<p>In the thesis we are concerned with actual problems on palindromic subwords and palindromic factors of finite and infinite words. The main course of the research are the ways of determining which of two given words is &ldquo;more palindromic&rdquo; than the other one, that is, defining a measure for the degree of &ldquo;palindromicity&rdquo; of a word. Particularly, we pay attention to two actual approaches: the so-called MP-ratio and the so-called <em>palindromic defect</em>, and answer several open questions about them.<br /><br />Namely, concerning the MP-ratio, a few plausible-looking question have been asked in the literature, which would have, if answered positively, made computations of MP-ratios significantly simpler. We add one more related question to these ones, and then show that, rather unexpectedly, all these questions have negative answer.<br /><br />Concerning the palindromic defect, the main result of this work is a construction of an infinite class of infinite words that have several properties that were sought after in some recent works in this area. Among the most interesting facts is that that all these words are aperiodic words of a finite positive defect, having the set of factors closed under reversal---in some recent works, the construction of even a single word having these properties turned out to be quite hard. Using these words, which we are calling <em>highly potential words</em>, we check the validity of several open&nbsp; conjectures, and for several of them we find out that they are false.</p> / <p> U tezi razmatramo aktuelne probleme u vezi s palindromskim podrečima i palindromskim faktorima konačnih i beskonačnih reči. Glavni pravac istraživanja jesu kriterijumi za određivanje koja od dve date reči je &bdquo;palindromičnija&ldquo; od druge, tj. određivanje stepena &bdquo;palindromičnosti&ldquo; date reči. Akcenat stavljamo na dva aktuelna pristupa: tzv. <em>MP-razmeru</em> i tzv. <em>palindromski defekt</em>, i odgovaramo na vi&scaron;e otvorenih pitanja u vezi s njima.<br /> <br /> Naime, u vezi sa MP-razmerom u literaturi je postavljeno vi&scaron;e pitanja, intuitivno uverljivih, koja bi, u slučaju pozitivnog razre&scaron;enja, znatno pojednostavila izračunavanje MP-razmere. Ovim pitanjima dodajemo jo&scaron; jedno srodno, a zatim pokazujemo da, prilično neočekivano, sva ova pitanja imaju negativan odgovor.<br /> <br /> U vezi s palindromskim defektom, glavni rezultat rada je konstrukcija beskonačne klase beskonačnih reči koje imaju vi&scaron;e osobina za kojima je iskazana potreba u skora&scaron;njim radovima iz ove oblasti. Među najzanimljivije spada činjenica da su sve aperiodične reči konačnog pozitivnog defekta, i da im je skup faktora zatvoren za preokretanje &ndash; u nekim skora&scaron;njim radovima konstrukcija makar jedne reči s ovim osobinama pokazala se kao prilično te&scaron;ka. Pomoću ovih reči, koje nazivamo <em>visokopotencijalne reči</em>, ispitujemo validnost vi&scaron;e otvorenih hipoteza, i za vi&scaron;e njih ustanovljavamo da nisu validne.</p>

La presente investigación tuvo como objetivo principal, determinar el riesgo geotécnico de excavaciones profundas utilizando anclajes post-tensados en edificaciones de Lima Metropolitana, aplicando métodos probabilísticos a partir de un abordaje estadístico simple, basado en la hipótesis fundamental de la distribución normal gaussiana de las variables envueltas.En primer lugar, se utilizó el parámetro fundamental de los anclajes post-tensados, la capacidad última de adherencia en la interacción suelo-lechada de cemento τult, (resistencia en la ruptura). Este parámetro se obtuvo de dieciséis (16) ensayos de arrancamiento a escala natural de anclajes post-tensados cimentados en el conglomerado de Lima Metropolitana, obtenidos de la tesis de maestría de Puelles (2011). En segundo lugar, se realizó un diseño de anclajes post-tensados de edificaciones en Lima Metropolitana de 3, 4 y 5 anillos de 10.50, 13.50 y 16.50 m de profundidad respectivamente. Para ello, se utilizó la metodología FHWA con el objetivo de obtener la capacidad de carga de diseño (TD) de anclajes post-tensados. Además, se ejecutó modelos y modelamientos en el software Slide v6.0 (método equilibrio límite), para realizar el análisis de estabilidad de los mismos. Para ello, se tuvo en cuenta las siguientes variables: los parámetros geotécnicos representativos de Lima Metropolitana, la profundidad de estudio (10.50 a 16.50 m.) y la sobrecarga de edificaciones colindantes. Por último, con los parámetros obtenidos (τult y TD) se definió las curvas estadísticas de distribución de solicitación y resistencia. Luego, se aplicó los métodos probabilísticos e interpretación respectiva, determinado así el riesgo geotécnico para cada caso de estudio. / The main objective of this research was to determine the geotechnical risk of deep excavations using post-tensioned anchors in buildings in Metropolitan Lima, applying probabilistic methods based on a simple statistical approach, based on the fundamental hypothesis of the Gaussian normal distribution of the variables wrapped. Firstly, the fundamental parameter of the post-tensioned anchors was used, the ultimate capacity