Dissertations / Theses: 'Sortitio'

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Dowlen, Oliver. "The political potential of sortition." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.443717.

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Bothorel, Julie. "Le tirage au sort des provinces sous la République romaine et au début du Principat (227 av. J.-C. - 14 ap. J.-C.)." Electronic Thesis or Diss., Paris 10, 2019. http://www.theses.fr/2019PA100108.

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Dans la Rome républicaine et impériale, le hasard occupait une place importante tant dans la vie quotidienne que dans le fonctionnement des institutions. Le tirage au sort (sors ou sortitio en latin) était ainsi utilisé dans des contextes familiaux et privés (jeux de hasard ou pratiques magiques), dans les sanctuaires oraculaires, mais également dans la sphère civique afin de sélectionner des citoyens ou attribuer des tâches. Cette enquête étudie le tirage au sort utilisé pour répartir les provinces consulaires et prétoriennes entre les consuls et les préteurs en charge et, après 52 av. J.-C., sortis de charge (sortitio prouinciarum). Ce tirage au sort jouait un rôle stratégique dans la mesure où il permettait chaque année de répartir le commandement des armées et les principales tâches juridiques, judiciaires et administratives à Rome et dans l’Empire entre les magistrats curules tout en limitant les effets délétères de la compétition aristocratique. L’enquête débute à l’époque républicaine, plus précisément au IIIe siècle av. J.-C., siècle marqué par l’expansion territoriale de l’Empire et le développement des magistratures, et s’achève à la fin du règne d’Auguste, fondateur du Principat. Deux parties la structurent. La première restitue la législation qui encadrait alors le tirage au sort des provinces et étudie son évolution entre l’époque républicaine et impériale. La seconde analyse la manière dont était effectué, dans la pratique, le rituel du tirage au sort et les significations que lui donnaient les Romains
In Republican and Imperial Rome, chance played an important role, both in the private and the public sphere. While drawing of lots — called sors or sortitio in Latin — was commonly called upon for everyday purposes (in games of chance or magic rituals, for instance), and played an important role in oracular prophesies, the procedure was also used in an official context to assign public offices. We examine here a specific kind of sortition : the random drawing of provinces among consuls and praetors and, after 52 BCE, among former consuls and praetors. This sortition played a strategic role. It allowed indeed the Senate to assign military commands, juridical and judicial missions as well as administrative tasks in Rome and in the Empire among the high-ranking magistrates, while reducing the harmful effects of aristocratic competition. This research aims to restore the legal framework for the drawing by lot of provinces and to show how it evolved from the end of the 3rd century BCE until the reign of Augustus during the 1st century CE. It will then describe how the sortition worked out in practice and the meanings that Roman people attached to this ritual

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Säreborn, Alexander. "Sharpe vs. Sortino : En kamp om investerarna." Thesis, Karlstads universitet, Handelshögskolan, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-55297.

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4

Campbell, Charles. "Sortilin is a Negative Regulator of Sonic Hedgehog Processing and Anterograde Trafficking in Neurons." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34560.

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Sonic Hedgehog (SHH) is a secreted morphogen that is an essential regulator of patterning and growth. The SHH protein requires cleavage of its full-length precursor (SHHFL) for secretion of biologically active SHH (SHHNp). Mutations in SHH that affect SHH processing are associated with human disease, which highlights the importance of processing for patterning in vivo. We identified Sortilin (SORT1), a member of the VPS10P receptor family, as a novel SHH interacting protein. SORT1 preferentially associates with SHHFL and SORT1 levels correlate inversely with cleavage of SHHFL. Consistent with an antagonistic relationship between SORT1 and SHH processing, loss of SORT1 results in an increase in SHH levels in axons and a partial rescue of Hedgehog-associated patterning defects in a mouse model of deficient SHH processing. Finally, we demonstrate a functional requirement for SORT1-mediated trafficking on SHH-dependent signaling from axons in the developing visual system in vivo. Our findings identify a novel role for SORT1 in the regulation of SHH processing and trafficking.

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Sutherland, John Keith Bell. "Election by lot and the democratic diarchy." Thesis, University of Exeter, 2017. http://hdl.handle.net/10871/31813.

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This thesis argues that ‘democracy’ can better be understood in terms of a conceptual diarchy of ‘isonomia’ (equal political rights) and ‘isegoria’ (equal speech rights), rather than the conventional diarchy of ‘will’ and ‘opinion’ that originated in the era of absolute monarchy. As the proposed diarchy has its origin in classical Greece, the thesis starts with a brief overview of the institutional changes in sixth-, fifth- and fourth-century Athenian democracy that implemented the distinction in different ways, and examines some of its dysfunctions. The particular aspect of Athenian democracy under focus is sortition – the random selection of citizens for public office – viewed in antiquity as democratic, whereas election was viewed as an aristocratic or oligarchic selection mechanism. The thesis takes issue with Bernard Manin’s claim that the ‘triumph of election’ was on account of the natural right theory of consent, arguing that sortition-based proxy representation is a better way of indicating (hypothetical) consent than preference election. The thesis then seeks to clarify the concept(s) of representation – essential to the implementation of the democratic diarchy in modern large-scale societies – and to study how the diarchy has been reincarnated in modern representative democracies, along with an examination of the pathologies thereof. Consideration is given as to what the deliberative style of assemblies selected by lot should be, alongside evaluation of the epistemic potential of cognitive diversity and the ‘wisdom of crowds’. Given the need for both isonomia and isegoria to assume a representative form in large modern states, Michael Saward’s Representative Claim is adopted as a theoretical model to extend the reach of political representation beyond elections. The thesis concludes with tentative proposals as to how the fourth-century reforms (delegation of the final lawmaking decision to randomly-selected nomothetic courts) might be used as a template for modern institutions to resolve some of the problems of mass democracy.

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Asaro, Antonino [Verfasser]. "The effect of apolipoprotein E isoforms and sortilin in brain lipid homeostasis and Alzheimer’s disease / Antonino Asaro." Berlin : Freie Universität Berlin, 2019. http://d-nb.info/1200409736/34.

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Yuan, Libin. "A stretch of 17 amino acids in the prosaposin C-terminus is critical for its binding to sortilin and targeting to lysosomes." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=92262.

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Newly synthesized soluble lysosomal proteins are transported from the Golgi apparatus to the lysosomes by two mannose 6-phosphate receptors. However, the sphingolipid activator protein prosaposin is targeted by the alternative trafficking receptor, sortilin. Prosaposin is the precursor of four lysosomal saposins required for the hydrolysis of sphingolipids. A previous study demonstrated that the removal of its C-terminus abolished the trafficking of prosaposin to the lysosomes.
To identify the sequences and amino acids involved in the interaction of prosaposin to sortilin and its transport to the lysosomes, we generated six prosaposin deletion constructs and examined the effect of truncation by co-immunoprecipitation and confocal microscopy. The experiments revealed that a 17 amino acid stretch in the first half of the C-terminus (aa524-540) was necessary for the binding of prosaposin to sortilin and essential for its transport to the lysosomes.
Since the pH is able to induce conformational changes in the four saposin domains, we performed a pH-dependent binding assay to test whether or not the binding of prosaposin to sortilin was affected by different pHs. The experiments demonstrated that binding of prosaposin to sortilin occurred at 6.0 or higher. A substantial decrease in binding was detected at pH 5.5, and at pH 5.0 both proteins did not form complexes. This result indicated that the binding of prosaposin to sortilin is pH-dependent.
Since hydrophilic residues usually modulate pH-dependent protein interactions we introduced six site-directed point mutations in hydrophilic residues within the first half of the C-terminus. The results showed that the mutation of single hydrophilic amino acids did not affect the binding of prosaposin to sortilin.
Considering that tryptophan, cysteine and proline residues are important in protein structure and function, we also introduced eight site-directed point mutations to these residues within the 17 amino acid stretch in the C-terminus. The experiments revealed that two tryptophans (W530 and W535), and two cysteines (C528 and C536) were essential for the transport of prosaposin to the lysosomes. In addition, one proline residue (P532) was critical for the proper folding of prosaposin during its synthesis, which was demonstrated by the MG132 Proteasome Inhibition Assay.
In conclusion, we have narrowed down the sortilin recognition site on the prosaposin molecule to a specific 17-residue stretch in the first half of the C-terminus and discovered the essential residues in this region for the lysosomal trafficking of prosaposin.
Les protéines lysosomiales solubles récemment identifiées et synthétisées sont transférées de l'appareil de Golgi des cellules vers les lysosomes par deux récepteurs, des mannoses 6-phosphates. Cependant l'activateur sphingolipidique de la prosaposine est ciblé sur la lysosomes par un récepteur alternatif, la sortiline. La prosaposine est le précurseur de quatre saposines lysosomiales requises pour l'hydrolyse des sphingolipides. Une étude récente a déjà démontré que l'élimination de la terminaison-C de la sphingolipide empêche le transport de la prosaposine vers les lysosomes.
Pour identifier les séquences d'acides aminés impliqués dans l'interaction de la prosaposine avec la sortiline et ainsi clarifier le mode de transport de ces séquences vers les lysosomes, nous avons procédé, par co-immunoprécipitation et immunomicroscopie confocale et à l'élimination de six séquences distinctes de la saposine. Ces expériences ont montré que la première moitié de la terminaison-C (aa524-540) la séquence des 17 résidus peptidiques est nécessaire pour permettre la liaison de la sortiline à la prosaposine et le transport de la prosaposine vers les lysosomes. fr
Le pH du milieu agit sur l'interaction d'un ligand à son récepteur. Nous avons donc analysé la liaison de la prosaposine à la sortiline à différents pH. Les résultats on montré que la liaison de la prosaposine à la sortiline se fait à un pH de 6.0 ou plus. Par contre la prosaposine ne forme pas de complexes avec la sortiline à des pH de 5.0 et 5.5. fr
Puisque les résidus hydrophiles modulent normalement l'interaction des protéines nous avons introduit des mutations focales (point mutations) sur six sites de tels résidus hydrophiles de la terminaison-C de la prosaposine. Les résultats ont montré que de telles mutations n'ont aucun effet sur la liaison de la sortiline à la prosaposine. fr
Considérant que le tryptophane, la cystéine et la proline forment des séquences importantes de la structure et de la fonction des protéines, nous avons inséré huit mutations focales additionnelles sur la séquence de 17 résidus de la terminaison-C de la prosaposine. Les résultats ont révélé que deux molécules de tryptophane (W530 etW535) et deux molécules de cystéine (C528 et C536) sont essentielles au transport de la prosaposine vers les lysosomes. Par ailleurs, une molécule de proline (P532) provoque la dégradation de la prosaposine par des protéosomes. fr
En conclusion nous avons circonscrit certains aspects moléculaires de la relation de la sortiline à la prosaposine. Nous avons montré en particulier que la liaison de la sortiline à la prosaposine se situe au niveau d'un site précis du segment de la terminaison-C de la prosaposine dont certains éléments jouent un rôle essentiel dans le transport de la prosaposine vers les lysosomes. fr

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Al-Akhrass, Hussein. "Un rôle inédit de la sortiline dans le contrôle du transport rétrograde de l'EGFR pour limiter la croissance tumorale." Thesis, Limoges, 2017. http://www.theses.fr/2017LIMO0035/document.

