Microtheories for SDI - Accounting for diversity of local conceptualisations at a global level

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Search for low-scale gravity signatures in multi-jet final states with the ATLAS detector at s√ = 8 TeV

We search for evidence of physics beyond the Standard Model in the production of final states with multiple high transverse momentum jets, using 20.3 fb−1 of proton-proton collision data recorded by the ATLAS detector at s√ = 8 TeV. No excess of events beyond Standard Model expectations is observed, and upper limits on the visible cross-section for non-Standard Model production of multi-jet final states are set. Using a wide variety of models for black hole and string ball production and decay, the limit on the cross-section times acceptance is as low as 0.16 fb at the 95% CL for a minimum scalar sum of jet transverse momentum in the event of about 4.3 TeV. Using models for black hole and string ball production and decay, exclusion contours are determined as a function of the production mass threshold and the gravity scale. These limits can be interpreted in terms of lower-mass limits on black hole and string ball production that range from 4.6 to 6.2 TeV.

Data quality in biofilm high-throughput routine analysis: intralaboratory protocol adaptation and experiment reproducibility

Biofilm research is growing more diverse and dependent on high-throughput technologies and the large-scale production of results aggravates data substantiation. In particular, it is often the case that experimental protocols are adapted to meet the needs of a particular laboratory and no statistical validation of the modified method is provided. This paper discusses the impact of intra-laboratory adaptation and non-rigorous documentation of experimental protocols on biofilm data interchange and validation. The case study is a non-standard, but widely used, workflow for Pseudomonas aeruginosa biofilm development, considering three analysis assays: the crystal violet (CV) assay for biomass quantification, the XTT assay for respiratory activity assessment, and the colony forming units (CFU) assay for determination of cell viability. The ruggedness of the protocol was assessed by introducing small changes in the biofilm growth conditions, which simulate minor protocol adaptations and non-rigorous protocol documentation. Results show that even minor variations in the biofilm growth conditions may affect the results considerably, and that the biofilm analysis assays lack repeatability. Intra-laboratory validation of non-standard protocols is found critical to ensure data quality and enable the comparison of results within and among laboratories.

High-aspect-ratio tridimensional electrode arrays for neural applications

Tese de Doutoramento em Engenharia Biomédica.

Dawn for the galaxy: creació d'un joc web d'estratègia en temps real, multijugador i massiu

“Dawn or the Galaxy” és un treball de final de carrera que té com a objectiu principal la creació i desenvolupament d’una versió de demostració per a un joc del tipus MMORTS (massive multiplayer online real-time strategy) tractant d’incloure elements innovadors en aquest gènere de jocs i oferint un ampli ventall estratègic des de l’inici del joc. Per tal d’assolir l’objectiu es realitzarà un petit sondeig de mercat inicial i un estudi de models de jocs d’estratègia. El joc estarà integrat per més de seixanta fitxers de codi, una base de dades amb catorze taules interrelacionades no normalitzades i podrà tenir cabuda per a uns cinc-cents jugadors. Un cop programat l’aplicatiu, el joc es provarà en un entorn real, amb usuaris reals. Per a resoldre els problemes durant el transcurs del joc de forma ràpida, la aplicació serà sotmesa a un seguiment exhaustiu. La col·laboració dels jugadors en aquest punt serà fonamental.

Nuevo disipador para edificación sismorresistente. 2ª parte: comportamiento de estructures duales de un grado de libertad con disipadores

The behaviour of a new elastoplastic shear link dissipator has been analysed in the first part of this paper. The second part describes experimental and numerical studies for a SDOF non-standard dual system protected with shear dissipators. High and intermediate stiff deal systems with this Device have presented smaller values of the shear base force and the interstory drift when compared to linear and elastic systems response. It has been appreciated that most of introduced energy is dissipated when a low ratio between the main frame stiffness and dissipation system stiffness is hold. It has been also observed that a higher ratio between the dissipator yielding force and the total mass drives to a more reduced structural response. Finally is has been appreciated than the absorbed energy might be predicted using the velocity pseudo-spectra and an effective fundamental period, that has been defined by using the minimum secant stiffness of dual system

Self-reported social class in adolescents: validity and relationship with gradients in self-reported health

Background: Analyzing social differences in the health of adolescents is a challenge. The accuracy of adolescent's report on familial socio-economic position is unknown. The aims of the study were to examine the validity of measuring occupational social class and family level of education reported by adolescents aged 12 to 18, and the relationship between social position and self-reported health.Methods: A sample of 1453 Spanish adolescents 12 to 18 years old from urban and rural areas completed a self-administered questionnaire including the Child Health and Illness Profile-Adolescent Edition (CHIP-AE), and data on parental occupational social class (OSC) and level of education (LE). The responsible person for a sub-sample of teenagers (n = 91) were interviewed by phone. Kappa coefficients were estimated to analyze agreement between adolescents and proxy-respondents, and logistic regression models were adjusted to analyze factors associated with missing answers and disagreements. Effect size (ES) was calculated to analyze the relationship between OSC, LE and the CHIP-AE domain scores.Results: Missing answers were higher for father's (24.2%) and mother's (45.7%) occupational status than for parental education (8.4%, and 8.1% respectively), and belonging to a non-standard family was associated with more incomplete reporting of social position (OR = 4,98; 95%CI = 1,3–18,8) as was agreement between a parent and the adolescent. There were significant social class gradients, most notably for aspects of health related to resilience to threats to illness.ConclusionAdolescents can acceptably self-report on family occupation and level of education. Social class gradients are present in important aspects of health in adolescents.

The domain and interpretation of utility functions: An exploration

This paper proposes an exploration of the methodology of utilityfunctions that distinguishes interpretation from representation. Whilerepresentation univocally assigns numbers to the entities of the domainof utility functions, interpretation relates these entities withempirically observable objects of choice. This allows us to makeexplicit the standard interpretation of utility functions which assumesthat two objects have the same utility if and only if the individual isindifferent among them. We explore the underlying assumptions of suchan hypothesis and propose a non-standard interpretation according towhich objects of choice have a well-defined utility although individualsmay vary in the way they treat these objects in a specific context.We provide examples of such a methodological approach that may explainsome reversal of preferences and suggest possible mathematicalformulations for further research.

Dealing with clients' diversity in test situations: Client categorisations in psychologists' accounts of their practices

Reducing a test administration to standardised procedures reflects the test designers' standpoint. However, from the practitioners' standpoint, each client is unique. How do psychologists deal with both standardised test administration and clients' diversity? To answer this question, we interviewed 17 psychologists working in three public services for children and adolescents about their assessment practices. We analysed the numerous "client categorisations" they produced in their accounts. We found that they had shared perceptions about their clients' diversity, and reported various non-standard practices that complemented standardised test administration, but also differed from them or were even forbidden. They seem to experience a dilemma between: (a) prescribed and situated practices; (b) scientific and situated reliability; (c) commutative and distributive justice. For practitioners, dealing with clients' diversity this is a practical problem, halfway between a problem-solving task and a moral dilemma.

Discounting Arduousness

[cat] Hi ha una literatura creixent que considera desviacions del descompte exponencial estàndar. En aquest article combinem preferències temporalment inconsistents (descompte no constant) amb preferències recursives. Aquest formalisme l’apliquem a les propietats relatives a la demanda del que anomenem bens ardus. La justificació del descompte no estàndar proposat ve donada pel fet que la producció i el consum no són separables per a aquest tipus de bens. L’esforç implica que els individus descompten el consum d’aquests bens d’una manera especial, amb la presència de preferències esbiaixades i d’un ajustament recursiu dinàmic. D’aquesta manera, la voluntat de realitzar un esforç, caracteritzada per un factor de descompte, resulta endògena.

