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This article focuses on potential of refining the CO2 storage capacity and rock parameters of a specific reservoir in Hungary. As part of a comprehensive laboratory measurement program, drilling core samples were analyzed using a human computed tomography (CT). The primary results of these evaluations provide critical insights that will be utilized as input parameters for developing a dynamic reservoir model. This approach aims to achieve a more accurate understanding of the reservoir. These preliminary data will be instrumental in enhancing our knowledge of this storage site, ultimately contributing to more effective CO2 storage solutions and advancing the field of geological carbon sequestration.

BackgroundSchistosomes are highly efficient evaders of human immunity, as evident by their ability to survive in human blood for years. How they protect themselves against the constant attack by a key element of innate immunity, the complement system, has remained unclear. In this study, new light is shed on the interaction between distinct life-cycle stages of Schistosoma mansoni and the human complement system.ResultsWe demonstrate that schistosomula, the young stage assumed immediately after cercaria penetration of the skin, are extremely vulnerable towards complement-mediated killing as only 10-20% survive. The survival rate increases to 70% already within 30 minutes and reaches close to 100% within two hours. Pathway-specific complement inhibitors revealed the alternative pathway of complement activation as the main contributor to killing and damage of the schistosomula. Moreover, the complement regulator factor H is recruited by the schistosomula in this early stage to evade killing. Surviving parasites appear fully viable despite the ongoing complement attack, as demonstrated by the deposition of C3 fragments. However, when exposed to the widely used schistocidal drug praziquantel, the vulnerability of 24 h-old schistosomula towards complement-mediated killing is notably increased; no such effect was observed for mefloquine or oxamniquine. Similar to the younger life-cycle stages, adult worms remain under complement attack. C3 fragments were found all over the outer surface (tegument), deposited mostly on the ridges and not on the tubercles.ConclusionThe recruitment of factor H merits more detailed studies that pinpoint the molecules involved and elucidate the novel possibilities to intercept the uncovered immune evasion therapeutically. That praziquantel and complement work in synergy is surprising and may in the future result in enhanced understanding of the drug’s mechanism of action.

Novel blend membranes containing S-PVA and PEBAX 1657 with a blend ratio of 8:2 (referred to as SPP) were prepared using a solution-casting technique. In the manufacturing process, sulfonated montmorillonite (S-MMT) in ratios of 0%, 3%, 5%, and 7% was used as a filler. The crystallinity of composite membranes has been investigated by X-ray diffraction (XRD), while the interaction between the components was evaluated using Fourier-transform infrared spectroscopy (FT-IR). With increasing filler content, good compatibility between the components due to hydrogen bonds was established, which ultimately resulted in improved tensile strength and chemical stability. In addition, due to the sulfonated moieties of S-MMT, the highest ion exchange capacity (0.46 meq/g) and water uptake (51.61%) can be achieved at the highest filler content with an acceptable swelling degree of 22.65%. The composite membrane with 7% S-MMT appears to be suitable for application in proton exchange membrane fuel cells (PEMFCs). Amongst the membranes studied, this membrane achieved the highest current density and power density in fuel cell tests, which were 149.5 mA/cm2 and 49.51 mW/cm2. Our fluorine-free composite membranes can become a promising new membrane family in PEMFC applications, offering an alternative to Nafion membranes.

