No / This study investigates the impact of LIFFE's introduction of individual equity futures contracts on the risk characteristics of the underlying stocks trading on the LSE. We employ the Fama and French three-factor model (TFM) to measure the change in the systematic risk of the underlying stocks which arises subsequent to the introduction of futures contracts. A GJR-GARCH(1,1) specification is used to test whether the futures contract listing affects the permanent and/or the transitory component of the residual variance of returns, and a control sample methodology isolates changes in the risk components that may be caused by factors other than futures contract innovation. The observed increase (decrease) in the impact of current (old) news on the residual variance implies that futures contract listing enhances stock market efficiency. There is no evidence that futures innovation impacts on either the systematic risk or the permanent component of the residual variance of returns.

No / This study assesses whether the widely documented momentum profits can be ascribed to time-varying risk as described by a GJR-GARCH(1,1)-M model. Consistent with rational pricing in efficient markets, we reveal that momentum profits are a compensation for time-varying unsystematic risks, common to the winner and loser stocks. We also find that, because losers have a higher propensity than winners of disclose bad news, negative return shocks increase their volatility more than it increases that of the winners. The volatility of the losers is also found to respond to news more slowly, but eventually to a greater extent, than that of the winners. Following Hong et al. (2000), we interpret this as a sign that managers of loser firms are reluctant to disclosing bad news, while managers of winner firms are eager to releasing good news

No / We study the price and liquidity effects following the FTSE 100 index revisions. We employ the standard GARCH(1,1) model to allow the residual variance of the single index model (SIM) to vary systematically over time and use a Kalman filter approach to model SIM coefficients as a random walk process. We show that the observed price effect depends on the abnormal return estimation methods. Specifically, the OLS-based abnormal returns indicate that the price effect associated with the index revision is temporary, whereas both SIM with random coefficients and GARCH(1,1) model suggest that both additions and deletions experience permanent price change. Added (removed) stocks exhibit permanent (temporary) change in trading volume and bid-ask spread. The analysis of the spread components suggests that the permanent change associated with additions is a result of non-information-related liquidity. We interpret the permanent price effect of additions and deletions combined with the permanent (temporary) shift in liquidity of added (removed) stocks as evidence in favour of the imperfect substitution hypothesis with some non-information-related liquidity effects in the case of additions.

Yes / Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptordependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720- phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER þ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context. / Diabetes UK; British Heart Foundation

