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Zervos, Cassandra. "The effect of cross-linked learning on visual arts education." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2004. https://ro.ecu.edu.au/theses/774.
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This study examined how computer technology had an effect on a Year 9 visual arts education class with regard to the Western Australian four Arts Learning Outcomes (WA 4ALO). The research was administered concurrently with a learning approach called Cross-Linked Leaming (CLL) (Zervos, 1997), which consisted of three components: (1) the subject (e.g., visual arts education in relation to the WA 4ALO); (2) the learner (i.e., a target group and how they learn); and (3) the tool (e.g., computer technology). This study addressed the problem of how to promote learning in visual arts education, especially with visual arts theory. Historically, students have preferred to make art than to study art theory subjects such as art history and art criticism/response. Furthermore, many students may have found, traditional ways of learning theory to be less engaging and stimulating than making art. For this study, a sample consisted of 19 female students from an independent secondary school in Perth for one school term. The students were divided into three groups for the three data collections methods: (l) the whole class completed pre and post-questionnaires; (2) five pairs of students participated in pre- and post-interviews; and, (3) nine students' art portfolios representative of different levels, of achievement, that were analysed at the end of the school term. The methodology was action research. Data was collected and interpreted to answer the primary research question through four sub-questions as follows: (1.0) What was the effect of CLL on students; (1.1) What were students' attitudes towards CLL; (1.2) What skills did students require for CLL; (1.3) What knowledge did students exercise with CLL; and (1.4) What were students' preferences for !earning with CLL?" The results showed that the three components of CLL had a predominately positive effect upon most students in terms of their attitudes, skills, knowledge, and preferences. Furthermore, the students showed a first preference for learning visual arts theory in a CLL framework reflecting a social constructivist and student-centered way of learning that included using, computers 75% of the-•time for visual arts theory instruction. This thesis demonstrates that CLL is an effective framework for the Year 9 visual arts students who participated in this study.
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Suchow, Ariella Flora. "Alternative Science: An Examination of Practice-Linked Identity Formation Within the Context of an Art Science Program." Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:108784.
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Thesis advisor: Michael Barnett<br>This dissertation documents the pilot year of an Art Science Program. This study asks: what is possible when we create learning environments modeled for the integration of theatre and other artistic media with science? What, in general, are the affordances of theatre and other art forms for fostering such meaning-making, what are good ways to make it happen, and what are the challenges? We analyze young learners’ participation and attitude changes in the context of the Art Science Program. Findings indicate that (1) access to identity resources impacts learners’ practice-linked identities (Nasir & Cooks, 2009); (2) face-saving behaviors impact practice-linked identities by inhibiting learners’ access to identity resources; (3) the development of practice-linked identities parallels the development of possible selves; (4) the extent to which a learner is able to engage in their learning as a “whole person” (Wenger, 2006) is correlated with a learner’s identity trajectory; (5) learners may fail to form new practice-linked identities despite robust access to identity resources; and (6) learners may succeed in forming new practice-linked identities despite lack of significant access to identity resources because the identity resources that they do access provide a strong hook into new, nascent practice-linked identities<br>Thesis (PhD) — Boston College, 2020<br>Submitted to: Boston College. Lynch School of Education<br>Discipline: Teacher Education, Special Education, Curriculum and Instruction
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Nguyen, Thi Minh-Ha. "Molecular recognition of ubiquitin and Lysine 63 linked diubiquitin by STAM2 : the effect of the linkers length and flexibility." Thesis, Lyon, 2019. https://n2t.net/ark:/47881/m6668chz.
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Les interactions protéine-proteine sont considérées comme un domaine de recherche important puisqu’elles contrôlent la plupart des processus cellulaires. Chez les cellules eucaryotes, les protéines multi-domaines (MDP), constituées d’au moins deux domaines, représentent plus de 70 % des protéines. Au sein d’une MDP, ces domaines peuvent être identiques ou différents et sont reliés par un segment intrinsèquement désordonné de longueur et de flexibilité variable. Ces protéines peuvent alors adopter de multiples conformations dans l’espace et interagir de manière spécifique avec leurs partenaires biologiques. Malgré de nombreux efforts de recherche dans le domaine, certaines questions restent encore non résolues ou nécessitent une étude approfondie. Mon projet de recherche est d’étudier et de définir le rôle des segments intrinsèquement désordonnés de la protéine STAM2 (Signal transducing adapter molecule 2) impliquée dans la machinerie ESCRT (Endosomal Sorting Complexe Required for Transport) , première étape dans le processus de dégradation lysosomale. Plus précisément, l’étude se focalise sur les effets de la flexibilité et la dynamique de ces segments dans le cas du processus de reconnaissance moléculaire entre STAM2 et l’ubiquitine ou di-ubiquitine. Différents mutants ont alors été conçus : soit avec un domaine totalement ou partiellement supprimé, soit avec un raccourcissement ou une suppression complète du segment ou soit avec de multiples mutations dans la séquence peptidique du segment. Ces différents construits ont été analysés en utilisant une combinaison de techniques biophysiques telles que la relaxation de spin par résonance magnétique nucléaire (RMN), la diffusion des rayons X aux petits angles (SAXS) et le dichroïsme circulaire (CD). Il a alors été démontré qu’une altération du segment désordonné peut entraîner un changement de la dynamique de la protéine et/ou un changement conformationnel. La modification de ce segment influe sur le mouvement inter-domaine et modifie l’affinité entre les construits de STAM2 et la di-ubiquitine sans modifier l’intégrité de chaque domaine et de leur site de liaison. En résumé, les segments intrinsèquement désordonnés procurent une certaine plasticité à la protéine ce qui lui permet de s’adapter et de remplir sa fonction biologique. Il est alors possible d’imaginer dans un futur proche que ces segments soient la nouvelle génération de cibles thérapeutiques pouvant réduire ou supprimer certaines interactions nocives<br>Protein-protein interaction is considered as an important field of research, as it is the key to control variable cell processes and pathways. In eucaryotic cells, multidomain proteins (MDPs), which consist of more than one domain, take up over 70 % of the pool. Those identical or different domains of a MDP are connected to each other by a linker of variable length and flexibility. For long flexible linker, it allows the protein to sample a wide range of conformation and to adjust interaction in a subtle way. Despite numerous efforts of research on the field, some issues remain unanswered or require further investigation. As part of this thesis, my work aims to define the role taken by the intrinsically disordered linker within MDPs. For that purpose, the STAM2 (Signal transducing adapter molecule 2) protein of the ESCRT (Endosomal Sorting Complexes Required for Transport) machinery was chosen to examine the effect of the flexibility and dynamics of the linker regions on the molecular recognition with ubiquitin and Lysine63-linked di-ubiquitin (K63-Ub2). Such efforts were carried out by designing specific mutants altering the linker regions in different ways. The various truncated versions undergo half or complete deletion of a domain or have their linker either shortened, deleted or modified in the amino acid composition. With a combination of the several biophysical methods namely NMR (Nuclear Magnetic Resonance) spin relaxation, SAXS (Small Angle X-ray Scattering) and CD (Circular Dichroism), the study has demonstrated that the alteration in the linker region modifies the flexibility and the dynamics of the protein, one among them possibly introduces slight change in conformation. Furthermore, the modification of the linker has an impact on the inter-domain motion and alter binding affinities between STAM2 constructs and di-ubiquitin without affecting domains integrity or binding sites. In brief, disordered linkers provide plasticity to the protein, which allow adaptability and specificity to molecular recognition process. As a further application, the linkers included in multidomain proteins could also be the next generation of druggable target as their modification may reduce or completely abolish interactions
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Signer, Robert Ariel Joshua. "Aging and tumor suppression are linked processes in hematopoietic progenitor cells." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1790313761&sid=7&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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LI, QUAN, and q. li@cqu edu au. "HIGH FREQUENCY TRANSFORMER LINKED CONVERTERS FOR PHOTOVOLTAIC APPLICATIONS." Central Queensland University. N/A, 2006. http://library-resources.cqu.edu.au./thesis/adt-QCQU/public/adt-QCQU20060830.110106.
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This thesis examines converter topologies suitable for Module Integrated Converters
(MICs) in grid interactive photovoltaic (PV) systems, and makes a contribution to
the development of the MIC topologies based on the two-inductor boost converter,
which has received less research interest than other well known converters.
The thesis provides a detailed analysis of the resonant two-inductor boost converter
in the MIC implementations with intermediate constant DC links. Under variable
frequency control, this converter is able to operate with a variable DC gain while
maintaining the resonant condition. A similar study is also provided for the resonant
two-inductor boost converter with the voltage clamp, which aims to increase the
output voltage range while reducing the switch voltage stress. An operating point
with minimized power loss can be also established under the fixed load condition.
Both the hard-switched and the soft-switched current fed two-inductor boost
converters are developed for the MIC implementations with unfolding stages. Nondissipative
snubbers and a resonant transition gate drive circuit are respectively
employed in the two converters to minimize the power loss.
The simulation study of a frequency-changer-based two-inductor boost converter is
also provided. This converter features a small non-polarised capacitor in a second
phase output to provide the power balance in single phase inverter applications.
Four magnetic integration solutions for the two-inductor boost converter have also
been presented and they are promising in reducing the converter size and power loss.
