”Minä elän äänimaisemassa”:luokanopettajien käsityksiä koulun äänimaisemasta

Tiivistelmä. Yksilö on jatkuvassa vuorovaikutuksessa erilaisten äänien ja äänilähteiden kanssa. Kuuloaisti ja aivot vastaanottavat, tulkitsevat ja käsittelevät ympäristön ääniä taukoamatta. Jo sikiöstä lähtien luomme subjektiivisia suhteita ääniin, jonka vuoksi aivomme ovat erikoistuneet tekemään havaintoja tietyistä äänistä ja niiden ominaisuuksista. Äänen sisältämä informaatio, voimakkuus, paine ja ennustettavuus vaikuttavat siihen, millä tavoin yksilö luokittelee äänen. R. Murray Schaferin luoma termi äänimaisema koostuu kaikista ympäristön, tilan tai musiikkiteoksen sisältämistä äänistä. Äänimaisema sisältää akustisen kommunikaation mallin, jossa kuuntelija,ääni ja ympäristö luovat vuorovaikutuksellisen kokonaisuuden. Tapahtuma on kuuntelijalleen aina subjektiivinen kokemus, jonka rakentumiseen vaikuttavat kuuntelijan mieliala, aikaisemmat kokemukset,ääniherkkyys, temperamentti sekä vallitsevan kulttuurin käsitykset hyväksyttävistä ja ei-hyväksyttävistä äänistä. Eri äänimaisemien ja melun vaikutuksia aikuisiin on tutkittu laajasti ja pitkäaikaisesti. Lapsiin keskittyviä tutkimuksia äänille altistumisesta on vähemmän, mutta tutkimustulokset ovat sitäkin huolestuttavampia. Melun vaikutukset lapsiin ja aikuisiin ovat osittain samankaltaisia, mutta kehityksen ja kasvun ollessa vielä kesken, terveydelliset haitat ovat lapsilla laajemmat. Kasvatustieteiden puolelle sijoittuvaa äänimaisematutkimusta ei ole juuri saatavissa. Opettajat eivät välttämättä osaa yhdistää lasten kouluissa havaittavaa oireilua meluun tai muihin häiritseviin ääniin, jolloin lapsi saattaa joutua väärinymmärretyksi. Tällä tutkimuksella pyrimme omalta osaltamme lisäämään tarvittavaa tietoa kenttätyöhön. Pro gradu -tutkielmamme on kvalitatiivinen tutkimus, joka empiiriseen tutkimustietoon perustuen pyrkii ymmärtämään luokanopettajien käsityksiä koulun äänimaisemien rakentumisesta. Tutkimusmetodina on fenomenografia ja aineistonkeruu on tehty teemahaastatteluna. Opetuksen tulisi ohjata lapsia äänimaisemien kriittiseen tarkasteluun sekä ottamaan huomioon äänten vaikutukset kuuloon. Hyvä oppimisympäristö tarjoaa tilat sekä hiljaiselle että toiminnalliselle työskentelylle. Tutkielman tarkoituksena on esitellä haastateltavien käsitysten kautta koulun äänimaiseman rakentumista ja siihen vaikuttavia tekijöitä

Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia

Disease relapse from standard chemotherapy in acute myeloid leukemia (AML) is poorly understood. The importance of protein phosphatase 2A (PP2A) as an AML tumor suppressor is emerging. Therefore, here, we examined the potential role of endogenous PP2A inhibitor proteins as biomarkers predicting AML relapse in a standard patient population by using three independent patient materials: cohort1 (n = 80), cohort2 (n = 48) and The Cancer Genome Atlas Acute Myeloid Leukemia (TCGA LAML) dataset (n = 160). Out of the examined PP2A inhibitors (CIP2A, SET, PME1, ARPP19 and TIPRL), expression of ARPP19 mRNA was found to be independent of the current AML risk classification. Functionally, ARPP19 promoted AML cell viability and expression of oncoproteins MYC, CDK1, and CIP2A. Clinically, ARPP19 mRNA expression was significantly lower at diagnosis (p = 0.035) in patients whose disease did not relapse after standard chemotherapy. ARPP19 was an independent predictor for relapse both in univariable (p = 0.007) and in multivariable analyses (p = 0.0001) and gave additive information to EVI1 expression and risk group status (additive effect, p = 0.005). Low ARPP19 expression was also associated with better patient outcome in the TCGA LAML cohort (p = 0.019). In addition, in matched patient samples from diagnosis, remission and relapse phases, ARPP19 expression was associated with disease activity (p = 0.034), indicating its potential usefulness as a minimal residual disease (MRD) marker. Together, these data demonstrate the oncogenic function of ARPP19 in AML and its risk group independent role in predicting AML patient relapse tendency

Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1

Protein phosphatase 2A (PP2A) critically regulates cell signaling and is a human tumor suppressor. PP2A complexes are modulated by proteins such as cancerous inhibitor of protein phosphatase 2A (CIP2A), protein phosphatase methylesterase 1 (PME-1), and SET nuclear proto-oncogene (SET) that often are deregulated in cancers. However, how they impact cellular phosphorylation and how redundant they are in cellular regulation is poorly understood. Here, we conducted a systematic phosphoproteomics screen for phosphotargets modulated by siRNA-mediated depletion of CIP2A, PME-1, and SET (to reactivate PP2A) or the scaffolding A-subunit of PP2A (PPP2R1A) (to inhibit PP2A) in HeLa cells. We identified PP2A-modulated targets in diverse cellular pathways, including kinase signaling, cytoskeleton, RNA splicing, DNA repair, and nuclear lamina. The results indicate nonredundancy among CIP2A, PME-1, and SET in phosphotarget regulation. Notably, PP2A inhibition or reactivation affected largely distinct phosphopeptides, introducing a concept of nonoverlapping phosphatase inhibition- and activation-responsive sites (PIRS and PARS, respectively). This phenomenon is explained by the PPP2R1A inhibition impacting primarily dephosphorylated threonines, whereas PP2A reactivation results in dephosphorylation of clustered and acidophilic sites. Using comprehensive drug-sensitivity screening in PP2A-modulated cells to evaluate the functional impact of PP2A across diverse cellular pathways targeted by these drugs, we found that consistent with global phosphoproteome effects, PP2A modulations broadly affect responses to more than 200 drugs inhibiting a broad spectrum of cancer-relevant targets. These findings advance our understanding of the phosphoproteins, pharmacological responses, and cellular processes regulated by PP2A modulation and may enable the development of combination therapies

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients

Alkali-activated adsorbents from slags:column adsorption and regeneration study for nickel(II) removal

Abstract Alkali-activated adsorbents were synthesized by mixing three different slags from the steel industry: blast furnace slag (BFS), ladle slag (LS), and Lintz–Donawitz converter slag (LD). These powdered slag-based geopolymers (GP) were used to remove nickel(II) from aqueous solutions in fixed-bed column studies. The experiments were conducted in pH 6 using a phosphate buffer with initial nickel(II) concentration of 50 mg/L. Samples were taken at time intervals of between 5 and 90 min. Three adsorption–desorption cycles were implemented with a flow rate of 5 mL/min. The geopolymers were characterized by Fourier-Transform Infrared Spectroscopy (FTIR), X-ray powder diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), X-ray fluorescence (XRF), specific surface area measurements, and a leaching test. The data were found to describe the Thomas, Adams–Bohart, and Yoon–Nelson models well. For GP (BFS, LS), experimental adsorption capacity was 2.92 mg/g, and for GP (LD, BFS, LS), it was 1.34 mg/g. The results indicated that the produced adsorbents have the potential to be used as adsorbents for the removal of nickel(II)

Conversion of furfural to 2-methylfuran over CuNi catalysts supported on biobased carbon foams

Abstract In this study, carbon foams prepared from the by-products of the Finnish forest industry, such as tannic acid and pine bark extracts, were examined as supports for 5/5% Cu/Ni catalysts in the hydrotreatment of furfural to 2-methylfuran (MF). Experiments were conducted in a batch reactor at 503 K and 40 bar H₂. Prior to metal impregnation, the carbon foam from tannic acid was activated with steam (S1), and the carbon foam from pine bark extracts was activated with ZnCl₂ (S2) and washed with acids (HNO₃ or H₂SO₄). For comparison, a spruce-based activated carbon (AC) catalyst and two commercial AC catalysts as references were investigated. Compressive strength of the foam S2 was 30 times greater than that of S1. The highest MF selectivity of the foam-supported catalysts was 48 % (S2, washed with HNO₃) at a conversion of 91 %. According to the results, carbon foams prepared from pine bark extracts can be applied as catalyst supports

