Tesi sul tema "CIN 2"

Les lesions cervicals intraepitelials estan causades per la infecció persistent del virus del papil·loma humà (VPH) en les variants d’alt risc. Si no es resolen, poden créixer i provocar l’aparició d’un càncer de cèrvix uterí. Les lesions CIN-2 són un grau intermig d’aquestes lesions, amb una capacitat de regressió aproximada del 40% (tot i que en noies joves s’estima un 60%) i amb una capacitat de progressió a CIN-3 (pre-càncer) del 22%. El CIN-3 només té una regressió del 32%. Actualment aquestes lesions CIN-2 i CIN-3 es tracten de la mateixa manera amb cirurgia tot i tenir un comportament diferent, de manera sobretractem pacients que no ho necessitarien perquè podrien eliminar la lesió. La intervenció quirúrgica, anomenada conització, es basa en exèresi del fragment més extern del coll uterí, i en cas de realitzar-se més d’una vegada, està associat a problemes obstètrics posteriors com part preterme. La p16 és una proteïna que regula el cicle cel·lular i es troba augmentada en una infecció per un VPH d’alt risc. El Ki-67 és una proteïna del nucli cel·lular que es troba en totes les cèl·lules en replicació. El nostre treball té l’objectiu de descriure la taxa de regressió de les lesions CIN-2 passats 12 mesos de control i veure la relació amb l’estat de la p16 i Ki-67 al diagnòstic. La nostra hipòtesi és que un augment de l’expressió de la p16 i del Ki-67 indiquen una lesió en replicació activa, que necessita de tractament quirúrgic. Vàrem dissenyar un estudi prospectiu observacional per al seguiment de pacients amb biòpsia de CIN-2. Es van reclutar 96 pacients que complien criteris d’inclusió i van entrar en l’estudi estadístic final. Es varen seguir les pacients amb citologies i colposcòpia cada 4 mesos, per un màxim de 12 mesos, moment en el qual es realitzava una biòpsia de control per a comprovar l’evolució de la lesió. Les pacients podien seguir si ho desitjaven amb el seguiment 12 mesos més, fins a completar 24 mesos dins l’estudi que compartia aquesta cohort sobre el paper de les cèl·lules Natural Killer en l’evolució del CIN-2. La taxa de regressió completa a curació als 12 mesos va ser del 64% (regressió total 26% i parcial 38%), i el 8% van progressar a un CIN-3. Les característiques epidemiològiques de les pacients (edat, hàbit tabàquic, contracepció, edat d’inici de les relacions sexuals, nombre total de parelles i paritat) no tenien diferències significatives. El 100% de les pacients amb p16 negativa van regressar a CIN<2. Totes les pacients que van progressar van ser p16 positives. El 57% de les pacients amb p16 positiva van regressar també. El 100% de les pacients amb Ki-67 negativa va regressar a CIN<2. Totes les pacients que van progressar eren Ki-67 positives, i el 59,3% de les pacients p16 positives també van regressar. Una citologia diagnòstica de H-SIL, la infecció pel VPH i en particular del VPH-16, van estar associades a la no regressió de les pacients. La detecció del VPH negativa estaba associada a la regressió. Els canvis majors de la colposcòpia, les lesions de més del 50% del cèrvix i els patrons irregulars estaven associats a la no regressió. Les nostres dades donen seguretat a un maneig més conservador de les lesions CIN-2 que siguin p16 i Ki-67 negatives, de manera que no sobretractem pacients que es beneficiarien de control amb observació i evitaríem possibles complicacions obstètriques posteriors.
Intraepithelial cervical lesions are caused by persistent infection of a high risk human papilloma (HPV). If they are not resolved, they can grow and cause cervical cancer. CIN-2 lesions are an intermediate degree, with a regression rate of 40% (although in young women is 60%) and with a progression rate of CIN-3 (pre-cancer) of 22%. CIN-3 only has a 32% chance of regression. CIN-2 and CIN-3 are treated with surgery despite having a different behavior, so we overtreat patients who would not need it because they could solve the lesion. The surgical intervention is called conization, and is based on removing the outermost fragment of the cervix. It is associated to later obstetric problems such as preterm delivery when performed more than once. Biological markers are proteins that can be identified in these lesions. P16 is a protein involved in cell cycle regulation and its overexpression appears in high-risk HPV infections. Ki-67 is a nuclear protein found in all replicating cells. Our work aims to describe the outcome of CIN-2 lesions followed without treatment during 12 months to evaluate regression rates according to p16 and Ki-67 staining status. Patients with first time histologic diagnosis of CIN-2, older than 18 years old, with satisfactory colposcopy, agreed to follow-up every 4 months for at least 2 years, were prospectively recruited. Previous abnormal cytology and high-risk HPV were reported at baseline. p16 and Ki-67 expression were analyzed on CIN-2 biopsies. Regression was defined as CIN1 biopsy or two consecutive negative cytology, persistence as CIN2 biopsy and progression as histologic diagnosis of CIN3. All patients with CIN3 biopsy were treated with cone excision. The rate of spontaneous regression at 12 months was 65.7%, while 7.8% progressed and 26.5% had a persistent disease. Regression was observed in all p16 negative cases and 56.8% of the p16 positive. All Ki-67 negative cases and 59.3% of the Ki-67 positive cases regressed. HSIL previous cytology, HPV-16 and HPV-18 infection were statistically associated to non-regression compared to regression while HPV-negative was associated to regression. Big lesions (more than 50% of the cervix surface), irregular pattern and major colposcòpic changes were related to non regression. Conclusion The high regression rate of CIN-2 supports clinical observation in selected patients. Our data support that CIN-2 patients with negative p16 and Ki-67 are safe to follow conservative management. It also suggests that HPV-negative and non-HSIL patients should follow less strict follow up. Biomarkers predicting CIN2 regression seem to have a great clinical value and could reduce unnecessary cone excisions and associated complications.

Introducción A principios de los años 70 quedó claramente establecido que el Virus del Papiloma Humano (VPH) es el agente causal del cáncer de cérvix. Además, su historia natural, de una decena de años, desde la infección hasta la aparición del cáncer, está muy bien estudiada. Estas características, hacen que el cáncer de cérvix sea una enfermedad idónea para establecer programas de prevención, tanto primaria como secundaria. Las lesiones preneoplásicas de cérvix, suponen un número muy elevado de consultas y reconsultas, generando ansiedad a las pacientes, generalmente jóvenes, que en ocasiones, deben ser sometidas a intervenciones quirúrgicas. Esto supone un elevado coste para la sanidad pública, por tanto debemos tratar de ser los más eficientes, seleccionando bien a las pacientes a seguir y tratar. Objetivos del estudio Valorar la idoneidad del uso de la clasificación en tres grados 1 – 2 y 3 de las neoplasias intrepiteliales de cérvix (CIN) estudiando la concordancia entre patólogos a la hora de establecer diagnósticos. Estudiar como modifica la concordancia entre ellos la tinción de Inmunohistoquímica p16 y valorar la idoneidad del uso de la clasificación binaria – lesiones de alto o bajo grado – para el diagnóstico de estas mismas lesiones. Estudiaremos también si p16 puede predecir qué lesiones evolucionaran peor. Material y método Hemos recogido de nuestro archivo 132 biopsias de cérvix diagnosticadas entre 1999 y 2007 de CIN 2, y las hemos mezclado con una muestra aleatoria de 154 biopsias de cérvix más, con diagnóstico de Negativo, CIN 1, CIN 2, CIN 3 o carcinoma. Las hemos hecho reevaluar por tres patólogos diferentes, estableciendo índices de concordancia. Posteriormente hemos realizado p16 a una representación de las biopsias para volver a establecer datos de concordancia. Después, pasamos una selección aleatoria de 50 biopsias teñidas sólo con HE para establecer el diagnóstico en base a la clasificación binaria. También hemos estudiado la relación entre el resultado de p16 de las biopsias de CIN 2 y el resultado de la conización posterior. Resultados y Discusión El índice de concordancia (índice Kappa) entre los diferentes patólogos a la hora de establecer un diagnóstico sobre la biopsia pequeña de cérvix con HE se sitúa alrededor de 0,40, siendo más bajo para las lesiones CIN 1 y CIN 2 que para los diagnósticos CIN3. Con el uso indiscriminado de p16 no sólo no mejora, si no que empeora, en cambio sí observamos una notable mejoría del índice Kappa utilizando la clasificación binaria (llega a alcanzar un valor de 0,75) que mejora utilizando p16 conjuntamente (hasta 0,82). En la mayor parte de los casos las biopsias CIN 2 que fueron positivas para p16 presentan una pieza de conización con una lesión de alto grado (CIN2+) pero no en el 100% de los casos, y también encontramos casos con p16 negativa que van seguidas de una lesión de alto grado. Conclusiones La clasificación binaria de las lesiones preneoplásicas de cérvix, mejora la concordancia interobservador a la hora de establecer diagnósticos. P16 ayuda, si se utiliza después de una formación, y se reserva para aquellos casos dudosos. No se pueden establecer diagnósticos basados sólo en el resultado de p16, es un complemento a la hematoxilina.
Introduction In the early 70's it was clearly established that the Human Papillomavirus (HPV) is the causative agent of cervical cancer. In addition, its natural history, of about ten years, from infection to the appearance of cancer, is very well studied. These characteristics make cervical cancer an ideal disease to establish prevention programs, both primary and secondary. The preneoplastic lesions of the cervix, suppose a very high number of consultations and reconsultations, generating anxiety to the patients, generally young, that sometimes, must be submitted to surgical interventions. This supposes a high cost for the public health, therefore we must try to be the most efficient, selecting the patients well to follow and treat.   Objectives of the study To assess the suitability of the use of the classification in three grades 1 - 2 and 3 of the intraepithelial neoplasms of the cervix (CIN), studying the agreement between pathologists when establishing diagnoses. To study how the agreement between them corrects the p16 Immunohistochemical staining and to evaluate the suitability of the use of the binary classification - high or low grade lesions - for the diagnosis of these same lesions. We will also study if p16 can predict which lesions will evolve worse.   Material and method We have collected from our archive 132 cervical biopsies diagnosed between 1999 and 2007 of CIN 2, and we have mixed them with a random sample of 154 more cervical biopsies, with a diagnosis of Negative, CIN 1, CIN 2, CIN 3 or carcinoma. We have reevaluated them by three different pathologists, establishing concordance rates. Subsequently we performed p16 to a representation of the biopsies to re-establish concordance data. Then, we passed a random selection of 50 biopsies stained with HE only to establish the diagnosis based on the binary classification. We have also studied the relationship between the p16 result of the CIN 2 biopsies and the result of the subsequent conization.   Results and Discussion The concordance index (Kappa index) between the different pathologists when establishing a diagnosis of small biopsies of the cervix with HE is around 0.40, being lower for the CIN 1 and CIN 2 lesions than for the diagnoses CIN3. With the indiscriminate use of p16 not only does it not improve, but it does get worse, however we do observe a notable improvement in the Kappa index using the binary classification (it reaches a value of 0.75) that improves using p16 together (up to 0, 82). In most cases the CIN 2 biopsies that were positive for p16 present a conization piece with a high-grade lesion (CIN2 +) but not in 100% of the cases, and we also found cases with negative p16 that are followed of a high-grade injury.   Conclusions The binary classification of preneoplastic lesions of the cervix improves the interobserver concordance when establishing diagnoses. P16 helps, if used after a training, and is reserved for those doubtful cases. You can not establish diagnoses based only on the result of p16, it is a complement to hematoxylin.

