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Dissertations / Theses on the topic 'Human Phenomenon'
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Wells, Cecilia Emily. "Institutional racism : human agency or structural phenomenon?" Thesis, Royal Holloway, University of London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430888.
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Donald, Emily, and Rebecca J. Milner. "Understanding the Phenomenon of Technology Facilitated Sexual Violence." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/5974.
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One needs only to turn to the media for a short time to be reminded that sexual violence is an ongoing societal issue. Sexual violence continues to be prevalent, and along with the rising popularity of dating apps and the anonymity provided by the online environment, this provides an opportunity for unwanted and unsolicited sexual content to be shared. All counselors-in-training must be prepared to work with clients affected by technology facilitated sexual violence (TFSV), as well as advocate for systemic changes needed to address this growing issue. In particular, school counselors must be prepared to address safety issues with students, so that TFSV does not become normalized in their environment. Join us for a timely discussion of how to prepare students and supervisees to work with and advocate for clients affected by TFSV
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Chan, Audrey Sze-ming. "The human veto phenomenon, an in vitro investigation of antigen-specific T lymphocyte suppression." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0014/MQ34052.pdf.
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Tam, Yat Fai Sunny. "The human veto phenomenon, an in vitro investigation of antigen-specific T lymphocyte suppression." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0026/MQ50462.pdf.
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Mahmood, Tariq. "The future of human reproduction : a 21st century phenomenon : a legal, theological and philosophical analysis." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/the-future-of-human-reproduction-a-21st-century-phenomenon-a-legal-theological-and-philosophical-analysis(cd9ae627-43ea-450a-a74a-e753ee6fb8db).html.
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This thesis seeks to examine various reproductive technologies whether old or new and draws conclusion from the legal, theological and philosophical perspective. My analysis starts by considering and is centred upon the Islamic perspective. The advancement of science and technology has brought many complex challenges to the modern world. I will argue that Islam is not a stagnant religion but a religion for all ages and all times. Islam has a solution to complex medical problems through the means of ‘Fatwa’s’ (Islamic legal ruling). The spirit of Islam should be the guiding force in assessing whether a certain treatment or advancement in medicine is permissible or not. It is important for medical practitioners to be religiously and culturally aware of the issues and the conundrum that many couples face when deciding whether a certain treatment is permissible within Islam or not. English Law has seen a change in the mind set of the judiciary but still when it comes to the question of surrogacy it seems that there are numerous logistical difficulties. In a world of social media it seems that a lot more agreements are done via the Internet without the individual couple considering the legal implications but rather using raw emotion to make decisions, which may ultimately be detrimental to them and the child. In my analysis from the Legal Perspective, I argue that the Judiciary needs to react more quickly to the advancement of new reproductive technologies. The Philosophical analysis considers the various reproductive technologies, in light of the bioethical principles. IVF is considered to be the least problematic option within my analysis, whereas surrogacy is the most problematic. It may be a matter of time as generations pass; moral attitudes may change the way we think on the question of surrogacy. The western world is coming to terms with gay marriages and a time may come where surrogacy can be a simple solution without the emotional attachment.
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Jesse, Mugero. "Uganda's response to the phenomenon of enforced disappearances and the transitional justice response in Uganda." University of the Western Cape, 2017. http://hdl.handle.net/11394/6143.
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Magister Legum - LLMEnforced disappearances are a heinous violation of numerous human rights enshrined in many international conventions. However, they have not been adequately addressed in many jurisdictions. This crime is very common within countries on the continent of Africa, which despite having plenty of conflicts, under report cases of enforced disappearances. This research paper investigates the transitional justice mechanisms implemented in Uganda to deal with the phenomenon of enforced disappearances. It analyses the mechanisms implemented by the Government of Uganda and those by Non- Governmental Organisations. The paper examines also how the phenomenon of enforced disappearances has been dealt with in other countries such as Morocco, Kenya and South Africa. The paper suggests several recommendations to Uganda after having made a comparison with the selected countries on how to deal with the crime of enforced disappearances.
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Rogers, Gordon H. (Gordon Hartt) Carleton University Dissertation Geography. "Mutation, mind and epistemology; an examination of the concept of territoriality in humans as an informational and evolutionary phenomenon." Ottawa, 1992.
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Molin, Victoria, and Sofia Nordgren. "Robot or Human? The Marketing Phenomenon of Virtual Influencers : A Case Study About Virtual Influencers’ Parasocial Interaction on Instagram." Thesis, Uppsala universitet, Företagsekonomiska institutionen, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-388646.
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Title: Robot or Human? The Marketing Phenomenon of Virtual Influencers: A Case Study About Virtual Influencers’ Parasocial Interaction on Instagram. Purpose: As it is already established that human influencers can create parasocial interaction with their followers, the purpose of this study is to explore parasocial interaction with virtual influencers through their perceived source credibility. Research Questions: How are consumers responding to interaction with virtual influencers on Instagram? What factors in source credibility facilitate parasocial interaction between the actors? Method: This case study has conducted semi-structured interviews with Swedish consumers along with information collected on two virtual fashion influencers: LilMiquela and Noonoouri. Before the interviews, a pretest in interacting with the virtual influencers on Instagram was conducted. Afterwards, the transcripts have been analyzed in accordance to the presented operationalization and led to subcategories found to be relevant for the facilitation of PSI. Conclusion: It was shown that consumers responded better to interaction with humanlike virtual influencers regarding their appearance and lifelike activities. Although, consumers also perceive their appearance and behavior as unpleasant and unrealistic when being too close to reality. Their perceived humanness affected the level of attractiveness, similarity and trustworthiness. As such, these are the factors that affect the degree of source credibility and thus facilitate PSI with them. Virtual influencers stand in front of a problem with both authenticity and transparency, as they are created and owned by companies. This has implications for their overall attractiveness, as authenticity is shown to be important for consumers on Instagram. However, lack of authenticity and transparency mostly implicates the trustworthiness of them, as the communicator is unknown. Virtual influencers are perceived to have a superior ability of being available online and personal in interaction. Therefore, it is shown to have a positive effect on the facilitation of PSI as it increases their attractiveness. However, it also indicates that they are controlled by a company which has a negative effect as it decreases the trustworthiness of them. To conclude, consumers’ virtual robot acceptance is proposed to be a precursor for developing PSI with virtual influencers in conjunction with the three factors in source credibility: trustworthiness, attractiveness and similarity.
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Smart, M. J. K. "A comparative study of the potential for human retinal pigment epithelium utilising an embryonic chick model of the phenomenon." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1417198/.
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The retinal pigment epithelial (RPE) cells of several species, including: chicken, rat, mouse and newt, have been observed to undergo a phenomenon known as transdifferentiation. This involves the re-specification of the RPE phenotype towards a neuroretinal, or lens phenotype, in response to various cues, including basic fibroblast growth factor (bFGF). Transdifferentiation has yet to be described in human RPE cells, however, this investigation has demonstrated that human cells, including primary fetal, and human embryonic stem cell-derived (HESC), RPE, may retain the capacity to undergo some level of bFGF-mediated transdifferentiation. It appears that the process is likely comparable to that observed in the embryonic chick model of the phenomenon, given that human transdifferentiation appears to be restricted to the earliest stages of RPE development (approximately 6 weeks). Additionally, the features of transdifferentiated RPE observed in the earliest available human tissue are shown to resemble that of a similar stage in chick development (HH27), which is shown to display limited transdifferentiation for the first time, in contrast with previous studies which report the loss of potential for transdifferentiation at this stage. It remains unclear as to why RPE cells lose the capacity for transdifferentiation with development, however, it appears to be linked to, but not exclusively a result of, a loss in the expression of Pax6 across the RPE monolayer, given both capacity for transdifferentiation, and Pax6 expression, are both variable in different regions of the same monolayer, in the chick model of transdifferentiation. Known RPE augmentation signaling pathways, including bone morphogenic protein (BMP) and Sonic hedgehog (Shh) were analysed for their potential involvement in the restriction of transdifferentiation, however, neither appeared to be directly involved. Further studies in the embryonic chick model of the phenomenon will be necessary to unlock this potential in human RPE cells.
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Mugero, Jesse. "Uganda's response to the phenomenon of enforced disappearances and the transitional justice response in Uganda." University of the Western Cape, 2016. http://hdl.handle.net/11394/6278.
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Magister Legum - LLM (Criminal Justice and Procedure)Enforced disappearances are a heinous violation of numerous human rights enshrined in many international conventions. However, they have not been adequately addressed in many jurisdictions. This crime is very common within countries on the continent of Africa, which despite having plenty of conflicts, under report cases of enforced disappearances. This research paper investigates the transitional justice mechanisms implemented in Uganda to deal with the phenomenon of enforced disappearances. It analyses the mechanisms implemented by the Government of Uganda and those by Non- Governmental Organisations. The paper examines also how the phenomenon of enforced disappearances has been dealt with in other countries such as Morocco, Kenya and South Africa. The paper suggests several recommendations to Uganda after having made a comparison with the selected countries on how to deal with the crime of enforced disappearances.
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Rosenthal-von, der Pütten Astrid [Verfasser], Nicole [Akademischer Betreuer] Krämer, and Matthias [Akademischer Betreuer] Brand. "Uncanniliy Human - Experimental Investigation of the Uncanny Valley Phenomenon / Astrid Rosenthal-von der Pütten. Gutachter: Matthias Brand. Betreuer: Nicole Krämer." Duisburg, 2014. http://d-nb.info/1049647440/34.
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Björk, Anna. "Not for Sale : Terminology and cultural references in a text on human trafficking." Thesis, Linnéuniversitetet, Institutionen för språk (SPR), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-32505.
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The aim of this paper is to analyse what strategies may be the most suitable ones when dealing with problems in the translation of a text on human trafficking. The focus of the study is how to translate terminology related to human trafficking, but also on how to deal with references to culture-specific phenomena. In order to find possible solutions for translation problems in the text, different dictionaries and term banks were used, as well as parallel texts and different translation strategies. The analysis is based on the translation strategies laid down by Vinay and Darbelnet, Ingo and Newmark. The findings of the study show that a number of different translation strategies had to be applied in order to solve the different translation problems. Regarding the translation of terminology, modulation, equivalence, addition and omission were the most useful strategies, as well as using parallel texts. The strategies found most useful in translating culture-specific phenomena were modulation, equivalence and addition, but componential analysis, transference and established translations were also used. Factors that decided what were the most appropriate strategies to apply in the different instances were the aim of the text, the perspective of the target reader and parallel texts.
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Achan-Okitia, Patricia. "The internal displacement crisis in Africa : implementation of national and international law on the child marriage phenomenon in Uganda." Diss., University of Pretoria, 2007. http://hdl.handle.net/2263/5276.
