Liveness-Driven Random Program Generation

Randomly generated programs are popular for testing compilers and program analysis tools, with hundreds of bugs in real-world C compilers found by random testing. However, existing random program generators may generate large amounts of dead code (computations whose result is never used). This leaves relatively little code to exercise a target compiler's more complex optimizations. To address this shortcoming, we introduce liveness-driven random program generation. In this approach the random program is constructed bottom-up, guided by a simultaneous structural data-flow analysis to ensure that the generator never generates dead code. The algorithm is implemented as a plugin for the Frama-C framework. We evaluate it in comparison to Csmith, the standard random C program generator. Our tool generates programs that compile to more machine code with a more complex instruction mix.Comment: Pre-proceedings paper presented at the 27th International Symposium on Logic-Based Program Synthesis and Transformation (LOPSTR 2017), Namur, Belgium, 10-12 October 2017 (arXiv:1708.07854

Diarrhoea in a large prospective cohort of European travellers to resource-limited destinations

BACKGROUND: Incidence rates of travellers' diarrhoea (TD) need to be updated and risk factors are insufficiently known. METHODS: Between July 2006 and January 2008 adult customers of our Centre for Travel Health travelling to a resource-limited country for the duration of 1 to 8 weeks were invited to participate in a prospective cohort study. They received one questionnaire pre-travel and a second one immediately post-travel. First two-week incidence rates were calculated for TD episodes and a risk assessment was made including demographic and travel-related variables, medical history and behavioural factors. RESULTS: Among the 3100 persons recruited, 2800 could be investigated, resulting in a participation rate of 89.2%. The first two-weeks incidence for classic TD was 26.2% (95%CI 24.5-27.8). The highest rates were found for Central Africa (29.6%, 95% CI 12.4-46.8), the Indian subcontinent (26.3%, 95%CI 2.3-30.2) and West Africa (21.5%, 95%CI 14.9-28.1). Median TD duration was 2 days (range 1-90). The majority treated TD with loperamide (57.6%), while a small proportion used probiotics (23.0%) and antibiotics (6.8%). Multiple logistic regression analysis on any TD to determine risk factors showed that a resolved diarrhoeal episode experienced in the 4 months pre-travel (OR 2.03, 95%CI 1.59-2.54), antidepressive comedication (OR 2.11, 95%CI 1.17-3.80), allergic asthma (OR 1.67, 95%CI 1.10-2.54), and reporting TD-independent fever (OR 6.56, 95%CI 3.06-14.04) were the most prominent risk factors of TD. CONCLUSIONS: TD remains a frequent travel disease, but there is a decreasing trend in the incidence rate. Patients with a history of allergic asthma, pre-travel diarrhoea, or of TD-independent fever were more likely to develop TD while abroad

Distant X-ray Galaxies: Insights from the Local Population

A full understanding of the origin of the hard X-ray background requires a complete and accurate census of the distant galaxies that produce it. Unfortunately, distant X-ray galaxies tend to be very faint at all wavelengths, which hinders efforts to perform this census. This chapter discusses the insights that can be obtained through comparison of the distant population to local X-ray galaxies, whose properties are well characterized. Such comparisons will ultimately aid investigations into the cosmic evolution of supermassive black holes and their environments.Comment: 19 pages, 10 figures, to appear as Chapter 7 in "Supermassive Black Holes in the Distant Universe" (2004), ed. A. J. Barger, Kluwer Academic Publishers, in pres

Axion-like-particle search with high-intensity lasers

We study ALP-photon-conversion within strong inhomogeneous electromagnetic fields as provided by contemporary high-intensity laser systems. We observe that probe photons traversing the focal spot of a superposition of Gaussian beams of a single high-intensity laser at fundamental and frequency-doubled mode can experience a frequency shift due to their intermittent propagation as axion-like-particles. This process is strongly peaked for resonant masses on the order of the involved laser frequencies. Purely laser-based experiments in optical setups are sensitive to ALPs in the $\mathrm{eV}$ mass range and can thus complement ALP searches at dipole magnets.Comment: 25 pages, 2 figure

Cost-effectiveness analysis of malaria chemoprophylaxis for travellers to West-Africa

