Hennessy-Milner Logic with Greatest Fixed Points as a Complete Behavioural Specification Theory

There are two fundamentally different approaches to specifying and verifying properties of systems. The logical approach makes use of specifications given as formulae of temporal or modal logics and relies on efficient model checking algorithms; the behavioural approach exploits various equivalence or refinement checking methods, provided the specifications are given in the same formalism as implementations. In this paper we provide translations between the logical formalism of Hennessy-Milner logic with greatest fixed points and the behavioural formalism of disjunctive modal transition systems. We also introduce a new operation of quotient for the above equivalent formalisms, which is adjoint to structural composition and allows synthesis of missing specifications from partial implementations. This is a substantial generalisation of the quotient for deterministic modal transition systems defined in earlier papers

Reverse Bisimulations on Stable Configuration Structures

The relationships between various equivalences on configuration structures, including interleaving bisimulation (IB), step bisimulation (SB) and hereditary history-preserving (HH) bisimulation, have been investigated by van Glabbeek and Goltz (and later Fecher). Since HH bisimulation may be characterised by the use of reverse as well as forward transitions, it is of interest to investigate forms of IB and SB where both forward and reverse transitions are allowed. We give various characterisations of reverse SB, showing that forward steps do not add extra power. We strengthen Bednarczyk's result that, in the absence of auto-concurrency, reverse IB is as strong as HH bisimulation, by showing that we need only exclude auto-concurrent events at the same depth in the configuration

Geometric, electronic, and magnetic structure of Co2_2FeSi: Curie temperature and magnetic moment measurements and calculations

In this work a simple concept was used for a systematic search for new materials with high spin polarization. It is based on two semi-empirical models. Firstly, the Slater-Pauling rule was used for estimation of the magnetic moment. This model is well supported by electronic structure calculations. The second model was found particularly for Co$_2$ based Heusler compounds when comparing their magnetic properties. It turned out that these compounds exhibit seemingly a linear dependence of the Curie temperature as function of the magnetic moment. Stimulated by these models, Co$_2$FeSi was revisited. The compound was investigated in detail concerning its geometrical and magnetic structure by means of X-ray diffraction, X-ray absorption and M\"o\ss bauer spectroscopies as well as high and low temperature magnetometry. The measurements revealed that it is, currently, the material with the highest magnetic moment ($6\mu_B$) and Curie-temperature (1100K) in the classes of Heusler compounds as well as half-metallic ferromagnets. The experimental findings are supported by detailed electronic structure calculations

Tunable Multifunctional Topological Insulators in Ternary Heusler Compounds

Recently the Quantum Spin Hall effect (QSH) was theoretically predicted and experimentally realized in a quantum wells based on binary semiconductor HgTe[1-3]. QSH state and topological insulators are the new states of quantum matter interesting both for fundamental condensed matter physics and material science[1-11]. Many of Heusler compounds with C1b structure are ternary semiconductors which are structurally and electronically related to the binary semiconductors. The diversity of Heusler materials opens wide possibilities for tuning the band gap and setting the desired band inversion by choosing compounds with appropriate hybridization strength (by lattice parameter) and the magnitude of spin-orbit coupling (by the atomic charge). Based on the first-principle calculations we demonstrate that around fifty Heusler compounds show the band inversion similar to HgTe. The topological state in these zero-gap semiconductors can be created by applying strain or by designing an appropriate quantum well structure, similar to the case of HgTe. Many of these ternary zero-gap semiconductors (LnAuPb, LnPdBi, LnPtSb and LnPtBi) contain the rare earth element Ln which can realize additional properties ranging from superconductivity (e. g. LaPtBi[12]) to magnetism (e. g. GdPtBi[13]) and heavy-fermion behavior (e. g. YbPtBi[14]). These properties can open new research directions in realizing the quantized anomalous Hall effect and topological superconductors.Comment: 20 pages, 5 figure

Association of immunotherapy and immunosuppression with severe COVID-19 disease in patients with cancer

