Target shape dependence in a simple model of receptor-mediated endocytosis and phagocytosis

Phagocytosis and receptor-mediated endocytosis are vitally important particle uptake mechanisms in many cell types, ranging from single-cell organisms to immune cells. In both processes, engulfment by the cell depends critically on both particle shape and orientation. However, most previous theoretical work has focused only on spherical particles and hence disregards the wide-ranging particle shapes occurring in nature, such as those of bacteria. Here, by implementing a simple model in one and two dimensions, we compare and contrast receptor-mediated endocytosis and phagocytosis for a range of biologically relevant shapes, including spheres, ellipsoids, capped cylinders, and hourglasses. We find a whole range of different engulfment behaviors with some ellipsoids engulfing faster than spheres, and that phagocytosis is able to engulf a greater range of target shapes than other types of endocytosis. Further, the 2D model can explain why some nonspherical particles engulf fastest (not at all) when presented to the membrane tip-first (lying flat). Our work reveals how some bacteria may avoid being internalized simply because of their shape, and suggests shapes for optimal drug delivery.Comment: 18 pages, 5 figure

Implementation of Psychological Therapies for Anxiety and Depression in Routine Practice: Two Year Prospective Cohort Study

publication-status: Publishedtypes: ArticleCopyright © 2011 Elsevier. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published Journal of Affective Disorders, 2011, Vol. 133, Issue 1, pp. 51 - 60 DOI: http://dx.doi.org/10.1016/j.jad.2011.03.024Introduction: Worldwide, health systems are improving access to empirically supported psychological therapies for anxiety and depression. Evaluations of this effort are limited by the cross sectional nature of studies, short implementation periods, poor data completeness rates and lack of clinically significant and reliable change metrics. Objective: Assess the impact of implementing stepped care empirically supported psychological therapies by measuring the prospective outcomes of patients referred over a two year period to one Improving Access to Psychological Therapies service in the UK. Method: We collected demographic, therapeutic and outcome data on depression (PHQ-9) and anxiety (GAD-7) from 7,859 consecutive patients for 24 months between1st July 2006 and 31st August 2008, following up these patients for a further one year. Results: 4,183 patients (53%) received two or more treatment sessions. Uncontrolled effect size for depression was 1.07 (95% CI: 0.88 to 1.29) and for anxiety was 1.04 (0.88 to 1.23). 55.4% of treated patients met reliable improvement or reliable and clinically significant change criteria for depression, 54.7% for anxiety. Patients received a mean of 5.5 sessions over 3.5 hours, mainly low-intensity CBT and phone based case management. Attrition was high with 47% of referrals either not attending for an assessment or receiving an assessment only. Conclusions: Recovery rates for patients receiving stepped care empirically supported treatments for anxiety and depression in routine practice are 40 to 46%. Only half of all patients referred go on to receive treatment. Further work is needed to improve routine engagement of patients with anxiety and depression

Charmonium excited state spectrum in lattice QCD

Working with a large basis of covariant derivative-based meson interpolating fields we demonstrate the feasibility of reliably extracting multiple excited states using a variational method. The study is performed on quenched anisotropic lattices with clover quarks at the charm mass. We demonstrate how a knowledge of the continuum limit of a lattice interpolating field can give additional spin-assignment information, even at a single lattice spacing, via the overlap factors of interpolating field and state. Excited state masses are systematically high with respect to quark potential model predictions and, where they exist, experimental states. We conclude that this is most likely a result of the quenched approximation.Comment: Fixed typos: normalisation of chi-squared, some operator projections in appendix, missing lattice irrep tabl

Excited state baryon spectroscopy from lattice QCD

We present a calculation of the Nucleon and Delta excited state spectrum on dynamical anisotropic clover lattices. A method for operator construction is introduced that allows for the reliable identification of the continuum spins of baryon states, overcoming the reduced symmetry of the cubic lattice. Using this method, we are able to determine a spectrum of single-particle states for spins up to and including J = 7/2, of both parities, the first time this has been achieved in a lattice calculation. We find a spectrum of states identifiable as admixtures of SU(6) x O(3) representations and a counting of levels that is consistent with the non-relativistic $qqq$ constituent quark model. This dense spectrum is incompatible with quark-diquark model solutions to the "missing resonance problem" and shows no signs of parity doubling of states.Comment: 29 pages, 18 figure