Do you really mean what you actually enforced?

In their works on the theoretical side of Polymer, Ligatti and his co-authors have identified a new class of enforcement mechanisms based on the notion of edit automata that can transform sequences and enforce more than simple safety properties. We show that there is a gap between the edit automata that one can possibly write (e.g., by Ligatti et?al in their IJIS running example) and the edit automata that are actually constructed according the theorems from Ligatti??s IJIS paper or from Talhi et?al. ??Ligatti??s automata?? are just a particular kind of edit automata. Thus, we re-open a question which seemed to have received a definitive answer: you have written your security enforcement mechanism (aka your edit automata); does it really enforce the security policy you wanted?     

Investigation of Bemethyl Biotransformation Pathways by Combination of LC–MS/HRMS and In Silico Methods

Bemethyl is an actoprotector, an antihypoxant, and a moderate psychostimulant. Even though the therapeutic effectiveness of bemethyl is well documented, there is a gap in knowledge regarding its metabolic products and their quantitative and qualitative characteristics. Since 2018, bemethyl is included to the Monitoring Program of the World Anti-Doping Agency, which highlights the challenge of identifying its urinary metabolites. The objective of the study was to investigate the biotransformation pathways of bemethyl using a combination of liquid chromatography-high-resolution mass spectrometry and in silico studies. Metabolites were analyzed in a 24 h rat urine collected after oral administration of bemethyl at a single dose of 330 mg/kg. The urine samples were prepared for analysis by a procedure developed in the present work and analyzed by high performance liquid chromatography–tandem mass spectrometry. For the first time, nine metabolites of bemethyl with six molecular formulas were identified in rat urine. The most abundant metabolite was a benzimidazole–acetylcysteine conjugate; this biotransformation pathway is associated with the detoxification of xenobiotics. The BioTransformer and GLORY computational tools were used to predict bemethyl metabolites in silico. The molecular docking of bemethyl and its derivatives to the binding site of glutathione S-transferase has revealed the mechanism of bemethyl conjugation with glutathione. The findings will help to understand the pharmacokinetics and pharmacodynamics of actoprotectors and to improve antihypoxant and adaptogenic therapy.     

Auxin and Root Gravitropism: Addressing Basic Cellular Processes by Exploiting a Defined Growth Response

Root architecture and growth are decisive for crop performance and yield, and thus a highly topical research field in plant sciences. The root system of the model plant Arabidopsis thaliana is the ideal system to obtain insights into fundamental key parameters and molecular players involved in underlying regulatory circuits of root growth, particularly in responses to environmental stimuli. Root gravitropism, directional growth along the gravity, in particular represents a highly sensitive readout, suitable to study adjustments in polar auxin transport and to identify molecular determinants involved. This review strives to summarize and give an overview into the function of PIN-FORMED auxin transport proteins, emphasizing on their sorting and polarity control. As there already is an abundance of information, the focus lies in integrating this wealth of information on mechanisms and pathways. This overview of a highly dynamic and complex field highlights recent developments in understanding the role of auxin in higher plants. Specifically, it exemplifies, how analysis of a single, defined growth response contributes to our understanding of basic cellular processes in general.     

Anisotropic Properties of Quasi-1D In4Se3: Mechanical Exfoliation,Electronic Transport,and Polarization-Dependent Photoresponse

Theoretical and experimental investigations of various exfoliated samples taken from layered In₄Se₃ crystals are performed. In spite of the ionic character of interlayer interactions in In₄Se₃ and hence much higher calculated cleavage energies compared to graphite, it is possible to produce few-nanometer-thick flakes of In₄Se₃ by mechanical exfoliation of its bulk crystals. The In₄Se₃ flakes exfoliated on Si/SiO₂ have anisotropic electronic properties and exhibit field-effect electron mobilities of about 50 cm² V⁻¹ s⁻¹ at room temperature, which are comparable with other popular transition metal chalcogenide (TMC) electronic materials, such as MoS₂ and TiS₃. In₄Se₃ devices exhibit a visible range photoresponse on a timescale of less than 30 ms. The photoresponse depends on the polarization of the excitation light consistent with symmetry-dependent band structure calculations for the most expected ac cleavage plane. These results demonstrate that mechanical exfoliation of layered ionic In₄Se₃ crystals is possible, while the fast anisotropic photoresponse makes In₄Se₃ a competitive electronic material, in the TMC family, for emerging optoelectronic device applications.     

