The study uses remotely sensed data from (1) air borne altimetry and radio echo sounding, (2) Landsat satellite imagery, and (3) aerial photography, to investigate aspects of the morphology and dynamics of the ice caps of Nordaustlandet, Svalbard. Data collection, methods of reduction and errors are discussed. Three principal topics are examined. First, as a preliminary to comprehensive radio echo sounding operations over Nordaustlandet, the ability of 60 MHz radar equipment to sound ice at or near its melting point was tested over a number of glaciers in Spitsbergen. Ice thickness data were obtained from 38 glaciers. The results are compared with previous geophysical investigations of ice thickness on Spitsbergen, revealing problems concerning existing Soviet radio echo sounding data obtained at higher frequencies. An internal layer echo was interpreted as the bed by Soviet workers. Second, the ice caps of Nordaustlandet, about which little glaciological information was previously available, are described and mapped. The coastline and ice margins are located using corrected satellite imagery. The surface of the ice caps is described in detail, and ice divides and drainage basins are mapped. Synoptic data on relative surface elevations from digitally enhanced Landsat imagery is calibrated using accurate airborne altimetric information available only along flight lines. The morphology of the underlying bedrock, and the thickness of the ice cover above it, is recorded. Ice thickness on Austfonna-Sorfonna reaches 583 m and 28% of the bed is below present sea level. Third, several aspects of the regional glaciology of the Nordaustlandet ice caps are examined. Digital analysis of ice cap surface radiance characteristics provides data on snow line position and mass balance. The spatial and temporal pattern of detector saturation in each band of the Landsat MSS over snow in the polar regions is predicted from analysis of the influence of sun elevation. Regions of ice cap basal melting are identified from enhanced Landsat imagery by the presence of suspended sediment plumes off shore. No plumes are observed off Brasvellbreen, which is probably stagnant and frozen to its bed after a recent surge. The recent fluctuations of 20 outlet glaciers are recorded from enhanced imagery, a method accurate to +150 m. Three groups of basins, with distinctive dynamic behaviour, are defined from an analysis of variations in long profiles and the pattern of driving stresses within the ice caps. First, basins which have surged and are now in the quiescent period between such activity are relatively stagnant. They typically have low surface profiles and driving stresses. Second, several outlet glaciers of southern Vestfonna have marked shear zones separating them from the surrounding ice and also have low surface slopes . They are interpreted as flowing fast over a lubricated bed on a continuous basis and may provide a small scale analogue for ice streams in the large ice sheets. Third, other basins in Nordaustlandet have high marginal driving stresses and relatively steep surface profiles and are interpreted as being frozen to their beds near the margins at least. Although three dynamic classes of basin have been identified, field data from them do not support the analysis and modelling of Budd (1975).

Like the majority of host cell mRNAs, the mRNAs of influenza virus are capped and polyadenylated. The NS1 protein of influenza has been implicated as a translational activator for both influenza and reporter gene mRNAs. Data is presented showing that influenza A virus infection resulted in an increased ratio of cap-dependent to cap-independent translation. This ratio increase was largely due to an increase in cap-dependent translation. These experiments employed a bicistronic reporter construct measuring cap-dependent and cap-independent translation in a single sample. Expression of NS1 alone resulted in a small, but reproducible increase in the ratio of cap-dependent to cap-independent translation. Additionally, with use of an NS1 deleted mutant influenza A virus (delNS1) it is shown that infection without NS1 expression produced less of a translation ratio increase compared to wild-type virus infection. Furthermore, expression of NS1 rescued a more wild-type ratio increase in delNS1 infected Vero cells. These results implicate NS1 as playing a role in increasing the ratio of cap-dependent to cap-independent translation in influenza A virus infected cells. Additionally, eIF4E-binding protein-1 (4E-BP1), a member of the protein family that inhibits cap-dependent translation through their inhibition of the cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is shown to be inactivated throughout the majority of the influenza A virus infection process.

