The 5 ' untranslated region of protein kinase C delta directs translation by an internal ribosome entry segment that is most active in densely growing cells and during apoptosis.

Protein kinase Cdelta (PKCdelta) is a member of the PKC family of phospholipid-dependent serine/threonine kinases and is involved in cell proliferation, apoptosis, and differentiation. Previous studies have suggested that different PKC isoforms might be translationally regulated. We report here that the 395-nt-long 5' untranslated region (5' UTR) of PKCdelta is predicted to form very stable secondary structures with free energies (DeltaG values) of around -170 kcal/mol. The 5' UTR of PKCdelta can significantly repress luciferase translation in rabbit reticulocyte lysate but does not repress luciferase translation in a number of transiently transfected cell lines. By using a bicistronic luciferase reporter, we show that the 5' UTR of PKCdelta contains a functional internal ribosome entry segment (IRES). The activity of the PKCdelta IRES is greatest in densely growing cells and during apoptosis, when total protein synthesis and levels of full-length eukaryotic initiation factor 4G are reduced. However, the IRES activity of the 5' UTR of PKCdelta is not enhanced during serum starvation, another condition shown to inhibit cap-dependent translation, suggesting that its potency is dependent on specific cellular conditions. Accumulating data suggest that PKCdelta has a function as proliferating cells reach high density and in early and later events of apoptosis. Our studies suggest a mechanism whereby PKCdelta synthesis can be maintained under these conditions when cap-dependent translation is inhibited

Flood frequency and magnitude estimates based on valley flood morphology and floodplain sedimentary sequences :the Tyne Basin, N.E. England

PhD ThesisThis study examines the sedimentary and morphological flood record of the River Tyne, northern England, over the last 400 years. Temporal trends in flooding and spatial variations in the timing and nature of river response to floods (flood "effectiveness") are investigated at 3 reaches representative of upland, piedmont and lowland locations in the Tyne catchment. Deposition of coarse flood sediments in headwater tributaries of the River Tyne appears to be strongly related to flood water:sediment ratios that is primarily controlled by sediment supply. Cobble - boulder bars, sheets and splays are deposited under Newtonian flow conditions from flows with relatively low sediment concentrations. Boulder berms and lobes result from floods with high sediment loads, associated with slope-channel coupling. Flood sedimentation in lower reaches of the Tyne comprises vertical accretion of fine-grained, well-bedded sediments at overbank and within-channel locations. Larger floods can be identified on the basis of textural discontinuities that reverse the overall fining-upward sequence. Estimation and interpretation of flow magnitude in each setting is complicated by progressive river bed incision over the period of investigation and significant changes in sediment supply which have affected the nature of flood sedimentation. Trace metal dating of fine-grained, and lichenometric dating of coarsegrained, flood units has enabled detailed and temporally well-defined records of channel and floodplain response to flooding to be established within the Tyne catchment. Since 1600 A.D. fluvial activity at all 3 study reaches has been characterised by alternating periods of river bed incision and stability. Episodic changes in vertical channel stability appear to coincide with non-random decadalscale fluctuatiions in flood frequency: 3 periods with distinct clustering of large floods (1740-1790, 1860-1899, 1940-1965) were associated with vertical instability (channel trenching) throughout the Tyne basin, while intervening periods with relatively few exceptional floods were associated with channel accretion and floodplain rebuilding in general, but with significant upstream/downstream variation. Distinct clustering in the timing of large floods correspond with shortterm hydroclimate changes associated with fluctuations in the configuration of the upper atmosphere. These findings have significant implications for longer-term fluvial development and interpretaion of Holocene alluvial sequences

