ALBERT

Description: There is growing evidence that histone deacetylase inhibitors (HDAC-I) may have benefit in the treatment of multiple myeloma (MM). We assessed the in vitro responses of the MM cell lines H929, JJN3, KMS11 and U266 to the HDAC-Is trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA) and sodium valproate (SV). All three HDAC-Is induced dose dependent cell killing and the ranked sensitivity of the lines was remarkably constant with U266 cells being most resistant to all three inhibitors. Real time RT-PCR based analyses of the HDAC expression profiles, identified that the greater resistence of U266 cells was associated with 5–10 fold increased expression of a single HDAC from the sirtuin family of deacetylases (SIRT5). Each HDAC-I displayed different potencies against the cell lines; TSA killed in the range 0.1–1μM, SAHA in the range 1–10μM and SV at the higher doses of 1–10mM. Despite being less potent, the doses of SV are commensurate with those that can be achieved in vivo. Furthermore, we have identified synergy/cooperation between suboptimal SV concentrations and the proteasome inhibitor Velcade (Bortezomib). MTT assays using JJN3 cells, demonstrated that 1mM SV had little effect reducing survival to 89% whereas 0.6 nM velcade reduced cell survival to 42±5.5%. Killing by velcade was not significantly enhanced by the additional presence of 1μM dexamethasone (Dex)(36±3.4%). However, the combination of SV, Dex and Velcade resulted in near total cell killing (4.7±2.6% survival). Collectively, these observations suggested that SV may have value in MM therapy. However, we wished to also investigate the potency of SV against primary MM cells. We have developed an in vitro culture system in which primary MM plasma cells survive for up to 30 days. In this culture system we have observed efficient and selective killing of MM cells by 1mM SV that has been comparable or indeed greater than that observed in response to 1μM SAHA. Thus it appears that primary MM cells are more SV sensitive than MM cell lines. Together our findings indicate that SV may have value in MM therapy and in particular when combined with proteasome inhibitors. Our data also indicate that SIRT5 overexpression may be a resistance factor against such therapies.

Description: The characteristics of aerodynamic noise generated by the interaction of an airstream with a flap surface are discussed. The location and behavior of various noise sources were investigated to determine optimal quieting techniques. A schematic diagram of the jet-flap concepts being considered for integrated-powered-lift systems for short takeoff aircraft is shown. Each of the concepts has in common high velocity turbulent air flowing over relatively rigid surfaces with resultant production of interaction noise. The nature, location, and control of noise sources which involve the interactions of air flows with airfoil surfaces are examined.

Description: Prediction techniques which can be or have been applied to subsonic rotors, and methods for designing helicopter rotors for reduced broadband noise generation are summarized. It is shown how detailed physical models of the noise source can be used to identify approaches to noise control.

Description: The development of concepts for reducing upper surface blown flap noise at the source through flap modifications and special nozzles is reviewed. In particular, recent results obtained on the aerodynamic and acoustic performance of flaps with porous surfaces near the trailing edge and multi-slotted nozzles are reviewed. Considerable reduction (6-10 db) of the characteristic low frequency peak is shown. The aerodynamic performance is compared with conventional systems, and prospects for future improvements are discussed.

Description: The feasibility of acoustical scale modeling techniques for modeling wind effects on long range, low frequency outdoor sound propagation was evaluated. Upwind and downwind propagation was studied in 1/100 scale for flat ground and simple hills with both rigid and finite ground impedance over a full scale frequency range from 20 to 500 Hz. Results are presented as 1/3-octave frequency spectra of differences in propagation loss between the case studied and a free-field condition. Selected sets of these results were compared with validated analytical models for propagation loss, when such models were available. When they were not, results were compared with predictions from approximate models developed. Comparisons were encouraging in many cases considering the approximations involved in both the physical modeling and analysis methods. Of particular importance was the favorable comparison between theory and experiment for propagation over soft ground.

Description: The interior noise levels and spectral characteristics of 18 single-and twin-engine propeller-driven light aircraft, and source-path diagnosis of a single-engine aircraft which was considered representative of a large part of the fleet were studied. The purpose of the flight surveys was to measure internal noise levels and identify principal noise sources and paths under a carefully controlled and standardized set of flight procedures. The diagnostic tests consisted of flights and ground tests in which various parts of the aircraft, such as engine mounts, the engine compartment, exhaust pipe, individual panels, and the wing strut were instrumented to determine source levels and transmission path strengths using the transfer function technique. Predominant source and path combinations are identified. Experimental techniques are described. Data, transfer function calculations to derive source-path contributions to the cabin acoustic environment, and implications of the findings for noise control design are analyzed.

Description: The feasibility of quieting the externally-blown-flap (EBF) noise sources which are due to interaction of jet exhaust flow with deployed flaps was demonstrated on a 1/15-scale 3-flap EBF model. Sound field characteristics were measured and noise reduction fundamentals were reviewed in terms of source models. Test of the 1/15-scale model showed broadband noise reductions of up to 20 dB resulting from combination of variable impedance flap treatment and mesh grids placed in the jet flow upstream of the flaps. Steady-state lift, drag, and pitching moment were measured with and without noise reduction treatment.

Description: A brief review of some fundamental aspects of sound arising from turbulent boundary layers, noise due to flow past a single discontinuity (trailing edge), noise from airfoils operating in turbulent flow, and noise due to rigid flow discontinuities (spoilers) immersed in rigid ducts is presented. Emphasis is on dipole-like sound fields associated with turbulent flow past a trailing edge, rigid bodies in turbulence and in-duct spoilers. Representative available data are reviewed and evaluated in terms of theoretical considerations and, where possible, empirical prediction techniques are given in terms of convenient aerodynamic and geometric parameters. Limitations on current knowledge are discussed.

Description: Measures to reduce the intensity of fan noise in the NASA Langley 30 ft x 60 ft subsonic wind tunnel were sought. Measurements were first performed to document existing aerodynamic and acoustic conditions. The purpose of these experiments was to (1) obtain the transfer function between the sound power output of the fan and the sound pressure on the test platform, (2) evaluate the sound attenuation around the tunnel circuit, (3) measure simultaneously the flow profile and the turbulence spectrum of the inflow to the fan and the noise on the test platform, and (4) perform flow observations and identify secondary noise sources. Subsequently, these data were used to predict (1) the relative contribution of the major aerodynamic parameters to total fan noise and (2) the effect of placing a dissipative silencer in the collector duct upstream of the fan. Promising noise control measures were identified and recommendations were made on how to evaluate them.

Description: Prediction of airframe noise radiation from the landing gear and wheel wells of commercial aircraft is examined. Measurements of these components on typical aircraft are presented and potential noise sources identified. Semiempirical expressions for the sound generation by these sources are developed from available experimental data and theoretical analyses. These expressions are employed to estimate the noise radiation from the landing gear and wheel wells for a typical aircraft and to rank order the component sources.