SPATIAL VARIABILITY AND VITALITY OF EPIGEOUS TERMITE MOUNDS IN PASTURES OF MATO GROSSO DO SUL, BRAZIL

Epigeous termite mounds are frequently observed in pasture areas, but the processes regulating their population dynamics are poorly known. This study evaluated epigeous termite mounds in cultivated grasslands used as pastures, assessing their spatial distribution by means of geostatistics and evaluating their vitality. The study was conducted in the Cerrado biome in the municipality of Rio Brilhante, Mato Grosso do Sul, Brazil. In two pasture areas (Pasture 1 and Pasture 2), epigeous mounds (nests) were georeferenced and analyzed for height, circumference and vitality (inhabited or not). The area occupied by the mounds was calculated and termite specimens were collected for taxonomic identification. The spatial distribution pattern of the mounds was analyzed with geostatistical procedures. In both pasture areas, all epigeous mounds were built by the same species, Cornitermes cumulans. The mean number of mounds per hectare was 68 in Pasture 1 and 127 in Pasture 2, representing 0.4 and 1 % of the entire area, respectively. A large majority of the mounds were active (vitality), 91 % in Pasture 1 and 84 % in Pasture 2. A “pure nugget effect” was observed in the semivariograms of height and nest circumference in both pastures reflecting randomized spatial distribution and confirming that the distribution of termite mounds in pastures had a non-standard distribution.

Discounting Arduousness

[cat] Hi ha una literatura creixent que considera desviacions del descompte exponencial estàndar. En aquest article combinem preferències temporalment inconsistents (descompte no constant) amb preferències recursives. Aquest formalisme l’apliquem a les propietats relatives a la demanda del que anomenem bens ardus. La justificació del descompte no estàndar proposat ve donada pel fet que la producció i el consum no són separables per a aquest tipus de bens. L’esforç implica que els individus descompten el consum d’aquests bens d’una manera especial, amb la presència de preferències esbiaixades i d’un ajustament recursiu dinàmic. D’aquesta manera, la voluntat de realitzar un esforç, caracteritzada per un factor de descompte, resulta endògena.

The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial.

The dic(9;20)(p13.2;q11.2) is reported to be present in ∼2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analyses-in a three-step manner-using probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P=0.002) and high hyperdiploidy (0.82; P=0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.

Bridge Rail and Approach Railing for Low-Volume Roads in Iowa, TR-592, 2010

Bridge rail and approach guardrails provide safety to drivers by shielding more hazardous objects and redirecting vehicles to the roadway. However, guardrail can increase both the initial cost and maintenance cost of a bridge, while adding another object that may be struck by vehicles. Most existing low volume road (LVR) bridges in the state of Iowa are currently indicated to not possess bridge rail meeting “current acceptable standards”. The primary objective of the research summarized in this report was to provide the nations bridge and approach rail state of practice and perform a state wide crash analysis on bridge rails and approach guardrails on LVR bridges in Iowa. In support of this objective, the criteria and guidelines used by other bridge owners were investigated, non-standard and innovative bridge and approach guardrails for LVR’s were investigated, and descriptive, statistical and economical analyses were performed on a state wide crash analysis. The state wide crash analysis found the overall number of crashes at/on the more than 17,000+ inventoried and non-inventoried LVR bridges in Iowa was fewer than 350 crashes over an eight year period, representing less than 0.1% of the statewide reportable crashes. In other words, LVR bridge crashes are fairly rare events. The majority of these crashes occurred on bridges with a traffic volume less than 100 vpd and width less than 24 ft. Similarly, the majority of the LVR bridges possess similar characteristics. Crash rates were highest for bridges with lower traffic volumes, narrower widths, and negative relative bridge widths (relative bridge width is defined as: bridge width minus roadway width). Crash rate did not appear to be effected by bridge length. Statistical analysis confirmed that the frequency of vehicle crashes was higher on bridges with a lower width compared to the roadway width. The frequency of crashes appeared to not be impacted by weather conditions, but crashes may be over represented at night or in dark conditions. Statistical analysis revealed that crashes that occurred on dark roadways were more likely to result in major injury or fatality. These findings potentially highlight the importance of appropriate delineation and signing. System wide, benefit-cost (B/C) analyses yielded very low B/C ratios for statewide bridge rail improvements. This finding is consistent with the aforementioned recommendation to address specific sites where safety concerns exist.

