Pathological Insight into 5-HT2B Receptor Activation in Fibrosing Interstitial Lung Diseases

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 conditions, of which primarily idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, hypersensitivity pneumonitis, ILD associated with autoimmune diseases and sarcoidosis may present a progressive fibrosing (PF) phenotype. Despite different aetiology and histopathological patterns, the PF-ILDs have similarities regarding disease mechanisms with self-sustaining fibrosis, which suggests that the diseases may share common pathogenetic pathways. Previous studies show an enhanced activation of serotonergic signaling in pulmonary fibrosis, and the serotonin (5-HT)₂ receptors have been implicated to have important roles in observed profibrotic actions. Our research findings in support by others, demonstrate antifibrotic effects with 5-HT_2B receptor antagonists, alleviating several key events common for the fibrotic diseases such as myofibroblast differentiation and connective tissue deposition. In this review, we will address the potential role of 5-HT and in particular the 5-HT_2B receptors in three PF-ILDs: ILD associated with systemic sclerosis (SSc-ILD), ILD associated with rheumatoid arthritis (RA-ILD) and IPF. Highlighting the converging pathways in these diseases discloses the 5-HT_2B receptor as a potential disease target for PF-ILDs, which today have an urgent unmet need for therapeutic strategies.     

Validation of selected temperament and personality questionnaires for diagnosing drivers’ aptitude for safe driving. A Polish study

This paper presents the results of a study aimed at validating psychological questionnaires evaluating temperamental and personality features. It discusses their usefulness in diagnosing drivers’ aptitude for safe driving and working as professional drivers. Three psychological questionnaires were validated: the Formal Characteristics of Behaviour – Temperament Inventory (FCB-TI), the Eysenck Personality Questionnaire – Revised and Short Scale (EPQ-R (S)) and the Impulsiveness Questionnaire (IVE). Three groups of drivers (n = 246) aged 19–75 participated in the study. Group I (professional drivers; n = 96) and Group II (nonprofessional drivers; n = 75) had never been involved in road crashes, whereas Group III (nonprofessional drivers; n = 75) were offenders involved in fatal injury road crashes. Criterion-related validity, Cronbach's alpha and Guttman split-half reliability coefficient were in assessing the psychometric properties of the questionnaires. There were some significant differences between Groups II and III for most traits. However, contrary to expectations, higher Emotional Reactivity, Perseveration and lower Endurance as well as higher Neuroticism, Impulsiveness and Venturesomeness were determined for Group II than for Group III. Additionally, the temperament and personality profile of Group II turned out to be less fitted to the profile of safe drivers than that of Group III, whose profile was actually similar to that of Group I. This seems to result from a high tendency for a positive self-presentation among Group I and Group III (a significantly higher result on the Lie scale in comparison with Group II). The results suggest that if psychological tests are to decide on whether a person may be a professional driver or may drive vehicles, the three questionnaires (FCB-TI, EPQ-R(S) and IVE) do not provide a valid diagnosis of professional drivers’ aptitude because of drivers’ high tendency for positive self-presentation. However, they can be used in job counselling and in screening high-risk drivers.     

Compact DSOP and Partial DSOP Forms

Given a Boolean function f on n variables, a Disjoint Sum-of-Products (DSOP) of f is a set of products (ANDs) of subsets of literals whose sum (OR) equals f, such that no two products cover the same minterm of f. DSOP forms are a special instance of partial DSOPs, i.e. the general case where a subset of minterms must be covered exactly once and the other minterms (typically corresponding to don’t care conditions of f) can be covered any number of times. We discuss finding DSOPs and partial DSOPs with a minimal number of products, a problem theoretically connected with various properties of Boolean functions and practically relevant in the synthesis of digital circuits. Finding an absolute minimum is hard, in fact we prove that the problem of absolute minimization of partial DSOPs is NP-hard. Therefore it is crucial to devise a polynomial time heuristic that compares favorably with the known minimization tools. To this end we develop a further piece of theory starting from the definition of the weight of a cube c as a functions of the number of fragments induced on other cubes by the selection of c, and show how cube weights can be exploited for building a class of minimization heuristics for DSOP and partial DSOP synthesis. A set of experiments conducted on major benchmark functions show that our method, with a family of variants, always generates better results than the ones of previous heuristics, including the method based on a BDD representation of f.     

Electrochemical characterization of alternate conducting carbazole-bisthiophene units

An electrochemical and theoretical character of alternate copolymer of carbazole and bithiophene units was investigated. Polymerization is processed as two steps bielectronic oxidation of molecule. With monoelectronic oxidation is connected stable radical cation with spin located mainly on carbazole. The electrochemical properties of polymer are dependent on thickness of film deposited on electrode. In case of the thin layers one it is observed characteristic redox couple of carbazole oxidation to radical cation. Analysis of polymer behavior and results of spectrochemical measurements indicate on mixed type of electroconductivity.Molecular structures, HOMO-LUMO gaps and nature of highest occupied and lowest unoccupied molecular orbitals were also studied in presented work for oligomers ranging from monomer to octamer. The studies applied density functional theory (DFT).     

Andreas Ritter von Ettingshausen (1796–1878)

Abstract

Andreas Ritter von Ettingshausen (figure 1) was born on 25 November 1796 in Heidelberg where his father was stationed with the Austrian military headquarters. His father was frequently transferred from one place to another in the call of duty and the young Ettingshausen was just as frequently transferred from one school to another.     

Stabilization of pluronic gels in the presence of different polysaccharides

Several different polysaccharides have been added to pluronic F127 (poloxamer 407) gels to test their ability to stabilize the gels against dissolution in aqueous media over time. The studied polysaccharides include κ‐carrageenan, chitosan, hyaluronic acid, pectin, alginate, hydroxyethylcellulose, and ethyl(hydroxyethyl)cellulose. Although all the considered polysaccharides slowed down the dissolution time of the pluronic gels, unmodified polysaccharides only had a modest stabilization effect. However, hydrophobic modification of polysaccharides with a sufficiently long hydrocarbon chain (C₁₆) was found to partly prevent the gels from dissolving for more than 6 months. Shorter hydrocarbon chains did not have the same effect, even at high degrees of hydrophobicity. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40465.     

Mathematical modelling of adult hippocampal neurogenesis: effects of altered stem cell dynamics on cell counts and bromodeoxyuridine-labelled cells

In the adult hippocampus, neurogenesis—the process of generating mature granule cells from adult neural stem cells—occurs throughout the entire lifetime. In order to investigate the involved regulatory mechanisms, knockout (KO) experiments, which modify the dynamic behaviour of this process, were conducted in the past. Evaluating these KOs is a non-trivial task owing to the complicated nature of the hippocampal neurogenic niche. In this study, we model neurogenesis as a multicompartmental system of ordinary differential equations based on experimental data. To analyse the results of KO experiments, we investigate how changes of cell properties, reflected by model parameters, influence the dynamics of cell counts and of the experimentally observed counts of cells labelled by the cell division marker bromodeoxyuridine (BrdU). We find that changing cell proliferation rates or the fraction of self-renewal, reflecting the balance between symmetric and asymmetric cell divisions, may result in multiple time phases in the response of the system, such as an initial increase in cell counts followed by a decrease. Furthermore, these phases may be qualitatively different in cells at different differentiation stages and even between mitotically labelled cells and all cells existing in the system.