Feasibility study for a numerical aerodynamic simulation facility. Volume 1

A Numerical Aerodynamic Simulation Facility (NASF) was designed for the simulation of fluid flow around three-dimensional bodies, both in wind tunnel environments and in free space. The application of numerical simulation to this field of endeavor promised to yield economies in aerodynamic and aircraft body designs. A model for a NASF/FMP (Flow Model Processor) ensemble using a possible approach to meeting NASF goals is presented. The computer hardware and software are presented, along with the entire design and performance analysis and evaluation

Potent Immunity to Low Doses of Influenza Vaccine by Probabilistic Guided Micro-Targeted Skin Delivery in a Mouse Model

Background: Over 14 million people die each year from infectious diseases despite extensive vaccine use [1]. The needle and syringe-first invented in 1853-is still the primary delivery device, injecting liquid vaccine into muscle. Vaccines could be far more effective if they were precisely delivered into the narrow layer just beneath the skin surface that contains a much higher density of potent antigen-presenting cells (APCs) essential to generate a protective immune response. We hypothesized that successful vaccination could be achieved this way with far lower antigen doses than required by the needle and syringe

Microneedle Enhanced Delivery of Cosmeceutically Relevant Peptides in Human Skin

Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides

Statement in Support of: "Virology under the Microscope-a Call for Rational Discourse"

Letter to the Editor. Published 25 April 2023Peter Speck, Jason Mackenzie, Rowena A. Bull, Barry Slobedman, Heidi Drummer, Johanna Fraser, Lara Herrero, Karla Helbig, Sarah Londrigan, Gregory Moseley, Natalie Prow, Grant Hansman, Robert Edwards, Chantelle Ahlenstiel, Allison Abendroth, David Tscharke, Jody Hobson-Peters, Robson Kriiger-Loterio, Rhys Parry, Glenn Marsh, Emma Harding, David A. Jacques, Matthew J. Gartner, Wen Shi Lee, Julie McAuley, Paola Vaz, Frank Sainsbury, Michelle D. Tate, Jane Sinclair, Allison Imrie, Stephen Rawlinson, Andrew Harman, Jillian M. Carr, Ebony A. Monson, Merilyn Hibma, Timothy J.Mahony, Thomas Tu, Robert J. Center, Lok Bahadur Shrestha, Robyn Hall, Morgyn Warner, Vernon Ward, Danielle E. Anderson, Nicholas S. Eyre, Natalie E. Netzler, Alison J. Peel, Peter Revill, Michael Beard, Alistair R. Legione, Alexandra J. Spencer, Adi Idris, Jade Forwood, Subir Sarker, Damian F. J. Purcell, Nathan Bartlett, Joshua M. Deerain, Bruce J. Brew, Sassan Asgari, Helen Farrell, Alexander Khromykh, Daniel Enosi Tuipulotu, David Anderson, Sevim Mese, Yaman Tayyar, Kathryn Edenborough, Jasim Muhammad Uddin, Abrar Hussain, Connor J. I. Daymond, Jacinta Agius, Karyn N. Johnson, Paniz Shirmast, Mahdi Abedinzadeshahri, Robin MacDiarmid, Caroline L. Ashley, Jay Laws, Lucy L. Furfaro, Thomas D. Burton, Stephen M. R. Johnson, Zahra Telikani, Mary Petrone, Justin A. Roby, Carolyn Samer, Andreas Suhrbier, April Van Der Kamp, Anthony Cunningham, Celeste Donato, Jackie Mahar, Wesley D. Black, Subhash Vasudevan, Roman Lenchine, Kirsten Spann, Daniel J. Rawle, Penny Rudd, Jessica Neil, Richard Kingston, Timothy P. Newsome, Ki Wook Kim, Johnson Mak, Kym Lowry, Nathan Bryant, Joanne Meers, Jason A. Roberts, Nigel McMillan, Larisa I. Labzin, Andrii Slonchak, Leon E. Hugo, Bennett Henzeler, Natalee D. Newton, Cassandra T. David, Patrick C. Reading, Camille Esneau, Tatiana Briody, Najla Nasr, Donna McNeale, Brian McSharry, Omid Fakhri, Bethany A. Horsburgh, Grant Logan, Paul Howley, Paul Youn

Statement in Support of: "Virology under the Microscope-a Call for Rational Discourse".

Letter to the Editor OnlinePublPeter Speck ... Michael Beard ... et al

Space- and time-resolved investigation on diffusion kinetics of human skin following macromolecule delivery by microneedle arrays

Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development of these devices is dependent on understanding the macro-molecular diffusion properties of skin. We hypothesised that diffusion varied according to specific skin layers. Using three different molecular weights of rhodamine dextran (RD) (MW of 70, 500 and 2000 kDa) relevant to the vaccine and therapeutic scales, we deposited molecules to a range of depths (0–300 µm) in ex vivo human skin using the Nanopatch device. We observed significant dissipation of RD as diffusion with 70 and 500 kDa within the 30 min timeframe, which varied with MW and skin layer. Using multiphoton microscopy, image analysis and a Fick’s law analysis with 2D cartesian and axisymmetric cylindrical coordinates, we reported experimental trends of epidermal and dermal diffusivity values ranging from 1–8 µm2 s-1 to 1–20 µm2 s-1 respectively, with a significant decrease in the dermal-epidermal junction of 0.7–3 µm2 s-1. In breaching the stratum corneum (SC) and dermal-epidermal junction barriers, we have demonstrated practical application, delivery and targeting of macromolecules to both epidermal and dermal antigen presenting cells, providing a sound knowledge base for future development of skin-targeting clinical technologies in humans

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

Expression of recombinant West Nile virus prM protein fused to an affinity tag for use as a diagnostic antigen

Previous studies have concluded that the Flavivirus prM protein is a suitable viral antigen to distinguish serologically between infections with closely related Flaviviruses (Cardosa et al., 2002). To express the recombinant West Nile virus (WNV) prM antigen fused to a suitable affinity tag for purification, a series of prM-His-tag and prM-V5-tag fusion proteins were generated. Analysis of the prM-His-tag fusion proteins revealed that either prM epitopes were disrupted or the His-tag was not presented properly depending on the location of the His tag and the presence of the prM transmembrane domains in these constructs. This identified domains critical for proper folding of prM, and arrangements that allowed the correct presentation of the His-tag. However, the inclusion of the V5 epitope tag fused to the C terminus of prM allowed formation of the authentic antigenic structure of prM and the proper presentation of the V5 epitope. Capture of tagged recombinant WNV(NY99) prM antigen to the solid phase with anti-V5 antibody in ELISA enabled the detection of prM-specific antibodies in WNV(NY99)-immune horse serum, confirming its potential as a useful diagnostic reagent. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved