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Molecular profiling of small extracellular vesicles (sEV) isolated from plasma of cancer patients emerges as promising strategy for biomarkers discovery. We investigated the proteomic profiles of sEV immunoselected using anti‐CSPG4 antibodies from 15 melanoma patients’ plasma. The proteomes of sEV separated into melanoma cell‐derived (MTEX) and non‐malignant cell‐derived (NMTEX) were compared using high‐resolution mass spectrometry. Paired analysis identified the MTEX‐associated profile of 16 proteins that discriminated MTEX from NMETEX. We also identified the MTEX profile that discriminated between seven patients with no evidence of melanoma (NED) after therapy and eight with progressive disease (PD). Among 75 MTEX proteins overexpressed in PD patients, PDCD6IP (ALIX) had the highest discriminating value, while CNTN1 (contactin‐1) was upregulated only in MTEX of NED patients. This is the first report documenting that proteomes of tumour‐derived sEV in patients’ plasma discriminate cancer from non‐cancer and identify proteins with potential to serve as prognostic biomarkers in melanoma.

The primary diagnosis of thyroid tumors based on histopathological patterns can be ambiguous in some cases, so proper classification of thyroid diseases might be improved if molecular biomarkers support cytological and histological assessment. In this work, tissue microarrays representative for major types of thyroid malignancies&mdash, papillary thyroid cancer (classical and follicular variant), follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer&mdash, and benign thyroid follicular adenoma and normal thyroid were analyzed by mass spectrometry imaging (MSI), and then different computation approaches were implemented to test the suitability of the registered profiles of tryptic peptides for tumor classification. Molecular similarity among all seven types of thyroid specimens was estimated, and multicomponent classifiers were built for sample classification using individual MSI spectra that corresponded to small clusters of cells. Moreover, MSI components showing the most significant differences in abundance between the compared types of tissues detected and their putative identity were established by annotation with fragments of proteins identified by liquid chromatography-tandem mass spectrometry in corresponding tissue lysates. In general, high accuracy of sample classification was associated with low inter-tissue similarity index and a high number of components with significant differences in abundance between the tissues. Particularly, high molecular similarity was noted between three types of tumors with follicular morphology (adenoma, follicular cancer, and follicular variant of papillary cancer), whose differentiation represented the major classification problem in our dataset. However, low level of the intra-tissue heterogeneity increased the accuracy of classification despite high inter-tissue similarity (which was exemplified by normal thyroid and benign adenoma). We compared classifiers based on all detected MSI components (n = 1536) and the subset of the most abundant components (n = 147). Despite relatively higher contribution of components with significantly different abundance and lower overall inter-tissue similarity in the latter case, the precision of classification was generally higher using all MSI components. Moreover, the classification model based on individual spectra (a single-pixel approach) outperformed the model based on mean spectra of tissue cores. Our result confirmed the high feasibility of MSI-based approaches to multi-class detection of cancer types and proved the good performance of sample classification based on individual spectra (molecular image pixels) that overcame problems related to small amounts of heterogeneous material, which limit the applicability of classical proteomics.

The objective of this study was to investigate how daily wear time (DWT) influences class II malocclusion treatment efficiency.The study group consisted of 55 patients (mean age 10.4 years) diagnosed with a class II/1 malocclusion. Twin block appliances, with built-in Theramon® microsensors (MC Technology, Hargelsberg, Austria) to monitor patients' cooperation (daily wear time assessment), were used for treatment. Cephalograms were taken and the following initial and final measurements were compared: Co-Gn, Co-Go, Co-Olp, Pg-Olp, WITS, SNA, SNB, ANB, Co-Go-Me, overjet, molar and canine relationships. The Shapiro-Wilk test, Wilcoxon signed-rank test, Student's t-test, Levene's test, Mann-Whitney U test, Kruskal-Wallis test, χDWT was very highly positively correlated with change of the Pg-Olp parameter and highly with an improvement in the ANB, SNA, and SNB angles, an increase in the WITS parameter and an increase in Co-Gn distance. DWTs 7.5 h correlated with significantly less improvement of the investigated variables. However, DWT 7.5 h did not significantly correlate with the improvement of the overjet and most of the linear parameters in the mandible. The ROC curve and its AUC (area under curve) allowed the determination of a DWT of 7 h and 48 min to be capable of establishing a class I relationship with 83% probability.Class II treatment efficiency was influenced by DWT; an 8 h threshold value had an 83% probability of establishing a class I relationship.ZIELSETZUNG: Ziel dieser Studie war es zu untersuchen, wie die tägliche Tragezeit (DWT) die Effizienz der Behandlung von Klasse-II-Malokklusionen beeinflusst.Die Studiengruppe bestand aus 55 Patienten (Durchschnittsalter 10,4 Jahre), bei denen eine Klasse-II/1-Malokklusion diagnostiziert wurde. Für die Behandlung wurden Twin-Block-Apparaturen mit eingebauten Theramon®-Mikrosensoren (MC Technology, Hargelsberg, Österreich) zur Überwachung der Mitarbeit der Patienten (tägliche Tragezeitbewertung) verwendet. Es wurden Kephalogramme aufgenommen und die folgenden Anfangs- und Endmessungen verglichen: Co-Gn, Co-Go, Co-Olp, Pg-Olp, WITS, SNA, SNB, ANB, Co-Go-Me, Overjet, Molaren- und Eckzahnbeziehungen. Der Shapiro-Wilk-Test, der Wilcoxon-Vorzeichen-Rang-Test, der Student-t-Test, der Levene-Test, der Mann-Whitney-U-Test, der Kruskal-Wallis-Test, der χDie DWT korrelierte sehr stark positiv mit der Veränderung des Pg-Olp-Parameters, hoch mit einer Verbesserung der ANB-, SNA- und SNB-Winkel, mit einer Erhöhung des WITS-Parameters und mit einer Erhöhung des Co-Gn-Abstands. DWTs 7.5 h korrelierten mit deutlich weniger Verbesserung der untersuchten Variablen. DWTs 7.5 h korrelierten jedoch nicht signifikant mit der Verbesserung des Overjet und der meisten linearen Parameter im Unterkiefer. Mithilfe der ROC-Kurve und ihrer AUC („area under curve“) konnte bei einer DWT von 7 h und 48 min mit 83%iger Wahrscheinlichkeit ein Zusammenhang der Klasse I festgestellt werden.Die Effizienz der Klasse-II-Behandlung wurde durch die DWT beeinflusst; ein Schwellenwert von 8 h war mit 83%iger Wahrscheinlichkeit in der Lage, eine Klasse-I-Beziehung zu etablieren.

Bacterial alginate initially consists of 1-4-linked beta-D-mannuronic acid residues (M) which can be later epimerized to alpha-L-guluronic acid (G). The family of AlgE mannuronan C-5-epimerases from Azotobacter vinelandii has been extensively studied, and three genes putatively encoding AlgE-type epimerases have recently been identified in the genome of Azotobacter chroococcum. The three A. chroococcum genes, here designated AcalgE1, AcalgE2 and AcalgE3, were recombinantly expressed in Escherichia coli and the gene products were partially purified. The catalytic activities of the enzymes were stimulated by the addition of calcium ions in vitro. AcAlgE1 displayed epimerase activity and was able to introduce long G-blocks in the alginate substrate, preferentially by attacking M residues next to pre-existing G residues. AcAlgE2 and AcAlgE3 were found to display lyase activities with a substrate preference toward M-alginate. AcAlgE2 solely accepted M residues in the positions - 1 and + 2 relative to the cleavage site, while AcAlgE3 could accept either M or G residues in these two positions. Both AcAlgE2 and AcAlgE3 were bifunctional and could also catalyze epimerization of M to G. Together, we demonstrate that A. chroococcum encodes three different AlgE-like alginate-modifying enzymes and the biotechnological and biological impact of these findings are discussed. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

