Vascular remodeling in pulmonary hypertension

Pulmonary hypertension (PH) is a progressive obliterative vasculopathy with multifactorial etiology and high mortality rate. Endothelial dysfunction, excessive vascular remodeling, inflammation and in situ thrombosis contribute to increased vascular resistance and gradual occlusion of pulmonary vessels. Sustained high pressure in the pulmonary circulation increases right heart afterload and ultimately results in right heart failure. Current pharmacological treatments, like endothelin receptor antagonists, prostacyclin analogues, and phosphodiesterase-5 inhibitors, are primarily vasodilators and exert limited effects on vascular remodeling. Survival has improved, but far from enough, and the demand for lung transplantation has not been reduced. Excessive growth of pulmonary artery smooth muscle cells (PASMCs) contributes to intimal hyperplasia, medial wall thickening, and plexiform lesions, the main features of vascular remodeling in PH. It is therefore important to explore factors which can control PASMC growth in order to identify potential targets for regression of PH. Here, the roles of growth factors and proteoglycans in vascular remodeling were investigated in animal models of PH as well as in tissue specimens from patients. In a rat model of PH associated with congenital diaphragmatic hernia, up-regulation of PDGF-B was found. Prenatal PDGF-B inhibition by imatinib, a tyrosine kinase inhibitor, was demonstrated to inhibit PASMC proliferation and to reduce pulmonary vascular remodeling in fetal rat lungs. In a murine model of hypoxia-induced PH, increased perlecan deposition was observed. Genetically modified mice expressing heparan sulfate-deficient perlecan developed less PH, accompanied by decreased pulmonary vascular remodeling and reduced right ventricular hypertrophy. In addition, defective mural cell recruitment in pulmonary vessels was observed in heparan sulfate-deficient mice. A possible mechanism is impaired interaction between FGF-2 and its receptor and a pro-proliferative function for perlecan heparan sulfate in pulmonary vessels. The role of PDGF-B retention motifs, the C-terminal region of PDGF-B that interacts with heparan sulfate, was also explored. Hypoxia-induced PH was reduced in PDGF-B retention motif knockout, possibly due to defective retention of PDGF-B in the extracellular matrix and disturbed recruitment of mural cells. Metabolic labeling experiments showed that a majority of the proteoglycans secreted by human PASMCs are decorated with chondroitin sulfate. Lung tissue sections from patients with PH revealed versican accumulation in vascular lesions. In vitro, mechanical strain and hypoxia increased versican production in PASMCs. The results suggested that versican is a pro-proliferative element in the vascular remodeling of PH. In summary, this thesis work emphasizes the role of growth factors and proteoglycans, and interactions between the two, in the regulation of PASMC growth during PH development. Inhibition of growth factor activity or specific targeting of important functional domains of proteoglycans may be effective anti-remodeling strategies for future PH treatment

L1-Penalized Ordinal Regression and Bayesian Variable Selection for Linear Models with Multiple Responses

Polychotomous ordinal response data are often analyzed by first introduce a latent continuous variable which can be modeled as an ordinary regression problem with the presence of covariates by using Markov chain Monte Carlo techniques. For variable selection purpose, we modified this approach by using the idea of Stochastic EM algorithm to infuse L-1 penalized regression in estimating the parameter of interest. This allows us to rank the variables in their order of significance based on posterior selection probabilities. We make comparisons with univariate Bayesian variable selection in the simulation and applied the proposed algorithm on data obtained from the MovieLens Project and the World Value Survey. Given the convenience of using Gibbs sampler to sample from the posterior distributions and choosing prior distributions based on the problems of our interest in Bayesian analyses, we extended the variable selection problem to consider multiple response data by allowing different sets of variables to be selected for different response variables through the infusion of additional information into the prior distribution of the selection variables. This contrasts with the usual approach to multiple response variable selection that selects a common set of variables for all of the response variables. In the simulation, we compared our proposed method against univariate Bayesian variable selection and it shows that the performance is improved after the infusion of relationship information

Evidence evaluation and functional data analysis

In forensic contexts, evidence gathered are valuable in suggesting possible crimes. The problems forensic scientists are often interested in are whether evidence found at the scene of the crime match those that are found related to some suspect. Prosecution and defense propositions are often put forward assuming the evidence came from the same source or they are not from the same source. A popular and objective measure of the value of evidence is the use of the likelihood ratios that is calculated as the ratio between the probabilities of observing the evidence given each proposition. In this thesis, we will provide methodologies for the evaluation of the likelihood ra- tio when evidence are characterised by functional data such as mass spectrophotometry data. Three models will be developed based on fundamental functional data analysis and use of systems of basis functions for the decomposition of means. Each of the three models considers a different covariance structure for between- and within-group variations. They are independent and constant variances across groups, independent and constant within-group variances and auto-covariance. Two models that only make use of the data after dimension reduction are also developed. One is multivariate nor- mal random-effects model with constant covariance matrix and the other one puts an inverse Wishart prior distribution on within-group covariance matrix. Both models consider two levels of variability, within- and between-group, for the mean. All models will be used to calculate likelihood ratios for three sets of data and re- sults will be compared using different measures of performances such of rates of mis- leading evidence, Tippett plots and empirical cross-entropy (ECE) plots. Sensitivity analysis is then done to test the effect of using different estimations of the hyperpa- rameters on likelihood ratios. Furthermore, we also preprocessed the data in another way, that is taking first order differences and replace the original data to feed into the models. Conclusions will be drawn based on the performances of each model on each dataset, including sensitivity analysis and more data preprocessing. Finally, guidances on how to choose the model for the calculation of likelihood ratios for other kinds of data will be provided

Gender and Posture are Significant Risk Factors to Musculoskeletal Symptoms during Touchscreen Tablet Computer Use

[Purpose] To investigate the prevalence of neck and shoulder symptoms during the use of tablet computer, and to identify the risk factors associated with these symptoms. [Subjects and Methods] A cross-sectional survey was conducted to study tablet computer usage, posture during use, and neck and shoulder symptoms in 412 participants in a school setting. Significant risk factors for musculoskeletal symptoms during tablet computer use were identified. [Results] Overall prevalence of musculoskeletal symptoms during tablet computer use was 67.9% with greater prevalence of neck symptoms (neck: 84.6%; shoulder/upper extremity: 65.4%). Significant risk factors associated with symptoms during use were: current musculoskeletal symptoms, gender, roles, and postural factors including: sitting without back support, sitting with device in lap, and lying on the side and on the back during tablet computer use. A multivariate analysis further showed that the odds for females to have symptoms were 2.059 times higher than males. [Conclusion] The findings revealed that female gender and other postural factors were significantly associated with musculoskeletal symptoms during the use of tablet computer. Among all postural factors, sitting without back support was identified as the most important risk factor for having musculoskeletal symptom

Photon and phonon statistics in a qubit-plasmon-phonon ultrastrong coupling system

We study photon/phonon statistics of a qubit-plasmon-phonon hybrid system in the ultrastrong coupling regime. The introduced qubit coupling causes parity conserving and non-conserving situations. We employ an analytic approximation approach for the parity conserving case to reveal the statistical behaviors of photons and phonons. It indicates that both photons and phonons show strong antibunching at the same frequency. Even though the bunching properties of photons/phonons occupy the dominant regions of the considered frequencies, phonons tend to weakly antibunching within the photonic strong-bunching area. In contrast, one can find that the configurations of correlation functions for both photons and phonons in the parity conserving case are squeezed towards the central frequency by parity breaking, which directly triggers the reverse statistical behaviors for the different parties at the low-frequency regions and the strong bunching properties at other frequency regions. The photon-phonon cross-correlation function also demonstrates similar parity-induced differences, indicating that the non-conserving parity induces the photon-phonon bunching behavior. We finally analyze the delayed second-order correlation function with different driving frequencies, which illustrates striking oscillations revealing the occurrence of simultaneous multiple excitations.Comment: 9 pages, 7 figures. To appear in PR

Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery.

Neurite initiation is the first step in neuronal development and occurs spontaneously in soft tissue environments. Although the mechanisms regulating the morphology of migratory cells on rigid substrates in cell culture are widely known, how soft environments modulate neurite initiation remains elusive. Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties

Political and social determinants of life expectancy in less developed countries: A longitudinal study

EstE livro corrEspondE à primeira experiência didática do Grupo de trabalho desenvolvimento Urbano do conselho latinoamericano de ciências sociais (clAcso), que reúne cerca de quarenta pesquisadores de diferentes instituições da região. Esta experiência tornou-se possível, graças ao fato da proposta deste curso ter sido aprovada no âmbito da cátedra Florestan Fernandes do conselho. completamente desenvolvida através do campus virtual do clAcso, teve, por principal objetivo, estimular a reflexão sobre alguns dos principais eixos teórico-conceituais e empíricos orientadores da análise da urbanização latino-americana

The Influence of Customer’s Sharing Behavior in Social Commerce

All transaction behaviors between enterprises and customers directly take place on social media. Using social media for people to interact with their friends and family become a routine in the daily life. This study aims to figure out the critical factors and relations of brand community and social commerce. Meanwhile, this study is to investigate the influence on consumers’ engagement by considering the building of a brand community for social commerce. This study reviews many key literatures of social commerce and brand community. This study employs a survey base strategy to figure out the proposed research questions

The Investigation of Hedonic Consumption, Impulsive Consumption and Social Sharing in E-commerce Live-streaming Videos

The use of online live-streaming videos to promote brands and products in e-commerce is “exploding” in China. Whereas, little is known about the mechanism underlying viewers/ audience participating behavior in the rapidly growing online live-streaming videos for commerce phenomenon. Based on the stimulus–organism–response paradigm, this study endeavors to investigate the effects of content and social features (information quality, broadcaster attractiveness and para-social interaction) of on customers cognitive and emotional state (cognitive assimilation and emotional energy) and the subsequently their responses (hedonic consumption, impulsive consumption, and social sharing). 200 valid respondents were collected via cross-sectional online survey websites. The research results provide empirical evidences to support most of our hypotheses, indicating that hedonic consumption and social sharing behavior are determined by emotional energy and cognitive assimilation. These cognitive and emotional states, are influenced by information quality, broadcaster attractiveness, and para-social interaction. Impulsive consumption is only determined by emotional energy