Scientific workflows with the jABC framework

The jABC is a framework for process modelling and execution according to the XMDD (eXtreme model-driven design) paradigm, which advocates the rigorous use of user-level models in the software development process and software life cycle. We have used the jABC in the domain of scientific workflows for more than a decade now—an occasion to look back and take stock of our experiences in the field. On the one hand, we discuss results from the analysis of a sample of nearly 100 scientific workflow applications that have been implemented with the jABC. On the other hand, we reflect on our experiences and observations regarding the workflow development process with the framework. We then derive and discuss ongoing further developments and future perspectives for the framework, all with an emphasis on simplicity for end users through increased domain specificity. Concretely, we describe how the use of the PROPHETS synthesis plugin can enable a semantics-based simplification of the workflow design process, how with the jABC4 and DyWA frameworks more attention is paid to the ease of data management, and how the Cinco SCCE Meta-Tooling Suite can be used to generate tailored workflow management tools.     

Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).     

Single-crystalline Te microtubes: Synthesis and NO2 gas sensor application

Tellurium tubular crystals were grown by direct thermal evaporation of tellurium metal in an inert atmosphere on quartz substrates at ambient pressure without employing any catalyst. Tellurium powder was evaporated by heating at 600 °C and was condensed at a substrate temperature of 300–350 °C in the downstream of argon gas at a flow rate of 100 mL/min. The structure and chemical composition of the as-synthesized samples were examined by X-ray diffraction analysis, scanning electron microscopy, energy-dispersive X-rays microanalysis and micro-Raman spectroscopy. Scanning electron microscopy images and X-ray diffraction patterns showed that the as-synthesized Te had a tubular single-crystalline morphology with a hexagonal cross-section. The Te microtubes were typically 0.5–6 mm long, 30–70 μm in external diameter, and 5–20 μm thick. NO₂ gas-sensing properties of the Te microtubes at room temperature were also investigated. They showed a promising sensitivity and response towards tested gas.     

Query representation and management in a multiparadigmatic visual query environment

We propose a framework for database querying providing the user with several interaction paradigms based on different (i.e., form-based, diagrammatic, iconic, and hybrid) visual representations of the database. A unified model, namely the Graph Model, is used as the common underlying model, in terms of which databases expressed in the most common data models can be easily converted. Graph Model databases can be queried by means of the multiparadigmatic interface. The semantics of the query operations is formally defined in terms of the Graphical Primitives. Such a formal approach enables the query manager to maintain the same query consistently in any representation. In the proposed multiparadigmatic environment, the user can switch from one interaction paradigm to another during query formulation, so that the most suitable query representation can be found.     

Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells

The carbazole compounds PK9320 (1-(9-ethyl-7-(furan-2-yl)-9H-carbazol-3-yl)-N-methylmethanamine) and PK9323 (1-(9-ethyl-7-(thiazol-4-yl)-9H-carbazol-3-yl)-N-methylmethanamine), second-generation analogues of PK083 (1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine), restore p53 signaling in Y220C p53-mutated cancer cells by binding to a mutation-induced surface crevice and acting as molecular chaperones. In the present paper, these three molecules have been tested for mutant p53-independent genotoxic and epigenomic effects on wild-type p53 MCF-7 breast adenocarcinoma cells, employing a combination of Western blot for phospho-γH2AX histone, Comet assay and methylation-sensitive arbitrarily primed PCR to analyze their intrinsic DNA damage-inducing and DNA methylation-changing abilities. We demonstrate that small modifications in the substitution patterns of carbazoles can have profound effects on their intrinsic genotoxic and epigenetic properties, with PK9320 and PK9323 being eligible candidates as “anticancer compounds” and “anticancer epi-compounds” and PK083 a “damage-corrective” compound on human breast adenocarcinoma cells. Such different properties may be exploited for their use as anticancer agents and chemical probes.     