The paper presents a novel mathematical model of coupled hygro-thermo-mechanical processes in a porous material, partially saturated with liquid water and exposed to temperatures below the freezing point of pore water. Water – ice phase change is modelled by means of a non-equilibrium approach considering both water supercooling and a hysteresis of ice content during freezing and thawing of moist porous materials. The hysteresis results in different crystallization pressure and material strains during freezing and thawing processes at a given temperature. The latter effect is modelled by means of the effective stress principle, considering crystallization pressure of ice in the material pores. Methods used for discretization of the model equations and their numerical solution are described. The model is applied for solving the numerical example dealing with laboratory Dynamic Mechanical Analysis test of two different cement mortars saturated with water and exposed to temperatures below the freezing point of water (down to −15 °C) where hysteresis of strains was observed. The results are used for experimental validation of the proposed model. Then, for a 1-D case concerning water freezing-thawing of a wall, the effects on the simulation results of the phase-change model parameters, of the material hygro-thermal state, of the supercooling phenomenon and finally of the rate of temperature variation, are analyzed and discussed.

Additional file 1: Statistical analysis [51]. Table S1. Holm-Šídák pairwise multiple comparison of the strains testing the effect of mutations on the production of model proteins. Figure S1. The GM-CSF data calculated per OD600 unit. Table S2. Oligonucleotides used in this study. Table S3. DNA sequences of the genes encoding the model proteins used in this study. Figure S2. SDS-PAGE of reduced periplasmic and cytoplasmic samples (10x diluted) of scFv173-2-5-AP producing strains. Figure S3. SDS-PAGE of reduced periplasmic and cytoplasmic samples (10x diluted) of GM-CSF producing strains.

A wide set of 65 diverse Ru metathesis catalysts was investigated in the ethenolysis reaction of biosourced ethyl oleate to allow the comparison between the catalyst structure and its activity and selectivity. Handling of the oleic substrate, weighing of the catalysts, and charging the reactor were done in air, with exclusion of a glovebox or Schlenk techniques. A catalyst bearing the unsymmetrical N-heterocyclic ligand featuring a thiophene fragment (Ru-63) was selected to offer the best combination between high selectivity and sufficient activity under conditions mimicking oil industry practice. A proof-of-concept large-scale ethenolysis experiment was also done with the selected catalyst to prove its high selectivity at the 1 L scale reaction with a 90% pure non-distilled substrate.

The article addresses the problem of Arendt’s criticism of human rights contained in her work “The Origins of Totalitarianism”. The criticism consists of three basic objections regarding: (1) the powerlessness of human rights; (2) the threats that human rights pose to politics; and (3) the problem of egalitarianism, characteristic of human rights, which may lead to the questioning of the human ability to act, which requires specific culture and competence from participants. In addition to reconstructing Arendt’s allegations regarding human rights, the article raises the problem of possible criticism directed against these allegations.

Cet ouvrage est une reedition de celui de 1999 intitule Pour une ethique de la mediation : Le sens des pratiques culturelles. Cette nouvelle parution, avec son remaniement – dix chapitres au lieu de douze, ordonnes differemment – et ses enrichissements, trouve sa raison d’etre dans le fait que durant ces vingt dernieres annees, l’usage du syntagme « mediation culturelle » en France s’est etendu a de nombreux domaines, et que ses emplois interrogent la pertinence de la notion dans les discours...

Identification of biomarkers for molecular classification of cancer and for differentiation between cancerous and normal epithelium remains a vital issue in the field of head and neck cancer. Here we aimed to compare the ability of proteome and lipidome components to discriminate oral cancer from normal mucosa. Tissue specimens including squamous cell cancer and normal epithelium were analyzed by MALDI mass spectrometry imaging. Two molecular domains of tissue components were imaged in serial sections—peptides (resulting from trypsin-processed proteins) and lipids (primarily zwitterionic phospholipids), then regions of interest corresponding to cancer and normal epithelium were compared. Heterogeneity of cancer regions was higher than the heterogeneity of normal epithelium, and the distribution of peptide components was more heterogeneous than the distribution of lipid components. Moreover, there were more peptide components than lipid components that showed significantly different abundance between cancer and normal epithelium (median of the Cohen’s effect was 0.49 and 0.31 in case of peptide and lipid components, respectively). Multicomponent cancer classifier was tested (vs. normal epithelium) using tissue specimens from three patients and then validated with a tissue specimen from the fourth patient. Peptide-based signature and lipid-based signature allowed cancer classification with a weighted accuracy of 0.85 and 0.69, respectively. Nevertheless, both classifiers had very high precision (0.98 and 0.94, respectively). We concluded that though molecular differences between cancerous and normal mucosa were higher in the proteome domain than in the analyzed lipidome subdomain, imaging of lipidome components also enabled discrimination of oral cancer and normal epithelium. Therefore, both cancer proteome and lipidome are promising sources of biomarkers of oral malignancies. Electronic supplementary material The online version of this article (10.1007/s10735-018-9802-3) contains supplementary material, which is available to authorized users.

Upon activation with C2Cl6 known latent Ru metathesis catalyst LatMet (13) exhibited activity in RCM and in ROMP of DCPD. A by-product of such activation, an aryloxybenzylidene ruthenium(III) complex 17 have been independently synthesised by reacting 13 with C2Cl6. This unique complex was characterised by spectroscopic and electrochemical methods, and by X-ray crystallography. To the best to our knowledge, this is the first isolated and structurally determined Ru(III) alkylidene complex reported.

Reaction of commercial ruthenium complexes M31 and M20 with 2-nitrostyrene gave a new nitroso-chelated cyclic η1-acyl ruthenium(II) complexes Ru-4 and Ru-6 respectively instead of expected Hoveyda-Grubbs type (pre)catalyst Ru-3. New complexes were characterized by means of standard analytical techniques and their crystallographic structure has been confirmed by X-ray structural analysis. It was found that Ru-4 and Ru-6 do not exhibit any activity in standard metathesis reactions. However, a dramatic increase of activity was observed upon treatment with (trimethylsilyl)diazomethane, allowed for the successful application of Ru-4 in ROMP of endo,exo-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid dimethyl ester. Moreover, such complexes can be effective catalysts of transfer hydrogenation of ketones as well as cycloisomerization reactions.

• Thermo-hygro-chemo-mechanical model of porous materials using the delayed damage approach.

Ruthenium-based catalysts bearing quaternary ammonium groups in their N-heterocyclic carbene (NHC) fragments and different counter-ions were synthesised and tested in various olefin metathesis transformations. Differences in catalytic activity in correlation with the nature of the present counter-ion were revealed. The unique properties of the described catalysts allow for the effective preparation of a variety of metathesis products with low ruthenium contamination and under green chemistry conditions.

In the calculations of buildings’ thermal comfort, the input parameters are usually considered as strictly determined values. Numerous of them may be characterized by certain probability density functions. In the energy related problems, the uncertainty analyses are usually performed using the Monte Carlo method. However, this method requires multiple calculations and, therefore, may be very time-consuming. In the proposed work, two approaches are applied for the probabilistic studies: the stochastic perturbation method and the transformed random variables method. The stochastic analysis is based on the response functions and their derivatives with respect to all random input parameters. The relation between the thermal comfort and the input (random) variables have been calculated using the Energy Plus software. Afterwards, the response functions were estimated using the polynomial regression. The expected value and central moments of the response functions were calculated by means of the perturbation method and the transformed random variable theorem. The latter method allowed to obtain, using the same response functions, the implicit form of probability distributions function of the output parameter.