El propòsit del nostre treball és valorar morfomètricament les diferències existents entre la Neoplàsia Intraepitelial Cervical (CIN) grau 2 i 3, així com el tipus de Virus del Papil·loma Humà (VPH) present, estudiat mitjançant Hibridació in situ.
Hem estudiat 66 peces quirúrgiques d'exèresi del coll uterí de pacients amb diagnòstic histològic de CIN 2 i 82 de CIN 3. Hem demostrat amb el nostre estudi que la superfície afectada en el coll cervical per CIN 3 és significativament més gran que la de CIN 2, a la vegada que són lesions longitudinalment majors, amb major afectació glandular, major profunditat en l'afectació glandular i major índex mitòtic. També hem pogut demostrar que VPH 16/18 predomina en CIN 3. No hem trobat diferències significatives en quant a la presència de papil·les vasculars en ambdues lesions i tampoc hem trobat relació entre tipus de VPH i àrea afectada per CIN, així com entre tipus de VPH i edat de la pacient.
El propósito de nuestro trabajo es valorar morfométricamente las diferencias existentes entre la Neoplasia Intraepitelial Cervical (CIN) grado 2 y 3, así como el tipo de Virus del Papiloma Humano (VPH) presente, estudiado mediante Hibridación in Situ.
Hemos estudiado 66 piezas quirúrgicas de exéresis del cuello cervical de pacientes con diagnóstico histológico de CIN 2 y 82 de CIN 3. Hemos demostrado con nuestro estudio que la superficie afectada en el cuello cervical por CIN 3 es significativamente mayor que la de CIN 2, a la vez que son lesiones longitudinalmente mayores, con mayor afectación glandular, mayor profundidad en la afectación glandular y mayor índice mitótico. También hemos podido demostrar que VPH 16/18 predomina en CIN 3. No hemos encontrado diferencias significativas en cuanto a la presencia de papilas vasculares en las dos lesiones y tampoco hemos encontrado relación entre tipo de VPH y área afectada por CIN, así como entre tipo de VPH y edad de la paciente.

Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos Santos
Texto em português e inglês
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-23T06:30:30Z (GMT). No. of bitstreams: 1 Westin_MariaCristinadoAmaral_D.pdf: 3122088 bytes, checksum: 3d2afed3690cd3566bbb3fe26bb492a3 (MD5) Previous issue date: 2013
Resumo: Introdução: O carcinoma escamoso do colo uterino é precedido pela neoplasia intraepitelial cervical grau 3 (NIC 3). A invasão tumoral envolve a degradação da matriz extracelular e membrana basal do epitélio por enzimas proteolíticas denominadas metaloproteinases (MMPs). Os inibidores teciduais das metaloproteinases (TIMPs) também interferem no processo de invasão. Angiogênese é condição indispensável para a progressão tumoral. Objetivo: Analisar a expressão de MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 e VEGF-A na NIC 3 e carcinoma do colo uterino. Sujeito e Métodos: Estudo do tipo comparativo observacional constituído de três grupos:- Grupo 1: 55 casos com diagnóstico de NIC 3, Grupo 2: 30 casos com NIC 3 e carcinoma associados e Grupo 3: 46 casos com carcinoma. A expressão protéica foi pesquisada separadamente nas células tumorais e estromais por reação imunoistoquímica. Para estabelecer a porcentagem de células imunopositivas utilizou-se software morfométrico. Análise Estatística: Aplicou-se o Teste T-pareado ou de Mann-Whitney ou Wilcoxon Signed Rank. Resultados: Em todos os grupos, a expressão tumoral de MMP-14 foi maior que a estromal. Inversamente, a expressão de TIMP-2 foi maior nas células estromais que nas tumorais, em cada grupo diagnóstico. A expressão de MMP-9 foi maior nas células estromais que nas tumorais, com exceção do componente invasor do Grupo 2. A expressão estromal de TIMP-1 foi maior que a tumoral no carcinoma e, ao contrário, sua expressão foi maior nas células tumorais da NIC 3. A expressão de VEGF-A foi maior apenas nas células tumorais da NIC 3. Comparando a expressão dos marcadores entre os grupos, foram encontradas as maiores diferenças entre grupos extremos, ou seja, entre NIC 3 e carcinoma. A expressão de MMP-2 nas células estromais foi maior no componente NIC 3 do Grupo 2 que no NIC 3 do Grupo 1. A expressão de VEGF-A nas células estromais do carcinoma foi maior que nas células estromais da NIC 3. Conclusões: Os resultados deste estudo sugerem que a expressão de TIMP-1 aumenta nas células do estroma e diminui nas células tumorais quando a NIC 3 progride para carcinoma invasor. MMP-9 e TIMP-2 tiveram expressão similar na NIC 3 e no carcinoma, o que limita inferências sobre seu papel na progressão neoplásica. O padrão imunoistoquímico da expressão das MMPs, TIMPs e VEGF-A na NIC 3 e no carcinoma invasivo, quando estas lesões estavam associadas, foi semelhante. A expressão do VEGF-A foi maior nas células tumorais do que nas estromais da NIC 3, porém quando esta lesão progride para carcinoma invasivo sua expressão aumenta nas células do estroma e não se altera nas tumorais. A expressão de MMP-14, MMP-2, TIMP-1 e VEGF-A aumentou com a gravidade da neoplasia
Abstract: Introduction: Squamous cell carcinoma of the cervix is preceded by cervical intraepithelial neoplasia grade 3 (CIN 3). Tumor invasion involves degradation of extracellular matrix and epithelium basement membrane by proteolytic enzymes called metalloproteinases (MMPs). Tissue inhibitors of metalloproteinases (TIMPs) are also involved in the invasion process. Angiogenesis is a prerequisite for tumor progression. Objective: To analyze the expression of MMP-2, MMP-9 and MMP-14, TIMP-1, TIMP-2 and VEGF-A in CIN 3 and invasive carcinoma. Subject and Methods: This comparative observational study was consists of three groups: Group 1: 55 cases diagnosed with CIN 3, Group 2: 30 cases with CIN 3 associated with invasive carcinoma and Group 3: 46 cases with invasive carcinoma. Protein expression was investigated separately in tumor and stromal cells by immunohistochemistry and evaluated by the percentage of cells positive for immunostaining using morphometric software. Statistical Analysis: Was performed applying paired t-test or Mann-Whitney or Wilcoxon Signed Rank. Results: In each diagnostic group, expression markers were significantly higher: MMP-14 in tumor cells, and TIMP-2 in stromal cells; also MMP-9 expression was significantly higher in stromal cells, except in invasive component of group 2, and TIMP-1 had significantly higher expression in stromal cells of invasive carcinoma and in tumor cells of CIN 3. VEGF-A expression was significantly higher only in tumor cells CIN 3. Comparing the expression of markers between groups, two by two, we find the greatest differences between the extreme groups, i.e. between invasive carcinoma and CIN 3. The expression of MMP-2 was significantly greater in the stromal component CIN 3 in group 2 than in CIN 3 only. The expression of VEGF-A was significantly higher in the group stromal cell carcinoma when compared to stromal cells CIN 3. Conclusions: The results of this study suggest that the expression of TIMP-1 increases in the stromal cells and decreases in tumor cells when CIN 3 progresses to invasive carcinoma. MMP-9 and TIMP-2 had similar expression in CIN 3 and invasive carcinoma, which limits inferences about its role in neoplastic progression. The immunohistochemical pattern of expression of MMPs, TIMPs and VEGF-A in CIN 3 and invasive carcinoma, as these lesions were associated, was similar. The expression of VEGF-A was higher in tumor cells than in stromal cells in CIN 3, but when the lesion progresses to invasive carcinoma its expression increases in the stromal cells and the tumor cells does not change. The expression of MMP-14, MMP-2, TIMP-1 and VEGF-A was increased with the severity of the neoplasia
Doutorado
Oncologia Ginecológica e Mamária
Doutora em Ciências da Saúde

CineScrúpulos es una revista digital que recopila los trabajos desarrollados por los alumnos en la clase de Historia del Cine de la Facultad de Comunicaciones de la UPC. El curso no pretende brindar una visión historicista del cine repleta de fechas, nombres de directores, títulos de películas y lugares exóticos, sino que intenta evidenciar la linealidad casi genética que es intrínseca al quehacer fílmico, una tradición que no solo se repite sino que se reinterpreta en distintos escenarios y en distintos momentos. Porque se entiende que el cine es, ante todo, la herencia permanente de lo que se ha hecho antes. Los textos de la revista CineScrúpulos han sido elaborados por los alumnos, profesores y colaboradores de la Facultad de Comunicaciones de la Universidad Peruana de Ciencias Aplicadas. Las imágenes utilizadas han sido obtenidas de distintas páginas web y el uso de las mismas se inscribe en lo estrictamente académico y divulgativo.
La presente edición de Cinescrúpulos se centra en la obra de Stanley Kubrick, excéntrico y extraño, alejado de los reflectores en los últimos años de su vida pero entregado en cuerpo y alma al entorno familiar. El director legó una filmografía del crecimiento, del descubrimiento, del enaltecimiento de la experimentación, del regocijo que origina evitar los formulismos del género, de encontrar la independencia tras haber flirteado con el monstruo corporativo, de no hacerle ascos al terror o al erotismo, de jugar cada una de sus piezas con la maestría del ajedrecista nato que era. También nos damos un tiempo para descubrir los vínculos que existen entre el cine de Charles Chaplin y la construcción de personajes y narrativas que han encumbrado a Pixar como una de las opciones más inteligentes en el terreno de los dibujos animados de los últimos años. Y como broche de oro, una pregunta válida: Francisco Lombardi, nuestro cineasta con la mayor cantidad de títulos estrenados en salas, ¿estará construyendo un cine de género en el Perú o apunta más bien hacia otro lado?.