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Fuller, Jeannette. "Are guilt and shame in male forensic patients linked to treatment motivation and readiness?" Thesis, University of Surrey, 2017. http://epubs.surrey.ac.uk/841667/.
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This thesis includes the research, assignments and clinical placements that were undertaken for the degree of Doctor of Psychology (Clinical Psychology). The Major Research Project was focused on the concepts of guilt and shame and treatment motivation and readiness in forensic patients. Treatment motivation and readiness are important considerations in forensic settings. Models and theories of these concepts suggest affective factors such as the experience of guilt and shame are likely to have some impact on motivation and readiness for treatment. These models have been validated in general forensic settings, but although applied to forensic mental health settings, the validity of the different aspects of these models has not been directly examined with forensic mental health patients. This thesis aimed to investigate whether there was any relationship between guilt and shame and motivation and readiness for treatment in a sample of forensic patients. Part one of this thesis presents a narrative review of guilt and shame in forensic mental health participants. The findings of the review suggested that guilt and shame were relevant emotional experiences for forensic patients. Links between these emotions and motivation and readiness for treatment had not been empirically tested. Part two presents an empirical paper that investigated the association between guilt and shame and treatment motivation and readiness in patients residing in forensic mental health settings. The findings suggested that offence-related guilt was associated with readiness for treatment, whereas shame did not have a relationship with motivation or readiness. Part three presents a summary of clinical experience gained within this training programme and Part four contains the assessments completed during training.
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Landgraf, Kathrin, Markus Scholz, Peter Kovacs, Wieland Kiess, and Antje Körner. "FTO obesity risk variants are linked to adipocyte IRX3 expression and BMI of children." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-213844.
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Background: Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte
function through targeting IRX3 and IRX5 and thermogenesis regulation. Aim: We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. Results: Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the
children. Conclusion: One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children.
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Paiwand, Frouz Frozan. "RHAMM, CD44 expression and erk activation are linked in malignant human breast cancer cells and are associated with cell motility." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ46047.pdf.
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Torssander, Jenny. "Equality in Death? : How the Social Positions of Individuals and Families are Linked to Mortality." Doctoral thesis, Stockholms universitet, Sociologiska institutionen, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-94134.
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Socioeconomic positions of individuals are clearly associated with the chances of living a healthy long life. In four empirical studies based on Swedish population registers, two topics are examined in this thesis: The relationships between different indicators of social position and mortality, and the importance of family members’ socioeconomic resources for the survival of the individual. The overall conclusion from the separate studies is that no single individual socioeconomic factor gives a complete picture of mortality inequalities. Further, the socioeconomic resources of partners and adult children are important in addition to the individual ones. The specific results from each study include that: I education, social class, social status and income are, to various extent, independently associated with mortality risk. Education and social status are related to women’s mortality, and education, social class, and income to men’s mortality. II one partner’s social position is related to the other partner’s survival, also when individual socioeconomic factors are statistically controlled for. In particular, men’s mortality is linked to their wives’ education and women’s mortality to their husbands’ social class. III adult children’s education is related to their parents’ risk of dying, also when both parents’ socioeconomic resources are taken into consideration. Further, the association between the offspring’s level of education and parental mortality cannot be explained by characteristics that parents share with their siblings. IV children’s social class and income are related to parental mortality, but not as strongly as the education of the children. There is no relationship between a mother’s own education and breast cancer mortality, while mothers seem to have better chances of surviving breast cancer if they have well-educated children.<br><p>At the time of doctoral defence the following paper was unpublished and had a status as follows: Paper 4: Manuscript</p>
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Sonobe, Makoto. "Mutations in the epidermal growth factor receptor gene are linked to smoking-independent, lung adenocarcinoma." Kyoto University, 2006. http://hdl.handle.net/2433/135889.
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Tello, Puerta Fernando. "Deductibility of the Spending Linked to the Expenditures Incurred as a Result of an Extrajudicial Transaction: Are We in the Face of a True Act of Liberality?" Derecho & Sociedad, 2015. http://repositorio.pucp.edu.pe/index/handle/123456789/118858.
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This essay pretends to offer a juridical analysis of recent pronouncements of the Peruvian Tax Adminstration, by virtue of which, such entity states that those disbursements linked to extra judicial transactions do not constitute deductible expenses for the calculation of the Peruvian Income Tax. Under such premises, we offer a civil analysis of the nature of such disbursements and later, cover the issue of their relation with the generation of taxable income for Income Tax purposes.<br>El presente artículo pretende efectuar un análisis jurídico de los recientes pronunciamientos de la Administración Tributaria, en el sentido que los pagos efectuados como consecuencia de transacciones extrajudiciales no resultan deducibles para efectos de la determinación del Impuesto a la Renta. Se trata pues, de un análisis de corte civil respecto de la real naturaleza de los desembolsos efectuados con ocasión de la celebración de una transacción extrajudicial, para luego abordar la problemática de su vinculación con la generación de rentas gravadas con elImpuesto a la Renta.
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Wood, Chantelle. "Associative strength determines prejudice-linked differences in automatic stereotype activation." University of Western Australia. School of Psychology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0238.
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There is little consensus in the social-cognitive literature concerning the way in which prejudice and stereotyping are related, though a number of explanatory models have been proposed. The present research program empirically examines one recent model; Lepore and Brown's Associative Strength Model (ASM: 1997; 1999; 2002). The main premise of the ASM is that differential endorsement of stereotypic content leads to individual variation in the content that is automatically activated upon categorisation. Specifically, it predicts that high-prejudice people automatically activate negative stereotypic traits, and low-prejudice people automatically activate positive stereotypic traits. The current research used a primed lexical decision task to examine prejudicelinked differences in automatic stereotype activation. In addition, an impression formation task based on that of Lepore and Brown was included to measure stereotype application. Experiments 1A and 1B attempted to evaluate the predictions of the ASM using the category and stereotype of Asians. However, neither experiment was able to demonstrate a priming effect, prejudice-linked or otherwise, using this social category. Experiments 2 and 3, in contrast, successfully induced stereotype activation using the category of gay men. Furthermore, results were consistent with the predictions of the ASM. After priming with the category of gay men, high-prejudice participants exhibited greater activation of negative stereotypic traits and low-prejudice participants exhibited greater activation of positive stereotypic traits. However, parallel patterns of stereotype application were not found in the impression formation task, with participants forming positive impressions, regardless of prejudice. Experiment 4 used an honesty manipulation to investigate the possibility that self-presentational concerns were responsible for the discrepancies between stereotype activation and application. Consistent with this argument, Experiment 4 found prejudice-linked patterns of stereotype application that mirrored the patterns of stereotype activation when self-presentation concerns were reduced. When instructed to be honest, high-prejudice participants in the gay prime condition formed negative impressions and low-prejudice participants in the gay prime condition formed positive impressions. The current program of research provides the first direct empirical support for the predictions of the Associative Strength Model concerning stereotype activation. In addition, new questions have been raised that future research should seek to explore.
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CAPPELLETTI, CRISTINA. "Type I interferons and toll-like receptors are linked to pathological alterations of idiopathic inflammatory myopathiens." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2009. http://hdl.handle.net/10281/9235.
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Objective: The triggering factor of inflammation in idiopathic inflammatory myopathies (IIMs) is
still unknown and an involvement of viruses or bacteria has been put forward. We sought to
investigate the expression of type I interferons (IFNα/β) and of endosomal Toll-like receptors
(TLRs) in IIM muscles.
Methods: Ten IIM and 5 control muscle biopsies were assessed by microarray analysis for the
expression of approximately 16,000 genes; 37 additional samples from IIM and controls were
studied for IFNα/β-dependent genes and intracellular TLR expression using
immunohistochemistry, confocal miscroscopy, real-time quantitative and qualitative PCR.
Results: IFNα/β-dependent gene transcripts were up-regulated in all IIM muscle specimens
compared to controls. In juvenile dermatomyositis (JDM) ISG15 (408-fold), IFIT3 (261-fold), MX1
(99-fold), IRF7 (37-fold) were those most expressed. TLR3, TLR7 and TLR9 were differentially
expressed in IIM muscles: TLR3 was highly up-regulated in JDM, localized on vascular endothelial
cells, muscle infiltrating cells and regenerating myofibers; TLR7 and TLR9 were frequently
detected in polymyositis (PM), mainly on cell infiltrates (particularly plasma cells), and on some
injured myofibers.
Conclusion: Transcriptome analysis indicated that IFNα/β-induced molecules play a key role in the
pathogenesis of IIMs, particularly in JDM. Endosomal TLRs represent important effector molecules
that link innate and adaptive immune responses in affected muscles, showing their potential as new
therapeutic targets for the IIM treatment.
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Haque, Rosenani S. M. Anwarul. "Silver, mercury and ruthenium complexes of N-heterocyclic carbene linked cyclophanes." University of Western Australia. Chemistry Discipline Group, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0236.
