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Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded T-cells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin. All the identified gold-specific clones were CD8+, whilst proinsulin-specific clones were both CD8+ and CD4+. Proinsulin-specific CD8+ clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained in situ for months to years, with a spectrum of tissue resident memory and effector memory phenotypes. As the T-cell response is divided between targeting the gold core and the antigenic cargo, this offers a route to improving resident memory T-cells formation in response to vaccines. In addition, our scRNAseq data indicate that focusing on clonally expanded skin infiltrating T-cells recruited to intradermally injected antigen is a highly efficient method to enrich and identify antigen-specific cells. This approach has the potential to be used to monitor the intradermal delivery of antigens and nanoparticles for immune modulation in humans.

‎The effect of restricting the set of primes dividing the orders of the finite quotients of a group is investigated‎. ‎Particular attention is paid to abelian‎, ‎soluble‎, ‎locally soluble and locally finite groups‎. ‎The connection with the extraction of roots is explored‎.

There is a paucity of information on nutrient stocks and distribution in the cocoa ecosystem for the management of production sites to improve its productivity. Apart, sites with long histories of cocoa production could differ in nutrient stocks and distribution relative to recent production regions. Therefore, some existing cocoa farms in Ghana were sampled on the basis of shade management (shaded and unshaded) and production site longevity (Eastern region > Western North region) to determine the nutrient stock and distributions in them. Over 93% of the total ecosystems’ elementary nutrients were stored in the soil. Higher nutrient stocks occurred under shaded cocoa ecosystem. Nutrient element concentrations in cocoa tree biomasses followed the order: N > Ca > K > Mg > P > S > Al = Fe > Zn = Mn, and mostly concentrated in leaf > root = husk > branch > stem. On average, region as a main factor affected nutrient distributions. There was a sharp distinction between macronutrient and micronutrient accumulations in favour of Eastern region and Western North region, respectively. Therefore, the regional distinction with respect to macro- and micronutrients could be used as a guide to fertilizer recommendation for cocoa systems in the two regions.

A study is made of groups with finitely many derived groups of subgroups or of infinite subgroups. These groups are classified completely in the locally graded case. In the general case, detailed structural information about groups in each class is found. [ABSTRACT FROM AUTHOR]

It is shown that there is an algorithm to decide if two given subgroups of a polycyclic-by-finite group permute. This is accomplished by finding an algorithm which is able to determine if a derivation is surjective. [ABSTRACT FROM AUTHOR]

Poor prenatal growth is associated with limited evidence of GH deficiency in adult humans, which may contribute to their increased risk of cardiovascular and metabolic disease. We therefore examined the effects of placental restriction of fetal growth (PR) on size at birth, neonatal fractional growth rate (FGR) and the circulating GH profile in adolescent and young adult sheep of both sexes. Moderate or severe PR decreased birth size and increased neonatal FGR of weight, crown-rump length and abdominal circumference. In adolescent males, mean and baseline GH concentrations correlated negatively and independently with birth weight and FGR of weight, and mean GH concentrations correlated negatively with current weight. In young adult males, mean GH concentrations correlated negatively and independently with birth shoulder height and FGR of shoulder height whilst, in young adult females, these correlations were positive. This suggests that restricted fetal growth and reduced neonatal growth rate in sheep are followed by elevated circulating GH in adolescent and adult males, but GH deficiency or increased GH clearance in adult females.