Understanding and enhancing selective Fab separations using multimodal chromatography

This research seeks to determine what conditions are required to achieve selective separations of similar protein variants and to provide fundamental insight into the mechanisms underlying these separations. The retention of protein libraries on several multimodal cation-exchange systems demonstrated that the retention of many proteins proved to be sensitive to subtle changes in the ligand chemistry and geometrical presentation. All-atom explicit Molecular Dynamics (MD) simulations were then carried out to shed light on the multiple weak interactions that resulted in the unique selectivities achieved in these multimodal chromatographic systems. A range of biophysics techniques including NMR, ITC and AFM were also employed to study the energetics, kinetics and thermodynamics of protein binding to self-assembled monolayers (SAMs) of MM ligands. Finally, quantitative structure activity relationship models were developed using unique molecular descriptors inspired by the biophysics and simulation studies for predicting the chromatographic behavior of proteins on a many multimodal resin systems and to provide insight into the relative importance of various regions on Fabs for interacting with these ligands. This work provides fundamental understanding of the nature of these interactions at the molecular level and insight into the design of MM ligands with important implications for addressing challenging problems in downstream bioprocessing

A perspective on polishing operations for the continuous removal of process and product related impurities

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Use of imaging in restorative stroke trials.

Restorative therapies aim to improve behavioral outcome after stroke by promoting repair and restoration. Measures of CNS injury and function might be useful to evaluate such therapies in a clinical trial, for example, by optimizing patient selection or treatment dose. These issues are considered in this review, with specific examples provided

An overview of therapies to promote repair of the brain after stroke.

Stroke remains a leading cause of disability. Most patients show some degree of spontaneous recovery, but this is generally incomplete. Studies on the neurobiology of this recovery are providing clues to therapeutic interventions that aim to improve patient outcomes. A number of potential such restorative therapies are reviewed. Numerous treatment strategies are under study. Most have a time window measured in days or weeks and so have the potential to help a large fraction of patients. This review considers these therapies, as well as points to consider in translating their application to human trials

Listening to fluoxetine: a hot message from the FLAME trial of poststroke motor recovery.

The fluoxetine for motor recovery after acute ischemic stroke study was a double blind, placebo-controlled trial examining the effects of fluoxetine in patients five- to 10 days after an ischemic stroke. The study found motor improvement to 90 days poststroke, measured as the change in the Fugl-Meyer score, was significantly greater in the fluoxetine group as compared with the placebo group, and that this finding was significant after adjusting for depression. Patients randomized to fluoxetine also had less disability (modified Rankin Scale 0-2). The study adds to the weight of data suggesting that viable strategies exist to improve patient outcomes by initiating a restorative agent, days after stroke injury is fixed. Stroke remains among the leading causes of human disability. Currently, a minority of patients can access approved reperfusion therapies, and among those so treated a substantial fraction derives limited benefit. Therapies that target restorative events have a time window measured in days-weeks and so hold the potential to help many patients with stroke