Type 2 diabetes mellitus is a chronic and debilitating disease whose prevalence continues to rise inexorably. Type 2 diabetes is usually preceded by a condition called prediabetes, which is characterised by impaired glucose regulation. Those with prediabetes have a significantly increased risk of developing type 2 diabetes compared to those with normal glucose control and therefore represent a key population in the prevention of type 2 diabetes. Physical inactivity is thought to be one of the key factors driving the increasing prevalence of prediabetes and type 2 diabetes and consequently forms a pivotal focus of initiatives aimed at their prevention. The principal aims of this thesis were to: 1) conduct a systematic review investigating the effectiveness of lifestyle and physical activity interventions at promoting physical activity in individuals with prediabetes and the effect of physical activity change on the risk of developing diabetes; 2) investigate the effect of walking activity on markers of chronic low grade inflammation; and 3) design and evaluate with objectively measured endpoints a physical activity intervention for adults at risk of developing type 2 diabetes that is suitable for implementation in a health care or community setting if found to be effective. The main findings are listed in the order of the stated aims. 1) Due to the dearth of controlled exercise training studies in those with prediabetes and the absence of evidence that previous diabetes prevention programmes have been successful at initiating clinically significant increases in physical activity, the evidence for the efficacy of physical activity behaviour change at prevention or delaying the progression to type 2 diabetes in those with prediabetes is equivocal. 2) Walking at levels that are consistent with the current physical activity recommendations is associated with reduced chronic low-grade inflammation, independent of other forms of physical activity. 3) The PREPARE programme, developed after a review of health behaviour theory and the current health care climate, is a theorydriven, group-based structured education programme designed to promote increased walking activity in individuals with prediabetes in a health care setting. A randomized controlled trial was conducted to test two versions of the PREPARE programme, a standard version and a pedometer version, against control conditions (advice leaflet). The standard version encouraged participants to set time-based goals based on generic exercise recommendations, whereas the pedometer version enabled participants to set personalized steps-per-day goals and to objectively self-monitor their daily physical activity levels using a pedometer. One hundred and three individuals were recruited to the study and follow-up was conducted at 3,6 and 12 months. At 12 months both intervention conditions were successful at achieving significant increases in objectively measured ambulatory activity; compared to the control group, those who received the pedometer version of the PREPARE programme increased their ambulatory activity by 1952 steps per day (95% CI 953 to 2951) and those who received the standard version by 1480 steps per day (95% CI 436 to 2522). However, significant improvements in glucose tolerance were only seen in the pedometer group, where 2-h glucose levels decreased by -0.94 mmol/l (95% Cl -1.79 to - 0.10) compared to control conditions, despite no significant change in body weight or waist circumference. This thesis has identified important limitations in the current evidence linking physical activity to the prevention of type 2 diabetes in those with prediabetes and has addressed several of these limitations by developing a theory-driven structured education programme which was shown to be successful at promoting physical activity and improving glucose tolerance in those with prediabetes to levels that are equal to or greater than previous multifactor diabetes prevention programmes. This is likely to have important implications for future diabetes prevention trials and clinical practice in the United Kingdom.

Bakgrund: Operativ risk är ett begrepp som har tilltagit i betydelse genom uppdagandet av skandaler och konkurser inom den finansiella sektorn. Varje svenskt försäkringsföretag är skyldigt att hantera operativa risker, men eftersom det är omöjligt att normalisera dess innebörd, åligger det företagen själva att avgöra dess omfång. Många ansträngningar har gjorts vad gäller att rama in och beskriva denna kategori för ”allmän rädsla”, en uppgift som fortsatt lider av brist på konsensus. Syfte: Syftet med denna studie är att fördjupa kunskapen om den operativa risken, sett ur de svenska försäkringsföretagens perspektiv, och sättet till vilket ett givet förhållningssätt inverkar på riskhanteringsprocessen. Metod: Studien har genomförts i två steg. Den första delen har utgjorts av en dokumentstudie, vilken sedermera har fördjupats genom två fallstudier. Slutsats: Studien visar att det finns en mängd tolkningar av operativ risk, vilka sträcker sig från väldigt enklar till väldigt komplexa. Studien visar också att vissa företag inte hanterar sina risker med utgångspunkt i konceptet ”operativ risk”, utan antar en mer pragmatisk inställning till verksamheternas risker. Detta innebär att det finns ett gap förhållande till god praxis kring hanteringen av operativ risk, vilket kompenseras för genom en ökad verksamhetsförståelse och tillämpningen av metoder som inte nödvändigtvis associeras med riskhantering.
Background: Operational risk is a notion that has gained a lot of notoriety due to a number of scandals and bankruptcies within the financial sector. Every Swedish insurance company is obliged to manage its operational risks, and due to the impossibility of normalizing its specific content, it is up to the companies themselves to judge its extent. Many efforts have been made to conceptualize and explain this “fear category”, an effort that in many respects still lacks in consensus. Purpose: The purpose of this study is to increase the knowledge of what constitutes operational risk, from the perspective of Swedish insurance companies, and the way in which a particular view affects the risk management process.  Methods: This study has been conducted in two parts. The first part constitutes a cross-sectional study, which has further been expanded on by conducting a multiple case study, encompassing two insurance companies. Conclusion: This study shows that there are many interpretations of operational risk, ranging from very simple to very complex. This study also shows that some companies do not manage risks based on the concepts of “operational risk”, but from a pragmatic approach towards the business, meaning that some of the foundational good practices are not applied. However, this is mitigated by an increased understanding of the business, as well as the application of methods not necessarily associated with risk management.

In today&
#8217
s market conditions, higher tool life and durable cutting tools which can stand high cutting speeds are required in chip removal process. In order to improve the performance of cutting tools, coatings are employed extensively. Cubic boron nitride (cBN) is a new kind of coating material for cutting tools due to its outstanding properties and testing of cBN as a hard coating for machining have been increasing in recent years. However, there are some challenges such as compressive residual stress, poor adhesion and limiting coating thickness during the deposition of cBN on substrates. In this study, cubic boron nitride (cBN) coatings are formed on cutting tools from hexagonal boron nitride (hBN) target plates. For this purpose, a physical vapor deposition (PVD) system is utilized. PVD system works on magnetron sputtering technique in which material transfer takes place from target plate to substrate surface. Firstly, cBN coatings are deposited on steel and silicon wafer substrates for measurements and analyses. Compositional, structural and mechanical measurements and analysis are performed for the characterization of coatings. Next, several types of cutting tools are coated by cBN and the effects of cBN coatings on cutting performance are investigated. Finally, it can be said that cubic boron nitride coatings are successfully formed on substrates and the improvement of wear resistance and machining performance of cBN coated cutting tools are observed.

Observation du passage d'un regime kondo mixte a un regime kondo pur ou a un regime de valence intermediaire sous l'effet de la pression chimique. Etude du diagramme de phases magnetiques. Determination du coefficient de couplage entre electrons 4 f et la bande de conduction jn(e::(f)). Coefficient de la chaleur specifique, temperature de kondo et coefficient de grueneisen electronique de ceincu::(2)

Expressing foreign proteins in E.coli is a major challenge because they often tend to develop into unsolvable and inactive proteins. They aggregate into so called  inclusion bodies which prevent expression of the protein. This problem might be avoided by fusing the gene of the foreign protein with a soluble protein called solubility tags, which  function is to enhance the solubility of the foreign protein. This report investigates whether Sterol Carrier Protein-2 (SCP-2) could function as a solubility tag. The experiment was carried out by fusing SCP-2 to two recombinant proteins, Green fluorescent protein (GFP) and a form of chloroamphenicol acetyl transferase (CATΔ9). The gene fusion was then inserted into a pET-15 vector and transformed into  the E.coli strain BL21(DE3) to be expressed. The results obtained from Western blot and PageBlue staining indicates that SCP-2 does not enhance the solubility of GFP or CATΔ9 since neither of them was expressed.  Furthermore, previous studies have shown that GFP can in fact be expressed  usingmaltose binding protein (MBP) as a solubility tag. Unfortunately, no success has been made regarding CATΔ9. In conclusion, regarding the results from this report, SCP-2 does not function as a solubility tag. However, further studies should be carried out on SCP-2 with more experiments before rejecting the possibility to use SCP-2 as a solubility tag.

En la actualidad, uno de los factores que impulsa el desarrollo de la economía de un país es la tecnología. En el Perú este desarrollo puede cimentarse sobre la base de utilizar nuestros recursos naturales como el cobre y zinc para ingresar a una nueva etapa moderna que nos permitirá estar a la vanguardia tecnológica en la fabricación de cojinetes autolubricados con aplicación industrial. Lo más importante para el progreso de nuestro país es desarrollar innovaciones tecnológicas y lograr una gran producción de lotes de piezas de precisión, con materiales o mezclas poco comunes controlando el coeficiente de rotura y el cambio dimensional. En el presente trabajo de investigación se demuestra que es viable la fabricación de cojinetes autolubricados con la nueva aleación 92Cu8Zn1Zn(C10H3502)2, para ello se prepararon probetas, las cuales fueron sometidas a diferentes condiciones de temperatura y tiempo de sinterizado, permitiendo de esta manera obtener valores de carga de rotura, porcentaje de cobre, porcentaje de zinc y variación dimensional en el diámetro exterior, en el interior y en la longitud de los cojinetes.
-- At the present time, one of the factors that impels the development of the economy of a country is the technology. In Peru this development can be built on the base of using our natural resources as copper and zinc to enter into a new modern stage that will allow us to be in the technological vanguard in the production of oil-impregnated bearings with industrial application. The most important thing for the progress of our country is to develop technological innovations and to achieve a great production of lots of pieces of precision, with materials or mixtures not conventional keeping in mind the rupture coefficient and the dimensional change of the oil-impregnated bearings. Presently investigation work is demonstrated that is possible the production of oil-impregnated bearings with the new alloy 92Cu8Zn1Zn(C10H3502)2, it was necessary that is why they got ready its samples, which were subjected at different conditions of temperature and time of sinterized, allowing us to get breaking load, copper percentage, zinc percentage and dimensional change in the external diameter, in the internal and in the longitude data of the oil-impregnated bearings.
Tesis

Resumo: A incidência do melanoma tem aumentado, e este câncer apresenta uma das piores taxas de resposta à quimioterapia. Além disso, poucos agentes demonstram atividade antitumoral significativa contra o melanoma metastático, o que justifica a busca por novos quimioterápicos. Neste sentido, muito esforço tem sido feito para se entender os mecanismos moleculares das etapas de progressão tumoral e metástase. A galectina-3 é uma proteína que participa de diversos processos importantes na biologia tumoral. Entretanto, a interpretação dos dados reportados é complexa, pois o papel desta proteína depende da sua localização celular, das interações protéicas envolvidas e da célula. Portanto, neste trabalho, investigamos a influência da expressão ectópica da galectina-3, nas respostas de células de melanoma ao tratamento com complexos de cobre. Complexos de cobre são compostos interessantes devido as suas propriedades redox, que podem ser moduladas pelos ligantes do íon cobre. Já foi demonstrado que complexos de cobre com isatinas ou derivados de isatinas possuem atividade anti-neuroblastoma. O composto [Cu(isaepy)2](ClO4)2 foi citotóxico tanto para as células que não expressam (TM1MNG3) como para as que expressam a galectina-3 (TM1G3), de forma dose-dependente nas concentrações de 25, 50 e 75 M por 24h de exposição. Além disso, este composto também induziu estresse carbonílico, e inibiu a adesão a proteínas da matriz extracelular (MEC) após 24h. Estes efeitos foram mais pronunciados nas células TM1G3, indicando que a galectina-3 aumenta a susceptibilidade celular a danos oxidativos, perda da adesão e morte celular. O composto [Cu(enim)H2O](ClO4)2, por sua vez, produziu efeitos citotóxicos apenas após 48h de tratamento e em concentrações mais altas, como 100 M, atingindo principalmente as células TM1MNG3. Estas células, de fato, apresentaram menos estresse carbonílico e mais inibição à adesão que as TM1G3 após tratamento com [Cu(enim)H2O](ClO4)2. O composto redox inativo [Zn(isaepy)2Cl2] não produziu nenhum efeito em nossas condições experimentais. Assim, nossos dados indicam que dependendo do ligante, a reatividade dos complexos de cobre pode variar, modulando a intensidade de suas propriedades pró-oxidantes, e que a expressão da galectina-3 nas células de melanoma determina as respostas celulares aos estímulos pró-oxidantes dos complexos metálicos.

