633 research outputs found

    A new monotypic genus and species from China, \u3cem\u3eLangxie feti\u3c/em\u3e gen. et sp. n. (Scorpiones: Buthidae)

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    A new monotypic genus, Langxie gen. n., is described from Xizang (Tibet), China. The new genus shares an important morphological character with Afrolychas Kovaƙík, 2019: absence of external accessory denticles (EADs) along the sixth row of median denticles (MDs) on the pedipalp movable finger. Langxie gen. n. is different from Afrolychas in the following aspects: loss of EAD near the proximally enlarged MD within each row (i. e., loss of all EAD on the movable finger; this also distinguishes the new genus from other related genera in the “(Ananteris + Isometrus)” clade (Ơtundlová et al., 2022)), subaculear tubercle armed with or without a secondary tubercle dorsally, immaculate color pattern, more slender appendages and metasoma, and less sexually dimorphic pectines. Langxie gen. n. further differs from another geographically close genus, Himalayotityobuthus Lourenço, 1997, by the presence of highly developed pectinal fulcra (vs. absent in Himalayotityobuthus), six rows of MDs on the pedipalp movable finger (vs. 7–8 in Himalayotityobuthus) and five pairs of lateral ocelli (vs. 3 in Himalayotityobuthus). The new species, Langxie feti sp. n., is small and slender, exhibiting no obvious sexual dimorphism in pedipalp and metasoma, but the sexes are visibly different in the relative size of median ocelli and coarseness of carapacial granulation. Lattice microstructures are prominently developed on its cuticle

    Stability evaluation of a DC micro-grid and future interconnection to an AC system

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    This paper presents the stability analysis of a DC micro-grid fed by renewable sources and the future interconnection with an AC micro-grid. This interconnection is realized through a voltage source converter, and the operation of the micro-grid is in island mode. The stability is analyzed by the Nyquist criteria with the impedance relation method. The frequency response of the models was obtained by the injection of a perturbation current at the operation point. Where this perturbation was at the input of the converter used to export power from the DC grid. Other perturbation was applied at the node of the micro-grid to evaluate its impedance. Finally the simulations show the impedance representation of the systems, and the stability for the interconnection of them. The experimental verification shows the impedance of the converter with the same tendency as the representation obtained by the analytical and simulation

    MEDBERT.de: A Comprehensive German BERT Model for the Medical Domain

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    This paper presents medBERTde, a pre-trained German BERT model specifically designed for the German medical domain. The model has been trained on a large corpus of 4.7 Million German medical documents and has been shown to achieve new state-of-the-art performance on eight different medical benchmarks covering a wide range of disciplines and medical document types. In addition to evaluating the overall performance of the model, this paper also conducts a more in-depth analysis of its capabilities. We investigate the impact of data deduplication on the model's performance, as well as the potential benefits of using more efficient tokenization methods. Our results indicate that domain-specific models such as medBERTde are particularly useful for longer texts, and that deduplication of training data does not necessarily lead to improved performance. Furthermore, we found that efficient tokenization plays only a minor role in improving model performance, and attribute most of the improved performance to the large amount of training data. To encourage further research, the pre-trained model weights and new benchmarks based on radiological data are made publicly available for use by the scientific community.Comment: Keno K. Bressem and Jens-Michalis Papaioannou and Paul Grundmann contributed equall

    Regulation of polarised growth in fungi

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    Polarised growth in fungi occurs through the delivery of secretory vesicles along tracks formed by cytoskeletal elements to specific sites on the cell surface where they dock with a multiprotein structure called the exocyst before fusing with the plasmamembrane. The budding yeast, Saccharomyces cerevisiae has provided a useful model to investigate the mechanisms involved and their control. Cortical markers, provided by bud site selection pathways during budding, the septin ring during cytokinesis or the stimulation of the pheromone response receptors during mating, act through upstream signalling pathways to localise Cdc24, the GEF for the rho family GTPase, Cdc42. Cdc42 in its GTP-bound activates a multiprotein protein complex called the polarisome which nucleates actin cables along which the secretory vesicles are transported to the cell surface. Hyphae can elongate at a rate orders of magnitude faster than the extension of a yeast bud, so understanding hyphal growth will require substantial modification of the yeast paradigm. The rapid rate of hyphal growth is driven by a structure called the Spitzenkörper, located just behind the growing tip and which is rich in secretory vesicles. It is thought that secretory vesicles are delivered to the apical region where they accumulate in the Spitzenkörper. The Spitzenkörper then acts as vesicle supply centre in which vesicles exit the Spitzenkörper in all directions, but because of its proximity, the tip receives a greater concentration of vesicles per unit area than subapical regions. There are no obvious equivalents to the bud site selection pathway to provide a spatial landmark for polarised growth in hyphae. However, an emerging model is the way that the site of polarised growth in the fission yeast, Schizosaccharomyces pombe, is marked by delivery of the kelch repeat protein, Tea1, along microtubules. The relationship of the Spitzenkörper to the polarisome and the mechanisms that promote its formation are key questions that form the focus of current research

    ZDHHC8 as a candidate gene for schizophrenia: Analysis of a putative functional intronic marker in case-control and family-based association studies

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    BACKGROUND: The chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia. METHODS: Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186). RESULTS: In the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity χ(2 )= 4.43; p = 0.035). The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions. CONCLUSION: The findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia

    Cesium activates the neurotransmitter receptor for glycine

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    The monovalent cations sodium and potassium are crucial for the proper functioning of excitable cells, but, in addition, other monovalent alkali metal ions such as cesium and lithium can also affect neuronal physiology. For instance, there have been recent reports of adverse effects resulting from self-administered high concentrations of cesium in disease conditions, prompting the Food and Drug Administration (FDA) to issue an alert concerning cesium chloride. As we recently found that the monovalent cation NH4+ activates glycine receptors (GlyRs), we investigated the effects of alkali metal ions on the function of the GlyR, which belongs to one of the most widely distributed neurotransmitter receptors in the peripheral and central nervous systems. Whole-cell voltage clamp electrophysiology was performed with HEK293T cells transiently expressing different splice and RNA-edited variants of GlyR α2 and α3 homopentameric channels. By examining the influence of various milli- and sub-millimolar concentrations of lithium, sodium, potassium, and cesium on these GlyRs in comparison to its natural ligand glycine (0.1 mM), we could show that cesium activates GlyRs in a concentration- and post-transcriptional-dependent way. Additionally, we conducted atomistic molecular dynamic simulations on GlyR α3 embedded in a membrane bilayer with potassium and cesium, respectively. The simulations revealed slightly different GlyR-ion binding profiles for potassium and cesium, identifying interactions near the glycine binding pocket (potassium and cesium) and close to the RNA-edited site (cesium) in the extracellular GlyR domain. Together, these findings show that cesium acts as an agonist of GlyRs

    Is Ankyrin a genetic risk factor for psychiatric phenotypes?

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    Background Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disorder, we tried to investigate common findings by analyzing association of ANK3 with schizophrenia, bipolar disorder and unipolar depression. Methods We genotyped three single nucleotide polymorphisms (SNPs) in ANK3 (rs9804190, rs10994336, and rs10761482) in a case-control sample of German descent including 920 patients with schizophrenia, 400 with bipolar affective disorder, 220 patients with unipolar depression according to ICD 10 and 480 healthy controls. Sample was further differentiated according to Leonhard's classification featuring disease entities with specific combination of bipolar and psychotic syndromes. Results We found no association of rs9804190 and rs10994336 with bipolar disorder, unipolar depression or schizophrenia. In contrast to previous findings rs10761482 was associated with bipolar disorder (p = 0.015) but not with schizophrenia or unipolar depression. We observed no association with disease entities according to Leonhard's classification. Conclusion Our results support a specific genetic contribution of ANK3 to bipolar disorder though we failed to replicate findings for schizophrenia. We cannot confirm ANK3 as a common risk factor for different diseases

    Blockchain for Organising Effective Grass-Roots Actions on a Global Commons: Saving The Planet

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    An overwhelming majority of experts has been flagging for decades that “Saving the Planet” requires immediate, persistent and drastic action to curb a variety of catastrophic risks over the 21st century. However, despite compelling evidence and a range of suggested solutions, transnational coordination of effective measures to protect our biosphere continues to fall short. To remedy, we propose a novel platform for addressing the central issue of affording trust, transparency and truth while minimizing administrative overheads. This will empower an even loosely organised, global grass-roots community to coordinate a large-scale project on a shared goal (“Commons”) spanning the digital and real world. The Web3 concept is based on the swiftly emerging “Blockchain” and related cryptographic, distributed and permissionless technologies. “Wisdom of the crowds” mechanisms involving competitive parallelisation and prediction markets are enabled by formalised reputation and staking to incentivise high-quality work, fair validation and best management practice. While these mechanisms have been (mostly separately) applied to science, business, governance, web, sensor, information and communication technologies (ICT), our integrative approach around Blockchain-enabled ‘operating principles and protocols’ sets the basis for designing novel forms of potentially crowdfunded Decentralised Autonomous Organisations (DAOs)

    Conserved Orb6 Phosphorylation Sites Are Essential for Polarized Cell Growth in Schizosaccharomyces pombe

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    The Ndr-related Orb6 kinase is a key regulator of polarized cell growth in fission yeast, however the mechanism of Orb6 activation is unclear. Activation of other Ndr kinases involves both autophosphorylation and phosphorylation by an upstream kinase. Previous reports suggest that the Nak1 kinase functions upstream from Orb6. Supporting this model, we show that HA-Orb6 overexpression partially restored cell polarity in nak1 ts cells. We also demonstrated by coimmunoprecipitation and in vitro binding assays that Nak1 and Orb6 physically interact, and that the Nak1 C-terminal region is required forNak1/Orb6 complex formation in vivo. However, results from in vitro kinase assays did not show phosphorylation of recombinant Orb6 by HA-Nak1, suggesting that Orb6 activation may not involve direct phosphorylation by Nak1. To investigate the role of Orb6 phosphorylation and activity, we substituted Ala at the ATP-binding and conserved phosphorylation sites. Overexpression of kinase-dead HA-Orb6K122A in wild-type cells resulted in a loss of cell polarity, suggesting that it has a dominant-negative effect, and it failed to rescue the polarity defect of nak1 or orb6 ts mutants. Recombinant GST-Orb6S291A did not autophosphorylate in vitro suggesting that Ser291 is the primary autophosphorylation site. HA-Orb6S291A overexpression only partially rescued the orb6 polarity defect and failed to rescue the nak1 defect, suggesting that autophosphorylation is important for Orb6 function. GST-Orb6T456A autophosphorylated in vitro, indicating that the conserved phosphorylation site at Thr456 is not essential for kinase activity. However, HA-Orb6T456A overexpression had similar effects as overexpressing kinase-dead HA-Orb6K122A, suggesting that Thr456 is essential for Orb6 function in vivo. Also, we found that both phosphorylation site mutations impaired the ability of Myc-Nak1 to coimmunoprecipitate with HA-Orb6. Together, our results suggest a model whereby autophosphorylation of Ser291 and phosphorylation of Thr456 by an upstream kinase promote Nak1/Orb6 complex formation and Orb6 activation
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