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More than 30 minutes before the earthquake event in Florina, Greece at 21:43:47(UTC) on 9th January 2022 an enhanced E\"otv\"os torsion balance registered unidentified signals in the J\'anossy Underground Research Laboratory in Budapest, Hungary. These signals were not visible on the seismograms, although seismic noises are continuously recorded by a side-by-side broadband seismometer. Moreover, seismological stations did not detect anything unusual, they presented a negative confirmation of the events. Our observation suggests that torsion balances might effectively detect precursory earthquake signals from a considerable distance. Such a finding could trigger the development of new observational devices and networks and can provide novel knowledge about the origin and mechanism of earthquake phenomena., Comment: 14 pages, 5+5 figures

Irradiation of solids with ultrashort pulses using laser sources in the mid-infrared (mid-IR) spectral region is a yet predominantly unexplored field that opens broad possibilities for efficient and precise surface texturing for a wide range of applications. In the present work, we investigate both experimentally and theoretically the impact of laser sources on the generation of surface modification related effects and on the subsequent surface patterning of metallic and semiconducting materials. Through a parametric study we correlate the mid-IR pulsed laser parameters with the onset of material damage and the formation of a variety of periodic surface structures at a laser wavelength of {\lambda}L=3200 nm and a pulse duration of {\tau}p=45 fs. Results for nickel and silicon indicate that the produced topographies comprise both high and low spatial frequency induced periodic structures, similar to those observed at lower wavelengths, while groove formation is absent. The investigation of the damage thresholds suggests the incorporation of nonlinear effects generated from three-photon-assisted excitation (for silicon) and the consideration of the role of the non-thermal excited electron population (for nickel) at very short pulse durations. The results demonstrate the potential of surface structuring with mid-IR pulses, which can constitute a systematic novel engineering approach with strong fields at long-wavelength spectral regions that can be used for advanced industrial laser applications.

More than 30 minutes before the earthquake event in Florina, Greece at 21:43:47(UTC) on 9th January 2022 an enhanced Eötvös torsion balance registered unidentified signals in the Jánossy Underground Research Laboratory in Budapest, Hungary. These signals were not visible on the seismograms, although seismic noises are continuously recorded by a side-by-side broadband seismometer. Moreover, seismological stations did not detect anything unusual, they presented a negative confirmation of the events. Our observation suggests that torsion balances might effectively detect precursory earthquake signals from a considerable distance. Such a finding could trigger the development of new observational devices and networks and can provide novel knowledge about the origin and mechanism of earthquake phenomena., 14 pages, 5+5 figures

At BME (Budapest University of Technology and Economics) NTI (Institute of Nuclear Technics), a 7 pin rod bundle test section has been built in order to investigate the hydraulic behavior of the coolant in such design and to develop CFD models that could properly simulate the flow conditions in the ALLEGRO core. PIROUETTE (PIv ROd bUndlE Test faciliTy at bmE) is a test facility, which was designed to investigate the emerging flow conditions in various nuclear fuel assembly rod bundles. The measurement method is based on Particle Image Velocimetry (PIV) with Matching of Index of Refractory (MIR) method. In the test loop, it was necessary to install a flow straightener that was able to condition the velocity field before the rod bundle. The results of CFD simulations could be used to improve the understanding of the inlet conditions in the rod bundle test section.The second part of the benchmark deals with the 3D CFD modeling of the velocity field within the 7 pin rod bundle placed in the test section. The geometry of the test section will be given to the participants in an easy-to-use 3D format (.obj, .stp or .stl)., Comment: 26 pages, 14 Figure, 6 Tables, Ancillary files are online available

Das Abstract ist Teil der vDHd Konferenz 2021 "Experimente", einer durch die Community des Verbandes "Digital Humanities im deutschsprachigen Raum" e.V. organisierten, virtuellen Konferenz. Die Abstracts haben kein Peer-Review-Verfahren durchlaufen.