La Leucoencefalopatia Megalencefàlica amb Quists subcorticals (MLC) és un tipus rar de leucodistròfia vacuolitzant de progressió lenta, que presenta com a principals característiques clíniques macrocefàlia acusada durant els primers anys de vida, deteriorament de les funcions motores, epilèpsia i retard mental de grau mig. Actualment encara es desconeix el mecanisme fisiopatològic de la malaltia, i per tant ni hi ha cap tractament possible per als pacients. S’han descrit dos gens implicats en la malaltia MLC. El primer gen descobert s’anomena MLC1 i codifica per una proteïna de membrana que porta el mateix nom. El segon gen s’anomena GLIALCAM i codifica per una proteïna transmembrana de tipus I que també porta el mateix nom. S’ha decrit que la proteïna GlialCAM actua com a subunitat ß de MLC1 ja que es capaç de dirigir-la i concentrar-la a les unions cel·lulars. Per altra banda, GlialCAM també s’ha descrit com a subunitat auxiliar del canal de Cl- ClC-2 ja que és capaç de modificar les propietats d’activació i rectificació del canal. Recentment s’ha descrit mutacions en ClC-2 associades a un tipus de leucodistròfia vacuolitzant. L’objectiu general d’aquesta Tesi és avançar en la comprensió del possible mecanisme d’acció i la funció de la proteïna GlialCAM i ClC-2 i així aprofundir en el coneixement de en el seu paper en les cèl·lules glials així com en la fisiopatologia de les leucoencefalopaties vacuolitzants. Per a realizar aquest objectiu es van realitzar estudis d’estructura-funció de GlialCAM mitjançant la caracterització bioquímica i funcional de noves mutacions en GLIALCAM associades a MLC. S’ha obtingut una classificació de les mutacions en GLIALCAM en funció del defecte que presentaven. S’ha descrit mutacions defectives en la expressió proteica, defectives en la homooligomerització i en el tràfic a les unions cel·lulars, defectives únicament en el tràfic cel·lular, mutacions sensibles a la manca de MLC1 i mutacions defectives en la internalització de la proteïna. Paral·lelament es va aprofundir en la relació bioquímica entre GlialCAM i ClC-2 a partir de l’estudi bioquímic i funcional de mutacions en CLCN2 associades a leucoencefalopaties vacuolitzants. S’ha observat que GlialCAM augmenta la funció del canal ClC-2 a través de la modificació del gating del canal i de la estabilització de ClC-2 a la membrana plasmàtica però no sembla que millori la sortida de ClC-2 del reticle endoplasmàtic. A més, aquesta estabilització requereix de la formació d’homocomplexes de GlialCAM. Per últim, es va generar i caracteritzar un model knock-down de la proteïna ClC-2 per aprofundir el paper de ClC-2 en els astròcits. Així com també es va avançar en la relació bioquímica i funcional entre GlialCAM i ClC-2 en la fisiologia astrocitària. S’ha descrit que en astròcits en cultiu en condicions d’alta concentració de K+, similar al que succeiria en situacions d’alta activitat neuronal, ClC-2 es transloca de l’aparell de Golgi a les membranes cel·lulars, modificant les seves propietats funcionals per l’efecte de GlialCAM. En canvi, en astròcits deficients de MLC1, ClC-2 es troba retinguda citoplasmàticament. Aquest fet, indicaria que aquestes proteïnes podrien tenir un paper en el procés de sifoneig del K+, i per tant, la deslocalització de ClC-2 podria donar lloc a un desordre en l’homeòstasi d’aigua i ions.
Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC) is a rare type of vacuolating leukodystrophy. Currently still unknown pathophysiological mechanism of the disease, and therefore there is no effective treatment possible for patients. There are two genes involved in the MLC disease. Gene was first discovered was MLC1 and this encodes for a membrane protein with the same name. The second gene is called GLIALCAM and encodes for a transmembrane protein type I that also carries the same name. In our group is has been described that GlialCAM acts as a protein ß subunit of MLC1 because it is able to direct and concentrate in the cellular junctions. Moreover, GlialCAM also act as auxiliary subunit of CLC-2 Cl channel as it is capable of modifying the activation and rectification properties of the channel. Recently, mutations in ClC-2 have been associated with a rare type of vacuolating leukodystrophy. The principal aim of this study is to advance in the knowledge of GlialCAM and ClC-2 in the glial cells and into the pathogenesis of vacuolating leukodistrophies. To accomplish the study, the group performed a biochemical and funcional characterization of new mutations in GLIALCAM associated with MLC. We suggest that the HEPACAM mutations described up to now can be classified in several groups. Some mutations can affect GlialCAM protein expression, affect its ability to cis-homooligomerize and consequently reduce their localization in cell–cell junctions. Some mutations can affect specifically only transinteractions between GlialCAM molecules or may be unstable without MLC1 and finally some mutations affect the protein internalization. Parallel progress was made in the biochemical relationship between GlialCAM and ClC-2 from biochemical and functional studies of mutations in CLCN2 associated with vacuolating leukodystrophies. GlialCAM has been observed to increase ClC-2 function by the modification of its gating and the stabilization of ClC-2 in the plasma membrane. In addition, the stabilization requires a previous formation of GlialCAM’s homocomplexes. Finally, a knock-down model of the CLC-2 protein was generated and characterized to deepen the role of CLC -2 astrocytes. As well as progress was made in biochemistry and functional relationship between CLC -2 and GlialCAM in the astrocitic physiology. It has been reported that astrocytes cultured in conditions of high concentrations of K + , similar to what happens in situations of high neuronal activity , CLC -2 translocates from the Golgi apparatus to the cell membrane , changing the its functional properties for the purpose of GlialCAM . However, in MLC1 deficient astrocytes, CLC -2 is retained intracellularly. This would indicate that these proteins could play a role in the potassium siphoning, and therefore the relocation of CLC -2 could lead to disorder in the homeostasis of water and ions.

This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.
Bachelors
Health and Public Affairs
Legal Studies

Nous avons etudie les deux canaux chlorure cic-2, dont la fonction precise est inconnue, et cftr afin de connaitre leur eventuel role dans la secretion et/ou la proliferation. Nous avons combine l'utilisation des techniques de patch-clamp sur cellule entiere, de mesure du ph i par sonde fluorescente (bcecf) et d'immunologie. Cic-2 : nous avons etudie la regulation du courant cic-2 (iclc-2) par le facteur de croissance tgfalpha. Le tgf (1 ng/ml) inhibe irreversiblement iclc-2 par l'activation d'une pkc. A la concentration de 50 ng/ml, s'ajoute a cet effet d'inhibition, une activation reversible mediee par l'echangeur na(+)/h(+). Ces resultats suggerent que clc-2 module la proliferation. L'inhibition de i c l c - 2 par la pkc pourrait etre directe car la proteine clc-2 contient 10 sites potentiels cibles de cette kinase. Nos resultats montrent que clc-2 est phosphorylee par la pkc in vitro et in vivo. La relation entre cette phosphorylation et l'activite de i c l c - 2 a ete teste par la mutation sequentielle des sites potentiels de phosphorylation. Les resultats preliminaires suggerent que la pkc inhibe clc-2 par phosphorylation directe. Parallelement, nous avons montre que clc-2 est localise au pole apical des cellules cilies bronchiolaires pulmonaires (homme, rat) ainsi qu'au pole apical des cellules coliques humaines ce qui suggere que clc-2 pourrait, apres activation pharmacologique, participer a la secretion de ci. Cftr : nous avons etudie les proprietes biophysiques d'un mutant double (r347h/d979r) de cftr identifie chez un patient atteint de mucoviscidose severe, alors que ces mutations seules sont associees a des formes non severes. Nous avons montre que les effets des deux mutations sur le routage de la proteine

Coactivators for the superfamily of nuclear receptors are defined as factors that enhance their transcriptional activity. Most of these coactivators exert their action through the receptor ligand-dependent activation function 2 (AF-2). This interaction occurs between a coactivator LXXLL motif (NR-box) and a hydrophobic cleft located on the ligand-binding domain of the receptor. Here we describe the cloning and characterization of CIA, a novel C&barbelow;oactivator I&barbelow;ndependent of A&barbelow;F-2 function. CIA displays specific interaction with the RVR orphan nuclear receptor and both specific interaction and transcriptional coactivation potential with the estrogen receptors (ER) alpha and beta. The interaction with ERalpha and beta is strongly enhanced by its natural ligand, estradiol (E2) and surprisingly also by pure antiestrogens EM 800 and ICI 164,384. While the E2-dependent CIA-ERalpha interaction requires an intact CIA LXXLL motif, CIA also interacts with an AF-2 null mutant of ERalpha. Therefore, CIA constitutes the first example of a novel type of ligand-dependent but AF-2 independent nuclear receptor coactivator that may play a specific role in the ER physiology via selective ER modulators (SERMs).

