935 resultados para Proteostasis Deficiencies
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Tutkielman päätavoitteena on selvittää kyselytutkimuksella, mikä on tutkittavan organisaation tämänhetkinen yrityskulttuurin tila, sekä etsiä teoriatiedon pohjalta yrityskulttuurin kehittämiseksi parhaiten sopivat sisäisen markkinoinnin menetelmät. Tutkimuksen kohteena on Nelipyörä-konsernin henkilökunta. Tutkielman alatavoitteena on selvittää yrityskulttuurin osatekijät sekä kartoittaa sisäisen markkinoinnin keinoja ja menetelmiä. Alatavoite pohjautuu kirjallisuuskatsaukseen ja tukee omalta osaltaan päätavoitteen saavuttamista. Tutkimuksen teoreettinen osa perustuu käsiteanalyyttisen tutkimusotteeseen ja empiirinen osa nomoteettiseen tutkimusotteeseen. Tutkimuksessa määritellään kohdeyrityksen yrityskulttuurin tavoitetila. Tutkimustulokset osoittavat puutteita ja ongelma-alueita tutkittavan yrityksen yrityskulttuurissa. Tutkimuksessa annetaan tuloksiin pohjautuen suunniteltu sisäisen markkinoinnin toimenpidemalli kohdeyrityksen yrityskulttuurin kehittämiseksi.
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Past temperature variations are usually inferred from proxy data or estimated using general circulation models. Comparisons between climate estimations derived from proxy records and from model simulations help to better understand mechanisms driving climate variations, and also offer the possibility to identify deficiencies in both approaches. This paper presents regional temperature reconstructions based on tree-ring maximum density series in the Pyrenees, and compares them with the output of global simulations for this region and with regional climate model simulations conducted for the target region. An ensemble of 24 reconstructions of May-to-September regional mean temperature was derived from 22 maximum density tree-ring site chronologies distributed over the larger Pyrenees area. Four different tree-ring series standardization procedures were applied, combining two detrending methods: 300-yr spline and the regional curve standardization (RCS). Additionally, different methodological variants for the regional chronology were generated by using three different aggregation methods. Calibration verification trials were performed in split periods and using two methods: regression and a simple variance matching. The resulting set of temperature reconstructions was compared with climate simulations performed with global (ECHO-G) and regional (MM5) climate models. The 24 variants of May-to-September temperature reconstructions reveal a generally coherent pattern of inter-annual to multi-centennial temperature variations in the Pyrenees region for the last 750 yr. However, some reconstructions display a marked positive trend for the entire length of the reconstruction, pointing out that the application of the RCS method to a suboptimal set of samples may lead to unreliable results. Climate model simulations agree with the tree-ring based reconstructions at multi-decadal time scales, suggesting solar variability and volcanism as the main factors controlling preindustrial mean temperature variations in the Pyrenees. Nevertheless, the comparison also highlights differences with the reconstructions, mainly in the amplitude of past temperature variations and in the 20th century trends. Neither proxy-based reconstructions nor model simulations are able to perfectly track the temperature variations of the instrumental record, suggesting that both approximations still need further improvements.
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The master’s thesis focuses on the ERP system of a project company that delivers large-scale industrial plants from a purchasing point of view. The point of time is couple of years after implementation. Opinion of the people working in purchasing is that the ERP system isn’t performing satisfyingly. The first objective for the thesis is to find out the causes of the problems based on theory. It’s possible the system may not be suitable for project business or there may be deficiencies in the system that cause the problems. The second objective for the thesis is to propose solutions to the observed problems based on theory and vision how the system should function. The outcome of the thesis was that the main causes for the problems were connected to the ways of using the system and engineering activities being left outside the scope of ERP. The processes connected to the ERP system are not documented, so the rules for using the system are missing. The thesis describes developing and influences to the organization of a function that enables uploading purchase requisitions to projects from a text file. It was discovered that the function solves many problems and enables other functions that enhance further ambitions to integrate even more of the company’s processes to the ERP system. Conclusion to the thesis is a vision how the system should function and development activities needed to achieve this vision.
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This thesis studies evaluation of software development practices through an error analysis. The work presents software development process, software testing, software errors, error classification and software process improvement methods. The practical part of the work presents results from the error analysis of one software process. It also gives improvement ideas for the project. It was noticed that the classification of the error data was inadequate in the project. Because of this it was impossible to use the error data effectively. With the error analysis we were able to show that there were deficiencies in design and analyzing phases, implementation phase and in testing phase. The work gives ideas for improving error classification and for software development practices.
