1,109 research outputs found
Tides, surges and mean sea-level (reprinted with corrections)
No full textPrefaceMoving water has a special fascination, and the regular tidal movements of coastal seas must have challenged human imagination from earliest times. Indeed, the ancients who were able to link the regular movements of the sea to the movements of the sun and moon regarded tides as a tangible terrestrial manifestation of the powers of the celestial gods. For them the tides had religious significance; for us there are obviously many practical and scientific reasons for needing to know about and understand the dynamics of the oceans and coastal seas.Modern practical studies are concerned with problems of marine transport, coastal erosion and the design of coastal defences against flooding. Interest in mean sea-level changes has recently focused attention on the possibility of significant increases over the coming century as a result of global warming. Scientifically, in addition to their position as a branch, perhaps the oldest branch, of physical oceanography, tides have a controlling influence on many marine biological and geological processes. One of the fascinations of studying tides is the diversity of the applications.During the past two decades, mainly as a result of developments in instrument design and in the computer sciences, our understanding of tides and their related phenomena has made considerable advances. The aim of this book is to present modern tidal ideas to those who are not tidal specialists, but for whom some tidal knowledge is involved in their own professional or scientific field. These include hydrographers, marine and coastal engineers, geologists who specialize in beach or marine sedimentation processes, and biologists concerned with the ways in which living organisms adapt to the rhythms of the sea.Some of the material presented here was originally prepared for a course of lectures in Liverpool University to third-year Combined Honours students, whose academic backgrounds varied from pure mathematics to field geology. This range of previous scientific experience inevitably causes difficulties in determining the level of mathematical treatment which should be adopted. In this book I have tried to keep the mathematics as simple as is consistent with a proper physical explanation, while developing the non-mathematical discussions in an essentially independent yet parallel way. Sections which may be omitted by the non-mathematical reader are marked with an asterisk.Discussions of the engineering applications of tides are based on several years of experience giving advice to consultants and to Government Departments on behalf of the Proudman Oceanographic Laboratory at Bidston Observatory. Many of my colleagues on the staff of the Laboratory have given me advice and constructive criticism during the preparation. To them and to many other friends and associates I extend my grateful thanks. In particular, it is a pleasure to thank Graham Alcock, M. Amin, Trevor Baker, David Blackman, Peter Claridge, Hilary Faull, Roger Flather, Tony Heathershaw, John Howarth, Ian James, Kathy Jones, Trevor Norton, Lesley Rickards, Ralph Rayner, Alun Thomas, Phillip Williamson, and Philip Woodworth for helpful comments on earlier versions of the text. It is also a pleasure to acknowledge specific or general guidance during the development of my ideas from Duncan Carr Agnew, David Cartwright, Mike Collins, Keith Dyer, Norman Heaps, Chester Jelesnianski, Geoff Lennon, Nick McCave, Robin Pingree, John Simpson, Ian Vassie and Klaus Wyrtki. Finally, I am grateful to my family for tolerating and even encouraging this personal indulgence through the evenings and weekends of four long winters. Cirencester, June, 1987 DAVID PUG
Interview with Robert Gordon
No full textThis interview with Robert Gordon, Illinois Tech architecture alumnus, architect, planner, artist, and author, was conducted on June 6, 2017 by Ralph Pugh and Adam Strohm
“High Crimes and Misdemeanors”: A Constitutional Critique of the Commander-in-Chief
No full textThe Impeachment Clause of the U.S. Constitution has been subject to competing interpretations. Whether impeachment is understood as a legal or a political process will have a great impact on future impeachment proceedings in the United States.
Author information: Emma Pugh is a senior at Samford University in Birmingham, AL. She is studying English and Political Science and is interested in how the two disciplines intersect. She completed this paper prior to the 2019 impeachment inquiry
Early Cancer Detection in Hereditary Breast and Ovarian Cancer Syndrome with Cell-Free DNA
No full textEarly cancer detection in individuals with Hereditary Breast and Ovarian Cancer syndrome (HBOC) remains limited by the sensitivity and generalizability of clinical surveillance methods. In this retrospective study, we analyzed 194 plasma cell-free (cf)DNA samples from 88 carriers of pathogenic germline mutations in BRCA1 or BRCA2 genes (BRCA1/2-carriers) using a multimodal assay integrating genomic, fragmentomic, and methylation features. Cancer-associated signals were detected in 73.8% (45 / 61) of cancer-positive patients. Cancer-associated signals were also detected in 47.4% (18 / 38) of cancer-negative patients a median of 30 months prior to diagnosis, demonstrating the detection of occult cancers missed by conventional surveillance. Multi-feature machine learning models effectively distinguished healthy controls from cancer-negative carriers (mean AUC-ROC: 0.824-0.871) and showed moderate accuracy for cancer-positive vs. cancer-negative carriers (mean AUC-ROCs: 0.635-0.705). These findings support the potential of longitudinal, multimodal liquid biopsy analysis to improve early cancer detection for BRCA1/2-carriers.M.Sc