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This thesis describes the synthesis and isolation of silver, mercury, ruthenium and palladium complexes of bidentate N-heterocyclic carbenes (NHCs), derived from imidazolium-linked cyclophanes and related bis-imidazolium salts. The cyclophane structures contain two imidazolyl links between ortho- and meta- substituted aromatic rings and the related structures are ortho-, meta- and para-xylyl linked bis-imidazolium salts. The complexes have been characterised by NMR spectroscopy and X-ray crystallography. The synthesis of five new silver complexes has been achieved via a simple complexation reaction of the cyclophane and bis-imidazolium salts with the basic metal source Ag2O. The new silver carbene systems are thermally stable. Three of the complexes are dinuclear, cationic complexes, while two are mononuclear complexes, one cationic and one neutral. A number of mono- and di-nuclear mercury(II)-NHC complexes have been synthesised from the ortho- and meta-linked cyclophanes and the related meta-linked bis-imidazolium salts. The mercury complexes were prepared by direct mercuration method using mercury(II) acetate. The syntheses were perfomed in air and the complexes are stable to air and moisture. Mercury complexes I and II represent the first example of mononuclear metal complexes derived from meta-substituted imidazolium-linked cyclophanes. NHC-ligand transfer reactions from NHC-silver complexes and NHC-mercury complexes are described. An ortho-cyclophane ligand was successfully transfered from a silver complex to its palladium counterpart. Furthermore, palladium complex III, bearing a para-xylyl linked bis-NHC ligand, was made by transmetallation from both a silver and mercury complex. This is the first reported NHC-palladium complex of a para-xylyl linked bis-NHC ligand. A new redox transmetallation method for NHC ligand transfer, using a mercury complex, is presented. A palladium complex was made via redox transmetallation using a mercury complex of an ortho-NHC-cyclophane. A ruthenium(II)-NHC complex, IV containing an ortho-cyclophane ligand has been prepared via silver transmetallation and in situ complexation methods. In the transmetallation route, a silver complex of an ortho-cyclophane was treated with RuCl2(PPh3)3 to form IV. This complex represents the first example of a ruthenium complex bearing an NHC-cyclophane ligand, v and is also the first example of a metal complex derived from an imidazolium-linked cyclophane where the arene unit of the cyclophane is also involved in bonding to the metal centre.
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Tymichova, Michaela. "Relation between toughness and molecular coupling at cross-linked polymer/solid interfaces." Access electronically, 2005. http://www.library.uow.edu.au/adt-NWU/public/adt-NWU20060712.125012/index.html.
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Naef, Michael. "Are the gonad abnormalities in whitefish from Lake Thun linked to elevated concentrations of persistent organic pollutants? /." Zürich, 2007. http://www.empa.ch/plugin/template/empa/*/66055/---/l=1.
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Panakova, Daniela. "Lipoprotein particles associate with lipid-linked proteins and are required for long-range Wingless and Hedgehog signaling." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2005. http://nbn-resolving.de/urn:nbn:de:swb:14-1122025765300-27455.
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Morphogens of the Wnt and Hedgehog families are secreted signaling molecules that coordinate growth and patterning of many different tissues. Both, Wingless and Hedgehog spread across long distances in developing wing of Drosophila melanogaster. However, both proteins are covalently modified with lipid moieties. The mechanisms that allow long-range movement of such hydrophobic molecules are unclear. Like Wingles and Hedgehog, glycosylphosphatidylinositol (gpi)-linked proteins also transfer between cells with their lipid anchor intact. It has been speculated that gpi-linked proteins and lipid-linked morphogens travel together on a membranous particle, which was termed an argosome. As yet however, no functional link between argosome production and dispersal of lipid-linked proteins has been established. The topic of this thesis is to understand the cell biological nature of the argosome and thus contribute to understanding of morphogen gradient formation. To address the question of argosome biosynthesis, at least two models have been proposed. One possibility is that argosomes are membranous exovesicles with a complete membrane bilayer. Alternatively, argosomes might resemble lipoprotein particles that comprise on of a family of apolipoproteins scaffolded around a phospholipid monolayer that surrounds a core of esterified cholesterol and triglyceride. Lipid-modified proteins of the exoplasmic face of the membrane (like GFPgpi, Wingless or Hedgehog) might fit well into the outer phospholipid monolayer of such a particle. Here, I utilize biochemical fractionation to determine the sort of particle that lipid-linked proteins associate with. I show that Wingless, Hedgehog and gpi-linked proteins bind Drosophila lipoprotein particles in vitro, and colocalize with them in wing imaginal discs. Next, I use genetic means to address the functional importance of this association. I demonstrate that reducing Lipophorin levels in Drosophila larvae perturbs long-range but not shor-range Wingless and Hedgehog signaling, and increases the sequestration of Hedgehog by Patched. I propose that Lipophorin particles are vehicles for the long-range movement of lipid-linked morphogens and gpi-linked proteins.
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Kipgen, Nathalie [Verfasser], and Dirk [Akademischer Betreuer] Hellhammer. "Are pre-/postnatal stress factors and chronic stress linked to breast cancer? / Nathalie Kipgen ; Betreuer: Dirk Hellhammer." Trier : Universität Trier, 2015. http://d-nb.info/1197701486/34.
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Cordes, Mikael, and Marko Stugbäck. "Selecting the Right Strategy : How are user innovations linked to the product life cycle for mature industries." Thesis, Blekinge Tekniska Högskola, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-12073.
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Companies are dependent on continuously provide the market with new products to keep its market position and profitability level. The companies examined in this thesis are two bigger Swedish enterprises that have a long history in a mature business-to-business context providing industrial goods to the market. This work examines how users are involved in the different innovation and product development activities. The problem is to understand how business-to-business companies co-operate with stakeholder and users, when in the product life cycle that is done, and who are the ones doing the actual innovation. The methodological approach for the work was deductive, building a theory including innovation, strategy and user theories that was empirically tested and followed by an analysis and conclusion of the found evidence. Key findings: Most if not all innovations in mature market are routine ones. There is lack of strategic focus due to micromanagement that shifts focus rapidly. Innovations are often found in the beginning and in the end of the product life cycle. Mature markets tend to utilize a more closed innovation model as opposite to an open model. Users are not heavily involved in the actual innovation process. Stickiness and tacit knowledge is quite big in large corporation event though there is said to be a strategic focus on the customers. Implications: More involvement of users, especially lead users, will lead to more innovations. Utilising strategic buckets of different sizes for spreading the resources on different innovation types (routine/disruptive/discontinuous) to become successful
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Persson, Elin, and Pauline Frelet. " How changes in banks in Västerbotten are linked to the current financial crisis, but are still normal organizational development : "Yes, but..."." Thesis, Umeå universitet, Handelshögskolan vid Umeå universitet, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-25621.
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Title: Yes, but… - How changes in banks in Västerbotten are linked to the current financial crisis, but are still normal organizational development Background: In the beginning of the 90’s, there was a financial crisis in Sweden which hit Swedish banks hard. The Swedish bank Gota banken went bankrupt and Nordbanken was taken over by the government, in large part because of their apathetic reactions to the situation they were so surprised to find themselves in. Today, almost 20 years later, the banks of Sweden find themselves in a new crisis. Because of the important position banks have in society, it is extremely important that they remain stable and have the capacity to ride out a crisis situation comfortably. As the banks did not show any crisis management strategy or skills in the 1992 crisis, it is relevant to explore if the previous experience has given Swedish banks the ability to handle a crisis situation in an efficient way. Purpose: The purpose of this study is to apply organizational development theory, crisis management theory and adversity reaction theory to the primary data collected from the interviews with the banks and through that analyze if Swedish banks are acting to prevent the financial crisis from affecting them badly. Method: The study has a hermeneutical approach and was carried out by interviewing managers from the five major banks in Västerbotten. The primary data collected has been analyzed to get an understanding of the current development in the banks and its possible link to the financial crisis. Conclusion: We found that banks are constantly changing in order to keep up with their competitors, changes in technology, society and the increasing demands from customers. The current events and changes in the banks are undoubtedly linked to the financial crisis, it has accelerated change, it has slowed down ongoing processes and it has facilitated harder decisions and less popular changes. But the crisis has not caused drastic changes in the organizations or their way of doing business. In fact, it can be said that the changes due to the financial crisis is normal organizational development, as the banks have responded to it in much the same fashion as they do to all changes in the external environment. Key words: crisis management, organizational development, threat rigidity, prospect theory, financial crisis
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Hireche, Farid. "Les jardins d'Alger de l'époque ottomane (XVIᵉ - XIXᵉ siècle). Histoire Paysage & Patrimoine". Electronic Thesis or Diss., Orléans, 2024. http://www.theses.fr/2024ORLE1077.