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This research focuses on the role that International Human Rights Law, policy and legislation should play in the protection of the rights of internally displaced children against child marriage. This thesis examines international treaties and domestic laws that purport to prohibit the
practice of child marriage with particular attention to laws relating to the protection of internally displaced children (IDPs).Mini Dissertation (LLM (Human Rights and Democratisation in Africa))--University of Pretoria, 2007.
Dissertation submitted to the Faculty of Law of the University of Pretoria, in partial fulfilment of the requirements for the degree of Masters of Law (LLM in Human Rights and Democratisation in Africa). Prepared under the supervision of Dr Lana Baydas at the Department of Law, American University in Cairo, Egypt. 29 October 2007
www.chr.up.ac.za
Centre for Human Rights
LLM
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Luci, Monica. "The phenomenon of torture : towards an integrated framework for the understanding of intrapsychic, relational, socio-political dimensions of torture and its implications for human rights." Thesis, University of Essex, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572807.
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This research is intended to examine the phenomenon of torture from a perspective as comprehensive as possible. Starting from definitions of torture in international law and discussing a wide range of literature, it focuses on its individual, relational and socio-political aspects. The aim of the research is to contribute to the development of a concise and integrated framework of understanding of torture based on psychoanalytic thinking that enable the examination of different levels of the phenomenon as well as a dialogue between psychoanalysis and human rights on the topic of torture. After a critical review of the literature that addresses the socio-political key features and the relational and individual aspects of social actors involved, the main framework of understanding of the phenomenon of torture is constructed through a selection of psychoanalytic theories on the functioning of self and its main dynamic principles. The main conceptual elements of this framework are those of splintered reflective triangle, monolithic self states and monolithic societal states, which are the original contributions of this .thesis but well grounded on existing psychoanalytic literature. They are an elaboration of selected key themes of psychoanalytic contributions of authors from different theoretical approaches (British Object Relations Theory, Relational Psychoanalysis and Analytical Psychology). These concepts with their emotional, relational and cognitive facets, aim to account for the crucial relational ' dynamics in torture that address the different but interconnected levels of experience in the social actors of torture. This framework is used to initiate a dialogue with the human rights field on the debate of permissibility of torture and other relevant themes, illustrating further lines of possible development for this study.
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Hanna, Kinora. "Elevers syn på klimatfrågan : Klimatundervsiningen i skolan." Thesis, Södertörn University College, Lärarutbildningen, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-3350.
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The aim of this study is to find out in which way the education about climate in school is taught and how the students experience the world situation today. There are various theories about the greenhouse effect and its origin and these theories should be addressed to ensure that students get a broader understanding of how climate change occurs. This includes the natural phenomena and also the human impact on climate change. Students in school are a source of concern that only human are the cause of global warming, and know little or almost nothing about the natural phenomena of global warming. I will mention what has emphasized in the national steering documents in the case of environmental education at school.
I have used a qualitative method, where interviews and document analysis were used as techniques. The interviews took place with five students in ninth grade and with three science teachers in the same school.
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Kempton, Gabrielle Elyse. "The United States of America and Lithuania: a cross cultural comparison of the social services and empowerment strategies delivered in relation to the phenomenon of human trafficking." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2013~D_20130614_102029-05767.
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Currently human trafficking is named the fastest growing criminal enterprise in the world. It is the second largest social problem in the global community, just behind narcotics and drug trade. Approximately 70% of trafficking is in the form of sexual exploitation. Victims of human trafficking often go undetected because of the deceptive nature of the crime, however once identified there are social services available to help re-integrate these individuals back into society.
This research seeks to illuminate social work in human sex trafficking and how the phenomenon of trafficking manifests itself in the United States and Lithuania. The question is asked what are the services provided to victims of sex trafficking in the United States and Lithuania and how does the perceived inherent differences between the victims of phenomenon in each nation impact the delivery of these services, and the understanding of empowerment? In relation to the above research question and objective, the concepts of human trafficking, prostitution, social services, empowerment and international social work will be theoretically explored.
In an effort to answer these questions qualitative research methodology was employed because of the freedom is gives to place importance on the subjective experiences of the research participants. To help capture the unique perspectives of the social service professionals working with trafficking victims semi structured interviews will be utilized as a means of... [to full text]Šiuo metu prekyba žmonėmis įvardyta kaip greičiausiai pasaulyje auganti nusikalstama veikla. Tai antra pagal dydį socialinė problema pasaulio visuomenėje, pirmą vietą užleisdama prekybai narkotinėmis medžiagomis. Apytiksliai 70% prekybos sudaro seksualinis išnaudojimas. Prekybos žmonėmis aukos dažnai lieka neatskleistos dėl apgaulingo nusikalstamos veiklos pobūdžio, tačiau jas aptikus, egzistuoja socialinės paramos organizacijos, galinčios padėti tokiems asmenims integruotis atgal į visuomenę. Šis tiriamasis darbas siekia informuoti, kokios socialinės paramos organizacijų paslaugos teikiamos nuo prekybos žmonėmis nukentėjusioms aukoms, ir tai, kaip prekybos žmonėmis reiškinys pasireiškia minėtose šalyse. Iškeliamas klausimas, kokios paslaugos suteikiamos nuo seksualinio išnaudojimo nukentėjusiems asmenims JAV ir Lietuvoje bei kaip kiekvienoje iš šių šalių jaučiami įgimti skirtumai tarp reiškinio aukų įtakoja minėtų paslaugų teikimą bei galios suteikimo supratimą. Atsižvelgiant į iškeltą klausimą bei tikslą, teoriškai nagrinėjama prekyba žmonėmis, prostitucija, socialinės paslaugos, galios suteikimas ir tarptautinis socialinis darbas. Stengiantis atsakyti į šiuos klausimus, pasinaudota kokybine tyrimo metodika, kadangi ji leidžia sutelkti dėmesį į subjektyvias tyrimo dalyvių patirtis. Norint užfiksuoti unikalias socialinių paslaugų profesionalų darbo su prekybos žmonėmis aukomis perspektyvas, naudojamas pusiau struktūruotas interviu, padėsiantis geriau suvokti interviu dalyvių... [toliau žr. visą tekstą]
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Vorster, Lize. "Shared mental models as a cultural phenomenon : fact or fiction? Using the card-sorting method to investigate the shared mental models of web users." Thesis, Stellenbosch : University of Stellenbosch, 2006. http://hdl.handle.net/10019.1/1049.
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Assignment (MPhil (Afrikaans and Dutch))--University of Stellenbosch, 2006.ENGLISH ABSTRACT: In this study, the mental models of the target audience of the FACT web site (official Stellenbosch University HIV/Aids web site) were investigated and compared with the structure of the web site (representing the mental model of the expert). The target audience were divided into six groups representing three different race groups (white, coloured and black) and the two sexes (male and female).
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Mensching, Johannes Ole Verfasser], Detlef [Akademischer Betreuer] [Fetchenhauer, and Robb [Akademischer Betreuer] Willer. "Can we trust trust explanations? : an experimental illustration of how outcome based accounts of trust struggle to explain a basic phenomenon of human life / Johannes Ole Mensching. Gutachter: Detlef Fetchenhauer ; Robb Willer." Köln : Universitäts- und Stadtbibliothek Köln, 2011. http://d-nb.info/1038065593/34.
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Espiner, Stephen. "The phenomenon of risk and its management in natural resource recreation and tourism settings : a case study of Fox and Franz Josef Glaciers, Westland National Park, New Zealand." Lincoln University, 2001. http://hdl.handle.net/10182/638.
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The significance of risk is growing in many Western societies, a phenomenon linked to increasing individualism, personal choice, and outcome uncertainty in multiple spheres of life. Despite being healthier and more physically protected from harm than any previous society, a serious concern for safety and risk control is emerging as a defining characteristic of modern social life. Within the context of a risk-averse society, this thesis investigates the nature and relevance of risk in natural resource recreation and tourism settings. Millions of people every day visit national parks and other protected areas around the world in which natural hazards inhere. Many visitors fail to recognise these hazards, creating moral, legal, and ethical issues for natural resource managers. People travel to national parks anticipating a degree of adventure, to escape routines, and to witness the grandeur of nature. Ironically, the very qualities that attract people to natural areas may also put them at risk. Managers of natural resource tourism and recreation areas in New Zealand are confronted with a paradox born out of visitor demand for nature experiences, a legal obligation to facilitate free access, and a growing social emphasis on health and safety. In particular, this study assesses the risk perceptions of visitors to the Fox and Franz Josef glaciers, popular tourist attractions on the West Coast of New Zealand's South Island, and explores the risk perceptions and beliefs of resource management agency staff. The study also investigates the issue of risk communication at these two sites, and the degree to which existing hazard messages are successful at encouraging appropriate visitor behaviour. Pictorial hazard warning signs are introduced to the sites and their effectiveness evaluated. The findings show that many visitors (especially international visitors) have relatively poor awareness of natural hazards, and behave in ways which potentially compromise physical safety. It is argued that perceptions and behaviour are a consequence of diverse individual and situational factors including limited knowledge of the sites, beliefs about management, poor comprehension of hazard warning signs, and freedom from the normative constraints of everyday life. In contrast to visitors, managers at the glacier sites consider the risks to be significant, and, potentially, severe. It is argued that managers' perceptions of risk are influenced by several important social and site-specific factors, including their own experiences of hazards at the glaciers, perceived legal and moral obligations, the organisational culture, and impressions of high societal expectation concerning safety. The situation is further complicated by the freedom of access principle in national parks, and increasing tourist demand for nature-based experiences. These factors governed beliefs about the subject of risk. This study identifies several dimensions of risk in nature-based recreation and tourism settings. Visitors are at risk of personal accident or injury at certain tourism attractions. Awareness of hazards is limited, visitor behaviour compromises safety, and existing communication strategies are only partially effective. Risk is also apparent in the agency responsible for management of outdoor recreation areas. Site managers perceive a risk in their failure to prevent visitors from harm, whereas senior managers identify risk as primarily financial, legal, and political. Collectively, these factors demonstrate that the phenomenon of risk is increasingly important in the tourism and recreation context, and has the potential to influence significantly both management and experience of protected natural areas in New Zealand.
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Kamada, Kohji. "Rightward movement phenomena in human language." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/5820.