Otherwordly others : racial representation in fantasy literature

Mémoire en recherche-créationMalgré un potentiel quasiment illimité en ce qui concerne la création des mondes fictifs et la représentation sociale, la littérature « Fantasy » a souvent été accusée à juste titre d’être plagiaire, sans ambition et remplie de thèmes ou d’éléments narratifs racistes. Cependant, je disputerais plutôt que les caractéristiques les plus définissants du genre et son historique de pastiche sont les meilleurs outils à la disponibilité de la Fantasy pour adresser des concepts tels que la race ou le racisme de manière dignifiée, ou même avec l’intention de promouvoir la justice sociale. Ainsi, le but de ma thèse est de légitimiser la Fantasy comme forme d’art digne d’être étudiée et respectée, tout en prouvant comment les éléments et les traditions qui ont menés le genre à mériter sa réputation raciste peuvent être utilisés différemment, afin de démolir des discours de racialisation ou de racisme institutionnalisé. La première moitié de la thèse examinera de manière critique comment la relation de la Fantasy avec la représentation raciale et le racisme a fluctué à travers le temps, en plus d’expliquer pourquoi le racisme est aussi prévalent dans ce sous-ensemble de littérature populaire. La seconde moitié consiste d’un projet de création littéraire qui prouvera par exemple que la Fantasy peut être utilisée pour adresser la race ou le racisme sans renforcer des idéologies discriminatoires, ni approprier des discours d’identité raciales préexistantes. La portion théorique de ma thèse illustrera comment la lignée raciste du genre se manifeste à travers différents récits et périodes historiques, tout en élaborant comment la Fantasy peut involontairement encourager des idéologies racistes, le résultat indirect des éléments les plus définissants du genre. Cette partie expliquera ensuite comment ces mêmes tendances génériques peuvent devenir les fondements de nouveaux récits qui rejettent ou renversent ces mêmes discours racistes. Finalement, il y aura un résumé détaillé des intentions et des stratégies qui ont informées l’écriture de la portion créative. La portion créative de la thèse vise à démontrer comment la littérature Fantasy peut adresser la race et la représentation raciale, sans vulgariser la discussion, ni trop la distancier d’instances de racisme réelles. Elle est divisée en quatre nouvelles littéraires situées dans le même « monde » imaginaire; chaque récit représente le racisme institutionalisé qui existe dans ce monde Fantasy du point de vue d’un personnage avec des défis uniques concernant l’identité raciale, en tant qu’individu et que membre d’une « Tribu ». Chaque chapitre se propose comme « anti-récit », reconfigurant les caractéristiques génériques uniques de la littérature Fantasy qui, normalement, légitiment des racismes provenant du monde réel, afin d’examiner, de critiquer, et de discréditer ces mêmes racismes.Despite nigh-limitless potential for worldbuilding and social representation, Fantasy literature has often been rightfully accused of being plagiaristic, unambitious, filled with racist narratives and themes. However, I would instead argue that the genre’s most defining generic characteristics and its history of pastiche are the best tools at Fantasy’s disposal to address concepts such as race or racism in a dignified way, or even with the intent of promoting social justice. Therefore, the goal of my thesis is both to legitimize Fantasy as an art form worthy of study and respect, all while proving how the elements and traditions that led the genre to earn its racist reputation can be used differently, in order to demolish discourses of racialization or institutionalized racism. The first half of the thesis will act as a critical examination of how Fantasy’s relationship to racial representation and racism has fluctuated over time, as well as explain why racism is so prevalent in this subset of popular literature. The second half consists of a creative writing project that will prove by example that Fantasy can be used to address race and racism without reinforcing discriminatory ideologies, nor appropriating pre-existing racial identity discourses. The theory portion of my thesis will illustrate how the genre’s racist lineage manifests itself within different narratives and historical periods, all while elaborating how Fantasy can involuntarily encourage racist ideologies, as an indirect result of the genre’s most defining elements. This part will then explain how these same generic trends can become the foundations of new narratives that reject or upend these same racist discourses. Finally, there will be a detailed summary of the intentions and strategies that informed the creative portion’s writing. The creative portion of the thesis aims to demonstrate how Fantasy literature can address race and racial representation, without over-simplifying the discussion, nor distancing it too much from real-world instances of racism. It is divided into four short stories set in the same imaginary “world”; each tale depicts the institutionalized racism that exists within this Fantasy world from the point of view of a character with unique racial identity challenges, both as an individual as member of a “Tribe”. Each chapter acts as a sort of “counter-narrative”, reconfiguring Fantasy literature’s unique generic characteristics that, normally, legitimize racisms from the real world, in order to examine, criticize and discredit these racisms instead

Regulation of the cell division cycle by ubiquitin and ubiquitin-like modifications in yeast