Resumo:
Tämä diplomityö on selvitystyö mittakuvien ja kolmiulotteisten CAD-mallien tuottamisesta. Mittakuvat ja 3D-CAD-mallit halutaan Neles-tuotemerkin omaaville tuotteille. Olennaisena osana työssä on tuotetiedonhallintajärjestelmä AtonPDM, koska mittakuvia ja malleja toivottaisiin hallittavan AtonPDM-järjestelmällä. Työ tehdään Metso Automationin (MA) Flow Control (FC) –liiketoimintalinjalle. Nykyiset mittakuvat aiheuttavat ongelmia sekä MA:ssa että asiakkaille. MA:ssa mittakuvien tekeminen kestää kauemmin kuin asiakas toivoisi. Nykyisen mittakuvaohjelmiston riittämättömät ominaisuudet aiheuttavat lisätyötä mittakuvien valmistuksessa. Asiakkaille mittakuvien viivästyminen on suunnittelua hidastava tekijä. Mittakuvissa olevat virheet ja puutteet vaikeuttavat asiakkaan suunnittelutyötä ja saattavat päästä läpi tarkatuksien myös loppusuunnitelmiin, jolloin seurauksena voi olla rahallisia menetyksiä. Tämän päivän putkistosuunnittelu hoidetaan suurimmaksi osaksi 3D-CADohjelmistoilla. Suunnittelua helpotetaan ja nopeutetaan valmiilla komponenttien 3Dmalleilla, joihin on liitetty tuotetietoa. Työssä on haastateltu MA:n henkilökuntaa, CAD-järjestelmien toimittajia ja asiakkaita. Haastattelut ovat työn tärkein tiedonlähde. Teoriatietoa on selvitetty kirjoista, lehdistä ja internetistä. Teoriaosiossa käydään läpi tuotetiedonhallinta (Product Data Management, PDM), tietokanta ja parametrinen mallintaminen. Työn lopputuloksena on pyritty saamaan kuvaus siitä miten tuotetaan 3D-CAD-mallit ja mittakuvat Neles-tuotteista käyttäen tiedonlähteenä AtonPDM:ää ja millaisia 3Dmallien ja mittakuvien tulee olla. Malleja ja mittakuvia tuottavaan järjestelmään on etsitty ratkaisuja CAD-ohjelmistoista. Ratkaisuja on verrattu keskenään ominaisuuksien, joustavuuden ja AtonPDM yhteensopivuuden perusteella.
Resumo:
Diplomityön tavoitteena on suunnitella ja toteuttaa tuotannon budjettimalli elektroniikka-alalla toimivalle yritykselle. Työn onnistumisen kannalta keskeistä on löytää vanhan budjettimallin puutteet sekä uudet tietotarpeet, joita tuotannon johto tarvitsee pyrittäessä kustannustehokkaaseen ja kannattavaan tuotantotoimintaan. Näiden tietojen pohjalta suunnitellaan ja toteutetaan uusi budjettimalli sekä kuvataan sen toimintaperiaatteet. Työn teoreettisessa osuudessa esitellään budjetoinnin tavoitteet, hyödyt, kritiikin kohteet sekä tyypillisen teollisuusyrityksen osabudjetit. Myös perinteiseen budjetointiin läheisesti liittyvät muodot ja sovellukset, kuten toimintopohjainen budjetointi, vastuualuelaskenta ja nollapohjabudjetointi esitellään. Budjettiseurannan ja eroanalyysin tärkeä merkitys tuodaan esiin. Ennen uuden mallin esittämistä tutkitaan vanhan budjettimallin toimintaperiaatteet ja heikkoudet. Empiirisessä osassa keskitytään tuotannon budjetin toimintaperiaatteisiin sen sisältämien osabudjettien kautta. Työn loppupuolella esitellään uuden budjettimallin antamat tulokset ja poikkeamat sekä arvioidaan budjettimallin toimivuutta. Budjettimallin tuottaman informaation pohjalta tuotannonjohtoa ja suunnittelua ryhdyttiin välittömästi tehostamaan välillisten kustannusten alentamiseksi. Tehostustoimet ilmenivät konkreettisesti positiivisena erona poikkeama-analyysissä suhteessa budjettiin. Rakennetun budjettimallin mallinnustarkkuus osoittautui hyväksi ja uudet esiin tuodut kustannuserät hyödylliseksi informaatioksi.