El presente trabajo académico tiene como objetivo principal analizar el papel que desempeñó el marketing digital en la promoción y resultados de las películas Asu Mare 2 y Desaparecer; identificando la correlación que hubo entre la interacción en las redes sociales y los resultados de taquilla en las semanas que ambas películas estuvieron en cartelera.
Trabajo de investigación

Los videojuegos como medio audiovisual han evolucionado; sin embargo, esto ha traído consigo la creación de diferentes géneros los cuales han logrado adaptarse mejor a los tipos de trama propuestas por el cine. No obstante, dentro de este abanico de géneros existe el Sandbox o mundo abierto, el cual ha tenido una acogida muy favorable por los jugadores o gamers; no por las historias que transmiten si no por la libertad de exploración. Pero con la salida del videojuego Red Dead Redemption 2 (2018) la perspectiva de Sandbox por su libertad y no historias cambio. Esta investigación analiza la existencia de la trama audiovisual del cine y cuáles serían las características de dicha trama en el videojuego Red Dead Redemption 2, para su aplicación en futuros lanzamientos de géneros Sandbox.
Videogames as an audiovisual medium have evolved; However, this has brought with it the creation of different genres which have managed to better adapt to the types of plots proposed by the cinema. However, within this range of genres there is the Sandbox or open world, which has had a very favorable reception by players or gamers; not for the stories they convey but for the freedom of exploration. But with the release of the video game Red Dead Redemption 2 (2018) the perspective of Sandbox for its freedom and not stories changed. This research analyzes the existence of the audiovisual plot of the cinema and what would be the characteristics of said plot in the video game Red Dead Redemption 2, for its application in future releases of Sandbox genres.
Trabajo de investigación

Submitted by Carla Santos (biblioteca.cp2.carla@bahiana.edu.br) on 2018-11-20T18:29:59Z No. of bitstreams: 1 VANESSA BRITO Vers??o Final.pdf: 9402373 bytes, checksum: 34605018ccc9454d43d004bd15990560 (MD5)
Approved for entry into archive by JOELMA MAIA (ebmsp-bibliotecacp2@bahiana.edu.br) on 2018-11-20T18:42:19Z (GMT) No. of bitstreams: 1 VANESSA BRITO Vers??o Final.pdf: 9402373 bytes, checksum: 34605018ccc9454d43d004bd15990560 (MD5)
Made available in DSpace on 2018-11-20T18:42:19Z (GMT). No. of bitstreams: 1 VANESSA BRITO Vers??o Final.pdf: 9402373 bytes, checksum: 34605018ccc9454d43d004bd15990560 (MD5) Previous issue date: 2018-07-20
O diagn??stico da infec????o pelo HTLV pode ser realizado atrav??s de testes de triagem, seguidos de testes confirmat??rios sorol??gicos e testes moleculares. Devido ?? heterogeneidade do desempenho relatado pelos testes para triagem para esta infec????o e a necessidade de uma avalia????o sistem??tica dos testes comerciais, este estudo tem o objetivo de analisar a acur??cia diagn??stica dos testes comerciais de triagem e avaliar os testes confirmat??rios sorol??gicos. Neste estudo de acur??cia diagn??stica de fase II, utilizou-se 416 amostras anonimizadas de bioreposit??rio, formando um painel de estudo. Foram avaliados os testes comerciais de triagem sorol??gica Gold ELISA HTLV-1/2, ELISA Murex HTLV-1/2, SYM Solution anti-HTLV-1/2 e Architect rHTLV-1/2, e os testes confirmat??rios comerciais WB 2.4 e INNO-LIA. Todos testes de triagem mostraram 100% de sensibilidade e especificidade > 90% nos testes de ELISA e 98,1% no chemiluminescence immuno assays (CLIA). Os valores do par??metro area under the curve (AUC) foram> 97%. O par??metro odds ratio diagn??stico (ORD), revelou valores altos para os testes de triagem. O teste INNO-LIA classificou 85% das amostras de resultado indeterminado no WB, demonstrando boa capacidade discriminat??ria. Conclu??mos que os testes comerciais para triagem sorol??gica para HTLV-1/2 usados no Brasil s??o seguros para detec????o desta infec????o. Sendo o teste Gold HTLV-1/2 o que possui os melhores par??metros de desempenho entre os testes ELISA. No entanto, quando o CLIA ?? analisado em conjunto, o Architect rHTLV-1/2 apresentou o maior desempenho dentre os testes de triagem. O teste INNO-LIA ?? a melhor escolha dentre os testes confirmat??rios sorol??gicos. S??o necess??rios mais estudos de acur??cia diagn??stica dos testes de triagem para HTLV-1/2 empregando RV, ORD e AUC como par??metros de an??lise do desempenho, especialmente no Brasil que apresenta taxas elevadas dessa infec????o, em especial para os testes Gold ELISA e SYM Solution.

