The activating mutation R201C in GNAS promotes intestinal tumourigenesis in Apc(Min/+) mice through activation of Wnt and ERK1/2 MAPK pathways.

Somatically acquired, activating mutations of GNAS, the gene encoding the stimulatory G-protein Gsalpha subunit, have been identified in kidney, thyroid, pituitary, leydig cell, adrenocortical and, more recently, in colorectal tumours, suggesting that mutations such as R201C may be oncogenic in these tissues. To study the role of GNAS in intestinal tumourigenesis, we placed GNAS R201C under the control of the A33-antigen promoter (Gpa33), which is almost exclusively expressed in the intestines. The GNAS R201C mutation has been shown to result in the constitutive activation of Gsalpha and adenylate cyclase and to lead to the autonomous synthesis of cyclic adenosine monophosphate (cAMP). Gpa33(tm1(GnasR201C)Wtsi/+) mice showed significantly elevated cAMP levels and a compensatory upregulation of cAMP-specific phosphodiesterases in the intestinal epithelium. GNAS R201C alone was not sufficient to induce tumourigenesis by 12 months, but there was a significant increase in adenoma formation when Gpa33(tm1(GnasR201C)Wtsi/+) mice were bred onto an Apc(Min/+) background. GNAS R201C expression was associated with elevated expression of Wnt and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK) pathway target genes, increased phosphorylation of ERK1/2 MAPK and increased immunostaining for the proliferation marker Ki67. Furthermore, the effects of GNAS R201C on the Wnt pathway were additive to the inactivation of Apc. Our data strongly suggest that activating mutations of GNAS cooperate with inactivation of APC and are likely to contribute to colorectal tumourigenesis

Hyperon semileptonic decays and quark spin content of the proton

We investigate the hyperon semileptonic decays and the quark spin content of the proton $\Delta \Sigma$ taking into account flavor SU(3) symmetry breaking. Symmetry breaking is implemented with the help of the chiral quark-soliton model in an approach, in which the dynamical parameters are fixed by the experimental data for six hyperon semileptonic decay constants. As a result we predict the unmeasured decay constants, particularly for $\Xi^0 \to \Sigma^+$, which will be soon measured and examine the effect of the SU(3) symmetry breaking on the spin content $\Delta \Sigma$ of the proton. Unfortunately large experimental errors of $\Xi^-$ decays propagate in our analysis making $\Delta \Sigma$ and $\Delta s$ practically undetermined. We conclude that statements concerning the values of these two quantities, which are based on the exact SU(3) symmetry, are premature. We stress that the meaningful results can be obtained only if the experimental errors for the $\Xi$ decays are reduced.Comment: The final version accepted for publication in Phys. Rev. D. 18 pages, RevTex is used with 4 figures include

Strange and singlet form factors of the nucleon: Predictions for G0, A4, and HAPPEX-II experiments

We investigate the strange and flavor-singlet electric and magnetic form factors of the nucleon within the framework of the SU(3) chiral quark-soliton model. Isospin symmetry is assumed and the symmetry-conserving SU(3) quantization is employed, rotational and strange quark mass corrections being included. For the experiments G0, A4, and HAPPEX-II we predict the quantities $G^{0}_E + \beta G^{0}_M$ and $G^{\rm s}_E + \beta G^{\rm s}_M$. The dependence of the results on the parameters of the model and the treatment of the Yukawa asymptotic behavior of the soliton are investigated.Comment: 16 pages, 3 figures, Final version for publication in Eur. Phys. J.

Predicting Chronic Disease Hospitalizations from Electronic Health Records: An Interpretable Classification Approach

Urban living in modern large cities has significant adverse effects on health, increasing the risk of several chronic diseases. We focus on the two leading clusters of chronic disease, heart disease and diabetes, and develop data-driven methods to predict hospitalizations due to these conditions. We base these predictions on the patients' medical history, recent and more distant, as described in their Electronic Health Records (EHR). We formulate the prediction problem as a binary classification problem and consider a variety of machine learning methods, including kernelized and sparse Support Vector Machines (SVM), sparse logistic regression, and random forests. To strike a balance between accuracy and interpretability of the prediction, which is important in a medical setting, we propose two novel methods: K-LRT, a likelihood ratio test-based method, and a Joint Clustering and Classification (JCC) method which identifies hidden patient clusters and adapts classifiers to each cluster. We develop theoretical out-of-sample guarantees for the latter method. We validate our algorithms on large datasets from the Boston Medical Center, the largest safety-net hospital system in New England

Transit timing variation in exoplanet WASP-3b

Photometric follow-ups of transiting exoplanets may lead to discoveries of additional, less massive bodies in extrasolar systems. This is possible by detecting and then analysing variations in transit timing of transiting exoplanets. We present photometric observations gathered in 2009 and 2010 for exoplanet WASP-3b during the dedicated transit-timing-variation campaign. The observed transit timing cannot be explained by a constant period but by a periodic variation in the observations minus calculations diagram. Simplified models assuming the existence of a perturbing planet in the system and reproducing the observed variations of timing residuals were identified by three-body simulations. We found that the configuration with the hypothetical second planet of the mass of about 15 Earth masses, located close to the outer 2:1 mean motion resonance is the most likely scenario reproducing observed transit timing. We emphasize, however, that more observations are required to constrain better the parameters of the hypothetical second planet in WASP-3 system. For final interpretation not only transit timing but also photometric observations of the transit of the predicted second planet and the high precision radial-velocity data are needed.Comment: MNRAS accepte

Analysis of optical flow models in the framework of calculus of variations

In image sequence analysis, variational optical flow computations require the solution of a parameter dependent optimization problem with a data term and a regularizer. In this paper we study existence and uniqueness of the optimizers. Our studies rely on quasiconvex functionals on the spaces W¹,P(Ω, IRd), with p > 1, BV(Ω, IRd), BD(&Omeag;). The methods that are covered by our results include several existing techniques. Experiments are presented that illustrate the behavior of these approaches

Program trace optimization with constructive heuristics for combinatorial problems

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.EvoCOP: 19th European Conference on Evolutionary Computation in Combinatorial Optimisation, 24-26 April 2019, Leipzig, GermanyProgram Trace Optimisation (PTO), a highly general optimisation framework, is applied to a range of combinatorial optimisation (COP) problems. It effectively combines \smart" problem-specifi c constructive heuristics and problem-agnostic metaheuristic search, automatically and implicitly designing problem-appropriate search operators. A weakness is identifi ed in PTO's operators when applied in conjunction with smart heuristics on COP problems, and an improved method is introduced to address this. To facilitate the comparison of this new method with the original, across problems, a common format for PTO heuristics (known as generators) is demonstrated, mimicking GRASP. This also facilitates comparison of the degree of greediness (the GRASP alpha parameter) in the heuristics. Experiments across problems show that the novel operators consistently outperform the original without any loss of generality or cost in CPU time; hill-climbing is a sufficient metaheuristic; and intermediate levels of greediness are usually best

Hadron Production in Heavy Ion Collisions

We review hadron production in heavy ion collisions with emphasis on pion and kaon production at energies below 2 AGeV and on partonic collectivity at RHIC energies.Comment: 31 pages, 26 figures, accepted for publication in Landolt-Boernstein Volume 1-23