A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin

In a low inflammatory skin environment, Langerhans cells (LCs) - but not dermal dendritic cells (dDCs) - contribute to the pivotal process of tolerance induction. Thus LCs are a target for specific-tolerance therapies. LCs reside just below the stratum corneum, within the skin's viable epidermis. One way to precisely deliver immunotherapies to LCs while remaining minimally invasive is with a skin delivery device such as a microprojection arrays (MPA). Today's MPAs currently achieve rapid delivery (e.g. within minutes of application), but are focussed primarily at delivery of therapeutics to the dermis, deeper within the skin. Indeed, no MPA currently delivers specifically to the epidermal LCs of mouse skin. Without any convenient, pre-clinical device available, advancement of LC-targeted therapies has been limited. In this study, we designed and tested a novel MPA that delivers ovalbumin to the mouse epidermis (eMPA) while maintaining a low, local inflammatory response (as defined by low erythema after 24 h). In comparison to available dermal-targeted MPAs (dMPA), only eMPAs with larger projection tip surface areas achieved shallow epidermal penetration at a low application energy. The eMPA characterised here induced significantly less erythema after 24 h (p = 0.0004), less epidermal swelling after 72 h (p

Allometric scaling of skin thickness, elasticity, viscoelasticity to mass for micro-medical device translation:From mice, rats, rabbits, pigs to humans

Abstract Emerging micro-scale medical devices are showing promise, whether in delivering drugs or extracting diagnostic biomarkers from skin. In progressing these devices through animal models towards clinical products, understanding the mechanical properties and skin tissue structure with which they interact will be important. Here, through measurement and analytical modelling, we advanced knowledge of these properties for commonly used laboratory animals and humans (~30 g to ~150 kg). We hypothesised that skin’s stiffness is a function of the thickness of its layers through allometric scaling, which could be estimated from knowing a species’ body mass. Results suggest that skin layer thicknesses are proportional to body mass with similar composition ratios, inter- and intra-species. Experimental trends showed elastic moduli increased with body mass, except for human skin. To interpret the relationship between species, we developed a simple analytical model for the bulk elastic moduli of skin, which correlated well with experimental data. Our model suggest that layer thicknesses may be a key driver of structural stiffness, as the skin layer constituents are physically and therefore mechanically similar between species. Our findings help advance the knowledge of mammalian skin mechanical properties, providing a route towards streamlined micro-device research and development onto clinical use

Sensors for foetal hypoxia and metabolic acidosis: a review

This article reviews existing clinical practices and sensor research undertaken to monitor fetal well-being during labour. Current clinical practices that include fetal heart rate monitoring and fetal scalp blood sampling are shown to be either inadequate or time-consuming. Monitoring of lactate in blood is identified as a potential alternative for intrapartum fetal monitoring due to its ability to distinguish between different types of acidosis. A literature review from a medical and technical perspective is presented to identify the current advancements in the field of lactate sensors for this application. It is concluded that a less invasive and a more continuous monitoring device is required to fulfill the clinical needs of intrapartum fetal monitoring. Potential specifications for such a system are also presented in this paper

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

The Atacama Cosmology Telescope: The LABOCA/ACT Survey of Clusters at All Redshifts

We present a multi-wavelength analysis of eleven Sunyaev Zel'dovich effect (SZE)-selected galaxy clusters (ten with new data) from the Atacama Cosmology Telescope (ACT) southern survey. We have obtained new imaging from the Large APEX Bolometer Camera (345GHz; LABOCA) on the Atacama Pathfinder EXperiment (APEX) telescope, the Australia Telescope Compact Array (2.1GHz; ATCA), and the Spectral and Photometric Imaging Receiver (250, 350, and $500\,\rm\mu m$; SPIRE) on the Herschel Space Observatory. Spatially-resolved 345GHz SZE increments with integrated S/N > 5 are found in six clusters. We compute 2.1GHz number counts as a function of cluster-centric radius and find significant enhancements in the counts of bright sources at projected radii $\theta < \theta_{2500}$. By extrapolating in frequency, we predict that the combined signals from 2.1GHz-selected radio sources and 345GHz-selected SMGs contaminate the 148GHz SZE decrement signal by ~5% and the 345GHz SZE increment by ~18%. After removing radio source and SMG emission from the SZE signals, we use ACT, LABOCA, and (in some cases) new Herschel SPIRE imaging to place constraints on the clusters' peculiar velocities. The sample's average peculiar velocity relative to the cosmic microwave background is $153\pm 383\,\rm km\,s^{-1}$.Comment: 19 pages, 11 figures, Accepted for Publication in The Astrophysical Journa

Rapid mechanosensitive migration and dispersal of newly divided mesenchymal cells aid their recruitment into dermal condensates

