Filling in gaps of Drosophila melanogaster urate degradation metabolic pathway using metabolomics approaches: towards the core metabolome of the fruit fly

The primary goal of systems biology is to integrate complex omics data, and data obtained from traditional experimental studies in order to provide a holistic understanding of organismal function. One way of achieving this aim is to generate genome-scale metabolic models (GEMs), which contain information on all metabolites, enzyme-coding genes, and biochemical reactions in a biological system. Drosophila melanogaster GEM has not been reconstructed to date. Constraint-free genome-wide metabolic model of the fruit fly has been reconstructed in our lab, identifying gaps, where no enzyme was identified and metabolites were either only produced or consume. The main focus of the work presented in this thesis was to develop a pipeline for efficient gap filling using metabolomics approaches combined with standard reverse genetics methods, using 5-hydroxyisourate hydrolase (5-HIUH) as an example. 5-HIUH plays a role in urate degradation pathway. Inability to degrade urate can lead to inborn errors of metabolism (IEMs) in humans, including hyperuricemia. Based on sequence analysis Drosophila CG30016 gene was hypothesised to encode 5- HIUH. CG30016 knockout flies were examined to identify Malpighian tubules phenotype, and shortened lifespan might reflect kidney disorders in hyperuricemia in humans. Moreover, LC-MS analysis of mutant tubules revealed that CG30016 is involved in purine metabolism, and specifically urate degradation pathway. However, the exact role of the gene has not been identified, and the complete method for gap filling has not been developed. Nevertheless, thanks to the work presented here, we are a step closer towards the development of a gap-filling pipeline in Drosophila melanogaster GEM. Importantly, the areas that require further optimisation were identified and are the focus of future research. Moreover, LC-MS analysis confirmed that tubules rather than the whole fly were more suitable for metabolomics analysis of purine metabolism. Previously, Dow/Davies lab has generated the most complete tissue-specific transcriptomic atlas for Drosophila – FlyAtlas.org, which provides data on gene expression across multiple tissues of adult fly and larva. FlyAtlas revealed that transcripts of many genes are enriched in specific Drosophila tissues, and that it is possible to deduce the functions of individual tissues within the fly. Based on FlyAtlas data, it has become clear that the fly (like other metazoan species) must be considered as a set of tissues, each 2 with its own distinct transcriptional and functional profile. Moreover, it revealed that for about 30% of the genome, reverse genetic methods (i.e. mutation in an unknown gene followed by observation of phenotype) are only useful if specific tissues are investigated. Based on the FlyAtlas findings, we aimed to build a primary tissue-specific metabolome of the fruit fly, in order to establish whether different Drosophila tissues have different metabolomes and if they correspond to tissue-specific transcriptome of the fruit fly (FlyAtlas.org). Different fly tissues have been dissected and their metabolome elucidated using LC-MS. The results confirmed that tissue metabolomes differ significantly from each other and from the whole fly, and that some of these differences can be correlated to the tissue function. The results illustrate the need to study individual tissues as well as the whole organism. It is clear that some metabolites that play an important role in a given tissue might not be detected in the whole fly sample because their abundance is much lower in comparison to other metabolites present in all tissues, which prevent the detection of the tissue-specific compound.

Brief report: preliminary proposal of a conceptual model of a digital environment for developing mathematical reasoning in students with Autism Spectrum Disorders

There is clear evidence that in typically developing children reasoning and sense-making are essential in all mathematical learning and understanding processes. In children with autism spectrum disorders (ASD), however, these become much more significant, considering their importance to successful independent living. This paper presents a preliminary proposal of a digital environment, specifically targeted to promote the development of mathematical reasoning in students with ASD. Given the diversity of ASD, the prototyping of this environment requires the study of dynamic adaptation processes and the development of activities adjusted to each user’s profile. We present the results obtained during the first phase of this ongoing research, describing a conceptual model of the proposed digital environment. Guidelines for future research are also discussed.

