1,324 research outputs found
An unusual pi* shape resonance in the near-threshold photoionization of S(1) para-difluorobenzene
Previously reported dramatic changes in photoelectron angular distributions (PADs) as a function of photoelectron kinetic energy following the ionization of S1 p-difluorobenzene are shown to be explained by a shape resonance in the b(2g) symmetry continuum. The characteristics of this resonance are clearly demonstrated by a theoretical multiple-scattering treatment of the photoionization dynamics. New experimental data are presented which demonstrate an apparent insensitivity of the PADs to both vibrational motion and prepared molecular alignment, however, the calculations suggest that strong alignment effects may nevertheless be recognized in the detail of the comparison with experimental data. The apparent, but unexpected, indifference to vibrational excitation is rationalized by considering the nature of the resonance. The correlation of this shape resonance in the continuum with a virtual pi* antibonding orbital is considered. Because this orbital is characteristic of the benzene ring, the existence of similar resonances in related substituted benzenes is discussed.Bellm, SM: Davies, JA: Whiteside, PT; Guo, J: Powis, I; and Reid KL
A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I molecules
AbstractAn important mammalian defence strategy against intracellular pathogens is the presentation of cytoplasmically derived short peptides by major histocompatibility complex (MHC) class I molecules to cytotoxic T lymphocytes. MHC class I molecules assemble in the endoplasmic reticulum (ER) with chaperones, including calnexin and calreticulin, before binding to the transporter associated with antigen processing (TAP). We show here that the thiol-dependent reductase ERp57 (also known as ER60 protease) is involved in MHC class I assembly. ERp57 co-purified with the rat TAP complex (comprising TAP1 and TAP2), and associated with MHC class I molecules at an early stage in their biosynthesis. This association was sensitive to castanospermine, which inhibits the processing of glycoproteins. Human MHC class I molecules were also found to associate with ERp57. We conclude that ERp57 is a newly identified component of the MHC class I pathway, and that it appears to interact with MHC class I molecules before they associate with TAP
Geometric quantisation and quantum mechanics in Dirac's front form
We give a brief review of geometric quantisation up to and including the Blattner-Kostant-Sternberg kernal. In general this leads to symmetric operators that are not essentially self-adjoint so motivating a study of Hermitian operators as observables in a generalised quantum mechanics. We show that a generalised squaring axiom can reproduce the results of Blattner-Kostant-Sternberg quantisation. We also show that quantisation with respect to polarisations with compact leaves gives results that conflict with the nonlocal nature of quantum mechanics. We develop a front form quantum mechanics of a free scalar particle using geometric quantisation. The front and instant forms are related via unitary maps derived from the pairing which intertwines quantisations with respect to the forms. The front form position operator has a maximally symmetric component so we are compelled to work within the framework of a generalised quantum mechanics; the result in there being no Hegerfeldt type instantaneous spreading of initially localised wavefunctions in the front form. Finally we show that this model can be lifted to a many particle free field theory
Suppression of MHC class I surface expression by calreticulin's P-domain in a calreticulin deficient cell line
AbstractCalreticulin (CRT) is an important chaperone protein, comprising an N-domain, P-domain and C-domain. It is involved in the folding and assembly of multi-component protein complexes in the endoplasmic reticulum, and plays a critical role in MHC class I antigen processing and presentation. To dissect the functional role and molecular basis of individual domains of the protein, we have utilized individual domains to rescue impaired protein assembly in a CRT deficient cell line. Unexpectedly, both P-domain fragment and NP domain of CRT not only failed to rescue defective cell surface expression of MHC class I molecules but further inhibited their appearance on the surface of cells. Formation of the TAP-associated peptide-loading complex and trafficking of the few detectable MHC class I molecules were not significantly impaired. Instead, this further suppression of MHC class I molecules on the cell surface appears due to the complex missing antigenic peptides, the third member of fully assembled MHC class I molecules. Therefore the P-domain of calreticulin appears to play a significant role in antigen presentation by MHC class I molecules
What is the role of HLA-I on cancer derived extracellular vesicles? Defining the challenges in characterisation and potential uses of this ligandome