Embryonic mesenchymal cells are dispersed within an extracellular matrix but can coalesce to form condensates with key developmental roles. Cells within condensates undergo fate and morphological changes and induce cell fate changes in nearby epithelia to produce structures including hair follicles, feathers, or intestinal villi. Here, by imaging mouse and chicken embryonic skin, we find that mesenchymal cells undergo much of their dispersal in early interphase, in a stereotyped process of displacement driven by 3 hours of rapid and persistent migration followed by a long period of low motility. The cell division plane and the elevated migration speed and persistence of newly born mesenchymal cells are mechanosensitive, aligning with tissue tension, and are reliant on active WNT secretion. This behaviour disperses mesenchymal cells and allows daughters of recent divisions to travel long distances to enter dermal condensates, demonstrating an unanticipated effect of cell cycle subphase on core mesenchymal behaviour

Cosmological Parameters from Pre-Planck CMB Measurements

Recent data from the WMAP, ACT and SPT experiments provide precise measurements of the cosmic microwave background temperature power spectrum over a wide range of angular scales. The combination of these observations is well fit by the standard, spatially flat LCDM cosmological model, constraining six free parameters to within a few percent. The scalar spectral index, n_s = 0.9690 +/- 0.0089, is less than unity at the 3.6 sigma level, consistent with simple models of inflation. The damping tail of the power spectrum at high resolution, combined with the amplitude of gravitational lensing measured by ACT and SPT, constrains the effective number of relativistic species to be N_eff = 3.28 +/- 0.40, in agreement with the standard model's three species of light neutrinos.Comment: 5 pages, 4 figure

The Atacama Cosmology Telescope: the stellar content of galaxy clusters selected using the Sunyaev-Zel'dovich effect

We present a first measurement of the stellar mass component of galaxy clusters selected via the Sunyaev-Zel'dovich (SZ) effect, using 3.6 um and 4.5 um photometry from the Spitzer Space Telescope. Our sample consists of 14 clusters detected by the Atacama Cosmology Telescope (ACT), which span the redshift range 0.27 < z < 1.07 (median z = 0.50), and have dynamical mass measurements, accurate to about 30 per cent, with median M500 = 6.9 x 10^{14} MSun. We measure the 3.6 um and 4.5 um galaxy luminosity functions, finding the characteristic magnitude (m*) and faint-end slope (alpha) to be similar to those for IR-selected cluster samples. We perform the first measurements of the scaling of SZ-observables (Y500 and y0) with both brightest cluster galaxy (BCG) stellar mass and total cluster stellar mass (M500star). We find a significant correlation between BCG stellar mass and Y500 (E(z)^{-2/3} DA^2 Y500 ~ M*^{1.2 +/- 0.6}), although we are not able to obtain a strong constraint on the slope of the relation due to the small sample size. Additionally, we obtain E(z)^{-2/3} DA^2 Y500 ~ M500star^{1.0 +/- 0.6} for the scaling with total stellar mass. The mass fraction in stars spans the range 0.006-0.034, with the second ranked cluster in terms of dynamical mass (ACT-CL J0237-4939) having an unusually low total stellar mass and the lowest stellar mass fraction. For the five clusters with gas mass measurements available in the literature, we see no evidence for a shortfall of baryons relative to the cosmic mean value.Comment: Accepted for publication in MNRAS; 12 pages, 10 figure

The Atacama Cosmology Telescope: Sunyaev-Zel'dovich Selected Galaxy Clusters at 148 GHz from Three Seasons of Data

[Abridged] We present a catalog of 68 galaxy clusters, of which 19 are new discoveries, detected via the Sunyaev-Zel'dovich effect (SZ) at 148 GHz in the Atacama Cosmology Telescope (ACT) survey of 504 square degrees on the celestial equator. A subsample of 48 clusters within the 270 square degree region overlapping SDSS Stripe 82 is estimated to be 90% complete for M_500c > 4.5e14 Msun and 0.15 < z < 0.8. While matched filters are used to detect the clusters, the sample is studied further through a "Profile Based Amplitude Analysis" using a single filter at a fixed \theta_500 = 5.9' angular scale. This new approach takes advantage of the "Universal Pressure Profile" (UPP) to fix the relationship between the cluster characteristic size (R_500) and the integrated Compton parameter (Y_500). The UPP scalings are found to be nearly identical to an adiabatic model, while a model incorporating non-thermal pressure better matches dynamical mass measurements and masses from the South Pole Telescope. A high signal to noise ratio subsample of 15 ACT clusters is used to obtain cosmological constraints. We first confirm that constraints from SZ data are limited by uncertainty in the scaling relation parameters rather than sample size or measurement uncertainty. We next add in seven clusters from the ACT Southern survey, including their dynamical mass measurements based on galaxy velocity dispersions. In combination with WMAP7 these data simultaneously constrain the scaling relation and cosmological parameters, yielding \sigma_8 = 0.829 \pm 0.024 and \Omega_m = 0.292 \pm 0.025. The results include marginalization over a 15% bias in dynamical mass relative to the true halo mass. In an extension to LCDM that incorporates non-zero neutrino mass density, we combine our data with WMAP7+BAO+Hubble constant measurements to constrain \Sigma m_\nu < 0.29 eV (95% C. L.).Comment: 32 pages, 21 figures To appear in J. Cosmology and Astroparticle Physic