<p>Obemannade flygplan med attackförmåga (UCAV) används i allt större utsträckning i konflikter idag. En av de främsta fördelarna med dessa är att det inte finns någon risk att mista en pilot, då dessa är fjärstyrda. I attacker utförda av amerikanska UCAV:er i framför allt Afghanistan och Pakistan, har collateral damage inträffat vid ett flertal tillfällen. Det innebär att civila oavsiktligt fallit offer för attacker. Enligt krigets lagar kan sådana händelser rättfärdigas av att militär nödvändighet föreligger, men det är tveksamt om det går att hävda det när man inte riskerar egna förluster. Detta innebär i så fall att collateral damage alltid är krigsbrott när det orsakats av UCAV. Då är det viktigt att det går att utkräva ansvar ur obemannade system och det finns farhågor att ansvarsförhållandena blir otydligare när det inte sitter en pilot i flygplanet som ”trycker på knappen”. Men så länge den obemannade farkosten fjärrstyrs och besluten tas av en människa går det inte att se några skillnader i möjligheten till ansvarsutkrävande från bemannade system.</p> / <p>The use of Unmanned combat aerial vehicles (UCAV) has seen an increasing use in modern conflicts. One of the main advantages of these is the fact that there is no risk of losing a pilot, as the aircraft are remote-controlled. The attacks carried out by U.S. UCAVs in Afghanistan and Pakistan have resultet in a number of incients with collateral damage. According to the laws of war, only military necessity can justify such incidents and it is highly doubtful if you can claim such necessity when you do not risk any loss of life yourself. This would mean that collateral damage caused by UCAVs automatically becomes a war crime. This raises the issue of accountability and wether it is possible to extract such from unmanned systems. There are fears that this would be difficult when no pilot is present in the aircraft to ”pull the trigger”. However, as long as operators remotely control the unmanned aircraft and the decision to release weapons in anger are made by humans, there are no differences to be found in terms of accountability between manned and unmanned systems.</p>

Obemannade flygplan med attackförmåga (UCAV) används i allt större utsträckning i konflikter idag. En av de främsta fördelarna med dessa är att det inte finns någon risk att mista en pilot, då dessa är fjärstyrda. I attacker utförda av amerikanska UCAV:er i framför allt Afghanistan och Pakistan, har collateral damage inträffat vid ett flertal tillfällen. Det innebär att civila oavsiktligt fallit offer för attacker. Enligt krigets lagar kan sådana händelser rättfärdigas av att militär nödvändighet föreligger, men det är tveksamt om det går att hävda det när man inte riskerar egna förluster. Detta innebär i så fall att collateral damage alltid är krigsbrott när det orsakats av UCAV. Då är det viktigt att det går att utkräva ansvar ur obemannade system och det finns farhågor att ansvarsförhållandena blir otydligare när det inte sitter en pilot i flygplanet som ”trycker på knappen”. Men så länge den obemannade farkosten fjärrstyrs och besluten tas av en människa går det inte att se några skillnader i möjligheten till ansvarsutkrävande från bemannade system. / The use of Unmanned combat aerial vehicles (UCAV) has seen an increasing use in modern conflicts. One of the main advantages of these is the fact that there is no risk of losing a pilot, as the aircraft are remote-controlled. The attacks carried out by U.S. UCAVs in Afghanistan and Pakistan have resultet in a number of incients with collateral damage. According to the laws of war, only military necessity can justify such incidents and it is highly doubtful if you can claim such necessity when you do not risk any loss of life yourself. This would mean that collateral damage caused by UCAVs automatically becomes a war crime. This raises the issue of accountability and wether it is possible to extract such from unmanned systems. There are fears that this would be difficult when no pilot is present in the aircraft to ”pull the trigger”. However, as long as operators remotely control the unmanned aircraft and the decision to release weapons in anger are made by humans, there are no differences to be found in terms of accountability between manned and unmanned systems.