Les inhibiteurs de BRAFV600-, dont le vemurafenib, sont efficaces contre les tumeurs présentant cette mutation activatrice de la voie des MAPK, ce qui est le cas d’un mélanome sur deux. Mais la plupart des malades traités rechutent dans l’année, et développent des tumeurs paradoxales secondaires.Divers mécanismes de résistance aux inhibiteurs de BRAF ont été décrits, cette résistance passant soit par réactivation de la voie des MAPK, soit par activation de la voie parallèle Akt/mTor, soit par anomalie de régulation de l’apoptose. Dans le cadre de cette thèse, nous avons mis en évidence une nouvelle cible thérapeutique: l’initiation de la traduction cap-dépendante. L’augmentation de la traduction de certains ARNm en protéines est une étape capitale de l’expression des gènes dans les processus oncogènes. Une étape limitante de cette traduction est son initiation. La protéine eIF4E (eukaryotic Initiation Factor 4E) se lie à la coiffe m7GTP des ARNm et régule la synthèse protéique en fonction de ses partenaires 4EBP1 et eIF4G. Quand eIF4E est assemblé à eIF4G et eIF4A, on parle du complexe « eIF4F », situé au point de convergence de la voie des MAPK et de la voie Akt/mTor via 4EBP1. Ce complexe est nécessaire à la traduction des protéines de survie et de prolifération cellulaire ayant une structure secondaire complexe en 5’UTR. Pour déterminer le statut d’activation du complexe eIF4F dans des lignées cellulaires, nous avons réalisé une immunoprécipitation des protéines liées au cap (« cap-binding assay »). Nous avons observé que le vemurafenib entraînait une diminution d’eIF4G fixé à eIF4E dans les cellules sensibles mais aucune modification dans les lignées résistantes. Parallèlement, la fixation de 4EBP1 à eIF4E augmente sous vemurafenib pour les lignées sensibles. Pour confirmer ces résultats, nous avons utilisé la technique de « Proximity Ligation Assay » (PLA), qui nous a permis de visualiser les complexes eIF4E-eIF4G et eIF4E-4EBP1 sous forme de points fluorescents observables en microscopie. Le nombre de complexes eIF4E-eF4G était bien diminué dans les cellules sensibles sous vemurafenib ce qui n’était pas le cas dans les cellules résistantes. Parallèlement, le nombre d’interactions eIF4E-4EBP1 augmentait dans les cellules sensibles et restait stable dans les cellules résistantes. De même, dans les tumeurs de patients, le rapport des complexes eIF4E-eIF4G sur eIF4E-4EBP1 diminuait dans les métastases en réponse au vemurafenib puis réaugmentait lors des récidives tumorales. De plus, nous avons testé des composés ciblant la traduction cap-dépendante et plus particulièrement eIF4A : les flavaglines. Nous avons montré que leur capacité à cibler l’initiation de la traduction était corrélée à l’inhibition de la prolifération des lignées cellulaires résistantes. Enfin, nous avons testé l’une d’elles in vivo. Les résultats montrent un effet synergique de cette drogue combinée au vemurafenib et une inhibition de la croissance tumorale.Concernant l’autre inconvénient majeur des anti-BRAF, l’induction fréquente de tumeurs secondaires, nous avons visualisé, aussi par PLA, les dimères BRAF-CRAF pour la première fois dans une série de tumeurs paradoxales de patients, cutanées et extra-cutanées. Ces dimères sont significativement plus nombreux dans les tumeurs cutanées apparaissant sous anti-BRAF que dans une série tumeurs contrôles de même type.En conclusion, nous avons identifié un nouveau biomarqueur de résistance aux anti-BRAF, visualisable par PLA. Pour optimiser la réponse tumorale à ces thérapies ciblées, qui constituent le traitement de choix des mélanomes métastatiques mutés, nous proposons d’y associer un inhibiteur de l’initiation de la traduction. Nous avons en parallèle mis au point le PLA BRAF-CRAF dans les tumeurs paradoxales induites par les anti-BRAF, et nous avons identifié des sous-populations plus à risque de développer ce type de tumeurs. / BRAFV600- inhibitors, including vemurafenib, are efficient against tumors harboring this MAPK pathway activating mutation, which is the case of ~50% of melanomas. But most of the patients under treatment progress within a year, and develop paradoxical secondary tumors. Most resistance mechanisms to drugs that target the BRAF and/or MEK kinases in cancer rely on reactivation of the RAS-RAF-MEK-ERK signal transduction pathway (ERK-dependent), on activation of the alternative PI3K-AKT-mTOR pathway (ERK-independent) or on modulation of the caspase-dependent apoptotic cascade. All three pathways converge to regulate the formation of the eIF4F translation initiation complex that binds to the 7-methyl-guanine cap at the 5’ end of mRNAs, thereby modulating mRNA translation of specific mRNAs. We show here that persistent formation of the eIF4F complex, comprising the eIF4E cap binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, is associated with resistance to anti-BRAF, anti-MEK and to anti-BRAF + anti-MEK combinations in BRAFV600- mutant melanoma, colon and thyroid cell lines. Unresponsiveness to treatment and maintenance of eIF4F complex formation is associated with either reactivation of MAPK signaling or absence of ERK-independent decreased phosphorylation of the inhibitory eiF4E binding protein 4EBP1 or increased pro-apoptotic Bcl-2 modifying factor (BMF)-dependent degradation of eIF4G. Development of an in situ method shows by proximity ligation assay (PLA) that the formation of the eIF4F complex is decreased in tumors responding to anti-BRAF therapy and increased in resistant metastases. Strikingly, inhibiting the eIF4F complex, either by blocking the eIF4E-eIF4G interaction or by targeting eIF4A with small compounds is synergistic with BRAFV600- inhibition. The other main problem arising during anti-BRAF treatment is the frequent induction of secondary cutaneous and extra-cutaneous tumors, through the formation of BRAF-CRAF dimers that we visualized in vivo for the first time. In conclusion, we have identified by PLA a novel biomarker of resistance against BRAF inhibitors, which is also a promising therapeutic target. Combinations of drugs targeting BRAF (and/or MEK) and eIF4F may overcome most of the resistance mechanisms arising in BRAFV600- cancers. In parallel, we established a BRAF-CRAF PLA method in paradoxical secondary tumors induced by BRAF inhibitors, leading to the identification of several subpopulations more at risk of developing this type of tumors.

