A oxidação de proteínas é um fenômeno metabólico e a degradação de proteínas oxidativamente modificadas confere uma proteção para a célula, evitando acúmulo e a agregação das mesmas. A ineficiência na remoção destas proteínas está relacionada ao processo de envelhecimento e ao aparecimento de doenças neurodegenerativas. A unidade catalítica do proteassomo, denominada de 20S (PT20S), é a principal via de degradação de proteínas danificadas pela oxidação sem que haja gasto de ATP, acoplamento de subunidades regulatórias ou poli-ubiquitinação do substrato proteico. A unidade PT20 por sua vez, pode sofrer modificação pós-traducional chamada de S-glutationilação, que aumenta a velocidade degradação proteica por processo independente de poli-ubiquitinação. Em levedura (Saccharomyces cerevisiae), foram identificados apenas dois resíduos de Cys glutationilados, ambos na subunidade α5 (α5-76 e α5-221). A S-glutationilação ocasiona a abertura da câmara catalítica e uma maior eficiência na degradação de proteínas. Mutações sítio-específicas foram realizadas nessas Cys pela substituição por Ser. As consequências estruturais e funcionais dessas mutações foram o aumento da frequência da conformação fechada da câmara catalítica no α5-76S-PT20S e α5-221S-PT20S. As linhagens que carregam essas mutações apresentaram menor tempo de vida cronológico. Uma dupla mutação randômica na subunidade α5 (S35P / C221S) induziu a abertura da câmera catalítica do 20SPT e esta linhagem apresentou tempo de vida cronológico significativamente aumentado e , aumento na resistência ao estresse oxidativo em paralelo ao aumento da atividade catalítica do 20SPT. O objetivo neste projeto de pesquisa foi realizar uma análise proteômica quantitativa no extrato celular das linhagens mutantes, com o objetivo de identificar proteínas que possam estar relacionadas com a regulação da longevidade celular. Foram selecionadas as linhagens que carregam as mutações: α5-76S e α5-S35P/C221S uma vez que apresentaram expectativa de vida oposta em relação à linhagem selvagem, além de queda e aumento da frequência da conformação aberta da câmera catalítica, respectivamente. A partir da quantificação sem marcação (Label-free quantification), foram identificadas 723-1000 proteínas nas amostras das linhagens selvagem e mutantes. Dentre elas, destacam-se as proteínas 3-isopropilmalato isomerase e argininossuccinato sintase, envolvidas na síntese de leucina e arginina, respectivamente, aumentadas na linhagem mutante C76S e reduzidas na linhagem S35P/C221S. O metabolismo de ambos os aminoácidos está relacionado com a via de sinalização TOR que, por sua vez, está envolvida com o tempo de vida cronológico em levedura. / The protein oxidation is a metabolic phenomenon and the degradation of oxidatively modified proteins confers a protection to cell, avoiding accumulation and aggregation of these proteins. The inefficiency in the removal of these proteins is related to aging process and neurodegenerative diseases. The catalytic unit of the proteasome, named 20S (PT20S) is the main degradative pathway of oxidized proteins in an ATP-independent manner, without proteasomal regulatory units assembly or protein poliubiquitination. The PT20 unit undergoes a post-translational modification named S-glutationilation, which increases the protein degradation by the ATP-independent process. In yeast, only two Cys residues were identified glutationilated, both in the α5 subunit (α5-C76 e α5-C221). The S-glutationilation causes opening of the catalytic chamber and higher efficiency of protein hydrolysis. Site-specific mutations were performed in those Cys residues by their replacement to Ser. The structural and functional consequences of mutations were the increasedfrequency of theclosed conformation of the catalytic chamber in the α5-76S-PT20S and α5-221S-PT20S. The strains carrying those mutations presented shorter chronological life span. A double random mutation in the α5 subunit (S35P / C221S) induced the opening of 20SPT catalytic chamber together toextended chronological life span and, increased resistant to oxidative stress in parallel to increased catalytic activity of the 20SPT. The goal of this project was to perform a label-free quantitative proteomic analysis in the mutant strains to identify proteins that could be related with the regulation of cellularlifespan. From that quantification, 723 - 1000 proteins were identified in the samples of the wild-type and mutant strains. Among these proteins, 3-isopropylmalate isomerase and argininesuccinate sintase, involved in the leucine and arginine biosynthesis, respectively, were found increased in the C76S mutant strain and reduced in the S35P/C221S mutant strain. The metabolism of both amino acids is related with TOR signallingthat, in turn,modulates chronological lifespan in yeast

