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Les cellules lymphoïdes innées de groupe 3 (ILC3) contribuent activement à l’homéostasie intestinale par leur production d’Interleukin-22 (IL-22). Ces ILC3 regroupent 2 sous-populations majeures, les LTi (« Lymphoid Tissue inducer »), caractérisées par l’expression du récepteur au chimiokine CCR6, et les ILC3 exprimant le facteur de transcription (FT) T-bet, qui comprennent une population positive pour le marqueur de surface NKp46, récepteur originalement utilisé pour identifier les ILC de groupe 1 (ILC1). Les ILC1 jouent un rôle prépondérant dans la réponse aux pathogènes intracellulaires et anti-tumorale. Jusqu’à présent, trois populations majeures composent les ILC1 : les lymphocytes cytotoxiques Natural Killer (NK ou ILC1b), qui dépendent largement du FT Eomes et expriment l’intégrine CD49b ; les ILC1 hépatiques et intestinaux, qui dépendent du FT T-bet et expriment CD49a (ILC1a) ; et une population CD49a+ et DX5+ indépendante du FT Nfil3 localisée dans les glandes salivaires ou l’utérus (ILC1ab). Mes travaux visent à comprendre la biologie des ILC exprimant NKp46, ainsi que les facteurs impliqués dans leur développement, leur maturation et leur fonction. La majeure partie de ma thèse se concentre sur les NKp46+ ILC3. Premièrement, nous démontrons un rôle majeur pour le récepteur aux chimiokine CXCR6 dans la localisation des NKp46+ ILC3 dans les villi de la lamina propria intestinale (Satoh-Takayama et al. 2014). Deuxièmement, j’ai mis en évidence que NKp46+ ILC3 pouvait perdre l’expression de NKp46 (Verrier et al. 2016). Déclenchée par le TGFβ, cette perte d’expression est associée à une plus forte capacité à produire de l’IL-22, mais aussi à l’acquisition de marqueurs identifiant les LTi (CCR6, MHC-II), démontrant ainsi la plasticité des NKp46+ ILC3. Enfin, en collaboration avec le groupe de Rachel Golub, nous avons confirmé le rôle présumé de la molécule Notch dans cette plasticité (Chea et al. 2016). Dans ce manuscrit, je discuterai du développement et de l’hétérogénéité des ILC3, ILC1a, ILC1b et ILC1ab. L’ensemble de mes résultats soutient une vision dynamique de la biologie des ILC reflétant l’adaptation de ces cellules effectrices face à leur environnement. En caractérisant les différents acteurs impliqués dans ce processus dynamique, mes travaux pourront servir au développement de thérapies visant à contrôler l’équilibre entre ces différentes populations dans divers pathologies comme le cancer, les infections virales, ou encore les maladies intestinales / Group 3 Innate Lymphoid cells (ILC3) actively maintain mucosal homeostasis through the production of Interleukin-22 (IL-22). ILC3 encompass 2 major populations, LTi (« Lymphoid Tissue inducer »), characterized by the expression of the chemokine receptor CCR6, and ILC3 that express the transcription factor T-bet, which include a population expressing the surface marker NKp46, a receptor originally used to identify group 1 ILC (ILC1). ILC1 plays a major role in the defense against intracellular pathogens and anti-tumoral responses. Three major ILC1 populations have been identified: the cytotoxic lymphocytes « Natural Killer » (NK or ILC1b), which largely rely for on the transcription factor Eomes their generation and express the integrin CD49b; hepatic and intestinal ILC1 that depends on the T-bet transcription factor and express CD49a (ILC1a); and a population that expresses CD49a and CD49b (ILC1ab) and populates the salivary gland and the uterus, which is independent of the transcription factor Nfil3. My work aimed to understand the biology of NKp46 expressing ILC, as well as factor involved in their development, maturation and function. The major part of my work focuses on NKp46+ ILC3. First, we demonstrate a major role for the chemokine receptor CXCR6 in their localisation in the lamina propria villi (Satoh-Takayama et al. 2014). Second, I showed that NKp46+ ILC3 could lose NKp46 expression (Verrier et al. 2016). Induced by TGFβ, this loss of expression was associated with higher IL-22 production and by the acquisition of markers identifying LTi (CCR6, MHC-II), demonstrating NKp46+ ILC3 plasticity. Finally, in collaboration with Rachel Golub’s group, we confirmed a putative role for Notch-signaling in this plasticity (Chea et al. 2016). In this manuscript, I will discuss the development and the heterogeneity of ILC3, ILC1a, ILC1b and ILC1ab. All the results I generated support a dynamic vision of ILC biology, which reflects how they adapt in response to environmental cues. By characterizing the different actors involved in this dynamic process, my work could be used to design therapies aiming at controlling the equilibrium between these different populations in diverse pathologies such as cancer, viral infection, or intestinal diseases

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資產證券化源自1970年代，第一筆擔保債權憑證交易自1988年出現在美國，然後在歐美迅速發展，目前已成為重要的之債券市場。台灣金融產業發展正值轉型期，銀行除面對低利率帶來經營壓力之外，同時亦需規避評等較差之企業貸款的信用風險，而保險業者在低利率時代來臨卻無良好報酬之投資標的可供投資。因此，此環境乃為推動證券化之良好契機。自1997年發生東南亞金融危機，乃至1998年韓國的亞洲金融危機，造成許多跨國企業紛紛裁員、關廠、甚至倒閉，造成一連串的金融危機連鎖效應。因此，公司間或產業間之榮枯是相互關聯的，且均會受總體經濟因素所影響。是以，近年來除信用風險亦成為近年來財務領域上重要議題。理論或實證上，當多個標的資產之信用衍生性商品被加以開發，並用來管理信用風險的時候，需考慮多個標的資產間的違約相關性，方能準確地衡量信用風險。故在信用風險管理與信用衍生性商品的評價中，違約相關性的估計與考量顯得格外重要。結構式或縮減式模型在發展違約相關性的多變數模型中是困難的，因為其衍生性商品價值的理論推導繁複或其數值計算是相當費時。本文在多標的資產之信用風險評價模型中，透過適當個別資產之邊際違約機率與Copula函數之選擇，及其相關參數之估算，即可快速求算具違約相關性之多變數聯合機率函數，以利擔保債權憑證(CDO)之評價。因此，本文針對BET、Copula、Factor Copulas等三種方法與分析架構做一剖析，再以國內153家上市公司所發行無擔保債券作為連結標的之擔保債權憑證為例，進行模擬實證並分析結果。

Thesis (Ph. D.)--Universiṭat Bar-Ilan, 2001. / Includes bibliographical references.

Populations of cells live in uncertain environments, where they encounter large variations in nutrients, oxygen and toxic compounds. In the fluctuating environment, cells can sense their surroundings and express proteins to protect themselves against harmful substances. However, if the stressor appears infrequently or abruptly, sensing can be too costly or too slow, and cells cannot rely solely on it. To hedge against the sudden appearance of a stressor, cell populations can also rely on phenotypic diversification through bet-hedging. In bet-hedging, cells exploit noise in gene expression or use multistable genetic networks to produce an heterogeneous distribution of resistance-conferring protein levels. In this thesis, we analyze novel roles of noise in biological systems. Through a combination of modeling and stochastic simulations, we find that noise can coordinate multi-component stress response mechanisms in a subset of the population with no extra cost. In addition, we use evolutionary algorithms to analyze the conditions where the benefits provided by noise in gene expression are equivalent to those of a more complicated, bistable distribution of protein levels. Our results show that for cells living in noisy fluctuating environments, both noise in gene expression and bistability show similar growth rates, meaning that noise in gene expression can be an effective bet-hedging strategy.

This thesis was designed to investigate the effect of task complexity upon how humans estimate duration. Previous task complexity research suggests that duration is overestimated with simple tasks and underestimated with complex tasks. One-hundred and forty-two first and second year university students participated. Twelve experiments were conducted, which required participants to complete computer generated jigsaw puzzles and periodically estimate how long they thought they had been doing the puzzle. In Experiment 1, participants were required to complete a jigsaw puzzle before making an estimate. In the remaining eleven experiments, estimates were made throughout the session whilst participants worked on the jigsaw puzzle. In the first four experiments, a task was complex if there were more puzzle pieces and simpler if there were fewer puzzle pieces. There were no significant results obtained from the first four experiments. Given the lack of effect from the first four experiments, the next two experiments partially replicated two task complexity studies to determine how task complexity can be used as an explanation for why estimations of duration differ. Again, there were no significant results obtained from these two experiments. The next four experiments tested whether people's estimates of duration were affected by the rate of reinforcement they receive (i.e., successfully moving a puzzle piece to a new location per unit time). In the first of these two experiments (7 and 8) there was no effect of the manipulation, which consisted of decreasing the distance which a puzzle piece could be moved on the screen, relative to the distance the computer mouse was moved and fixing the speed at which a puzzle piece could be moved. In Experiments 9 and 10, more discriminative stimuli were used to indicate to participants that a change in the reinforcement rate was occurring. There was a significant result in Experiment 9 in one condition but this effect was not replicated in Experiment 10. In Experiment 11, the reinforcement rate was reduced to zero and there was a significant effect on participants' estimates of duration. However, these results suggested a confound between whether the reinforcement rate or not being able to access the jigsaw puzzle was affecting estimates of duration. In Experiment 12, access to the jigsaw puzzle was limited, whilst simultaneously controlling the reinforcement rate and the results showed that not having access to the jigsaw puzzle affected how participants estimate duration. These findings suggest that information can act as reinforcement, enabling a person to engage in private behaviour. When there is no access to reinforcement, time 'drags' for humans.

An onset coarsening-coalescence event based on the incubation time of cylindrical mesopore formation and a significant decrease of specific surface area by 50% relative to the dry pressed samples was determined by N2 adsorption-desorption hysteresis isotherm for cassiterite SnO2 nanoparticles (rutile-type structure with bimodal size distribution). In the temperature range of 800-1100oC, the nanoparticles underwent onset sintering coupled with coarsening-coalescence without appreciable polymorphic transformation or decomposition of SnO2. The apparent activation energy of such a rapid process for SnO2 nanoparticles was estimated as 75 ¡Ó 5 kJ/mol, respectively. The minimum temperature for sintering/coarsening/coalescence of the SnO2 nanoparticles is 735oC based on the extrapolation of steady specific surface area reduction rates to null. PLA fragmentation of cassiterite SnO2 powder (rutile type, 20-50 nm in size) in water was conducted under Q-switch mode (532 nm, 400 mJ per pulse) having laser focal point fixed at 5, 10, 15 and 20 mm beneath the water level for an accumulation time of 5, 15, 20 and 30 min at 10 Hz. The 532 nm laser incidence suffered little water absorption and was effective to produce cassiterite nanocondensates as small as 5 nm in diameter and occasional nanocondensates of £\-PbO2-type structure more or less in coalescence. The combined effects of nanosize, internal compressive stress and H+ and Sn2+ co-signature in the lattice may account for a lower minimum band gap.

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