Béla Kiss, Zsolt Némethy, Károly Fazekas, Dalma Kurkó, István Gyertyán, Katalin Sághy, István Laszlovszky, Bence Farkas, Norbert Kirschner, Etelka Bolf-Terjéki, Ottilia Balázs, Balázs Lendvai Pharmacological and Drug Safety Research, Gedeon Richter Plc, Budapest, HungaryCorrespondence: Béla KissPharmacological and Drug Safety Research, Gedeon Richter Plc, P.O. Box 27, Budapest H-1475, HungaryTel +361 431 4226Fax +361 889 8400Email b.kiss@richter.huIntroduction:Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, has two major human metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). The metabolite pharmacology was profiled to understand the contribution to cariprazine efficacy.Methods: In vitro receptor binding and functional assays, electrophysiology, animal models, microdialysis, and kinetic-metabolism approaches were used to characterize the pharmacology of DCAR and DDCAR. Results: Similar to cariprazine, both metabolites showed high affinity for human D3, D2L, 5-HT1A, 5-HT2A, and 5-HT2B receptors, albeit with higher selectivity than cariprazine for D3 versus D2 receptors. In [35S]GTPγS binding assays, cariprazine and DDCAR were antagonists in membranes from rat striatum and from cells expressing human D2 and D3 receptors, and were partial agonists in membranes from rat hippocampus. In cAMP signaling assays, cariprazine, DCAR, and DDCAR acted as partial agonists at D2 and D3 receptors; cariprazine and DDCAR were full agonists, whereas DCAR was a partial agonist at 5-HT1A receptors. Cariprazine, DCAR, and DDCAR were pure antagonists at human 5-HT2B receptors. Cariprazine and DDCAR increased rat striatal dopamine and reduced cortical serotonin turnover. Cariprazine and DDCAR showed similar in vivo D3 receptor occupancy in rat brain; however, cariprazine was more potent for D2 receptor occupancy. Both cariprazine and DDCAR dose-dependently but partially suppressed the spontaneous activity of midbrain dopaminergic neurons in rats, with the parent compound being more potent but shorter acting than its metabolite. Consistent with the D2 receptor occupancy profile, DDCAR was 3- to 10-fold less potent than cariprazine in rodent models of antipsychotic-like activity. Following acute cariprazine administration, DDCAR was detected in the rodent brain but at much lower levels than cariprazine.Conclusion: Overall, in vitro and in vivo pharmacological profiles of DCAR and DDCAR demonstrated high similarity with cariprazine, suggesting that the major metabolites of cariprazine contribute significantly to its clinical efficacy.Keywords: dopamine, serotonin, schizophrenia, bipolar disorder, desmethyl-cariprazine, didesmethyl-cariprazine

We present single-shot electron velocity-map images of nanoplasmas generated from doped helium nanodroplets and neon clusters by intense near-infrared and mid-infrared laser pulses. We report a large variety of signal types, most crucially depending on the cluster size. The common feature is a two-component distribution for each single-cluster event: A bright inner part with nearly circular shape corresponding to electron energies up to a few eV, surrounded by an extended background of more energetic electrons. The total counts and energy of the electrons in the inner part are strongly correlated and follow a simple power-law dependence. Deviations from the circular shape of the inner electrons observed for neon clusters and large helium nanodroplets indicate non-spherical shapes of the neutral clusters. The dependence of the measured electron energies on the extraction voltage of the spectrometer indicates that the evolution of the nanoplasma is significantly affected by the presence of an external electric field. This conjecture is confirmed by molecular dynamics simulations, which reproduce the salient features of the experimental electron spectra.

Background/objectives The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. Methods We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. Results Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia 80% for all items, explaining the higher overall specificity of the criteria set. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Objectives The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. Methods Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. Results The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to

Background: EULAR/ACR 2019 SLE Classification Criteria were validated in an international cohort. Objectives: To evaluate performance characteristics of SLE classification systems in sex, race/ethnicity, and disease duration subsets. Methods: Sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated in the validation cohort. Results: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), Black (n=68), Hispanic (n=124) and White (n=941) patients ; and patients with an SLE duration of 1-3 years (n=196), 3-5 years (n=157), and ≥5 years (n=879). Among patients with 1-3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% (95%CI 92-99%) vs 81% (95%CI 72-88%). The new criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). The new criteria had better sensitivity than the ACR criteria in White (95% vs 83%), Hispanic (100% vs 86%) and Asian patients (97% vs 77%). Conclusion: The EULAR/ACR 2019 criteria perform well in patients with early disease, and across sexes and ethnicities.

