Lipid changes within the epidermis of living skin equivalents observed across a time-course by MALDI-MS imaging and profiling

© 2015 Mitchell et al. Abstract Background: Mass spectrometry imaging (MSI) is a powerful tool for the study of intact tissue sections. Here, its application to the study of the distribution of lipids in sections of reconstructed living skin equivalents during their development and maturation is described. Methods: Living skin equivalent (LSE) samples were obtained at 14 days development, re-suspended in maintenance medium and incubated for 24 h after delivery. The medium was then changed, the LSE re-incubated and samples taken at 4, 6 and 24 h time points. Mass spectra and mass spectral images were recorded from 12 μm sections of the LSE taken at each time point for comparison using matrix assisted laser desorption ionisation mass spectrometry. Results: A large number of lipid species were identified in the LSE via accurate mass-measurement MS and MSMS experiments carried out directly on the tissue sections. MS images acquired at a spatial resolution of 50 μm × 50 μm showed the distribution of identified lipids within the developing LSE and changes in their distribution with time. In particular development of an epidermal layer was observable as a compaction of the distribution of phosphatidylcholine species. Conclusions: MSI can be used to study changes in lipid composition in LSE. Determination of the changes in lipid distribution during the maturation of the LSE will assist in the identification of treatment responses in future investigations

Exotic Smoothness and Physics

The essential role played by differentiable structures in physics is reviewed in light of recent mathematical discoveries that topologically trivial space-time models, especially the simplest one, ${\bf R^4}$, possess a rich multiplicity of such structures, no two of which are diffeomorphic to each other and thus to the standard one. This means that physics has available to it a new panoply of structures available for space-time models. These can be thought of as source of new global, but not properly topological, features. This paper reviews some background differential topology together with a discussion of the role which a differentiable structure necessarily plays in the statement of any physical theory, recalling that diffeomorphisms are at the heart of the principle of general relativity. Some of the history of the discovery of exotic, i.e., non-standard, differentiable structures is reviewed. Some new results suggesting the spatial localization of such exotic structures are described and speculations are made on the possible opportunities that such structures present for the further development of physical theories.Comment: 13 pages, LaTe

A statistical investigation of the effects contributed by tape recorders and by wow and flutter of magnetic tape on the accuracy of a telemetry system Technical report no. 15

Effects contributed by tape recorders and by wow and flutter of magnetic tape on accuracy of telemetry syste

N=2 Topological Yang-Mills Theory on Compact K\"{a}hler Surfaces

We study a topological Yang-Mills theory with $N=2$ fermionic symmetry. Our formalism is a field theoretical interpretation of the Donaldson polynomial invariants on compact K\"{a}hler surfaces. We also study an analogous theory on compact oriented Riemann surfaces and briefly discuss a possible application of the Witten's non-Abelian localization formula to the problems in the case of compact K\"{a}hler surfaces.Comment: ESENAT-93-01 & YUMS-93-10, 34pages: [Final Version] to appear in Comm. Math. Phy

A qualitative exploration of the experiences of living with and being treated for fibromyalgia

This study explores the life and treatment experience of people in the United Kingdom with fibromyalgia in order to inform the development of treatments which are both effective and acceptable to users. Qualitative interviews were conducted with 14 participants with interpretative phenomenological analysis used as the theoretical framework and analytical method. The themes identified were as follows: Inauthenticity of fibromyalgia, An Unconventional healthcare experience, Re-creating support networks, Challenging the working identity, Threatening the family dynamic and Fighting, accepting or accommodating? The biopsychosocial impacts of fibromyalgia disrupted the identity, lifestyle, roles and relationships of our participants with such challenges further exacerbated by the contested nature of the illness

Optical Coronagraphic Spectroscopy of AU Mic: Evidence of Time Variable Colors?

