Parallel Implementation of Efficient Search Schemes for the Inference of Cancer Progression Models

The emergence and development of cancer is a consequence of the accumulation over time of genomic mutations involving a specific set of genes, which provides the cancer clones with a functional selective advantage. In this work, we model the order of accumulation of such mutations during the progression, which eventually leads to the disease, by means of probabilistic graphic models, i.e., Bayesian Networks (BNs). We investigate how to perform the task of learning the structure of such BNs, according to experimental evidence, adopting a global optimization meta-heuristics. In particular, in this work we rely on Genetic Algorithms, and to strongly reduce the execution time of the inference -- which can also involve multiple repetitions to collect statistically significant assessments of the data -- we distribute the calculations using both multi-threading and a multi-node architecture. The results show that our approach is characterized by good accuracy and specificity; we also demonstrate its feasibility, thanks to a 84x reduction of the overall execution time with respect to a traditional sequential implementation

Efficient computational strategies to learn the structure of probabilistic graphical models of cumulative phenomena

Structural learning of Bayesian Networks (BNs) is a NP-hard problem, which is further complicated by many theoretical issues, such as the I-equivalence among different structures. In this work, we focus on a specific subclass of BNs, named Suppes-Bayes Causal Networks (SBCNs), which include specific structural constraints based on Suppes' probabilistic causation to efficiently model cumulative phenomena. Here we compare the performance, via extensive simulations, of various state-of-the-art search strategies, such as local search techniques and Genetic Algorithms, as well as of distinct regularization methods. The assessment is performed on a large number of simulated datasets from topologies with distinct levels of complexity, various sample size and different rates of errors in the data. Among the main results, we show that the introduction of Suppes' constraints dramatically improve the inference accuracy, by reducing the solution space and providing a temporal ordering on the variables. We also report on trade-offs among different search techniques that can be efficiently employed in distinct experimental settings. This manuscript is an extended version of the paper "Structural Learning of Probabilistic Graphical Models of Cumulative Phenomena" presented at the 2018 International Conference on Computational Science

A lattice study of the strangeness content of the nucleon

We determine the quark contributions to the nucleon spin Delta s, Delta u and Delta d as well as their contributions to the nucleon mass, the sigma-terms. This is done by computing both, the quark line connected and disconnected contributions to the respective matrix elements, using the non-perturbatively improved Sheikholeslami-Wohlert Wilson Fermionic action. We simulate n_F=2 mass degenerate sea quarks with a pion mass of about 285 MeV and a lattice spacing a = 0.073 fm. The renormalization of the matrix elements involves mixing between contributions from different quark flavours. The pion-nucleon sigma-term is extrapolated to physical quark masses exploiting the sea quark mass dependence of the nucleon mass. We obtain the renormalized value sigma_{piN}=38(12) MeV at the physical point and the strangeness fraction f_{Ts}=sigma_s/m_N=0.012(14)(+10-3) at our larger than physical sea quark mass. For the strangeness contribution to the nucleon spin we obtain in the MSbar scheme at the renormalization scale of 2.71 GeV Delta s = -0.020(10)(2).Comment: 7 pages, 3 figures, Invited Talk at the 33rd Erice School on Nuclear Physics, Erice, 16-24 September 2011, Ital

Acute pulmonary hypertension caused by tumor embolism: a report of two cases.

Acute pulmonary hypertension leading to right ventricular failure and circulatory collapse is usually caused by thromboembolic obstruction of the pulmonary circulation. However, in rare instances, other causes can be associated with a similar clinical presentation. We present and discuss the clinical histories of two patients with acute right ventricular failure due to an atypical cause of pulmonary hypertension, disseminated pulmonary tumor embolism

Altered Prostasin (CAP1/Prss8) Expression Favors Inflammation and Tissue Remodeling in DSS-induced Colitis.

Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are diseases with impaired epithelial barrier function. We aimed to investigate whether mutated prostasin and thus, reduced colonic epithelial sodium channel activity predisposes to develop an experimentally dextran sodium sulfate (DSS)-induced colitis. Wildtype, heterozygous (fr/+), and homozygous (fr/fr) prostasin-mutant rats were treated 7 days with DSS followed by 7 days of recovery and analyzed with respect to histology, clinicopathological parameters, inflammatory marker mRNA transcript expression, and sodium transporter protein expression. In this study, a more detailed analysis on rat fr/fr colons revealed reduced numbers of crypt and goblet cells, and local angiodysplasia, as compared with heterozygous (fr/+) and wildtype littermates. Following 2% DSS treatment for 7 days followed by 7 days recovery, fr/fr animals lost body weight, and reached maximal diarrhea score and highest disease activity after only 3 days, and strongly increased cytokine levels. The histology score significantly increased in all groups, but fr/fr colons further displayed pronounced histological alterations with near absence of goblet cells, rearrangement of the lamina propria, and presence of neutrophils, eosinophils, and macrophages. Additionally, fr/fr colons showed ulcerations and edemas that were absent in fr/+ and wildtype littermates. Following recovery, fr/fr rats reached, although significantly delayed, near-normal diarrhea score and disease activity, but exhibited severe architectural remodeling, despite unchanged sodium transporter protein expression. In summary, our results demonstrate a protective role of colonic prostasin expression against experimental colitis, and thus represent a susceptibility gene in the development of inflammatory bowel disease

<x>_{u-d} from lattice QCD at nearly physical quark masses

We determine the second Mellin moment of the isovector quark parton distribution function _{u-d} from lattice QCD with N_f=2 sea quark flavours, employing the non-perturbatively improved Wilson-Sheikholeslami-Wohlert action at a pseudoscalar mass of 157(6) MeV. The result is converted non-perturbatively to the RI'-MOM scheme and then perturbatively to the MSbar scheme at a scale mu = 2 GeV. As the quark mass is reduced we find the lattice prediction to approach the value extracted from experiments.Comment: 4 pages, 3 figures, v2: minor updates including journal ref

Coriolis Effect on Dynamic Stall in a Vertical Axis Wind Turbine at Moderate Reynolds Number

The immersed boundary method is used to simulate the flow around a two-dimensional rotating NACA 0018 airfoil at sub-scale Reynolds number in order to investigate the separated flow occurring on a vertical-axis wind turbine. The influence of dynamic stall on the forces is characterized as a function of tip-speed ratio. The influence of the Coriolis effect is also investigated by comparing the rotating airfoil to one undergoing a equivalent planar motion, which is composed of surging and pitching motions that produce an equivalent speed and angle-of-attack variation over the cycle. When the angle of attack of a rotating airfoil starts to decrease in the upwind half cycle, the Coriolis force leads to a wake-capturing phenomenon of a vortex pair at low tip-speed ratio. This effects occurs at a slightly different phase in each cycle and leads to a significant decrease in the average lift during the downstroke phase. Moreover, the wake-capturing is only observed when the combination of surging, pitching, and Coriolis force are present. Finally, an actuator model is placed at an appropriate location on the suction side of the airfoil surface to control the wake-capturing phenomenon. Based on preliminary simulations, a momentum coefficient above 0.02 was able to increase the average lift by more than 70% over the upwind-half cycle

Smolyak's algorithm: A powerful black box for the acceleration of scientific computations

We provide a general discussion of Smolyak's algorithm for the acceleration of scientific computations. The algorithm first appeared in Smolyak's work on multidimensional integration and interpolation. Since then, it has been generalized in multiple directions and has been associated with the keywords: sparse grids, hyperbolic cross approximation, combination technique, and multilevel methods. Variants of Smolyak's algorithm have been employed in the computation of high-dimensional integrals in finance, chemistry, and physics, in the numerical solution of partial and stochastic differential equations, and in uncertainty quantification. Motivated by this broad and ever-increasing range of applications, we describe a general framework that summarizes fundamental results and assumptions in a concise application-independent manner