Cette hantologie de l’œuvre o’brienesque dépasse le postulat selon lequel Tim O’Brien est un écrivain de la guerre du Vietnam. S’il est indéniable que l’expérience personnelle du combat a influé sur la fiction et la non-fiction de l’auteur, les récits sont avant tout marqués par la hantise, au sens géographique, spatial et psychique du terme. La psychologie des lieux investis ou remémorés par l’auteur, les narrateurs et les protagonistes, est associée à des événements marquants dont on retrouve la trace dans le corps, la mémoire individuelle et collective, ainsi qu’au niveau formel. De fait, les êtres sont habités par la hantise timérique, le poids de la perte ou les séquelles de la traumatisation. O’Brien souligne l’appréhension, l’obsession, la mélancolie et les revenances traumatiques dans des thanatographies pénétrées de spectres et de fantômes, tout autant de manifestations de restances qui ne cessent de faire retour. La fréquentation des mêmes lieux, leur pouvoir hantologique, ainsi que la symbolisation du hantement psychique constituent une habitation thématique dont l’ascendance est perceptible d’un point de vue structurel et stylistique. Par conséquent, le texte o’brienesque se fait à son tour hantise : un lieu scriptural où l’auteur se spectralise, (re)visite d’autres écrivains et sa propre discursivité. L’ambiguïté née de l’autofictionnalisation et de l’énigmatisation, la configuration métafictionnelle ou métanarrative, enfin la tension narrative, ont pour effet de générer des textes intrigants et autoréflexifs. Au terme de l’analyse, il apparaît qu’O’Brien compose une spectropoétique ancrée dans un hantissage empreint d’une sensibilité baroque et d’une quintessence thanatologique qui assurent à l’auteur l’immortalité symbolique. / While critics tend to consider Tim O’Brien as a writer of the Vietnam War, this hauntology of the author’s works goes beyond such postulate. Though it is indisputable that the personal experience of combat has influenced O’Brien’s fictional and non-fictional writing, the latter primarily deals with haunting, in the geographical, spatial and psychological sense of the term. The places visited or remembered by the author, the narrators and the protagonists, are associated with unforgettable events, lingering memories and reviviscences that can be traced in the body, in individual and collective memory, as well as in the form of the texts. Thus, individuals are haunted by disquietude, loss or the side effects of traumatization. O’Brien stresses apprehension, obsession, melancholy and traumatic revivification in thanatographies penetrated by specters and ghosts that keep returning. The hauntological power of geographical, spatial and psychological haunts establishes a recurring theme that impacts structure and style. Therefore, the o’brienesque text becomes a haunted and a haunting space, marked by the spectrality of the author. O’Brien (re)visits other writers and his previous writings. Ambiguous and enigmatic utterances, metafictional or metanarrative configurations and narrative tension generate intriguing and self-reflexive texts. In the end, it appears that O’Brien’s spectropoetics reads like a hantissage imbued with baroque traits and thanatological quintessence that provide the author with symbolic immortality.

Abstract Enzymes are potentially superior as catalysts for many industrial chemical processes because of their high specificity, selectivity, minimum energy requirement and environmental friendliness. However, many challenges remain in order to exploit fully the potential of industrial enzymes. The qualities which are needed are catalytic proficiency, availability in high quantities, low price, low product inhibition, and high activity and stability under process conditions. Directed evolution and rational design are the most common strategies to produce enzymes with the desired properties. The TIM barrel is the most frequent and most versatile fold among naturally occurring enzymes. In all known TIM barrel enzymes, the catalytically active residues are located at one end of the barrel structure, while residues maintaining the stability of the fold are found on the opposite end of the barrel. This special architecture of the TIM barrel proteins makes it possible to change catalytic activity of the protein without compromising its stability, which is a perfect start for protein engineering studies. In this research project, a monomeric triosephosphate isomerase (TIM) variant with an engineered binding groove (A-TIM) was created by using a rational design approach. The major aims of this work were (i) to find novel binders and (ii) characterize the new, bigger binding groove using X-ray crystallographic methods. These studies have discovered that monomeric A-TIM can bind compounds completely different from the natural substrate. Studies on three different classes of binder molecules are reported: (i) true substrate analogues of wild type TIM, (ii) substrate analogues that have an extended hydrophobic tail, and (iii) more extended, phosphate containing substrate analogues. In addition to this, the A-TIM active site was shown to be competent. In general these studies illustrate the importance of protein crystallography for characterizing the binding properties of enzyme variants being studied in enzyme discovery projects. / Tiivistelmä Entsyymit voivat toimia ylivoimaisina katalyytteinä monissa kemianteollisuuden prosesseissa johtuen niiden hyvästä spesifisyydestä, valikoimiskyvystä, alhaisesta energiantarpeesta ja ympäristöystävällisyydestä. Näistä ominaisuuksista huolimatta entsyymien kaikkien mahdollisuuksien hyödyntämisen esteenä on monia haasteita. Tarvittavia ominaisuuksia ovat katalyyttinen tehokkuus, saatavuus suurina määrinä, alhainen hinta, alhainen tuoteinhibitio sekä korkea aktiivisuus ja stabiilisuus prosessiolosuhteissa. TIM-tynnyrirakenne on yleisin ja monipuolisin proteiinien laskostumisrakenne luonnossa esiintyvissä entsyymeissä. Tässä rakenteessa katalyyttisesti aktiiviset aminohappotähteet ovat sijoittuneet tynnyrirakenteen toiselle puolelle, kun taas stabiilisuuden kannalta tärkeät aminohappotähteet ovat sijoittuneet kokonaan toiselle puolelle. Tämä erityinen rakenne antaa mahdollisuuden muokata proteiinin katalyyttistä aktiivisuutta vaikuttamatta haitallisesti sen stabiilisuuteen. Tämä on täydellinen lähtökohta proteiininmuokkaukselle. Tässä tutkimusprojektissa käytettiin ns. järkiperäistä suunnittelua monomeerisen trioosifosfaatti-isomeraasivariantin (A-TIM) luomisessa. Tämän tutkimustyön pääasialliset tavoitteet olivat (i) uusien sitoutujien löytäminen ja (ii) uuden, suuremman sitoutumistaskun ominaisuuksien määrittäminen röntgenkristallografisilla menetelmillä. Tässä tutkimuksessa havaittiin, että A-TIM kykenee sitomaan yhdisteitä, jotka ovat täysin erilaisia luonnolliseen substraattiin verrattuna. Tässä tutkimuksessa kuvaillaan kolmenlaisia sitoutujia: (i) todelliset villityypin entsyymin substraattianalogit, (ii) substraattianalogit, joihin on liitetty hydrofobinen hiilivetyketju ja (iii) villityypin substraattia suuremmat sokerifosfaatit. Tämän lisäksi A-TIM:n aktiivisen keskuksen todistettiin olevan toimintakykyinen. Yleisellä tasolla tämä tutkimus osoittaa röntgenkristallografisten menetelmien tärkeyden entsyymienmuokkausprojekteissa, joissa entsyymivarianttien ominaisuuksien määritys on tärkeää.

Thesis Abstract The present thesis offers to read six plays by three contemporary British playwrights - Sarah Kane's Crave (1997) and 4.48 Psychosis (1999), Caryl Churchill's The Skriker (1994) and Far Away (2000), and Tim Crouch's ENGLAND (2007) and The Author (2009) through the lens of Julia Kristeva's essay on abjection, Powers of Horror (1982). Kristeva theorizes abjection as that which retains some resemblance to the subject or object, but is neither - or no longer belongs to the subject. Being confronted with the abject is unpleasant because it is threatening for the subject. It contains all that is habitually removed from life and does not belong in the symbolic order - corpses and excrements. Likewise, the maternal body needs to become abject for the infant to realize its own borders and bodily integrity. Kristeva proposes that the abject finds its way back into the symbolic order through literature, and reads a number of writers as being concerned with the abject. In the theatre, as well as in the visual arts, abjection has been a useful theoretical starting point, despite the fact that it is seen by a number of critics as something which cannot truly be grasped, and as resisting description and verbal imposition. Each playwright and each play includes a different aspect of the abject. Central to...

