Dissertations / Theses on the topic 'NWF'

I denna rapport utforskas möjligheterna med BIM-modeller som finns på dagens byggarbetsplatser.  Trots att BIM erbjuder effektivare lösningar inom områden som bland annat visualisering, samordning och kvalitetsarbete, är det få projekt som aktivt använder sig av BIM på byggarbetsplatsen. Den här rapporten syftar till att belysa potentialen med BIM under produktionsfasen samt analysera svårigheter som finns, då produktionspersonal vill använda sig av BIM-modellen. Det långsiktiga målet med rapporten är att främja framtida användning av BIM i produktionsfasen. I arbetet produktionsanpassas delar av BIM-modellen för Skanskas och Vasakronans samverkansprojekt Klara C till att den kan användas ifrån en handhållen enhet. Genom att visa praktiska tillämpningar, med verktyg och BIM-modeller som finns tillgängliga idag, synliggörs möjligheter med BIM i byggproduktionen. För att ha möjlighet att påverka kvalitet och format på den BIM-modell, vilken ändå uppförs vid projekteringen, är det av stor vikt att tidigt beakta vilka effekter ett aktivt användande av BIM har i produktionsfasen. Slutsatsen sammanfattas i ett antal frågeställningar som planerande personal bör ha i åtanke, detta för att främja en utvecklande och värdeskapande användning av BIM även ute på byggarbetsplatsen. Vilken nytta tillför modellen i det specifika projektet? Ex. Samordning, tidsplanering eller visualisering. Hur ska modellen användas av produktionspersonalen? Ex. Vilken enhet (Surfplatta/PC) Vilka krav ställs då på BIM-modellen? Ex. Detaljeringsnivå, parametrar. Vad krävs av arbets- och informationsflöden? Ex. Format på leverans av modell/modeller. Är tillämpningen anpassad till användaren? Ex. Behövs det ytterligare stöd i form av kortare utbildningar eller kurser?
This thesis explores the potential of the BIM-models available at today's construction sites. There are few projects that actively use BIM on the construction sites, despite the fact that BIM offers efficient solutions in areas such as visualization, coordination and quality control. This report aims to highlight the potential of BIM during the production phase and to analyze the difficulties that exist when production staff wants to use the BIM model. The long term goal of this report is to promote use of BIM in the production phase. In this report, parts of the BIM-model of Skanska and Vasakronan collaborative project Klara C, is adapted so that it can be used from a handheld device. Positive effects from active use of BIM-models are shown with the tools and BIM-models that are available today. In order to influence the quality and setup of the BIM-model, which is produced during the design stage, it is of great importance that all potential applications of the model is taken in to account. The conclusion is summarized in a number of questions that planning staff should keep in mind in order to promote value-adding use of BIM. What benefits does the model bring the specific project? E.g. Coordination, time planning or visualization. How will the model be used by the staff? E.g. What kind of unit? (E.g. Tablet or PC) What is required from the model? E.g. Level of detailing, parameters. What work- and information flows are required? E.g. How is the model/models updated and delivered. Is the application user friendly? E.g. Is additional, supporting education required?

Studien syftar till att bidra med ökad förståelse om musiklärares arbete med elever med NPF (neuropsykiatrisk funktionsnedsättning) i den ordinarie undervisningen. Jag har sökt finna både musiklärares arbetssätt och uppfattningar kring elever med NPF. Studien utgår från ett relationellt perspektiv. Jag har genomfört fyra kvalitativa intervjuer med musiklärare som arbetar på grundskolan samt en som jobbar på ett särgymnasium. Resultatet visade på en mängd arbetssätt och uppfattningar så som vikten av: anpassningar i miljön, struktur, samarbete med andra lärare, följa elevernas intresse och fysiska hjälpmedel. Resultatet visade också på vikten av att göra anpassningar som kommer alla till gagn. I slutsatsen tar jag bland annat upp att genom ordnad miljö, struktur, fysiska hjälpmedel, samverkan, flexibilitet, och adekvata lokaler och gruppstorlekar går det att möta elever med NPF på ett framgångsrikt sätt i musik i den ordinarie undervisningen.
This thesis aims to contribute to an increased understanding of music teachers' work with students with special needs, such as ADHD and autism, (called NPF) in the ordinary school in Sweden. I have tried to find both music teachers' working methods and their perceptions about students with NPF. The study is based on a relational perspective. I have done four qualitative interviews with music teachers who work in the primary school and one teacher that works in a special high school. The results showed a variety of working methods and perceptions, such as the importance of: adjustments and changes in the environment, structure, collaboration with other teachers, following students' interests and physical tools. The results also showed the importance of making adjustments that benefit every student. In the conclusion I mention that through an orderly environment, structure, physical tools, collaboration, flexibility, and adequate premises and group sizes, it is possible to meet all students needs successfully in music in the regular school.

To constrain the thermal histories of two complex L chondrite melt breccia samples (NWA 5964 and NWA 6580) we compare textures and chemical compositions of metal and sulfide to L melt rock (NWA 6454 and NWA 6579) and strongly shocked (shock stage S6) (NWA 4860) samples. The inferred thermal histories can be used to evaluate formation settings on the L chondrite parent body. The L melt samples probably formed as different melt units within warm but largely unmelted material relatively close to the surface of the parent body, and the same is true for the S6 sample, except it experienced less melting. The breccia samples likely formed deeper, below different impact craters, by the injection of shock melt into a cooler chondritic basement. Carbide grains in the melt breccias could have formed by a contact metamorphic process caused by heating of the chondritic basement in proximity to the melt. Within the melt regions of the various samples, inferred cooling rates are on the order of 1-10 °C/sec, whereas in the chondritic portions of the melt breccias, the inferred cooling rates are many orders of magnitude slower, ~1-100 °C/My. The complex intergrowths of metal and FeS (hereafter referred to as dendritic grains) within the melt are recording cooling rates above the metal-sulfide eutectic, while the metal grains outside of the melt regions are recording cooling rates at much lower temperatures. It is likely the melt regions in the breccias cooled substantially prior to coming to rest against the chondritic basement, and thereafter the melt-chondrite rocks cooled more slowly.

The present study investigates the structural and functional roles of the metalloclusters present within the MoFe protein of nitrogenase from Azotobacter vinelandii. A gene replacement strategy was developed for oligonucleotide-directed mutagenesis of these proteins and the resulting biological and biochemical effects of these changes were examined. Identification of structurally important regions in the MoFe protein subunits and assignment of specific amino acid residues as potential metal cluster ligands were based upon several criteria: i. metallocluster extrusion requirements; spectroscopic properties of the MoFe protein; interspecies and intersubunit comparisons; iv. comparison of the MoFe protein subunit sequences to iron-molybdenum cofactor biosynthetic gene products. This mutagenesis strategy has permitted the construction of thirty-three mutant strains having specific amino acid substitutions within the MoFe protein subunits. Based on the diazotrophic growth characteristics and substrate reduction capabilities of these mutant strains, a model is presented in which potential metallocluster binding sites within the MoFe protein subunits are defined. In addition to analysis of the MoFe protein subunits, this site-directed mutagenesis and gene replacement strategy can be used to place specific mutations into any gene product encoded within the A. vinelandii nif gene cluster. Finally, nucleotide sequence analysis of the regions flanking the nifEN genes revealed the presence of three nif genes (nifT, nifY, and nifX) and four open reading frames (ORF1, ORF2, ORF3, and ORF4). Two of these genes, nifX and ORF3, were shown to be under nif control and synthesis of their products elevated in response to a demand for fixed nitrogen. Mutant strains with deletions in ORF3 appeared to accumulate an excess amount of MoFe protein when compared to wild type. The ORF3 gene product has been overproduced in E. coli. This provides an important step toward characterizing the protein and elucidating the molecular basis for its control of nifDK gene expression.
Ph. D.

Samhällsutvecklingen går från industrisamhälle till informationssamhälle och Försvarsmakten (FM) går fråninvasionsförsvar till insatsförsvar. Tidigare var det mer regel än undantag att civil teknologi hade sitt ursprung imilitär teknologi, t.ex. Internet. Idag är det precis tvärtom med marknadskrafterna som driver utvecklingen avt.ex. IT i ett högt tempo. Väpnade styrkor strävar efter att ta till vara på denna utveckling inom kommunikationoch informationsteknologi, i syfte att ha förmåga att möta framtida hot. Den militära utvecklingen inom dettaområde benämns Revolution in Military Affairs (RMA). Den svenska FM:s motsvarighet benämnsnätverksbaserat försvar (NBF) och är en tillämpning av tankegångarna kring konceptet RMA. Omfattandeforskning pågår inom IT generellt och telematiken är inte undantagen.Det amerikanska dokumentet Joint Vision 2010 FOCUSED LOGISTICS menar att teknologiutvecklingkommer att spela en avgörande roll för logistikledning, och att förbättringar av bl.a. built in test (BIT) ochtelemaintenance kommer att höja den tekniska personalens effektivitet. Telemaintenance är en delmängd avbegreppet telematik och består av: Fordonstjänster innehållande diagnostik för övervakning avfordonssystemet, larm för påkallning om allvarliga fel håller på att uppstå samt ”Vehicle Control” förfjärrstyrning av fordons funktioner. Underhållstjänster innehållande driftsinformation om t.ex. antaldriftstimmar, bränsleförbrukning, vibration, etc. Tjänsterna undersöks i denna uppsats med bakgrund avteknisk tjänst, vars syfte är att understödja krigsförbandens förmåga att lösa sina uppgifter. Teknisk tjänstbidrar till teknisk och taktisk tillgänglighet genom att säkerställa att ett tillräckligt antal materielsystem kanverka med erforderlig effekt.Uppsatsen tydliggör förväntningar på ett telemaintenance-system hos svensk trupp insatta i internationellaoperationer, närmare bestämt vilket behov av telemaintenance som 1993 förelåg vid den första bataljonen(BA01) som sattes in i Bosnien ingående i UNPROFOR.
As our industrial society has become more information based, ournational defense requirements have changed focus from an invasion defenceto an operations defence. For many years, new information technologiessuch as the internet were first developed for military use. Today the oppositeis true. Market forces are now driving the development of new technologiessuch as IT, at a fast pace. Armed forces must strive to make use of thesedevelopments within the areas of communication and informationtechnology, to better prepare for future threats. The military development inthis sector in called a “Revolution in Military Affairs” (RMA). The SwedishArmed Forces equivalency is called a “network-based defense” (NBF) andmakes use of the RMA concept. Extensive research is underway within ITin general and telematics is not an exception.The American document, “Joint Vision 2010 FOCUSED LOGISTICS”claims that the development of technology will play a decisive part inlogistics management, and that improvement in among other things, BITand telemaintenance will raise the effectiveness of technical servicepersonnel. Telemaintenance is one part within the concept of telematics andconsists of:Vehicle service consisting of diagnostic surveillance of vehicle systems,alarms for indication of serious faults, and Vehicle Control for remotecontrolling of vehicle functions.Maintenance service consisting of operational information such as thenumber of hours in operation, fuel consumption, vibration etc.Telemaintenance is investigated in this thesis with a background ofSwedish Army maintenance concept, which purpose is to support militaryfield units in their ability to solve their tasks. The maintenance conceptoffers greater technical and tactical availability by keeping optimal numbersof material systems operational.This thesis describes the expectations of a telemaintenence system of aSwedish troop in international operation, or more precisely, thetelemaintenence needs that were evident in 1993 at the first battalion(BA01) in Bosnia as part of UNPROFOR.
Avdelning: ALB - Slutet Mag 3 C-upps.Hylla: Upps. ChP 01-03

In order to study the functions of SIV Nef in vivo, in a small animal model, transgenic (Tg) mice expressing the SIVmac239 nef gene, under the control of the human CD4 gene promoter (CD4C) were generated. The transgene was found to be expressed in the same cells targeted by the virus, in vivo. These CD4C/SHIV-nef SIV Tg mice develop a severe AIDS-like disease, including premature death, failure to thrive/weight loss, wasting, thymic atrophy, exhibit an especially low number of peripheral CD8+ T cells as well as low number of peripheral CD4+ T cells, diarrhea, splenomegaly, kidney (interstitial nephritis, segmental glomerulosclerosis), lung (lymphocytic interstitial pneumonitis) and heart disease. In addition, these Tg mice fail to mount a class-switched antibody response after immunization with ovalbumin, produce anti-DNA autoantibodies and some of them develop P. Carinii lung infection. These CD4C/SHIV-nefSIV Tg mice develop an AIDS-like disease very similar to that of CD4C/HIV Tg mice, except that the kidney and cardiac diseases were more severe, and that a thymic developmental defect was observed. Heart enlargement was very severe in CD4C/SIV Tg mice during early breeding on the C3H background. Histopathological lesions in the heart of these mice were also multifocal and were similar to those found in CD4C/HIV Tg mice. Data from echocardiography analysis are not yet available for these Tg mice. The low number of peripheral CD8+ and CD4 + T cells likely reflects a thymic defect and may be similar to the DiGeorge-like "thymic defect" immunophenotype described in a subgroup of HIV-1 infected children. Ontogeny studies show that the Tg mice were born with a smaller thymus and that this phenotype is not progressive in nature. As young as embryonic day 17, the thymic absolute cell numbers are lower in the Tg mice when compared to their non-Tg controls and there is a defect in thymocyte maturation in the transition between DN3 and DN4, with a failure to generate normal numbers of DP cells. Fetal liver transplantation studies have ruled out a significant impairment of the thymic epithelium and have suggested that this defect is likely a direct consequence of abnormal T cell progenitors in the thymus.
Therefore, it appears that SIV Nef alone expressed in mice, in appropriate cell types and at sufficient levels, can elicit many of the phenotypes of simian and human AIDS. These Tg mice should be instrumental in studying the pathogenesis of SIV Nef-induced phenotypes.

I have in this essay looked at what stand NWT took to the three leading countries in The First World War, Germany, France and England, and if it changed during the course of the war.

I worked based on the theory that NWT, as a politically conservative newspaper was pro-Germany, which also showed to be true.

I have look at the official stand, what is shown in the published material, what stand that the newspaper showed outwards. The result shows that NWT held a neutral stand during the war being loyal to the conservative government. At the end of the war the papers sympathies for Germany are shown more openly in its political material.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O declínio mundial da cárie dentária é atribuído ao uso abrangente do flúor. Embora esse elemento seja capaz de proteger os dentes, seu uso excessivo pode levar a uma ação citotóxica causando a inibição do crescimento celular, da síntese de proteínas e até mesmo a morte celular. O primeiro objetivo deste estudo foi investigar a concentração ideal do NaF (NaF) capaz de ativar os fibroblastos gengivais de camundongos sem induzir morte celular. Observou-se que, nesses fibroblastos, a concentração de 40 μg F/mL induziu morte celular de 62,6 %. Na concentração de 20 μg F/mL a morte celular foi de apenas 22,1%. Com base nesses resultados, optou-se por utilizar a concentração de 20 μg F/mL como dose máxima para investigar os mecanismos envolvidos na ativação dos fibroblastos gengivais. Dessa forma, avaliou-se a capacidade do NaF induzir a expressão de MMP-2 e MMP-9 pelos fibroblastos gengivais de camundongos na presença ou ausência de LPS, assim como a produção da quimiocina CCL-3/MIP-1α e óxido nítrico. Avaliou-se também a participação das vias de sinalização intracelular p44/42, p38, PI3K e NF-кB envolvidas durante essa ativação, por meio da utilização dos respectivos inibidores PD98059 (50 μM), SB202190 (10 μM), LY294002 (30 μM) e dexametasona (10 μM). Observou-se que o NaF foi capaz de estimular os fibroblastos gengivais a expressarem MMP-9, mas não MMP-2, na concentração de 20 μg F/mL com pico máximo 6 horas após, retornando aos níveis normais 24 horas após. A produção da quimiocina CCL3/MIP-1α pelos fibroblastos estimulados pelo NaF também foi observada com a concentração de 20 μg F/mL com pico máximo 6 horas após estímulo. Na presença de LPS, observou-se uma potenciação da expressão de MMP-9 e produção de CCL3/MIP-1α na concentração de 20 μg F/mL, 6 horas após.
The worldwide decline of the dental caries is attributed to the widespread use of fluoride. Although this element is capable of protecting the teeth, its excessive use, can lead to a cytotoxic action, causing an inhibition of the cell growth, of the protein synthesis and even the cellular death. Based on these results, we have chosen to use a concentration of 20 μ g F/mL as maximum concentration to investigate the mechanisms involved in the activation of the gingival fibroblasts. It was observed that, on those fibroblasts, the concentration of 40 μg F/mL has resulted in a death cellular index of 62.6%. In the concentration of 20 μg F/mL the cellular death was of 22.1% only. Based on these results, the concentration of 20 μg F/mL has been chosen as maximum concentration to investigate the mechanisms involved in the activation of the gingival fibroblasts. Later, the ability of NaF to induce the expression of MMP-2 and MMP-9 in gingival fibroblasts of mice in the presence or absence of LPS has been assessed, as well as the production of chemokine CCL-3/MIP-1a and nitric oxide. It also evaluated the participation of intracellular signaling pathways p44/42, p38, PI3K e NF-kB involved in this activation, through inhibitors PD98059 (50 μM), SB202190 (10 μM), LY294002 (30 μM) e dexamethasone (10 μM). It was observed that the NaF was capable to stimulate the gingival fibroblasts to express MMP-9, at the concentration of 20 μgF/mL with maximum peak 6 hours after, returning to normal levels 24 hours after. The expression of MMP-2 was not observed. The production of chemokine CCL3/MIP-1α was also observed with the concentration of 20 μgF/mL with maximum peak 6 hours after the stimulation. In the presence of LPS, it was observed an intensification in the expression of MMP-9 and also in the production of CCL3/MIP-1α at the concentration of 20 μgF/mL, 6 hours later.