Através dos números, os homens são capazes de comparar, ordenar, medir e quantificar tudo o que há à sua volta. Além da sua utilização para a matemática, muitos números receberam significados simbólicos. Na Bíblia Hebraica, os números são freqüentes, e possuem diversas funções e significados. Alguns números se destacam, como é o caso do número cento e vinte, utilizado para medidas ou contagens de tempo, espaço (áreas ou territórios), peso, pessoas ou animais. Este número figura no Livro do Gênese (6:3), como medida de tempo, no momento em que um limite de cento e vinte anos é decretado como expectativa máxima de vida do homem uma punição às transgressões do homem, falível e mortal, comparável à expulsão de Adão e Eva do Jardim do Éden (Gn 3:23-24) ou à diversificação das línguas faladas durante o episódio da Torre de Babel (Gn 11:7). Este decreto é estabelecido em uma interpolação de uma narrativa lacônica, aparentemente mitológica, em que seres conhecidos como filhos de Deus se relacionam com as filhas dos homens, dando origem a descendentes conhecidos como gigantes ou heróis. O número cento e vinte está relacionado ao período de cento e vinte anos em que Noé construiu a arca para sobreviver ao dilúvio (Gn 6), aos cento e vinte dias em que Moisés esteve sobre o Monte Sinai em três períodos de quarenta dias cada (Ex 24:12-18, 32:15, 30-31, 34:4, 29), como também ao período de três gerações convencionais de quarenta anos cada, exemplificado pelo pacto de Deus com o povo de Israel: ...guardes todos os Seus estatutos e os Seus preceitos que eu te ordeno tu, teu filho e o filho de teu filho... (Dt 6:2). Assim, apesar de que o número cento e vinte possui uma quantidade enorme de divisores, sua subdivisão em três períodos ou gerações de quarenta anos cada possui um simbolismo que instiga a investigação. / Through the numbers, men are able to compare, sort, measure and quantify everything there is around them. Besides their use for mathematics, many numbers have symbolic meanings. In the Hebrew Bible, numbers are frequent, and have different functions and meanings. Some numbers are highlighted, such as the number one hundred and twenty, used to measure or counting of time, space (areas or territories), weight, people or animals. This number can be found in the Book of Genesis (6:3), as a measure of time, at the moment when a limit of one hundred and twenty years is decreed as the maximum life expectancy of man a punishment for man\'s transgressions comparable to the expulsion of Adam and Eve from the Garden of Eden (Gen. 3:23-24) or the confusion of speech during the episode of the Tower of Babel (Gen. 11:7). This decree is established on an interpolation of a seemingly mythological, laconic narrative in which beings known as the \"sons of God\" had relationships to the \"daughters of men\", giving rise to offspring known as \"giants\" or \"heroes\". The number one hundred and twenty is related to the period of one hundred and twenty years in which Noah built the ark to survive the flood (Gen. 6), to one hundred and twenty days in which Moses was on Mount Sinai in three forty-day periods each (Ex 24 :12 -18 , 32:15 , 30-31 , 34:4, 29), as well as the conventional period of three generations of forty years each, exemplified by the covenant of God with the people of Israel: \" ... keep all His rules and laws that I am prescribing to you you, your children and your childrens children\" (Deut. 6:2). Thus, although the number one hundred and twenty has a huge amount of dividers, its subdivision into three periods or generations of forty years each has a symbolism that instigates the investigation.

The U.S. Congressional Research Service issued a report for Congress in May 2016, entitled” Earthquake Risk and U.S. Highway Infrastructure: Frequently Asked Questions” which highlighted the absence of a national database on the status of seismic vulnerability of bridges or other infrastructure, and thus no estimate of costs to retrofit vulnerable bridges. Low to moderate seismicity regions exist in each of the continental United States, with over 30 states having mostly or entirely low-to-moderate seismicity. Resources at state transportation agencies and municipalities are focused on higher seismicity regions, creating a gap in quantifying the system-wide seismic vulnerability despite an overall aging bridge inventory, much of which was built before current seismic design standards. This research addressed this data gap and reduces barriers to quantifying seismic vulnerability of existing bridges in low-to-moderate seismicity regions. The work included nonlinear dynamic numerical modeling of typical multiple span bridge configurations in both pristine and deteriorated conditions, by subjecting them to seventy ground motions across four low-to-moderate seismic hazard levels, to evaluate their seismic performance. These typical bridge configurations represent over 160,000 bridges, which comprise 55 % of the multiple span bridges nationwide. The research results indicate that there is an overall low probability of significant seismic damage to these typical bridges in such regions. The results also show that current seismic hazard thresholds used for the design of new bridges, and for retrofit of existing bridges, which provide the basis for exempting some bridges from specific seismic analysis and design, can underestimate the expected seismic forces. Those results can be used to refine those exemption thresholds to provide appropriate protection against potential seismic damage in those cases. The study results also formed the basis for a system-wide rapid seismic vulnerability screening algorithm developed for the Vermont bridge inventory, which is applicable to other states with low to moderate seismicity regions.