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Le cancer du poumon est le troisième cancer le plus fréquent chez les femmes et le deuxième chez les hommes, il est la cause principale de décès par cancer dans le monde, avec une mortalité annuelle supérieure à 1 million. Malgré des progrès remarquables dans la thérapie ciblée, la majorité des patients atteints de cancer du poumon sont diagnostiqués dans un stade avancé où ils ne connaissent pas d'amélioration significative de leur survie globale. Les récepteurs à domaine tyrosine kinase, tels que le récepteur du facteur de croissance épidermique (EGFR), traduisent les informations du microenvironnement dans la cellule en activant des voies de signalisation homéostatiques. L'internalisation et la dégradation de l'EGFR suite à la liaison du ligand limitent l'intensité de la signalisation proliférative, ce qui contribue à maintenir l'intégrité cellulaire. Dans les cellules cancéreuses, la dérégulation du trafic de l’EGFR aboutit à des effets divers sur la progression tumorale. Dans cette étude, nous avons identifié la sortiline comme un régulateur clé de l'internalisation de l'EGFR à partir de la membrane plasmique. La perte de l’expression de la sortiline dans les cellules tumorales augmente la prolifération cellulaire en soutenant la signalisation de l’EGFR à la surface de la cellule, ce qui accélère la croissance tumorale. Chez les patients atteints de cancer du poumon, l'expression de la sortiline diminue avec l’augmentation du grade pathologique et l’expression de son gène, SORT1, est fortement corrélée à une meilleure survie globale, en particulier chez les patients présentant une forte expression de l'EGFR. Ainsi, la sortiline représente un nouveau régulateur du trafic intracellulaire de l’EGFR, elle agit en contrôlant l'internalisation de ce récepteur et en limitant la croissance tumorale
Lung cancer is the third most common cancer in women and the second in men, it is the leading cause of cancer-related death worldwide, with an annual mortality of more than 1 million. Despite remarkable advances in targeted therapy, the majority of patients with lung cancer are diagnosed at an advanced stage where they do not experience a significant improvement in overall survival. Tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) transduce information from the microenvironment into the cell and activate homeostatic signalling pathways. Internalisation and degradation of EGFR after ligand binding limits the intensity of its proliferative signalling, thereby helping to maintain cell integrity. In cancer cells, deregulation of EGFR trafficking has a variety of effects on tumour progression. Here, we report that sortilin is a key regulator of EGFR internalisation. Loss of sortilin in tumour cells promotes cell proliferation by sustaining EGFR signalling at the cell surface, ultimately accelerating tumour growth. In lung cancer patients, sortilin expression decreases with increased pathologic grade, and the expression of SORT1 (the gene encoding sortilin) is strongly correlated with a better survival, notably in patients with high EGFR expression. Thus, sortilin is a novel regulator of EGFR intracellular trafficking acting by controlling receptor internalisation and limiting tumour growth

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McCartney, Daniel Lawrence. "Investigating genome-wide transcriptional and methylomic consequences of a balanced t(1;11) translocation linked to major mental illness." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28873.

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Schizophrenia, bipolar disorder and major depressive disorder are devastating psychiatric conditions with a complex, overlapping genetic and environmental architecture. Previously, a family has been reported where a balanced chromosomal translocation between chromosomes 1 and 11 [t(1;11)] shows significant linkage to these disorders. This translocation transects three genes: Disrupted in schizophrenia- 1 (DISC1) on chromosome 1, a non-coding RNA, Disrupted in schizophrenia-2 (DISC2) antisense to DISC1, and a non-coding transcript, DISC1 fusion partner-1 (DISC1FP1) on chromosome 11, all of which could result in pathogenic properties in the context of the translocation. This thesis focuses on the genome-wide effects of the t(1;11) translocation, primarily examining differences in gene expression and DNA methylation, using various biological samples from the t(1;11) family. To assess the genome-wide effects of the t(1;11) translocation on methylation, DNA methylation was profiled in whole-blood from 41 family members using the Infinium HumanMethylation450 BeadChip. Significant differential methylation was observed within the translocation breakpoint regions on chromosomes 1 and 11. Downstream analysis identified additional regions of differential methylation outwith these chromosomes, while pathway analysis showed terms related to psychiatric disorders and neurodevelopment were enriched amongst differentially methylated genes, in addition to more general terms pertaining to cellular function. Using induced pluripotent stem cell (iPSC) technology, neuronal samples were developed from fibroblasts in a subset of individuals profiled for genome-wide methylation in whole blood (N = 6) with an aim to replicate the significant findings around the breakpoint regions. Here, methylation was profiled using the Infinium HumanMethylation450 BeadChip’s successor: the Infinium MethylationEPIC BeadChip. The results from the blood-based study failed to replicate in the neuronal samples, which could be attributed to low statistical power or tissue-specific factors such as methylation quantitative trait loci. The differences in methylation in the most significantly differentially methylated loci were found to be driven by a single individual, rendering further interpretation of the findings from this analysis difficult without additional samples. Cross-tissue analyses of DNA methylation were performed on blood and neuronal DNA from these six individuals, revealing little correlation between cell types. DISC1 is central to a network of interacting protein partners, including the transcription factor ATF4, and PDE4; both of which are associated with the cAMP signalling pathway. Haploinsufficiency of DISC1 due to the translocation may therefore be disruptive to cAMP-mediated gene expression. In order to identify transcriptomic effects which may be related to the t(1;11) translocation, genome-wide expression profiling was performed in lymphoblastoid cell line RNA from 13 family members. No transcripts were found to be differentially expressed at the genome-wide significant level. A post-hoc power analysis suggested that more samples would be required in order to detect genome-wide significant differential expression. However, imposing a fold-change cut-off to the data identified a number of candidate genes for follow-up analysis, including SORL1: a member of the brain-expressed Sortilin gene family. Sortilin genes have been linked to multiple psychiatric disorders including schizophrenia, bipolar disorder and Alzheimer’s disease. Follow-up analyses of Sortilin family members were performed in a Disc1 mouse model of schizophrenia, containing an amino acid substitution (L100P). Here, developmental gene expression profiling was performed with an additional aim to optimise and validate work performed by others using this mouse model. However, results from these experiments were variable between two independent batches mice tested. Additional investigation of Sortilin family genes was performed using GWAS data from human samples, using machine learning techniques to identify epistatic interactions linked to depression and brain function, revealing no statistically significant interactions. The results presented in this thesis suggest a potential mechanism for differential DNA methylation in the context of chromosomal translocations, and suggests mechanisms whereby increased risk of illness is conferred upon translocation carriers through dysregulation of transcription and DNA methylation.

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Moreno, Sébastien. "Le récepteur 3 de la neurotensine/Sortiline dans la régulation de l’état dépressif." Thesis, Université Côte d'Azur (ComUE), 2017. http://www.theses.fr/2017AZUR4136/document.

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Le trouble dépressif majeur est une pathologie qui atteint 20% de la population et qui représente le premier facteur de morbidité et d’incapacité au niveau mondial. Récemment, le canal potassique TREK-1 est une cible potentielle avérée dans le traitement de la dépression. La délétion de ce canal ou son blocage par un peptide dérivé résultant de la maturation de la sortiline, le propeptide (PE) ou son analogue synthétique la Spadine, résulte en un phénotype de résistance à la dépression. La sortiline est une protéine capable de s’associer à TREK-1 mais également au facteur neurotrophique BDNF important pour la viabilité neuronale et la régulation de l’état dépressif. La sortiline est donc impliquée dans la régulation de l’adressage intracellulaire de TREK-1 et du BDNF. Mes travaux se sont d’abords focalisés sur les conséquences de la délétion du gène codant pour la sortiline (Sort1-/-) sur l’adressage de TREK-1 et du BDNF, et également sur le système neurotensinergique. Les résultats révèlent au niveau cérébral une diminution de l’expression membranaire de TREK-1 et une augmentation de BDNF. L’ensemble de ces modifications conduisent les souris Sort1-/- à développer un phénotype de résistance à la dépression. De plus, ces souris présentent une augmentation de la concentration en neurotensine cérébrale ainsi que de son récepteur 2, ce qui entraine une résistance à la douleur. Par la suite, nous avons montré une diminution de la concentration sérique du PE chez les personnes dépressives, un niveau restauré après traitement avec des antidépresseurs. En conclusion, la sortiline joue un rôle prépondérant dans la régulation du trouble dépressif et aussi dans la nociception
Major depressive disorder is a condition that affects 20% of the population and is the leading cause of morbidity and disability worldwide. Recently, the TREK-1 potassium channel has been shown to be a potential target in the treatment of depression. The deletion of this channel or its blocking by a derived peptide resulting from the maturation of Sortilin, propeptide (PE), or its synthetic analogue Spadin, results in a phenotype of resistance to depression in mice. Sortilin is a protein able to bind with TREK-1 but also with the neurotrophic factor BDNF, an important factor for neuronal viability and depressive state regulation. Sortilin is therefore involved in regulating the intracellular addressing of TREK-1 and BDNF. Initially, my work focused on the consequences of the deletion of the Sortilin gene (sort1-/-) on the TREK-1 and BDNF addressing, and the neurotensinergic system. The results showed a decrease in TREK-1 membrane expression at the cerebral level and an increase in BDNF. All of these changes lead the Sort1-/- mice to develop a phenotype of resistance to depression. In addition, these mice show an increase in brain neurotensin concentration and its receptor 2, leading to increased resistance to pain perception. In a second phase, I was interested in whether PE, a potential antidepressant, showed serum variations in depressed patients and could be an indicator of depressive syndrome. We showed that the serum PE level is significantly reduced in depressed people, a level restored after treatment with antidepressants. In conclusion, Sortilin plays a major key in the regulation of depressive disorder and also in nociception

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Hivelin, Céline. "Étude des mécanismes de libération du propeptide de la sortiline et de ses effets sur l’homéostasie glucidique." Thesis, Université Côte d'Azur (ComUE), 2016. http://www.theses.fr/2016AZUR4109/document.

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En France, l’obésité touche 15% de la population et est en perpétuelle augmentation. Elle est une cause majeure du diabète de type 2. Elle se traduit par un accroissement du nombre de cellules de stockage du gras (adipocytes) et une résistance périphérique à l’insuline. Chez des individus obèses, l’augmentation du nombre d’adipocytes est associée à une diminution de l’expression de la sortiline, protéine transmembranaire dont le clivage entraine la formation du propeptide (PE) et sa libération dans la circulation sanguine. L’analogue synthétique du PE, la spadine, est connu pour moduler l’activité du canal potassique TREK-1. Ce canal étant exprimé dans la cellule bêta pancréatique qui sécrète l’insuline, une hormone participant à la régulation du taux de glucose dans le sang, il est possible que la spadine joue un rôle dans l’homéostasie du glucose. Mes résultats confirment cette hypothèse. En effet, la spadine améliore la tolérance au glucose des souris, en favorisant la libération d’insuline. La spadine est également connue pour interagir avec sortiline, indispensable au trafic du transporteur de glucose Glut4 vers la membrane des adipocytes. Cette interaction spadine-sortiline suggère que la spadine pourrait moduler l’entrée du glucose dans les adipocytes via la sortiline. Mes résultats montrent que la spadine ne modifie pas les capacités de stockage du glucose des adipocytes. En conclusion, la spadine joue un rôle dans la sécrétion de l’insuline et dans la régulation de la glycémie, ce qui peut présenter un intérêt pharmaceutique
In France, approximately 15% of the population is obese and this number keeps rising up every year. Obesity is a major cause of diabetes, inducing an increase of the number of fat-filled cells, called the adipocytes, and a peripheral insulin resistance. This increase of the number of adipocytes is associated with a decrease of sortilin expression, a transmembrane protein which is involved in the release of a propeptide (PE) in the blood circulation. Spadin, a synthetic PE analog, is known to modulate the potassium TREK-1 channel activity. Since, this channel is expressed in pancreatic beta cells which secrete insulin, a hormone involved in blood glucose regulation, spadin may play a role in glucose homeostasis. Consistent with this hypothesis, spadin improves glucose tolerance in mice, by stimulating insulin release. Spadin is a natural peptide derived from sortilin, which is known to control the glucose transporter Glut4 trafficking to the plasma membrane of adipocytes. This suggests that spadin may regulate glucose storage in adipocytes by affecting the sortilin function. However, my results show that spadin has no effect on glucose storage. In summary, spadin is involved in insulin secretion and glucose homeostasis and may be an alternative treatment against obesity and diabetes

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Rocha, Matheus Quinete. "Medidas de desempenho para hedge funds no Brasil com destaque para a medida Ômega." reponame:Repositório Institucional do FGV, 2006. http://hdl.handle.net/10438/2247.

