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

Toward the excited meson spectrum of dynamical QCD

We present a detailed description of the extraction of the highly excited isovector meson spectrum on dynamical anisotropic lattices using a new quark-field construction algorithm and a large variational basis of operators. With careful operator construction, the combination of these techniques is used to identify the continuum spin of extracted states reliably, overcoming the reduced rotational symmetry of the cubic lattice. Excited states, states with exotic quantum numbers (0+-, 1-+ and 2+-) and states of high spin are resolved, including, for the first time in a lattice QCD calculation, spin-four states. The determinations of the spectrum of isovector mesons and kaons are performed on dynamical lattices with two volumes and with pion masses down to ~ 400 MeV, with statistical precision typically at or below 1% even for highly excited states.Comment: 26 pages, 26 figure

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

Isoscalar meson spectroscopy from lattice QCD

We extract to high statistical precision an excited spectrum of single-particle isoscalar mesons using lattice QCD, including states of high spin and, for the first time, light exotic JPC isoscalars. The use of a novel quark field construction has enabled us to overcome the long-standing challenge of efficiently including quark-annihilation contributions. Hidden-flavor mixing angles are extracted and while most states are found to be close to ideally flavor mixed, there are examples of large mixing in the pseudoscalar and axial sectors in line with experiment. The exotic JPC isoscalar states appear at a mass scale comparable to the exotic isovector states.Comment: 4 pages, 4 figure

First Lattice Study of the NN-P11(1440)P_{11}(1440) Transition Form Factors

Experiments at Jefferson Laboratory, MIT-Bates, LEGS, Mainz, Bonn, GRAAL, and Spring-8 offer new opportunities to understand in detail how nucleon resonance ($N^*$) properties emerge from the nonperturbative aspects of QCD. Preliminary data from CLAS collaboration, which cover a large range of photon virtuality $Q^2$ show interesting behavior with respect to $Q^2$ dependence: in the region $Q^2 \le 1.5 {GeV}^2$, both the transverse amplitude, $A_{1/2}(Q^2)$, and the longitudinal amplitude, $S_{1/2}(Q^2)$, decrease rapidly. In this work, we attempt to use first-principles lattice QCD (for the first time) to provide a model-independent study of the Roper-nucleon transition form factor.Comment: 4 pages, 2 figures, double colum

Radiative Transitions in Charmonium from Lattice QCD

Radiative transitions between charmonium states offer an insight into the internal structure of heavy-quark bound states within QCD. We compute, for the first time within lattice QCD, the transition form-factors of various multipolarities between the lightest few charmonium states. In addition, we compute the experimentally unobservable, but physically interesting vector form-factors of the $\eta_c, J/\psi$ and $\chi_{c0}$. To this end we apply an ambitious combination of lattice techniques, computing three-point functions with heavy domain wall fermions on an anisotropic lattice within the quenched approximation. With an anisotropy $\xi=3$ at $a_s \sim 0.1 \mathrm{fm}$ we find a reasonable gross spectrum and a hyperfine splitting $\sim 90 \mathrm{MeV}$, which compares favourably with other improved actions. In general, after extrapolation of lattice data at non-zero $Q^2$ to the photopoint, our results agree within errors with all well measured experimental values. Furthermore, results are compared with the expectations of simple quark models where we find that many features are in agreement; beyond this we propose the possibility of constraining such models using our extracted values of physically unobservable quantities such as the $J/\psi$ quadrupole moment. We conclude that our methods are successful and propose to apply them to the problem of radiative transitions involving hybrid mesons, with the eventual goal of predicting hybrid meson photoproduction rates at the GlueX experiment.Comment: modified version as publishe