Plusieurs études ont démontré que le virus d'immunodéficience humaine de type 1 (VIH-1) possède la propriété d’incorporer diverses protéines de la cellule-hôte. Certaines observations indiquent que ce processus d'incorporation est sélectif. Cependant, les mécanismes expliquant la sélectivité des protéines incorporées demeurent largement inconnus. Les travaux présentés ciblent l'identification du facteur responsable de l'incorporation sélective de la protéine cellulaire ICAM-1 par le VIH-1. Parallèlement, nous avons évalué la sensibilité des virus porteurs de l’ICAM-1 à l’action de l’inhibiteur de fusion, T-20. Un système de transfection et d'expression transitoire a été utilisé afin de produire des particules virales isogéniques avec ou sans l’ICAM-1, et de certains de ses variants. Ce système nous a permis de démontrer que le VIH-1 s’approprie la molécule d’adhésion ICAM-1 par un processus indépendant de l’enveloppe virale (Env), mais dépendant de la portion intracytoplasmique de l’ICAM-1. Cette incorporation serait dirigée par une interaction directe ou indirecte entre la molécule d’adhésion et le précurseur immature Gag du VIH-1. Par ailleurs, la présence de l’’ICAM 1 sur le VIH-1 augmente la résistance des virions à l’action du T-20 en accélérant la cinétique de fusion du virion. La présence de l’ICAM-1 à la surface des virions et son rôle dans le cycle réplicatif du VIH 1 sont très importants dans la pathogenèse du VIH-1. / INTRODUCTION Previous works have indicated that incorporation of surface glycoprotein into retroviruses such as the human immunodeficiency virus type 1 (HIV-1) is not a highly specific process since several cellular glycoproteins can be inserted within the mature viral particle. The mechanism(s) that govern the acquisition of such host constituents have remained so far elusive. OBJECTIVES We have examined the molecular basis, associate to ICAM-1 localization and structural viral proteins responsible for the selective incorporation of the adhesion molecule ICAM-1 within HIV-1. We also investigated whether sensitivity to the newly developed fusion inhibitor T-20 is affected by incorporation of the adhesion molecule ICAM-1 in HIV 1. METHODS We have first investigated the role played by the viral envelope (Env) of HIV-1 in the acquisition of host ICAM-1. The incorporation process of ICAM-1 was also investigated by using different ICAM-1 constructs in which both transmembranes and intracytoplasmic tails were modified. These investigations were performed in combination with virus capture and immunoprecipitation studies, Western blot, confocal microscopy analyses, and infectivity assays. We finally used laboratory isolates of HIV-1 (X4- and R5-tropic) either lacking or bearing ICAM-1 as well as clinical variants into infectivity tests to both evaluate their respective IC50 for the fusion inhibitor and to understand the mechanism of resistance bring by the presence of this host molecule. RESULTS Mutation in the matrix (MA) domain or on Env-deficient viruses produced either in immortalized or primary human cell lines does not affect the incorporation of ICAM-1 by HIV-1. However, the incorporation seems to be conducted by the cytosolic tail of ICAM-1. Further experiments suggested that there is an association – direct or indirect – between ICAM-1 and virus-encoded Pr55Gag. We also demonstrate that ICAM-1-bearing virions are more resistant to T-20 than isogenic HIV-1 particles lacking this host adhesion molecule probably based on a reduction of the kinetic window during which the viral envelope is sensitive to T-20. CONCLUSION This study represents the first demonstration that structural Gag polyproteins mediate the uptake of a host-derived cell surface constituent (ICAM-1) by interacting directly with its cytoplasmic domain or by interacting with a partner into the cytosol. This observation describes a new strategy by which HIV-1 can modulate its replicative cycle considering that insertion of ICAM-1 within nascent virions has been shown to affect virus life cycle and also the sensitivity to the newly develop class of inhibitor including T-20.

La present tesi doctoral comprèn una anàlisi del conflicte palestí-israelià a partir de l'obra i el pensament d'Edward W. Said. És un treball des de la reflexió d'un autor a l'exili. En primer lloc, es conforma el marc teòric a partir de l'anàlisi de les obres de Said sobre orientalisme, cultura, imperialisme i resistència. En segon lloc, s'estudia el sionisme des de Said, és a dir, des del punt de vista de les seves víctimes i com a arrel del conflicte palestí-israelià. En tercer lloc, s'analitza el conflicte palestí-israelià a partir de l'obra filosòfica i política de Said des de la Naqbah de 1948, passant per la Naqsah de 1967, les Intifadas palestines contra l'ocupació sionista, els Acords d'Oslo, i les últimes reflexions contra l'atac a l'Iraq de 2003. En darrer lloc, es porta a terme un excurs dels últims deu anys del conflicte després de la mort del nostre autor a partir dels instruments saidians adquirits al llarg de la investigació. També s'analitza, en forma d'epíleg, la Primavera àrab a partir del pensament crític, híbrid i en contrapunt que va vertebrar tota l'obra de Said. Al mateix temps, en forma d’annexos, s’analitzen la paradoxa de les identitats jueva i àrab, i la lluita pels recursos naturals en el conflicte per Palestina / La presente tesis doctoral comprende un análisis del conflicto palestino-israelí a partir de la obra y el pensamiento de Edward W. Said. Es un trabajo desde la reflexión de un autor en el exilio. En primer lugar, se conforma el marco teórico a partir del análisis de las obras de Said sobre orientalismo, cultura, imperialismo y resistencia. En segundo lugar, se estudia el sionismo desde Said, es decir, desde el punto de vista de sus víctimas y como raíz del conflicto palestino-israelí. En tercer lugar, se analiza el conflicto palestino-israelí a partir de la obra filosófico-política de Said desde la Naqbah de 1948, pasando por la Naqsah de 1967, las Intifadas palestinas contra la ocupación sionista, los Acuerdos de Oslo, y las últimas reflexiones contra el ataque a Iraq de 2003. En último lugar, se lleva a cabo un excurso de los últimos diez años del conflicto tras la muerte de nuestro autor a partir de los instrumentos saidianos adquiridos a lo largo de la investigación. También se realiza una reflexión, en forma de epílogo, sobre la Primavera árabe a partir del pensamiento crítico, híbrido y en contrapunto que vertebró toda la obra de Said. A su vez, a modo de anexos, se analiza la paradoja de las identidades judía y árabe, y la lucha por los recursos naturales en el conflicto por Palestina. / This dissertation consists of an analysis of the Palestinian-Israelian conflict taking as a point of departure the ideas of Edward W. Said, the reflective work of an author in exile. The theoretical framework takes into account Said’s works on orientalism, culture, imperialism and resistance. Together with this, the concept of Zionism is studied through Said, that is, from the point of view of its victims as well as the root of the Palestinian-Israelian conflict. Third, this friction is analyzed taking as a starting point Said’s philosophical and political works from the 1948 Naqbah, through the 1967 Naqsah, and also the Palestinian intifadas against Zionist occupation, the Oslo Agreements, and Said’s last reflections on the Iraq War in 2003. Last, a survey of the last ten years of the conflict after Said’s death is carried out using Saidian elements that have come up along the research. The afterword attempts to work out as a reflection on the Arab Spring taken from Said’s critical, hybrid view and counterpoint, which assembled most of his writings. An annex is later included, in which both Jewish and Arab identities are analyzed, as well as the state of the natural resources at the time of the conflict.

