Ranking and Repulsing Supermartingales for Reachability in Probabilistic Programs

Computing reachability probabilities is a fundamental problem in the analysis of probabilistic programs. This paper aims at a comprehensive and comparative account on various martingale-based methods for over- and under-approximating reachability probabilities. Based on the existing works that stretch across different communities (formal verification, control theory, etc.), we offer a unifying account. In particular, we emphasize the role of order-theoretic fixed points---a classic topic in computer science---in the analysis of probabilistic programs. This leads us to two new martingale-based techniques, too. We give rigorous proofs for their soundness and completeness. We also make an experimental comparison using our implementation of template-based synthesis algorithms for those martingales

Thermodynamics of Chemical Waves

Chemical waves constitute a known class of dissipative structures emerging in reaction-diffusion systems. They play a crucial role in biology, spreading information rapidly to synchronize and coordinate biological events. We develop a rigorous thermodynamic theory of reaction-diffusion systems to characterize chemical waves. Our main result is the definition of the proper thermodynamic potential of the local dynamics as a nonequilibrium free energy density and establishing its balance equation. This enables us to identify the dynamics of the free energy, of the dissipation, and of the work spent to sustain the wave propagation. Two prototypical classes of chemical waves are examined. From a thermodynamic perspective, the first is sustained by relaxation towards equilibrium and the second by nonconservative forces generated by chemostats. We analytically study step-like waves, called wavefronts, using the Fisher-Kolmogorov equation as representative of the first class and oscillating waves in the Brusselator model as representative of the second. Given the fundamental role of chemical waves as message carriers in biosystems, our thermodynamic theory constitutes an important step toward an understanding of information transfers and processing in biology.Comment: 12 pages, 2 figure

Oscillation threshold of a clarinet model: a numerical continuation approach

This paper focuses on the oscillation threshold of single reed instruments. Several characteristics such as blowing pressure at threshold, regime selection, and playing frequency are known to change radically when taking into account the reed dynamics and the flow induced by the reed motion. Previous works have shown interesting tendencies, using analytical expressions with simplified models. In the present study, a more elaborated physical model is considered. The influence of several parameters, depending on the reed properties, the design of the instrument or the control operated by the player, are studied. Previous results on the influence of the reed resonance frequency are confirmed. New results concerning the simultaneous influence of two model parameters on oscillation threshold, regime selection and playing frequency are presented and discussed. The authors use a numerical continuation approach. Numerical continuation consists in following a given solution of a set of equations when a parameter varies. Considering the instrument as a dynamical system, the oscillation threshold problem is formulated as a path following of Hopf bifurcations, generalizing the usual approach of the characteristic equation, as used in previous works. The proposed numerical approach proves to be useful for the study of musical instruments. It is complementary to analytical analysis and direct time-domain or frequency-domain simulations since it allows to derive information that is hardly reachable through simulation, without the approximations needed for analytical approach

Microenvironment in neuroblastoma: Isolation and characterization of tumor-derived mesenchymal stromal cells

Background: It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. Methods: Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. inhibition of phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cytotoxic function, was examined. Gene expression profiles, known to be related to tumor cell stemness, Wnt pathway activation, epithelial-mesenchymal transition (EMT) and tumor metastasis were also evaluated. Healthy donor bone marrow-derived MSCs (BM-MSC) were employed as controls. Results: NB-MSCs presented the typical MSC morphology and phenotype. They showed a proliferative capacity superimposable to BM-MSCs. Stemness marker expression (Sox2, Nanog, Oct3/4) was comparable to BM-MSCs. NB-MSC in vitro osteogenic and chondrogenic differentiation was similar to BM-MSCs, but NB-MSCs lacked adipogenic differentiation capacity. NB-MSCs reached senescence phases at a median passage of P7 (range, P5-P13). NB-MSCs exhibited greater immunosuppressive capacity on activated T lymphocytes at a 1:2 (MSC: PBMC) ratio compared with BM-MSCs (p = 0.018). NK cytotoxic activity was not influenced by co-culture, either with BM-MSCs or NB-MSCs. Flow-cytometry cell cycle analysis showed that NB-MSCs had an increased number of cells in the G0-G1 phase compared to BM-MSCs. Transcriptomic profiling results indicated that NB-MSCs were enriched with EMT genes compared to BM-MSCs. Conclusions: We characterized the biological features, the immunomodulatory capacity and the gene expression profile of NB-MSCs. The NB-MSC gene expression profile and their functional properties suggest a potential role in promoting tumor escape, invasiveness and metastatic traits of NB cancer cells. A better understanding of the complex mechanisms underlying the interactions between NB cells and NB-derived MSCs should shed new light on potential novel therapeutic approaches

Decomposing Tool-Action Observation: A Stereo-EEG Study

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Retrospective analysis of mantle cell lymphoma: experience of the Gruppo Italiano per lo Studio dei Linfomi (GISL)

Background and Objective. Mantle cell lymphoma is a recently recognized histologic entity with specific biological and clinical features. Clinically, the reported unfavorable outcome of these patients has focused attention on this category of non-Hodgkin's lymphoma (NHL). Design and Methods. The slide specimens of 69 NHL patients, originally classified as Working Formulation (WF) group B and E, were reviewed. The clinical features at presentation, response to therapy, response duration and survival were analyzed in cases reclassified as MCL. The correlation between clinical and histologic characteristics and the final outcome was evaluated. Results. Out of 69 cases, 34 specimens were reclassified as MCL; in 6 patients, previously classified as WF group B, the nodular pattern was confirmed; in 2 instances the blastoid form was recognized. After a median follow-up of 35.7 months, the entire series displayed a median overall survival of 41.2 months; a significantly longer survival was associated with the nodular histologic pattern, IPI score <2, response achievement, and a higher Hb level. The vast majority of patients received anthracycline-containing combination chemotherapy. Complete remission rate was 38.8% and overall response rate was 67.6%; response achievement was significantly influenced only by Hb level. Median response duration was 23.3 months. Interpretation and Conclusions. The present study confirms the unfavorable clinical course of MCL and the possible need for an alternative therapeutic strategy for this NHL category. Therefore, the correct identification of MCL at diagnosis appears of relevance. (C)1998, Ferrata Storti Foundation