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2017-04-18T14:03:26Z No. of bitstreams: 1 MarceloPereiraMagalhaesdeSalesTese2016.pdf: 33116858 bytes, checksum: d66cc0e5bd4a2a18939274bbf98efba8 (MD5)
Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2017-04-18T14:04:52Z (GMT) No. of bitstreams: 1 MarceloPereiraMagalhaesdeSalesTese2016.pdf: 33116858 bytes, checksum: d66cc0e5bd4a2a18939274bbf98efba8 (MD5)
Made available in DSpace on 2017-04-18T14:04:52Z (GMT). No. of bitstreams: 1 MarceloPereiraMagalhaesdeSalesTese2016.pdf: 33116858 bytes, checksum: d66cc0e5bd4a2a18939274bbf98efba8 (MD5) Previous issue date: 2016-02-29
Diabetes is associated with endothelial dysfunction and several cardiovascular disorders, such as systemic arterial hypertension. Moreover, hypertension and diabetes coexist very frequently, as 60-65% of diabetics are hypertensive. The coexistence of hypertension and diabetes can reduce endothelium-mediated vasodilatation, which can be partially explained by a reduced production of nitric oxide (NO) or a decreased response to NO in the vascular smooth muscle. On the other hand, it has been shown that a single session of exercise can promote significant reductions in blood pressure (BP). This occurrence is known as post-exercise hypotension (PEH) and appears to be associated with the activity of the kallikrein-kinin system and release of NO. Although studies have observed PEH in individuais with T2D the molecular mechanisms have not been fully elucidated. ln addition, the prescription of exercise intensities based on lactate threshold (L T) has been suggested for individuais with T2D.Moreover, in spite of previous studies showing that individuais with T2D exhibit PEH when exercising at intensities around LT , There is evidence that subjects with T2D exhibit lower plasma kallikrein activity (PKA) compared to healthy individuais, suggesting that lower NO release and reduced endothelium-dependent vasodilation would be occurring in response to exercise for this population. However, no investigations were made on the integrated responses of PKA, BK, dessArg9-BK and NO and its association to the occurrence of PEH in individuais with or without T2D.Furthermore, to the best of our Knowledge, there is only one study that has investigated the effects of exercise (aerobic and / or resistance) on the 24-hour BP response in individuais with T2D. Not to mention that it is not of our knowledge, studies that have investigated the effects of different aerobic exercise intesities on BP 24 hours in subjects with T2D.Additionally, Several studies have investigated the effects of different exercise modes ( e.g., aerobic vs. resistance ), intensities, and durations on BP responses during the post-exercise recovery period. Studies regarding the effects of different sports modalities, especially martial arts, have also been performed, such as: Tai Chi Chuan, Jiu Jitsu, and Judo. However, until now, no study has explored the BP responses after a single Contact Karate (CK) session. It is worth mentioning that the scientific literature related to combat sports has hardly been explored, especially regarding health-related variables (i.e., post-exercise BP reduction). Most studies have investigated performance-related parameters in athletes, making the evaluation of health-related variables (such as PEH) a scientific gap. Therefore, investigations related to this issue have been strongly encouraged. It should be noted that given the known complications of type 2 diabetes and characteristics of sport (high physical contact of high impact), it is wise to initially investigate the effects of a contact karate session on the blood pressure response after exercise in apparently healthy subjects and then, if possible, in special populations as diabetes and hypertension. With regard to chronic exercise, in particular the resistance exercise, the available literature concerning their effects on the response of NO and, in tum, on BP in individuais with T2D, it is still incipient. To the best of our knowledge, there have been only two randomized clinical trials ofRT's effects on NO concentration and BP levels in T2D patients, only one of which, verified the NO response (along with BP) due to R T. Therefore, there is an apparent lack of evidence on R T' s effects on the responses of NO and BP in T2D patients. Objectives: Study 1) to investigate and compare the responses of PKA, BK, desArg9-BK, NO and BP after a single session of moderate-intensity aerobic exercise in T2D and non-diabetic (ND) individuais; study 2) To verify the effects of different intensities of aerobic exercise on 24-hour ambulatory BP responses in individuais with T2D and prehypertension; study 3) to verify the effects of a Contact Karate (CK) session on BP responses during a post-exercise recovery period in young adults; study 4) to determine the effects of eight weeks RT on the responses of NO and BP in T2D patients and their controls peers. Methods: study l)Ten subjects with T2D and 10 Non-diabetics (ND) underwent three sessions: 1) maximal incremental test on cycle ergometer to determine lactate threshold (L T); 2) 20- min of constant-load exercise on cycle ergometer, at 90% LT and; 3) control session. BP and oxygen uptake were measured at rest and at 15, 30 and 45 min post-exercise. Venous blood samples were collected at 15 and 45 minutes of the recovery period for further analysis of PKA, BK and desArg9-BK. NO was analyzed at 15 minutes post exercise. Study 2) ten individuals with T2D and prehypertension completed three sessions applied in random order: non-exercise control (CON) and exercise at moderate (MOD) and maximal (MAX) intensities. Heart rate (HR), BP, blood lactate concentrations ([Lac ]), oxygen uptake (VO2), and rate of perceived exertion (RPE) were measured at rest, during the experimental sessions, and during the 60 min recovery period. After this period, ambulatory blood pressure was monitored for 24 h. Study 2) ten individuals with T2D and prehypertension completed three sessions applied in random order: non-exercise control (CON) and exercise at moderate (MOD) and maximal (MAX) intensities. Heart rate (HR), BP, blood lactate concentrations ([Lac ]), oxygen uptake (VO2), and rate of perceived exertion (RPE) were measured at rest, during the experimental sessions, and during the 60 min recovery period. After this period, ambulatory blood pressure was monitored for 24 h. Study 3) Thirty-two male CK athletes volunteered and underwent one CK session (50 min) anda control session. BP was measured during rest (before sessions), as well as on the 15th, 30th, 45th, and 60th min of the post-exercise recovery. Study 4) We performed eight-weeks of randomized controlled trial in T2D patients and ND individuals. After initial screening, were randomly allocated into four groups: (1) trained T2D (T2DTRAINED; n = 9), (2) trained ND (NDTRAINED; n = 10), (3) control T2D (T2DCON; n = 8) and (4) control ND (NDCON; n = 7). NO and BP were determined before and after the intervention. Results: study 1) The ND group presented PEH of systolic blood pressure (SBP) and mean arterial pressure (MAP) on the 90% L T session but T2D group did not. Plasma NO increased ~24.4% for ND and ~13.8% for T2D group 15min after the exercise session. Additionally, only ND individuais showed increases in PKA and BK in response to exercise and only T2D group showed increased desArg9-BK production. Study 2) Compared with CON, only MAX elicited post-exercise BP reduction that lasted for 8 h after exercise and during sleep. Study 3) The SBP, diastolic blood pressure, and MAP were significantly lower at the post-exercise period compared to pre-exercise rest (p<.05), with the largest reductions being observed at the 60th min of recovery and at the sarne periods of post-exercise recovery of the control session. Study 4) After eight weeks of RT (three times per week), the T2D and ND experimental groups decreased systolic blood pressure (SBP) by 7.0 and 3.4 mmHg, respectively. However, the control groups showed maintenance (0.24 mmHg for T2D) or elevation (2.2 mmHg for ND) of systolic blood pressure. Although none of these changes were significant (p > .05). As regards the absolute values of BP, T2D subjects who did not undergo the training (T2DCON) tended (p = .057) to have increase SBP and significantly (p = .05) increased MAP. Conclusions: studyl) it was concluded that T2D individuals presented lower PKA, BK and NOx release as well as higher desArg9-BK production and reduced PEH in relation to ND participants after a single exercise session. Study 2) A single session of aerobic exercise resulted in 24 h BP reductions in individuals with T2D, especially while sleeping, and this reduction seems to be dependent on the intensity of the exercise performed. Study 3) a single CK session can promote a decrease in BP for at least 60 min after performing this type of exercise in young adults. Study 4) eight weeks of RT does not increase NO concentrations and, in tum, does not reduce BP in T2D patients-though it prevented its increase.
Introdu????o: o diabetes est?? associado com disfun????o endotelial, bem como com diversas desordens cardiovasculares, como hipertens??o arterial sist??mica (HAS). A HAS e o diabetes coexistem muito frequentemente. Aproximadamente, 60-65% dos diab??ticos s??o hipertensos. A coexist??ncia do diabetes e HAS pode reduzir a vasodilata????o endot??lio-dependente, que pode ser parcialmente explicada por uma reduzida produ????o ou resposta ao ??xido n??trico (ON) na nusculatura vascular lisa. Por outro lado, estudos t??m demonstrado que uma ??nica sess??o de exerc??cio pode promover redu????es significativas na press??o arterial (PA). Esta ocorr??ncia ?? conhecida como hipotens??o p??s-exerc??cio (HPE) e parece estar associada com a atividade do sistema calicre??na-cinina e libera????o do ON. Embora estudos tenham observado HPE em indiv??duos com diabetes tipo 2 (DT2), os mecanismos moleculares relacionados ?? sua ocorr??ncia n??o foram completamente elucidados. Adicionalmente, a prescri????o de intensidades de exerc??cio baseada em cargas relativas ao limiar de lactato (LL) t??m sido sugerida para indiv??duos com DT2. No entanto, apesar de estudos anteriores demonstrarem que os indiv??duos com DT2 apresentam HPE quando submetidos a exerc??cios em intensidades em torno LL . Existe evid??ncia que indiv??duos com DT2 apresentam menor atividade da calicre??na plasm??tica (ACP) em compara????o aos indiv??duos n??o diab??ticos, sugerindo uma menor libera????o de ON e redu????o da vasodilata????o endot??lio-dependente em resposta ao exerc??cio para essa popula????o. Contudo, para o nosso melhor conhecimento, ainda n??o foram realizadas investiga????es sobre as respostas integradas de ACP, bradicinina (BK), des-Arg9-bradicinina, ON e sua associa????o com a ocorr??ncia de HPE em indiv??duos com ou sem DT2. Ademais, salvo melhor ju??zo, existe apenas um estudo que tenha investigado os efeitos do exerc??cio f??sico (aer??bio e/ou resistido) sobre a resposta da PA de 24 horas em indiv??duos com DT2. Sem mencionar que tamb??m n??o ?? do nosso conhecimento, estudos que tenham investigado os efeitos de diferentes intensidades de exerc??cio aer??bio sobre a PA de 24 horas em indiv??duos com DT2. Somando a isso, diversos estudos t??m investigado os efeitos de diferentes modos de exerc??cio (aer??bio vs. resistido), intensidades, e dura????es, sobre as respostas da P A p??s-exerc??cio. Estudos sobre os efeitos de diferentes modalidades esportivas, especialmente artes marciais, tamb??m foram realizados, tais como: Tai Chi Chuan, Jiu Jitsu e Jud??. Contudo, at?? o presente momento, nenhum estudo investigou a resposta da P A ap??s uma ??nica sess??o de Carat?? de contato (CC). Vale ressaltar que a literatura cient??fica relacionada a esportes de combate t??m sido pouco explorada, especialmente em rela????o ??s vari??veis relacionadas com a sa??de ( ou seja, a redu????o da PA p??s-exerc??cio). A maioria dos estudos investigaram os par??metros relacionados com o desempenho em atletas, tornando a avalia????o de vari??veis relacionadas com a sa??de, uma evidente lacuna cient??fica. Portanto, investiga????es relacionadas a este assunto t??m sido fortemente encorajada. Cabe salientar que, dado as conhecidas complica????es do DT2 e as caracter??sticas da modalidade em quest??o ( elevado contato f??sico de alto impacto), torna-se prudente inicialmente investigar os efeitos de uma sess??o de CC sobre a resposta da P A p??s-exerc??cio em indiv??duos aparentemente saud??veis e posteriormente, se poss??vel, em popula????es especiais como diab??ticos e hipertensos. No que se refere ao exerc??cio cr??nico, em particular sobre o exerc??cio de for??a, a literatura dispon??vel a respeito dos seus efeitos sobre a resposta do ON e, por sua vez, sobre a PA em indiv??duos com DT2, ainda ?? muito incipiente. Para o melhor do nosso conhecimento, existem apenas dois ensaios cl??nicos randomizados sobre os efeitos do treinamento resistido (TR) sobre a resposta do ON e P A em pacientes com DT2, dos quais apenas um, verificou a resposta do ON juntamente com a P A frente ao TR. Portanto, h?? uma aparente falta de evid??ncias a respeito dos efeitos do TR sobre as respostas do NO e PA em pacientes com DT2. Objetivos: estudo 1) investigar e comparas as respostas de ACP, BK, desArg9-bradicinina, ON e PA ap??s uma ??nica sess??o de exerc??cio aer??bio realizada em intensidade moderada (90% da carga de LL) em indiv??duos com e sem DT2; estudo 2) verificar e comparar os efeitos de uma ??nica sess??o de exerc??cio aer??bio sobre a resposta da PA de 24 horas e verificar os efeitos da intensidade do exerc??cio aer??bio sobre a resposta da PA 24 h em indiv??duos com DT2 e pr??-hipertensos; estudo 3) avaliar os efeitos de uma ??nica sess??o de CC sobre a resposta da PA p??s-exerc??cio em adultos jovens; estudo 4) investigar os efeitos de oito semanas de TR sobre as respostas de ON e P A em pacientes com DT2 e seus pares controles. M??todos: estudo 1) Dez indiv??duos com e DT2 e 10 n??o diab??ticos (ND) foram submetidos a tr??s sess??es: 1) teste incremental m??ximo em bicicleta ergom??trica para determinar o limiar de lactato (LL); 2) 20 min de exerc??cio de carga constante em cicloerg??metro, em 90% L T e; 3) sess??o controle. PA e consumo de oxig??nio foram mensurados em repouso e aos 15, 30 e 45 min p??s-exerc??cio. Amostras de sangue venoso foram coletadas em 15 e 45 minutos do per??odo de recupera????o para posterior an??lise de ACP, BK e desArg9- bradicinina. ON foi analisado aos 15 minutos ap??s o exerc??cio. Estudo 2) Dez indiv??duos com diabetes tipo 2 e pr??-hipertens??o foram submetidos a tr??s sess??es aplicadas em ordem rand??mica: 1) controle ( CON), sem exerc??cio e exerc??cio em intensidades moderadas (MOD) e m??xima (MAX). A frequ??ncia card??aca (FC), P A, as concentra????es de lactato sangu??neo ([Lac ]), consumo de oxig??nio (V02) e taxa de percep????o de esfor??o (TPE) foram coletados em repouso, durante as sess??es experimentais e durante o per??odo de recupera????o de 60 min. Ap??s esse per??odo, a P A de 24 h foi monitorada. Estudo 3) Trinta e dois atletas CC foram submetidos a uma sess??o de CC (50 min) e uma sess??o CON. A PA foi medida durante o repouso, bem como aos 15, 30, 45 e 60 min da recupera????o p??s-exerc??cio. Estudo 4) Foi realizada oito semanas de estudo randomizado controlado em pacientes DT2 e ND). Ap??s a triagem inicial, foram distribu??dos aleatoriamente em quatro grupos: (1) treinados com DT2 (TREINADODT2; n = 9), (2) treinados ND (TREINADOND; = n 1 O), ( 3) controle DT2 (CON DT2; n = 8) e (4) controle ND (CONND; n = 7). NO e BP foram determinadas antes e ap??s a interven????o. Resultados: estudo 1) somente o grupo n??o diab??tico (ND) apresentou HPE para press??o arterial sist??lica e press??o arterial m??dia na sess??o LT 90%. O ON plasm??tico aumentou ~ 24,4% no grupo ND e ~ 13,8% para o DT2 15 min ap??s a sess??o de exerc??cios. Al??m disso, apenas os indiv??duos ND mostraram aumentos de ACP e BK em resposta ao exerc??cio e somente os DT2 mostraram um aumento da produ????o desArg9-bradicinina. estudo 2) Ademais, comparado com a sess??o CON, somente a sess??o de exerc??cio MAX apresentou HPE, que durou at?? 8 h ap??s o exerc??cio e durante o sono. estudo 3) Em rela????o ao CC, a press??o arterial sist??lica (PAS), diast??lica (PAD) e press??o arterial m??dia (MAP) foi significativamente menor no per??odo p??s-exerc??cio em rela????o ao pr??-exerc??cio repouso, bem como em rela????o a sess??o CON, com as maiores redu????es sendo observadas aos 60 min de recupera????o. estudo 4) Ap??s oito semanas de RT, ambos os grupos experimentais (DT2 e ND), apresentaram diminui????o da PAS em 7,0 e 3,4 mmHg, respectivamente. No entanto, os grupos controle (DT2 e ND) demonstrou manuten????o (0,24 mmHg para DT2) ou eleva????o (2,2 mmHg para ND) da PAS. Embora nenhuma das mudan??as foram significativas (p> 0,05). Conclus??es: estudol) concluiu-se que os indiv??duos comDT2 apresentaram menor libera????o ACP, bradicinina e ON, bem como maior produ????o desArg9-bradicinina e reduzida HPE em rela????o aos participantes do grupo ND ap??s uma ??nica sess??o de exerc??cio. Estudo 2) uma ??nica sess??o de exerc??cio aer??bio resultou em redu????o da PA de 24 h em indiv??duos com DT2, especialmente durante o sono, e esta redu????o parece ser dependente da intensidade do exerc??cio realizado. Estudo 3) uma ??nica sess??o CC pode promover uma diminui????o da PA durante pelo menos 60 minutos depois de realizar este tipo de exerc??cio em adultos jovens. Estudo 4) oito semanas de TR n??o aumenta as concentra????es de ON e, por sua vez, n??o reduz a P A em indiv??duos com DT2, por??m parece impedir o seu aumento.

O presente trabalho consistiu na síntese da primeira forma (& do sulfeto de ortonitrodifenila [1-nitro, 2-(feniltio) - benzeno], preparação da segunda forma (ß) por semeadura, caracterização desta forma e obtenção dos espectros infravermelho e Raman de ambas as formas para analisar as possíveis diferenças estruturais. Foi feita uma tentativa de atribuição de frequências, explicando-se as diferenças entre as duas formas. A análise se baseou mais nos espectros da fase sólida que caracteriza o fenômeno polimorfismo. Os espectros da forma ß são inéditos. Os espectros das formas & e ß em soluções e fundidos são praticamente idênticos aos do sólido ß. Conclui-se que as formas $ e ß apresentam a mesma estrutura em soluções e fundidos, diferindo somente em sólidos. Observou-se também que o fundido de forma ß apresenta dois espectros diferentes. Logo acima do ponto de fusão, o espectro mostra algumas características da forma &. Nesta fase de transição, o fundido se comporta como cristal líquido. A transição polimórfica ß & produzida entre dois cristais de NaCl, formando uma camada fina, mostrou um tipo de transição que é mais facilmente explicado pelo processo cooperativo das moléculas (Transformação homogênea).