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Les syndromes de déficiences cérébrales en créatine (CCDS) sont dus à des mutations dans les gènes GATM et G AMT (codant pour les enzymes AGAT et G AMT de la voie de synthèse de créatine) ainsi que SLC6A8 (transporteur de créatine), et génèrent une absence ou une très forte baisse de créatine (Cr) dans le cerveau, mesurée par spectroscopic de résonance magnétique. Les patients CCDS développent des handicaps neurologiques sévères. Les patients AGAT et GAMT peuvent être traités avec des doses importantes de Cr, mais gardent dans la plupart des cas des séquelles neurologiques irréversibles. Aucun traitement efficace n'existe à ce jour pour la déficience en SLC6A8. Bien que de nombreux modèles aient été développés pour comprendre la Cr cérébrale en conditions physiologiques, les pathomécanismes des CCDS ne sont pas encore compris. Des souris transgéniques pour les gènes Gatm, Gamt et Slc6a8 ont été générées, mais elles ne miment que partiellement la pathologie humaine. Parmi les CCDS, la déficience en GAMT est la plus sévère, en raison de l'accumulation cérébrale de l'intermédiaire guanidinoacétate (GAA). Alors que la toxicité cérébrale du GAA a été étudiée par exposition directe au GAA d'animaux adultes sains, les mécanismes de la toxicité du GAA en condition de déficience en GAMT dans le cerveau en développement sont encore inconnus. Le but de ce projet était donc de développer un modèle de déficience en GAMT dans des cultures 3D primaires de cellules nerveuses de rat en agrégats par knock-down du gène GAMT, en utilisant un virus adéno-associé (AAV) induisant le mécanisme d'interférence à l'ARN (RNAi). Le virus scAAV2, à la multiplicité d'infection de 1000, s'est révélé le plus efficace pour transduire tous les types de cellules nerveuses des cultures (neurones, astrocytes, oligodendrocytes), et générer un knock-down maximal de la protéine GAMT de 85% (jour in vitro 18). Cette déficience partielle en GAMT s'est révélée insuffisante pour générer une déficience en Cr, mais a causé l'accumulation attendue de GAA, à des doses comparables aux niveaux observés dans le LCR des patients GAMT. Le GAA a induit une croissance axonale anarchique accompagnée d'une baisse de l'apoptose naturelle, suivis par une induction tardive de mort cellulaire non-apoptotique. Le co-traitement par la Cr a prévenu tous les effets toxiques du GAA. Ce travail montre que l'accumulation de GAA en absence de déficience en Cr est suffisante pour affecter le développement du tissu nerveux, et suggère que des formes de déficiences en GAMT supplémentaires, ne présentant pas de déficiences en Cr, pourraient être découvertes par mesure du GAA, en particulier à travers les programmes récemment proposés de dépistage néonatal de la déficience en GAMT. -- Cerebral creatine deficiency syndromes (CCDS) are caused by mutations in the genes GATM and GAMT (respectively coding for the two enzymes of the creatine synthetic pathway, AGAT and GAMT) as well as SLC6A8 (creatine transporter), and lead to the absence or very strong decrease of creatine (Cr) in the brain when measured by magnetic resonance spectroscopy. Affected patients show severe neurological impairments. While AGAT and GAMT deficient patients can be treated with high dosages of Cr, most remain with irreversible brain sequelae. No treatment has been successful so far for SLC6A8 deficiency. While many models have helped understanding the cerebral Cr pathways in physiological conditions, the pathomechanisms underlying CCDS are yet to be elucidated. Transgenic mice carrying mutations in the Gatm, Gamt and Slc6a8 genes have been developed, but only partially mimic the human pathology. Among CCDS, GAMT deficiency is the most severe, due to the CNS accumulation of the guanidinoacetate (GAA) intermediate. While brain toxicity of GAA has been explored through direct GAA exposure of adult healthy animals, the mechanisms underlying GAA toxicity in GAMT deficiency conditions on the developing CNS are yet unknown. The aim of this project was thus to develop and characterize a GAMT deficiency model in developing brain cells by gene knockdown, by adeno-associated virus (AAV)-driven RNA interference (RNAi) in rat 3D organotypic primary brain cell cultures in aggregates. scAAV2 with a multiplicity of infection of 1000 was shown as the most efficient serotype, was able to transduce all brain cell types (neurons, astrocytes, oligodendrocytes) and to induce a maximal GAMT protein knockdown of 85% (day in vitro 18). Metabolite analysis showed that partial GAMT knockdown was insufficient to induce Cr deficiency but generated the awaited GAA accumulation at concentrations comparable to the levels observed in cerebrospinal fluid of GAMT-deficient patients. Accumulated GAA induced axonal hypersprouting paralleled with inhibition of natural apoptosis, followed by a later induction in non-apoptotic cell death. Cr supplementation led to the prevention of all GAA-induced toxic effects. This work shows that GAA accumulation without Cr deficiency is sufficient to affect CNS development, and suggests that additional partial GAMT deficiencies, which may not show the classical brain Cr deficiency, may be discovered through GAA measurement including by recently proposed neonatal screening programs for GAMT deficiency.