Testförbättringsmodeller har utvecklats och blivit fler sedan 90-talet. Dessa modeller strävar efter att ge team och organisationer struktur inom testarbete. TMM, som är en av de äldsta testförbättingsmodellerna, togs fram i början av 90-talet och har sedan gett inspiration till flera testförbättringsmodeller med mognadsnivåer. Två av dem är TMMi och TIM. Modellerna, som båda ursprungligen är bearbetningar av TMM, har olika strukturer när det kommer till hur olika delar av testfunktionen förbättras. I en fallstudie har TMMi och TIM jämförts mot varandra för att få fram skillnaderna i modellerna samt rekommendationer hos ett team som arbetar med flera konsultuppdrag. TIM utvärderas även om hur aktuell den är i ett agilt konsultföretag.Enkät och intervju användes för att samla in data och modellerna användes för att generera rekommendationer till teamet.Det framkommer att TIM kan appliceras på en agil konsultverksamhet, främst för att TIM lägger fram vad som ska göras och det agila arbetssättet lägger fram hur det ska göras.Den främsta skillnaden som upptäcktes mellan TIM och TMMi ligger i deras struktur gällande mognadsnivåer. TIM uppmuntrar till en balanserad förbättring genom individuell bedömning av testprocessområden (KPA), så att det studerade teamet har en bättre förståelse för vilka av de som främst behöver förbättras, till skillnad från TMMi som är striktare vid sin bedömning.TIM i förhållande till TMMi har rekommendationer som riktar sig till enskilda testare på en lägre mognadsnivå, vilket påverkar graden av självständighet för testning. TMMi:s rekommendationer betonar att röktester bör utföras av teamet i större utsträckning än vad som sker för tillfället. / Test improvement models have evolved and become more common since the 1990s. These models strive to give teams and organizations structure in their testing work. TMM, one of the oldest models, was developed in the early 90's and has since provided inspiration for several test improvement models with maturity levels thereafter. Two of them are TMMi and TIM. Both models, which are further worked on from TMM originally, have two different structures when it comes to how different parts of the test function are improved. In a case study, TMMi and TIM have been compared against each other to identify the differences in the models and recommendations from a team working on several consulting assignments. TIM is also evaluated on how current it is in an agile consulting company. The questionnaire and interview were used to collect data and the models were used to generate recommendations for the team. It appears that TIM can be applied to an agile consulting business, mainly because TIM focuses on what to do and the agile methodology focuses on how to do it. The main difference found between TIM and TMMi lies in their structure regarding maturity levels. TIM encourages balanced improvement through separate assessment of key process areas (KPA), so that the studied team has a better understanding of which of them needs to be improved primarily, unlike TMMi, which is stricter in its assessment. TIM in relation to TMMi has recommendations aimed at individual testers at a lower maturity level, which affects the degree of independence for testing. TMMi's recommendations emphasize that smoke tests should be performed by the team to a greater extent than is currently happening.

