Colour and texture image analysis in a Local Binary Pattern framework

In this Thesis we use colour and Local Binary Pattern based texture analysis for image classification and reconstruction. In complementary work we offer a new texture description called the Sudoku transform, an extension of the Local Binary Pattern. Our new method when used to classify members of benchmark datasets shows a performance increment over traditional methods including the Local Binary Pattern. Finally we consider the invertibility of texture descriptions and show how with our new method - Quadratic Reconstruction - that a highly accurate image can be recovered purely from its textural information

The ERBB network facilitates KRAS-driven lung tumorigenesis

KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRASG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies

T Cell Responses to Human Endogenous Retroviruses in HIV-1 Infection

Human endogenous retroviruses (HERVs) are remnants of ancient infectious agents that have integrated into the human genome. Under normal circumstances, HERVs are functionally defective or controlled by host factors. In HIV-1-infected individuals, intracellular defense mechanisms are compromised. We hypothesized that HIV-1 infection would remove or alter controls on HERV activity. Expression of HERV could potentially stimulate a T cell response to HERV antigens, and in regions of HIV-1/HERV similarity, these T cells could be cross-reactive. We determined that the levels of HERV production in HIV-1-positive individuals exceed those of HIV-1-negative controls. To investigate the impact of HERV activity on specific immunity, we examined T cell responses to HERV peptides in 29 HIV-1-positive and 13 HIV-1-negative study participants. We report T cell responses to peptides derived from regions of HERV detected by ELISPOT analysis in the HIV-1-positive study participants. We show an inverse correlation between anti-HERV T cell responses and HIV-1 plasma viral load. In HIV-1-positive individuals, we demonstrate that HERV-specific T cells are capable of killing cells presenting their cognate peptide. These data indicate that HIV-1 infection leads to HERV expression and stimulation of a HERV-specific CD8+ T cell response. HERV-specific CD8+ T cells have characteristics consistent with an important role in the response to HIV-1 infection: a phenotype similar to that of T cells responding to an effectively controlled virus (cytomegalovirus), an inverse correlation with HIV-1 plasma viral load, and the ability to lyse cells presenting their target peptide. These characteristics suggest that elicitation of anti-HERV-specific immune responses is a novel approach to immunotherapeutic vaccination. As endogenous retroviral sequences are fixed in the human genome, they provide a stable target, and HERV-specific T cells could recognize a cell infected by any HIV-1 viral variant. HERV-specific immunity is an important new avenue for investigation in HIV-1 pathogenesis and vaccine design

Detection of Carbon Monoxide in the Atmosphere of WASP-39b Applying Standard Cross-Correlation Techniques to JWST NIRSpec G395H Data

Carbon monoxide was recently reported in the atmosphere of the hot Jupiter WASP-39b using the NIRSpec PRISM transit observation of this planet, collected as part of the JWST Transiting Exoplanet Community Early Release Science (JTEC ERS) Program. This detection, however, could not be confidently confirmed in the initial analysis of the higher resolution observations with NIRSpec G395H disperser. Here we confirm the detection of CO in the atmosphere of WASP-39b using the NIRSpec G395H data and cross-correlation techniques. We do this by searching for the CO signal in the unbinned transmission spectrum of the planet between 4.6 and 5.0 $\mu$m, where the contribution of CO is expected to be higher than that of other anticipated molecules in the planet's atmosphere. Our search results in a detection of CO with a cross-correlation function (CCF) significance of $6.6 \sigma$ when using a template with only ${\rm ^{12}C^{16}O}$ lines. The CCF significance of the CO signal increases to $7.5 \sigma$ when including in the template lines from additional CO isotopologues, with the largest contribution being from ${\rm ^{13}C^{16}O}$. Our results highlight how cross-correlation techniques can be a powerful tool for unveiling the chemical composition of exoplanetary atmospheres from medium-resolution transmission spectra, including the detection of isotopologues.Comment: Accepted for publication in The Astrophysical Journal Letter

Repression of the type I interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in pancreatic ductal adenocarcinoma

