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1
Lewandowski, Sara L. "Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles in Cardiac Progenitor Cells." eScholarship@UMMS, 2012. http://escholarship.umassmed.edu/gsbs_diss/883.
Full textAbstract:
Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational lethality. In primary heart field progenitors, Hdac3 interacts with, deacetylates, and functionally suppresses transcription factor Tbx5. Furthermore, a disease-associated Tbx5 mutation disrupts this interaction, rendering Tbx5 hyperacetylated and hyperactive. By contrast, deletion of Hdac3 in second heart field progenitors bypasses these defects, instead causing malformations in the outflow tract and semilunar valves, with lethality prior to birth. Affected semilunar valves and outflow tract vessels exhibit extracellular matrix and EndMT defects and activation of the Tgfβ1 signaling pathway. In normal second heart field development, Hdac3 represses Tgfβ1 transcription, independent of its deacetylase activity, by recruiting the PRC2 methyltransferase complex to methylate the Tgfβ1 promoter. Importantly, knockouts of Hdac3 in differentiated cardiac cells do not fully recapitulate the progenitor-specific knockout phenotypes. These results illustrate spatiotemporal roles of Hdac3, both deacetylase-dependent and deacetylase-independent, in cardiac development, suggesting that dysregulation of Hdac3 in cardiac progenitor cells could be a contributing factor in congenital heart disease pathogenesis.
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Lewandowski, Sara L. "Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles in Cardiac Progenitor Cells." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/883.
Full textAbstract:
Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational lethality. In primary heart field progenitors, Hdac3 interacts with, deacetylates, and functionally suppresses transcription factor Tbx5. Furthermore, a disease-associated Tbx5 mutation disrupts this interaction, rendering Tbx5 hyperacetylated and hyperactive. By contrast, deletion of Hdac3 in second heart field progenitors bypasses these defects, instead causing malformations in the outflow tract and semilunar valves, with lethality prior to birth. Affected semilunar valves and outflow tract vessels exhibit extracellular matrix and EndMT defects and activation of the Tgfβ1 signaling pathway. In normal second heart field development, Hdac3 represses Tgfβ1 transcription, independent of its deacetylase activity, by recruiting the PRC2 methyltransferase complex to methylate the Tgfβ1 promoter. Importantly, knockouts of Hdac3 in differentiated cardiac cells do not fully recapitulate the progenitor-specific knockout phenotypes. These results illustrate spatiotemporal roles of Hdac3, both deacetylase-dependent and deacetylase-independent, in cardiac development, suggesting that dysregulation of Hdac3 in cardiac progenitor cells could be a contributing factor in congenital heart disease pathogenesis.
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Kněžická, Šárka. "Evropská koordinace sociálního zabezpečení: pravidla určování aplikovatelné legislativy." Master's thesis, Vysoká škola ekonomická v Praze, 2013. http://www.nusl.cz/ntk/nusl-197673.
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The aim of this master thesis is to analyse practical impacts of special rules for determination of applicable legislation in accordance with the Regulation No. 883/2004 and its implementing Regulation No. 987/2009. Further the thesis seeks to identify potential negative effects connected to application of the single insurance principle as well as deficiencies arising out of practical performance of European coordination and to discuss the eventual solutions to undesirable effects caused by weak sides of coordination regulations. The thesis is divided into four chapters: an introduction is followed by a chapter about general principles of European coordination of social security systems and about current developments in this field. The topic of a second part is an institute of posting according to Art. 12 of the Regulation No. 883/2004, a distinction here is made between employees and self-employed persons. This chapter further contains procedural rules and an overview of issued portable documents A1 (E 101 forms) during the years 2009 - 2011. Third chapter deals with pursuit of activities in two or more Member States in accordance to Art. 13 of the Regulation No. 883/2004. Special attention is paid to a fine line between posting and pursuit of activities. A problem with retroactive determination of applicable legislation is discussed in the last subchapter of the thesis. This problem is being recently solved by Czech institutions and employers. They are trying to find a solution preventing negative consequences of such a retroactive determination. Exception governed in Art. 16 of the Regulation No. 883/2004 is a subject of the fourth chapter. Situations where an exception is a possible and suitable solution are presented here as well as statistics about requests for exemption from Czech resp. foreign laws.
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Bortfeldt, Alexander. "Disparities in EU legal instruments regarding crossborder healthcare : A comparative study of Regulation 883/2004 and Directive 2011/24/EU and their potential effect on Union goals; especially the free movement provisions." Thesis, Stockholms universitet, Juridiska institutionen, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-185270.
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The statutory health care systems of EU member states show a lot of differences, e.g. in financing, reimbursing, availability, form of membership, etc. The European health insurance card gives EU citizens the possibility to see a doctor while abroad, extending their right from receiving emergency treatment to receiving full necessary treatment under the laws of the member state. The scope of the insurance claim abroad is governed by the respective national law. This can result in a significantly higher cost sharing compared to the domestic situation. Depending on the country, this can include both fixed amounts (additional payments) and percentage shares of up to more than half of the costs.[1] While exercising the right to free movement EU citizens might need way more than emergency care, especially in relation to the rise of chronic diseases like diabetes etc. But quality treatment of patients residing abroad requires a seamless coordination of the member states’ health insurance systems. The access to member states health care systems is not seldomly tricky, in some cases it is even denied to nationals of the state. This thesis seeks to spot access difficulties in different member states asking for the question whether or not this might impede the EU’s free movement provisions.
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Bohuslavová, Eliška. "Komparace bilaterálních smluv o sociálním zabezpečení." Master's thesis, Vysoká škola ekonomická v Praze, 2013. http://www.nusl.cz/ntk/nusl-197877.
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Coordination of social security by bilateral agreements on social security is a specific area of international law that is essential to pay attention to. Czech Republic has up to now signed 16 bilateral agreements that are valid in their entirety. This thesis focuses on these 16 bilateral agreements and compares them with Regulation (EC) 883/2004 which became valid as the Czech Republic became member of European Union and which replaced bilateral agreements that were concluded with member states of European Union. The aim of this thesis is to perform a detailed analysis and to answer on following questions that are directly related to this issue. Firstly the thesis focuses on personal scale and answers a question of who is covered by bilateral agreements. Secondly the thesis focuses on material scale and answers a question of what subsystems are covered by agreements and compares them with the principles applied by Regulation (EC) 883/2004. Finally the thesis deals with a question of a future possible approach to coordination of social security in a global scale. It can be concluded that bilateral agreements concluded by the Czech Republic are each unique legal instruments. Therefore it is essential to study each agreement separately and not to make conclusions based on general knowledge of the issue.
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Kamber, Kaya Hatem E. "Regulation of the Drosophila Initiator Caspase Dronc through Ubiquitylation." eScholarship@UMMS, 2001. http://escholarship.umassmed.edu/gsbs_diss/885.
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Apoptosis is a programmed cell death mechanism that is evolutionary conserved from worms to humans. Apoptosis is mediated by initiator and effector caspases. The initiator caspases carry long pro-domains for their interaction with scaffolding proteins to form a cell-death platform, which is essential for their activation. Activated initiator caspases then cleave effector caspases that execute cell death through cleaving downstream targets. In addition to their apoptotic function, caspases also participate in events where caspase activity is not required for cell killing, but for regulating other functions, so-called non-apoptotic functions of caspases. The Drosophila initiator caspase Dronc, the ortholog of mammalian caspase-2 and caspase-9 has a CARD domain that is essential for its interaction with the scaffolding protein Dark to form the apoptosome. Apoptosome formation is crucial for activation of Dronc. Activity of both initiator and effector caspases are further kept in control by the ubiquitin system to avoid inappropriate caspase activity. However, mechanistic details of how the ubiquitin system regulates activation of Dronc are not clear. Therefore, I investigated the ubiquitylation status of Dronc and its function in Drosophila. I found that Dronc is mono-ubiquitylated at Lys78 (K78) in its CARD domain, which blocks its interaction with Dark and formation of the apoptosome. Furthermore, I demonstrated that K78 mono-ubiquitylation plays an inhibitory role in Dronc’s non-apoptotic functions, which may not require its catalytic activity but may be important for the survival of the fly. This thesis study unveils the link between the ubiquitin system and caspases through a regulatory mechanism where a single mono-ubiquitylation event could inhibit both apoptotic and non-apoptotic functions of a caspase.
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Kamber, Kaya Hatem E. "Regulation of the Drosophila Initiator Caspase Dronc through Ubiquitylation." eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/885.
Full textAbstract:
Apoptosis is a programmed cell death mechanism that is evolutionary conserved from worms to humans. Apoptosis is mediated by initiator and effector caspases. The initiator caspases carry long pro-domains for their interaction with scaffolding proteins to form a cell-death platform, which is essential for their activation. Activated initiator caspases then cleave effector caspases that execute cell death through cleaving downstream targets. In addition to their apoptotic function, caspases also participate in events where caspase activity is not required for cell killing, but for regulating other functions, so-called non-apoptotic functions of caspases. The Drosophila initiator caspase Dronc, the ortholog of mammalian caspase-2 and caspase-9 has a CARD domain that is essential for its interaction with the scaffolding protein Dark to form the apoptosome. Apoptosome formation is crucial for activation of Dronc. Activity of both initiator and effector caspases are further kept in control by the ubiquitin system to avoid inappropriate caspase activity. However, mechanistic details of how the ubiquitin system regulates activation of Dronc are not clear. Therefore, I investigated the ubiquitylation status of Dronc and its function in Drosophila. I found that Dronc is mono-ubiquitylated at Lys78 (K78) in its CARD domain, which blocks its interaction with Dark and formation of the apoptosome. Furthermore, I demonstrated that K78 mono-ubiquitylation plays an inhibitory role in Dronc’s non-apoptotic functions, which may not require its catalytic activity but may be important for the survival of the fly. This thesis study unveils the link between the ubiquitin system and caspases through a regulatory mechanism where a single mono-ubiquitylation event could inhibit both apoptotic and non-apoptotic functions of a caspase.
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Smith, Jill Kay. "Evaluating a vital dimension of self-regulation of nonprofits: the relationship between the Iowa Register of Accountability and voluntary website disclosure." Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/888.
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This study evaluated one important dimension of nonprofit self-regulation, the relationship between the Iowa Register of Accountability and voluntary website disclosure by Iowa nonprofits. The purpose of this study was to assess the effectiveness of self-regulation in Iowa to improve accountability as measured by voluntary website disclosure and transparency. As part of the study, an instrument was developed to reliably measure nonprofit website disclosure and transparency. The disclosure score ratings from Iowa Register of Accountability nonprofit organizations were compared to those not listed on the Register. Other factors relevant to disclosure and transparency (e.g. the method to become listed on the Iowa Register of Accountability and the type and number of organization staff members who received training) were also tested.
Results indicated that nonprofit organizations listed on the Iowa Register of Accountability were more likely to have active websites and to voluntarily disclose recommended information on their websites than those Iowa nonprofits that have not sought or achieved listing on the Register. In particular, the Register group had statistically higher mean disclosure scores in four areas (Key Staff, Strategic Plan, Annual Reports, and Audit and Financial Statements) compared to the Non-Register group. Contrary to expectations, the method to become listed on the Iowa register of Accountability and the type and number of staff members who received training were not related to higher disclosure scores.