BackgroundHaemostasis is a crucial process by which the body stops bleeding. It is achieved by the formation of a platelet plug, which is strengthened by formation of a fibrin mesh mediated by the coagulation cascade. In proinflammatory and prothrombotic conditions, multiple interactions of the complement system and the coagulation cascade are known to aggravate thromboinflammatory processes and increase the risk of arterial and venous thrombosis. Whether those interactions also play a relevant role during the physiological process of haemostasis is not yet completely understood. The aim of this study was to investigate the potential role of complement components and activation during the haemostatic response to mechanical vessel injury.MethodsWe used a microvascular bleeding model that simulates a blood vessel, featuring human endothelial cells, perfusion with fresh human whole blood, and an inducible mechanical injury to the vessel. We studied the effects of complement inhibitors against components of the lectin (MASP-1, MASP-2), classical (C1s), alternative (FD) and common pathways (C3, C5), as well as a novel triple fusion inhibitor of all three complement pathways (TriFu). Effects on clot formation were analysed by recording of fibrin deposition and the platelet activation marker CD62P at the injury site in real time using a confocal microscope.ResultsWith the inhibitors targeting MASP-2 or C1s, no significant reduction of fibrin formation was observed, while platelet activation was significantly reduced in the presence of the FD inhibitor. Both common pathway inhibitors targeting C3 or C5, respectively, were associated with a substantial reduction of fibrin formation, and platelet activation was also reduced in the presence of the C3 inhibitor. Triple inhibition of all three activation pathways at the C3-convertase level by TriFu reduced both fibrin formation and platelet activation. When several complement inhibitors were directly compared in two individual donors, TriFu and the inhibitors of MASP-1 and C3 had the strongest effects on clot formation.ConclusionThe observed impact of complement inhibition on reducing fibrin clot formation and platelet activation suggests a role of the complement system in haemostasis, with modulators of complement initiation, amplification or effector functions showing distinct profiles. While the interactions between complement and coagulation might have evolved to support haemostasis and protect against bleeding in case of vessel injury, they can turn harmful in pathological conditions when aggravating thromboinflammation and promoting thrombosis.

Mental and psychological disorders are serious health problems worldwide. Anxiety among high school students can affect school performance, relationships, and family life. Objective: Our aim is to understand the anxiety levels and associated factors among high school students and compare the results of psychological tests measuring anxiety with the cortisol levels obtained from biological sampling. Method: In our longitudinal follow-up study, we involved 125 individuals in May 2019. Validated measurement tools were used during questionnaire data collection, including the State–Trait Anxiety Inventory, Clear Communication Scale, Multiple Social Perceived Support Scale, and related HBSC questions. As objective data, we collected hair samples for cortisol level measurement. Results: At the end of the school year, the anxiety levels measured by psychological tests were significantly higher (p = 0.001) compared to the anxiety levels at the beginning of the next school year. Anxiety levels were higher among girls and were influenced by the type of school and parental expectations. Both state anxiety and trait anxiety showed a strong correlation with psychosomatic symptoms (p < 0.001) and anxiety arising from school expectations (p < 0.05). The changes in cortisol levels did not follow the changes in psychological tests. Cortisol level increased (p = 0.01) in the second sample.

BackgroundComplement lectin pathway components, in particular mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) have been shown to interact with coagulation factors and contribute to clot formation. Here we investigated the role of MBL and MASP-1 in the haemostatic response following mechanical vessel injury in a human microfluidic bleeding model.MethodsWe studied haemostasis in a microvascular bleeding model in the presence of human endothelial cells and human whole blood under flow conditions. We monitored incorporation of proteins into the clot with fluorescently labelled antibodies and studied their effects on clot formation, platelet activation, and bleeding time with specific inhibitors. Platelet activation was also studied by flow cytometry.ResultsUpon vessel injury, MBL accumulated at the injury site in a well-defined wall-like structure. MBL showed partial colocalisation with fibrin, and strong colocalisation with von Willebrand factor and (activated) platelets. Flow cytometry ruled out direct binding of MBL to platelets, but confirmed a PAR4- and thrombin-dependent platelet-activating function of MASP-1. Inhibiting MBL during haemostasis reduced platelet activation, while inhibiting MASP-1 reduced platelet activation, fibrin deposition and prolonged bleeding time.ConclusionWe show in a microvascular human bleeding model that MBL and MASP-1 have important roles in the haemostatic response triggered by mechanical vessel injury: MBL recognises the injury site, while MASP-1 increases fibrin formation, platelet activation and shortens bleeding time. While the complement lectin pathway may be harmful in the context of pathological thrombosis, it appears to be beneficial during the physiological coagulation response by supporting the crucial haemostatic system.