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Mutual funds performance evaluation is, traditionally, made using Sharpe Ratio that considers only the first and the second moments of the return distribution (mean and variance), but it requires assumptions on the normality of the returns distribution and on the investor’s utility function as quadratic. However, it is well known that a quadratic utility function is inconsistent with investor behavior and some funds, like hedge funds, have returns distributions far from a normal distribution Keating and Shadwick (2002a, 2002b) proposed a new measure called Omega that incorporates all the moments of the distribution, and has the advantage of requiring no assumptions on the returns distribution or on the utility function of a risk averse investor. The purpose of this work is to verify if this measure has a greater forecast power than other performance measures, like Sharpe and Sortino Ratios. The empiric study indicated that Omega measure makes a ranking, most of the time, different from the other measures. Despite the portfolios constructed with Omega have had an average return greater than the average return of the portfolios constructed using the other measures, in almost all the tests, this difference of averages of returns was significant only in some cases. In spite of this, there is a light indication that Omega measure is the most appropriate for the use of investors when is made the performance evaluation of mutual funds.
A avaliação de desempenho de fundos de investimentos é, tradicionalmente, realizada utilizando-se o Índice de Sharpe, que leva em consideração apenas os dois primeiros momentos da distribuição de retornos (média e variância), assumindo as premissas de normalidade da distribuição de retornos e função quadrática de utilidade do investidor. Entretanto, é sabido que uma função de utilidade quadrática é inconsistente com o comportamento do investidor e que as distribuições de retornos de determinados fundos, como os hedge funds, estão longe de serem uma distribuição normal. Keating e Shadwick (2002a, 2002b) introduziram uma nova medida denominada Ômega que incorpora todos os momentos da distribuição, e tem a vantagem de não ser necessário fazer premissas sobre a distribuição dos retornos nem da função de utilidade de um investidor avesso ao risco. O objetivo deste trabalho é verificar se esta medida Ômega tem um poder de previsibilidade maior que outras medidas de avaliação de desempenho, como o Índice de Sharpe e o Índice de Sortino. O estudo empírico indicou que a medida Ômega gera um ranqueamento, na maioria das vezes, relativamente diferente das outras medidas testadas. Apesar das carteiras formadas com base na medida Ômega terem gerado um retorno médio maior que o retorno médio das carteiras formadas pelas outras medidas em praticamente todos os testes, esta diferença entre as médias dos retornos só foi significativa em alguns casos. Mesmo assim, há uma leve indicação de que a medida Ômega é a mais apropriada para utilização do investidor ao fazer a avaliação de desempenho dos fundos de investimentos.

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Gaqa, Nandipa. "The Development Role Played by Targeted Development Investments in South Africa and Their Risk-Adjusted Performance Over a 10-Year Period." Master's thesis, Faculty of Commerce, 2021. http://hdl.handle.net/11427/32687.

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The study evaluated the development role of targeted development investments in South Africa and their risk adjusted performance over a 10-Year period, that is from 2008 to 2017. Targeted development investments as a subset of socially responsible investments have transformed the way capital is allocated towards development funding needs. In the South African context this study is relevant given it offers a contrast between investments made in the public sector where development impact is a key objective, versus private sector targeted investments that aim to achieve financial returns whilst also driving development impact objectives aligned to sustainable development goals. The role and impact of these investments in the post democratic era is put in the spotlight given the country is dealing with economic, social, and environmental challenges that have necessitated the need to assess the nature and role of the investment industry in solving these complex development challenges (Giampocaro & Pretorius, 2012). The study on the role of the public sector focused on the investments and development impact indicators tracked by the Top 3 public sector investment institutions or corporations. The analysis on the performance of the private sector TDI funds examined their risk adjusted performance using Treynor, Sharpe, Sortino, and Information ratios. The risk adjusted performance was used to test whether the TDI fund returns under or outperformed against five benchmark categories. The research findings showed mixed results where TDI funds either underperformed or outperformed against the benchmark categories. The findings highlighted the need for a hybrid development model where both the public and private sector actively play a role in the development landscape as guided by their respective investment mandates. The findings advocate for corporate and institutional investors to increase capital allocations and investments towards financing development needs given the scope to maximise investor returns, whilst considering socially responsible investing and issues relating to the development and empowerment of previously disadvantaged communities.

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Andrén, Erik, and Oskar Fors. "Actively Managed Investments : A comparison of US hedge and equity mutual funds." Thesis, Internationella Handelshögskolan, Högskolan i Jönköping, IHH, Företagsekonomi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-35570.

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Over the past years, the total assets under management among hedge funds and equity mutual fundshave increased significantly. The question from an investor point of view iswhich investment vehicle can provide the greatest return adjusted for risk. The purpose of this study involves an analysis on the historical net asset values todetermine and evaluate what one can except from actively managed hedge andequity mutual funds. It supports the determination of the most profitable asset, adjusted for risk, as part of a diversified portfolio. The performance is measured net of fees and costs with the inclusion of potential performance fees individual hedge funds may apply. Hedge funds practice different investment approaches depending on what strategy is applied and hence, return levels can vary dramatically. The study is designed to answer questions by comparing net returns and risk-adjusted returns for respective investments and the different hedge fund strategies. With a deductive research approach, the analysis is conducted by applying existing models and theories as the Fama-French three-factor model through time-series regressions measuring excess returns (alpha), risk-adjusted performance measures as Sharpe ratio, M-squared and the Sortino ratio. The results show that hedge funds outperform equity mutual funds in all examined aspects and produce positive monthly net alphas,on average. Equity mutual funds are unable to provide investors with positive excess returns and subsequently fail the purpose of an actively managed fund by providing returns lower than the return of the market. The results are increasingly strengthened with both time-series regressions and performance measures showing homogenous results and reaching the equal conclusions. From the conclusions that hedge funds provide the most profitable investment compared to equity mutual funds, the hedge fund strategy CTA/managed futures strategies perform best in both net and risk-adjusted terms.

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Blondy, Sabrina. "Implication de la sortiline dans la résistance des cellules cancéreuses au 5-Fluorouracile. Cas du cancer colorectal." Thesis, Limoges, 2019. http://www.theses.fr/2019LIMO0020.

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Le cancer colorectal (CCR) représente la seconde cause de mortalité par cancer dans le monde. Les tumeurs sont classées selon les grades histologiques (état de différenciation cellulaire), en bas et haut grades. Les grades les plus avancés sont associés à de faibles taux de survie globale après chimiothérapie à base de 5-Fluorouracile (5-FU). Les taux de réponse aux traitements basés sur l’utilisation du 5-FU en première ligne de traitement demeurent relativement faibles (20–30%) et associés à de mauvais pronostics et des échappements thérapeutiques, dus à la résistance des cellules cancéreuses. Ces données soulignent donc la nécessité d’identifier de nouveaux biomarqueurs de résistance des cellules de CCR au 5-FU. Les travaux réalisés au cours de cette thèse ont porté sur l’étude de la sortiline, une protéine « multi-tâches » appartenant à la famille des récepteurs à domaine VPS10P avec sorLA et sorCS1-3, qui agit comme un (co)récepteur et un régulateur du traffic et de la sécrétion de protéines. La sortiline (et non sorLA), constitue un biomarqueur d’agressivité dans le CCR et est de mauvais pronostique. In vivo et in vitro, au sein des tumeurs et des cellules de CCR (lignées cellulaires et cultures primaires) résistantes au 5-FU, seule la sortiline apparait surexprimée au niveau transcriptomique et protéique. Ces données indiquent que la sortiline constitue également un biomarqueur de résistance au 5-FU, quels que soient les grades, stades et statuts mutationnels. Cette surexpression de la sortiline est majoritairement localisée au sein de l’appareil de Golgi des cellules résistantes et semble être régulée transcriptionnellement via une down-régulation d’ATF-3. L’inhibition génétique (shRNA) ou pharmacologique (CADA) de la sortiline potentialise les effets cytotoxiques du 5-FU, résultant en une forte augmentation de la mort cellulaire. La sortiline semble donc être également impliquée dans la résistance des cellules de CCR au 5-FU ; l’expression de sorLA ne variant pas après son inhbition. Ces résultats suggèrent que la sortiline pourrait constituer un biomarqueur d’agressivité et de résistance des cellules de CCR au 5-FU, mais aussi une nouvelle cible thérapeutique potentielle
Worldwide, colorectal cancer (CRC) is the second leading cause of cancer-related deaths. Colorectal adenocarcinomas are divided into low and high grades. More advanced tumor grade is associated with poorer global survival following 5-fluorouracil (5-FU)-based systemic chemotherapy. Even when 5-FU is used as the first-line molecule, responsiveness is only 20–30%, and drug resistance contributes to both poor patient prognosis and relapses, emphasizing the need to identify biomarkers involved in this process. In this study, we focused on sortilin, a multifunctional protein among VPS10P domain-related receptors with sorLA and sorCS1-3, that acts as a receptor and co-receptor as well as a regulator of intra- and extracellular protein sorting and trafficking. We obtained evidence that sortilin, but not sorLA, is a biomarker of CRC aggressiveness associated with poor clinical outcomes. In vivo and in vitro, in both 5-FU–resistant CRC cell lines and primary cultures, only sortilin was overexpressed at both protein and mRNA levels, indicating that it could serve as a biomarker of 5-FU resistance regardless of tumor grade and mutational status. Sortilin overexpression is especially localized in Golgi apparatus of 5-FU resistant cells and seems to be transcriptionally regulated through ATF-3 downregulation. Genetic (shRNA) and pharmacological (CADA) inhibition of sortilin potentiated 5-FU–induced cytotoxicity, resulting in a significant increase in cancer cell eradication, implying that sortilin is also actively involved in 5-FU resistance. Moreover, sorLA expression is unchanged upon sortilin inhibition. Our findings indicate that sortilin is a promising biomarker of 5-FU resistance in CRC, as well as a potential therapeutic target for overcoming 5-FU resistance

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Fredriksen, Petter, and Madeleine Lundberg. "Riskjusterad avkastning i nynoteringar på Aktietorget : En jämförelse av Sharpe- och Sortinokvoten." Thesis, Linköpings universitet, Företagsekonomi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-139206.

