Structural basis for tuning activity and membrane specificity of bacterial cytolysins

Cholesterol-dependent cytolysins (CDCs) are pore-forming proteins that serve as major virulence factors for pathogenic bacteria. They target eukaryotic cells using different mechanisms, but all require the presence of cholesterol to pierce lipid bilayers. How CDCs use cholesterol to selectively lyse cells is essential for understanding virulence strategies of several pathogenic bacteria, and for repurposing CDCs to kill new cellular targets. Here we address that question by trapping an early state of pore formation for the CDC intermedilysin, bound to the human immune receptor CD59 in a nanodisc model membrane. Our cryo electron microscopy map reveals structural transitions required for oligomerization, which include the lateral movement of a key amphipathic helix. We demonstrate that the charge of this helix is crucial for tuning lytic activity of CDCs. Furthermore, we discover modifications that overcome the requirement of cholesterol for membrane rupture, which may facilitate engineering the target-cell specificity of pore-forming proteins

Wittgenstein on Practice and the Myth of the Giving

This is the text of The Lindley Lecture for 1995, given by Susan Hurley (1954-2007), an American philosopher

Turbulence effects on the drag coefficient of sharp-edged objects

Determination of drag coefficients from the conventional plots of drag coefficient versus Reynolds number is inadequate in the case of turbulent flow

The influence of microstructure on the creep properties of 441 ferritic stainless steel

Includes bibliographical references.The objectives of this report were to determine the influence of microstructure on the creep properties of 441 stainless steel. Of particular interest was the effect of grain size and of the niobium content. A further requirement of this investigation was to design and manufacture two lever-arm type, constant load creep rigs in response to the need for a high quality creep test facility. These rigs were to be used to satisfy the initial objective and to evaluate an industry benchmark test used for determining the creep resistance of a particular alloy, known as the sag test

Landscape approaches for ecosystem management in Mediterranean Islands

This book presents a series of essays, drawing on the twm concepts of ecosystem management and landscape approaches, to elucidate and reflect on the present situation and future evolution of Mediterranean islands. This publication brings together contributions from Mediterranean individuals, non-Mediterranean individuals, islanders and non-islanders there is, after all, no geographical limit on who and what we can learn from. The essays presented here each contribute a specific perspective on the future evolution of Mediterranean islands. This book presents a series of essays, drawing on the twin concepts of ecosystem management and landscape approaches, to elucidate and reflect on the present situation and future evolution of Mediterranean islands. This publication brings together contributions from Mediterranean individuals, non-Mediterranean individuals, islanders and non-islanders; there is, after all, no geographical limit on who and what we can learn from. The essays presented here each contribute a specific perspective on the future evolution of Mediterranean islands. Following this introductory chapter, the first section of the book focuses on the contributions that can be made by the discipline of landscape ecology. loannis Vogiatzakis and Geoffrey Griffiths first explain the concepts and relevance of landscape ecology, also presenting and discussing a range of applied tools that can facilitate landscape planning in Mediterranean islands. Louis F. Cassar then reviews the 'offshoot' discipline of restoration ecology, making a strong case for offsetting the environmental damage inflicted on natural ecosystems over millennia of human occupation, with constructive efforts to effectively restore and/or rehabilitate ecosystems. The two following chapters bring the socio-economic dimension into the discussion. Godfrey Baldacchino first presents two contrasting paradigms for the development of island territories, reviewing the dual influences of ecological and economic factors, and exploring ways in which the two can be brought together in successful development strategies. Gordon Cordina and Nadia Farrugia then address the demographic dimension of development, presenting a model to explain the economic costs of high population densities on islands. The third block of chapters expands on the relevance of social and cultural dynamics to the management of Mediterranean Islands. Isil Cakcï, Nur Belkayali and Ilkden Tazebay explain the evolution of the concept of a 'cultural landscape', focusing on the challenges of managing change in landscapes with strong heritage values. The chapter concludes with a case study on the Turkish island of Gökçeada (lmbros), which is experiencing major challenges in balancing the conservation of a cultural landscape on the one hand, and the management of inevitable change, on the other. Elisabeth Conrad then discusses the role of social capital in managing the landscape resources of Mediterranean islands, reviewing the potential for this intangible social fabric to facilitate or impede the sustainable evolution of island territories. The fourth section includes four chapters, each of which addresses a different aspect relevant to policy development and implementation in Mediterranean islands. Salvino Busuttil presents an essay outlining the political influences on the management of coastal landscapes, the latter so relevant to Mediterranean island territories. The essay derives from the author's professional experience in various policy-related institutions for environmental management within the Mediterranean region. Maggie Roe then reflects on issues of landscape sustainability, focusing on the neglected aspect of intelligence. She discusses ways in which landscape research, knowledge and understanding can feed directly into frameworks for 'sustainable' landscape planning. In the subsequent chapter, Adrian Phillips takes from his substantial experience with international landscape policy, reviewing the gradual emergence of international and national landscape 'tools', to draw out lessons for application in Mediterranean islands. In the final chapter of this section, Riccardo Priore and Damiano Galla present a comprehensive discussion of the European Landscape Convention, the first international instrument to focus exclusively on landscape. The authors explain the innovative character of this convention, and discuss its potential implementation in Mediterranean islands. The publication concludes with a series of case studies, highlighting specific constraints, experiences and opportunities in different Mediterranean islands. Theano Terkenli explores the landscapes of tourism in Mediterranean islands - perhaps no other industry has played such a fundamental role in shaping the evolution of Mediterranean landscapes in recent years. The author reviews the theoretical relationship between landscape and tourism across Mediterranean islands, before focusing on the specific case of the Greek Cycladic islands. In the following chapter, Alex Camilleri, Isabella Colombini and Lorenzo Chelazzi present an in-depth review of the context and challenges being faced on a number of minor Mediterranean islands, namely those of the Tuscan archipelago (Elba, Giglio, Capraia, Montecristo, Pianosa, Gorgona and Giannutri), and Comino, the latter forming part of the Maltese archipelago. The comparison between these various islands enables an appreciation of both commonalities across these islands, as well as considerations that are specific to the context of each in dividual island. JeremyBoissevain then adopts an anthropological lens to review the cautionary tale of landscape change in Malta, exploring underlying causes of landscape destruction and limited civil engagement. In the subsequent chapter, Jala Makhzoumi outlines the richness of Mediterranean islands' rural landscapes, focusing on olive landscapes in Cyprus. Her research demonstrates the economic and ecological robustness of various olive cultivation practices, and whilst warning of several threats to such sustainable regimes, she outlines strategies for reconfiguring our approach to rural heritage, in order to integrate such assets into sustainable development strategies. Finally, Stephen Morse concludes the section with an evaluation of sustainable development indicators, and the contribution that these can make towards enhancing the management of Mediterranean island territories. He illustrates his arguments with reference to the two island states of Malta and Cyprus. To conclude, in the final chapter of this publication, we review key insights emerging from the various chapters, and summarize considerations for ecosystem management and sustainable development in Mediterranean Islands. We truly hope that this publication makes some contribution towards safeguarding the "magic' of Mediterranean islands, whilst embracing their dynamic characteristics.Published under the patronage of UNESCO and with the support of the Maltese National Commission for UNESCOpeer-reviewe