Ecotin is a serine protease inhibitor produced by hundreds of microbial species, including pathogens. Here we show, that ecotin orthologs from Escherichia coli, Yersinia pestis, Pseudomonas aeruginosa and Leishmania major are potent inhibitors of MASP-1 and MASP-2, the two key activator proteases of the complement lectin pathway. Factor D is the key activator protease of another complement activation route, the alternative pathway. We show that ecotin inhibits MASP-3, which is the sole factor D activator in resting human blood. In pathway-specific ELISA tests, we found that all ecotin orthologs are potent lectin pathway inhibitors, and at high concentration, they block the alternative pathway as well. In flow cytometry experiments, we compared the extent of complement-mediated opsonization and lysis of wild-type and ecotin-knockout variants of two E. coli strains carrying different surface lipopolysaccharides. We show, that endogenous ecotin provides significant protections against these microbicidal activities for both bacteria. By using pathway specific complement inhibitors, we detected classical-, lectin- and alternative pathway-driven complement attack from normal serum, with the relative contributions of the activation routes depending on the lipopolysaccharide type. Moreover, in cell proliferation experiments we observed an additional, complement-unrelated antimicrobial activity exerted by heat-inactivated serum. While ecotin-knockout cells are highly vulnerable to these activities, endogenous ecotin of wild-type bacteria provides complete protection against the lectin pathway-related and the complement-unrelated attack, and partial protection against the alternative pathway-related damage. In all, ecotin emerges as a potent, versatile self-defense tool that blocks multiple antimicrobial activities of the serum. These findings suggest that ecotin might be a relevant antimicrobial drug target.

Pathologically increased vascular permeability is an important dysfunction in the pathomechanism of life-threatening conditions, such as sepsis, ischemia/reperfusion, or hereditary angioedema (HAE), diseases accompanied by uncontrolled activation of the complement system. HAE for example is caused by the deficiency of C1-inhibitor (the main regulator of early complement activation), which leads to edematous attacks threatening with circulatory collapse. We have previously reported that endothelial cells become activated during HAE attacks. A natural target of C1-inhibitor is mannan-binding lectin-associated serine protease-1 (MASP-1), a multifunctional serine protease, which plays a key role in the activation of complement lectin pathway. We have previously shown that MASP-1 induces the pro-inflammatory activation of endothelial cells and in this study we investigated whether MASP-1 can directly affect endothelial permeability. All experiments were performed on human umbilical vein endothelial cells (HUVECs). Real-time micro electric sensing revealed that MASP-1 decreases the impedance of HUVEC monolayers and in a recently developed permeability test (XperT), MASP-1 dose-dependently increased endothelial paracellular transport. We show that protease activated receptor-1 mediated intracellular Ca2+-mobilization, Rho-kinase activation dependent myosin light chain (MLC) phosphorylation, cytoskeletal actin rearrangement, and disruption of interendothelial junctions are underlying this phenomenon. Furthermore, in a whole-transcriptome microarray analysis MASP-1 significantly changed the expression of 25 permeability-related genes in HUVECs—for example it up-regulated bradykinin B2 receptor expression. According to our results, MASP-1 has potent permeability increasing effects. During infections or injuries MASP-1 may help eliminate the microbes and/or tissue debris by enhancing the extravasation of soluble and cellular components of the immune system, however, it may also play a role in the pathomechanism of diseases, where edema formation and complement lectin pathway activation are simultaneously present. Our findings also raise the possibility that MASP-1 may be a promising target of anti-edema drug development.