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Les jardins historiques d'Algérie de l'époque ottomane (XVIe - XIXe siècles) ont subi de nombreuses amputations. De nombreux jardins ont tout simplement disparu, voire subi des transformations irrémédiables. L'urbanisation des campagnes dans lesquelles ils s'épanouissaient a rendu leur lecture difficile, d'un point de vue purement paysager. Lorsque ces propriétés sont du ressort du domaine public, se pose l'épineuse question de la patrimonialisation de cet héritage culturel, qui peine à former un centre d'intérêt partagé, une identité commune, malgré les réglementations patrimoniales mises en place par les autorités politiques successives. D'un point de vue urbanistique, les jardins aujourd'hui insérés dans un tissu dense sont amenés à évoluer du fait même du métabolisme urbain. Se pose alors la question de la place des jardins historiques ottomans dans la planification urbaine. Quels modes d'appropriation sont à l'œuvre par leurs nouveaux propriétaires privés ou publics ? Comment rendre accessible ces jardins historiques au grand public ? Quelles stratégies doctrinales entériner pour la valorisation culturelle de ces jardins historiques ? Quel rôle peuvent-ils jouer dans la fabrique de la ville durable et écologique de demain ? Quelle approche territoriale et paysagère employer pour les intégrer aux trames verte et bleue existantes ? Quelle place attribuer aux éléments hydrauliques disséminés dans le tissu urbain dense et aux paysages culturels liés à l'eau encore en place ? C'est ce type de questionnement que cette thèse de doctorat en Histoire, mention patrimoine tentera d'approfondir et de solutionner<br>The historic gardens of Algeria from the Ottoman era (16th - 19th centuries) have suffered numerous amputations. Many gardens have simply disappeared, or even undergone irremediable transformations. The urbanization of the countryside in which they flourished made them difficult to read, from a purely landscape point of view. When these properties are in the public domain, the thorny question of cultural heritage arises, which struggles to form a shared center of interest, a common identity, despite the heritage regulations put in place by the successive political authorities. From an urban planning point of view, gardens today inserted into a dense fabric are bound to evolve due to urban metabolism. The question then arises of the place of historic Ottoman gardens in urban planning. What modes of appropriation are at work by their new private or public owners? How can we make these historic gardens accessible to the general public? What doctrinal strategies should be endorsed for the cultural valorization of these historic gardens? What role can they play in creating the sustainable and ecological city of tomorrow? What territorial and landscape approach should be used to integrate them into the existing green and blue framework? What place should be given to hydraulic elements scattered throughout the dense urban fabric and to cultural landscapes linked to water still in place? It is this type of questioning that this doctoral thesis in History option Heritage will attempt to explore and resolve
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Persson, Andreas. "Leisure in adolescence : youths' activity choices and why they are linked to problems for some and not others /." Örebro : Universitetsbiblioteket : Örebro University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-790.
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Flieger, Wolfgang. "Die "Taz" : vom Alternativblatt zur linken Tageszeitung /." München : Ölschläger, 1992. http://catalogue.bnf.fr/ark:/12148/cb35599365c.
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Hesler, Valerie Jane. "N-Heterocyclic carbene-metal complexes derived from imidazolium-linked cyclophane and biimidazolium salts." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2008. http://theses.library.uwa.edu.au/adt-WU2009.0088.
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This thesis presents an investigation into the synthesis of metal complexes of (Nheterocyclic carbene)-based cyclophanes. There were three main areas of focus: synthesis and complexation of bis(4,5-dihydroimidazolium) salts; the synthesis and complexation of phenol-functionalised imidazolium cyclophanes; and the synthesis and complexation of (N-heterocyclic carbene)-based cyclophanes by C-C bond activation of biimidazolium salts with electron-rich metals. The synthesis of xylyl-linked bis(4,5-dihydroimidazolium) salts was investigated. Attempts to prepare these compounds by the cyclisation of a tetraamine (linear or macrocyclic) were unsuccessful due difficulties in preparing the tetraamines. The target compounds could be prepared by adapting the methods developed for the synthesis of bis(imidazolium) salts however problems associated with purification and stability of the products prevented complexation studies. A series of phenol-, phenoxide- and anisole-functionalised imidazolium cyclophanes were prepared. Their structural properties were investigated using dynamic nmr studies and X-ray crystallography. Complexation of the functionalised cyclophanes was investigated. The phenol cyclophane I formed a dinuclear complex with mercury(II). This complex is the first example of a complex derived from a phenol-functionalised imidazolium cyclophane. However the anisole cyclophane II and the unsymmetrical phenol/ortho cyclophane III were unable to form complexes possibly due to steric hindrance and instability of the cyclophane respectively. Preliminary complexation studies of the bis(imidazolium)phenol V suggested that complexation with palladium(II) and mercury(II) were possible but more work is required to determine the optimum reaction conditions. A series of biimidazolium salts VI (both new and known) were prepared. Previously reported biimidazolium salts have very low solubility in common solvents therefore the incorporation of long alkyl chains to the bridging group was investigated as a means to improve the solubility. The structure of the salts was explored using a range of techniques including dynamic nmr spectroscopy, cyclic voltammetry, UV/Visible spectroscopy, X-ray crystallography and mass spectrometry. Some of the biimidazolium salts were able to rotate about the C2-C2' bond and the free energy of activation for this process was estimated using dynamic nmr studies. C-C bond activation of the biimidazolium salts with palladium(0) was used to form a series of palladium(II) complexes (VII) of (NHC)-based cyclophanes. These reactions are the first examples of the synthesis of bis(NHC) complexes by C-C bond activation. The reactivity of the biimidazolium salts with palladium(0) was compared to their solution structure and it was found that only the biimidazolium that were able to rotate about the C2-C2' bond could react with palladium(0).
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Liggett, Joshua B. "Geek As a Constructed Identity and a Crucial Component of Stem Persistence." Thesis, University of North Texas, 2014. https://digital.library.unt.edu/ark:/67531/metadc500004/.
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The fields of science, technology, engineering and mathematics (STEM) have long been the bastions of the white male elite. Recently, academia has begun to recognize gender and ethnic disparities. In an effort to expand the recruitment pool for these STEM fields in college, various efforts have been employed nationally at the secondary level. In California, the latest of these efforts is referred to as Linked Learning, a pedagogy that combines college preparation with career preparation. The current study is investigating the connection between what has been referred to in current scholarship as "Geeking Out" with higher academic performance. The phenomenon of “Geeking Out” includes a variety of non-school related activities that range from participating in robotics competitions to a simple game of Dungeons & Dragons. The current project investigates the relationship between long term success in STEM fields and current informal behaviors of secondary students. This particular circumstance where Linked Learning happens to combine with "Geeking Out" is successful due to the associated inclusionary environment. Methods included a yearlong ethnographic study of the Center for Advanced Research and Technology, a Central Valley school with a diverse student body. Through participant observation and interviews, the main goal of this research is to examine the circumstances that influence the effectiveness found in the environment of the Center for Advanced Research and Technology.
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Xie, Wa. "Surface Topography and Aesthetics of Recycled Cross-Linked Polyethylene Wire and Cable Coatings." Thesis, University of North Texas, 2014. https://digital.library.unt.edu/ark:/67531/metadc799512/.
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Our research focuses on re-using a waste a material, cross-linked polyethylene abbreviated XLPE, which is a widely used coating for wires. XLPE is strong and has excellent thermal properties due to its chemical structure - what leads to the significance of recycling this valuable polymer. Properties of XLPE include good resistance to heat, resistance to chemical corrosion, and high impact strength. A wire is usually composed of a metal core conductor and polymeric coating layers. One creates a new coating, including little pieces of recycled XLPE in the lower layer adjacent to the wire, and virgin XLPE only in the upper layer. Industries are often wasting materials which might be useful. Mostly, some returned or excess products could be recycled to create a new type of product or enable the original use. This method helps cleaning the waste, lowers the costs, and enhances the income of the manufacturing company. With the changing of the thickness of the outer layer, the roughness changes significantly. Moreover, different processing methods result in surfaces that look differently.
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Haller, Armin, Javier D. Fernández, Maulik R. Kamdar, and Axel Polleres. "What are Links in Linked Open Data? A Characterization and Evaluation of Links between Knowledge Graphs on the Web." Department für Informationsverarbeitung und Prozessmanagement, WU Vienna University of Economics and Business, 2019. http://epub.wu.ac.at/7193/1/20191002ePub_LOD_link_analysis.pdf.
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Linked Open Data promises to provide guiding principles to publish interlinked knowledge graphs on the Web in the form of findable, accessible, interoperable and reusable datasets. We argue that while as such, Linked Data may be viewed as a basis for instantiating the FAIR principles, there are still a number of open issues that cause significant data quality issues even when knowledge graphs are published as Linked Data. Firstly, in order to define boundaries of single coherent knowledge graphs within Linked Data, a principled notion of what a dataset is, or, respectively, what links within and between datasets are, has been missing. Secondly, we argue that in order to enable FAIR knowledge graphs, Linked Data misses standardised findability and accessability mechanism, via a single entry link. In order to address the first issue, we (i) propose a rigorous definition of a naming authority for a Linked Data dataset (ii) define different link types for data in Linked datasets, (iii) provide an empirical analysis of linkage among the datasets of the Linked Open Data cloud, and (iv) analyse the dereferenceability of those links. We base our analyses and link computations on a scalable mechanism implemented on top of the HDT format, which allows us to analyse quantity and quality of different link types at scale.<br>Series: Working Papers on Information Systems, Information Business and Operations
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Telemeco, Rory S. "Are reproductive life history traits of Australian three-lined skinks fixed or phenotypically plastic? /." Read online, 2009. http://library.uco.edu/UCOthesis/TelemecoRS2009.pdf.
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Clarke, Patrick. "Assessing the role of attentional engagement and attentional disengagement in anxiety-linked attentional bias." University of Western Australia. School of Psychology, 2009. http://theses.library.uwa.edu.au/adt-WU2010.0024.