The important finding of this research is that nonprofit organizations listed on the Iowa Register of Accountability were more likely to voluntarily disclose recommended information on their websites than those Iowa nonprofits that have not sought or achieved listing on the Register. Recommendations are made in terms of ways to improve nonprofit website disclosure and transparency by enhancing and expanding training opportunities. A major contribution of this study for future research in the field was the development of a disclosure scoring instrument to assess and compare website disclosure and transparency.
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Fulton, Ross Bane. "Regulation of virus-specific T cells in the lung during respiratory virus infections." Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/803.
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The respiratory system forms a major mucosal interface with the external environment. Consequently, the respiratory tract is constantly exposed to inhaled foreign antigens, commensal microorganisms, and potential pathogens. The respiratory system has evolved a complex regulatory network designed to prevent unnecessary inflammation to harmless antigens and to limit immune-mediated damage to the fragile lung epithelium in response to infection. The lung maintains a default anti-inflammatory state that is coordinated by the respiratory epithelium, alveolar macrophages, dendritic cells, and regulatory Foxp3+ CD4 T cells (Tregs). It is likely that all of these cells influence the development of pathogen-specific T cell responses in the lung. Following infection with a respiratory virus, virus-specific CD8 T cells in the lung are inhibited in their ability to produce cytokines. Current studies suggest that this functional inactivation occurs following infection with respiratory viruses within the Paramyxoviridae family. The data presented here demonstrate that suppression of effector functions of virus-specific CD8 T cells in the lungs occurs following infection with several unrelated respiratory viruses. These results indicate that the functional inhibition of virus-specific T cell responses is not restricted to infection with viruses from the Paramyxoviridae family. Furthermore, I show data indicating that the functional inactivation of virus-specific CD8 T cells in the lungs occurs in the absence of infection. I also demonstrate for the first time that the lung environment also regulates the effector functions of virus-specific CD4 T cells. Inhibition of cytokine production by pulmonary T cells is reversible as stimulation with exogenous peptide-pulsed antigen-presenting cells rescues IFN-gamma production. The inhibition of IFN-gamma production by virus-specific T cells occurs in other organs such as the kidney. These data suggest that regulation of T cell cytokine production by peripheral tissues may serve as an important mechanism to prevent immunopathology and preserve normal tissue function.
Foxp3+ Tregs have been shown to inhibit conventional effector T cell responses in a large number of chronic infection models. However, their role during acute infections remains unclear. Examination of Foxp3+ Tregs during RSV infection showed that Tregs are rapidly recruited into the lungs and acquire an activated phenotype. Depletion of Foxp3+ Tregs prior to RSV infection revealed that Tregs facilitate the early recruitment of RSV-specific CD8 T cells from the draining lymph nodes to the lung and later limit the overall magnitude of the virus-specific CD8 T cell response. Depletion of Tregs increased TNF-αa production by RSV-specific CD8 T cells and enhanced T-cell-mediated immunopathology. These data demonstrate that Foxp3+ Tregs play a major role in regulating CD8 T cell responses to respiratory virus infections. Collectively, the data presented here demonstrate that CD8 T cell responses to respiratory pathogens are tightly regulated within the lung environment.
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Salagoor, Jamaludden Yousef. "The influence of building regulations on urban dwelling in Jeddah." Thesis, University of Newcastle Upon Tyne, 1990. http://hdl.handle.net/10443/863.
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Jeddah City is one of the largest cities in Saudi Arabia. It is not a new city, but is a result of a long period of history in which many experiences and regulations of urban dwelling were practised, based on trial and error. Jeddah's society has its own cultural values, traditions, systems, laws, and way of life, based on Islamic beliefs, which form its identity. It is a known fact that Islam does not prevent the benefit and adaptation of systems from other societies, through cross culture, but rather encourages this, with the stipulation that no harm will come to the Muslim socio-culture, and that there is no conflict with Islamic Shari'ah (law). Jeddah, through its long life, has experienced many regulations applied to its built environment. Some conformed with its socio-culture, but were abandoned one way or another, and new policies and regulations were substituted. It was thought that they would be suitable because they had succeeded in other societies, or it was thought that they would lead to urbanisation or that they would be easy to apply. Thus they were adopted, without being analysed against the need of Jeddah's Muslim society and its micro climate, to establish their suitability. Consequently, many problems occurred in the built environment. The main goal of this thesis is to analyse the regulations that have been applied in Jeddah City through it's long life by identifying their nature, their positive and negative impact on the urban dwelling and their conformity with Islamic Shari'ah (law). Based on the analysis, solutions and regulations, recommendations are suggested, aiming to be suitable for Jeddah's inhabitants and environment. To achieve this goal, the thesis is designed to have two main parts, each with chapters. Each chapter represents a distinctive stage in the planning of Jeddah City. The first part deals with evolution and analysis of Jeddah's urban dwelling components, urban fabric, building form, and typology, with a concentration on the influential factors that caused the evolutions. The second part deals with evolution and analysis of the influential regulation on Jeddah's urban dwelling, with concentration on the conformity with 'socioculture and values of the inhabitants. Thu s. the background of Islam and it's legal system is included in this second part as a prerequisite for the analysis. The study revealed that two distinctive factors regulate Jeddah's urban dwelling. The first is characterised by tradition and has great conformity with socio-culture with the effect of creating architecture suitable and fit for Jeddah's society and environment. The second is characterised by contemporary design and greatly conflicts with the society and environment of Jeddah. From the analysis of the causes and effects of the traditions and contemporary regulation on the urban dwelling. proposed solutions and recommendations of regulations and method of enforcement are drawn in the thesis conclusion to overcome the deficiency and conflict of the present applied regulations with Jeddah's socio-culture and environment.
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Hovey, Adriann Marie. "Characterization of miR-888 expression and regulation in endometrial cancer." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4649.
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Endometrial cancer is the fourth most common cancer in women and the most common gynecological malignancy. While patient outcome has improved for the majority of cancers, the outlook for endometrial cancer has steadily decreased. In order to address this problem, we must better understand the different mechanisms involved in endometrial cancer development and progression. To this end, we quantified expression of 667 miRNAs in four endometrioid adenocarcinoma and four serous adenocarcinoma using Taqman Low Density Arrays (TLDAs). miR-888 was one of the most highly overexpressed miRNAs in both endometrial cancer subtypes. Analysis of miR-888 expression across multiple cancer types using the The Cancer Genome Atlas database revealed that miR-888 was selectively expressed in endometrial cancer, with a significant association to invasive and high grade tumors. In addition, miR-888 was most predominantly expressed in endometrial carcinosarcoma, a rare but deadly form of endometrial cancer. Therefore, we conclude that miR-888 expression marks an aggressive endometrial tumor phenotype.
One of the top predicted targets of miR-888 by TargetScan is the progesterone receptor (PR). PR is a potent tumor suppressor of the endometrium whose expression is often lost in advanced endometrial cancers. We quantified PR mRNA expression in a panel of endometrial tumors and found a statistically significant, negative correlation between miR-888 and PR mRNA expression. Furthermore, overexpression of miR-888 in endometrial cancer cell lines was capable of decreasing PR at the protein level. To determine if miR-888 directly targets PR, we cloned each of the four miR-888 binding sites downstream of Renilla luciferase into the psiCHECK2 reporter vector. miR-888 overexpression was capable of decreasing luciferase activity for all four binding sites, with the second and third binding sites producing the most prominent results. Here we describe a novel mechanism by which miR-888 inhibits PR mRNA translation to negatively regulate PR expression in endometrial tumors.
To determine the endogenous function of miR-888 in human cells, we quantified miR-888 in a panel of 21 normal human tissues. Interestingly, miR-888 was highly expressed in testes, with minimal or absence of expression in all other tissues investigated. The restricted expression pattern of miR-888 in testes and cancer suggested that miR-888 may qualify as a novel cancer-testis (CT) antigen. CT-antigens are a large class of genes that demonstrate selective expression normally in testes germ cells and abnormally in various types of cancer. Furthermore, CT-antigen genes are predominantly located on the X chromosome and are part of evolutionarily novel multicopy gene families. Indeed, miR-888 is part of a multicopy, primate-specific miRNA gene family located on the X-chromosome. Furthermore, miRNA in situ hybridization localized miR-888 expression to the early stages of spermatogenesis, as is often observed for CT antigens. Together, these data identify miR-888 as the first miRNA CT antigen and expand the CT antigen field to noncoding RNAs.
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Warner, Nichola Maxine. "Unravelling the roles of two senescent enhanced MYB transcription factors in the regulation of anthocyanin biosynthesis in Arabidopsis thaliana." Thesis, University of Warwick, 2008. http://wrap.warwick.ac.uk/873/.
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MYB90 and MYB75 are two MYB transcription factors that regulate anthocyanin biosynthesis in Arabidopsis. Prior to this study a microarray experiment indicated that MYB90 was required for senescence associated anthocyanin biosynthesis. The role of MYB90 during senescence was investigated using a MYB90 knockout insertion mutant, IM28. Gene expression studies at different time points during the development of the seventh rosette leaf showed that MYB90 regulates anthocyanin biosynthesis genes and MYB75 during senescence. The absence of MYB90 expression reduced photosynthetic performance at two time points during development. Analysis of anthocyanin and flavonoid content showed that there was reduced anthocyanin biosynthesis in the absence of MYB90 expression. The role of MYB90 and MYB75 during high light stress was investigated by analysing the photosynthetic performance and anthocyanin content of high light treated IM28 and MYB75 RNAi plants. MYB90 is required for increased resistance during high light stress, which reflected anthocyanin levels. However, there was eventual compensation for the absence of MYB90 expression in prolonged high light stress. MYB75 was also required for increased resistance to high light stress, but this was not reflected in the anthocyanin levels. The spatial and temporal regulation of MYB90 and MYB75 was investigated using transgenic plants containing promoter: GUS fusions. MYB90 promoter activity was mainly localised to vascular tissue during senescence and low nitrogen/high glucose treatment. MYB75 showed differential tissue specificity in different treatments. The transcriptional regulation of the MYB90 promoter was analysed using promoter deletion GUS: fusions. A senescence specific activation region and a repressor region of the promoter were identified.
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Fuchs, Evelyn. "Regulation of membrane traffic at the golgi apparatus by rab GTPases and their GAPs." kostenfrei, 2007. http://edoc.ub.uni-muenchen.de/8283/.
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Schneider, Joseph. "A look into water conservation : an evaluation of landscape water regulations." Thesis, Manhattan, Kan. : Kansas State University, 2008. http://hdl.handle.net/2097/882.
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Seymour, Brett. "Making and breaking order via clothing Clothing regulation, cross-dressing, and the ordering mentality in later medieval and early modern England." Thesis, Department of History, 2012. http://hdl.handle.net/2123/8837.
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Following the events which disrupted social stability in fourteenth and fifteenth-century England, individuals from a variety of social contexts demonstrated a particular necessity to see order visibly displayed in society. This thesis examines sumptuary regulations and cross-dressing side by side to demonstrate clothing's relationship to both making and breaking order. In the act of revealing this relationship, this thesis will argue that the two cases demonstrate clothing’s importance in creating a visible confirmation of social order which ultimately brings to the surface an underlying collective ordering mentality that equated a sense of security with arranging everyone in society in their rightful place.
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Rohatgi, Rasika. "Autophagy-Independent Role for Beclin 1 in the Regulation of Growth Factor Receptor Signaling: A Dissertation." eScholarship@UMMS, 2015. http://escholarship.umassmed.edu/gsbs_diss/873.