The complement and coagulation systems closely interact with each other. These interactions are believed to contribute to the proinflammatory and prothrombotic environment involved in the development of thrombotic complications in many diseases. Complement MASP-1 (mannan-binding lectin-associated serine protease-1) activates coagulation factors and promotes clot formation. However, this was mainly shown in purified or plasma-based static systems. Here we describe the role of MASP-1 and complement activation in fibrin clot formation in a microvascular, whole blood flow model. This microfluidic system simulates blood flow through microvessels at physiological flow and shear rates and represents the closest model system to human physiology so far. It features parallel microchannels cultured with endothelial cells in a transparent microfluidic chip allowing real-time evaluation of clot formation by confocal microscopy. To test their effects on clot formation, we added the following activators or inhibitors (individually or in combination) to whole blood and performed perfusion experiments: rMASP-1cf (recombinant active form of MASP-1), complement activator zymosan, selective MASP-1 inhibitor SGMI-1 (based on the Schistocerca gregaria protease inhibitor scaffold), classical pathway inhibitor rSALO (recombinant salivary anti-complement from Lutzomyia longipalpis). Addition of rMASP-1cf resulted in accelerated fibrin clot formation while addition of SGMI-1 delayed it. Complement activation by zymosan led to increased clot formation and this effect was partially reversed by addition of rSALO and almost abolished in combination with SGMI-1. We show for the first time a strong influence of MASP-1, complement activation and pathway-specific inhibition on coagulation in a microvascular flow system that is closest to human physiology, further underpinning the in vivo relevance of coagulation and complement interactions.

Protein-protein interactions (PPIs) formed between short linear motifs and globular domains play important roles in many regulatory and signaling processes but are highly underrepresented in current protein-protein interaction databases. These types of interactions are usually characterized by a specific binding motif that captures the key amino acids shared among the interaction partners. However, the computational proteome-level identification of interaction partners based on the known motif is hindered by the huge number of randomly occurring matches from which biologically relevant motif hits need to be extracted. In this work, we established a novel bioinformatic filtering protocol to efficiently explore interaction network of a hub protein. We introduced a novel measure that enabled the optimization of the elements and parameter settings of the pipeline which was built from multiple sequence-based prediction methods. In addition, data collected from PPI databases and evolutionary analyses were also incorporated to further increase the biological relevance of the identified motif hits. The approach was applied to the dynein light chain LC8, a ubiquitous eukaryotic hub protein that has been suggested to be involved in motor-related functions as well as promoting the dimerization of various proteins by recognizing linear motifs in its partners. From the list of putative binding motifs collected by our protocol, several novel peptides were experimentally verified to bind LC8. Altogether 71 potential new motif instances were identified. The expanded list of LC8 binding partners revealed the evolutionary plasticity of binding partners despite the highly conserved binding interface. In addition, it also highlighted a novel, conserved function of LC8 in the upstream regulation of the Hippo signaling pathway. Beyond the LC8 system, our work also provides general guidelines that can be applied to explore the interaction network of other linear motif binding proteins or protein domains.

LC8 dynein light chain (DYNLL) is a eukaryotic hub protein that is thought to function as a dimerization engine. Its interacting partners are involved in a wide range of cellular functions. In its dozens of hitherto identified binding partners DYNLL binds to a linear peptide segment. The known segments define a loosely characterized binding motif: [D/S](-4)K(-3)X(-2)[T/V/I](-1)Q(0)[T/V](1)[D/E](2). The motifs are localized in disordered segments of the DYNLL-binding proteins and are often flanked by coiled coil or other potential dimerization domains. Based on a directed evolution approach, here we provide the first quantitative characterization of the binding preference of the DYNLL binding site. We displayed on M13 phage a naïve peptide library with seven fully randomized positions around a fixed, naturally conserved glutamine. The peptides were presented in a bivalent manner fused to a leucine zipper mimicking the natural dimer to dimer binding stoichiometry of DYNLL-partner complexes. The phage-selected consensus sequence V(-5)S(-4)R(-3)G(-2)T(-1)Q(0)T(1)E(2) resembles the natural one, but is extended by an additional N-terminal valine, which increases the affinity of the monomeric peptide twentyfold. Leu-zipper dimerization increases the affinity into the subnanomolar range. By comparing crystal structures of an SRGTQTE-DYNLL and a dimeric VSRGTQTE-DYNLL complex we find that the affinity enhancing valine is accommodated in a binding pocket on DYNLL. Based on the in vitro evolved sequence pattern we predict a large number of novel DYNLL binding partners in the human proteome. Among these EML3, a microtubule-binding protein involved in mitosis contains an exact match of the phage-evolved consensus and binds to DYNLL with nanomolar affinity. These results significantly widen the scope of the human interactome around DYNLL and will certainly shed more light on the biological functions and organizing role of DYNLL in the human and other eukaryotic interactomes.

Mental and psychological disorders are serious health problems worldwide. Anxiety among high school students can affect school performance, relationships, and family life. Objective: Our aim is to understand the anxiety levels and associated factors among high school students and compare the results of psychological tests measuring anxiety with the cortisol levels obtained from biological sampling. Method: In our longitudinal follow-up study, we involved 125 individuals in May 2019. Validated measurement tools were used during questionnaire data collection, including the State–Trait Anxiety Inventory, Clear Communication Scale, Multiple Social Perceived Support Scale, and related HBSC questions. As objective data, we collected hair samples for cortisol level measurement. Results: At the end of the school year, the anxiety levels measured by psychological tests were significantly higher (p = 0.001) compared to the anxiety levels at the beginning of the next school year. Anxiety levels were higher among girls and were influenced by the type of school and parental expectations. Both state anxiety and trait anxiety showed a strong correlation with psychosomatic symptoms (p < 0.001) and anxiety arising from school expectations (p < 0.05). The changes in cortisol levels did not follow the changes in psychological tests. Cortisol level increased (p = 0.01) in the second sample. [ABSTRACT FROM AUTHOR]

Perfluorosulfonic acid (PFSA) polymers such as Nafion are the most frequently used Proton Exchange Membrane (PEM) in PEM fuel cells. Nafion XL is one of the most recently developed membranes designed to enhance performance by employing a mechanically reinforced layer in the architecture and a chemical stabilizer. The influence of the water and acid pre-treatment process on the physicochemical properties of Nafion XL membrane and Membrane Electrode Assembly (MEA) was investigated. The obtained results indicate that the pre-treated membranes have higher water uptake and dimensional swelling ratios, i.e., higher hydrophilicity, while the untreated membrane demonstrated a higher ionic exchange capacity. Furthermore, the conductivity of the acid pre-treated Nafion XL membrane was ~ 9.7% higher compared to the untreated membrane. Additionally, the maximum power densities obtained at 80 °C using acid pre-treatment were ~ 0.8 and 0.93 W/cm2 for re-cast Nafion and Nafion XL, respectively. However, the maximum generated powers for untreated membranes at the same condition were 0.36 and 0.66 W/cm2 for re-cast Nafion and Nafion XL, respectively. The overall results indicated that the PEM's pre-treatment process is essential to enhance performance. [ABSTRACT FROM AUTHOR]

The proton exchange membrane (PEM) represents a pivotal material and a key challenge in developing fuel cell science and hydrogen technology. Nafion is the most promising polymer which will lead to its commercialisation. Hybrid membranes of nanosized tungsten oxide (WO3) and Nafion were fabricated, characterised, and tested in a single cell. The incorporation of 10 wt% WO3 resulted in 21% higher water uptake, 11.7% lower swelling ratio, almost doubling the hydration degree, and 13% higher mechanical stability of the hybrid membrane compared to the Nafion XL. Compared to commercial Nafion XL, the rNF–WO-10 hybrid membrane showed an 8.8% and 20% increase in current density of the cell at 0.4 V operating at 80 and 95 °C with 1.89 and 2.29 A/cm2, respectively. The maximum power density has increased by 9% (0.76 W/cm2) and 19.9% (0.922 W/cm2) when operating at the same temperatures compared to the commercial Nafion XL membrane. Generally, considering the particular structure of Nafion XL, our Nafion-based membrane with 10 wt% WO3 (rNF–WO-10) is a suitable PEM with a comparable performance at different operating conditions. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the common narrative in literary history that the inner lives of characters became a central preoccupation of literary modernism – a phenomenon commonly referenced as the “inward turn”. We operationalize this notion via a proxy, tracing the use of verbs relating to inner life across 10 language corpora from the ELTeC collection, which comprises novels from the period between 1840–1920. We expected to find an increase in the use of inner-life verbs corresponding to the traditional periodisation of modernism in each of the languages. However, different experiments conducted with the data do not confirm this hypothesis. We therefore look at the results in a number of more granular ways, but we cannot identify any common trends even when we split the verbs into individual categories, or take canonicity or gender into account. We discuss the obtained results in detail, proposing potential reasons for them and including potential avenues of further research as well as lessons learned.

The topic was to spot and potentially measure the amount of floating waste on the river Tisza and its offsets. It was a two-year long study in which a complete system was designed and built and performed measurements 50-70 % of waste dumped into rivers are plastics. Ranging from micro-plastics (< 0.1 µm) to macro-plastics (>5 cm). The nature of the plastic pollution depends greatly on the source of the pollution. In the river Tisza and its offsets, the pollution is mainly coming from landfills located near the upstream. In the first phase, an experimental motion-detection camera system was developed to try out multiple configurations during the research. The open-source motion software has been implemented, running on Raspberry Pi 3 as data collectors. The system uploaded data into a data server running in the cloud (Azure). The camera system was operating for more than a year and collected over 440,000 pictures. At the end of this phase, the conclusion was that individual plastic objects are not recognisable, only bigger groups of them. On top of this, we have seen that the optical noise is very high, rendering many of the pictures unfit for analysis, but the results still served as a very good starting point for the collection of AI training data. During the second phase, software was experimented. YOLOv3 and Faster R-CNN have been applied, eventually settling for Faster R-CNN with a ResNet-50-FPN base network.

The tomato as a raw material for processing is globally important and is pivotal in dietary and agronomic research due to its nutritional, economic, and health significance. This study explored the potential of machine learning (ML) for predicting tomato quality, utilizing data from 48 cultivars and 28 locations in Hungary over 5 seasons. It focused on °Brix, lycopene content, and colour (a/b ratio) using extreme gradient boosting (XGBoost) and artificial neural network (ANN) models. The results revealed that XGBoost consistently outperformed ANN, achieving high accuracy in predicting °Brix (R² = 0.98, RMSE = 0.07) and lycopene content (R² = 0.87, RMSE = 0.61), and excelling in colour prediction (a/b ratio) with a R² of 0.93 and RMSE of 0.03. ANN lagged behind particularly in colour prediction, showing a negative R² value of −0.35. Shapley additive explanation’s (SHAP) summary plot analysis indicated that both models are effective in predicting °Brix and lycopene content in tomatoes, highlighting different aspects of the data. SHAP analysis highlighted the models’ efficiency (especially in °Brix and lycopene predictions) and underscored the significant influence of cultivar choice and environmental factors like climate and soil. These findings emphasize the importance of selecting and fine-tuning the appropriate ML model for enhancing precision agriculture, underlining XGBoost’s superiority in handling complex agronomic data for quality assessment.

In this paper, we investigate the common narrative in literary history that the inner lives of characters became a central preoccupation of literary modernism. We operationalise this notion via a proxy, tracing the use of verbs relating to inner life across 10 language corpora from the ELTeC collection, which comprises novels from the period between 1840–1920. We expected to find an increase in the use of inner-life verbs corresponding to the traditional periodisation of modernism in each of the languages. However, different experiments conducted with the data do not confirm this hypothesis. We therefore look at the results in a number of more granular ways, but we cannot identify any common trends even when we split the verbs into individual categories, or take canonicity or gender into account. We discuss the obtained results in detail, proposing potential reasons for them and including potential avenues of further research as well as lessons learned.

