Cette thèse porte sur la synthèse et la caractérisation de nouvelles phases bidimensionnelles par microscopie électronique in-situ, notamment la silice (SiO2), des cages nanométriques de carbone similaire à des molécules C20 et le chalcocite (β-Cu2S). Ces études ont permis de mettre en évidence les conditions préalables de croissance afin que celle-ci soit reproductible. La caractérisation de ces structures a été réalisée par imagerie haute résolution (HRTEM) ainsi que par spectroscopie de perte d’énergie (EELS). La première partie de la thèse est consacrée à l’étude de la nucléation et la croissance in-situ d’une phase cristalline 2D ordonnée et désordonnée sur différents métaux de transition (Co, Ru, Fe) ainsi qu’une phase 1D qui croît le long des marches atomiques sur la surface métallique. La seconde partie est consacrée à la croissance in-situ de cages de carbone d’un diamètre de l’ordre de 0.36 nm en présence d’un catalyseur métallique, tel que Co, Fe et Ru. La dernière partie est consacrée à l’étude de la croissance de la plus fine structure cristalline du β-Cu2S sur la surface du graphène. Toutes ces études ont été appuyées par des simulations d’images de microscopie. / The aim of this thesis is the synthesis and characterization of new two-dimensional phases in an in-situ transmission electron microscopy experiment. These studies concerned the nucleation and growth of three deferent materials: quasi-two-dimensional silica (SiO2), the smallest possible carbon cages with the size of C20, and two-dimensional chalcocite (β-Cu2S). The characterization of these structures has been performed using high resolution imaging (HRTEM) and electron energy-loss spectroscopy (EELS). The first part of this thesis is devoted to the study of the nucleation and growth of an ordered or disordered 2D crystalline phase of silica on different substrates (Co, Ru, Fe) and a 1D silica phase grown at atomic steps of a metal surface. The second part illustrates the in-situ growth of the smallest possible carbon cages with a diameter of about 0.36 nm on catalytically active metal surfaces such as Co, Fe, or Ru. The last part is devoted to the growth of the thinnest stable layer of β-Cu2S on a graphene surface. All these studies were accompanied by image simulations.

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Ce mémoire présente une comparaison de deux algorithmes de reconnaissance de plan, soit YAPPR (Yet Another Probabilistic Plan Recognizer) et PR-Plan (Plan Recognizer as Planning). Afin de comparer les algorithmes, nous avons voulu utiliser un domaine plus complexe et réaliste que ceux utilisés jusqu’à présent. Pour ce faire, nous avons établi un protocole de comparaison en utilisant le concept d’observation in situ. Nous avons utilisé le jeu de stratégie en temps réel StarCraft comme environnement de simulation. Puis, nous avons créé un agent jouant à StarCraft qui utilise la reconnaissance de plan comme élément central pour le système de prise de décision. Pour valider que notre principe d’observation in situ fonctionne, nous avons créé des agents témoins et exécuté de nombreuses simulations.

