Publications by authors named "Daniel Spencer"

Article Synopsis
  • The study focuses on a new microfluidic technique that uses non-contact shear flow deformability cytometry to analyze the electrical and mechanical properties of individual cells swiftly.
  • The method involves cells being elongated by shear forces while their electrical impedance is measured to assess both shape change and dielectric properties.
  • The technique shows a strong correlation between optical and electrical measurements and can process around 100 cells per second without needing complex setups like sheath flow or high-speed imaging.*
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We have developed a deformability cytometer that simultaneously measures the optical and electrical shape change of single cells in a viscoelastic shear flow. The optical deformability of single cells is measured using a low-cost CMOS camera illuminated with a high-power LED triggered from an electrical impedance signal created by a passing cell. Simultaneously the electrical deformability of the cell is determined using electrode arrays that measure shape changes along different axes.

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In this work, a flexible textile-based capacitive respiratory sensor, based on a capacitive sensor structure, that does not require direct skin contact is designed, optimised, and evaluated using both computational modelling and empirical measurements. In the computational study, the geometry of the sensor was examined. This analysis involved observing the capacitance and frequency variations using a cylindrical model that mimicked the human body.

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Both microplastics and phytoplankton are found together in the ocean as suspended microparticles. There is a need for deployable technologies that can identify, size, and count these particles at high throughput to monitor plankton community structure and microplastic pollution levels. In situ analysis is particularly desirable as it avoids the problems associated with sample storage, processing, and degradation.

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Engineered nanoparticles (NPs) pose a broad spectrum of interesting properties that make them useful for many applications. However, continuous exposure to NPs requires the need to deeply understand the outcomes when these NPs interact with different biological environments. After exposure within (to) these environments, the pristine surfaces of NPs strongly interact with the molecules from the surrounding medium, including metabolites, lipids, glycan, and proteins, forming the so-called protein corona (PC).

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Article Synopsis
  • The study reviews the role of glycosylation in human IgE (Immunoglobulin E) and how it affects its structure, function, and relation to diseases, especially allergies.
  • It emphasizes that despite inconsistent findings from various studies, there is evidence of different glycosylation patterns in allergic vs. healthy individuals and their functional implications in allergic reactions.
  • The review suggests that certain glycosylation changes could lead to potential therapeutic targets and underscores the need for improved research methods to further investigate these effects.
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Article Synopsis
  • * A study focused on 15 α-L-fucosidases from the GH29 family utilized sequence similarity network analysis to evaluate their specificities for various fucosylated sugars and established their structural basis through advanced imaging techniques.
  • * The research combined experimental data with machine-learning models to categorize over 34,000 GH29 sequences into similarity clusters, paving the way for future identification of novel glycoside hydrolases with tailored functionalities.
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Recombinant human erythropoietin (EPO) is a biopharmaceutical frequently used in the treatment of anemia. It is a heavily glycosylated protein with a diverse and complex glycome. EPO -glycosylation influences important pharmacological parameters, prominently serum half-life.

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Introduction: An increasing number of pediatric patients with mental and behavioral health (MBH) conditions present to Emergency Department (ED) and inpatient settings with behavioral events that require physical restraint (PR). PR usage is associated with adverse outcomes. Clinical debriefing (CD) programs have been associated with improved performance but have not been studied in this population.

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Cardiovascular disease (CVD) is a group of health conditions affecting the heart and vascular system with very high prevalence and mortality rates. The presence of CVD is characterised by high levels of inflammation which have previously been associated with increased plasma concentrations of N-acetyl neuraminic acid (Neu5Ac). While Neu5Ac has been studied in the context of CVD, Neu5,9Ac has not, despite being the second most abundant sialic acid in human plasma.

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A newly developed analytical strategy was applied to profile the total serum -glycome of 64 colorectal cancer (CRC) patients before and after surgical intervention. In this cohort, it was previously found that serum -glycome alterations in CRC were associated with patient survival. Here, fluorescent labeling of serum -glycans was applied using procainamide and followed by sialic acid derivatization specific for α2,6- and α2,3-linkage types via ethyl esterification and amidation, respectively.

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Rapid tests to assess the susceptibility of bacteria to antibiotics are required to inform antibiotic stewardship. We have developed a novel test, which measures changes in the impedance of a 100 nanoliter volume of bacterial suspension to determine an "electrical" minimum inhibitory concentration (eMIC). Two representative strains of , , , and were tested against a panel of frontline antibiotics with different modes of action (ciprofloxacin, doxycycline, colistin and imipenem, gentamicin, and ceftazidime).

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Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated.

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Introduction: Analysis of task fMRI studies is typically based on using ordinary least squares within a voxel- or vertex-wise linear regression framework known as the general linear model. This use produces estimates and standard errors of the regression coefficients representing amplitudes of task-induced activations. To produce valid statistical inferences, several key statistical assumptions must be met, including that of independent residuals.

