Even more novel to the English speaker than the fact that foreign words should represent a problem at all are the frequent, often concerted reactions against them in Germany from the seventeenth century on. These reactions - attempts to eliminate borrowed words and replace them with German expressions - have been relatively little studied and the references in histories of language usually apply to the baroque <u>Sprachgesellschaften</u> and one or two individual purists. No detailed general survey of German purism is available, there is no bibliography on the subject, and the contribution of the purists has not been fully assessed. This study is intended as a preliminary step towards meeting these needs and offers a critical, fully documented account of purism in the hundred years between 1789 and 1889. This period begins with J.H. Campe, the most important German purist, who was the first to approach the question systematically and in great detail, and ends with the Berlin Declaration of 1889 objecting to the policies of the newly founded <u>Allgemeiner Deutscher Sprachverein</u>. The <u>Sprachverein</u> has fully documented its own history and achievements, but for the rest only Campe and F.L. Jahn have been studied critically. I have sought to investigate who the purists were, how they approached language, why they considered purism necessary, what foreign words they rejected, how they tried to replace them, and to give an account of their activity.

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The purpose of this study was to explore the ways tuning to A = 432 Hz affects emotional response, timbre, sound quality, character and tone compared to the standard tuning of A = 440 Hz, and whether or not it is humanly possible to discern a difference between these two. This was all done in an effort to evaluate claims that A = 432 Hz is superior to standard tuning in regards the previously mentioned factors. For this to be done, the history and development of tuning standards as well as intonation systems, presented alongside theories on the basic physics of sound, the effect of spectral manipulation on timbre and sound, and finally memory structures for remembering musical pitches. As a musician and composer, exploring new ways of creating emotion and controlling the effects of a composition, and dispelling potential misinformation is always a worthwhile pursuit. The study was performed by way of surveys where respondents were asked to listen to a composition in two versions, one in A = 440 Hz and the other in A = 432 Hz and then rate the perceived similarity between these two. They were then asked to give their answer regarding preference and associations of character and emotional response to each version. Results show that the claims of the A = 432 Hz proponents might not be as simple as portrayed, but rather a more complex series of relationships. There is support for the idea that the two tunings are unique enough for the average human to discern a difference between the two, and that some type of unique character is contained in each tuning.

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El objetivo principal de este trabajo de título fue estudiar las cargas de diseño de viento para las estructuras ubicadas a lo largo de Chile siguiendo los criterios de la norma ASCE 7-05 y contrastar los resultados obtenidos al considerar la actual Norma Chilena NCh432.Of71. Para determinar las cargas de diseño sobre una estructura ubicada en una localidad en particular la norma ASCE 7-05 define un valor de referencia para la velocidad del viento que considere la máxima intensidad que las solicitaciones de viento pueden alcanzar durante su vida útil. Este valor de referencia se denomina comúnmente velocidad básica del viento y se estima estadísticamente a partir de registros de velocidades de viento en el pasado, medidos en una determinada localidad y en condiciones particulares de altura, exposición y período de promedio de registros. En este trabajo de título se determinaron los valores de la velocidad básica del viento en once localidades a lo largo de Chile, calculados a partir de registros de velocidades de viento medidos en estaciones meteorológicas. Para ello se consideró un procedimiento estadístico de Análisis de Valores Extremos, así como también aspectos tales como el largo del registro, error muestral, intervalo de promedio, altura del anemómetro, calidad de los datos y exposición del terreno. Los registros utilizados fueron proporcionados por la Dirección Meteorológica de Chile (DMC) y la Comisión Nacional de Energía (CNE). Finalmente se realizó una comparación entre las cargas de viento obtenidas a partir de la norma ASCE 7-05, considerando las velocidades básicas calculadas anteriormente, con las cargas de viento obtenidas aplicando la Norma Chilena NCh432.Of71. La comparación se estableció a partir de los principales factores que definen la presión del viento en cada una de estas normas, así como a partir de las cargas obtenidas de la aplicación de los métodos más simplificados de ambos reglamentos. Se concluye que el criterio de la norma chilena generado a partir de un único valor para la velocidad del viento en todo Chile no es representativo de las condiciones nacionales y además subestima las cargas de viento en el sur del país. Por otra parte se observa una excesiva simplificación en la norma chilena para la determinación de los factores que establecen algunos de sus parámetros, así como también la no consideración de algunos efectos.

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<p>Lung cancer is the third most prevalent cancer in the world; however it is the leading cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for ~85% of the lung cancer cases. The current strategies to treat NSCLC patients with frequent causal genetic mutations is through targeted therapeutics. Approximately 10-35% of NSCLC patient tumors have activated mutations in the Epidermal Growth Factor Receptor (EGFR) resulting in uncontrolled cellular proliferation. The standard-of care for such patients is EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs), a class of targeted therapeutics that specifically inhibit EGFR activity. One such EGFR-TKI used in this study is erlotinib. Following erlotinib treatment, tumors rapidly regress at first; however, over 50% of patients develop erlotinib resistance within a year post treatment. Development of resistance remains to be the major challenge in treatment of NSCLC using EGFR-TKIs such as erlotinib. </p> <p>In approximately 60% of cases, acquired erlotinib resistance in patients is attributed to a secondary mutation in EGFR, whereas in about 20% of cases, activation of alternative signaling pathways is the reported mechanism. For the remaining 15-20% of <a>cases</a> the mechanism of resistance remains unknown. Therefore, it can be speculated that the common methods used to identify genetic mutations in tumors post erlotinib treatment, such as histologic analysis and genetic screening may fail to identify alterations in epigenetic mediators of erlotinib resistance, also including microRNAs (miRNAs). MiRNAs are short non-coding RNAs that post-transcriptionally negatively regulate their target transcripts. Hence, in this study two comprehensive screens were simultaneously conducted in erlotinib sensitive cells: 1) a genome-wide knock-out screen, conducted with the hypothesis that loss of function of certain genes drive erlotinib resistance, 2) a miRNA overexpression screen, conducted with the hypothesis that certain miRNAs drive the development of erlotinib resistance when overexpressed. The overreaching goal of the study was to identify novel drivers of erlotinib resistance such as microRNAs or other epigenetic factors in NSCLC.</p><p>The findings of this study led to the identification of a tumor suppressive protein and an epigenetic regulator, SUV420H2 (KMT5C) that has never been reported to be involved in erlotinib resistance. On the other hand, the miRNA overexpression screen identified five miRNAs that contribute to erlotinib resistance that were extensively analyzed using multiple bioinformatic tools. It was predicted that the miRNAs mediate erlotinib resistance via multiple pathways, owing to the ability of each miRNA to target multiple transcripts via partial complementarity. Importantly, a correlation between the two screens was identified clearly supporting the use of two simultaneous screens as a reliable technique to determine highly significant miRNA-target interactions. Overall, the findings from this study suggest that epigenetic factors, such as histone modifiers and miRNAs function as critical mediators of erlotinib resistance, possibly belonging to the 15-20% of NSCLC cases with unidentified mechanisms involved in erlotinib resistance.</p><p></p>

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