The Daya Bay reactor neutrino experiment is a high sensitivity experiment designed to determine the last unknown neutrino mixing angle $theta_{13}$ by measuring disappearance of reactor antineutrinos emitted from six 2.9 $GW_{th}$ reactors at the Daya Bay Nuclear Power Station. There are eight identical Gd-loaded liquid scintillator detectors deployed in two near (flux-weighted baseline 512 $m$ and 561 $m$) and one far (1579 $m$) underground experimental halls to detect the inverse beta decay interaction. This dissertation describes the Daya Bay Experiment and individual contributions to this experiment. Chapter 1 reviews the history of the neutrino and the neutrino oscillation phenomena. The reactor based neutrino experiments in different times are described in this chapter in detail. It presents the motivation of the Daya Bay Experiment. In Chapter 2, the neutrino detection method and the $theta_{13}$ relative measurement method are introduced. This chapter focuses on the design of the Daya Bay Experiment, including antineutrino detector, calibration system, muon veto system and muon tagging system. Chapter 3 shows the design, development, construction, and assembly of Muon Pool PMT calibration system, and presents an algorithm of calculating the muon pool PMT timing offset values. Chapter 4 focuses on the manufacture, installation and commissioning of RPC HV system. Chapter 5 presents the analyses of the radioactive isotopes induced by comic muons. The Daya Bay detector energy response model is also described in detail. The relative rate analysis results exclude a zero value from $sin^22theta_{13}$ with a significance of 7.7 standard deviation using 139 days of data, 28909 (205308) antineutrino candidates which were recorded at the far hall (near halls) and shows $sin^22theta_{13} = 0.089pm0.011$ in a three-neutrino framework. A combined analysis of the $overline nu_e$ rates and energy spectra based on the detector energy response model improved measurement of the mixing angle $sin^22theta_{13} = 0.090^{+0.008}_{-0.009}$ by using 217 days of data, 41589 (203809 and 92912) antineutrino candidates were detected in the far hall (near halls). Also the first direct measurement of the $overline nu_e$ mass-squared difference $|Delta m^2_{ee}|= (2.59^{+0.19}_{-0.20})times10^{-3}$ $eV^2$. It is consistent with $|Delta m^2_{mumu}|$ measured by muon neutrino disappearance, supporting the three-flavor oscillation model. / Ph. D.

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Få personer säkerhetskopierar tillräckligt ofta, trots att de riskerar att förlora viktiga filer. Vad beror det på? Denna uppsats har genom en kvantitativ undersökning försökt klarlägga vilka faktorer som har störst påverkan på detta beteende och om det finns ett samband mellan dessa. Datainsamlingen skedde genom en enkätundersökning, med över 300 svar från olika studenter på Uppsala universitet. Resultaten analyseras med hjälp av det teoretiska ramverket “Protection Motivation Theory” (PMT) och jämförs sedan med liknande forskning. Resultaten visar att lättja och glömska är de två faktorer som respondenterna själva anser har störst påverkan. Utöver detta har även det studieprogram vilket studenten går på betydelse. Resultaten visar också att hur studenterna bedömer sannolikheten för dataförlust och graden av de problem som kan uppstå vid en dataförlust båda har ett positivt samband med hur ofta säkerhetskopiering utförs. Av dessa har uppskattat problem störst påverkan. Detta resultat skiljer sig från vad delar av tidigare forskningen har visat, men ligger i linje med vad PMT säger om detta beteende. / Few people backup their files frequently enough, even though they risk losing important files. Why is this? This paper has through a quantitative survey attempted to elucidate which factors have the biggest impact on this behavior and if there is a correlation between these. The data was collected using a questionnaire which got over 300 answers from students at Uppsala University. The results were analyzed using the theoretical framework “Protection Motivation Theory” (PMT) and was then compared to similar research. The results show that laziness and forgetfulness are the two biggest factors that the respondents themselves say have the biggest impact on their behavior. In addition to this the kind of program the student is attending also has an effect. The results show that the assessed probability of losing data and the severity of the problem of losing data have a positive correlation with how often backup is done, where assessed problem has the biggest impact. These results differ from what some of the earlier research has shown, but is in line with what PMT says about this behavior.

Malgré les efforts extrêmement importants réalisés pour la recherche de nouveaux agents anticancéreux, les traitements par chimiothérapie ne permettent toujours pas de traiter efficacement un grand nombre de tumeurs. En effet, les molécules utilisées cliniquement ne sont généralement pas sélectives des tissus cancéreux et la destruction des tissus sains qu'elles engendrent provoque de lourds effets secondaires. Le développement de nouvelles stratégies thérapeutiques plus sélectives représente donc un intérêt majeur en chimie médicinale. Dans ce cadre, nous avons développé plusieurs vecteurs non toxiques conçus pour reconnaître des spécificités liées à la malignité puis libérer de manière contrôlée des agents cytotoxiques exclusivement au niveau de la tumeur. Dans le cadre de cette thèse, le concept de vecteur glucuronylé a été adapté à la MMAE et à la cyclopamine. Ces vecteurs pourront être sélectivement activé par la B-glucuronidase présente en concentration importante dans les zones nécrotiques de nombreuses tumeurs solides et ainsi libérer ces agents anticancéreux au niveau des tissus cancéreux. Des études préliminaires visant à évaluer l'efficacité de ces composés in-vitro et in-vivo ont montré la validité de cette approche. Dans un deuxième temps, un vecteur glucuronylé de la doxorubicine pouvant se lier à l'albumine plasmatique a été conçu. Une étude réalisée chez la souris a montré que ce composé possède une efficacité thérapeutique similaire à celle de la doxorubicine et ne provoque pas les effets secondaires constatés lors du traitement avec la drogue seule. La troisième partie est consacrée au développement du premier vecteur activable par la B-galactosidase ut / Despite several years of intensive research devoted to the discovery of novel anticancer agents, chemotherapy is still not entirely effective for the treatment of many solid tumors. Most of the drugs used clinically act by anti-proliferative mechanisms and lack any intrinsic selectivity, leading to severe adverse effects due to the destruction of normal tissues. Therefore, the development of more selective therapeutic approaches has become a major goal in medicinal chemistry. Within this framework, we have developed several nontoxic drug carriers designed for both the efficient recognition of malignant specificities and the controlled release of anti-neoplastic agents exclusively at the tumour site. First, we applied the concept of glucuronide prodrugs to MMAE and Cyclopamine in order to deliver these anticancer drugs at the tumor site. Indeed, glucuronide prodrugs can be selectively activated by B-glucuronidase present in high concentration in necrotic area of numerous solid tumors. Preliminary in vitro and in vivo evaluations of these prodrugs demonstrated the potential of this approach. Second, we studied the first B-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. In vivo experiment conducted in mice show that this compound inhibits tumor growth in a similar manner to doxorubicin whilst avoiding side effects induced by the free drug. We also developed the first B-galactosidase-responsive drug delivery system suitable for the treatment of solid tumors in PMT. Such a targeting system can be selectively activated by lysosomal B-galactosidase located inside malignant cells expressing a specific tumor-a

De senaste åren har visat på en ökning av så kallade ransomware-attacker riktade mot sjukvården. Sjukvården är en samhällssektor som besitter en samhällskritisk verksamhet och hanterar känsliga data vilket gör den extra utsatt mot dessa typer av attacker. Under covid-19 pandemin var läget inom sjukvården pressat och detta har setts utnyttjas av angripare som utfört ransomware-attacker riktade mot sjukhus i hopp om att dra nytta av det pressade läget och få en lösensumma utbetald. Effekterna av en sådan attack mot sjukvården kan innebära stora konsekvenser och dessa konsekvenser bör tas i beaktning då skyddsarbetet mot ransomware-attacker utformas vid sjukhusen. För att bilda en förståelse hur svenska sjukhus ser på dessa konsekvenser vid utformningen av säkerhetsarbetet undersöker denna studie ämnet genom en intervjustudie med en teoretisk grund i den informationssäkerhetsmässigt beprövade teorin Protection Motivation Theory (PMT). Sammantaget visade studien på att olika konsekvenser tas olika mycket hänsyn till vid utformningen av säkerhetsarbetet. Konsekvenser för patientsäkerhet är de konsekvenser som studien visade tas störst hänsyn till vid utformningen av säkerhetsarbetet. / Recent years have seen an increase in so-called ransomware attacks targeting healthcare. Healthcare is a sector of society that possesses a socially crucial business and handles sensitive data which makes it particularly vulnerable to these types of attacks. During the covid-19 pandemic, the healthcare sector was under pressure, and this have seen to be exploited by attackers who carried out ransomware attacks targeting hospitals in the hope of taking advantage of the pressured situation and getting the ransom paid. The effects of such an attack against healthcare can have major consequences and should be considered when designing protection against ransomware attacks at hospitals. To form an understanding of whether these consequences have been included in the design of the protection work at hospitals in Sweden, this study examines the subject through an interview study with a theoretical basis in the information security-proven theory Protection Motivation Theory (PMT). Overall, the study showed that different consequences are considered to varying degrees when designing the safety work. Consequences for patient safety are the consequences that the study showed are most considered when designing the safety work.

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Recent research in Australia has found that people with a mental illness experience higher mortality rates from preventable illnesses, such as cardiovascular disease, respiratory disease and diabetes compared to the general population. Lifestyle and other behavioural factors contribute significantly to these illnesses. Lifestyle behaviours that affect these illnesses include lack of physical activity, consumption of a poor diet and cigarette smoking. Research on the influence of these factors has been mainly directed towards the mainstream population in Australia. Consequently, there remains limited understanding of health behaviours among individuals with psychiatric disabilities, their health needs, or factors influencing their participation in protective health behaviours. This thesis presents findings from two studies. Study 1 evaluated the utility of the main components of Roger’s (1983) Protection Motivation Theory (PMT) to explain health behaviours among people with a mental illness. A clinical population of individuals with schizophrenia (N=83), Major Depressive Disorder (MDD) (N=70) and individuals without a mental illness (N=147) participated in the study. Respondents provided information on intentions and self-reported behaviour of engaging in physical activity, following a low-fat diet, and stopping smoking. Study 2 investigated the health care service needs of people with psychiatric disabilities (N=20). Results indicated that the prevalence of overweight, cigarette smoking and a sedentary lifestyle were significantly greater among people with a mental illness compared to that reported for individuals without a mental illness. Major predictors of the lack of intentions to adopt health behaviours among individuals with schizophrenia and MDD were high levels of fear of cardiovascular disease, lack of knowledge of correct dietary principles, lower self-efficacy, a limited social support network and a high level of psychiatric symptoms. In addition, findings demonstrated that psychiatric patients are disproportionately higher users of medical services, but they are under-users of preventive medical care services. These differences are primarily due to a lack of focus on preventive health, feelings of disempowerment and lower satisfaction of patient-doctor relationships. Implications of these results are discussed in terms of designing education and preventive programs for individuals with schizophrenia and MDD.

Alkaloids are a class of plant secondary metabolites produced in about 20% of plant families. Domesticated tobacco, Nicotiana tabacum produces nicotine as the predominant alkaloid. The biosynthesis of nicotine occurs exclusively in the roots of tobacco, yet accumulates in the leaves of tobacco where it is acts as a defense compound to deter insect herbivory. The research detailed in this dissertation addresses two aspects of nicotine physiology in tobacco: 1) an investigation of hypothesized protein-protein interactions among nicotine biosynthetic enzymes and 2) the characterization of a novel nicotine transporter. A hypothesized metabolic channel including the two nicotine biosynthetic enzymes putrescine N-methyltransferase (PMT), N-methylputrescine Oxidase (MPO) and the S-adenosylmethionine (SAM) recycling enzyme S-adenosylhomocysteine hydrolase (SAHH) has been proposed. To further explore this hypothesis, protein-protein interactions among nicotine biosynthetic enzymes PMT, MPO and SAHH were investigated using yeast two-hybrid assays and co-immunoprecipitation experiments. The yeast two-hybrid was conducted as both a directed screen to detect interactions between the hypothesized metabolic channel members and as a library screen to detect interactions between hypothesized metabolic channel members and proteins from a tobacco root cDNA library. Co-immunoprecipitation experiments were conducted using proteins produced in an in vitro transcription/ translation system and using native proteins from a tobacco root extract. The outcome of these experiments provided no further evidence of a nicotine metabolic channel and a discussion of the methods and outcomes of the experiments conducted is presented. The nicotine uptake permease, NUP1, was identified in tobacco roots and was shown to preferentially transport nicotine when expressed in Schizosaccharomyces pombe. This report presents the characterization of tobacco plants and hairy roots with diminished NUP1 transcripts created by using RNAi. The NUP1-RNAi hairy roots and plants showed a decreased level of nicotine and the hairy root cultures displayed an altered distribution of nicotine from the root to the culture medium. Additionally NUP1-GFP was used to determine that NUP1 localized to the plasma membrane of tobacco BY-2 protoplasts. Potential models for the role of NUP1 in nicotine physiology will be discussed. / Ph. D.

