Identification and characterization of CIP2A as a novel oncogenic inhibitor of PP2A

Inhibition of the tumor suppressor protein phosphatase 2A (PP2A) activity has been identified as one of the five key alterations required for human cell transformation. Regardless of this crucial role in human cancer development, the detailed mechanisms by which PP2A inhibition occurs in human cancers remain largely uncharacterized. PP2A regulates a plethora of cellular signaling cascades. One of the targets of PP2A is Myc oncoprotein, which is destabilized and degraded in response to PP2A-mediated dephosphorylation of Myc serine 62. In this study we identify Cancerous Inhibitor of PP2A (CIP2A) as a previously uncharacterized endogenous inhibitor of PP2A in human cancer cells. CIP2A inhibits PP2A activity leading to subsequent stabilization of the Myc protein. CIP2A promotes malignant growth of cancer cells in vitro and xenograft tumor formation in vivo and is overexpressed in cancer. Moreover, we explored the effect of CIP2A on global transcriptional profiles and validated a CIP2A-dependent transcriptional signature. Analysis of the CIP2A signature revealed both Myc-dependent and -independent functions for CIP2A. Importantly, we demonstrate that the CIP2A signature has clinical relevance in human breast cancer subtypes. Finally, we identify the genes potentially mediating the long-term growth suppression in CIP2A depleted cancer cells. Taken together, this work identifies CIP2A as a novel human oncoprotein and describes its function in cancer cells. These results may open novel possibilities for patient stratification and therapeutic intervention of cancer.Siirretty Doriast

AN AIR POLLUTION EPISODE CAUSED BY REGIONALLY TRANSPORTED SMOKE IN FINLAND ON 21 AUG 2006: A CASE STUDY USING MESOSCALE NWP MODEL

The purpose of this study is to identify the prevailing synoptic and mesoscale conditions related to severe air quality episode in Finland utilizing AROME mesoscale NWP model. The summer of 2006 was exceptionally dry in the areas surrounding the Gulf of Finland; this resulted in frequently occurring wild land fires, especially in north-western part of Russia and Estonia. Easterly winds were prevailing with an exceptional long period in August and spread occasionally smoke to Finland. Mesoscale phenomena, such as sea breeze and low-level jet (LLJ) have been identified to play a significant role on 21st of August 2006. A high model resolution is needed to catch these phenomena

AN AIR POLLUTION EPISODE CAUSED BY REGIONALLY TRANSPORTED SMOKE IN FINLAND ON 21 AUG 2006: A CASE STUDY USING MESOSCALE NWP MODEL

The purpose of this study is to identify the prevailing synoptic and mesoscale conditions related to severe air quality episode in Finland utilizing AROME mesoscale NWP model. The summer of 2006 was exceptionally dry in the areas surrounding the Gulf of Finland; this resulted in frequently occurring wild land fires, especially in north-western part of Russia and Estonia. Easterly winds were prevailing with an exceptional long period in August and spread occasionally smoke to Finland. Mesoscale phenomena, such as sea breeze and low-level jet (LLJ) have been identified to play a significant role on 21st of August 2006. A high model resolution is needed to catch these phenomena

Oulun kaupungin turvapalvelulaitteiden selvitystyö

Tämän opinnäytetyön aiheena oli tehdä selvitystyö Oulun kaupungin turvapalvelun turvapuhelinratkaisuista. Oulun kaupungin turvapalvelujen hankintakausi päättyi vuoden 2010 alussa ja perinteisen turvapuhelimen lisäksi tarjouspyynnössä oli mukana lisäpalveluna helppokäyttöinen GSM-puhelin, telecare-tyyppinen turvapuhelinratkaisu, GPS-henkilöpaikannin ohjelmistoineen, IP-turvapuhelin ja IP-kameravalvonta tilaajan määräämistä tahoista. Lisäpalveluna olevia turvapuhelinratkaisuja käytetään turvapuhelinasiakkailla yksilöllisen tarpeen mukaan. Käyttäjänä voi olla myös turvapalvelujen auttajataho tai kotihoidon henkilöstö. Palvelutarpeen arvioinnissa on asiakkaan ideaalisimman turvapuhelinratkaisun määrittelemiseksi oltava tietoinen käytössä olevien laitteiden ominaisuuksista. Opinnäytetyö aloitettiin tutustumalla Oulun kaupungin turvapalvelun toimintaan ja turvapalvelujen hankinnan tarjousasiakirjoihin. Tämän jälkeen tutustuttiin turvapuhelinratkaisuihin, jotka turvapalvelulla oli käytettävissä. Opinnäytetyön tuloksena pidettiin kolme turvalaitteiden esittelytilaisuutta. Tilaisuudet oli tarkoitettu henkilöille, joiden tuli olla tietoisia turvapalveluratkaisuista, eli esimerkiksi palvelutarpeenarvioijille. Lisäksi turvalaitteista laadittiin kirjallinen materiaali, jota voidaan hyödyntää turvalaitteiden esittelyssä