We present coronagraphic long slit spectra of AU Mic's debris disk taken with the STIS instrument aboard the Hubble Space Telescope (HST). Our spectra are the first spatially resolved, scattered light spectra of the system's disk, which we detect at projected distances between approximately 10 and 45 AU. Our spectra cover a wavelength range between 5200 and 10200 angstroms. We find that the color of AU Mic's debris disk is bluest at small (12-35 AU) projected separations. These results both confirm and quantify the findings qualitatively noted by Krist et al. (2005), and are different than IR observations that suggested a uniform blue or gray color as a function of projected separation in this region of the disk. Unlike previous literature that reported the color of AU Mic's disk became increasingly more blue as a function of projected separation beyond approximately 30 AU, we find the disk's optical color between 35-45 AU to be uniformly blue on the southeast side of the disk and decreasingly blue on the northwest side. We note that this apparent change in disk color at larger projected separations coincides with several fast, outward moving "features" that are passing through this region of the southeast side of the disk. We speculate that these phenomenon might be related, and that the fast moving features could be changing the localized distribution of sub-micron sized grains as they pass by, thereby reducing the blue color of the disk in the process. We encourage follow-up optical spectroscopic observations of the AU Mic to both confirm this result, and search for further modifications of the disk color caused by additional fast moving features propagating through the disk.Comment: Accepted by AJ, 13 pages, 8 figures, 1 tabl

S-duality and Topological Strings

In this paper we show how S-duality of type IIB superstrings leads to an S-duality relating A and B model topological strings on the same Calabi-Yau as had been conjectured recently: D-instantons of the B-model correspond to A-model perturbative amplitudes and D-instantons of the A-model capture perturbative B-model amplitudes. Moreover this confirms the existence of new branes in the two models. As an application we explain the recent results concerning A-model topological strings on Calabi-Yau and its equivalence to the statistical mechanical model of melting crystal.Comment: 13 page

Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants

Late-onset bloodstream infection (LO-BSI) is a common complication of prematurity, and lack of timely diagnosis and treatment can have life-threatening consequences. We sought to identify clinical characteristics and microbial signatures in the gastrointestinal microbiota preceding diagnosis of LO-BSI in premature infants.Daily faecal samples and clinical data were collected over two years from 369 premature neonates (<32 weeks gestation). We analysed samples from 22 neonates who developed LO-BSI and 44 matched control infants. Next-generation sequencing of 16S rRNA gene regions amplified by PCR from total faecal DNA was used to characterise the microbiota of faecal samples preceding diagnosis from infants with LO-BSI and controls. Culture of selected samples was undertaken, and bacterial isolates identified using MALDI-TOF. Antibiograms from bloodstream and faecal isolates were compared to explore strain similarity.From the week prior to diagnosis, infants with LO-BSI had higher proportions of faecal aerobes/facultative anaerobes compared to controls. Risk factors for LO-BSI were identified by multivariate analysis. Enterobacteriaceal sepsis was associated with antecedent multiple lines, low birth weight and a faecal microbiota with prominent Enterobacteriaceae. Staphylococcal sepsis was associated with Staphylococcus OTU faecal over-abundance, and the number of days prior to diagnosis of mechanical ventilation and of the presence of centrally-placed lines. In 12 cases, the antibiogram of the bloodstream isolate matched that of a component of the faecal microbiota in the sample collected closest to diagnosis.The gastrointestinal tract is an important reservoir for LO-BSI organisms, pathogens translocating across the epithelial barrier. LO-BSI is associated with an aberrant microbiota, with abundant staphylococci and Enterobacteriaceae and a failure to mature towards predominance of obligate anaerobes

Small coupling limit and multiple solutions to the Dirichlet Problem for Yang Mills connections in 4 dimensions - Part I

In this paper (Part I) and its sequels (Part II and Part III), we analyze the structure of the space of solutions to the epsilon-Dirichlet problem for the Yang-Mills equations on the 4-dimensional disk, for small values of the coupling constant epsilon. These are in one-to-one correspondence with solutions to the Dirichlet problem for the Yang Mills equations, for small boundary data. We prove the existence of multiple solutions, and, in particular, non minimal ones, and establish a Morse Theory for this non-compact variational problem. In part I, we describe the problem, state the main theorems and do the first part of the proof. This consists in transforming the problem into a finite dimensional problem, by seeking solutions that are approximated by the connected sum of a minimal solution with an instanton, plus a correction term due to the boundary. An auxiliary equation is introduced that allows us to solve the problem orthogonally to the tangent space to the space of approximate solutions. In Part II, the finite dimensional problem is solved via the Ljusternik-Schirelman theory, and the existence proofs are completed. In Part III, we prove that the space of gauge equivalence classes of Sobolev connections with prescribed boundary value is a smooth manifold, as well as some technical lemmas used in Part I. The methods employed still work when the 4-dimensional disk is replaced by a more general compact manifold with boundary, and SU(2) is replaced by any compact Lie group