89 research outputs found
Enhancing the Tunability of Multidomain Peptides: Composite Systems and Synthetic Glycosylation
No full textMolecular self-assembly, the process of molecules organizing themselves into hierarchical structures through non-covalent forces, is responsible for many of life’s most important processes. Inspired by nature, scientists have created synthetic, self-assembling systems to tackle a wide range of biomedical problems. One area that these systems have shown promise is in the field of drug delivery. The ability to control where and when a drug is delivered, i.e. spatiotemporal control, is an issue for many drugs but most notably for chemotherapeutics in cancer treatment. As chemotherapeutics do not discriminate between cancerous and healthy cells, many horrible side effects occur due to off-target toxicity. Self-assembled, nano-sized structures such as nanofibers made from peptides and particles made from lipids have been used to deliver drugs more efficiently, but drawbacks such as subpar release kinetics or short half-lives leave much to be desired.
The first part of this work explores the use of multi-component, or composite, systems made up of multiple self-assembling systems to gain finer control over drug release kinetics. We use MultiDomain Peptides (MDPs), a class of self-assembling peptide hydrogels, and liposomes to create drug delivery systems with tunable release kinetics based on peptide-lipid interactions. We show that electrostatic interactions can be used to tailor the release kinetics, and when tuned correctly, can result in delayed release kinetics longer than either system alone. We go on to use these composite systems in an aggressive oral cancer model and show that a single injection of our immunotherapeutic-loaded composite system is as effective as six separate injections of free immunotherapeutic.
The second part of this work looks to expand the synthetic toolbox of MDPs through glycosylation. We show, for the first time, the use of MDPs in organic solution phase reactions, resulting in a library of eleven novel glycosylated MDPs. We investigate the effects of position, frequency, and stereochemistry of carbohydrates on MDP self-assembly. We then explore the utility of these glycosylated hydrogels as lectin delivery systems, showing affinity-based delayed release of lectins from hydrogels with specific carbohydrates. These works look to advance the use of MDPs as highly tunable drug delivery systems
Photoimmunotherapy of Ovarian Cancer: A Unique Niche in the Management of Advanced Disease
No full textOvarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths in the United States, with five-year survival rates of 15–20% for stage III cancers and 5% for stage IV cancers. The standard of care for advanced OvCa involves surgical debulking of disseminated disease in the peritoneum followed by chemotherapy. Despite advances in treatment efficacy, the prognosis for advanced stage OvCa patients remains poor and the emergence of chemoresistant disease localized to the peritoneum is the primary cause of death. Therefore, a complementary modality that is agnostic to typical chemo- and radio-resistance mechanisms is urgently needed. Photodynamic therapy (PDT), a photochemistry-based process, is an ideal complement to standard treatments for residual disease. The confinement of the disease in the peritoneal cavity makes it amenable for regionally localized treatment with PDT. PDT involves photochemical generation of cytotoxic reactive molecular species (RMS) by non-toxic photosensitizers (PSs) following exposure to non-harmful visible light, leading to localized cell death. However, due to the complex topology of sensitive organs in the peritoneum, diffuse intra-abdominal PDT induces dose-limiting toxicities due to non-selective accumulation of PSs in both healthy and diseased tissue. In an effort to achieve selective damage to tumorous nodules, targeted PS formulations have shown promise to make PDT a feasible treatment modality in this setting. This targeted strategy involves chemical conjugation of PSs to antibodies, referred to as photoimmunoconjugates (PICs), to target OvCa specific molecular markers leading to enhanced therapeutic outcomes while reducing off-target toxicity. In light of promising results of pilot clinical studies and recent preclinical advances, this review provides the rationale and methodologies for PIC-based PDT, or photo-immunotherapy (PIT), in the context of OvCa management
Making negotiated land reform work : initial experience from Brazil, Colombia, and South Africa
No full textThe author describes a new type of negotiated land reform that relies on voluntary land transfers negotiated between buyers and sellers, with the government's role restricted to establishing the necessary framework for negotiation and making a land purchase grant available to eligible beneficiaries. This approach has emerged-following the end of the Cold War and broad macroeconomic adjustment--as many countries face a second generation of reforms to address deep-rooted structural problems and provide a basis for sustainable economic growth and poverty reduction. The author describes initial experiences in Brazil, Colombia, and South Africa. It is too soon to know whether negotiated land reform can rise to the challenges administrative land reform failed to solve but the data so far suggests that: 1) Negotiated land reform can succeed only if measures are taken to make the market for land sales and rentals more fluid transparent. 2) Productive projects are likely to be the key to market-assisted land reform. The potential for project productivity establishes an upper bound on the price to be paid and a basis for financial intermediaries to evaluate the project. It also requires beneficiaries to familiarize themselves with the realities they're likely to confront as independent farmers and the limits to how much land reform can help them achieve their goals. 3) The only way to effectively coordinate the entities involved in the process is through decentralized, demand-driven implementation. 4) The long-run success of land reform depends on getting the private sector involved and using the land purchase grant to"crowd in"private money.Banks&Banking Reform,Environmental Economics&Policies,Agricultural Knowledge&Information Systems,Municipal Housing and Land,Land Use and Policies,Environmental Economics&Policies,Agricultural Knowledge&Information Systems,Municipal Housing and Land,Rural Land Policies for Poverty Reduction,Banks&Banking Reform
The Role of Narrative Fiction and Semi-Fiction in Organizational Studies