This thesis investigates the use of satellite altimetry techniques for measuring surface elevation changes of ice caps. Two satellite altimeters, Radar Altimeter 2 (RA-2) and Geoscience Laser Altimeter System (GLAS) are used to assess the surface elevation changes of three Arctic ice caps. This is the first time the RA-2 has been used to assess the elevation changes of ice caps - targets much smaller than the ice sheets which are the instrument’s primary land ice targets. Algorithms for the retrieval of elevation change rates over ice caps using data acquired by RA-2 and GLAS are presented. These algorithms form a part of a European Space Agency (ESA) glacier monitoring system GlobGlacier. A comparison of GLAS elevation data to those acquired by the RA-2 shows agreement between the two instruments. Surface elevation change rate estimates based on RA-2 are given for three ice caps: Devon Ice Cap in Arctic Canada (−0.09 ± 0.29 m/a), Flade Isblink in Greenland (0.03 ± 0.03 m/a) and Austfonna on Svalbard (0.33 ± 0.08 m/a). Based on RA-2 and GLAS measurements it is shown that the areas of Flade Isblink below the late summer snow line have been thinning whereas the areas above the late summer snow line have been thickening. Also GLAS observed dynamic thickening rates of more than 3 m/a are presented. On Flade Isblink and Austfonna RA-2 measurements are compared to surface mass balance (SMB) estimates from a regional atmospheric climate model RACMO2. The comparison shows that SMB is the driver of interannual surface elevation changes at Austfonna. In contrast the comparison reveals areas on Flade Isblink where ice dynamics have an important effect on the surface elevation. Furthermore, RACMO2 estimates of surface mass budget at Austfonna before the satellite altimeter era are presented. This thesis shows that both traditional radar and laser satellite altimetry can be used to quantify the response of ice caps to the changing climate. Direct altimeter measurements of surface elevation and, in consequence volume change of ice caps, can be used to improve their mass budget estimates.

Problembakgrund och problemdiskussion: Företagens utdelningar är av intresse för investerare ur ett flertal synvinklar. De ger aktieägaren en direktavkastning på investerat kapital, men beskrivs också kunna förklara ett företags framtida prestationer. För de teorier som presenterats inom det företagsekonomiska området finns de som förespråkar både positiva och negativa samband kring utdelningars effekt på företagets resultattillväxt. De senaste åren har nya empiriska studier som visar på motsatta samband presenterats. Tidigare studier tillsammans med att forskning ej hittats för den svenska marknaden har ökat författarnas intresse kring det samband som resulterat i följande problemformulering. Problemformulering: Finns det ett positivt samband mellan svenska börsbolags utdelningsandel och deras resultattillväxt? Syfte: Studiens syfte är att förklara om det finns ett positivt samband mellan utdelningsandel och framtida tillväxt i resultat för urvalet av svenska företag listade vid Large Cap på Nasdaq OMX Stockholm vid utförandet av studien, våren 2012. Studien inkluderar även ett motsvarande test av aggregerade värden för Sveriges 70 mest omsatta aktier, i indexet Thomson Reuters Country Index Sverige. Dessa resultat jämförs därefter med varandra för att stärka ett samband som förväntas vara positivt och är direkt relaterad till studiens problemformulering. Teori: Tidigare empirisk forskning som grundar sig i resultaten av Arnott och Asness (2003) och efterföljande forskning inom ämnet har denna studie, i mån av kunskap och tidshorisont, försökt replikera. Tillsammans utgår studierna från teorier av Lintner (1956) om företagens optimala utdelningsandel, Modigliani & Miller (1961) med teorin om utdelningars irrelevans och Gordons (1962) teori om företagsvärdering givet konstant tillväxttakt. Slutligen Myers (1984) Pecking Order theory om finansieringsalternativ. Metod: Studiens genomförs med en kvantitativ metod. Undersökningsperioden är 1983 till 2010, med tidsperioder om ett-, tre- och fem år, för vilka företag i urvalet, Large Cap, ur populationen Nasdaq OMX Stockholm. Den statistiska undersökningen har genomfört med en multilinjär regressionsmodell för vilka oberoende variabler undersökt förhållandet till dem beroende variabeln, resultattillväxt. Empiri, Analys & Slutsats: Resultatet visar ett positivt samband mellan utdelningsandel och resultattillväxt för de noterade företagen på Large Cap, 2012. Studiens resultat har tydliga likheter med de utfall som tidigare empirisk forskning presenterat och likaså det positiva samband som återfinns för variablerna utdelningsandel och resultattillväxt. För den svenska marknaden kan huvudhypotesen bekräftas och därmed ett positivt förhållande som besvarar studiens problemformulering för tidshorisonten 1983-2010.