The Human Leukocyte Antigen class I (HLA-I) system is an essential part of the immune system that is fundamental to the successful activation of cytotoxic lymphocytes, and an effective subsequent immune attack against both pathogen-infected and cancer cells. The importance of cytotoxic T cell activity and ability to detect foreign cancer-related antigenic peptides has recently been highlighted by the successful application of monoclonal antibody-based checkpoint inhibitors as novel immune therapies. Thus, there is an increased interest in fully characterising the repertoire of peptides that are being presented to cytotoxic CD8+ T cells by cancer cells. However, HLA-I is also known to be present on the surface of extracellular vesicles, which are released by most if not all cancer cells. Whilst the peptide ligandome presented by cell surface HLA class I molecules on cancer cells has been studied extensively, the ligandome of extracellular vesicles remains relatively poorly defined. Here, we will describe the current understanding of the HLA-I peptide ligandome and its role on cancer-derived extracellular vesicles, and evaluate the aspects of the system that have the potential to advance immune-based therapeutic approaches for the effective treatment of cancer.Publisher PDFPeer reviewe
Deep learning enabled laser speckle wavemeter with a high dynamic range
Funding: This work was supported by a Medical Research Scotland PhD studentship PhD 873-2015 awarded to R.K.G, and grant funding from Leverhulme Trust (RPG-2017-197) and UK Engineering and Physical Sciences Research Council (grant EP/P030017/1).The speckle pattern produced when a laser is scattered by a disordered medium has recently been shown to give a surprisingly accurate or broadband measurement of wavelength. Here it is shown that deep learning is an ideal approach to analyse wavelength variations using a speckle wavemeter due to its ability to identify trends and overcome low signal to noise ratio in complex datasets. This combination enables wavelength measurement at high precision over a broad operating range in a single step, with a remarkable capability to reject instrumental and environmental noise, which has not been possible with previous approaches. It is demonstrated that the noise rejection capabilities of deep learning provide attometre-scale wavelength precision over an operating range from 488 nm to 976 nm. This dynamic range is six orders of magnitude beyond the state of the art.Publisher PDFPeer reviewe
Skin colour changes during experimentally-induced sickness
This project was supported by Swedish foundation for humanities and social sciences and a British Academy Wolfson Foundation Research Professorship grant. AH is supported by a studentship from the Biotechnology and Biological Sciences Research Council.Skin colour may be an important cue to detect sickness in humans but how skin colour changes with acute sickness is currently unknown. To determine possible colour changes, 22 healthy Caucasian participants were injected twice, once with lipopolysaccharide (LPS, at a dose of 2 ng/kg body weight) and once with placebo (saline), in a randomised cross-over design study. Skin colour across 3 arm and 3 face locations was recorded spectrophotometrically over a period of 8 hours in terms of lightness (L∗), redness (a∗) and yellowness (b∗) in a manner that is consistent with human colour perception. In addition, carotenoid status was assessed as we predicted that a decrease it skin yellowness would reflect a drop in skin carotenoids. We found an early change in skin colouration 1-3 hours post LPS injection with facial skin becoming lighter and less red whilst arm skin become darker but also less red and less yellow. The LPS injection also caused a drop in plasma carotenoids from 3 hours onwards. However, the timing of the carotenoid changes was not consistent with the skin colour changes suggesting that other mechanisms, such as a reduction of blood perfusion, oxygenation or composition. This is the first experimental study characterising skin colour associated with acute illness, and shows that changes occur early in the development of the sickness response. Colour changes may serve as a cue to health, prompting actions from others in terms of care-giving or disease avoidance. Specific mechanisms underlying these colour changes require further investigation.PostprintPeer reviewe
Troup Factory: Archaeological Investigations of a Nineteenth Century Mill Site in LaGrange, Georgia.
Troup Factory, the first cotton mill in Troup County, and the second such plant in Georgia, was established in 1846 on Flat Shoal\u27s Creek. The mill was in operation throughout the latter half of the 19th century before being relocated to the city of LaGrange. Troup Factory sheetings and homespun were standards of excellence across a widespread area of Georgia. The purpose of this paper is to document the history of the mill site through archival research and archaeological survey. Through these means a better understanding of a once prestigious mill site was obtained in order to illuminate an important period of Georgia history
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