Nowadays, natural environment protection and sustainable development became common and necessary issues for all the economic sectors. It is extremely important to focus on all the efforts resulting in the most efficient and sustainable power sources and electric power grid. Typically, the residential districts are connected by electric grids, which with an application of the appropriate technologies might be considered as so-called smart-grids. In the smart-grid neighbourhoods, houses are the consumers, energy supply is performed by the local or/and national power plants, while energy distribution is performed using some monitoring and management systems. Such a residential area can be considered as a Building Cluster, the novel paradigm in the energy and environmental analysis of the built environments. In this article, the exemplary single-family houses neighbourhood is examined, following the Building Cluster paradigm. The analysed area is located in Lodz (Poland), consisting of 202 buildings. The study is performed by means of the home-developed software named TEAC (Tool for Energy Efficiency Analyses of an Energy Cluster). The analysis is focused on the energy, economic and environmental issues of the considered Building Cluster.

In the decision-making process during the office buildings' design or management, a significant problem arises from the necessity of simultaneous satisfaction of the users’ thermal comfort and minimization of the energy demand. Since the features of the materials, the comfort perception and the number of people are uncertain quantities, the energy demand and parameters describing thermal comfort should be treated as random variables as well. The parameters, which influence mostly the energy demand and thermal comfort are gathered in two groups: the material properties of facade and the human-related factors. The thermal transmittance , solar heat gain coefficient of the transparent facade, number of people and internal temperature are Gaussian uncertainties, but meanwhile they should fulfil the specific requirements concerning health and safety. In the proposed framework, the perturbation theory and approaches based on the transformed random variables method, which enable to determine the probability density function of the energy demand and predicted thermal comfort, are employed and compared. The proposed approach is applied to investigate the uncertainty propagation considering the reference office building unit. The results show that the Gaussian randomness extends into the non-symmetrical uncertainty of energy demand and predicted thermal comfort. In comparison with the Monte Carlo method , the introduced methodology provides the explicit form of the probability density function of analysed random variables at a much lower computational cost.

Can digital competencies be acquired by solving real problems? The educational intervention MadeByKids called an external educational provider to 17 schools to conduct a series of workshops, having pupils age 7 – 12 solve challenges such as designing the schoolbag 4.0 or the future classroom. The workshops were designed by adopting the Stanford Design Thinking Method for Kids (http://www.ideaco.org) and digital technologies with the goal to “teach” children computational thinking, collaborating in teams, resolving conflicts, presenting, giving/receiving feedback, etc. In this paper, we take a participatory action research (PAR) approach with the goal of exposing significant chunks of the incredibly rich experience. A content analysis of a qualitative survey among teachers and findings from a focus group reflect the teachers’ view. The study indicates that the acquisition of digital competences needs to be backed by personal and social capacities that take time to mature. Furthermore, we learned that the children’s teachers must be included consistently to ensure their cooperation and improve sustainability. Besides providing inspiration for teachers, implications for teacher education are derived and the national project is related to the findings from studies conducted abroad in order to contribute to constructive educational innovations crossing national boundaries.

Variable inlet guide vanes (VIGVs) are most commonly used as the major control unit of integrally geared centrifugal compressors (IGCCs). In order to enhance the efficient operating range of the compressor, the loss mechanisms and utilization limits of state-of-the-art VIGVs need to be better understood. Field measurements in the wake of a typical, commercially used configuration were therefore conducted at the VIGV test facility of the Bundeswehr University Munich. The investigations were carried out at application oriented subsonic flow conditions and stagger angles from 50∘ to 90∘ covering the full low-loss operating range, including the limits of efficient operation. For a precise local loss characterization, an inflow correlation was developed and applied to consider total pressure inhomogeneities caused by the radial inflow velocity profile and minor circumferential velocity deviations. Contrary to previous research efforts, not only the profile losses, but also the secondary flow losses induced by the open blade tips and wall-blade interactions were resolved in full detail. For this reason, a more precise and comprehensive loss assessment of realistic VIGV cascades is acquired.

