LTSmin: high-performance language-independent model checking

In recent years, the LTSmin model checker has been extended with support for several new modelling languages, including probabilistic (Mapa) and timed systems (Uppaal). Also, connecting additional language front-ends or ad-hoc state-space generators to LTSmin was simplified using custom C-code. From symbolic and distributed reachability analysis and minimisation, LTSmin’s functionality has developed into a model checker with multi-core algorithms for on-the-fly LTL checking with partial-order reduction, and multi-core symbolic checking for the modal μ calculus, based on the multi-core decision diagram package Sylvan.\ud In LTSmin, the modelling languages and the model checking algorithms are connected through a Partitioned Next-State Interface (Pins), that allows to abstract away from language details in the implementation of the analysis algorithms and on-the-fly optimisations. In the current paper, we present an overview of the toolset and its recent changes, and we demonstrate its performance and versatility in two case studies

Simulation of organ patterning on the floral meristem using a polar auxin transport model

An intriguing phenomenon in plant development is the timing and positioning of lateral organ initiation, which is a fundamental aspect of plant architecture. Although important progress has been made in elucidating the role of auxin transport in the vegetative shoot to explain the phyllotaxis of leaf formation in a spiral fashion, a model that explains the whorled organ patterning in the expanding floral meristem is not available yet. We present an initial simulation approach to study the mechanisms that are expected to play an important role. Starting point is a confocal imaging study of Arabidopsis floral meristems at consecutive time points during flower development. These images reveal auxin accumulation patterns at the positions of the organs, which strongly suggests that the role of auxin in the floral meristem is similar to the role it plays in the shoot apical meristem. This is the basis for a simulation study of auxin transport through a growing floral meristem, which may answer the question whether auxin transport can in itself be responsible for the typical whorled floral pattern. We combined a cellular growth model for the meristem with a polar auxin transport model. The model predicts that sepals are initiated by auxin maxima arising early during meristem outgrowth. These form a pre-pattern relative to which a series of smaller auxin maxima are positioned, which partially overlap with the anlagen of petals, stamens, and carpels. We adjusted the model parameters corresponding to properties of floral mutants and found that the model predictions agree with the observed mutant patterns. The predicted timing of the primordia outgrowth and the timing and positioning of the sepal primordia show remarkable similarities with a developing flower in nature

Role of metformin in diabetes treatment--is metformin falling from grace?

Two recent meta-analyses focused on the risk-benefit ratio of metformin in the treatment of type 2 diabetes mellitus. Both studies conclude that the risk-benefit ratio of metformin monotherapy or combined with insulin is uncertain. In our opinion, the interpretation of the known literature in these meta-analyses could be flawed. To ascertain the effects of metformin on cardiovascular end-points, a follow-up period of at least 8 years proved necessary. However, these meta-analyses included a number of studies with a limited follow-up period, thus impairing the possibility to make a proper comparison of the long-term effects of metformin. In addition, one meta-analysis based the weight of included studies on the number of events in all studies, including two safety studies, as opposed to the number of studied patients.</p

Salinity-induced increase of the hydraulic conductivity in the hyporheic zone of coastal wetlands

In coastal zones globally, salinization is rapidly taking place due to the combined effects of sea level rise, land subsidence, altered hydrology, and climate change. Although increased salinity levels are known to have a great impact on both biogeochemical and hydrological processes in aquatic sediments, only few studies have included both types of processes and their potential interactions. In the present paper, we used a controlled 3-year experimental mesocosm approach to test salinity induced interactions and discuss mechanisms explaining the observed hydrological changes. Surface water salinity was experimentally increased from 14 to 140 mmol Cl per L (0.9 and 9 PSU) by adding sea salt which increased pore water salinity but also increased sulfate reduction rates, leading to higher sulfide, and lower methane concentrations. By analyzing slug test data with different slug test analysis methods, we were able to show that hydraulic conductivity of the hyporheic zone increased 2.8 times by salinization. Based on our hydrological and biogeochemical measurements, we conclude that the combination of pore dilation and decreased methane production rates were major controls on the observed increase in hydraulic conductivity. The slug test analysis method comparison allowed to conclude that the adjusted Bouwer and Rice method results in the most reliable estimate of the hydraulic conductivity for hyporheic zones. Our work shows that both physical and biogeochemical processes are vital to explain and predict hydrological changes related to the salinization of hyporheic zones in coastal wetlands and provides a robust methodological approach for doing so

Hogere zoutconcentratie leidt tot een verhoogde waterdoorlatendheid van de waterbodem