Aims: To assess the diagnostic accuracy of four undiagnosed Type 2 diabetes mellitus risk scores accounting for erectile dysfunction status. Methods: This was a population-based cross-sectional study. Type 2 diabetes was defined according to a oral glucose tolerance test and self-reported physician diagnosis. Erectile dysfunction was defined according to the answer to the question, ‘Have you had difficulties obtaining an erection in the last 6 months?’ (yes/no). The risk scores used were the FINDRISC, LA-FINDRISC, American Diabetes Association score and the Peruvian Risk Score. A Poisson regression model was fitted to assess the association between Type 2 diabetes and erectile dysfunction. The area under the receiver-operating characteristic curve was estimated overall and by erectile dysfunction status. Results: A total of 799 men with a mean (sd) age of 48.6 (10.7) years were included in the study. The overall prevalence of Type 2 diabetes was 9.3%. Compared with healthy men, men with Type 2 diabetes had 2.71 (95% CI 1.57–4.66) higher chances of having erectile dysfunction. Having excluded men aware of Type 2 diabetes status (N=38), the area under the receiver-operating characteristic curve of three of the risk scores (not the American Diabetes Association score) improved among those who had erectile dysfunction in comparison with those who did not; for example, the area under the receiver-operating characteristic curve of the LA-FINDRISC score was 89.6 (95% CI 78.7–99.9) in men with erectile dysfunction and 76.5 (95% CI 68.5–84.4) overall. Conclusions: In a population-based study, erectile dysfunction was more common in men with Type 2 diabetes than in the otherwise healthy men. Screening for erectile dysfunction before screening for Type 2 diabetes seems to improve the accuracy of well-known risk scores for undiagnosed Type 2 diabetes.
Antonio Bernabe-Ortiz is a Research Training Fellow in Public Health and Tropical Medicine (103994/Z/14/Z), funded by the Wellcome Trust.
Revisión por pares

Aims: To assess the diagnostic accuracy of four undiagnosed Type 2 diabetes mellitus risk scores accounting for erectile dysfunction status. Methods: This was a population-based cross-sectional study. Type 2 diabetes was defined according to a oral glucose tolerance test and self-reported physician diagnosis. Erectile dysfunction was defined according to the answer to the question, ‘Have you had difficulties obtaining an erection in the last 6 months?’ (yes/no). The risk scores used were the FINDRISC, LA-FINDRISC, American Diabetes Association score and the Peruvian Risk Score. A Poisson regression model was fitted to assess the association between Type 2 diabetes and erectile dysfunction. The area under the receiver-operating characteristic curve was estimated overall and by erectile dysfunction status. Results: A total of 799 men with a mean (sd) age of 48.6 (10.7) years were included in the study. The overall prevalence of Type 2 diabetes was 9.3%. Compared with healthy men, men with Type 2 diabetes had 2.71 (95% CI 1.57–4.66) higher chances of having erectile dysfunction. Having excluded men aware of Type 2 diabetes status (N=38), the area under the receiver-operating characteristic curve of three of the risk scores (not the American Diabetes Association score) improved among those who had erectile dysfunction in comparison with those who did not; for example, the area under the receiver-operating characteristic curve of the LA-FINDRISC score was 89.6 (95% CI 78.7–99.9) in men with erectile dysfunction and 76.5 (95% CI 68.5–84.4) overall. Conclusions: In a population-based study, erectile dysfunction was more common in men with Type 2 diabetes than in the otherwise healthy men. Screening for erectile dysfunction before screening for Type 2 diabetes seems to improve the accuracy of well-known risk scores for undiagnosed Type 2 diabetes.
Antonio Bernabe-Ortiz is a Research Training Fellow in Public Health and Tropical Medicine (103994/Z/14/Z), funded by the Wellcome Trust.
Revisión por pares

Aims: To assess the diagnostic accuracy of four undiagnosed Type 2 diabetes mellitus risk scores accounting for erectile dysfunction status. Methods: This was a population-based cross-sectional study. Type 2 diabetes was defined according to a oral glucose tolerance test and self-reported physician diagnosis. Erectile dysfunction was defined according to the answer to the question, ‘Have you had difficulties obtaining an erection in the last 6 months?’ (yes/no). The risk scores used were the FINDRISC, LA-FINDRISC, American Diabetes Association score and the Peruvian Risk Score. A Poisson regression model was fitted to assess the association between Type 2 diabetes and erectile dysfunction. The area under the receiver-operating characteristic curve was estimated overall and by erectile dysfunction status. Results: A total of 799 men with a mean (sd) age of 48.6 (10.7) years were included in the study. The overall prevalence of Type 2 diabetes was 9.3%. Compared with healthy men, men with Type 2 diabetes had 2.71 (95% CI 1.57–4.66) higher chances of having erectile dysfunction. Having excluded men aware of Type 2 diabetes status (N=38), the area under the receiver-operating characteristic curve of three of the risk scores (not the American Diabetes Association score) improved among those who had erectile dysfunction in comparison with those who did not; for example, the area under the receiver-operating characteristic curve of the LA-FINDRISC score was 89.6 (95% CI 78.7–99.9) in men with erectile dysfunction and 76.5 (95% CI 68.5–84.4) overall. Conclusions: In a population-based study, erectile dysfunction was more common in men with Type 2 diabetes than in the otherwise healthy men. Screening for erectile dysfunction before screening for Type 2 diabetes seems to improve the accuracy of well-known risk scores for undiagnosed Type 2 diabetes.
Antonio Bernabe-Ortiz is a Research Training Fellow in Public Health and Tropical Medicine (103994/Z/14/Z), funded by the Wellcome Trust.
Revisión por pares

The thesis focus on the availibility of the time series of producer price index (PPI) in the selected countries from Eastern Europe. The PPI time series are necessary for assets price estimation. The aim of the thesis is to proove if there could be a "converter" between the PPI total and PPI for individual activity which could be used for creating time series in countries where the data are not available.

Background: Effective treatment of patients with type 2 diabetes needs a good communication between nurse and patient. This creats a good relation and leads to a more effective patient education. Aim: The aim with the literature study was to describe how nurses trough patient education can achieve self-care for patients with diabetes type 2. Methods: Literature studies with both qualitative and quantitative articles were examined. Findings: The articles that were chosen for the results were sorted in the two categories relation and communication. Conclusion: A good communication can win the patient’s trust. This can creat trust which is successful by patient education.

The purpose of this bachelor thesis is to present a comparison of housing standards between Sweden and China, in terms of the development of design codes and regulations during the last fifteen years. The study focuses mainly on dwelling sizes and accessibility. The Swedish Building Regulations, BBR7:1999 and BBR18:2011-2013, and the Chinese code Design Code for Residential buildings GB1999:2003 and GB2011 were used as a reference frame. It showed that China has improved its regulations on accessibility greatly, whereas standards on dwelling sizes decreased during the last fifteen years. The study also shows Sweden has reached a sufficient level in terms of dwelling size and accessibility, as only minor difference are found between the codes during the last fifteen years. The comparison between Sweden and China shows that Sweden’s regulations are more developed and user-friendly for the disabled. Sweden can be used as an example for China, in the purpose of carry on improving their requirements covering accessibility. On the other hand, Sweden can improve the accessibility by considering certain measures taken in China, e.g. the design of ramps.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
Lectins are ubiquitous proteins or glycoproteins with at least one non-catalytic domain binding reversibly to a specific mono- or oligosaccharide. Lectins are ubiquitously distributed in plants, animals and microorganisms. Marine algal lectins have been isolated and characterized from only a few species and at a much slower pace since the first report, more than 40 years ago, of the haemagglutinating activity in these organisms. This paucity is mainly due to difficulties in obtaining sufficient material for study. However, among characterized lectins, proteins observed with different biochemical characteristics. Lectins from genus Codium have been isolated and characterized in some detail. In general, have specificity for GalNAc and/or GlcNAc and glycoproteins mucin, fetuin and thyroglobulin, have no requirement for metal ions and were composed by low molecular subunits and may present oligomerization. The present work deals with the purification and characterization of two lectins (CiL-1 and CiL-2) from green marine alga Codium isthmocladum, compare their characteristics and evaluate the ability in agglutinate bacterial cells and toxicity against Artemia. The lectins was purified by a combination of ammonium sulphate precipitation and ion-exchange chromatography on a DEAE-Sephacel column. The main differences observed were the metal dependence, oligomerization state and thermostability. The amino acid sequence of CiL-2 showed no similarity with CiL-1 or other lectins from protein data bank. Only CiL-1 was able to agglutinate bacterial cells whereas CiL-2 showed toxicity against Artemia after 48 hours. In the evaluation of lectin interaction, the data suggest that the CiL-2 recognizes the glycoproteins present in the microcrustacean digest tract. The work has shown that the marine green alga has at least two different lectins with differences in amino acid sequences, biochemical characteristics and biological response.
Lectinas sÃo (glico) proteÃnas com pelo menos um domÃnio nÃo catalÃtico que podem se ligar especÃfica e reversivelmente a carboidratos aglutinando cÃlulas e/ou glicoconjugados. SÃo ubÃquas na natureza, presentes em todos os organismos. Comparando com lectinas de plantas terrestres, poucas lectinas de algas marinhas tÃm sido isoladas e caracterizadas, principalmente devido à dificuldade de obtenÃÃo de material suficiente para estudo. Entretanto, entre as lectinas de algas caracterizadas, observam-se proteÃnas com caracterÃsticas bioquÃmicas diferentes. VÃrias lectinas do gÃnero Codium jà foram isoladas e caracterizadas em algum detalhe. Em geral, possuem especificidade para GalNAc e/ou GlcNAc e glicoproteÃnas, mucina, fetuÃna e tiroglobulina, nÃo dependem de cÃtions divalentes para exibir sua atividade e sÃo compostas de subunidades de baixo peso molecular podendo apresentar formas oligomÃricas. Neste trabalho objetivou-se isolar e caracterizar bioquimicamente duas lectinas isoladas da alga marinha verde Codium isthmocladum (CiL-1 e CiL-2), comparar suas caracterÃsticas e avaliar a capacidade das duas lectinas de aglutinar cÃlulas bacterianas e a toxicidade contra Artemia sp. As lectinas foram purificadas atravÃs da combinaÃÃo de precipitaÃÃo com sulfato de amÃnio e cromatografia de troca iÃnica. Entre as principais diferenÃas bioquÃmicas observadas foram: dependÃncia de metais, oligomerizaÃÃo e estabilidade tÃrmica. No entanto, ambas foram inibidas por Mucina e nÃo por carboidratos simples. Quando comparada a sequÃncia de aminoÃcidos de CiL-2, nÃo houve similaridade com a sequÃncia parcial da CiL-1 ou de qualquer outra sequÃncia de lectinas de algas disponÃveis nos bancos de dados. Somente CiL-1 foi capaz de aglutinar cÃlulas bacterianas enquanto que a CiL-2 apresentou toxicidade contra Artemia sp. apÃs 48 horas de contato. Na avaliaÃÃo da interaÃÃo da lectina, os dados sugerem que a proteÃna reconhece as glicoproteÃnas presentes no trato digestÃrio do microcrustÃceo. O trabalho evidenciou que alga marinha verde C. isthmocladum Vickers possui pelo menos duas lectinas com sequÃncia de aminoÃcidos distinta, mostrando respostas biolÃgicas diferentes, onde a CiL-1 teve capacidade de aglutinar cÃlulas bacterianas e a foi CiL-2 tÃxica contra Artemia sp.