BACKGROUND: The importation of malaria to non-endemic countries remains a major cause of travel-related morbidity and a leading cause of travel-related hospitalizations. Currently they are three priority medications for malaria prophylaxis to West Africa: mefloquine, atovaquone/proguanil and doxycycline. We investigate the cost effectiveness of a partial reimbursement of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers to high risk areas of malaria transmission compared with the current situation of no reimbursement. METHODS: This study is a cost-effectiveness analysis based on malaria cases imported from West Africa to Switzerland from the perspective of the Swiss health system. We used a decision tree model and made a literature research on the components of travel related malaria. The main outcome measure was the cost effectiveness of malaria chemoprophylaxis reimbursement based on malaria and deaths averted. RESULTS: Using a program where travellers would be reimbursed for 80% of the cost of the cheapest malaria chemoprophylaxis is dominant (i.e. cost saving and more effective than the current situation) using the assumption that currently 68.7% of travellers to West Africa use malaria chemoprophylaxis. If the current usage of malaria chemoprophylaxis would be higher, 82.4%, the incremental cost per malaria case averted is € 2'302. The incremental cost of malaria death averted is € 191'833.The most important factors influencing the model were: the proportion of travellers using malaria chemoprophylaxis, the probability of contracting malaria without malaria chemoprophylaxis, the cost of the mefloquine regimen, the decrease in the number of travellers without malaria chemoprophylaxis in the reimbursement strategy. CONCLUSIONS: This study suggests that a reimbursement of 80% of the cost of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers from Switzerland to West Africa is highly effective in terms of malaria cases averted and is cost effective to the Swiss health system. These data are relevant to discussions about the cost effectiveness of malaria chemoprophylaxis reimbursement for vulnerable groups such as those visiting friends and relatives who have the highest risk of malaria, who are least likely to use chemoprophylaxis

Loss of Dictyostelium HSPC300 causes a scar-like phenotype and loss of SCAR protein

<p>Abstract</p> <p>Background</p> <p>SCAR/WAVE proteins couple signalling to actin polymerization, and are thus fundamental to the formation of pseudopods and lamellipods. They are controlled as part of a five-membered complex that includes the tiny HSPC300 protein. It is not known why SCAR/WAVE is found in such a large assembly, but in <it>Dictyostelium </it>the four larger subunits have different, clearly delineated functions.</p> <p>Results</p> <p>We have generated <it>Dictyostelium </it>mutants in which the HSPC300 gene is disrupted. As has been seen in other regulatory complex mutants, SCAR is lost in these cells, apparently by a post-translational mechanism, though PIR121 levels do not change. HSPC300 knockouts resemble <it>scar </it>mutants in slow migration, roundness, and lack of large pseudopods. However <it>hspc300</it>-colonies on bacteria are larger and more similar to wild type, suggesting that some SCAR function can survive without HSPC300. We find no evidence for functions of HSPC300 outside the SCAR complex.</p> <p>Conclusion</p> <p>HSPC300 is essential for most SCAR complex functions. The phenotype of HSPC300 knockouts is most similar to mutants in <it>scar</it>, not the other members of the SCAR complex, suggesting that HSPC300 acts most directly on SCAR itself.</p

Response to Merritts et al. (2023): The Anthropocene is complex. Defining it is not

Merritts et al. (2023) misrepresent Paul Crutzen's Anthropocene concept as encompassing all significant anthropogenic impacts, extending back many millennia. Crutzen's definition reflects massively enhanced, much more recent human impacts that transformed the Earth System away from the stability of Holocene conditions. His concept of an epoch (hence the ‘cene’ suffix) is more consistent with the strikingly distinct sedimentary record accumulated since the mid-20th century. Waters et al. (2022) highlighted a Great Acceleration Event Array (GAEA) of stratigraphic event markers that are indeed diverse and complex but also tightly clustered around 1950 CE, allowing ultra-high resolution characterization and correlation of a clearly recognisable Anthropocene chronostratigraphic base. The ‘Anthropocene event’ offered by Merritts et al., following Gibbard et al. (2021, 2022), is a highly nuanced concept that obfuscates the transformative human impact of the chronostratigraphic Anthropocene. Waters et al. (2022) restricted the meaning of the term ‘event’ in geology to conform with usual Quaternary practice and improve its utility. They simultaneously recognized an evidence-based Anthropogenic Modification Episode that is more explicitly defined than the highly interpretive interdisciplinary ‘Anthropocene event’ of Gibbard et al. (2021, 2022). The advance of science is best served through clearly developed concepts supported by tightly circumscribed terminology; indeed, improvements to stratigraphy over recent decades have been achieved through increasingly precise definitions, especially for chronostratigraphic units, and not by retaining vague terminology