A common notion of time is essential to avoid collisions in distributed radio networks using TDMA. Local clocks with limited accuracy are normally used to control time in each individual node. These clocks require regular synchronization to prevent the local time of these clocks from diverging. Synchronization of these clocks is controlled by a synchronization algorithm that estimates the correct time based on the information exchanged between nodes.This thesis present a survey of synchronization algorithms that can be used by NATO Narrowband Wave Form (NBWF). NBWF requires that synchronization must be performed without the use of dedicated synchronization messages. It is possible to achieve this by using the correct reception of messages inside certain TDMA slots. Reception of these messages enables the receiving node to estimate the local time of the sender without transmission of an actual timestamp. This information can be used by a synchronization algorithm in the receiving node to estimate the correct local time.The survey of potential synchronization algorithms shows that there are several potential candidates for NBWF. A hybrid algorithm, divided into several layer, fulfills most of the NBWF requirements, and it is the most promising candidate. The actual synchronization of nodes is performed in the lowest layer by Discrete Network Synchronization (DNS) algorithm. Simulations with the DNS algorithm show that this algorithm might not be the optimal choice for NBWF networks. This thesis recommends that a modified version of the hybrid algorithm, utilizing the CS-MNS algorithm in the lowest layer, should be considered for further work with NBWF networks.

Thesis: S.B. in Geoscience, Massachusetts Institute of Technology, Department of Earth, Atmospheric, and Planetary Sciences, 2008.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 26-27).
Angrites are among the oldest known rocks and may record planetesimal dynamo activity and protoplanetary disk fields in the early solar system. Towards this goal, the natural remanent magnetism and its origin were examined in newly discovered angrite NWA 4931. Measurements were conducted on subsamples cut from various distances along a drilled core sample of the meteorite. The samples were then progressively demagnetized to isolate primary magnetization from contaminant overprints and to calculate paleofield intensity. Dust produced during the subsampling process was analyzed to determine that the mineralogical source of the magnetism was magnetite. Analyses of fusion crusted and adjacent samples showed that the exterior of the meteorite had been contaminated by a collector's hand magnet. However, the interior of the core yielded a pristine record, indicative of a paleointensity strength on the order of 25 [mu]T. These results, in light of magnetic measurements on other angrite samples, are suggestive of a core dynamo active for at least seven million years on the angrite parent body, beginning by 4564 Ma.
by James Scott Berdahl.
S.B. in Geoscience

In introduction this graduation theses discource about phase diagrams and thein fission. Next part is about concrete phase diagrams NaF – KF, NaF – LiF, KF – LiF. Their determination trough use of cooling surves and their specification trough use of numerical method. Conclusion contains proposal of method for concrete phase diagram of NaF – KF – LiF.

La proteine nef des lentivirus de primates joue un role important dans l'expression du pouvoir pathogene de ces virus chez l'homme ou chez le macaque. Afin d'etudier les proprietes de nef hiv-1 non seulement in vitro mais aussi in vivo, nous avons substitue le gene nefhiv-1 lai a nefsiv dans le genome du sivmac239 pour creer le shivneflai4. La partie c-terminale de nefsivmac239 etant absente de nefhiv, nous avons cree une proteine de fusion en ajoutant ce domaine en 3' de nefhiv, generant ainsi le shivc-term. Par l'introduction dans le gene nefhiv-1 d'une mutation conduisant a la substitution d186n nous entrainons une diminution de la stabilite de la proteine. Ce gene mute a ete introduit dans le contexte du siv (shiv186n). In vitro, ces virus ont une cinetique de replication similaire aux virus parentaux sivmac239 et hiv-1 lai. Par contre, en utilisant un test d'infection a cycle unique, nous montrons que la substitution de nef hiv a nef siv conduit a une diminution du pouvoir infectieux du virus chimerique. L'introduction de nef186n restaure le pouvoir infectieux mais non l'ajout de la partie c-terminale de nefsiv. L'utilisation de ces virus siv chimeriques exprimant nefhiv permettra d'evaluer in vivo de nouvelles strategies therapeutiques ciblant les fonctions de nef. Effet, l'etude des proprietes infectieuses du shivneflai4 chez le macaque a permis de conclure que, dans une large mesure, nefhiv-1 peut etre substitue a nefsiv. Finalement, nous avons observe que la stabilite de nefhiv-1 est en fonction du contexte viral et nous avons montre que la presence de vpu entraine une diminution de la demi-vie de la proteine nefhiv. Une interaction directe nef/vpu a ete demontree par transfert d'energie de bioluminescence. L'etude

Based on longitudinal qualitative research, the paper analyses manifestations and mechanisms of the repression of activists of the Spanish protest movement 15M, and effects of this repression perceived by activists. To contextualize this, the background of the movement, its goals, and its achievements are described. The movement started in 2011, protesting the social crisis, the consequences of austerity policies, and corruption. It had viable effects on the framing of the current situation, in political attitudes and also, indirectly, on the political system. The Spanish government has responded to movement activities with repression and with new laws that interviewees characterize as a further restriction of the civil right to demonstrate and protest. Findings indicate that the combination of overt and covert repression have effects far beyond the manifest acts of the repression itself.

In the literature it is generally assumed that activities of voluntary membership based associations operating in stable institutional environments are multi-faceted, contributing simultaneously to societal, economic and political spheres. This article, drawing on the concept of functions of non-profit organizations investigates, whether the multi-functional character of associations holds true in the context of transitional Russia. The paper examines the relative importance of the advocacy, community building and service delivery functions, fulfilled by different types of associations. The original empirical data from exploratory interviews with 15 leading experts on associational activities was triangulated by a confirmatory survey of 215 associations across Russia. The results confirm that the absolute majority of the examined associations are multifunctional. Advocacy is considered to be the most important function for all types of associations. The findings suggest that business associations and intermediary unions are more active in policy advocacy directed toward the government, while liberal professional societies are more engaged in public advocacy addressing society at large. This study highlights importance of domestic associations for countries in transition as an institutional infrastructure of organized civil society, democratic development and market economy.

Black-footed albatross (Phoebastria nigripes) are among the many species of seabirds whose numbers are affected every year by anthropogenic impacts. Until now, no one has looked at the transfer of contaminants via soil to P. nigripes. However, studies have been done on how the Laysan albatross (P. immutabilis) is affected by lead in the soil (Work and Smith, 1996; Finkelstein et aI., 2003). Studies on endocrine disruption and effects of PCB contamination in wildlife have shown that estradiol and testosterone levels may be ahered and skewed as a result of anthropogenic sources (Fry and Toone, 1981; Grasman et aI., 1996; Auman et aI., 1997). Thus, the levels of gonadal steroids may function as indicators of exposure to polycWorinated biphenyls in the soil affecting these long-lived seabirds. The objective of this study was to determine if nesting in PCB-contaminated areas affects hormone balance due to endocrine disruption in both adult and chick black-footed albatross on Midway Atoll National Wildlife Refuge (NWR) and black-footed albatross chicks on Tern Island, Hawaiian Islands National Wildlife Refuge (HINWR). This thesis is divided into four parts. Chapter 1 contains the literature review and information on research background. The results for each island are presented in following chapters with the methods section similar at both locations. Chapter 2 compares hormone variation and soil contamination in two nesting sites on Midway Atoll. Chapter 3 discusses hormone variation between two nesting sites on Tern Island. Chapter 4 summarizes the work done in this study and suggests research that might be done in the future.
viii, 73 leaves

In this thesis we describe and discuss the reality for a central clearing party clearinghouse. The importance of sound risk management is discussed. We specifically validate the usage of a Historical Simulation/VaR approach for managing the risk when acting as a CCP for the Non Delivery Forward FX instrument. The method is back tested and some alternative approaches are proposed.
Sedan finanskrisen 2008 har regelverken för central clearing av OTC handlade produkter stärkts. I Europa tvingar EMIR regelverket in de OTC handlade financiella produkter att clearas på ett så kallad CCP Clearinghus. Mer och mer av dessa finansiella produkter kommer nu cleareas på clearinghusen. Clearinghusen blir därmed mer och mer riskabla och ett antal studier har gjorts angående vad denna komplexa miljö kan innebära i form av spridningseffekt etc. Därför är det av stor vikt att clearinghusen kan hantera risken som det innebär att clearea dessa nya produkter. Ett exempel på sådan centralt clearad produkt är FX instrument som tex NDF. På NASDAQ Clearing så är förslaget att använda Historical Simultion/VaR för att räkna ut de säkerheter som ska tas in från medlemmarna. ESMA ställer vissa krav på denna modell men är i övrigt positivt inställda till just HS/VaR. Jag har i detta arbete redogjort för hur ett clearinghus fungerar, hur ett FX instrument som NDF fungerar och slutligen gjort en Back test av HS/VaR som riskmått för en NDF portfölj. Speciellt fokuserar jag på hur denna modell skulle ha klarat den turbulenta perioden under 2008/2009 med efterföljande lugna period. Back testet visar att den inte skulle vara lämplig under denna period och avslutningsvis diskuterar jag runt några alternativa adaptioner för att modellen skulle vara bättre anpassad till karakteristiken i FX tidsserien.