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The aim of my thesis is to show that some properties of rightward movement constructions (a cover term referring to sentences where an element appears to be “displaced” to the right) may be derived from syntactic principles and interface conditions within the framework of the minimalist program, and also to claim that properties which have up to now been dealt with purely in syntax receive a better account in terms of language processing. I develop a nonmovement approach to the Japanese Post-Verbal Construction (JPVC) by claiming that a postverbal phrase is adjoined to an element by External Merge, and that it is permitted as a syntactic object by a licensing condition which allows it to be construed as an argument or a modifier by interpretive rules at the interface level (SEM/LF). Many syntactic properties of the JPVC are accounted for in terms of independently motivated interface conditions and syntactic principles. I assume that the parser is a system that can make use of UG principles as well as language particular rules, and that the parser should be universal. The interaction of syntactic principles with parsing strategies makes it possible to cope with elusive problems concerning scope ambiguity as well as locality effects observed in the JPVC. This interaction may also account for the Right Roof Constraint effect displayed by the rightward movement constructions in English (i.e., Heavy "P Shift (H"PS), Extraposition from "P, and Right Dislocation). Furthermore, it predicts that languages fall into three types with respect to the possibility of the HNPS construction: (i) both subjects and objects can appear in postverbal position (e.g., Italian, Japanese, Turkish); (ii) subjects cannot do so (e.g., English); (iii) neither subjects nor objects can appear in postverbal position (e.g., Dutch, German). The claim that there is a parsing strategy relating to linear distance is supported by an experiment designed as a test for the effect of the length of intervening elements on acceptability of the JPVC, with the data obtained using Magnitude Estimation, a technique used in psychophysics to measure judgements of sensory stimuli.
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Nguyen, Anh Dung. "Contributions to Modeling, Structural Analysis, and Routing Performance in Dynamic Networks." Phd thesis, Institut National Polytechnique de Toulouse - INPT, 2013. http://tel.archives-ouvertes.fr/tel-00908502.
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Cette thèse apporte des contributions à la modélisation, compréhension ainsi qu'à la communication efficace d'information dans les réseaux dynamiques peuplant la périphérie de l'Internet. Par réseaux dynamiques, nous signifions les réseaux pouvant être modélisés par des graphes dynamiques dans lesquels noeuds et liens évoluent temporellement. Dans la première partie de la thèse, nous proposons un nouveau modèle de mobilité - STEPS - qui permet de capturer un large spectre de comportement de mobilité humains. STEPS mets en oeuvre deux principes fondamentaux de la mobilité humaine : l'attachement préférentiel à une zone de prédilection et l'attraction vers une zone de prédilection. Nous proposons une modélisation markovienne de ce modèle de mobilité. Nous montrons que ce simple modèle paramétrique est capable de capturer les caractéristiques statistiques saillantes de la mobilité humaine comme la distribution des temps d'inter-contacts et de contacts. Dans la deuxième partie, en utilisant STEPS, nous analysons les propriétés comportementales et structurelles fondamentales des réseaux opportunistes. Nous redéfinissons dans le contexte des réseaux dynamiques la notion de structure petit monde et montrons comment une telle structure peut émerger. En particulier, nous montrons que les noeuds fortement dynamiques peuvent jouer le rôle de ponts entre les composants déconnectés, aident à réduire significativement la longueur du chemin caractéristique du réseau et contribuent à l'émergence du phénomène petit-monde dans les réseaux dynamiques. Nous proposons une façon de modéliser ce phénomène sous STEPS. À partir d'un réseau dynamique régulier dans lequel les noeuds limitent leur mobilité à leurs zones préférentielles respectives. Nous recablons ce réseau en injectant progressivement des noeuds nomades se déplaçant entre plusieurs zones. Nous montrons que le pourcentage de tels nœuds nomades est de 10%, le réseau possède une structure petit monde avec un fort taux de clusterisation et un faible longueur du chemin caractéristique. La troisième contribution de cette thèse porte sur l'étude de l'impact du désordre et de l'irrégularité des contacts sur la capacité de communication d'un réseau dynamique. Nous analysons le degré de désordre de réseaux opportunistes réels et montrons que si exploité correctement, celui-ci peut améliorer significativement les performances du routage. Nous introduisons ensuite un modèle permettant de capturer le niveau de désordre d'un réseau dynamique. Nous proposons deux algorithmes simples et efficaces qui exploitent la structure temporelle d'un réseau dynamique pour délivrer les messages avec un bon compromis entre l'usage des ressources et les performances. Les résultats de simulations et analytiques montrent que ce type d'algorithme est plus performant que les approches classiques. Nous mettons également en évidence aussi la structure de réseau pour laquelle ce type d'algorithme atteint ses performances optimum. Basé sur ce résultat théorique nous proposons un nouveau protocole de routage efficace pour les réseaux opportunistes centré sur le contenu. Dans ce protocole, les noeuds maintiennent, via leurs contacts opportunistes, une fonction d'utilité qui résume leur proximité spatio-temporelle par rapport aux autres noeuds. En conséquence, router dans un tel contexte se résume à suivre le gradient de plus grande pente conduisant vers le noeud destination. Cette propriété induit un algorithme de routage simple et efficace qui peut être utilisé aussi bien dans un contexte d'adressage IP que de réseau centré sur les contenus. Les résultats de simulation montrent que ce protocole superforme les protocoles de routage classiques déjà définis pour les réseaux opportunistes. La dernière contribution de cette thèse consiste à mettre en évidence une application potentielle des réseaux dynamiques dans le contexte du " mobile cloud computing ". En utilisant les techniques d'optimisation particulaires, nous montrons que la mobilité peut augmenter considérablement la capacité de calcul des réseaux dynamiques. De plus, nous montrons que la structure dynamique du réseau a un fort impact sur sa capacité de calcul.
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Haigh, Charles. "The caffeine 8-hydroxylation in humans, a predominantly intestinal phenomenon." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ63171.pdf.
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La, Morlière Jacques Rochette. "Identification d'hemoglobines hyperaffines pour l'oxygene : techniques d'etudes et relation structure fonction." Paris 7, 1987. http://www.theses.fr/1987PA077153.
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Les relations structure/fonction des hemoglobines humaines a fonction modifiee, exprimees a l'etat heterozygote sont etudiees. Des proprietes de 2 nouveaux mutants a affinite augmentee pour l'oxygene sont decrits. L'analyse tridimensionnelle met en evidence que la substitution a pour consequence un deplacement de la region helicale ef avec une modification d'accessibilite du dpg dans la carte centrale
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Tsapeli, Theofania Kleio. "Understanding real-world phenomena from human-generated sensor data." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8445/.
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Nowadays, there is an increasing data availability. Smartphones, wearable devices, social media, web browsing information and sales recordings are only few of the newly available information sources. Analysing this kind of information is an important step towards understanding human behaviour. In this dissertation, I propose novel techniques for uncovering the complex dependencies between factors extracted from raw sensor data and real-world phenomena and I demonstrate the potential of utilising the vast amount of human digital traces in order to better understand human behaviour and factors influenced by it. In particular, two main problems are considered: 1) whether there is a dependency between social media data and traded assets prices and 2) how smartphone sensor data can be used to understand factors that influence our stress level. In this thesis, I focus on uncovering the structural dependencies among factors of interest rather than on the detection of mere correlation. Special attention is given on enhancing the reliability of the findings by developing techniques that can better handle the specific characteristics of the examined datasets. Although the developed approaches are motivated by specific problems related to human-generated sensor data, they are general and can be applied in any dataset with similar characteristics.
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Barbosa, Bárbara Conceição de Oliveira. "Ciberespaço e dependência: uma análise dos vínculos do humano com o glocal interativo como habitus." Pontifícia Universidade Católica de São Paulo, 2008. https://tede2.pucsp.br/handle/handle/5130.
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The present Master s Degree Dissertation is intended to analyze the technological dependence its origins, its state-of-the-art and its consequences in the sphere of the relationship between human being and interactive media. The research contexts, of an exclusively theoretical nature, is the cyberculture, understood as a social organization of epoch, originated from the technological development that followed the Second World War. The main objective is to analyze the dependence phenomenon to which the cybercultural civilization is subject. The research problem lies in the following questionings: how a relationship so presented is configured? Which factors favor it? In the social-historic sphere, does dependence provides the preservation of technological lifestyles? Would it be present both in the collective plan and in the individual plan? As a main hypothesis, the study redefines and overvalues as dependence the strict social subjects bond to interactive technologies and networks, a bond whose analysis should consider the civilizatory and anthropological aspects involved, as it implies, simultaneously, recent history, society and individual. The research fundamentation privileges theoretical proposals articulated by the criticism category and consolidated in the last twenty years, based on the following authors: David Harvey, Fredric Jameson, Krishan Kumar and Jean-François Lyotard (post modernity); Paul Virilio (the concept of dromology); Eugênio Trivinho (cyberculture, cybercultural dromocracy and glocal phenomenon); Francisco Rüdiger and David Le Breton (cybercultural imaginary), Philippe Breton (communication as an utopian value); Pierre Bourdieu (concept of habitus); Vilém Flusser (technical image); Jean Baudrillard (the concept of excess). The reflection also incorporates references to researches who study the pathological use of Internet, such as Rosa Maria Farah and Denise Razzouk, among other authors and theoretical-epistemological perspectives. In relation to the achieved results, we can highlight, as favoring dependence, the context of cybercultural dromocracy (the velocity regime in the digital era), the glocal context (real-time living) and the inherent characteristics to interactive glocal, such as velocity, virtuality, deterritorialization, personalization, etc. This panorama gives cause to practices that, incorporated by the subject, are objectified in the glocalized habitus and affect it in body and in subjectivity. Such transformations and their consequences require gradual deepening in researches about the factors that endanger them, which justifies the present work. The research is inserted in the Culture and mediatic environments Research Line of PEPGCOS-PUC-SP, as it deals with the interactive technologies impact on the social-historic and cultural spheres; and finds support in the Communication area in Brazil, beside researches more and more concerned about cyberculture and its communicational practices
A presente Dissertação de Mestrado se destina à análise da dependência tecnológica suas origens, seu estado da arte e suas conseqüências no âmbito da relação entre ser humano e media interativos. O contexto da pesquisa, de natureza exclusivamente teórica, é o da cibercultura, entendida como organização social de época, originada do desenvolvimento tecnológico posterior à Segunda Guerra Mundial. O principal objetivo é analisar o fenômeno da dependência à qual está sujeita a civilização cibercultural. O problema de pesquisa reside nos seguintes questionamentos: como se configura uma relação assim posta? Quais fatores a favorecem? No âmbito social-histórico, a dependência propicia a conservação de estilos de vida tecnológicos? Estaria presente tanto no plano coletivo quanto no individual? Como hipótese principal, o estudo redefine e sobrevalora como dependência , o vínculo estrito dos sujeitos sociais às tecnologias e redes interativas, vínculo cuja análise deve considerar os aspectos civilizatórios e antropológicos envolvidos, pois implica, a um só tempo, história recente, sociedade e indivíduo. A fundamentação da pesquisa privilegia propostas teóricas articuladas pela categoria da crítica e consolidadas nos últimos vinte anos, com base nos seguintes autores: David Harvey, Fredric Jameson, Krishan Kumar e Jean-François Lyotard (pós-modernidade); Paul Virilio (conceito de dromologia); Eugênio Trivinho (cibercultura, dromocracia cibercultural e fenômeno glocal); Francisco Rüdiger e David Le Breton (imaginário cibercultural), Philippe Breton (comunicação como valor utópico); Pierre Bourdieu (conceito de habitus); Vilém Flusser (imagem técnica); Jean Baudrillard (conceito de excesso). A reflexão incorpora, também, referências a pesquisadores que estudam o uso patológico da internet, como Rosa Maria Farah e Denise Razzouk, entre outros autores e perspectivas teórico-epistemológicas. Em relação aos resultados alcançados, destacam-se, como favorecedores da dependência, o contexto da dromocracia cibercultural (regime da velocidade na era digital), o contexto glocal (vivência em tempo real) e as características inerentes ao glocal interativo, como a velocidade, a virtualidade, a desterritorialização, a personalização etc. Esse panorama enseja práticas, que, incorporadas pelo sujeito, são objetivadas no habitus glocalizado e o afetam no corpo e na subjetividade. Tais transformações e suas conseqüências requerem gradual aprofundamento nas pesquisas dos fatores que as engendram, o que justifica o presente trabalho. A pesquisa se insere na Linha de Pesquisa Cultura e ambientes midiáticos do PEPGCOS-PUC-SP por versar sobre o impacto das tecnologias interativas nos âmbitos social-histórico e cultural; e encontra guarida na área da Comunicação no Brasil, ao lado de pesquisas cada vez mais preocupadas com a cibercultura e suas práticas comunicacionais
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Danarti, Retno. "Paradominance and didymosis : two etiologically related mosaic phenomena in human skin /." Marburg : Tectum-Verl, 2004. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=012894057&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Monteiro, Márcio Wariss. "A falácia da interatividade: crítica das práticas glocais na cibercultura." Pontifícia Universidade Católica de São Paulo, 2006. https://tede2.pucsp.br/handle/handle/4846.