of adhesion in the soil-cement grout interaction τult, (resistance to rupture). This parameter was obtained from sixteen (16) natural scale pull-out tests of post-tensioned anchorages cemented in the conglomerate of Metropolitan Lima, obtained from the master's thesis of Puelles (2011). Secondly, a design of post-tensioned anchorages of buildings in Metropolitan Lima of 3, 4 and 5 rings of 10.50, 13.50 and 16.50 m depth, respectively, was carried out. For this, the FHWA methodology was used with the objective of obtaining the design load capacity (TD) of post-tensioned anchors. In addition, models and modeling were executed in the Slide v6.0 software (limit equilibrium method), to perform their stability analysis. For this, the following variables were taken into account: the representative geotechnical parameters of Metropolitan Lima, the study depth (10.50 to 16.50 m.) And the overload of neighboring buildings. Finally, with the obtained parameters (τult and TD) the statistical curves of the distribution of stress and resistance were defined. Then, the probabilistic methods and respective interpretation were applied, thus determining the geotechnical risk for each case study. / Tesis

The aim of this study is to describe breast cancer survivors' experiences and the associated meanings participating in their important activities during and after breast cancer treatment and the relationship among the survivor, environment, occupation, and performance, using a concurrent mixed method design. Ten survivors between the ages of 45 and 64 with Stage I, II, or III breast cancer who had been treated consecutively with surgery, chemotherapy, and radiation therapy were recruited for the study. Each survivor completed the Activity Card Sort-modified scoring system (ACSm) during the first and last week of radiation therapy and 3 and 6 months post radiation therapy. Additionally, each survivor participated in a semi-structured interview at the end of radiation therapy and 6 months afterwards. Qualitative data was analyzed using interpretative phenomenological analysis (IPA) to understand the survivors' experiences participating in their most important activities. The means and standard deviations of the proportion of activities resumed for the participants' global and category activities were calculated at each time point. A desire to resume participation in meaningful activities emerged from the data and demonstrated the interrelationship between environment, person, and occupation. Themes from the last week of radiation were (a) individual outlook influences how activities are approached, (b) social support reduces the stress of life, (c) side effects influence how activities are completed, and (d) personal and treatment stresses and struggles influenced their perspectives on life. At 6 months post radiation therapy, the themes were (a) emotional effect on activities, (b) life after cancer has changed due to cancer diagnosis and treatment, and (c) side effects continue to influence daily activities. Using the seven stages of analyzing mixed method data developed by Onwuegbuzie and Teddlie (2003), the qualitative and quantitative data were integrated. The results illustrated that the participants resumed a greater proportion of instrumental activities, which were reported consistently as one of their five most important activities. Additionally, supportive extrinsic factors appeared to be more influential in resuming participation important activities than intrinsic factors. Findings from this study support using the Person-Environment-Occupational-Performance (PEOP) model to develop treatment plans for women undergoing or recovering from breast cancer treatment.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第17780号 / 医博第3806号 / 新制||医||999(附属図書館) / 30587 / 京都大学大学院医学研究科医学専攻 / (主査)教授 妻木 範行, 教授 武藤 学, 教授 松田 道行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20807号 / 医博第4307号 / 新制||医||1025(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 椛島 健治, 教授 瀬原 淳子, 教授 上杉 志成 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

The expression of calcium sensing receptor (CaSR) in the human colonic crypt epithelium is linked to cellular differentiation while its lack of expression is associated with undifferentiated and invasive colon carcinoma. Recent studies show that CaSR suppresses the malignant phenotype through a variety of pathways that inhibits growth and promotes differentiation. CaSR also promotes cytotoxic response to fluorouracil. These studies, taken together, have led me to formulate the following working hypotheses: (i), CaSR is a robust inducer of differentiation by virtue of its ability to activate and integrate diverse growth and differentiation control signals; (ii), loss of CaSR expression enable cellular escape from CaSR control and (iii), loss of CaSR expression is an underlying mechanism of malignant transformation, progression and drug resistance in colon cancer. Previous studies showed that there are endogenous small subpopulations that do not express CaSR in colon carcinoma cell lines. These cells are highly drug resistant. Indeed, immunocytochemical analyses of CaSR showed that the expression of CaSR