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Bakgrund: De senaste åren har en stark underprissättningstrend observerats i det ökande antalet börsnoteringar, vilket har skapat ett starkt investerarintresse. En stor del av dessa nyintroducerade bolag är småbolag, varav de flesta noteras på mindre handelsplatsformer, så kallade MTF:er. MTF:en Aktietorget introducerade flest företag till den svenska aktiemarknaden 2010-2014, varför detta har valts till studiens undersökningsområde.Tidigare studier har bevisat att det finns en hög volatilitet i nyintroduktioner och småbolag, vilket i finansiella sammanhang betyder att en sådan investering är mer riskfylld. Dock saknas liknande studier på downside volatilitet, alltså risken för förlust. Denna studie ämnar därför att jämföra den traditionellt riskjusterade avkastningen i form av sharpekvoten, mot avkastningen justerad för downside risk, den så kallade sortinokvoten. Detta nyare mått på risk är en del av den postmoderna portföljteorin, som tar hänsyn till en mer förlustaversiv investerare. Syfte: Syftet med denna uppsats är att analysera den riskjusterade avkastningen i nynoteringar på Aktietorget för att jämföra med etablerade bolag på OMX Stockholm. Den riskjusterade avkastningen beräknas genom sharpe-respektive sortinokvoten och jämförs sedan för att undersöka eventuella skillnader i bedömningen av aktiernas prestation. Genomförande: Uppsatsen är en eventstudie med deduktiv ansats. Undersökningen har inkluderat nynoteringar på Aktietorget mellan 2010-2014 och jämförelseaktier består av branschindex från OMXSPI.Den riskjusterade avkastningen har beräknats via modifierade kvoter. Samband mellan sharpe-respektive sortinokvoten har undersökts genom icke-parametrisk rangordningskorrelation. Slutsats: Studien kan inte bevisa en signifikant abnormal avkastning i nynoteringar på Aktietorget, men observerar en genomsnittlig överavkastning upp till en månad. De riskjusterade kvoterna har mycket stark rangordningskorrelation, vilket innebär att studiens resultat inte kan motivera en fortsatt användning av sortinokvoten.
Background: In recent years, a strong underpricing trend has been observed in the increasing number of IPOs, which has created a strong investor interest. A large part of these IPO companies are small firms, most of which are listed on smaller trading venues, known as MTFs. The MTF Aktietorget introduced most companies to the Swedish stock market during 2010-2014, so it has been chosen as the area for this research.Previous studies have shown that there is high volatility in new introductions and small companies, which in financial terms means that such an investment contains more risk. However, similar studies on downside risk are lacking. This study therefore aims to compare the traditional risk-adjusted return in the form of the sharpe ratio, against the return adjusted for downside risk, the so-called sortino ratio. This newer measure of risk is part of the postmodern portfolio theory, which takes into account a more loss-aversive investor. Purpose: The purpose of this paper is to analyze the risk-adjusted return in IPOs on Aktietorget and compare it with the return of established companies on OMX Stockholm. The risk-adjusted return is calculated by the sharpe and sortino ratios, respectively, and are later compared with each other to investigate possible differences in the estimation of performance for the stocks. Methodology: This paper is an event study with a deductive approach. The study has included IPOs on Aktietorget between 2010-2014 and comparative stocks, consisted of industry index from OMXSPI.The risk-adjusted return has been calculated using modified ratios and the relationship between the sharp and sortino ratios has been investigated by non-parametric ranking correlations. Conclusion: The study can't prove any significant abnormal return in IPOs on Aktietorget, but observes an average excess return of up to one month. The risk-adjusted ratios have very strong rank correlation, thus empirical results can't motivate the continued use of the sortino ratio.

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Carlos, Gustavo Barreto Bernardo. "Asset portfolio of an health insurer : the multicare case." Master's thesis, Instituto Superior de Economia e Gestão, 2014. http://hdl.handle.net/10400.5/7686.

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Mestrado em Finanças
A Indústria Seguradora tem várias particularidades, mas eventualmente uma das mais importantes é a incerteza relativamente aos cash flows futuros, devido à natureza imprevisível de catástrofes naturais ou doenças, no caso dos seguros de saúde. Todavia, as seguradoras tentam gerir o risco, entre outras formas, utilizando técnicas de Gestão de Activos-Passivos. De qualquer modo, devido à dificuldade em prever com exactidão os passivos futuros, ao alinhar as maturidades de activos e passivos pode criar uma desarticulação entre ambos, caso acontecimentos inesperados ocorram e os custos com sinistros sejam bastante maiores do que o estimado. Como tal, este estudo visa encontrar uma abordagem alternativa à escolha da carteira de investimentos: ao estabelecer um floor razoável para o rácio de financiamento, procura rentabilizar-se os fundos excedentários de forma a atingir melhores rentabilidades que podem ser úteis como almofadas de capital em períodos com maiores taxas de sinistralidade, ao mesmo tempo que se procura encontrar um equilíbrio nas proporções entre classes de activos, de forma a não penalizar os requisitos de capital da seguradora, ao abrigo do estabelecido na Directiva Solvência II. Para este fim foi rastreado o índice EUROSTOXX 600, o benchmark do mercado accionista utilizado neste estudo, aplicando critérios pré-estabelecidos a partir dos quais foi possível chegar a uma carteira de acções, utilizando os pressupostos do Modelo de Índice Único (MIU). Por fim, tanto o portfolio original como o que foi calculado, foram avaliados em função dos respectivos rácios de Sortino.
The Insurance Industry has many particularities, but probably one of the most important is the uncertainty regarding future cash flows, due to the unpredictability nature of future catastrophes or illnesses, in the case of health insurance. Nonetheless, insurers try to manage risk, among others, by using Asset-Liability Management (ALM) techniques, which rely mainly on future cash flow matching between assets and liabilities, according to the company's expected future responsibilities. However, as liabilities are difficult to predict in an accurate way, indexing assets to the liabilities' maturities can create a mismatch should unforeseen events occur and claims costs develop worse than expected. As such, this study aims an alternative approach to portfolio selection: by establishing a reasonable floor value to the funding ratio, it tries to monetize the surplus funds to achieve greater returns which can be used as buffers in periods with higher loss ratios, while attempting to find an equilibrium asset mix not to penalize the company?s capital requirements under the Solvency II Directive. For this purpose, the EUROSTOXX 600, the stock benchmark used in this study, was screened using specified criteria and from which a portfolio of stocks was chosen under the Single Index Model (SIM) assumptions. Lastly, the current and the new portfolio were measured against each other using the respective Sortino ratios.

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Piccoli, Pedro Guilherme Ribeiro. "Avaliação de carteiras de investimeno (i.e. investimento) em mercados de baixa eficiência :um estudo comparativo entre o índice de sharpe e o índice de sortino / Pedro Guilherme Ribeiro Piccoli ; orientador, Wesley Vieira da Silva." reponame:Biblioteca Digital de Teses e Dissertações da PUC_PR, 2010. http://www.biblioteca.pucpr.br/tede/tde_busca/arquivo.php?codArquivo=1895.

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Dissertação (mestrado) - Pontifícia Universidade Católica do Paraná, Curitiba, 2010
Bibliografia: f.93-100
A Hipótese dos Mercados Eficientes concebida por Fama (1970) defende a eficiência do mercado financeiro afirmando que o investidor é racional, bem informado e maximizador da utilidade esperada. O aparecimento de fenômenos contrários a esse comportamento r
The Efficient Market Hypothesis (EMH) proposed by Fama (1970) defends the efficiency of financial market asserting that the investor is rational, well informed and maximizes the utility expected. The arise of phenomena contradicting this market?s rational

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Brand, Wilhelmine Helena. "Evaluation of US and European hedge funds and associated international markets : a risk-performance measure approach / Wilhelmine Helana Brand." Thesis, North West University, 2014. http://hdl.handle.net/10394/13055.

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The 2007–2009 financial crisis led to a decrease in consumer and investor confidence worldwide (SARB, 2008:2). Along with the weakened business sentiment and consumer demand, tightened funding conditions in financial markets, increased inflationary pressures, and declining global manufacturing activities, the world economic recession that followed the collapse of the world financial sector led to an estimated wealth destruction of approximately US$50 trillion (SARB, 2008:2; Aisen & Franken, 2010:3; Karunanayake et al., 2010). Apart from this estimate, the International Monetary Fund (IMF) also projected that the global bank balance sheets in advanced countries suffered losses of approximately US$4 trillion during the period 2009–2010 (Aisen & Franken, 2010:3). As a result, investors have become more risk-adverse (Guiso et al., 2013:1), and the consequences of the financial crisis, made insurable profitable investment decisions extremely difficult as market volatility tends to increase during crises periods (Karunanayake et al., 2010; Schwert, 1989:83). With the financial environment in distress, some fund managers consider equities as the preferred asset class to protect the purchasing power of their clients (Ivan, 2013). However, the studies of Ennis and Sebastian (2003) and Nicholas (2004) found evidence that hedge funds will outperform equity markets during a downswing in financial markets. In addition, hedge funds are considered market-neutral due to these investment funds’ unrestricted investment flexibility and more efficient market timing abilities (Ennis & Sebastian, 2003). Hedge funds are also considered to be more unconventional assets for improving portfolio diversification (Lamm, 1999:87), where the variation of investment strategies available in a hedge fund has the ability to satisfy investors with several different risk preferences (Shin, 2012). Still, a number of previous studies have debated conflicting evidence regarding the performance of hedge funds and the persistence in outperforming other markets. This led to the objective of this study; to evaluate the risk-adjusted performance of US and EU hedge funds compared to the associated world equity markets over the 2007–2009 financial crisis. The evidence from this study confirmed the dominance of hedge funds over the CAC 40, DAX, S&P 500 and Dow Jones, from 2004 to 2011, emphasising that the performance of the US and EU hedge funds would overshadow a normal buy-and-hold strategy on the world equity markets under investigation. Overall, the Sharpe-, Sortino-, Jensen’s alpha-, Treynor- and Calmar ratios illustrated that US hedge funds outperformed both EU hedge funds and the associated equity markets over this period. The presence of non-normality among the return distributions led to the use of the Omega ratio as the proper benchmark, which also confirmed the outperformance of US hedge funds over EU hedge funds and associated world equity markets.
MCom (Risk Management), North-West University, Vaal Triangle Campus, 2014

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Benson, Jonathan. "An epistemic theory of deliberative democracy." Thesis, University of Manchester, 2019. https://www.research.manchester.ac.uk/portal/en/theses/an-epistemic-theory-of-deliberative-democracy(6583716a-470d-4b9e-b80e-44a1e71a4ff7).html.

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Democracy has been encountering an increasing number of critics. Whether it comes from a sympathy for autocrats, free-markets, or the more knowledgeable, this increasing democratic scepticism often takes an epistemic form. Democracy's critics argue that democratic procedures and institutions are unlikely to make good decisions or produce good outcomes in terms of justice or the common good, and should, therefore, be restricted if not completely rejected in favour of its more able alternatives. In the face of such scepticism, this thesis develops an epistemic theory of deliberative democracy. This theory has two principal aims. The first is to analyse and define the epistemic properties of deliberative democracy, and the second is to clarify the possible role epistemic values can play in a wider justification of democratic rule. In accordance with the first, the thesis analyses the ability of deliberative democratic institutions to make good or correct decisions in comparison to a broad range of prominent alternatives. These include traditional rivals such as autocracy and aristocracy, but also more modern and less considered alternatives such as free-markets, limited epistocracy and forms of technical calculation. Through these comparisons, it is argued that we have no good or clear epistemic reason to reject democracy. Deliberative democracy is found to be epistemically superior to many of its alternatives and epistemically equivalent to even its best competitors. The thesis, therefore, mounts a strong reply to democracy's epistemic sceptics. The analysis, however, also helps clarify which form of deliberative democracy is epistemically most valuable, pointing to the value systems approaches which give a prominent role to direct citizen deliberation. The epistemic theory of deliberative democracy also aims to clarify what role epistemic values can play in a wider justification of democratic rule. The thesis argues that deliberative democracy is epistemically superior to many of its rivals and no worse epistemically than even its best alternatives. This suggests that although epistemic values cannot mount a stand-alone defence of democracy, democrats would only be required to defend very weak non-epistemic values to produce a mixed justification. Far from being 'rule by the incompetent many' and therefore highly reliant on procedural values, the thesis will demonstrate that epistemic values can carry significant weight in an argument for democratic rule.

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Silvestre, Bruna Filipa Afonso. "Principais determinantes da fidelização do consumidor no retalho de calçado : um estudo exploratório." Master's thesis, Instituto Superior de Economia e Gestão, 2020. http://hdl.handle.net/10400.5/20659.

