153 research outputs found

    A preliminary comparison between the SR-6 propeller noise in flight and in a wind tunnel

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    High speed turboprops offer an attractive candidate for aircraft because of their high propulsive efficiency. However, one of the possible problems associated with these propellers is their high noise level at cruise condition that may create a cabin environment problem. Models of these propellers were tested for acoustics in the 8 by 6-foot wind tunnel and on the Jet Star airplane. Comparisons between the airplane and wind tunnel data for the SR-6 propeller are shown. The comparison of maximum blade passing tone variation with helical tip Mach number between the tunnel and flight data was good when corrected to the same test conditions. Directivity comparisons also showed fairly good agreement. These good comparisons indicate that the wind tunnel is a viable location for measuring the blade passage tone noise of these propellers

    Landing approach airframe noise measurements and analysis

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    Flyover measurements of the airframe noise produced by the AeroCommander, JetStar, CV-990, and B-747 airplanes are presented for various landing approach configurations. Empirical and semiempirical techniques are presented to correlate the measured airframe noise with airplane design and aerodynamic parameters. Airframe noise for the jet-powered airplanes in the clean configuration (flaps and gear retracted) was found to be adequately represented by a function of airplane weight and the fifth power of airspeed. Results show the airframe noise for all four aircraft in the landing configuration (flaps extended and gear down) also varied with the fifth power of airspeed, but this noise level could not be represented by the addition of a constant to the equation for clean-configuration airframe noise

    Effects of inlet distortion on a static pressure probe mounted on the engine hub in an F-15 airplane

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    An inlet static pressure (PS2) probe was mounted on the hub of an F100 engine in an F-15 airplane. Flight test results showed that for low distortion conditions, the ratio of engine-face total pressure to static pressure agreed well with previous altitude facility data. Off-schedule operation of the inlet third ramp angle caused increased distortion of the inlet airflow during steady-state flight conditions. Data are shown for inlet third ramp excursions leading to engine stall. The relationships of inlet face total to static pressure ratio as a function of several distortion descriptors are also described

    Impact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy

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    The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-Thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median prechemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. © 2014 Cillo et al

    A Development Environment for Visual Physics Analysis

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    The Visual Physics Analysis (VISPA) project integrates different aspects of physics analyses into a graphical development environment. It addresses the typical development cycle of (re-)designing, executing and verifying an analysis. The project provides an extendable plug-in mechanism and includes plug-ins for designing the analysis flow, for running the analysis on batch systems, and for browsing the data content. The corresponding plug-ins are based on an object-oriented toolkit for modular data analysis. We introduce the main concepts of the project, describe the technical realization and demonstrate the functionality in example applications

    Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer

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    <p>Abstract</p> <p>Background</p> <p>Active-specific immunotherapy used as an adjuvant therapeutic strategy is rather unexplored for cancers with poorly characterized tumor antigens like gastric cancer. The aim of this study was to augment a therapeutic immune response to a low immunogenic tumor cell line derived from a spontaneous gastric tumor of a CEA424-SV40 large T antigen (CEA424-SV40 TAg) transgenic mouse.</p> <p>Methods</p> <p>Mice were treated with a lymphodepleting dose of cyclophosphamide prior to reconstitution with syngeneic spleen cells and vaccination with a whole tumor cell vaccine combined with GM-CSF (a treatment strategy abbreviated as LRAST). Anti-tumor activity to subcutaneous tumor challenge was examined in a prophylactic as well as a therapeutic setting and compared to corresponding controls.</p> <p>Results</p> <p>LRAST enhances tumor-specific T cell responses and efficiently inhibits growth of subsequent transplanted tumor cells. In addition, LRAST tended to slow down growth of established tumors. The improved anti-tumor immune response was accompanied by a transient decrease in the frequency and absolute number of CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+ </sup>T cells (Tregs).</p> <p>Conclusions</p> <p>Our data support the concept that whole tumor cell vaccination in a lymphodepleted and reconstituted host in combination with GM-CSF induces therapeutic tumor-specific T cells. However, the long-term efficacy of the treatment may be dampened by the recurrence of Tregs. Strategies to counteract suppressive immune mechanisms are required to further evaluate this therapeutic vaccination protocol.</p

    Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response

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    BACKGROUND: Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in ASCT patients. METHODOLOGY/PRINCIPAL FINDINGS: To verify whether this observation could be secondary to intrinsic HIV-correlated T cell defects, we performed in-depth immunologic analyses in 10 patients with comparable CD4 counts in whom lymphopenia was secondary either to HIV-infection or ASCT-associated immunosuppressive therapy and compared them to age-matched healthy subjects. Results showed the presence of profound alterations in CD4+ T lymphocytes in both groups of patients with respect to healthy controls. Thus, a low percentage of CCR7+ CD4+ T cells and a compensative expansion of CD45RA-CCR7- CD4+ T cells, a reduced IL-2/IFN-gamma cytokine production and impaired recall antigens-specific proliferative responses were detected both in ASCT and HIV patients. In stark contrast, profound differences were detected in CD8+ T-cells between the two groups of patients. Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA-CCR7- cells, higher CD45RA+CCR7- CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-gamma +/TNFalpha production and granzyme CD8+ expression. The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients. CONCLUSION/SIGNIFICANCE: These results indicate that CD8 T cells maturation and functions can be observed even in the face of a profound impairment of CD4+ T lymphocytes in ASCT but not in HIV patients. Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results

    Prophylactic ciprofloxacin treatment prevented high mortality, and modified systemic and intestinal immune function in tumour-bearing rats receiving dose-intensive CPT-11 chemotherapy

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    Infectious complications are a major cause of morbidity and mortality from dose-intensive cancer chemotherapy. In spite of the importance of intestinal bacteria translocation in these infections, information about the effect of high-dose chemotherapy on gut mucosal immunity is minimal. We studied prophylactic ciprofloxacin (Cipro) treatment on irinotecan (CPT-11) toxicity and host immunity in rats bearing Ward colon tumour. Cipro abolished chemotherapy-related mortality, which was 45% in animals that were not treated with Cipro. Although Cipro reduced body weight loss and muscle wasting, it was unable to prevent severe late-onset diarrhoea. Seven days after CPT-11, splenocytes were unable to proliferate (stimulation index=0.10±0.02) and produce proliferative and inflammatory cytokines (i.e., Interleukin (IL)-2, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) IL-1β, IL-6) on mitogen stimulation in vitro (P<0.05 vs controls), whereas mesenteric lymph node (MLN) cells showed a hyper-proliferative response and a hyper-production of pro-inflammatory cytokines on mitogen stimulation. This suggests compartmentalised effects by CPT-11 chemotherapy on systemic and intestinal immunity. Cipro normalised the hyper-responsiveness of MLN cells, and in the spleen, it partially restored the proliferative response and normalised depressed production of IL-1β and IL-6. Taken together, Cipro prevented infectious challenges associated with immune hypo-responsiveness in systemic immune compartments, and it may also alleviate excessive pro-inflammatory responses mediating local gut injury

    Clinical Predictors of Immune Reconstitution following Combination Antiretroviral Therapy in Patients from the Australian HIV Observational Database

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    A small but significant number of patients do not achieve CD4 T-cell counts >500 cells/µl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART.Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count <500 cells/µl, HIV RNA<500 copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts >500 cells/µl and >200 cells/µl.501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32-47) years and 236 (130-350) cells/µl, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3-10) years. Most patients (80%) achieved CD4 T-cell counts >500 cells/µl, but in 8%, this took >5 years. Among the patients who failed to reach a CD4 T-cell count >500 cells/µl, 16% received cART for >10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count >500 cells/µl was associated with higher baseline CD4 T-cell counts (p<0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts >200 cells/µl included higher baseline CD4 T-cell count (p<0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p<0.001).The time taken to achieve a CD4 T-cell count >500 cells/µl despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen) is associated with more rapid recovery of a CD4 T-cell count >500 cells/µl
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