Higher Order Polarizabilities of the Proton

Compton scattering results are used to probe proton structure via measurement of higher order polarizabilities. Values for $\alpha_{E2}^p,\beta_{E2}^p,\alpha_{E\nu}^p,$ $\beta_{E\nu}^p$ determined via dispersion relations are compared to predictions based upon chiral symmetry and from the constituent quark model. Extensions to spin-polarizabilities are also discussed.Comment: 18 pages, revised version with one reference adde

Compton Scattering and the Spin Structure of the Nucleon at Low Energies

We analyze polarized Compton scattering which provides information on the spin-structure of the nucleon. For scattering processes with photon energies up to 100 MeV the spin-structure dependence can be encoded into four independent parameters-the so-called spin-polarizabilities $\gamma_i, i=1...4$ of the nucleon, which we calculate within the framework of the "small scale expansion" in SU(2) baryon chiral perturbation theory. Specific application is made to "forward" and "backward" spin- polarizabilities.Comment: 8 pages revtex file, separation between pion-pole and regular contributions detailed + minor wording changes, results and conclusions unchange

Effects of rapid prey evolution on predator-prey cycles

We study the qualitative properties of population cycles in a predator-prey system where genetic variability allows contemporary rapid evolution of the prey. Previous numerical studies have found that prey evolution in response to changing predation risk can have major quantitative and qualitative effects on predator-prey cycles, including: (i) large increases in cycle period, (ii) changes in phase relations (so that predator and prey are cycling exactly out of phase, rather than the classical quarter-period phase lag), and (iii) "cryptic" cycles in which total prey density remains nearly constant while predator density and prey traits cycle. Here we focus on a chemostat model motivated by our experimental system [Fussmann et al. 2000,Yoshida et al. 2003] with algae (prey) and rotifers (predators), in which the prey exhibit rapid evolution in their level of defense against predation. We show that the effects of rapid prey evolution are robust and general, and furthermore that they occur in a specific but biologically relevant region of parameter space: when traits that greatly reduce predation risk are relatively cheap (in terms of reductions in other fitness components), when there is coexistence between the two prey types and the predator, and when the interaction between predators and undefended prey alone would produce cycles. Because defense has been shown to be inexpensive, even cost-free, in a number of systems [Andersson and Levin 1999, Gagneux et al. 2006,Yoshida et al. 2004], our discoveries may well be reproduced in other model systems, and in nature. Finally, some of our key results are extended to a general model in which functional forms for the predation rate and prey birth rate are not specified.Comment: 35 pages, 8 figure

Generalized Polarizabilities of the Nucleon in Chiral Effective Theories

Using the techniques of chiral effective field theories we evaluate the so called generalized polarizabilities of the nucleon, which characterize the structure dependent components in virtual Compton scattering (VCS) as probed in the electron scattering reaction e N \to e' N gamma. Results are given for both spin-dependent and spin-independent structure effects to O(p^3) in SU(2) Heavy Baryon Chiral Perturbation Theory and to O(epsilon^3) in the SU(2) Small Scale Expansion. Finally we compare our calculations with results from the pioneering VCS experiment on the proton from Mainz.Comment: 39 pages, 12 figures, revte

Plasma lipoxin A4 and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas

Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4) and resolvin D1(RvD1)] with risk for recurrent adenoma. In this pilot study, we used data and biosamples from an adenoma chemoprevention study investigating the effects of aspirin and/or folic acid on the occurrence of colorectal adenomas. In the parent study, 1121 participants with a recent adenoma were randomized to study agents to be taken until the next surveillance colonoscopy about 3 years later. In this pilot study, LXA4 and RvD1 from samples taken near the end of study treatment were measured in a randomly selected sub-set of 200 participants. Commercially available ELISA kits to assay the analytes were validated using a metabololipidomic LC-MS/MS assay. Poisson regression with a robust error variance was used to calculate risk ratios and 95% confidence intervals. Plasma LXA4 and RvD1 were not associated with the risk of adenoma occurrence. LXA4 at the end of study follow-up was 32% (P = 0.01) proportionately higher in women compared to men. A similar non-significant trend toward higher levels among women was observed for RvD1. Our preliminary findings provided no evidence that plasma LXA4 or RvD1 are associated with reduced risk of colorectal adenoma occurrence, but suggest LXA4 may differ among men and women. Future studies focusing on SPM's local effects and levels in the colon are needed

Evaluation of a Deep Neural Network for Automated Classification of Colorectal Polyps on Histopathologic Slides

Importance: Histologic classification of colorectal polyps plays a critical role in screening for colorectal cancer and care of affected patients. An accurate and automated algorithm for the classification of colorectal polyps on digitized histopathologic slides could benefit practitioners and patients. Objective: To evaluate the performance and generalizability of a deep neural network for colorectal polyp classification on histopathologic slide images using a multi-institutional data set. Design, Setting, and Participants: This prognostic study used histopathologic slides collected from January 1, 2016, to June 31, 2016, from Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, with 326 slides used for training, 157 slides for an internal data set, and 25 for a validation set. For the external data set, 238 slides for 179 distinct patients were obtained from 24 institutions across 13 US states. Data analysis was performed from April 9 to November 23, 2019. Main Outcomes and Measures: Accuracy, sensitivity, and specificity of the model to classify 4 major colorectal polyp types: tubular adenoma, tubulovillous or villous adenoma, hyperplastic polyp, and sessile serrated adenoma. Performance was compared with that of local pathologists' at the point of care identified from corresponding pathology laboratories. Results: For the internal evaluation on the 157 slides with ground truth labels from 5 pathologists, the deep neural network had a mean accuracy of 93.5% (95% CI, 89.6%-97.4%) compared with local pathologists' accuracy of 91.4% (95% CI, 87.0%-95.8%). On the external test set of 238 slides with ground truth labels from 5 pathologists, the deep neural network achieved an accuracy of 87.0% (95% CI, 82.7%-91.3%), which was comparable with local pathologists' accuracy of 86.6% (95% CI, 82.3%-90.9%). Conclusions and Relevance: The findings suggest that this model may assist pathologists by improving the diagnostic efficiency, reproducibility, and accuracy of colorectal cancer screenings

Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions

Background Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. Methods We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. Results Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. Conclusions Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis

Phase Behavior of Aqueous Na-K-Mg-Ca-CI-NO3 Mixtures: Isopiestic Measurements and Thermodynamic Modeling

A comprehensive model has been established for calculating thermodynamic properties of multicomponent aqueous systems containing the Na{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}, Cl{sup -}, and NO{sub 3}{sup -} ions. The thermodynamic framework is based on a previously developed model for mixed-solvent electrolyte solutions. The framework has been designed to reproduce the properties of salt solutions at temperatures ranging from the freezing point to 300 C and concentrations ranging from infinite dilution to the fused salt limit. The model has been parameterized using a combination of an extensive literature database and new isopiestic measurements for thirteen salt mixtures at 140 C. The measurements have been performed using Oak Ridge National Laboratory's (ORNL) previously designed gravimetric isopiestic apparatus, which makes it possible to detect solid phase precipitation. Water activities are reported for mixtures with a fixed ratio of salts as a function of the total apparent salt mole fraction. The isopiestic measurements reported here simultaneously reflect two fundamental properties of the system, i.e., the activity of water as a function of solution concentration and the occurrence of solid-liquid transitions. The thermodynamic model accurately reproduces the new isopiestic data as well as literature data for binary, ternary and higher-order subsystems. Because of its high accuracy in calculating vapor-liquid and solid-liquid equilibria, the model is suitable for studying deliquescence behavior of multicomponent salt systems

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases