In Girum (version/round 1.3, 2008) – Dir. Nick Cope: Video/DVD in collaboration with Composer Tim Howle, 6’05”. Awards: Abstracta International Abstract Cinema Exhibition, Rome, August 2009 – Honourable Mention of the Jury.

Short film/video exploring the encounter of electroacoustic music composition and moving image practice

A new model for the segmentation, propagation and linkage of the Tan-Lu fault zone, East Asia

The Tan-Lu fault zone (TLF) is a major strike-slip fault with a long and complex history in East Asia, whose evolution provides a new perspective on the formation of large-scale faults (\u3e1000 km long). Fault displacement analysis, geological mapping and U-Pb LA-ICP-MS dating have been performed to understand the evolution of the TLF. Along-strike displacement variation reveals that the TLF consists of two kinematically independent segments, the northern and southern TLF, with opposite long-term propagation directions. Structural and geochronological studies in the eastern Yanshan belt, located around the linkage area of the southern and northern TLF, indicate that NNE-trending sinistral strike-slip faults initiated at 167–164 Ma and were reactivated at 124–121 Ma. Structural analysis suggests that these early NNE-trending strike-slip faults transferred sinistral motion along the northern TLF into southward thrusting along the Yanshan belt, representing the Middle Jurassic southern termination of the northern TLF. Our studies suggest that the through-going TLF formed when the younger southward-propagating northern TLF merged with the older northward-propagating southern TLF in the Late Jurassic. A new model is thus proposed for the Mesozoic evolution of the TLF. The initiation and southward propagation of the northern TLF is interpreted to have resulted from the southward indentation of the Siberian craton into the amalgamated Central Asian Orogenic Belt and North China block. The divergent mega-splays of the northern TLF likely resulted from westward-younging formation during the clockwise rotation of northeast Asia. Coalescence of two genetically unrelated faults could be an alternative mode for large-scale fault formation

Is there a role of synovial biopsy in drug development?

Rheumatoid arthritis (RA) is an autoimmune disease which causes significant pain, joint deformity, functional disability. The pathological hallmark of RA is inflammation of the synovium characterized by involvement of inflammatory and resident stromal cells, soluble mediators and signalling pathways leading to irreversible joint destruction. The treatment goal in RA has evolved over the last decade towards a target of disease remission that is achieved in less than a third of patients in clinical trials. The lack of therapeutic response to current treatments is suggestive of alternative drivers of RA pathogenesis that might serve as promising therapeutic targets. There are data to justify the use of synovial tissue in early drug development. Synovial tissue represents an appropriate compartment to be studied in patients with inflammatory arthritis and provides information that is distinct from peripheral blood. Modern techniques have made the procedure much more accessible and ultrasound guided biopsies represent a safe and acceptable option. Advances in analytic technologies allowing transcriptomic level of analysis can provide unique inside to target organ/tissue following the exposure to investigational medicinal product. However, there are still caveats with regard to both the choice of technique and analytical methods. Therefore the significance of synovial biopsy remains to be determined in future clinical trials. The aim of the current debate is to explore the potential for accessing and evaluating synovial tissue in early drug development, to summarize lessons we have learned from clinical trials and to discuss the challenges that have arisen so far

Transport to thrive: Why we shouldn’t ignore the transport needs of young people

In the UK many disadvantaged groups lack transport choices, including young people aged 16-24. There has been little research to identify and understand the transport issues and barriers experienced by young people. This report is the first of its kind to focus on the 16-24 age group who are leaving behind youth and moving into adulthood. It presents new analyses of national travel data, combined with insights from in-depth interviews with young people leaving school and college.Young people aged 16-24 year made 21% fewer trips compared to working age adults of 25-64 years in 2019 and this gap has widened over the past 20 years. This is limiting their access to education, employment and social opportunities. Only 40% of young people have a full driving licence in comparison to 74% of adults aged 16 or over. Young people are more likely to travel using a range of transport options including public transport, walking, cycling and new shared mobility option such as e-scooters. They contribute less to carbon emissions, as well as being likely to see the most adverse effects of future climate change.It is essential that we better meet the transport needs of young people and other disadvantaged groups. At the heart of this is improving active travel and public transport in parallel to support multi-modal, low car lifestyles. Improving transport for 16–24-year-olds will support social and economic outcomes for the next generation of leaders and for society as a whole

Importing ArrayExpress datasets into R/Bioconductor

Summary:ArrayExpress is one of the largest public repositories of microarray datasets. R/Bioconductor provides a comprehensive suite of microarray analysis and integrative bioinformatics software. However, easy ways for importing datasets from ArrayExpress into R/Bioconductor have been lacking. Here, we present such a tool that is suitable for both interactive and automated use

