181 research outputs found

    Experimental and analytical studies of flow through a ventral and axial exhaust nozzle system for STOVL aircraft

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    Flow through a combined ventral and axial exhaust nozzle system was studied experimentally and analytically. The work is part of an ongoing propulsion technology effort at NASA Lewis Research Center for short takeoff, vertical landing (STOVL) aircraft. The experimental investigation was done on the NASA Lewis Powered Lift Facility. The experiment consisted of performance testing over a range of tailpipe pressure ratios from 1 to 3.2 and flow visualization. The analytical investigation consisted of modeling the same configuration and solving for the flow using the PARC3D computational fluid dynamics program. The comparison of experimental and analytical results was very good. The ventral nozzle performance coefficients obtained from both the experimental and analytical studies agreed within 1.2 percent. The net horizontal thrust of the nozzle system contained a significant reverse thrust component created by the flow overturning in the ventral duct. This component resulted in a low net horizontal thrust coefficient. The experimental and analytical studies showed very good agreement in the internal flow patterns

    Rocket-Based Combined Cycle Engine Technology Development: Inlet CFD Validation and Application

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    A CFD methodology has been developed for inlet analyses of Rocket-Based Combined Cycle (RBCC) Engines. A full Navier-Stokes analysis code, NPARC, was used in conjunction with pre- and post-processing tools to obtain a complete description of the flow field and integrated inlet performance. This methodology was developed and validated using results from a subscale test of the inlet to a RBCC 'Strut-Jet' engine performed in the NASA Lewis 1 x 1 ft. supersonic wind tunnel. Results obtained from this study include analyses at flight Mach numbers of 5 and 6 for super-critical operating conditions. These results showed excellent agreement with experimental data. The analysis tools were also used to obtain pre-test performance and operability predictions for the RBCC demonstrator engine planned for testing in the NASA Lewis Hypersonic Test Facility. This analysis calculated the baseline fuel-off internal force of the engine which is needed to determine the net thrust with fuel on

    A Monte Carlo study of the three-dimensional Coulomb frustrated Ising ferromagnet

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    We have investigated by Monte-Carlo simulation the phase diagram of a three-dimensional Ising model with nearest-neighbor ferromagnetic interactions and small, but long-range (Coulombic) antiferromagnetic interactions. We have developed an efficient cluster algorithm and used different lattice sizes and geometries, which allows us to obtain the main characteristics of the temperature-frustration phase diagram. Our finite-size scaling analysis confirms that the melting of the lamellar phases into the paramgnetic phase is driven first-order by the fluctuations. Transitions between ordered phases with different modulation patterns is observed in some regions of the diagram, in agreement with a recent mean-field analysis.Comment: 14 pages, 10 figures, submitted to Phys. Rev.

    Flow Field of a Dual-Stream Jet with External Wedge- Shaped Deflector

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    The research effort is a Reynolds-Averaged Navier-Stokes (RANS) investigation that looks at the flow-field and performance of a bypass ratio 8 nozzle with an external wedgeshaped noise suppressor, simulating the exhaust of a turbofan engine at takeoff conditions. Peak turbulence was reduced by the wedge on the side opposite the deflector, and it was increased in the initial region of the jet behind the deflector. Flow-field trends agreed with the expectations based on static jet experiments. The calculated thrust loss was 1.1% at takeoff conditions

    The structure of the ternary Eg5–ADP–ispinesib complex

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    The human kinesin Eg5 is responsible for bipolar spindle formation during early mitosis. Inhibition of Eg5 triggers the formation of monoastral spindles, leading to mitotic arrest that eventually causes apoptosis. There is increasing evidence that Eg5 constitutes a potential drug target for the development of cancer chemotherapeutics. The most advanced Eg5-targeting agent is ispinesib, which exhibits potent antitumour activity and is currently in multiple phase II clinical trials. In this study, the crystal structure of the Eg5 motor domain in complex with ispinesib, supported by kinetic and thermodynamic binding data, is reported. Ispinesib occupies the same induced-fit pocket in Eg5 as other allosteric inhibitors, making extensive hydrophobic interactions with the protein. The data for the Eg5-ADP-ispinesib complex suffered from pseudo-merohedral twinning and revealed translational noncrystallographic symmetry, leading to challenges in data processing, space-group assignment and structure solution as well as in refinement. These complications may explain the lack of available structural information for this important agent and its analogues. The present structure represents the best interpretation of these data based on extensive data-reduction, structure-solution and refinement trials

    Geometry parametrization and aerodynamic characteristics of axisymmetric afterbodies

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    A key aspect of the preliminary design process for a new generation combat aircraft is the prediction of afterbody aerodynamic drag. Current prediction methods for preliminary design are constrained in terms of number of independent geometric degrees of freedom that can be studied due to the classic circular arc or conical afterbody geometry parametrization. In addition, the amount of data available for the construction of the reliable performance correlations is too sparse. This paper presents a methodology for the generation of aerodynamic performance maps for transonic axisymmetric afterbody and exhaust systems. It uses a novel parametric geometry definition along with a compressible flow solver to conduct an extensive design space exploration. The proposed geometry parametrization is based on the Class Shape Transformation method and it enables the assessment of the aerodynamic performance of a wider range of afterbodies at the expense of one additional geometric degree of freedom. Relative to the conventional approach, this enables the exploration of a wider design space and the construction of more complete aerodynamic performance maps. This research quantifies the impact of a number of geometric degrees of freedom on the aerodynamic performance of transonic afterbody and exhaust systems at different operating conditions

    The potential role of the extracellular matrix in the activity of trabectedin in UPS and L-sarcoma: evidences from a patient‐derived primary culture case series in tridimensional and zebrafish models

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    Background: Soft tissue sarcomas (STS) are a rare group of solid neoplasm including among others liposarcoma, leiomyosarcoma (L-sarcoma) and undifferentiated pleomorphic sarcoma (UPS) entities. The current first-line treatment is represented by anthracycline based- regimens, second-line may include trabectedin. Currently the activity of trabectedin and its mechanism of action is not completely elucidated. Methods: Taking the advantages of our 3D patient-derived primary culture translational model we performed genomic-, chemobiogram, proteomic- and in vivo analysis in a UPS culture (S1). Furthermore pharmacological profiling of a UPS and L-sarcoma patient-derived case series and in silico analysis were carried out. Results: Trabectedin exhibited an increased activity in 3D respect to 2D cultures suggesting an extracellular matrix (ECM) and timp1 involvement in its mechanism of action. Moreover 3D S1 xenotranspanted zebrafish model showed an increased sensitivity to trabectedin. Finally the results were further validated in a UPS and L-sarcoma case series. Conclusions: Taken together these results confirmed the activity of trabectedin in these STS histotypes. Moreover the data underline the ECM involvement in the cytotoxic effect mediated by trabectedin and could open the door for researches aimed to focus on the patient setting that could benefit from this agent

    Prime movers : mechanochemistry of mitotic kinesins

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    Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

    Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line

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    BACKGROUND: Kinesin spindle proteins (KSP) are motor proteins that play an essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the formation of the bipolar spindle, which is critical for proper cell division during mitosis. The function of HsEg5 provides a novel target for the manipulation of the cell cycle and the induction of apoptosis. SB715992, an experimental KSP inhibitor, has been shown to perturb bipolar spindle formation, thus making it an excellent candidate for anti-cancer agent. Our major objective was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3 human prostate cancer cell line, b) to investigate whether the growth inhibitory effects of SB715992 could be enhanced when combined with genistein, a naturally occurring isoflavone and, c) to determine gene expression profile to establish molecular mechanism of action of SB715992. METHODS: PC-3 cells were treated with varying concentration of SB715992, 30 μM of genistein, and SB715992 plus 30 μM of genistein. After treatments, PC-3 cells were assayed for cell proliferation, induction of apoptosis, and alteration in gene and protein expression using cell inhibition assay, apoptosis assay, microarray analysis, real-time RT-PCR, and Western Blot analysis. RESULTS: SB715992 inhibited cell proliferation and induced apoptosis in PC-3 cells. SB715992 was found to regulate the expression of genes related to the control of cell proliferation, cell cycle, cell signaling pathways, and apoptosis. In addition, our results showed that combination treatment with SB715992 and genistein caused significantly greater cell growth inhibition and induction of apoptosis compared to the effects of either agent alone. CONCLUSION: Our results clearly show that SB715992 is a potent anti-tumor agent whose therapeutic effects could be enhanced by genistein. Hence, we believe that SB715992 could be a novel agent for the treatment of prostate cancer with greater success when combined with a non-toxic natural agent like genistein

    Survival of patients with metastatic breast cancer: twenty-year data from two SEER registries

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    BACKGROUND: Many researchers are interested to know if there are any improvements in recent treatment results for metastatic breast cancer in the community, especially for 10- or 15-year survival. METHODS: Between 1981 and 1985, 782 and 580 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries of the Surveillance, Epidemiology, and End Results (SEER) database. The lognormal statistical method to estimate survival was retrospectively validated since the 15-year cause-specific survival rates could be calculated using the standard life-table actuarial method. Estimated rates were compared to the actuarial data available in 2000. Between 1991 and 1995, further 752 and 632 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries. The data were analyzed to estimate the 15-year cause-specific survival rates before the year 2005. RESULTS: The 5-year period (1981–1985) was chosen, and patients were followed as a cohort for an additional 3 years. The estimated 15-year cause-specific survival rates were 7.1% (95% confidence interval, CI, 1.8–12.4) and 9.1% (95% CI, 3.8–14.4) by the lognormal model for the two registries of Connecticut and San Francisco-Oakland respectively. Since the SEER database provides follow-up information to the end of the year 2000, actuarial calculation can be performed to confirm (validate) the estimation. The Kaplan-Meier calculation for the 15-year cause-specific survival rates were 8.3% (95% CI, 5.8–10.8) and 7.0% (95% CI, 4.3–9.7) respectively. Using the 1991–1995 5-year period cohort and followed for an additional 3 years, the 15-year cause-specific survival rates were estimated to be 9.1% (95% CI, 3.8–14.4) and 14.7% (95% CI, 9.8–19.6) for the two registries of Connecticut and San Francisco-Oakland respectively. CONCLUSIONS: For the period 1981–1985, the 15-year cause-specific survival for the Connecticut and the San Francisco-Oakland registries were comparable. For the period 1991–1995, there was not much change in survival for the Connecticut registry patients, but there was an improvement in survival for the San Francisco-Oakland registry patients
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