Regulation of soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNARE) mediated exocytosis is dependent upon four key proteins; the vesicular SNARE synaptobrevin, target SNAREs SNAP-25 and syntaxin and the Sec1/Munc18 (SM) protein munc18-1. Despite the munc18-1-syntaxin interaction being central to regulated vesicle exocytosis the spatial and temporal pattern of their molecular distribution and interaction in neuroendocrine and neuronal cells remains undefined. Using in vitro and molecular approaches this thesis shows that disruption of the munc18- 1-syntaxin-N-terminal interaction results in significant changes in syntaxin localisation, membrane-proximal vesicle dynamics and fusion efficiency within neuroendocrine cells. Using the super-resolution techniques Ground State Depletion-Individual molecule return (GSDIM) Microscopy and Photoactivation Localisation Microscopy (PALM) this thesis has demonstrated that the spatial distribution of single munc18-1 molecules is non-random and that few munc18-1 molecules are required for exocytosis to proceed in neuroendocrine cells. Furthermore, targeted disruption of the N-terminal interaction resulted only in a reorganisation of interaction with syntaxin with no change in the molecular spatial pattern of secretory vesicles, syntaxin or munc18-1. Single molecule imaging PALM (sptPALM) enabled the investigation of the complex spatio-temporal behaviours of single munc18-1 molecules in living neuroendocrine cells. Spatially resolved maps of single munc18-1 molecules demonstrated that munc18-1 exhibits a caged motion within areas of the plasma membrane and were found to move between molecular storage depots distinct from vesicle docking sites. To explore the precise spatial and temporal sequence of interactions between syntaxin and munc18-1 in living neurons, super-resolution imaging techniques PALM and sptPALM were employed. Two kinetically and spatially distinct populations of munc18-1 molecules co-exist within a living neuron and munc18-1 requires syntaxin to traffic efficiently in axons but not for its retention in nerve terminals. Moreover, Fluorescence Correlation Spectroscopy (FCS) revealed that the majority of munc18-1 molecules do not interact with syntaxin in nerve terminals and the diffusion rate of syntaxin is significantly slowed down upon neuronal depolarisation.