<p>C-uppsatsen baseras på en fallstudie över ABB Communication Centers internkommunikation, den övergripande kommunikativa enheten på ABB Sverige AB. Syftet är att beskriva informationsdesignens roll i såväl den dagliga verksamheten som den övergripande inställningen till det internkommunikativa arbetet. Samt jämföra teorier inom organisations- och kommunikationsvetenskap samt informationsdesign och resultaten från den empiriska undersökningen.</p> / <p>This thesis is based on a case study carried out at ABB Communication Center, the comprehensive department for communication within ABB Sweden AB. The purpose of the work is to describe how internal communications are accomplished in a real organisation and which role information design has in the process, and then to compare this with the theories within communications, organisation and information design and to evaluate the results.</p>

After the Snow: The Oakland County Child Murders and the Search for the Killer is a work of nonfiction that recounts the murders of four children who lived in the suburbs of Oakland County, Michigan and the subsequent search for their murderer, the Oakland County Child Killer. The first of the four murders occurred in February 1976 and the last in March 1977. This thesis chronicles the unsolved case and the police investigation that began in 1976 and seems close to a successful conclusion in the spring of 2009. Over the course of the last two-and-a-half years, I have conducted lengthy interviews with Cathy King, the sister of one of the victims, and researched primary sources, the Detroit Free Press and the Detroit News, as well as other materials. My research also includes the use of Cathy King’s private and confidential correspondences with people involved in this case.

Ebola viruses, and other members of the family filoviridae, are enveloped, negative sense, RNA viruses that can cause hemorrhagic fever. Currently, there are no antivirals or approved vaccines available that target or protect from Ebola virus infection. However, recently, T-cell immunoglobulin and mucin domain-1 (TIM-1) has been identified as an epithelial-cell receptor for filoviruses and could be a potential target for antivirals. However, little is known about how TIM-1 enhances virus entry and the role of TIM-1 during in vivo infection. In order to determine the key residues of TM-1 involved in interaction with virus, we generated a panel of point-mutations in the immunoglobulin-like variable (IgV) domain of TIM-1. We determined that several residues within the IgV domain that are involved in binding of phosphatidylserine (PtdSer) are also critical for Ebola virus entry. Further, we found that TIM-1 interacts with Ebola virus through binding of PtdSer on the viral envelope. PtdSer liposomes, but not phosphatidylcholine liposomes, competed with TIM-1 for EBOV pseudovirion binding and transduction. In addition, annexin V (AnxV) substituted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism. Our findings suggest that TIM-1-dependent uptake of EBOV occurs by apoptotic mimicry. We also determined that TIM-1 expression can enhance infection of a wide range of enveloped viruses, including alphaviruses and a baculovirus. As further evidence of the critical role of enveloped virion associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internalization of pseudovirions and virus-like particles (VLPs) lacking a glycoprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake independent of a glycoprotein. These results provide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped virus uptake. The PtdSer-binding activity of the IgV domain is essential for both virus binding and internalization by TIM-1. However, another member of the TIM family, TIM-3, whose IgV domain also binds PtdSer, does not effectively enhance virus entry. These data indicate that other domains of TIM proteins are functionally important. We investigated the domains of the TIM family members that play a role in the enhancement of enveloped virus entry, thereby defining the features necessary for a functional PVEER. Using a variety of chimeras and deletion mutants, we found that in addition to a functional PtdSer binding domain PVEERs require a stalk domain of sufficient length, containing sequences that promote an extended structure. Neither the cytoplasmic nor the transmembrane domain of TIM-1 is essential for enhancing virus entry, provided the protein is still plasma membrane bound. Based on these defined characteristics, we generated a mimic lacking TIM sequences and composed of annexin V, the mucin-like domain of α-dystroglycan, and a glycophosphatidylinositol anchor that functioned as a PVEER to enhance transduction of virions displaying Ebola, Chikungunya, Ross River, or Sindbis virus glycoproteins. This identification of the key features necessary for PtdSer-mediated enhancement of virus entry provides a basis for more effective recognition of unknown PVEERs. Provided that expression of TIM-1 in cells enhances virus entry through binding of PtdSer on the viral membrane, we wanted to determine whether virus entry would still be enhanced if this interaction was reversed with TIM-1 present on the viral membrane. Further, we reasoned that this might allow for targeting of virus to cells with greater amounts of PtdSer exposed on their outer leaflet, such as cancer cells. In order to test this hypothesis, we generated virions in cells coexpressing a glycoprotein and one of the TIM family members. We found that expression of TIMs in virus-producing cells resulted in TIM proteins being released into the virus-containing medium and enhanced Ebola virus GP pseudovirion titers. Further, this enhancement was dependent on the amount of PtdSer exposed on the target-cell membrane. However, we also determined that TIMs were not being incorporated into virions and that coexpression of TIMs with non-ebolavirus glycoproteins in virus-producing cells resulted in virus stocks with both reduced titers and the quantity of virions.