Asiakaslähtöinen palvelupolkumalli tulevaisuuden sote-keskusten lähtökohdaksi

Tässä työpaperissa hahmotellaan sosiaalipalveluihin palvelupolkumalli, jonka avulla sosiaali- ja ter-veydenhuollon uudistaminen on mahdollista tehdä asiakkaiden tarpeista lähtien. Esitetyssä mallis-sa asiakkaan palvelupolku ja siten myös palvelujen uudistaminen, organisointi ja resursointi raken-netaan asiakkaiden tarpeista käsin. Työpaperissa tarkastellaan, millaiset palvelupolut tukevat asiakkaiden tavoitteisiin pääsyä. Ha-vainnollistavana aineistona käytetään aiempia tutkimuksia ja selvityksiä sekä Terveyden ja hyvin-voinnin laitoksen (THL) osallistavan sosiaaliturvan kokeilun arviointitietoa onnistuneista aikuissosi-aalityön asiakkaiden palvelupoluista. Palvelupolkumallissa avainkysymyksinä ovat asiakkuussegmentointiin perustuvat palvelukategori-at ja palvelupolut, palveluintegraatio, hyvinvointivaltion inkluusiotehtävä ja siirtyminen virastojoh-tamisesta verkostojen ja ekosysteemien johtamiseen. Palvelupolkumalli mahdollistaa eri tahojen (julkinen, yksityinen ja kolmas sektori) kohdistamaan palvelut sinne, jossa asiakkaiden tarpeet ja usein niin monimutkaiset ongelmat ovat. Mallin avulla myös kansalaisjärjestöjen ja paikallisyhteisöjen toiminta on mahdollista nivoa osaksi asukkaiden ja asiakkaiden hyvinvointia. Haasteina mallin toteuttamisessa ovat opitut toimintatavat sekä tarkastelu resursseista ja organisaatioiden vanhoista rakenteista käsin. Mallin jatkokehittelyssä on kerättävä tietoa siitä, miten nämä haasteet ratkaistaan

Tannin-Based Microbicidal Coatings for Hospital Privacy Curtains

The goal of this study was to develop a sustainable, tannin-based option for silver-based and other current antimicrobial solutions for hospital privacy curtains. Commercial tree-derived tannins were characterized and their in vitro antibacterial properties against Staphylococcus aureus and Escherichia coli were determined. Hydrolysable tannins showed greater antibacterial efficacy than condensed tannins but differences in antibacterial efficacy between any of the tannins could not be attributed to their functional group content or molar mass. Outer membrane disruption was not a significant factor in antibacterial efficacy of tannins against E. coli. In a hospital field study, draw patches coated with hydrolysable tannins and affixed to privacy curtains reduced total bacteria count by 60% over eight weeks compared to their matching uncoated reference sides. In a follow-up laboratory study with S. aureus, very light spraying with water improved contact between bacteria and coating, enhancing the antibacterial effect by several orders of magnitude.publishedVersionPeer reviewe

The Association of Atrial Fibrillation Before Percutaneous Coronary Intervention With 1-Year Outcome in ST-Elevation Myocardial Infarction Patients

Cited by: 1; All Open Access, Gold Open Access, Green Open AccessPeer reviewe

Polygenic Risk Scores and Physical Activity

Purpose Polygenic risk scores (PRS) summarize genome-wide genotype data into a single variable that produces an individual-level risk score for genetic liability. PRS has been used for prediction of chronic diseases and some risk factors. As PRS has been studied less for physical activity (PA), we constructed PRS for PA and studied how much variation in PA can be explained by this PRS in independent population samples. Methods We calculated PRS for self-reported and objectively measured PA using UK Biobank genome-wide association study summary statistics, and analyzed how much of the variation in self-reported (MET-hours per day) and measured (steps and moderate-to-vigorous PA minutes per day) PA could be accounted for by the PRS in the Finnish Twin Cohorts (FTC;N= 759-11,528) and the Northern Finland Birth Cohort 1966 (NFBC1966;N= 3263-4061). Objective measurement of PA was done with wrist-worn accelerometer in UK Biobank and NFBC1966 studies, and with hip-worn accelerometer in the FTC. Results The PRS accounted from 0.07% to 1.44% of the variation (R-2) in the self-reported and objectively measured PA volumes (Pvalue range = 0.023 toPeer reviewe