Combining k-Induction with Continuously-Refined Invariants

Bounded model checking (BMC) is a well-known and successful technique for finding bugs in software. k-induction is an approach to extend BMC-based approaches from falsification to verification. Automatically generated auxiliary invariants can be used to strengthen the induction hypothesis. We improve this approach and further increase effectiveness and efficiency in the following way: we start with light-weight invariants and refine these invariants continuously during the analysis. We present and evaluate an implementation of our approach in the open-source verification-framework CPAchecker. Our experiments show that combining k-induction with continuously-refined invariants significantly increases effectiveness and efficiency, and outperforms all existing implementations of k-induction-based software verification in terms of successful verification results.Comment: 12 pages, 5 figures, 2 tables, 2 algorithm

A multistate model for early decision making in oncology

The development of oncology drugs progresses through multiple phases, where after each phase a decision is made about whether to move a molecule forward. Early phase efficacy decisions are often made on the basis of single arm studies based on RECIST tumor response as endpoint. This decision rules are implicitly assuming some form of surrogacy between tumor response and long-term endpoints like progression-free survival (PFS) or overall survival (OS). The surrogacy is most often assessed as weak, but sufficient to allow a rapid decision making as early phase studies lack the survival follow up and number of patients to properly assess PFS or OS. With the emergence of therapies with new mechanisms of action, for which the link between RECIST tumor response and long-term endpoints is either not accessible yet because not enough data is available to perform a meta-regression, or the link is weaker than with classical chemotherapies, tumor response based rules may not be optimal. In this paper, we explore the use of a multistate model for decision making based on single-arm early phase trials. The multistate model allows to account for more information than the simple RECIST response status, namely, the time to get to response, the duration of response, the PFS time and time to death. We propose to base the decision on efficacy on the OS hazard ratio (HR), predicted from a multistate model based on early phase data with limited survival follow-up, combined with historical control data. Using three case studies and simulations, we illustrate the feasibility of the estimation of the OS HR using a multistate model based on limited data from early phase studies. We argue that, in the presence of limited follow up and small sample size, and on assumptions within the multistate model, the OS prediction is acceptable and may lead to better decisions for continuing the development of a drug

In situ measurements of soil and plant water isotopes: a review of approaches, practical considerations and a vision for the future

The number of ecohydrological studies involving water stable isotope measurements has been increasing steadily due to technological (e.g., field-deployable laser spectroscopy and cheaper instruments) and methodological (i.e., tracer approaches or improvements in root water uptake models) advances in recent years. This enables researchers from a broad scientific background to incorporate water-isotope-based methods into their studies. Several isotope effects are currently not fully understood but might be essential when investigating root water uptake depths of vegetation and separating isotope processes in the soil–vegetation–atmosphere continuum. Different viewpoints exist on (i) extraction methods for soil and plant water and methodological artifacts potentially introduced by them, (ii) the pools of water (mobile vs. immobile) measured with those methods, and (iii) spatial variability and temporal dynamics of the water isotope composition of different compartments in terrestrial ecosystems. In situ methods have been proposed as an innovative and necessary way to address these issues and are required in order to disentangle isotope effects and take them into account when studying root water uptake depths of plants and for studying soil–plant–atmosphere interaction based on water stable isotopes. Herein, we review the current status of in situ measurements of water stable isotopes in soils and plants, point out current issues and highlight the potential for future research. Moreover, we put a strong focus and incorporate practical aspects into this review in order to provide a guideline for researchers with limited previous experience with in situ methods. We also include a section on opportunities for incorporating data obtained with described in situ methods into existing isotope-enabled ecohydrological models and provide examples illustrating potential benefits of doing so. Finally, we propose an integrated methodology for measuring both soil and plant water isotopes in situ when carrying out studies at the soil–vegetation–atmosphere continuum. Several authors have shown that reliable data can be generated in the field using in situ methods for measuring the soil water isotope composition. For transpiration, reliable methods also exist but are not common in ecohydrological field studies due to the required effort. Little attention has been paid to in situ xylem water isotope measurements. Research needs to focus on improving and further developing those methods. There is a need for a consistent and combined (soils and plants) methodology for ecohydrological studies. Such systems should be designed and adapted to the environment to be studied. We further conclude that many studies currently might not rely on in situ methods extensively because of the technical difficulty and existing methodological uncertainties. Future research needs to aim on developing a simplified approach that provides a reasonable trade-off between practicability and precision and accuracy

Tourismus als Instrument für eine nachhaltige Wirtschaftsentwicklung

Die touristische Wertschöpfungskette kann langfristige Beschäftigungseffekte in Entwicklungsländern erzielen und aktiv zur Armutsbekämpfung beitragen. Dafür darf die Tourismusentwicklung nicht rein profit- und wachstumsorientiert erfolgen, sondern muss sozialen, kulturellen und ökologischen Belangen umfassend Rechnung tragen

