δ13C analysis of bulk organic matter in speleothems using liquid chromatography-isotope ratio mass spectrometry

The determination of δ13C values in speleothems is of considerable importance in palaeoenvironmental research, but has focussed solely on analysis of the carbonate. Here we demonstrate a new method for analysing the δ13C values of organic matter (OM) trapped in speleothems, utilising flow injection liquid chromatography-isotope ratio mass spectrometry (LCIRMS).Developmental analysis using a homogenised speleothem powder showed that the method is robust, with repeated digests and analyses having an average standard deviation of 0.1‰. Dilution tests with samples of 4-23µg total organic carbon (TOC) show relatively small linearity effects, with the overall standard deviation across a peak response range of 1700-9000 mV being 0.2‰

Meta-Learning with Variational Semantic Memory for Word Sense Disambiguation

A critical challenge faced by supervised word sense disambiguation (WSD) is the lack of large annotated datasets with sufficient coverage of words in their diversity of senses. This inspired recent research on few-shot WSD using meta-learning. While such work has successfully applied meta-learning to learn new word senses from very few examples, its performance still lags behind its fully supervised counterpart. Aiming to further close this gap, we propose a model of semantic memory for WSD in a meta-learning setting. Semantic memory encapsulates prior experiences seen throughout the lifetime of the model, which aids better generalization in limited data settings. Our model is based on hierarchical variational inference and incorporates an adaptive memory update rule via a hypernetwork. We show our model advances the state of the art in few-shot WSD, supports effective learning in extremely data scarce (e.g. one-shot) scenarios and produces meaning prototypes that capture similar senses of distinct words.Comment: 15 pages, 5 figure

ACTUALITY OF GOLDEN RULE OF MORALITY FOR THE YOUNG PEOPLE

В наши дни актуальной становится проблема понимания золотого правила нравственности. В статье обсуждаются результаты исследования того, как молодые люди интерпретируют “золотое правило” нравственности. Выявлена потребность в объяснении базовых этических концепций, в целом положительное отношение к “золотому правилу”, склонность следовать собственным интересам в ситуации нравственного выбора.Today the problem related to the understanding of the “Golden Rule” of morality is increasing. The article considers the interpretation of the “Golden Rule” principle by young people. The results of the study show that young people lack an understanding of basic ethical concepts, however in general aware of the “Golden Rule”, have a positive view of this principle, but a tendency to follow their own interests in a situation of moral choice

Clinical guidelines ‘Hyperprolactinemia’ (draft)

Hyperprolactinemia is a persistent excess of the blood serum prolactin. The syndrome contains various symptoms, the most characteristic is a violation of the reproductive system. There are multiple endogenous and exogenous causes of hyperprolactinemia. The main treatment method is dopamine agonist therapy, in case of prolactinoma existence, surgical and radiation methods can be applied. About 15% of patients are resistant to dopamine agonist therapy, which determines creation of individual management tactics. The article presents a draft of clinical guidelines for the diagnosis and treatment of hyperprolactinemia, which provides a modern examination algorithm, discusses the basic principles of diagnostics and treatment approaches

Importance of Post-Translational Modifications for Functionality of a Chloroplast-Localized Carbonic Anhydrase (CAH1) in Arabidopsis thaliana

Background: The Arabidopsis CAH1 alpha-type carbonic anhydrase is one of the few plant proteins known to be targeted to the chloroplast through the secretory pathway. CAH1 is post-translationally modified at several residues by the attachment of N-glycans, resulting in a mature protein harbouring complex-type glycans. The reason of why trafficking through this non-canonical pathway is beneficial for certain chloroplast resident proteins is not yet known. Therefore, to elucidate the significance of glycosylation in trafficking and the effect of glycosylation on the stability and function of the protein, epitope-labelled wild type and mutated versions of CAH1 were expressed in plant cells. Methodology/Principal Findings: Transient expression of mutant CAH1 with disrupted glycosylation sites showed that the protein harbours four, or in certain cases five, N-glycans. While the wild type protein trafficked through the secretory pathway to the chloroplast, the non-glycosylated protein formed aggregates and associated with the ER chaperone BiP, indicating that glycosylation of CAH1 facilitates folding and ER-export. Using cysteine mutants we also assessed the role of disulphide bridge formation in the folding and stability of CAH1. We found that a disulphide bridge between cysteines at positions 27 and 191 in the mature protein was required for correct folding of the protein. Using a mass spectrometric approach we were able to measure the enzymatic activity of CAH1 protein. Under circumstances where protein N-glycosylation is blocked in vivo, the activity of CAH1 is completely inhibited. Conclusions/Significance: We show for the first time the importance of post-translational modifications such as N-glycosylation and intramolecular disulphide bridge formation in folding and trafficking of a protein from the secretory pathway to the chloroplast in higher plants. Requirements for these post-translational modifications for a fully functional native protein explain the need for an alternative route to the chloroplast.This work was supported by the Swedish Research Council (VR), the Kempe Foundations and Carl Tryggers Foundation to GS, and grant numbers BIO2006-08946 and BIO2009-11340 from the Spanish Ministerio de Ciencia e Innovación (MICINN) to A

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF