1,720,969 research outputs found

    Conformations and antigenicity of the HCV glycoprotein E2 receptor binding domain

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    This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Well On/Off Time Classification Using RNNs and a Developed Well Simulator to Generate Realistic Well Production Data

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    Supervised machine learning (ML) projects require data for model training, validation, and testing. However, the confidential nature of field and well production data often hinders the progress of ML projects. To address this issue, we developed a well simulator that generates realistic well production data based on physical, governing differential equations. The simulation models the reservoir, wellbore, flowline, and choke coupled using transient nodal analysis to solve for transient flow rate, pressure, and temperature as a function of variable choke opening over time in addition to a wide range of static parameters for each component. The simulator’s output is then perturbed using the gauge transfer function to introduce systematic and random errors, creating a dataset for ML projects without the need for confidential production data. We then generated a simulated dataset to train a recurrent neural network (RNN) on the task of classifying well on/off times. This task typically requires a significant number of manhours to manually filter and verify data for hundreds or thousands of wells. Our RNN model achieves high accuracy in classifying the correct on/off labels, representing a promising step towards a fully-automated rate allocation process. Our simulator for well production data can be used for other ML projects, circumventing the need for confidential data, and enabling the study and development of different ML models to streamline and automate various oil and gas work processes. Overall, the success of our RNN model demonstrates the potential of ML to improve the operational efficiency of various oil and gas work processes

    Functions of hepatitis C virus glycoprotein E2 variable regions

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    HCV chronically infects ~3% of the global human population, including 200,000 Australians, causing recurring, progressively worsening liver disease, and cirrhosis and hepatocellular carcinoma. Preventative vaccines are not available. However, the advent of direct acting antivirals for the treatment of HCV results in viral clearance in at least 90% of treated individuals. Hepatitis C virus encodes two structural glycoproteins; E1 and E2. Glycoproteins E1 and E2 associate covalently and non-covalently to form heterodimers that mediate HCV binding to cell surface receptors. The E2 ectodomain region spanning residues 384-661 constitutes the receptor binding domain (RBD; E2661) that includes three highly variable regions: hypervariable region 1 (HVR1), HVR2 and the intergenotypic variable region (igVR). The HVR1 is known to elicit type-specific neutralizing antibodies (NAb). The HVR2 is located downstream of HVR1 within a region flanked by two cysteine residues (Cys-459 and Cys-486). HVR2 is not a direct target of the antibody response and the reason for variation within its sequence is unknown. Similar to HVR2, the igVR is flanked by two cysteine residues (Cys-569 and Cys-581). The igVR is relatively conserved within subtypes but the sequence and length of this region varies widely between genotypes. Patients infected with HCV develop NAb during their infection. The natural targets for NAb are the envelope glycoproteins E1 and E2 especially within the E2 RBD. The majority of NAb are directed to the binding sites within E2 for the major cell surface receptor CD81. In this study, the role of HVRs in modulating the exposure of both neutralizing and non-neutralizing epitopes within E2 has been examined. Examination of sequence evolution within HCV infected patients revealed that in addition to HVR1, both HVR2 and igVR are under selective pressure. In the case of the igVR, this contrasts to earlier reports suggesting that the igVR does not vary within genotypes. Mutations in the igVR were shown to directly modulate the exposure of non-neutralizing antibody epitopes in the patient that cleared their infection. In addition, the CD81 binding site was more occluded in E2 RBDs isolated during the chronic phase of the disease and was partly attributable to mutation in HVR2. In another approach, intragenotypic HVR2 and igVR replacement attenuate genotype 2 (G.2) HCVcc virus, whereas intergenotypic HVR2 and igVR chimeras between G.2a and G.1a results in non-infectious HCVcc. Passaging attenuated virus restored replication due to acquisition of adaptive mutations in the E2 transmembrane domain. With the aid of neutralizing antibodies, we also show that neutralizing epitope I encompassing 411-428 is more accessible when replacing HVR1 of G.1a to that of G.1b, but becomes occluded by replacing igVR. In contrast, neutralizing epitope III covering residues 512-529 is occluded by HVR1 and becomes inaccessible by exchanging igVR of G.1a to that of G.1b. The results show that HCV variable regions play a role in modulating the exposure of NAb epitopes and access to the CD81 binding site on the E2 RBD

    Characterisation of peroxisomes in the fission Yeast Schizosaccharomyces pombe and slime mold Dictyostelium discoideum

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    Peroxisome is a compartment that is found in most eukaryotic organisms' cells. It has several crucial roles, such as fatty acid beta (β) oxidation and hydrogen peroxide (H2O2) detoxification. It contains many essential enzymes, including oxidase and catalase, and has several metabolic and non-metabolic pathways, depending on the environment and the organisms within its cells. This study investigates the role of peroxisomes in two organisms, S. pombe and D. discoideum. Although S. pombe is a well-studied yeast, there is only one study of this yeast that has focused on peroxisomes. This study offers a few crucial observations, including that S. pombe contains peroxisomes, that GFP containing a well-characterized PTS1 (SKL) is efficiently imported, and that peroxisome numbers increase in cells grown on a fatty acid as the sole carbon source, suggesting a role for peroxisomes in fatty acid degradation. The starting point in my research was initially a bioinformatics screen. This screening recognized the enzymes imported into peroxisomes based on the presence of a potential peroxisomal targeting signal. A few proteins were found. However, the low number of proteins with a classical PTS might be the result of different targeting signals that are not recognized by our bioinformatics parameters. Indeed, in other organisms, there are proteins without PTS1 that still use Pex5 for import. The first example is S. cerevisiae Acyl-CoA oxidase. In a global yeast two-hybrid screen, S. pombe Pex5 was found to bind S. pombe Str3 and Lys3. Consequently, we think that there is conserved targeting of a peroxisomal protein lacking a PTS1 and PTS2 imported into the peroxisome by Pex5. One of these is the Str3 case. Interestingly, proteins involved in peroxisomal fatty acid β -oxidation are absent from the S. pombe genome, casting doubt on the conclusions from the previous study and explaining the low number of potential peroxisomal enzymes. In D. discoideum, this study investigates the dynamic regulation of peroxisome numbers in response to growth conditions and identifies peroxisomal import and contents through a proximity labeling approach (BioID). Overall, this study sheds light on the roles and regulation of peroxisomes in these two organisms

    Variations on the Author

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    “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

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    We 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

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    We 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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