Imprecise Continuous-Time Markov Chains

Continuous-time Markov chains are mathematical models that are used to describe the state-evolution of dynamical systems under stochastic uncertainty, and have found widespread applications in various fields. In order to make these models computationally tractable, they rely on a number of assumptions that may not be realistic for the domain of application; in particular, the ability to provide exact numerical parameter assessments, and the applicability of time-homogeneity and the eponymous Markov property. In this work, we extend these models to imprecise continuous-time Markov chains (ICTMC's), which are a robust generalisation that relaxes these assumptions while remaining computationally tractable. More technically, an ICTMC is a set of "precise" continuous-time finite-state stochastic processes, and rather than computing expected values of functions, we seek to compute lower expectations, which are tight lower bounds on the expectations that correspond to such a set of "precise" models. Note that, in contrast to e.g. Bayesian methods, all the elements of such a set are treated on equal grounds; we do not consider a distribution over this set. The first part of this paper develops a formalism for describing continuous-time finite-state stochastic processes that does not require the aforementioned simplifying assumptions. Next, this formalism is used to characterise ICTMC's and to investigate their properties. The concept of lower expectation is then given an alternative operator-theoretic characterisation, by means of a lower transition operator, and the properties of this operator are investigated as well. Finally, we use this lower transition operator to derive tractable algorithms (with polynomial runtime complexity w.r.t. the maximum numerical error) for computing the lower expectation of functions that depend on the state at any finite number of time points

Systemic oxidative stress and antioxidant capacity in cancer patients

Various factors impact the outcome of patients with the diagnosis of cancer. Common treatment modalities of cancer, including surgery, radiation therapy and cytostatic agents, all lead to a systemic inflammatory reaction. In particular, this reaction is of physiological importance as it is crucial for patient recovery. However, in some patients, a self-perpetuating inflammatory response develops due to the presence of unfavorable risk factors, several of which are still unknown, but might lead to a worse disease prognosis. Inflammation has been intimately associated with oxidative stress, that is characterized by an imbalance between pro-oxidants, also termed reactive species, and antioxidants. Systemically, oxidative stress can be quantified by measuring thiols (R-SH, sulfhydryl compounds), which are considered to be regulatory nodes within the extracellular antioxidant network. Most importantly, thiol measurements in serum or plasma form a robust and powerful read-out of the in vivo reduction-oxidation (redox) status as thiols are highly redox-active and thus readily oxidized by circulating reactive species. Therefore, systemic quantification of thiols might be a valuable addition to the clinically available diagnostic and prognostic armamentarium as it is able to reliably capture the overall balance between oxidants and the antioxidant capacity of patients. In this review, we summarized the currently available literature on thiol levels as amendable markers for oxidative stress in patients with lung, prostate and colorectal cancer. Total thiols, native (free) thiols and disulfide levels are significantly altered in these patients compared to healthy individuals. In general, these findings indicate that the extracellular antioxidant capacity is severely affected in patients with these types of cancer. Moreover, lower thiol levels are associated with a lowered overall survival. Future research should focus on exploration of the clinical significance of thiols in cancer

Intrinsic NLRP3 inflammasome activity is critical for normal adaptive immunity via regulation of IFN-γ in CD4+ T cells

The NLRP3 inflammasome controls interleukin-1b maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described.We found that the NLRP3 inflammasome assembles in human CD4+ Tcells and initiates caspase-1–dependent interleukin-1b secretion, thereby promoting interferon-g production and T helper 1 (TH1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in Tcells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to “innate immune cells” but is an integral component of normal adaptive TH1 responses

Stopping power and collective flow of nuclear matter in the reaction Ar+Pb at 0.8 GeV/u

Charged-particle exclusive data for Ar+Pb collisions at 0.772 GeV/u are analyzed in terms of collective variables for the event shapes in momentum space. Semicentral collisions lead to sidewards flow whereas nearly head-on collisions have spherical shapes in the c.m. frame, resulting from complete stopping of projectile motion. The hydrodynamical model predictions agree qualitatively with the data whereas the standard cascade model disagrees, lacking in stopping power and collective flow

Collective motion in nucleus-nucleus collisions at 800 MeV/nucleon

Semicentral Ar+KCl, La+La, and Ar+Pb collisions at 800 MeV/nucleon were studied using a streamer chamber. The results are analyzed in the framework of the transverse momentum analysis and in terms of the average sphericity matrix. A critical examination of the analysis procedures, both experimental and theoretical, is given. New procedures are described to account for overall momentum conservation in the reaction, and to correct for azimuthal variations in the detection efficiency. Average transverse momenta per nucleon in the reaction plane are presented for deuterons emitted in the forward hemisphere, as these provide the most reliable information. A Vlasov-Uehling-Uhlenbeck calculation with a stiff equation of state gives a good fit to the momenta in the Ar+Pb reaction. Flow effects parametrized further using the sphericity tensor are found stronger than in the cascade model and consistently weaker than predicted by hydrodynamics. Parameters from the sphericity tensor exhibit a larger variation as a function of multiplicity than do the average momenta per nucleon

Compression effects in relativistic nucleus-nucleus collisions

The negative-pion multiplicity is measured for central collisions of 40Ar with KCl at eight energies from 0.36 to 1.8 GeV/nucleon and for 4He on KCl and 40Ar on BaI2 at 977 and 772 MeV/nucleon, respectively. A systematic discrepancy with a cascade-model calculation which fits proton- and pion-nucleus cross sections but omits potential-energy effects is used to derive the energy going into bulk compression of the system. A value of the incompressibility constant of K=240 MeV is extracted in a parabolic form of the nuclear-matter equation of state

Collective motion in Ar+Pb collision at beam energies between 400 and 1800 MeV/nucleon

The energy dependence of rapidity distributions and flow effects was studied in central Ar+Pb collisions at 400, 800, and 1800 MeV/nucleon using a streamer chamber. Rapidity distributions for proton and pions are found to have a Gaussian shape whereas those for deuterons exhibit a two-peak structure at the two higher energies. The average in-plane transverse momentum per/nucleon and per/event shows saturation of flow around 800 MeV/nucleon for this asymmetric system. The aspect ratio of the sphericity tensor is closely correlated with the flow angle. This correlation appears to be independent of beam energy. The number of participating nucleons in central collisions varies from 213 at 400 to 135 at 1800 MeV/nucleon indicating that at the lowest energy almost the entire target nucleus participates in the collision.weitere Autoren