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Beclin 1 is a haplo-insufficient tumor suppressor that is decreased in many human tumors. The function of Beclin 1 in cancer has been attributed primarily to its role in the degradative process of autophagy. However, the role of autophagy itself in tumorigenesis is context-dependent and can be both preventive and promoting. Due to its dual function in cancer a better understanding of this process is necessary to develop potential novel cancer therapies. To gain insight into the role of autophagy in breast carcinoma, I analyzed the autophagydependency of different subtypes of breast cancer. My results implicate that triple-negative breast carcinoma cells are more dependent on autophagy than luminal breast carcinoma cells. Chemical inhibition of autophagy decreased the tumorigenicity of triple-negative breast carcinoma cells with regard to proliferation and anchorage-independent growth. However, RNAi-mediated suppression of two autophagy genes, ATG5 and Beclin 1, revealed different outcomes. While suppression of ATG5 decreased glycolysis, Beclin 1 depletion did not affect the glycolytic rates. These results suggest autophagy-independent pro-tumorigenic effects of loss of Beclin 1 in cancer.
Beclin 1 is a core component of the Vps34/Class III PI3K (PI3KC3) and Vps15/p150 complex that regulates multiple membrane trafficking events. I describe a novel mechanism of action for Beclin 1 in breast cancer involving its control of growth factor receptor signaling. I identify a specific stage of early endosome maturation that is regulated by Beclin 1, the transition of APPL1- containing phosphatidyIinositol 3-phosphate-negative (PI3P-) endosomes to PI3P+ endosomes. Beclin 1 regulates PI3P production in response to growth factor stimulation to control the residency time of growth factor receptors in the PI3P-/APPL+ signaling competent compartment. As a result, suppression of BECN1 sustains growth factor stimulated AKT and ERK activation resulting in increased breast carcinoma cell invasion. In human breast tumors, Beclin 1 expression is inversely correlated with AKT and ERK phosphorylation. Taken together my data identify a novel role for Beclin 1 in regulating growth factor signaling and reveal a mechanism by which loss of Beclin 1 expression would enhance breast cancer progression independent of its impact on autophagy.
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Pope, Catherine. "The regulation of female identity in the novels of Florence Marryat." Thesis, University of Sussex, 2014. http://sro.sussex.ac.uk/id/eprint/49563/.
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This thesis evaluates the contribution to Victorian literary and cultural debate of Florence Marryat (1833-99) a prolific and varied writer yet to receive sustained critical attention. Specifically, I examine her many fictional representations of the legal, medical, and religious regulation of female identity in novels published between 1865 and 1899. I argue that Marryat goes further than other contemporary writers in subverting gender norms and theorising in fiction a transgressive female. By considering Marryat's output in relation to comparator authors, I demonstrate how her work represents a uniquely radical protest, anticipating and prefiguring the New Woman writing of the fin de siècle. I also show how Marryat appropriates different styles of rhetoric to expose and challenge various mid-Victorian notions of ‘woman' constructed for the purposes of regulation. By representing and then challenging the regulation of female identity, Marryat's novels provide an important insight into how Victorian gender roles were constructed. My research shows that her work constitutes an effective protest against this regulation, evidenced by the critical response which attempted to undermine her reputation and arguments. I examine these criticisms in detail, showing how Marryat's novels became a space in which she engaged with her critics, thereby pushing literary and gender boundaries. By bringing critical insight and contextual knowledge to close readings of Marryat's novels, I reveal the feminist meaning hitherto occluded by literary regulation and subsequent superficial interpretations. Through extensive archival research, I also explain how Marryat used her own experiences to educate her readers, often appearing as a character in the novels. I propose that this direct relationship with her audience, presenting feminist ideas in a quasi-polemical style, makes Marryat's oeuvre distinctive and worthy of further consideration. While Marryat is often considered a writer of ephemeral romances, I establish her as an early feminist who questioned and subverted nineteenth-century notions of femininity.
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Spåhr, Henrik. "The transcription machinery in Schizosaccharomyces pombe and its regulation /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-863-7/.
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Horn, Henrik von. "Regulation of insulin-like growth factor-II in human liver /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-880-0/.
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Lajoie, Bryan R. "Computational Approaches for the Analysis of Chromosome Conformation Capture Data and Their Application to Study Long-Range Gene Regulation: A Dissertation." eScholarship@UMMS, 2016. http://escholarship.umassmed.edu/gsbs_diss/833.
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Over the last decade, development and application of a set of molecular genomic approaches based on the chromosome conformation capture method (3C), combined with increasingly powerful imaging approaches have enabled high resolution and genome-wide analysis of the spatial organization of chromosomes. The aim of this thesis is two-fold; 1), to provide guidelines for analyzing and interpreting data obtained from genome-wide 3C methods such as Hi-C and 3C-seq and 2), to leverage the 3C technology to solve genome function, structure, assembly, development and dosage problems across a broad range of organisms and disease models.
First, through the introduction of cWorld, a toolkit for manipulating genome structure data, I accelerate the pace at which *C experiments can be performed, analyzed and biological insights inferred. Next I discuss a set of practical guidelines one should consider while planning an experiment to study the structure of the genome, a simple workflow for data processing unique to *C data and a set of considerations one should be aware of while attempting to gain insights from the data.
Next, I apply these guidelines and leverage the cWorld toolkit in the context of two dosage compensation systems. The first is a worm condensin mutant which shows a reduction in dosage compensation in the hermaphrodite X chromosomes. The second is an allele-specific study consisting of genome wide Hi-C, RNA-Seq and ATAC-Seq which can measure the state of the active (Xa) and inactive (Xi) X chromosome. Finally I turn to studying specific gene – enhancer looping interactions across a panel of ENCODE cell-lines.
These studies, when taken together, further our understanding of how genome structure relates to genome function.
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Wu, Sijia. "Novel Mechanisms Regulating Dopamine Transporter Endocytic Trafficking: Ack1-Controlled Endocytosis And Retromer-Mediated Recycling." eScholarship@UMMS, 2001. http://escholarship.umassmed.edu/gsbs_diss/887.
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Dopamine transporters (DAT) facilitate high-affinity presynaptic dopamine (DA) reuptake in the central nervous system, and are required to constrain extracellular DA levels and maintain presynaptic DAergic tone. DAT is the primary target for addictive and therapeutic psychostimulants, which require DAT binding to elicit reward. DAT availability at presynaptic terminals ensures its proper function, and is dynamically regulated by endocytic trafficking. My thesis research focused on two fundamental questions: 1) what are the molecular mechanisms that control DAT endocytosis? and 2) what are the mechanism(s) that govern DAT’s post-endocytic fate? Using pharmacological and genetic approaches, I discovered that a non-receptor tyrosine kinase, activated by cdc42 kinase 1 (Ack1), stabilizes DAT plasma membrane expression by negatively regulating DAT endocytosis. I found that stimulated DAT endocytosis absolutely requires Ack1 inactivation. Moreover, I was able to restore normal DAT endocytosis to a trafficking dysregulated DAT coding variant identified in an Attention Deficit Hyperactivity Disorder (ADHD) patient via constitutively activating Ack1. To address what mechanisms govern DAT’s post-endocytic fate, I took advantage of a small molecule labeling approach to directly couple fluorophore to the DAT surface population, and subsequently tracked DAT’s temporal-spatial post-endocytic itinerary in immortalized mesencephalic cells. Using this approach, I discovered that the retromer complex mediates DAT recycling and is required to maintain DAT surface levels via a DAT C-terminal PDZ-binding motif. Taken together, these findings shed considerable new light on DAT trafficking mechanisms, and pave the way for future studies examining the role of regulated DAT trafficking in neuropsychiatric disorders.
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Wu, Sijia. "Novel Mechanisms Regulating Dopamine Transporter Endocytic Trafficking: Ack1-Controlled Endocytosis And Retromer-Mediated Recycling." eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/887.
Full textAbstract:
Dopamine transporters (DAT) facilitate high-affinity presynaptic dopamine (DA) reuptake in the central nervous system, and are required to constrain extracellular DA levels and maintain presynaptic DAergic tone. DAT is the primary target for addictive and therapeutic psychostimulants, which require DAT binding to elicit reward. DAT availability at presynaptic terminals ensures its proper function, and is dynamically regulated by endocytic trafficking. My thesis research focused on two fundamental questions: 1) what are the molecular mechanisms that control DAT endocytosis? and 2) what are the mechanism(s) that govern DAT’s post-endocytic fate? Using pharmacological and genetic approaches, I discovered that a non-receptor tyrosine kinase, activated by cdc42 kinase 1 (Ack1), stabilizes DAT plasma membrane expression by negatively regulating DAT endocytosis. I found that stimulated DAT endocytosis absolutely requires Ack1 inactivation. Moreover, I was able to restore normal DAT endocytosis to a trafficking dysregulated DAT coding variant identified in an Attention Deficit Hyperactivity Disorder (ADHD) patient via constitutively activating Ack1. To address what mechanisms govern DAT’s post-endocytic fate, I took advantage of a small molecule labeling approach to directly couple fluorophore to the DAT surface population, and subsequently tracked DAT’s temporal-spatial post-endocytic itinerary in immortalized mesencephalic cells. Using this approach, I discovered that the retromer complex mediates DAT recycling and is required to maintain DAT surface levels via a DAT C-terminal PDZ-binding motif. Taken together, these findings shed considerable new light on DAT trafficking mechanisms, and pave the way for future studies examining the role of regulated DAT trafficking in neuropsychiatric disorders.
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Nxawe, Sinovuyo. "Effects of regulating hydroponic, solution temperature on plant growth, accumulation of nutrients and other metabolites." Thesis, Cape Peninsula University of Technology, 2011. http://hdl.handle.net/20.500.11838/843.
Full textAbstract:
Thesis (Dissertation (Masters Degree(Horticultural Science))--Cape Peninsula University of Technology, 2011The experiment was conducted with the objectives of establishing effects of regulating hydroponic solution temperatures on the chlorophyll content and photosynthesis processes, accumulation of anthocyanins and flavonoids, nutrient uptake and growth and development of pregnant onion (Ornithogalum longibracteatum L.) in the glasshouse during winter periods in 2009 and 2010. The plants were exposed to four hydroponic solution temperatures (control (10 - 15°C), 26°C, 30°C and 34°C). The treatments were arranged in a complete randomized design.Results from this study conducted in the glasshouse in 2009 and verified in 2010 showed that photosynthesis rate (A) and the gas exchange parameters [stomata conductance (gs), intercellular CO2 concentration (Ci) and transpiration (E)] were significantly increased by elevating the hydroponic solution temperatures to 26-30°C compared with the control and then decreased significantly at 34°C. Furthermore, increasing hydroponics solution temperature from 26°C to 34°C significantly increased the levels of flavonoids and anthocyanins in roots, bulbs, shoots and flowers of O. longibracteatum in both years 2009 and 2010.Warming of the hydroponic solution to 26, 30 and 34oC significantly increased the uptake of (N, P, K, Ca, Mg, S, Na Fe, Cu Zn, Mn and B and Mo) in organs of O. longibracteatum (root, bulbs shoot, and whole plant) in 2009 and verified in 2010. The control treatments 10/15°C (day/night) had the lowest uptake of most nutrients.Results from the two years study also showed that plant growth parameters such as number of bulbs per plant, bulb circumference, flower stalk length, flower length, and dry and fresh weights of root, bulb, shoot and flower respectively were significantly increased by warming the hydroponic solution. Elevating the hydroponic solution temperature to a range of 26 - 30°C induced best growth and produced the highest dry matter yield in O. longibracteatum under glasshouse conditions whereas further increase to 34°C resulted in reduced growth and yield.