The global financial crisis of 2007 caused abrupt changes in the financial markets. Interest rates that were known to follow each other diverged. Furthermore, both regulation and an increased awareness of counterparty credit risks have fuelled a growth of collateralised contracts. As a consequence, pre-crisis swap pricing methods are no longer valid. In light of this, the purpose of this thesis is to apply a framework to the Swedish swap market that is able to consistently price interest rate and cross currency swaps in the presence of non-negligible cross currency basis spreads, and to investigate the pricing differences arising from the use and type of collat- eral. Through the implementation of a framework proposed by Fujii, Shimada and Takahashi (2010b), it is shown that the usage of collateral has a noticeable impact on the pricing. Ten year forward starting swaps are found to be priced at lower rates under collateral. Moreover, the results from pricing off-market swaps show that disregarding the impact of collateral would cause one to consistently underestimate the change in value of a contract, whether in or out of the money. The choice of collateral currency is also shown to matter, as pricing under SEK and USD as the collateral currencies yielded different results, in terms of constructed curves as well as in the pricing of spot starting, forward starting and off-market swaps. Based on the results from the pricing of off-market swaps, two scenarios are outlined that exemplify the importance of correct pricing methods when terminating and novating swaps. It is concluded that a market participant who fails to recognise the pricing implications from the usage and type of collateral could incur substantial losses. / Finanskrisens utbrott år 2007 orsakade abrupta förändringar i finansmarknaden. Räntor som tidigare följt varandra divergerade. Vidare gav både reglering av finansmarknaden och en ökad medvetenhet om motparters kreditrisk upphov till en tillväxt av kontrakt med ställda säkerheter. Följaktligen är det inte längre korrekt att prissätta swappar enligt metoder från tiden före finanskrisen. Mot bakgrund av detta är syftet med denna uppsats att applicera ett ramverk på den svenska swapmarknaden som på ett konsekvent sätt kan prissätta ränte- och valutaswappar med icke negligerbara räntespreadar, samt att undersöka prisskillnaderna som uppstår från användandet och typen av ställda säkerheter. Genom implementering av ett ramverk av Fujii, Shimada och Takahashi (2010b) visar denna studie att användandet av ställda säkerheter har en noterbar påverkan på prissättningen. Swappar med tio års löptider och framtida startdatum prissattes lägre när ställda säkerheter inkluderades i prissättningen. Vidare visar resultaten från prissättningen av off-market swappar att genom att bortse från effekten av ställda säkerheter så undervärderas ett kontrakts värdeförändring genomgående, oavsett om kontraktet är in the money eller out of the money. Valet av valuta på de ställda säkerheterna visade sig också spela roll, då prissättningen med SEK och USD som säkerhetsvalutor gav olika resultat i termer av konstruerade kurvor och i prissättning av spot-startande, framtida startande och off-market swappar. Baserat på resultaten ovan genererades två scenarion som påvisade vikten av en korrekt prissättningsmetod vid byte av motpart eller stängning av en swap. Härifrån dras slutsatsen att en marknadsaktör som inte inser vilken påverkan valet av ställda säkerheter har på prissättningen kan drabbas av betydande förluster.

No description available.

<p>Cerebrovascular disease (stroke), especially ischemic stroke, is a major cause of death and neurological disability in adults. Because of its clinical heterogeneity, stroke is considered as a multi-factorial and polygenic disorder. Most current genetic studies of ischemic stroke focus on genetic susceptibility rather than factors determining stroke outcome. The genetic components of ischemic stroke outcome are difficult to study in humans due to environmental factors and medical intervention. Thus, we proposed to use a surgically induced, permanent, focal cerebral ischemic stroke mouse model to investigate genetic factors of ischemic stroke outcome measured by infarct volume. This model is the middle cerebral artery occlusion (MCAO) model. First, we screened infarct volumes across 32 inbred mouse strains. The infarct volume varies between strains, and this strongly suggests that infarct volume is genetically determined. To identify these genetic factors, we used genome-wide association study [Efficient Mixed-Model Association (EMMA) analysis] on infarct volume from 32 inbred mouse strains. Using the EMMA analysis, we identified 11 infarct volume-associated loci; however, most loci were mapped with missing alleles. This suggests that these loci might be false positives. Thus, we used specifically designed scripts of EMMA analysis with updated mouse SNP database to correct for potential false positives. The loci identified by the updated EMMA analyses will led us to the identification of genes involved in ischemic stroke outcome. </p><p> There are two major mechanisms were proposed to be determinants of infarct volume, the extent of native collateral circulation and neuroprotection. Using the infarct volume screening panel from 32 inbred strains, we observed that infarct volume is inversely correlated with the native collateral vessel number. However, among these inbred strains, we also observed several strains differ significantly in infarct volumes but harbor similar collateral numbers. In order to identify genetic factors determining infarct volume in a collateral-independent manner (neuroprotection), we used quantitative trait locus (QTL) mapping on mouse strains that exhibit the most difference in infarct volumes but the least difference in collateral numbers (C57BL/6J and C3H/HeJ). From the F2 B6 x C3H cross, we mapped 4 loci determining infarct volume (cerebral infarct volume QTL 4 to 7, Civq4 to Civq7). The Civq4 locus is the strongest locus (LOD 9.8) that contributes 21% of phenotypic variance in infarct volume. We also used a parallel F2 B6 x C3H cross to perform a QTL mapping on collateral vessel traits to further verify these collateral-independent loci. Among these 4 loci, the Civq4 and Civq7 loci appear to be truly collateral-independent. Based on strain-specific sequence variants and mRNA expression differences, we proposed Msr1 and Mtmr7 are the potential candidate genes of the Civq4 locus. Identification of the collateral-independent genetic factors will help to understand the genetic architecture, disease pathophysiology and potential therapeutic targets for of ischemic stroke</p> / Dissertation