MYC is implicated in the development and progression of Pancreatic cancer, yet the precise level of MYC deregulation required to contribute to tumour development has been difficult to define. We used modestly elevated expression of human MYC, driven from the Rosa26 locus, to investigate the pancreatic phenotypes arising in mice from an approximation of MYC trisomy. We show that this level of MYC alone suffices to drive pancreatic neuroendocrine tumours, and to accelerate progression of KRAS-initiated precursor lesions to metastatic pancreatic ductal adenocarcinoma. Our phenotype exposed suppression of the Type I Interferon pathway by the combined actions of MYC and KRAS and we present evidence of repressive MYC/MIZ1 complexes binding directly to the promoters of type I Interferon regulators IRF5, IRF7, STAT1 and STAT2. De-repression of Interferon regulators allows pancreatic tumour infiltration of B and NK cells, resulting in increased survival

Can the performance effect be ignored in the attendance policy discussion?

Should universities require students to attend? Academics disagree. One side in the discussion of university attendance policies has tried to dismiss any association between attendance and student performance, insisting that students have a fundamental right to choose what and when to attend. By merging student record data and course attendance data for three cohorts of final-year undergraduate students at a London-based university, we are able to isolate attendance effects for 674 students, giving us a large sample, without the inherent weaknesses of more traditional survey methods. We provide fresh empirical evidence for the positive association between attendance and exam performance, and argue for a more balanced view in the attendance policy discussion. Politicians and higher education policies are increasingly focused on employability, student retention, and completion indicators. Carefully crafted attendance policies can have positive effects on pass and completion rates, primary policy targets of higher education funders and policymakers. Attendance effects therefore cannot be ignored

A broadband thermal emission spectrum of the ultra-hot Jupiter WASP-18b

Close-in giant exoplanets with temperatures greater than 2,000 K (''ultra-hot Jupiters'') have been the subject of extensive efforts to determine their atmospheric properties using thermal emission measurements from the Hubble and Spitzer Space Telescopes. However, previous studies have yielded inconsistent results because the small sizes of the spectral features and the limited information content of the data resulted in high sensitivity to the varying assumptions made in the treatment of instrument systematics and the atmospheric retrieval analysis. Here we present a dayside thermal emission spectrum of the ultra-hot Jupiter WASP-18b obtained with the NIRISS instrument on JWST. The data span 0.85 to 2.85 $\mu$m in wavelength at an average resolving power of 400 and exhibit minimal systematics. The spectrum shows three water emission features (at $>$6$\sigma$ confidence) and evidence for optical opacity, possibly due to H$^-$, TiO, and VO (combined significance of 3.8$\sigma$). Models that fit the data require a thermal inversion, molecular dissociation as predicted by chemical equilibrium, a solar heavy element abundance (''metallicity'', M/H = 1.03$_{-0.51}^{+1.11}$ $\times$ solar), and a carbon-to-oxygen (C/O) ratio less than unity. The data also yield a dayside brightness temperature map, which shows a peak in temperature near the sub-stellar point that decreases steeply and symmetrically with longitude toward the terminators.Comment: JWST ERS bright star observations. Uploaded to inform JWST Cycle 2 proposals. Manuscript under review. 50 pages, 14 figures, 2 table

Early Release Science of the exoplanet WASP-39b with JWST NIRISS

Transmission spectroscopy provides insight into the atmospheric properties and consequently the formation history, physics, and chemistry of transiting exoplanets. However, obtaining precise inferences of atmospheric properties from transmission spectra requires simultaneously measuring the strength and shape of multiple spectral absorption features from a wide range of chemical species. This has been challenging given the precision and wavelength coverage of previous observatories. Here, we present the transmission spectrum of the Saturn-mass exoplanet WASP-39b obtained using the SOSS mode of the NIRISS instrument on the JWST. This spectrum spans $0.6 - 2.8 \mu$m in wavelength and reveals multiple water absorption bands, the potassium resonance doublet, as well as signatures of clouds. The precision and broad wavelength coverage of NIRISS-SOSS allows us to break model degeneracies between cloud properties and the atmospheric composition of WASP-39b, favoring a heavy element enhancement ("metallicity") of $\sim 10 - 30 \times$ the solar value, a sub-solar carbon-to-oxygen (C/O) ratio, and a solar-to-super-solar potassium-to-oxygen (K/O) ratio. The observations are best explained by wavelength-dependent, non-gray clouds with inhomogeneous coverage of the planet's terminator.Comment: 48 pages, 12 figures, 2 tables. Under review at Natur

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability