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

Frequency Domain Functional Near-Infrared Spectrometer (fNIRS) for Crew State Monitoring

A frequency domain functional near-infrared spectrometer (fNIRS) and accompanying software have been developed by the NASA Glenn Research Center as part of the Airspace Operations and Safety Program (AOSP) Technologies for Airplane State Awareness (TASA)SE211 Crew State Monitoring (CSM) Project. The goal of CSM was to develop a suite of instruments to measure the cognitive state of operators while performing operational activities. The fNIRS was one of the instruments intended for the CSM, developed to measure changes in oxygen levels in the brain noninvasively

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

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

Multimodal discrimination of immune cells using a combination of Raman spectroscopy and digital holographic microscopy

This work was supported by the UK Engineering and Physical Sciences Research Council under grant EP/J01771X/1, A European Union FAMOS project (FP7 ICT, 317744), and the ’BRAINS’ 600th anniversary appeal, and Dr. E. Killick. We would also like to thank The RS Macdonald Charitable Trust for funding support. KD acknowledges support of a Royal Society Leverhulme Trust Senior Fellowship. This work was also supported by the PreDiCT-TB consortium [IMI Joint undertaking grant agreement number 115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution (www.imi.europa.eu)]The ability to identify and characterise individual cells of the immune system under label-free conditions would be a significant advantage in biomedical and clinical studies where untouched and unmodified cells are required. We present a multi-modal system capable of simultaneously acquiring both single point Raman spectra and digital holographic images of single cells. We use this combined approach to identify and discriminate between immune cell populations CD4+ T cells, B cells and monocytes. We investigate several approaches to interpret the phase images including signal intensity histograms and texture analysis. Both modalities are independently able to discriminate between cell subsets and dual-modality may therefore be used a means for validation. We demonstrate here sensitivities achieved in the range of 86.8% to 100%, and specificities in the range of 85.4% to 100%. Additionally each modality provides information not available from the other providing both a molecular and a morphological signature of each cell.Publisher PDFPeer reviewe