Observation of Small Cluster Formation in Concentrated Monoclonal Antibody Solutions and Its Implications to Solution Viscosity

AbstractMonoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions

The DARE study of relapse prevention in depression: design for a phase 1/2 translational randomised controlled trial involving mindfulness-based cognitive therapy and supported self monitoring

<p>Abstract</p> <p>Background</p> <p>Depression is a common condition that typically has a relapsing course. Effective interventions targeting relapse have the potential to dramatically reduce the point prevalence of the condition. Mindfulness-based cognitive therapy (MBCT) is a group-based intervention that has shown efficacy in reducing depressive relapse. While trials of MBCT to date have met the core requirements of phase 1 translational research, there is a need now to move to phase 2 translational research - the application of MBCT within real-world settings with a view to informing policy and clinical practice. The aim of this trial is to examine the clinical impact and health economics of MBCT under real-world conditions and where efforts have been made to assess for and prevent resentful demoralization among the control group. Secondary aims of the project involve extending the phase 1 agenda to an examination of the effects of co-morbidity and mechanisms of action.</p> <p>Methods/Design</p> <p>This study is designed as a prospective, multi-site, single-blind, randomised controlled trial using a group comparison design between involving the intervention, MBCT, and a self-monitoring comparison condition, Depression Relapse Active Monitoring (DRAM). Follow-up is over 2 years. The design of the study indicates recruitment from primary and secondary care of 204 participants who have a history of 3 or more episodes of Major Depression but who are currently well. Measures assessing depressive relapse/recurrence, time to first clinical intervention, treatment expectancy and a range of secondary outcomes and process variables are included. A health economics evaluation will be undertaken to assess the incremental cost of MBCT.</p> <p>Discussion</p> <p>The results of this trial, including an examination of clinical, functional and health economic outcomes, will be used to assess the role that this treatment approach may have in recommendations for treatment of depression in Australia and elsewhere. If the findings are positive, we expect that this research will consolidate the evidence base to guide the decision to fund MBCT and to seek to promote its availability to those who have experienced at least 3 episodes of depression.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry: <a href="http://www.anzctr.org.au/ACTRN12607000166471.aspx">ACTRN12607000166471</a></p

Dynamic properties of different liquid states in systems with competing interactions studied with lysozyme solutions

Recent studies of colloidal systems with a short-range attraction and long-range repulsion (SALR) have been demonstrated to have a generalized phase diagram with multiple liquid states defined by their structures. In this paper, we identify the different liquid states of previous experimentally studied lysozyme samples within this proposed generalized state diagram and explore the dynamic properties of each liquid state. We show that most lysozyme samples studied here and previously at low and intermediate concentrations are dispersed fluids while a few high concentration samples are randomly percolated liquids. In the dispersed fluid region, the short-time diffusion coefficient measured by neutron spin echo agrees well with the long time diffusion coefficient estimated with the solution viscosity. This dynamic feature is maintained even for some samples in the random percolated region. However, the short-time and long-time diffusion coefficients of random percolated fluids deviate at larger concentration and attraction strength. At high enough concentrations, the mean square displacement can be as slow as those of many glassy colloidal systems at time scales near the characteristic diffusion time even though these lysozyme samples remain in liquid states at the long-time limit. We thus identify the region in the generalized phase diagram where these equilibrium states with extremely slow local dynamics exist relative to bulk percolation and kinetic arrest (gel and glassy) transitions.National Institute of Standards and Technology (U.S.) (Contract 70NANB12H239)National Institute of Standards and Technology (U.S.) (Contract 70NANB10H256

EURECA – setting the scene for scintillators

voir fichier complet des proceedingsInternational audienceEURECA (European Underground Rare Event Calorimeter Array) will be an astro-particle physics facility aiming to directly detect galactic dark matter. TheLaboratoire Souterrain de Modane has been selected as host laboratory. TheEURECA collaboration concentrates effort on cryogenic detector research inEurope into a single facility by bringing together colleagues from CRESST,EDELWEISS, ROSEBUD and additional new member institutes. EURECA will use atarget mass of up to one ton for exploring WIMP-nucleon scalar scattering crosssections in the region of 10 −9 – 10 −10 picobarn. A major advantage of EURECAis the planned use of more than just one target material (multi targetexperiment for WIMP identification)

EURECA - THE FUTURE OF CRYOGENIC DARK MATTER DETECTION IN EUROPE

EURECA (European Underground Rare Event Calorimeter Array) is an astro-particle physics facility aiming to directly detect galactic dark matter. The Laboratoire Souterrain de Modane has been selected as host laboratory. The EURECA collaboration unites CRESST, EDELWEISS and the Spanish-French experiment ROSEBUD, thus concentrating and focussing effort on cryogenic detector research in Europe into a single facility. EURECA will use a target mass of up to one ton, enough to explore WIMP - nucleon scalar scattering cross sections in the region of 10-9 - 10-10 picobarn. A major advantage of EURECA is the planned use of more than just one target material (multi target experiment for WIMP identification). © EAS, EDP Sciences 2009

EURECA

EURECA (European Underground Rare Event Calorimeter Array) is an astro-particle physics facility aiming to directly detect galactic dark matter. The Laboratoire Souterrain de Modane has been selected as host laboratory. The EURECA collaboration unites CRESST, EDELWEISS and the Spanish-French experiment ROSEBUD, thus concentrating and focussing effort on cryogenic detector research in Europe into a single facility. EURECA will use a target mass of up to one ton, enough to explore WIMP - nucleon scalar scattering cross sections in the region of 10-9 - 10-10 picobarn. A major advantage of EURECA is the planned use of more than just one target material (multi target experiment for WIMP identification). © Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike Licence