Discovery of a Novel CIP2A Variant (NOCIVA) with Clinical Relevance in Predicting TKI Resistance in Myeloid Leukemias

From Crossref journal articles via Jisc Publications RouterHistory: epub 2021-03-05, issued 2021-03-05, ppub 2021-05-15Publication status: PublishedFunder: Sigrid Juselius FoundationFunder: Turku Doctoral Program of Molecular MedicineFunder: Turku University Hospital ERVA; Grant(s): 13283, 13336Funder: Päivikki and Sakari Sohlbergin Foundation; FundRef: 10.13039/501100004212Funder: Cancer Foundation Väre; FundRef: 10.13039/100010128Funder: Finnish Cultural Foundation; FundRef: 10.13039/501100003125Abstract Purpose: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that inhibits the tumor suppressor PP2A-B56α. However, CIP2A mRNA variants remain uncharacterized. Here, we report the discovery of a CIP2A splicing variant, novel CIP2A variant (NOCIVA). Experimental Design: Characterization of CIP2A variants was performed by both 3′ and 5′ rapid amplification of cDNA ends from cancer cells. The function of NOCIVA was assessed by structural and molecular biology approaches. Its clinical relevance was studied in an acute myeloid leukemia (AML) patient cohort and two independent chronic myeloid leukemia (CML) cohorts. Results: NOCIVA contains CIP2A exons 1 to 13 fused to 349 nucleotides from CIP2A intron 13. Intriguingly, the first 39 nucleotides of the NOCIVA-specific sequence are in the coding frame with exon 13 of CIP2A and code for a 13-amino acid peptide tail nonhomologous to any known human protein sequence. Therefore, NOCIVA translates to a unique human protein. NOCIVA retains the capacity to bind to B56α, but, whereas CIP2A is predominantly a cytoplasmic protein, NOCIVA translocates to the nucleus. Indicative of prevalent alternative splicing from CIP2A to NOCIVA in myeloid malignancies, AML and CML patient samples overexpress NOCIVA, but not CIP2A mRNA. In AML, a high NOCIVA/CIP2A mRNA expression ratio is a marker for adverse overall survival. In CML, high NOCIVA expression is associated with inferior event-free survival among imatinib-treated patients, but not among patients treated with dasatinib or nilotinib. Conclusions: We discovered a novel variant of the oncoprotein CIP2A and its clinical relevance in predicting tyrosine kinase inhibitor therapy resistance in myeloid leukemias

Vastuullisuudesta kilpailuetua:opas pienyritykselle vastuullisuussuunnitelman laatimiseen

Alkusanat Vastuullisuus on usein sisäänrakennettuna suomalaisen pienyrityksen yrityskulttuuriin, vaikka sitä ei olisi tietoisesti pohdittukaan. Suomalaiset yritykset toimivat tyypillisesti rehellisesti, vilpittömästi, kunniallisesti ja avoimesti, jolloin vastuullisuus on jo hyvällä pohjalla. Vastuullinen yritys on myös haluttu työnantajana ja yhteistyökumppanina. Asiakkaan arvostaminen on keskeistä vastuullisen yrityksen toiminnalle. Vastuullisuus ei välttämättä tarkoita isoja vastuullisuusohjelmia vaan käytännön toiminta arjessa riittää. Taloudellisella tasolla vastuullisuutta on mm. kannattava yritystoiminta, sosiaalista vastuullisuutta on mm. henkilöstön hyvinvoinnista huolehtiminen. Sosiaalinen vastuullisuus tarkoittaa myös toimintaa paikallisyhteisön edistämiseksi, työyhteisön ja työolojen kehittämistä sekä ihmisarvon kunnioittamista yrityksen kaikissa toiminnoissa. Tämä opas on suunnattu pien- ja mikroyrityksille. Oppaaseen on koottu mikroyrittäjän vastuullisuusvalmennuksessa käytettyä materiaalia ja valmennuksissa hyödynnettyjä työkaluja. Tarkoituksena on, että saat laadittua yrityksellesi vastuullisuuden kehittämissuunnitelman, ViVa Road Mapin. Opas on tuotettu osana ViVa – Vihreä vastuullisuus mikroyrityksissä -hanketta, jonka vastuullisuusvalmennus on auttanut pieniä ja mikroyrityksiä suunnitelmalliseen vastuullisuuteen ja sitä kautta kilpailuedun lisäämiseen Pohjois-Pohjanmaalla vuosina 2021–2023