Immunological mechanisms underlying infectious and chronic lung diseases

Le système respiratoire permet l'échange de gaz entre un organisme et son environnement. Pour fonctionner efficacement, il doit lutter contre les infections tout en maintenant une tolérance aux particules inoffensives. Les cytokines sont des petites protéines qui permettent la communication entre les différentes cellules et jouent un rôle important dans la régulation de l'homéostasie et de l'immunité des surfaces pulmonaires. Une production altérée des cytokines sous-tend beaucoup de maladies du système pulmonaire. Ainsi, la compréhension de la biologie fondamentale des cytokines pourrait contribuer à la mise au point de nouveaux traitements. Dans le cadre de cette thèse, nous avons étudié le rôle de deux cytokines, le TSLP (Thymic stromal lymphopoietin) et l'IL-17 (Interleukin 17) dans les réponses immunitaires bénéfiques et nuisibles en utilisant des modèles précliniques de souris des maladies pulmonaires. L'asthme est une maladie qui est caractérisée par la bronchoconstriction réversible, l'inflammation des voies respiratoires inférieures, l'hyperréactivité bronchique et le remodelage tissulaire. Le type d'inflammation affectant les voies respiratoires et la présence ou non d'allergie permettent d'établir les différents types d'asthme. La TSLP est une cytokine qui est principalement exprimée à des niveaux élevés dans les poumons de patients souffrant d'asthme allergique. En conséquence, la majeure partie de la recherche sur la TSLP a mis l'accent sur le rôle joué par celle- ci dans les réponses négatives conduisant au développement de l'asthme allergique. Dans cette thèse, nous montrons que la TSLP joue aussi un rôle bénéfique dans les réponses immunitaires pulmonaires. Nous avons découvert que la TSLP atténue la grippe en augmentant les réponses des lymphocytes T cytotoxiques contre le virus. Nous avons également étudié la fonction de la TSLP dans l'asthme non allergique. Contrairement à l'asthme allergique, nous avons constaté que la TSLP diminue les réponses inflammatoires dans l'asthme non allergique en réglant la production de l'IL-17, une cytokine qui favorise la maladie. Ainsi, nous démontrons les fonctions pleiotropes de la TSLP dans des contextes spécifiques de la maladie. Nos résultats ont des implications importantes pour le développement de thérapies ciblant la TSLP dans l'asthme. Dans la deuxième partie de la thèse, nous avons étudié les mécanismes pathogéniques qui sous-tendent le développement de la broncho-pneumopathie chronique obstructive (BPCO). La BPCO est une maladie chronique le plus largement associée aux fumeurs. Elle est caractérisée par une limitation progressive et irréversible du débit d'air et la destruction de la structure des poumons. L'augmentation globale de l'incidence de la maladie encourage grandement la compréhension des mécanismes pathogéniques et l'identification de nouvelles cibles thérapeutiques. Nous avons découvert que les micro-organismes trouvés dans les voies respiratoires aggravent la maladie en augmentant la production de l'IL-17. L'IL-17 est une cytokine inflammatoire qui est impliquée dans plusieurs maladies pulmonaires chroniques, dont la BPCO. Dans notre modèle animal de la maladie, nous avons neutralisé 1ÌL-17A en utilisant un anticorps spécifique et observé une reprise de la fonction pulmonaire. Dans cette étude, nous avons identifié 2 axes potentiels pour l'intervention thérapeutique contre la BPCO. Cibler les bactéries dans les voies respiratoires soit par l'utilisation d'antibiotiques ou l'utilisation de thérapies à base immunitaire qui antagonisent l'activité spécifiques de l'IL-17. Dans l'avenir, notre laboratoire va collaborer avec des cliniciens pour acquérir des échantillons humains et tester la pertinence de nos résultats dans la maladie humaine. -- L'interaction avec l'environnement extérieur est vitale pour le fonctionnement du système respiratoire. Par conséquent, ce dernier a adopté une multitude de réseaux effecteurs et régulateurs qui permettent de distinguer les particules inhalées comme «dangereuses» ou «inoffensives» et de réagir en conséquence. L'équilibre entre ces réseaux est essentielle pour lutter contre le «danger» déclenché par une infection ou des dommages, et finalement pour le retour à l'homéostasie. Le milieu de cytokine local contribue de manière significative à la mise au point de ces réponses. Ainsi, la caractérisation du rôle des cytokines dans l'état d'équilibre et la maladie a des implications claires pour les interventions thérapeutiques dans les maladies respiratoires aiguës et chroniques. Cette thèse a porté sur le rôle des cytokines, la lymphopoïétine stromale thymique (TSLP) et TIL-17A dans l'élaboration de réponses immunitaires pulmonaires. La TSLP est principalement produite par les cellules épithéliales et peut cibler une myriade de cellules immunitaires. Bien qu'elle ait été montrée être un puissant inducteur des réponses de type Th2, son rôle dans d'autres contextes inflammatoires est relativement inexploré. Dans le premier projet de cette thèse, nous avons découvert une nouvelle fonction de la TSLP dans l'immunité antivirale contre la grippe, une infection virale. Nous avons constaté que la TSLP a réglementé la réponse neutrophile au début de l'infection, en amplifiant l'immunité adaptative spécifique du virus. Mécaniquement, la TSLP a augmenté l'expression de l'IL-15 et du CD70 sur les cellules dendritiques recrutées dans les poumons suite à l'infection et a renforcé leur capacité de stimuler localement les lymphocytes T CD8+ spécifiques du virus. En outre, nous avons étudié la TSLP dans le cadre de divers phénotypes de l'asthme et également démontré l'impact pléiotropique qu'elle a sur les réponses immunitaires pulmonaires. En accord avec les rapports précédents, nous avons constaté que la TSLP a exacerbé l'inflammation atopique médiée par le Th2. En revanche la TSLP a réduit les réponses de l'IL-17A et l'inflammation neutrophile subséquente dans le modèle non atopique, ainsi que l'exacerbation du modèle atopique provoqué par une infection virale. Nos résultats démontrent une dichotomie dans le rôle de la TSLP dans la pathogenèse de l'asthme et soulignent la nécessité d'envisager plusieurs phénotypes d'asthme pour une évaluation approfondie de son potentiel thérapeutique dans cette maladie. Dans la seconde partie de cette thèse, nous avons caractérisé les mécanismes pathogènes qui sous-tendent la broncho-pneumopathie chronique obstructive (BPCO). La BPCO est une maladie hétérogène définie par une diminution progressive de la fonction pulmonaire. Bien que des déclencheurs environnementaux puissent aggraver la maladie, chez les personnes sensibles une maladie établie peut progresser à travers un cercle inflammatoire auto-entretenu. Nous avons cherché à définir les mécanismes sous-jacents à l'aide d'un modèle murin d'inflammation chronique, qui reproduit les caractéristiques pathologiques de la maladie humaine. Puisqu'ont été associés à la BPCO sévère des changements dans le microbiome des voies respiratoires, nous avons supposé que les signaux dérivés de certains microbes pourraient favoriser des voies inflammatoires chroniques de progression de la maladie. Nous avons observé que, en l'absence d un microbiome, la maladie s'est améliorée tel que démontré par une réduction de l'inflammation des voies respiratoires et une amélioration de la fonction pulmonaire. Cela a été lié spécifiquement à une production réduite d'IL-17A, une cytokine qui a été impliquée dans la maladie humaine. De plus la cinétique de production de 1IL- 17A dépendant du microbiote est corrélé à la sévérité de la maladie. Sur la base de ces données, la neutralisation de l'IL-17A a également eu un effet bénéfique sur l'évolution de la maladie. Le rôle significatif de 1TL-17A dans l'aggravation de la maladie a été couplé à sa capacité à engager un dialogue entre les voies inflammatoires innées et adaptatives. Il a influencé le recrutement et le phénotype des neutrophiles et des macrophages, ce qui a eu un impact direct et indirect sur la formation et la fonction des tissus lymphoïdes tertiaires associée à des stades sévères de la maladie. -- The interaction with the external environment is vital for the functioning of the respiratory system. Consequently, it has adopted a multitude of effector and regulatory networks that enable it to distinguish inhaled particles as 'dangerous' or 'innocuous' and respond accordingly. The balance between these networks is crucial to counteract the 'danger' triggered by infection or damage, and ultimately return to homeostasis. The local cytokine milieu contributes significantly to the fine- tuning of these responses. Thus, characterizing the role of cytokines in steady state and disease has clear implications for therapeutic interventions in acute and chronic respiratory disorders. This thesis focused on the role of the cytokines, thymic stromal lymphopoietin (TSLP) and IL-17A in shaping pulmonary immune responses. TSLP is primarily produced by barrier epithelial cells and can target a myriad of immune cells. Although it has been shown to be potent inducer of Th2 type responses, its role in other inflammatory settings is relatively unexplored. In the first project of this thesis, we discovered a novel function of TSLP in antiviral immunity to Influenza A infection. We found that while TSLP regulated the early neutrophilic response to infection, it amplified virus specific adaptive immunity. Mechanistically, TSLP enhanced the expression of IL-15 and CD70 on the lung recruited inflammatory dendritic cells and strengthened their ability to stimulate virus specific CD8+ T cell responses locally. In addition we investigated TSLP in the context of diverse asthma phenotypes and further demonstrated the pleiotropic impact it has on pulmonary immune responses. In concurrence with previous reports we found that TSLP exacerbated Th2 mediated atopic inflammation. In contrast TSLP curtailed IL-17A responses and subsequent neutrophilic inflammation in the non-atopic model as well as virus induced exacerbation of the atopic model. Our findings demonstrate a dichotomy in the role of TSLP in asthma pathogenesis and emphasize the need to consider multiple asthma phenotypes for a thorough evaluation of its therapeutic potential in this disease. In the next part of this thesis we characterized the pathogenic mechanisms underlying chronic obstructive pulmonary disease. COPD is a heterogeneous disease defined by a progressive decline in lung function. Although environmental triggers exacerbate the disease, in susceptible individuals the established disease can progress through a self-sustained inflammatory circle. We sought to delineate the underlying mechanisms by using a murine model of chronic inflammation, which reproduced key pathological features of the human disease. As changes in the airway microbiome have been linked to severe COPD, we speculated that microbial derived signals could facilitate the establishment of chronic inflammatory pathways that favour disease progression. We found that the absence of a microbiota ameliorated disease, exhibited by a reduction in airway inflammation and an improvement in lung function. This was linked specifically to an impaired production of IL-17A, a cytokine that has been implicated in human disease. Moreover the kinetics of microbiota-dependent IL-17A production correlated with the disease severity. Based on these data targeted neutralization of IL-17A also had a beneficiai effect on the disease outcome. The prominent role played by IL-I7A in driving the disease was coupled to its ability in engaging and mediating cross talk between pathogenic innate and adaptive immune pathways. It influenced the recruitment and phenotype of neutrophils and macrophages, as well as impacted upon the formation and function of tertiary lymphoid tissue associated with severe disease. Thus, temporal and spatial changes in cytokine production, their cellular targets and interaction with the local milieu determine the balance between immunity and pathology in the lung. Collectively our findings provide novel mechanistic insights in the complex role played by cytokines in orchestrating pulmonary immune responses and have clear implications for human disease.