Дисертації: "Department of Human Biology"

1

Gerow, Lynn Ellen. "Children's understanding of human biology /." view abstract or download file of text, 2000. http://wwwlib.umi.com/cr/uoregon/fullcit?p9963444.

Повний текст джерела

Анотація:

Thesis (Ph. D.)--University of Oregon, 2000.
Typescript. Includes vita and abstract. Includes bibliographical references (leaves 110-113). Also available for download via the World Wide Web; free to University of Oregon users. Address: http://wwwlib.umi.com/cr/uoregon/fullcit?p9963444.

Стилі APA, Harvard, Vancouver, ISO та ін.

2

Hedley, Paula Louise. "Molecular and functional characterisation of Long QT Syndrome causing genes." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/86480.

Повний текст джерела

Анотація:

Thesis (PhD)-- Stellenbosch University, 2014.
ENGLISH ABSTRACT: Ventricular arrhythmias are the most important cause of sudden cardiac death (SCD) among adults living in industrialised nations. Genetic factors have substantial effects in determining population-based risk for SCD and may also account for inter-individual variability in susceptibility. Great progress has been made in identifying genes underlying various Mendelian disorders associated with inherited arrhythmia susceptibility. The most well studied familial arrhythmia syndrome is the congenital long QT syndrome (LQTS) caused by mutations in genes encoding subunits of myocardial ion channels. Not all mutation carriers have equal risk for experiencing the clinical manifestations of disease (i.e. syncope, sudden death). This observation has raised the possibility that additional genetic factors may modify the risk of LQTS manifestations. This study establishes the genetic aetiology of LQTS in South Africa and Denmark through the identification and characterisation of LQTS-causative mutations in five previously identified genes, as well as examining possible novel genetic causes of LQTS in a cohort comprising Danish and British probands. We have functionally characterised several of the mutations identified in this study and examined other cardiac phenotypes that may be explained by variants causing repolarisation disorders.
AFRIKAANSE OPSOMMING: Ventrikulêre aritmie bly die enkele belangrikste oorsaak van skielike hart dood (SCD) onder volwassenes wat in geïndustrialiseerde lande woon. Genetiese faktore het aansienlike gevolge in die bepaling van bevolking-gebaseerde risiko vir SCD en kan ook verantwoordelik wees vir die inter-individuele variasie in vatbaarheid. Groot vordering is gemaak in die identifisering van gene onderliggende verskeie Mendeliese siektes wat verband hou met geërf aritmie vatbaarheid. Die mees goed bestudeerde familie aritmie sindroom is die aangebore lang QT-sindroom (LQTS) wat veroorsaak word deur mutasies in gene kode subeenhede van miokardiale ioonkanale. Nie alle mutasie draers het 'n gelyke risiko vir die ervaring van die kliniese manifestasies van die siekte (dws sinkopee, skielike dood). Hierdie waarneming het die moontlikheid genoem dat genetiese faktore anders as die primêre siekte-verwante mutasie kan die risiko van LQTS manifestasies verander. Hierdie studie stel die genetiese oorsake van LQTS in Suid-Afrika en Denemarke deur die identifisering en karakterisering van LQTS-veroorsakende mutasies in vyf voorheen geïdentifiseer gene, asook die behandeling van moontlike nuwe genetiese oorsake van LQTS in 'n groep wat bestaan uit van die Deense en die Britse probands. Ons het funksioneel gekenmerk verskeie van die mutasies wat in hierdie studie ondersoek en ander kardiovaskulêre fenotipes wat deur variante veroorsaak repolarisasie versteurings verduidelik word.
South African National Research Foundation
Harry and Doris Crossley Foundation
Danish Strategic Research Foundation.

Стилі APA, Harvard, Vancouver, ISO та ін.

3

Huguet, Emmanuel L. "Wnt genes in human breast biology." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297228.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

4

Liu, Binlei. "Molecular biology of human enteric caliciviruses." Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242419.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

5

Nibbe, Rod K. "Systems Biology of Human Colorectal Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1264179836.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

6

King, L. A. "Molecular biology of insect picornaviruses." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370278.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

7

Kwok, Wai-shun, and 郭威信. "An analysis of human resource management in the Fire Services Department." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B46757648.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

8

Yan, Sheng. "Evaluation of human respiratory muscle fatigue." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41180.

Повний текст джерела

Анотація:

The first part of my work evaluates bilateral supramaximal transcutaneous phrenic nerve stimulation as a diagnostic test for respiratory muscle fatigue. I found that twitch transdiaphragmatic pressure (Pdi,T) was inversely and linearly related to lung volume (V$ sb{ rm L}$) both before and after fatigue. Although fatigue caused significant decrease in Pdi,T amplitude at all V$ sb{ rm L}$, the fractional decrease in Pdi,T was greater at high V$ sb{ rm L}$, indicating the importance of V$ sb{ rm L}$ as an independent variable that needs to be controlled whenever Pdi,T is determined. Twitch mouth pressure (Pm,T) was found to be linearly related to twitch esophageal pressure (Pes,T), to Pdi,T, and to V$ sb{ rm L}$. All these relationships were reproducible. Diaphragmatic fatigue resulted in significant decrease in Pm,T proportional to the decrease in Pdi,T for a given V$ sb{ rm L}$ so that Pm,T-Pes,T and Pm,T-Pdi,T relationships were unchanged. Thus the Pm,T-V$ sb{ rm L}$ relationship can be used to assess diaphragmatic fatigue non-invasively. Paired phrenic nerve shocks which were well tolerated by normal subjects can be used to obtain a measure of the pressure-frequency curves of the diaphragm, which were reproducible. In particular, I showed that the pressure ratio of diaphragmatic twitch elicited by the second shock at 10Hz over that at 100Hz (T2$ sb{10/100}$) is a valuable index of low frequency fatigue.
In the second part of my work I studied the effect of respiratory muscle fatigue on ventilatory response to CO$ sb2$ and respiratory muscle recruitment. The data showed that ventilatory response and respiratory muscle recruitment patterns were different in a number of aspects between diaphragmatic fatigue and global inspiratory muscle fatigue. After diaphragmatic fatigue, the only change was an increase in the recruitment of rib cage muscles, which fully compensated for decreased diaphragmatic contractility because all the ventilatory parameters were constant. After global fatigue, both the diaphragm and rib cage muscles contributed less to breathing but expiratory muscles were recruited resulting in a decrease in end-expiratory P$ sb{ rm L}$ and an increased contribution of elastic energy stored within the respiratory system to inspiratory tidal volume generation. In spite of this, rapid shallow breathing developed while minute ventilation remained constant. These data suggest that the ventilatory control system can detect fatigue and has sufficient plasticity to alter inspiratory drive appropriately. The overall ventilation level can thus be maintained.

Стилі APA, Harvard, Vancouver, ISO та ін.

9

Woods-Samuels, Patricia. "Nonhomologous recombination in the human genome : deletions and insertions in the human factor VIII gene /." The Ohio State University, 1989. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487676261011256.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

10

Nair, Parameswaran K. O'Byrne Paul M. "Novel cysteinyl leukotriene biology in human airways /." [Hamilton, Ont.] : McMaster University, 2004.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

11

Lohmueller, Jason Jakob. "Synthetic Biology Approaches to Engineering Human Cells." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11030.

