High-throughput miRNA profiling of human melanoma blood samples

<p>Abstract</p> <p>Background</p> <p>MicroRNA (miRNA) signatures are not only found in cancer tissue but also in blood of cancer patients. Specifically, miRNA detection in blood offers the prospect of a non-invasive analysis tool.</p> <p>Methods</p> <p>Using a microarray based approach we screened almost 900 human miRNAs to detect miRNAs that are deregulated in their expression in blood cells of melanoma patients. We analyzed 55 blood samples, including 20 samples of healthy individuals, 24 samples of melanoma patients as test set, and 11 samples of melanoma patients as independent validation set.</p> <p>Results</p> <p>A hypothesis test based approch detected 51 differentially regulated miRNAs, including 21 miRNAs that were downregulated in blood cells of melanoma patients and 30 miRNAs that were upregulated in blood cells of melanoma patients as compared to blood cells of healthy controls. The tets set and the independent validation set of the melanoma samples showed a high correlation of fold changes (0.81). Applying hierarchical clustering and principal component analysis we found that blood samples of melanoma patients and healthy individuals can be well differentiated from each other based on miRNA expression analysis. Using a subset of 16 significant deregulated miRNAs, we were able to reach a classification accuracy of 97.4%, a specificity of 95% and a sensitivity of 98.9% by supervised analysis. MiRNA microarray data were validated by qRT-PCR.</p> <p>Conclusions</p> <p>Our study provides strong evidence for miRNA expression signatures of blood cells as useful biomarkers for melanoma.</p

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

PALVELUTUOTTEEN HINNOITTELUN KEHITTÄMINEN

Tämän opinnäytetyön aiheena on palvelutuotteen hinnoittelun kehittäminen. Tutkimuksen kohteena on Tili- ja isännöitsijätoimisto Ky. Tili- ja isännöitsijätoimisto Ky on Vaasassa toimiva tili- ja isännöintitoimisto, joka tarjoaa taloushallinto- ja isännöintipalveluita yrityksille. Tutkimuksen tavoitteena on kehittää Tili- ja isännöitsijätoimisto Ky:n isännöitsijän palvelutuotteiden hinnoittelua. Hinnoittelumenetelmäksi valittiin toimintoperusteinen hinnoittelu, jonka lähtökohtana on selvittää asiakaskohtaisia välillisiä kustannuksia. Kysymys oli suorite-kohtaisten kustannusten laskemisesta, eli toimintoperusteisesta prosessilaskennasta. Toimintoperusteinen prosessilaskenta tukee hinnoittelun päätöstä. Toiminto-analyysin jälkeen selvitettiin resurssien kohdistumista yrityksen eri toiminnoille. Aluksi selvitettiin yrityksen kustannusajuri, jonka perusteella kustannukset on kohdistettu eri toiminnoille. Seuraavaksi selvitettiin toimintoajurin avulla toimintoihin liittyvät yksikkökustannukset. Tuotteiden hinnoittelussa myyntihinnan on tarkoituksena sisältää kaikkien kustannusten lisäksi voittotavoite. Tutkimuksen teoriaosuuden keskeisiä asioita ovat toimintoperusteisen kustannuslaskennan, sekä hinnoittelun perusteiden esittely. Niiden avulla voidaan perustella hinnoittelupäätöstä tukeva toimintolaskenta. Opinnäytetyössä esitellään lisäksi kustannusperusteista hinnoittelua sekä isännöintiä ja tilitoimistoa yleisesti. Tutkimusmenetelmänä käytettiin kvalitatiivista eli laadullista tutkimusta. Tutkimuksen teoriaosuuteen käytettiin toimintolaskennan, taloushallinnon alan sekä hinnoittelun teoriaan liittyvää kirjallisuutta. Aineistonkeruussa havainnoitiin yrityksen tilinpäätöstä vuodelta 2016 ja yrityksen toimintaa liittyviä ohjelmia sekä tietokantoja. Lisäksi haastateltiin Tili- ja isännöitsijätoimisto Ky:n omistajaa ja työntekijöitä.This research was designed to develop the used pricing method for the case firm Tili- ja isännöitsijätoimisto Ky. The main area of this research focused on the main service products in property management. The case firm offers financial accounting and management services to house companies and other customer companies. Activity based costing was selected as the new pricing method in order to identify the customer-specific indirect costs. The aim of activity-based costing was to support pricing decisions for the case firm. In the implementation steps, activities must be identified first, and then the process continues with an activity analysis. Once the costs of activity and its drivers have been identified and its costs have been determined, then the costs of activity is allocated to the service product. In the allocation process, when the activity driver has been determined, the cost per unit can then be determined. Once the product cost per unit has been determined then the case firm considers the generated value of its service product, so the pricing of all the service product sales cover the fixed expenses with any remaining contribution margin providing profits. The theoretical study of this thesis introduced activity based costing and pricing to support activity based cost implementation and pricing decisions. In addition, it introduced cost based pricing and property management business and accounting firms in general. This research was implemented using the qualitative research method. The research material consists of related activity based costing, financial management, management accounting and pricing literature. The theoretical information was gathered from scientific research, academic books and some material was collect-ed from the Internet. The empirical data in this research was gathered by observing the case company’s financial statement from the year 2016 together with some business activities related programs and databases. In addition, was collected by interviewing the case company owner and the other employers of the company

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits

Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

[This corrects the article DOI: 10.1371/journal.pgen.1005378.].status: publishe