Organic materials for photovoltaic devices

This thesis is a contribution towards the understanding of the operation of bilayer solar cells, and the development of a theoretical basis for the selection of suitable pairs of materials for the fabrication of such cells. The work is divided into two main areas: (a) theoretical calculations on materials used in solar cells (b) fabrication of devices to test the calculations. Practically, many devices were made using some previously untried materials, the most successful of which was formed from dibromoanthanthrone and titanyl phthalocyanine. This sample was 0.30% efficient under incident white light of intensity 20mW/cm2 and had an open circuit voltage of 0.39V. Measurements of the response time of the sample were also recorded which provided information on the quality of the device made. Theoretically, calculations were performed using the extended Huckel method on potential materials for photovoltaic devices. Initially, these provided information on the variation of bandwidth with inter-ring separation for cofacially stacked phthalocyanines. They were also used to predict the position of the HOMO/LUMO for different materials. Then by deducing the position of the Fermi level, it is possible to simulate the junction formed between the two materials. Predicted behaviour for the phthalocyanine/perylene interface agreed with that found experimentally from UPS and optical absorption measurements of the ionisation potentials, work functions and band gaps for a similar junction. The calculations have also demonstrated how substituting or changing the two layers alters the performance of the device. This allowed a set of criteria to be established that should enable a more systematic approach to choosing potential pairs and then optimising their performance in future solar cells

Organic materials for photovoltaic devices

This thesis is a contribution towards the understanding of the operation of bilayer solar cells, and the development of a theoretical basis for the selection of suitable pairs of materials for the fabrication of such cells. The work is divided into two main areas: (a) theoretical calculations on materials used in solar cells (b) fabrication of devices to test the calculations. Practically, many devices were made using some previously untried materials, the most successful of which was formed from dibromoanthanthrone and titanyl phthalocyanine. This sample was 0.30% efficient under incident white light of intensity 20mW/cm2 and had an open circuit voltage of 0.39V. Measurements of the response time of the sample were also recorded which provided information on the quality of the device made. Theoretically, calculations were performed using the extended Huckel method on potential materials for photovoltaic devices. Initially, these provided information on the variation of bandwidth with inter-ring separation for cofacially stacked phthalocyanines. They were also used to predict the position of the HOMO/LUMO for different materials. Then by deducing the position of the Fermi level, it is possible to simulate the junction formed between the two materials. Predicted behaviour for the phthalocyanine/perylene interface agreed with that found experimentally from UPS and optical absorption measurements of the ionisation potentials, work functions and band gaps for a similar junction. The calculations have also demonstrated how substituting or changing the two layers alters the performance of the device. This allowed a set of criteria to be established that should enable a more systematic approach to choosing potential pairs and then optimising their performance in future solar cells

Adapting Water Management A Primer on Coping with Climate Change

This primer is intended as a guide to some of the basic issues surrounding water management from a climate change perspective. It includes information on climate change impacts on various freshwater ecosystems as well as precipitation. Also addressed is how the assessment of vulnerability should distinguish between impacts assessment, which attempts to project future biophysical and ecological changes in a deterministic manner, and vulnerability assessment, which attempts to combine an assessment of future suites of change with an assessment of the resilience of ecosystems and management institutions

Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial

Decline in Antigenicity of Tumor Markers by Storage Time Using Pathology Sections Cut From Tissue Microarrays.

Sectioning a whole tissue microarrray (TMA block) and storing the sections maximizes the number of sections obtained, but may impair the antigenicity of the stored sections. We have investigated the impact of TMA section storage on antigenicity. First, we reexamined existing TMA data to determine whether antigenicity in stored sections changes over time. Component scores for each marker, based on cellular compartment of staining and score-type, were evaluated separately. Residual components scores adjusted for grade, tumor size, and node positivity, were regressed on the number of days storage to evaluate the effect of storage time. Storage time ranged from 2 to 1897 days, and the mean change in antigenicity per year ranged from -0.88 (95% confidence interval, -1.11 to -0.65) to 0.035 (95% confidence interval, 0.016-0.054). Further analysis showed no significant improvement in the fit of survival models if storage time adjusted scores were included in the models rather than unadjusted scores. We then compared 3 ways of processing TMA sections after cutting-immediate staining, staining after 1 year, and staining after 1 year coated in wax-on the immunohistochemistry results for: progesterone receptor, a routinely used, robust antibody, and MKI67, which is generally considered less robust. The progesterone receptor scores for stored sections were similar to those for unstored sections, whereas the MKI67 scores for stored sections were substantially different to those for unstored sections. Wax coating made little difference to the results. Biomarker antigenicity shows a small decline over time that is unlikely to have an important effect on studies of prognostic biomarkers.We acknowledge the SEARCH team, the National Cancer Registration Service Eastern Office and Information Centre, the Histopathology Core Facility at the CRUK Cambridge Research Institute for immunohistochemical staining and digital image acquisition and the Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust. This work was funded through a programme grant from Cancer Research UK (C490/A10119, C490/A10124 and C490/A16561) and funding from the NIHR Biomedical Research Centre.This is the final version of the article. It was first published by Lippincott Williams & Wilkins at http://dx.doi.org/10.1097/PAI.000000000000017

Early detection of pre-malignant lesions in a KRASG12D-driven mouse lung cancer model by monitoring circulating free DNA.

Lung cancer is the leading cause of cancer-related death. Two-thirds of cases are diagnosed at an advanced stage that is refractory to curative treatment. Therefore, strategies for the early detection of lung cancer are urgently sought. Total circulating free DNA (cfDNA) and tumour-derived circulating tumour DNA (ctDNA) are emerging as important biomarkers within a 'liquid biopsy' for monitoring human disease progression and response to therapy. Owing to the late clinical diagnosis of lung adenocarcinoma, the potential for cfDNA and ctDNA as early detection biomarkers remains unexplored. Here, using a Cre-regulated genetically engineered mouse model of lung adenocarcinoma development, driven by KrasG12D (the KrasLSL-G12D mouse), we serially tracked the release of cfDNA/ctDNA and compared this with tumour burden as determined by micro-computed tomography (CT). To monitor ctDNA, a droplet digital PCR assay was developed to permit discrimination of the KrasLox-G12D allele from the KrasLSL-G12D and KrasWT alleles. We show that micro-CT correlates with endpoint histology and is able to detect pre-malignant tumours with a combined volume larger than 7 mm3 Changes in cfDNA/ctDNA levels correlate with micro-CT measurements in longitudinal sampling and are able to monitor the emergence of lesions before the adenoma-adenocarcinoma transition. Potentially, this work has implications for the early detection of human lung adenocarcinoma using ctDNA/cfDNA profiling.A video abstract for this article is available at https://youtu.be/Ku8xJJyGs3UThis article has an associated First Person interview with the joint first authors of the paper.Medical Research Counci

Reduced protumorigenic tumor-associated macrophages with statin use in premalignant human lung adenocarcinoma

Background Statins have anticancer properties by acting as competitive inhibitors of the mevalonate pathway. They also have anti-inflammatory activity, but their role in suppressing inflammation in a cancer context has not been investigated to date. Methods We have analyzed the relationship between statin use and tumor-associated macrophages (TAMs) in a cohort of 262 surgically resected primary human lung adenocarcinomas. TAMs were evaluated by multiplex immunostaining for the CD68 pan-TAM marker and the CD163 protumorigenic TAM marker followed by digital slide scanning and partially automated quantitation. Links between statin use and tumor stage, virulence, and cancer-specific survival were also investigated in a wider cohort of 958 lung adenocarcinoma cases. All statistical tests were two-sided. Results We found a statin dose-dependent reduction in protumorigenic TAMs (CD68+CD163+) in both stromal (P = .021) and parenchymal (P = .003) compartments within regions of in situ tumor growth, but this association was lost in invasive regions. No statistically significant relationship between statin use and tumor stage was observed, but there was a statin dose-dependent shift towards lower histological grade as assessed by growth pattern (P = .028). However, statin use was a predictor of slightly worse cancer-specific survival (P = .032), even after accounting for prognostic variables in a multivariable Cox proportional hazards survival model (hazard ratio = 1.38, 95% confidence interval = 1.04 to 1.84). Conclusions Statin use is associated with reduced numbers of protumorigenic TAMs within preinvasive lung adenocarcinoma and is related to reduced tumor invasiveness, suggesting a chemo-preventive effect in early tumor development. However, invasive disease is resistant to these effects, and no beneficial relationship between statin use and patient outcome is observed

A comparison of immunohistochemical assays and FISH in detecting the ALK translocation in diagnostic histological and cytological lung tumor material.