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Walter, Norbert, and Bernhard Speyer. "Zwischen Governance und Polymorphie." Universität Potsdam, 2005. http://opus.kobv.de/ubp/volltexte/2006/803/.
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The authors analyze the reasons for the establishment of a regulatory regime for international financial markets in accordance with the ideas of liberal internationalism. They argue that the system of international markets is affected by polymorphy, indicating the existence of different forms of regulation. Five factors produce this polymorphy: the non-existence of a homogenous object of steering, the dynamic nature of these objects, the fact that the purpose of governance is not clearly defined, the dominance of governance by the USA and Great Britain, and governance as a result of a multi-level game with various coalitions.
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Newman, Maria. "Law and Policy: Methods for Protecting the Arctic National Wildlife Refuge." Scholarship @ Claremont, 2016. http://scholarship.claremont.edu/scripps_theses/887.
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My thesis examines the Arctic National Wildlife Refuge (ANWR), which is the site of ongoing debate between environmentalists and the oil industry. I begin by analyzing both sides’ claims about the area’s value and establishing that the coastal zone of the ANWR, whose fate is the most precarious, should be protected for both environmental and cultural reasons. I then examine two methods for protection: the common law, and regulation. I conclude that only through proactive regulation can the ANWR continue to thrive.
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Lyman, Rachel C. "Cell cycle control and its modulation in HPV infected cells." Thesis, University of St Andrews, 2010. http://hdl.handle.net/10023/863.
Full textAbstract:
A key effect of human papillomavirus (HPV) infection is to disrupt the normal cell cycle in order to subvert the cellular DNA replication machinery. Morphologically, condylomata induced by high and low risk HPV types cannot be distinguished and many studies have shown that the pattern of viral gene expression is similar in condylomata caused by both high risk and low risk HPV types. Detailed morphological study of cell cycle protein expression has not previously been performed on condylomata infected with low risk HPV types. The findings presented suggest that the mechanisms employed by low risk HPV6 or HPV11 to subvert cellular functions in condylomata acuminata are similar to those employed by high risk HPVs, with the exception of cyclin D1 and p53 protein over-expression. The differences in p53 expression and cyclin D1 expression seen between high and low risk HPV infection, reflect the known differences between high and low risk types and are in agreement with the known differences between high risk and low risk E6 and E7 proteins. PHK transduction studies demonstrated HPV E6 and E7 induce changes in cell cycle protein expression and that there are differences in cell cycle abrogation between HPV6 and HPV16. Disruption of the p53-MDM2 interaction can lead to activation of the p53 pathway. HPV infected lesions almost always contain wild-type p53. The binding of HPV E6 to p53, and its subsequent targeting for degradation, prevents activation of the p53 pathway in HPV infected cells. Cells over expressing HPV genes were treated with Nutlin-3, a MDM2-small molecule antagonist. The findings presented suggest treatment with Nutlin-3 induces cell cycle arrest in cells expressing HPV16 E7 and HPV6 E6 and HPV6 E7. This suggests a potential role for Nutlin-3 in the treatment of HPV infected cells.
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Johansson, Susanne, and Pernilla Jacobsson. "Biståndshandläggare inom äldreomsorgen - mellan behov, lagar, riktlinjer och handlingsutrymme." Thesis, Linnaeus University, School of Social Work, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-8483.
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This study is about care managers, who process in the care of the elderly, regarding to needs, rules, regulations, guidelines and their freedom of space.
The purpose with this study is to understand how the care managers process out of the basis from the needs of the elderly, the municipal guidelines in relation to the caremanagers freedom of space.
The study has a qualitative approach and is based on semistructured interviews with five different care managers.
To analyze our interview material we have use the street-level bureaucrat theory by Lipsky and Johansson and the theoretical idea empowerment.
Before we started our research about care managers we had an understanding in that the organization had an influence in the judgment of the needs of the elderly. Now we have an understanding in that the relative to the elderly is the one who wants to affect the care manager during the judgment of needs in what effort to make.
Our study indicates that it exist insecurity regarding to the municipal guidelines, which was surprising. We thought that the guideline was something positive and a help full tool for the care managers.
The result in our research points out that the guidelines makes insecurity instead of comfort.
Our study shows that the care managers are contradictory regarding to their freedom of space. In the other hand they consider that their freedom of space is positive, but on the other hand when the municipal guidelines don´t work, they become worried and insecure.
It´s the none working municipal guidelines who gives the care managers a huge freedom of space. Which leads to that the care managers is afraid of doing misjudgments.
Our result don´t distinguish from other studies made in this subject area.
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Craft, Betty V. "A study of the impact of CLIA '88 on personnel needs in clinical laboratories of acute care facilities in Virginia." Diss., This resource online, 1995. http://scholar.lib.vt.edu/theses/available/etd-06062008-160411/.
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Stoltzfus, Patricia. "Molecular markers reflecting malignant transformation and tumor progression /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-888-2.
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Lam, Siu-chi, and 林少志. "Identification of microRNA 885-5p as a novel regulator of tumor metastasis in colorectal cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197135.
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MicroRNAs (miRNAs) are a small non-coding RNAs that play a crucial role in cellular proliferation, differentiation and apoptosis by regulating gene expression via post-translation repression or degradation. They are involved in the regulation of various human diseases including colorectal cancer (CRC). CRC is the third most common cancer in the world and second leading cause of cancer death in Hong Kong and United States. Distant metastasis is the main cause of high mortality rate. In most CRC patients, liver is the most common site of distant metastasis, which is often associated with treatment failure and poor prognosis. While some patients with liver metastasis may still be amenable to surgical resection, most patients can only be treated with chemotherapy, which has limited in controlling the tumor progression. The pathological mechanism of metastasis in CRC is poorly understood. Cell motility is important for tumor invasion and metastasis, which require the interaction between tumor cells and their extracellular matrix. This interaction is regulated by the focal adhesion molecules. Recent evidence suggested that miRNAs affect the cell motility and invasiveness of various cancers, and regulate key steps in metastatic cascade. Investigation of the role of miRNAs in tumor development and metastasis can provide potential novel targets for treatment of colorectal liver metastasis or even other advanced cancers.
In this study, expression of miR-885-5p was examined in CRC surgical specimens. Overexpression of miR-885-5p was observed in liver metastasis when compared with primary tumor and adjacent non-tumorous colon. The high expression level of miR-885-5p in primary colorectal tumors was positively associated with late TNM stage and development of metastasis, suggesting that its expression level can act a predictive marker for liver metastasis. Functional studies demonstrated that overexpression of miR-885-5p could significantly enhance the invasive phenotypes and metastatic properties of colorectal cancer cells through a series of in vitro and in vivo assays. Overexpression of miR-885-5p was correlated with increased expression of mesenchymal markers such as N-cadherin, vimentin and Snail, and decreased expression of epithelial marker such as E-cadherin. Moreover, overexpression of miR-885-5p enhanced the expression of Rho GTPases, which is a regulator of polarity, protrusion and adhesion. These results suggested that miR-885-5p overexpression might be a key step in tumor progression and metastasis via regulation of EMT pathway and Rho GTPases family. Knockdown of miR-885-5p enhanced chemosensitivity of CRC cells through induction of apoptosis. On the other hand, overexpression of miR-885-5p increased tumor proliferation through upregulation of the expression level of cyclin D1.published_or_final_version
Surgery
Doctoral
Doctor of Philosophy
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Neri, Lizzie Karen do Carmo. "Mudança de plano de saúde: informação para a regulação da saúde suplementar." Instituto Brasileiro de Informação em Ciência e Tecnologia/Universidade Federal do Rio de Janeiro, 2016. http://ridi.ibict.br/handle/123456789/887.
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A sociedade e os diversos tipos de organização precisam gerar, processar e aplicar a informação, de forma eficiente, baseada em conhecimentos, para obtenção apropriada de produtividade e de competitividade. Com o entendimento de que uma regulação eficiente do mercado de saúde suplementar exige informação e conhecimento profundo de sua dinâmica, a pesquisa, que teve como objetivo levantar e analisar as mudanças de planos de saúde realizadas pelos consumidores entre 2010 e 2014, com base nas informações enviadas pelas operadoras de planos de saúde à Agência Nacional de Saúde Suplementar (ANS), além de discutir como essa informação pode contribuir para a regulação da saúde suplementar, propõe a utilização dos sistemas de informação da ANS para o tratamento e análise de dados relacionados às mudanças de plano de saúde dos beneficiários entre as operadoras para colaborar para o conhecimento do mercado de planos privados de assistência à saúde e auxiliar no estabelecimento de prioridades e na formulação de diretrizes na área da saúde. A coleta dos dados foi realizada com auxílio de consultas SQL, nas bases de dados da ANS, com base nas especificações pré-determinadas, ou seja, a partir da prévia definição dos critérios, filtros e delimitações de campos, das tabelas e do intervalo de tempo para as extrações dos dados. Foi realizada a extração de dados das bases de dados de beneficiários de planos de saúde, de operadoras e de produtos, para análise e discussão dos dados relacionados às mudanças de planos de saúde no Brasil. Além disso, foram levantadas as estatísticas de acesso ao guia de planos da ANS e os resultados das buscas por termos selecionados, por haver relação com o tema mudança de plano de saúde na web com auxílio da ferramenta “google trends”. Esta pesquisa constatou a importância da grande base cadastral de beneficiários de planos de saúde, que pode ser analisada sob diversas óticas, para a compreensão do mercado da saúde privada, com a utilização de inúmeras variáveis e com focos diferentes. Como demonstraram os resultados, é possível a utilização dessa base para a compreensão da dinâmica das mudanças de plano de saúde e consequentemente para o aumento do conhecimento da saúde suplementar, o que traz importantes benefícios para o estabelecimento de diretrizes na área da saúde.
The society and the various types of organization need to generate, process and apply efficiently knowledge-based information appropriate for achieving productivity and competitiveness. With the understanding that effective regulation of the health insurance market requires information and thorough understanding of its dynamics, the research aimed to survey and analyze the health plan changes made by consumers between 2010 and 2014 based on the information sent by health insurance providers to the National Agency of Supplemental Health (ANS – Agência Nacional de Saúde Suplementar), and discuss how this information can contribute to the Regulation of Health Insurance, proposes the use of ANS information systems for the processing and analysis of data related to plan changes health of beneficiaries among operators to contribute to the knowledge of the private health plans market and assist in setting priorities and formulating guidelines in healthcare. Data collection was performed using SQL queries in the ANS database based on predetermined specifications, i.e. from the previous definition of the criteria, filters and boundaries of fields, tables and time interval for the extraction of data. It was held extraction of data in databases of health plans, providers and products for analysis and discussion of data related to health insurance changes in Brazil. In addition, they raised access statistics to guide the ANS plans and results of searches for selected terms to have relation with the theme health plan change on the web with the help of google trends tool. This survey found the importance of large cadastral base of beneficiaries of health plans, which can be analyzed in various, optical and understanding of the private healthcare market, and with the use of numerous variables and with different focuses. As shown by the results, using this basis for understanding the dynamics of health plan changes and consequently to the increase in supplementary health knowledge is possible, which has important benefits for the establishment of guidelines in health care.