Resumo:
Mertaniemen voimalaitoksien prosessitietokone (PTK) on uusittu keväällä 2005. Tämän työn tarkoituksena on ollut auttaa PTK:n virheiden korjaamisessa ja puut-teiden kartoittamisessa. Työssä on keskitytty etenkin prosessiraportoinnin tekemiseen. Työn alussa on kerrottu Mertaniemen voimalaitoksen tekniset tiedot ja PTK:n hankinnan taustatietoja. Uudesta PTK-järjestelmästä on kuvattu laitteisto, sovellus ja perusohjelmistot. PTK:n ja muiden järjestelmien välinen tiedonsiirto on myös kuvattu. PTK muuttujien nimeäminen on esitelty, jotta olisi helpompi hahmottaa työssä käytettyjen positioiden merkityksiä. Prosessiraportoinnin kehittämisessä kuvataan raporttien tarvetta ja niiden sisältöä sekä sitä kuinka raportit on tehty. Päästöraportointi on esitetty omana osa-alueenaan, koska voimalaitosten päästöjen seurantaa edellytetään tehtävän viran¬omaismääräysten ja EU-direktiivien vaatimusten mukaisesti. Raporttien lisäksi prosessiarvojen seuraamista helpottamaan on tehty yhteisiä trendi- ja työtilanäyttöjä. PTK:n ongelmakohtina on käsitelty muuttujien tunnuksissa ja nimissä olevat virheet sekä PTK laskennan tarkastaminen. Muuttujien nimien ja laskennan tarkas¬tusta tehtiin prosessiraportoinnin tekemisen yhteydessä sekä yhteistyössä PTK-järjestelmän toimittaneen Metso Automation Oy:n kanssa. Päästölaskennan korjaaminen oli erityisen tärkeää.
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This paper analyzes an innovative experience of formative assessment aimed at improving the teaching of Statistics, which could be easily extrapolated to other studies. We detail the implementation of the double correction, consisting of correcting students' work twice. With the first correction, carried out by classmates according to a rubric developed by the academic, possible errors or deficiencies are discovered, and students are provided with a feedback that allows them to correct and improve their work before being graded by the teacher; whereas in the second correction of the work, once upgraded, the professor evaluates and grades the work. As a result, there is a significant improvement in the quality of students" works, and an active learning from their own mistakes. Both contents and competencies are reinforced by the experience.
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La present investigació es fonamenta en l’anàlisi de la competència del professorat d’educació física envers un alumnat amb discapacitat. L’objectiu és tenir coneixement de com el professorat assoleix aquesta competència i detectar possibles mancances a través de la formació adquirida, la figura de suport a les classes i/o la implicació de la família de l’alumnat. S’han analitzat 4 professors que han tingut estudiants amb discapacitat entre el seu alumnat amb l’objectiu de relacionar les seves vivències i punts de vista amb les idees dels investigadors més rellevants que presento en el marc teòric. Els resultats obtinguts demostren, d’una banda, que a les universitats catalanes hi ha poca formació en aquest àmbit, de l’altra, que a la figura de suport tot i ser de gran ajut si l’administració la concedeix li manquen coneixements d’educació física i, finalment, que la implicació de la família de l’alumnat és, sovint, imprescindible. D’altra banda, també s’ha detectat que la formació universitària va enfocada a un alumnat “estàndard”, i, respecte la figura de suport, cal destacar la reivindicació del professorat per exercir el dret a decidir sobre la necessitat o no d’aquesta figura.
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Objective To evaluate the knowledge about diagnostic imaging methods among primary care and medical emergency physicians. Materials and Methods Study developed with 119 primary care and medical emergency physicians in Montes Claros, MG, Brazil, by means of a structured questionnaire about general knowledge and indications of imaging methods in common clinical settings. A rate of correct responses corresponding to ≥ 80% was considered as satisfactory. The Poisson regression (PR) model was utilized in the data analysis. Results Among the 81 individuals who responded the questionnaire, 65% (n = 53) demonstrated to have satisfactory general knowledge and 44% (n = 36) gave correct responses regarding indications of imaging methods. Respectively, 65% (n = 53) and 51% (n = 41) of the respondents consider that radiography and computed tomography do not use ionizing radiation. The prevalence of a satisfactory general knowledge about imaging methods was associated with medical residency in the respondents' work field (PR = 4.55; IC 95%: 1.18-16.67; p-value: 0.03), while the prevalence of correct responses regarding indication of imaging methods was associated with the professional practice in primary health care (PR = 1.79; IC 95%: 1.16-2.70; p-value: 0.01). Conclusion Major deficiencies were observed as regards the knowledge about imaging methods among physicians, with better results obtained by those involved in primary health care and by residents.