The purpose of this investigation was to identify key design parameters that might significantly affect the response of span wire traffic light systems during extreme wind events. The performance of these systems was assessed through physical testing in an effort to quantify the effect of sag ratio, wire tension and wire clearance. The Wall of Wind experimental facility at Florida International University was utilized for testing the systems at different wind speeds and wind directions. The findings showed that, at all tested wind directions, lift, drag and tension forces increased with increasing wind speeds. On the contrary, increasing the wind speed resulted in higher inclination on the traffic lights, lower drag coefficients and higher lift coefficients. Overall, when the wind was approaching from the rear face of the traffic signals, increased drag coefficients were recorded. When the sag was set at 7% lower drag coefficients were observed.

<p>The objectives of the present study were 1) to examine the effects of noise exposure on recall and recognition of orally presented text and 2) to examine the relation between working memory capacity and the performance of recall and recognition of orally presented text in noisy conditions. A total of 32 subjects, age 20-33, with no known hearing impairment, were paid to participate in the experiment. The hearing ability of all subjects was tested using recorded sentences with and without background noise. Their working memory capacity was tested using listening span, reading span and operation span tests measuring a) correctly recalled words of all three tests, b) the response latency in the reading span test and c) the processing time of the arithmetical operations in the operation span test. Finally all subjects took recall and recognition tests on texts presented orally with and without broadband background noise (white noise). The test results showed that 1) noise had no significant main effect on recall or recognition of the spoken texts, 2) ) the capacity of the central executive component of working memory, measured as the processing time of the arithmetical operations of the operation span test, correlated significantly with recall and recognition of the orally presented text in the noise condition, but not in the control condition, 3) noise exposure had a negative effect on the recognition performance of subjects with lower capacity of the central executive component of working memory.</p>

The objectives of the present study were 1) to examine the effects of noise exposure on recall and recognition of orally presented text and 2) to examine the relation between working memory capacity and the performance of recall and recognition of orally presented text in noisy conditions. A total of 32 subjects, age 20-33, with no known hearing impairment, were paid to participate in the experiment. The hearing ability of all subjects was tested using recorded sentences with and without background noise. Their working memory capacity was tested using listening span, reading span and operation span tests measuring a) correctly recalled words of all three tests, b) the response latency in the reading span test and c) the processing time of the arithmetical operations in the operation span test. Finally all subjects took recall and recognition tests on texts presented orally with and without broadband background noise (white noise). The test results showed that 1) noise had no significant main effect on recall or recognition of the spoken texts, 2) ) the capacity of the central executive component of working memory, measured as the processing time of the arithmetical operations of the operation span test, correlated significantly with recall and recognition of the orally presented text in the noise condition, but not in the control condition, 3) noise exposure had a negative effect on the recognition performance of subjects with lower capacity of the central executive component of working memory.

The overall aim of the study was to gain some understanding of the lived experience of the care-giving spouses regarding their experiences of the manifestations of the disease, perception of their own health, the possibility of influencing the interpretation of the past, the present and future, outlook on life, surrounding contacts and intimate relationships with their sick partners. The spouses (n=13) of Alzheimer victims were followed with the help of personal interviews, diaries and telephone interviews during a two-years period. The texts was analysed according to a phenomenological-hermeneutic method. The main findings in the study showed that the spouses own health remained quite stable over time. Their perception of the development of their own health seemed to be influenced by how they saw their power to influence their situation, which seemed to be determined by how they interpreted the cause of their health problems.The social network was another important factor for understanding the spouses' experiences. The findings imply that spouses' images of themselves in relation to others were important for their perception of the overall social network. The spouses mostly regarded their relationships positively and their social networks were described as quite stable over time. The spouse's marital relationships, in most cases, seemed to undergo changes with the progress of the disease. Some spouses could maintain feelings of love but mostly the relationships were transformed into ones of tenderness, pity and estrangement. The spouses' valuation of their demented partner was mostly in the form of one of two divergent perspectives. On the one hand, spouses who seemed to perceive their partner as a person separate from the disease, could function as complementary ego aids. On the other hand some spouses were unable to make a distinction between the spouse as a person and the disease.The spouses' experiences regarding their previous relationship with parents, value system, philosophy of life, competence and autonomy seemed to be critical in their experiences of their caring situation. It appears that there is a sub-group of vulnerable carers, as suggested by the concurrence of psychological, physical, and social morbidity, along with deterioration in their marital relationship.The findings are discussed in relation to searching for meaning, the importance of significant others, perceiving and valuing the other, and caring relationships within a life-span perspective. / digitalisering@umu