Повний текст джерела

Анотація:

The field of synthetic biology seeks to revolutionize the scope and scale of what is currently feasible by genetic engineering. By focusing on engineering general signal processing platforms using modular genetic parts and devices rather than `one-off' systems, synthetic biologists aim to enable plug-and-play genetic circuits readily adaptable to different contexts. For mammalian systems, the goal of synthetic biology is to create sophisticated research tools and gene therapies. While several isolated parts and devices exist for mammalian systems there are few signal processing platforms available. We addressed this need by creating a transcriptional regulatory framework using programmable zinc finger (ZF) and TALE transcription factors and a conceptual framework for logical T-cell receptor signaling. We first engineered a large set of ZF activator and repressor transcription factors and response promoters. ZFs are scalable elements as they can be engineered to bind to given DNA sequences. We demonstrated that we could ‘tune’ the activity of the ZF transcription factors by fusing them to protein homo-dimerization domains and by modifying their response promoters. We also created OR and NOR logic gates using hybrid promoters and AND and NAND logic gates by reconstituting split zinc finger activators and repressors with split inteins. Next, using a computational algorithm we designed a series of TALE transcriptional activators and repressors predicted to be orthogonal to all 2kb human promoter regions and thus minimally interfere with endogenous gene expression. TALEs can be designed to bind to even longer DNA sequences than ZFs, however off-target binding is predicted to occur. We tested our computationally designed TALEs in human cells demonstrating that they activated their intended target genes, but not their likely endogenous off-target genes, nor synthetic promoters with binding site mismatches. Finally, we created a conceptual framework for logical T-cell-mediated killing of target cells expressing combinations of surface antigens. The systems consist of conventional and novel chimeric antigen receptors (CARs) containing inhibitory or co-stimulatory cytoplasmic signaling domains. In co-incubation assays of engineered T-cells with target cells we demonstrated a functioning OR-Gate system and progress toward development of a functional NOT-Gate system using the CD300a and CD45 inhibitory receptor domains.

Стилі APA, Harvard, Vancouver, ISO та ін.

12

Robinson, Jayne. "The molecular biology of human enteric caliciviruses." Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302313.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

13

Trundley, Anita Elizabeth. "Aspects of human uterine NK cell biology." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620028.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

14

Malak, Tawfik M. "Structural biology of the human fetal membranes." Thesis, University of Leicester, 1995. http://hdl.handle.net/2381/34151.

Повний текст джерела

Анотація:

During pregnancy the fetus is surrounded by amniotic fluid which is enclosed within a sac formed by the fetal membranes. They maintain their structural integrity and remain intact until after the onset of labour at term. The structural characteristics of the fetal membranes is not established. It is not known therefore how they remain intact dtiring pregnancy and why they rupture easily during labour at term in comparison to earlier gestations. This knowledge is essential to understand why they sometimes rupture before the onset of labour leading to serious maternal and fetal complications. Immunohistochemical, immunofluorescence, and electron microscopic techniques are used to study the histological characteristics of the non-infected fetal membranes that spontaneously rupture at term after the onset of labour and to investigate the distribution and organization of the structural integrity-maintaining factors e.g. extracellular matrix, cytoskeletal, and cell-cell and cell-matrix adhesion molecules. A semi-quantitative immunofluorescence technique for the confocal laser microscopy is developed to measure the density and content of these factors. A novel zone of altered membrane structure is detected within the rupture site. It shows altered organization, density and content of the structural integrity- maintaining factors in comparison to the membranes obtained away from the rupture site where these factors are found to be distributed and integrated in such fashion to confer strength to the membranes. These alterations indicate that this zone is structurally the weakest area of the membranes and represent overlapping features of degradation and matrix deposition. These features together with the detected increase in tenascin expression and number of the myofibroblasts are analogous to those seen in a 'wound response'. A balance between these overlapping features keeps this zone intact during pregnancy and during labour membrane rupture may be facilitated by the presence of this structurally weak zone. The rupture site is then formed by tearing and extension of the initial rupture point during labour and delivery. The similarity of the membrane structural changes to those detected in the cervix and vagina at term indicates that they are a part of a preparatory phase necessary to prepare these structure to the events of labour. If these changes become severe they may predispose the fetal membranes to their prelabour rupture.

Стилі APA, Harvard, Vancouver, ISO та ін.

15

Nie, Yan. "Structural Molecular Biology of Human TFIID Complexes." Thesis, Grenoble, 2012. http://www.theses.fr/2012GRENV062/document.

Повний текст джерела

Анотація:

Les complexes multi-protéiques jouent un rôle crucial dans les cellules vivantes en catalysant et servant d'intermédiaires entre pratiquement toutes les activités cellulaires essentielles. Cependant, un grand nombre de ces machines se trouvent en très faibles quantités dans les cellules en particulier en ce qui concernent les complexes eucaryotes. Ceci est réfractaire à leur extraction à grande échelle et empêche sévèrement l'élucidation de leur structure et fonction. Dans le but de rendre les complexes multi protéiques accessibles par la voie de production recombinante, le groupe Berger a mis au point un ensemble de systèmes d'expression sur mesure pour la surproduction de complexes multi protéiques dans différents organismes hôtes incluant E. coli, les cellules d'insectes et les cellules de mammifères. Ces systèmes et en particulier le système MultiBac baculovirus/cellules d'insecte ont d'ors et déjà grandement contribués à l'étude de l'assemblage structural et fonctionnel à l'échelle moléculaire et atomique de nombreux complexes multi protéiques importants. Cela inclut en particulier le facteur général humain de transcription TFIID, un complexe de ~1.5 MDa qui constitue le sujet de recherche du laboratoire Berger. Mes contributions dans le développement de la technologie pour la production et dans l'élucidation des complexes TFIID humains sont discutées en détails dans cette thèse
Multiprotein complexes play a crucial role in living cells by catalyzing and mediating virtually all essential cellular activities. However, many of these essential machines exist in very low endogenous amount in cells, in particular for eukaryotic complexes. This is refractory to large-scale extraction from native source material, severely impeding the elucidation of their structure and function. In order to make multiprotein complexes accessible by means of recombinant production, the Berger laboratory has developed an array of advanced expression systems tailor-made for overproducing multiprotein complexes in various host organisms including E. coli, insect cells and mammalian cells. Those systems, in particular the MultiBac baculovirus/insect cell system have already greatly contributed to studying the structural and functional assemblies of numerous important multiprotein complexes in molecular and atomic detail. Notably, this includes also the human general transcription factor TFIID, a ~1.5 MDa complex, which is the research focus of the Berger laboratory. My contributions to the expression technology development and to the structural elucidation of human TFIID complexes are discussed in details in this thesis

Стилі APA, Harvard, Vancouver, ISO та ін.

16

Chen, Luxi. "Human Innate Lymphoid Cell Biology and Development." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1551901769401192.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

17

Paul, E. C. A. "The biology of tubulin in Physarum." Thesis, University of Kent, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371147.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

18

Sung, Ching-Ching. "Gangliosides in human primary brain tumors /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487864986609959.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

19

Gould, David R. (David Ross). "Prolactin in human breast cancer." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41006.