Ficaria verna Huds. extracts and their β-cyclodextrin supramolecular systems

<p>Abstract</p> <p>Background</p> <p>Obtaining new pharmaceutical materials with enhanced properties by using natural compounds and environment-friendly methods is a continuous goal for scientists. <it>Ficaria verna </it>Huds. is a widespread perennial plant with applications in the treat of haemorrhoids and to cure piles; it has also anti-inflammatory, astringent, and antibiotic properties. The goal of the present study is the obtaining and characterization of new <it>F. verna </it>extract/β-cyclodextrin complexes by using only natural compounds, solvents, and environment-friendly methods in order to increase the quality and acceptability versus toxicity indicator. Thus, the flavonoid content (as quercetin) of <it>Ficaria verna </it>Huds. flowers and leaves from the West side of Romania was determined and correlated with their antioxidant activity. Further, the possibility of obtaining β-cyclodextrin supramolecular systems was studied.</p> <p>Results</p> <p><it>F. verna </it>flowers and leaves extracts were obtained by semi-continuous solid-liquid extraction. The raw concentrated extract was spectrophotometrically analyzed in order to quantify the flavonoids from plant parts and to evaluate the antioxidant activity of these extracts. The <it>F. verna </it>extracts were used for obtaining β-cyclodextrin complexes; these were analyzed by scanning electron microscopy and Karl Fischer water titration; spectrophotometry was used in order to quantifying the flavonoids and evaluates the antioxidant activity. A higher concentration of flavonoids of 0.5% was determined in complexes obtained by crystallisation method, while only a half of this value was calculated for kneading method. The antioxidant activity of these complexes was correlated with the flavonoid content and this parameter reveals possible controlled release properties.</p> <p>Conclusions</p> <p>The flavonoid content of <it>F. verna </it>Huds. from the West side of Romania (Banat county) is approximately the same in flowers and leaves, being situated at a medium value among other studies. β-Cyclodextrin complexes of <it>F. verna </it>extracts are obtained with lower yields by crystallisation than kneading methods, but the flavonoids (as quercetin) are better encapsulated in the first case most probably due to the possibility to attain the <it>host</it>-<it>guest </it>equilibrium in the slower crystallisation process. <it>F. verna </it>extracts and their β-cyclodextrin complexes have antioxidant activity even at very low concentrations and could be used in proper and valuable pharmaceutical formulations with enhanced bioactivity.</p

Arp2/3 Complex Regulates Asymmetric Division and Cytokinesis in Mouse Oocytes

Mammalian oocyte meiotic maturation involves oocyte polarization and a unique asymmetric division, but until now, the underlying mechanisms have been poorly understood. Arp2/3 complex has been shown to regulate actin nucleation and is widely involved in a diverse range of processes such as cell locomotion, phagocytosis and the establishment of cell polarity. Whether Arp2/3 complex participates in oocyte polarization and asymmetric division is unknown. The present study investigated the expression and functions of Arp2/3 complex during mouse oocyte meiotic maturation. Immunofluorescent staining showed that the Arp2/3 complex was restricted to the cortex, with a thickened cap above the meiotic apparatus, and that this localization pattern was depended on actin. Disruption of Arp2/3 complex by a newly-found specific inhibitor CK666, as well as by Arpc2 and Arpc3 RNAi, resulted in a range of effects. These included the failure of asymmetric division, spindle migration, and the formation and completion of oocyte cytokinesis. The formation of the actin cap and cortical granule-free domain (CGFD) was also disrupted, which further confirmed the disruption of spindle migration. Our data suggest that the Arp2/3 complex probably regulates oocyte polarization through its effect on spindle migration, asymmetric division and cytokinesis during mouse oocyte meiotic maturation