Tomato-based products are significant components of vegetable consumption. The processing tomato industry is unquestionably in need of a rapid definition method for measuring soluble solids content (SSC) and lycopene content. The objective was to find the best chemometric method for the estimation of SSC and lycopene content from visible and near-infrared (Vis-NIR) absorbance and reflectance data so that they could be determined without the use of chemicals in the process. A total of 326 Vis-NIR absorbance and reflectance spectra and reference measurements were available to calibrate and validate prediction models. The obtained spectra can be manipulated using different preprocessing methods and multivariate data analysis techniques to develop prediction models for these two main quality attributes of tomato fruits. Eight different method combinations were compared in homogenized and intact fruit samples. For SSC prediction, the results showed that the best root mean squared error of cross-validation (RMSECV) originated from raw absorbance (0.58) data and with multiplicative scatter correction (MSC) (0.59) of intact fruit in Vis-NIR, and first derivatives of reflectance (R2 = 0.41) for homogenate in the short-wave infrared (SWIR) region. The best predictive ability for lycopene content of homogenate in the SWIR range (R2 = 0.47; RMSECV = 17.95 mg kg–1) was slightly lower than that of Vis-NIR (R2 = 0.68; 15.07 mg kg–1). This study reports the suitability of two Vis-NIR spectrometers, absorbance/reflectance spectra, preprocessing methods, and partial least square (PLS) regression to predict SSC and lycopene content of intact tomato fruit and its homogenate.

The caudal-related homeobox transcription factor CDX2 is expressed in leukemic cells in the majority of patients with leukemia but not during normal blood formation. Here, the authors report a mouse model with conditional Cdx2 expression showing de novo leukemic transformation, and use it to optimize treatment in high-risk AML.

The paper deals with the topic of functional regionalization and demonstrates some of the possible delimitation methodologies on the basis of commuting to work dataset provided by the 2011 census in Hungary. The main objective of the study is to compare the results of the different methods on the basis of the resulted territorial divisions, their centres and hinterlands. The method of local labour systems (LLS), the method of labour market areas (LMA) – called as EURO method – and the CURDS measure are introduced, applied and compared. The results of the calculations clearly demonstrate the different characters of the methods. The results of the LLS method are characterized by major disparities with an extremely extended Budapest LLS district. The EURO method results in a less extending central region around Budapest, however, the CURDS measure causes the most moderate inequalities among the functional regions with the smallest number of units. The differing character of the methods can be discovered in the centres as well. LLS centres indicate the polarizing character of the method preferring the largest centres, at the same time it gives possibility to the smaller centres to be delimited. The centres of the EURO method appear with the largest frequency and it gives the possibility that those centres are located in the surroundings of dominant centres. The CURDS measure is the ‘strictest’ one from this respect. The comparative results drew the attention to the differing character of centres in each part of Hungary.