Background: Cytokine storm due to COVID-19 can cause high morbidity and mortality. Patients with cancer treated with immunotherapy (IO) and those with immunosuppression may have higher rates of cytokine storm due to immune dysregulation. We sought to evaluate the association of IO and immunosuppression with COVID-19 outcomes and cytokine storm occurrence among patients with cancer and COVID-19, based on data from the COVID-19 and Cancer Consortium (CCC19). Methods: A registry-based retrospective cohort study was conducted on patients reported to the CCC19 registry from March 2020 to September 2021. The primary outcome was defined as an ordinal scale of COVID-19 severity. The secondary outcome was the occurrence of a cytokine storm using CCC19 variables, defined as biological and clinical evidence of severe inflammation, with end-organ dysfunction (Fajgenbaum D.C. et al., N Engl J Med., 2020). The association of IO or immunosuppression with the outcomes of interest were evaluated using a multivariable logistic regression balanced for covariate distributions through inverse probability of treatment weighting (IPTW). Results: A total of 10,214 patients were included, among which 482 (4.7%) received IO, 3,715 (36.4%) received non-IO systemic therapies, and 6,017 (58.9%) were untreated in the 3 months prior to COVID-19 diagnosis. No difference in COVID-19 severity or the development of a cytokine storm was found in the IO group compared to the untreated group (aOR: 0.77; 95%CI:0.45-1.32, and aOR: 1.06; 95%CI:0.42-2.67, respectively). On multivariable analysis, baseline immunosuppression was associated with worse outcomes both in relation to COVID-19 severity (aOR: 1.89; 95%CI:1.51-2.35) and the presence of a cytokine storm (aOR: 1.75; 95%CI:1.30-2.35). Conclusions: Administration of IO was not associated with severe outcomes in patients with cancer and COVID-19, whereas pre-existing baseline immunosuppression appears to be independently associated with worse clinical outcomes including cytokine storm

Adjuvant nivolumab for stage III/IV melanoma: Evaluation of safety outcomes and association with recurrence-free survival

Background Several therapeutic options are now available in the adjuvant melanoma setting, mandating an understanding of their benefit €'risk profiles in order to make informed treatment decisions. Herein we characterize adjuvant nivolumab select (immune-related) treatment-related adverse events (TRAEs) and evaluate possible associations between safety and recurrence-free survival (RFS) in the phase III CheckMate 238 trial. Methods Patients with resected stage IIIB-C or IV melanoma received nivolumab 3 mg/kg every 2 weeks (n=452) or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n=453) for up to 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. First-occurrence and all-occurrence select TRAEs were analyzed within discrete time intervals: from 0 to 3 months of treatment, from >3-12 months of treatment, and from the last dose (regardless of early or per-protocol treatment discontinuation) to 100 days after the last dose. Possible associations between select TRAEs and RFS were investigated post randomization in 3-month landmark analyses and in Cox model analyses (including a time-varying covariate of select TRAE), within and between treatment groups. Results From the first nivolumab dose to 100 days after the last dose, first-occurrence select TRAEs were reported in 67.7% (306/452) of patients. First-occurrence select TRAEs were reported most frequently from 0 to 3 months (48.0%), during which the most common were pruritus (15.5%) and diarrhea (15.3%). Most select TRAEs resolved within 6 months. There was no clear association between the occurrence (or not) of select TRAEs and RFS by landmark analysis or by Cox model analysis within treatment arms or comparing nivolumab to the ipilimumab comparator arm. Conclusion Results of this safety analysis of nivolumab in adjuvant melanoma were consistent with its established safety profile. In the discrete time intervals evaluated, most first-occurrence TRAEs occurred early during treatment and resolved. No association between RFS and select TRAEs was evident. Trial registration number NCT02388906

Adjuvant nivolumab versus ipilimumab (CheckMate 238 trial): Reassessment of 4-year efficacy outcomes in patients with stage III melanoma per AJCC-8 staging criteria

Nivolumab was approved as adjuvant therapy for melanoma based on data from CheckMate 238, which enrolled patients per American Joint Committee on Cancer version 7 (AJCC-7) criteria. Here, we analyse long-term outcomes per AJCC-8 staging criteria compared with AJCC-7 results to inform clinical decisions for patients diagnosed per AJCC-8

Approximation Techniques for Stochastic Analysis of Biological Systems

There has been an increasing demand for formal methods in the design process of safety-critical synthetic genetic circuits. Probabilistic model checking techniques have demonstrated significant potential in analyzing the intrinsic probabilistic behaviors of complex genetic circuit designs. However, its inability to scale limits its applicability in practice. This chapter addresses the scalability problem by presenting a state-space approximation method to remove unlikely states resulting in a reduced, finite state representation of the infinite-state continuous-time Markov chain that is amenable to probabilistic model checking. The proposed method is evaluated on a design of a genetic toggle switch. Comparisons with another state-of-art tool demonstrates both accuracy and efficiency of the presented method