La cytogénétique est une branche de la génétique qui étudie les chromosomes et leur intégrité ainsi que les conséquences de leur transmission et de leur expression. Plusieurs syndromes et maladies ont pu être expliqués par cette discipline. Certaines anomalies chromosomiques de structure ont d'ailleurs contribué à identifier des gènes, des fonctions de gènes ou à caractériser des structures chromosomiques. Dans cet ordre d'idées, nous avons utilisé deux isodicentriques du bras long du chromosome Y (idic(Y)(p11.3)) pour étudier la fonction d'une protéine du kinétochore, CENP-B, dans le mécanisme d'inactivation de kinétochore. Pour ce faire, nous avons premièrement fait une caractérisation cytogénétique des deux idic(Y)(p11.3) à l'aide des techniques de cytogénétique classique et de cytogénétique moléculaire. Nous avons ainsi déterminé approximativement le point de cassure des deux isodicentriques, soit en Yp11.3. Comme les deux chromosomes avaient une structure très semblable, mais que les patients présentaient un phénotype clinique très différent, nous avons investigué les niveaux de mosaïcisme dans différents tissus chez les deux patients. Il est connu qu'un chromosome possédant deux centromères capables de former le kinétochore peut être très instable lors des divisions cellulaires. Ainsi, la cellule a mis au point un mécanisme permettant d'inactiver un des kinétochores du chromosome dicentrique. Une récente revue a proposé que la protéine CENP-B jouerait un rôle dans ce mécanisme. Cependant, comme le chromosome Y ne possède pas la séquence d'ADN liant cette protéine, il était intéressant de vérifier si une inactivation des kinétochores avait eu lieu dans nos idic(Y)(p11.3). À l'aide d'un anticorps dirigé contre la protéine CENP-C, connue comme un marqueur de kinétochore actif, nous avons montré que plus de 40% des chromosomes dicentriques avaient subi une inactivation d'un de leur kinétochore. Enfin, la présence de la protéine CENP-B dans ces kinétochores a été étudiée. Nous avons montré que la protéine CENP-B était présente à tous les autres centromères, sauf ceux de l'idic(Y)(p11.3). Ainsi, nous proposons que la protéine CENP-B n'est pas impliquée directement dans le mécanisme d'inactivation de kinétochore du chromosome Y. Par contre, nous ne pouvons pas exclure qu'elle joue un rôle indirect, soit par une interaction protéine/protéine, soit à une étape en amont dans le mécanisme d'inactivation.

BACKGROUND:Detection of B cell clonality is useful for assisting in the diagnosis of B cell lymphomas. Clonality assessment can be accomplished through evaluation of KAPPA and LAMBDA light chain expression. Currently, only slide based methods are available for the majority of patient biopsies and do not detect light chain protein or mRNA in many B-cell lymphomas. Herein we evaluated a new method, known as colorimetric in situ hybridization (CISH), with improved sensitivity and multiplexing capacity, for its usefulness in clonality detection in mature B cell malignancies.METHODS:The KAPPA and LAMBDA ISH was performed on a Ventana Benchmark XT utilizing two color chromogenetic detection. The probes comprised 2 haptenated riboprobes each approximately 500 base pairs long directed against the conserved regions of either KAPPA or LAMBDA mRNA. The dual colors consisted of silver deposition (black) for KAPPA light chain and a novel (pink) chromogen for LAMBDA light chain. Following optimization, CISH allowed visualization of mRNA in benign B cells in reactive tissues including germinal center, mantle zone, and post-germinal center cells. We then identified 79 cases of B cell lymphoma with formalin-fixed paraffin-embedded (FFPE) biopsies including: follicular (36 cases), mantle cell (6 cases), marginal zone (12 cases), lymphoplasmacytic (6 cases), small lymphocytic (4 cases), and diffuse large B cell (15 cases), which were selected on the basis of either prior flow cytometry or immunohistochemistry (IHC) results to serve as the predicate, "gold standard," comparator.RESULTS:39/79 (49.4%) cases were classified as KAPPA and 29/79 (36.7%) as LAMBDA light chain restricted / while 9/79 (11.3%) cases were classified as indeterminate. Of the 70 cases with KAPPA or LAMBDA light chain restricted CISH, 69/70 (98.6%) were concordant with the reference method, while 1/70 (1.4%) was discordant.CONCLUSIONS:Optimized CISH detected lower levels of mRNA than can be visualized with current slide based methods, making clonality assessment in FFPE biopsies possible for mature B cell neoplasms. In this preliminary study, CISH was highly accurate compared to flow cytometry or IHC. CISH offers the possibility of wider applicability of light chain ISH and is likely to become a useful diagnostic tool.Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1430491067123856