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[Truncated abstract] It has consistently been found that individuals who are more highly vulnerable to anxious mood selectively attend to emotionally negative stimuli as compared to those lower in anxiety vulnerability, suggesting that such anxiety-prone individuals possess an attentional bias favouring negative information. Two of the most consistent tasks used to reveal this bias have been the attentional probe and emotional Stroop tasks. It has been noted, however, that these tasks have not been capable of differentiating the relative role of attentional engagement with, and attentional disengagement from emotionally valenced stimuli, suggesting that either of these attentional processes could account for the attentional bias observed in individuals with high levels of anxiety vulnerability on the attentional probe and emotional Stroop tasks. A number of resent studies have claimed support for the operation of biased attentional disengagement in anxiety using a modified attentional cueing paradigm, concluding that individuals more vulnerable to anxious mood have a selective difficulty disengaging attention from emotionally negative stimuli. The current thesis highlights the possibility, however, that the structure of the modified cueing paradigm could allow individual differences in initial attentional engagement with differentially valenced stimuli to be interpreted as a selective disengagement bias. ... The modified emotional Stroop task employed in the current research measured participant's ability to engage with the emotional content of differentially valenced stimuli having initially processed non-emotional information (stimulus colour), and measured their relative ability to disengage attention from such emotional content to process non-emotional stimulus information. Results using this modified Stroop task suggested that those with high vulnerability to anxious mood were disproportionately fast to engage with the content of negative as compared to non-negative stimuli whereas those with low vulnerability to anxious mood did not display this pattern. The results provided no support for presence of an anxiety-linked bias in attentional disengagement from the content of differentially valenced stimuli. Results derived from the modified emotional Stroop task therefore provided support for the presence of an anxiety-linked bias in attentional engagement with the content of emotionally negative stimuli, but no support for a bias in attentional disengagement from the content of such material. The final study in the present series of experiments was designed to address the novel possibility that a bias in attentional disengagement could result in ongoing semantic activation of negatively valenced stimuli which would not necessarily be indexed by previous tasks assessing biased attentional disengagement. The results of this final study, however, provided no evidence to suggest the presence of anxiety-linked differences in ongoing semantic activation of differentially valenced stimuli. The present series of studies therefore provide support for the presence of an anxiety-linked bias in attentional engagement with the content of emotionally negative stimuli, while providing no support for the presence of an anxiety-linked bias in attentional disengagement from negative stimuli.
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au, Helenallison@ozemail com, and Helen Elizabeth Allison. "Linked Social-Ecological Systems: A Case Study of The Resilience of The Western Australian Agricultural Region." Murdoch University, 2003. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20040730.144640.
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In the Western Australian agricultural region, an area of approximately 14 million hectares (70,000 square miles), widespread areas of native vegetation have been cleared and replaced with annual cropping systems, predominantly wheat. Only1.3 million hectares (10%) of small and scattered native vegetation remnants remain. By 2000 16% of land in the region was at risk from soil salinity and was largely unproductive for commercial agriculture. A new hydrological equilibrium affecting 33% of the Western Australian agricultural region is predicted to be reached between 2050 and 2300.
The starting premise of this dissertation is that normal disciplinary science was adopted as the dominant intellectual influence on natural resource management policy and thus natural resource degradation was treated as a problem for science, extracted from its social, economic and historical contexts. The second premise of this dissertation is that natural resource problems are not isolated scientific or technical problems, and are exacerbated by human failure to predict the complex inter-relationships among the social, ecological and economic systems.
This dissertation initially provides an analytical narrative on the Western Australian agricultural region between 1889 and 2003 (114 years) with the main finding being that in the years pre-1970 a development-driven Western Australian Government was responsible for extensive land clearing for agriculture, often contrary to scientific advice. In the 1980s and 1990s the severity and extent of soil salinity and the prognosis of future negative trends in other natural resource indicators caused a rapid proliferation and evolution of Federal and State policies designed to solve the problem. Nonetheless many natural resource problems remain intractable. The second part of the dissertation investigates the epistemology of the normal science paradigm as it was applied to natural resource management problems in the 20th century as a potentially contributing cause.
The evolution of an alternative epistemology, post-normal science paradigm, is then examined for explicating our current understanding of reality. A research framework was constructed which defines the post-normal science paradigm; the systemic approach; the bodies of theoryorganisational, ecology, resilience and system dynamics theory; the social-ecological system perspective; and the methodsresilience analysis and system dynamics. This framework provides a novel way in which to gain a greater understanding of the fundamental or root causes of natural resource management problems. Using the case study of the Western Australian agricultural region a dynamic model was constructed based on descriptive information. An examination of the historical events and processes of the Western Australian agricultural region reveals that over a 114-year history it has evolved through two interactions of the adaptive cycle. Further investigation reveals these two cycles were synchronous with the second and third economic long-wave cycles or Kondratiev Cycles, that show the behaviour over time of the evolution of modern industrial societies. The model suggests that the reasons for the dynamic behaviour of the Western Australian agricultural region lie in the interaction of the three production growth drivers of the international commodity system, which have resulted in a pathological system, the Lock-in Trap. Increased total commodity production, reinvestment and declining prices in real terms have tended to produce the unintended negative impacts of resource decline, environmental pollution and rural population decline. I suggest that the expansion of thresholds through the reinvestment in technology is a principle reason why there has not yet been a profound collapse of exploited renewable resources in the Western Australian agricultural region. Regional natural resource management strategies will need to take account of not only spatial cross-scale issues, in particular the linkages between the individual farmer and the international commodity system, but also the temporal variables, in particular the slowly emerging changes in ecological/physical variables, such as the hydrological cycle.
This research can help to provide the information and heuristic metaphors to encourage natural resource policy makers to take long-term and whole system perspectives. It includes a powerful set of tools for communicating dynamic processes in an integrated method to inform policy and management decisions. The ideas in this interdisciplinary research are essential for making science relevant within a social and ecological context.
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Allison, Helen Elizabeth. "Linked social-ecological systems : a case study of the resilience of the Western Australian agricultural region /." Access via Murdoch University Digital Theses Project, 2003. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20040730.144640.
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Jones, Lauren Brittany. "Defining Components Linked to Bacterial Nutritional Utilization of Cyanide as a Sole Nitrogen Source." Thesis, University of North Texas, 2019. https://digital.library.unt.edu/ark:/67531/metadc1505253/.
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One of the challenges in biology is placing a function on the myriad of gene sequences having become available from rapid advances in genome sequencing. One such example is a gene cluster (Nit1C) found in bacteria that is tied to the unusual ability of certain bacteria to grow when supplied cyanide as the sole nitrogen source. The term cyanotrophs has been applied to such bacteria, for which a genetic linkage between cyanotrophy and Nit1C was demonstrated for 10 separate bacteria. In addition to growth, cyanide induced the expression of Nit1C genes in all organisms tested, and in one case, deletion of one of the Nit1C genes (nitC) caused a loss of growth. Of the ten bacteria able to grow cyanotrophically, all gave evidence of harboring Nit1C on their genome except for two (Pseudomonas fluorescens Pf11764 and P. monteilii BCN3), which were sequenced and the presence of Nit1C was also confirmed. A broader search of bacteria identified 270 separate strains with the cluster, all limited to bacteria spanning the phyla Firmicutes, Actinobacteria, Proteobacteria and Cyanobacteria. Remarkably, many examples of a single representative of a given taxon contained Nit1C, most poignantly displayed by Pf11764 and PmBCN3; the interpretation being the cluster was likely acquired by horizontal gene transfer in response to cyanide as an environmental cue. Consistent with its absence in Archaea is the time line for the emergence of cyanide producing organisms (cyanogens) on earth dating back only 400-500 million years.
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Galt, Cynthia P. "Impact of Stress Inoculation on Performance Efficacy Linked to Instrumental Activities of Daily Living." Thesis, University of North Texas, 1999. https://digital.library.unt.edu/ark:/67531/metadc278069/.
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Utilizing a sample of community-residing older adults, this pretest-posttest design evaluated the short term (approximately 1 week) impact on everyday functioning of Stress Inoculation (SI) training, a cognitive-behavioral intervention that is essentially a coping skills enhancement program. The targets of training were anxiety and concern about being able to successfully perform everyday living tasks. The training program was contrasted with a no contact (waiting list) control. In an effort to maximize the practical aspects of this study, the assessment battery included the use of two ecologically valid measures of everyday problem solving skills (one self-rated and one interviewer-rated). Also included were a measure of everyday intelligence widely used in gerontological research, two measures of self-efficacy, a geriatric depression scale, a state-trait anxiety scale, and a self-report measure of failures in perception, memory, and motor function. The results suggest that Stress Inoculation training is an effective intervention for improving everyday competence but that personal perceptions of self-efficacy and the emotional states of anxiety and depression mediate treatment effects. In general, only persons with lower levels of self-efficacy and higher levels of anxiety and/or depression saw improvement in their cognitive performance following SI training.
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Khodeneva, Natalya <1988>. "Epigenetic changes promoting HeLa cell apoptosis are linked to valproic acid-induced down-regulation of REST and its corepressor CoREST." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7651/1/Khodeneva_Natalya_PhD_Thesis_310316.pdf.