Exploration of the dendritic cell algorithm with the duration calculus

As one of the newest members in Articial Immune Systems (AIS), the Dendritic Cell Algorithm (DCA) has been applied to a range of problems. These applications mainly belong to the eld of anomaly detection. However, real-time detection, a new challenge to anomaly detection, requires improvement on the real-time capability of the DCA. To assess such capability, formal methods in the research of real-time systems can be employed. The ndings of the assessment can provide guideline for the future development of the algorithm. Therefore, in this paper we use an interval logic based method, named the Duration Calcu- lus (DC), to specify a simplied single-cell model of the DCA. Based on the DC specications with further induction, we nd that each individual cell in the DCA can perform its function as a detector in real-time. Since the DCA can be seen as many such cells operating in parallel, it is potentially capable of performing real-time detection. However, the analysis process of the standard DCA constricts its real-time capability. As a result, we conclude that the analysis process of the standard DCA should be replaced by a real-time analysis component, which can perform periodic analysis for the purpose of real-time detection.

CHARACTERIZATION OF THE ATMOSPHERIC EFFECTS ON THE TRANSMISSION OF THERMAL RADIATION

Atmospheric scattering plays a crucial rule in degrading the performance of electro optical imaging systems operating in the visible and infra-red spectral bands, and hence limits the quality of the acquired images, either through reduction of contrast or increase of image blur. The exact nature of light scattering by atmospheric media is highly complex and depends on the types, orientations, sizes and distributions of particles constituting these media, as well as wavelengths, polarization states and directions of the propagating radiation. Here we follow the common approach for solving imaging and propagation problems by treating the propagating light through atmospheric media as composed of two main components: a direct (unscattered), and a scattered component. In this work we developed a detailed model of the effects of absorption and scattering by haze and fog atmospheric aerosols on the optical radiation propagating from the object plane to an imaging system, based on the classical theory of EM scattering. This detailed model is then used to compute the average point spread function (PSF) of an imaging system which properly accounts for the effects of the diffraction, scattering, and the appropriate optical power level of both the direct and the scattered radiation arriving at the pupil of the imaging system. Also, the calculated PSF, properly weighted for the energy contributions of the direct and scattered components is used, in combination with a radiometric model, to estimate the average number of the direct and scattered photons detected at the sensor plane, which are then used to calculate the image spectrum signal to- noise ratio (SNR) in the visible near infra-red (NIR) and mid infra-red (MIR) spectral wavelength bands. Reconstruction of images degraded by atmospheric scattering and measurement noise is then performed, up to the limit imposed by the noise effective cutoff spatial frequency of the image spectrum SNR. Key results of this research are as follows: A mathematical model based on Mie scattering theory for how scattering from aerosols affects the overall point spread function (PSF) of an imaging system was developed, coded in MATLAB, and demonstrated. This model along with radiometric theory was used to predict the limiting resolution of an imaging system as a function of the optics, scattering environment, and measurement noise. Finally, image reconstruction algorithms were developed and demonstrated which mitigate the effects of scattering-induced blurring to within the limits imposed by noise.

Workplace aggression: A reconceptualization of the construct & an exploration of strain based outcomes