International Telemetering Conference Proceedings / October 26-29, 1987 / Town and Country Hotel, San Diego, California / The Deep Space Network is responsible for the acquisition of in-situ science and engineering measurements and navigation data from spacecraft whose missions are to explore the Solar System. It must respond to new opportunities in the mission set supported so as to maintain or enhance mission science value. The large capital investment in such a Network mandates an evolutionary design approach wherein upgrades can be effected at low cost, and if appropriate, on existing capability. The 64-Meter antenna design, completed in 1963, is an example of this approach, in that it has permitted a relatively low-cost upgrade which increases performance significantly. The technology assessment was completed in 1975, and the option was exercised in 1986, when needed. Several key characteristics of the DSN design approach, the costs to upgrade performance over the past several decades, and some fundamental constraints on performance are discussed. Finally, the specific 70-Meter upgrade task and resulting overall benefits to Voyager-Neptune and the mission set are summarized.

Target-guided synthesis is an approach to drug discovery that uses the biological target as a template to direct synthesis of its own best inhibitors from small molecule fragments. The process bridges the gap between chemical synthesis of drug candidates and their biological binding assay, merging the two operations into a single process whereby the active site or a binding pocket within the structure of the biological target directly controls the assembly of the best inhibitor in situ. Two different approaches to target-guided synthesis, the thermodynamic approach, making use of reversible reactions, and the kinetic approach, which uses an irreversible reaction, have been employed to discover novel, isoform selective inhibitors of the glutathione transferase (GST) enzyme family – possible drug targets in cancer and parasitic disease treatments. The thermodynamic approach described in this thesis uses the aniline-catalysed reversible acyl hydrazone formation reaction to create a dynamic covalent library of bivalent ligands designed to bind the dimeric structure of GST. In the presence of GST one of the bivalent ligands was selectively amplified at the expense of the other library members. This ligand was shown, via biological assays, to be a specific inhibitor for one isoform of GST, the mu isoform mGSTM1-1. A kinetic approach has also been investigated as a way to identify novel bivalent GST inhibitors utilising the Huisgen 1, 3 dipolar cycloaddition reaction. An azide and alkyne fragment library was designed to bind across the dimeric GST structure. The inhibitor structures are therefore bivalent, containing two anchoring fragments known to bind to the GST active site, linked by a triazolopeptide spacer. The triazole provides the click chemistry disconnection, enabling rapid in situ screening of candidate alkyne and azide fragments for inhibitor discovery. Whilst the in situ reaction with GST yielded inconclusive results, a number of the triazole products were found to have low nanomolar inhibitory activity towards GST.

International Telemetering Conference Proceedings / October 23-26, 2000 / Town & Country Hotel and Conference Center, San Diego, California / Combating harsh and unpredictable channel environments is a part of the design of any in-situ communication system (i.e. rover to lander, rover to orbiter, etc.). Channel characteristics can range from simple additive white Gaussian noise (AWGN) channels to more bursty fading channels found in rover to orbiter links (i.e. canyon scenarios and typical orbiter passes around mountain ranges). A combination of forward error correction and automatic repeat request (ARQ) schemes are commonly used to provide a more robust communications link. ARQ enhances the communication link particularly for bursty fading channels. Go-Back-N is a commonly used ARQ scheme and is an option in the newly developed Consultative Committee for Space Data Systems (CCSDS) Proximity-1 Link protocol [7], a data link layer protocol targeted specifically for in-situ applications. Optimization of frame sizes and retransmission persistence of the ARQ scheme require a good analytical model of how the scheme performs over various channel conditions. In this paper, an analytical framework for modeling the COP-1 protocol is presented for both AWGN channels along with bursty fading channels. A Gilbert-Elliot two-state Markov model is used to model a bursty fading channel.

