The Anglo-American Reception of Carl Schmitt from the 1930s to the Early 2000s

This thesis examines the Anglo-American reception, from the 1930s to the early 2000s, of the ideas of the German political theorist Carl Schmitt. The introduction provides an overview the key concepts in Schmitt’s writings in the 1920s. Chapter one examines Schmitt’s influence on the German-Jewish émigré political theorists Leo Strauss and Hans Morgenthau, in an attempt to explain how Schmitt’s ideas were initially transported from Germany to the U.S. The second chapter is a more detailed case study of the American leftist journal, Telos, which played a key role in introducing Schmitt’s writings to a broader, English language audience in the late 1980s and 1990s. Chapter three examines the reception of Schmitt among left and left-liberal Anglo-American political theorists more generally. Both chapter two and three address the larger question of which elements of the Anglo-American left were drawn to Schmitt and why the ideas of this conservative German thinker – and former Nazi – still seemed relevant to them

The role of chromosomal instability and parallel evolution in cancer

Although chromosomal instability (CIN) is recognised as an initiating process in cancer, the extent and relevance of ongoing somatic copy number alterations (SCNAs) that result from it later in tumour development is unclear. In this thesis I describe a comprehensive analysis, including 1421 tumour samples (394 patients; 22 tumour types), to evaluate ongoing CIN and SCNAs in tumour evolution and show that intratumor heterogeneity mediated through chromosomal instability is associated with an increased risk of recurrence or death in non-small cell lung cancer (NSCLC), a finding that supports the potential value of CIN as a prognostic predictor. I also uncover pervasive SCNA intratumour heterogeneity across cancers, with recurrent clonal and subclonal events identified and found to demonstrate enrichment for cancer genes. I develop novel techniques for obtaining a phasing of heterozygous SNPs from multi-region next generation sequencing data and apply them to observe recurrent parallel evolutionary events converging upon disruption to the same genes in distinct subclones within 146 individual tumours. The most prevalent recurrent parallel loss event involved chromosome 14, including HIF1A and HIF1B. In addition, chromosome 5p, including TERT, was recurrently gained and subject to parallel evolution in 7 tumour types. Tumour type-specific constraints to early tumour development were identified in the form of obligatory clonal LOH, including LOH of 3p in clear cell renal cell carcinoma, lung squamous cell carcinoma (LUSC) and triple-negative breast cancer and LOH of 17p in LUSC, colorectal adenocarcinoma, triple negative and HER2+ breast cancer. Wholegenome doubling (WGD) was generally an early event in tumour evolution, associated with an increased acquisition of both clonal and subclonal SCNAs. For instance, CCNE1 amplifications, which occurred exclusively in WGD tumours, were subclonal in 45% of these cases, suggesting this event may be selected following a WGD event. Mathematical modelling of subclonal SCNA evolution demonstrated that models that incorporate ongoing selection with respect to SCNAs significantly outperform evolutionary neutral models, particularly in the context of WGD. This thesis highlights the importance of ongoing CIN and recurrent subclonal chromosomal alterations in tumour evolution, reveals parallel evolution of SCNAs, and sheds light on the dynamics and order of events that influence metastasis

Students' Views of Macroscopic and Microscopic Energy in Physics and Biology

Energy concepts are fundamental across the sciences, yet these concepts can be fragmented along disciplinary boundaries, rather than integrated into a coherent whole. To teach physics effectively to biology students, we need to understand students' disciplinary perspectives. We present interview data from an undergraduate student who displays multiple stances towards the concept of energy. At times he views energy in macroscopic contexts as a separate entity from energy in microscopic (particularly biological) contexts, while at other times he uses macroscopic physics phenomena as productive analogies for understanding energy in the microscopic biological context, and he reasons about energy transformations between the microscopic and macroscopic scales. This case study displays preliminary evidence for the context dependence of students' ability to translate energy concepts across scientific disciplines. This points to challenges that must be taken into account in developing curricula for biology students that integrate physics and biology concepts.Comment: 4 pages, submitted to PERC 201

The association between neurodegeneration and local complement activation in the thalamus to progressive multiple sclerosis outcome

The extent of grey matter demyelination and neurodegeneration in the progressive multiple sclerosis (PMS) brains at post‐mortem associates with more severe disease. Regional tissue atrophy, especially affecting the cortical and deep grey matter, including the thalamus, is prognostic for poor outcomes. Microglial and complement activation are important in the pathogenesis and contribute to damaging processes that underlie tissue atrophy in PMS. We investigated the extent of pathology and innate immune activation in the thalamus in comparison to cortical grey and white matter in blocks from 21 cases of PMS and 10 matched controls. Using a digital pathology workflow, we show that the thalamus is invariably affected by demyelination and had a far higher proportion of active inflammatory lesions than forebrain cortical tissue blocks from the same cases. Lesions were larger and more frequent in the medial nuclei near the ventricular margin, whilst neuronal loss was greatest in the lateral thalamic nuclei. The extent of thalamic neuron loss was not associated with thalamic demyelination but correlated with the burden of white matter pathology in other forebrain areas (Spearman r = 0.79, p < 0.0001). Only thalamic neuronal loss, and not that seen in other forebrain cortical areas, correlated with disease duration (Spearman r = −0.58, p = 0.009) and age of death (Spearman r = −0.47, p = 0.045). Immunoreactivity for the complement pattern recognition molecule C1q, and products of complement activation (C4d, Bb and C3b) were elevated in thalamic lesions with an active inflammatory pathology. Complement regulatory protein, C1 inhibitor, was unchanged in expression. We conclude that active inflammatory demyelination, neuronal loss and local complement synthesis and activation in the thalamus, are important to the pathological and clinical disease outcomes of PMS

Suitability of the height above nearest drainage (HAND) model for flood inundation mapping in data-scarce regions: a comparative analysis with hydrodynamic models

Unprecedented floods from extreme rainfall events worldwide emphasize the need for flood inundation mapping for floodplain management and risk reduction. Access to flood inundation maps and risk evaluation tools remains challenging in most parts of the world, particularly in rural regions, leading to decreased flood resilience. The use of hydraulic and hydrodynamic models in rural areas has been hindered by excessive data and computational requirements. In this study, we mapped the flood inundation in Huron Creek watershed, Michigan, USA for an extreme rainfall event (1000-year return period) that occurred in 2018 (Father’s Day Flood) using the Height Above Nearest Drainage (HAND) model and a synthetic rating curve developed from LIDAR DEM. We compared the flood inundation extent and depth modeled by the HAND with flood inundation characteristics predicted by two hydrodynamic models, viz., HEC-RAS 2D and SMS-SRH 2D. The flood discharge of the event was simulated using the HEC-HMS hydrologic model. Results suggest that, in different channel segments, the HAND model produces different degrees of concurrence in both flood inundation extent and depth when compared to the hydrodynamic models. The differences in flood inundation characteristics produced by the HAND model are primarily due to the uncertainties associated with optimal parameter estimation of the synthetic rating curve. Analyzing the differences between the HAND and hydrodynamic models also highlights the significance of terrain characteristics in model predictions. Based on the comparable predictive capability of the HAND model to map flood inundation areas during extreme rainfall events, we demonstrate the suitability of the HAND-based approach for mitigating flood risk in data-scarce, rural regions

Influence of ions on two-dimensional and three-dimensional atomic force microscopy at fluorite-water interfaces

Recent advancement in liquid-environment atomic force microscopy (AFM) has enabled us to visualize three-dimensional (3D) hydration structures as well as two-dimensional (2D) surface structures with subnanometer-scale resolution at solid-water interfaces. However, the influence of ions present in solution on the 2D- and 3D-AFM measurements has not been well understood. In this study, we perform atomic-scale 2D- and 3D-AFM measurements at fluorite-water interfaces in pure water and a supersaturated solution of fluorite. The images obtained in these two environments are compared to understand the influence of the ions in solution on these measurements. In the 2D images, we found clear difference in the nanoscale structures but no significant difference in the atomic-scale contrasts. However, the 3D force images show clear difference in the subnanometer-scale contrasts. The force contrasts measured in pure water largely agree with those expected from the molecular dynamics simulation and the solvent tip approximation model. In the supersaturated solution, an additional force peak is observed over the negatively charged fluorine ion site. This location suggests that the observed force peak may originate from cations adsorbed on the fluorite surface. These results demonstrate that the ions can significantly alter the subnanometer-scale force contrasts in the 3D-AFM images. © 2017 IOP Publishing Ltd.Embargo Period 12 month