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REST (RE-1 silencing transcription factor, or NRSF –neuron-restrictive silencing factor) binds to a conserved RE-1 motif present in the promoter region of regulated genes and represses their transcription in neuronal and non-neuronal cells (Bruce et al., 2004). REST recruits corepressors (CoREST, mSin3a) and multiple chromatin modifying enzymes (HDAC1/2, demethylase LSD1 and methyltransferase G9a), causing chromatin compaction and altering gene expression by changing epigenetic tagets (Ballas et al., 2005). REST contributes to orchestrate the epigenetic regulation of target genes through several miRNAs including miR-9/9*, miR-29a, miR-124a, miR-218 and others (Wu and Xie, 2006).
My thesis has ascertained an anti-tumor properties of transcription factor REST on a model of cervical adenocarcinoma where class I histone deacetylase (HDAC) inhibitor: valproic acid (VPA) down-regulates REST and its corepressors CoREST and HDAC1 at mRNA and protein level. These effects are related to a potent effect on cell apoptosis, possibly mediated by miR-9 overexpression as consequence of REST and CoREST down-regulation. I report the presence of a double-negative feedback loop between REST and miR-9 in HeLa cell line: in absence of REST, miR-9 levels substantially increase while miR-9 overexpression promotes REST down-regulation. Interestingly, I have observed that REST is sufficient to induce a noteworthy chromatin remodeling in HeLa cells.
HeLa cell apoptosis induced by these events, involves mitochondrial control of apoptosis signaling pathways, particularly Bcl-2 family gene BAX.
In conclusion, the present study aims to contribute to a more accurate comprehension of the processes responsible for REST activity in a model of epithelial cervical adenocarcinoma, and relevant for a detailed knowledge of important events causing oncogenesis. Moreover, considering the crucial role of epigenetic regulation of gene transcription in the etiology of many pathological conditions, any further knowledge in this field could find important and innovative pharmacological applications.
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Khodeneva, Natalya <1988>. "Epigenetic changes promoting HeLa cell apoptosis are linked to valproic acid-induced down-regulation of REST and its corepressor CoREST." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7651/.
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REST (RE-1 silencing transcription factor, or NRSF –neuron-restrictive silencing factor) binds to a conserved RE-1 motif present in the promoter region of regulated genes and represses their transcription in neuronal and non-neuronal cells (Bruce et al., 2004). REST recruits corepressors (CoREST, mSin3a) and multiple chromatin modifying enzymes (HDAC1/2, demethylase LSD1 and methyltransferase G9a), causing chromatin compaction and altering gene expression by changing epigenetic tagets (Ballas et al., 2005). REST contributes to orchestrate the epigenetic regulation of target genes through several miRNAs including miR-9/9*, miR-29a, miR-124a, miR-218 and others (Wu and Xie, 2006).
My thesis has ascertained an anti-tumor properties of transcription factor REST on a model of cervical adenocarcinoma where class I histone deacetylase (HDAC) inhibitor: valproic acid (VPA) down-regulates REST and its corepressors CoREST and HDAC1 at mRNA and protein level. These effects are related to a potent effect on cell apoptosis, possibly mediated by miR-9 overexpression as consequence of REST and CoREST down-regulation. I report the presence of a double-negative feedback loop between REST and miR-9 in HeLa cell line: in absence of REST, miR-9 levels substantially increase while miR-9 overexpression promotes REST down-regulation. Interestingly, I have observed that REST is sufficient to induce a noteworthy chromatin remodeling in HeLa cells.
HeLa cell apoptosis induced by these events, involves mitochondrial control of apoptosis signaling pathways, particularly Bcl-2 family gene BAX.
In conclusion, the present study aims to contribute to a more accurate comprehension of the processes responsible for REST activity in a model of epithelial cervical adenocarcinoma, and relevant for a detailed knowledge of important events causing oncogenesis. Moreover, considering the crucial role of epigenetic regulation of gene transcription in the etiology of many pathological conditions, any further knowledge in this field could find important and innovative pharmacological applications.
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Xu, Yan. "Using data to answer questions of public health importance for ACT Health, with an emphasis on routinely-collected linked data." Master's thesis, Canberra, ACT : The Australian National University, 2017. http://hdl.handle.net/1885/144601.
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My field placement was with the Epidemiology Section in the Population Health Protection and Prevention Division at ACT Health. Within this placement, I have completed four projects for this thesis: an analysis of Emergency Department (ED) data; a gastroenteritis outbreak investigation; an evaluation of a population health survey and, for my main project, a study of unplanned hospital readmissions. One of the motivations for undertaking these projects was to promote better use of the routinely-collected linked data to answer questions of public health importance for ACT Health. My data analysis project was an analysis of frequent ED use in the Australian Capital Territory (ACT). This is the first study to quantify and characterise ED frequent users in the ACT. The results support existing evidence that frequent users tend to be older, female, and/or single, and commonly present with pain-related conditions. The data also showed that compared to non-frequent ED users, frequent users were more likely to be referred by police, corrective or community services; arrive by ambulance, not wait to be assessed, or leave at their own risk. In addition, we investigated visit intervals, rarely reported on in other studies. This study found around one third of frequent users returned within 7 days, with 41% of their visits having the same diagnosis as the last visit. Early identification and follow-up in the community for frequent users will assist in the development of targeted strategies to improve health service delivery to this vulnerable group. Unexpected return to hospital has negative impacts on families and healthcare systems. We examined which conditions have the highest rates of readmission and contribute most to 30-day unplanned readmissions in the ACT, and which patient characteristics are associated with readmissions. The study identified a 30-day unplanned readmission rate of 6.2%, with admission rates highest for alcohol-related liver disease (19.2%), and heart valve disorders (17.4%). Older age and comorbidities are strong predictors for 30-day unplanned readmissions. For some conditions the rates were relatively high, suggesting areas to target for reducing readmissions. Therefore, when developing preventative strategies and post-discharge plans, particular consideration should be given to patients at older age or with underlying comorbidities. As part of the ACT Health Survey Program (HSP), the ACT General Health Survey (GHS) is a computer-assisted telephone interviewing survey conducted every year among ACT residents. My evaluation of the GHS found that it is a useful tool to monitor trends of overweight, obesity, nutrition and physical activity for adults and children in the ACT. The data collected are used to provide evidence to understand and analyse overweight and obesity patterns in the ACT and create awareness of unhealthy lifestyles. However, improvements could be made in a few areas, including: developing a proper evaluation plan and a data quality statement, increasing the sample size and the proportion of young people in the sample population. I also carried out an outbreak investigation of foodborne gastroenteritis that occurred among staff and public members at a large national institution in Canberra. I conducted two studies for this outbreak – a retrospective cohort study and a case control study. The epidemiological, environmental and laboratory evidence suggested the outbreak was caused by C. perfringens toxin Type A, with the likely vehicles of transmission being butter chicken and rice. The findings of this investigation suggest that a breakdown in temperature control and good food handling practices may have resulted in C. perfringens bacterium growing rapidly and producing a toxin which caused the illness. This project also indicated that the value of a second epidemiological study was questionable given the limited time and resources available.
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Halliday, Lorna F. "Are auditory processing deficits linked to literacy problems : a comparison of specific reading disability and mild to moderate sensorineural hearing loss." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427616.
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Halverson, Ranette Hudson. "Efficient Linked List Ranking Algorithms and Parentheses Matching as a New Strategy for Parallel Algorithm Design." Thesis, University of North Texas, 1993. https://digital.library.unt.edu/ark:/67531/metadc278153/.
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The goal of a parallel algorithm is to solve a single problem using multiple processors working together and to do so in an efficient manner. In this regard, there is a need to categorize strategies in order to solve broad classes of problems with similar structures and requirements. In this dissertation, two parallel algorithm design strategies are considered: linked list ranking and parentheses matching.
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Durfee, Alexandra Zezinka. "Are Input and Output Language Networks Linked?: Evidence from the Verification Task Paradigm and its Role in Assessing Language Impairment After Stroke." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1573833017141002.
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Casas, Lamesa Anna. "Analysis of the contribution of linker histone H1 to the dynamics of RNA:DNA hybrids." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/666593.
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Histone H1 is a key determinant of higher-order chromatin structures and for a long time it has been considered a main transcriptional repressor. So consistent with its biochemical properties, the absence of histone H1 was expected to have extended consequences in gene expression. On the contrary, upon depletion of histone H1 in Drosophila melanogaster (dH1), only a subset of genes was significantly affected (1–3). These differentially expressed genes were mainly heterochromatic inactive genes that got transcribed 2. Further studies showed that apart from affecting silencing of heterochromatin, dH1 depletion also induced double-strand breaks (DSBs) on the same heterochromatic sequences that were being up- regulated, suggesting that abnormal transcription of these sequences was resulting in DNA damage (4).