Det svenska skolsystemet syftar till att erbjuda ”en skola till alla” där alla elever borde få jämlik undervisning och på så sätt nå sin fulla potential. Funktionsvariationer ställer utmaningar till konceptet. Neuropsykiatriska funktionsvariationer (NPF) innehåller några stereotypiska drag som påverkar lärandet och deltagandet i skolan, och det erbjuds specialinriktade praktiker för NPF-elever i grundskolan och gymnasiet. Studien syftar till att kartlägga de erfarenheter som elever med neuropsykiatriska funktionsvariationer (NPF) har ifrån högstadiet och gymnasiet för att få en bredare förståelse av deras faktiska behov. Det andra syftet med studien var att försöka hitta möjliga specialpedagogiska förbättringar i den naturvetenskapliga undervisningen. Undersökningen som genomfördes med webbaserade intervjufrågor. Från elevsvaren valdes tio elever, vems svar analyserades genom kvalitativ analys med kvantitativt inslag. I elevsvaren uttrycktes de typiska svårigheter som NPF-elever upplever under skolundervisningen, vilket tyder på att det finns ett behov att utveckla pedagogisk kompetens och kunskap. Många elevsvar uttryckte önskan av att ha en bra kommunikativ kontakt med läraren och lärarledd undervisning med visuellt stöd. Psykosociala svårigheter uttrycktes i elevsvaren som ett stort problem innan man fått specialpedagogiskt stöd. Det visades att många elever i undersökningsgruppen, speciellt flickor, fick sin diagnos sent under skolåren. Resultat indikerar på att det finns stora brister i elevhälsans fungerande och organiseringen av det specialpedagogiska stödet. Elevernas positiva erfarenheter inom specialanpassade inriktningar tyder också på att det finns efterfrågan för dessa skol- och undervisningsformer utifrån elevens behov, som borde uppmärksammas i den skolpolitiska diskussionen.

La protéine Nef des virus de l’immunodéficience humaine (VIH-1 et VIH-2) joue un rôle essentiel dans la physiopathologie de l’infection et induction du SIDA. La capacité de Nef à perturber le trafic intracellulaire de protéines membranaires, et notamment du récepteur CD4, circulant entre les compartiments de la voie d’endocytose pourrait rendre compte de son importance comme facteur de virulence au cours de l’infection naturelle. Les mécanismes responsables des perturbations de la voie d’endocytose induites par Nef au cours de l’infection ne sont pas totalement élucidés, mais il est admis qu’elles résultent d’interactions avec les complexes adaptateurs (AP) associés à la clathrine et participant au transport vésiculaire entre les différents compartiments de la voie d’endocytose. Notre objectif était de déterminer les mécanismes par lesquels Nef influe positivement sur le pouvoir infectieux du VIH-1 en interagissant avec la machinerie cellulaire de la voie d’endocytose. Notre programme s’est organisé autour de deux axes principaux: le premier a consisté à étudier l’implication respective des différents types de complexes AP (AP-1, -2 et -3) sur les perturbations du fonctionnement de la voie d’endocytose induites par Nef en analysant son impact sur le niveau d’expression de surface de CD4; le deuxième axe a consisté à évaluer l’impact de l’interaction de Nef avec les complexes AP sur les capacités infectieuses des particules virales. Le rôle respectif des différents complexes AP dans ces fonctions de Nef a donc été étudié après déplétion de l’expression des complexes AP-1, AP-2 et AP-3 par une approche d’ARN interférence. Les résultats obtenus montrent que contrairement à certaines données de la littérature, la déplétion des complexes AP de la voie d’endocytose ne semble pas avoir un impact majeur sur la capacité de Nef à moduler l’expression de surface de CD4, même si une légère diminution de l’activité de Nef a pu être révélée dans notre étude réalisée sur des cellules HeLa-CD4 transduites par les shRNA ciblant les complexes AP-2. Inversement, nos résultats confirment que la déplétion des complexes AP-1, AP-2 et AP-3 dans les cellules productrices des particules virales se traduit par une diminution importante des propriétés infectieuses de ces particules sur lesquelles l’impact positif de Nef n’est plus alors capable de se manifester. En conclusion, ce travail a donc permis de montrer que les complexes AP de la voie d’endocytose sont indispensables pour que Nef puisse exercer son rôle positif sur le pouvoir infectieux du VIH-1. Il est maintenant important de confirmer ces résultats en analysant le rôle fonctionnel des complexes AP sur les activités de Nef dans les cibles cellulaires naturelles du VIH-1, lymphocytes et macrophages
Nef protein of human immunodeficiency virus (HIV-1 and HIV-2) plays an essential role in the pathophysiology of infection and induction of AIDS. The ability of Nef to disrupt intracellular trafficking of membrane proteins, including the CD4 receptor, moving between the compartments of the endocytic pathway could account for its importance as a virulence factor during natural infection. The mechanisms responsible for disruption of the endocytic pathway induced by Nef during infection are not fully understood, but it is accepted that they arise from interactions with adaptor complexes (AP) associated with clathrin and participant in vesicular transport between the different compartments of the endocytic pathway. Our objective was to determine the mechanisms by which Nef positively affects the infectivity of HIV-1 by interacting with the cellular machinery of the endocytic pathway. Our program has been organized around two main axes: the first was to investigate the respective involvement of different types of complexes (AP-1, -2 and -3) on the Nef induced disruption of the endocytic pathway by analyzing its impact on the level of surface expression of CD4; the second axis was to evaluate the impact of the interaction of Nef with AP complexes on the infectious capacity of the viral particles. The respective roles of the different AP complexes in these functions of Nef has been studied after depletion of the expression of complex AP-1, AP-2 and AP-3 by RNA interference approach. The results show that, contrary to some literature data, depletion of AP complex endocytic pathway does not appear to have a major impact on the ability of Nef to modulate the surface expression of CD4, although a slight decreased activity of Nef could be revealed in our study on HeLa-CD4 cells transduced with the shRNA targeting complex AP-2. Conversely, our results confirm that the depletion of complex AP-1, AP-2 and AP-3 in the cells producing viral particles resulted in a significant decrease in infectious properties of these particles on which the positive impact of Nef is no longer able to manifest. In conclusion, this work has shown that complex AP of endocytic pathway are essential for Nef to exercise its positive role in the infectivity of HIV-1. It is now important to confirm these findings by analyzing the functional role of AP complexes on the activities of Nef in the natural cellular targets of HIV-1, lymphocytes and macrophages

L’infection des cellules cibles par le Virus de l’Immunodéficience Humaine de type 1(VIH-1) suit une succession d’étapes finement régulées par de nombreux facteurs cellulaires et viraux. Mon travail de thèse a consisté à étudier certains aspects de cette régulation, en particulier la protéine virale Nef et son impact sur l’infectivité des virus, mais aussi la susceptibilité des cellules cibles à l’infection. Tout d’abord, nous nous sommes intéressés aux mécanismes selon lesquels Nef augmente l’infectivité virale. Pour cela, nous avons identifié les différences entre le protéome des virus sauvages et des virus dépourvus du gène nef (Δnef) grâce à deux méthodes protéomiques, laDIGE et l’iTRAQ. Nous avons pu mettre en évidence que les protéines Ezrine et EHD4 sont impliquées dans des processus qui rendent les virus sauvages plus infectieux que les virusΔnef. L’augmentation de l’infectivité virale par Nef dépend des glycoprotéines d’enveloppes avec lesquelles les particules virales sont pseudotypées. Dans le but d’identifier les bases moléculaires de ce mécanisme, nous avons généré des constructions chimériques entre des glycoprotéines d’enveloppes qui permettent (enveloppes permissives) ou ne permettent pas(enveloppes non permissives) au phénotype Nef de se manifester. Cette approche a permis démontrer que le domaine cytoplasmique de la protéine d’enveloppe est un des déterminants qui dictent l’acquisition du phénotype Nef. Mon travail s’est aussi axé sur le mécanisme de co-infection cellulaire par le VIH-1.Après co-incubation des cellules avec des virus VIH rapporteur GFP et DsRed, nos résultats ont montré que les événements de co-infection sont plus fréquents qu’attendus dans le cas d’une infection stochastique. Nous montrons que ce biais qui semble favoriser la co-infection et qui suggère l’hétérogénéité de la population cible en terme de susceptibilité à l’infection par le VIH-1 provient en fait d’une sous-estimation des fréquences de cellules infectées en raison d’un phénomène de latence post-intégrative. Ainsi, mes études ont permis de mieux comprendre les mécanismes permettant à Nef d’augmenter l’infectivité des particules virales ouvrant de nouvelles perspectives à ce sujet, de même qu’elles ont permis de mettre en évidence que la co-infection était bien un processus aléatoire mais qui permettait de révéler des cellules arborant un provirus silencieux
Pas de résumé en anglais

