Fine time scaling of purifying selection on human nonsynonymous mtDNA mutations based on the worldwide population tree and mother-child pairs

A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (∼11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.

Relatório de atividade profissional

Dissertação de mestrado em Ciências – Formação Contínua de Professores (área de especialização em Biologia e Geologia)

Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs).

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c. − 124 and c. − 146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c. − 124C4T mutation was the most common event, present in 2.3% (3/130), and the c. − 146C4T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient’s clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.

Influence of the hip joint modeling approaches on the kinematics of human gait

The influence of the hip joint formulation on the kinematic response of the model of human gait is investigated throughout this work. To accomplish this goal, the fundamental issues of the modeling process of a planar hip joint under the framework of multibody systems are revisited. In particular, the formulations for the ideal, dry, and lubricated revolute joints are described and utilized for the interaction of femur head inside acetabulum or the hip bone. In this process, the main kinematic and dynamic aspects of hip joints are analyzed. In a simple manner, the forces that are generated during human gait, for both dry and lubricated hip joint models, are computed in terms of the system’s state variables and subsequently introduced into the dynamics equations of motion of the multibody system as external generalized forces. Moreover, a human multibody model is considered, which incorporates the different approaches for the hip articulation, namely ideal joint, dry, and lubricated models. Finally, several computational simulations based on different approaches are performed, and the main results presented and compared to identify differences among the methodologies and procedures adopted in this work. The input conditions to the models correspond to the experimental data capture from an adult male during normal gait. In general, the obtained results in terms of positions do not differ significantly when the different hip joint models are considered. In sharp contrast, the velocity and acceleration plotted vary significantly. The effect of the hip joint modeling approach is clearly measurable and visible in terms of peaks and oscillations of the velocities and accelerations. In general, with the dry hip model, intra-joint force peaks can be observed, which can be associated with the multiple impacts between the femur head and the cup. In turn, when the lubricant is present, the system’s response tends to be smoother due to the damping effects of the synovial fluid.

Optical properties of zirconium oxynitride films: the effect of composition, electronic and crystalline structures

tThis work is devoted to the investigation of zirconium oxynitride (ZrOxNy) films with varied opticalresponses prompted by the variations in their compositional and structural properties. The films wereprepared by dc reactive magnetron sputtering of Zr, using Ar and a reactive gas mixture of N2+ O2(17:3).The colour of the films changed from metallic-like, very bright yellow-pale and golden yellow, for low gasflows to red-brownish for intermediate gas flows. Associated to this colour change there was a significantdecrease of brightness. With further increase of the reactive gas flow, the colour of the samples changedfrom red-brownish to dark blue or even to interference colourations. The variations in composition dis-closed the existence of four different zones, which were found to be closely related with the variationsin the crystalline structure. XRD analysis revealed the change from a B1 NaCl face-centred cubic zirco-nium nitride-type phase for films prepared with low reactive gas flows, towards a poorly crystallizedover-stoichiometric nitride phase, which may be similar to that of Zr3N4with some probable oxygeninclusions within nitrogen positions, for films prepared with intermediate reactive gas flows. For highreactive gas flows, the films developed an oxynitride-type phase, similar to that of -Zr2ON2with someoxygen atoms occupying some of the nitrogen positions, evolving to a ZrO2monoclinic type structurewithin the zone where films were prepared with relatively high reactive gas flows. The analysis carriedout by reflected electron energy loss spectroscopy (REELS) revealed a continuous depopulation of thed-band and an opening of an energy gap between the valence band (2p) and the Fermi level close to 5 eV.The ZrN-based coatings (zone I and II) presented intrinsic colourations, with a decrease in brightness anda colour change from bright yellow to golden yellow, red brownish and dark blue. Associated to thesechanges, there was also a shift of the reflectivity minimum to lower energies, with the increase of thenon-metallic content. The samples lying in the two last zones (zone III, oxynitride and zone IV, oxide films)revealed a typical semi-transparent-optical behaviour showing interference-like colourations only dueto the complete depopulation of the d band at the Fermi level. The samples lying in these zones presentedalso an increase of the optical bandgap from 2 to 3.6 eV.

