509 resultados para Häkkinen, Sakari


Relevância:

10.00% 10.00%

Publicador:

Resumo:

Acknowledgements This paper belongs to the studies carried out by Kuopio Birth Cohort consortium (www.KuBiCo.fi). We thank Ms Pirjo Hänninen for expert laboratory assistance at University of Eastern Finland, Ms Margaret Fraser, Dr Panagiotis Filis and the Proteomics Core Facility at the University of Aberdeen for their expert assistance. We also thank the staff of the Department of Obstetrics and Gynaecology in Kuopio University Hospital for skilful collection of these specimens. This work was supported by the Academy of Finland [122859/2007], the Helena Vuorenmies Foundation, the Emil Aaltonen Foundation, the University of Eastern Finland Doctoral Programme in Drug Research and the Medical Research Council, UK [MR/L010011/1]. The funders played no roles in study design, data collection, data analysis, manuscript preparation and/or publication decisions.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

In over 90% of cervical cancers and cancer-derived cell lines, the p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV). The HPV E6 protein promotes the degradation of p53 and thus inhibits the stabilization and activation of p53 that would normally occur in response to HPV E7 oncogene expression. Restoration of p53 function in these cells by blocking this pathway should promote a selective therapeutic affect. Here we show that treatment with the small molecule nuclear export inhibitor, leptomycin B, and actinomycin D leads to the accumulation of transcriptionally active p53 in the nucleus of HeLa, CaSki, and SiHa cells. Northern blot analyses showed that both actinomycin D and leptomycin B reduced the amount of HPV E6-E7 mRNA whereas combined treatment with the drugs showed almost complete disappearance of the viral mRNA. The combined treatment activated p53-dependant transcription, and increases in both p21WAF1/CIP1 and Hdm2 mRNA were seen. The combined treatment resulted in apoptotic death in the cells, as evidenced by nuclear fragmentation and PARP-cleavage indicative of caspase 3 activity. These effects were greatly reduced by expressing a dominant negative p53 protein. The present study shows that small molecules can reactivate p53 in cervical carcinoma cells, and this reactivation is associated with an extensive biological response, including the induction of the apoptotic death of the cells.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Aim: Concepts about patterns and rates of post-glacial tree population migration are changing as a result of the increasing amount of palaeobotanical information being provided by macroscopic plant remains. Here we combine macrofossil, pollen and stomata records from five sites in north-eastern European Russia and summarize the results for the late-glacial-early Holocene transition. The late-glacial-early Holocene transition encompasses the first indications of trees (tree-type Betula, Picea abies, Abies sibirica and Larix sibirica) and subsequent forest development. Considerable time-lags between the first macrobotanical and/or stomata finds of spruce (Picea abies) and the establishment of a closed forest are reconsidered. Location: Pechora basin, north-eastern European Russia. Methods: We used plant macrofossil, stomata, pollen and radiocarbon analyses to reconstruct late-glacial and early Holocene tree establishment and forest development. The data were derived from lake sediment and peat archives. Results: Palaeobotanical data reveal an early Holocene presence (11,500-10,000 cal. yr bp) of arboreal taxa at all five sites. One site presently located in the northernmost taiga zone, shows the presence of spruce and reproducing tree birch during the late-glacial. Given the current view of post-glacial population dynamics and migration rates, it seems likely that the source area of these early tree populations in north-eastern European Russia was not located in southern Europe but that these populations had local origins. Results thus support the emerging view that the first post-glacial population expansions in non-glaciated regions at high latitudes do not reflect migration from the south but were a result of an increase in the size and density of small persisting outlying tree populations. Main conclusions: Results suggest that the area east of the margin of the Scandinavian ice sheet to the Ural Mountains had isolated patches of trees during the late-glacial and early Holocene and that these small populations acted as initial nuclei for population expansion and forest development in the early Holocene.