Caractérisation de NEF-sp: une exoribonucléase 3'→ 5' spécifique du testicule. Les études biochimiques et génétiques ont révélé que de nombreuses protéines jouent un rôle important dans la voie des ARNpi (ARN interagissant avec Piwi). Néanmoins, certaines caractéristiques mécanistes ne sont pas encore complètement comprises. D’autre part, certaines protéines impliquées dans la voie des ARNpi pourraient ne pas encore être caractérisées. Lorsque ce projet a commencé, le traitement 3’ des ARNpi n'avait pas été complètement identifié. Par contre la directionnalité 3’ à 5’ avait été observée avec une dépendance au Mg2+. Toutefois, la protéine responsable du raccourcissement des ARNpi à leur longueur mature n'était toujours pas connue.NEF-sp devrait être une exo nucléase d'ARN avec une directionnalité de 3' à 5'. Sa prédiction de domaine a révélé que cela se compose d'un domaine de nucléase N-terminal et de deux motifs de reconnaissance d'ARN (RRM). NEF-sp est également prévue comme une nucléase spécifique aux testicules, mais son rôle biologique n'a pas été caractérisé auparavant. Ce projet s'est concentré sur une hypothèse initiale selon laquelle NEF-sp pourrait potentiellement agir comme une nucléase impliquée dans la voie des ARNpi.Globalement, nous avons démontré que NEF-sp humaine est une exoribonucléase avec une directionnalité 3'→ 5'qui est active sur les substrats de l'ARN simple brin. Cette protéine est exprimée exclusivement dans les testicules des souris. En plus, NEF-sp pourrait fonctionner dans le compartiment nucléaire. Notre analyse de la souris Nef-sp mutante n'a révélé aucun phénotype évident. Nous avons observé que les homozygotes des deux sexes sont viables et présentent une fertilité normale. De plus, NEF-sp ne semble pas jouer un rôle dans la voie des ARNpi. Il est possible que le recadrage du/des substrat(s) inconnu(s) ne soit pas important pour la viabilité et fertilité en raison de la compensation potentielle par d'autres nucléases. Néanmoins, notre étude fournit une caractérisation biochimique et génétique de l'exoribonucléase NEF-sp des mammifères
Genetic and biochemical studies have identified more than twenty different proteins involved in the piRNA pathway. However, some mechanistic features are still not fully understood. When this project started, piRNAs 3' end trimming was not completely characterized. Trimming was observed before in BmN4 cells and an Mg2+-dependent 3′ to 5′ exonuclease was implicated in this process. However, the protein responsible for shortening piRNAs to their mature length was still not known.NEF-sp is predicted to be an RNA exonuclease with 3′ to 5′ directionality. This protein is composed by three domains: a nuclease domain at N-terminal and two RNA binding motifs at C-terminal. NEF-sp is also predicted to be a testis-specific nuclease, however its biological role was not previously characterized. This project was based on the hypothesis that NEF-sp could potentially act as a nuclease involved in the piRNA maturation.We examined the biochemical properties of the uncharacterized mammalian nuclease family member NEF-sp. We show that Nef-sp transcripts are detected exclusively in mouse testes. We demonstrate that hNEF-sp is a 3ʹ→5ʹ exoribonuclease that is active on ssRNA substrates and likely functions in the nucleolar compartment. Our own analysis of the Nef-sp mouse knock-out mutant revealed no obvious phenotype. We observed that homozygous animals of both sexes are viability and display normal fertility. NEF-sp does not seem to play a role in piRNA pathway. It is possible that precise trimming of the unknown substrate(s) may not be important for viability/fertility due to potential complementation by other nucleases. Nevertheless, our study provides a biochemical and genetic characterization of the mammalian NEF-sp exoribonuclease

Det nätverksbaserade försvaret (NBF) är en vision som kommer att ställa många nya krav. Såväl rent tekniskasom organisatoriska. För mig har de organisatoriska aspekterna av NBF varit av särskilt intresse. När jaghar tagit del av skrifter och samtal rörande det nätverksbaserade försvaret har jag speciellt fäst mig vid att detibland framkommer att en självsynkroniserande organisation skulle vara det optimala slutmålet. Jag har självtjänstgjort inom olika befattningar inom flygvapnets ledningssystem, först STRIL – 60 och sedan Flygvapnet2000. De erfarenheter jag själv har gjort under min tid i Flygvapnet har lett mig fram till slutsatsen att själsynkroniseringvar den sämsta tänkbara av reservnivåer. För att komma lösning på gåtan om organiseringsproblematikennärmare har jag med utgångspunkt från teorier om organisatoriska framgångsfaktorer valt attgenomföra ett antal simuleringar. Jag har vid två tillfällen simulerat ett luftförsvarsscenario, vid dessa tvåtillfällen användes två olika uppsättningar av deltagare. Vid första simuleringstillfället gavs deltagarna tydligaroller och arbetsbeskrivningar, i denna uppsats kallade ”Beslutsregler”. Vid det andra tillfället fick deltagarnaendast en roll tilldelad, de fick sedan utifrån sina tidigare erfarenheter forma dessa roller. Vid varjetillfälle har det dessutom gjorts två delsimuleringar med skilda organisatoriska och tekniska förutsättningar.De kategorier av personal som funnits med under simuleringarna är, flygförare, flygstridsledare, chefsflygstridsledareoch luftförsvarsledare. Vid båda tillfällena fick deltagarna i uppgift att luftförsvara Stockholm.För att mäta effektskillnader i vad de olika organisationerna lyckades uppnå vid de olika simuleringstillfällenaså erhölls poäng för varje mål deltagarna lyckades bekämpa. Målen i scenarierna har haft olika poängvärdeberoende på om de har varit på väg mot Stockholm eller andra geografiska områden, där målen motStockholm gett högst poäng. Vid analys av slutresultaten framkommer en del mycket intressanta skillnaderpå vad de olika organisationerna lyckades åstadkomma och även hur de agerade, bl.a. visade det sig att centraliseradledning inte alltid är av ondo.
During my career in the Royal Swedish Air Force I have served in several different positions,amongst them I can mention the ones as weapons controller and fighter allocater.During the recent years, I have through the reading of different books and discussionswith my colleagues, encountered the opinion that self-synchronised organisationswould be the ultimate goal when organising Network Centric Warfare. My own experiencewas that this was the last option used after everything else had failed. In Swedishlitterateur regarding Network Centric Warfare, you can see the expression of a will to beable to change command philosophy from centralised command to a decentralised anddelegated (Auftragstaktik) command. In this essay I have examined the effectiveness oftwo different organisations, the first one more like a classic hierarchic organisationcomplemented with rules regarding responsibilities for each participant. The participantsin the second organisation only got a role and then had to fulfil this role drawingon their previous experience from working in the Air Force. The participants were allAir Force officers and each one of them could only participate in one of the organisations.The organisations were then tasked to carry out counter air operations in a simulator.Their only mission during the simulations was to protect the city of Stockholm. Inthe simulation the participants met a pre-recorded adversary, for the elimination of atarget the organisations were awarded points. The target heading towards Stockholmearned each organisation more points then other targets. The accumulated points thengave a rating for their effectiveness. The result was then analysed with the help of theoriesregarding what is needed for organisational success and theories regarding networkorganisations. The conclusions clearly state that the organisation with the rules achieveda better result, especially when the technical conditions degenerated. This organisationeven succeeded to improve their result with degraded technical conditions, the otherorganisation got a lower result during the same circumstances. One of the main reasonsthe organisation who had to rely on their previous experience from the Air Force nevergot up to the same standard as the other organisation, was due to the fact that they hadto spend more time to get them selves organised. Furthermore my examination showsthat networks are very complex and hard to overlook for an individual person. Thisleads to problems when you want to communicate in the network and also severe problemswhen it comes to optimizing the efficiency of the network.
Avdelning: ALB - Slutet Mag 3 C-upps.Hylla: Upps. ChP 03-05

Development of a suitable animal model of AIDS is much needed in AIDS research to study infection and pathogenesis as well as to evaluate methods of prevention and treatment of HIV infection. Small animals such as rodents are attractive candidates for AIDS research due to the availability of various inbred and genetically engineered strains, extensive knowledge or their immune system, especially in mice, and the relative ease of breeding and maintaining animal colonies. Transgenic small animal models carrying entire HIV genome or selected genes have been instrumental to understand functions of HIV genes in vivo and their role in HIV pathogenesis. The type of cells in which HIV genes are expressed seems to be an import prerequisite for the study of HIV gene functions in transgenic mice. Mice constitutively expressing the entire HIV-1 genome or HIV-1 nef gene in CD4 + T cells and in the cells of macrophage/dendritic lineage develop an AIDS-like disease very similar to AIDS disease in humans. Similarly, expression of Nef in adult mice, using inducible system, results in the AIDS-like disease. This disease is characterized by thymic atrophy, impaired thymocyte maturation, loss of CD4+ T cells, increased activation and turnover of T cells, which can occur in the absence of lymphypenia, and non-lymphoid organ disease involving the lungs and kidneys. Susceptibility of adult mice to the pathological effects of Nef suggests that the AIDS-like disease in the constitutively expressing Nef Tg mice is not due to developmental defects caused by early expression of Nef. This model highlights the important role of Nef in HIV-1 pathogenesis. The high similarity in the disease in these Tg mice with human AIDS strongly suggest that these mice are a relevant model to study AIDS. This study further evidence that mouse cells can support functions of Nef and these Tg mice represent a unique model to study Nef functions in vivo in the context of the primary immune system. Moreover, the inducible Nef Tg model has given us the ability to control the level and time of expression of Nef which was impossible to do in the previously reported constitutive Nef Tg mouse models. These mice will be useful to study immune reconstitution since Nef expression can be turned off after withdrawal from dox.