Results reported here suggested that the heterochromatic transcripts up-regulated upon depletion of dH1 induced genomic defects because they were not correctly metabolized and, consequently, formed RNA:DNA hybrids (R-loops). Thus, histone H1 is important in preventing abnormal R-loop accumulation in heterochromatin. On this direction, our approach showed that it was the absence of histone H1 and not simply the relieve of silencing that induced accumulation of R-loops in heterochromatin, as depletion of HP1a (another important heterochromatic element) up-regulated heterochromatin transcription as well, but it neither induced R-loops or DNA damage. Then, further experiments showed that histone H1 was necessary for the binding of hnRNP36 and hnRP48 to heterochromatin. These two proteins are involved in mRNA quality control and, therefore, in the prevention of R-loop formation. Thus, in conditions where histone H1 was absent, the hnRNP36/48 could not bind to the newly synthesized transcript, favoring the formation of abnormal R-loops. Further analyses of the genome-wide distribution of R-loops in D. melanogaster showed that histone H1 is important for the regulation of R-loop dynamics beyond heterochromatin, as depletion of histone H1 not only produced a strong accumulation of R-loops in heterochromatin, but also induced important changes in the distribution of physiological R- loops.
Together, we provide evidence of a novel and essential function of linker histones H1 to the regulation of RNA:DNA hybrids in heterochromatin and, thus, to the maintenance of genome integrity and stability. However, further studies are needed to understand the biological importance of the euchromatic changes in R-loop distribution in dH1-depleted cells compared to that of physiological conditions.
References:
1. Lu, X. et al. Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure. Genes Dev. 23, 452–65 (2009).
2. Vujatovic, O. et al. Drosophila melanogaster linker histone dH1 is required for transposon silencing and to preserve genome integrity. Nucleic Acids Res. 40, 5402– 5414 (2012).
3. Lu, X. et al. Drosophila H1 regulates the genetic activity of heterochromatin by recruitment of Su(var)3-9. Science 340, 78–81 (2013).
4. Bayona-Feliu, A., Casas-Lamesa, A., Reina, O., Bernués, J. & Azorín, F. Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin. Nat. Commun. 8, 283 (2017).<br>La histona H1 és clau en l’empaquetament d’ordre superior de la cromatina i durant molt de temps se li ha atribuït el paper de repressor transcripcional. Així doncs, d’acord amb les seves propietats bioquímiques, amb la supressió de la histona H1 s’esperava que es produïssin canvis importants d’expressió gènica. En canvi, davant la depleció de la histona H1 (dH1) a Drosophila melanogaster, només un petit grup de gens heterocromàtics es va veure afectat significativament. Posteriors estudis van demostrar que l’absència d’histona H1 també produïda trencaments de cadena doble del DNA en les mateixes seqüències heterocromàtiques que estaven sent activades, suggerint que la transcripció anormal d’aquestes seqüències estava produint dany en el DNA.
Els resultats presentats en aquesta tesi proposen que els transcrits heterocromàtics que s’activen en deplecionar la histona dH1 acaben produint defectes genòmics perquè no poden ser correctament metabolitzats i, conseqüentment, formen híbrids d’RNA:DNA (R-loops). Així doncs, la histona H1 és important per prevenir l’acumulació anormal d’R-loops en l’heterocromatina. En aquesta direcció, els nostres resultats demostren que és l’absència de dH1 i no només l’atenuació del silenciament el que provoca l’acumulació d’R-loops en l’heterocromatina i que, a més, la histona H1 és necessària per la unió d’hnRNP36 i hnRP48 en l’heterocromatina. Aquestes dues proteïnes participen en el control de qualitat de l’mRNA i, per tant, en prevenir la formació d’R-loops. Així doncs, en absència d’histona H1, les hnRNP36/48 no s’uneixen als nous transcrits heterocromàtics, facilitant la formació anormal d’R-loops. Altres anàlisis en la distribució dels R-loops al llarg del genoma de D. melanogaster demostren que la histona H1 és important en la regulació de la dinàmica dels R-loops més enllà de l’heterocromatina, ja que la seva absència no només provoca l’acumulació d’R-loops en l’heterocromatina, sinó que també produeix canvis importants en la distribució fisiològica dels R-loops.
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Shaikh, Mearaj Ahmed A. J. "Identification and Characterization of a Mutation Causing Stunted Growth in Arabidopsis that is Linked to Phosphate Perception." Thesis, University of North Texas, 2020. https://digital.library.unt.edu/ark:/67531/metadc1752397/.
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Plant yield is an agronomic trait dependent on the transport of photosynthate from mature source leaves to sink tissues. Manipulating phloem transport may lead to increased yield, however in a previous study, Arabidopsis thaliana overexpressing sucrose transporter AtSUC2 in the phloem resulted in stunted growth and an apparent P-deficiency. In the course of further characterizing the phenotype and identifying the causative mutation, this research included 1) reverse genetics to test genes hypothesized to modulate carbon-phosphate interactions; 2) whole genome sequencing to identify all T-DNA insertions in plants displaying the phenotype; 3) genetic crosses and segregation analysis to isolate the causative mutation; and 4) transcriptomics to capture gene-expression profiles in plants displaying the phenotype. These phenotypes were traced to a T-DNA insertion located on chromosome 4. Transcriptomics by RNA-Seq and data analysis through bioinformatics pipelines suggest disruptions in metabolic and transport pathways that include phosphate, but do not support a direct role of well-established phosphate acquisition mechanisms. Gene At1G78690 is immediately downstream of the T-DNA insertion site and shows modestly increased expression relative to wild type plants. At1G78690 encodes O-acyl transferase, which is involved in processing N-acylphosphotidyl ethanolamine (NAPE) to N-acyl ethanolamine (NAE). Exogenous NAE application causes stunted growth in specific conditions. From the experiments described herein, At1G78690 emerges as the strongest candidate for causing the observed phenotypes.
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Thissen, Jürgen. "Jäger und Sammler : Paläolithikum und Mesolithikum im Gebiet des linken Niederrhein /." Köln : [S.n.], 1997. http://catalogue.bnf.fr/ark:/12148/cb36994721g.
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Inaug.-Diss.--Philosophische Fakultät--Universität zuKöln, 1995.<br>Inventaire des campagnes de fouilles de 1984 et 1985 ; publication complète prévue dans la série "Rheinische Ausgrabungen" du "Rheinisches Amt für Bodendenkmalpflege" Bibliogr. p. VIII-LV.
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Fisher, Judith L. "Fundamental changes to ecosystem properties and processes linked to plant invasion and fire frequency in a biodiverse woodland." University of Western Australia. School of Plant Biology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0109.
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[Truncated abstract] Mediterranean southwest Australia, a global biodiversity hotspot, has nutrient deficient soils, exacting climatic conditions and is species rich with 7380 native vascular plant species, of which 49% are endemic. The region is expected to experience one of the world's highest degrees of biodiversity loss and change in the coming decades, with introduced species presenting a major threat. Limited knowledge is available on the mechanisms of ecosystem change associated with invasion and fire in this biodiversity hotspot region. Banksia woodland, an iconic complex species-rich natural ecosystem is one of the major vegetation types of the coastal sandplain, extending from 15 to 90 km inland and 400 kms along the west coast. The following hypothesis was tested to explore the ecological impacts of invasion: Is invasion of Banksia woodland by the introduced species Ehrharta calycina and Pelargonium capitatum accompanied by an alteration in ecosystem properties and processes, whereby the degree of change is related to fire frequency and abundance of introduced species? Different vegetation conditions, i.e. Good Condition (GC), Medium Condition (MC), Poor Condition invaded by Ehrharta calycina (PCe) and Poor Condition invaded by Pelargonium capitatum (PCp) were utilized for field assessments. ... In the soil seed bank, species numbers and germinant density decreased significantly for native and seeder (fire sensitive) species between GC sites and invaded sites. Surprisingly 52% of germinants at GC sites were from introduced species, with much of the introduced soil seed bank being persistent. Native species were dominated by perennial shrubs, herbs and sedges, while introduced species were dominated by perennial and annual grasses and herbs. Invasion by introduced species, associated with frequency of fire, altered the ecosystem, thus disadvantaging native species and improving conditions for even greater invasion within the Banksia woodland. Significantly higher soil phosphorus P (total) and P (HCO3) were found at PCe and PCp sites compared to GC sites. Leaf nutrient concentrations of phosphorus were significantly higher, and potassium and copper significantly lower in PCe and PCp sites, with introduced species having significantly greater concentrations than native species (except Manganese). This study demonstrated the key role of phosphorus in the Banksia woodland, in contrast to other research which identified nitrogen as the major nutrient affected by invasion. Higher levels of soil and leaf phosphorus, loss of species diversity and function, changes in fire ecology and canopy cover and a limited native soil seed bank make restoration of a structural and functional Banksia woodland from the soil seed bank alone unlikely. Without management intervention, continuing future fire is likely to result in a transition of vegetation states from GC to MC and MC to PC. The knowledge gained from this study provides a better ecological understanding of the invasive process. This enhanced understanding will enable the development of adaptive management strategies to improve conservation practices within a biodiversity hotspot and reduce the impact of the key threatening process of invasion.
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Williams, Teresa Ann. "Long-term outcomes for patients treated in the Intensive Care Unit (ICU) : a cohort study using linked data." University of Western Australia. School of Population Health, 2009. http://theses.library.uwa.edu.au/adt-WU2010.0005.