The aim of this thesis is to investigate the role of the wholesale funding in the modern credit intermediation process and to estimate the possible impact of pro- posed regulation of the wholesale funding on lending activity of a bank or its risk profile. Throughout the analysis we used data set of 132-1167 banks from the European Union (number of banks depends on the hypotheses tested) during the period 2006-2012. We found that the banks that are more exposed to the whole- sale funding are able to increase their lending relatively more in comparison to the less exposed banks; this advantage is wiped out during the times of liquidity or collateral crunch. Results of defined simultaneous equation model suggest that stricter eligibility criteria, higher margins and introduction of 100% threshold for the Net Stable Funding Ratio will significantly decrease the wholesale funding ra- tio and thus limit the supply of loans. We consider those results alarming since the majority of European enterprises is financed by the financial intermediaries, not on the capital market and therefore additional limitation of the wholesale funding activities could negatively influence the overall economic activity within the Euro- pean Union. We discovered that the commercial banks tent to transfer the costs of the wholesale...

La surexpression de pompes d'efflux par les cellules cancéreuses permet l'élimination d'agents cytotoxiques, induisant alors une résistance à la chimiothérapie. Trois transporteurs ABC sont principalement impliqués dans cette résistance : P-gp/ABCB1, MRP1-ABCC1 et BCRP/ABCG2. La surexpression des ces transporteurs peut également être le "talon d'Achille" des cellules cancéreuses résistantes en les sensibilisant à certains composés. Ce phénomène, appelé sensibilité collatérale, pourrait constituer un nouvel outil thérapeutique conter les les cancers intrinséquement ou rendus résistants en éliminant sélectivement les cellules cancéreuse résistances. Ainsi, le S-vérapamil provoque la mort sélective par apoptose des cellules surexprimant suite à l'extrusion rapide et massive du glutathion 5GSH) intracellulaire par MRP1. Nous avons démontré que le vérapamil est capable de dépléter s"lectivement de leur contenu en GSH les tumeurs de cancer du poumon H69AR, MRP1 positives et résistantes, dès 3 heures d'exposition aiguë. Le vérapamil étant fortemnt carditoxique, nous avons développé de nouveaux agents de sensibilité collatérale, plus sélectif que le vérapamil, comme le xanthone 9, le flavonoïde 36 et le dimère de flavonoïde 4e. Enfin, grâce à l'étude de chimères MRP1/MRP2, nous avons démontré que la région comprenant les boucles L0 et L1-TM12 pourrait constituter les sites modualteurs et substrat du GSH sur MRP1. / Resistance to chemotherapy is partly due to efflux pumps expressed in the plasma membrane, which prevent the accumulation of anticancer drugs in tumor cells. Three human ABC transporters are particulary involved in this chemoresistance : P-gp/ABCB1, MRP1-ABCC1 and BCRP/ABCG2. The overexpression of these trnasporters can also be an "Achille heel" for resistant cancer cells by sensitizing them to various drugs. This phenomenom, called collateral sensitivity, could constitute a new chemotherapy to eradicate cancers becoming resistant or cancer which ara resistant prioir to any treatment. Thus, S-verapamil triggers selective apoptosis of MRP1 overexpressing correlated to the massive and rapide extrusion of cellular glutathione by MRP1. We showed that verapamil is able to selectivity deprive H69AR MRP1 positive and resistant lung tumors, as soon as 3 hours of acute exposure. Verapamil being highly cardiotoxic, we have developed new collateral sensitivity drugs, more selective than verapamil, such as xanthone 9, flavonoïdd 36 and flavonoïd dimer 4e. Finally, thanks to the characterization of MRP1/MRP2 chimera, we showed that the MRP1 region including the intracellular loop L0 L1-TM12 might constitute the substrate and the modulator binding sites for GSH.