Impact of Androgen Receptor Activity on Prostate-Specific Membrane Antigen Expression in Prostate Cancer Cells

Prostate-specific membrane antigen (PSMA) is an essential molecular regulator of prostate cancer (PCa) progression coded by the FOLH1 gene. The PSMA protein has become an important factor in metastatic PCa diagnosis and radioligand therapy. However, low PSMA expression is suggested to be a resistance mechanism to PSMA-based imaging and therapy. Clinical studies revealed that androgen receptor (AR) inhibition increases PSMA expression. The mechanism has not yet been elucidated. Therefore, this study investigated the effect of activation and inhibition of androgen signaling on PSMA expression levels in vitro and compared these findings with PSMA levels in PCa patients receiving systemic therapy. To this end, LAPC4, LNCaP, and C4-2 PCa cells were treated with various concentrations of the synthetic androgen R1881 and antiandrogens. Changes in FOLH1 mRNA were determined using qPCR. Open access databases were used for ChIP-Seq and tissue expression analysis. Changes in PSMA protein were determined using western blot. For PSMA staining in patients’ specimens, immunohistochemistry (IHC) was performed. Results revealed that treatment with the synthetic androgen R1881 led to decreased FOLH1 mRNA and PSMA protein. This effect was partially reversed by antiandrogen treatment. However, AR ChIP-Seq analysis revealed no canonical AR binding sites in the regulatory elements of the FOLH1 gene. IHC analysis indicated that androgen deprivation only resulted in increased PSMA expression in patients with low PSMA levels. The data demonstrate that AR activation and inhibition affects PSMA protein levels via a possible non-canonical mechanism. Moreover, analysis of PCa tissue reveals that low PSMA expression rates may be mandatory to increase PSMA by androgen deprivation.     

Fatty Acid Amide Hydrolase (FAAH) Inhibition Plays a Key Role in Counteracting Acute Lung Injury

Acute lung injury (ALI) is a group of lung illnesses characterized by severe inflammation, with no treatment. The fatty acid amide hydrolase (FAAH) enzyme is an integral membrane protein responsible for the hydrolysis of the main endocannabinoids, such as anandamide (AEA). In pre-clinical pain and inflammation models, increasing the endogenous levels of AEA and other bioactive fatty acid amides (FAAs) via genetic deletion or the pharmacological inhibition of FAAH produces many analgesic benefits in several different experimental models. To date, nobody has investigated the role of FAAH inhibition on an ALI mouse model. Mice were subjected to a carrageenan injection and treated orally 1 h after with the FAAH inhibitor URB878 dissolved in a vehicle consisting of 10% PEG-400, 10% Tween-80 and 80% saline at different doses: The inhibition of FAAH activity was able to counteract not only the CAR-induced histological alteration, but also the cascade of related inflammatory events. URB878 clears the way for further studies based on FAAH inhibition in acute lung pathologies.     

Diffusion coefficient measurements in consolidated clay by RBS micro-scale profiling

The determination of radionuclide diffusion coefficients is necessary for performance assessment of clay formations as a geological barrier for deep geological repositories for high-level radioactive waste.Diffusion coefficients of elements that are retained by the clay and have short diffusion lengths are quite difficult to measure over reasonable time spans, by conventional techniques.This paper presents a novel application of the Rutherford Backscattering Spectrometry (RBS) technique to determine solute diffusion coefficients in consolidated clays. The RBS technique was selected because it allows the measurement of concentration profiles at short range distances (μm).The proposed methodology was tested on the Opalinus clay (OPA) from the Swiss Jura, where the Mont Terri underground laboratory is located. The diffusion of four elements with different adsorption behaviors onto the clay was analyzed: Eu and U as adsorbing elements, Sr as low adsorbing, and Re as a non-adsorbing element with anionic behavior.Apparent diffusion coefficients (D_a) could be experimentally determined for Re, Eu and U after a few days of diffusion time, while for Sr it was only possible to estimate a lower limit for the diffusion coefficient. The uncertainties of the proposed methodology are discussed on the basis of sensitivity studies.