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Previous issue date: 2006-10-19Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
This present work has as its own background the theoretical understanding of cyberculture, which is considered as the worldwide mediatic arrangement shaped by the encounter between telecommunications and informatics. It deals, specifically, with interactivity understood as the social process that organizes and structures the world, both in its sociocultural activities and in its everyday life, by the glocal cybercultural practices. It is an academic research on the inner logics of the sociotechnological development after Second World War, taking into consideration the last three decades, when the microinformatics has appeared and developed. Within this context, in which the interactive technologies became essential, the present work tries to make tension with approaches which proposes the interactivity as the solution for all human body and intellectual limitations, as well as for social problems and democratic realizations. In this sense, the research tries to demonstrate that the interactivity, before fulfilling all these promises, works like a fallacy, updating in new bases and improperly the utopian ideals of the cybernetic theory. This way, the work maps different theoretical perspectives about the theme and then it makes articulations and developments to comprehend the importance of the interactivity for the contemporary civilizatory process, markedly mediatic. Even though what has been written in this field is vast and abundant, this work expects to contribute with the researches about interactivity, considering it not only as a ordinary and practical informatics procedure observed in the relation between humans and computers, but, as well, as the main structuring vector of the contemporary civilization. The theoretical perspectives of Philippe Breton e Serge Proulx on communications as utopia, of Paul Virilio, with regards to dromology, and of Eugênio Trivinho, relating to cyberculture and glocal phenomenon, represent, along all the work, interesting and fundamental contributions for our research
O presente trabalho se insere no cenário teórico da cibercultura, atual arranjamento mediático planetário configurado pela convergência entre telecomunicações e informática. Aborda, especificamente, a interatividade tomada como o processo social que, por meio de práticas glocais ciberculturais, organiza e dinamiza o mundo, no que tange tanto a atividades socioculturais, quanto à vida cotidiana. Trata-se de um trabalho exclusivamente reflexivo que se debruça sobre a lógica do processo sociotecnológico posterior ao final da Segunda Guerra Mundial, com destaque para as três últimas décadas, nas quais a microinformática surgiu e se desdobrou. Nesse contexto, em que as tecnologias interativas tornaram-se imprescindíveis, o presente trabalho busca fazer tensão com correntes de pensamento celebrativas que atribuem à interatividade o condão para superar limitações corporais e intelectuais humanas, assim como para solucionar mazelas relacionadas aos laços sociais e à realização democrática. Nesse sentido, procura-se demonstrar que a interatividade, antes de cumprir tais promessas, vigora como falácia a principal hipótese da pesquisa , atualizando de modo reescalonado e indevido os ideais utópicos da teoria cibernética. Para tanto, recorre-se à pesquisa bibliográfica com o objetivo de se mapear os vários enfoques sobre o tema, para, então, se realizar articulações e desdobramentos que subsidiem uma compreensão apurada do processo civilizatório contemporâneo, marcadamente mediático. Não obstante o vasto leque de livros, ensaios e artigos, acadêmicos ou não, disponíveis, o trabalho espera contribuir com as pesquisas sobre a interatividade, abordando-a não apenas como procedimento informático pontual e pragmático observado na relação entre humanos e computadores, mas também, e principalmente, como vetor de organização do modus operandi da civilização contemporânea. As intenções se alinham, portanto, e não por acaso, às perspectivas teóricas que vêm sendo desenvolvidas por Philippe Breton e Serge Proulx, sobre a comunicação como utopia, por Paul Virilio, a respeito da dromologia, e por Eugênio Trivinho, no que se refere à cibercultura e ao fenômeno glocal
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Maurakis, Stavros. "Characterization of the Novel Interaction Between Neisseria gonorrhoeae TdfJ and its Human Ligand S100A7." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5710.
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Neisseria gonorrhoeae is an obligate human pathogen that causes the common STI gonorrhea, which presents a growing threat to global health. The WHO estimated 78 million new cases of gonorrhea worldwide in 2017, with estimates of 820,000 new cases in the United States alone according to the CDC. High-frequency phase and antigenic variation inherent in N. gonorrhoeae, coupled with its natural ability to rapidly acquire and stably integrate antimicrobial resistance factors into its genome, have culminated in an infection against which there is no effective vaccine, and for which the list of viable therapeutic options is quickly shrinking. Moreover, no protective immunity against subsequent infections is elicited upon exposure to N. gonorrhoeae, which highlights the need for research of novel antimicrobial and vaccination strategies. Within the human host, N. gonorrhoeae utilizes a unique strategy to overcome host sequestration of essential nutrients – termed nutritional immunity (NI) – such as ions of trace metals. The pathogen produces a family of outer membrane proteins called TonB-dependent transporters (TdTs) capable of binding to host NI factors and stripping them of their nutritional cargo for use by the pathogen. Importantly, these TdTs are very highly conserved and expressed among Neisseria species. TbpA is a well-characterized TdT that allows N. gonorrhoeae to acquire iron from human transferrin, and recent studies from our lab have shown that TdfH is capable of binding to a zinc-sequestering S100 protein called calprotectin and stripping it of its zinc ion. The S100 proteins are EF-hand calcium-binding proteins that naturally play an integral role in Ca2+ homeostasis, but due to their ability to bind transition metals, they have also demonstrated an innate immunity role by participating in nutrient sequestration.
The S100 proteins are expressed in all human cells, and all are capable of binding transition metals including zinc, manganese, and cobalt. Calprotectin, S100A7, and S100A12 have demonstrated an ability to hinder the infection potential of pathogenic E. coli, S. aureus, C. albicans, and various other pathogens via zinc sequestration. Herein, we demonstrate that N. gonorrhoeae is able to overcome this phenomenon and actually utilize these proteins as a zinc source in vitro. Furthermore, we identify S100A7 as the specific ligand for TdfJ, which utilizes this ligand to internalize zinc during infection. S100A7 growth support in vitro is dependent upon a functional TonB, TdfJ, and the cognate ABC transport system ZnuABC, and isogenic mutants incapable of producing znuA or tdfJ recover S100A7 utilization by complementation. Whole-cell binding assays and affinity pulldowns show that S100A7 binds specifically to both gonococcal and recombinant TdfJ, and growth and binding experiments show that these described phenomena are specific to human and not mouse S100A7. Finally, we show that a His-Asn double mutant S100A7 that is incapable of binding zinc cannot be utilized for growth by gonococci. These data illustrate the unique nature of the gonococcus’ ability to co-opt host defense strategies for its own purposes, and further identify the TdTs as promising targets for strategies to combat and prevent gonococcal infection.
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Stults, Dawn Michelle. "Human ribosomal RNA gene clusters are recombinational hotspots in cancer." Lexington, Ky. : [University of Kentucky Libraries], 2009. http://hdl.handle.net/10225/1122.
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Thesis (M.S.)--University of Kentucky, 2009.Title from document title page (viewed on May 6, 2009). Document formatted into pages; contains: v, 27 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 25-26).
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Krishnaswamy, Aravind. "BioSpec: A Biophysically-Based Spectral Model of Light Interaction with Human Skin." Thesis, University of Waterloo, 2005. http://hdl.handle.net/10012/1022.
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Despite the notable progress in physically-based rendering, there is still a long way to go before we can automatically generate predictable images of biological materials. In this thesis, we address an open problem in this area, namely the spectral simulation of light interaction with human skin, and propose a novel biophysically-based model that accounts for all components of light propagation in skin tissues, namely surface reflectance, subsurface reflectance and transmittance, and the biological mechanisms of light absorption by pigments in these tissues. The model is controlled by biologically meaningful parameters, and its formulation, based on standard Monte Carlo techniques, enables its straightforward incorporation into realistic image synthesis frameworks. Besides its biophysicallybased nature, the key difference between the proposed model and the existing skin models is its comprehensiveness, i. e. , it computes both spectral (reflectance and transmittance) and scattering (bidirectional surface-scattering distribution function) quantities for skin specimens. In order to assess the predictability of our simulations, we evaluate their accuracy by comparing results from the model with actual skin measured data. We also present computer generated images to illustrate the flexibility of the proposed model with respect to variations in the biological input data, and its applicability not only in the predictive image synthesis of different skin tones, but also in the spectral simulation of medical conditions.
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Lindgren, Susanne. "Reliability of discerning humans using microwave polarisation and diffraction phenomena." Thesis, Mälardalens högskola, Akademin för innovation, design och teknik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-48702.