Simple Summary Alfalfa protein-xantophyll concentrate is a rich source of nutrients and bioactive compounds. It provides protein, lutein, vitamins, minerals, phytoestrogens, and other plant metabolites. Thus, it may affect animal health in many ways; however, its impact is not fully recognized. Therefore, the aim of the study was to determine the effect of dietary supplementation with 1.5% and 3% concentrate on growth performance, blood biochemical profile, and large intestine physiology of rats as a model animals. The results showed that feeding a diet supplemented with alfalfa concentrate could reduce thickness of the protective mucus layer in the colon of rats but did not affect animal growth and microbial activity in the caecum. Abstract The effect of dietary levels of alfalfa protein-xanthophyll concentrate (PXC) was determined in growing rats. Three groups of eight four-week-old male Wistar rats, with an average initial body weight of 61 g, were fed for 28 days either natural-ingredient diets without PXC or supplemented with 1.5% or 3% PXC. Growth performance, blood biochemistry, caecal fermentation, morphology of the large intestine, and mucin gene expression were evaluated. PXC did not affect growth performance but tended to decrease relative liver weight. Among biochemical blood parameters, only bilirubin decreased and uric acid increased in response to 1.5% and 3% PXC, respectively. Caecal fermentation was not affected, with the exception of isovaleric acid concentration, which tended to be higher in rats fed the diet containing 3% PXC. Colonic crypts tended to be deeper in rats fed the 3% PXC diet and the thickness of the colonic mucus layer was reduced by both PXC levels. In conclusion, PXC did not affect growth performance or caecal fermentation but decreased thickness of the protective mucus layer in the colon.

Background Phylactolaemata is commonly regarded the earliest branch within Bryozoa and thus the sister group to the other bryozoan taxa, Cyclostomata and Gymnolaemata. Therefore, the taxon is important for the reconstruction of the bryozoan morphological ground pattern. In this study the myoanatomy of Pectinatella magnifica, Cristatella mucedo and Hyalinella punctata was analysed by means of histology, f-actin staining and confocal laser-scanning microscopy in order to fill gaps in knowledge concerning the myoanatomy of Phylactolaemata. Results The retractor muscles and muscles of the aperture, gut, body wall, tentacle sheath, lophophore constitute the most prominent muscular subsets in these species. The lophophore shows longitudinal muscle bands in the tentacles, lophophoral arm muscles, epistome musculature and hitherto undescribed muscles of the ring canal. In general the muscular system of the three species is very similar with differences mainly in the body wall, tentacle sheath and epistome. The body wall contains an orthogonal grid of musculature. The epistome exhibits either a muscular meshwork in the epistomal wall or muscle fibers traversing the epistomal cavity. The whole tentacle sheath possesses a regular mesh of muscles in Pectinatella and Cristatella, whereas circular muscles are limited to the tentacle sheath base in Hyalinella. Conclusion This study is the first to describe muscles of the ring canal and contributes to reconstructing muscular features for the last common ancestor of all bryozoans. The data available suggest that two longitudinal muscle bands in the tentacles, as well as retractor muscles and longitudinal and circular muscles in the tentacle sheath, were present in the last common bryozoan ancestor. Comparisons among bryozoans shows that several apomorphies are present in the myoanatomy of each class- level taxon such as the epistomal musculature and musculature of the lophophoral arms in phylactolaemates, annular muscles in cyclostomes and parietal muscles in gymnolaemates. Electronic supplementary material The online version of this article (10.1186/s12862-017-1068-y) contains supplementary material, which is available to authorized users.

This study investigates data sources for Business Intelligence solutions, which provide a foundation for holistic analyses, optimization, and forecasting of electrical power consumption within Facility Management for retail facilities networks. A multiple case study among Polish subsidiaries of Sweden, France, and UK-based companies along with a domestic Polish has been conducted. The authors identify, verify, and organize the determinants augmenting an energy efficiency-oriented decision-making process and introduce a set of potential benchmarking scenarios for managing it.