Plant cuticles are extracellular membranes covering aerial organs of plants, whose main functions rely on the protection against water loss, mechanical injury from the environment, attack of microorganism, and also regulation of gas exchange. Among the several constituents of plant cuticles, waxes are those that play an important role in their barrier properties. In order to enhance the mechanical properties of wax, NFC was applied in. In the project, mainly two kinds of methods were used to prepare wax-NFC composites. One way was wax and NFC were dissolved in toluene and casted to be a film, another way was to prepare NFC aerogel firstly, and then, impregnated the aerogel into wax liquid. After pressing it the structure was more compact. In order to characterize the properties of samples, SEM, XRD, TGA, DSC, Contact angle testing, tensile test and oxygen permeability methods were applied in.

Forskning visar att flickor med NPF-problematik inte får det stöd och de insatser som de behöver i skolan. Det framkommer också i forskning att samverkan mellan skola och hem är viktigt när det kommer till elevers resultat, men att det brister i samverkan mellan skolan och hemmet när det handlar om flickor med NPF-problematik. Eftersom flickors symptombild skiljer sig från pojkars finns ofta en förutfattad mening om hur NPF tar sig uttryck och flickan med NPF riskerar att missas. Syftet med den här studien är dels att bidra med kunskap om hur föräldrar upplever att neuropsykiatriska funktionsnedsättningar (NPF) tar sig uttryck för flickor i både hemmiljön och skolmiljön. Vi vill också med studien bidra med kunskap om hur hem och skola kan samverka för att kunna arbeta främjande och förebyggande både kunskapsmässigt och socialt. Vi har valt att använda oss av en kvalitativ forskningsmetod som inspirerats av andra fenomenologiska studier med induktiv ansats. Vår metod bygger på självrapporteringar av föräldrar till flickor med NPF. Vi skickade ut våra frågor till en grupp på facebook som vänder sig till föräldrar som har barn med NPF och resultatet bygger på de 51 svar som kom in. I vår diskussion har vi valt att titta på vårt resultat utifrån systemteoretiskt perspektiv och Antonovskys begrepp KASAM.  Resultatet visar att föräldrar till flickor med NPF ofta upplever sig förbisedda av förskolan och skolan när det kommer till vilket stöd flickorna ska ha. Om en elev klarar sig bra i skolan och uppnår målen i undervisningen visar vårt resultat att flickorna inte heller får adekvat stöd när det gäller det sociala samspelet. I vårt resultat kan vi se att i takt med att flickornas ålder ökar, ökar kraven i skolan och i det sociala samspelet, vilket för med sig att flickorna med NPF drabbas av utanförskap, ångest och skoltiden präglas av mycket frånvaro. Vår analys visar att om skolan istället tog ett systemteoretiskt perspektiv och insåg vidden av KASAM skulle förståelsen för flickor med NPF skulle öka. Detta skulle troligtvis leda till mindre svårigheter och en anpassad skolmiljö som är mer tillgänglig för alla.

L'activite des regions regulatrices (ltr) du vih-1 (virus de l'immuno-deficience humaine type 1) est augmentee par la co-transfection de vecteurs d'expression du proto-oncogene c-ha-ras ou de l'oncogene c-ha-ras*. Nous avons defini les sequences critiques pour l'activite inductrice de la proteine p21#r#a#s et montre qu'il s'agissait de la region activatrice du ltr viral. Celle-ci est necessaire et semble suffisante pour observer les effets activateurs de la proteine p21#r#a#s. Cette proteine est associee au groupe des proteines regulees par des nucleotides cycliques. Elle est connue pour etre impliquee dans la transduction de signaux aussi specifiques que ceux lies a l'activation de lymphocytes t par la reconnaissance de l'antigene. Nous avons observe que la proteine p21#r#a#s augmentait l'activite d'un vecteur proviral du vih et en ce sens pourrait etre impliquee dans la cascade des evenements cellulaires lies a l'activation du vih. D'autre part nous avons teste l'hypothese d'une activite de la proteine virale nef sur les regions regulatrices du vih-1. Nous avons realise une lignee astrocytaire produisant de facon constitutive la proteine nef comme nous l'avons observe par la detection du gene nef integre, la presence du transcrit dans une majorite des cellules et l'expression de son produit. Dans ce systeme quelque soit le niveau d'expression du gene indicateur (place sous le controle du ltr) basal ou amplifie par la co-transfection d'un vecteur produisant la proteine virale tat aucune modulation (stimulation ou repression) de l'activite du ltr n'est attribuable a la presence de la proteine nef. La controverse actuelle sur les effets fonctionnels de nef pourrait refleter les systemes d'analyses en jeu. Enfin dans la lignee monocytaire u937 ou l'infection par le vih est persistante nous avons detecte au cours de la phase de replication chronique, ou la majorite des cellules pres

