Transient stability analysis in Multi-terminal VSC-HVDC grids

A novel approach to transient stability analysis in multi-terminal high voltage direct current (MTDC) grids is presented in this paper. A symmetrical three-phase fault in an ac grid connected to a rectifier terminal of the MTDC grid causes the power injected into the dc grid to decrease, which in turn leads to a lower dc voltage in the MTDC grid. If dc voltage drops below a critical voltage limit before the ac fault is cleared, then the dc grid becomes unstable and its operation is disrupted. An analytical approach is proposed in this paper to calculate the critical clearing time of a fault in an ac grid behind a rectifier terminal beyond which dc voltage collapse occurs. A five-terminal MTDC grid modeled in EMTDC/PSCAD is used to validate the results obtained with the analytical method

Stainless-steel crowns in children : Norwegian and Finnish dentists' knowledge, practice and challenges

BackgroundStainless-steel crowns (SSCs) are recommended for restorative treatment of young teeth severely affected by caries, fractures or dental developmental disorders (DDDs). However, despite recommendations and clinical evidence, SSCs are not widely used by general dentists, who favour extraction and more conventional restorations. The present study aimed to investigate the views of and use of SSCs among Norwegian and Finnish dentists.MethodsThe present study was a cross-sectional survey among Norwegian and Finnish dentists. An electronic questionnaire was sent to Norwegian and Finnish dentists asking whether they used SSCs and on which indications. In addition, the questionnaire assessed reasons for non-use and dentists' perceptions regarding advantages and challenges in the use of SSCs, as well as the need for additional training. Distributions of background characteristics, use of and views on SSCs were calculated, and statistical significance of the associations between respondents' background and their answers were evaluated.ResultsOf the 574 Norwegian and 765 Finnish respondents, only 12.0% and 12.9% reported to use SSCs, respectively. The most frequently reported barrier reported by those who did not use SSCs was lack of practical training. The most frequent challenge reported by those using SSCs was difficulties in crown adjustment followed by aesthetic issues, and the most frequently reported advantage was that SSCs maintain the function and occlusion. The majority of respondents reported a need for more information and practical training in the use of SSCs, with hands-on course as their most frequently preferred education type.ConclusionAlthough the value of SSCs for restoring young molars is recognized by Norwegian and Finnish dentists, SSCs are rarely used by general dentists. The majority of the respondents reported lack of training and materials and was interested in receiving more information and education.Peer reviewe

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria

Initial Quantitative Proteomic Map of 28 Mouse Tissues Using the SILAC Mouse

Identifying the building blocks of mammalian tissues is a precondition for understanding their function. In particular, global and quantitative analysis of the proteome of mammalian tissues would point to tissue-specific mechanisms and place the function of each protein in a whole-organism perspective. We performed proteomic analyses of 28 mouse tissues using high-resolution mass spectrometry and used a mix of mouse tissues labeled via stable isotope labeling with amino acids in cell culture as a "spike-in" internal standard for accurate protein quantification across these tissues. We identified a total of 7,349 proteins and quantified 6,974 of them. Bioinformatic data analysis showed that physiologically related tissues clustered together and that highly expressed proteins represented the characteristic tissue functions. Tissue specialization was reflected prominently in the proteomic profiles and is apparent already in their hundred most abundant proteins. The proportion of strictly tissue-specific proteins appeared to be small. However, even proteins with household functions, such as those in ribosomes and spliceosomes, can have dramatic expression differences among tissues. We describe a computational framework with which to correlate proteome profiles with physiological functions of the tissue. Our data will be useful to the broad scientific community as an initial atlas of protein expression of a mammalian species

Mol. Cell. Proteomics

The term “proteomics” encompasses the large-scale detection and analysis of proteins and their post-translational modifications. Driven by major improvements in mass spectrometric instrumentation, methodology, and data analysis, the proteomics field has burgeoned in recent years. It now provides a range of sensitive and quantitative approaches for measuring protein structures and dynamics that promise to revolutionize our understanding of cell biology and molecular mechanisms in both human cells and model organisms. The Proteomics Specification in Time and Space (PROSPECTS) Network is a unique EU-funded project that brings together leading European research groups, spanning from instrumentation to biomedicine, in a collaborative five year initiative to develop new methods and applications for the functional analysis of cellular proteins. This special issue of Molecular and Cellular Proteomics presents 16 research papers reporting major recent progress by the PROSPECTS groups, including improvements to the resolution and sensitivity of the Orbitrap family of mass spectrometers, systematic detection of proteins using highly characterized antibody collections, and new methods for absolute as well as relative quantification of protein levels. Manuscripts in this issue exemplify approaches for performing quantitative measurements of cell proteomes and for studying their dynamic responses to perturbation, both during normal cellular responses and in disease mechanisms. Here we present a perspective on how the proteomics field is moving beyond simply identifying proteins with high sensitivity toward providing a powerful and versatile set of assay systems for characterizing proteome dynamics and thereby creating a new “third generation” proteomics strategy that offers an indispensible tool for cell biology and molecular medicine

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome

neXtProt: a knowledge platform for human proteins

neXtProt (http://www.nextprot.org/) is a new human protein-centric knowledge platform. Developed at the Swiss Institute of Bioinformatics (SIB), it aims to help researchers answer questions relevant to human proteins. To achieve this goal, neXtProt is built on a corpus containing both curated knowledge originating from the UniProtKB/Swiss-Prot knowledgebase and carefully selected and filtered high-throughput data pertinent to human proteins. This article presents an overview of the database and the data integration process. We also lay out the key future directions of neXtProt that we consider the necessary steps to make neXtProt the one-stop-shop for all research projects focusing on human proteins

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Troppo - A Python framework for the reconstruction of context-specific metabolic models

The surge in high-throughput technology availability for molecular biology has enabled the development of powerful predictive tools for use in many applications, including (but not limited to) the diagnosis and treatment of human diseases such as cancer. Genome-scale metabolic models have shown some promise in clearing a path towards precise and personalized medicine, although some challenges still persist. The integration of omics data and subsequent creation of context-specific models for specific cells/tissues still poses a significant hurdle, and most current tools for this purpose have been implemented using proprietary software. Here, we present a new software tool developed in Python, troppo - Tissue-specific RecOnstruction and Phenotype Prediction using Omics data, implementing a large variety of context-specific reconstruction algorithms. Our framework and workflow are modular, which facilitates the development of newer algorithms or omics data sources.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also thank the PhD scholarships funded by national funds through Fundacao para a Ciencia e Tecnologia, with references: SFRH/BD/133248/2017 (J.F.), SFRH/BD/118657/2016 (V.V.).info:eu-repo/semantics/publishedVersio

Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate

Base excision repair (BER) represents the most important repair pathway of endogenous DNA lesions. Initially, a base damage is recognized, excised and a DNA single-strand break (SSB) intermediate forms. The SSB is then ligated, a process that employs proteins also involved in SSB repair, e.g. XRCC1, Ligase III and possibly PARP1. Here, we confirm the role of XRCC1 and PARP in direct SSB repair. Interestingly, we uncover a synthetic lethality between XRCC1 deficiency and PARP inhibition. We also treated cells with alkylating agent dimethyl sulfate (DMS) and monitored the SSB intermediates formed during BER. DMS-induced SSBs were quickly repaired in wild-type cells; while a rapid accumulation of SSBs was observed in cells where post-incision repair was blocked by a PARP inhibitor or by XRCC1 deficiency (EM9 cells). Interestingly, DMS-induced SSBs did not accumulate in PARP1 siRNA depleted cells, demonstrating that PARP1 is not required for efficient completion of BER. Based on these results we suggest no immediate role for PARP1 in BER, but that PARP inhibitors trap PARP on the SSB intermediate formed during BER. Unexpectedly, addition of PARP inhibitor 2 h after DMS treatment still increased SSB levels indicating ongoing repair even at this late time point