A salutation to the Britains, to call them from the many things, to the one thing needful, for the saving of their souls; especially, to the poor unlearned tradesmen, plowmen and shepherds, those that are of a low degree like my self, this in order to direct you to know God and Christ, the only wise God, which is life eternal, and to learn of him, that you may become wiser than your teachers. / By Ellis Pugh. ; Translated from the British language by Rowland Ellis, ; revis'd and corrected by David Lloyd. ; [Three lines from Jeremiah]
No full textxv, [1], 222, [2] p. ; 16 cm. (8vo)Signatures: pi^8 A-O^8 (O8 blank).An account of the author."--p. iii-vii."The testimony of the Monthly Meeting at Gwynedd, in the county of Philadelphia, in Pennsylvania, concerning our friend, Ellis Pugh, the author of the following treatise."--p. viii-xv
Dissecting Genetic and Cellular Heterogeneity in Glioblastoma at Single Cell Resolution
No full textGlioblastoma (GBM) is the most common and aggressive form of adult primary brain cancer. Therapeutic resistance in GBM is rooted in its layered genetic and cellular heterogeneity, including rare glioblastoma stem cells (GSCs) that drive tumour growth and disease relapse. Despite extensive profiling of primary tumours, heterogeneity within the GSC fraction and its relationship to the tumour bulk remains poorly characterized. To address this gap, I used whole genome sequencing of 44 GSC-tumour pairs to demonstrate that purified GSC cultures recapitulate the somatic landscape of tumours. I then performed single-cell RNA-sequencing (scRNA-seq) on >69,000 GSCs isolated from 26 tumours to characterize functional diversity within the tumour-initiating fraction of GBM. GSCs exhibited extensive transcriptional heterogeneity that translated to variable, subpopulation-specific drug sensitivity profiles. Although a portion of intra-GSC heterogeneity was explained by subclonal somatic alterations at the DNA level, we found GSCs mapped to a unifying transcriptional gradient spanning two cellular states reminiscent of normal neural development and inflammatory wound responses. Genome-wide CRISPR–Cas9 dropout screens independently recapitulated this observation and identified targetable sensitivities within each GSC state. Additional scRNA-seq of >56,000 malignant cells from primary tumours found that the majority organize along an orthogonal astrocyte maturation gradient yet retain expression of founder GSC transcriptional programs. Finally, to investigate transcriptional programs and cellular dynamics underpinning disease progression in glioma, I performed single nuclei RNA-sequencing on >270,000 cells isolated from 52 cryopreserved gliomas, including a subset of patients with longitudinal samples before and after therapy. Compositional analysis revealed gliomas separated into distinct groups based on the frequency of malignant phenotypes, each with an associated microenvironmental niche and GSC state mirroring the Developmental to Injury Response gradient. Collectively, this work has two important consequences. First, gliomagenesis may be explained by a single biological model that involves mixtures of inflammatory wound-healing cells and neurodevelopmental-like cells that cause aberrant neural growth and underpin therapeutic resistance. Second, the heterogeneity discovered at the GSC level suggests combination therapies must be developed to simultaneously target both developmental and inflammatory subpopulations. This paradigm may help identify new approaches to target treatment-refractory cells that reside at the apex of GBM cellular hierarchies.Ph.D
The Pugh Controlled Convergence Method: Model-Based Evaluation and Implications for Design Theory
No full textThis paper evaluates the Pugh Controlled Convergence method and its relationship to recent developments in design theory. Computer executable models are proposed simulating a team of people involved in iterated cycles of evaluation, ideation, and investigation. The models suggest that: 1) convergence of the set of design concepts is facilitated by the selection of a strong datum concept; 2) iterated use of an evaluation matrix can facilitate convergence of expert opinion, especially if used to plan investigations conducted between matrix runs; and 3) ideation stimulated by the Pugh matrices can provide large benefits both by improving the set of alternatives and by facilitating convergence. As a basis of comparison, alternatives to Pugh's methods were assessed such as using a single summary criterion or using a Borda count. These models suggest that Pugh's method, under a substantial range of assumptions, results in better design outcomes than those from these alternative procedures
The Landscape and Role of Structural Variants in Gliomas: Integrative Analysis with Linked-Read Whole Genome Sequencing and Single-Cell Transcriptomics
No full textGlioma, a prevalent type of brain malignancy, is marked by its complex genetic landscape that informs treatment response and prognosis. Despite extensive efforts to genetically profile gliomas, the role of structural variants (SVs) has been underexplored due to previous technological limitations. To address this gap in knowledge, we adopted an integrated approach to profile 36 glioma samples using linked-read whole-genome sequencing (LR-WGS) and single-nuclei RNA sequencing (snRNA-seq). Our results demonstrated the ability of LR-WGS to precisely detect glioma-relevant SVs, including deletions, duplications, and inversions. Our analyses have also revealed the pattern of SV accumulation and nominated candidate genes involved in early tumour development. Integrating LR-WGS and snRNA-seq data, we identified SVs linked to differential gene expression in key biological processes and assessed the link between SVs and transcriptomic subtypes. Together, this study establishes a reference dataset for future research using advanced sequencing technologies for the characterization of SVs in cancer.M.Sc
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