Src homology-3 (SH3) domains mediate important protein–protein interactions in a variety of normal and pathological cellular processes, thus providing an attractive target for the selective interference of SH3-dependent signaling events that govern these processes. Most SH3 domains recognize proline-rich peptides with low affinity and poor selectivity, and the goal to design potent and specific ligands for various SH3 domains remains elusive. Better understanding of the molecular basis for SH3 domain recognition is needed in order to design such ligands with potency and specificity. In this report, we seek to define a clear recognition preference of the specificity pocket of the Abl SH3 domain using targeted synthetic peptide libraries. High-resolution affinity panning coupled with mass spectrometric readout allows for quick identification of Trp as the preferred fourth residue in the decapeptide ligand APTWSPPPPP, which binds to Abl SH3 four times stronger than does the decapeptide containing Tyr or Phe in the fourth position. This finding is in contrast to several reports that Tyr is the only residue selected from phage displayed peptide libraries that interacts with the specificity pocket of Abl SH3. This simple, unbiased approach can fine-tune the affinity and selectivity of both natural and unnatural SH3 ligands whose consensus binding sequence has been pre-defined by combinatorial library methods. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the prevalence and pattern of psychoactive substances among suspected DUID (Driving Under the Influence of Drugs) drivers in Hungary in 2014 and 2015. Blood and/or urine samples of 1252 suspected drivers (600 in 2014 and 652 in 2015) were analyzed for classical illicit and licit drugs, stimulant designer drugs (SDDs), and for synthetic cannabinoids, with 78.3% and 79.6% positive cases for at least one substance in 2014, and 2015, respectively. Impairment was proven in 39.2% (2014) and 35.7% (2015) of all drivers tested, based on the legal criteria of Hungary. Classical illicit drugs were found to be present in blood or urine of 89-61%, drivers tested. Drivers also tested positive for legal medications in 20-22%, SDDs in 21-28%, and synthetic cannabinoids in 15-19% of all cases. This indicates a drop in prevalence for classical illicit drugs and a slight but statistically non-significant increase for the other three substance groups. The distribution of drug types in each category were: [1] classical illicit drugs: cannabis (432), amphetamine (321), and cocaine (79); [2] medicines: alprazolam (94) and clonazepam (36); [3] SDDs: pentedrone (137) and α-PVP (33); [4] synthetic cannabinoids: AB-CHMINACA (46) and MDMB-CHMICA (30). The average age of illicit drug and SDD users was 30 years, while legal medications users were 36 years old on average, and the mean age of synthetic cannabinoid users was 26.5 years. The presence of both alcohol and at least one drug in samples was found in about 10% of the cases, both years. The ratio of multi-drug use was 33.0% in 2014 and 41.3% in 2015. Compared to former years the number of drivers who tested positive for drugs doubled in Hungary, but it is still low compared to alcohol positive cases. The relatively low detected rate of DUID can be explained by (1) combined alcohol consumption masking drug symptoms, (2) the absence of road-side tests for illicit and designer drugs and, (3) police officers not adequately trained to recognize milder symptoms of impairment. Targeted education of police officers, prompt medical examination and the use of a symptom-focused on-site survey, could improve the efficacy of DUID investigations. Our findings are not comparable with drug consumption habits of the general driving population. The last roadside survey (DRUID EU-6 Project) was performed in Hungary in 2008-2009, prior to the mass spreading of designer drugs. As their appearance has drastically changed the pattern of drug consumption of the population, a new roadside survey, targeting general drivers, would be necessary. [ABSTRACT FROM AUTHOR]

Five acylation reagents have been compared for use as derivatizing agents for the analysis of amphetamine-type stimulants (ATS) in urine by gas chromatography-mass spectrometry (GC-MS). The evaluated reagents were heptafluorobutyric anhydride, pentafluoropropionic anhydride, trifluoroacetic anhydride, acetic anhydride (AA) and N-methyl-bis(trifluoroacetamide). The ATS included amphetamine, methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA). A mixture of the ATS was added to urine (1 mL) followed by KOH solution and saturated NaHCO(3) solution. The sample was then extracted with dichloromethane and the derivatizing agent and 2 µL were injected into the GC-MS instrument. The derivatizing agents were compared with reference to the signal-to-noise (S/N) ratios, peak area values, relative standard deviations (RSDs), linearities, limits of detection (LODs) and selectivities. The acetic anhydride proved to be the best according to the S/N ratio and peak area results for amphetamine, MA, MDMA and MDEA. The best RSD values of peak areas and of S/N ratios at 3 µg/mL were also given by AA in cases of MDA, MDMA and MDEA. At 20 µg/mL, the lowest RSD values of peak areas for MDA and the lowest RSD values of S/N ratios for MA, MDA, MDMA and MDEA were again given by AA. Additionally, the highest correlation coefficients for MA, MDA, MDMA and MDEA and the lowest LOD results for MA, MDMA and MDEA were produced by AA.