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MAZZOLINI, GABRIELE. "Infortuni sul Lavoro e Rischi nel Mercato del Lavoro: Evidenze Empiriche." Doctoral thesis, Università Cattolica del Sacro Cuore, 2011. http://hdl.handle.net/10280/888.
Full textAbstract:
La presente tesi si focalizza sullo studio delle determinanti e delle conseguenze del rischio sul lavoro e degli incidenti occupazionali nel mercato del lavoro. Il primo contributo (Capitolo 1) fornisce una rassegna critica all'interno di un quadro di analisi armonizzato allo scopo di evidenziare le debolezze della letteratura teorica ed empirica, che si occupa di rischio sul lavoro e dei incidenti occupazionali. Nell’ indagare le determinanti degli incidenti sul lavoro (Capitolo 2), si analizza il ruolo delle condizioni di lavoro e della sicurezza sul posto di lavoro nel ridurre la probabilità di un infortunio e la durata della relativa assenza, tema inesplorato nella limitata letteratura empirica. I nostri risultati forniscono evidenze cross-country che una maggiore sicurezza contribuisce a ridurre la probabilità che un incidente si verifichi e le corrispondenti conseguenze, in termini di giorni di assenza per infortunio. Particolare attenzione viene posta nel considerare il ruolo delle regolamentazioni sulla sicurezza e delle pratiche di organizzazione del lavoro. Il Capitolo 3 studia le conseguenze degli infortuni. Ci si concentra a determinare come un incidente possa influenzare i costi sostenuti dal lavoratori, vale a dire una riduzione delle probabilità di occupazione e perdite salariali, sia nel breve sia lungo periodo. Utilizzando i dati BHPS, si trova che, nel breve periodo, uno stato di infortunio, in seguito ad un incidente occupazionale, porta ad una maggiore probabilità di perdere il lavoro; nel lungo periodo, i lavoratori infortunati possono subire consistenti perdite salariali che possono essere evitate se il lavoratore è occupato nel settore pubblico o in imprese sindacalizzate.This dissertation focuses on investigating the determinants and the consequences of risk at work and occupational accidents in the labour market. The first contribution (Chapter 1) provides a critical survey within an harmonized framework of analysis to highlight the weaknesses of the theoretical and empirical literature. In investigating the determinants of accidents at work (Chapter 2), we analyze the role of working conditions and safety at work in reducing the probability of accidents at work and the corresponding duration of absence, which is an unexplored issue in the limited empirically literature on risk at work and occupational accidents. Our findings provide cross-country evidence that more safety at work contributes to reduce the probability that an accident occurs and its consequences, in terms of days off from work. Particular attention is used in considering the role of safety at work regulations and of work organization practices. Chapter 3 studies the consequences of occupational injuries. We focus in determining how an accident may affect workers’ costs, namely a decline of employment probabilities and earning losses, either in the short or in the long term. Using the BHPS data, we find that, in the short term, a state of injury, following an occupational accident, leads to a higher probability of losing job; in the long term, injured workers may support significant earning losses that may vanish if they are employed in the public sector or in unionized firms.
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MAZZOLINI, GABRIELE. "Infortuni sul Lavoro e Rischi nel Mercato del Lavoro: Evidenze Empiriche." Doctoral thesis, Università Cattolica del Sacro Cuore, 2011. http://hdl.handle.net/10280/888.
Full textAbstract:
La presente tesi si focalizza sullo studio delle determinanti e delle conseguenze del rischio sul lavoro e degli incidenti occupazionali nel mercato del lavoro. Il primo contributo (Capitolo 1) fornisce una rassegna critica all'interno di un quadro di analisi armonizzato allo scopo di evidenziare le debolezze della letteratura teorica ed empirica, che si occupa di rischio sul lavoro e dei incidenti occupazionali. Nell’ indagare le determinanti degli incidenti sul lavoro (Capitolo 2), si analizza il ruolo delle condizioni di lavoro e della sicurezza sul posto di lavoro nel ridurre la probabilità di un infortunio e la durata della relativa assenza, tema inesplorato nella limitata letteratura empirica. I nostri risultati forniscono evidenze cross-country che una maggiore sicurezza contribuisce a ridurre la probabilità che un incidente si verifichi e le corrispondenti conseguenze, in termini di giorni di assenza per infortunio. Particolare attenzione viene posta nel considerare il ruolo delle regolamentazioni sulla sicurezza e delle pratiche di organizzazione del lavoro. Il Capitolo 3 studia le conseguenze degli infortuni. Ci si concentra a determinare come un incidente possa influenzare i costi sostenuti dal lavoratori, vale a dire una riduzione delle probabilità di occupazione e perdite salariali, sia nel breve sia lungo periodo. Utilizzando i dati BHPS, si trova che, nel breve periodo, uno stato di infortunio, in seguito ad un incidente occupazionale, porta ad una maggiore probabilità di perdere il lavoro; nel lungo periodo, i lavoratori infortunati possono subire consistenti perdite salariali che possono essere evitate se il lavoratore è occupato nel settore pubblico o in imprese sindacalizzate.This dissertation focuses on investigating the determinants and the consequences of risk at work and occupational accidents in the labour market. The first contribution (Chapter 1) provides a critical survey within an harmonized framework of analysis to highlight the weaknesses of the theoretical and empirical literature. In investigating the determinants of accidents at work (Chapter 2), we analyze the role of working conditions and safety at work in reducing the probability of accidents at work and the corresponding duration of absence, which is an unexplored issue in the limited empirically literature on risk at work and occupational accidents. Our findings provide cross-country evidence that more safety at work contributes to reduce the probability that an accident occurs and its consequences, in terms of days off from work. Particular attention is used in considering the role of safety at work regulations and of work organization practices. Chapter 3 studies the consequences of occupational injuries. We focus in determining how an accident may affect workers’ costs, namely a decline of employment probabilities and earning losses, either in the short or in the long term. Using the BHPS data, we find that, in the short term, a state of injury, following an occupational accident, leads to a higher probability of losing job; in the long term, injured workers may support significant earning losses that may vanish if they are employed in the public sector or in unionized firms.
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JÃnior, Josà Nilo Rodrigues da Silva. "Sintonia Ãtima de Regulador AutomÃtico de TensÃo e Estabilizador de Sistema de PotÃncia Utilizando Algoritmo de OtimizaÃÃo por Enxame de PartÃculas." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8831.
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nÃo hÃEste trabalho apresenta a aplicaÃÃo do algoritmo de OtimizaÃÃo por Enxame de PartÃculas (PSO â Particle Swarm Optimization) para sintonia Ãtima de controladores associados à regulaÃÃo de tensÃo e ao aumento do amortecimento de geradores sÃncronos utilizados em plantas termelÃtricas de ciclo combinado. Para representaÃÃo matemÃtica do gerador sÃncrono, utiliza-se o modelo linearizado de terceira ordem do sistema mÃquina conectada a uma barra infinita, vÃlido para estudos de estabilidade a pequenos sinais. Os parÃmetros do regulador automÃtico de tensÃo (AVR â Automatic Voltage Regulator) e do estabilizador de sistema de potÃncia (PSS â Power System Stabilizer) sÃo determinados de maneira Ãtima pela ferramenta computacional proposta. Os parÃmetros obtidos para o AVR e PSS sÃo comparados com valores calculados por tÃcnicas de sintonia convencionais, baseadas em aproximaÃÃes das equaÃÃes que descrevem o sistema. Os resultados de simulaÃÃes a variaÃÃes na tensÃo de referÃncia, considerando a anÃlise da resposta temporal do sistema controlado, demonstram que o PSO à uma tÃcnica eficiente na sintonia dos parÃmetros do AVR e PSS, destacando-se sua simplicidade, baixo esforÃo computacional e boa caracterÃsticas de convergÃncia.
This work presents the application of the Particle Swarm Optimization (PSO) algorithm for optimal tuning of controllers associated with voltage regulation and damping enhancement of synchronous generators used in combined cycle power station. For mathematic representation of the synchronous generator, the third order linearized model of a single machine connected to an infinite bus, valid for small signal stability studies, is used. The Automatic Voltage Regulator (AVR) and Power System Stabilizer (PSS) parameters are optimally determined by the proposed computational tool. The parameters obtained for AVR and PSS are compared with values calculated by conventional tuning techniques based on approximations of the equations that describe the system. The simulations results to reference voltage disturbances, considering the time response analysis of the controlled system, show that PSO is an efficient technique in the tuning of AVR and PSS parameters, with emphasis on its simplicity, low computational effort and good convergence characteristics.
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Azevedo, Henrique Sampaio de. "A Legitimidade institucional da estrutura regulatória brasileira pós-88." reponame:Repositório Institucional do FGV, 2017. http://hdl.handle.net/10438/23924.
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The central theme of this paper is the regulatory paradigm in post-88 Brazilian law and the process of justification of its legitimacy. Specifically, we investigate the theoretical basis from which the structure of independent regulatory agencies was interpreted and legitimized within the legal framework established by the Federal Constitution of 1988. Thus, The present work seeks to explore the evolution of the concept of the legitimacy of regulatory action, insofar as it adds different elements for the ratification of its own logic and structure. We first analyze the discussions about the legitimacy that is based only on its formal compatibility with the rule of law, that is, its conflicting nature with principles of legality and separation of powers. Furthermore, we study the efficiency argument, from which the whole regulatory system must be reinterpreted in order to promote specific goals and obtain good result. Later, the problem of the agencies' “democratic déficit” is reconstructed, from which their legitimacy should be extracted from models of popular participation, in order to close some kind of democratic gap. Finally, it’s presented an institutional model that considers itself able to couple different values present in the concept of democracy, making it ideal for dealing with the problema of regulatory legitimacy.
O tema central do presente trabalho é o paradigma regulatório no direito brasileiro e o processo de construção da legitimidade desse modelo de organização administrativa do Estado. Especificamente, investiga-se a base teórica a partir da qual a estrutura das agências reguladoras independentes foi interpretada e legitimada no âmbito do ordenamento jurídico instituído pela Constituição Federal de 1988. O presente trabalho busca, então, explorar a evolução do conceito da legitimidade da atuação regulatória, na medida em que ele agrega diferentes elementos para a ratificação de sua estrutura e lógica próprias. Analisa-se, primeiramente, as discussões acerca da legitimidade jurídico-forma da regulação, ou seja, a sua natureza conflitante com princípios da legalidade e separação de poderes. Em seguida, passa-se ao estudo do argumento da eficiência, a partir do qual todo o sistema regulador deve ser reinterpretado de modo a promover fins específicos e bons resultados, razão pela qual seria legítima a estrutura das agências. Mais adiante, é reconstruído o problema do déficit democrático das agências, a partir do qual a sua legitimidade deveria ser extraída de modelos de participação popular. Por fim, apresenta-se um modelo institucional que julga ser capaz de acoplar diferentes valores presentes na democracia, tornando-o assim ideal para tratar da legitimidade regulatória.
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Hardy, Pénélope. "Le droit à la sécurité sociale du travailleur hypermobile dans l'Union européenne : le cas de l'artiste du spectacle vivant en France, en Belgique et aux Pays-Bas." Electronic Thesis or Diss., Strasbourg, 2024. https://publication-theses.unistra.fr/restreint/theses_doctorat/2024/HARDY_Penelope_2024_ED101.pdf.
