Conjugated polymers (CPs) are intrinsically fluorescent materials that have been used for various biological applications including imaging, sensing, and delivery of biologically active substances. The synthetic control over flexibility and biodegradability of these materials aids the understanding of the structure-function relationships among the photophysical properties, the self-assembly behaviors of the corresponding conjugated polymer nanoparticles (CPNs), and the cellular behaviors of CPNs, such as toxicity, cellular uptake mechanisms, and sub-cellular localization patterns. Synthetic approaches towards two classes of flexible CPs with well-preserved fluorescent properties are described. The synthesis of flexible poly(p-phenylenebutadiynylene)s (PPBs) uses competing Sonogashira and Glaser coupling reactions and the differences in monomer reactivity to incorporate a small amount (~10%) of flexible, non-conjugated linkers into the backbone. The reaction conditions provide limited control over the proportion of flexible monomer incorporation. Improved synthetic control was achieved in a series of flexible poly(p-phenyleneethynylene)s (PPEs) using modified Sonogashira conditions. In addition to controlling the degree of flexibility, the linker provides disruption of backbone conjugation that offers control of the length of conjugated segments within the polymer chain. Therefore, such control also results in the modulation of the photophysical properties of the materials. CPNs fabricated from flexible PPBs are non-toxic to cells, and exhibit subcellular localization patterns clearly different from those observed with non-flexible PPE CPNs. The subcellular localization patterns of the flexible PPEs have not yet been determined, due to the toxicity of the materials, most likely related to the side-chain structure used in this series. The study of the effect of CP flexibility on self-assembly reorganization upon polyanion complexation is presented. Owing to its high rigidity and hydrophobicity, the PPB backbone undergoes reorganization more readily than PPE. The effects are enhanced in the presence of the flexible linker, which enables more efficient π-π stacking of the aromatic backbone segments. Flexibility has minimal effects on the self-assembly of PPEs. Understanding the role of flexibility on the biophysical behaviors of CPNs is key to the successful development of novel efficient fluorescent therapeutic delivery vehicles.

This thesis aims to identify main possible ways how to develop Mělník III coal power plant in the future. The other goal is to evaluate all of them using methods with flexibility and to recommend the most valuable one for the realization. The theoretical part of the thesis describes all key principles used during the valuation and the analytical part contains detailed situation analysis, valuation results and the sensitivity analysis with discussion of the results.