SILVA, Suzete Roberta da. Purificação e caracterização de CiL-2, uma nova lectina isolada da alga marinha verde Codium isthmocladum Vickers. 2013. 71 f. : Dissertação (mestrado) - Universidade Federal do Ceará, Centro de Ciências Agrárias, Departamento de Engenharia de Pesca, Fortaleza-CE, 2013
Submitted by Nádja Goes (nmoraissoares@gmail.com) on 2016-07-22T13:15:28Z No. of bitstreams: 1 2013_dis_srsilva.pdf: 1234725 bytes, checksum: 55b286fd2482006a3f365a7578cde4de (MD5)
Approved for entry into archive by Nádja Goes (nmoraissoares@gmail.com) on 2016-07-22T13:15:48Z (GMT) No. of bitstreams: 1 2013_dis_srsilva.pdf: 1234725 bytes, checksum: 55b286fd2482006a3f365a7578cde4de (MD5)
Made available in DSpace on 2016-07-22T13:15:48Z (GMT). No. of bitstreams: 1 2013_dis_srsilva.pdf: 1234725 bytes, checksum: 55b286fd2482006a3f365a7578cde4de (MD5) Previous issue date: 2013
Lectins are ubiquitous proteins or glycoproteins with at least one non-catalytic domain binding reversibly to a specific mono- or oligosaccharide. Lectins are ubiquitously distributed in plants, animals and microorganisms. Marine algal lectins have been isolated and characterized from only a few species and at a much slower pace since the first report, more than 40 years ago, of the haemagglutinating activity in these organisms. This paucity is mainly due to difficulties in obtaining sufficient material for study. However, among characterized lectins, proteins observed with different biochemical characteristics. Lectins from genus Codium have been isolated and characterized in some detail. In general, have specificity for GalNAc and/or GlcNAc and glycoproteins mucin, fetuin and thyroglobulin, have no requirement for metal ions and were composed by low molecular subunits and may present oligomerization. The present work deals with the purification and characterization of two lectins (CiL-1 and CiL-2) from green marine alga Codium isthmocladum, compare their characteristics and evaluate the ability in agglutinate bacterial cells and toxicity against Artemia. The lectins was purified by a combination of ammonium sulphate precipitation and ion-exchange chromatography on a DEAE-Sephacel column. The main differences observed were the metal dependence, oligomerization state and thermostability. The amino acid sequence of CiL-2 showed no similarity with CiL-1 or other lectins from protein data bank. Only CiL-1 was able to agglutinate bacterial cells whereas CiL-2 showed toxicity against Artemia after 48 hours. In the evaluation of lectin interaction, the data suggest that the CiL-2 recognizes the glycoproteins present in the microcrustacean digest tract. The work has shown that the marine green alga has at least two different lectins with differences in amino acid sequences, biochemical characteristics and biological response.
Lectinas são (glico) proteínas com pelo menos um domínio não catalítico que podem se ligar específica e reversivelmente a carboidratos aglutinando células e/ou glicoconjugados. São ubíquas na natureza, presentes em todos os organismos. Comparando com lectinas de plantas terrestres, poucas lectinas de algas marinhas têm sido isoladas e caracterizadas, principalmente devido à dificuldade de obtenção de material suficiente para estudo. Entretanto, entre as lectinas de algas caracterizadas, observam-se proteínas com características bioquímicas diferentes. Várias lectinas do gênero Codium já foram isoladas e caracterizadas em algum detalhe. Em geral, possuem especificidade para GalNAc e/ou GlcNAc e glicoproteínas, mucina, fetuína e tiroglobulina, não dependem de cátions divalentes para exibir sua atividade e são compostas de subunidades de baixo peso molecular podendo apresentar formas oligoméricas. Neste trabalho objetivou-se isolar e caracterizar bioquimicamente duas lectinas isoladas da alga marinha verde Codium isthmocladum (CiL-1 e CiL-2), comparar suas características e avaliar a capacidade das duas lectinas de aglutinar células bacterianas e a toxicidade contra Artemia sp. As lectinas foram purificadas através da combinação de precipitação com sulfato de amônio e cromatografia de troca iônica. Entre as principais diferenças bioquímicas observadas foram: dependência de metais, oligomerização e estabilidade térmica. No entanto, ambas foram inibidas por Mucina e não por carboidratos simples. Quando comparada a sequência de aminoácidos de CiL-2, não houve similaridade com a sequência parcial da CiL-1 ou de qualquer outra sequência de lectinas de algas disponíveis nos bancos de dados. Somente CiL-1 foi capaz de aglutinar células bacterianas enquanto que a CiL-2 apresentou toxicidade contra Artemia sp. após 48 horas de contato. Na avaliação da interação da lectina, os dados sugerem que a proteína reconhece as glicoproteínas presentes no trato digestório do microcrustáceo. O trabalho evidenciou que alga marinha verde C. isthmocladum Vickers possui pelo menos duas lectinas com sequência de aminoácidos distinta, mostrando respostas biológicas diferentes, onde a CiL-1 teve capacidade de aglutinar células bacterianas e a foi CiL-2 tóxica contra Artemia sp.

In 2020, the meatpacking district of Stockholm (Slakthusområdet) is at the beginning of a period of change. A lot of its buildings are being demolished, or at least gutted, to transform a historical area of industry into a more urban district of housing, offices, trade, and services along with new parks and squares (Stockholms Stad, 2020). This thesis project is specifically about the first building that was torn down as part of the development of the area, Sandhagen 2. We should consider our condemned buildings a precious resource and extract from them rather than from the earth. In every house there is invested energy which is lost the day it is demolished but there is also something else that is lost other than precious resources. The research aims to highlight the importance of reuse not from the more obvious sustainability point of view, but as something that can be aesthetically motivated. The method involves a dissection of Sandhagen 2, extracting interior architectural elements without excessive alterations, and making an organized taxonomy. The taxonomy is then rearranged into a new spatial composition. How can a space be created from a taxonomy defined by an interior architect? How does a material’s earlier life add or take away potential in its future life?  The proposal is a strange space where the tension created by reuse is completely between the elements themselves, a result of having to become the conventional parts of architecture that complete a space; steps, something to sit on, floor, partitions.

Cette étude révèle le comportement d'une matrice de détection infrarouge portée à la température de l'hélium liquide (4. 2 K). La Société Anonyme de Télécommunications (France) réalise la matrice de détection 32 x 32 éléments senseurs, à lecture CID (Charge Injected Devices) sur susbtrat InSb (antimoniure d'indium). Son utilisation à la température de l'hélium liquide est différente de celle prévue par son fabricant (77 K). En particulier, le comportement du courant d'obscurité varie fortement entre ces deux valeurs de T. Seul le courant tunnel est encore actif à la température de l'hélium liquide (les courants d'origine thermique s'annulent). Sensible au potentiel de surface du semi-conducteur, le courant tunnel de la structure MIS-InSb ne sature pas les puits de potentiel de la matrice InSb­ CID. La recherche du temps d'intégration maximum, la contrainte liée à la linéarité de la réponse photonique (spécialement sous faible flux de photons), l'optimisation du rendement quantique et la réduction du bruit de lecture constituent les points fondamentaux de cette étude. Cependant, les mesures expérimentales de la caméra ont révélé des effets secondaires liés au détecteur (dérive, réponse inertielle) ou au cablage électrique (diaphonie). Un chapitre spécial t réservé au comportement des matrices CID-SAT en environment Ƴ·Le résultat de cette phase d'études est la réalisation de la caméra infrarouge CIRCUS (Caméra Infra-Rouge Courte longueur d'onde pour Utilisation au Sol).

La polykystose rénale autosomique dominante (ADPKD) est la maladie monogéniquehumaine la plus fréquente (prévalence 1/800). Les gènes responsables de cette maladie sont PKD1(codant pour PC1) ou PKD2 (codant pour PC2). La maladie évolue vers l’insuffisance rénale terminale.Aujourd’hui, seul un traitement symptomatique est proposé aux malades. Les mécanismes à l’originede l’ADPKD sont mal connus. Les modèles animaux permettent de mieux comprendre laphysiopathologie d’une maladie. Il n’existe pas de bon modèle de polykystose (même causemoléculaire, même mode de transmission, même signes cliniques). En utilisant la transgénose degrands fragments, nous avons créé un modèle de surexpression de PKD2 humain. Le transgène estsous le contrôle de son promoteur naturel humain. Cette souris exprime deux fois plus de PC2 queles sauvages. Elle ne présente que quelques microkystes mais une tubulopathie associant défaut deconcentration des urines et protéinurie tubulaire. La surexpression de PC2 inhibe l’expression degènes codant pour des protéines de la matrice extracellulaire. Le phénotype cellulaire de cesanimaux est remarquable : un tiers des cellules présentent un nombre élevé de centrosomes. Cephénotype cellulaire a été retrouvé chez des souris sous exprimant Pkd2 et chez des souris sousexprimant Pkd1. Ce caractère multicentrosomique est corrigé en incubant les cellules avec uninhibiteur de CaMKII ou en croisant nos souris transgéniques avec une souris KO de Camk2. Nousavons réussi à lier CaMKII, la duplication des centrosomes et les polycystines, in vitro et in vivo. Ceciamène un éclairage nouveau sur la duplication du centrosome et la physiopathologie de l’ADPKD
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic human disease (prevalence 1/800). Genes responsible for this disease are PKD1 (encoding PC1) or PKD2 (encoding PC2). The disease progresses to end stage renal disease. Today, only symptomatic treatment is offered to patients. The mechanisms underlying the ADPKD are unknown. Animals models allow better understand the disease’s pathophysiology. There is no good model of ADPKD (same molecular cause, same clinical signs). We created a mice model of human PKD2 overexpression. The transgène is under the control of its human natural promoter. This mouse expresses PC2 twice as much as the wild. It shows only few microcysts but tubulopathy involving lack of urine concentration and tubular proteinuria. PC2 overexpression inhibits the expression of genes encoding proteins of the extracellular matrix. The cellular phenotype of these animals is special : one third of the cells have a high number of centrosomes. This cellular phenotype was found in Pkd2 Knockout mice and in Pkd1 knockout mice. This multicentrosomic character is corrected by incubating the cells with a CaMKII inhibitor or by crossing our transgenic mice with Camk2 knockout mice. We propose a link between CaMKII, Centrosome duplication and polycystin in vitro and in vivo. This brings a new light on centrosome duplication and pathophysiology of ADPKD