The Digital Revolution, including technologies such as virtual and augmented reality, additive manufacturing or 3D-printing, (general purpose) artificial intelligence, or the Internet of Things, has entered the public discourse in many countries. Looking back, it is almost impossible to believe that digitalization is barely featured in the 2030 Agenda or the Paris Agreement. It is increasingly clear that digital changes, we refer to them as the Digital Revolution, are becoming a key driving force in societal transformation. The transformation towards sustainability for all must be harmonized with the threats, opportunities and dynamics of the Digital Revolution, the goals of the 2030 Agenda and the Paris Agreement. At the same time, the digital transformation will radically alter all dimensions of global societies and economies and will therefore change the interpretation of the sustainability paradigm itself. Digitalization is not only an ‘instrument’ to resolve sustainability challenges, it is also fundamental as a driver of disruptive change. This report that focuses on the Digital Revolution is the second one by The World in 2050 (TWI2050) that was established by the International Institute for Applied Systems Analysis (IIASA) and other partners to provide scientific foundations for the 2030 Agenda. This report is based on the voluntary and collaborative effort of more than 50 authors and contributors from about 20 institutions, and some 100 independent experts from academia, business, government, intergovernmental and non-governmental organizations from all the regions of the world, who met four times at IIASA to develop science-based strategies and pathways toward achieving the Sustainable Development Goals (SDGs). Presentations of the TWI2050 approach and work have been made at many international meetings such as the United Nations Science, Technology and Innovation Forums and the United Nations High-level Political Forums. In 2018, the first report by TWI2050 on Transformations to Achieve the Sustainable Development Goals identified Six Exemplary Transformations needed to achieve the SDGs and long-term sustainability to 2050 and beyond: i) Human Capacity & Demography; ii) Consumption & Production; iii) Decarbonization & Energy, iv) Food, Biosphere & Water; v) Smart Cities and vi) Digital Revolution. The focus of this report is the Sixth Transformation, The Digital Revolution. Although it is arguably the single greatest enabler of sustainable development, it has, in the past, helped create many negative externalities like transgression of planetary boundaries. Progress on the SDGs will be facilitated if we can build and implement detailed science, technology and innovation (STI) roadmaps at all levels that range from local to global. STI is a forceful driver of change connected to all 17 SDGs. The Digital Revolution provides entirely new and enhanced capacities and thus serves as a major force in shaping both the systemic context of transformative change and future solutions; at the same time it potentially carries strong societal disruptive power if not handled with caution, care, and innovativeness. This report assesses all the positive potential benefits digitalization brings to sustainable development for all. It also highlights the potential negative impacts and challenges going forward, particularly for those impacted by the ‘digital divide’ that excludes primarily people left behind during the Industrial Revolution like the billion that go hungry every night and the billion who do not have access to electricity. The report outlines the necessary preconditions for a successful digital transformation, including prosperity, social inclusion, environmental sustainability and good governance. Importantly it outlines some of the dramatic social implications associated with an increasingly digital future. It also covers a topic that so far has not been sufficiently dealt with in the cross-over discussions between sustainability and the Digital Revolution, that is, the considerations about related governance aspects.

Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

The Digital Revolution, including technologies such as virtual and augmented reality, additive manufacturing or 3D-printing, (general purpose) artificial intelligence, or the Internet of Things, has entered the public discourse in many countries. Looking back, it is almost impossible to believe that digitalization is barely featured in the 2030 Agenda or the Paris Agreement. It is increasingly clear that digital changes, we refer to them as the Digital Revolution, are becoming a key driving force in societal transformation. The transformation towards sustainability for all must be harmonized with the threats, opportunities and dynamics of the Digital Revolution, the goals of the 2030 Agenda and the Paris Agreement. At the same time, the digital transformation will radically alter all dimensions of global societies and economies and will therefore change the interpretation of the sustainability paradigm itself. Digitalization is not only an ‘instrument’ to resolve sustainability challenges, it is also fundamental as a driver of disruptive change. This report that focuses on the Digital Revolution is the second one by The World in 2050 (TWI2050) that was established by the International Institute for Applied Systems Analysis (IIASA) and other partners to provide scientific foundations for the 2030 Agenda. This report is based on the voluntary and collaborative effort of more than 50 authors and contributors from about 20 institutions, and some 100 independent experts from academia, business, government, intergovernmental and non-governmental organizations from all the regions of the world, who met four times at IIASA to develop science-based strategies and pathways toward achieving the Sustainable Development Goals (SDGs). Presentations of the TWI2050 approach and work have been made at many international meetings such as the United Nations Science, Technology and Innovation Forums and the United Nations High-level Political Forums. In 2018, the first report by TWI2050 on Transformations to Achieve the Sustainable Development Goals identified Six Exemplary Transformations needed to achieve the SDGs and long-term sustainability to 2050 and beyond: i) Human Capacity Demography; ii) Consumption Production; iii) Decarbonization Energy, iv) Food, Biosphere Water; v) Smart Cities and vi) Digital Revolution. The focus of this report is the Sixth Transformation, The Digital Revolution. Although it is arguably the single greatest enabler of sustainable development, it has, in the past, helped create many negative externalities like transgression of planetary boundaries. Progress on the SDGs will be facilitated if we can build and implement detailed science, technology and innovation (STI) roadmaps at all levels that range from local to global. STI is a forceful driver of change connected to all 17 SDGs. The Digital Revolution provides entirely new and enhanced capacities and thus serves as a major force in shaping both the systemic context of transformative change and future solutions; at the same time it potentially carries strong societal disruptive power if not handled with caution, care, and innovativeness. This report assesses all the positive potential benefits digitalization brings to sustainable development for all. It also highlights the potential negative impacts and challenges going forward, particularly for those impacted by the ‘digital divide’ that excludes primarily people left behind during the Industrial Revolution like the billion that go hungry every night and the billion who do not have access to electricity. The report outlines the necessary preconditions for a successful digital transformation, including prosperity, social inclusion, environmental sustainability and good governance. Importantly it outlines some of the dramatic social implications associated with an increasingly digital future. It also covers a topic that so far has not been sufficiently dealt with in the cross-over discussions between sustainability and the Digital Revolution, that is, the considerations about related governance aspects.

Electrodynamical processes induced in complex systems like semiconductors by strong electromagnetic fields, have traditionally/conventionally been described using semi-classical approaches. Although these approaches, allowed the investigation of ultrafast dynamics in solids culminating in multi-petahertz electronics, they do not provide any access in the quantum optical nature of the interaction as they treat the driving-field classically and unaffected by the interaction. Here, using a full quantum-optical approach, we demonstrate that the sub-cycle electronic response in a strongly driven semiconductor crystal is imprinted in the quantum-state of the driving-field resulting in non-classical light-states carrying the information of the interaction. This vital step towards strong-field ultrafast quantum electrodynamics unravels information inaccessible by conventional approaches and leads to the development of a new class non-classical light sources., 24 pages, 9 figures

Background/Purpose: Correct classification of patients with systemic lupus erythematosus (SLE) is critical for clinical trials and clinical and translational science. The ACR 1997 criteria were criticized for their suboptimal sensitivity. The Systemic Lupus International Cooperating Clinics (SLICC) 2012 criteria increased sensitivity, but at the price of reduced specificity. This and further advances in the field led to the current four phase SLE criteria project. Following an item generation phase and item reduction via a Delphi and a nominal group exercise (1), the provisional criteria were derived from a multicriteria decision analysis exercise (2). These criteria were hence simplified and validated in a large international cohort. Methods: A large international cohort of 2, 321 patients was collected from 23 SLE expert centers, contributing up to 100 patients with SLE and with non-SLE, each. Diagnoses were verified by 3 independent reviewers for 1, 193 SLE and 1, 059 non- SLE patients. 501 randomly selected SLE and 500 non-SLE patients formed the derivation cohort. All other patients with confirmed SLE or non-SLE diagnosis formed the validation cohort. Sensitivity and specificity were compared to the ACR 1997 and the SLICC 2012 criteria. Results: The criteria were fine-tuned and simplified, using ANA of ≥1:80 as entry criterion and a classification threshold of 10. Items can only be counted for classification if there is no more likely cause, and at least one clinical item must be present.

What will the urban forest in 2100 look like? What will be the key issues, threats and opportunities facing urban green spaces? Answering these questions was the focus of a ‘horizon scanning’ workshop held in Lund, Sweden on 10 October 2018, the fourth in a series of workshops organised by the Clean Air and Urban Landscapes (CAUL) Hub, as part of the Urban Greening for Liveability and Biodiversity research project. This Urban forest horizon scanning research aims to further the knowledge of the potential changes to species, resources and conditions facing future urban forests, through a horizon scanning exercise involving end-users and researchers from CAUL Hub and other institutions. This process canvasses a range of issues including changing climate, urban densification, demographic change, technological changes, water and waterways issues, biodiversity and human health and wellbeing. This project extends previous CAUL Hub research on climate change risks, particularly temperature vulnerabilities, to urban forest species. The workshop outcomes will contribute to improved understanding of the challenges facing urban forests in a changing environment, and inform research, policy and practitioner priorities to build capacity and effectiveness in urban forest management.