Inledning:Avsikten med studien är att ta reda på hur lärare uppfattar styrdokumenten och avsaknad av kunskapskrav i ämnet teknik för årskurs 1-3. Vi vill undersöka hur lärarna tror att eleverna upplever lektionerna, både innehållsmässigt och ur genusperspektiv, samt hur lärares kompetens, tillgång till material, tid och lokal påverkar undervisningen.Studiens syfte:Studiens syfte är att undersöka förutsättningar för undervisning i teknikämnet i årskurs 1-3, lärares attityd och tolkning till teknikämnet och genus.Metod:Kvalitativ metod är vald, med semistrukturerad intervju som verktyg. Sex lärare intervjuades för årskurs 1-3, med behörighet att undervisa i teknik.Resultat:Det visade sig att de lärare som intervjuades upplevde att det kan vara svårt att undervisa i teknik. Detta på grund av att det inte finns läromedel eller material och att de ibland kunde uppleva att ämnet inte ansågs viktigt i skolan. Lärarna tolkade styrdokumenten olika i ämnet teknik. De intervjuade lärarna ville synliggöra för eleverna att teknik är en del av samhället och att de möts av teknik överallt, vilket överensstämmer med läroplanen. Överlag upplevde lärarna att alla elever ställde sig positiva till den undervisning de fick ta del av och någon skillnad i genus fanns inte, enligt lärarna. De upplevde att det kan vara möjligt att det synliggörs i högre årskurser. Studien visade att det var skillnader i vilken årskurs eleverna fick ta del av teknikundervisning, enligt Skollagen ska skolan vara likvärdig över hela landet.

Tras comprobar en investigaciones preliminares relacionadas con el Trabajo de Final de Máster la ausencia de un estudio crítico completo y ordenado sobre el recurso a Heráclito en la obra de Friedrich Nietzsche, se evidenció la necesidad de desarrollar una investigación exhaustiva al respecto. La presente tesis doctoral atiende esta necesidad y contribuye en el campo de los estudios nietzscheanos con la aportación de un trabajo crítico en el que se presentan y analizan siguiendo el orden cronológico en que fueron escritos, todos los pasajes de las obras y los textos para las lecciones y conferencias impartidas por el autor que contienen alusiones a Heráclito. Cada uno de estos pasajes se ha contextualizado y comentado detalladamente, revisando las fuentes bibliográficas relacionadas y contrastándolo con las aportaciones más relevantes de la tradición interpretativa, tanto de los estudios nietzscheanos como de los heraclíteos, y aportando después nuestras propias consideraciones sobre el sentido del recurso en cada caso. Los comentarios de los diversos pasajes se complementan con el análisis de las alusiones a Heráclito contenidas en apuntes y fragmentos póstumos. También se revisan algunas cuestiones derivadas de la exploración, que suelen generar bastante confusión y a las que se ha dedicado un apartado específico que contribuye a mejorar su comprensión. Por último, en un documento anexo a la tesis doctoral se presenta la relación completa y cronológicamente ordenada de todas las citas, facilitando así una consulta rápida de los pasajes en cuestión, a la vez que una visión de conjunto del proceso de las citas a lo largo de toda la obra del autor, junto con la posibilidad de contrastar de manera directa las alusiones realizadas en las anotaciones de los póstumos, y en las obras y otros textos, en un mismo periodo cronológico. La presente investigación ofrece así un estudio completo, sistemático y cronológicamente ordenado del recurso a Heráclito en el conjunto de la obra del autor, con indicaciones precisas sobre el interés, sentido y contexto de cada una de las citas, que permite comprobar el alcance real de la cuestión a partir de la evidencia de los propios textos, ante la frecuente tendencia a utilizar las citas de manera aislada, superficial o incluso supeditada a determinados intereses interpretativos. / After checking in preliminary investigations, related to my Master Thesis, the absence of a full and orderly critical study on the use of Heraclitus in the work of Friedrich Nietzsche, we realized the need to develop a thorough investigation on the matter. This PhD thesis serves this need and contributes in the field of Nietzschean studies with a critical work that is presented and analysed according to the chronological order in which all the passages of the works and texts, for the lessons and lectures given by the author, containing allusions to Heraclitus, were written. Each of these passages has been contextualized and commented on in detail, reviewing related bibliographic sources and contrasting it with the most relevant contributions of the interpretive tradition, both for the Nietzschean studies and for those of Heraclitus, and then providing our own considerations on the meaning of the resource in each case. The comments of the various passages are complemented by the analysis of the allusions to Heraclitus contained in notes and posthumous fragments. In a document attached to the doctoral thesis I present a complete and chronologically ranked list of all the citations, thus facilitating a quick reference of the passages in question, as well as an overview of the processing of citations throughout the work of the author, along with the possibility to compare directly the allusions made in the annotations of the posthumous, and in the works and other texts, in a same chronological period. This research offers a full, systematic and chronologically ordered study on the reference to Heraclitus in all the work of the author, with precise indications on interest, meaning, and context of each one of the citations, allowing to show the real scope of the question from the evidence of the texts, in contrast with the frequent tendency to use citations in an isolated and superficial manner, or even subject to certain interpretive interests. I am also attaching an annex that addresses some issues arising from my exploration, which tend to create confusion, and to which a somewhat more detailed attention has been paid, helping to improve its understanding. / Dopo aver constatato negli studi preliminari relativi al Lavoro Finale di Master Fondamenti per un studio sull’influenza di Eraclito in Nietzsche l’assenza di uno studio critico completo e ordinato sui riferimenti ad Eraclito nell’opera di Nietzsche, si evidenziò la necessità di sviluppare un’investigazione esaustiva al riguardo. La presente tesi di dottorato soddisfa questa necessità e contribuisce nel campo degli studi nietzscheani con un lavoro critico nel quale si presentano e analizzano seguendo l’ordine cronologico in cui furono scritti, tutti i passi delle opere e i testi per le lezioni e conferenze tenute dall’autore che contengono allusioni a Eraclito. Ciascuno di questi passi è stato contestualizzato e commentato dettagliatamente, controllando le relative fonti bibliografiche ed è stato confrontato con i contributi più rilevanti della tradizione interpretativa, tanto degli studiosi nietzscheani come di quelli eraclitei. I commenti dei diversi passi si completano anche con l’analisi delle allusioni a Eraclito contenuti in appunti e frammenti postumi, e con le nostre considerazioni sul significato del riferimento, in ogni singolo caso. Sono trattate anche alcune questioni derivate dall’analisi, che solitamente generano abbastanza confusione, e alle quali si è dedicata un’attenzione un po’ più dettagliata che contribuisce a migliorarne la comprensione. In un documento annesso alla tesi di dottorato si presenta la relazione completa e cronologicamente ordinata di tutte le citazioni, facilitando così una consultazione rapida dei passi in questione, contemporaneamente ad una visione della totalità del processo di citazioni nell’arco di tutta l’opera dell’autore, insieme alla possibilità di confrontare in modo diretto le allusioni ad Eraclito nelle annotazioni dei frammenti postumi e nelle opere e in altri testi in uno stesso periodo cronologico. Il presente studio offre così un’analisi completa, sistematica e cronologicamente ordinata dei riferimenti a Eraclito nella totalità dell’opera di Nietzsche, con indicazioni precise sull’interesse, sul significato e sul contesto di ciascuna delle citazioni che permette così di confrontare l’importanza della questione a partire dall’evidenza dei testi stessi, di fronte alla frequente tendenza ad utilizzare le citazioni in maniera isolata, superficiale o perfino subordinata a particolari interessi interpretativi.