Door de combinatie van klimaatverandering (zeespiegelstijging en langere droogteperiodes) en ontwatering voor landbouw neemt de kans op stijgende zoutconcentratiesin het oppervlaktewater in laag Nederland toe. Hoewel bekend is dat dit chemische enfysische effecten kan hebben, is de interactie tussen fysische en biogeochemische processen onderbelicht gebleven. In dit artikel wordt een veldexperiment gepresenteerdwaarin de effecten van verhoogde zoutconcentraties op de combinatie van chemischeen fysische processen in een voormalig brak laagveen zijn bestudeerd. Met behulp vanbiogeochemische analyses en de omgekeerde boorgatmethode in de waterbodem wordtaangetoond dat een verhoogde zoutconcentratie in het oppervlaktewater kan leiden toteen verhoogde waterdoorlatendheid van de waterbodem

Factors influencing submerged macrophyte presence in fresh and brackish eutrophic waters and their impact on carbon emissions

In agricultural landscapes of North-Western Europe, the majority of water bodies do not meet the targets set by the European Water Framework Directive due to a lack of submerged macrophytes and associated biodiversity. These eutrophic waters can also be a substantial source of methane (CH4) and carbon dioxide (CO2) to the atmosphere. Here we present a two-year field experiment on the island of Goeree-Overflakkee (southwest Netherlands), conducted in six drainage ditches varying in salinity, where we monitored four permanent plots per ditch and varied the presence of both fish and macrophytes. We aimed to: 1) investigate factors limiting submerged macrophyte growth, focussing on exclusion of grazing pressure and bioturbation by fish; and 2) quantify the CO2 and CH4 emission under these conditions. Even in highly eutrophic, semi turbid ditches with fluctuating salinity levels and sulphide presence in the root zone, submerged macrophytes established successfully after introduction when the influence of grazing and bioturbation by fish was excluded. In the exclosures, diffusive CH4 and CO2 emissions, but not ebullitive CH4 emissions were significantly reduced. The spontaneous development of submerged macrophytes in the exclosures without macrophyte introduction underlined the effect of grazing and bioturbation by fish and suggest that abiotic conditions did not hamper submerged macrophyte development. Our results provide important insights into the influential factors for submerged macrophyte development and potential for future management practices. Large-scale fish removal may stimulate submerged macrophyte growth and reduce methane emissions, albeit that the macrophyte diversity will likely stay low in our study region due to fluctuating salinity and eutrophic conditions.</p

Association of epicardial adipose tissue with different stages of coronary artery disease:A cross-sectional UK Biobank cardiovascular magnetic resonance imaging substudy

Objective: Increased epicardial adipose tissue (EAT) has been identified as a risk factor for the development of coronary artery disease (CAD). However, the exact role of EAT in the development of CAD is unclear. This study aims to compare EAT volumes between healthy controls and individuals with stable CAD and a history of myocardial infarction (MI). Furthermore, associations between clinical and biochemical parameters with EAT volumes are examined.& nbsp;Methods: This retrospective cross-sectional study included 171 participants from the United Kingdom Biobank (56 healthy controls; 60 stable CAD; 55 post MI), whom were balanced for age, sex and body mass index (BMI). EAT volumes were quantified on end-diastolic cardiac magnetic resonance (CMR) imaging short-axis slices along the left and right ventricle and indexed for body surface area (iEAT) and iEAT volumes were compared between groups.& nbsp;Results: iEAT volumes were comparable between control, CAD and MI cases (median [IQR]: 66.1[54.4-77.0] vs. 70.9[55.8-85.5] vs. 67.6[58.6-82.3] mL/m(2), respectively (p > 0.005 for all). Increased HDL-cholesterol was associated with decreased iEAT volume (8 =-14.8, CI =-24.6 to-4.97, p = 0.003) and suggestive associations (P-value = 0.005) were observed between iEAT and triglycerides (beta = 3.26, CI = 0.42 to 6.09, p = 0.02), Apo-lipoprotein A (beta =-16.3, CI =-30.3 to-2.24, p = 0.02) and LDL-cholesterol (beta = 3.99, CI =-7.15 to-0.84, p = 0.01).& nbsp;Conclusions: No significant differences in iEAT volumes were observed between patients with CAD, MI and healthy controls. Our results indicate the importance of correcting for confounding by CVD risk factors, including circulating lipid levels, when studying the relationship between EAT volume and CAD. Further mechanistic studies on causal pathways and the role of EAT composition are warranted