Techn. Hochsch., Diss.--Aachen, 2007.

Thesis (doctoral)--Rheinisch-Westfälische Technische Hochschule Aachen, 1991.

With the advent of globalisation the sports industry has shown exponential growth in the last 20 years. The surge of commercialisation of sport, the unprecedented internationalisation of the sports labour market, the enormous sums of money paid for the broadcasting rights of big sporting events, the attraction by multinational blue chip sponsors as well as the direct private investment by the worlds super wealthy have all contributed to the growing economic and social importance of sports. This massive influx of big money into sports does have its drawbacks. The criminal world has always shown adaptability in finding new channels to launder the proceeds of their illegal activities. Ever increasing and stricter measures and standards put in place by inter-governmental bodies like the Financial Action Task Force (FATF) as well as the increasing compliance of financial institutions the world over with these standards has meant that various legitimate sectors are at risk of being infected with criminal money. In a Report released by the FATF entitled ‘Money Laundering through the Football Sector’ one of the vulnerabilities of football clubs that was identified was the increased strain on their financial needs. Big Clubs require large budgets to be able to compete and afford the best players. Prices for players appear irrational and are very difficult to control. Player salaries comprise a substantial portion of the clubs total budgets. The result of this factor is that a large percentage of clubs are in financial trouble. This financial vulnerability can make clubs more susceptible to offers made from criminals looking for avenues to launder their ill-gotten gains. A salary cap is simply put a limit on the amount of money a club is permitted to spend on salaries. This limit or cap comes in various forms but is usually implemented as a percentage of the club’s annual average revenues. It is a rather controversial measure and certainly has its detractors, but it has shown to increase competitive balance and maintain financial stability in the leagues that they have been introduced. Salary caps are in effect in professional team sports all around the world. It has been used successfully in North America in their National Football and National Basketball leagues respectively, as well as in Australia in the Australian Football League and the National Rugby League and into UK professional rugby by the Rugby Football League and later by the Rugby Football Union. This mini dissertation aims to illustrate the threat posed to professional football by criminal organisations seeking to find new ways to launder the proceeds of their crimes as well as provide an overview of money laundering as a crime. It further aims to provide an overview of salary capping and then tie in the purpose and benefits of the implementation of a salary cap and how it may inadvertently be used to curb money laundering. / Dissertation (LLM)--University of Pretoria, 2014. / Mercantile Law / unrestricted

No description available.

The 5' end of eukaryotic and viral mRNAs contain a "cap" structure with the sequence m7G(5')pppN(5'). The methylation of the 7-position on the guanine cap is very important to proper mRNA processing and initiation of translation. The enzyme responsible for this methylation, RNA guanine-7-methyltransferase, has been cloned and studied from a number of different species, including human, X. laevis, yeast, and C. elegans. The sequences for mouse guanine-7-methyltransferase cDNA and protein have been deduced based upon identity of mouse ESTs to the cDNA of the human enzyme. The deduced mouse cDNA encodes an ORF of 465 amino acids and is 76.4% identical to the human enzyme, or 86.5% within the C-terminal domain. Active site characterization of mouse and human guanine-7-methyltransferase indicates a cysteine residue is important to proper enzyme activity. Enzyme activity was completely eliminated when N-ethylmaleimide (NEM) was added to the assay mixture. When the product of the reaction, S-adenosyl-L-homocysteine (SAH), was added at a concentration of 40uM the mouse enzyme retained 60% activity while enzyme isolated from Human Osteosarcoma (HOS) cells retained 100% of the original activity. SAH demonstrated no protective effects on the cloned human enzyme. Factors that affect binding of RNA to the active site were also investigated. UV-cross-linking of RNA to the active site of the mouse enzyme was inhibited 35% by NEM. Cap analog, GpppG, at a concentration of 1mM, inhibited cross-linking, but the similar nucleotide GMP, at a concentration of 1mM, did not inhibit cross-linking. These analyses have given a clearer understanding of this very important enzyme. / Master of Science