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There is no question that students majoring in chemistry graduate with underdeveloped writing skills. Many educators have expressed concern about the obvious deficiencies in student writing. This article is designed to aid professors interested in teaching writing skills in their classrooms and laboratories.
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Training of highly qualified personnel is the most transversal axis among those identified in the document "Mobilizing Axes in Chemistry", published by SBQ, in 2002, which demands to deep the discussions, initiated in the symposium "The Chemist's Education", whose main objective was to discuss the repercussions of that training in the teaching and in the industrial section. After the publication of an initial paper, a couple of meetings and workshops held in Rio de Janeiro, in December 2003, involving the national chemist community, discussed the "The role of the graduate degrees in the Chemist's Education" and "The Chemist's Education", and confirmed the need to invest in the formation of qualified human resources in profusion and in all levels. Actions to be taken were delineated. Presently, the graduate programs in Chemistry are showing expressive results. However, although these professionals are mostly absorbed by the academy (the absorption of the industry is less significant), only a few programs give special attention to the didactical and pedagogical training. The regional decentralization is actually a tendency in most programs, but the interaction academy-economic activities is still a challenge. It is necessary to establish with the industrial section, the highly qualified professional's profile in Chemistry that the industry can absorb. The undergraduation is growing in number and quality, however still excessively concentrated in the Southeast area. The national "Curricula Guidelines" for Chemistry Courses, through its flexible approach, propitiate the integral, interdisciplinary (non compartmentalized) and critical-reflexive training of the professionals as citizens and as entrepreneurs. However, deficiencies are still recognized. The evaluation system of undergraduate courses has been able to identify the most fragile modalities of courses and other indicators. It was also verified that Brazilian chemistry industry absorbs minimally the highly qualified professionals, which is attributed to the fact that the Federal Council of Chemistry is vertically organized and does not recognize the graduate degrees as professional qualification. In the conclusion, it stands out, among other aspects, the importance of the effective implantation of the national curricula guidelines, bringing out courses whose didactical and pedagogical projects may offer a solid formation in Chemistry, but comprehensive and general enough to enable the Chemistry professionals to develop varied skills.
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The discussions sponsored by the Brazilian Chemical Society, over the past five years, intending to produce a chemistry agenda with perspectives and needs for the next decade for the country, have involved the national chemistry community and several related sectors of Brazilian society. Chemistry education has been the theme throughout these discussions. It is known that the low level of basic and secondary education and the recent increase in high school courses and institutions adversely affect the quality of undergraduate teaching. The recent national "Curriculum Guidelines" for Chemistry Courses, through their flexible approach, encourage the integral, interdisciplinary (non compartmentalized) and critical-reflexive training of professionals as citizens and as entrepreneurs. However, deficiencies are still recognized. The system of undergraduate course evaluation has identified the most fragile modalities of the courses and other indicators. Also, it has been verified that the Brazilian chemistry industry absorbs only minimally the highly qualified professionals, which is attributed to the fact that the Federal Council of Chemistry is vertically organized and does not recognize the graduate degrees as professional qualifications. In conclusion, the importance of the effective implantation of the national curriculum guidelines is apparent, among other aspects, highlighting courses whose didactical and pedagogical projects may offer a solid formation in Chemistry. However, at the same time the guidelines are comprehensive and general enough to enable the chemistry professionals to develop varied skills.
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Glucosidases are involved in key steps in the processing of oligosaccharides by cleaving O-glucose residues. Since they catalyze breaking and transfer reactions of glucosidic groups for the normal growth and development of all the cells, defects or genetic deficiencies in these enzymes are associated with serious disorders of the carbohydrate metabolism. Thus, glucosidases represent important targets to develop inhibitors, owing to their potential activities against viruses, tumoral growth and metastasis, diabetes, Gaucher's disease and other syndromes associated with the lisosomal storage of glucoesphingolipids, and osteoarthritis. This paper presents a description of the biochemical pathways and mechanisms of alpha and beta-glucosidases, and the currently available drugs capable to inhibit these enzymes.