2,294 research outputs found
SERS active colloidal nanoparticles for the detection of small blood biomarkers using aptamers
Functionalized colloidal nanoparticles for SERS serve as a promising multifunctional assay component for blood biomarker detection. Proper design of these nanoprobes through conjugation to spectral tags, protective polymers, and sensing ligands can provide experimental control over the sensitivity, range, reproducibility, particle stability, and integration with biorecognition assays. Additionally, the optical properties and degree of electromagnetic SERS signal enhancement can be altered and monitored through tuning the nanoparticle shape, size, material and the colloid's local surface plasmon resonance (LSPR). Aptamers, synthetic affinity ligands derived from nucleic acids, provide a number of advantages for biorecognition of small molecules and toxins with low immunogenicity. DNA aptamers are simpler and more economical to produce at large scale, are capable of greater specificity and affinity than antibodies, are easily tailored to specific functional groups, can be used to tune inter-particle distance and shift the LSPR, and their intrinsic negative charge can be utilized for additional particle stability.1,2 Herein, a "turn-off" competitive binding assay platform involving two different plasmonic nanoparticles for the detection of the toxin bisphenol A (BPA) using SERS is presented. A derivative of the toxin is immobilized onto a silver coated magnetic nanoparticle (Ag@MNP), and a second solid silver nanoparticle (AgNP) is functionalized with the BPA aptamer and a Raman reporter molecule (RRM). The capture (Ag@MNP) and probe (AgNP) particles are mixed and the aptamer binding interaction draws the nanoparticles closer together, forming an assembly that results in an increased SERS signal intensity. This aptamer mediated assembly of the two nanoparticles results in a 100x enhancement of the SERS signal intensity from the RRM. These pre-bound aptamer/nanoparticle conjugates were then exposed to BPA in free solution and the competitive binding event was monitored by the decrease in SERS intensity
Modeling CRISPR gene drives for suppression of invasive rodents using a supervised machine learning framework
Funding: This study was supported by funding from New Zealand’s Predator Free 2050 program under Predator Free 2050 Ltd. award SS/05/01 to PWM, and from National Institutes of Health award R01GM127418 to PWM. PG-D received funding from the New Zealand BioHeritage National Science Challenge (contract 1617-28-033 A to Manaaki Whenua – Landcare Research) and from Natural Environment Research Council grant NE/S011641/1 under the Newton Latam programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
Comparison of Fe2O3 and Fe2CoO4 core-shell plasmonic nanoparticles for aptamer mediated SERS assays
Conjugation of oligonucleotides or aptamers and their corresponding analytes onto plasmonic nanoparticles mediates the formation of nanoparticle assemblies: molecularly bound bundles of nanoparticles which cause a measurable change in the colloid's optical properties. Here, we present further optimization of a "SERS off" competitive binding assay utilizing plasmonic and magnetic nanoparticles for the detection of the toxin bisphenol A (BPA). The assay involves 1) a 'target' silver nanoparticle functionalized with a Raman reporter dye and PEGylated BPA-binding DNA aptamers, and 2) a version of the toxin BPA, bisphenol A diglycidyl ether (BADGE), PEGylated and immobilized onto a silver coated magnetic 'probe' nanoparticle. When mixed, these target and probe nanoparticles cluster into magnetic dimers and trimers and an enhancement in their SERS spectra is observed. Upon introduction of free BPA in its native form, target AgNPs are competitively freed; reversing the nanoparticle assembly and causing the SERS signal to "turn-off" and decrease in response to the competitive binding event. The assay particles were housed inside two types of optofluidic chips containing magnetically active nickel pads, in either a straight or spotted pattern, and both Fe2O3 and Fe2CoO4 were compared as magnetic cores for the silver coated probe nanoparticle. We found that the Ag@ Fe2O3 particles were, on average, more uniform in size and more stable than Ag@ Fe2CoO4, while the addition of cobalt significantly improved the collection time of particles within the magnetic chips. Using 3D Raman mapping, we found that the straight channel design with the Ag@ Fe2O3 particles provided the most uniform nanoparticle organization, while the spotted channel design with Ag@ Fe2CoO4 demonstrated a larger SERS enhancement, and thus a lower limit of detection
Dyslipidemia impairs mitochondrial trafficking and function in sensory neurons
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154247/1/fsb2fj201700206r.pd
Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial.
BACKGROUND: Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock.
METHODS AND DESIGN: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000. This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018
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Celtic censure: representing Wales in eighteenth-century Germany
Drawing on Pierre Bourdieu's notion of regionalist discourse as the performative legitimation of specific frontiers, this article examines how the English traveller Samuel Jackson Pratt mediated a picture of the Welsh to late eighteenth-century readers in his Gleanings Through Wales, Holland and Westphalia (1795). This process of mediation was further complicated by the translation of this work into German as the Aehrenlese auf einer Reise durch Wallis, which appeared with the Leipzig publisher Lincke in 1798. While this work made an important contribution to German Celtophilia in the Romantic period, the German translator was careful to omit its more Sternean passages, in favour of factual narrative. Pratt's account of his travel through Wales, mediated in turn to a German audience through its Leipzig translator, therefore embodies several layers of cultural transfer that generate a complex and multifaceted image of Wales at the close of the eighteenth century
Delirium and the risk of developing dementia: a cohort study of 12 949 patients
Background: Delirium is an important risk factor for subsequent dementia. However, the field lacks large studies with long-term follow-up of delirium in subjects initially free of dementia to clearly establish clinical trajectories.
Methods: We undertook a retrospective cohort study of all patients over the age of 65 diagnosed with an episode of delirium who were initially dementia free at onset of delirium within National Health Service Greater Glasgow & Clyde between 1996 and 2020 using the Safe Haven database. We estimated the cumulative incidence of dementia accounting for the competing risk of death without a dementia diagnosis. We modelled the effects of age at delirium diagnosis, sex and socioeconomic deprivation on the cause-specific hazard of dementia via cox regression.
Results: 12 949 patients with an incident episode of delirium were included and followed up for an average of 741 days. The estimated cumulative incidence of dementia was 31% by 5 years. The estimated cumulative incidence of the competing risk of death without dementia was 49.2% by 5 years. The cause-specific hazard of dementia was increased with higher levels of deprivation and also with advancing age from 65, plateauing and decreasing from age 90. There did not appear to be a relationship with sex.
Conclusions: Our study reinforces the link between delirium and future dementia in a large cohort of patients. It highlights the importance of early recognition of delirium and prevention where possible
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Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer
Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these
relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in
483 tumors from the METABRIC cohort. Single-cell analysis revealed cell phenotypes spanning epithelial, stromal and immune
types. Distinct combinations of cell phenotypes and cell–cell interactions were associated with genomic subtypes of breast
cancer. Epithelial luminal cell phenotypes separated into those predominantly impacted by mutations and those affected by
copy number aberrations. Several features of tumor ecosystems, including cellular neighborhoods, were linked to prognosis,
illustrating their clinical relevance. In summary, systematic analysis of single-cell phenotypic and spatial correlates of genomic
alterations in cancer revealed how genomes shape both the composition and architecture of breast tumor ecosystems and will
enable greater understanding of the phenotypic impact of genomic alterations
Electrospun amplified fiber optics
A lot of research is focused on all-optical signal processing, aiming to
obtain effective alternatives to existing data transmission platforms.
Amplification of light in fiber optics, such as in Erbium-doped fiber
amplifiers, is especially important for an efficient signal transmission.
However, the complex fabrication methods, involving high-temperature processes
performed in highly pure environment, slow down the fabrication and make
amplified components expensive with respect to an ideal, high-throughput and
room temperature production. Here, we report on near infrared polymer fiber
amplifiers, working over a band of about 20 nm. The fibers are cheap, spun with
a process entirely carried out at room temperature, and show amplified
spontaneous emission with good gain coefficients as well as low optical losses
(a few cm^-1). The amplification process is favoured by the high fiber quality
and low self-absorption. The found performance metrics promise to be suitable
for short-distance operation, and the large variety of commercially-available
doping dyes might allow for effective multi-wavelength operation by electrospun
amplified fiber optics.Comment: 27 pages, 8 figure
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