PhD ThesisThe ability of a cell to regulate its cell cycle in response to external stimuli, such as oxidative stress, is important to maintain viability by preventing damage and allowing time for repair. However, the underlying sensing and signalling mechanisms behind cell cycle regulation in response to oxidative stress remain largely unclear. Ubiquitin and ubiquitin-like (Ubl) proteins are a family of highly conserved protein modifiers with a role in many cellular processes including cell cycle regulation. The use of catalytic cysteine residues in the conjugation pathways of ubiquitin and Ubls suggest a mechanism by which these modifiers can be redox-regulated. Thus the aim of this project was to investigate the regulation of the cell division cycle by ubiquitin and Ubls in response to two conditions previously observed to lead to G1 phase cell cycle arrest in S. cerevisiae, treatment with the oxidising agent diamide and glutathione depletion. We find that in response to diamide the ubiquitin E2, Cdc34 is particularly sensitive to oxidation compared to the other E2s examined. Oxidation of Cdc34 was shown to lead to an increase in the stability of the Cdc34 substrate Sic1, coincident with G1 phase arrest. We also find that the Rub1 Ubl modifier is essential for regulation of the cell cycle in response to diamide. Interestingly, we find that Rub1 is also required to prevent budding in response to glutathione depletion. Importantly, here we reveal that SIC1 is essential to maintain viability by preventing replication-induced DNA damage following glutathione depletion. Our studies demonstrate that G1 phase cell cycle arrest in response to diamide and glutathione depletion is multifaceted, involving many of the same proteins but that these proteins are regulated differently in response to the two conditions

Metal-Based Antireflective Coatings with Improved Durability for Ophthalmic Applications

Dans une ère de supraconducteurs et d’isolants topologiques, les matériaux typiques peuvent sembler comme il n’ont plus rien à nous offrir. Mais au contraire, la plasmonique a prouvé qu’avec de la physique classique et un concept ingénieux, les métaux peuvent produire des phénomènes optiques intéressants et inattendus, et a inspiré une multitude de nouveaux moyens d’utiliser les métaux en optique. Dans ce travail, nous avons tenté d’utiliser des couches métalliques pour améliorer la performance et la durabilité des lunettes. Plus précisément, le but était de produire un revêtement optique contenant une couche mince métallique permettant un effet antireflet important, et offrant une durabilité suffisante afin de résister à l’usage quotidien d’une paire de lunettes. Les revêtements antireflets (AR), ont été produits selon une architecture diélectrique-métaldiélectrique. L’argent (Ag) fût sélectionné pour la couche métallique en raison de ses propriétés optiques hautement désirables, même parmi les métaux nobles. Cela étant dit, l’utilisation de l’Ag apporte son lot de défis. Tout d’abord, les couches minces d’Ag tendent à former des îlots lorsque déposées sur un diélectrique; ces îlots mènent alors à une absorption indésirable par résonance plasmon localisée. De plus, l’Ag est susceptible chimiquement, pouvant être dégradé par le chlore dans les huiles naturelles de la peau ou l’oxygène de l’air ambiant. Ainsi ce travail traitait de deux aspects: la performance optique devait être contrôlée via la dynamique de croissance, sans introduire de susceptibilités à l’environnement et des mesures de protection devaient être implémentées tout en minimisant leur impact sur la transparence et la performance de l’AR. L’étude a été menée sur des échantillons produits par pulvérisation magnétron et par évaporation par faisceau d’électrons. La dynamique de croissance et les propriétés optiques des couches d’argent ont été étudiées par ellipsométrie spectroscopique in situ, ainsi que par des mesures de la résistance de feuille, par spectrophotométrie et par ellipsométrie ex situ. Les effets des différentes architectures et conditions de dépôt sur la nanostructure et la durabilité des revêtements ont été étudiés par diffraction de rayons-X et dans divers tests de durabilité standardisés conçus pour les lentilles ophthalmiques, tels que la résistance à l’abrasion, à la délamination, à l’humidité et à la corrosion dans une solution aqueuse de NaCl. Le recouvrement de l’Ag par un diélectrique et le dopage à l’aluminium se sont révélés être des mesures de protection insuffisantes.----------Abstract In an era of superconductors and topological insulators, common materials may sometimes seem like they have nothing left to offer. But on the contrary, the field of plasmonics has proved that, with classical physics and a clever concept, metals can provide us with interesting and unexpected optical phenomena and has inspired a multitude of novel uses for metals in optics. In this work, we have attempted to use metallic layers to improve both the performance and durability of eyeglasses. More precisely, the goal was to create an optical coating containing a thin metallic layer to enable a strong antireflective effect, while proving durable enough to survive the daily ordeals of a pair of glasses. Antireflective (AR) coatings were made following a dielectric-metal-dielectric architecture. Silver (Ag) was chosen to constitute the metal layer, due to its highly coveted optical properties even amongst noble metals. That being said, the use of Ag brings about challenges of its own. First, thin Ag layers tend to form islands when deposited on dielectrics; these islands then lead to undesirable absorption due to localized plasmon resonance. Moreover, Ag is susceptible to degradation by a host of chemicals, including the chlorine found in oils naturally coating our skin and the oxygen we breathe. Thus, the work was twofold: optical performance was to be improved through control of the film growth without introducing durability issues and protective measures were to be implemented while minimising their impact on coating transparency and AR performance. The study was performed on samples deposited by magnetron sputtering and electron beam evaporation. Growth dynamics and optical properties of silver films were studied by in situ spectroscopic ellipsometry, as well as ex situ ellipsometry, spectrophotometry and sheet resistance measurements. The effects of these different deposition conditions and architectures on the nanostructure and durability of the coatings were investigated by X-ray diffraction measurements and standardized durability tests designed for ophthalmic lenses, such as resistance to abrasion and delamination, humidity and corrosion in an aqueous NaCl solution. Coating Ag with a dielectric layer and aluminum doping both proved to be insufficient protective measures. The use of nickel (Ni) and chromium nitride (CrNx) based coatings of a few angstroms allow increased chemical and mechanical durability. By separating the Ni and CrNx depositions and using a zinc oxide (ZnO) seed layer, chemically and vii mechanically durable stacks with less than 11% absorption and 1% reflection in the visible spectrum were produced