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Mestrado em Marketing
O setor de retalho tem registado alterações profundas. A concorrência intensificou-se, quer por parte de empresas nacionais, quer de empresas estrangeiras. Assim, os retalhistas devem diferenciar-se da concorrência e conhecer melhor as necessidades dos consumidores. A vantagem competitiva do retalhista pode derivar da sua atuação a nível de sortido de produto, preço, qualidade de serviço e atributos da loja. Se o retalhista satisfizer as necessidades do seu target nesses atributos pode conseguir níveis mais elevados de satisfação e lealdade (Dabholkar, Thorpe & Rentz, 1996). O principal objetivo desta investigação foi avaliar os principais determinantes da fidelização do consumidor no retalho de calçado. Para tal, desenvolveu-se um estudo qualitativo com uma amostra não probabilística, por conveniência. Foram realizadas seis entrevistas em profundidade com o intuito de aprofundar o entendimento sobre como os atributos investigados podem ser relevantes para entender a satisfação e a lealdade. O estudo adotou uma abordagem interpretativista, tendo os resultados evidenciado como principais determinantes o sortido do produto, o preço, a qualidade de serviço e a lealdade.
The retail sector has undergone profound changes. Competition has intensified, both by domestic and foreign companies. Thus, retailers must differentiate themselves from the competition and better understand the needs of consumers. The retailer's competitive advantage may derive from its performance in terms of product assortment, price, service quality and store attributes. If the retailer meets the needs of its target in these attributes, it can achieve higher levels of satisfaction and loyalty (Dabholkar, Thorpe & Rentz, 1996). The main objective of this investigation was to evaluate the main determinants of consumer loyalty in the footwear retail. To this end, a qualitative study was developed with a non-probabilistic sample, for convenience. Six in-depth interviews were conducted in order to deepen the understanding of how the investigated attributes can be relevant to understand satisfaction and loyalty. The study adopted an interpretive approach, with the results showing the product assortment, price, service quality and loyalty as the main determinants.
info:eu-repo/semantics/publishedVersion

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Sundqvist, Daniel. "Hedge Funds in a Traditional Portfolio : A Quantitative Case Study Made on the Swedish Hedge Fund Market." Thesis, Umeå University, Umeå School of Business, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-23363.

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Hedge funds are a debated subject in today’s financial industry. During 2008, despite hedge funds absolute return target, the global hedge fund industry showed a negative performance whilst the Swedish hedge fund market performed relatively well in comparison. Many studies have been made investigating the effect on incorporating hedge funds in a traditional portfolio though none focused separately on the Swedish market. In a global perspective it is quite easy to invest in hedge fund portfolios due to the existence of investable indices. To invest on the Swedish market is a more complex matter. SIX Harcourt HFXS Index is a Swedish hedge fund index representing the Swedish hedge fund market though it is not investable. Hence it would be interesting to see if it is possible to create an investable version of SIX Harcourt HFXS. When creating an investable index, several administrative costs will arise and in order to cover these costs it would be interesting to see whether or not it possible to optimize SIX Harcourt HFXS Index in purpose of achieving a outperformance which could cover any administrative costs for setting up the investable version. Also, since the optimized version must replicate the standard SIX Harcourt HFXS Index it must maintain a certain level of correlation.

This thesis, which is based on a positivistic epistemology, is built upon a quantitative case study where SIX Harcourt HFXS Index is optimized in purpose of achieving an outperformance in terms of the risk-adjusted return. The optimization uses an adjusted mean-variance methodology and is limited to a maintained correlation above 0,9 towards the standard SIX Harcourt HFXS Index. The optimization is created through the use of an Excel application created by Harcourt Investment Consulting.

Also, based on the outperformance by Swedish hedge funds compared to global hedge funds, this study aims to show the effect of incorporating Swedish hedge funds in a traditional portfolio consisting of equities and bonds. This effect is analyzed by the use of several performance-and risk measures.

The study shows that it is possible to optimize SIX Harcourt HFXS Index and produce an outperformance of approximately 1,5% per annum with a maintained correlation above 0,9. It also shows that the effect of incorporating Swedish hedge funds to a traditional portfolio is positive in regards to both risk and return.

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Egea, Fernando Galvão. "Análise de desempenho dos fundos de investimento em ações brasileiros no período de Janeiro de 1997 a outubro de 2006." reponame:Repositório Institucional do FGV, 2008. http://hdl.handle.net/10438/3814.

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Made available in DSpace on 2009-11-18T19:01:04Z (GMT). No. of bitstreams: 1 ACF189.pdf: 1048760 bytes, checksum: 6056ed3b4b46f5ee586cfd69fdbc22bf (MD5) Previous issue date: 2007
This research evaluated the quality of the management of Brazilian stock funds on the period from January 1997 to October 2006. The analysis was based on the Modern Portfolio Theory measures of performance. In addition, this research evaluated the relevance of the performance measures The sample with 21 funds was extracted from the 126 largest Brasilian stock options funds because they were the only with quotas on the whole period. The monthly mean rate of return and the following indexes were calculated: total return, mean monthly return, Jensen Index, Treynor Index, Sharpe Index, Sortino Index, Market Timing and the Mean Quadratic Error. The initial analysis showed that the funds in the sample had different objectives and limitations. To make valuable comparisons, the ANBID (National Association of Investment Banks) categories were used to classify the funds. The measured results were ranked. The positions of the funds on the rankings based on the mean monthly return and the indexes of Jensen, Treynor, Sortino and Sharpe were similar. All of the ten ACTIVE funds of this research were above the benchmark (IBOVESPA index) in the measures above. Based on the CAPM, the managers of these funds got superior performance because they might have compiled the available information in a superior way. The six funds belonging to the ANBID classification of INDEXED got the first six positions in the ranking based on the Mean Quadratic Error. None of the researched funds have shown market timing skills to move the beta of their portfolios in the right direction to take the benefit of the market movements, at the significance level of 5%.
Esta pesquisa analisou a qualidade da gestão dos fundos de ações brasileiros através da análise do desempenho obtido por eles no período de janeiro de 1997 a outubro de 2006. A análise foi feita com base na Teoria Moderna das Carteiras. Ela analisou também a aplicação dos critérios de desempenho na medida do desempenho deles. A amostra de 21 fundos foi selecionada do universo composto pelos 126 maiores fundos de aços Brasileiros. Os seguintes critérios de desempenho foram calculados a partir das cotas mensais dos fundos: retorno absoluto, retorno Médio Mensal, Índice de Jensen, Índice de Treynor, Índice de Sharpe, Índice de Sortino, capacidade de prever os movimentos do mercad (Market Timing) e o Erro Quadrático Médio. A análise dos dados começou com a classificação dos fundos de acordo com os tipos ANBID, pois os objetivos e as limitações dos fundos da amostra não eram homogêneos. Posteriormente, os resultados obtidos nas medições de desempenho foram ordenados em rankings e analisados. Dez dos 21 fundos da amostra, todos ativos, tiveram desempenho superior ao mercado (representado pelo IBOVESPA) nos critérios do retorno médio mensal e nos Índices de Jensen, Treynor, Sortino e Sharpe. De acordo com o CAPM, esses gestores devem ter compilado as informações disponíveis de uma forma superior, e por isso, conseguiram um desempenho superior ao mercado. Os seis fundos da categoria IBOVESPA INDEXADO ficaram com as seis primeiras posições na calcificação pelo Erro Quadrático Médio, o que já era esperado, pois a missão desses fundos é reproduzir o retorno do índice. Nenhum dos gestores dos 21 fundos demonstrou ter capacidade de prever o movimento do mercado (Market Timing), ao nível de significância de 5%, e movimentar o beta de sua carteira na direção correta a fim de maximizar o retorno do investidor.

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Mandon, Pierre. "New empirics on transdisciplinary political economics : essays on the economics of democratic modalities." Thesis, Université Clermont Auvergne‎ (2017-2020), 2017. http://www.theses.fr/2017CLFAD021.

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L'objet de la présente thèse concerne l'étude de l'impact économique de trois modalités démocratiques, à savoir (i) l'agenda électoral, (ii) l'affiliation partisane des dirigeants en place dans un cadre de multipartisme, et (iii) les changements de gouvernance constitutionnellement définis. Afin d'introduire notre étude, nous décrivons la relation qui existe entre les modalités démocratiques et la démocratie directe d'une part et la politique budgétaire d'autre part, aux Etats-Unis sur la période 1790-2014 dans l'Introduction Générale. Dans le Chapitre 2 nous étudions l'effet authentique et potentiellement néfaste des cycles politico-budgétaires. Notre méta-analyse suggère que les dirigeants nationaux manipulent effectivement le budget dans un but de réélection mais l'ampleur du phénomène est largement exagérée par la littérature. Toutefois, le biais de publication mis en lumière s'est significativement réduit lors des 25 dernières années de recherches. Dans le Chapitre 3 nous étudions comment l'affiliation partisane des gouverneurs américains affecte le statut de pauvreté des immigrants, aux Etats-Unis, sur la période 1994-2014. Pour ce faire, nous comparons le niveau de pauvreté des immigrants dans les Etats gouvernés par les Démocrates au niveau de pauvreté des immigrants constaté dans les Etats gouvernés par les Républicains. En accord avec la littérature sur l'affiliation partisane, nous trouvons que les immigrants ont plus d'opportunités de sortir de la pauvreté sous les Démocrates que sous les Républicains. Une analyse formelle de médiation révèle que nos résultats empiriques sont médiatisés par un meilleur accès au marché du travail et possiblement de meilleures rétributions du travail, pour les immigrants. Dans le Chapitre 4 nous cherchons à vérifier l'évolution des notations souveraines lors des périodes d'inauguration des nouveaux dirigeants sur un échantillon de 18 pays d'Amérique Latine et des Caraïbes ayant des systèmes présidentiels. A partir de données de panel journalières s'étendant du 1er janvier 1994 au 31 décembre 2014, nous trouvons que les notations souveraines sont de meilleure qualité durant les périodes d'inauguration anticipées comparées aux autres périodes d'inauguration. En outre, nos résultats montrent que durant ces périodes d'inauguration anticipées, les notations sont encore meilleures lorsque le dirigeant entrant (i) est économiquement de droite, (ii) dispose d'un diplôme universitaire d'un pays de l'OCDE, (iii) a un parcours professionnel traditionnel, (iv) a une approche non populiste, et (v) dispose de marges électorales de victoire importantes. Il apparaît également un biais de genre potentiel à la faveur des nouveaux dirigeants de sexe masculin. En prenant avantage d'un modèle de durée et de régressions de Cox -- modèle à risque proportionnel, nous mettons en lumière que les périodes d'inauguration des dirigeants affectent également la probabilité instantanée de dégradation des notations souveraines. Enfin, dans la Conclusion Générale nous explorons les racines des pensées antisystèmes en Occident, puis nous discutons des avantages et inconvénients de quelques formes alternatives de démocratie, à savoir (i) la démocratie directe, (ii) le tirage au sort, et (iii) le développement participatif comme bien public. Finalement, nous explorons les controverses concernant les formes alternatives de démocratie sur l'agora virtuelle que constitue Twitter
The aim of the present dissertation is to empirically investigate the economic impact of three democratic modalities, namely (i) the electoral agenda; (ii) the partisan affiliation of incumbents in a multipartism framework; and (iii) constitutionally defined leadership changes. To introduce the scope of the dissertation we describe the democratic modalities and direct democracy behind the U.S. fiscal policy from 1790 to 2014, in the General Introduction.In Chapter 2 we study the genuine detrimental effect of political budget cycles. Our meta-analysis suggests that national leaders do manipulate fiscal tools in order to be re-elected, but to an extent that is significantly exaggerated in the literature. The publication selection bias highlighted has nonetheless been reduced during the past 25 years of research. In Chapter 3 we investigate how governors' partisan affiliation affects the poverty status of immigrants to the U.S for the period 1994-2014. To this end, we compare the poverty outcomes of immigrants in states ruled by Democratic governors relative to the outcomes for those in states ruled by Republican governors. Consistent with the literature on partisan affiliation, we find that immigrants are more likely to get out of poverty in states with Democratic governors than states with Republican governors. A formal mediation analysis reveals that the empirical results are mediated through better access to the labor market and possibly through higher wages and labor earnings for immigrants. In Chapter 4 we assess whether sovereign credit ratings change during the inauguration periods of incoming leaders, on a sample of 18 Latin American and Caribbean countries with presidential systems. Building on a daily panel dataset covering the period from January 1, 1994 to December 31, 2014, we find that credit ratings are better during anticipated inauguration periods compared to other inauguration periods. Moreover, our results reveal that, during anticipated inauguration periods, incoming leaders with (i) an economically right-wing orientation; (ii) an OECD college degree; (iii) a traditional professional background; (iv) a non-populist approach; and (v) large electoral margins of victory are associated to even better ratings. There also appears to be a potential gender bias effect in favor of male incoming leaders. Last but not least, the quality of the credit rating also matters. In the General Conclusion we explore the roots of anti-systemism in the West, then we discuss some alternative forms of democracy, and we explore the controversies regarding the alternative forms of democracy on the virtual \emph{agora} of Twitter

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DI, VINCENZO MARKO. "Diritti, poteri, conflitti. Strumenti giuridici per le tecniche decisionali nel diritto romano (pubblico e privato)." Doctoral thesis, 2019. http://hdl.handle.net/11573/1563108.

