142 research outputs found
Mßnzen in Gräbern: Eine Studie zur Ursache, Bedeutung und Entwicklung eines kulturßbergreifenden Phänomens im mittelalterlichen Ostmitteleuropa
Trotz seiner epochen- und kulturĂźbergreifenden Anwendung wird der wissenschaftliche Diskurs um den sog. Charonspfennig bis heute vorwiegend durch die Popularität seiner altgriechischen Ăberlieferung bestimmt. Mehr noch nahm die inhaltliche Vorbestimmung der âklassischenâ TotenmĂźnze einen prägnanten Einfluss auf die Klassifikation ihrer modalen Erscheinung, die aus archäologischer Sicht das wohl gängigste Mittel inhaltlicher Differenzierung darstellt. Damit provozierte sie jedoch eine kĂźnstliche Spaltung des Befundspiegels, die sich als nicht immer sinnvoll erwies.
Die Studie behandelt Mßnzen in Gräbern mithilfe eines methodischen Ansatzes, der in erster Linie numismatisch definierbare Objekteigenschaften der Mßnzen selbst fokussiert und hieraus bestimmte ursächliche AuslÜser der Handlung herleitet. Die Ausgangsbasis bildet der Befundspiegel des ostmitteleuropäischen, vorwiegend westslawischen Mittelalters und beinanhaltet sowohl numismatische, als auch archäologische und anthropologische Daten.
Die Ergebnisse suggerieren ein vielschichtiges Phänomen, das im Detail sehr unterschiedlich adaptiert und ausgelegt werden konnte. Zentral diskutierte Ăśkonomische, politische und religiĂśse Aspekte der MĂźnzen lieĂen sich in variierender Gewichtung Ăźber weite Strecken als intentional primäre und/oder sekundäre Merkmale bestimmen, aus denen sich sowohl ihre modale Erscheinung, als auch ihre narrative Tradierung abgeleitet haben mĂśgen. Im GefĂźge ihres gesamthistorischen Befundbildes scheint die MĂźnze im Grab die Rolle eines Stellvertreterobjektes zu Ăźbernehmen, das als Nicht-Bestandteil traditioneller Bestattungssitten die MĂśglichkeit eines additiven Ausdrucks von Identität, Wohlstand und Versorgung bot. Derart grundlegende AnsprĂźche intakter Gemeinschaften berechtigen dazu die MĂźnzbeigabe als kulturunabhängiges Phänomen zu definieren, das zwar kulturspezifisch variiert, dabei jedoch stets an symbolische und/oder materialgebundene Eigenschaften der Objekte selbst gebunden bleibt
Crystal structure of 5,11-dihydropyrido-[2,3-b][1,4]benzodiazepin-6-one
Acknowledgements The authors thank Andreas Lorbach and Todd B. Marder (Institute of Inorganic Chemistry, Wuerzburg University) for the data collection and structure solution. We appreciate the financial support provided to NMR by the Deutscher Akademischer Austauschdienst (DAAD). Thanks are also due to the Deutsche Forschungsgemeinschaft for financial support (SFB 630, Recognition, Preparation and Functional Analysis of Agents against Infectious Diseases, project A1).Peer reviewedPublisher PD
Observation of nano-indent induced strain fields and dislocation generation in silicon wafers using micro-raman spectroscopy and white beam x-ray topography
In the semiconductor manufacturing industry, wafer handling introduces micro-cracks at the wafer edge. During heat treatment these can produce larger, long-range cracks in the wafer which can cause wafer breakage during manufacture. Two complimentary techniques, micro-Raman spectroscopy (ÎźRS) and White Beam Synchrotron X-ray Topography (WBSXRT) were employed to study both the micro-cracks and the associated strain fields produced by nano-indentations in Si wafers, which were used as a means of introducing controlled strain in the wafers. It is shown that both the spatial lateral and depth distribution of these long range strain fields are relatively isotropic in nature. The Raman spectra suggest the presence of a region under tensile strain beneath the indents, which can indicate a crack beneath the indent and the data strongly suggests that there exists a minimum critical applied load below which cracking will not initiate
Melatonin receptors in GtoPdb v.2023.1
Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [40]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon
Melatonin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [36]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon
Melatonin receptors in GtoPdb v.2021.3
Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [40]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon
Piloting the United Kingdon 'Prescribing Safety Assessment' with pharmacist prescribers in Scotland.
Background: Prescribing is a complex task requiring considerable knowledge and skills. The Prescribing Safety Assessment (PSA) was developed by the British Pharmacological Society and the United Kingdom (UK) Medical Schools Council. Between February and June 2014, over 7000 final year medical students undertook the PSA, with an overall pass rate of 94%. Independent prescribing for suitably trained pharmacists was introduced in the UK in 2006. To date there has been little focus on any objective measures of prescribing safety. Objective: To determine the PSA performance of a pilot group of pharmacist prescribers in Scotland relative to medical students and to test the feasibility and acceptability of running the PSA. Methods: A group of 59 pharmacist prescribers took part in ten events. The PSA consisted of 30 questions to be completed over 60 min. All questions had been used in the 2014 assessments for final year medical students. The PSA was undertaken online under invigilated conditions, mirroring the medical student assessment. One month later, participants were invited to complete an online evaluation questionnaire. Results: The mean overall PSA scores (ÂąSD) were 87.5% Âą 8.7 (range 52â98) compared to a 88.5% for medical students. Based on an Angoff passmark of 76.0%, 53 pharmacists (89.8%) passed compared to an overall pass rate in PSA 2014 of 94%. Pharmacists performed equivalently to medical students in all assessment areas, with a slightly lower performance in the prescribing, drug monitoring and data interpretation questions offset by better performance in prescription review and adverse drug reactions. Feedback was positive in relation to appropriateness, relevance and level of difficulty of the PSA although several commented that they were practicing in very specific clinical areas. Conclusion: These pilot events have benchmarked the PSA performance of pharmacist prescribers with final year medical students, and feedback confirmed feasibility and acceptability
PPAR Gamma Activators: Off-Target Against Glioma Cell Migration and Brain Invasion
Today, there is increasing evidence that PPARÎł agonists, including thiazolidinediones (TDZs) and nonthiazolidinediones, block the motility and invasiveness of glioma cells and other highly migratory tumor entities. However, the mechanism(s) by which PPARÎł activators mediate their antimigratory and anti-invasive properties remains elusive. This letter gives a short review on the debate and adds to the current knowledge by applying a PPARÎł inactive derivative of the TDZ troglitazone (Rezulin) which potently counteracts experimental glioma progression in a PPARÎł independent manner
Structure-based discovery of potent and selective melatonin receptor agonists
Melatonin receptors MT1 and MT2 are involved in synchronizing circadian rhythms and are important targets for treating sleep and mood disorders, type-2 diabetes and cancer. Here, we performed large scale structure-based virtual screening for new ligand chemotypes using recently solved high-resolution 3D crystal structures of agonist-bound MT receptors. Experimental testing of 62 screening candidates yielded the discovery of 10 new agonist chemotypes with sub-micromolar potency at MT receptors, with compound 21 reaching EC50 of 0.36 nM. Six of these molecules displayed selectivity for MT2 over MT1 . Moreover, two most potent agonists, including 21 and a close derivative of melatonin, 28, had dramatically reduced arrestin recruitment at MT2, while compound 37 was devoid of Gi signaling at MT1, implying biased signaling. This study validates the suitability of the agonist-bound orthosteric pocket in the MT receptor structures for the structure-based discovery of selective agonists. Š Patel et al
Photoactive assemblies of organic compounds and biomolecules: drug-protein supramolecular systems
[EN] The properties of singlet and triplet excited states are strongly medium-dependent.
Hence, these species constitute valuable tools as reporters to probe compartmentalised
microenvironments, including drug@protein supramolecular systems. In the present
review, the attention is focused on the photophysical properties of the probe drugs
(rather than those of the protein chromophores) using transport proteins (serum
albumins and 1-acid glycoproteins) as hosts. Specifically, fluorescence measurements
allow investigating the structural and dynamic properties of biomolecules or their
complexes. Thus, the emission quantum yields and the decay kinetics of the drug singlet
excited states provide key information to determine important parameters such as the
stoichiometry of the complex, the binding constant, the relative degrees of occupancy of
the different compartments, etc. Application of the FRET concept allows determining
donor-acceptor interchromophoric distances. In addition, anisotropy measurements can
be related to the orientation of the drug within the binding sites, where the degrees of
freedom for conformational relaxation are restricted. Transient absorption spectroscopy
is also a potentially powerful tool to investigate the binding of drugs to proteins, where
formation of encapsulated triplet excited states is favoured over other possible processes
leading to ionic species (i. e. radical ions), and their photophysical properties are
markedly sensitive to the microenvironment experienced within the protein binding
sites. Even under aerobic conditions, the triplet lifetimes of protein-complexed drugs are
remarkably long, which provides a broad dynamic range for identification of distinct
triplet populations or for chiral discrimination. Specific applications of the laser flash
photolysis technique include the determination of drug distribution among the bulk
solution and the protein binding sites, competition of two types of proteins to bind a
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drug, occurrence of drug-drug interactions within protein binding sites, enzymatic-like
activity of the protein or determination of enantiomeric compositions.
The use of proteins as supramolecular hosts modifies the photoreactivity of
encapsulated substrates by providing protection against oxygen or other external
reagents, by imposing conformational restrictions in the binding pockets, or by
influencing the stereochemical outcome. In this review, a selected group of examples is
presented including decarboxylation, dehalogenation, nucleophilic addition,
dimerisation, oxidation, Norrish type II reaction, photo-Fries rearrangement and 6
electrocyclisationFinancial support from the Spanish Government (CTQ2010-14882, JCI-2011-09926, RyC-2007-00476), from the EU (PCIG12-GA-2012-334257), from the Universitat Politènica de València (SP20120757) and from the ConsellerĂa de EducaciĂł, Cultura i Esport (PROMETEOII/2013/005, GV/2013/051) is gratefully acknowledged.VayĂĄ PĂŠrez, I.; Lhiaubet-Vallet, VL.; JimĂŠnez Molero, MC.; Miranda Alonso, MĂ. (2014). Photoactive assemblies of organic compounds and biomolecules: drug-protein supramolecular systems. Chemical Society Reviews. 43:4102-4122. https://doi.org/10.1039/C3CS60413FS410241224
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