The World in 2050 (TWI2050) initiative endeavors to demonstrate how the objectives of sustainable development within planetary boundaries can be met, ensuring prosperity, social inclusion, and good governance for all. TWI2050 is a global research initiative launched by the International Institute for Applied Systems Analysis (IIASA), the Sustainable Development Solutions Network (SDSN), and the Stockholm Resilience Centre (SRC). The initiative brings together a network of more than 150 participants that includes leading policymakers, analysts, modelling and analytical teams from 60 organizations from around the world to collaborate in developing pathways toward sustainable futures and the policy frameworks needed for implementing the SDGs, and more importantly, for achieving the needed transformational change. This report of the international TWI2050 scientific initiative was prepared by more than 60 authors and 20 organization and was launched at UN High-level Political Forum, 9-18 July 2018. It comprises key messages, synthesis and four chapters. Chapter 1 introduced TWI2050 framework. The narrative and target spaces are presented briefly in Chapter 1 and will be further refined in the next phase of TWI2050 and published. Chapter 2 examines, at the global scale, some major current trends in demography, economics, finance, society and politics. It presents potential major tipping points and dynamics that are likely to interact thereby creating a very different world from the present. It assesses currently observable megatrends and historical patterns with corresponding path dependencies. The chapter points to several of these megatrends that need to be taken into consideration how to achieve the transformation to sustainability. Chapter 3 investigates the characteristics of pathways that would lead to sustainable future. It first assess the scientific literature on pathways that achieve several SDGs. Next, implications of the linkages across SDGs are highlighted by presenting model-based pathways which follow an integrated approach with special emphasis on the six transformations. Pathways are presented that feature SDGs under review at HLPF 2018 (SDGs 6, 7, 11, 12 and 15). The chapter concludes with a discussion of research implications. Chapter 4 presents - from multiple perspectives - the governance framework required to achieve and steer transformations toward sustainability. This governance framework comprises of both fine tailored policy principles across the social, economic and political domains as well as enabling conditions for the great (societal) transformation that is needed to achieve the sustainability aspirations. The main findings and conclusions of the four chapters are summarized in the Synthesis presented at the beginning of the report that also connects them to policy interventions.

Item does not contain fulltext OBJECTIVE: Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underlying muscle weakness are poorly understood, but might involve the length of the thin filament, an important determinant of force generation. METHODS: We investigated the sarcomere length-dependence of force, a functional assay that provides insights into the contractile strength of muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1, TPM2, TPM3, TNNT1, KBTBD13, KLHL40, and KLHL41. RESULTS: Lower force generation was observed in muscle fibers from patients of all genotypes. In a subset of patients who harbor mutations in NEB and ACTA1, the lower force was associated with downward shifted force-sarcomere length relations, indicative of shorter thin filaments. Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients. A conditional Neb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanism; the lower force generation that was associated with shorter thin filaments was compensated for by increasing the number of sarcomeres in series. This allowed muscle fibers to operate at a shorter sarcomere length and maintain optimal thin-thick filament overlap. INTERPRETATION: These findings might provide a novel direction for the development of therapeutic strategies for thin filament myopathy patients with shortened thin filament lengths. Ann Neurol 2016;79:959-969.