Review: Influence of 25(OH)D Blood Concentration and Supplementation during Pregnancy on Preeclampsia Development and Neonatal Outcomes

Briefly, 25-hydroxyvitamin D (25(OH)D) plays an essential role in embryogenesis and the course of intra- and postnatal periods and is crucially involved in the functioning of the mother–placenta–fetus system. The low quantity of 25(OH)D during pregnancy can lead to an elevated risk for preeclampsia occurrence. Despite the numerous studies on the association of 25(OH)D deficiency and preeclampsia development, the current research on this theme is contradictory. In this review, we summarize and analyze study data on the effects of 25(OH)D deficiency and supplementation on pregnancy, labor, and fetal and neonatal outcomes.     

Protein Expression of Angiotensin-Converting Enzyme 2 (ACE2) is Upregulated in Brains with Alzheimer’s Disease

Alzheimer’s disease is a chronic neurodegenerative disorder and represents the main cause of dementia globally. Currently, the world is suffering from the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. In COVID-19, neurological manifestations have been reported to occur. The present study demonstrates that the protein expression level of ACE2 is upregulated in the brain of patients with Alzheimer’s disease. The increased ACE2 expression is not age-dependent, suggesting the direct relationship between Alzheimer’s disease and ACE2 expression. Oxidative stress has been implicated in the pathogenesis of Alzheimer’s disease, and brains with the disease examined in this study also exhibited higher carbonylated proteins, as well as an increased thiol oxidation state of peroxiredoxin 6 (Prx6). A moderate positive correlation was found between the increased ACE2 protein expression and oxidative stress in brains with Alzheimer’s disease. In summary, the present study reveals the relationships between Alzheimer’s disease and ACE2, the receptor for SARS-CoV-2. These results suggest the importance of carefully monitoring patients with both Alzheimer’s disease and COVID-19 in order to identify higher viral loads in the brain and long-term adverse neurological consequences.     

miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer

Background: Dissemination of breast cancer (BC) cells through the hematogenous or lymphogenous vessels leads to metastatic disease in one-third of BC patients. Therefore, we investigated the new prognostic features for invasion and metastasis. Methods: We evaluated the expression of miRNAs and epithelial-to-mesenchymal transition (EMT) genes in relation to CDH1/E-cadherin changes in samples from 31 patients with invasive ductal BC including tumor centrum (TU-C), tumor invasive front (TU-IF), lymph node metastasis (LNM), and CD45-depleted blood (CD45-DB). Expression of miRNA and mRNA was quantified by RT-PCR arrays and associations with clinico-pathological characteristics were statistically evaluated by univariate and multivariate analysis. Results: We did not verify CDH1 regulating associations previously described in cell lines. However, we did detect extremely high ZEB1 expression in LNMs from patients with distant metastasis, but without regulation by miR-205-5p. Considering the ZEB1 functions, this overexpression indicates enhancement of metastatic potential of lymphogenously disseminated BC cells. In CD45-DB samples, downregulated miR-205-5p was found in those expressing epithelial and/or mesenchymal markers (CTC+) that could contribute to insusceptibility and survival of hematogenously disseminated BC cells mediated by increased expression of several targets including ZEB1. Conclusions: miR-205-5p and potentially ZEB1 gene are promising candidates for markers of metastatic potential in ductal BC.     

Citation count prediction as a link prediction problem

The citation count is an important factor to estimate the relevance and significance of academic publications. However, it is not possible to use this measure for papers which are too new. A solution to this problem is to estimate the future citation counts. There are existing works, which point out that graph mining techniques lead to the best results. We aim at improving the prediction of future citation counts by introducing a new feature. This feature is based on frequent graph pattern mining in the so-called citation network constructed on the basis of a dataset of scientific publications. Our new feature improves the accuracy of citation count prediction, and outperforms the state-of-the-art features in many cases which we show with experiments on two real datasets.