in both the CBS and HCT116 colon carcinoma cell lines are heterogeneous. Human colon carcinoma cell lines contain small subpopulations (10-20%) that do not express CaSR (termed CaSR null cells). In order to further test my hypotheses, the isolation and characterization of CaSR null cells are required. Here, I report on the isolation, propagation, maintenance and characterization of CaSR null cells from the CBS and HCT116 human colon carcinoma cell lines. CaSR null cells grew as three-dimensional non-adherent spherical clusters with increased propensity for anchorage independent growth, cellular proliferation and invasion of matrigels. CaSR null cells were highly resistant to fluorouracil and expressed abundant amount of thymidylate synthase and survivin. Molecular profiling showed a high level of expression of the previously reported cancer stem cell markers CD133, CD44 and Nanog in CaSR null cells. A significant increase in the expression of epithelial-mesenchymal transitional (EMT) molecules and transcription factors was also observed. These include N-cadherin, β-catenin, vimentin, fibronectin, Snail1, Snail2, Twist and FOXC2. The expression of the tumor suppressive E-cadherin and miR145, on the other hand, was greatly reduced while the expression of oncogenic micro RNAs: miR21, miR135a and miR135b was significantly up-regulated. CaSR null cells possess a myriad of cellular and molecular features that drive and sustain the malignant phenotype. I conclude that CaSR null constitutes a highly malignant and drug resistant phenotype of colon cancer. I discovered that CaSR null cells, cultured in defined human embryonic stem cell culture medium, can be induced to differentiate and acquire CaSR expression when the medium of the null cells was changed to conventional cell culture medium containing fetal bovine serum. I hypothesize that expression of CaSR can alter the phenotype of the CaSR null cells. The objectives of this study were then three folds: (i), determine if induction of CaSR expression could circumvent the molecular phenotype of the CaSR null cells; (ii), determine if CaSR was required in altering the null phenotype and (iii), determine the underlying mechanism of CaSR induction. I hypothesize that if CaSR is a strong promoter of differentiation, then without CaSR, the constraint exerted by CaSR will not be functional and pathways normally inhibited by CaSR will be activated. I found that induction of CaSR expression led to a more indolent phenotype which includes the acquisition of epithelial morphology, down-regulated expression of cancer stem cell markers, down-regulated expression of thymidylate synthase and survivin and increased sensitivity to fluorouracil. Molecular profiling also revealed that the induction of CaSR expression was linked to a down-regulated expression of EMT molecules, EMT associated transcription factors and oncogenic miRNAs with a concurrent up-regulated expression of tumor-suppressive molecules. With the exception of the cancer stem cell markers, the reversal of molecular features, upon the induction of CaSR expression, was directly linked to the expression and function of CaSR because blocking CaSR induction by shRNA circumvented such reversal. I further report that demethylation of the CaSR gene promoter underlie CaSR induction. I conclude that induction of CaSR expression in CaSR null cells resulted in a more indolent phenotype concurrent with a variety of molecular changes and that these changes (with the exception of stem cell markers) are dependent on the expression and function of CaSR. I further conclude that methylation of the CaSR gene promoter is an underlying mechanism of maintaining the CaSR null phenotype while promoter demethylation is an underlying mechanism responsible for CaSR induction. CaSR null is a phenotype of the rapidly proliferating, undifferentiated crypt stem cells at the base of colonic crypts. Differentiation of crypt stem cells toward the apex of a crypt (in the direction of the lumen), on the other hand, is tightly linked to CaSR expression. What induces CaSR expression as the crypt stem cells migrate up the crypts is unknown. I hypothesize that as the colonic crypt stem cells migrate up the crypt, they become increasingly exposed to the colonic fluid in the lumen and components in the colonic fluid can trigger the induction of CaSR expression. Both Ca2+ and vitamin D are good candidates because either Ca2+ or vitamin D can stimulate CaSR expression in the parental CBS and HCT116 human colon carcinoma cells. Certainly, Ca2+ and vitamin D are not the only components involved in regulating CaSR expression. A variety of minerals in the colonic fluid may also serve as good candidates in the induction of CaSR. Of interest is Aquamin, a calcium-rich mineralized extract from the red marine algae, Lithothamnion calcareum, which has been shown to induce differentiation in colon carcinoma cells and possess chemopreventive properties against colon polyp formation in mice fed a high fat diet. CaSR null cells cultured in defined human embryonic stem cell culture medium were used to test this hypothesis because they offer an in vitro model in determining the triggers