1,721,105 research outputs found
Positively charged mineral surfaces promoted the accumulation of organic intermediates at the origin of metabolism.
Full text linkIdentifying plausible mechanisms for compartmentalization and accumulation of the organic intermediates of early metabolic cycles in primitive cells has been a major challenge in theories of life's origins. Here, we propose a mechanism, where positive membrane potentials elevate the concentration of the organic intermediates. Positive membrane potentials are generated by positively charged surfaces of protocell membranes due to accumulation of transition metals. We find that (i) positive membrane potentials comparable in magnitude to those of modern cells can increase the concentration of the organic intermediates by several orders of magnitude; (ii) generation of large membrane potentials destabilize ion distributions; (iii) violation of electroneutrality is necessary to induce nonzero membrane potentials; and (iv) violation of electroneutrality enhances osmotic pressure and diminishes reaction efficiency, resulting in an evolutionary driving force for the formation of lipid membranes, specialized ion channels, and active transport systems
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Advancing Mass Spectrometry-Based Discovery and Quantification of Biomarkers for Human Disease Stratification and Prognostics
No full textProteins are essential for cellular function and for the health of an organism in general. However, their dysfunction can potentially lead to diseases, making them diagnostically informative biomarkers that provide insights into biological processes and various disease mechanisms. Liquid chromatography-mass spectrometry (LC-MS) enables large-scale identification and quantification of proteins, demonstrating immense potential in clinical studies. Discovery LC-MS approaches profiles proteomes, identifies potential biomarkers, which can then be translated into biomarker panels for routine-applicable, absolute quantified targeted approaches. However, challenges such as insufficient quantification and comparability of high-throughput techniques hinders the widespread application of LC-MS in clinics.
This thesis addresses these challenges by advancing technologies and integrating discovery and targeted proteomics to achieve a tangible solution that balances sensitivity, selectivity, as well as comparability between platforms with cost efficiency.
After an introduction (Chapter I) to the topic, Chapter II introduces the Zeno SWATH method, which improves throughput and analytical coverage while minimising sample input and thus costs. Chapter III describes the development and application of a targeted LC-MRM biomarker panel for the stratification of disease severity and prognosis of COVID-19 plasma cohort. In Chapter IV, discovery and targeted proteomics were employed for the first plasma proteomics analysis of Mpox, demonstrating the value of LC-MS in meeting urgent clinical demands and the versatility of LC-MRM biomarker panel in diverse diseases.
To harmonise quantification between LC-MS platforms and methods, Chapter V develops the ‘Charité Open Peptide Standard for Plasma Proteomics (OSPP)’, a panel of 211 stable isotope-labelled peptides, which enables cross-platform comparability at minimal cost and high sample throughput in large-scale clinical plasma-based studies.
Overall, this thesis advances LC-MS technologies for blood biomarker studies and their clinical applications, providing tangible solutions for clinical proteomics by introducing streamlined workflows and universal biomarker panels that are adaptable across diseases and analytical platforms, bringing proteomics closer to routine clinical applications.Proteine sind essentiell für eine normale Zellfunktion und für die Gesundheit eines Organismus generell. Ihre Fehlfunktion kann jedoch auch zu Krankheiten führen, was sie zu diagnostisch informativen Biomarkern macht, die Einblicke in biologische Prozesse und diverse Krankheitsmechanismen bieten. Die Flüssigchromatographie-Massenspektrometrie (LC-MS) ermöglicht die großangelegte Identifizierung und Quantifizierung von Proteinen und zeigt großes Potenzial in der klinischen Proteomik. Mittels explorativer LC-MS-Ansätze können potenzielle Biomarker identifiziert werden, die anschließend in routinetaugliche Panels für absolute Proteinquantifizierung übersetzt werden können. Zahlreiche Herausforderungen, wie etwa eine begrenzte Fähigkeit zur Quantifizierung, sowie eine limitierte Vergleichbarkeit erschweren bislang eine breite klinische Anwendung von LC-MS.
Diese Dissertation adressiert die genannten Herausforderungen durch technologische Weiterentwicklungen und die Integration von explorativer und zielgerichteter Proteomik, hin zu einer Lösung, die eine ausgeglichene Sensitivität und Selektivität, als auch Vergleichbarkeit zwischen Plattformen bei Kosteneffizienz ermöglicht.
Nach der Einleitung (Kapitel I), führt Kapitel II die explorative Zeno-SWATH LC-MS Methodik ein, die sowohl den Probendurchsatz, als auch die analytische Abdeckung von Proteinen bei minimalem Probenverbrauch verbessert und dadurch auch Kosten reduziert.
Kapitel III beschreibt die Erstellung und Anwendung eines zielgerichteten LC-MRM-Biomarker-Panels, welches die Stratifizierung der Krankheitsschwere und Prognose einer COVID-19 Erkrankung ermöglicht.
Kapitel IV wendet explorative und zielgerichtete Proteomik-Techniken erstmals auf Mpox an und demonstriert die vielseitige Nutzbarkeit des LC-MRM-Biomarker-Panels für eine Patientenstratifizierung anderer Krankheiten.
Kapitel V entwickelt den „Charité Open Peptide Standard for Plasma Proteomics (OSPP)“, ein Panel bestehend aus 211 stabil-isotopen-markierten Peptiden, welches plattformübergreifende Vergleichbarkeit bei minimalen Kosten und hohem Probendurchsatz in großangelegten klinischen Studien ermöglicht.
Insgesamt trägt diese Dissertation zur Weiterentwicklung der LC-MS-Technologien für Blut-Biomarker-Studien bei und bringt die Proteomik näher an eine routinemäßige Anwendung in der Klinik
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Proteomics approaches to study the novel SARS coronavirus
Full text linkIn der vorliegenden Arbeit wurden modernste Multiplexing-Ansätze der quantitativen Proteomanalyse angewandt, um das neuartige Virus SARS-CoV-2 zu untersuchen, den Erreger der globalen COVID-19 Pandemie, die Ende 2019 begann. Trotz enormer internationaler Anstrengungen zur Erforschung dieser Krankheit sind viele Aspekte der grundlegenden Virusbiologie, Virus-Wirt-Interaktionen und der COVID-19-Pathophysiologie noch immer unbekannt. Dies verhindert die Entwicklung gezielter Behandlungen, insbesondere für COVID-19-Patienten mit schwerem Verlauf.
Im ersten Teil dieser Arbeit wurde die Infektionsdynamik in lungenähnlichen Zelllinien untersucht. Der Vergleich von SARS-CoV mit SARS-CoV-2-Infektion in Zellen mit niedriger ACE2 Expression ermöglichte es, die Rolle anderer Membranproteine als Virus Eintrittsfaktoren neu zu bewerten. In SARS-CoV-2 infizierten Calu-3-Zellen konnten Reaktionen der Wirtszellen beobachtet werden, die die Interaktion zwischen viralen Proteinen und Proteikinasen der Wirtszelle vermitteln.
Im nächsten Teil wurde die angeborene Immunantwort des Wirts auf das Virus untersucht. Primäre, aus Blut isolierte Monozyten, die mit SARS-CoV-2 behandelt wurden, wiesen eine spezifische Protein-Signatur auf, die auf eine Polarisierung der Zellen zu einem profibrischen Makrophagen-Phänotyp hindeutet. Weitere Analysen zeigten, dass dieser Prozess weitgehend unabhängig von bekannten antiviralen Reaktionen und viraler RNA-Sensoren in Monozyten abläuft. Die durch das Virus hervorgerufene Phosphoproteom-Signatur deutet an, dass die profibrotische Polarisierung durch die kombinierte Wechselwirkung von viralen Proteinen und Infektionsnebenprodukten mit Wirtsrezeptoren induziert wurde.
Zusammenfassend liefert diese Arbeit einen wertvollen Beitrag zur Aufklärung von Mechanismen, die zu einem schweren COVID-19 Verlauf führen können und hebt dabei die Bedeutung von Proteomanalysen in der Erforschung viraler Erkrankungen hervor.In this thesis, we used cutting-edge multiplexed quantitative proteomics and phosphoproteomics approaches to study the virus SARS-CoV-2. The newly emerged betacoronavirus is the causative agent of the global pandemic of COVID-19 that began in late 2019. Despite the tremendous research effort in studying this disease, many aspects of the basic viral biology, virus-host interactions and COVID-19 pathophysiology still remain obscure. This prevents the development of targeted treatments, especially for severe COVID-19 patients.
In the first part of this thesis, we studied infection dynamics in lung-like cell lines. Comparison between SARS-CoV and SARS-CoV-2 infections in low-ACE2-expressing cells allowed us to re-evaluate the role of other membrane proteins as entry factors. In Calu-3 cells, we could observe host responses mediating the interactions between viral proteins and host kinases.
Next, we focused on the innate immune response of the host to the virus. Ex vivo monocytes treated with SARS-CoV-2 exhibited a specific proteomic signature indicating a polarization toward a profibric macrophage phenotype. Further dissection of this response revealed it to be largely independent from the viral RNA sensing and antiviral response cellular mechanisms. Furthermore, the specific phosphoproteomics signature induced by the virus indicated that the profibrotic polarization was induced by the combined interaction between viral proteins and infection byproducts with host receptors.
In summary, this thesis shows the power of mass spectrometry based proteomics to study the complex dynamics between viruses and host cells. Furthermore, we uncovered a potential mechanism contributing to the development of severe COVID-19
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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