1,720,960 research outputs found
Dataset for in support of the thesis 'Characterising a 3D culture model of triple-negative breast cancer through systems-based molecular phenotyping'
No full textComparative proteomic and transcriptomic analysis between ULA and 2D cell culture models of triple-negative breast cancer.
Comparative proteomic analysis of ULA and 2D cell culture models of triple-negative breast cancer treated with paclitaxel (PTX) or doxorubicin (DOX).
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers
10.6019/PXD055504 and 10.6019/PXD055519.</span
Characterising a 3D culture model of triple-negative breast cancer through systems-based molecular phenotyping
No full textTriple-negative breast cancer (TNBC) presents a worse prognosis than other subtypes, characterised by frequent distant recurrence, shorter recurrence-free period and limited therapeutic options. Developing effective oncology therapeutics proves particularly challenging, as indicated by the low success rate observed in oncology clinical trials. The use of 3D cell culture models is a potential approach to advance preclinical therapeutic assessment by more closely representing the in vivo tumour microenvironment than conventional 2D cell culture models. Furthermore, the ultra-low adherent (ULA) 3D culture system has shown compatibility with ultra-high throughput drug screening assays and provides distinct hit detection compared to 2D culture drug screens.In this study, we performed LC-MS/MS proteomic characterisation of TNBC cell lines cultured in the ULA culture system, providing insights into the cellular processes and signalling pathways in comparison to the 2D culture model. The pathway analysis revealed a significant increase in antioxidant expression and proteins associated with drug detoxification in the ULA culture system. Additionally, the HCC1143, HCC1806 and HCC1937 cell lines formed dense spheroids, while MDA-MB-231 cells displayed a loose aggregate morphology in the ULA culture system. The spheroid-forming cell lines exhibited a more pronounced elevation of glycolytic enzymes, as well as HIF-1 and AMPK signalling proteins, compared to MDA-MB-231 cells in the ULA culture system. This suggests that the morphological characteristics observed in the ULA culture system may be associated with the modulation of these pathways.For the MDA-MB-231 cell line, transcriptomic profiling of the ULA and 2D culture models was performed to complement the proteomic dataset. Revealing diminished expression of genes and proteins associated with cell cycle, DNA replication and ECM-receptor interactions. Additionally, we performed a comparison of the MDA-MB-231 gene expression with The Cancer Genome Atlas TNBC patient data to assess the potential for clinical translation. The results indicated a good correlation between the patient data and both culture models, with the ULA culture system exhibiting a slightly closer correlation than the 2D culture system.Compared to the 2D culture model, the HCC1143 ULA culture model exhibited reduced sensitivity to the chemotherapeutic agents, doxorubicin and paclitaxel. Proteomic assessment of chemotherapy treated HCC1143 spheroids revealed an increased expression of proteins associated with the oxidative stress response under doxorubicin treatment and elevated cell cycle proteins induced by paclitaxel treatment. This not only identified previously established therapeutic targets, validating the 3D culture model, but also revealed novel observations that warrant further investigation.The findings of this study contribute to the understanding of the TNBC in vitro 3D culture model and its application in 3D culture drug screens. The adoption of 3D culture models in early drug screening is expected to improve the selection of therapeutics in the preclinical phase, ultimately supporting the development of more effective therapeutic options for TNBC
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
A proteomic discovery study of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage
No full textBackground: proteomic analysis of cerebrospinal fluid (CSF) has the potential to provide insight into the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH) and target trials to improve outcome. The aim of this study was to perform a definitive proteomic analysis of CSF following aSAH to identify proteins associated with neurological injury.Methods: retrospective proteomic analysis of CSF was collected at neurosurgical centers in the United Kingdom between 2013 and 2023 either from external ventricular drain or lumbar puncture on day 7 after aSAH. Adults with confirmed aSAH were included. Exclusions were pregnancy, severe comorbidities, inability to follow-up, and those not expected to survive 24 hours. Proteomic analysis was performed using mass spectrometry to identify CSF proteins differentially expressed between patients with good (modified Rankin Scale score of 0–2) and poor (modified Rankin Scale score of 3–6) outcomes at 6 months following aSAH. Controlling for CSF albumin (a marker of blood-brain interface permeability and volume of hemorrhage), differentially expressed proteins were identified. Differential pathway activity was explored using protein interaction, gene set enrichment and TopMD analyses.Results: a total of 152 patients were included (101 good and 51 poor outcome), and 4952 unique proteins were identified across all samples. The CSF proteomic profile differed between good and poor outcome individuals as evidenced by clustering of individuals by outcome using topological data analysis. Controlling for CSF albumin 16 intracellular and secreted proteins were differentially expressed between good and poor outcome patients. Two cellular pathways were identified to have differential activity by all 3 pathway analysis approaches: the PI3K-Akt signaling pathway and glycolysis/gluconeogenesis.Conclusions: in this study, 16 proteins were differentially expressed between good and poor outcome aSAH patients. The proteomic evidence, both on an individual protein and pathway level highlights that inflammation and oxidative injury are associated with the pathophysiology of neurological injury following aSAH. These results support the exploration of treatments targeting these pathways to improve outcome after aSAH
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
Prototype of a tool for automatic generation of commit messages for Java applications
Get PDFAlthough version control systems allow developers to describe and explain the rationale behind code changes in commit messages, the state of practice indicates that most of the time such commit messages are either very short or even empty. In fact, in a recent study of 23K+ Java projects it has been found that only 10% of the messages are descriptive and over 66% of those messages contained fewer words as compared to a typical English sentence. However, accurate and complete commit messages summarizing software changes are important to support a number of development and maintenance tasks. This thesis presents an approach, coined as ChangeScribe, which is designed to generate commit messages automatically from change sets. ChangeScribe generates natural language commit messages by taking into account commit stereotype, the type of changes (e.g., files rename, changes done only to property files), as well as the impact set of the underlying changes. This work presents the evaluation of ChangeScribe in an evaluative survey involving 23 developers in which the participants analyzed automatically generated commit messages from real changes and compared them with commit messages written by the original developers of six open source systems. The results demonstrate that automatically generated messages by ChangeScribe are preferred in about 62% of the cases for large commits, and about 54% for small commitsResumen. Aunque los sistemas de control de versiones le permiten a los desarrolladores de software describir y explicar las razones por la cuales modificaron el código fuente utilizando un mensaje en el commit, en la práctica estos mensajes son muy cortos o incluso vacíos. De hecho, en recientes estudios de 23K+ de proyectos Java se ha encontrado que el 10% de los mensajes son descriptivos y alrededor del 66% de estos contienen pocas palabras comparado con el tamaño promedio de una oración escrita en el idioma inglés. Sin embargo, resumir los cambios en el software de una manera precisa y completa es muy importante para apoyar las tareas que se realizan en el desarrollo y mantenimiento de un software. Este trabajo presenta ChangeScribe un prototipo para generar mensajes de commit usando lenguaje natural y teniendo en cuenta el estereotipo del commit, el tipo de cambio (rename de un archivo, cambios a archivos de propiedades, etc ), y también el conjunto de impacto de los cambios realizados. De otro lado, presenta la evaluación de ChangeScribe en un estudio de usuarios que involucró 23 desarrolladores de software que analizaron los mensajes de commit generados automáticamente por ChangeScribe y los mensajes de commit escritos por los desarrolladores originales de seis sistemas open source. Los resultados demuestran que los mensajes generados de forma automática por ChangeScribe son preferidos en cerca del 62% de los casos en commits largos, y en cerca de 54% de los casos en commits cortos (pocas modificaciones).Maestrí
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