The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury

Background & Aims: In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration; however, the mechanism of activation in chronic liver injury is poorly understood. This study aimed to characterise Hh pathway activation upon thioacetamide (TAA)- induced chronic liver injury in vivo by defining Hh-responsive cells, namely cells harbouring Pc and Pc-localised SMO. Methods: C57BL/6 mice (wild-type or Ptc1+/_) were TAA-treated. Liver injury and Hh ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI manipulation and SMO dependent/ independent activation of GLI-mediated transcriptional response in Pc-positive (Pc+) cells were studied in vitro. Results: In vivo, Hh activation was progressively induced following TAA. At the epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands. Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2+. Pc+ cells increased following TAA, but only EpCAM+/GLI2+ progenitors were Pc+/SMO+. In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in Pc+ progenitors, whilst increased proliferation occurred with hGli1 overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO. Ptc1+/_ mice exhibited increased progenitor, myofibroblast and fibrosis responses. Conclusions: In chronic liver injury, Pc+ progenitors receive Hh ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc_/GLI2+ cells. Increased fibrosis in Hh gain-of-function mice likely occurs by primary progenitor expansion/proliferation and secondary fibrotic myofibroblast expansion, in close contact with progenitors

Revisiting Soil C and N Sampling: Quantitative Pits vs. Rotary Cores

Increasing atmospheric carbon dioxide and its feedbacks with global climate have sparked renewed interest in quantifying ecosystem carbon (C) budgets, including quantifying belowground pools. Belowground nutrient budgets require accurate estimates of soil mass, coarse fragment content, and nutrient concentrations. It has long been thought that the most accurate measurement of soil mass and coarse fragment content has come from excavating quantitative soil pits. However, this methodology is labor intensive and time consuming. We propose that diamond-tipped rotary cores are an acceptable if not superior alternative to quantitative soil pits for the measurement of soil mass, coarse fragment content, C and total nitrogen (N) concentrations. We tested the rotary core methodology against traditional quantitative pits at research sites in California, Nevada, and New York. We found that soil cores had 16% higher estimates of less than 2-mm soil mass than estimates obtained from quantitative pits. Conversely, soil cores had 8% lower estimates of coarse fragment mass compared with quantitative pits. There were no statistical differences in measured C or N concentrations between the two methods. At the individual site level, differences in estimates for the two methods were more pronounced, but there was no consistent tendency for cores to overestimate or underestimate a soil parameter when compared with quantitative pits

'Reaching the hard to reach' - lessons learned from the VCS (voluntary and community Sector). A qualitative study.

Background The notion 'hard to reach' is a contested and ambiguous term that is commonly used within the spheres of social care and health, especially in discourse around health and social inequalities. There is a need to address health inequalities and to engage in services the marginalized and socially excluded sectors of society. Methods This paper describes a pilot study involving interviews with representatives from eight Voluntary and Community Sector (VCS) organisations . The purpose of the study was to explore the notion of 'hard to reach' and perceptions of the barriers and facilitators to accessing services for 'hard to reach' groups from a voluntary and community sector perspective. Results The 'hard to reach' may include drug users, people living with HIV, people from sexual minority communities, asylum seekers, refugees, people from black and ethnic minority communities, and homeless people although defining the notion of the 'hard to reach' is not straight forward. It may be that certain groups resist engaging in treatment services and are deemed hard to reach by a particular service or from a societal stance. There are a number of potential barriers for people who may try and access services, including people having bad experiences in the past; location and opening times of services and how services are funded and managed. A number of areas of commonality are found in terms of how access to services for 'hard to reach' individuals and groups could be improved including: respectful treatment of service users, establishing trust with service users, offering service flexibility, partnership working with other organisations and harnessing service user involvement. Conclusions: If health services are to engage with groups that are deemed 'hard to reach' and marginalised from mainstream health services, the experiences and practices for engagement from within the VCS may serve as useful lessons for service improvement for statutory health services

An object memory bias induced by communicative reference

In humans, a good proportion of knowledge, including knowledge about objects and object kinds, is acquired via social learning by direct communication from others. If communicative signals raise the expectation of social learning about objects, intrinsic (permanent) features that support object recognition are relevant to store into memory, while extrinsic (accidental) object properties can be ignored. We investigated this hypothesis by instructing participants to memorise shape-colour associations that constituted either an extrinsic object property (the colour of the box that contained the object, Experiment 1) or an intrinsic one (the colour of the object, Experiment 2). Compared to a non-communicative context, communicative presentation of the objects impaired participants’ performance when they recalled extrinsic object properties, while their incidental memory of the intrinsic shape-colour associations was not affected. Communicative signals had no effect on performance when the task required the memorisation of intrinsic object properties. The negative effect of communicative reference on the memory of extrinsic properties was also confirmed in Experiment 3, where this property was object location. Such a memory bias suggests that referent objects in communication tend to be seen as representatives of their kind rather than as individuals