Esta pesquisa teve como principal objetivo, validar o teste de flexibilidade da coluna lombar (Testprop), utilizando-se da radiografia como teste critério e o teste flexibilidade da coluna lombar de ADRICHEM e KORST (1973) para o sexo feminino e masculino. Participaram 19 mulheres (média de idade= 23,2 anos e desvio padrão= 1,3) e 18 homens (média de idade= 22,3 anos e desvio padrão= 1,4), universitários, saudáveis e ativos do Curso de Educação Física e Ciências do Esporte da Universidade Estadual de Londrina - PR. Inicialmente, verificou-se a fidedignidade e objetividade dos testes de flexibilidade da coluna lombar (Testprop e Testeips). O coeficiente de correlação intraclasse mostrou que o teste de flexibilidade Testprop apresenta fidedignidade elevada para o sexo feminino (R= 0,86) e elevada para o sexo masculino (R=0,85), e demonstrou haver objetividade moderada (R= 0,73) para o sexo feminino e elevada (R= 0,96) para o sexo masculino. Quanto ao teste de flexibilidade Testeips, a fidedignidade foi elevada (R= 0,85) e (R= 0,86) para o sexo feminino e masculino, respectivamente. A objetividade do teste de flexibilidade Testeips foi moderada (R= 0,62) para o sexo feminino e elevada para o sexo masculino (R= 0,91). Em relação à validade, o coeficiente de correlação de Pearson mostrou correlação baixa para o teste de flexibilidade Testprop (r= 0,11) para o sexo feminino e correlação moderada (r= 0,52) para o sexo masculino. No que diz respeito ao teste de flexibilidade Testeips, o coeficiente de correlação de Pearson foi baixo para o sexo feminino (r= 0,24) e moderado para o sexo masculino (r= 0,50). Concluiu-se que os testes de flexibilidade da coluna lombar Testprop e Testeips foram fidedignos e objetivos, mas não foram considerados válidos. / The main goal was to validate the flexibility test for the lumbar spine (Testprop), using x-ray as a criteria and the flexibility test of the lumbar spine designed by ADRICHEM and KORST (1973) for females and males, 19 women participated (mean age= 23,2 years old; standard deviation= 1,3 year old) and 18 men (mean= 22,3 year old and standard deviation = 1,4) healthy and active students from the Physical Education and Sport Science Course at the Universidade Estadual de Londrina-PR. Initially, it was verified reliability and objectivity (Testprop and Testeips) the lumbar spine flexibility. The intraclass correlation coefficient showed that the reliability of test of flexibility Testprop was high for woman (R= 0.86) and high for men (R= 0.85), there was a moderate objectivity (R= 0.73) for women and high (R= 0.96) for men. Concerning the flexibility test Testeips, the reliability was high (R= 0.85) and (R= 0.86) for woman and men, respectively. The objectivity for the flexibility test Testeips was moderate (R= 0.62) for women and high for men (R= 0.91). Concerning the validity, Pearson correlation coeficient demonstrated a low correlation for the flexibility test Testprop (r= 0.11) for women and moderate for men (r= 0.52). About the flexibility test, Testeips, Pearson correlation coefficient was low for woman (r= 0.24) and moderate for men (r= 0.50). It was concluded that the flexibility tests of the lumbar spine Testprop and Testeips were reliable and objective, but they were not considered valid.

Background: Chronic pain conditions are pervasive, debilitating, and costly problems across the globe, yet medical treatments often fail to relieve the patients of pain. As a result, complementary treatments, such as yoga, are often used in an attempt to reduce pain and disability. Yoga seems to be effective in short-term relief of pain and, in some cases, helps alleviate psychological comorbidities associated with pain, such as depression and anxiety. The purpose of the current study was to evaluate the efficacy of an eight-week Forrest Yoga intervention on pain interference, pain severity, and psychological outcomes. Methods: Seventy-nine participants were randomly assigned to yoga or usual care and completed a battery of self-report assessments at baseline, mid-intervention (4-weeks), post-intervention (8-weeks), and follow-up (16-weeks). Measures of pain interference, pain severity, number of painful body parts, sensory and affective experience of pain, psychological flexibility, pain catastrophizing, fear of movement, depression and anxiety, and social support were included. Results: There were significant reductions in pain interference and activity avoidance in the yoga group compared to usual care post-intervention. Differences trended towards significance for pain severity and number of painful body parts. Compared to usual care, yoga participants showed significant early reductions in pain interference, pain severity, number of painful body parts, affective experience of pain, depression, overall fear of movement, and activity avoidance. Compared to usual care, these changes were not maintained at 16-weeks (2 months following the intervention). Conclusions: The yoga intervention provided some relief of pain and pain-related problems while the intervention was ongoing but did not provide sustained relief.

Animal models are essential for making the transition from scientific concepts to clinical application. Such models have proven valuable for spinal research. The cervical spine of sheep is often used because there is similar geometry between sheep and human. Although anatomical similarities are important, biomechanical correspondence is imperative to understand the effects of disorders, surgical techniques, and implant designs. Therefore, the purpose of this study was to conduct a comprehensive study of the sheep cervical spine biomechanics, including experimental and finite element analysis. To determine the flexibility of the multilevel spine, ten adult Suffolk sheep C2-C7 spines were tested, undergoing flexion-extension, lateral bending, and axial rotation. In addition to intact multilevel testing, the roles of the stabilizing structures were studied by sequentially destabilizing function spinal units. The sheep spine is highly flexible, especially in lateral bending (±65˚); motion increases with caudal progression. The sheep spine also has a large neutral zone accounting for 50-75% of the total motion. The facets and capsular ligaments play a key role in stabilization, providing the most stability at the C2-C3 level. In addition to flexibility testing, the sheep spinal ligaments underwent tensile testing until failure to determine the material properties. The ligamentum flavum has the largest failure stress and the capsular ligaments have the largest mean failure force. The longitudinal ligaments have the largest failure strain and the lowest failure force. Overall, the C2-C3 ligaments had the highest failure forces as compared to the ligament type at different levels. This corresponds to the stability the ligaments have at the C2-C3 level during flexibility testing. Moreover, a finite element model of the C2-C7 sheep cervical spine was developed and validated to provide additional insight in the sheep biomechanics. The model compared favorably with experimental testing for all loading cases except extension. In general, the model matched the experimental results within one standard deviation for the multilevel motion as well as the motion at each level. Since the sheep is highly flexible and there is a large neutral zone it was difficult to capture the nonlinearity in all loading directions. The model was used to study the effects of fusion at the C3-C4 level. As expected the motion at the fusion was less than one degree, with the non-fused levels accommodating the loss in motion. The motion increased 15-27%, with the largest increase at C6-C7. To obtain the same rotation as the intact model (±2.5 Nm), larger moments were required, increasing to over 5 Nm for flexion and lateral bending and over 3 Nm for extension and axial rotation. The study provides insight into the sheep cervical spine biomechanics. Researchers and scientists should consider the high flexibility and large neutral zone when designing a study that is to correlate to human spines. The model provides additional details such as stresses in the bone and intervertebral disc that can help researchers determine the effects of different surgical techniques and implant designs. Overall, this study provides valuable biomechanical data that can aid designing preclinical animal studies of the sheep.

Shattered assumptions theory posits that each individual has a core set of assumptions about the world and the self, often termed the assumptive world which includes: the world is a benevolent place, the world is meaningful, and the self is worthy. Experiencing a traumatic event is believed to lead individuals to question these assumptions in light of the new contradictory information that causes the assumptive world to shatter, leaving the individual to rebuild a more negative perception of the world and themselves. This rebuilding of a fragile new set of core beliefs is believed to be a cause of posttraumatic stress disorder (PTSD) symptoms. Although shattered assumptions theory has been widely accepted in the field of trauma psychology, the shattering of the assumptive world has not been empirically supported due to measurement issues and poor research designs. The current study implemented a prospective design to assess a new measure of the individual’s assumptive world when there is an intervening trauma. In a college sample (N = 336), individuals who experienced a traumatic event over the course of the semester (n = 40) evidenced decreases in optimism in their assumptive worlds, in comparison to individuals who did not experience a traumatic event. The results suggest there is a limited shattering of the assumptive world for those who experienced a traumatic event. Applications, limitations and future directions are discussed.

abstract: This study investigated low regulatory flexibility as a mechanism of the associations of rumination with affect, internalizing symptoms, and substance use and problems. 403 first-year college students completed an online baseline survey assessing rumination, regulatory flexibility, internalizing symptoms, alcohol use, cannabis use, alcohol problems, and cannabis problems. Roughly 2.67 months later, 261 of these participants completed a follow-up survey assessing internalizing symptoms and substance use and problems. Additionally, 71 of the 403 participants completed an experimental study. Thirty-three participants were randomly assigned to undergo a rumination induction, and 38 were assigned to a control condition. All lab participants underwent an interpersonal stress task during which regulatory flexibility was observed and completed pre-test and post-role-play measures of positive and negative affect. Experimental study results showed regulatory flexibility did not mediate effects of rumination induction on positive (indirect effect: standardized beta (β)=-0.01, unstandardized beta (b)=-0.12, 95% Confidence Interval (CI) [-0.64, 0.41], p=.66) or negative affect (indirect effect: β=0.01, b=0.17, 95% CI [-0.29, 0.63], p=.48). Longitudinal study results showed regulatory flexibility did not mediate associations between baseline rumination and follow-up internalizing symptoms (indirect effect: b=0.01, 95% CI [-0.03, 0.05], p=.57), alcohol use (indirect effect: b=-0.03, 95% CI [-0.09, 0.04], p=.39), cannabis use (indirect effect: b=0.10, 95% CI [-0.06, 0.26], p=.21), alcohol problems (indirect effect: b=-0.05, 95% CI [-0.18, 0.07], p=.40), or cannabis problems (indirect effect: b=-0.10, 95% CI [-0.36, 0.16], p=.43). However, rumination predicted greater internalizing symptoms (Incidence Rate Ratio (IRR)=1.26, b=0.23, 95% CI [0.08, 0.37], p=.003) and cannabis problems (IRR=1.73, b=0.55, 95% CI [0.23, 0.87], p=.001). Regulatory flexibility predicted fewer alcohol use days (IRR=0.76, b=-0.27, 95% CI [-0.49, -0.05], p=.015) and problems (IRR=0.58, b=-0.55, 95% CI [-0.95, -0.15], p=.007), and less cannabis use for women (IRR=0.59, b=-0.53, 95% CI [-0.92, -0.14], p=.007) and fewer cannabis problems for men (IRR=0.21, b=-1.55, 95% CI [-2.50, -0.60], p=.001). Lack of agreement about how best to measure regulatory flexibility makes it unclear whether null associations were due to measurement problems or actual null effects. Research on how best to measure this construct is a priority. Findings indicate rumination and regulatory flexibility may be promising intervention targets. / Dissertation/Thesis / Doctoral Dissertation Psychology 2020

付記する学位プログラム名: 霊長類学・ワイルドライフサイエンス・リーディング大学院 / 京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第22878号 / 理博第4644号 / 新制||理||1668(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)准教授 足立 幾磨, 准教授 Michael Alan Huffman, 教授 高田 昌彦 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

The ability to adapt fuel usage to nutrient availability is termed metabolic flexibility, and is influenced by activity of the pyruvate dehydrogenase complex (PDC). The Virginia lines of chickens are a unique model of anorexia and obesity that have resulted from 56 generations of artificial selection for high (HWS) or low (LWS) juvenile body weight. We hypothesized that hyperphagia and obesity in juvenile HWS chickens are associated with altered fatty acid oxidation efficiency and metabolic flexibility in tissues associated with energy sensing and storage, and relative cellular hypertrophy in white adipose tissue. Hypothalamus, liver, Pectoralis major, gastrocnemius, abdominal fat, clavicular fat and subcutaneous fat were collected from juvenile (56-65 day-old) HWS and LWS chickens for metabolic, gene expression and histological assays. The HWS chickens had reduced fatty acid oxidation efficiency in abdominal fat (P < 0.0001) and reduced rates of oxidation in abdominal fat and gastrocnemius (P < 0.0001) as compared to LWS. There was reduced citrate synthase activity in white adipose tissue (P < 0.0001) and greater metabolic inflexibility in skeletal muscle (P = 0.006) of HWS compared to LWS. Greater pyruvate dehydrogenase kinase 4 (PDK4) and forkhead box O1 (FoxO1) mRNA were found in skeletal muscle and white adipose tissue of 56-day-old HWS than LWS. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in all adipose tissue depots was greater (P < 0.05) in LWS than in HWS chickens. The HWS chickens had larger (P < 0.0001) and fewer (P < 0.0001) adipocytes per unit area than LWS. These results suggest that the HWS chickens have impaired metabolic flexibility and fatty acid oxidation efficiency due to an up-regulation of pyruvate dehydrogenase activity to accommodate the influx of acetyl CoA from fatty acid oxidation in skeletal muscle and white adipose tissue. These metabolic adaptations can be linked to differences in gene expression regulation and body composition between the lines. Adipocyte cellularity data are consistent with greater oxidative efficiency in the adipose tissue of LWS, because of the greater number of unfilled cells in all depots that were sampled. Results can be extrapolated to agricultural production in the understanding of factors regulating the amount of lipid deposition in chicken carcass fat. Results may also provide insight into eating disorders and the development of obesity. / Master of Science

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