119 research outputs found

    Progress toward sonifying Napoleon’s march and fluid flow simulations through binaural horizons

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    Cross-modal data analytics—that can be rendered for experience through vision, hearing, and touch—poses a fundamental challenge to designers. Non-linguistic sonification is a well-researched means for non-visual pattern recognition but higher density datasets pose a challenge. Because human hearing is optimized for detecting locations on a horizontal plane, our approach recruits this optimization by employing an immersive binaural horizontal plane using auditory icons. Two case studies demonstrate our approach: A sonic translation of a map and a sonic translation of a computational fluid dynamics simulation

    Comparison of 24-hour parasympathetic activity in endurance-trained and untrained young men

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    AbstractObjectives. This study compares 24-h parasympathetic activity in aerobically trained and untrained healthy young men.Background. Higher values of parasympathetic nervous system activity are associated with a low mortality rate in patients after myocardial infarction, but it remains uncertain what therapeutic interventions can be used to increase parasympathetic activity. Although it is thought that exercise training can increase parasympathetic activity, studies have reported conflicting results, perhaps because this variable was measured for only brief intervals and usually inferred from changes in reflex responses induced by pharmacologic blockade.Methods. Parasympathetic activity was assessed noninvasively from 24-h ECG recordings by calculating high frequency (0.15 to 0.40 Hz) beat to beat heart period variability in eight endurance-trained men (maximal oxygen consumption ≥ 55 ml/kg per min) and eight age-matched (mean = 29 yr) untrained men (maximal oxygen consumption ≤ 40 ml/kg per min). The data were analyzed separately for sleeping hours when parasympathetic activity is dominant and also for waking hours.Results. The geometric mean of high frequency power was greater in the trained than in the untrained men during the day (852 vs. 177 ms2, p < 0.005), during the night (1,874 vs. 427 ms2, p < 0.005) and over the entire 24 h (1,165 vs. 276 ms2, p < 0.001).Conclusions. Parasympathetic activity is substantially greater in trained than in untrained men, and this effect is present during both waking and sleeping hours. These data suggest that exercise training may increase parasympathetic activity over the entire day and may therefore prove to be a useful adjunct or alternative to drug therapy in lessening the derangements of autonomic balance found in many cardiovascular diseases

    Sonification of Flow Instabilities in CFD Aneurysm Models

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    Paper presented at 2018 Canadian Society of Mechanical Engineers International Congress, 27-30 May 2018.Recent investigations using image-based computational flow dynamics (CFD) have revealed turbulent-like blood flow instabilities (hemodynamics) within intracranial cerebral aneurysms and surrounding vasculature, which may contribute to aneurysm initiation, growth, and rupture. We describe a method derived from spectral decomposition of flow for inspecting and characterizing these “turbulent-like” hemodynamic structures in intracranial aneurysms by sonification of CFD generated data. Motivated by auscultation techniques, the current research seeks to address the limitations of conventional CFD animations by allowing the user to listen to complex flow patterns that are often difficult to discern visually. In the process, the proposed method of sonification is successfully applied to a series of datasets resulting from highfidelity numerical simulations of intracranial aneurysms. The resulting framework is shown to be highly efficient in performing parametric sonification in real time

    Using Downhole Probes to Locate and Characterize Buried Transuranic and Mixed Low Level Waste

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    Borehole logging probes were developed and tested to locate and quantify transuranic elements in subsurface disposal areas and in contaminated sites at USDOE Weapons Complex sites. A new method of measuring very high levels of chlroine in the subsurface was developed using pulsed neutron technology from oilfield applications. The probes were demonstrated at the Hanford site in wells containing plutonium and other contaminants

    Thymic Selection Determines γδ T Cell Effector Fate: Antigen-Naive Cells Make Interleukin-17 and Antigen-Experienced Cells Make Interferon γ

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    γδ T cells contribute uniquely to host immune competence, but how they do so remain unclear. Here, by analyzing T10/T22-specific γδ T cells in mice with different T10/T22 expression patterns, we find that encountering antigen in the thymus is neither required nor inhibitory for the development of these cells. Instead, ligand recognition determines which of two distinct functional subsets γδ T cells will become. When triggered through the TCR, lymphoid-γδ T cells that encounter ligand during development produce IFNγ, while those that develop in the absence of ligand make IL-17, a major inducer of granulopoiesis during inflammation. Indeed, we find large fractions of IL-17+ γδ T cells from the draining lymph nodes immediately after peptide/CFA immunization and days before the appearance of antigen specific IL-17+ αβ T cells. This suggests a critical role for γδ T cells as ‘initial providers’ of IL-17 in an inflammatory response to novel antigens

