1,720,962 research outputs found
Magnetic field imaging in biological systems with nanometric resolution
No full textRecent developments of engineered nitrogen-vacancy (NV) centres in diamonds offer promising avenues for the creation of sensitive nanoscale probes, pivotal for quantum measurements and diagnostic applications in nanomedicine. The aim of this work is to enable these sensor applications by studying NV photodynamics, investigating the effects of the environment and developing advanced quantum sensor chips. In this thesis, we include both fluorescent nanodiamond particles (NDs) and NV-containing single crystal diamond. Initially, we study the fundamental physics governing signal generation, exploring the photodynamics of a single NV center and analysing its spin-contrast properties. Subsequently, we probe the impact of the crystal environment on the photoelectrical signals and quantum efficiency, determining the possible origins of non-standard phenomena such as positive photocurrent detected magnetic resonance (PDMR). We demonstrate the usage of ground-state level anti-crossing (GSLAC) in photoelectrical spin-state readout.
In the second part of the thesis, we focused on the development of a quantum chip for both single-crystal diamond and ND particles. Two types of prototypes were designed and fabricated, with numerical modelling employed to elucidate microwave field distribution and resonance patterns. For single crystal diamond chips, in-depth testing is conducted to mitigate microwave-induced interference, which is critical for detecting low photocurrents from single NV centres. Additionally, we explore the potential for integrating this chip into a microfluidic chamber. The chip for the nanodiamond particles was evaluated for its heating properties, which are crucial for keeping neurons alive, using theoretical calculations and experimental measurements using a nanodiamond probe. Furthermore, we also perform the in vitro sensing of the magnetic field at the attached nanodiamonds to the neuron cells.
In summary, our research represents a significant step forward in harnessing the capabilities of engineered NV centers in diamond for quantum sensing applications, offering promising prospects in both fundamental research and practical diagnostics in nanomedicine
Structural Basis for the Biological Activities of Bovine Seminal Ribonuclease
No full textBovine seminal ribonuclease (BS-RNase) is a homolog of RNase A with special biological properties that include specific antitumor, aspermatogenic, and immunosuppressive activities. Unlike RNase A, BS-RNase is a dimer cross-linked by disulfide bonds between Cys(31) of one subunit and Cys(32) Of the other. At equilibrium, this dimer is a mixture of two distinct quaternary forms, M=M and MxM. The conversion of M=M to MxM entails the exchange of NH2-terminal alpha-helices between subunits. Here, the cytotoxic activities of purified MxM were shown to be greater than those of purified M=M, despite extensive equilibration of M=M and MxM during the time course of the assays. Replacing Cys(31) or Cys(32) with a serine residue did not compromise the enzymatic activity of dimeric BS-RNase, but reduced both the fraction of MxM at equilibrium and the cytotoxicity. We conclude that the MxM form is responsible for the special biological properties of BS-RNase. Since cytosolic ribonuclease inhibitor binds tightly to monomeric but not dimeric BS-RNase and only the MxM form can remain dimeric in the reducing environment of the cytosol, we propose that BS-RNase has evolved its MxM form to retain its lethal enzymatic activity in vivo.Y
Catalytic activity of bovine seminal ribonuclease is essential for its immunosuppressive and other biological activities
Get PDFBovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with special biological properties, including potent immunosuppressive activity. A mutant BS-RNase was created in which His-119, the active-site residue that acts as a general acid during catalysis, was changed to an aspartic acid. H119D BS-RNase formed a dimer with quaternary structure similar to that of the wild-type enzyme but with values of k(cat) and k(cat.)/K-m for the cleavage of UpA [uridylyl(3' --> 5')adenosine] that were 4x10(3)-fold lower. The mutant protein also demonstrated dramatically decreased immunosuppressive, anti-tumour, aspermatogenic, and embryotoxic activities. The catalytic activity of BS-RNase is therefore necessary for its special biological properties.Y
Mechanism of ribonuclease cytotoxicity
No full textBovine seminal ribonuclease (BS-RNase), a dimeric homolog of bovine pancreatic ribonuclease A (RNase A), is toxic to mammalian cells. In contrast to dimeric BS-RNase, monomeric BS-RNase and RNase A are not cytotoxic and are bound tightly by cytosolic ribonuclease inhibitor. To elucidate the mechanism of ribonuclease cytotoxicity, we constructed a series of hybrid and semisynthetic enzymes and examined their properties. In five hybrid enzymes, divergent residues in BS-RNase were replaced with the analogous residues of RNase A so as to diminish an interaction with a putative cellular receptor, In a semisynthetic enzyme, the disulfide bonds that cross-link the monomeric subunits of dimeric BS-RNase were replaced with thioether bonds, which can withstand the reducing environment of the cytosol. Each hybrid and semisynthetic enzyme had ribonucleolytic and cytotoxic activities comparable with those of wild-type BS-RNase. These results suggest that dimeric BS-RNase (pI = 10.3) enters cells by adsorptive rather than receptor-mediated endocytosis and then evades cytosolic ribonuclease inhibitor so as to degrade cellular RNA. This mechanism accounts for the need for a cyto solic ribonuclease inhibitor and for the cytotoxicity of other homologs of RNase A.Y
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
Get PDFWe 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
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