Le facteur de transcription NF-kappaB constitue une famille de cinq protéines qui régule l'expression d'un grand nombre de gènes impliqués dans diverses fonctions biologiques, notamment l'immunité, l'inflammation, le développement et l'apoptose. Les membres de la famille NF-kappaB comprennent les protéines p65, RelB, c-Rel, p50 et p52 qui forment des homo- et des hétérodimères. Le facteur de transcription NF-kappaB est normalement séquestré dans le cytoplasme, en association avec les membres de la famille IkB (inhibitor of kappa B). La phosphorylation et l'ubiquitination médiée par IKK (IkB Kinase) conduisent à la dégradation de IkB et à la translocation de NF-kappaB dans le noyau où la régulation transcriptionnelle des gènes cibles a lieu. L'activation de IKK est tributaire entre autres des protéines adaptatrices TRAF et RIP. Ainsi la voie de signalisation NF-kappaB se compose des dimères NF-kappaB, des protéines IkB, du complexe IKK et des protéines adaptatrices. L'activation de la voie de signalisation NF-kappaB est fréquente au cours des infections virale. NF-kappaB étant un composant essentiel de la réponse immunitaire innée antivirale, il participe à la réaction de l'hôte contre les agents pathogènes. Les virus ont développé des stratégies pour moduler la voie de signalisation NF-kappaB en leur faveur notamment pour faciliter leur réplication, empêcher l'apoptose des cellules infectées et favoriser l'échappement à la réponse immunitaire. Par ailleurs, les virus ont incorporé des sites de fixation de NF-kappaB dans leurs promotteurs. Ainsi l'activation de NF-kappaB résulte en une transactivation des promoteurs viraux et en une transcription virale augmentée. En effet de nombreux virus et certaines protéines virales activent ou inhibent la voie de signalisation NF-kappaB pour créer un environnement favorable au développement du cycle viral dans la cellule hôte. Dans la première partie de notre étude, nous nous sommes intéressés au rôle du facteur de transcription NF-kappaB dans la transcription du cytomégalovirus humain (HCMV) en infectant des macrophages dérivés de monocytes sanguins (MDMs). Les macrophages jouent un rôle important dans la pathogenèse liée à HCMV et l'effet de l'infection virale sur la signalisation cellulaire dans ces cellules reste peu documenté. Nous avons montré que les souches virales AD169 (souche de laboratoire) et HCMV-DB (souche issue d'un isolat clinique) pouvaient se multiplier dans des cultures de cellules primaires MDMs mais que le titre viral demeurait inférieur à celui observé dans des cellules plus permissives telles que les fibroblastes de la lignée MRC5. Etant donné que le facteur de transcription NF-kappaB joue un rôle essentiel dans la réplication virale notamment par la transactivation du promoteur viral très précoce IE et du gène tardif viral, nous avons étudié l'activation et la composition du complexe NF-kappaB dans des cellules MDMs et des fibroblastes MRC5 infectés par HCMV. Par des techniques de retard sur gel (EMSA) et de colorimétrie (Microwell colorimetric NF-kappaB assay), nous avons montré que l'infection par HCMV entraînait une activation du complexe p52/Bcl-3 dans les cellules MDMs alors qu'il activait le complexe classique NF-kappaB p50/p65 dans les fibroblastes de la lignée MRC5. L'utilisation des cellules monocytoïdes U937 transfectées par un vecteur pCMV-Luc, vecteur d'expression de la luciférase sous la dépendance du promoteur viral du gène très précoce EA (MIEP), nous a permis de montrer que le complexe p52/Bcl-3 activait le promoteur viral MIEP. Par la technique d'immunoprécipitation de chromatine (technique ChIP), nous avons mis en évidence l'interaction entre le complexe p52/Bcl-3 et le MIEP dans les cellules MDMs infectées par le HCMV. Ainsi, l'activation du complexe NF-kappaB p52/Bcl-3 dans les cellules MDMs pourrait être à l'origine de la réplication limitée d'HCMV dans ces cellules. Dans la deuxième partie de notre étude, nous avons étudié le rôle de NF-kappaB dans la transcription du VIH-1 dans les cellules MDMs lors de la co-infection par le virus de l'hépatite C (VHC) et le VIH-1. L'infection par VIH favorise l'évolution de l'hépatite C chronique et augmente la charge virale VHC, mais le rôle deu VHC sur la réplication virale de VIH reste mal connu. Les cellules mononuclées périphériques (PBMC) sont permissives aux virus VIH et VHC et peuvent constituer un réservoir extra-hépatique de virions. Il a été montré que la transcription de NF-kappaB est activée lors de l'infection par VHC et VIH-1. Nous nous sommes proposés d'étudier le rôle de NF-kappaB sur la transcription du VIH-1 dans les cellules MDMs lors d'une co-infection VHC/VIH-1. Des études préliminaires conduites dans notre laboratoire ont montré que la charge virale VIH-1 était plus élevée dans les cellules PBMC et MDMs provenant de sujets co-infectés que chez les sujets mono-infectés. Nous avons observé, in vitro, que les protéines Nef du VIH-1 et Core du VHC activent le complexe p50/p65 de NF-kappaB dans les cellules MDM. Grâce à une technique reposant sur l'expression de la luciférase, nous avons montré que les deux protéines activaient la transcription du LTR du VIH-1. Nous avons également démontré que les protéines Nef et Core activent la réplication du VIH-1 dans les cellules promonocytaires chroniquement infectés U1. De plus, ces protéines stimulaient également la réplication du VIH-1 dans des macrophages primaires infectés par le virus. Par conséquent, les deux protéines Nef et Core pourraient favoriser la formation de réservoirs cellulaires contenant les deux virus. L'ensemble de ces études nous a permis de mieux comprendre le rôle de NF-kappaB dans la transcription virale au sein des macrophages
The mammalian nuclear factor-kB (NF-kB) is a family of live DNA-binding proteins that regulate expression of a large number of genes involved in diverse biological functions including immunity, inflammation, development and apoptosis. Members of NF-kappaB family include p65 (RelA), RelB, c-Rel, p50 (NF-kappaB) and p52 (NF-kappaB2), which are found as homo-and heterodimers. The transcription factor NF-kappaB is normally sequestred in the cytoplasm in association with the members of the inhibitor of kappa B (IkB) family. IkB Kinase (IKK) mediated phosphorylation, ubiquitination and degradation of IkB frees NF-kappaB to translocate to the nucleus to regulate the transcription of target genes. Activation of IKK is dependent upon intracellular adapter proteins such as TRAF and RIP. Thus NF-kappaB pathway consists of NF-kappaB dimers, IkB proteins, IKK complex and intracellular adapter proteins. Activation of NF-kappaB is a common feature during viral infections. NF-kappaB is an essential component of innate antiviral immune response and is a part of the protective reaction of the host against pathogens. Viruses have evolved strategies to modulate NF-kappaB signaling pathway for their own benefit especially to facilitate their replication, prevent apoptosis of infected cells and evasion of immune responses. In addition a number of viruses contain NF-kappaB binding sites in their promoters. Thus activation of NF-kappaB results in the transactivation of viral promoters, thus enhancing viral transcription and replication. In fact, several viruses and a number of viral proteins have been reported either to stimulate or inhibit NF-kappaB activation to create an environment for successful viral life cycle in the host cell. In the first part of our study we studied the role of NF-kappaB in the transcription and replication of HCMV in primary human monocyte-derived macrophages (MDMs). Monocytes/macrophages are key cells in the pathogenesis of human cytomegalovirus (HCMV) infection, but the in vitro rate of viral production in MDMs is considerably lower than in fibroblasts. Considering that the NF-kappaB signaling pathway is potentially involved in the replication strategy of HCMV through efficient transactivation of the major immediate-early promoter (MIEP), efficient viral replication, and late gene expression, we investigated the composition of the NF-kappaB complex in HCMV-infected MDMs and fibroblasts. Preliminary studies showed that HCMV could grow in primary MDMs culture but that the viral titer in culture supernatants was lower than that observed in the supernatants of more permissive MRC5 fibroblasts. EMSA and microwell colorimetric NF-kappaB assay demonstrated that HCMV infection of MDMs increased p52 binding activity without activating the canonical p50/p65 complex. Moreover, Bcl-3 was up-regulated and was demonstrated to associate with p52, indicating p52/Bcl-3 complexes as the major component of the NF-kappaB complex in MDMs. Luciferase assays in promonocytic U937 cells transfected with an MIEP-luciferase reporte construct demonstrated MIEP activation in response to p52 and Bcl-3 overexpression. Chromatin immunoprecipitation assay demonstrated that p52 and Bcl-3 bind the MIEP in acutely HCMV-infected MDMs. In contrast, HCMV infection of MRC5 fibroblasts resulted in activation of p50/p65 heterodimers. Thus, activation of p52/Bcl-3 complexes in MDMs and p50/p65 heterodimers in fibroblasts in response to HCMV infection might explain the low-level growth of the virus in MDMs vs efficient growth in fibroblasts. In the second part of our study, we studied the role of NF-kappaB in the transcription and replication of HIV-1 in macrophages during HIV-1/hepatitis C virus (HCV) coinfection. HIV infection favors the progression of HCV disease and enhances the viral load of HCV but the effect of HCV on replication of HIV-1 is not well studied. Macrophages are permissive to HCV and HIV-1 infection so can constitute extra-hepatic reservoir of these viruses. As transcription factor NF-kappaB is activated during HIV-1 and HCV infection we studied the role of NF-kappaB in the transcription of HIV-1 in MDMs. Preliminary studies from our laboratory demonstrate higher levels of HIV-1 viral load in MDMs isolated from the peripheral blood of HIV-1/HCV coinfected subjects in comparison with HIV-1 monoinfected patients. To assess the potential role of HIV-1 Nef and HCV Core proteins in this phenomenon, we studied their respective role regarding NF-kappaB activation and HIV-1 replication in primary macrophages. Following the treatment of MDMs with exogenous HIV-1 Nef and HCV Core proteins, we observed activation of NF-kappaB which consist of p50/p65. Consistently, degradation of NF-kappaB, and phosphorylation of IKKalpha, IKK beta was observed in response to both HIV-1 Nef and HCV Core proteins. In addition, HIV-1 Nef and HCV Core proteins stimulated synergistically the HIV-1 long terminal repeat (LTR), and subsequently enhanced HIV-1 replication in both chronically infected promonocytic U1 cells and acutely HIV-1 infected MDMs. Therefore, our results indicate that HIV-1 Nef and HCV Core proteins synergise to enhance NF-kappaB activation and HIV-1 replication in primary macrophages and thereby could fuel the progression of the HIV-1 disease in HIV/HCV coinfected patients. All together our results have important implication in terms of viral persistence and formation of viral reservoirs in macrophages during chronic viral infections

La séparation de sources est la tâche qui consiste à récupérer plusieurs signaux dont on observe un ou plusieurs mélanges. Ce problème est particulièrement difficile et de manière à rendre la séparation possible, toute information supplémentaire connue sur les sources ou le mélange doit pouvoir être prise en compte. Dans cette thèse, je propose un formalisme général permettant d'inclure de telles connaissances dans les problèmes de séparation, où une source est modélisée comme la réalisation d'un processus gaussien. L'approche a de nombreux intérêts : elle généralise une grande partie des méthodes actuelles, elle permet la prise en compte de nombreux a priori et les paramètres du modèle peuvent être estimés efficacement. Ce cadre théorique est appliqué à la séparation informée de sources audio, où la séparation est assistée d'une information annexe calculée en amont de la séparation, lors d'une phase préliminaire où à la fois le mélange et les sources sont disponibles. Pour peu que cette information puisse se coder efficacement, cela rend possible des applications comme le karaoké ou la manipulation des différents instruments au sein d'un mix à un coût en débit bien plus faible que celui requis par la transmission séparée des sources. Ce problème de la séparation informée s'apparente fortement à un problème de codage multicanal. Cette analogie permet de placer la séparation informée dans un cadre théorique plus global où elle devient un problème de codage particulier et bénéficie à ce titre des résultats classiques de la théorie du codage, qui permettent d'optimiser efficacement les performances.