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Efficient characterization of IgE antibodies and their glycan structures is required for understanding their function in allergy and in the emerging AllergoOncology field for antibody immunotherapy. We report the generation, glyco-profiling and functional analysis of native and sialic acid-deficient glyco-engineered human IgE. The antibodies produced from human embryonic kidney cells were purified via a human IgE class-specific affinity matrix and structural integrity was confirmed by SDS-PAGE and size-exclusion chromatography (SEC).

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Background: Free testosterone (FT) determination may be helpful in evaluating men suspected of testosterone deficiency especially in conditions with altered binding-protein concentrations. However, methods for measuring FT by equilibrium dialysis and reference intervals vary among laboratories.

Objective: To determine reference intervals for FT in healthy, nonobese men by age groups as well as in healthy young men, 19-39 years, using a standardized equilibrium dialysis procedure METHODS: We measured FT in 145 healthy, nonobese men, 19 years or older, using a standardized equilibrium dialysis method performed for 16-h at 37°C using undiluted serum and dialysis buffer that mimicked the ionic composition of human plasma.

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The major nutrients available to the human colonic microbiota are complex glycans derived from the diet. To degrade this highly variable mix of sugar structures, gut microbes have acquired a huge array of different carbohydrate-active enzymes (CAZymes), predominantly glycoside hydrolases, many of which have specificities that can be exploited for a range of different applications. Plant -glycans are prevalent on proteins produced by plants and thus components of the diet, but the breakdown of these complex molecules by the gut microbiota has not been explored.

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Biomolecular corona is spontaneously formed on the surface of nanoparticles (NPs) when they are in contact with biological fluids. It plays an important role in the colloidal stability of NPs, which is of importance for most of their medical applications and toxicity assessment. While typical studies use either blood plasma or serum from a pooled biobank, it is unclear whether differences in the media, such as cholesterol level or protein concentration, might affect the NP colloidal stability and corona composition.

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Sialidases are glycosyl hydrolase enzymes targeting the glycosidic bond between terminal sialic acids and underlying sugars. The NanH sialidase of Tannerella forsythia, one of the bacteria associated with severe periodontal disease plays a role in virulence. Here, we show that this broad-specificity enzyme (but higher affinity for α2,3 over α2,6 linked sialic acids) digests complex glycans but not those containing Neu5,9Ac.

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Sialylglycopeptide (SGP) is a readily available naturally occurring glycopeptide obtained from hen egg yolk which is now commercially available. During SGP extraction, other minor glycopeptide species are identified, bearing -glycan structures that might be of interest, such as asymmetrically branched and triantennary glycans. As the scale of SGP production increases, recovery of minor glycopeptides and their -glycans can become more feasible.

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High Mannose glycans (HM) are intermediates for the eukaryotic glycosylation pathway but are not commonly found on mature glycoproteins. HM, particularly Man9GlcNAc2 (M9), are present on the glycan shield of viral envelopes and have received attention as elements for semi-synthetic vaccines. The most common strategy to produce HM is extensive pronase digestion from soybean agglutinin (SBA) to obtain Asn-M9.

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Sialic acids have diverse biological roles, ranging from promoting up to preventing protein and cellular recognition in health and disease. The various functions of these monosaccharides are owed, in part, to linkage variants, and as a result, linkage-specific analysis of sialic acids is an important aspect of glycomic studies. This has been addressed by derivatization strategies using matrix-assisted laser desorption/ionization mass spectrometry (MS) or sialidase digestion arrays followed by liquid chromatography (LC)-MS.

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Microfluidic impedance cytometry is a label-free technique for high-throughput single-cell analysis. Multi-frequency impedance measurements provide data that allows full characterisation of cells, linking electrical phenotype to individual biophysical properties. To efficiently extract the information embedded in the electrical signals, potentially in real-time, tailored signal processing is needed.

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Biomolecular corona formation has emerged as a recurring and important phenomenon in nanomedicine that has been investigated for potential applications in disease diagnosis. In this study, we have combined the "personalized protein corona" with the N-glycosylation profiling that has recently gained considerable interest in human plasma biomarker discovery as a powerful early warning diagnostic and patient stratification tool. We envisioned that the protein corona formation could be exploited as an enrichment step that is critically important in both proteomic and proteoglycomic workflows.

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Hypothesis: Following blood administration, the pristine surface of nanoparticles (NPs) associates with biomolecules from the surrounding environment forming the so-called "biomolecular corona". It is well accepted that the biomolecular corona dramatically affects the NP fate in the biological medium while the pristine surface is no longer available for binding. Recent studies have shown that the glycans associated with the proteins forming the corona have a role in the NP interaction with macrophages, but the glycan identities remain unknown.

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