As stated earlier in the title, the overall aim of the project has been to investigate “Synthesis, Characterisation and Photocatalytic Application of Rhodium-doped Oxides upon Irradiation with Visible Light”. The key considerations in photocatalyst design, assessment and challenges and energy requirements in application is reviewed in the Introduction chapter. In the Discussion chapters, first, a simple one-step strategy was employed to produce a high surface area, phase pure metal oxide that is active in UV light. Various structures have been produced as parent phases such as SrTiO3, BaTiO3 and Y2Ti2O7, and once the presence of phase pure material was confirmed, rhodium substitution was initiated by B site doping of structures by adding soluble Rh salts during phase formation. The idea of using rhodium was to provide active, new rhodium states within the band gap therefore induce e- and h+ transfer that will presumably facilitate photochemical reduction/oxidation reactions with a longer excited wavelength than 400 nm, visible light photons. The series of nanoparticulate SrTi1-xRhxO3 and BaTi1-xRhxO3 materials with x = 0; 0.01; 0.025; 0.050; 0.075 and 0.1 rhodium content have been fully characterised. The functionality of well-known SrTi1-xRhxO3 H2 generating p-type oxide was extended to be successfully applied in water remediation and disinfection with excellent performance in model Methyl Orange molecule degradation and reasonable efficiency in E. coli Gram-negative bacteria inactivation when exposed to visible light (λ > 420 mm). So far, of semiconductor oxides, nitrogen-doped titania in particular have demonstrated activity under visible light in all three functionalities mentioned above, making this new finding very encouraging in the application of SrTi0.95Rh0.05O3 compound. As the investigation of novel advanced materials is crucial in the field, following up on this, a novel stable visible-light-driven photocatalyst (λ ≥ 450 nm) for water oxidation is reported. Rhodium substitution into the pyrochlore Y2Ti2O7 is demonstrated by monitoring the Vegard’s law evolution of the unit-cell parameters with changing rhodium content, to a maximum content of 3% dopant. Substitution renders the solid solutions visible-light active. The overall rate of oxygen evolution is comparable to WO3 but with superior light-harvesting and surface-area-normalized turnover rates, making Y2Ti1.94Rh0.06O7 an excellent candidate for use in a Z-scheme water splitting system and photoanode.

Mitogen-activated protein kinases (MAPK) promote MAPK activated protein kinase (MAPKAPK) activation. In the MAPK pathway responsible to cell growth, ERK2 initiates the first phosphorylation event on RSK1, which is inhibited by calcium-binding S100 proteins in malignant melanomas. Here we present a detailed in vitro biochemical and structural characterization of the S100B-RSK1 interaction. The calcium-dependent binding of S100B to the calcium/calmodulin dependent protein kinase (CaMK)-type domain of RSK1 is reminiscent to the better known binding of calmodulin to CaMKII. Although S100B-RSK1 and the calmodulin-CAMKII system are clearly distinct functionally, they demonstrate how unrelated intracellular Ca2+ binding proteins could influence the activity of CaMK domain containing protein kinases. Our crystallographic, small angle X-ray scattering (SAXS) and NMR analysis revealed that S100B forms a ''fuzzy'' complex with RSK1 peptide ligands. Based on fast-kinetics experiments we conclude that the binding involves both conformation selection and induced fit steps. Knowledge of the structural basis of this interaction could facilitate therapeutic targeting of melanomas.

TNF-α, a potent proinflammatory cytokine, is generated in a precursor form called transmembrane (m)TNF-α that is expressed as a type II polypeptide on the surface of certain cells. mTNF-α was shown to act both as a ligand by binding to TNF-α receptors, as well as a receptor that transmits outside-to-inside (reverse) signals back into the mTNF-α-bearing cells. In this study, we show that nonactivated macrophages express basal levels of mTNF-α and respond to anti-TNF-α Abs by triggering the MAPK kinase 4 signaling pathway. The pathway induces TGF-β. Based on inhibitory experiments, the production of TGF-β1 is regulated via Jun kinases, whereas that of other TGF-βs is regulated via p38 MAPKs. Exposure to LPS further induced the expression of mTNF-α, and triggering of mTNF-α strongly suppressed the LPS-induced proinflammatory response. Neutralizing TGF-β by Abs prevented the mTNF-α-mediated suppression of LPS-induced proinflammatory cytokine formation, indicating that the immunesuppressive effect of mTNF-α is mediated via TGF-β. Although apoptotic cells are also known to suppress LPS-induced proin-flammatory cytokine formation in macrophages by upregulating TGF-β, we show that they do not use the mTNF-α signaling pathway. Because TGF-β possesses a wide range of immune-suppressive effects, our data indicate that upregulation of TGF-β synthesis by those TNF-α-targeting molecules, which are able to trigger mTNF-α, might contribute to their therapeutic effect in the treatment of certain inflammatory diseases such as Crohn's disease, Wegener's granulomatosis, or sarcoidosis. Additionally, none of the TNF-α-targeting molecules is expected to interfere with the immune-silencing effects of apoptotic cells. © 2016 by The American Association of Immunologists, Inc.

