Serine/arginine-protein kinase 1 (SRPK1) regulates alternative splicing of VEGF-A to pro-angiogenic isoforms and SRPK1 inhibition can restore the balance of pro/antiangiogenic isoforms to normal physiological levels. The lack of potency and selectivity of available compounds has limited development of SRPK1 inhibitors, with the control of alternative splicing by splicing factor-specific kinases yet to be translated. We present here compounds that occupy a binding pocket created by the unique helical insert of SRPK1, and trigger a backbone flip in the hinge region, that results in potent (<10 nM) and selective inhibition of SRPK1 kinase activity. Treatment with these inhibitors inhibited SRPK1 activity and phosphorylation of serine/arginine splicing factor 1 (SRSF1), resulting in alternative splicing of VEGF-A from pro-angiogenic to antiangiogenic isoforms. This property resulted in potent inhibition of blood vessel growth in models of choroidal angiogenesis in vivo. This work identifies tool compounds for splice isoform selective targeting of pro-angiogenic VEGF, which may lead to new therapeutic strategies for a diversity of diseases where dysfunctional splicing drives disease development.

A more complete understanding of the physical relationships, between wall-pressure and turbulence, is required for modeling flow-induced noise and developing noise reduction strategies. In this study, the wall-pressure fluctuations, induced by low Reynolds number turbulent boundary layers, are experimentally studied using a high-resolution microphone array. Statistical characteristics obtained using traditional cross-correlation and cross-spectra analyses are complimented with wall-pressure-velocity cross-spectra and wavelet cross-correlations. Wall-pressure-velocity correlations revealed that turbulent activity in the buffer layer contributes at least 40% of the energy to the wall-pressure spectrum at all measured frequencies. As Reynolds number increases, the low-frequency energy shifts from the buffer layer to the logarithmic layer, as expected for regions of uniform streamwise momentum formed by hairpin packets. Conditional cross-spectra suggests that the majority of broadband wall-pressure energy is concentrated within the packets, with the pressure signatures of individual hairpin vortices estimated to decay on average within traveling ten displacement thicknesses, and the packet signature is retained for up to seven boundary layer thicknesses on average.

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This paper discusses the development of analytical models for the prediction of aircraft cabin noise induced by the external turbulent boundary layer (TBL). While, in previous works, the contribution of an individual panel to the cabin interior noise was considered, here, the simultaneous contribution of multiple flow-excited panels is analyzed. Analytical predictions are presented for the interior sound pressure level (SPL) at different locations inside the cabin of a Blended Wing Body (BWB) aircraft, for the frequency range 0–1000 Hz. The results show that the number of vibrating panels significantly affects the interior noise levels. It is shown that the average SPL, over the cabin volume, increases with the number of vibrating panels. Additionally, the model is able to predict local SPL values, at specific locations in the cabin, which are also affected with by number of vibrating panels, and are different from the average values.

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The present study investigates the vibration and sound radiation by panels exited by turbulent flow and by random noise. Composite and aluminum panels are analyzed through a developed analytical framework. The main objective of this study is to identify the difference between the vibroacoustic behaviour of these two types of panels. This topic is of particular importance, given the growing interest in applying composite materials for the construction of aircraft structures, in parts where aluminum panels were traditionally being used. An original mathematical framework is presented for the prediction of noise and vibration for composite panels. Results show the effect of panel size, thickness of core, and thickness of face layers on the predictions. Smaller composite panels generally produced lower levels of sound and vibration than longer and wider composite panels. Compared with isotropic panels, the composite panels analyzed generated lower noise levels, although it was observed that noise level was amplified at certain frequencies.

The turbulent boundary layer is a major source of interior noise in transport vehicles, mainly in aircraft during cruise flight. Furthermore, as new and quieter jet engines are being developed, the turbulent flow-induced noise will become an even more important topic for investigation. However, in order to design and develop systems to reduce the cabin interior noise, the understanding of the physical system dynamics is fundamental. In this context, the main objective of the current research is to develop closed-form analytical models for the prediction of turbulent boundary-layer-induced noise in the interior of aircraft cylindrical cabins. The mathematical model represents the structural-acoustic coupled system, consisted by the aircraft cabin section coupled with the fuselage structure. The aircraft cabin section is modeled as a cylindrical acoustic enclosure, filled with air. The fuselage structure, excited by external random excitation or by turbulent flow, is represented through two different models: (1) as a whole circular cylindrical shell with simply supported end caps and (2) as a set of individual simply supported open circular cylindrical shells. This paper presents the results obtained from the developed analytical framework and its validation through the successful comparison with several experimental studies. Analytical predictions are obtained for the shell structural vibration and sound pressure levels, for the frequency range up to 10,000 Hz.

This study presents an evaluation of semi-empirical single-point wall pressure spectrum models by comparing model predictions with wind tunnel and flight test data. The mean squared error was used to compare the power spectral density of the wall pressure fluctuations predicted by semi-empirical models with a large amount of experimental data. Results show that the models proposed by Goody and Smol’yakov have the lowest mean squared error when predicting the power spectral density for wind tunnel experiments and the Rackl and Weston model has the lowest mean squared error when predicting the power spectral density for flight test data. In addition, although current studies of the power spectra obtained in the wind tunnel are similar, they are not generally an accurate representation of flight test experiments.