1,720,973 research outputs found
Development of a Bioorthogonal and Highly Efficient Conjugation Method for Quantum Dots using Tetrazine-Norbornene Cycloaddition
No full textWe present a bioorthogonal and modular conjugation method for efficient coupling of organic dyes and biomolecules to quantum dots (QDs) using a norbornene−tetrazine cycloaddition. The use of noncoordinating functional groups combined with the rapid rate of the cycloaddition leads to highly efficient conjugation. We have applied this method to the in situ targeting of norbornene-coated QDs to live cancer cells labeled with tetrazine-modified proteins.National Institutes of Health (U.S.) (NIH Grant 5-U54-CA119349-05)National Institutes of Health (U.S.) (NIH Grant 5R01CA126642-02)National Institutes of Health (U.S.) (NIH Grant U01-HL080731)National Institutes of Health (U.S.) (NIH Grant T32-CA79443
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
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
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
Development of multifunctional compounds for the modulation and detection of amyloid beta species
Full text linkAlzheimer’s disease (AD) is the most common neurodegenerative disease, associated with loss of memory and cognitive decline. An estimated 5.8 million Americans of all ages are living with Alzheimer’s dementia currently. The presence of amyloid plaques and neurofibrillary tangles in the brain is the hallmark of AD. Amyloid β (Aβ) peptides, the main component of amyloid plaques, are formed from the cleavage of amyloid precursor protein (APP) by β- and γ-secretases. The main alloforms of Aβ are Aβ40 and Aβ42, containing 40 and 42 amino acids, respectively. Even though Aβ40 is present in the deposits in larger amounts, Aβ42 exhibits higher neurotoxicity and aggregates more easily. In the past two decades, soluble Aβ oligomers have been found to be the most toxic form among all Aβ species through their interactions with membrane and synaptic receptors that influence intracellular systems and affect neurotransmission, leading to neurodegeneration.
In addition, the amyloid deposits contain uncommonly high concentrations of metal ions such as Fe2+, Cu2+ and Zn2+, and it has been found that these metal ions promote the formation of neurotoxic Aβ aggregates. Cu and Fe ions can also cause the formation of reactive oxygen species (ROS), which exacerbates Aβ toxicity. Previously, we have reported that Cu2+ ions can slow down Aβ fibrillization and stabilize Aβ oligomers, and thus small molecules that can inhibit the interaction between metal ions and Aβ peptides, can be used as potential therapeutic compounds for AD.
Positron emission tomography (PET) is a functional imaging technique that can be used for the diagnosis of AD. Recently, several PET imaging agents have been approved by FDA and can be used to visualize amyloid plaques in AD patients. However, these radiolabeled agents are employing short-lived radionuclides, such as 11C and 18F (t1/2 = 20.4 min and 109.8 min), respectively), thus limiting their widespread use. Thus, the development of longer-lived radiolabeled compounds is essential for further expanding the use of PET imaging in healthcare, and diagnostic agents employing longer-lived radionuclides such as 64Cu (t1/2 = 12.7 h, β+ = 17%, β– = 39%, EC = 43%, Emax = 0.656 MeV) are viewed as optimal PET imaging agents.
Firstly, we developed a series of benzothiazole-based multifunctional compounds (MFCs) with an appreciable affinity for amyloid aggregates that can be potentially used for both the modulation of Aβ aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Aβ aggregates. Among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Aβ oligomerization into the formation of less toxic amyloid fibrils. In addition, HYR-16 can also alleviate the formation of reactive oxygen species (ROS) caused by Cu2+ ions through Fenton-like reactions. Secondly, these MFCs can be easily converted to PET imaging agents by pre-chelation with the 64Cu radioisotope, and the Cu complexes of HYR-4 and HYR-17 exhibit good fluorescent staining and radiolabeling of amyloid plaques both in vitro and ex vivo. Importantly, the 64Cu-labeled HYR-17 is shown to have a significant brain uptake of up to 0.99 ± 0.04 %ID/g. Overall, by evaluating the various properties of these MFCs valuable structure-activity relationships (SAR) were obtained that should aid the design of improved therapeutic and diagnostic agents for AD.
Then, we found the key limitation of 64Cu PET agents is that they release free radioactive isotopes due to the low binding affinity of ligands, which further decrease the signal-to-noise ratio and accuracy of imaging. As a result, a series of 1,4,7-triazacyclononane (TACN) and 2,11-diaza[3.3]-(2,6)pyridinophane (N4)-based pyridine metal-chelating compounds were designed and synthesized by incorporating Aβ interacting fragments with metal binding ligands, which allows excellent Cu chelation without losing Aβ binding affinity. Crystal structures of corresponding Cu complexes confirmed the N atom in pyridine was involved in metal binding process. In the following radiolabeling studies, the developed compounds could efficiently chelate with 64Cu according to their radio-HPLC traces and show up to 6.3 times higher radio-signal of AD over WT brain sections in autoradiography.
Moreover, transition metal complexes have emerged as a viable alternative to organic compounds with distinct biological properties and have been wildly utilized for the treatment of cancer. Recently, transition metal complexes have been developed as chemical reagents capable of altering Aβ aggregation. Consequently, a series of benzothiazole-based luminescent Ir(III) complexes HN-1-8 were reported with appreciable Aβ inhibition ability in vitro and in living cells. In addition, they are capable of inducing obvious fluorescence increase when they bind to Aβ fibrils and oligomers. More importantly, compared to previously reported cationic Ir complexes, some of these inert complexes have higher log D values, which potentially allows them to have a better blood-brain barrier (BBB) permeability and hold promise to be used in vivo.
Lastly, in order to understand and probe the Cu-mediated Aβ aggregation process, we rationally designed and synthesized a series of Cu-based activable sensors to detect the Cu-Aβ species in vitro and ex vivo. By linking the picolinic ester moiety with the strong Aβ binding fragment, the copper ions can rapidly catalyze the hydrolysis reaction of the ester bond to generate the high fluorescent Aβ binding molecules in vitro. More interestingly, the Cu-responsive sensors can also promptly react with Cu-Aβ oligomers and fibrils, resulting in a significant fluorescence turn-on, indicating that the probes are also able to detect Cu-Aβ species in vitro. To confirm the Aβ binding specificity of the probes, 5xFAD brain sections were stained with the developed sensors. As expected, if the brain sections are only stained with the compounds, the fluorescence images show that the sensor has poor ability to detect amyloid plaque with low fluorescence intensity. However, to mimic the Cu-rich environment in the AD brain, with the addition of excess amounts of Cu(II) to the solution, the fluorescence images clearly indicate that the Cu-responsive sensors were activated by Cu(II) and release the high fluorescent amyloid binding fluorophores which can specifically label the amyloid plaques on the 5xFAD brain sections.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2023-05-01The student, Yiran Huang, accepted the attached license on 2021-02-24 at 08:32.The student, Yiran Huang, submitted this Dissertation for approval on 2021-02-24 at 08:37.This Dissertation was approved for publication on 2021-02-25 at 16:59.DSpace SAF Submission Ingestion Package generated from Vireo submission #16177 on 2021-09-16 at 20:06:53Made available in DSpace on 2021-09-17T04:03:56Z (GMT). No. of bitstreams: 2
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Previous issue date: 2021-02-25Embargo set by: Seth Robbins for item 118618
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Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 118618
Lift date: 2023-09-17T04:07:01Z
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Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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