Structures in stratified plane mixing layers and the effects of cross-shear

A two-dimensional temporal mixing layer is generated in a stratified tilting tank similar to that used by Thorpe (1968). Extensive flow dynamics visualization is carried out using, for the top and bottom layers, fluids of different densities but of the same index of refraction. The two-dimensional density field is measured with the laser-induced fluorescence technique (LIF). The study examines further the classical problem of the two-dimensional mixing layer and explores the effects of cross-shear on a nominally two-dimensional mixing layer, a situation widespread in complex industrial and natural flows. Cross-shear is another component of shear, in plane with but perpendicular to the main shear of the base flow, generated by tilting the tank around a second axis

A plane mixing layer with cross-shear

The effect of cross‐shear on a nominally two‐dimensional plane mixing layer is investigated. A temporal mixing layer is generated with a stratified tilting tank similar to that used by Thorpe [J. Fluid Mech. 32, 693 (1968)], and cross‐shear is introduced to this mixing layer to simulate situations the authors believe are widespread in industrial and natural flows. A new type of ‘‘co‐rotating’’ streamwise vortices arises from the introduction of cross‐shear, and the mixing rate is found to be greatly enhanced

Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders

Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death with average survival times of 2 ‐ 5 years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a protein whose stability and aggregation propensity are affected by point mutations spanning the protein. Here, we use an epitope‐specific, high‐throughput screen to identify peptides that both stabilize the native conformation of SOD1 as well as accelerate its folding by 2.5‐fold. Ligands targeted to the electrostatic loop on the periphery of the protein tightened the non‐metalated structure and accelerated its folding. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics

The Specialist Committee on Detailed Flow Measurements. Final Report and Recommendations to the 26th ITTC

The scope of this report is to review up-todate measurement systems and methods available for flow-field and wave-field measurements and describe applications of Particle Image Velocimetry (PIV), stereoscopic PIV (SPIV), Laser Doppler Velocimetry (LDV),Particle Tracking Velocimetry (PTV),holography, and other emergent methods, for the measurements of flow separation, wake,vortex strength, etc, for ship hydrodynamics problems. Furthermore, practical issues related to the application of these measurement techniques, especially PIV and SPIV, in largescale tow tank facilities and cavitation tunnels will be discussed, with recommendations for future work for the ITTC in these areas

Experimental Investigation of Roll and Heave Excitation and Damping

ABSTRACT This paper will discuss a systematic series of model tests performed at NSWCCD on a conventional combatant hull form at varying Froude numbers, beam wave steepness, and beam wave frequencies near the natural roll frequency of the model. The model was free in roll and heave while constrained in the remaining four degrees of freedom. The model was fully appended, yielding lateral force on the bilge keels, lift, drag and torque on the rudders and all six force and moment components on the propellers. Stereo particle-image velocimetry (SPIV) measurement was used to study the threedimensional unsteady flow patterns around the bilge keels at the model LCG. Model motion results were analyzed with respect to the excitation waves to yield normalized heave and roll amplitudes and phase angles. Force and moment results were analyzed to yield individual appendage viscous drag and added mass coefficients which were in turn used to extend and refine previous theoretical models to include the effects of beam seas. SPIV results were compiled and analyzed to provide a verification and validation dataset for CFD computations. INTRODUCTION A collaborative effort is underway to develop a 6-degreeof-freedom (DOF) Reynolds Averaged Navier-Stokes (RANS) model for ship maneuvering. This cooperative research is being conducted by the Department of Defense (DoD) of the United States of America and the Ministry of Defense (MoD) of the Republic of Italy. The goal of the effort is to improve prediction of all 6-DOF motions of surface ships operating in a seaway, with particular emphasis on the prediction of roll motions. The RANS code under development is intended to address complex viscous free surface flows including unsteady separation around the ship and surface wave interaction with the hull

Modulating SOD1 Folding Landscapes with Targeted Molecular Binders

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the deterioration of motor neurons that abates essential biological functions and exhibits survival times of 3 - 5 years after diagnosis. One driver of this disease derives from inherited mutations to the protein superoxide dismutase 1 (SOD1), which hinder proper folding and result in the accumulation of toxic aggregates. We identified cyclic peptides that target precise epitopes on SOD1 through an emerging screening platform that furnishes high-affinity binders against regions of a protein independent of secondary or tertiary structure. Binding these epitopes both stabilizes the native state and accelerates folding. In this context, these small peptides function as molecular chaperones and mitigate the impact of deleterious mutations to SOD1. They also display the traditional benefits of small molecules, such as straightforward chemical modifications and long-term stability. Overall, this method provides a route to rationally perturb the energy landscape of any protein through noncovalent binding, making it useful in fundamental studies of protein folding as well as designing therapeutics for misfolding diseases

Molecular Modulation of Protein Energy Landscapes

Protein catalyzed capture agents are an emerging class of oligopeptides that combine the benefits of small molecules and antibodies to furnish ligands with picomolar binding affinity, serum stability, and cell permeability. Their identification involves screening a synthetic, alkyne-functionalized epitope from a target protein against a library of cyclic peptides bearing terminal azides. We identified ligands that bind regions of superoxide dismutase 1 (SOD1), a protein that misfolds to cause amyotrophic lateral sclerosis (ALS), consistently destabilized upon mutation. Treatment of the disease is challenging because there are over 180 heritable mutations of SOD1 and virtually no well-defined binding sites addressable by traditional ligand identification strategies. These mutations ultimately cause the protein to adopt toxic conformations that aggregate and damage cellular functions within the central nervous system. PCC agents targeting regions consistently destabilized across several mutations bind and stabilize its native conformation. We characterized the impact of binding, both on the ground state stability of several mutants as well as the kinetics of SOD1 folding and denaturation