Estudo comparativo entre indicadores de desempenho da JCI e do Contrato Programa Cirurgia Segura

Dissertação de mestrado em Engenharia e Gestão da Qualidade

High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16

Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention.

A dimensão interna da responsabilidade social nas organizações: equilíbrio entre o trabalho e a vida familiar

Dissertação de mestrado em Sociologia (área de especialização em Organizações e Trabalho)

Controlo e limites dos princípios constitucionais da proporcionalidade e da igualdade no contexto da inspeção tributária

Dissertação de mestrado em Direito Tributário e Fiscal

Vector of coordinates, velocities and accelerations

This chapter describes the how the vector of coordinates are defined in the formulation of spatial multibody systems. For this purpose, the translational motion is described in terms of Cartesian coordinates, while rotational motion is specified using the technique of Euler parameters. This approach avoids the computational difficulties associated with the singularities in the case of using Euler angles or Bryant angles. Moreover, the formulation of the velocities vector and accelerations vector is presented and analyzed here. These two sets of vectors are defined in terms of translational and rotational coordinates.

Kinematic constraint equations

This chapter presents a general methodology for the formulation of the kinematic constraint equations at position, velocity and acceleration levels. Also a brief characterization of the different type of constraints is offered, namely the holonomic and nonholonomic constraints. The kinematic constraints described here are formulated using generalized coordinates. The chapter ends with a general approach to deal with the kinematic analysis of multibody systems.

Correction of the initial conditions

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

Discurso mediático e sociedade: repensar a Análise Crítica do Discurso

A análise do discurso jornalístico e do seu enraizamento social tem conhecido avanços significativos nas últimas duas décadas, especialmente devido ao surgimento e desenvolvimento da Análise Crítica do Discurso. No entanto, há três aspectos importantes que merecem mais investigação: o plano temporal na análise do discurso, as estratégias discursivas dos atores sociais, e os efeitos extra e supra-textual do discurso mediatizado. Em primeiro lugar, a compreensão da biografia dos assuntos públicos exige uma análise longitudinal dos textos mediatizados e dos seus contextos sociais, mas a maioria das formas de análise do discurso jornalístico não tem em conta a sequência temporal dos textos e as suas implicações. Em segundo lugar, como a representação mediática das questões sociais é, em grande medida, função da construção discursiva de eventos, problemas e posições por diferentes atores sociais, as estratégias discursivas que eles empregam numa variedade de arenas e canais ‘antes’ e ‘depois’ dos textos jornalísticos precisam de ser examinados. Em terceiro lugar, o facto de que muitos dos modos de operação do discurso são extra- ou supra-textuais requer que se tenha em consideração vários processos sociais ‘fora’ do texto. Este trabalho tem como objetivo produzir um contributo teórico e metodológico para a integração destas questões em análise do discurso, propondo um quadro analítico que combina uma dimensão textual com uma contextual.

Media(ted) discourse and society: rethinking the framework of critical discourse analysis

The analysis of journalistic discourse and its social embeddedness has known significant advances in the last two decades, especially due to the emergence and development of Critical Discourse Analysis. However, three important aspects remain under-researched: the time plane in discourse analysis, the discursive strategies of social actors, and the extra- and supra-textual effects of mediated discourse. Firstly, understanding the biography of public matters requires a longitudinal examination of mediated texts and their social contexts but most forms of analysis of journalistic discourse do not account for the time sequence of texts and its implications. Secondly, as the media representation of social issues is, to a large extent, a function of the discursive construction of events, problems and positions by social actors, the discursive strategies that they employ in a variety of arenas and channels ‘‘before’’ and ‘‘after’’ journalistic texts need to be examined. Thirdly, the fact that many of the modes of operation of discourse are extra- or supra-textual calls for a consideration of various social processes ‘‘outside’’ the text. This paper aims to produce a theoretical and methodological contribution to the integration of these issues in discourse analysis by proposing a framework that combines a textual dimension with a contextual one

Newtonize this!: um jogo de computador para auxiliar os alunos do Ensino Básico e Secundário no estudo da Mecânica

Relatório da atividade profissional de mestrado em Ciências - Formação Contínua de Professores (área de especialização em Física e Química)