Degree sequences

A nonincreasing sequence pi = (d1, d2,···,dn) of nonnegative integers is said to be graphic if it is the degree sequence of a simple graph of order n and such graph is referred to as a realization of pi.;Let H be a simple graph. A graphic sequence pi is said to be potentially H-graphic if it has a realization G containing H as its subgraph.;In this paper, we characterize the potentially Ck graphic sequence for k = 3, 4, 5. These characterizations imply theorems due to P. Erdos, M. S. Jacobson and J. Lehel, R. J. Gould, M. S. Jacobson and J. Lehel and C. H. Lai

Developing Chemical Proteomic Tools Connecting Proteins and Small Molecules

Ph.DDOCTOR OF PHILOSOPH

Foundations of Software Science and Computation Structures

This open access book constitutes the proceedings of the 24th International Conference on Foundations of Software Science and Computational Structures, FOSSACS 2021, which was held during March 27 until April 1, 2021, as part of the European Joint Conferences on Theory and Practice of Software, ETAPS 2021. The conference was planned to take place in Luxembourg and changed to an online format due to the COVID-19 pandemic. The 28 regular papers presented in this volume were carefully reviewed and selected from 88 submissions. They deal with research on theories and methods to support the analysis, integration, synthesis, transformation, and verification of programs and software systems

Phosphoproteomic investigation of kinase signalling network plasticity in response to chronic PI3K and mTORC1/2 inhibition

PhDClass I phosphoinositide 3-kinases (PI3K) and mammalian target of rapamycin complexes 1/2 (mTORC1/2) are enzymes that play important roles in elementary biology and disease. As a consequence, numerous small-molecule inhibitors of their catalytic activity have been developed and these have shown clinical utility in certain cancers. Unfortunately, acquired resistance to these therapies is a common phenomenon and often occurs relatively quickly following treatment. Our understanding of how resistance develops is hampered by the difficulty of measuring the circuitry and plasticity of the signalling networks that these and other kinases signal within. Advances in mass spectrometric technologies have rendered the routine quantitative interrogation of the phosphoproteome (the set of phosphorylated proteins expressed in a particular biological system at a specific time) more tractable than ever before. The aim of this project therefore, was to improve upon existing mass spectrometry (MS)-based phosphoproteomics methods, and to utilise these to contribute to our understanding of kinase signalling networks and examine their plasticity in models of acquired resistance to PI3K and mTORC1/2-targeted therapies. Novel approaches for the enrichment of phosphopeptides from complex biological matrices (and their analysis by MS) were designed, tested and optimised. These methods were then used to systematically characterise a kinase signalling network comprising the Akt/PI3K/mTOR and MEK/ERK signalling axes in MCF7 breast cancer cells. The biological relevance of this network was confirmed through the assessment of its dynamics upon EGF and IGF-1 stimulation. Finally, the plasticity of this network following chronic treatment with targeted PI3K and mTORC1/2 inhibitors (GDC-0941 and KU-0063794) was examined in cell-line models of acquired resistance to these two compounds. This revealed that these cells each remodelled this network in a different manner, thus indicating that the initial conditions of the system were not the sole determinant of how resistance was acquired.Cancer Research UK (CRUK

