Bayesian inference of accurate population sizes and FRET efficiencies from single diffusing biomolecules.

It is of significant biophysical interest to obtain accurate intramolecular distance information and population sizes from single-molecule Förster resonance energy transfer (smFRET) data obtained from biomolecules in solution. Experimental methods of increasing cost and complexity are being developed to improve the accuracy and precision of data collection. However, the analysis of smFRET data sets currently relies on simplistic, and often arbitrary methods, for the selection and denoising of fluorescent bursts. Although these methods are satisfactory for the analysis of simple, low-noise systems with intermediate FRET efficiencies, they display systematic inaccuracies when applied to more complex systems. We have developed an inference method for the analysis of smFRET data from solution studies based on rigorous model-based Bayesian techniques. We implement a Monte Carlo Markov chain (MCMC) based algorithm that simultaneously estimates population sizes and intramolecular distance information directly from a raw smFRET data set, with no intermediate event selection and denoising steps. Here, we present both our parametric model of the smFRET process and the algorithm developed for data analysis. We test the algorithm using a combination of simulated data sets and data from dual-labeled DNA molecules. We demonstrate that our model-based method systematically outperforms threshold-based techniques in accurately inferring both population sizes and intramolecular distances.This is the final published version. It's also available from ACS in Analytical Chemistry: http://pubs.acs.org/doi/pdf/10.1021/ac501188r

Primary splenic diffuse large B‐cell lymphoma presenting as a splenic abscess

Abstract Diffuse large B‐cell lymphoma (DLBCL) arising in the spleen, also known as primary splenic DLBCL (PS‐DLBCL), is a rare form of malignant lymphoma. It is defined as a lymphoma confined to the spleen or involving splenic hilar lymph nodes. Here we report a case of PS‐DLBCL with CD30. The patient was a 62‐year‐old who presented with 2 weeks of left flank pain, chills, and abdominal distension. Computed tomography identified an 8‐cm splenic mass with central necrosis interpreted as an abscess. A drain was placed, yielding purulent necrotic material; cytologically, only neutrophils were identified. However, purulent drainage continued for 28 days without resolution, prompting splenectomy. Pathological dissection revealed a multinodular mass with central necrosis. Microscopic examination revealed extensive karyorrhexis, abundant ghosts of large cells, and scattered large cells with pleomorphic, multilobated, and vesicular nuclei with moderately abundant cytoplasm. Immunohistochemical staining revealed large, atypical cells positive for CD20, CD30, CD45, PAX5, MYC (>40%), MUM1 (>30%), and p53 (focally). The large cells were negative for CD3 (polyclonal), CD4, CD5, CD8, CD10, CD15, CD34, BCL2, BCL6, AE1/AE3, S100, HHV8, and ALK. The Ki‐67 proliferation rate was approximately 80% in large cells. Notably, this PS‐DLBCL was positive for CD30, an unusual finding among non‐Hodgkin B‐cell lymphomas, which, coupled with the Reed‐Sternberg‐like morphology, raised the possibility of classic Hodgkin lymphoma. Therefore, we reviewed the literature to confirm the unique features of this large B‐cell lymphoma, its abscess‐like appearance, and its expression of CD30

American College of Cardiology; American Heart Association Task Force; European Society of Cardiology Committee for Practice Guidelines. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death).

The purpose this document is to update and combine the previously published recommendations into one source approved by the major cardiology organizations in the United States and Europe. We have consciously attempted to create a streamlined document, not a textbook, that would be useful specifically to locate recommendations on the evaluation and treatment of patients who have or may be at risk for ventricular arrhythmias. Thus, sections on epidemiology, mechanisms and substrates, and clinical presentations are brief, because there are no recommendations for those sections. For the other sections, the wording has been kept to a minimum, and clinical presentations have been confined to those aspects relevant to forming recommendations