Ciomadul is the youngest volcano in the Carpathian-Pannonian region produced crystal-rich high-K dacites that contain abundant amphibole phenocrysts. The amphiboles in the studied dacites are characterized by large variety of zoning patterns, textures, and a wide range of compositions (e.g., 6.4-15 wt% Al2O3, 79-821 ppm Sr) often in thin-section scale and even in single crystals. Two amphibole populations were observed in the dacite: low-Al hornblendes represent a cold (900 °C) mafic magma. Amphibole thermobarometry suggests that the silicic crystal mush was stored in an upper crustal storage (~8-12 km). This was also the place where the erupted dacitic magma was formed during the remobilization of upper crustal silicic crystal mush body by hot mafic magma indicated by simple-zoned and composite amphiboles. This includes reheating (by ~200 °C) and partial remelting of different parts of the crystal mush followed by intensive crystallization of the second mineral population (including pargasites). Breakdown textures of amphiboles imply that they were formed by reheating in case of hornblendes, suggesting that pre-eruptive heating and mixing could take place within days or weeks before the eruption. The decompression rim of pargasites suggests around 12 days of magma ascent in the conduit. Several arc volcanoes produce mixed intermediate magmas with similar bimodal amphibole cargo as the Ciomadul, but in our dacite the two amphibole population can be found even in a single crystal (composite amphiboles). Our study indicates that high-Al pargasites form as a second generation in these magmas after the mafic replenishment into a silicic capture zone; thus, they cannot unambiguously indicate a deeper mafic storage zone beneath these volcanoes. The simple-zoned and composite amphiboles provide direct evidence that significant compositional variations of amphiboles do not necessarily mean variation in the pressure of crystallization even if the Al-tschermak substitution can be recognized, suggesting that amphibole barometers that consider only amphibole composition may often yield unrealistic pressure variation

Repair mortars mainly used in the restoration of porous limestone and sandstone were studied under laboratory conditions for salt durability. Cubic specimens of various types of repair mortars were exposed to sodium-sulphate solution by applying standard salt crystallization test methods. Loss of weight and changes of mechanical properties were detected. The response of repair mortar and porous limestone to typical wetting–drying experiments and salt exposure experiments were compared. Uniaxial compressive strength was measured after 14, 28 days of casting, while durability was assessed by comparing strength test results of samples kept dry conditions, in water or after salt exposition. The results show that damaging of limestones and repair mortars are closely related to material properties and especially to the pore-size distribution of samples. In: I. Ioannou, M Theodoridou (Eds.), SWBSS2011 -Salt weathering on Buildings and Stone Sculpture,19.-22. October, Limassol, Cyprus, S. 323-330, ISBN 978-9963-7355-1-8

The oxidation of ethene on the Pd(111) surface was studied in the temperature range of 330–923 K by in situ XPS and mass spectrometry both heating and cooling in a reaction mixture of 5 × 10−4 mbar C2H4 and 1.5 × 10−3 mbar O2. Carbon-containing surface species were found to be strongly predominant over oxygen species within the whole temperature range, despite the excess of oxygen in the gas phase. Diffusion of carbon into the palladium bulk started at 480 K, leading to the appearance of an electronically altered, dissolved carbon phase with a C1s energy of 284.45 eV at ~500 K, which extended over several layers in the near-surface region and was stable up to ~650 K. This spectroscopic trend was clearly related to a pronounced shift of catalytic selectivity toward CO. Above 660 K, the dissolved carbon species decomposed, the reaction occurred on an adsorbate-depleted Pd metal surface, with CO as the main product. During the cooling ramp, the same near-carbon modification formed at a 70-degree-lower threshold temperature, inducing pronounced hysteresis of the catalytic selectivity.

AIMS To compare the efficacy and safety of lanoteplase, a single-bolus thrombolytic drug derived from alteplase tissue plasminogen activator, with the established accelerated alteplase regimen in patients presenting within 6 h of onset of ST elevation acute myocardial infarction. METHODS AND RESULTS 15,078 patients were recruited from 855 hospitals worldwide and randomized in a 2:1 ratio to receive either lanoteplase 120 KU. kg(-1)as a single intravenous bolus, or up to 100 mg accelerated alteplase given over 90 min. The primary end-point was all-cause mortality at 30 days and the hypothesis was that the two treatments would be equivalent. By 30 days, 6.61% of alteplase-treated patients and 6.75% lanoteplase-treated patients had died (relative risk 1.02). Total stroke occurred in 1.53% alteplase- and 1.87% lanoteplase-treated patients (ns); haemorrhagic stroke rates were 0.64% alteplase and 1.12% lanoteplase (P=0.004). The net clinical deficit of 30-day death or non-fatal disabling stroke was 7.0% and 7.2%, respectively. By 6 months, 8.8% of alteplase-treated patients and 8.7% of lanoteplase-treated patients had died. CONCLUSION Single-bolus weight-adjusted lanoteplase is an effective thrombolytic agent, equivalent to alteplase in terms of its impact on survival and with a comparable risk-benefit profile. The single-bolus regimen should shorten symptoms to treatment times and be especially convenient for emergency department or out-of-hospital administration.

Ciomadul is the youngest volcano in the Carpathian–Pannonian region produced crystal-rich high-K dacites that contain abundant amphibole phenocrysts. The amphiboles in the studied dacites are characterized by large variety of zoning patterns, textures, and a wide range of compositions (e.g., 6.4–15 wt% Al2O3, 79–821 ppm Sr) often in thin-section scale and even in single crystals. Two amphibole populations were observed in the dacite: low-Al hornblendes represent a cold ( 900 °C) mafic magma. Amphibole thermobarometry suggests that the silicic crystal mush was stored in an upper crustal storage (~8–12 km). This was also the place where the erupted dacitic magma was formed during the remobilization of upper crustal silicic crystal mush body by hot mafic magma indicated by simple-zoned and composite amphiboles. This includes reheating (by ~200 °C) and partial remelting of different parts of the crystal mush followed by intensive crystallization of the second mineral population (including pargasites). Breakdown textures of amphiboles imply that they were formed by reheating in case of hornblendes, suggesting that pre-eruptive heating and mixing could take place within days or weeks before the eruption. The decompression rim of pargasites suggests around 12 days of magma ascent in the conduit. Several arc volcanoes produce mixed intermediate magmas with similar bimodal amphibole cargo as the Ciomadul, but in our dacite the two amphibole population can be found even in a single crystal (composite amphiboles). Our study indicates that high-Al pargasites form as a second generation in these magmas after the mafic replenishment into a silicic capture zone; thus, they cannot unambiguously indicate a deeper mafic storage zone beneath these volcanoes. The simple-zoned and composite amphiboles provide direct evidence that significant compositional variations of amphiboles do not necessarily mean variation in the pressure of crystallization even if the Al-tschermak substitution can be recognized, suggesting that amphibole barometers that consider only amphibole composition may often yield unrealistic pressure variation.

A series of potent inhibitors of NADPH- and Fe(2+)-dependent lipid peroxidation has been found among new pyrimido[1'6':1,2]pyrido[3,4-b]indole derivatives. According to preliminary structure-activity relationship analysis the saturated pyrimidine moiety was responsible for this effect. Some members of this family were effective in a bilateral carotid occlusion model in mice, and some derivatives showed protective effect in a mouse head injury model.

Cloud based computing is among the top present-day research areas. Datacenters serving as the backend for cloud solutions have to satisfy the demands set by the time-critical applications emerging in our rushing world. In order to provide physical redundancy, the datacenters are equipped with redundant interserver connections that are left idle during normal operation via the traditional TCP protocol, e.g. with regards to link-capacity aggregation. Our paper provides a comparison between two technologies (MPTCP and MPT-GRE) that support multipath operation and could prove useful in datacenter environments by increasing efficiency and enhancing user experience in the cloud.

Multipath communication technologies is one of the current research fields for infocommunications. No better proof for this than having the specification of the MPTCP protocol, considered the field’s mothership, integrated into the operating systems of multiple corporations (e.g. Apple, Cisco) shorty after being released. The MPTCP multipath solution is practically the extension of the classic TCP protocol with the application of TCPsubflows. Besides its numerous advantages, this multipath protocol has a big drawback as well, namely that it supports data transfer over TCP only. However, for transmitting multimedia traffic, the UDP protocol is the practical choice. Stemming from this idea, the Networks Research Group at the Faculty of Informatics, University of Debrecen, has started development of a multipath communication technology (MPT-GRE) that aims to fulfil this need, providing an alternate solution besides MPTCP. In this paper we provide a comparison based on performance measurements between the MPTCP as a reference and the MPT solution developed by our research group, illustrated via numerous scenarios implemented over quad-path Gigabit Ethernet and IPv4/IPv6 connections.