Hmong Christian elites as political and development brokers : competition, cooperation and mimesis in Vietnam's highlands

This article focuses on the role of new Hmong religious leaders – predominantly young men – who have played an important role in spreading Protestant Christianity across Vietnam’s highlands over the past 30 years. These pastors and evangelists have directly challenged the authority of previously established Hmong local elites, whose legitimacy rested on traditional religious authority and/or state patronage, causing significant social conflict along the way. Some new Christian pioneers have gained local elite status as political and development brokers for their community, enjoying a potent combination of spiritual authority, strong external networks and financial success. As such, international religious networks can function as alternative patrons to the state for well-placed Hmong Christian elites to tap into and redistribute to their communities – to varying degrees. Contextualising such leadership dynamics within wider anthropological scholarship of upland Southeast Asia affirms the ‘pioneering ethos’ of local elites in challenging, complying with or mimicking state forms of governance in their attempts to draw in and channel external potency. This highlights the degree of political manoeuvring space available to non-state actors in a supposedly authoritarian state, as well as ongoing tensions and controversies facing pastors who negotiate ambiguous relationships with powerful external forces

Hmong Christianisation, the will to improve and the question of neoliberalism in Vietnam’s highlands

This article focuses on the convergence of mass Christianisation and economic transformations among the Hmong of Vietnam’s northern highlands over the past thirty years. A history of impoverishment and ethnic discrimination has led hundreds of thousands of Hmong to follow Christianity as a perceived alternative path to progress instead of the state-led development agenda, despite sharing the same ‘will to improve’. By exploring local understandings about the means to development as well as new religious teaching on prosperity, entrepreneurialism and calculativity in a rapidly developing Hmong village, this paper queries the ‘elective affinity’ between new Christian movements and neoliberalism posited by other scholars. The case study highlights the awkward combination of ‘cooperative competitiveness’ accompanying a community-benefit tourism development model. Hmong Christian activity can both overlap and sit at odds with government agendas and market expansion, resulting in complex transformations and subjectivities which cannot simply be reduced to neoliberal logic