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To accomplish its role of signaling hub in all Wnt signaling pathways, Dishevelled (DVL) protein needs to dynamically relocalize to the inner leaflet of the cellular plasma membrane (PM). Combined experimental and computational evidence showed that the binding of DVL to the PM is mainly driven by the electrostatic attraction between a stretch of positively charged amino acids located on the C-terminal DEP domain of DVL and anionic phospholipid species, with a striking preference for phosphatidic acid (PA). Here, by means of computational simulations and QCM-D experiments, we demonstrate that four recently identified phosphorylation sites on DEP domain, alter the electrostatic potential of the membrane binding interface, but do not prevent the recruitment to anionic membranes. On the contrary, the phosphorylated residues are involved in hydrogen bond and ion-mediated interactions with the lipid headgroup of PA. Our results suggest that the effect of phosphorylation on protein-membrane association could be counterintuitive and sensitive to changes in the local environment including specific lipids, salts, and pH.SIGNIFICANCEPhosphorylation regulates the cellular activity and localization of many peripheral proteins by, among others, decreasing the affinity for negatively charged membranes. Here, we report how phosphorylation affects the membrane interaction of DEP domain from Dishevelled protein, the intracellular signaling hub in Wnt pathways. We found that despite the negative charge induced by phosphorylation, DEP domain was steadily adsorbed to the surface of negatively charged PA-rich membranes, due to a dense network of cation-mediated interactions and hydrogen bonds.

Over the past decades an extensive effort has been made to provide a more comprehensive understanding of Wnt signaling, yet many regulatory and structural aspects remain elusive. Among these, the ability of Dishevelled (DVL) protein to relocalize at the plasma membrane is a crucial step in the activation of all Wnt pathways. The membrane binding of DVL was suggested to be mediated by the preferential interaction of its C-terminal DEP domain with phosphatidic acid (PA). However, due to the scarcity and fast turnover of PA, we investigated the role on the membrane association of other more abundant phospholipids. The combined results from computational simulations and experimental measurements with various model phospholipid membranes, demonstrate that the membrane binding of DEP/DVL constructs is governed by the concerted action of generic electrostatics and finely-tuned intermolecular interactions with individual lipid species. In particular, while we confirmed the strong preference for PA lipid, we also observed a weak but non-negligible affinity for phosphatidylserine, the most abundant anionic phospholipid in the plasma membrane, and phosphatidylinositol 4,5-bisphosphate. The obtained molecular insight into DEP-membrane interaction helps to elucidate the relation between changes in the local membrane composition and the spatiotemporal localization of DVL and, possibly, other DEP-containing proteins.

In line with the requirements of the circular economy, the European Union's waste management legislative changes also concern the treatment of sewage sludge. Although sewage sludge production cannot be prevented, its quantities may be reduced by the synergetic effect of energy recovery via choosing a proper technology. Sewage sludge is difficult to apply as fuel alone, because of its high moisture and ash content. However, its energy use will be increased by adding suitable waste materials (different types of plastics, waste tires and paper rejects). Most recently, the thermal utilization of sewage sludge via incineration or pyrolysis has grown in importance. This article describes the fuel parameters of particular waste materials and of their blends with sewage sludge in connection with laboratory-scale thermal decomposition in an inert atmosphere, for their potential use in a semi-pilot plant pyrolysis unit. For pyrolytic application, the results of thermogravimetric analysis are needed in order to know the maximal temperature of thermal decomposition in an inert atmosphere, maximal mass losses, and weight loss rates. The samples of different thermoplastics mixed with sewage sludge, and low-density polyethylene blends with sewage sludge, had the lowest residual masses (70-74%) and the highest weight loss rates (11-19%/min). On the other hand, the blend of polyester rejects from tire processing, paper rejects and sewage sludge had the second highest residual mass (60%) and the lowest weight loss rate (3%/min). Web of Science 11 4 art. no. 1610