No full textIn this chapter, we discuss the use of narrative fiction and semi-fiction in organizational research and explore the strengths and weaknesses of these alternative approaches. We begin with an introduction reviewing the existing literature and clarifying what we mean by fiction and semi-fiction. We then present and discuss examples of fiction and semi-fiction focusing on how these approaches can be used in organizational research. We argue that fiction is more useful as a source of data and as a way of representing theory to an audience. Semi-fiction, on the other hand, provides a novel approach to the production and representation of theory. In both cases, researchers face a number of challenges, but also gain access to new and powerful techniques for developing insights into organizational topics.Organizational studies;Narrative fiction;Semi-fiction
INDIGENOUS LAND TENURE AND LAND USE IN ALASKA: COMMUNITY IMPACTS OF THE ALASKA NATIVE CLAIMS SETTLEMENT ACT
No full textThrough the utilization of qualitative methods such as archival analysis, semi-structured interviewing, comparative and extended case studies, and observation, this paper closely examines two related Alaska Native communities. Our purpose is to document the impact of the Alaska Native Claims Settlement Act of 1971 (ANCSA) on land tenure, land use, and community structure. In all, 41 interviews were conducted, focusing on the following issues: (1) the role of the tribal government in relation to the regional and village corporate structure; (2) the recent changes in traditional land uses; and (3) how group decisions are made regarding land management and distribution of resources. By locating ANCSA within a broader context of economic, political, and cultural globalization that seeks to substitute traditional collective rights in land with individual tenure in a "free market" economy, the findings of this research may carefully and cautiously be applied beyond North America to other indigenous-state struggles regarding control of land and resources.United States. -- [Alaska Native Claims Settlement Act], Indians of North America -- Legal status, laws, etc. -- Alaska, Land tenure -- Law and legislation -- Alaska, Indians of North America -- Alaska -- Claims, Indians of North America -- Land tenure -- Alaska, Indians of North America -- Alaska -- Government relations -- History, Land Economics/Use,
Landscape-painter as landscape-gardener : the case of Alfred Parsons R.A.
No full textIn 2 vols.Available from British Library Document Supply Centre-DSC:DXN016830 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
'A secret pleasure in being mastered': Play, Power and the Morality of Art in J. M. Barrie's Sentimental Tommy and Tommy and Grizel.
No full textThis dissertation analyses J.M. Barrie's novels Sentimental Tommy (1896) and Tommy and Grizel (1900) in terms of their narrative explorations of the moral implications of art. In particular, it finds the novels preoccupied with the power relations between reader and text, and with the question of whether the playful pleasures of art can ever justify the moral problems created when its power relations are reproduced in social relationships.
The introduction identifies these concerns in the style of the novels through close reading. Chapter one establishes the thesis that, within these novels, art is defined as excess and inconsistency, producing some surprising correspondences to late Nineteenth-Century art theory. This ‘art’ is personified by the protagonist, Tommy, who is shown to have both learned and inherited his artistic disposition. Chapter two identifies a complementary personification, of social morality, in the character of Grizel, which enables their relationship symbolically to play out tensions between art and society. This chapter also finds that these tensions are conceived in the novels as a debate on the gendering of power within heterosexual erotic relationships, wherein the intruding power dynamics of art disturb normative gender roles.
Chapter three, conversely, examines a selection of Tommy's non-romantic relationships and finds them to reveal a model of human selfhood as innately inconsistent, though necessarily modified by social relations. As such, Barrie also, and equally, portrays art as potentially therapeutic, since it allows the expression of individualistic concerns. Finally, the conclusion proposes that this ambivalence towards the morality of art culminates, both in these novels and in Barrie's later work, in a symbolic and paradigmatic mother/eternal boy relationship. Acknowledgement of the complexity of this symbolism, I propose, is of consequence, partly because it is precisely this aspect of Barrie's work that has survived and become significant within Western culture
The Re-invention of Sociology of Community
No full textIn today’s society the term ‘Community’ is frequently used. Politicians, religious leaders, policy makers and the media are repeatedly utilizing the concept to describe a particular scenario. Traditionally, sociologists have been fascinated with community, within a theoretical and geographical context. At the centre of the community is the debate of how external agencies work with the local community and how social policy can work at a local level. The aim of this paper is to critically explore the debate around community and how the subject has re-established itself within the discipline of sociology. To justify the arguments surrounding the Sociology of Community the author uses a case study of The United Kingdom
The Gospel on the Margins: The Ideological Function of the Patristic Tradition on the Evangelist Mark
No full textIn spite of the virtually unanimous patristic opinion that the evangelist Mark was the interpreter of Peter, one of the most prestigious apostolic founding figures in Christian memory, the Gospel of Mark was mostly neglected in the patristic period. Not only is the text of Mark the least well represented of the canonical Gospels in terms of the number of patristic citations, commentaries and manuscripts, the explicit comments about the evangelist Mark reveal some ambivalence about its literary or theological value. In my survey of the reception of Mark from Papias of Hierapolis until Clement of Alexandria, I will argue that the reason why the patristic writers were hesitant to embrace the Gospel of Mark was that they perceived the text to be amenable to the Christological beliefs and social praxis of rival Christian factions. The patristic tradition about Mark may have little historical basis, but it had an important ideological function in appropriating the text in the name of an apostolic authority from the margins or periphery
- …