and the underlying mechanisms of CaSR induction that may resemble that of the colonic crypt stem cells in vivo. I found that all three agonists (Ca2+, vitamin D and Aquamin) induced CaSR mRNA and protein expression and inhibited cellular proliferation in the parental cells which express a heterogeneous mixture of cells with different level of CaSR expression. These agonists also induced CaSR mRNA and protein expression and inhibited cellular proliferation in the homogeneous isolated CaSR null cells. In both cases, Aquamin was found to be most potent in this regard. Induction of CaSR expression by these agonists in the CaSR null cells resulted in demethylation of the CaSR gene promoter with a concurrent increase in CaSR promoter reporter activity. Induction of CaSR expression resulted in a down-regulated expression of tumor inducers and up-regulated expression of tumor suppressors in the CaSR null cells. Again, Aquamin was found to be most potent in this regard. Taken together, I conclude that nutrients are good candidate in the induction of CaSR and differentiation in colonic epithelia cells. Similar to CaSR, transforming growth factor β (TGFβ) is also a robust promoter of differentiation in the colonic epithelium. The expression profile of both CaSR and TGFβ in the colonic epithelium is tightly linked to differentiation. Both CaSR and TGFβ expression progressively increases as the undifferentiated crypt stem cells migrate and differentiate toward the apex of a crypt in the direction of the lumen. Similar to the loss of CaSR in cancer cells, loss of TGFβ responsiveness has long been considered an underlying mechanism of early colon carcinogenesis. I hypothesize that there is functional linkage between CaSR and TGFβ function. Human colonic epithelial CBS cells originally developed from a differentiated human colon tumor, retain CaSR expression and function, TGFβ responsiveness and TGFβ receptor expression. Thus, these cells offer an opportunity to determine the functional linkage (if any) between CaSR and TGFβ. I found that knocking down CaSR expression in the CBS cells abrogated TGFβ-mediated cellular responses and attenuated the expression of TGFβ receptors. Ca2+ or vitamin D treatment induced CaSR expression with a concurrent up-regulation of TGFβ receptor expression. Ca2+ or vitamin D, however, did not induce CaSR in CaSR knocked down cells and without CaSR, there was no up-regulation of TGFβ receptor. I conclude that TGFβ receptor expression and TGFβ mediated responses requires CaSR expression and function. In summary, my research has revealed the important role of CaSR in controlling differentiation. CaSR also function as a robust tumor suppressor. My study clearly discerns the multifarious molecular signaling cascades involved in CaSR function and that methylation and demethylation regulates CaSR expression. My work has also established the importance of CaSR in the chemoprevention of colon cancer. My thoughts in regard to future studies and the potential role that CaSR could play in the management of colon cancer are given in the perspective section of this dissertation.

This study uses a sample of 600 companies from Europe to investigate the risk-adjusted returns of four portfolios with high and low ESG ratings between 2011 and 2021. Four asset pricing models and additional measures for risk and return are tested on different portfolio weights. The findings show that there are no statistical differences in risk-adjusted returns between portfolios with high and low ESG scores. These findings are evident when sole capital gain is considered, and when dividends are reinvested. Differences can however be discerned between portfolio weights. All portfolios show excess returns when adjusted for risk factors in the market. The results from this study contribute to the literature surrounding ESG assets by providing evidence of how high- and low-rated ESG stocks have performed in the European market. This study has practical implications for actors in the capital markets, as it is evident from the results that ESG ratings have no apparent effect on the risk-adjusted returns of a portfolio. If sustainability is of high importance, high ESG companies offer the advantage of aligning financial performance with stakeholder goals, as well as providing adequate returns.

No description available.

The TPACK framework is becoming increasingly pervasive in teacher education. Researchers and practitioners have been seeking reliable and valid ways to measure the constructs associated with the TPACK framework. This study describes the results of both an item review and the reliability and construct validity investigation of the scores from an instrument measuring self-efficacy for the constructs in the TPACK framework. Content-matter experts and the literature were used in order to perform the item review, while both an exploratory and a confirmatory factor analysis were performed in order to assess construct validity. Cronbach's alpha and Raykov's rho were used to assess the reliability. While the reliability was high, the validity was weak. Specific changes to the instrument were suggested as a means of improving validity.