Ideas and Explorations : Brouwer's Road to Intuitionism

This dissertation is about the initial period of Brouwer's role in the foundational debate in mathematics, which took place during the first decades of the twentieth century. His intuitionistic and constructivistic attitude was a reaction to logicism (Russell, Couturat) and to Hilbert's formalism. Brouwer's own dissertation (1907) is a first introduction to his intuitionism, which was the third movement in the foundational debate. This intuitionism reached maturity from 1918 onwards, but one of my aims is to show that there are demonstrable traces of this new development of mathematics as early as 1907 and even before, viz. in his personal notes, which are composed of his numerous ideas in the field of mathematics and philosophy. To mention some important ones: 1. Mathematics is entirely independent of language. Mathematics is created by the individual mind (Brouwer certainly is a solipsist) and the role of language is limited to that of communication a mathematical content to others and is also useful for one's own memory. 2. The ur-intuition of the 'move of time', that is, the experience that two events are not coinciding, is the most fundamental basis of all mathematics. A separate space intuition (Kant) is not needed. 3. A strict constructivism. Only that what is constructed by the individual mind counts as a mathematical object. 4. Logic only describes the structure of the language of mathemqatics. Hence logic comes after mathematics, instead of being its basis. 5. An axiomatic foundation is rejected by Brouwer. Axioms only serve the purpose of describing concisely the properties of a mathematical construction. These five items have far-reaching consequences for Brouwer's mathematical building. To mention the most relevant ones: - The only possible cardinalities for sets are: finite, denumerably infinite, denumerably infinite unfinished and the continuum. - The continuum is not composed of points (Aristotle already said so), but is given to us in its entirety in the ur-intuition. It can be turned into an everywhere dense measurable continuum by constructing a rational scale on it. - Cantor's second number class does not exist as a finished totality for Brouwer, since there is no conceivable closure for the elements of this class. - The continuum problem is a trivial one: Every well-defined subset of the continuum is finite, denumerably infinite, or has the cardinality of the continuum. Finally, in my dissertation the sixth chapter is devoted to Brouwer's view on the application of mathematics to the human evironment and on his outlook on man and on human society in general (chapter 2 of Brouwer's dissertation). His opinion about humanity turns out to be a pessimistic one: All man's effort, when applying mathematics to the surrounding world, is aimed at a domination over his environment and over his fellow men

Endothelin system in human cardiovascular physiology and pathophysiology

The experiments presented here arose from an interest in endothelial function and, particularly, a wish to better understand the pharmacology and physiology of the endothelin (ET) system in human blood vessels in health, and the influence of cardiovascular disease on the ET system. This work followed from the discovery of ET-1 as a peptide endothelial mediator of vascular tone in 1988. Publications are grouped into sections representing different aspects of the work.Section 1 is concerned with exploring pharmacological responses to the ET family of peptides, the sarafotoxin analogue peptides, and ET antagonists, in human blood vessels in vivo. This was amongst the first work with ET-1 in humans, and certainly the first to use the sarafotoxins, ET receptor antagonists and ET converting enzyme (ECE) inhibitors. After characterisation of the pharmacological tools, it was possible to show clearly that endogenous ET-1 plays a physiological role in the control of peripheral resistance and blood pressure in healthy humans, suggesting important clinical applications for these agents. It was also shown that the ETA receptor is the major vasocontrictor receptor and that the major role in health of the ETB receptor is endothelium-dependent vasodilatation, enhancement of which may contribute to the beneficial clinical attributes of ETA receptor antagonism. In addition, local ET-1 infusion in the forearm circulation was shown to be a system whereby the clinical efficacy of systemically administered ET receptor antagonists could be modelled pharmacodynamicallySections 2-4 cover work confirming the substantial clinical utility of ET receptor antagonists and ECE inhibitors as vasodilators, particularly in essential hypertension, heart failure and renal failure. Other work, following congenital heart surgery, suggests that a cautious approach may be needed in some cases of pulmonary hypertension. Studies with neutral endopeptidase (NEP) inhibitors show unequivocally, but unexpectedly, that these agents are peripheral vasoconstrictors, and the evidence presented is consistent with this effect occurring because endogenously generated vascular ET-1 is an important substrate for NEP.Section 5 contains some miscellaneous but related studies, together with a series of review articles written from 1991-98 synthesising the literature at each stage and drawing conclusions about potential areas of major clinical interest in cardiovascular diseasePUBLICATIONS: • SECTION 1: CARDIOVASCULAR PHYSIOLOGY, Papers 1-19 • 1. Clarke JG, Benjamin N, Larkin SW, Webb DJ, Davies GJ, Maseri A. Endothelin is a potent long-lasting vasoconstrictor in men. Am J Physiol 1989;257:H2033-5. • 2. Cockcroft JR, Clarke JG, Webb DJ. The effect of intra-arterial endothelin on resting blood flow and sympathetically mediated vasoconstriction in the forearm of man. Br J Clin Pharmacol 1991;31:521-4. • 3. Waugh CJ, Dockrell MEC, Haynes WG, Olverman HJ, Williams BC, Webb DJ. The potassium channel opener BRL 38227 inhibits binding of [l25I]-labelled endothelin-1 to rat cardiac membranes. Biochem Biophys Res Commun 1992;185:630-5. • 4. Haynes WG, Webb DJ. Endothelium dependent modulation of responses to endothelin-1 in human veins. Clin Sci 1993;84:427-33. • 5. Dockrell MEC, Haynes WG, Williams BC, Webb DJ. Endothelin-1 and aggregation of human platelets in vitro. J Cardiovasc Pharmacol 1993;22(suppl 8), S204-6. • 6. Haynes WG, Webb DJ. Venoconstriction to endothelin-1 in humans: role of calcium and potassium channels. Am J Physiol 1993;265:H1676-81. • 7. Haynes WG, Webb DJ. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet 1994;344:852-4. • 8. Haynes WG, Strachan FE, Webb DJ. Endothelin ETA and ETb receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation 1995;92:357-63. • 9. Strachan FE, Haynes WG, Webb DJ. Endothelium-dependent modulation of venoconstriction to sarafotoxin S6c in human veins in vivo. J Cardiovasc Pharmacol 1995;26(suppl. 3):S 180-2. • 10. Smith PJW, McQueen DS, Webb DJ. The effect of cooling on the contractile response to endothelin-1 in small arteries from humans. J Cardiovasc Pharmacol 1995;26(suppl3):S230-2. • 11. Plumpton C, Haynes WG, Webb DJ, Davenport AP. Phosphoramidon inhibition of the in vivo conversion of big endothelin-1 to endothelin-1 in the human forearm. Br J Pharmacol 1995; 116:1821-8. • 12. Haynes WG, Moffat S, Webb DJ. An investigation into the direct and indirect venoconstrictor effects of endothelin-1 and big endothelin-1 in man. Br J Clin Pharmacol 1995;40:307-11. • 13. Haynes WG, Ferro CJ, O'Kane KPJ, Somerville D, Lomax CC, Webb DJ. Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. Circulation 1996;93:1860-70. • 14. Dockrell MEC, Webb DJ, Williams BC. Activation of the endothelin B receptor causes a dose-dependent accumulation of cyclic GMP in human platelets. Blood Coag Fibrinolysis 1996;7:178-80. • 15. Plumpton C, Ferro CJ, Haynes WG, Webb DJ, Davenport AP. The increase in human plasma immunoreactive endothelin but not big endothelin-1 or its C-terminal fragment induced by systemic administration of the endothelin antagonist TAK-044. Br J Pharmacol 1996;119:311-4. • 16. Haynes WG, Hand MH, Dockrell MEC, Eadington DW, Lee MR, Benjamin N, Webb DJ. Physiological role of nitric oxide in regulation of renal function in humans. Am J Physiol 1997;272:F364-71. • 17. Ferro CJ, Haynes WG, Johnston NR, Lomax CC, Newby DE, Webb DJ. The peptide endothelin receptor antagonist, TAK-044, produces sustained inhibition of endothelin1 mediated arteriolar vasoconstriction. Br J Clin Pharmacol 1997;44:377-383. • 18. Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ, Webb DJ. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 1998;97:752-6. • 19. Strachan FE, Spratt JC, Wilkinson IB, Gray GA, Johnston NR, Webb DJ. Systemic blockade of the endothelin-B receptor increases peripheral vascular resistance in healthy men. Hypertension 1999;33:581-5. • SECTION 2: HYPERTENSION AND RENAL DYSFUNCTION Papers 20-24 | 20. Haynes WG, Hand MF, Johnstone HA, Padfield PL, Webb DJ. Direct and sympathetically mediated venoconstriction in essential hypertension: enhanced responses to endothelin-1. J Clin Invest 1994;94:1359-64. • 2 1. Sturrock NDC, Lang CC, MacFarlane LJ, Dockrell MEC, Ryan M, Webb DJ, Struthers AD. Serial changes in blood pressure, renal function, endothelin and lipoprotein (a) during the first 9 days of cyclosporin therapy in males. J Hypertens 1995;13:667-73. • 22. Hand MF, Haynes WG, Johnstone HA, Anderton JL, Webb DJ. Erythropoietin enhances vascular responsiveness to norepinephrine in renal failure. Kidney Int 1995;48:806-13. • 23. Ferro CJ, Spratt JCS, Haynes WG, Webb DJ. Inhibition of neutral endopeptidase causes vasoconstriction of human resistance vessels in vivo. Circulation 1998;97:2323-30. • 24. Hand MH, Haynes WG, Webb DJ. Reduced endogenous endothelin-1-mediated vascular tone in chronic renal failure. Kidney Int 1999;55:613-20. • SECTION 3 | ISCHAEMIC HEART DISEASE Papers 25-27 | 25. Wieczorek I, Haynes WG, Webb DJ, Ludlam CA, Fox KAA. Raised plasma endothelin in unstable angina and non-Q wave myocardial infarction: relation to cardiovascular outcome. Br Heart J 1994;72:436-41. • 26. Flaynes WG, Hamer DW, Robertson CE, Webb DJ. Plasma endothelin following cardiac arrest: differences between survivors and non-survivors. Resuscitation 1994;27:117-22. • 27. Newby DE, Flint LL, Fox KAA, Boon NA, Webb DJ. Reduced responsiveness to endothelin-1 in peripheral resistance vessels of patients with syndrome X. J Am Coll Cardiol 1998;31:1585-90. • SECTION 4 | HEART FAILURE AND PULMONARY HYPERTENSION Papers 28-30 | 28. Davidson NC, Coutie WJ, Webb DJ, Struthers AD. Hormonal and renal differences between low dose and high dose angiotensin converting enzyme inhibitor treatment in patients with chronic heart failure. Heart 1996;75:576-81. • 29. Love MP, Haynes WG, Gray GA, Webb DJ, McMurray JJV. Vasodilator effects of endothelin-converting enzyme inhibition and endothelin ETA receptor blockade in chronic heart failure patients treated with ACE inhibitors. Circulation 1996;94:2131-7. • 30. Prendergast B, Newby DE, Wilson LE, Webb DJ, Mankad PS. Early therapeutic experience with the endothelin antagonist, BQ-123, in pulmonary hypertension after congenital heart surgery. Heart 1999;82:505-8 • SECTION 5 | MISCELLANEOUS TOPICS AND REVIEWS Papers 31-34 and 35-46 | 31. Sanai L, Haynes WG, McKenzie A, Grant IS, Webb DJ. Endothelin production in sepsis and the adult respiratory distress syndrome. Intens Care Med 1996;22:52-6. • 32. Mickley EJ, Gray GA, Webb DJ. Activation of endothelin ETa receptors masks the constrictor role of endothelin ETg receptors in rat isolated small esenteric arteries. Br J Pharmacol 1997;120:1376-82. • 33. McEwan PE, Valdenaire O, Sutherland L, Webb DJ, Gray GA. A non-radioactive method for localization of endothelin receptor mRNA in situ. J Cardiovasc Pharmacol 1998;31(suppl l):S443-6. • 34. Smith PJW, Ferro CJ, McQueen DS, Webb DJ. Functional studies in small arteries do not support a primary role for endothelin in the pathogenesis of Raynaud's disease. J Cardiovasc Pharmacol 1998;31(suppl l):S473-6. • 35. Webb DJ. Endothelin receptors cloned, endothelin converting enzyme characterised and pathophysiology explored. TiPS 1991;12:43-6. • 36. Haynes WG, Webb DJ. The endothelin family of peptides: local hormones with diverse roles in health and disease. Clin Sci 1993;84:485-500. • 37. Haynes WG, Davenport AP, Webb DJ. Endothelin: progress in pharmacology and physiology. TiPS 1993;14:225-8. • 38. Kennedy RL, Haynes WG, Webb DJ. Endothelins as regulators of growth and function in endocrine tissues. Clin Endocrinol 1993;39:259-65. • 39. Webb DJ, Haynes WG. Endothelins come of age. Lancet 1993;342:1439-40. • 40. Webb DJ. Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure: endothelin antagonism in heart failure. Circulation 1995;92:3372. • 41. Ferro CJ, Webb DJ. The clinical potential of endothelin receptor antagonists in cardiovascular medicine. Drugs 1996;51:12-27. • 42. Gray GA, Webb DJ. The endothelin system and its potential as a therapeutic target in cardiovascular disease. Pharmacol Ther 1996;72:109-48. • 43. Newby DN, Webb DJ. The endothelin system in cardiovascular disease: discovery to drug development in under a decade. BMJ 1997;314:531-2. • 44. Webb DJ. Endothelin: from molecule to man [BPS Research Prize Lecture]. Br J Clin Pharmacol 1997;44:9-20. • Webb DJ, Monge JC, Rabelink A, Yanagisawa M. Endothelin: new discoveries and rapid progress in the clinic. Trends Pharmacol Sci 1998;19:5-8. • 46. Haynes WG, Webb DJ. Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens 1998;16:1081-98