Повний текст джерела

Анотація:

The function of prolactin in human breast cancer was studied using four different approaches. First, purification and characterization of the prolactin receptor from breast cancer cells indicated that the receptor has a molecular mass of 88 000 Da, 67 000 Da being protein, and the other 21 000 Da presumably carbohydrate. Secondly, prolactin was tested for mitogenic activity in breast cancer in vitro. No consistent mitogenic response to prolactin could be demonstrated in these experiments. Thirdly studies upon the regulation of the prolactin receptor in breast cancer cells indicated that the prolactin receptor is stimulated by lactogen, estrogen and progesterone at the protein level. Estrogen, progesterone, thyroid hormone, and forskolin (but not lactogen) increase prolactin receptor steady state RNA levels, and the phorbol ester PMA and retinoic acid inhibited receptor RNA levels. However, effects at the RNA level were of a much lesser magnitude than effects at the protein level. Mechanisms other than transcriptional regulation alone are likely involved in prolactin receptor regulation. Fourthly, prolactin receptor and prolactin inducible protein/gross cystic disease fluid protein (PIP/GCDFP-15) RNA levels were examined in breast cancer tumors. Highly significant correlations were observed between the prolactin receptor and the progesterone receptor; the prolactin receptor and PIP/GCDFP-15; and PIP/GCDFP-15 and progesterone receptor.

Стилі APA, Harvard, Vancouver, ISO та ін.

20

Weirather, Jason Lee. "Computational approaches to the study of human trypanosomatid infections." Thesis, The University of Iowa, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3609102.

Повний текст джерела

Анотація:

Trypanosomatids cause human diseases such as leishmaniasis and African trypanosomiasis. Trypanosomatids are protists from the order Trypanosomatida and include species of the genera Trypanosoma and Leishmania, which occupy a similar ecological niche. Both have digenic life-stages, alternating between an insect vector and a range of mammalian hosts. However, the strategies used to subvert the host immune system differ greatly as do the clinical outcome of infections between species. The genomes of both the host and the parasite instruct us about strategies the pathogens use to subvert the human immune system, and adaptations by the human host allowing us to better survive infections. We have applied unsupervised learning algorithms to aid visualization of amino acid sequence similarity and the potential for recombination events within Trypanosoma brucei 's large repertoire of variant surface glycoproteins (VSGs). Methods developed here reveal five groups of VSGs within a single sequenced genome of T. brucei, indicating many likely recombination events occurring between VSGs of the same type, but not between those of different types. These tools and methods can be broadly applied to identify groups of non-coding regulatory sequences within other Trypanosomatid genomes. To aid in the detection, quantification, and species identification of leishmania DNA isolated from environmental or clinical specimens, we developed a set of quantitative-PCR primers and probes targeting a taxonomically and geographically broad spectrum of Leishmania species. This assay has been applied to DNA extracted from both human and canine hosts as well as the sand fly vector, demonstrating its flexibility and utility in a variety of research applications. Within the host genomes, fine mapping SNP analysis was performed to detect polymorphisms in a family study of subjects in a region of Northeast Brazil that is endemic for Leishmania infantum chagasi, the parasite causing visceral leishmaniasis. These studies identified associations between genetic loci and the development of visceral leishmaniasis, with a single polymorphism associated with an asymptomatic outcome after infection. The methods and results presented here have capitalized on the large amount of genomics data becoming available that will improve our understanding of both parasite and host genetics and their role in human disease.

Стилі APA, Harvard, Vancouver, ISO та ін.

21

Zhong, Wangjian. "Regulatory effect of human c-reactive protein on human neutrophil activities : chemotaxis, respiratory burst, and their signaling /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488186329502093.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

22

Vendette, Marc. "Recombinant human prorenin expression in baculovirus-infected cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0001/MQ44309.pdf.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

23

Kauffman, Robert Clark. "Genetic Diversity of RT-SHIV Viremia and Viral Reservoirs in a Non-human Primate Model of Human HIV-1 Highly Active Antiretroviral Therapy." Thesis, University of California, Davis, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3626762.

Повний текст джерела

Анотація:

In most human immunodeficiency virus type 1 (HIV−1) infected individuals, highly active antiretroviral therapy (HAART) suppresses viremia to levels below standard clinical detection limits and delays the progression to AIDS. More sensitive assays have demonstrated that low−level residual viremia is present during HAART. Furthermore, viremia rebounds upon cessation of therapy and thus, life−long treatment is required to prevent the progression to AIDS. This is presumably due to viral persistence within anatomical and cellular viral reservoirs that are not eliminated during long−term HAART. During HAART, viral persistence has been principally attributed to a latent viral reservoir; however, instances of complete viral replication cycles, termed residual replication, may occur. Human studies have provided evidence for and against the hypothesis that residual replication occurs in tissues and contributes to residual viremia.

To address questions regarding viral persistence, this dissertation research utilized a rhesus macaque model of HIV−1 HAART. This model uses RT−SHIV, a chimeric simian immunodeficiency virus (SIV) with the HIV−1 reverse transcriptase (RT) replacing the native SIV RT gene. This modification renders RT−SHIV susceptible to non−nucleoside RT inhibitors, which are an important component of frontline therapies. Chapter 2 describes a longitudinal phylogenetic analysis of residual viremia during 42 weeks of therapy in five macaques that initiated HAART eight weeks after infection. This is the first non−human primate phylogenetic study to characterize residual viremia for a period greater than five weeks. The results did not provide substantial evidence that residual replication contributed to residual viremia. Additionally, one of the five macaques maintained a predominant plasma clone (PPC) population, which is an enigmatic feature of human residual viremia. Chapter 3 describes viral DNA diversification in lymphoid and gastrointestinal tissues relative to pre−HAART viremia. Similar to many human studies, there was no discernible evidence of residual replication or selection of resistance mutations. The origins of PPC populations were also not identified. Importantly, this dissertation advances the relevancy of HAART in RT−SHIV infected macaques as a model of human HAART. Thus, this model may be ideal in studies designed to improve human health, investigate the nature of viral persistence, and potentially develop a cure for HIV−1.

Стилі APA, Harvard, Vancouver, ISO та ін.

24

Munn, Kemal. "Analysis of XYZ company's powder transfer in the processing department." Menomonie, WI : University of Wisconsin--Stout, 2006. http://www.uwstout.edu/lib/thesis/2006/2006munnk.pdf.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

25

Huard, Sylvain. "Human telomerase determinants of processivity and fidelity." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85075.

Повний текст джерела

Анотація:

Telomeres are dynamic nucleoprotein complexes that protect the fragile termini of chromosomes. Without telomeres, chromosome ends are recognized as DNA breaks and inclined to nucleolytic degradation and end-to-end fusions. Telomeres consist of DNA repeats that are synthesized by telomerase, a specialized reverse transcriptase (RT) enzyme minimally composed of a catalytic protein subunit (TERT) and an essential RNA component (TR). Although the functional aspects of telomerase are not well elucidated, this ribonucleoprotein enzyme clearly regulates cellular life-span through its ability to maintain or elongate telomeres. Human TERT (hTERT) has a central region containing conserved (RT)-like motifs, and N- and C-terminal regions that are unique to the TERT family. We analysed the precise role of the C-terminus of hTERT by introducing small deletions and amino acid substitutions throughout the C-terminal region, and demonstrated that the hTERT C-terminal region is essential for enzyme catalysis in vitro. We reported that hTERT multimerization requires the presence of catalytically essential C-terminal amino acid residues and intact RT-like motifs on the same hTERT molecule. We also examined DNA synthesis at nucleotide resolution with a direct primer extension assay, and found that the hTERT C-terminus modulates telomerase processivity. In addition, we reported that human telomerase reconstituted in rabbit reticulocyte lysate (RRL) and partially purified telomerase from human cells catalyze the cleavage of DNA substrates prior to their elongation. Finally, we determined the experimental conditions for human telomerase expression in insect cells in order to obtain an abundant source of catalytically active recombinant telomerase.

Стилі APA, Harvard, Vancouver, ISO та ін.

26

Zhao, Shijie Ph D. Massachusetts Institute of Technology. "Evolutionary dynamics of the human gut microbiome." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122423.