The examination of Workplace Aggression as a global construct conceptualization has gained considerable attention over the past few years as organizations work to better understand and address the occurrence and consequences of this challenging construct. The purpose of this dissertation is to build on previous efforts to validate the appropriateness and usefulness of a global conceptualization of the workplace aggression construct. ^ This dissertation has been broken up into two parts: Part 1 utilized a Confirmatory Factor Analysis approach in order to assess the existence of workplace aggression as a global construct; Part 2 utilized a series of correlational analyses to examine the relationship between a selection of commonly experienced individual strain based outcomes and the global construct conceptualization assessed in Part 1. Participants were a diverse sample of 219 working individuals from Amazon’s Mechanical Turk participant pool. ^ Results of Part 1 did not show support for a one-factor global construct conceptualization of the workplace aggression construct. However, support was shown for a higher-order five-factor model of the construct, suggesting that it may be possible to conceptualize workplace aggression as an overarching construct that is made up of separate workplace aggression constructs. Results of Part 2 showed support for the relationships between an existing global construct workplace aggression conceptualization and a series of strain-based outcomes. Utilizing correlational analyses, additional post-hoc analyses showed that individual factors such as emotional intelligence and personality are related to the experience of workplace aggression. Further, utilizing moderated regression analysis, the results demonstrated that individuals experiencing high levels of workplace aggression reported higher job satisfaction when they felt strongly that the aggressive act was highly visible, and similarly, when they felt that there was a clear intent to cause harm. ^ Overall, the findings of this dissertation do support the need for a simplification of its current state of measurement. Future research should continue to examine workplace aggression in an effort to shed additional light on the structure and usefulness of this complex construct.^

Family supportive work environment, perceptions of the employment relationship and employee work outcomes

Data obtained from employed parents and their supervisors (N=230) in twelve South Korean organizations were used to test a model of the antecedents and outcomes of organizational social exchange. Structural equation modeling (SEM) results showed family supportive supervisor and perceived organizational family support to be related to organizational social exchange. Additionally, organizational social exchange was shown to be related to contextual performance and work withdrawal but indirectly through organization-based self-esteem. We discuss the implications of these findings for managing the employee-organization relationship in an increasingly diverse workforce.

Credit spreads and monetary policy in a small open economy: an analysis of the colombian economy

This paper estimates Bejarano and Charry (2014)’s small open economy with financial frictions model for the Colombian economy using Bayesian estimation techniques. Additionally, I compute the welfare gains of implementing an optimal response to credit spreads into an augmented Taylor rule. The main result is that a reaction to credit spreads does not imply significant welfare gains unless the economic disturbances increases its volatility, like the disruption implied by a financial crisis. Otherwise its impact over the macroeconomic variables is null.

Inversion of ambient seismic noise HVSR to evaluate velocity and structural models of the Lower Tagus Basin, Portugal

During its history, several significant earthquakes have shaken the Lower Tagus Valley (Portugal). These earthquakes were destructive; some strong earthquakes were produced by large ruptures in offshore structures located southwest of the Portuguese coastline, and other moderate earthquakes were produced by local faults. In recent years, several studies have successfully obtained strong-ground motion syntheses for the Lower Tagus Valley using the finite difference method. To confirm the velocity model of this sedimentary basin obtained from geophysical and geological data, we analysed the ambient seismic noise measurements by applying the horizontal to vertical spectral ratio (HVSR) method. This study reveals the dependence of the frequency and amplitude of the low-frequency (HVSR) peaks (0.2–2 Hz) on the sediment thickness. We have obtained the depth of the Cenozoic basement along a profile transversal to the basin by the inversion of these ratios, imposing constraints from seismic reflection, boreholes, seismic sounding and gravimetric and magnetic potentials. This technique enables us to improve the existing three-dimensional model of the Lower Tagus Valley structure. The improved model will be decisive for the improvement of strong motion predictions in the earthquake hazard analysis of this highly populated basin. The methodology discussed can be applied to any other sedimentary basin.

The Pros and Cons of a Field Project: The case of the Laboratory School in Heredia

This article reviews some of the most important characteristics of the Laboratory School in Heredia, Costa Rica, for recognizing the success aspects and setbacks that an innovative experience of an educational project has within the national education system. It is a description of the pedagogical model of the school and includes the vision that different participants have in this educational project, around which it is showed the different positions of the actors who live and reflect daily in the school.

Investigation of the Impacts of Parental Chronic Illness on Youth Caregiving Experiences and Psychosocial Adjustment.

Objective: Parental chronic illness has an impact on several aspects of offspring’s life. Three major impediments to research progress in this field are undeveloped and untested theoretical frameworks, no clear conceptualization of youth caregiving, and no available instrument to assess such construct in Italian. To address these weaknesses, the aims of this PhD dissertation were: (1) to investigate the psychometric properties of the Italian version of the Young Caregiver of Parents Inventory-Revised (YCOPI-R); (2) to empirically examine a model of the effects of parental illness on youth and family functioning innovatively analyzing the role of psychological flexibility; (3) to test a refined conceptualization of youth caregiving. Methods: A total of 501 adolescents aged 11 to 24 (295 young caregivers and 206 young noncaregivers) completed a questionnaire regarding youth caregiving, parental illness, and youth adjustment. In the first study, young caregivers were compared to noncaregivers, while the other studies used only the young carers subgroup. Results: The first study indicated that the Italian version of the YCOPI-R demonstrated sound psychometric and was able to discriminate between young caregivers and noncaregivers. The second study underlined the key protective role of psychological flexibility in shaping youth adjustment and family functioning in the context of parental illness. The third study innovatively clarified the nature of youth caregiving, indicating that it is a tripartite construct related to both positive and negative youth adjustment outcomes. Conclusions. This PhD project drew attention towards youth of chronically ill parents, a segment of the young population which is presently almost completely neglected in Italy by health policies and healthcare providers. This PhD project ultimately shed light into the processes through which parental illness results in detrimental youth outcomes and highlighted avenues for interventions that target empirically supported mechanisms which ameliorate the detrimental effects of parental illness on youth.

Optimization of the power electronics system associated with ocean wave electric generators

The present thesis is focused on wave energy, which is a particular kind of ocean energy, and is based on the activity carried out during the EU project SEA TITAN. The main scope of this work is the design of a power electronic section for an innovative wave energy extraction system based on a switched-reluctance machine. In the first chapter, the general features of marine wave energy harvesting are treated. The concept of Wave Energy Converter (WEC) is introduced as well as the mathematical description of the waves, their characterization and measurement, the WEC classification, the operating principles and the standardization framework. Also, detailed considerations on the environmental impact are presented. The SEA TITAN project is briefly described. The second chapter is dedicated to the technical issues of the SEA TITAN project, such as the operating principle, the performance optimization carried out in the project, the main innovations as well as interesting demonstrations on the behavior of the generator and its control. In the third chapter, the power electronics converters of SEA TITAN are described, and the design choices, procedures and calculations are shown, with a further insight into the application given by analyzing the MATLAB Simulink model of the system and its control scheme. Experimental tests are reported in the fourth chapter, with graphs and illustrations of the power electronic apparatus interfaced with the real machine. Finally, the conclusion in the fifth chapter offers a global overview of the project and opens further development pathways.

Numerical simulations of the spine for patient-specific models of severe scoliosis

In silico methods, such as musculoskeletal modelling, may aid the selection of the optimal surgical treatment for highly complex pathologies such as scoliosis. Many musculoskeletal models use a generic, simplified representation of the intervertebral joints, which are fundamental to the flexibility of the spine. Therefore, to model and simulate the spine, a suitable representation of the intervertebral joint is crucial. The aim of this PhD was to characterise specimen-specific models of the intervertebral joint for multi-body models from experimental datasets. First, the project investigated the characterisation of a specimen-specific lumped parameter model of the intervertebral joint from an experimental dataset of a four-vertebra lumbar spine segment. Specimen-specific stiffnesses were determined with an optimisation method. The sensitivity of the parameters to the joint pose was investigate. Results showed the stiffnesses and predicted motions were highly depended on both the joint pose. Following the first study, the method was reapplied to another dataset that included six complete lumbar spine segments under three different loading conditions. Specimen-specific uniform stiffnesses across joint levels and level-dependent stiffnesses were calculated by optimisation. Specimen-specific stiffness show high inter-specimen variability and were also specific to the loading condition. Level-dependent stiffnesses are necessary for accurate kinematic predictions and should be determined independently of one another. Secondly, a framework to create subject-specific musculoskeletal models of individuals with severe scoliosis was developed. This resulted in a robust codified pipeline for creating subject-specific, severely scoliotic spine models from CT data. In conclusion, this thesis showed that specimen-specific intervertebral joint stiffnesses were highly sensitive to joint pose definition and the importance of level-dependent optimisation. Further, an open-source codified pipeline to create patient-specific scoliotic spine models from CT data was released. These studies and this pipeline can facilitate the specimen-specific characterisation of the scoliotic intervertebral joint and its incorporation into scoliotic musculoskeletal spine models.