I denna studie har vi undersökt hur utbudet av barnböcker ser ut på sex olika förskoleavdelningar med avseende på genus och jämställdhet. Detta gjordes på fyra olika åldersindelade förskolor, med inriktning mot de yngsta åldrarna 1-3 år. Avdelningar för barn mellan 1-3 år valdes eftersom att tidigare forskning visar att barnen redan under dessa första år får en uppfattning om hur de ska förhålla sig gentemot varandra, samt vilka förväntningar som finns på dem själva beroende på vilket kön de har. Via samtal med en pedagog per avdelning har vi fått reda på hur böckerna lånas och används. Vi har analyserat förskoleavdelningarnas sammanlagda utbud, 107 böcker, med hjälp av en modell som vi själva utformat. Denna har vi gjort utifrån tidigare forskning samt utifrån egna reflektioner från vår verksamhetsförlagda utbildning. Utifrån analysen framkom att bilderna såg relativt jämställda ut mellan könen, i jämförelse med tidigare forskning. Resultatet visade att det går 1,2 manliga karaktärer per kvinnlig bild. I textanalysen är skillnaden dock större mellan könen, där manliga pronomen är vanligare än kvinnliga pronomen. Resultatet här blev 2,3 manliga pronomen per kvinnligt pronomen. Sammanfattningsvis kan slutsatsen dras att det är relativt jämställt mellan könen i det undersökta barnboksutbudet.