNA and H3K27 Methylation at the Imprinted Rasgrf1 Locus

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    At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other. We demonstrated this in five ways: using 5-azacytidine treatments and mutations at the endogenous locus that disrupt DNA methylation; using a transgenic model in which the maternal DMD inappropriately acquired DNA methylation; and by analyzing materials from cells and embryos lacking SUZ12 and YY1. SUZ12 is part of the PRC2 complex, which is needed for placing H3K27me3, and YY1 recruits PRC2 to sites of action. Results from each experimental system consistently demonstrated antagonism between H3K27me3 and DNA methylation. When DNA methylation was lost, H3K27me3 encroached into sites where it had not been before; inappropriate acquisition of DNA methylation excluded normal placement of H3K27me3, and loss of factors needed for H3K27 methylation enabled DNA methylation to appear where it had been excluded. These data reveal the previously unknown antagonism between H3K27 and DNA methylation and identify a means by which epigenetic states may change during disease and development

    Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells

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    <p>Abstract</p> <p>Background</p> <p>3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both <it>in vivo </it>and <it>in vitro </it>models. We have previously determined that DIM (0 – 30 ΞΌmol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells.</p> <p>Methods</p> <p>HT-29 cells were cultured with various concentrations of DIM (0 – 30 ΞΌmol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [<sup>3</sup>H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and <it>in vitro </it>kinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted.</p> <p>Results</p> <p>The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21<sup>CIP1/WAF1 </sup>and p27<sup>KIPI</sup>. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1.</p> <p>Conclusion</p> <p>Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.</p

    Endothelial Progenitor Cells, Cardiovascular Risk Factors, Cytokine Levels and Atherosclerosis – Results from a Large Population-Based Study

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    EPC number and functionality are assumed to reflect the endogenous vascular repair capacity with the EPC pool declining in higher ages and being exhausted by unfavorable life-style and risk factors. This intriguing and clinically highly relevant concept, however, has so far been derived from small case-control studies and patient series.In the population-based Bruneck Study EPC number and EPC-colony forming units (EPC-CFU) were assessed as part of the fourth follow-up evaluation (2005) in 571 and 542 subjects, respectively. EPC number declined with age (p = 0.013), was significantly lower in women (p = 0.006) and higher in subjects on statin, hormone replacement or ACE inhibitor/angiotensin-receptor blockers, and correlated positively with moderate alcohol consumption. Unexpectedly, a positive relation between EPC number and several vascular risk factors emerged. In a step forward multivariate linear regression analysis EPC number was independently related with SDF1alpha, MMP-9, triglycerides, alcohol consumption, and Hba1c. EPC-CFU in turn was related to SDF1alpha and diastolic blood pressure. Moreover, EPC number showed a significant positive association with the Framingham risk score (P = 0.001). Finally, there was an inverse association between EPC number and common carotid artery intima-media thickness (p = 0.02) and the carotid artery atherosclerosis score (p = 0.059).Our population-based data confirm the decline of EPC number with advancing age and lend first epidemiological support to a role of SDF-1alpha and MMP9 in EPC differentiation, mobilization and homing, but are conflict with the view that EPC number is unfavorably affected by cardiovascular risk factors. EPC number increases with the cardiovascular risk estimated by the Framingham risk score (FRS), which in the absence of similar changes for EPC-CFU. Finally, we demonstrate a significant inverse association between EPC number and extent of carotid atherosclerosis even though this association was only of moderate strength and not entirely consistent in other vascular territories

    Anodal Transcranial Direct Current Stimulation Reduces Psychophysically Measured Surround Suppression in the Human Visual Cortex

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    Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex
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