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Presented here is an examination of the feasibility to utilise basic microwave phenomena for reliable human discernment. Being able to distinguishing a person from other objects is essential around society. For example, near railway tracks where lives could be saved if a system could alert the driver. Microwave technologyhasseveralbenefitsoverotherdetectionsystems. Forexample, itallowscompletelyanonymous detection. Microwavesarealsoinsensitivetodarkness,brightsunlight,andrain. Theprinciplesofantenna polarisation and diffraction phenomena have been investigated with the purpose of locating parameters that can reliable discern a human. By modelling analysis, calculations, examination of related work and measurements, it has been seen that a large number of parameters affect the diffracted fields that occurs around an object under some circumstances. For impartial comparison and the ability to change single parameters at a time, a human phantom has been investigated and constructed. Modelling analysis has been performed in order to visualise how the diffraction changes due to the relationship between object circumference and wavelength, and also due to the dielectric properties of the object. The diffracted fields caused by two different frequencies has been compared, giving a difference signal that in a certain range is potentially reliable for human discernment. Analysis of the measurements conducted in an anechoic chamber show some similarities between the real measurements and the modelled scenarios, and also that the phantom was a successful substitute for a pair of human legs.
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Maja, Wikborg. "The absence of human remains in Valsgärde cemetery. Natural process or ritual phenomena?" Thesis, Uppsala universitet, Institutionen för arkeologi och antik historia, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-324492.
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Lloyd, Kenneth P. "Understanding Human Erythrocyte Glucose Transporter (GLUT1) Mediated Glucose Transport Phenomena Through Structural Analysis." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/962.
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GLUT1-mediated, facilitated sugar transport is proposed to be an example of transport by a carrier that alternately presents exofacial (e2) and endofacial (e1) substrate binding sites, commonly referred to as the alternating access carrier model. This hypothesis is incompatible with observations of co-existent exo- and endofacial ligand binding sites, transport allostery, and e1 ligand (e.g. cytochalasin B) induced GLUT1 sugar occlusion. The fixed-site carrier model proposes co-existent, interacting e2 and e1 ligand binding sites but involves sugar translocation by geminate exchange through internal cavities. Demonstrations of membrane-resident dimeric and tetrameric GLUT1 and of e2, e1 and occluded GLUT conformations in GLUT crystals of monodisperse, detergent-solubilized proteins suggest a third model. Here, GLUT1 is an alternating access carrier but the transporter complex is a dimer of GLUT1 dimers, in which subunit interactions produce two e2 and two e1 conformers at any instant. The crystallographic structures in different conformations can be utilized to further understand the transport cycle, ligand binding behavior and complex kinetics observed in GLUT1. Specifically, the GLUT1 crystal structure and homology models based upon related major facilitator superfamily proteins were used in this study, to understand inhibitor binding, ligand binding induced GLUT1 transport allostery and the existence of helix packing/oligomerization motifs and glycine induced flexibility. These studies suggest that GLUT1 functions as an oligomeric allosteric carrier where cis-allostery is an intramolecular behavior and trans-allostery is an intermolecular behavior. Additionally, mutations of a dynamic glycine affect the turnover of the transporter while mutations to helix packing motifs affect affinity.
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Sage, Jay M. "Support of Mitochondrial DNA Replication by Human Rad51: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/574.
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The function of homologous DNA recombination in human mitochondria has been a topic of ongoing debate for many years, with implications for fields ranging from DNA repair and mitochondrial disease to population genetics. While genetic and biochemical evidence supports the presence of a mitochondrial recombination activity, the purpose for this activity and the proteins involved have remained elusive. The work presented in this thesis was designed to evaluate the mitochondrial localization of the major recombinase protein in human cells, Rad51, as well as determine what function it plays in the maintenance of mitochondrial DNA (mtDNA) copy number that is critical for production of chemical energy through aerobic respiration. The combination of subcellular fractionation with immunoblotting and immunoprecipitation approaches used in this study clearly demonstrates that Rad51 is a bona fide mitochondrial protein that localizes to the matrix compartment following oxidative stress, where it physically interacts with mtDNA. Rad51 was found to be critical for mtDNA copy number maintenance under stress conditions. This requirement for Rad51 was found to be completely dependent on ongoing mtDNA replication, as treatment with the DNA polymerase gamma (Pol ϒ) inhibitor, ddC, suppresses both recruitment of Rad51 to the mitochondria following the addition of stress, as well as the mtDNA degradation observed when Rad51 has been depleted from the cell.
The data presented here support a model in which oxidative stress induces a three-part response: (1) The recruitment of repair factors including Rad51 to the mitochondrial matrix, (2) the activation of mtDNA degradation systems to eliminate extensively or persistently damaged mtDNA, and (3) the increase in mtDNA replication in order to maintain copy number. The stress-induced decrease in mtDNA copy number observed when Rad51 is depleted is likely the result of failure to stabilize or repair replication forks that encounter blocking lesions resulting in further damaged to the mtDNA and its eventual degradation.
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Ng, Li Huang Honey. "Evaluating models of verbal serial short-term memory using temporal grouping phenomena." University of Western Australia. School of Psychology, 2007. http://theses.library.uwa.edu.au/adt-WU2008.0059.
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[Truncated abstract] Various capabilities such as the ability to read or conduct a conversation rely on our ability to maintain and recall information in the correct order. Research spanning more than a century has been devoted to understanding how units of information are retained in order in short-term memory. The nature of the mechanisms that code the positions of items in serial short-term verbal recall can be investigated by examining a set of phenomena that can be termed temporal grouping effects. Inserting extended pauses to break a list of verbal items into sub-lists (e.g. SHD-QNR-BJF, where the dashes represents the pauses) improves the accuracy of serial recall relative to performance observed without this temporal grouping. In addition, two other effects are linked to temporal grouping. One of these effects is a shift in the shape of the serial position function, which changes from a single bowed function to a multiple-bowed function. That is, the serial position curve for ungrouped sequences is typically characterized by better performance for the beginning and ending items compared to the mid-list items. For grouped lists, the multiple-bowed function comprises better recall for the beginning and ending items within each group. Another effect associated with temporal grouping is a change in the patterns of order errors. For ungrouped sequences (e.g. SHDQNRBJF), order errors often involve the swapping of items in neighbouring positions, such as exchanging D for Q or R for B. By contrast, grouped sequences (such as SHD-QNR-BJF) show a reduction in order errors that cross group boundaries such as exchanging items D and Q or R and B; instead, there tend to be an increased incidence of exchanging items that share similar within-group positions such as swapping H and N or Q and B. According to several current models of short-term memory, items are retained by associating them with extra-list information such as contextual information. ... This was done by unconfounding temporal position (time from group onset) and ordinal position (number of items from group onset) for certain key items in sequences comprising two groups of four consonants. The critical manipulation was to vary the SOAs within and across the two groups. Errors that involve items migrating across groups should preserve within-group temporal position according to oscillator models, but should preserve within-group ordinal position according to non-oscillator models. Results from the intergroup errors strongly favored preservation of ordinal rather than temporal position. Finally, the Appendix reports an unpublished experiment that examined patterns of errors in recalling sequences of nine visually presented letters, where the letters were grouped into threes using temporal gaps. A critical manipulation was the insertion of a tobe- ignored item (an asterisk) between the first and second letters of selected groups. Inclusion of this item failed to alter the patterns of errors observed, indicating that the coding of serial position is based on only those events represented for recall. The central conclusion based on all the studies is that serial order for verbal items is retained using contextual positional codes that change with each presentation of a tobe- remembered item, are influenced by large temporal gaps that lead to grouping, but otherwise are not dependent on the timing of events.
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Wright, Kenneth Lynn. "Functional and Structural Characterization of a Human H4 Histone Gene Promoter: a Thesis." eScholarship@UMMS, 1990. https://escholarship.umassmed.edu/gsbs_diss/52.
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Expression of the cell cycle dependent FO10S human H4 histone gene is regulated at both the transcriptional and post-transcriptional levels. We have investigated the 5' promoter elements mediating the transcriptional aspects of its regulation. A detailed in vivo and in vitro transcriptional analysis of promoter deletion mutants from this gene has identified three positive regulatory elements and two potentially negative regulatory elements within the first 1000 base pairs upstream of the transcription initiation site. In addition, the minimal promoter located within the first 70 base pairs is required for accurate transcription initiation and contains one of two in vivo identified protein-DNA interactions, site II. Binding of the nuclear factor HiNF-D to this region was correlated with the turn-on of histone gene transcription following stimulation of quiescent normal diploid fibroblasts to re-enter the proliferative phase. The most proximal positive regulatory element contains the other in vivo identified protein-DNA interaction, site I. Results from a series of in vitroprotein-DNA interaction studies revealed the binding of two nuclear factors to this element. One protein, HiNF-C, is indistinguishable from the transcription factor Sp1 while the other, HiNF-E, is a novel, potentially histone-specific member of the ATF transcription factor family. Binding of HiNF-C was required to stabilize the interaction of HiNF-E and together this region stimulated transcription 5 fold.
The near-distal transcription activator region lies between -418 and -213 base pairs and forms a single protein- DNA complex, H4UA-1. The interaction domain for H4UA-1 contains recognition sequences for both the thyroid hormone receptor and the nuclear factor CTF/NF-1. The far-distal activator region (-730 and -589 base pairs) was the strongest positive regulatory element identified in the H4 promoter. This region increased transcription 10 fold and contains three protein-DNA interactions. One of the factors, H4UA-2, is an ATF transcription factor closely related to the HiNF-E interaction in the proximal positive element.
These studies have defined the functional human H4 histone promoter to be a complex, modular structure extending at least 1000 base pairs.
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Matassini, Lorenzo. "Signal analysis and modelling of non-linear non-stationary phenomena from human voice to financial markets /." [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963273256.
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Lloyd, Janice A. "The Human Rad52 Protein: a Correlation of Protein Function with Oligomeric state: a Dissertation." eScholarship@UMMS, 2002. https://escholarship.umassmed.edu/gsbs_diss/248.
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The regulation of protein function through oligomerization is a common theme in biological systems. In this work, I have focused on the effects of the oligomeric states of the human Rad52 protein on activities related to DNA binding. HsRad52, a member of the RAD52 epistasis group, is thought to play an important and as yet undefined role in homologous recombination. HsRad52 preferentially binds to ssDNA over dsDNA and stimulates HsRad51-mediated strand exchange (Benson et al., 1998). In either the presence or absence of DNA, HsRad52 has been observed to form both 10 nm ring-like structures as well as higher order oligomers consisting of multiple 10 nm rings (Van Dyck et al., 1998; Van Dyck et al., 1999). Earlier protein-protein interaction studies mapped the domain responsible for HsRad52 self-association in the N-terminus (residues 85-159) (Shen et al., 1996). Data presented here identifies a novel self-association domain in the C-terminus of HsRad52 that is responsible for the formation of higher order oligomers.
VanDyck et al. observed DNA ending binding complexes consisting of multiple rings (Van Dyck et al., 1999). They proposed that these higher order oligomers may be functionally relevant. In this work, we demonstrate that DNA binding depends on neither ring shaped oligomers nor higher order oligomers but that activities of HsRad52 that require simultaneous interaction with more than one DNA molecule depend on the formation of higher order oligomers consisting of multiple HsRad52 rings.
Early studies of HsRad52 proposed that the DNA binding domain resides in the highly conserved N-terminus of the protein (Park et al., 1996). A series of studies using truncation mutants of HsRad52 have provided evidence that supports this hypothesis. For example, we demonstrated that a truncation mutant containing only the first 85 residues of the protein is still able to bind DNA (Lloyd, submitted 2002). In this study, we demonstrate that aromatic (Y65, F79 and Y81) and hydrophobic (L43, I52 and I66) residues within the N-terminus contribute to DNA binding by either directly contacting the DNA or by stabilizing the structure of the protein.
In summary, through the work presented in this dissertation, we have determined that the formation of 10 nm rings is mediated by a self-association domain in the N-terminus and that the formation of higher order oligomers consisting of multiple HsRad52 rings is mediated by an additional self-association domain in the C-terminus. We have correlated the oligomeric properties of HsRad52 with its biochemical functions related to DNA binding. Additionally, we have demonstrated that aromatic and hydrophobic residues contribute to DNA binding. Further studies will differentiate between the contribution of these residues to the DNA binding by stabilizing the overall structure of the protein versus making specific DNA contacts. Additional studies will also address how the oligomeric state of HsRad52 contributes to its role in HsRad51-mediated strand exchange.
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Heilman, Susan Ann. "Cooperative Oncogenesis and Polyploidization in Human Cancers: A Dissertation." eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/327.
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A common phenotype observed in most cancers is chromosomal instability. This includes both structural and numerical chromosomal aberrations, which can promote carcinogenesis. The fusion gene CBFB/MYH11 is created by the structural chromosomal inversion(16)(p13.1q22), resulting in the fusion protein CBFβ-SMMHC, which blocks differentiation in hematopoietic progenitor cells. This mutation alone, however, is not sufficient for transformation, and at least one additional cooperating mutation is necessary.
The role of wildtype Cbfb in modulating the oncogenic function of the fusion protein Cbfβ-SMMHC in mice was examined. Transgenic mice expressing the fusion protein, but lacking a wild-type copy of Cbfb, were created to model the effects of these combined mutations. It was found that wild-type Cbfb is necessary for maintaining normal hematopoietic differentiation. Consequently, complete loss of wild-type Cbfb accelerates leukemogenesis in Cbfb/MYH11 mice compared to mice expressing both the fusion and wild-type proteins. While there is no evidence in human patient samples that loss of wild-type Cbfb expression cooperates with the fusion protein to cause transformation, it is apparent from these experiments that wild-type Cbfβ does play a role in maintaining genomic integrity in the presence of Cbfβ-SMMHC. Experiments have also shown that loss of Cbfb leads to accumulation of hematopoietic progenitor cells, which may acquire additional cooperating mutations.
Not unlike CBFB/MYH11, the human papillomavirus (HPV) E6 and E7 proteins are not sufficient for cellular transformation. Instead, high risk HPV E7 causes numerical chromosomal aberrations, which can lead to accumulation of additional cooperating mutations. Expression of HPV-16 E7 and subsequent downregulation of the retinoblastoma protein (Rb) has been shown to induce polyploidy in human keratinocytes. Polyploidy predisposes cells to aneuploidy and can eventually lead to transformation in HPV positive cells.
There are several possible mechanisms through which E7 may lead to polyploidization, including abrogation of the spindle assembly checkpoint, cleavage failure, abrogation of the postmitotic checkpoint, and re-replication. Rb-defective mouse and human cells were found to undergo normal mitosis and complete cytokinesis. Furthermore, DNA re-replication was not found to be a major mechanism to polyploidization in HPV-E7 cells upon microtubule disruption. Interestingly, upon prolonged mitotic arrest, cells were found to adapt to the spindle assembly checkpoint and halt in a G1-like state with 4C DNA content. This post-mitotic checkpoint is abrogated by E7-induced Rb-downregulation leading to S-phase induction and polyploidy.
This dissertation explores two examples of the multi-step pathway in human cancers. While certain genes or genetic mutations are often characteristic of specific cancers, those mutations are often not sufficient for transformation. The genetic or chromosomal abnormalities that they produce often stimulate the additional mutations necessary for oncogenesis. The studies with Cbfb/MYH11 and HPV E7 further exemplify the significance of numerical and structural chromosomal aberrations in multi-step carcinogenesis.
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O'Bryan, Joel M. "Telomere Length Dynamics in Human T Cells: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/568.
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Telomere length has been shown to be a critical determinant of T cell replicative capacity and in vivo persistence in humans. We evaluated telomere lengths in virus-specific T cells to understand how they may both shape and be changed by the maintenance of memory T cells during a subsequent virus re-infection or reactivation. We used longitudinal peripheral blood samples from healthy donors and samples from a long-term HCV clinical interferon therapy trial to test our hypotheses.
To assess T cell telomere lengths, I developed novel modifications to the flow cytometry fluorescence in situ hybridization (flowFISH) assay. These flowFISH modifications were necessary to enable quantification of telomere length in activated, proliferating T cells. Adoption of a fixation-permeabilization protocol with RNA nuclease treatment prior to telomere probe hybridization were required to produce telomere length estimates that were consistent with a conventional telomere restriction fragment length Southern blot assay.
We hypothesized that exposure to a non-recurring, acute virus infection would produce memory T cells with longer telomeres than those specific for recurring or reactivating virus infections. We used two acute viruses, vaccinia virus (VACV) and influenza A virus (IAV) and two latent-reactivating herpesviruses, cytomegalovirus (CMV) and varicella zoster virus (VZV) for these studies. Combining a proliferation assay with flowFISH, I found telomeres in VACV-specific CD4 + T cells were longer than those specific for the recurring exposure IAV; data which support my hypothesis. Counter to my hypothesis, CMV-specific CD4 + T cells had longer telomeres than IAV-specific CD4 + T cells.
We assessed virus-specific CD4 + T cell telomere length in five donors over a period of 8-10 years which allowed us to develop a linear model of average virus-specific telomere length changes. These studies also found evidence of long telomere, virus-specific CD45RA + T cell populations whose depletion may precede an increased susceptibility to latent virus reactivation.
I tested the hypothesis that type I interferon therapy would accelerate T cell telomere loss using PBMC samples from a cohort of chronic hepatitis C virus patients who either did or did not receive an extended course of treatment with interferon-alpha. Accelerated telomere losses occurred in naïve T cells in the interferon therapy group and were concentrated in the first half of 48 months of interferon therapy. Steady accumulation of CD57 + memory T cells in the control group, but not the therapy group, suggested that interferon also accelerated memory turnover.
Based on our data, I present proposed models of memory T cell maintenance and impacts of T cell telomere length loss as we age.
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Xu, Yongqin. "Studies on parental genomic imprinting of insulin-like growth factor-IImannose 6-phosphate receptor gene in humans : phenomenon, mechanism, and relevance to disease." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37552.
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Castillo, Jonathan Patrick. "The Role of Human Cytomegalovirus Immediate Early Proteins in Cell Growth Control: A Dissertation." eScholarship@UMMS, 2002. https://escholarship.umassmed.edu/gsbs_diss/49.
Full textAbstract:
The proper maintenance of the pathways governing cell growth is critical to ensure cell survival and DNA fidelity. Much of our understanding of how the cell cycle is regulated comes from studies examining the relationship between DNA viruses and the mechanisms of cell proliferation control. There are numerous examples demonstrating that viruses can alter the host cell environment to their advantage. In particular, the small DNA tumor viruses, which include adenovirus, simian-virus 40 (SV-40), and human papillomavirus (HPV), can modulate the host cell cycle to facilitate viral DNA replication. Due to the fact that these viruses infect quiescent, non-cycling cells and lack the necessary enzymes and resources to replicate their DNA (e.g. DNA polymerase), the small DNA tumor viruses must activate the host cell replication machinery in order to expedite viral DNA replication. The capacity of these viruses to perturb normal cell proliferation control is dependent upon their oncogene products, which target p53 and members of the Retinoblastoma (RB) family of proteins and inactivate their respective functions. By targeting these key cell cycle regulatory proteins, the small DNA tumor viruses induce the infected host cells to enter S-phase and activate the components involved with host cell DNA synthesis thereby generating an environment that is conducive to viral DNA replication.
In contrast, the larger, nuclear-replicating DNA viruses such as those from the family Herpesviridae, do not share the same stringent requirement as the small DNA viruses to induce the infected host cell to enter S-phase. The herpesviruses encode many of the components to stimulate nucleotide biosynthesis and the necessary factors to facilitate virus DNA replication including a viral DNA polymerase and other accessory factors. Additionally, many herpesviruses encode gene products that arrest the host cell cycle, in most instances, prior to the G1/S transition point. Inducing cells to growth arrest appears to be a prerequisite for the replication of most herpesviruses.
However, in addition to encoding factors that inhibit the cell cycle, many herpesviruses encode proteins that can promote cell cycle progression in a manner similar to the small DNA tumor virus oncoproteins. By targeting members of the RB family and p53 protein, the herpesvirus proteins induce S-phase and activate S-phase associated factors that playa role in DNA replication. In this manner, the herpesviruses may promote an environment that is favorable for DNA replication.
Consistent with the other herpesviruses, human cytomegalovirus (HCMV)induces human fibroblasts to growth arrest. However, in other cell types, virus infection causes cells to enter S-phase. In addition, HCMV replication requires several cellular factors that are present only during S-phase. Furthermore, HCMV induces the activation of S-phase-associated events as well as the increased expression of numerous S-phase genes following infection.
HCMV encodes two immediate early (IE) gene products, IE1-72 and IE2-86, which can interact with members of the RB family of proteins. Additionally, the IE2-86 protein can bind to and inhibit p53 protein function. Given the functional resemblance between the HCMV IE proteins and the oncoproteins of the small DNA tumor viruses, we hypothesized that expression of the HCMV IE proteins could modulate cell cycle control.
Specifically, we determined that expression of either IE1-72 or IE2-86 can induce quiescent cells to enter S-phase and delay cell cycle exit following serum withdrawal. Moreover, IE2-86 mediates this effect in the presence or absence of p53, whereas IE1-72 fails to do so in p53-expressing cells. Furthermore, both IE1-72 and IE2-86 induce p53 protein accumulation that is nuclear localized.
Because IE1-72 fails to promote S-phase entry in cells expressing p53 and induces p53 protein levels, the mechanism by which IE1-72 alters p53 levels was examined. IE1-72 elevates p53 protein levels by inducing both p19ARF protein and an ATM-dependent phosphorylation of p53 at Ser15. IE1-72 also promotes p53 nuclear accumulation by abrogating p53 nuclear shuttling. As consequence of this IE1-72-mediated increase in p53 levels, p21 protein is induced leading to a p21-dependent growth arrest in cells expressing IE1-72.
These findings demonstrate that the HCMV IE proteins can alter cell proliferation control and provide further support to the notion that HCMV, through the expression of its IE proteins, induces S-phase and factors associated with S-phase while blocking cell DNA synthesis, to possibly generate an environment that is suitable for viral DNA replication.
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van, Wijnen Andre John. "Transcriptional Control of Human Histone Gene Expression: Delineation and Regulation of Protein/DNA Interactions: A Thesis." eScholarship@UMMS, 1991. https://escholarship.umassmed.edu/gsbs_diss/237.
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Transcriptional regulation of cell cycle controlled genes is fundamental to cell division in eukaryotes and a broad spectrum of physiological processes directly related to cell proliferation. Expression of the cell cycle dependent human H4, H3 and H1 histone genes is coordinately regulated at both the transcriptional and posttranscriptional levels. We have systematically analyzed the protein/DNA interactions of the immediate 5'regions of three prototypical cell cycle controlled histone genes, designated H4-F0108, H3-ST519 and H1-FNC16, to define components of the cellular mechanisms mediating transcriptional regulation.
Multiple biochemically distinct protein/DNA interactions were characterized for each of these genes, and the binding sites of several promoter-specific nuclear DNA binding activities were delineated at single nucleotide resolution using a variety of techniques. These findings were integrated with results obtained by others and revealed that the in vitro factor binding sites in H4, H3 and H1 histone promoters coincide with genomic protein/DNA interaction sites defined in vivofor the H4-F0108 and H3-STS19 genes, and with evolutionarily conserved cis-acting sequences shown to affect the efficiency of histone gene transcription. Specifically, we have defined binding sites for Sp1, ATF, CP1/NF-Y, HiNF-D, HiNF-M, HiNF-P and HMG-I related factors. Based on sequence-similarities and cross-competition experiments, we postulate that most of these protein/DNA interaction elements are associated with more than one class of histone genes. Thus, the protein/DNA interactions characterized in this study may represent components of a cellular mechanism that couples transcription rates of the various histone gene classes.
Regulation of the protein/DNA interactions involved in transcriptional control of these H4, H3 and H1 histone genes was investigated in a spectrum of cell types using several distinct in vitro cell culture models for the onset of differentiation and quiescence, as well as cell cycle progression. Moreover, we studied control of histone gene associated DNA binding activities during hepatic development from fetus to adult in transgenic mice reflecting the onset of differentiation and quiescence in vivo. We show that the H4 histone promoter protein/DNA interaction mediated by factor HiNF-D is selectivelymodulated, and directly at the level of DNA binding activity, during the entry into, progress through and exit from the cell cycle in normal diploid cells, as well as during hepatic development. The regulation of this protein/DNA interaction occurs in parallel with analogous interactions occurring in H3 and H1 histone genes. Moreover, these proliferation-specific protein/DNA interactions are collectively deregulated during the cell cycle in four distinct cell types displaying properties of the transformed phenotype. Hence, the cellular competency to coordinately transcribe distinct classes of histone genes during the cell cycle may be mediated by the intricate interplay of constitutively expressed general transcription factors and temporally regulated, cell growth controlled nuclear factors interacting specifically with cell cycle dependent histone genes.
Finally, we show that HiNF-D is represented by two electrophoretically distinct species. The ratio of these forms of HiNF-D fluctuates dramatically during the cell cycle of normal diploid cells, but remains relatively constant in tumor cells. Total HiNF-D binding activity embodied by both HiNF-D species is negatively influenced in vitro by incubation with exogenous phosphatase activity. These observations provide a first indication for the hypothesis that HiNF-D may exist in distinct post-translationally modified forms that are subject to a stringent cell growth control mechanism involving protein kinases and phosphatases. Such a cellular post-translational modification mechanism, which directly impinges on (or activates) the DNA binding activity of a key factor controlling histone genes, would provide a highly efficient means by which to influence the rate of transcription in rapid response to intra-cellular requirements for histone mRNA and extra-cellular cues signalling the onset and cessation of cell proliferation.
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Pande, Sandhya. "Regulation of Runx Proteins in Human Cancers: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/559.
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Runt related transcription factors (Runx) play an important role in mammalian development by regulating the expression of key genes involved in cell proliferation, differentiation and growth. The work described in this thesis details the mechanisms by which the activity of two members of this family are regulated in human cells. Chapter One provides a brief introduction of Runx transcription factors.
Chapter Two describes the regulation of Runx2 protein by the PI3 kinase/Akt pathway in human breast cancer cells. The PI3 kinase/Akt pathway is one of the major signal transduction pathways through which growth factors influence cell proliferation and survival. It is also one of the most frequently dysregulated pathways in human cancers. We identify Runx2 protein, a key regulator of breast cancer invasion as a novel substrate of Akt kinase and map residues of Runx2 that are phosphorylated by Akt in breast cancer cells. Our results show that phosphorylation by Akt increases the binding of Runx2 protein to its target gene promoters and we identify the phosphorylation events that enhance DNA binding of Runx2. Our work establishes Runx2 protein as a critical effecter downstream of Akt that regulates breast cancer invasion.
In Chapter Three we describe the subnuclear localization of the tumor suppressor protein Runx3 during interphase and mitosis. We find that similar to other Runx family members, Runx3 protein resides in nuclear matrix associated foci during interphase. We delineate a subnuclear targeting signal that directs Runx3 to these nuclear matrix associated foci. Our work establishes that this association of Runx3 protein with the nuclear matrix plays a vital role in regulating its transcriptional activity.
Chromatin immunoprecipitation results show that Runx3 occupies rRNA promoters during interphase. We also find that Runx3 remains associated with chromosomes during mitosis and localizes with nucleolar organizing regions (NORs), reflecting an interaction with epigenetic potential.
This thesis provides novel insights into various mechanisms by which cells regulate the activity of Runx proteins.
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Xu, Yongqin. "Studies on parental genomic imprinting of insulin-like growth factor-II/mannose 6-phosphate receptor gene in humans, phenomenon, mechanism, and relevance to disease." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0019/NQ44633.pdf.
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Last, Thomas J. "Transcriptional Regulation of a Human H4 Histone Gene is Mediated by Multiple Elements Interacting with Similar Transcription Factors: A Dissertation." eScholarship@UMMS, 1998. https://escholarship.umassmed.edu/gsbs_diss/15.
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Synthesis of histone proteins occurs largely during the S phase of the cell cycle and coincides with DNA replication to provide adequate amounts of histones necessary to properly package newly replicated DNA. Controlling transcription from cell cycle dependent and proliferation specific genes, including histone H4, is an important level of regulation in the overall governance of the cell growth process. Coordination of histone gene transcription results from the cumulative effects of cell signaling pathways, dynamic chromatin structure and multiple transcription factor interactions. The research of this dissertation focused on the characterization and identification of transcription factors interacting on the human histone H4 gene FO108. I also focused on the elucidation of regulatory elements within the histone coding region. Our results suggest a possible mechanism by which a transcription factor facilitates reorganization of histone gene chromatin structure.
The histone promoter region between -418 nt and -215 nt, Site III, was previously identified as both a positive and negative cis-regulatory element for transcription. Results of in vitroanalyses presented in this dissertation identified multiple transcription factors interacting at Site III. These factors include H4UA-1/YY1, AP-2, AP-2 like factor and distal factor (NF-1 like factor). Transient transfection experiments show that Site III does not confer significant influence on transcription; however, there may exist a physiological role for Site III which would not be detected in these assay systems.
We analyzed the histone H4 gene sequences for additional transcription factor binding motifs and identified several putative YY1 binding sites. Using electrophoretic mobility shift assays (EMSA), we found that Site IV, Site I and two elements within the histone H4 coding region are capable of interacting with YY1. In transient transfection experiments using reporter constructs containing either Site III or one of the coding region elements as potential promoter regulatory elements, and an expression vector encoding YY1, we observed levels of expression up to 2.7 fold higher than from the reporters lacking these elements. Therefore, YY1 appears to interact at multiple regulatory sites of the histone gene and can influence transcription through these elements.
Prior to this study, the role of the coding region in histone gene expression was not known. To determine if the coding region is involved in regulating transcription, I constructed and tested a series of heterologous reporter constructs containing various sequences of the histone coding region. Results from these experiments demonstrated that the histone coding region contains three repressor elements. Extensive in vitro analysis indicated that the three repressor elements interact with the repressor CDP/cut. Further analysis showed that CDP/cut interactions with the repressor elements are cell cycle regulated and proliferation specific. CDP/cut interactions increase during the cell cycle when histone transcription decreases. These observations are consistent with the hypothesis that CDP/cutis a cell cycle regulated repressor factor which influences transcription of the histone H4 gene as such.
The proximal promoter region of the histone H4 gene between -70 nt and +190 nt is devoid of normal nucleosome structure. This same region contains multiple CDP/cut binding sites. We hypothesized that CDP/cut is involved with chromatin remodeling of the histone gene. DNase I footprinting and EMSA results show purified recombinant CDP/cut interacts specifically with the histone promoter reconstituted into nucleosome cores. Thus, CDP/cutmay facilitate the organization of chromatin of the histone gene.
In conclusion, the research presented in this dissertation supports the hypothesis that expression from the human histone H4 gene FO108 is regulated by multiple cis-regulatory elements which interact with several proteins. CDP/cut interacts with Site II, the three repressor elements in the histone coding region and at Distal Site I. YY1 interacts at Site IV, Site III, Site I, and twice in the coding region. ATF/CREB interacts with Site IV and Site I. Distal factor interacts with Site III and within the histone coding region. IRF 2 interacts with Site II and Distal Site I. Thus, histone gene expression is probably regulated by transcription factors CDP/cut, YY1, IRF 2 and ATF/CREB interacting with multiple regulatory elements dispersed throughout its promoter and the coding region. Cell cycle regulation of these transcription factors may contribute to cell cycle dependent expression of the histone gene.
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Kayatekin, Can. "The Coupling Between Folding, Zinc Binding, and Disulfide Bond Status of Human Cu, Zn Superoxide Dismutase: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/515.
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Cu, Zn superoxide dismutase (SOD1) is a dimeric, β-sandwich, metalloenzyme responsible for the dismutation of superoxide. Mutations covering nearly 50% of the amino acid sequence of SOD1 have been found to acquire a toxic gain-of-function leading to amyotrophic lateral sclerosis. A hallmark of this disease is the presence of insoluble aggregates containing SOD1 found in the brain and spinal cord. While it is unclear how these aggregates or smaller, precursor oligomeric species may be the source of the toxicity, mutations leading to increased populations of unstable, partially folded species along the folding pathway of SOD1 may be responsible for seeding and propagating aggregation.
In an effort to determine the responsible species, we have systematically characterized the stability and folding kinetics of five well studied ALS variants: A4V, L38V, G93A, L106V and S134N. The effect of the amino acid substitutions was determined on a variety of different constructs characterizing the various post-translational maturation steps of SOD1: folding, disulfide bond formation and Zn binding. Zn was found to bind progressively tighter along the folding pathway of SOD1, minimizing populations of monomeric species. In contrast, ALS variants were found to have the greatest perturbation in the equilibrium populations of the folded and unfolded state for the most immature, disulfide-reduced metal-free SOD1. In this species, at physiological temperature, four out of five ALS variants were >50% unfolded.
Finally the energetic barriers in the folding and unfolding reaction were studied to investigate the unusually slow folding of SOD1. These results reveal that both unfolding and refolding are dominated by enthalpic barriers which may be explained by the desolvation of the chain and provide insights into the role of sequence in governing the folding pathway and rate.
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Silva, Fábio Eduardo da. "Um hipotético efeito antecipatório anômalo para estímulos aparentemente imprevisíveis poderia afetar a tomada de decisão humana?" Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/47/47134/tde-11122014-103827/.
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A pesquisa focaliza-se em experiências supostamente anômalas, especificamente num hipotético efeito antecipatório anômalo (HEAA) o qual prevê que o sistema nervoso responde de forma diferente antes de eventos calmos versus eventos emocionais, isto ocorrendo sob condições que excluem tendências antecipatórias conhecidas (ex. aprendizado implícito) e pistas sensoriais. Busca, uma possível correlação entre HEAA e a Tomada de Decisão (TD) humana. Considera, em especial, o modelo dos marcadores somáticos sobre TD desenvolvida por Antônio Damásio e colaboradores. Em paralelo com esta exploração teórica, desenvolve um estudo experimental que busca replicar estudos prévios do HEAA, registrando dados fisiológicos de participantes antes durante e depois de observarem fotografias, divididas em calmas e emocionais (eróticas e violentas) sendo que as fotografias emocionais foram acompanhadas por estímulos auditivos. Participaram desse estudo 32 colaboradores brasileiros entre 30 e 50 anos de idade (média de 43 anos) e 16 colaboradores estadunidenses entre 22 e 81 anos de idade (média 48) de ambos os sexos (totalizando 16 homens e 32 mulheres, sendo 10 homens e 22 mulheres do Brasil e 6 homens e 10 mulheres dos Estados Unidos), não se constituindo grupos vulneráveis, não havendo distinção ou seleção por classe social, ou qualquer outro critério. Considerando os 48 participantes, três grupos foram constituídos: (1) - Participantes estadunidenses instruídos quanto ao objetivo específico do teste (n=16); (2) - Participantes brasileiros instruídos quanto ao objetivo específico do teste (n=16); (3) - Participantes brasileiros ingênuos quanto ao objetivo específico do teste (n=16); O grupo (1) participou do experimento desenvolvido no laboratório do IONS, nos EUA, enquanto que os grupos (2) e (3) participaram do experimento no CIPE, Brasil. Foram feitas três hipóteses: H1. Espera-se que a média dos resultados da condutância da pele (do período de 6 segundos que antecede a apresentação dos alvos) seja significantemente maior para os alvos emocionais que para os alvos calmos, considerando-se todos os grupos em conjunto. H2. Espera uma correlação positiva e significativa entre os valores de alerta das fotografias utilizadas (segundo avaliação dos participantes da pesquisa) e os valores médios da condutância da pele relativos aos 6 segundos que antecedem a apresentação das fotografias, considerando-se todos os grupos em conjunto. H3. Considerando a comparação das médias dos resultados da condutância da pele (do período de 6 segundos que antecede a apresentação dos alvos) para os alvos emocionais versus calmos o grupo de brasileiros instruídos terá um melhor desempenho que o grupo de brasileiros ingênuos. Em síntese, os resultados gerais suportam, ainda que moderadamente, a existência do HAAE (Hipótese 1). Explorou-se uma forma alternativa de avaliar a emotividade dos estímulos, feita pelos próprios participantes, a qual não tinha sido até então realizada neste tipo de pesquisa. Mesmo com a refutação da hipótese feita para esta avaliação (hipótese 2), explorou-se caminhos alternativos que podem ser úteis em estudos futuros. Também se confirmou a hipótese 3. Nas explorações livres, sobre fatores de personalidade, absorção e características pessoais, foram encontrados resultados coerentes e díspares com a literatura. Na conclusão sobre as características neuropsicológicas da TD e do HAAE refletiu-se que as semelhanças são favoráveis à perspectiva de um fenômeno modelo integrativoThis research focuses on allegedly anomalous experiences, specifically a hypothetical anomalous anticipatory effect (HAAE) which predicts that the nervous system responds differently before calm versus emotional events, that occur under conditions that exclude known anticipatory trends (eg implicit learning) and sensory cues. Search also a possible correlation between HAAE and human Decision Making (DM). Considers, in particular, the DM somatic markers model developed by Antonio Damasio and colleagues.In parallel with this theoretical exploration, develops an experimental study that seeks to replicate previous studies of HAAE, recording physiological data from participants before during and after observing pictures , divided into calm and emotional (erotic and violent) being that emotional pictures were accompanied by auditory stimuli. There were 32 Brazilian participants between 30 and 50 years of age (mean 43 years), and 16 U.S. participants between 22 and 81 years ( mean 48 ) of both sexes (totaling 16 men and 32 women, 10 men and 22 women in Brazil and 6 men and 10 women in the United States). They do not constitute vulnerable groups, with no distinction or selection by social class, or any other criteria. Considering the 48 participants, three groups were formed: (1) - U.S. Participants instructed as to the specific purpose of testing (n = 16) , (2) - Brazilian participants instructed as to the specific purpose of testing (n = 16) , (3) - Brazilian participants naive as to the specific purpose of testing (n = 16), group (1) participated in the experiment carried out in the IONS laboratory in the U.S. , while the groups (2) and (3) participated in the experiment in CIPE, Brazil.Three hypotheses were made. H1. It was expected that the results of the average skin conductance (in the 6 seconds prestimulus period) would be significantly higher for the emotional targets than for calm ones, considering all groups together. H2. It was expected a positive and significant correlation between the values of the alert photographs used (according to the participants evaluation) and the mean values of skin conductance for the 6 seconds prior to pictures presentation, considering all groups together. H3. Considering the comparison of skin conductance mean values (in the 6 seconds prestimulus period) for emotional versus calm targets, the Brazilian participants instructed group would have a better performance than the naive group of Brazilians. In summary, the overall results we found supported, albeit slightly, the existence of HAAE (hypothesis 1). We explored an alternative way to assess the emotionality of the stimuli (by the participants evaluation), which had not been hitherto performed in this type of research. Even with the refutation of the hypothesis made for this evaluation (hypothesis 2), we found alternative paths that can be tested in future studies. We confirmed the hypothesis 3 and in the \"free\" explorations, NEO PI personality factors, personal characteristics and absorption were considered, and we found mixed and consistent results with the literature. Finally, when comparing the neuropsychological characteristics of DM and HAAE we concluded that the similarities are favorable to consider them as an integrative phenomenon
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Shandilya, Shivender. "Structural Studies of the Anti-HIV Human Protein APOBEC3G Catalytic Domain: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/562.
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HIV/AIDS is a disease of grave global importance with over 33 million people infected world-wide and nearly 2 million deaths each year. The rapid emergence of drug resistance, due to viral mutation, renders anti-retroviral drug candidates ineffective with alarming speed and regularity. Instead of targeting mutation prone viral proteins, an alternative approach is to target host proteins that interact with viral proteins and are critical for the HIV life-cycle. APOBEC3G is a host anti-HIV restriction factor that can exert tremendous negative pressure by hypermutating the viral genome and has the potential to be a promising candidate for anti-retroviral therapeutic research.
The work presented in this thesis is focused on investigating the A3G catalytic domain structure and implications of various observed structural features for biological function. High-resolution crystal structures of the A3G catalytic domain were solved using data from macromolecular X-ray crystallographic experiments, revealing a novel intermolecular zinc coordinating motif unique to A3G. Major intermolecular interfaces observed in the crystal structure were investigated for relevance to biochemical activity and biological function.
Co-crystallization with a small-molecule A3G inhibitor, discovered using high-throughput screening assays, revealed a cysteine residue near the active site that is critical for inhibition of catalytic activity by catechol moieties. The serendipitous discovery of covalent interactions between this inhibitor and a surface cysteine residue led to further biochemical experiments that revealed the other cysteine, near the active site, to be critical for inhibition.
Computational modeling was used to propose a steric-hinderance based mechanism of action that was supported by mutational experiments. Structures of other human APOBEC3 homologs were modeled using in-silico methods examined for similarities and differences with A3G catalytic domain crystal structures. Comparisons based on these homology models suggest putative structural features that may endow substrate specificity and other characteristics to the APOBEC3 family members.
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Harris, Alan C. Jr. "N-methyl 4-methyl amphetamine N-alkyl chain extension differentially affects ion flux at the human dopamine and norepinephrine transporters." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4440.
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Amphetamine (AMPH) and its derivatives embody a remarkable breadth of pharmacology. These molecules exert their effects, both therapeutic and pathological, at the human monoamine transporters, which tune synaptic dynamics by evacuating monoamine neuromodulators from the synapse subsequent to neuronal impulses. These transporters are electrogenic, and the transporter-mediated current can be correlated to a surrogate measure of the change in membrane voltage: Ca++ currents from co-transfected L-type Ca++ channels. The present work makes use of this assay, with which it is possible to derive pharmacodynamic metrics from both substrates and inhibitors. This work presents data on a heretofore-unstudied class of amphetamine analogs: the enantiomers of N-Me 4-Me AMPH and N-Et 4-Me AMPH. Remarkably, while both enantiomers of the N-Me version of this compound function as substrates at hDAT, both enantiomers of the N-Et version are inhibitors. This switch does not occur at hNET, where all enantiomers of both N-Me and N-Et 4-Me AMPH function as substrates. Further, (S)-N-Et 4-Me AMPH is a substrate at dDAT. EC50 and IC50 values for all drugs at both transporters are presented. I present the results of super-resolution microscopic co-localization studies on the plasmalemmal spatial relation of the human dopamine transporter and voltage gated calcium channel, L-type 1.2 (CaV1.2). I discuss future aims toward a unified understanding of the mechanisms of monoamine transporter function, with an emphasis on what amphetamine can illuminate in this regard.