Tim-1 (T cell immunoglobulin mucin domain 1) is a transmembrane protein expressed by many cell types, including activated T cells and B cells. Antibodies to Tim-1 have been shown to decrease severity of airway hyperreactivity and Th2 cytokine production in mice. Current literature suggests Tim-1 functions as a co-stimulatory molecule. We hypothesize that Tim-1 signals in lymphocytes, and that Tim-1 signaling modulates allergic airway disease. Chapter one provides a brief overview of current literature exploring identification of the Tim family of receptors, genetic associations between TIM-1 polymorphisms and human diseases, Tim-1 expression, Tim-1 ligands, studies of antibodies to Tim-1 in various mouse models of human disease, and signaling events downstream of Tim-1 engagement. Chapter two provides detailed experimental methodology. Chapter three details the characterization of Tim-1 deficient mice. Tim-1 deficient mice do not exhibit defects in lymphocyte or myeloid cell development, as determined by numbers of cells present in bone marrow, thymus, spleen, and lymph nodes. C57BL/6 Tim-1 deficient female mice appear to develop an increased number of lymph node cells and also develop anti-double stranded DNA antibodies. Chapter four explores the impact of Tim-1 deficiency in a murine allergic airway disease model, which demonstrated that Tim-1 deficient mice developed increased lung inflammation and increased antigen-specific Th2 cytokine production that was evident in mice backcrossed to both BALB/c and C57BL/6 backgrounds. These phenotypes were not evident using purified naïve CD4+ T cells polarized in vitro. As Tim-1 expression is not restricted to CD4+ T cells, adoptive transfer experiments were performed to determine whether the phenotype observed was due to the deficiency of Tim-1 on CD4+ T cells, non-CD4+ T cells, or Tim-1 deficiency on both CD4+ T cells and non-CD4+ T cells. Chapter five explores the impact of Tim-1 deficiency in a chronic Leishmania major intradermal infection model. Tim-1 deficient mice crossed to both BALB/c and C57BL/6 backrounds demonstrated similar parasite burden over the course of time, but in vitro restimulation of lymph node cells revealed a striking increase in cytokine production that extended to Th1, Th2, and Th17 lineages. Tim-1 signaling in murine B cell lines is explored in Chapter six. A Tim-1 monoclonal antibody conjugated to beads induces phosphorylation of Tim-1 and recruitment of the Src family kinase Fyn. This phosphorylation of Tim-1 is reduced in Fyn-deficient B cell lines. Chapter seven discusses the significance of these findings, relates current literature to these results, and provides some avenues for further exploration of Tim-1 function and signaling.

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(S)-3-O-Geranylgeranylglyceryl Phosphate Synthase (GGGPS) is a TIM (βα)8 barrel protein found in Archaea and the enzyme catalyzing the first step in the biosynthesis of archaeal membrane lipids. The TIM (βα)8 barrel protein fold is thought to have evolved by duplication and fusion of (βα)4 half barrels. We propose that the GGGPS has also evolved from (βα)4 half barrels. One way to test this hypothesis is to generate putative half-barrels experimentally. GGGPS from Archaeaglobus fulgidus, is a dimer of (βα)8 barrels. Thus, before constructing half barrels, a stable monomer is needed to be engineered. Introducing three substitutions into the dimer interface formed the GGGPS monomer. AUC showed ~50 % of the protein is in the monomeric state. CD experiments confirmed that the engineered protein was properly folded but had decreased thermal stability. In an enzymatic assay, the monomeric GGGPS protein proved as active as the WT protein on a subunit basis.