"Boring formal methods" or "Sherlock Holmes deduction methods"?

This paper provides an overview of common challenges in teaching of logic and formal methods to Computer Science and IT students. We discuss our experiences from the course IN3050: Applied Logic in Engineering, introduced as a "logic for everybody" elective course at at TU Munich, Germany, to engage pupils studying Computer Science, IT and engineering subjects on Bachelor and Master levels. Our goal was to overcome the bias that logic and formal methods are not only very complicated but also very boring to study and to apply. In this paper, we present the core structure of the course, provide examples of exercises and evaluate the course based on the students' surveys.Comment: Preprint. Accepted to the Software Technologies: Applications and Foundations (STAF 2016). Final version published by Springer International Publishing AG. arXiv admin note: substantial text overlap with arXiv:1602.0517

Mutual information between geomagnetic indices and the solar wind as seen by WIND : implications for propagation time estimates

The determination of delay times of solar wind conditions at the sunward libration point to effects on Earth is investigated using mutual information. This measures the amount of information shared between two timeseries. We consider the mutual information content of solar wind observations, from WIND, and the geomagnetic indices. The success of five commonly used schemes for estimating interplanetary propagation times is examined. Propagation assuming a fixed plane normal at 45 degrees to the GSE x-axis (i.e. the Parker Spiral estimate) is found to give optimal mutual information. The mutual information depends on the point in space chosen as the target for the propagation estimate, and we find that it is maximized by choosing a point in the nightside rather than dayside magnetosphere. In addition, we employ recurrence plot analysis to visualize contributions to the mutual information, this suggests that it appears on timescales of hours rather than minutes

Age-related endothelial dysfunction in human skeletal muscle feed arteries: the role of free radicals derived from mitochondria in the vasculature

Aim This study sought to determine the role of free radicals derived from mitochondria in the vasculature in the recognized age-related endothelial dysfunction of human skeletal muscle feed arteries (SMFAs). Methods A total of 44 SMFAs were studied with and without acute exposure to the mitochondria-targeted antioxidant MitoQ and nitric oxide synthase (NOS) blockade. The relative abundance of proteins from the electron transport chain, phosphorylated (p-) to endothelial (e) NOS ratio, manganese superoxide dismutase (MnSOD) and the mitochondria-derived superoxide () levels were assessed in SMFA. Endothelium-dependent and endothelium-independent SMFA vasodilation was assessed in response to flow-induced shear stress, acetylcholine (ACh) and sodium nitroprusside (SNP). Results MitoQ restored endothelium-dependent vasodilation in the old to that of the young when stimulated by both flow (young: 68 ± 5; old: 25 ± 7; old + MitoQ 65 ± 9%) and ACh (young: 97 ± 4; old: 59 ± 10; old + MitoQ: 98 ± 5%), but did not alter the initially uncompromised, endothelium-independent vasodilation (SNP). Compared to the young, MitoQ in the old diminished the initially elevated mitochondria-derived levels and appeared to attenuate the breakdown of MnSOD. Furthermore, MitoQ increased the ratio of p-eNOS to NOS and the restoration of endothelium-dependent vasodilation in the old by MitoQ was ablated by NOS blockade. Conclusion This study demonstrated that MitoQ reverses age-related vascular dysfunction by what appears to be an NO-dependent mechanism in human SMFAs. These findings suggest that mitochondria-targeted antioxidants may have utility in terms of counteracting the attenuated blood flow and vascular dysfunction associated with advancing age

Mitochondrial function in heart failure: The impact of ischemic and non-ischemic etiology

Background Although cardiac mitochondrial dysfunction is associated with heart failure (HF), this is a complex syndrome with two predominant etiologies, ischemic HF (iHF) and non-ischemic HF (niHF), and the exact impact of mitochondrial dysfunction in these two distinct forms of HF is unknown. Methods and results To determine the impact of HF etiology on mitochondrial function, respiration was measured in permeabilized cardiac muscle fibers from patients with iHF (n = 17), niHF (n = 18), and healthy donor hearts (HdH). Oxidative phosphorylation capacity (OXPHOS), assessed as state 3 respiration, fell progressively from HdH to niHF, to iHF (Complex I + II: 54 ± 1; 34 ± 4; 27 ± 3 pmol·s− 1·mg− 1) as did citrate synthase activity (CSA: 206 ± 18; 129 ± 6; 82 ± 6 nmol·mg− 1·min− 1). Although still significantly lower than HdH, normalization of OXPHOS by CSA negated the difference in mass specific OXPHOS between iHF and niHF. Interestingly, Complex I state 2 respiration increased progressively from HdH, to niHF, to iHF, whether or not normalized for CSA (0.6 ± 0.2; 1.1 ± 0.3; 2.3 ± 0.3; pmol·mg− 1·CSA), such that the respiratory control ratio (RCR), fell in the same manner across groups. Finally, both the total free radical levels (60 ± 6; 46 ± 4 AU) and level of mitochondrial derived superoxide (1.0 ± 0.2; 0.7 ± 0.1 AU) were greater in iHF compared to niHF, respectively. Conclusions Thus, the HF-related attenuation in OXPHOS actually appears to be independent of etiology when the lower mitochondrial content of iHF is taken into account. However, these findings provide evidence of deleterious intrinsic mitochondrial changes in iHF, compared to niHF, including greater proton leak, attenuated OXPHOS efficiency, and augmented free radical levels

Isolated quadriceps training restores whole body exercise capacity in CHF

Patients with Chronic Heart Failure (CHF) are commonly characterized by exercise limitation. The benefit of isolated (i.e., small muscle mass) muscle training and its potential translation to whole body exercise in patients CHF has been recognized, however the mechanisms responsible for this positive outcome remain poorly understood. To study oxygen (O2) transport and metabolism at maximal cycle (whole body) and knee extensor (KE, small muscle mass) exercise in this pathological condition, eight healthy controls and six patients with CHF with reduced ejection fraction commenced 8 weeks of KE training (both legs, separately). Before and after training, they underwent cycle and KE maximal exercise studies. Pre-training cycling and KE exercise peak leg O2 uptake (VO2) were 17% and 15% lower, respectively, in the patients compared to controls. Although KE training did not alter cardiac output at maximal KE or cycle exercise, it increased O2 delivery (by 54%), arterial-venous O2 difference (by 10%), and muscle O2 conductance (by 39%) at maximal KE exercise, yielding an increase in peak single leg VO2 of 53%, which exceeded untrained control subject values. Post-training, during maximal cycling, O2 delivery (40%), arterial-venous O2 difference (15%), and muscle O2 conductance (DMO2) (52%) all increased, yielding a 40% greater peak leg VO2, matching that of the controls. Small muscle mass exercise training-induced improvements in both peripheral convective and diffusive O2 transport and subsequent O2 utilization were the main mechanisms responsible for the increased whole body exercise capacity in patients with CHF. Such clear improvements in these factors and exercise capacity support the efficacy of small muscle mass training as a powerful approach to promote a metabolic reserve and maintain physical function in the face of continuing central limitations associated with CHF

Altered skeletal muscle mitochondrial phenotype in COPD: disease vs. disuse

Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered skeletal muscle mitochondrial phenotype, which often includes reduced mitochondrial density, altered respiratory function, and elevated oxidative stress. As this phenotype may be explained by the sedentary lifestyle that commonly accompanies this disease, the aim of this study was to determine whether such alterations are still evident when patients with COPD are compared to control subjects matched for objectively measured physical activity (PA; accelerometry). Indexes of mitochondrial density [citrate synthase (CS) activity], respiratory function (respirometry in permeabilized fibers), and muscle oxidative stress [4-hydroxynonenal (4-HNE) content] were assessed in muscle fibers biopsied from the vastus lateralis of nine patients with COPD and nine PA-matched control subjects (CON). Despite performing similar levels of PA (CON: 18 ± 3, COPD: 20 ± 7 daily minutes moderate-to-vigorous PA; CON: 4,596 ± 683, COPD: 4,219 ± 763 steps per day, P \u3e 0.70), patients with COPD still exhibited several alterations in their mitochondrial phenotype, including attenuated skeletal muscle mitochondrial density (CS activity; CON 70.6 ± 3.8, COPD 52.7 ± 6.5 U/mg, P \u3c 0.05), altered mitochondrial respiration [e.g., ratio of complex I-driven state 3 to complex II-driven state 3 (CI/CII); CON: 1.20 ± 0.11, COPD: 0.90 ± 0.05, P \u3c 0.05), and oxidative stress (4-HNE; CON: 1.35 ± 0.19, COPD: 2.26 ± 0.25 relative to β-actin, P \u3c 0.05). Furthermore, CS activity (r = 0.55), CI/CII (r = 0.60), and 4-HNE (r = 0.49) were all correlated with pulmonary function, assessed as forced expiratory volume in 1 s (P \u3c 0.05), but not PA (P \u3e 0.05). In conclusion, the altered mitochondrial phenotype in COPD is present even in the absence of differing levels of PA and appears to be related to the disease itself

Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration

This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P \u3c 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P \u3c 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P \u3c 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P \u3c 0.05), which was related to exercise tolerance of the patients (r = 0.64, P \u3c 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease

Photometry of cometary nuclei: Rotation rates, colours and a comparison with Kuiper Belt Objects

We present time-series data on Jupiter Family Comets (JFCs) 17P/Holmes, 47P/Ashbrook-Jackson and 137P/Shoemaker-Levy 2. In addition we also present results from `snap-shot' observations of comets 43P/Wolf-Harrington, 44P/Reinmuth 2, 103P/Hartley 2 and 104P/Kowal 2 taken during the same run. The comets were at heliocentric distances of between 3 and 7 AU at this time. We present measurements of size and activity levels for the snap-shot targets. The time-series data allow us to constrain rotation periods and shapes, and thus bulk densities. We also measure colour indices (V-R) and (R-I) and reliable radii for these comets. We compare all of our findings to date with similar results for other comets and Kuiper Belt Objects (KBOs). We find that the rotational properties of nuclei and KBOs are very similar, that there is evidence for a cut-off in bulk densities at ~ 0.6 g cm^{-3} in both populations, and the colours of the two populations show similar correlations. For JFCs there is no observational evidence for the optical colours being dependant on either position in the orbit or on orbital parameters.Comment: 15 pages, 19 figures, accepted for publication in MNRA