Introduction:Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment. The current test of choice is fluorescence in situ hybridization (FISH), but various cheaper and more convenient immunohistochemical (IHC) assays have been proposed as alternatives.Methods:Fifteen FISH-positive cases from patients, seven with data on crizotinib therapy and clinical response, were evaluated for the presence of ALK protein using three different commercially available antibodies: D5F3, using the proprietary automated system (Ventana), ALK1 (Dako), and 5A4 (Abcam). A further 14 FISH-negative and three uncertain (<15% rearrangement detected) cases were also retrieved. Of the total 32 specimens, 17 were excisions and 15 were computed tomography-guided biopsies or cytological specimens. All three antibodies were applied to all cases. Antibodies were semiquantitatively scored on intensity, and the proportion of malignant cells stained was documented. Cutoffs were set by receiver operating curve analysis for positivity to optimize correct classification.Results:All three IHC assays were 100% specific but sensitivity did vary: D5F3 86%, ALK 79%, 5A4 71%. Intensity was the most discriminating measure overall, with a combination of proportion and intensity not improving the test. No FISH-negative IHC-positive cases were seen. Two FISH-positive cases were negative with all three IHC assays. One of these had been treated with crizotinib and had failed to show clinical response. The other harbored a second driving mutation in the EGFR gene.Conclusions:IHC with all three antibodies is especially highly specific (100%) although variably sensitive (71%-86%), specifically in cases with scanty material. D5F3 assay was most sensitive in these latter cases. Occasional cases are IHC-positive but FISH-negative, suggesting either inaccuracy of one assay or occasional tumors with ALK rearrangement that do not express high levels of ALK protein

SOX9 has distinct roles in the formation and progression of different non-small cell lung cancer histotypes

The transcription factor SOX9 is a key regulator of multiple developmental processes and is frequently re-expressed in non-small cell lung cancer (NSCLC). Its precise role in the progression of NSCLC histotypes has, however, remained elusive. We show that SOX9 expression relates to poor overall survival and invasive histopathology in human non-mucinous adenocarcinoma and is absent in murine early minimally invasive and low in human in situ adenocarcinoma. Interestingly, despite wide SOX9 expression across advanced NSCLC histotypes, its genetic deletion in the murine Kras(G12D);Lkb1(fl/fl) model selectively disrupted only the growth of papillary NSCLC, without affecting the initiation of precursor lesions or growth of mucinous or squamous tissue. Spatial tissue phenotyping indicated a requirement of SOX9 expression for the progression of surfactant protein C-expressing progenitor cells, which gave rise to papillary tumours. Intriguingly, while SOX9 expression was dispensable for squamous tissue formation, its loss in fact led to enhanced squamous tumour metastasis, which was associated with altered collagen IV deposition in the basement membrane. Our work therefore demonstrates histopathology-selective roles for SOX9 in NSCLC progression, namely as a promoter for papillary adenocarcinoma progression, but an opposing metastasis-suppressing role in squamous histotype tissue. This attests to a pleiotropic SOX9 function, linked to the cell of origin and microenvironmental tissue contexts. (c) 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.Peer reviewe

Assessing the risk of climate change to aquaculture: a national-scale case study for the Sultanate of Oman

Aquaculture is expanding globally and is an increasingly important component of world food security. However, climate change can impact aquaculture through a variety of mechanisms varying by location and aquaculture type with implications for future productivity. Understanding the risks that climate change poses on different culture systems in different locations is important to enable the design of targeted adaptation and resilience building actions. Here we present an aquaculture climate risk assessment framework, applied to the aquaculture sector of the Sultanate of Oman, that identifies the sensitivity and exposure of different components of the sector to climate change risk. Oman has aspirations to significantly expand aquaculture over the next decade focussing on coastal shrimp ponds, finfish sea cages, land-based recirculating aquaculture systems, and ponds and raceways. We quantify overall climate risk as the combination of four risks: (1) species’ temperature sensitivity, (2) flooding and storm surge exposure, (3) low-oxygen hazard and (4) disease vulnerability. Shrimp culture is identified as highest risk due to high exposure of shrimp ponds to flooding and storm surges, and high disease vulnerability. Seabream cage farming also faces high risk due to high thermal sensitivity and high potential of low-oxygen levels affecting sea cages. Following the risk assessment a stakeholder workshop was conducted to identify targeted adaptation measures for the different components of the sector. The framework for assessing climate risk to aquaculture demonstrated here is equally applicable at the regional, national or sub-national scale to support design of targeted resilience building actions and enhance food security