Qualität adhäsiv befestigter Einzelzahnkronen auf Basis der Lithium-Disilikatkeramik „emax-press“ im mittelfristigen klinischen Verlauf

Ziel: Um die klinische Bewährung und Leistungsfähigkeit gepresster Einzelzahnrestaurationen zu bewerten wurden Patienten aus einem prospektiv angelegten Nachsorgeprogramm identifiziert, untersucht und ausgewertet. Methoden/Patienten: 58 Patienten wurden mit 375 gepressten Kronen aus e.max press (Fa. Ivoclar-Vivadent) versorgt. Diese Kronen wurden adhäsiv mit Multilink automix (Fa. Ivoclar Vivadent) befestigt. Die Patienten wurden zur jährlichen Nachuntersuchung eingeladen, um neben einem Zahn- und Hygienestatus zu erheben auch sämtliche Restaurationen anhand der CDA-Kriterien zu bewerten. Jegliches Ereignis welches eine Intervention erforderte, wurde als Komplikation gewertet – jedes Versagen kompromittierte das Überleben. Zur Errechnung von Überlebens- und Komplikationsraten wurden jeweils zwei Analysen nach Kaplan-Meier für alle Kronen und für eine randomisierte Auswahl einer Krone aus einem jedem Patienten durchgeführt. Ergebnisse: 327 (176 Frontzahnbereich, 151 Seitenzahnbereich; 203 Obekiefer, 124 Unterkiefer) Kronen von 45 Patienten (31 w, 14m) mit einem Durchschnittsalter von 43 Jahren (17-73) wurden zwischen 4 und 51 Monaten (Median = 28) beobachtet. In dieser Zeit wurden: 4 chip-offs, 3 Retentionsverluste, 3 Frakturen, 3 Sekundärkaries, 1 Endodontisches Problem und eine Zahnfraktur beobachtet. Vier Kronen mussten in Folge dessen entfernt werden. Überlebens- und Komplikationsraten wurden auf 98.2% sowie 5.4% in 24 Monaten sowie auuf 96.8% und 7.1% auf 48 Monate geschätzt. Die Komplikationsrate war significant höher bei wurzelkanalbehandelten Zähnen (12%, p<.01) nach 24 Monaten. Zum letzten Untersuchungszeitpunkt wurden 90% der Kronen hinsichtlich Randpassung, Farbe und Karies als exzellent (CDA-rating Alfa) bewertet

Vulnerability of coastal and estuarine habitats in the GBR to climate change

Coastal and estuarine habitats occupy a central place in the functioning of tropical marine ecosystems. Their location at the interface between land and sea means they function to modulate the movement of terrestrial materials (eg freshwater, nutrients and pollutants) into the marine environment. Coastal and estuarine habitats also act as a filter, with functional units such as mangrove forests inhibiting trapping and retaining sediments and nutrients. Coastal habitats are also crucial nursery grounds for many species of fish111 and crustaceans, and act as links in the life cycles of species that migrate between marine and freshwater habitats. Beyond this, their close proximity to population and industrial centres makes them the marine habitats most vulnerable to human impacts. The east coast of tropical Queensland comprises a diversity of habitats, ranging from freshwater and littoral marshes, through estuaries, to nearshore open oceans and reefs. These habitats do not function alone but are an interlinked coastal ecosystem mosaic (CEM), connected at a variety of spatial, temporal, functional and conceptual scales. This complex mix of habitats is inhabited by one of the most diverse faunas on earth with organisms covering the full taxonomic spectrum, from viruses and bacteria to cetaceans. Unfortunately, detailed ecological knowledge is limited to a very small subset of the range of these organisms, with many species unknown, unidentified or unquantified. Although it is clear species interact in complex ways, our understanding of this is critically deficient. Moreover, many of the individual components are poorly understood, and details of the links between them largely absent

The "Lake of Olympia": geoarchaeological evidence of a lake environment in the vicinity of ancient Olympia (western Peloponnese, Greece)

Our results yield evidence of a large lake environment that existed near the ancient site of Olympia which was so far unknown. The limnic sequence reveals considerable changes in the ecological conditions over time, based on Direct Push sensing, sedimentary and micropalaeontological analyses. Radiocarbon data show that the “Lake of Olympia“ existed from the 8th/7th millennium BC until, at least, the 1st century AD. The existence of the “Lake of Olympia” next to the cult site of Olympia has considerable historical, archaeological and geographical implications (e.g., as waterway or water supplier)

Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE cells

Purpose: Polymorphisms in complement genes are risk-associated for age-related macular degeneration (AMD). Functional analysis revealed a common deficiency to control the alternative complement pathway by risk-associated gene polymorphisms. Thus, we investigated the levels of terminal complement complex (TCC) in the plasma of wet AMD patients with defined genotypes and the impact of the complement activation of their plasma on second-messenger signaling, gene expression, and cytokine/chemokine secretion in retinal pigment epithelium (RPE) cells. Design: Collection of plasma from patients with wet AMD (n = 87: 62% female and 38% male; median age 77 years) and controls (n = 86: 39% female and 61% male; median age 58 years), grouped for risk factor smoking and genetic risk alleles CFH 402HH and ARMS2 rs3750846, determination of TCC levels in the plasma, in vitro analysis on RPE function during exposure to patients' or control plasma as a complement source. Methods: Genotyping, measurement of TCC concentrations, ARPE-19 cell culture, Ca2+ imaging, gene expression by qPCR, secretion by multiplex bead analysis of cell culture supernatants. Main outcome measures: TCC concentration in plasma, intracellular free Ca2+, relative mRNA levels, cytokine secretion. Results: TCC levels in the plasma of AMD patients were five times higher than in non-AMD controls but did not differ in plasma from carriers of the two risk alleles. Complement-evoked Ca2+ elevations in RPE cells differed between patients and controls with a significant correlation between TCC levels and peak amplitudes. Comparing the Ca2+ signals, only between the plasma of smokers and non-smokers, as well as heterozygous (CFH 402YH) and CFH 402HH patients, revealed differences in the late phase. Pre-stimulation with complement patients' plasma led to sensitization for complement reactions by RPE cells. Gene expression for surface molecules protective against TCC and pro-inflammatory cytokines increased after exposure to patients' plasma. Patients' plasma stimulated the secretion of pro-inflammatory cytokines in the RPE. Conclusion: TCC levels were higher in AMD patients but did not depend on genetic risk factors. The Ca2+ responses to patients' plasma as second-messenger represent a shift of RPE cells to a pro-inflammatory phenotype and protection against TCC. We conclude a substantial role of high TCC plasma levels in AMD pathology

Sparks of Artificial General Intelligence: Early experiments with GPT-4

Artificial intelligence (AI) researchers have been developing and refining large language models (LLMs) that exhibit remarkable capabilities across a variety of domains and tasks, challenging our understanding of learning and cognition. The latest model developed by OpenAI, GPT-4, was trained using an unprecedented scale of compute and data. In this paper, we report on our investigation of an early version of GPT-4, when it was still in active development by OpenAI. We contend that (this early version of) GPT-4 is part of a new cohort of LLMs (along with ChatGPT and Google's PaLM for example) that exhibit more general intelligence than previous AI models. We discuss the rising capabilities and implications of these models. We demonstrate that, beyond its mastery of language, GPT-4 can solve novel and difficult tasks that span mathematics, coding, vision, medicine, law, psychology and more, without needing any special prompting. Moreover, in all of these tasks, GPT-4's performance is strikingly close to human-level performance, and often vastly surpasses prior models such as ChatGPT. Given the breadth and depth of GPT-4's capabilities, we believe that it could reasonably be viewed as an early (yet still incomplete) version of an artificial general intelligence (AGI) system. In our exploration of GPT-4, we put special emphasis on discovering its limitations, and we discuss the challenges ahead for advancing towards deeper and more comprehensive versions of AGI, including the possible need for pursuing a new paradigm that moves beyond next-word prediction. We conclude with reflections on societal influences of the recent technological leap and future research directions

Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE cells

PurposePolymorphisms in complement genes are risk-associated for age-related macular degeneration (AMD). Functional analysis revealed a common deficiency to control the alternative complement pathway by risk-associated gene polymorphisms. Thus, we investigated the levels of terminal complement complex (TCC) in the plasma of wet AMD patients with defined genotypes and the impact of the complement activation of their plasma on second-messenger signaling, gene expression, and cytokine/chemokine secretion in retinal pigment epithelium (RPE) cells.DesignCollection of plasma from patients with wet AMD (n = 87: 62% female and 38% male; median age 77 years) and controls (n = 86: 39% female and 61% male; median age 58 years), grouped for risk factor smoking and genetic risk alleles CFH 402HH and ARMS2 rs3750846, determination of TCC levels in the plasma, in vitro analysis on RPE function during exposure to patients’ or control plasma as a complement source.MethodsGenotyping, measurement of TCC concentrations, ARPE-19 cell culture, Ca2+ imaging, gene expression by qPCR, secretion by multiplex bead analysis of cell culture supernatants.Main outcome measuresTCC concentration in plasma, intracellular free Ca2+, relative mRNA levels, cytokine secretion.ResultsTCC levels in the plasma of AMD patients were five times higher than in non-AMD controls but did not differ in plasma from carriers of the two risk alleles. Complement-evoked Ca2+ elevations in RPE cells differed between patients and controls with a significant correlation between TCC levels and peak amplitudes. Comparing the Ca2+ signals, only between the plasma of smokers and non-smokers, as well as heterozygous (CFH 402YH) and CFH 402HH patients, revealed differences in the late phase. Pre-stimulation with complement patients’ plasma led to sensitization for complement reactions by RPE cells. Gene expression for surface molecules protective against TCC and pro-inflammatory cytokines increased after exposure to patients’ plasma. Patients’ plasma stimulated the secretion of pro-inflammatory cytokines in the RPE.ConclusionTCC levels were higher in AMD patients but did not depend on genetic risk factors. The Ca2+ responses to patients’ plasma as second-messenger represent a shift of RPE cells to a pro-inflammatory phenotype and protection against TCC. We conclude a substantial role of high TCC plasma levels in AMD pathology

The Ontology of Biological Attributes (OBA)-computational traits for the life sciences.

Existing phenotype ontologies were originally developed to represent phenotypes that manifest as a character state in relation to a wild-type or other reference. However, these do not include the phenotypic trait or attribute categories required for the annotation of genome-wide association studies (GWAS), Quantitative Trait Loci (QTL) mappings or any population-focussed measurable trait data. The integration of trait and biological attribute information with an ever increasing body of chemical, environmental and biological data greatly facilitates computational analyses and it is also highly relevant to biomedical and clinical applications. The Ontology of Biological Attributes (OBA) is a formalised, species-independent collection of interoperable phenotypic trait categories that is intended to fulfil a data integration role. OBA is a standardised representational framework for observable attributes that are characteristics of biological entities, organisms, or parts of organisms. OBA has a modular design which provides several benefits for users and data integrators, including an automated and meaningful classification of trait terms computed on the basis of logical inferences drawn from domain-specific ontologies for cells, anatomical and other relevant entities. The logical axioms in OBA also provide a previously missing bridge that can computationally link Mendelian phenotypes with GWAS and quantitative traits. The term components in OBA provide semantic links and enable knowledge and data integration across specialised research community boundaries, thereby breaking silos

The Bowen–Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Ψ1191 in yeast 18S rRNA

The Nep1 (Emg1) SPOUT-class methyltransferase is an essential ribosome assembly factor and the human Bowen–Conradi syndrome (BCS) is caused by a specific Nep1D86G mutation. We recently showed in vitro that Methanocaldococcus jannaschii Nep1 is a sequence-specific pseudouridine-N1-methyltransferase. Here, we show that in yeast the in vivo target site for Nep1-catalyzed methylation is located within loop 35 of the 18S rRNA that contains the unique hypermodification of U1191 to 1-methyl-3-(3-amino-3-carboxypropyl)-pseudouri-dine (m1acp3Ψ). Specific 14C-methionine labelling of 18S rRNA in yeast mutants showed that Nep1 is not required for acp-modification but suggested a function in Ψ1191 methylation. ESI MS analysis of acp-modified Ψ-nucleosides in a Δnep1-mutant showed that Nep1 catalyzes the Ψ1191 methylation in vivo. Remarkably, the restored growth of a nep1-1ts mutant upon addition of S-adenosylmethionine was even observed after preventing U1191 methylation in a Δsnr35 mutant. This strongly suggests a dual Nep1 function, as Ψ1191-methyltransferase and ribosome assembly factor. Interestingly, the Nep1 methyltransferase activity is not affected upon introduction of the BCS mutation. Instead, the mutated protein shows enhanced dimerization propensity and increased affinity for its RNA-target in vitro. Furthermore, the BCS mutation prevents nucleolar accumulation of Nep1, which could be the reason for reduced growth in yeast and the Bowen-Conradi syndrome

3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine

Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-l-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-gamma mediated STAT1/NF-kappa Beta pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1 beta, IFN-gamma, and IL-17 production, and inhibiting generation of effector CD8(+) T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance. 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.Peer reviewe