A representação social do cuidado no Programa Saúde da Família na cidade do Natal

The aim of this study was to learn about the social representations of the care provided by the Family Health Program (FHP) in the city of Natal, Brazil and determine how these representations guide the daily actions of doctors, dentists, nurses, nurse s assistants and oral health assistants during the work process. In this sense, we used the theoreticalmethodological approach to the Theory of Social Representations. For data collection, we used the following instruments: a two-part questionnaire, where the first part recorded sociodemographic data and the second part was adapted to the free word association technique (FWAT), which was applied to 90 professionals belonging to 18 FHP units. Interviews were also used as collection instruments. These were based on inductive stimuli and on direct observations of 30 of these professionals. After a superficial reading of the material, we constructed a corpus from which ten categories emerged. To analyze FWAT we used lexicographic analysis, combining frequency and the mean order of responses. The interviews and sociodemographic variables were analyzed using content analysis and descriptive statistical analysis, respectively. The study showed that the central nucleus of the social representation in question is composed of the elements attention, receptivity and love, revealing that the subjects have different understandings of the FHP care process and that the knowledge accumulated in this respect is supported by an approximate vision of the meaning of care. However, traditional elements with trivializing connotations about care predominate, which compromises the development of strategies to overcome traditional practices. In the set of analyses, we were able to capture the invariance of a contradiction: on one hand, professionals know and affirm the importance of providing care for FHP patients; on the other, the experience of daily practice translates into the negation of this concept. In this contradictory context, professionals build gradual and successive syntheses that allow them to act and affirm themselves by associating information from their academic formation, structured knowledge acquired in other experiences, values and symbols of their daily routine. Thus, they shape and reshape themselves, according to what is concretely and specifically required, at the same time both plural and multiple. The composition of the central nucleus indicates that any measure that intends to modify attitudes that is, the daily actions of FHP professionals with respect to care must take into account and give priority to the debate about the redefining of the semantic fields of the central nucleus (love/attention/receptivity and humanization), especially those of love and attention

Sobre revoluções científicas na matemática

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ex combatientes y proceso de reintegración: representaciones sociales de un grupo estudiantes del área de la salud

La presente investigación tuvo como objetivo describir las representaciones sociales de un grupo de estudiantes del área de la salud frente a los excombatientes de grupos armados al margen de la ley en Colombia y frente a los procesos de reintegración. El estudio es cualitativo, desde un enfoque procesual de la teoría de las representaciones sociales, participaron estudiantes del área de la salud de una universidad privada de la ciudad de Bogotá. Los datos fueron recogidos mediante un ejercicio de asociación libre para conocer el componente semántico de las representaciones y una entrevista semiestructurada de forma individual con el fin de identificar las dimensiones de información, actitud y campo representacional. Se encontró la prevalencia de prejuicios hacia los excombatientes y la influencia de los medios de comunicación en el nivel y calidad de la información sobre estos objetos de representación, y se identificó una ambigüedad frente al proceso de reintegración; lo que de alguna forma sugiere las dificultades para la inclusión de este grupo a la sociedad, la presencia de una discriminación negativa y las bajas expectativas frente a procesos de cambio en el marco del proceso de paz.