An investigation of computer based nominal data record linkage

The Internet now provides access to vast volumes of nominal data (data associated with names e. g. birth/death records, parish records, text articles, multimedia) collected for a range of different purposes. This research focuses on parish registers containing baptism, marriage, and burial records. Mining these data resources involves linkage investigating as to how two records are related with regards to attributes like surname, spatio-temporal location, legal association and inter-relationships. Furthermore, as well as handling the implicit constraints of nominal data, such a system must also be able to handle automatically a range of temporal and spatial rules and constraints. The research examines the linkage rules that apply and how such rules interact. In this investigation a report is given of the current practices in several disciplines (e. g. history, demography, genealogy, and epidemiology) and how these are implemented in current computer and database systems. The practical aspects of this study, and the workbench approach proposed are centred on the extensive Lancashire & Cheshire Parish Register archive held on the MIMAS database computer located at Manchester University. The research also proposes how these findings can have wider applications. This thesis describes some initial research into this problem. It describes three prototypes of nominal data workbench that allow the specification and examination of several linkage types and discusses the merits of alternative name matching methods, name grouping techniques and method comparisons. The conclusion is that in the cases examined so far, effective nominal data linkage is essentially a query optimisation process. The process is made more efficient if linkage specific indexes exist, and suggests that query re-organization based on these indexes, though a complex process, is entirely feasible. To facilitate the use of indexes and to guide the optimization process, the work suggests the use of formal ontologies

4. International reservoir characterization technical conference

This volume contains the Proceedings of the Fourth International Reservoir Characterization Technical Conference held March 2-4, 1997 in Houston, Texas. The theme for the conference was Advances in Reservoir Characterization for Effective Reservoir Management. On March 2, 1997, the DOE Class Workshop kicked off with tutorials by Dr. Steve Begg (BP Exploration) and Dr. Ganesh Thakur (Chevron). Tutorial presentations are not included in these Proceedings but may be available from the authors. The conference consisted of the following topics: data acquisition; reservoir modeling; scaling reservoir properties; and managing uncertainty. Selected papers have been processed separately for inclusion in the Energy Science and Technology database

Cone Penetration Testing 2022

This volume contains the proceedings of the 5th International Symposium on Cone Penetration Testing (CPT’22), held in Bologna, Italy, 8-10 June 2022. More than 500 authors - academics, researchers, practitioners and manufacturers – contributed to the peer-reviewed papers included in this book, which includes three keynote lectures, four invited lectures and 169 technical papers. The contributions provide a full picture of the current knowledge and major trends in CPT research and development, with respect to innovations in instrumentation, latest advances in data interpretation, and emerging fields of CPT application. The paper topics encompass three well-established topic categories typically addressed in CPT events: - Equipment and Procedures - Data Interpretation - Applications. Emphasis is placed on the use of statistical approaches and innovative numerical strategies for CPT data interpretation, liquefaction studies, application of CPT to offshore engineering, comparative studies between CPT and other in-situ tests. Cone Penetration Testing 2022 contains a wealth of information that could be useful for researchers, practitioners and all those working in the broad and dynamic field of cone penetration testing

Aspects of coordination chemistry / Frank Richard Keene.

Includes bibliographical references.1 v. :Thesis (D.Sc.) -- University of Adelaide, Dept. of Chemistry, 199