32 research outputs found

    Simultaneous electronphoton excitation of helium in a CO2 laser field

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    International audienceThe R-matrix Floquet method is used to study electron-impact excitation of helium in the presence of a CO 2 laser field, for collision energies between 19 and 21.5 eV and laser intensities of 10 7 and 10 8 W cm −2. Collision geometries with the electron incident at various angles to the laser polarization axis are considered. The signal for production of metastable states is in good agreement with the results of a low-frequency approximation and a semi-classical approach, while agreement with experiment is reasonable

    R-matrix Floquet theory for laser-assisted electron-atom scattering

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    A new version of the R-matrix Floquet theory for laser-assisted electron-atom scattering is presented. The theory is non-perturbative and applicable to a non-relativistic many-electron atom or ion in a homogeneous linearly polarized field. It is based on the use of channel functions built from field-dressed target states, which greatly simplifies the general formalism.Comment: 18 pages, LaTeX2e, submitted to J.Phys.

    Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in Type 1 diabetes

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    Antigen-specific immunotherapy is immunomodulatory strategy for autoimmune diseases, such as Type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune beta-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNP), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well-tolerated in participants with Type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies

    Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

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    Aims/hypothesis Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes. Methods A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays. Results A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells. Conclusions/interpretation Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration

    Photodetachment of C− in the ground state

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    Absolute total cross sections and asymmetry parameters for photodetachment of C−(4So) have been measured using animated-crossed-beam and velocity map imaging techniques, for photon energies from threshold up to 6eV. The cross sections are 15% to 25% larger than earlier experimental results above 2.2 eV. They are in very good agreement with those from a new R-matrix calculation using polarized pseudostates

    The two-photon detachment of O−^-

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    Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in Type 1 diabetes patients: a randomised clinical trial

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    Aim To examine the metabolic, gluco-regulatory-hormonal and inflammatory cytokine responses to large reductions in rapid-acting insulin dose administered prandially before and after intensive running exercise in male type 1 diabetes patients. Methods This was a single centre, randomised, controlled open label study. Following preliminary testing, 8 male patients (24±2 years, HbA1c 7.7±0.4%/61±4 mmol.l−1) treated with insulin's glargine and aspart, or lispro attended the laboratory on two mornings at ∌08:00 h and consumed a standardised breakfast carbohydrate bolus (1 g carbohydrate.kg−1BM; 380±10 kcal) and self-administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes of intensive treadmill running at 73.1±0.9% VO2peak. At 60 minutes post-exercise, patients ingested a meal (1 g carbohydrate.kg−1BM; 660±21 kcal) and administered either a Full or 50% reduced rapid-acting insulin dose. Blood glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, ÎČ-Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF-α concentrations were measured for 180 minutes post-meal. Results All participants were analysed. All glycaemic, metabolic, hormonal, and cytokine responses were similar between conditions up to 60 minutes following exercise. Following the post-exercise meal, serum insulin concentrations were lower under 50% (p<0.05) resulting in 75% of patients experiencing hyperglycaemia (blood glucose ≄8.0 mmol.l−1; 50% n = 6, Full n = 3). ÎČ-Hydroxybutyrate concentrations decreased similarly, such that at 180 minutes post-meal concentrations were lower than rest under Full and 50%. IL-6 and TNF-α concentrations remained similar to fasting levels under 50% but declined under Full. Under 50% IL-6 concentrations were inversely related with serum insulin concentrations (r = −0.484, p = 0.017). Conclusions Heavily reducing rapid-acting insulin dose with a carbohydrate bolus before, and a meal after intensive running exercise may cause hyperglycaemia, but does not augment ketonaemia, raise inflammatory cytokines TNF-α and IL-6 above fasting levels, or cause other adverse metabolic or hormonal disturbances. Trial Registration ClinicalTrials.gov NCT0153185
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