Повний текст джерела

Анотація:

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 156-168).
The composite members of the human gut microbiome encounter a myriad of selective pressures from the host environment and other microbial members in the ecosystem. Understanding the evolutionary dynamics of microbial species in the gut microbiome requires sequencing information that differentiates strains and even single cells. In this thesis, I present efforts that investigate the evolution of bacterial strains in their complex natural environments. In the first project, I discover that a commensal species, Bacteroides fragilis, undergoes within-person adaptive evolution in the absence of antibiotics. Combining culture-based whole genome sequencing with metagenomes, I uncover genes important to B. fragilis survival in the human gut microbiome and describe evolutionary dynamics within individuals and across populations. In the second project, I developed a strain-tracking method that predicts personal microbiomes. Using this method to track closely-related strains, I discover signals of adaptive evolution for Bacteroidetes strains, potentially over decades of colonization in adult twins. In the final project, this strain-tracking method is applied to advance the analysis of microbial transmission within social networks of Fiji islanders. These projects demonstrate the power of genome-resolved and strain-resolved methods in revealing insights of evolutionary dynamics of the gut microbiome. Future studies are expected to further investigate other taxonomical groups in depth and technical breakthroughs are needed to improve the throughput of evolutionary studies of complex systems like the gut microbiome.
by Shijie Zhao.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biology

Стилі APA, Harvard, Vancouver, ISO та ін.

27

Belzile, Jean-Philippe. "Redirecting lentiviral integration : a study of human immunodeficiency virus integrase." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97906.

Повний текст джерела

Анотація:

Despite great advances in our understanding of the human immunodeficiency virus (HIV) life cycle, the mechanisms that underlie the progression of HIV from cellular entry of the viral core to stable integration of the provirus are poorly understood. Sites of integration of the HIV provirus are distributed along the full length of actively transcribed genes and appear to be determined through protein-protein interactions between the viral integrase and cellular proteins.
Two cellular proteins have been proposed to perform integration targeting roles, the chromatin-remodeling factor integrase interactor 1 (INI1/hSNF5/BAF47) and the lens epithelium-derived growth factor/transcriptional co-activator (LEDGF). Here, we report the initiation of two novel integration assays to study the contribution of INI1 and LEDGF in target site selection. Elucidating these molecular determinants and their functional implications is also of particular interest to anti-HIV therapy and could have major impact on the safety of gene therapy protocols.

Стилі APA, Harvard, Vancouver, ISO та ін.

28

Raiser, David Michael. "Interrogation of the RP-MDM2-P53 Axis in Human Ribosomopathies." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467484.

Повний текст джерела

Анотація:

Ribosomopathies such as Diamond-Blackfan anemia (DBA) and 5q- syndrome are human diseases characterized by heterozygous loss or mutation of ribosome-associated genes. Hallmarks of these diseases include a macrocytic anemia in an otherwise normocellular bone marrow and, in some cases, developmental defects such as craniofacial or thumb abnormalities. Haploinsufficiency of ribosome-associated genes leads to dysfunctional ribosome biogenesis, which ultimately results in inhibition of MDM2 and consequent aberrant activation of the p53 pathway. Multiple genetic models have shown that p53 loss partially or completely rescues phenotypes associated with ribosomal protein (RP) haploinsufficiency, implicating p53 as the primary driver of those phenotypes in these diseases. However, the details of the molecular cascade leading to p53 activation – the RP-MDM2-p53 axis – are not fully understood. The thesis work presented here aimed to better characterize the molecular players downstream of ribosome dysfunction involved in modulation of ribosomopathy-associated phenotypes, as well as to identify novel therapeutic opportunities. The proteomics screen characterized the protein binding partner profiles of MDM2 in cells with and without ribosome dysfunction. We found several RPs, including RPL5, RPL11, RPL23, and RPL38, to be commonly associated with MDM2, though RP deficiency may enhance the binding of RPL5 and RPL11. We also identified IGF1R as associated with MDM2 and selectively degraded in RP-deficient hematopoietic stem and progenitor cell (HSPC) cultures, and we showed that this protein loss contributes to defective erythropoiesis. In addition, a chemical screen identified calmodulin inhibitors as effective in rescuing ribosomopathy-associated phenotypes in zebrafish, mouse, and primary human HSPC models. We showed that these compounds (including the antipsychotic trifluoperazine) modulated p53 activity by inhibiting its nuclear localization, probably through inhibition of calmodulin-dependent CHK2. Lastly, we found that heterozygous RP gene deletion is a common feature of many human cancers. We further showed that silencing of a number of RPs frequently deleted in cancer results in p53 pathway activation, and that RP-deleted cancers have defects in ribosomal RNA processing. Together, this work adds novel insight to several aspects of ribosomopathy pathology and the RP-MDM2-p53 axis, and it further provides foundational evidence for novel therapeutic approaches to both ribosompathies and RP-deficient cancers.
Medical Sciences

Стилі APA, Harvard, Vancouver, ISO та ін.

29

Patel, Amar. "The effects of human heme oxygenase-1 (hHO-1) on wild type and mutant (A30P) alpha-synuclein expression in human neuroblastoma cells /." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98762.

Повний текст джерела

Анотація:

Alpha-synuclein is a major protein constituent of neuronal Lewy bodies (LB) in Parkinson's disease (PD). Astroglial over-expression of the heme-degrading enzyme, heme oxygenase-1 (HO-1) in the PD substantia nigra promotes mitochondrial iron sequestration and may sensitize dopaminergic neurons to oxidative injury (51). The effects of transient hHO-1 transfection on levels of endogenous or co-transfected alpha-synuclein (WT or A30P) were measured by Western blot in M17 cells in the presence or absence of the HO and proteasome inhibitors, SnMP and lactacystin, respectively. Deferoxamine and bilirubin were administered to sister cultures to delineate the role(s) of iron and bilirubin (heme breakdown products) on altered alpha-synuclein metabolism. hHO-1 transfection significantly decreased endogenous and transgenic WT alpha-synuclein levels, effects reversed by SnMP, lactacystin or deferoxamine (but not bilirubin), but had no effects on A30P levels. Thus, iron liberated by HO-1 over-expression may induce proteasomal degradation of WT alpha-synuclein, thereby promoting synaptic dysfunction. Conversely, failure of HO-1 to suppress mutant alpha-synuclein and its putative toxic gain of function may predispose to familial PD.

Стилі APA, Harvard, Vancouver, ISO та ін.

30

Lakins, Johnathon N. "Structure and activity of human clusterin." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0021/NQ45178.pdf.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

31

Qian, Jin. "Human IFITM2 inhibits SIV agm entry." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121374.