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Royal Perth Hospital is the largest hospital in Western Australia and also has the largest intensive care unit (ICU) in the State. It was the first public hospital to provide intensive care services in Western Australia. This thesis examines the intermediateand long-term outcomes of patients admitted to the Royal Perth Hospital ICU between 1987 and 2002. Intermediate-term survival, defined as survival after discharge from hospital to one year and long-term survival, that exceeding one year after discharge, are important outcomes. Information on outcomes can be used by ICU staff in discussions with patients and their families and to inform policy decision-making and future research. The aim of this research was to examine one-year and long-term outcomes of patients admitted to the ICU between 1987 and 2002 and explore the factors that might be associated with the outcomes for 22,298 patients admitted to the ICU. A clinical ICU database was linked to morbidity and mortality databases by Data Linkage WA. A wide range of demographic and clinical factors were examined for their effect on outcome. These included age, sex, comorbidity, severity of illness, organ failure, ICU diagnostic groups, type of admission (medical, elective surgical and non-elective surgical), length of stay in ICU and era of admission (1987-1990, 1991-1994, 1995-1998, 1999-2002). Patients were followed-up to study end, 31st December 2003 or death if it occurred before study end, that is, up to 17 years after the index ICU admission. Kaplan Meier survival curves and Cox regression models were used to examine intermediate and long-term survival for patients who survived to hospital discharge. A comparison of admissions to hospital before and after the index ICU admission was made using descriptive statistics and logistic regression. Throughout the study period survival for the ICU cohort was shorter when compared to the Australian population. This was consistent throughout the follow-up period. The most important determinants of long-term survival were age, comorbidity, severity of illness and diagnostic group but the strength of association varied with the duration of follow-up. Although age, comorbidity and severity of illness increased among the critically ill survival improved over time. Hospital admissions were more frequent after a discharge from hospital that required an admission to ICU than before the index admission, even after adjusting for the ageing of the cohort. This study provides unique information about the survival and other outcomes of patients discharged from a hospital admission that included an ICU stay. The strength of this study lies in the follow-up to 17 years and the more comprehensive range of explanatory factors than in previous studies. This thesis demonstrates that follow-up studies after intensive care should be of sufficient duration to account for the changes that occur in survival over time and indicates the range of factors that should be taken into account when making comparisons of long-term survival.
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Zavalin, Vyacheslav I. "Exploration of RDA-Based MARC21 Subject Metadata in Worldcat Database and Its Readiness to Support Linked Data Functionality." Thesis, University of North Texas, 2020. https://digital.library.unt.edu/ark:/67531/metadc1707353/.
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Subject of information entity is one of the fundamental concepts in the field of information science. Subject of any document represents its intellectual potential -- 'aboutness' of the document. Traditionally, subject (along with title and author) is the one of three major ways to access information, so subject metadata plays a central role in this process and the role is constantly growing. Previous research concluded that the larger bibliographic database is, the richer subject vocabularies and classification schemes are needed to support information discovery. Further, a high proportion of information objects are unretrievable without subject headings in metadata records. This exploratory study provides the analysis of the subject metadata in MARC 21 bibliographic records created in 2020; and develops understanding of the level and patterns of 'aboutness' representation in the MARC 21 bibliographic records. Study also examines how these records apply the recent RDA and MARC21 guidelines and features intended to support functionality in a Linked Data environment. Methods of Social Network Analysis were applied along with content analysis, to answer research questions of this study. Suggestions for future research, implications for education, and practical recommendations for library metadata creation and management are discussed.
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Häfner, Lutz. "Die Partei der Linken Sozialrevolutionäre in der Russischen Revolution von 1917-18 /." Köln : Böhlau, 1994. http://catalogue.bnf.fr/ark:/12148/cb390320194.
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Reiter, Margit. "Unter Antisemitismus-Verdacht : die österreichische Linke und Israel nach der Shoah /." Innsbruck ; Wien ; München : Studien-Verl, 2001. http://catalogue.bnf.fr/ark:/12148/cb38918693n.
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Sukplang, Patamaporn. "The Removal of Linseed Oil Vapors by Biodegradation." Thesis, University of North Texas, 1996. https://digital.library.unt.edu/ark:/67531/metadc278809/.
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Linseed oil is very important in industry but its use is limited due to noxious vapors produced by oxidation on exposure to air. Since some of the products are toxic, release of linseed oil vapors to the environment is normally prohibited. In order to remove the odorous compounds, a biofilter system based on bacterial metabolism was designed and the major premises of bioremediation were studied. A total of five bacterial strains capable of using linseed oil vapors as their sources of carbon and energy were isolated from soil. The individual organisms were also mixed to form a bacterial consortium. The mixed population was able to degrade linseed oil vapors with more than 99 per cent efficiency. According to this research, a successful biodegradation system was designed and, theoretically, this system could be applied to the removal of linseed oil vapors in any industrial plant air stream.
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Österström, Philip, and Ludvig Kamlin. "How well are the two chains linked together? : A study about the perceived effects of blockchain on transaction costs within supply chains handling physical goods." Thesis, Uppsala universitet, Institutionen för informatik och media, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-412796.
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The purpose of this study is to produce new knowledge concerning the perceived effects of blockchain technology on transaction costs within supply chains handling physical goods through the created and hypothetical TCE-matrix. The study followed an abductive research approach where initial found facts were matched against an appropriate theory in order to be put in context and understood. The study’s data was gathered through semi-structured interviews with experts who were active within the research area and chosen based on their practical experience. The results imply that blockchain holds the possibility to affect five out of nine cells within the TCE-matrix out of the experts’ perception, through its increased trust and transparency between its supply chain actors within the network and the enhanced traceability of physical goods. This study further highlights practical implications concerning the technology’s adoption in practice. It is concluded that the blockchain is perceived to have an effect on transaction costs activities out of the TCE-matrix, which is found to be partly applicable when assessing the blockchains potential effect on transaction cost activities in a general manner, where further studies should apply the matrix in the assessment of one specific transaction to take full advantage of the matrix’ potential.
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Lo, Susan Z. Y. "NF-kB- and mitochondria-linked signaling events that contribute to TNFa action in deferring physiological and chemotherapeutic drug-induced apoptosis in macrophages." University of Western Australia. School of Medicine and Pharmacology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0095.
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TNF defers apoptosis in macrophages undergoing spontaneous or pharmacologically (thapsigargin, ceramide, CCCP, etoposide or cisplatin)-induced apoptosis, as determined by measurements of caspase-3 activity and annexin-V staining (Chapter 2). The action requires TNF interaction with TNF-R1, not TNF-R2. Survival is uniquely reliant on the activity of the NF-B signaling pathway, and does not require activities arising from the PI3K/Akt, JNK, ERK, p38 MAP kinase or iNOS pathways (Chapter 3). Further, the general anti-apoptotic property of TNF and its specific antagonism of CCCP-induced apoptosis led to the finding that TNF action prevents cytochrome c release. This protection is likely mediated through effects on components of the MPTP itself, as TNF exhibited functional redundancy with the pore inhibitor cyclosporin A, and did not modify upstream events that promote MPTP opening during apoptosis, namely ROS production, cytosolic Ca2+ increase, or a reduction of total ATP (Chapter 4). Subsequent experiments with the mRNA synthesis inhibitor, actinomycin D, and the translation inhibitor, cycloheximide revealed that the protein(s) responsible for TNF-induced survival was transcribed and translated within 1 hr. However, western analyses provided no convincing evidence of the involvement of Mn-SOD, cIAP-1, XIAP, Bcl-2 or A1 in TNF cytoprotection (Chapter 5). Rather, microarray experiments identified the consistent induction of an early response gene, pim-1, within 30 min of TNF exposure (Chapter 6). This result was verified at the protein level with a specific Pim-1 antibody. Evidence was also found for induction of the anti-apoptotic protein A20, but only at mRNA level. Parthenolide, wortmannin, SP600125, PD98059, SB203580 or L-NAME1 acted against TNF-induced Pim-1 expression in a pattern that exactly matched the effects of these inhibitors on TNF-induced survival. That is, only parthenolide-mediated inactivation of NF-B abolished TNF-induced induction of Pim-1. TNF also stimulated the rapid phosphorylation (inactivation) of the pro-apoptotic BH3-only protein, Bad at Ser112 in a manner sensitive to NF-B inhibition, but not PI3K/Akt, JNK, ERK or p38 MAP kinase inhibition (Chapter 7). As Bad is a known substrate of Pim-1 and Bad 1 Parthenolide, wortmannin, SP600125, PD98059 and SB203580 are inhibitors of the NF-B, PI3K/Akt, JNK, ERK and p38 MAP kinase pathways, respectively. L-NAME inhibits iNOS. NF-B- and mitochondria-linked signaling events that contribute to TNF action in deferring physiological and chemotherapeutic drug-induced apoptosis in macrophages ii phosphorylation occurred coincident with Pim-1 upregulation, it is likely that Pim-1 kinase activity mediates the inactivation of Bad. The overall data therefore supports a model in which TNF ligation of TNF-R1 at the cell surface results in intracellular NF- B activation, leading to the induction of Pim-1 mRNA and protein, and the ensuing phosphorylation of Bad. Inactivation of pro-apoptotic Bad increases the resistance threshold of mitochondria to apoptotic insults, thereby reducing the occurrence of mitochondrial permeability transition, cytochrome c release and subsequent caspase-3 activation.