496 research outputs found

    Security-sensitive tackling of obstructed workflow executions

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    Imposing access control onto workflows considerably reduces the set of users authorized to execute the workflow tasks. Further constraints (e.g. Separation of Duties) as well as unexpected unavailabilty of users may finally obstruct the successful workflow execution. To still complete the execution of an obstructed workflow, we envisage a hybrid approach. If a log is provided, we partition its traces into “successful” and “obstructed” ones by analysing the given workflow and its authorizations. An obstruction should then be solved by finding its nearest match from the list of successful traces. If no log is provided, we flatten the workflow and its authorizations into a Petri net and encode the obstruction with a corresponding “obstruction marking”. The structural theory of Petri nets shall then be tweaked to provide a minimized Parikh vector, that may violate given firing rules, however reach a complete marking and by that, complete the workflow.Peer ReviewedPostprint (published version

    Development of a Gamow No-Core Shell-Model Framework for Nuclear Resonances

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    The development of sophisticated ab initio methods and the improvement of nuclear interactions derived from chiral effective field theory allow a very precise description of nuclear bound-state observables. In recent years, the development of ab initio methods that include the continuum degrees of freedom have made significant progress. Those methods allow the description of nuclear resonances. In this work, we develop an ab initio Gamow no-core shell model (GNCSM) framework for the description of nuclear resonances. The GNCSM is an extension of the NCSM, which is a very common ab initio method for a precise calculation of bound-state observables. The GNCSM makes use of the Berggren completeness relation, which enables the use of single-particle resonance and scattering continuum states in an orthonormal single-particle basis. As a consequence, the GNCSM Hamilton matrix becomes complex symmetric. The complex eigenvalues are able to describe the decay rate of nuclear resonances. The matrix elements for the GNCSM are calculated using an expansion in harmonic-oscillator matrix elements in order to regulate the infinite single-particle continuum states. The GNCSM with the Berggren single-particle basis is used to calculate a reference state. For this reference state, we compute a set of optimized Gamow natural orbitals in order to enhance the convergence rate in a subsequent GNCSM calculation. Finally, multiple Gamow natural orbital sets are used to compute a final result with a many-body uncertainty. The GNCSM framework is applied to resonances of various light nuclei. For some of these nuclei, we present a more precise calculation than the current spread of experimental results. Furthermore, we investigate different realistic interactions derived from chiral effective field theory with respect to their influence on the resonance energy and find that the dependence on the interaction is negligible compared to the many-body uncertainty of our framework. As a final application, we study the tetraneutron and find indications for a low-lying resonance

    Achieving a stealth effect of nanocarriers through controlled protein adsorption

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    Drug delivery by nanocarriers has evolved into a momentous field of interdisciplinary research. A crucial aspect for the success of any form of future nanotherapeutic is the protein corona, which forms around the surface of a nanocarrier immediately once it enters a bodily fluid like blood plasma. Certain apolipoproteins in this corona are responsible for the ‘stealth effect’, i.e. the non-uptake of a nanocarrier by phagocytes and a resulting long blood circulation time. The aim of controlled biological behavior through a defined ‘stealth’ protein corona was approached from different sides in this work. Firstly, with the physical adsorption of poly(phosphoester) surfactants a new approach to the stealth effect of polystyrene nanoparticles was introduced to facilitate and generalize the stealth functionalization strategy. A similar composition of the protein corona as for nanocarriers with poly(ethylene glycol) chains grafted to their surface could be observed. Cellular uptake experiments confirmed a stealth effect for the surfactant-coated nanoparticles. Afterwards, the role of lipids for the formation of a stealth corona and the consequences for cellular uptake were investigated. Lipoprotein adsorption to nanoparticles was analyzed with various methods and new insights into the mechanism of the interaction with nanoparticles could be gained. Evidence for the disintegration of lipoprotein complexes upon adsorption was found. Moreover, denaturation of important stealth corona proteins by surfactants was analyzed with complementary methods. In this context, the effect of additional cetyltrimethylammonium chloride on the composition of the protein corona was studied and a clear shift could be observed. Two selected apolipoproteins were screened for their sensitivity to surfactant denaturation and significant differences were found. Further, a possible influence of heat inactivation on the folding state and adsorption behavior of proteins was investigated. Finally, the commonly used stealth polymer poly(ethylene glycol) has been tested for possible interaction with proteins. In conclusion, new findings on the complex interactions of nanoparticle formulations with single proteins and blood plasma could be gained and the potential influence of surfactants could be illuminated. The results gained in this work provide valuable knowledge for future research on this subject.Die Wirkstoffverabreichung durch NanotrĂ€ger hat sich zu einem wichtigen Feld interdisziplinĂ€rerer Forschung entwickelt. Ein entscheidender Aspekt fĂŒr den Erfolg von jeglicher Form eines Nanotherapeutikums ist die Proteincorona, die sich um die OberflĂ€che eines NanotrĂ€gers bildet, sobald dieser in eine KörperflĂŒssigkeit wie Blutplasma eintritt. Bestimmte Apolipoproteine in dieser Corona sind fĂŒr den ‚Stealth Effekt‘ verantwortlich, dieser bezeichnet die verhinderte Aufnahme eines NanotrĂ€gers durch Phagozyten und eine resultierende lange Zirkulationszeit im Blut. Dem Ziel eines kontrollierten biologischen Verhaltens durch eine definierte ‚Stealth‘ Proteincrona wurde sich in dieser Arbeit von verschiedenen Seiten genĂ€hert. ZunĂ€chst wurde mit der physikalischen Adsorption von Polyphosphoester-Tensiden ein neuer Ansatz fĂŒr den Stealth-Effekt von Polystyrol-Nanopartikeln vorgestellt, um die Strategie der Stealth-Funktionalisierung zu vereinfachen und zu verallgemeinern. Eine Ă€hnliche Zusammensetzung der Proteincorona wie fĂŒr NanotrĂ€ger mit auf der OberflĂ€che aufgepfropften Polyethylenglycol-Ketten konnte beobachtet werden. Zellaufnahmeversuche bestĂ€tigten einen Stealth-Effekt fĂŒr Tensid-beladene Nanopartikel. Anschließend wurde die Rolle von Lipiden fĂŒr die Ausbildung einer Stealth-Corona und die Konsequenzen fĂŒr die Zellaufnahme untersucht. Die Adsorption von Lipoproteinen an Nanopartikel wurde mit vielfĂ€ltigen Methoden analysiert und neue Erkenntnisse ĂŒber den Mechanismus der Wechselwirkung mit Nanopartikeln konnten gewonnen werden. Anhaltspunkte fĂŒr den Zerfall von Lipoprotein-Komplexen bei der Adsorption wurden festgestellt. Zudem wurde die Denaturierung wichtiger Stealth-Corona-Proteine durch Tenside mit einander ergĂ€nzenden Methoden analysiert. In diesem Zusammenhang wurde der Effekt von zusĂ€tzlichem Cetyltrimethylammoniumchlorid auf die Zusammensetzung der Protein-Corona studiert und eine klare Verschiebung konnte beobachtet werden. Zwei ausgewĂ€hlte Apolipoproteine wurden hinsichtlich ihrer SensitivitĂ€t gegenĂŒber Tensid-Denaturierung ĂŒberprĂŒft und signifikante Unterschiede wurden festgestellt. Weiterhin wurde ein möglicher Einfluss von Hitzeinaktivierung auf den Faltungszustand und das Adsorptionsverhalten von Proteinen untersucht. Abschließend wurde das ĂŒblicherweise genutzte Stealth-Polymer Polyethylenglycol auf mögliche Wechselwirkung mit Proteinen getestet. Schließlich konnten neue Erkenntnisse ĂŒber die komplexen Wechselwirkungen von Nanopartikel-Formulierungen mit einzelnen Proteinen und Blutplasma gewonnen werden und der potentielle Einfluss von Tensiden konnte beleuchtet werden. Die in dieser Arbeit gewonnen Ergebnisse liefern wertvolles Wissen fĂŒr zukĂŒnftige Forschung an diesem Thema

    Aberglaube und Occultismus

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    ABERGLAUBE UND OCCULTISMUS Aberglaube und Occultismus / MĂŒller, Karl Julius (Public Domain) ( - ) Title page ( - ) Preface ( - ) Text ([5]) I. (6) II. (22) Anhang ([39]) Advertising (45) Imprint (48

    Association of diet, lifestyle, and chronotype with metabolic health in Ukrainian adults: a cross-sectional study

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    Morning chronotypes are associated with healthier metabolic profiles and lifestyles compared to evening chronotypes. However, limited research examined the relationship between chronotype, dietary intake, and metabolic health using accurate measures such as food records. This cross-sectional study aimed to investigate the association between chronotype, dietary intake, and metabolic health markers in a cohort of Ukrainian individuals. Chronotypes were determined using the Morningness-Eveningness Questionnaire (MEQ) in 110 healthy to obese individuals (30–75 years) without type 2 diabetes. Dietary intake was derived from weighed seven days food diaries, anthropometrics and blood markers of glucose and lipid metabolism were measured. Morning chronotypes were significantly older and exhibited distinct dietary patterns, including lower intake of fat and animal protein and higher intake of carbohydrates when compared to evening chronotypes (p < 0.01). Higher MEQ scores, reflecting a tendency toward a morning chronotype, were associated with lower BMI, waist circumference, fasting triglycerides, and glucose (p < 0.05). Further, being of morning chronotype predicted better overall metabolic health. These associations remained significant after adjusting for confounders. The findings suggest that morning chronotypes have a different dietary pattern characterized by a more balanced diet and favorable metabolic profile. Synchronizing daily routines with morning preferences could positively influence metabolic health

    Association between potassium concentrations, variability and supplementation, and in‑hospital mortality in ICU patients: a retrospective analysis

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    BACKGROUND: Serum potassium concentrations are commonly between 3.5 and 5.0 mmol/l. Standardised protocols for potassium range and supplementation in the ICU are lacking. The purpose of this retrospective analysis of ICU patients was to investigate potassium concentrations, variability and supplementation, and their association with in-hospital mortality. METHODS: ICU patients ≄ 18 years, with ≄ 2 serum potassium values, treated at the CharitĂ© - UniversitĂ€tsmedizin Berlin between 2006 and 2018 were eligible for inclusion. We categorised into groups of mean potassium concentrations:  3.5-4.0, > 4.0-4.5, > 4.5-5.0, > 5.0-5.5, > 5.5 mmol/l and potassium variability: 1st, 2nd and ≄ 3rd standard deviation (SD). We analysed the association between the particular groups and in-hospital mortality and performed binary logistic regression analysis. Survival curves were performed according to Kaplan-Meier and tested by Log-Rank. In a subanalysis, the association between potassium supplementation and in-hospital mortality was investigated. RESULTS: In 53,248 ICU patients with 1,337,742 potassium values, the lowest mortality (3.7%) was observed in patients with mean potassium concentrations between > 3.5 and 4.0 mmol/l and a low potassium variability within the 1st SD. Binary logistic regression confirmed these results. In a subanalysis of 22,406 ICU patients (ICU admission: 2013-2018), 12,892 (57.5%) received oral and/or intravenous potassium supplementation. Potassium supplementation was associated with an increase in in-hospital mortality in potassium categories from > 3.5 to 4.5 mmol/l and in the 1st, 2nd and ≄ 3rd SD (p < 0.001 each). CONCLUSIONS: ICU patients may benefit from a target range between 3.5 and 4.0 mmol/l and a minimal potassium variability. Clear potassium target ranges have to be determined. Criteria for widely applied potassium supplementation should be critically discussed. Trial registration German Clinical Trials Register, DRKS00016411. Retrospectively registered 11 January 2019, http://www.drks.de/DRKS00016411

    Strategic responses to global challenges: The case of European banking, 1973–2000

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    In applying a strategy, structure, ownership and performance (SSOP) framework to three major clearing banks (ABN AMRO, UBS, Barclays), this article debates whether the conclusions generated by Whittington and Mayer about European manufacturing industry can be applied to the financial services sector. While European integration plays a key role in determining strategy, it is clear that global factors were far more important in determining management actions, leading to significant differences in structural adaptation. The article also debates whether this has led to improved performance, given the problems experienced with both geographical dispersion and diversification, bringing into question the quality of decision-making over the long term

    Conservation of S20 as an Ineffective and Disposable IFNÎł-Inducing Determinant of Plasmodium Sporozoites Indicates Diversion of Cellular Immunity.

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    Despite many decades of research to develop a malaria vaccine, only one vaccine candidate has been explored in pivotal phase III clinical trials. This candidate subunit vaccine consists of a portion of a single Plasmodium antigen, circumsporozoite protein (CSP). This antigen was initially identified in the murine malaria model and shown to contain an immunodominant and protective CD8+ T cell epitope specific to the H-2K d (BALB/c)-restricted genetic background. A high-content screen for CD8+ epitopes in the H2K b /D b (C57BL/6)-restricted genetic background, identified two distinct dominant epitopes. In this study, we present a characterization of one corresponding antigen, the Plasmodium sporozoite-specific protein S20. Plasmodium berghei S20 knockout sporozoites and liver stages developed normally in vitro and in vivo. This potent infectivity of s20(-) sporozoites permitted comparative analysis of knockout and wild-type parasites in cell-based vaccination. Protective immunity of irradiation-arrested s20(-) sporozoites in single, double and triple immunizations was similar to irradiated unaltered sporozoites in homologous challenge experiments. These findings demonstrate the presence of an immunogenic Plasmodium pre-erythrocytic determinant, which is not essential for eliciting protection. Although S20 is not needed for colonization of the mammalian host and for initiation of a blood infection, it is conserved amongst Plasmodium species. Malarial parasites express conserved, immunogenic proteins that are not required to establish infection but might play potential roles in diverting cellular immune responses
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