1,720,962 research outputs found
Development of Nanostructured Triggerable Biosensors for Prostate Cancer Early Detection
Get PDFCancer remains a leading cause of global mortality, with Prostate Cancer (PCa) ranking as the second most common cancer in men. Early detection poses a significant challenge due to cancer's growth rate and limitations in current diagnostic assays. Despite Prostate Specific Antigen (PSA) being a longstanding biomarker for PCa diagnosis, its lack of specificity leads to a high rate of false positives. In response, alternative biomarkers like Prostate Specific Membrane Antigen (PSMA), detectable in urinary exosomes have emerged. Additionally, PSA in serum facilitates early detection of PCa recurrence post-prostatectomy. We developed two triggerable oligonucleotide-gold nanoparticle (AuNPs) architectures (AuNPs-Aggregates) that selectively disassembles in the presence of a protein biomarker (PSMA or PSA). The AuNPs-Aggregates were prepared by mixing two batches of AuNPs, functionalised with different ssDNA strands, including a sequence that contains an aptamer responsive to the protein marker. After in silico and in vitro sequences characterisation, I synthetized and functionalised AuNPs with thiolated-ssDNA strands. The PSMA responsive Aggregate is composed by 13 nm AuNPs, and is aimed to ex vivo early detection of PSMA in urinary exosomes. Its response was determined by monitoring changes in its size and optical properties. I obtained a significant specific PSMA response from the high femtomolar range, with purified PSMA protein, and from low picomolar range with the protein extract of PSMA positive exosomes. The second sensor, the AS2-US-AuNPs-Aggregate, is thought for an in vivo application to early detect PSA in the blood of totally resected patients and is composed by ultrasmall AuNPs, a size suitable for renal clearance. This Aggregate has a size of hundreds of nanometres, compatible with prolonged circulation time in bloodstream. In this way, the release of single AuNPs from the Aggregate upon aptamer recognition could permit its analysis in urine. The AS2-AuNPs-Aggregate response to PSA was monitored following its changes in size; its specific response started to be significant in the low fM range. Then, we compared the stability of AS2 annealed sequences to nucleases, both in their free dsDNA form and when integrated into the AS2-AuNPs-Aggregate. This nanostructure has the potential to be tailored for detecting various biomarkers, such as proteins or DNA, by modifying the nucleotide sequences involved in the recognition process. Furthermore, it offers flexibility in selecting the nanoparticles incorporated in the structure, with the possibility of different methods of detection
Aptamer-based gold nanoparticle aggregates for ultrasensitive amplification-free detection of PSMA
Get PDFEarly diagnosis is one of the most important factors in determining the prognosis in cancer. Sensitive detection and quantification of tumour-specific biomarkers have the potential to improve significantly our diagnostic capability. Here, we introduce a triggerable aptamer-based nanostructure based on an oligonucleotide/gold nanoparticle architecture that selectively disassembles in the presence of the biomarker of interest; its optimization is based also on in-silico determination of the aptamer nucleotides interactions with the protein of interest. We demonstrate this scheme for the case of Prostate Specific Membrane Antigen (PSMA) and PSMA derived from PSMA-positive exosomes. We tested the disassembly of the system by diameter and count rate measurements in dynamic light scattering, and by inspection of its plasmon resonance shift, upon addition of PSMA, finding appreciable differences down to the sub-picomolar range; this points towards the possibility that this approach may lead to sensors competitive with diagnostic biochemical assays that require enzymatic amplification. More generally, this scheme has the potential to be applied to a broad range of pathologies with specific identified biomarkers
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
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
Measuring pH in insulin secretory granules by phasor-based fluorescence lifetime imaging of a genetically encoded sensor
Get PDFIt is widely accepted that the pH of insulin granules is acidic, and that its active regulation during granule maturation plays a role in the process of insulin secretion by β-cells. Yet, a calibrated measurement of the absolute granule pH with organelle specificity is still lacking. To tackle this issue, we use the genetically encoded E1GFP pH reporter inserted into the C-peptide of proinsulin and expressed in Insulinoma 1E cells. Following verification of correct targeting of the E1GFP reporter in the insulin granules, phasor-based Fluorescence Lifetime Imaging Microscopy (FLIM) is applied to obtain a calibrated and probe-concentration-independent measurement of insulin-granule pH. Our results confirm the acidic nature of insulin granules under maintenance cell culture conditions, with an average luminal pH of ~5.8, and show that acidity is actively maintained, as evidenced by its near-neutralization upon treatment with the vacuolar H+-ATPase inhibitor concanamycin. Additionally, by ..
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