Polychlorinated substances, polyaromatic hydrocarbons, heavy metals and pesticides are among the priority even at low concentrations. The problem, however, is that such low concentrations are impossible to measure using most available methods. This research focused on the determination of selected priority substances - heavy metals, namely lead and cadmium, in which the determination of Pb and Cd in wastewater by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was preceded by water sample pre-treatment. The paper deals with the influence of the pre-treatment on the resulting measured values. Two processes were selected as pre-treatment processes. The first pre-treatment procedure was a simple filtration using a filter paper for moderate filtration. As the second procedure, we applied decomposition of the sample by nitric acid in the open system. The pre-treated wastewater samples were subsequently examined using ICP-MS. Based on the obtained results, we can conclude that decomposition of the sample by nitric acid in the open system is a more suitable pre-treatment method for water samples. Zawartość substancje polichlorowanych, węglowodorów poliaromatycznych, metali ciężkich i pestycydów ma ogromne znaczenie nawet przy niskich stężeniach. Problem polega na tym, że niskich stężeń nie można zmierzyć przy użyciu większości dostępnych metod. Badania koncentrowały się na oznaczeniu wybranych substancji priorytetowych – metali ciężkich, a mianowicie ołowiu i kadmu, w których oznaczanie Pb i Cd w ściekach metodą indukcyjnie sprzężonej plazmowej spektrometrii masowej (ICP-MS) poprzedziło wstępne uzdatnianie próbki wody. Artykuł dotyczy wpływu obróbki wstępnej na uzyskane wartości pomiarowe. Dwa procesy wybrano jako procesy obróbki wstępnej. Pierwszą procedurą wstępnej obróbki była prosta filtracja z użyciem bibuły filtracyjnej do umiarkowanej filtracji. W drugiej procedurze zastosowano rozkład próbki kwasem azotowym w układzie otwartym. Wstępnie oczyszczone próbki ścieków zostały następnie zbadane przy użyciu ICP-MS. Na podstawie uzyskanych wyników stwierdzono, że rozkład próbki kwasem azotowym w układzie otwartym jest bardziej odpowiednią metodą wstępnej obróbki próbek wody. Web of Science 2 1 70 67

Besides other issues, the global pandemic caused by SARS CoV-2 also brought a number of water management questions which mainly concern the likelihood of virus spread through drinking water and possible contamination of wastewater. This paper reviews principal data on the virus and the recent course of the pandemics. It shows that there is no risk of the virus spread through drinking water and that drinking water disinfection is sufficiently effective. On the contrary, wastewater was observed for SARS CoV-2 RNA particles. As a result, a number of papers deal with research in the observation of the virus in wastewater, which may become an early-warning tool before an epidemic develops. The monitoring of the virus in wastewaters may also enable researchers to predict the course of Covid-19 illness rates in the future.

Tento článek představuje aplikaci ShinyItemAnalysis pro psychometrickou analýzu testů a jejich položek. ShinyItemAnalysis nabízí psychometrické modely v rámci grafického rozhraní pro volně šiřitelné statistické prostředí R a zpřístupňuje tak jeho funkcionalitu širší veřejnosti. Aplikace pokrývá širokou škálu psychometrických metod, od tradiční položkové analýzy až po složitější latentní modely, nabízí cvičné datové soubory, uvádí rovnice modelů, odhady parametrů a jejich interpretaci, jakož i vybraný zdrojový kód, a je tak vhodným nástrojem pro výuku psychometrických konceptů a jejich implementace v R. Aplikace však také nabízí možnost analýzy vlastních dat a generování reportů a aspiruje tak na to být jednoduchým nástrojem pro rutinní analýzu testů a jejich položek. Závěr článku ukazuje, že ShinyItemAnalysis je dostupným, flexibilním a uživatelsky příjemným nástrojem, který může pomoci tomu, aby se statistická analýza přijímacích i jiných znalostních či psychologických testů stala v praxi samozřejmou záležitostí.In this paper we introduce ShinyItemAnalysis application for psychometric analysis of educational and psychological tests and their items. ShinyItemAnalysis provides graphical interface and web framework to open source statistical software R and thus opens up its functionality to wide audience. Application covers broad range of methods and offers data examples, model equations, parameter estimates, interpretation of results, together with selected R code, and is thus suitable for teaching psychometric concepts with R. The application also aspires to be a simple tool for routine analysis by allowing the users to upload and analyze their own data and by generating analysis report. We conclude by arguing that psychometric analysis should be a routine part of test development in order to gather proofs of reliability and validity of the measurement. With example of admission test to medical faculty, we demonstrate how ShinyItemAnalysis may provide a simple and free tool to routinely analyze tests.

The solubilization of targeted compounds represents key criteria in the sophisticated field of medical chemistry but also in technical applications like scale removal. Especially, the simultaneous dissolution of two chemically different compounds remains challenging. Herein, macromolecular solubilizers are introduced for the simultaneous dissolution and encapsulation of poorly water‐soluble cholesterol and hydroxyapatite. The peptide‐based, amphiphilic block copolymers possess physicochemically disparate segments combined in one polymer chain as binding sites for hydrophobic as well as ionic materials. Small polymer libraries are synthesized and screened for structure–property relationships. Complementary analytical techniques suggest polymeric self‐assembly into spherical adaptive nanoparticles with the fundamental ability to passively absorb significant amounts of hydrophobic cholesterol up to 33 wt%. Furthermore, the additional incorporation of acidic domains enables the simultaneous dissolution of hydrophobic compounds and mineral phases such as hydroxyapatite. Ultimately, those nontoxic block copolymers can be used to solubilize and absorb other lipophilic and ionic compounds such as Sudan III dye and calcium ions. Such multifunctional nanomaterials have a wide range of direct application for simultaneous dissolution or delivery of hydrophobic molecules and cations resp. minerals for instance in the field of atherosclerosis. published