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Tutkielmani tarkoituksena on selvittää voimassa olevan oikeuden perusteella, millaiseksi vierasvelkapantinsaajan asema muodostuu velallisen ja pantinantajan konkurssissa. Panttausta koskevaa yleistä lainsäädäntöä on melko vähän, mutta vierasvelkapanttauksen osalta keskeisimmät säännökset ovat kodifioitu lakiin takauksesta ja vierasvelkapanttauksesta. Takauksesta ja vierasvelkapanttauksesta annettu laki ei kuitenkaan sääntele esimerkiksi tehokkaan panttioikeuden perustamista eikä pantin realisointiin liittyviä tilanteita. Soveltamisohjeita näihin tilanteisiin tulee hakea panttausta koskevasta muusta, varsin hajanaisesta lainsäädännöstä. Tutkimuksen tarkoituksena onkin selvittää tämän pohjaltaan hajanaisen lainsäädännön, lainvalmistelutöiden sekä oikeuskirjallisuuden perusteella, minkälaista suojaa vierasvelkapantinsaaja saa konkurssissa ja millä edellytyksin. Selvitän tutkielman alussa vierasvelkapanttauksen tehokkaalle perustamiselle asetettuja edellytyksiä sekä niiden merkitystä konkurssitilanteessa. Tämän jälkeen tutkin panttioikeuden voimassapysymistä konkurssissa sekä pantinsaajalle tähän liittyen asetettuja velvoitteita. Lisäksi tutkin pantinsaajalla olevia realisointioikeuksia ja niiden rajoituksia sekä pantinsaajan mahdollisuuksia suojautua konkurssitakaisinsaannilta. Tutkielmani kannalta tärkeimpiä lähdeteoksia ovat Erkki Havansi: Esinevakuusoikeudet 1992; Risto Koulu: Konkurssioikeus 2009; Jarno Tepora – Janne Kaisto – Esa Hakkola: Esinevakuudet 2009; Sakari Wuolijoki – Mika Hemmo: Pankkioikeus 2013; Jarmo Tuomisto: Saatavan panttaus 2015 sekä Vierasvelkavakuus ja velallisen insolvenssista johtuva takaisinsaantiriski oikeuskäytännön valossa 2004. Vierasvelkapantinsaajalla on edelleen vahva asema sekä päävelallisen että pantinantajan konkurssissa. Vahvan suojan saaminen edellyttää kuitenkin, että panttioikeus on tehokkaasti perustettu noudattaen muun muassa julkivarmistukselle asetettuja vaatimuksia. Lisäksi nykyiset luotonantajan tiedonantovelvollisuutta koskevat säännökset asettavat luotoantajalle velvollisuuksia, joiden laiminlyöminen tarkoittaa luotonantajan saaman panttihyödyn vähenemistä. Edes vuoden 2004 konkurssilakiin otetuilla säännöksillä, joilla heikennettiin pantinsaajan etuoikeuksia entisestä, ei ole ollut merkittäviä negatiivisia vaikutuksia pantinsaajan oikeuksiin konkurssissa. Pantinsaajan tärkeimpiä taloudellisia etuoikeuksia ei ole tarkoituksenmukaista kaventaa. Lähinnä vain menettelyllisiin etuoikeuksiin voidaan lainsäädännöllä puuttua.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Augmented Reality (AR) applications often require knowledge of the user’s position in some global coordinate system in order to draw the augmented content to its correct position on the screen. The most common method for coarse positioning is the Global Positioning System (GPS). One of the advantages of GPS is that GPS receivers can be found in almost every modern mobile device. This research was conducted in order to determine the accuracies of different GPS receivers. The tests included seven consumer-grade tablets, three external GPS modules and one professional-grade GPS receiver. All of the devices were tested with both static and mobile measurements. It was concluded that even the cheaper external GPS receivers were notably more accurate than the GPS receivers of the tested tablets. The absolute accuracy of the tablets is difficult to determine from the test results, since the results vary by a large margin between different measurements. The accuracy of the tested tablets in static measurements were between 0.30 meters and 13.75 meters.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The International FItness Scale (IFIS) is a self-reported measure of physical fitness that could easily. This scale has been validated in children, adolescents, and young adults; however, it is unknown whether the IFIS represents a valid and reliable estimate of physical fitness in Latino-American youth population. In the present study we aimed to examine the validity and reliability of the IFIS on a population-based sample of schoolchildren in Bogota, Colombia. Participants were 1,875 Colombian youth (56.2% girls) aged 9 to 17.9 years old. We measured adiposity markers (body fat, waist-to-height ratio, skinfold thicknesses and BMI), blood pressure, lipids profile, fasting glucose, and physical fitness level (self reported and measured). Also, a validated cardiometabolic risk index was used. An age- and sex-matched sample of 229 Schoolchildren originally not included in the study sample fulfilled IFIS twice for reliability purposes. Our data suggest that both measured and self-reported overall fitness were associated inversely with adiposity indicators and a cardiometabolic risk score. Overall, schoolchildren who self-reported “good” and “very good” fitness had better measured fitness than those who reported “very poor” and “poor” fitness (all p<0.001). Test–retest reliability of IFIS items was also good, with an average weighted Kappa of 0.811. Therefore, our findings suggest that self-reported fitness, as assessed by IFIS, is a valid, reliable, and health-related measure, and it can be a good alternative for future use in large studies with Latin-schoolchildren from Colombia.