Exile Vol. XIV No. 1

POETRY For George Wallace by Tom Cook 5 For Candy by Tom Cook 6-7 G. M. by Nancy Scott 13 Spinning Song by Karen Cozart 14 Traps by Bob Martin 21 Potato Cellar by Bob Martin 21 untitled by Jeffrey Smith 23 Summer Correspondence I by Lauren Shakely 39 Untitled by Hank Vyner 40 When He Returns, Tell Him by Barb Ingle 40 untitled by Tim Cope 41 FICTION The Elephants by Cem Kozlu 9-12 A Hill by Dick Devine 15-20 Man Minus 1 by Tom Cook 26-38 A Playmate by Jim Ruddock 43-44 ART Pen and Ink by Charles Greacen 4 Illustration For The Elephants by Kee MacFarlane 8 Pen and Ink by Bob Willis 20 Illustration For Career Girl 22 Illustration for A Playmate by Bob Tauber 42 Cover art by Kee MacFarlan

Exile Vol. XVI No. 1

DRAMA God\u27s Pocket by Robert R. Bowie, Jr. 5-12 FICTION The Wagon by John Anderson 18-19 An Infinity of Mirrors by Keith McWalter 23-25 Commitment by John Whitt 28-29 It began not long ago... by Linda Notzelman 32-33 Jaundiced Evening by John Benes 35-39 POETRY Paralysis Outline by Lauren Shakely 13 A Woman Reads Camus by Lauren Shakely 14 don\u27t sell my rings by Lauren Shakely 14 Drift by John Whitt 17 Haiku by M. S. Wallace 19 To Begin W. K. Mayo 19 Dark is Right by Louise Tate 20 I am waiting by Louise Tate 21 My mother died as I shall die by Tim Cope 20 I never blamed you by Tim Cope 26 For Miss Didawick by Tim Cope 34 Separidian by Bill Whitmore 27 He walks on into by Whitney Carman 31 As Drowned Men Rise by Paul Bennett 34 The Tolling of the Bell by Keith McWalter 39 ARTWORK by Wandi Solez 4, 13, 16, 22, 36 by W. A. Hoffman 21, 30 by Stephen Sneeringer 27 by Christine Michael 19 Cover & Title Page Design: Keith McWalter Layouts: Keith McWalter Publicity- Special thanks to Gail Moore and Karen Baker Photographs courtesy the Sierra Club- From NOT MAN APART, Copyright 196

Cloud Cover in the Australian Region: Development and Validation of a Cloud Masking, Classification and Optical Depth Retrieval Algorithm for the Advanced Himawari Imager

This paper presents a cloud masking, cloud classification and optical depth retrieval algorithm and its application to the Advanced Himawari Imager (AHI) on the Himawari-8/9 satellites using visible, near infrared and thermal infrared bands. A time-series-based approach was developed for cloud masking which was visually assessed and quantitatively validated over 1 year of daytime data for both land and ocean against the level 2 Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) 1 km cloud layer product (version 4.10). An overall hit rate (the proportion of pixels identified by both sensors as either clear or cloudy) of 87% was found. However, analysis revealed that, when partially cloudy conditions were experienced, the small footprint of the CALIOP sensor (70 meters beam size sampling every 330 meters along the ground track) had a major impact on the hit rate. When partially cloudy pixels are excluded a hit rate of ~98% was found, even for thin clouds with optical depth less than 0.25. A two-way confidence index for the cloud mask was developed which could be used to reclassify the pixels depending on applications, either biasing toward clearness or cloudiness. On the basis of the cloud masking, classification and optical depth retrieval was performed based on radiative transfer modeling. Small modeling error was found, and inspection of typical cloud classification examples showed that the results were consistent with cloud texture and cloud top temperatures. While difficult to validate retrieved cloud properties directly, an indirect quantitative validation was performed by comparing surface-level solar flux computed from the retrieved cloud properties with in-situ measurements at 11 sites across Australia for up to 3 years. Excellent agreement between calculated and measured solar flux was found, with a mean monthly bias of 2.96 W/m2 and RMSE of 8.91 W/m2, and the correlation coefficient exceeding 0.98 at all sites. Further assessment was conducted by comparing seasonal and annual cloud fraction with that of ISCCP (International Satellite Cloud Climatology Project) over Australia and surrounding region. It showed high degree of resemblance between the two datasets in their total cloud fraction. The geographical distribution of cloud classes also showed broad resemblance, though detailed differences exist, especially for high clouds, which is probably due to the use of different cloud classification systems in the two datasets. The products generated from this study are being used in several applications including ocean color remote sensing, solar energy, vegetation monitoring and detection of smoke for the study of their health impacts, and aerosol and land surface bidirectional reflectance distribution function (BRDF) retrieval. The method developed herein can be applied to other geostationary sensors

Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum.