The aim of this thesis is to investigate the relationship between working memory, English as a second language and academic achievement of secondary school students between the ages of 12-14. The study also examines the effects of age and gender factors on working memory capacity and its relation with academic attainments. Data were collected from 12-14 year-old children (N=54) in two state secondary schools in Kirsehir, Turkey. Verbal working memory was assessed by a reading span (RS) test and a backward digit span (BDS) test. Academic achievement was determined by performance on basic secondary school courses which were English (foreign language), Turkish (mother tongue), Social Sciences, Mathematics and Science. The study examined the predictive role of working memory capacity on success on each course. The results revealed that verbal working memory tests significantly correlated with the tests of both general academic achievement (for RS: r=42, for BDS: r=43) and specific courses (.001&le / p &lt / .01). The results also indicated that verbal working memory capacity had a far more predictive role on school success for females than males.

Comparisons of raw span (i.e., number of staff who report directly to a manager) within and across organizations can misrepresent managerial capacity to support staff because managers may not allocate the same amount of time to staff contact. The purpose was to examine the influence of alternative measures of managerial span on nurse satisfaction with manager’s supervision and on multidisciplinary teamwork. The alternative measures were (a) raw span as a measure of reporting structure and (b) time in staff contact as a measure of closeness of contact by the manager. The main effects of the alternative measures, leadership, hours of operation, and other covariates on outcomes were examined. The interaction effects of the alternative measures with leadership and hours of operation were investigated. The study framework was based on Open System Theory and the boundary spanning functions of managers. A descriptive, correlational design was used to collect survey and administrative data from employees, managers, and organizations. Managerial time allocation data were collected through self-logging and validated through observation. Acute care hospitals were selected through purposive sampling. For supervision satisfaction, the final sample size was 31 first-line managers and 558 nurses. For teamwork, the final sample size was 30 first-line managers and 754 staff. The Leadership Practices Inventory, the Satisfaction with my Supervisor Scale, and the Relational Coordination Scale were used. Hierarchical linear modeling was the main type of analysis conducted. Raw span interacted with leadership and hours of operation to explain supervision satisfaction. Teamwork was explained by leadership, clinical support roles, hours of operation, total areas, and non-direct reports, but not by raw span or time in staff contact. Large acute care hospitals can improve satisfaction with supervision and teamwork by modifying first-line management positions.

Comparisons of raw span (i.e., number of staff who report directly to a manager) within and across organizations can misrepresent managerial capacity to support staff because managers may not allocate the same amount of time to staff contact. The purpose was to examine the influence of alternative measures of managerial span on nurse satisfaction with manager’s supervision and on multidisciplinary teamwork. The alternative measures were (a) raw span as a measure of reporting structure and (b) time in staff contact as a measure of closeness of contact by the manager. The main effects of the alternative measures, leadership, hours of operation, and other covariates on outcomes were examined. The interaction effects of the alternative measures with leadership and hours of operation were investigated. The study framework was based on Open System Theory and the boundary spanning functions of managers. A descriptive, correlational design was used to collect survey and administrative data from employees, managers, and organizations. Managerial time allocation data were collected through self-logging and validated through observation. Acute care hospitals were selected through purposive sampling. For supervision satisfaction, the final sample size was 31 first-line managers and 558 nurses. For teamwork, the final sample size was 30 first-line managers and 754 staff. The Leadership Practices Inventory, the Satisfaction with my Supervisor Scale, and the Relational Coordination Scale were used. Hierarchical linear modeling was the main type of analysis conducted. Raw span interacted with leadership and hours of operation to explain supervision satisfaction. Teamwork was explained by leadership, clinical support roles, hours of operation, total areas, and non-direct reports, but not by raw span or time in staff contact. Large acute care hospitals can improve satisfaction with supervision and teamwork by modifying first-line management positions.