37 research outputs found

    Abstracting strings for model checking of C programs

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    Data type abstraction plays a crucial role in software verification. In this paper, we introduce a domain for abstracting strings in the C programming language, where strings are managed as null-terminated arrays of characters. The new domain M-String is parametrized on an index (bound) domain and a character domain. By means of these different constituent domains, M-Strings captures shape information on the array structure as well as value information on the characters occurring in the string. By tuning these two parameters, M-String can be easily tailored for specific verification tasks, balancing precision against complexity. The concrete and the abstract semantics of basic operations on strings are carefully formalized, and soundness proofs are fully detailed. Moreover, for a selection of functions contained in the standard C library, we provide the semantics for character access and update, enabling an automatic lifting of arbitrary string-manipulating code into our new domain. An implementation of abstract operations is provided within a tool that automatically lifts existing programs into the M-String domain along with an explicit-state model checker. The accuracy of the proposed domain is experimentally evaluated on real-case test programs, showing that M-String can efficiently detect real-world bugs as well as to prove that program does not contain them after they are fixed

    Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

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    Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p \u3c 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials

    Production of D+(2010)D^{*+}(2010) mesons by high energy neutrinos from the Tevatron

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    Charged vector D+(2010)D^{*+}(2010) meson production is studied in a high energy neutrino bubble chamber experiment with mean neutrino energy of 141 GeV. The D+D^{*+} are produced in (5.6±1.8)%(5.6 \pm 1.8)\% of the neutrino charged current interactions, indicating a steep increase of cross section with energy. The mean fractional hadronic energy of the D+D^{*+} meson is 0.55±0.060.55 \pm 0.06

    Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

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    Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

    Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

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    [Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease

    String Abstraction for Model Checking of C Programs

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    Automatic abstraction is a powerful software verification technique. In this paper, we elaborate an abstract domain for C strings, that is, null-terminated arrays of characters. We describe the abstract semantics of basic string operations and prove their soundness with regards to previously established concrete semantics of those operations. In addition to a selection of string functions from the standard C library, we provide semantics for character access and update, enabling automatic lifting of arbitrary string-manipulating code into the domain. The domain we present (called M-String) has two other abstract domains as its parameters: an index (bound) domain and a character domain. Picking different constituent domains allows M-String to be tailored for specific verification tasks, balancing precision against complexity. In addition to describing the domain theoretically, we also provide an executable implementation of the abstract operations. Using a tool which automatically lifts existing programs into the M-String domain along with an explicit-state model checker, we have evaluated the proposed domain experimentally on a few simple but realistic test programs

    1H-1,2,3-triazole: from structure to function and catalysis

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    The heterocyclic family of azoles have recently become one of the most widely used members of the N-heterocycles; the most prominent one being 1H-1,2,3-triazole and its derivatives. The sudden growth of interest in this structural motif was sparked by the advent of click chemistry, first described in the early 2000s. From the early days of click chemistry, when the accessibility of triazoles made them into one of the most versatile linkers, interest has slowly turned to the use of triazoles as functional building blocks. The presence of multiple N-coordination sites and a highly polarized carbon atom allows for metal coordination and the complexation of anions by both hydrogen and halogen bonding. Exploitation of these multiple binding sites makes it possible for triazoles to be used in various functional materials, such as metallic and anionic sensors. More recently, triazoles have also shown their potential in catalytic systems, thus increasing their impact far beyond the initial purpose of click chemistry. This report gives an overview of the structure, functionalities, and use of triazoles with a focus on their use in catalytic systems

    Tunable properties based on regioselectivity of 1,2,3-triazole units in axially chiral 2,2′-linked 1,1′-binaphthyl-based copolymers for ions and acid responsiveness

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    The synthesis and optical studies of a new chiral binaphthyl-based polymeric sensor are described herein. The polymers were prepared using the copper-catalyzed azide–alkyne cycloaddition reaction between fluorene and binaphthyl monomeric units. Resulted polymers differ in the orientation of the 1,2,3-triazole unit as a linker in polymeric backbone based on monomeric character. The responses of these polymers to both exposure to metal ions and the acidic medium were investigated by UV–vis absorbance, circular dichroism and fluorescence analysis. The changes in the absorption, chiroptical and fluorescence properties of the polymers indicate a change of the dihedral angle between the two naphthalene units on the binaphthyl moiety and tunability in conjugation. Moreover, an influence of regioselectivity of 1,2,3-triazole unit in polymer backbone in regards to complexation was discussed. The modulation in signal was detected in real time and makes this system a suitable candidate for further applications as an ion sensor or acid-responsive material

    Перевод итальянской диалектной устной речи на русский язык (на материале художественного фильма "Benvenuti al sud"): дипломная работа (проект) специалиста по направлению подготовки: 45.05.01 - Перевод и переводоведение

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    A lack of gravity experienced during space flight has been shown to have profound effects on human physiology including muscle atrophy, reductions in bone density and immune function, and endocrine disorders. At present, these physiological changes present major obstacles to long-term space missions. What is not clear is which pathophysiological disruptions reflect changes at the cellular level versus changes that occur due to the impact of weightlessness on the entire body. This review focuses on current research investigating the impact of microgravity at the cellular level including cellular morphology, proliferation, and adhesion. As direct research in space is currently cost prohibitive, we describe here the use of microgravity simulators for studies at the cellular level. Such instruments provide valuable tools for cost-effective research to better discern the impact of weightlessness on cellular function. Despite recent advances in understanding the relationship between extracellular forces and cell behavior, very little is understood about cellular biology and mechanotransduction under microgravity conditions. This review will examine recent insights into the impact of simulated microgravity on cell biology and how this technology may provide new insight into advancing our understanding of mechanically driven biology and disease
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