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L’analyse du droit européen et international montre que le droit à la sécurité sociale est un droit fondamental de l’homme. Pourtant, l’hypermobilité des travailleurs soulève de nombreuses questions relatives à la protection de ce droit dans l’UE qui sont révélées à la lumière du cas des artistes du spectacle vivant. La reconnaissance et la protection de ce droit au sein de l’ordre juridique de l’UE sont tout d’abord étudiées dans les mécanismes de protection des droits de l’homme, ainsi qu’à travers les enjeux de la liberté de circulation et de la citoyenneté sociale, qui encadrent la mobilité intra-UE des travailleurs. La thèse explore ensuite ces enjeux au prisme de l’européanisation de la sécurité sociale. En mettant en évidence la place prépondérante de la coordination en droit de l’UE de la sécurité sociale, la recherche interroge la contribution de cette approche à l’effectivité de la protection du droit à la sécurité sociale. Face aux insuffisances observées, nous proposons enfin des pistes d’amélioration qui pourraient être appliquées sur le fondement du droit en vigueurThe analysis of the EU and international legal orders shows that the right to social security is a fundamental human right. However, the high mobility of workers raises several questions about the protection of this right within the EU. These issues are analysed through the relevant example of performing artists. The recognition and protection of this right within the EU is examined in the light of human rights mechanisms, and in the context of the challenges arising from workers’ (hyper)mobility within the EU, which is determined by the freedom of movement and social citizenship. These challenges are then further explored through the prism of the Europeanisation of social security. Given the predominant role of coordination in EU social security law, the research questions whether this approach contributes to the effectiveness of the protection of the right to social security. Finally, in view of the shortcomings observed, we propose improvements that could be applied on the basis of current legislation
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Marta, Mónica Sofia Calado. "Gene regulation and immune mechanisms in multiple sclerosis experimental models /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-280-4/.
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Погорельцев, Максим Сергійович, and Maksym Pohoreltsev. "Розробка автоматизованої системи керування краном для складування виробленої продукції." Bachelor's thesis, Тернопіль, ТНТУ, 2021. http://elartu.tntu.edu.ua/handle/lib/35414.
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Роботу виконано на кафедрі ком’пютерно-інтегрованих технологій Тернопільського національного технічного університету імені Івана Пулюя Міністерства освіти і науки України Захист відбудеться 23 червня 2021 р. о 09 .00 годині на засіданні екзаменаційної комісії № 23 у Тернопільському національному технічному університеті імені Івана Пулюя за адресою: 46001, м. Тернопіль, вул.Руська, 56, навчальний корпус №1, ауд. 403Погорельцев М. С. Розробка автоматизованої системи керування краном для складування виробленої продукції. 151 – автоматизація та комп’ютерно-інтегровані технології. – Тернопільський національний технічний університет імені Івана Пулюя. – Тернопіль, 2021. У роботі розроблено автоматизовану систему керування процесом виробництва керамічної У роботі було проаналізовано режими роботи козлового крану. На основі аналізу розглянуто основні аспекти ПІД регулювання роботою крану з метою зменшення часу на розвантажувальні операції. Проведено розрахунок та моделювання роботи усіх регуляторів для запобігання розхитування вантажу. При цьому повинна забезпечуватись максимальна швидкість розвантаження. Розраховано всі параметри автоматичних регуляторів для управління електроприводом. Впровадження такої системи керування дозволить значно скоротити час вантажно-розвантажувальних робіт.
Pohoreltsev M.. Development of an automatic control system of finished products store crane. 151 - automation and computer integrated technologies. - Ivan Puliuyi Ternopil National Technical University. - Ternopil, 2021. The modes of operation of the gantry crane were analyzed in the work. Based on the analysis, the main aspects of PID control of the crane in order to reduce the time for unloading operations are considered. The calculation and simulation of all regulators to prevent load shaking. The maximum unloading speed must be ensured. All parameters of automatic regulators for control of the electric drive are calculated. The introduction of such a control system will significantly reduce the time of loading and unloading operations.
ВСТУП 5 1. АНАЛІТИЧНА ЧАСТИНА 6 1.1. Опис складу будівельних матеріалів 6 1.2. Види козлових кранів та огляд підходів до керування краном 9 2. ПРОЄКТНА ЧАСТИНА 16 2.1Автоматизація електромеханічної системи козлового крану 16 2.2. Розрахунок параметрів регулювання приводу крану 20 3 СПЕЦІАЛЬНА ЧАСТИНА 24 3.1 Моделювання руху крану та визначення налаштувань регуляторів 24 4. БЕЗПЕКА ЖИТТЄДІЯЛЬНОСТІ, ОСНОВИ ХОРОНИ ПРАЦІ 42 4.1. Технічні рішення з питань гігієни праці та виробничої санітарії 42 4.1.1. Мікроклімат та склад повітряного середовища робочої зони. 42 4.1.2. Основні вимоги до виробничого освітлення 44 4.2. Основи безпеки в надзвичайних ситуаціях 46 4.3 Розробка заходів по підвищенню безпеки роботи в умовах надзвичайних ситуацій. 47 ВИСНОВКИ 49 БІБЛІОГРАФІЯ 50
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Balian, Marcelo de Souza. "O MASCARAMENTO DE CONTRATOS DE EMPREGO COMO CAUSA DE DESCUMPRIMENTO DA FUNÇÃO SOCIAL DA PROPRIEDADE DO IMÓVEL AGRÁRIO NO BRASIL: uma nova regulamentação do art. 186, III da CF/88 para além da Lei nº 8.629/1993." Pontifícia Universidade Católica de Goiás, 2012. http://localhost:8080/tede/handle/tede/3449.
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MARCELO DE SOUZA BALIAN.pdf: 989339 bytes, checksum: 0198ece7030895d3304b6ff9e4a69245 (MD5)Made available in DSpace on 2016-09-05T13:27:10Z (GMT). No. of bitstreams: 1 MARCELO DE SOUZA BALIAN.pdf: 989339 bytes, checksum: 0198ece7030895d3304b6ff9e4a69245 (MD5) Previous issue date: 2012-12-13
The Constitution of 1988 has as a basic principle ensure compliance with the social function of land (art. 5, XXIII), providing the expropriation penalty when the misuse of landed property is find. The art. 186, III of CF/88 establishes that compliance with the legal provisions governing fair labor relations is a key requirement for the verification of the fulfillment of the social function of land ownership. Law nº. 8.629/1993, which provides the regulation of constitutional provisions relating to land reform, is evasive when regulating the section III of article. 186 of CF. The various forms of incorporation of labor relations in a broad sense, however, make it extremely difficult for real verification on compliance with the rules governing labor relations, especially in agrarian activities. The objective of this work is to propose a new regulation of art. 186, III, of CF/88, to give effect to the constitutional provision under discussion. The methodology used was the doctrinal study, analyzing legislation and court decisions on the subject. Study was developed on the principles of labor law; training requirements for employment relations, ways of working in the broad sense that most commonly masked employee relations, suggesting in each case, the possibilities to regulate art. 186, III, of CF/88. It was concluded that, in the way the article 186, III CF/1988 is currently regulated, is not possible to expropriate rural property in breach of the provisions governing labor relations.
A Constituição Federal de 1988 tem por princípio fundamental assegurar o cumprimento da função social da terra (art. 5º, XXIII), prevendo a desapropriação sanção quando for constatado o mau uso da propriedade agrária. O art. 186, III, da CF/88 estabelece que o cumprimento das disposições legais que regulam as justas relações de trabalho é um dos requisitos indispensáveis para a verificação do cumprimento da função social da propriedade agrária. A Lei nº 8.629/1993, que dispõe sobre a regulamentação dos dispositivos constitucionais relativos à reforma agrária, é evasiva ao regulamentar o inciso III do art. 186 da CF. As várias formas de constituição das relações de trabalho em sentido amplo, todavia, tornam extremamente difícil a real constatação sobre o cumprimento das normas que regulam as relações de trabalho, em especial nas atividades agrárias. O objetivo deste trabalho é propor uma nova regulamentação do art. 186, III, da CF/88, para dar efetividade ao dispositivo constitucional em comento. Utilizou-se como metodologia o estudo doutrinário, análise legislativa e jurisprudencial sobre o tema. Foi elaborado estudo sobre os princípios de Direito do Trabalho; os requisitos para formação das relações de emprego; as formas de trabalho em sentido amplo que mais comumente mascaram relações empregatícias, sugerindo-se, em cada caso, possibilidades de regulamentar o art. 186, III, da CF/88. Concluiu-se que, na forma como está atualmente regulamentado o art. 186, III da CF/1988, não é possível desapropriar-se imóvel rural galgando-se no descumprimento das disposições que regulamentam as relações de trabalho.
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Arndt, Jody. "Individual differences in emotion regulation and their impact on selective attention." Master's thesis, 2010. http://hdl.handle.net/10048/883.
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Studies were conducted to investigate relationships between trait emotion regulation variables (including reappraisal and suppression) and selective attention to negative emotional information. Correlation analyses of data in experiment 1 showed that trait-suppression was related to early attentional avoidance of angry faces, while reappraisal showed no relationship to attention. Experiment 2 directly compared selective attention to angry faces in groups of high trait-suppressors and high trait-reappraisers. Since reappraisers are also low trait-anxious and suppressors are high trait-anxious, low emotion regulating high- and low-anxious control groups were included. Contrary to findings from experiment 1, trait-suppressors did not have lower selective attention to angry faces than low-regulating high anxious controls. Trait-reappraisers in experiment 2 showed pronounced vigilance for angry faces compared to both trait suppressors and low-regulating low anxious controls. These results suggest that trait-suppression may reduce attentional threat biases. Conversely, trait-reappraisal combined with low anxiety may allow individuals to prioritize threat in attention.
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Arndt, Jody Elizabeth. "Individual differences in emotion regulation and their impact on selective attention." 2010. http://hdl.handle.net/10048/883.
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Thesis (M. Sc. ) -- University of Alberta, 2010."A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science, Department of Psychiatry, University of Alberta." Title from pdf file main screen (viewed on January 14, 2010). Includes bibliographical references.
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Domingos, Marta Cristina Prata. "Coordenação dos sistemas de segurança social dos estados membros da UE : o enigma da dimensão externa." Master's thesis, 2020. http://hdl.handle.net/10400.14/33689.