The distribution of the conjunct verb form in Western Naskapi and related morpho-syntactic issues

This thesis analyzes the distribution of the Conjunct verb in Western Naskapi using a Minimalist framework. Western Naskapi is spoken in the Northern Quebec community of Kawawachikamach. It is one of a number of dialects which constitute the Central Algonquian language referred to as the Cree-Montagnais-Naskapi (CMN) language complex. -- The Conjunct is one of the two principal verb types attested in the CMN complex. This thesis examines the syntactic environments in which the Conjunct occurs: subordinate clauses, clauses (main and subordinate) containing a w/r-question word, negated clauses, and main clause focus constructions. -- I argue that wherever a CP projection is motivated in the phrase structure, a conjunct verb is required to raise to the head of that projection (C). The constructions that are the focus of this thesis are assumed to contain at least one CP projection, thus allowing the distribution of the Conjunct to be restated in terms of CP distribution. Two key pieces of evidence are offered to support this hypothesis: (i) conjunct verbs undergo a morpho-phonological process which takes place at C; (ii) conjunct verbs occur in contexts that are cross-linguistically associated with a CP projection. Wh-phrases raise overtly to the SpecCP of the clause in which they are base-generated. Thus, simple direct wh-questions are analyzed as uni-clausal constructions. -- The thesis reassesses the status of the Algonquian Person/Gender hierarchy. The grammatical functions and thematic roles of the arguments of transitive verbs can be uniquely identified without appealing to the hierarchy. Raising constructions in both Western Naskapi and Cree are examined. Evidence is provided to support the view that the grammar of Algonquian makes a null expletive available. For Case-theory reasons the expletive is not available to raising constructions, thus allowing the subject requirements of the raising predicate to be met by raise-NP or raise-CP. -- Equivalent data from a number of other CMN dialects (Plains Cree, Moose Cree, Swampy Cree, Woods Cree, East Cree, and Sheshatshu Innu-aimun) are considered in order to show that the analysis in this thesis applies to the CMN complex in general. Dialect differences are accounted for in terms of microparametric variatio

Form and structure of some of Edwin Arlington Robinson\u27s Tilbury Town poems

It is the purpose of this study to explore several of Edwin Arlington Robinson’s poems in order to show the poet’s force of language and prosody and to reveal as much as possible his total poetic artistry. The poems are representative of his familiar, shorter Tilbury Town portraits and are taken from his early, middle, and late periods. An honest appraisal will be made to determine the true worth of the poetry, and an attempt will be made to show that Edwin Arlington Robinson deserves a respected position in modern American letters

Certain aspects of the pharmacology of a histamine liberator, compound 48/80.

Thesis (Ph.D.)--Boston UniversityThe phenomenon of anaphylactic shock, the methods by which it can be produced, the symptomatology involved in various animal species and the role of certain substances in the production of this state have occupied the attention of a large number of investigators during the last fifty years. Much evidence has accumulated which indicates that histamine causes the major reactions in the syndrome of anaphylaxis. This evidence has been reviewed. [TRUNCATED