Повний текст джерела

Анотація:

Interferon-inducible transmembrane proteins (IFITMs) restrict entry of many pH-dependent enveloped viruses such as Influenza A virus, dengue virus, hepatitis C virus, Ebola virus, and even non-enveloped virus such as Reovirus. These proteins are believed to have two transmembrane or intramembrane domains and prevent viral membrane fusion without relocating the virus to other sites or changing the pH of the endosome environment. Previously, our group reported that IFITMs inhibit human immunodeficiency virus type 1 (HIV-1), a virus that does not require access to endosome for entry. In this study, we set to provide more evidence for restriction at entry of a pH-independent virus and explore the mechanism of inhibition. Simian immunodeficiency virus strains that infect African green monkey (SIVAGM) are found to be significantly restricted by human IFITM2. SIV strain from sooty mangabey is partially restricted, while strain from macaque is unaffected. The restriction of SIVAGM by human IFITM2 occurs at entry. Interestingly, IFITM2 restricts these viruses better than IFITM3 does, despite their high homology at the amino acid level. We found that 2 amino acid residues at the N-terminal domain are responsible for the higher restriction efficiency by IFITM2. We also cloned AGM IFITMs to test whether the monkey proteins can inhibit HIV-1. Surprisingly, AGM do not have IFITM2 (similar to macaque), but AGM IFITM3 inhibits all tested strains including SIVMAC better than it inhibits HIV strains. These findings have therefore expanded the pH-independent viruses that are inhibited by IFITM proteins and provide a new avenue to explore the antiviral actions of IFITM.
Les protéines transmembranaires inductibles par interféron (IFITM) limitent l'entrée de nombreux virus enveloppés dont l'entrée dépend du pH, tels que les virus de la grippe, le virus de la dengue, le virus de l'hépatite C, le virus Ebola, et même des virus non enveloppés tels que le reovirus. Ces protéines ont deux domaines transmembranaires ou intramembranaires et peuvent empêcher la fusion des membranes virales sans altérer le site d'entrée ou de modifier le pH de l'environnement des endosomes. Notre groupe a rapporté auparavant que les protéines IFITM pouvaient aussi inhiber le virus de l'immunodéficience humaine de type I (HIV-1), un virus qui ne nécessite pas l'accès aux endosomes lors de l'entrée. Dans cette étude, nous avons décidé à la fois de fournir plus de preuves quant à la restriction d'un virus dont l'entrée est indépendante du pH mais également d'explorer le mécanisme d'inhibition. Les souches de virus d'immunodéficience simienne (SIV) qui infectent les singes verts d'afrique (SIVAGM) se trouvent être considérablement inhibées par les protéines IFITM humaines. Les souches de SIV provenant des mangabeys (SIVSMM) sont partiellement affectées, tandis que la souche de SIV infectant le macaque (SIVMAC) est résistante aux protéines IFITM. De plus, nous avons démontré que les protéines IFITM humaines inhibent l'étape d'entrée de SIVAGM et que ces virus sont plus affectés par IFITM2 que par IFITM3. Nous avons aussi constaté que les acides aminés situés à l'extrémité N-terminale sont responsables de l'inhibition plus importante d'IFITM2 par rapport à IFITM3. Nous avons également cloné les gènes IFITM issus des singes verts d'Afrique pour tester s'ils peuvent inhiber HIV-1. De manière surprenante, les singes verts d'Afrique n'ont pas de IFITM2, mais IFITM3 issu de ces mêmes singes, inhibe toutes les souches examinées, y compris SIVMAC, plus efficacement qu'il inhibe les souches de HIV. Ces résultats ont donc élargi les virus pH-indépendant qui sont inhibés par des protéines IFITM et fournir une nouvelle avenue à explorer concernant les actions antivirales de IFITM.

Стилі APA, Harvard, Vancouver, ISO та ін.

32

Varsani, Arvind. "Development of candidate Human papillomavirus vaccines." Doctoral thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/5970.

Повний текст джерела

Анотація:

Bibliography: leaves 180-218.
The objective of this thesis was to investigate novel and plant-based vaccines against the Human papillomavirus type 16 (HPV-16), which is primarily responsible for cervical cancer. As a first study, the L1 gene of a South Africna variant of HPV-16 (L1 504) and a mutant (504[ΔA266T]), where the alanine at 266 was mutated to a threonine, were expressed in insect cells by recombinant baculovirus, and the resulting virus-like particles (VLPs) were tested with a panel of well-characterised monoclonal antibodies (Mabs).

Стилі APA, Harvard, Vancouver, ISO та ін.

33

Ratnasinghe, Duminda D. "Unusual Structure of a Human Middle Repetitive DNA." Digital Commons @ East Tennessee State University, 1993. https://dc.etsu.edu/etd/2767.

Повний текст джерела

Анотація:

The L2Hs sequences are a polymorphic, interspersed, middle repetitive DNA family unique to human genomes. Genomic fingerprinting indicates that these DNAs vary from one individual to another and between tissues of the same individual. Sequence analysis reveals that they are AT-rich (76%) and contain many unusual sequence arrangements (palindromes, inverted and direct repeats). These sequence properties confer on the L2Hs elements the potential to fold into non-B-form structures, a characteristic of recombination hot spots. To test this hypothesis carbodiimide, osmium tetroxide and S$\sb1$ nuclease were used as single-strand specific probes to study a recombinant plasmid, pN6.4.39, containing a single L2Hs segment. Different forms of the plasmid substrate were analyzed, including linear molecules and circular forms of low, intermediate and high superhelical densities. In addition, plasmid DNA in growing E. coli cells were analyzed. Modified plasmid DNA was analyzed by primer extension in a sequencing-type reaction format. These studies demonstrate that the L2Hs sequences: (1) assume non-B-form structures both in vitro and in vivo, (2) map to predicted cruciform structures, (3) behave as C-type extrusion sequences, and (4) that these unusual DNA structures are dependent on plasmid superhelicity.

Стилі APA, Harvard, Vancouver, ISO та ін.

34

Vong, Tze Ngai. "Managing human resource development." Thesis, University of Macau, 2000. http://umaclib3.umac.mo/record=b1636787.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

35

Saridogan, Ertan. "Cell biology and metabolism of human Fallopian tube." Thesis, Queen Mary, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286201.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

36

Liu-Cordero, Shau Neen 1970. "Patterns of linkage disequilibrium in the human genome." Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/89344.

Повний текст джерела

Анотація:

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, 2002.
Includes bibliographical references.
Although enormous progress has occurred in the field of human genetics, the cloning of complex trait mutations remains a challenging and unresolved process. This continuing difficulty is responsible for an ever-increasing awareness of the phenomenon of linkage disequilibrium (LD). The principle behind LD is relatively simple. Over the lifetime of a population, the genetic markers that are adjacent to an ancestral mutation will recombine less often than more distant markers. Therefore, the ancestral alleles of the markers closest to the mutation should be most frequent in a collection of disease chromosomes. The allelic association should decrease as the distance from the ancestral disease mutation increases. This thesis is a collection of ideas and experiments aimed at dissecting the behavior of LD in the human genome. Specific studies examine LD in a variety of populations including isolated founder populations, as well as globally diverse population samples. A large number of regions throughout the genome are investigated using both pairwise comparisons of markers, as well as multimarker haplotypes. The X chromosome is more closely scrutinized because of its unique population history, as well as the advantages afforded to haplotyping due to hemizygosity of the X chromosome in males. Major conclusions include the observation that LD between pairs of markers is highly variable even at extremely close distances and multimarker haplotypes better serve to resolve the underlying haplotype structure of the genome.
(cont.) The genome appears to be structured as blocks of limited haplotype diversity that do not exhibit much internal recombination but which are separated by segments that show little or no LD. The lack of LD between haplotype blocks appears to be due to clustering of recombination events into specific hotspots. The size of the blocks and haplotype diversity varies slightly by population. In addition, the identity of the haplotypes varies between populations. The existence of 3-4 major haplotypes for specific regions in a diverse human population sample is a surprising finding that was originally believed to have only existed in very special isolated and young populations.
by Shau Neen Liu-Cordero.
Ph.D.

Стилі APA, Harvard, Vancouver, ISO та ін.

37

Hamilton, Monica L. (Monica Lauren). "Conservation of exon scrambling in human and mouse." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72822.

Повний текст джерела

Анотація:

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biology, 2012.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 21-23).
Exon scrambling is a phenomenon in which the exons of an mRNA transcript are spliced in an order inconsistent with that of the genome. In this thesis, I present a computational analysis of scrambled exons in human and mouse. RNA-seq data was mapped to the genome and all unaligned reads were subsequently mapped to a database of all possible exon-exon junctions. Eight conserved genes were found to undergo scrambled splicing in both species. In several cases, not only the gene was conserved, but the particular exons involved were conserved as well. Reading frame was preserved in just over half of the events, indicating that although some transcripts may be translated into protein, some may be non-functional or may play a regulatory role. The introns flanking scrambled exons were significantly longer than average, providing clues to the mechanism for this abnormal splicing pattern. The results of this study demonstrate that presence of scrambled transcripts in the cell is infrequent, but can be conserved over tens of millions of years of evolution, suggesting it has a biological function.
by Monica L. Hamilton.
S.M.

Стилі APA, Harvard, Vancouver, ISO та ін.

38

Hamburger, Agnes Eva 1976. "Structural studies of the human polymeric immunoglobulin receptor." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/28935.

Повний текст джерела

Анотація:

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2005.
Includes bibliographical references.
The human polymeric immunoglobulin receptor, pIgR, is a glycosylated type I transmembrane protein expressed on the basolateral surface of secretory epithelial cells. pIgR plays a key role in mucosal immunity and, together with bound immunoglobulins (Igs), provides a first line of specific defense against pathogens and their toxins. pIgR binds dimeric IgA (dIgA) and pentameric IgM (pIgM) produced by local plasma cells and transports these polymeric Igs to the apical surface of the cell where the complexes are cleaved from the membrane and deposited into mucosal secretions. The Fc portion of dIgA initially interacts non-covalently with the N-terminal domain (D1) of pIgR, followed by a covalent interaction with D5. In order to gain insight into the molecular details of the initial interaction, we solved the 1.9 [angstrom] resolution crystal structure of D1 of pIgR. The structure reveals a folding topology similar to variable Ig domains with differences in the complementarity determining regions (CDRs). CDR1, the primary determinant in dimeric IgA binding, contains a single helical turn. CDR2, the main determinant in binding to pIgM is very short and contains a potentially critical glutamic acid involved in pIgM binding. CDR3 points away from the other CDRs, preventing dimerization of D1 analogous to the variable heavy and light chains in antibodies. Surface plasmon resonance studies showed that D1, regardless of its glycosylation state, binds dIgA with an equilibrium dissociation constant of 300 nM in the absence of other pIgR domains, but does not bind to monomeric IgAl-Fcα. The structure of D1 allows interpretation of previous mutagenesis studies and structure-based comparisons with other IgA and IgM receptors. To further characterize the interaction
(cont.) intact pIgR and dIgA, we have also initiated structural studies of the other extracellular domains of pIgR, both alone and in complex with the Fc portion of dIgA. Finally, we have also undertaken structural studies of pIgR in complex with the choline-binding protein A, CbpA, a protein found on the surface of Streptococcus pneumoniae, a pathogen that uses pIgR as a receptor to invade the human mucosal epithelium.
by Agnes Eva Hamburger.
Ph.D.

Стилі APA, Harvard, Vancouver, ISO та ін.

39

Maresco, Diane L. "Biological studies of the human IgG Fc receptors /." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487948440825252.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

40

Haun, Mathias. "Human cytomegalovirus interactions with human fibroblast cells: Characterization of a neutralization epitope and identification of cell signalling events." Thesis, University of Ottawa (Canada), 1995. http://hdl.handle.net/10393/9474.

Повний текст джерела

Анотація:

Human cytomegalovirus (HCMV) hyperimmune globulins or intravenous immunoglobulin (IVIG) have been widely used as a means of passive immunoprophylaxis. The efficacy of these blood products has not been clearly demonstrated in terms of the correlation between anti-HCMV titres assayed by enzyme-linked immunoassay (ELISA) and viral neutralizing activity measured in vitro by plaque reduction assay. Recent advances in the characterization of HCMV surface glycoproteins have led to the identification of the immunodominant regions of these molecules. The mouse monoclonal anti-HCMV antibody CMVB1 was utilized to study the properties of a neutralization epitope. Chemical cross-linking experiments with a photoactivable, heterobifunctional and cleavable reagent identified a viral antigen with an apparent molecular weight of approximately 70 kDa. Microtitre plate binding assays verified that the epitope was unique to HCMV and not homologous to herpesvirus-1 or -2 (HSV-1, -2) antigenic sites. The lectin concanavalin A was found to partially block CMVB1 from binding to the viral epitope, suggesting that carbohydrate moieties may be part of the antigen. Lectin specific sugars such as D-glucose, D-mannose and N-acetylglucosamine did not block CMVB1 binding to HCMV. Cell signalling events induced by HCMV particle binding to human foreskin fibroblast cells were also examined. Central molecules involved in three major signal transduction pathways were studied. Tyrosine phosphorylation was investigated with immunoprecipitation and immunoblotting techniques. Intracellular cyclic adenosine monophosphate (cAMP) concentrations were measured by immunoassay and protein kinase C (PKC) activation was established by a peptide radiolabelling assay. With the methodologies utilized, no evidence of HCMV-induced tyrosine phosphorylation or elevated cAMP concentrations was detected. PKC activity was found to increase to levels typically observed in activated cells. (Abstract shortened by UMI.)

Стилі APA, Harvard, Vancouver, ISO та ін.

41

Hlamandana, Zukiswa. "Resolving the service delivery backlog at the Eastern Cape Department of Human Settlements." Thesis, Nelson Mandela Metropolitan University, 2016. http://hdl.handle.net/10948/5303.

Повний текст джерела

Анотація:

The purpose of this study is resolving the service delivery backlog at the Eastern Cape Department of Human Settlements. The problem of service delivery backlogs is not one unique to South Africa but a problem faced by many developing nations. South African government in all spheres still faces a challenge of creating the good life for its citizen, even more on local Municipality as they are government closest to the people and interacts more closely with communities. It is two decades since South Africa became a democratic state and despite promises and efforts to improve service delivery to the public there still exist backlog in service delivery. In order to address the research problem and to fulfil the research objectives, an in-depth literature study was done on the current state and the role of the Department of Human settlements as well as the current backlog facing the department. Housing process and procedures, challenges, policies, finance, factors influencing housing allocation and delivery were also reviewed. Empirical studies were also performed by means of questionnaires with the community and officials in the Eastern Cape Department of Human Settlements. The literature and empirical study made it possible to identify causes, challenges and impact of service delivery backlog and to recommend possible solutions for resolving service delivery backlogs. These recommendations should be of value to the department and the country as a whole. In this study research methodology was focused on the research design, target population of study, sampling design and procedures, data collection instrument, data collection procedures, data presentation, analysis and interpretation. The major findings were identified in the study such as poor workmanship, delays in procurement processes, illegal acts, vandalism, poor planning, finance, project management and quality assurance. The study also offers recommendations such as revising procurement policy, source more funds from National, employ more qualified staff, involve community and all stakeholders in decision making in order to address the service delivery backlog successfully .All kinds of approaches that the government needs to employ in order to also improve its performance of delivering service to the public in South Africa were determined.

Стилі APA, Harvard, Vancouver, ISO та ін.

42

Ho, Siu-chun Terina, and 何少珍. "Reform of the Leisure and Cultural Services Department: implications for human resource management." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31966524.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

43

Legodi, Koena Olivia. "Assessment of human resources records management practices in the Limpopo Department of Agriculture." Thesis, Stellenbosch : University of Stellenbosch, 2011. http://hdl.handle.net/10019.1/6618.

Повний текст джерела

Анотація:

Thesis (MPA)--University of Stellenbosch, 2011.
ENGLISH ABSTRACT: The research study assessed records management practices in the Limpopo Department of Agriculture (LDA), with the focus being on human resources records. Human resources records management practices were assessed in four key performance areas, namely: policy and regulatory framework, storage requirements, integrity of paper-based and electronic records, and efficiency and effectiveness of the registry system. The assessment tool, as prescribed in the Best Practice Model for Keeping and Managing Paper-Based Employee Records, was used. Research findings showed that LDA's performance in terms of records management practices do not comply with the set policies and regulatory framework and that the storage conditions are insecure. Research findings were evaluated and possible strategies for improving the management of human resources records are recommended. The adoption of awareness campaigns for staff, a coordinated training programme as well as the provision of support of top management, are some of the strategies recommended.
AFRIKAANSE OPSOMMING: In hierdie navorsingstudie is rekords van bestuurpraktyke in die Limpopo Departement van Landbou (LDL) geassesseer, met die fokus op menslikehulpbronrekords. Die menslikehulpbronrekords is geassesseer op grond van vier kernprestasie-areas, naamlik die beleids- en regulatoriese raamwerk, bergingsvereistes, integriteit van papiergebaseerde en elektroniese rekords, en doeltreffendheid en effektiwiteit van die registerstelsel. Die assesseringstelsel soos voorgeskryf deur die Best Practice Model for Keeping and Managing Paper-Based Employee Records is gebruik. Navorsingsbevindings het getoon dat die LDL se prestasie ten opsigte van rekordbestuurpraktyke nie voldoen aan beleide nie en dat ‟n regulatoriese raamwerk en veilige bergingstoestande nie bestaan nie. Navorsingsbevindings is geëvalueer en moontlike strategieë om die bestuur van menslikehulpbronrekords te verbeter, is aanbeveel. Die ingebruikneming van bewusmakingsveldtogte vir personeel, 'n gekoördineerde opleidingsprogrm en ook die verskaffing van steun deur topbestuur is van die strategieë wat aanbeveel word.

Стилі APA, Harvard, Vancouver, ISO та ін.

44

Ho, Siu-chun Terina. "Reform of the Leisure and Cultural Services Department : implications for human resource management /." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk:8888/cgi-bin/hkuto%5Ftoc%5Fpdf?B23295715.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

45

Angeles, Vanessa Therese. "Characterization of NANOS expression and function in human germ cells." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3390030.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

46

Liu, Jing 1963. "Molecular analysis of the telomeric half of human chromosome 2q." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40179.

Повний текст джерела

Анотація:

The first part of my thesis dealt with the physical mapping of human chromosome 2 employing the yeast artificial chromosome (YAC) cloning system. To generate a chromosome 2 YAC sublibrary, over 1,000 interspersed repetitive sequence (IRS)-PCR probes were generated and used to screen the CEPH midi YAC library and approximately 2,000 chromosome 2-specific midi YACs were identified. These YACs were divided into 223 YAC groups, i.e., sets of unordered overlapping YACs, and using publicly available contig analysis software, a tentative order of YACs within each YAC group could be established. To order YAC groups, the chromosome 2 YAC sublibrary was screened with 87 genetically mapped microsatellites and cytogenetically mapped expressed sequence tags (ESTs), and 44 YAC groups were localized along the genetic map of chromosome 2q. In addition, 16 known genes were physically linked with microsatellites within YAC groups, thus providing integration points for genetic, cytogenetic and YAC-based physical maps of chromosome 2q. In a subsequent step of the analysis, the chromosome 2 YAC mapping data created by the Whitehead Institute (WI)/MIT Genome Center were integrated into our dataset. The integrated dataset consisted of 240 YAC groups, of which 14 large groups containing both our and WL/MIT Genome Center YAC groups were located on chromosome 2q. These 14 groups consisted of 1,195 YACs, which will form the backbone for the construction of a complete YAC contig for human chromosome 2q.
The second part of my thesis dealt with the identification of genetic markers within or in the vicinity of NRAMP1, a candidate tuberculosis susceptibility locus. The human NRAMP1 gene was mapped to chromosome 2q35 by PCR analysis in a monochromosomal hybrid panel and by YAC contig analysis. Nine sequence variants and polymorphisms were identified within the NRAMP1 gene by single strand conformation analysis (SSCA), DNA sequencing and Southern analyses. Furthermore, two highly informative microsatellites, D2S104 and D2S173 were shown to be linked to NRAMP1 within a 1.5 Mbp YAC contig. Together, these markers provide molecular tools for further genetic analysis of inherited susceptibility to tuberculosis and related diseases of the macrophage.

Стилі APA, Harvard, Vancouver, ISO та ін.

47

Bourbonnière, Martin. "Transcriptional regulation of the human b-amyloid precursor protein gene." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=34702.

Повний текст джерела

Анотація:

The beta-amyloid precursor protein (APP) is an extensively processed membrane protein with a single membrane spanning domain. One of the natural proteolytic products of APP is a peptide of 39 to 43 amino acids in length, beta-amyloid, that has been identified as a major constituent of senile plaques, a neuropathological hallmark of Alzheimer disease (AD). In Down syndrome (DS) (trisomy 21), overexpression of the APP gene, located on chromosome 21, is thought to be responsible for the early formation of senile plaques in the brain of DS patients. We investigated the transcriptional regulation of the APP gene in order to identify the cis-elements located in its promoter and the trans-acting factors recognizing these elements. Identification of the factors regulating APP gene expression, could help define conditions leading to the development of AD. The APP promoter possesses multiple transcriptional start sites, has a high percentage of GC and lacks a consensus TATA box. We have characterized, using electrophoretic mobility shift analysis (EMSA), DNase I footprinting, site-directed mutagenesis and transient transfection studies, three elements located in close proximity of the major transcriptional start sites of APP. We present evidence that two of the elements are recognized by the ubiquitous transcription factors Sp1 and USF respectively. Both the Sp1 and USF elements are essential for full activity of the APP promoter, regulate the APP promoter in an additive manner and synergize with the factor(s) recognizing a GC-rich element located upstream in transient transfection assays in NG108-15 and HepG2 cell lines. We also show that treatment by cyclic AMP of NG108-15 cells which had been transiently transfected with reporter constructs driven by different portions of the APP promoter caused an increase in reporter gene activity mediated by sequences located between --2991 to --488 and --303 to --204, even though the upstream sequences of APP do not contain a canoni

Стилі APA, Harvard, Vancouver, ISO та ін.

48

Ling, Alvin Jee Yee. "Screening the Human Genome for New Mitochondrial and Longevity Regulators." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467501.