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A liberdade de circulação de trabalhadores representa uma das pedras basilares do ordenamento jurídico da União Europeia. No entanto, para que o movimento de trabalhadores aconteça, é necessário garantir a portabilidade dos direitos sociais já adquiridos ou em curso de aquisição. É neste ponto que se torna clara a preponderância do mecanismo de coordenação dos sistemas de segurança social dos Estados Membros da União Europeia. Não obstante, para além de percebermos a eficácia e flexibilidade deste mecanismo a nível europeu e os princípios que pautam o principal instrumento legislativo dedicado à matéria (Reg. n.º 883/2004), tornar-se-á relevante o estudo da interação deste instituto com os países externos à União. As soluções atuais, que permitem fazer a ponte entre o mecanismo europeu e os países terceiros, apresentam algumas fragilidades e limitações, desde logo, e num estágio inicial, a querela em torno da base legal para a adoção destas medidas a nível europeu, enfraquece a viabilidade de uma abordagem uniforme centrada nas instituições europeias. Com recurso a elementos doutrinais e jurisprudenciais, estudaremos as virtudes e lacunas das respostas atualmente em vigor, mas também das propostas apresentadas pela doutrina.Freedom of movement for workers is one of the cornerstones of the European Union's legal system. However, for the movement of workers to take place it is necessary to guarantee the portability of social rights already acquired or in the process of being acquired. This is where the preponderance of the mechanism for coordinating the social security systems of the Member States of the European Union becomes clear. Nevertheless, in addition to understanding the effectiveness and flexibility of this mechanism at European level and the principles underlying the main legislative instrument dedicated to the matter (Reg. No. 883/2004), it will become relevant to study the interaction of this institute with countries outside the Union. The current solutions, which allow bridging the gap between the European mechanism and third countries, have some weaknesses and limitations, from the very start, and at an early stage, the controversy over the legal basis for the adoption of these measures at European level weakens the feasibility of a uniform approach focused on the European institutions. Resorting to doctrinal and case-law elements, we will study the virtues and gaps in the responses currently in force, but also in the proposals presented by the academic doctrine.
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Grim, Brian Jeffrey. "Religious regulation's impact on religious persecution the effects of de facto and de jure religious regulations /." 2005. http://etda.libraries.psu.edu/theses/approved/WorldWideIndex/ETD-884/index.html.
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Alsyaideh, Ala'a S. "Notch Regulation of Adam12 Expression in Glioblastoma Multiforme." 2012. https://scholarworks.umass.edu/theses/889.
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Glioblastoma is the most common malignant brain tumor, accounting for 17% of all primary brain tumors in the United States. Despite the available surgical, radiation, and chemical therapeutic options, the invasive and infiltrative nature of the tumor render current treatment options minimally effective. Recent reports have identified multiple regulators of glioblastoma progression and invasiveness. It has been demonstrated that ADAM12, A Disintegrin And Metalloproteinase encoded by ADAM12 gene, is over-expressed in glioblastoma and directly correlated with tumor proliferation. Additionally, dysregulation of the Notch signaling pathway has been implicated in the pathogenesis of many gliomas. Lastly, an evolving role of microRNAs, small noncoding RNAs, in carcinogenesis is progressively growing. A recent study has identified ADAM12 as a notch-related gene, and another demonstrated that inhibition of notch signaling decreased glioblastoma recurrence. However the mechanisms of regulation are still unknown. In this study, we hypothesize that direct downregulation of microRNA-29, downstream of over-expression of notch enhances glioblastoma malignancy through upregulation of ADAM12. Although our data demonstrate upregulation of Notch1, its downstream target HES1, and ADAM12 in U87MG glioblastoma cell line. Expression of the cleaved intracellular Notch1 was not detected. Furthermore, we were unable to demonstrate an inhibitory effect of ɣ-secretase inhibitor on Notch signaling, likely reflecting the requirement for modifying culturing conditions or detection in our assays. Furthermore, miR-29 was detected in glioblastoma cells. The expression of miR-29 was further elevated by ɣ-secretase inhibitor treatment, suggesting a role for Notch1 inhibition on miR-29 expression. Although no conclusive results are shown in our work, a role of Notch1 through miR-29 is implicated in the pathogenesis of glioblastoma pathogenesis warranting further investigation into the role downstream target genes in the Notch signaling pathway.
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Jackson, Thomas. "Regulation of energy efficiency by voluntary agreement : South Africa's energy efficiency accord." Thesis, 2008. http://hdl.handle.net/10413/887.
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Energy efficiency is an issue currently generating huge interest as a potentially costeffective
solution to the twin challenges of environmental pollution from energy production,
and the increasing scarcity of energy resources. This research aims to interrogate the
practicalities of regulation of energy efficiency to ask what scope there is for public-led
encouragement of greater energy savings in industry. Shortcomings of current theory
addressed include a discounting of the impact of heterogeneity of industrial activity on
prospects to effectively regulate for energy efficiency, and a conflation of the different
aspects of societal functioning to which energy efficiency regulations and incentives can
be applied. The research argues that the scope for energy savings has been exaggerated
and the factors which drive pursuit of energy efficiency within firms of different sizes poorly
understood and articulated. The Voluntary Agreement form of environmental regulation is
assessed for its applicability to regulating for energy efficiency in the context of these
characteristics of energy efficiency in industrial settings. An in-depth interview approach
with core participants in an example of a Voluntary Agreement for energy efficiency in
South Africa, the Energy Efficiency Accord (Accord), reveals the difficulties of regulating
for specific technologies, the generally targeted nature of energy efficiency incentive
schemes which provide household and commercial-type programmes to heavy industry,
and the fact that environmental objectives and capacities are highly developed within firms
interviewed and in most cases precede participation in Accord activities. The inference is
that participation at this stage of the Accord's existence is driven by the need to develop
and maintain relations between key stakeholders, and to exploit opportunities to influence
the form of energy efficiency regulation enacted as opposed to the need to obtain forms of
technical guidance. The particular pattern of participation in the Accord is argued to result
in part from the historical dominance of large, energy-intensive firms in South Africa, and
to be consistent with the theory that the more energy-intensive firms in a society will be
motivated to participate in voluntary initiatives such as the Accord.Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2008.
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Tranbarger, Timothy John. "Isolation and regulation of genes expressed during Douglas-fir germination and post-germination." Thesis, 1998. https://dspace.library.uvic.ca//handle/1828/8803.
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To identify genes expressed during Douglas-fir (Pseudotsuga menziesii [Mirb] Franco)
germination and early seedling development, a cDNA library was constructed with mRNA
pooled from 4-6-day-old seedlings. The library was then screened differentially with
cDNA probes synthesized using mRNA isolated from mature seeds and 6-day-old
seedlings. Partial DNA sequence analysis and predicted amino acid sequences revealed
cDNA clones that encoded polypeptides with similarity to several plant proteins including:
a chaperonin 606 (cpn60β), a low molecular weight heat shock protein (LMW HSP), a
luminal binding protein (BiP), a type II chlorophyll a/b-binding protein (CAB), and a
cysteine protease (CysP). In northern blots, each cDNA clone detected transcripts that
increased during seed germination. A clone detected RNA at similar levels in both mature
seeds and in 6-day-old seedlings was isolated and found to share similarity to a
NADPH-cytochrome P450 reductase (CPR) (EC 1.6.2.4). The cDNA clones encoding the
CysP and the CPR were selected for further sequence and gene expression analysis.
The CysP cDNA consists of a 5’ untranslated region (UTR) of 153 bp followed by an
open reading frame (ORF) of 1362 bp encoding a putative mature CysP flanked by N- and
C-terminal propeptides. A 364 bp 3’ UTR contains multiple putative AU-rich elements that
may be involved in the destabilization of transcripts. The CysP from Douglas-fir
(pseudotzain) contains the same invariant amino acid residues that are involved in the catalytic reaction and make up the catalytic center of CysP from other plants and animals.
Pseudotzain transcripts were most abundant in the megagametophyte (MG) after
germination and were not detected in the MG or embryo during embryogenesis. Various
osmotic stresses slightly enhanced pseudotzain transcript quantities during early seedling
development, whereas abscisic acid, gibberellic acid and other plant growth regulators and
changes in environmental conditions had little or no effect. Pseudotzain transcripts were
present in different amounts in the cotyledons, root and seed coat of 10-day-old seedlings,
but were most abundant in the MG, suggesting a role for this protease in storage protein
mobilization. Phylogenetic analysis of mature pseudotzain groups it with other angiosperm
CysP having both N- and C-terminal propeptides, suggesting a conserved function and/or
targeting of this subgroup of enzymes.
The CPR cDNA encodes a polypeptide of approximately 79.6 kDa. A cDNA probe detected a single transcript of 3 kb that was expressed differentially in cotyledons, radicle and MG. CPR transcript quantities were low during seed maturation, higher in mature
seeds, and remained constant throughout germination and early seedling development
before they declined in 14-day-old seedlings. An antiserum against a synthetic CPR-peptide
was produced and western blot analysis detected a single 80 kDa polypeptide in the
membrane fraction of microsomal extracts from seeds and seedlings. CPR accumulation
during germination and early seedling development indicated regulation is at the
transcriptional or post-transcriptional level. However, CPR activity (measured by
NADPH-cytochrome-c reduction) present in the microsomes increases during stratification,
germination and post-germination and decreases in 7-14-day-old seedlings. These results
indicate CPR may be post-translationally activated during Douglas-fir stratification and
germination.
This study describes the isolation of the first cDNAs that share identity with a CysP,
cpn60β, a LMW HSP, BiP and CPR (EC 1.6.2.4) from a gymnosperm. The
developmental expression of these cDNAs suggests that their gene products play critical
roles during the process of germination and post-germination and provides the necessary
framework for future studies.Graduate
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Kaufman, Viktor. "Struktur und Dynamik kritischer boolescher Zufallsnetzwerke als Modelle der genetischen Regulation." Phd thesis, 2007. https://tuprints.ulb.tu-darmstadt.de/880/1/final_keythemes_hom.pdf.
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Das XXI Jahrhundert wird wahrscheinlich im Zeichen der Erforschung der lebenden Materie stehen. Von rapide steigenden Aktivitäten auf diesem Gebiet zeugen die 260 vollständig sequenzierten und 1100 sich in Arbeit befindenden Genome (Stand März 2005). Von der Struktur der Genome zur Funktion der Organismen liegt ein langer Weg. Immense Datenmengen suchen ihre Erforscher, während die Komplexität der Organismen nicht annähernd erfasst ist. Ein Lichtblick in diesem Wirrwarr verspricht die Einsicht, dass universelle, von den biochemischen und anderen Details unabhängige Mechanismen diese Komplexität erzeugen. Das Aufstellen und die Analyse der entsprechenden Modelle haben unter anderem das Interesse der Physiker geweckt. In dieser Arbeit beschäftige ich mich mit einem der ältesten und zugleich erfolgreichsten generischen dynamischen Modelle der für das komplexe Verhalten von Organismen maßgeblichen genetischen Regulation. Gemeint ist das deterministische Modell der booleschen Zufallsnetzwerke (RBN) mit zwei eingehenden Verbindungen und einer booleschen Funktion pro Knoten. Die Knoten repräsentieren die Gene, die entweder aktiv oder inaktiv sein können, die Verbindungen repräsentieren die Genregulationen, der Zustand des Netzwerks beschreibt das momentane Aktivitätsmuster. Das Modell befindet sich bei einer bestimmten Wahl der Funktionen am kritischen Punkt. An diesem Punkt wirkt sich eine lokale Zustandsänderung im Mittel auf eine nicht trivial mit der Netzwerkgröße skalierende Anzahl der Knoten aus. Folglich reagiert das Netzwerk empfindlich auf Änderungen, ist aber schon deswegen geordnet und nicht chaotisch, weil Änderungen nicht alle Knoten betreffen. Man spricht von der Ordnung an der Grenze zum Chaos. Um dieses biologisch interessante Verhalten zu zeigen, müssen die Knoten, gegebenenfalls erst im Laufe der Dynamik, nach ihrer Beteiligung an der Ausbildung der Attraktoren der Dynamik unterschieden werden können. Eine gewisse Struktur muss für das Modell charakteristisch sein. Es war das Hauptziel dieser Arbeit, die Dynamik der kritischen RBN mit zwei Eingängen pro Knoten im Grenzfall großer Netzwerke zu verstehen, insbesondere die Struktur zu untersuchen und damit verbundene Folgerungen für die Dynamik zu identifizieren. Nach einem Überblick über das Thema der booleschen Modelle und der Modellierung der genetischen Regulation wird im ersten Teil dieser Arbeit die Struktur der kritischen RBN untersucht. Die Beschreibung der Struktur hat sich als der Heilige Gral für ein intuitives Verständnis des Modells erwiesen. Viele dynamische Eigenschaften, die in der Literatur seit Langem mit mäßigem Erfolg numerisch untersucht wurden, lassen sich direkt aus den Strukturkenntnissen folgern. Zu den wichtigsten strukturellen Erkenntnissen gehören die analytischen Ergebnisse für so genannte relevante Knoten. Unter allen Knoten bestimmen die relevanten Knoten die Dynamik. Für sie werden unter anderem die Anzahl und die Wahrscheinlichkeitsverteilung bestimmt. Man findet Universalität im Skalenverhalten mit der Netzwerkgröße. Dabei kommen Methoden der statistischen Physik und der mathematischen Statistik zum Einsatz. Relevante Knoten sind in unabhängige relevante Komponenten organisiert. Die einfacheren relevanten Komponenten können losgelöst vom Netzwerkensemble betrachtet werden. Sie sind interessant, weil sie als generische Modelle der echten genetischen regulatorischen Teilnetzwerke oder als Bausteine der komplexeren Netzwerke angesehen werden können. Ihre relativen Gewichte und Verteilungen im Netzwerkensemble der kritischen RBN werden bestimmt. Biologisch relevanten kanalisierenden Netzwerken kommt viel Aufmerksamkeit zu. Es stellt sich heraus, dass sie in fast jeder Hinsicht einen Spezialfall der kritischen RBN bilden. Im zweiten Teil der Arbeit wird die Dynamik der kritischen RBN unter die Lupe genommen. Zuerst werden charakteristische Verhaltensmuster in den einfacheren Netzwerkkomponenten gefunden. Es zeigt sich anschließend, dass bereits einfache Komponenten sehr viele sehr lange Attraktoren haben und damit ein sehr kompliziertes Verhalten zeigen. Es verwundert dann nicht, dass man mit Hilfe der Erkenntnisse aus dem ersten Teil der Arbeit für die allgemeinen kritischen Netzwerke folgert, dass ihre mittlere Anzahl und Länge der Attraktoren mit der Netzwerkgröße exponentiell ansteigt. Numerische Simulationen werden daraufhin untersucht, diese und andere Eigenschaften zuverlässig wiedergeben zu können. Eine möglicherweise triviale Einsicht aus dieser Arbeit besteht darin, dass es sinnvoll ist, komplexe Systeme im Bezug auf das Zusammenspiel der Struktur und Dynamik mit Hilfe einer passenden Kombination der analytischen und numerischen Methoden zu studieren. Auf jeden Fall führt diese Strategie zum intuitiven Verständnis des RBN - Modells aus dem Jahr 1969. Dieses Modell hat seinen Platz in vielen Wissenschaftszweigen gefunden. Im biologischen Kontext kann es generisch Vorgänge wie Zelldifferenzierung, Multistabilität, Oszillation, Homöostase, Signaltransduktion und andere beschreiben.
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Ginja, Daniel Machado Nicolau. "Estudo da viabilidade de aplicação de primários alternativos na pintura de aeronaves face ao Regulamento da UE REACH." Master's thesis, 2018. http://hdl.handle.net/10400.6/8863.
Full textAbstract:
A aplicação de revestimentos em sistemas aeronáuticos é imperativa para a sua operação numa vasta gama de condições ambientais. Estes revestimentos conferem propriedades que permitem proteger a superfície metálica contra o aparecimento precoce de corrosão, assim como características especiais, como tornar a aeronave indetetável aos radares de forças inimigas, no caso das militares.
Até à data, na indústria aeronáutica, foram utilizados maioritariamente os compostos de crómio hexavalente nos processos de pintura, devido às suas propriedades anticorrosivas e baixo custo. Todavia, surge necessidade para a sua substituição, devido a exibir elevados níveis de toxicidade e ser reconhecido como um carcinogénico humano via inalação.
Este trabalho estudou a viabilidade de substituição de primários utilizados na pintura de aeronaves na OGMA por outros que satisfaçam o regulamento relativo ao registo, avaliação, autorização e restrição de substâncias químicas, que foi criado para restringir o uso de substâncias prejudiciais à saúde humana e ao ambiente na União Europeia.
Com os resultados obtidos foi possível constatar que os primários alternativos testados para o setor militar, comparativamente aos com crómio hexavalente, são inviáveis economicamente. Isto deve-se ao facto de apresentarem um preço superior, uma capacidade de cobertura inferior e uma espessura requerida maior, o que por sua vez aumenta consideravelmente a quantidade de primário necessário para pintar uma aeronave.
Por outro lado, o primário alternativo do setor civil testado mostrou rivalizar todos os parâmetros considerados, relativamente ao primário com crómio hexavalente. Isto leva-nos a concluir que, no presente, embora haja uma oferta de primários alternativos qualificados no mercado, apenas alguns reúnem todos os atributos necessários para serem implementados. A dificuldade em substituir substâncias em sistemas já estabelecidos, devido à complexidade dos mesmos, da sua cadeia de abastecimento e aos longos períodos de aprovação, fazem com que seja somente viável implementar tais primários em sistemas em desenvolvimento. Recomenda-se num futuro estudar a implementação de um pré-tratamento de superfície compatível com as operações da empresa, a implementação de sistemas automatizados de pintura de forma a reduzir o impacto da exposição no fator humano.The application of coatings in aeronautical systems is imperative for their operation in a wide range of environmental conditions. These coatings confer properties that allow the metal surface to be protected against the early appearance of corrosion, as well as special features such as rendering the aircraft undetectable to the radars of enemy forces, in the case of the military. Until now, in the aeronautical industry, chromium hexavalent Cr(VI) compounds have been broadly used in painting schemes due to their anticorrosive properties and low cost. Nonetheless, there is a need for their replacement due to exhibiting high levels of toxicity and being recognized as a human carcinogen via inhalation. This work studied the feasibility of replacing primers used in aircraft painting at OGMA by others that comply with REACH Regulation, which was created to restrict the use of substances harmful to human health and the environment in the European Union. With the results obtained, it was possible to verify that the alternative military primers tested, compared to the one containing Cr(VI), are economically unfeasible. This is due to the fact that they have a higher price per liter, a lower coverage capacity and a greater required thickness, which in turn greatly increases the amount of primer required to paint an aircraft. On the other hand, the alternative primer of the civil sector tested proved to rival all the considered parameters relative to the primer with Cr(VI). This leads us to conclude that at present, although there is qualified alternative primers in the market, only a few have all the attributes necessary to be implemented. The difficulty of replacing substances in already established systems, due to their complexity, supply chain and long approval periods, makes it only feasible to implement such primers in systems in development. It is recommended in the future to study the implementation of a surface pretreatment compatible with the company's operations, the implementation of automated painting systems in order to reduce the impact of exposure on the human factor.
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Modrusan, Zora. "Molecular and genetic analyses of the Bel1 gene regulating ovule development in Arabidopsis thaliana." Thesis, 1995. http://hdl.handle.net/2429/8873.
Full textAbstract:
Phenotypic characterization of the Arabidopsis thaliana mutant Bel1 revealed
numerous morphological abnormalities of Bel1 ovules, including the absence of the
inner integuments, homeotic transformation of the outer integuments into carpel-like
structures, and incomplete development of the female gametophytes. The homeotic
transformation of outer integuments into carpelloid structures in Bel1 has been
correlated with abnormal expression of class C gene expression in the Arabidopsis
ovule. Both direct and indirect evidence established such correlation: first, transcripts
of AGAMOUS, the only class C gene identified to date, were detected throughout
Bel1 ovules at the time of formation of carpel-like structures and second, the highest
frequency of carpel-like structures was found in Bel1 plants grown under
environmental conditions that also stimulate class C function. These data suggested
that the BEL1 product functions as a negative regulator of AG during ovule
development. Similar to Bel1, occasional transformation of ovules into structures with
carpelloid features occurs in Ap2-6 mutant plants, indicating a role of the APETALA2
gene in ovule development not previously described. AP2 function during early
Arabidopsis flower development is to suppress AG in the outermost whorls. My data
suggests that AP2 functions in a similar manner during ovule development.
Two mutant alleles, bel1-2 and bel1-3, originate from Agrobacterium T-DNA
mutagenized populations of Arabidopsis and both of them are due to T-DNA
insertions into the BEL1 locus. Genomic sequences adjacent to the T-DNA insert in
the bel1-2 were used to isolate the putative BEL1 gene (L. Reiser and R. Fischer,
unpublished data). The identity of the cloned BEL1 sequence was confirmed by
cloning the bel1-3 allele and demonstrating that the T-DNA lies within putative BEL1
gene and by complementation of the Bel1 mutant phenotype with the cloned
sequence. Characterization of the BEL1 gene revealed its amino acid sequence
identity to DNA binding domain of the homeobox family of transcription factors,
suggesting that the BEL1 protein itself may function as a transcriptional regulator.
The search for genes homologous to BEL1 resulted in identification of three new
homeobox genes, ABH1, ABH2, and ABH3. Together with BEL1, these three genes
define a novel homeobox gene subfamily in Arabidopsis.
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Rhee, David Beomjin. "Characterizing the Role of DNA Repair Proteins in Telomere Length Regulation and Maintenance: Fanconi Anemia Complementation Group C Protein and 8-Oxoguanine DNA Glycosylase." 2010. http://trace.tennessee.edu/utk_graddiss/843.
Full textAbstract:
Telomeres are the chromosome end structures consisting of telomere-associated proteins and short tandem repeat sequences, TTAGGG, in humans and mice. Telomeres prevent chromosome termini from being recognized as broken DNA ends. The structural integrity of DNA including telomeres is constantly threatened by a variety of DNA damaging agents on a daily basis. To counteract the constant threats from DNA damage, organisms have developed a number of DNA repair pathways to ensure that the integrity of genome remains intact. A number of DNA repair proteins localize to telomeres and contribute to telomere maintenance; however, it is still unclear as to what extent.
Telomere shortening has been linked to rare human disorders that present with bone marrow failure including Fanconi anemia (FA). FANCC is one of the most commonly mutated FA genes in FA patients and the FANCC subtype tends to have a relatively early onset of bone marrow failure and hematologic malignancies. Here, we studied the role of Fancc in telomere length regulation in mice. We demonstrated that deletion of Fancc did not affect telomerase activity, telomere length or telomeric end-capping in mice with long telomeres. We also showed that Fancc deficiency accelerates telomere shortening during high turnover of hematopoietic cells and promotes telomere recombination initiated by short telomeres.
Telomere shortening has also been linked to human aging and cancer development, with oxidative stress as a major contributing factor. 8-oxo-7, 8-dihydroguanine is among the most common oxidative DNA lesions, and is substrates for OGG1-initiated DNA base excision repair. Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity. We demonstrated that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. We also examined if telomeric DNA is particularly susceptible to oxidative guanine damage and if telomere specific factors affect the incision of oxidized guanines by OGG1. We showed that the GGG sequence context of telomere repeats and certain telomere configurations may contribute to telomere vulnerability to oxidative DNA damage processing.