Compte tenu du récent taux alarmant d'épuisement des réserves de combustibles fossiles et de l'augmentation drastique des niveaux de CO2 dans l'atmosphère qui a conduit au réchauffement de la planète et à des changements climatiques sévères, l'exploitation de toutes sortes d'énergies renouvelables a été la Parmi les principales priorités de la recherche Champs à travers le monde. L'une des nombreuses voies de ce genre est la réduction du CO2 aux combustibles utilisant des énergies renouvelables, plus communément appelées cellules photoélectro-catalytiques (PEC). Des essais expérimentaux sur la réduction du CO2 ont été réalisés sur différents types de catalyseurs dans les deux cellules (Conçu par un laboratoire) afin de comprendre la sélectivité, la productivité et les produits de réaction obtenus. Des essais expérimentaux ont été réalisés sur différents types de catalyseurs à la fois dans les cellules en phase gazeuse et en phase liquide pour comprendre la sélectivité, la productivité et les produits de réaction obtenus. Pour les études sur la réduction EC du CO2 en phase gazeuse, une série d'électrodes (à base de nanoparticules (NPs) de Cu, Fe, Pt et CuFe déposées sur des nanotubes de carbone ou de noir de carbone puis placées à l'interface entre une membrane Nafion et Une électrode à couche de diffusion de gaz). Les résultats démontrent le type divers de produits formés et leurs productivités. Dans des conditions sans électrolyte, la formation de produits ≥C1 tels que l'éthanol, l'acétone et l'isopropanol a été observée la plus élevée étant pour Fe et suivie de près par Pt. Pour améliorer Combustibles nets, un ensemble différent d'électrodes a été préparé sur la base de revêtements MOF de type imidazolate de type zéolitique substitué (SIM-1) (Fe-CNT, Pt-CNT et CuFe-CNT basés sur MOF) Et Pt-MOF a montré des carburants améliorés. En se reportant aux études sur la réduction EC du CO2 dans une cellule en phase liquide, un ensemble similaire d'électrodes a été prepare (NP - Cu, Fe, Pt, Ru, Co déposées sur des nanotubes de carbone ou du noir de carbone ont). Pour les conditions de phase liquide, en termes de produits C nets, les électrodes catalytiques à base de Pt sont en tête de la catégorie, suivies de près par Ru et Cu, tandis que Fe a obtenu la position la plus basse. Le mécanisme réactionnel sous-jacent probable a également été fourni. Afin d'améliorer encore les performances, on a synthétisé des NP de metal (Ru, Fe, Pt et Cu) de différentes tailles en utilisant différentes techniques de synthèse: (i) l'itinéraire d'imprégnation (ImR) pour obtenir des NP dans la plage de tailles de 10 à 50 nm; (Ii) Approche organométallique (OM) pour synthétiser des NPs uniformes et ultrafines dans la plage de tailles de 1-5 nm. Fe ont été synthétisés par une nouvelle voie de synthèse et des conditions pour atteindre des NP de 1 à 3 nm. (Iii) Approche de haut en bas de Nanowire pour obtenir des NP de cuivre ultrafin dans la plage de taille de 2-3,8 nm. Les améliorations apportées à la productivité du carburant se sont révélées être de 5 à 30 fois plus élevées pour les petites NP sur les NP plus importantes et, en outre, une charge réduite de 10 à 1-2% en poids. Un autre ensemble d'électrodes à base de nano-mousses (Cu NF et Fe NF sur Feuille de Cu, Feuille de Foie, Al Foil, Inconel foil et Al grid / mesh) préparés par électrodéposition ont également été étudiés afin d'améliorer encore la conversion de CO2 / carburant. Après, l'optimisation du dépôt et de la tension à l'aide de la voltamétrie cyclique, les carburants se sont améliorés de 2 à 10 fois par rapport aux combustibles nets les plus élevés obtenus à l'aide d'électrodes CNT dopées à base de NP
In view of the recent alarming rate of depletion of fossil fuel reserves and the drastic rise in the CO2 levels in the atmosphere leading to global warming and severe climate changes, tapping into all kinds of renewable energy sources has been among the top priorities in the research fields across the globe. One of the many such pathways is CO2 reduction to fuels using renewable energies, more commonly referred as photo-electro-catalytic (PEC) cells. Experimental tests were carried out on various types of catalysts in both the gas and liquid phase cells (lab-designed) to understand the different selectivity, productivity and the reaction products obtained. For the studies on the EC reduction of CO2 in gas phase cell, a series of electrodes (based on Cu, Fe, Pt and Cu/Fe metal nanoparticles – NPs - deposited on carbon nanotubes – CNTs - or carbon black and then placed at the interface between a Nafion membrane and a gas-diffusion-layer) were prepared. Under gas phase, the formation of ≥C1 products (such as ethanol, acetone and isopropanol) were observed, the highest being for Fe and closely followed by Pt, evidencing that also non-noble metals can be used as efficient catalysts under these conditions. To enhance the net fuels, a different set of electrodes were also prepared based on substituted Zeolitic Imidazolate (SIM-1) type MOF coatings (MOF-based Fe-CNTs, Pt-CNTs and Cu/Fe-CNTs) and Pt-MOF showed improved fuels. Moving to the studies on the EC reduction of CO2 in liquid phase cell, a similar set of electrodes were prepared (metal NPs of Cu, Fe, Pt, Ru and Co deposited on CNTs or carbon black). For liquid phase conditions, in terms of net C-products, catalytic electrodes based on Pt topped the class, closely followed by Ru and Cu, while Fe got the lowest position. The probable underlying reaction mechanism was also provided. In order to improve further the performances, varied sized metal NPs (Ru, Fe, Pt and Cu) have been synthesized using different techniques: (i) impregnation (ImR) route to achieve NPs in the size range of 10-50 nm; (ii) organometallic (OM) approach to synthesize uniform and ultrafine NPs in the size range of 1-5 nm (i.e., Fe NPs were synthesized through a novel synthesis route to attain 1-3 nm NPs); (iii) Nanowire (NW) top-down approach to obtain ultrafine copper metal NPs in the size range of 2-3.8 nm. The enhancements in the fuel productivity were found to be 5-30 times higher for the smaller metal NPs over the larger metal NPs and moreover, with reduced metal loading from 10 to 1-2 wt %. A different set of electrodes based on nano-foams (Cu NF and Fe NF on Cu foil, Fe foil, Al foil, Inconel foil and Al grid/mesh) prepared via electro-deposition were also investigated, to further improve CO2 to fuels conversion. After, optimization of deposition and voltage using cyclic voltammetry, the fuels improved by 2-10 times over the highest net fuels achieved using metal NPs doped CNT electrodes

Ett syfte med nätverksbaserat försvar är att erhålla snabbare reaktionstider i ledningssystem.Ad hoc-näten utgör en framtida möjlighet att erbjuda taktiskt rörliga enheteruppkoppling i nätverk även under förflyttning. Det kan på sikt inkludera de funktionersom har krav på liten fördröjning i uppkopplingarna. Exempel på en sådan funktion ärsensorintegration genom sensornät. Ett av problemen i ad hoc-nätverksutvecklingenligger i att de dataprotokoll som ska utnyttjas för att erbjuda en kompabilitet mot denfasta nätstrukturen, inte har den funktionsduglighet som krävs i ett ad hoc-nät. För att gesnabb överföring krävs en utvecklad variant av de nätverksprotokoll (TCP/IP) somhanterar uppkomna fel på förbindelsen. Detta är avgörande för ad hoc-nätverkensfunktionsduglighet. Det skulle resultera i minskade fördröjningar och därmed ökadkapacitet. Mycket talar för att snabbheten kommer att bli så stor att multisensordatafusionkan realiseras i ad hoc-nät.
Avdelning: ALB - Slutet Mag 3 C-upps.Hylla: Upps. ChP T 00-02

Nerve growth factor (NGF) belongs to the neurotrophin family of growth factors. NGF can bind to two transmembrane receptors, TrkA and p75. TrkA is the NGF specific tyrosine kinase receptor; p75 is a receptor which is common to all neurotrophins. NGF is required for the development, maintenance and repair of the nervous system. NGF dependent neuronal populations are affected in many diseases and the use of NGF was proposed. Difficulties associated with therapeutic application of proteins and polypeptides could be overcome by the use of small peptidomimetics. Small molecule that can either mimic or inhibit NGF-TrkA signaling could be useful in therapy of a wide range of pathologies from neurodegeneration to cancer.
Peptide mimetics represent an intermediate step towards the development of potent drugs. Small NGF mimetics could be found either in random peptide libraries or by rational drug design. Rational design is based on structure-function knowledge about the binding interface. We approach the problem by designing a series of cyclic peptides from the C-D loop of NGF that is known to interact with TrkA receptor. Nuclear Magnetic Resonace (NMR) was used to determine the structure and dynamics of the peptides in solution. The structural information was combined with bioactivity tests. Comparison of the structures revealed close similarity between the peptides and the conformation of the C-D loop in X-ray crystal structures of NGF. Structural similarity ensures an appropriate backbone conformation and orientation of the sidechains involved in interactions with receptor. This work contributes to our understanding of the structure-function relationships in NGF-TrkA binding. The designed bioactive peptides could serve as a template for further design of smaller peptidomimetics of NGF with improved potency and stability. A similar approach could be used to design functional mimetics of the other neurotrophins.