Fighting Platforms and the People, not the Pandemic: #ResignModi and Disinformation Governance in India - an update

It is not usually a good sign that you are asked to write a follow-up to a Verfassungsblog post. In late February, we described the travails of Twitter in India, which largely bowed to government pressure to block users and censor hashtags. Now, this fight has become larger. To control social media-driven criticism against its handling of the COVID-19 crisis, the Indian government, led by Prime Minister Narendra Modi, can now take advantage of new powers via the Information Technology (Guidelines for Intermediaries and Digital Media Ethics Code) Rules 2021 (IT Rules 2021). For Big Tech, who have been fending off external regulation globally and consider India as their largest market, this is an acid test. The IT Rules 2021 empower the Modi government to counter disinformation, whose definition seems to have been stretched to include content that portrays the government negatively. The government can override the platforms' agency here and make them toe its line. How platforms react will have a domino effect on users' freedom of expression and right to privacy across the world

Energy-filtered transmission electron microscopy of biological samples on highly transparent carbon nanomembranes

Ultrathin carbon nanomembranes (CNM) comprising crosslinked biphenyl precursors have been tested as support films for energy-filtered transmission electron microscopy (EFTEM) of biological specimens. Due to their high transparency CNM are ideal substrates for electron energy loss spectroscopy (EELS) and electron spectroscopic imaging (ESI) of stained and unstained biological samples. Virtually background-free elemental maps of tobacco mosaic virus (TMV) and ferritin have been obtained from samples supported by ~ 1 nm thin CNM. Furthermore, we have tested conductive carbon nanomembranes (cCNM) comprising nanocrystalline graphene, obtained by thermal treatment of CNM, as supports for cryoEM of ice-embedded biological samples. We imaged ice-embedded TMV on cCNM and compared the results with images of ice-embedded TMV on conventional carbon film (CC), thus analyzing the gain in contrast for TMV on cCNM in a quantitative manner. In addition we have developed a method for the preparation of vitrified specimens, suspended over the holes of a conventional holey carbon film, while backed by ultrathin cCNM

Combined Application of 17β-Estradiol and Progesterone Enhance Vascular Endothelial Growth Factor and Surfactant Protein Expression in Cultured Embryonic Lung Cells of Mice

Preterm delivery is associated with disruption of the placental supply with 17β-estradiol (E2) and progesterone (P). The aim is to evaluate the role of E2 and P on the regulation of key proteins in lung development in embryonic lung cells. Alveolar cell type II (AT-II) and central lung fibroblast cultures were established from mouse embryos. Cells were exposed for 24 hours to E2 and/or P, the estrogen receptor antagonist ICI 182.780 (ICI) and the progesterone receptor antagonist mifepristone (RU 486). The mRNA expression of vascular endothelial growth factor (VEGF) and surfactant protein B and C (SB-B, SB-C) was determined, and protein levels of VEGF were measured. Only the combined treatment with E2 and P increased mRNA expression and VEGF protein in AT-II cells and lung fibroblasts. Combined treatment also promoted SP-B and SP-C expression in AT-II cells. Pretreatment with ICI and RU 486 completely abolished the E2 and P induced effects. E2 and P enhanced expression of VEGF and surfactant proteins in primary embryonic lung cells and may be involved in regulating expression of key molecules for the prenatal lung development and postnatal lung function

Unterstützung der ukrainischen Behörden beim Ausbau der verbesserten betrieblichen Überwachung für die KKW Rovno und Saporoshje

Für den 3. Block vom KKW Rovno - WWER-1000/W-320 - wurde in Analogie zu den 6 typengleichen Blöcken des KKW Saporoshje eine verbesserte betriebliche Überwachung eingerichtet. Dazu werden der Aufsichtsbehörde vor Ort und in Kiew einmal pro Minute 57 aktuelle sicherheitsrelevante Parameter zur Erfassung und Bewertung mittels moderner technischer Mittel on-line zur Verfügung gestellt. Die entwickelte Auswertesoftware gestattet die Darstellung der Bewertungsergebnisse in Form von Tabellen, Grafiken und Schemata, wobei durch einen Archivmodus auch Trendanalysen von allen Parametern möglich sind. Des Weiteren wurde die Leistungsfähigkeit und Zuverlässigkeit des gesamten Fernüberwachungssystem weiter erhöht, so dass derzeit mehr als 60 % der ukrainischen KKW-Kapazität unter einer deutlich verbesserten behördlichen Aufsicht stehen