The clinical syndromes of frontotemporal dementia are clinically and neuropathologically heterogeneous, but processes such as neuroinflammation may be common across the disease spectrum. We investigated how neuroinflammation relates to the localization of tau and TDP-43 pathology, and to the heterogeneity of clinical disease. We used PET in vivo with (i) 11C-PK-11195, a marker of activated microglia and a proxy index of neuroinflammation; and (ii) 18F-AV-1451, a radioligand with increased binding to pathologically affected regions in tauopathies and TDP-43-related disease, and which is used as a surrogate marker of non-amyloid-β protein aggregation. We assessed 31 patients with frontotemporal dementia (10 with behavioural variant, 11 with the semantic variant and 10 with the non-fluent variant), 28 of whom underwent both 18F-AV-1451 and 11C-PK-11195 PET, and matched control subjects (14 for 18F-AV-1451 and 15 for 11C-PK-11195). We used a univariate region of interest analysis, a paired correlation analysis of the regional relationship between binding distributions of the two ligands, a principal component analysis of the spatial distributions of binding, and a multivariate analysis of the distribution of binding that explicitly controls for individual differences in ligand affinity for TDP-43 and different tau isoforms. We found significant group-wise differences in 11C-PK-11195 binding between each patient group and controls in frontotemporal regions, in both a regions-of-interest analysis and in the comparison of principal spatial components of binding. 18F-AV-1451 binding was increased in semantic variant primary progressive aphasia compared to controls in the temporal regions, and both semantic variant primary progressive aphasia and behavioural variant frontotemporal dementia differed from controls in the expression of principal spatial components of binding, across temporal and frontotemporal cortex, respectively. There was a strong positive correlation between 11C-PK-11195 and 18F-AV-1451 uptake in all disease groups, across widespread cortical regions. We confirmed this association with post-mortem quantification in 12 brains, demonstrating strong associations between the regional densities of microglia and neuropathology in FTLD-TDP (A), FTLD-TDP (C), and FTLD-Pick's. This was driven by amoeboid (activated) microglia, with no change in the density of ramified (sessile) microglia. The multivariate distribution of 11C-PK-11195 binding related better to clinical heterogeneity than did 18F-AV-1451: distinct spatial modes of neuroinflammation were associated with different frontotemporal dementia syndromes and supported accurate classification of participants. These in vivo findings indicate a close association between neuroinflammation and protein aggregation in frontotemporal dementia. The inflammatory component may be important in shaping the clinical and neuropathological patterns of the diverse clinical syndromes of frontotemporal dementia

18F-AV-1451 positron emission tomography in Alzheimer's disease and progressive supranuclear palsy.

The ability to assess the distribution and extent of tau pathology in Alzheimer's disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer 18F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer's pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls. Regional analysis of variance and a support vector machine were used to compare and discriminate the clinical groups, respectively. We also examined the 18F-AV-1451 autoradiographic binding in post-mortem tissue from patients with Alzheimer's disease, progressive supranuclear palsy, and a control case to assess the 18F-AV-1451 binding specificity to Alzheimer's and non-Alzheimer's tau pathology. There was increased 18F-AV-1451 binding in multiple regions in living patients with Alzheimer's disease and progressive supranuclear palsy relative to controls [main effect of group, F(2,41) = 17.5, P 2.2, P's 2.7, P's < 0.02). The support vector machine assigned patients' diagnoses with 94% accuracy. The post-mortem autoradiographic data showed that 18F-AV-1451 strongly bound to Alzheimer-related tau pathology, but less specifically in progressive supranuclear palsy. 18F-AV-1451 binding to the basal ganglia was strong in all groups in vivo. Postmortem histochemical staining showed absence of neuromelanin-containing cells in the basal ganglia, indicating that off-target binding to neuromelanin is an insufficient explanation of 18F-AV-1451 positron emission tomography data in vivo, at least in the basal ganglia. Overall, we confirm the potential of 18F-AV-1451 as a heuristic biomarker, but caution is indicated in the neuropathological interpretation of its binding. Off-target binding may contribute to disease profiles of 18F-AV-1451 positron emission tomography, especially in primary tauopathies such as progressive supranuclear palsy. We suggest that 18F-AV-1451 positron emission tomography is a useful biomarker to assess tau pathology in Alzheimer's disease and to distinguish it from other tauopathies with distinct clinical and pathological characteristics such as progressive supranuclear palsy.This study was funded by the National Institute for Health Research (NIHR, RG64473) Cambridge Biomedical Research Centre and Biomedical Research Unit in Dementia, PSP Association, the Wellcome Trust (JBR 103838), the Medical Research Council of Cognition and Brain Sciences Unit, Cambridge (MC-A060-5PQ30), and partially by a Medical Research Council grant (MR/K02308X/1) held by J.T.O., J.B.R., and F.I.A. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre