A calculus for modular loop acceleration and non-termination proofs

Loop acceleration can be used to prove safety, reachability, runtime bounds, and (non-)termination of programs. To this end, a variety of acceleration techniques have been proposed. However, so far all of them have been monolithic, i.e., a single loop could not be accelerated using a combination of several different acceleration techniques. In contrast, we present a calculus that allows for combining acceleration techniques in a modular way and we show how to integrate many existing acceleration techniques into our calculus. Moreover, we propose two novel acceleration techniques that can be incorporated into our calculus seamlessly. Some of these acceleration techniques apply only to non-terminating loops. Thus, combining them with our novel calculus results in a new, modular approach for proving non-termination. An empirical evaluation demonstrates the applicability of our approach, both for loop acceleration and for proving non-termination.

     

Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells

1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na⁺/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics.     

Uncertainties in the determination of pyrrolizidine alkaloid levels in naturally contaminated honeys and comparison of results obtained by different analytical approaches

The contamination of honey with hepatotoxic pyrrolizidine alkaloids (PAs) is a well-known hazard for food safety. While management strategies and controls of the honey industry aim to reduce the PA levels, uncertainties remain with regard to the safety of regionally produced and marketed honey. In addition, a previous study showed large differences of results obtained after various periods of storage and apparent differences between the analytical results of different laboratories. Therefore, this study aimed at examining these uncertainties by monitoring the impact of storage on the PA and PA N-oxide (PANO) content of two freshly harvested honeys and on possible demixing effects caused by pollen settling. Additionally, three analytical approaches – target analysis with matrix-matched calibration or standard addition and a sum parameter method – were applied for a comparative analysis of 20 honeys harvested in summer 2016. All samples originated from Schleswig-Holstein in Northern Germany where the PA plant Jacobaea vulgaris is currently observed on a massive scale. The results of the time series analyses showed that PANO levels markedly decreased within a few weeks and practically reached the LOD 16 weeks after harvest. Tertiary PAs, by contrast, remained stable and did not increase as a consequence of PANO decrease. The experiments on a putative demixing, which may result in a heterogeneous distribution of PAs/PANOs, revealed that there was no such effect during storage of up to 12 weeks. A comparison of the PA/PANO levels obtained by different analytical approaches showed that in some cases the sum parameter method yielded much higher levels than the target approaches, whereas in other cases, the target analysis with standard addition found higher levels than the other two methods. In summary, the results of this study highlight uncertainties regarding the validity and comparability of analytical results and consequently regarding health risk assessment.     

Task-Independent Spiking Central Pattern Generator: A Learning-Based Approach

Neural Processing Letters - Legged locomotion is a challenging task in the field of robotics but a rather simple one in nature. This motivates the use of biological methodologies as solutions to...     

Ag2O–Al2O3–ZrO2 Trimetallic Nanocatalyst for High Performance Photodegradation of Nicosulfuron Herbicide

Topics in Catalysis - In the present study, Ag2O–Al2O3–ZrO2 based trimetallic oxide nanocatalyst was designed using simple microwave assisted reduction method. It was characterized...     

Measuring Local Crystallization Fouling in a Double-Pipe Heat Exchanger

Abstract

Although fouling is a problem varying in space and time, sizing and assessment of a process apparatus is almost always based on one single integral fouling resistance value. Furthermore, the integral fluid dynamic behavior, e.g. the development of time-dependent pressure drop in a heat exchanger, can be influenced by local constrictions. While it is generally possible to determine the time dependency of the integral fouling behavior, local differences are not taken into consideration at present. Therefore, this paper introduces a metrological, an incremental and a segmental approach to study the local development of crystallization fouling by calcium sulfate in a countercurrent double-pipe heat exchanger. The consecutive approaches allow for thermal, volumetric, gravimetric, and optical fouling investigations, aiming to examine the axial distribution of deposit as well as local differences in the deposit morphology. All methods provided congruent results and local fouling could be described properly. An almost clean surface at the colder end of the heat exchanger and an exponential increase of deposit thickness were observed towards the hot end. Hence, the section near to the hot water inlet turned out to be a key area with regards to increasing fouling mass and structural changes of the layer.     

Long term stability of electrocaloric response in barium zirconate titanate

The stability of the electrocaloric effect under electric field cycling is an important consideration in the development of solid-state cooling devices. Here we report measurements carried out on Ba(Zr_0.2Ti_0.8)O₃ ceramics which reveal that the adiabatic temperature change, polarization-electric field hysteresis loops and dielectric permittivity/loss show stable behavior up to 10⁵ cycles. We further demonstrate that the loss in electrocaloric response observed after 10⁵ cycles is associated with the migration of oxygen vacancies. As a result, the electrical properties of the material are changed leading to an increase in leakage current and Joule heating. Reversing the polarity of the electric field after every 10⁵ cycles changes the migration direction of oxygen vacancies, thereby preventing charge accumulation at grain boundaries and electrodes. By doing so, the electrocaloric stability is improved and the adiabatic temperature remains constant even after 10⁶ cycles, much higher than achieved in commercially available barium titanate ceramics.     

Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate

Ergothioneine has emerged as a crucial cytoprotectant in the pathogenic lifestyle of Mycobacterium tuberculosis. Production of this antioxidant from primary metabolites may be regulated by phosphorylation of Thr213 in the active site of the methyltransferase EgtD. The structure of mycobacterial EgtD suggests that this post-translational modification would require a large-scale change in conformation to make the active-site residue accessible to a protein kinase. In this report, we show that, under in vitro conditions, EgtD is not a substrate of protein kinase PknD.