Characterizing Potentials by a Generalized Boltzmann Factor

Based on the concept of a nonequilibrium steady state, we present a novel method to experimentally determine energy landscapes acting on colloidal systems. By measuring the stationary probability distribution and the current in the system, we explore potential landscapes with barriers up to several hundred \kT. As an illustration, we use this approach to measure the effective diffusion coefficient of a colloidal particle moving in a tilted potential

Probing live cells with optically driven and monitored micro-rotors

Optically trapped particles can be used as probes to study the mechanical properties of substances on a microscopic scale. Such experiments have been performed on colloids, single bio-molecules such as DNA and proteins, and components of living cells. A particularly promising type of probe particle is the micro-rotor - an optically trapped and powered microscopic rotating particle. Such a probe allows steady-state motion, and is ideal for the measurement of viscosity on a microscopic scale. The change in polarisation of the trapping beam due to scattering by the probe particle can be used to measure the optical torque acting on, and the rotation of, the probe particle. We present results from experiments showing that it is possible to rotate small calcite crystals adhering to the membrane of a cell in vitro, and measure the applied torque and rotation speed

Dynamic Phase Transitions in Cell Spreading

We monitored isotropic spreading of mouse embryonic fibroblasts on fibronectin-coated substrates. Cell adhesion area versus time was measured via total internal reflection fluorescence microscopy. Spreading proceeds in well-defined phases. We found a power-law area growth with distinct exponents a_i in three sequential phases, which we denote basal (a_1=0.4+-0.2), continous (a_2=1.6+-0.9) and contractile (a_3=0.3+-0.2) spreading. High resolution differential interference contrast microscopy was used to characterize local membrane dynamics at the spreading front. Fourier power spectra of membrane velocity reveal the sudden development of periodic membrane retractions at the transition from continous to contractile spreading. We propose that the classification of cell spreading into phases with distinct functional characteristics and protein activity patterns serves as a paradigm for a general program of a phase classification of cellular phenotype. Biological variability is drastically reduced when only the corresponding phases are used for comparison across species/different cell lines.Comment: 4 pages, 5 figure

Phase ordering and shape deformation of two-phase membranes

Within a coupled-field Ginzburg-Landau model we study analytically phase separation and accompanying shape deformation on a two-phase elastic membrane in simple geometries such as cylinders, spheres and tori. Using an exact periodic domain wall solution we solve for the shape and phase ordering field, and estimate the degree of deformation of the membrane. The results are pertinent to a preferential phase separation in regions of differing curvature on a variety of vesicles.Comment: 4 pages, submitted to PR

Cell adhesion and cortex contractility determine cell patterning in the Drosophila retina

Hayashi and Carthew (Nature 431 [2004], 647) have shown that the packing of cone cells in the Drosophila retina resembles soap bubble packing, and that changing E- and N-cadherin expression can change this packing, as well as cell shape. The analogy with bubbles suggests that cell packing is driven by surface minimization. We find that this assumption is insufficient to model the experimentally observed shapes and packing of the cells based on their cadherin expression. We then consider a model in which adhesion leads to a surface increase, balanced by cell cortex contraction. Using the experimentally observed distributions of E- and N-cadherin, we simulate the packing and cell shapes in the wildtype eye. Furthermore, by changing only the corresponding parameters, this model can describe the mutants with different numbers of cells, or changes in cadherin expression.Comment: revised manuscript; 8 pages, 6 figures; supplementary information not include

Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases: A Single Institution Experience

Purpose. We sought to evaluate our experience using yttrium-90 (90Y) resin microsphere hepatic radioembolization as salvage therapy for liver-dominant metastatic colorectal cancer (mCRC). Methods. A retrospective review of consecutive patients with unresectable mCRC who were treated with 90Y after failing first and second line systemic chemotherapy. Demographics, treatment dose, biochemical and radiographic response, toxicities, and survival were examined. Results. Fifty-one patients underwent 90Y treatments of which 69% were male. All patients had previously undergone extensive chemotherapy, 31% had undergone previous liver-directed therapy and 24% had a prior liver resection. Using RECIST criteria, either stable disease or a partial response was seen in 77% of patients. Overall median survival from the time of first 90Y treatment was 10.2 months (95% CI = 7.5–13.0). The absence of extrahepatic disease at the time of treatment with 90Y was associated with an improved survival, median survival of 17.0 months (95% CI = 6.4–27.6), compared to those with extrahepatic disease at the time of treatment with 90Y, 6.7 months (95% CI = 2.7–10.6 Conclusion: 90Y therapy is a safe locoregional therapy that provides an important therapeutic option to patients who have failed first and second line chemotherapy and have adequate liver function and performance status

Interactions between proteins bound to biomembranes

We study a physical model for the interaction between general inclusions bound to fluid membranes that possess finite tension, as well as the usual bending rigidity. We are motivated by an interest in proteins bound to cell membranes that apply forces to these membranes, due to either entropic or direct chemical interactions. We find an exact analytic solution for the repulsive interaction between two similar circularly symmetric inclusions. This repulsion extends over length scales of order tens of nanometers, and contrasts with the membrane-mediated contact attraction for similar inclusions on tensionless membranes. For non circularly symmetric inclusions we study the small, algebraically long-ranged, attractive contribution to the force that arises. We discuss the relevance of our results to biological phenomena, such as the budding of caveolae from cell membranes and the striations that are observed on their coats.Comment: 22 pages, 2 figure

Pseudorapidity distributions of charged particles from Au+Au collisions at the maximum RHIC energy, Sqrt(s_NN) = 200 GeV

We present charged particle densities as a function of pseudorapidity and collision centrality for the 197Au+197Au reaction at Sqrt{s_NN}=200 GeV. For the 5% most central events we obtain dN_ch/deta(eta=0) = 625 +/- 55 and N_ch(-4.7<= eta <= 4.7) = 4630+-370, i.e. 14% and 21% increases, respectively, relative to Sqrt{s_NN}=130 GeV collisions. Charged-particle production per pair of participant nucleons is found to increase from peripheral to central collisions around mid-rapidity. These results constrain current models of particle production at the highest RHIC energy.Comment: 4 pages, 5 figures; fixed fig. 5 caption; revised text and figures to show corrected calculation of and ; final version accepted for publicatio

Implementation and assessment of a novel non-clinical skills curriculum for urology residents

BackgroundUrology is an increasingly competitive specialty that procures a highly selected and clinically excellent cohort of residents. However, other training needs such as leadership and professional development go underrecognized despite an identified need for formal training in these areas. The aim of this study was to implement, evaluate, and pilot a non-clinical skills curriculum, a novel individualized professional development workshop series, at a single institution.MethodsEighteen urology residents (15/year, 3 graduates/year) participated in this study over the course of two academic years. A pre-curriculum needs assessment was completed by 15 residents in Year 1 for purposes of curriculum design. The curriculum itself was a series of 1-hour monthly workshops given by an expert speaker on topics relevant to healthcare delivery, leadership and career promotion across various contexts. Survey-based assessments tracked gains in subject knowledge and satisfaction via a pre-post test design.ResultsThe pre-curriculum needs assessment indicated that trainees desired additional instruction in non-clinical skills (ps&gt;0.1) and endorsed formal teaching to ensure success in their future careers (p&lt;0.001). Trainees reported pre- to post-curriculum gains across each individual learning topic (Mean=20%, p&lt;0.001) with an aggregate increase in subject knowledge of 17% for senior residents and 21% for junior residents (p&lt;0.001).ConclusionA non-clinical skills curriculum implemented as a pilot ‘Hidden Curriculum’ for urology trainees was feasible and resulted in significant gains in non-clinical subject knowledge. Workshops were highly rated and trainees reported high satisfaction with the curriculum