[pt] Em economias competitivas com mercados incompletos e horizonte infinito, quando a tomada de garantias previamente constituídas é o único mecanismo que dá incentivos contra a inadimplência em operações de crédito, esquemas de Ponzi são evitados e há equilíbrio independemente da escolha destas garantias. Nestas economias, adiciono mecanismos contra inadimplência que são efetivos, isto é, induzem os credores a efetuarem pagamentos além do valor das garantias. Neste contexto, provo que a escolha das exigências de garantias se tornam relevantes para assegurar a existência planos individuais ótimos. Enfatizo também que este resultado não depende de tipos de mecanismos contra inadimplência específicos, contanto que os tomadores de empréstimos se deparem com pagamentos adicionais ao valor das garantias como uma porcentagem da dívida remanescente. / [en] In infnite horizon incomplete market economies, when the seizure of collateral guarantees is the only mechanism enforcing borrowers not to entirely default on their promises, equilibrium exists independently of the choice of collateral bundles. In these economies, we add default enforcement mechanisms that are effective, i.e. induce payments besides the value of collateral guarantees. We prove that the choice of collateral requirements become relevant to assure the existence of individual's optimal plans. This result does not depend on specific types of such mechanisms, as long lenders face payments besides the value of collateral guarantees as a percentage of the remaining debt.

[pt] Este trabalho desenvolve e estabelece a existência de equilíbrio para um modelo sequencial com dois estágios, mercados financeiros incompletos, risco de crédito e colateral endógeno. No primeiro estágio, ao escolherem o colateral, de acordo com uma regra exogenamente determinada, os agentes emitem ativos personalizados que serão transacionados no segundo estágio, em uma economia Walrasiana com dois períodos. A nossa estrutura permite o surgimento de modelos nos quais os próprios agentes escolhem suas garantias, de forma similar aos modelos já existentes de colateral endógeno. Tais modelos exibem o que podemos chamar de A Maldição do Vencedor, situação na qual o agente escolhe, racionalmente, oferecer colateral nulo, inviabilizando, em equilíbrio, a transação de ativos. Com isso, a economia é jogada para um equilíbrio Pareto inferior no qual não existem mercados financeiros. Ao introduzir uma sequencialidade nas escolhas, conseguimos resolver esse problema, pois os agentes antecipam o efeito da escolha de colateral sobre os payoffs de equilíbrio, escolhendo, racionalmente, colaterais positivos. Assim, conseguimos não somente solucionar uma limitação dos modelos existentes, como ainda, permitir o surgimento de inúmeros sub-modelos através das diversas possibilidades para a regra de escolha na determinação do colateral. / [en] This paper develops and establishes the existence of equilibrium for a sequential model with two stages, incomplete financial markets, credit risk and endogenous collateral. In the first stage, by choosing the collateral, according to a predetermined and exogenously given rule, the agents issue personalized securities that will be traded in the second stage in aWalrasian economy with two periods. Our structure allows for models in which the agents choose their own collateral, similar to the existing endogenous collateral models. Those models exhibit what we might call, The Winner s Curse, a situation in which the agent choose, rationally, to offer no collateral, making asset trading impossible, in equilibrium. The economy is then thrown in a Paretoinferior equilibria in which there are no financial markets. By introducing the agent s choice in a sequential fashion, we avoid such a problem, because the agents anticipate the effects of their collateral choice over the equilibrium payoffs, therefore choosing rationally, positive collateral. That way, we are able, not only to solve a shortcoming of the existing models, but also to allow for a variety of sub-models through the several possible choices for the collateral determining rule.

Embora o objetivo primário da contratação administrativa seja a aquisição de bens e serviços nos melhores termos possíveis, os entes estatais frequentemente se utilizam de seu inquestionável poder de compra para promover questões nacionais outras, que são industriais, sociais ou ambientais em sua natureza. Todavia, essas políticas, também conhecidas como políticas secundárias, colaterais ou horizontais, legitimamente perseguidas pelos governos nacionais, podem estar em contraste com outros propósitos nacionais ou internacionais legítimos, tais como livre comércio, transparência e lealdade. Esta tese analisa a taxonomia do que denominamos função horizontal da licitação e da contratação administrativa, bem como o modo por meio do qual o regime brasileiro de compras públicas lida atualmente com essas preocupações secundárias (mas de igual importância) econômicas, sociais e ambientais e com os limites impostos à adoção de tais políticas. / Although the primary objective of procurement is the acquisition of goods or services on the best possible terms, governments have frequently used their unquestionable power of procurement to promote further national concerns, which are industrial, social and environmental in their nature. However, these public policies, also known as secondary, colateral or horizontal policies, legitimately pursued by national government, could be in contrast with other nacional and international legitimate purposes, such as free trade, transparency and fairness. This essay analyzes the taxonomy of what we name horizontal function of public procurement and the way in which brazilian regime of public purchasing is dealing nowadays with these economic, social and environmental secondary (but not less importante) concerns and the limits imposed on the adoption of such policies.