Background A wide variety of interventions exists in physical therapy (PT), but knowledge about their use across different geographical regions is limited. This study investigated the use of PT interventions in people with Multiple Sclerosis (MS) across Europe. It aimed to determine whether regions differ in applying interventions, and explore whether factors other than regions play a role in their use. Methods In an online cross-sectional survey, 212 respondents from 115 European workplaces providing PT services to people with MS representing 26 countries (four European regions) participated. Cluster analysis, Pearson Chi-squared test and a Poisson regression model were used to analyze the data. Results Thirteen of 45 listed PT interventions were used by more than 75% of centers, while nine interventions were used by less than 25%. For 12 interventions, regions differed markedly in their use. Cluster analysis of centers identified four clusters similar in their intervention use. Cluster assignment did not fully align with regions. While center region was important, center size, number and gender of physical therapists working in the center, and time since qualification also played a role. Cluster analysis exploring the use of the interventions provided the basis for a categorization of PT interventions in line with their primary focus: 1. Physical activity (fitness/endurance/resistance) training; 2. Neuroproprioceptive "facilitation/inhibition"; 3. Motor/skill acquisition (individualized therapy led); 4. Technology based interventions. Conclusions To our knowledge this is the first study that has explored this topic in MS. The results broaden our understanding of the different PT interventions used in MS, as well as the context of their use.

University admission exams belong to so-called high-stakes tests, i. e. tests with important consequences for the exam taker. Given the importance of the admission process for the applicant and the institution, routine evaluation of the admission tests and their items is desirable. In this work, we introduce a quick and efficient methodology and on-line tool for semi-real-time evaluation of admission exams and their items based on classical test theory (CTT) and item response theory (IRT) models. We generalize some of the traditional item analysis concepts to tailor them for specific purposes of the admission test. On example of medical school admission test we demonstrate how R-based web application may simplify admissions evaluation work-flow and may guarantee quick accessibility of the psychometric measures. We conclude that the presented tool is convenient for analysis of any admission or educational test in general.

A test may be unfair when students with the same knowledge but from different demographic groups perform differently on its items. Identifying and addressing this differential item functioning (DIF) helps ensure a fair, unbiased test. This Research Methods paper will help biology education researchers identify DIF items in their assessments., We provide a tutorial on differential item functioning (DIF) analysis, an analytic method useful for identifying potentially biased items in assessments. After explaining a number of methodological approaches, we test for gender bias in two scenarios that demonstrate why DIF analysis is crucial for developing assessments, particularly because simply comparing two groups’ total scores can lead to incorrect conclusions about test fairness. First, a significant difference between groups on total scores can exist even when items are not biased, as we illustrate with data collected during the validation of the Homeostasis Concept Inventory. Second, item bias can exist even when the two groups have exactly the same distribution of total scores, as we illustrate with a simulated data set. We also present a brief overview of how DIF analysis has been used in the biology education literature to illustrate the way DIF items need to be reevaluated by content experts to determine whether they should be revised or removed from the assessment. Finally, we conclude by arguing that DIF analysis should be used routinely to evaluate items in developing conceptual assessments. These steps will ensure more equitable—and therefore more valid—scores from conceptual assessments.

In this article, we present a new method for estimation of Item Response Function and for detection of uniform and non-uniform Differential Item Functioning (DIF) in dichotomous items based on Non-Linear Regression (NLR). Proposed method extends Logistic Regression (LR) procedure by including pseudoguessing parameter. NLR technique is compared to LR procedure and Lord’s and Raju’s statistics for three-parameter Item Response Theory (IRT) models in simulation study based on Graduate Management Admission Test. NLR shows superiority in power at low rejection rate over IRT methods and outperforms LR procedure in power for case of uniform DIF detection. Our research suggests that the newly proposed non-IRT procedure is an attractive and user friendly approach to DIF detection.

In this work we deal with survival models, when we consider that with positive probability some patients never relapse because they are cured. We focus on two-component mixture model and model with biological motivation. For each model, we derive estimate of probability of cure and estimate of survival function of time to relaps of uncured patients by maximum likelihood method. Further we consider, that both probability of cure and survival time can depend on regressors. Models are then compared through simulation study. 1