    Microvolt T-Wave Alternans and the Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction

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    ObjectivesThis study hypothesized that microvolt T-wave alternans (MTWA) improves selection of patients for implantable cardioverter-defibrillator (ICD) prophylaxis, especially by identifying patients who are not likely to benefit.BackgroundMany patients with left ventricular dysfunction are now eligible for prophylactic ICDs, but most eligible patients do not benefit; MTWA testing has been proposed to improve patient selection.MethodsOur study was conducted at 11 clinical centers in the U.S. Patients were eligible if they had a left ventricular ejection fraction (LVEF) ≤0.40 and lacked a history of sustained ventricular arrhythmias; patients were excluded for atrial fibrillation, unstable coronary artery disease, or New York Heart Association functional class IV heart failure. Participants underwent an MTWA test and then were followed for about two years. The primary outcome was all-cause mortality or non-fatal sustained ventricular arrhythmias.ResultsIschemic heart disease was present in 49%, mean LVEF was 0.25, and 66% had an abnormal MTWA test. During 20 ± 6 months of follow-up, 51 end points (40 deaths and 11 non-fatal sustained ventricular arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests, the hazard ratio for the primary end point was 6.5 at two years (95% confidence interval 2.4 to 18.1, p < 0.001). Survival of patients with normal MTWA tests was 97.5% at two years. The strong association between MTWA and the primary end point was similar in all subgroups tested.ConclusionsAmong patients with heart disease and LVEF ≤0.40, MTWA can identify not only a high-risk group, but also a low-risk group unlikely to benefit from ICD prophylaxis

    Local Delivery of Interleukin 4 by Retrovirus-Transduced T Lymphocytes Ameliorates Experimental Autoimmune Encephalomyelitis

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    Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system which serves as a model for the human disease multiple sclerosis. We demonstrate here that encephalitogenic T cells, transduced with a retroviral gene, construct to express interleukin 4, and can delay the onset and reduce the severity of EAE when adoptively transferred to myelin basic protein–immunized mice. Thus, T lymphocytes transduced with retroviral vectors can deliver “regulatory cytokines” in a site-specific manner and may represent a viable therapeutic strategy for the treatment of autoimmune disease

    TLR-4 ligation of dendritic cells is sufficient to drive pathogenic T cell function in experimental autoimmune encephalomyelitis

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    <p>Abstract</p> <p>Background</p> <p>Experimental autoimmune encephalomyelitis (EAE) depends on the initial activation of CD4<sup>+</sup> T cells responsive to myelin autoantigens. The key antigen presenting cell (APC) population that drives the activation of naïve T cells most efficiently is the dendritic cell (DC). As such, we should be able to trigger EAE by transfer of DC that can present the relevant autoantigen(s). Despite some sporadic reports, however, models of DC-driven EAE have not been widely adopted. We sought to test the feasibility of this approach and whether activation of the DC by toll-like receptor (TLR)-4 ligation was a sufficient stimulus to drive EAE.</p> <p>Findings</p> <p>Host mice were seeded with myelin basic protein (MBP)-reactive CD4+ T cells and then were injected with DC that could present the relevant MBP peptide which had been exposed to lipopolysaccharide as a TLR-4 agonist. We found that this approach induced robust clinical signs of EAE.</p> <p>Conclusions</p> <p>DC are sufficient as APC to effectively drive the differentiation of naïve myelin-responsive T cells into autoaggressive effector T cells. TLR-4-stimulation can activate the DC sufficiently to deliver the signals required to drive the pathogenic function of the T cell. These models will allow the dissection of the molecular requirements of the initial DC-T cell interaction in the lymphoid organs that ultimately leads to autoimmune pathology in the central nervous system.</p

    IL-3 and oncogenic Abl regulate the myeloblast transcriptome by altering mRNA stability

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    The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6 (IL-6) 3′-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/ Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth. © 2009 Ernst et al

    Ovarian cancer immunotherapy: opportunities, progresses and challenges

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    Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer
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