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Viene operata una selezione tra tutte quelle situazioni giuridiche coinvolgenti poteri (ius publicum) e diritti (ius privatum), che possono essere tra loro diversi oppure eguali, ma, in quest’ultimo caso, propri di più ʿcontitolariʾ; in ogni caso, singolarmente presi, diritti e poteri comunque idonei a generare un ʿconflittoʾ. Con detto termine, molto in voga nel gergo costituzionale, si identificano tutti quei veri e propri ʿscontriʾ tra poteri, che manifestano momenti e fatti giuridici bisognosi di una risoluzione per evitare la paralisi; se così intese, tale situazioni, non possono che verificarsi e presentarsi, con le medesime problematicità, anche nel diritto privato. Sorge dunque la necessità di soluzioni - nella veste di ‘tecniche decisionali’ e ‘strumenti giuridici’ - per evitare che il ʿconflittoʾ si crei (laddove questo possa essere quindi considerato come ʿpotenzialeʾ) ovvero per dirimere un ʿconflittoʾ già sorto (che può ben definirisi come ʿattualeʾ). Si pensi esemplarmente per il primo caso alla comproprietà, laddove lo ius prohibendi si pone come strumento per il socio di impedire il sorgere di un effetto giuridico irreparabile; per il secondo si pensi invece alla intercessio, ove il tribuno, appurata la lesione, e ravvisata dunque la ʿconflittualitàʾ con gli interessi della pars populi che egli tutela, oppone con esito favorevole la sacrosanctitas agli auspicia. E talvolta la soluzione può esser la medesima per diversi e distanti ʿconflittiʾ, e nello ius publicum e nello ius privatum (si pensi, tra tutte, alla sortitio o allo stesso ius prohibendi, ai criteri della unanimità o della maggioranza): ciò è ulteriore riprova di come diritto pubblico e privato non siano altro che due semplici, ma diverse, posizioni di studio (I. 1, 1, 4; D. 1, 1, 1, 2). Si chiarisce infine che il ‘conflitto’ non deve considerarsi sotto una prospettiva ʿnegativaʾ, verso un inesorabile rallentamento del sistema, ma come elemento imprescindibile per la crescita della civitas, in un sistema giuridico-religioso ove il rapporto tra ius e fas rappresenta una solida ‘garanzia costituzionale’.

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Pai, Tzu-Hsuan, and 白子玄. "Heuristics for Railway Booking System based on a Reservation-Sortition Scheme." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/94727857751158393059.

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碩士
國立交通大學
管理學院運輸物流學程
104
East region of Formosa mainly depends on railway outbound to another area. Because of these two reasons, the Taiwan Railways Administration (TRA) operating the new Tze-Chiang Limited Express(Puyuma and Taroko) with non-standing seats in the most recent year and the number of tourists has been increasing rapidly and booming, the growth of the amount in public transportation supply are far less than the demand quantity. Its cause the passenger complains about the service satisfaction of the booking system. This study aims to offer another mechanism to replace the current FIFO (First-in First-out) booking and dispatching rule. This architecture collects all order requirement before drawing of lots to sale tickets at the sometime point. Under the process of the reservation sortition scheme, the study will propose optimized algorithms to implement ticket assigned procedure in my simulated booking system. And proposed three new creative functions, divide route into several unsold segment and combine it with entire journey, split group booking tickets by non-adjacent seat, deferred the order of non-success buying ticket into next train, to increase ticket sales results matchmaking success rate, so the utilization of the train seats can reach highest. According to statistical information from TRA website, the parameters as the traveling data generated by passenger’s entry and exit at each station on holiday, the ranking level of stopping station, the area passed by train, the distance of the OD station. My study using Monte Carlo simulation theory to generate demand data by static discrete and random approach to validation the possibility and effectiveness of proposed algorithms. With constructing holiday booking patterns as a simple simulation model to verify and analysis the priority and distance algorithms if it could make expected result in operational efficiency and utilization of the seats.

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Shunmugan, Serena. "An investigation of plasmodium falciparum sortilin in trafficking of invasion proteins of the human malaria parasite." Thesis, 2018. https://hdl.handle.net/10539/26867.

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Malaria is arguably one of the most overwhelming infectious diseases throughout the world's existence. The most virulent parasite, Plasmodium falciparum, has a redundancy of invasion proteins, allowing it to switch between different receptors on the host red blood cell. These invasion proteins are stored in the apical organelles, the rhoptries and micronemes, but very little is known about how newly synthesized proteins are transported to these organelles. The hypothesis in this study was that a common protein is involved in trafficking invasion proteins from the trans-Golgi network and PfSORTILIN was investigated as a potential escorter protein. The CCys domain of PfMAEBL, a rhoptry protein, and the prodomain of PfAMA-l, a microneme protein, have been implicated in trafficking to the apical organelles. These domains and the VPS 10 domain of PfSORTILIN were cloned into expression vectors encoding a GST- or Histag. Recombinant proteins were expressed in E. coli and purified by affinity chromatography on glutathione- or Ni-particles. In vitro binding assays were performed, which showed that PfSORTILIN VPS 10 bound to PfMAEBL ccys but not to the PfAMA-1 prodomain, suggesting that PfSORTILIN is a rhoptry protein escorter and is not involved in microneme trafficking. To identify novel binding partners of PfSORTILIN VPS 10, the protein was biopanned against a P. falciparum phage display library. No binding partners were identified, most likely because the library is not schizont-stage specific, which is when PfSORTILIN and invasion proteins are predominantly expressed. The results from this study were integrated with other studies and a trafficking model for PfMAEBL was proposed. This study enhances our knowledge of trafficking pathways and suggests that PfSORTILIN may serve as a common rhoptry protein escorter.
MT 2019

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Salgado, Flávio Pereira. "Análise do processo de definição do sortido de produtos numa empresa de retalho do vestuário." Master's thesis, 2015. http://hdl.handle.net/1822/37144.

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Dissertação de mestrado integrado em Engenharia e Gestão Industrial
O projeto de investigação, apresentado neste documento, foi realizado numa empresa do setor de retalho de vestuário. A empresa alvo do estudo trabalha essencialmente segundo a estratégia tradicional de duas coleções anuais. No entanto, é cada vez mais importante a aplicação da estratégia de Fast-Fashion num mercado tão competitivo pelo que o processo de definição do sortido de produtos assume um papel fundamental. Por essa razão, o principal objetivo deste trabalho foi analisar o processo de definição do sortido de produtos e apresentar propostas que visavam o aumento da sua eficiência. Numa primeira fase procede-se à descrição e justificação da metodologia de investigação, o estudo de caso, procedendo-se, posteriormente, a um enquadramento científico do projeto através da revisão bibliográfica, revelando a ausência de estudos relevantes sobre a importância da informação que deve estar na base do processo e da integração dos diversos departamentos para o aumento da eficiência do mesmo. Numa segunda fase, procede-se à apresentação da empresa, da sua estrutura, dos seus produtos e à descrição do problema que esteve na origem de toda a investigação. Posteriormente, apresenta-se o processo de definição do sortido de produtos da empresa em estudo e identificam-se os principais problemas que levam a uma excessiva quantidade de desperdícios no fim de cada coleção. Detetadas e descritas as principais causas dos problemas, procede-se à apresentação e discussão de propostas de melhoria. Os resultados deste caso de estudo mostram que este processo está ao encargo da experiência e expetativas de apenas um departamento, ignorando as contribuições e a importância de outros departamentos na definição do sortido de produtos. Este documento apresenta as consequências desta situação, não apenas no processo referido, mas também no funcionamento e nos resultados da empresa como um todo. Para resolver este problema, é apresentado um conjunto de propostas focadas essencialmente nos documentos e informação utilizada no processo assim como na organização das lojas com o objetivo de aumentar a sua eficiência e integrar os vários departamentos num processo essencial para o sucesso de uma empresa de retalho de vestuário.
This research project focuses on an apparel retail company. This particular company mainly works in the traditional fashion system, with two annual collections. However, in such a competitive market the integration of Fast-Fashion system is imperative. The Product Assortment process is essential for the traditional system but vital for the Fast-Fashion one. The main objective was to analyse this process and present proposals that would allow the company to improve the efficiency of the process mentioned. In particular, it would allow to reduce the waste or, in other words, the amount of product left over at the end of the collections. Initially, we present the description and justification of the investigation methodology as case study. Furthermore, we proceed with the literature review in order to frame the scientific level of the investigation project. It allowed us to understand the absence of studies on the importance of an effective relationship between departments for an efficient product assortment. In a second stage of the research project the company, their products and the problem that is the reason of this study are presented. This study present the product assortment process of this particular company and try to identify the main problems that leave the company to have an excessive amount of waste at the end of each collection. Once detected and descripted the main causes of the problem, we proceed to the presentation and discussion of proposals to improve the process efficiency and foster the integration of several departments, instead of just one as it is done today. This should be seen as a process that seek for continuous improvement because is the only way to survive in such a competitive market. The results of the case study showed that the studied company focuses this process in the experience and expectations of only one department, ignoring the contributions and importance of other departments for this particular process. This document shows the consequences of this situation in the process and in the company results. To solve this problem, it is presented a set of proposals that aims to improve the efficiency of the process and the final results of each collection. The proposals mainly concerned with the documents used as well as the organization of the stores in order to make this process more efficient and integrate various departments in a process which is essential for the success of the company.

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Kubíková, Kateřina. "Demokracie a losování: historická a teoretická perspektiva." Master's thesis, 2019. http://www.nusl.cz/ntk/nusl-405823.

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The thesis deals with the historical perspective of the sortition in the period of the Athenian democracy and the Italian city republics of the Middle Ages and the Renaissance. The thesis tries to reveal the potential of the sortition and the reasons why the sortition was used as a primary tool for choosing citizens for public offices. The objective of the thesis is to find the potential of the sortition for contemporary liberal democracy. The thesis follows two historical cases in which the sortition was viewed as a democratic (or civil) instrument that breaks personal relations and limits the power of elite groups in the society. In this sense, the sortition should help to widen the civic participation in public affairs, to provide equal and fair distribution of public offices within the society, and to prevent corruption and factionalism.

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Chen, Hung-Hsin, and 陳紘昕. "Genetic Programming for the Investment of the Mutual Fund with Sortino Ratio and Mean Variance Model." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/90090776257976174693.

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碩士
國立中山大學
資訊工程學系研究所
98
In this thesis, we propose two genetic-programming-based models that improve the trading strategies for mutual funds. These two models can help investors get returns and reduce risks. The first model increases the return by selecting funds with high Sortino ratios and allocates the capital equally, achieving the best annualized return. The second model also selects funds with high Sortino ratios, but reduces the risk by allocating the capital with the mean variance model. Most importantly, our model utilizes the genetic programming to generate feasible trading strategies to gain return, which is suitable for the market that changes anytime. To verify our models, we simulate the investment for mutual funds from January 1999 to December 2009 (11 years in total). The experimental results show that our first model can gain return from 2004/1/1 to 2008/12/31, achieving the best annualized return 9.11%, which is better than the annualized return 6.89% of previous approaches. In addition, our second model with smaller downside volatility can achieve almost the same return as previous results.

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Parker, Joel Matthew. "Randomness and legitimacy in selecting democratic representatives." Thesis, 2011. http://hdl.handle.net/2152/ETD-UT-2011-12-4923.

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The addition of random selection to our arsenal of methods for selecting political officials would enhance performance against norms of representative democracy. I employ historical and analytic methods to explore the nature of sortition and its relation to political equality, rational decision-making, and legitimate representation. Sortition both expresses a democratic commitment to political equality and facilitates improved performance under this democratic norm. It can be rational to eschew reasons in the process of selecting political officials, and decision-making bodies chosen randomly can be expected to make good decisions. I also address concerns stemming from representative norms, surrounding random selection of officials, arguing that random selection can enhance the resemblance and responsiveness of representatives. Finally, I detail some possibilities for institutional arrangements that would deliver the benefits of sortition while addressing the challenges it presents.
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Gao, Fangfang. "ProNGF/NGF, their receptors and nerves in human cancers." Thesis, 2020. http://hdl.handle.net/1959.13/1423270.

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Research Doctorate - Doctor of Philosophy (PhD)
Nerve infiltration is emerging as an important process in the tumour microenvironment. Cancer cells release neurotrophic factors that are capable of stimulating nerve infiltration and are increasingly regarded as potential therapeutic targets in oncology. More specifically in this study, nerve growth factor (NGF), its precursor (proNGF) and their receptors that include the neurotrophic tyrosine kinase receptor (TrkA), the common neurotrophin receptor (p75NTR) and the proNGF receptor sortilin, were examined in lung, pancreatic and esophageal cancers. Moreover, we have also investigated how endoplasmic reticulum (ER) stress facilitates neural infiltration during cancer progression. The aims of this thesis were to develop a greater understanding of the role of nerves and neurotrophic growth factors in influencing cancer progression and dissemination. In lung cancers, NGF and its receptor TrkA were found increased in squamous cell carcinoma compared to other malignant histological subtypes and normal lung. ProNGF was increased in both squamous cell carcinoma and adenocarcinoma while sortilin was higher in adenocarcinoma and small cell carcinoma. Nerves in the tumour microenvironment were negative for NGF, proNGF, TrkA, p75NTR and sortilin. This study was published in Scientific Reports. In pancreatic ductal adenocarcinoma (PDAC), sortilin expression was higher in cancer cells compared to normal pancreatic ductal epithelial cells, as demonstrated by both Western blot and mass spectrometry. The increased sortilin level in pancreatic cancer tissues was confirmed by immunohistochemistry in a cohort of PDAC tissues. Sortilin inhibition through utilizing siRNA or pharmacological inhibitor AF38469 could strongly reduce pancreatic cancer cells adhesion and invasion while could not affect cell survival and proliferation. The inhibition of sortilin, however, decreased the phosphorylation level of the focal adhesion kinase (FAK) in Tyr925. This study was published in The American Journal of Pathology. Together, these data suggest the preferential therapeutic value of targeting the NGF-TrkA axis in squamous cell carcinomas of the lung and targeting sortilin in pancreatic adenocarcinomas. We have also investigated nerve infiltration in esophageal cancer tissues and found that the presence of nerves was significantly correlated to squamous cell carcinomas where TrkA was also overexpressed. Nerves were found to express TrkA and p75NTR and an association was observed between high production of NGF by cancer cells and the presence of nerves in the tumour microenvironment. In vitro, NGF production in esophageal cancer cells was demonstrated by Western blot and esophageal cancer cells were able to induce neurite outgrowth in the PC12 neuronal cells. By using anti-NGF blocking antibodies, we observed a reduced neurotrophic activity of esophageal cancer cells. These data demonstrate that innervation is a significant feature in esophageal cancers that may be driven by cancer cell-released NGF. This study was published in The American Journal of Pathology. Furthermore, in cancer cells of various origins, we reported that the release of pro-brain derived neurotrophic factor (proBDNF) by ER stressed-cancer cells, which was controlled by X-box-binding protein 1 (XBP1), induced ER stress in neurons and promoted neuronal outgrowth. Myc-mediated transcriptional upregulation of Egl-9 family hypoxia inducible factor 3 (Egln3) in neurons contributed to receiving ER stress signal and fostering neurite outgrowth. This final part of our study reveals the essential contribution of ER stress to tumour axonogenesis and is currently submitted for publication. Taken together, the work presented in this thesis has provided novel evidence for therapeutic targeting in carcinomas of the lung, pancreas and esophageal. We have highlighted the importance of proNGF/NGF and their receptors in cancers and the association with nerve infiltration, as well as the potential intervention of ER stress in tumour axonogenesis.

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Yuan, Libin. "A stretch of 17 amino acids in the prosaposin C-terminus is critical for its binding to sortilin and targeting to lysosomes." 2009. http://digitool.Library.McGill.CA:8881/R/?func=dbin-jump-full&object_id=92262.

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Humphreys, Mark. "Covered call trading strategies in the South African retail equity market." Thesis, 2015. http://hdl.handle.net/10539/17047.

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Thesis (M.M. (Finance & Investment))--University of the Witwatersrand, Faculty of Commerce, Law and Management, Graduate School of Business Administration, 2014.
The use of a Covered Call strategy has long been favoured by investors the world over for its potential to enhance yield in a long-only equity portfolio. There already exists a wealth of research examining the risk and return features and theories of this strategy. This paper aims to contribute to this debate by conducting research that is specific to the South African equity market and considered from the perspective of a retail investor, particularly by tracking the negative friction induced by transaction costs. It also seeks to answer the question of which Covered Call strategies provide the best risk-adjusted returns by pricing various expiry range and moneyness combinations over differing market trend phases during a 13-year period of trade on the JSE.

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Verlan, Inna. "The Role of Cardiotrophin-Like Cytokine Factor 1 on the Development of Atherosclerosis." Thèse, 2017. http://hdl.handle.net/1866/21386.

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Martins, Marta Isabel. "Segmentação dos pontos de venda: aplicação da segmentação à rede de lojas dos CTT - Correios de Portugal." Master's thesis, 2011. http://hdl.handle.net/10071/4876.

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A dissertação que se apresenta enquadra-se na problemática da gestão do sortido com base na identificação dos factores que determinam a segmentação dos pontos de venda, com enfoque nos produtos de retalho do sector postal. Para se proceder à segmentação teve-se por base informação referente à quantidade vendida de cada categoria de produto, sendo esta variável um indicador importante para se analisar as vendas de um produto, como tal, foi-lhe dada relevância ao longo de toda a investigação. Por outro lado, procura-se avaliar a importância da variável quantidade e de outros factores para diferentes categorias de produtos e segmentos de Lojas/Estações. Este estudo serve-se de um exemplo representativo de lojas que operam no sector postal português, pertencente a um dos principais operadores. Relativamente à metodologia adoptada nesta investigação, recorreu-se com base na informação disponibilizada pela empresa, à análise factorial, com o objectivo de representar ou descrever um número de variáveis iniciais a partir de um menor número de variáveis tendo em conta o elevado número de variáveis iniciais. De seguida aplica- -se a análise de agrupamento de forma a proceder à segmentação das Lojas/Estações, ou seja, efectuar a selecção dos segmentos de Lojas/Estações. Como resultado da análise factorial, foram extraídos 26 factores explicando 84% da variabilidade das 59 variáveis originais – quantidades vendidas de categorias de produtos. A partir das variáveis mais correlacionadas com estes factores efectua-se uma análise de agrupamento obtendo-se 6 grupos diferenciados de estações. Concluiu-se que as quantidades vendidas relativas às categorias de telecomunicações, temas temáticos (Religiosos, Futebol, Festivos, entre outros), Cheques ofertas e Livros de Desenvolvimento Pessoal são os factores mais determinantes para a segmentação. Esta análise adoptada, para se obter a segmentação, foi útil porque permitiu identificar grupos homogéneos de Lojas/Estações, facultando ao gestor informação útil para a definição de políticas direccionadas a estes grupos.
The present dissertation is set around assortment planning of the various products based in the identification of the sale points, with particular emphasis in the retail products of the postal sector. In order to proceed with segmentation, the information relating to the quantities sold was taken as a basis for each category of products, being this variable an important indicator for the analysis of sales of a product, and as such, it was given relevance throughout the investigation. On the other hand, it was sought to evaluate the importance of the variable quantity and of other factors for various categories of products and shop/post offices segments. This study was based on an example representative of shops, which operate in the Portuguese postal sector, belonging to one of the main operators. As regards the method adopted in this investigation, factor analysis was done on the basis of the information given by the company, with the objective to represent or describe a limited number of initial variables taken from a smaller number of variables taking into account the high number of initial variables, then we proceeded to do a cluster analysis, in order to segment the shops/post offices, that being, to select the shop/post office segments. As a result of factorial analysis, that being: from the 26 factors explaining 84% of variability of the original 59 variables – quantity sold for product categories. From the variables most correlated with these factors is carried out a cluster analysis resulting in 6 distinct groups of post offices. We may conclude that the quantities sold on the categories relating to telecommunications, which are theme related (religious, football, special occasions, others) prize checks and Personal Development Books are the most determinant factors for segmentation. This analysis, adopted to achieve segmentation was useful as it allowed the identification of homogeneous groups of shops/post offices, giving the managers useful information for the definition of policies directed at these groups.

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Horsch, André René. "How to launch an online retail business : the case of BECONVIDA." Master's thesis, 2020. http://hdl.handle.net/10400.14/31239.

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Motivated by the current development towards online retailing, the purpose of this dissertation is to give insights into the launch of BECONVIDA, the first online retail business of medicallyapproved food and non-food products specifically for pregnant women in Germany. When launching a business in the retail sector significant questions emerge. Is the target market large enough and is it likely to grow in the future? What does the competitive environment look like? What should the assortment in terms of breadth and depth look like and what product categories to include? To answer those questions this dissertation first examines the market concerning the current and future trends, the past and forecasted development of its size, and its competitive landscape. Next, the market segmentation of BECONVIDA’s potential customers revealed two attractive segments to be targeted. Then, this dissertation outlines how BECONVIDA can be positioned. Further, the evaluation of three different operating models showed that BECONVIDA will be launched as a traditional retail shop instead of a subscription model or a marketplace. Finally, the initial assortment structure and specific product lines for the launch of BECONVIDA are discussed. This dissertation approaches all questions building from the related literature, analysis of survey results, and interviews with three industry experts. As a result, this dissertation finally suggests an agenda for future research on a framework for launching online retail businesses, especially in light of the current digitization trend in the COVID-19 era.
Motivada pelo atual desenvolvimento da venda a retalho online, o objetivo desta dissertação é dar a conhecer o lançamento da BECONVIDA, o primeiro negócio de venda a retalho online de produtos alimentares e não alimentares aprovados medicamente, especificamente para mulheres grávidas na Alemanha. Ao lançar um negócio no sector do retalho, surgem questões significativas. O mercado alvo é suficientemente grande e é provável que venha a crescer no futuro? Qual é o ambiente competitivo? Que amplitude e profundidade deve ter a oferta por parte da empresa, e que categorias de produtos devem ser incluídas? Esta dissertação começa por examinar o mercado relativamente às tendências atuais e futuras, o desenvolvimento passado e previsto da sua dimensão e a sua paisagem competitiva. Seguidamente, os potenciais clientes da BECONVIDA são segmentados e os dois segmentos mais promissores são escolhidos como alvo. Em seguida, esta dissertação traça uma linha orientadora para o posicionamento da BECONVIDA. Além disso, são avaliados três modelos operacionais diferentes e esta dissertação defende o lançamento da BECONVIDA como um retalhista tradicional. Por último, é discutida a estrutura inicial do conjunto de produtos e as linhas de produtos específicas para o lançamento da BECONVIDA. Esta dissertação aborda todas as questões colocadas a partir da literatura relacionada, análise dos resultados do inquérito e entrevistas com três peritos do sector. Como resultado, esta dissertação sugere uma agenda de investigação futura sobre um quadro para o lançamento de negócios de retalho online, especialmente à luz da atual tendência para a digitalização na era COVID-19.