Le paclitaxel (Taxol®) et son analogue hémisynthétique le docetaxel (Taxotere®) appartiennent à une famille d'agents antitumoraux dont l'originalité réside dans leur structure tétracyclique inusuelle et complexe, et surtout dans leur mécanisme d'action. Ils ont en effet pour cible principale une protéine constitutive du fuseau mitotique, la tubuline.<br /> Bien que très utilisés en clinique (cancers du sein, de l'ovaire, du poumon), ils présentent un inconvénient majeur pour leur emploi : leur grande toxicité et leur mode d'administration induisent de graves effets secondaires. De plus, des phénomènes de résistance apparaissent également.<br /> Une méthode efficace d'amélioration de ces composés est de les transformer en prodrogues moins cytotoxiques et plus hydrosolubles. L'intérêt prépondérant de cette transformation apparaît dans la possibilité de délivrer ces produits de manière mieux ciblée, plus spécifique des tumeurs. Elles pourront alors être utilisés dans le cadre du concept PMT (Prodrug Mono Therapy) ou dans une stratégie immunociblée de type ADEPT (Antibody Directed Enzyme Prodrug Therapy).<br /><br /> Dans cette optique, des prodrogues glucuronylées du paclitaxel et du docetaxel ont été conçues et synthétisées. L'espaceur employé est un espaceur double, reliant un carbamate de p-hydroxybenzyle à une chaîne diamine. Ces prodrogues ont été évaluées biologiquement (stabilité, cytotoxicité, hydrolyse enzymatique) pour valider cette approche. L'utilisation du nouvel espaceur a donné des résultats satisfaisants, en particulier pour les hydrolyses enzymatiques qui ont été améliorées par rapport à celles des prodrogues décrites précédemment. La conception et la synthèse de différents espaceurs applicables à la préparation d'autres prodrogues sont également présentées.

Gulf oysters are harvested and consumed year-round, with more than 90% consumed in a raw, unprocessed state. A chief concern of policymakers in recent years is the incidence of Vibrio vulnificus infection following raw seafood consumption. V.vulnificus refers to a halophilic bacterium naturally occurring in brackish coastal waters, which concentrates in filter-feeding oysters. Proposed FDA legislation requiring processing of all raw Gulf oysters sold during warmer summer months threatens the Gulf oyster industry, as little to no research regarding demand for post-harvest processing (PHP) has preceded the potential mandate. This research endeavors to examine the relationship between oyster consumers' fears of V.vulnificus infection and their willingness-to-pay (WTP) for processing of an oyster meal. The psychological model of Protection Motivation Theory (PMT) is employed alongside the economic framework of contingent valuation (CV) to result in an analysis of oyster processing demand with respect to threats and efficacy. A survey administered to 2,172 oyster consumers in six oyster producing states elicits projected consumption and PMT data. Principal Component Analysis is used to reduce the number of PMT variables to a smaller size, resulting in five individual principal components representing the PMT elements of source information, threat appraisal, coping appraisal, maladaptive coping, and protection motivation. Using survey data, the marginal willingness-to-pay (MWTP) for PHP per oyster meal is also calculated, and the five created PMT variables are regressed on this calculation using four separate OLS models. Results indicate significant correlation for four of the five created PMT variables. In addition, a mean MWTP for PHP of $0.31 per oyster meal is determined, contributing to the demand analysis for processing of Gulf oysters. The findings suggest a strong relationship between the fear elements and the demand for processing, and support arguments in favor of further research on specific PHP treatments and the necessity for a valid PMT survey instrument.