The production of methyl mercury, an acute neurotoxin which readily accumulates in the tissue of organisms, is a biologically mediated process facilitated by sulfate reducing bacteria in aquatic sediments. In-situ capping is a frequently considered risk management strategy for contaminated sediments. Since placement of an in-situ cap will induce anaerobic conditions that are known to be favorable for the growth of sulfate reducing bacteria, there is justifiable concern that capping could increase mercury methylation in underlying sediments. This research builds an understanding of the effects of in-situ capping on underlying biogeochemical processes and elucidates their importance in controlling methyl mercury production. Laboratory experiments and mathematical models were implemented to simulate mercury methylation in redox conditions likely to be induced by capping using sediment from different environments. Mathematical descriptions of processes known to be involved in methylation were incorporated into the model to quantify the effects of these processes. Observations in both well-mixed slurry conditions and intact sediment columns showed that methyl mercury concentrations are strongly dependent upon biogeochemical conditions. Results from experiments with sediment spanning a range of redox conditions and organic contents suggested that sulfate reduction rates, aqueous speciation, and solid phase partitioning are involved in limiting methylation depending on bulk geochemical characteristics. A model with a mechanistic basis that incorporates the effects of these processes provides a useful means of qualitatively and quantitatively considering their cumulative impact in limiting methyl mercury production. High methyl mercury concentrations observed in some lab experiments suggest that there is reason to be concerned about anoxic conditions induced by capping; however, not all anoxic conditions led to equivalent increases in methyl mercury. Experimental and modeling results suggest that in a high organic environment, in-situ capping may produce conditions which accelerate methylation in (formerly) surficial sediment while in a low organic environment, with an overall lower potential for methylation, capping can be expected to have a less dramatic effect. Over time, two processes will temper capinduced increases in methyl mercury. Increases will only last until sulfide builds up to inhibitory levels in underlying sediment or until organic carbon is depleted and overall bacterial activity slows. By providing a more fundamental understanding of the effects of capping on mercury methylation, the results of this research will aid in identifying situations and conditions in which cap-induced increases in methyl mercury have the potential to limit the effectiveness of the management strategy. / text

Earthquake-induced soil liquefaction that occurs within the built environment is responsible for billions of dollars of damage to infrastructure and loss of economic productivity. There is an acute need to accurately predict the risk of soil liquefaction as well as to quantify the effectiveness of soil improvement techniques that are meant to decrease the risk of soil liquefaction. Current methods indirectly measure the risk of soil liquefaction by empirically correlating certain soil characteristics to known instances of surficial evidence of soil liquefaction, but these methods tend to overpredict the risk in sands with silts, to poorly predict instances of soil liquefaction without surface manifestations, and fail to adequately quantify the effectiveness of soil improvement techniques. Direct in-situ evaluation of liquefaction susceptibility was performed at a single site at the Wildlife Liquefaction Array (WLA) in Imperial Valley, California, in March 2012. The project included a CPT sounding, crosshole testing, and liquefaction testing. The liquefaction testing involved the measurement of water pressure and ground particle motion under earthquake-simulating cyclic loading conditions. The objective of this testing technique is to observe the relationship between shear strain in the soil and the resulting generation of excess pore water pressure. This fundamental relationship dictates whether or not a soil will liquefy during an earthquake event. The direct in-situ evaluation of liquefaction susceptibility approach provides a more accurate and comprehensive analysis of the risks of soil liquefaction. It also has the ability to test large-scale soil improvements in-situ, providing researchers an accurate representation of how the improved soil will perform during a real earthquake event. The most important results in this thesis include the identification of the cyclic threshold strain around 0.02% for the WLA sand, which is very similar to results achieved by other researchers (Vucetic and Dobry, 1986, and Cox, 2006) and is a characteristic of liquefiable soils. Another key characteristic is the 440 to 480 ft/sec (134 to 146 m/s) shear wave velocity of the soil, which are well below the upper limit 656 ft/sec (200 m/s) and an indication that the soil is loose enough for soil liquefaction to occur. The third significant point is that the compression wave velocity of the sand is greater than 4,500 ft/sec (1,370 m/s), indicating that it is at least 99.9% saturated and capable of generating large pore water pressure due to cyclic loading. These three conditions (cyclic threshold strain, shear wave velocity, and compression wave velocity) are among the most important parameters for characterizing a soil liquefaction risk and must all be met in order for soil liquefaction to occur. / text