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Jules, Felix. "Fonction de la protéine Ceroid lipofuscinosis neuronal 5 (CLN5) dans le tri et le recyclage à l’endosome." Thèse, 2015. http://hdl.handle.net/1866/13029.

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Le tri et le transport efficace des hydrolases acides vers le lysosome jouent un rôle critique pour la fonction des cellules. Plus de 50 maladies humaines sont dues à des mutations des enzymes lysosomales, des protéines régulant des processus-clés du transport vers le lysosome ou des enzymes effectuant des modifications posttraductionnelles importantes pour la fonction du lysosome. L’objectif de cette thèse est d’identifier des protéines et des mécanismes permettant à la cellule de réguler le transport des enzymes vers le lysosome. Nous avons formulé l’hypothèse que des protéines mutées dans des maladies lysosomales et dont les fonctions étaient inconnues pouvaient jouer un rôle dans le transport vers le lysosome. Les céroïdes-lipofuscinoses neuronales forment une famille de maladies lysosomales rares mais sont aussi les maladies neurodégénératives infantiles les plus fréquentes. Plusieurs gènes impliqués dans les NCL encodent des protéines aux fonctions inconnues. Les travaux présentés dans cette thèse ont identifié la protéine « ceroid lipofuscinosis neuronal-5 » (CLN5) qui est localisée à l’endosome et au lysosome comme élément nécessaire au recrutement et à l’activation de rab7. Rab7 est une protéine Rab-clé qui contrôle le trafic à l’endosome tardif. Cette petite GTPase est impliquée dans le recrutement de retromer, un complexe protéique qui régule le trafic de l’endosome vers l’appareil de Golgi des récepteurs de tri lysosomal comme sortilin et le récepteur du mannose-6-phosphate. Dans les cellules où CLN5 est déplété, les récepteurs de tri lysosomal sont moins recyclés plus rapidement dégradés. En utilisant des expériences de photomarquage nous avons aussi pu démontrer que Rab7 est moins activées en l’absence de CLN5. Pour exécuter leur fonction les protéines rabs doivent être recrutée à la membrane et activées par l’échange d’une molécule de GDP pour une molécule de GTP. Le recrutement des Rabs à la membrane nécessite une modification posttraductionnelle lipidique pour être facilités. En utilisant un modèle de levures nous avons démontré que l’homologue de Rab7, Ypt7 est palmitoylée. Nous avons aussi démontré que la palmitoyltransférase Swif1 est nécessaire au recrutement de Ypt7 à la membrane. Nous avons aussi remarqué que les sous- unités de retromer chez la levure sont moins recrutées lorsque les palmitoyltransférases sont déplétées. Dans les cellules de mammifères nous avons démontré que Rab7 est également palmitoylé et que cette palmitoylation est possiblement effectuée par les palmitoyltransférases DHHC1 et DHHC8. La palmitoylation de Rab7 a lieu sur les cystéines en C-terminal qui sont nécessaires au recrutement membranaire et qui auparavant étaient uniquement décrites comme prénylées. En utilisant la méthode de « click chemistry » nous avons découvert que lorsque la prénylation de Rab7 est bloquée le niveau de palmitoylation augmente. Pour caractériser l’interaction entre CLN5 et Rab7 nous avons performé des expériences afin d’établir définitivement la topologie de cette protéine. Nous avons ainsi démontré que CLN5 est une protéine hautement glycosylée qui est initialement traduite en protéine transmembranaire et subséquemment clivée par un membre de la famille des peptidase de peptide signal (SPP). Cette protéine soluble peut alors possiblement interagir avec CLN3 qui est aussi palmitoylée pour recruter et activer Rab7. Nos études suggèrent pour la première fois que CLN5 pourrait être un recruteur et un activateur de Rab7 qui agirait avec la protéine CLN3 pour séquestrer Rab7 avec les autres récepteurs palmitoylés et permettre leur recyclage vers l’appareil de Golgi.
The proper sorting and trafficking of acid hydrolases plays a critical role in the normal function of cells. Over 50 known human diseases are caused by mutations of lysosomal enzymes, of proteins that regulate key processes of transport to the lysosome or of enzymes that perform posttranslational modifications which are important for the function of the lysosome. The main objective of this thesis is to identify proteins and mechanisms that allow the cell to regulate the transport of enzymes toward the lysosome. We formulated the hypothesis that proteins mutated in lysosomal diseases and that have no known functions could play a role in transport toward the lysosome. Neuronal ceroid-lipofuscinoses form a family of lysosomal storage disorders that are very rare but are also the most frequent infantile neurodegenerative diseases. The work presented in this thesis identified ceroid-lipofuscinosis neuronal-5 (CLN5), which is located at the late-endosomal/lysosomal compartment as a necessary element for the recruitment and activation of Rab7. Rab7 is an important GTPase that controls traffic from the late-endosome to the trans-Golgi network. Rab7 has been implicated in the recruitment of the retromer complex, which regulates retrograde transport of the lysosomal sorting receptor such as sortilin and the mannose-6-phosphate receptor. In the cells where CLN5 is depleted, the lysosomal sorting receptors are less recycled and degraded more rapidly. Using photolabelling assays we were also able to show that Rab7 is less activated in the absence of CLN5. To perform their function, Rab proteins have to be recruited to membranes and activated by the exchange of a GDP nucleotide for GTP. The recruitment of Rabs to membranes necessitates a lipidic posttranslational modification to raise the affinity. Using yeast as a model we demonstrated that the Rab7 homolog, Ypt7 is palmitoylated. We have also showed that the yeast palmitoyltransferase Swif1 is required for Ypt7 membrane recruitment. We have also observed that retromer subunits in yeast are less recruited when palmitoyltranferases are depleted. In mammals we have shown that Rab7 is also palmitoylated and that this palmitoylation may be done by palmitoyltransferases DHHC1 and DHHC8. The palmitoylation of Rab7 occurs on the C-terminal cysteines that are required for membrane recruitment and were previously only shown to be prenylated. By using Click chemistry we have discovered that when Rab7 prenylation is blocked the level of palmitoylation is augmented. To characterize the interaction of Rab7 and CLN5 we performed experiments to definitively establish the topology of this latter protein. Our results show that CLN5 is a heavily glycosylated protein that is initially translated as a type II transmembrane protein and subsequently cleaved by a member of the signal-peptide peptidase (SPP) family. This protein can then possibly interact with another member of the CLN family, CLN3 that is predicted to be palmitoylated to recruit and activate Rab7. Our studies establish for the first time that CLN5 is required for the recruitment and activation of Rab7 and may cooperate with the possibly palmitoylated protein CLN3 to sequester Rab7 in specific membrane domains with sorting receptors to allow their recycling toward the trans-Golgi network.

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du, Plessis Ruschelle. "Performance of socially responsible investment funds in South Africa." Thesis, 2015. http://hdl.handle.net/10394/17040.

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Socially responsible investing has presented itself as a growing, multifaceted, advanced and sophisticated investment philosophy. Socially responsible investment (SRI) involves incorporating social, ethical and responsible investment objectives with financial investment objectives during the investment decision-making process. Social, ethical and responsible investment objectives are set in line with environmental, social and corporate governance (ESG) criteria which are established within the SRI strategy followed. SRI strategies include screening (negative, positive and best-of-sector), shareholder activism and cause-based investing. Although international SRI markets such as that of the United States of America and the United Kingdom are sophisticated and established markets, the South African SRI market is still relatively new and is yet to reach its full potential. Thus, as a growing market, little research regarding the long term risk-adjusted performance of SRI funds in South Africa has been conducted. The long term risk-adjusted performance of the sample of SRI funds was measured through the use of five risk-adjusted performance measures, namely the Treynor ratio, Sharpe ratio, Jensen’s alpha, Sortino ratio and Omega ratio, and through the use of three performance measurement models which included the capital asset pricing model (CAPM), Fama-French three-factor model and Carhart four-factor model. The risk-adjusted performance of the sample of SRI funds was measured with the intent to establish if these funds out- or underperformed against three benchmark categories, namely the Financial Times Stock Exchange/Johannesburg Stock Exchange (FTSE/JSE) SRI Index, a matched sample of conventional investment (non-SRI) funds and the FTSE/JSE All Share Index. The probable effect of the 2007/08 global financial crisis was also measured to analyse whether such a hazardous market event affected the performance of the SRI funds. According to the results and findings, the risk-adjusted performance of the SRI funds has improved over the research period. However, the SRI funds neither outperformed nor underperformed against the three benchmark categories over the research period. The performance measurement models’ analysis indicated that the SRI funds were less sensitive to market fluctuations, more exposed to small capitalisation portfolios, more growth-oriented, and exhibited significant momentum after the period of the 2007/08 global financial crisis. Furthermore, the analysis indicated that the SRI funds significantly underperformed against the non-SRI funds during the Performance of socially responsible investment funds in South Africa research period. Mixed results were obtained with regards to the probable effect of the 2007/08 global financial crisis on the performance of the SRI funds.

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40

Godinho, Sandra. "O tempo pressiona-nos ou nós pressionamo-nos contra o tempo?: processo de decisão de compra sob pressão de tempo em sortidos díspares." Master's thesis, 2013. http://hdl.handle.net/10071/7175.

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Consumer Behavior literature reports that when facing complex decisions and experiencing time presssure, consumers tend to adopt noncompensatory strategies to process information (Payne, Bettman, & Johnson, 1993), using lexicographic decision rules (Mowen e Mirror, 2001) mainly if choosing among low involvement products (Solomon, 2001 ), defer choice less (Dhar e Nowlis, 1999) but accomplish, still, high utility choices (Payne et al.,1988). In the present study participants were asked to visit e-commerce stores offering various-sized assortments and choose both a product and a service. The combined effect of decision complexity (assortment size) and time pressure (at three levels: experimental, objective refering to a price discount and subjective such a stock out warning) in information processing models, coice deferral and final choice utility was measured. Our results support previous research: time pressure leads to the adoption of noncompensatory information processing models, deferral decreases and overall choice utility remains high. However, the differences found at the product level (complex products requires a deeper level of processing, whereas sensory products are perceived on a more holistic way; Krengle & Langner, 2011) as well as between the results from different time pressure types (in a product choice cenario experimental time pressure decreases deferral, but when the decision is upon services, only subjective pressure produces such effect) suggest that researchers should pay more attention to variable operacionalization and to the ecological validity of consumer behavior experimental scenarios.
A literatura na área do comportamento do consumidor reporta que perante decisões complexas e pressão de tempo, optamos por estratégias não-compensatórias de processamento de informação (Payne, Bettman, & Johnson, 1993), como a lexicográfica (Mowen e Mirror, 2001), sobretudo em produtos de baixo envolvimento (Solomon, 2001); tomamos decisões com mais intensidade (Dhar e Nowlis, 1999), mas globalmente a utilidade final das nossas decisões não é afectada (Payne et al.,1988). Através da simulação de dois processos de compra online (produto / serviço), foi examinado o impacto da complexidade da decisão (tamanho do sortido) e da pressão de tempo (em três níveis: experimental, objectiva simulando uma promoção de preço e subjectiva replicando uma ameaça de ruptura de stock), nas estratégias de processamento, capacidade de decidir e utilidade final da decisão tomada. Os resultados confirmam que a pressão de tempo induz estratégias de processamento não compensatório, diminui o Deferral e que globalmente a utilidade final das decisões não é afectada. Contudo, as diferenças significativas encontradas ao nível do tipo de produto – produtos mais complexos indiciam um processamento mais cognitivo e produtos sensoriais um processamento mais generalista (Krengle & Langner, 2011) - como entre diferentes tipos de pressão de de tempo - a pressão experimental diminui o deferral na selecção de produtos, enquanto que na selecção de serviços o Deferral apenas diminui com pressão subjectiva - promovem o debate sobre as limitações da operacionalização de variáveis e do realismo dos cenários experimentais na área do comportamento do consumidor.

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Dissertations / Theses on the topic 'Sortitio'

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