Повний текст джерела

Анотація:

Over the past two decades, genes and pathways have been discovered that can prolong lifespan and delay the onset of age-related diseases. The vast majority of these longevity genes were discovered in screens conducted in lower organisms such as yeast and worms. Given that similar large-scale genetic screens in mammals would be cost prohibitive, it is likely that many mammalian longevity genes remain to be discovered. One way to circumvent this issue is to conduct the screen in mammalian cells and instead use cellular phenotypes that correlate with lifespan extension as a read-out. Mitochondrial dysfunction has been observed in aging and implicated in many age-related diseases. Conversely, calorie restriction, a dietary regimen found to extend lifespan and delay the onset of age-related diseases, is associated with maintained or increased mitochondrial function. Thus, increased mitochondrial content and function is a candidate phenotype for a cell-based screen for mammalian lifespan-regulating genes. We have performed a genetic screen of 15,483 human genes for open reading frames (ORFs) that modulate mitochondrial function. A total of 76 ORFs were found and validated to be positive regulators of mitochondrial mass while 18 were negative regulators. The gene products of these ORFs include secreted factors, transcription factors and a variety of predicted polypeptides with unknown function. One of the hits identified from the screen was GLTSCR2 (glioma tumor suppressor candidate region gene 2), a nucleolar protein that has been found to be involved in apoptosis and the cell cycle. GLTSCR2 was discovered as a positive regulator of mitochondrial mass and its overexpression was found to increase cellular respiration. This upregulation of respiration was found to be mediated by Myc, connecting role of GLTSCR2 in oxidative metabolism discovered in this study to its previously reported role in the cell cycle. Another hit identified from the screen was Cpne2 (copine 2), a member of the Copine family of proteins. Members of the Copine family are calcium-dependent phospholipid binding proteins and although discovered over a decade ago, the cellular role of Cpne2 remains unknown. Cpne2 was found as a negative regulator of mitochondria and its depletion was found to increase mitochondrial mass and function. This increase in mitochondria was not due to an increase in the transcriptional program of mitochondrial biogenesis or a defect in depolarization-induced mitophagy, suggesting the involvement of another independent pathway. Collectively, this study describes the discovery and characterization of novel mitochondrial regulators, some of which may be longevity genes and may provide a better understanding of the aging process.
Biological Sciences in Public Health

Стилі APA, Harvard, Vancouver, ISO та ін.

49

Kong, Fanrong Ph D. Massachusetts Institute of Technology. "Contributions of aromatic pairs of human Gamma-D-Crystallin to its folding, stability, aggregation, and interaction with human Alpha B-Crystallin." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72931.

Повний текст джерела

Анотація:

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2012.
Cataloged from PDF version of thesis. Vita.
Includes bibliographical references (p. 139-158).
Two distinct groups of proteins, a-crystallins and [Beta][gamma]-crystallins, constitute 90% of the vertebrate eye lens soluble proteins. Long-term solubility and stability against unfolding and aggregation are essential properties of crystallins and crucial to the function of the lens. Aggregation of crystallins in the lens causes light scattering and directly contributes to development of cataract, the leading cause of blindness in the world. The amino acid determinants of these biochemical/biophysical properties of crystallins are not entirely understood. Aromatic residues in proteins have been shown to be important determinants of their folding pathways, native-state stability, aggregation propensity and other intermolecular interactions. In this thesis study, I have investigated the contributions of the paired aromatic residues of human yD-crystallin (H[gamma]D-Crys) to its folding, stability, aggregation, and interaction with the chaperone human aB-crystallin (H[alpha][Beta]-Crys). H[gamma]D-Crys is a highly stable protein that remains folded in the nucleus of the eye lens for the majority of an individual's lifetime. Like other [Beta][gamma]-crystallins, H[gamma]D-Crys exhibits two homologous crystallin domains, each containing two Greek key motifs and eight [Beta]-strands. Six conserved aromatic pairs (four Tyr/Tyr, one Tyr/Phe and one Phe/Phe) are present in H[gamma]D-Crys. Four among them are located at conserved [Beta]-hairpins of the Greek key motifs, thus termed "Greek key pairs". The Greek key pairs have the consensus sequence Y/FXXXXY/FXG and are one of the defining features of the [Beta][[gamma]-crystallin family. Ultraviolet (UV) damage to these aromatic residues in [Beta][gamma]-crystallins may contribute to unfolding and aggregation of the proteins, leading to development of cataract. [Alpha]-Crystallins belong to the small heat shock protein (sHsp) family and have both structural and chaperone functions in the lens. Human a-crystallins form polydisperse oligomers of 15-60 subunits, with aA:aB ratio about 3:1 in vivo. The core a-crystallin domain (aCD) of acrystallins has an immunoglobulin (Ig)-like p-sandwich fold, but the quaternary structure of acrystallin remains to be fully solved. Like other sHsps, a-crystallins exert their chaperone function by sequestering partially-unfolded and aggregation-prone substrates in an ATPindependent manner, thus preventing their aggregation. The chaperone-substrate interactions of a-crystallins and other sHsps remain poorly understood. To investigate the roles of the paired aromatic residues in H[gamma]D-Crys, mutant proteins with these aromatic residues substituted with alanines were constructed and expressed in E. coli. All mutant proteins maintained native-like secondary structures by circular dichroism (CD). Except F 115A and F 117A, all mutant proteins had lower thermal stability than the wildtype (WT) protein. Equilibrium unfolding/refolding experiments in guanidine hydrochloride (GuHCl) showed that all mutant proteins had lower thermodynamic stability than the WT protein. Nterminal domain (N-td) substitutions shifted the N-td transitions to lower GuHCl concentrations, but the C-terminal domain (C-td) transitions remained unaffected. C-td substitutions led to a more synchronized unfolding/refolding process of the N-td and C-td, and the overall transitions shifted to lower GuHCl concentrations. These results were consistent with a sequential unfolding/refolding model of H[gamma]D-Crys, in which the N-td unfolds first and refolds last. The Greek key pairs had larger contributions to both thermal stability and thermodynamic stability than the non-Greek-key pairs. Aromatic-aromatic interaction energy was estimated by double mutant cycles as 1.5-2.0 kcal/mol. To distinguish the effects in unfolding and refolding, kinetic experiments were also performed. In kinetic unfolding experiments, N-td substitutions accelerated the early phase of unfolding, while C-td substitutions accelerated the late phase. For refolding, only substitutions of the second Greek key pair of each crystallin domain slowed refolding: N-td substitutions Y45A and Y5OA affected the late phase while Y133A and Y138A affected the early phase of the overall refolding reaction. The second Greek key may serve as a nucleation site during the folding of the double-Greek-key crystallin domain. The aggregation pathway that competes with productive refolding in vitro, as well as the suppression of aggregation by chaperone H[alpha]B-Crys were also investigated for mutant H[gamma]D-Crys variants with replacements of the Greek key paired residues. The WT and the mutant H[gamma]D-Crys behaved very similarly, in term of aggregation kinetics and final aggregation level, indicating that these aromatic pairs played minimal role in the aggregation process. The efficiencies of aggregation suppression by H[alpha]B-Crys, as well as the H[alpha]B-bound conformations characterized by the fluorescence of H[gamma]B-H[gamma]D complexes were also very similar for the WT and mutant HyDCrys, arguing against a critical role of these aromatic pairs in the chaperone recognition process. Together with the earlier results, it can also be concluded that stability and refolding kinetics of H[gamma]D-Crys were not critical determinants for its refolding-induced aggregation as well as HaBCrys recognition. Both of these processes may rely on features of the folding intermediate in a very early stage of Greek key refolding. The tryptophan fluorescence of the H[alpha]B-H[gamma]D complexes with WT or mutant H[gamma]D-Crys resembled a partially unfolded state of HyD-Crys, consistent with the tryptophans being part of the contact sites with the chaperone H[alpha]B-Crys.
by Fanrong Kong.
Ph.D.

Стилі APA, Harvard, Vancouver, ISO та ін.

50

Oh, Karen. "Mutational analysis of the human oxytocin receptor." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0031/MQ64421.pdf.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Дисертації з теми "Department of Human Biology"

Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями