Hemap: An nteractive online resource for characterizing molecular phenotypes across hematologic malignancies

Large collections of genome-wide data can facilitate the characterization of disease states and subtypes, permitting pan-cancer analysis of molecular phenotypes and evaluation of disease contexts for new therapeutic approaches. We analyzed 9,544 transcriptomes from over 30 hematologic malignancies, normal blood cell types and cell lines, and show that the disease types can be stratified in a data-driven manner. We utilized the obtained molecular clustering for discovery of cluster-specific pathway activity, new biomarkers and in silico drug target prioritization through integration with drug target databases. Using known vulnerabilities and available drug screens in benchmarking, we highlight the importance of integrating the molecular phenotype context and drug target expression for in silico prediction of drug responsiveness. Our analysis implicates BCL2 expression level as important indicator of venetoclax responsiveness and provides a rationale for its targeting in specific leukemia subtypes and multiple myeloma, links several polycomb group proteins that could be targeted by small molecules (SFMBT1, CBX7 and EZH1) with CLL, and supports CDK6 as disease-specific target in AML. Through integration with proteomics data, we characterized target protein expression for pre-B leukemia immunotherapy candidates, including DPEP1. These molecular data can be explored using our freely available interactive resource, Hemap, for expediting therapeutic innovations in hematologic malignancies

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.Peer reviewe

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk

Asiakkaan datan mallinnus ja sen analysointi Business Intelligence -järjestelmässä

Opinnäytetyön tavoitteena oli toteuttaa asiakkaalle Business Intelligence -järjestelmää käyttäen ympäristö kyselytutkimuksella kerätyn datan analysointia varten. Asiakkaan analyyseille asettamien vaatimusten vuoksi aiemmin kerätty data oli muutettava Business Intelligence -järjestelmän, ja erityisesti tietovarastoinnin kannalta optimaaliseen, moniulotteiseen muotoon. Asiakkaalle luotiin uusi relaatiotietokanta moniulotteisessa mallinnuksessa yleisesti käytetyn tähtimallin pohjalta. Asiakkaan alkuperäinen data siirrettiin luotuun relaatiotietokantaan. Toteutukseen kuului myös valitun Business Intelligence -järjestelmän asentaminen, ja analyysien luominen siihen liitetyn uuden tietokannan pohjalta. Toteutuksessa käytettäviksi ohjelmistoiksi valikoituivat Pentaho Community Edition Business Intelligence -järjestelmäksi ja MySQL tietokannan hallintajärjestelmäksi. Opinnäytetyön teoreettisessa osuudessa käsiteltiin Business Intelligence -käsitteen sisältöä erityisesti toteutuksessa käytettävien Business Intelligencen osa-alueiden ja komponenttien osalta. Opinnäytetyön valmistuttua asiakkaalla on käytössään tietokanta ja Business Intelligence -järjestelmä, sekä sen sisältämät työkalut aiemman ja myös mahdollisesti uuden datan analysointiin ja niistä raportointiin.The purpose of this thesis was to implement a Business Intelligence system for the client to enable analysis of the survey data. Due to the client's requirements for the analyzes, the previously collected data had to be re-modeled using dimensional model optimized for Data Warehouse / Business Intelligence environment. A new database was created for a client using most widely used dimensional model, star schema. The client’s old data was migrated to the created database. The implementation also included the installation of the selected Business Intelligence system and data analysis from the connected database. The programs used in this thesis were Pentaho Community Edition as a Business Intelligence software and MySQL as a database management system. The theory section of the thesis focused on the concept of Business Intelligence, particularly on the parts and components used in the implementation. After the implementation is completed, the client has a database and a functional Business Intelligence system including the tools for data analysis and reporting

Ympäristövastuun haasteet Alkon arvo- ja toimitusketjussa

Alko Oy on tekemässä yksityiskohtaisempaa arvo- ja toimitusketjukuvausta muiden pohjoismaisten alkoholimonopolien kanssa. Kuvauksessa huomioidaan vastuullisuuden ja arvontuottamisen näkökulmat. Vastuullisuuden merkitys on kasvanut lähivuosina ja sen voidaan katsoa muodostuvan kolmesta osa-alueesta, jotka ovat taloudellinen, sosiaalinen ja ympäristöllinen vastuu. Tutkimusongelma oli vastuullisuuden haasteet logistiikan arkipäivässä. Opinnäytetyö tehtiin kuvaukseen liittyvänä toimeksiantona Alkolle ja työ rajattiin käsittelemään ympäristövastuuta, koska se koettiin logistiikan osalta selkeimmäksi osa-alueeksi. Työn tarkoituksena oli selvittää ja tutkia haasteita, sekä miettiä mahdollisia mittauskohteita arvo- ja toimitusketjuun. Opinnäytetyön tietoperustassa esitellään vastuullisuuden eri muodot Alkon ja yhteistyökumppaneiden osalta, tarkastellaan arvo- ja toimitusketjuja omina kokonaisuuksinaan, sekä kerrotaan mittausmenetelmistä ja käytössä olevista mittareista. Tietoperustassa esitettyä teoriaa peilataan Alkon toimintaan. Työ toteutettiin vuoden 2014 kesän ja syksyn aikana. Tutkimus on kvalitatiivinen ja se suoritettiin puolistrukturoituina asiantuntijahaastatteluina. Haastateltaviksi valittiin logistiikan ja vastuullisuuden ammattilaisia Alkosta ja yhteistyökumppanien keskuudesta. Tutkimuksen tuloksissa ilmeni, että asiakkaiden kiinnostus vastuullisuuteen on kasvanut ja se tuo erilaisia haasteita logistiikan arkipäivään. Logistiikan osalta se tarkoittaa kattavampia päästöraportointeja sekä toimia niiden pohjalta. Lisähaasteen päästömittauksiin asettaa yritysten erilaiset raportointimallit, jotka luovat hankalasti vertailukelpoisia tuloksia. Lisäksi tuloksissa esiin nousi juomapakkausten aiheuttamien ympäristövaikutusten minimoiminen niiden elinkaaren aikana. Mahdollisia mittauskohteita löytyi tutkimuksessa kolme, jotka olivat hiilijalanjäljen mittausosuuden kasvattaminen, pakkausmateriaalien hyödyntämisaste ja kuljetusapuvälineiden uudelleenkäyttöaste.Alko Inc is preparing a more detailed description of its value and supply chain with other Nordic alcohol monopolies. This description takes into account responsibility and value creation perspectives. Responsibility has grown in importance in the recent years, and it can be considered into three categories that are economic, social and environmental responsibility. The research problem was about challenges of responsibility in everyday life of logistics. The thesis was part of the larger value and supply chain description and it was made as an assignment for Alko. The work was limited to environmental responsibility, because it was seen as the most important area of CSR regarding logistics. The purpose was to examine and explore the challenges and think about the potential measurements to the value and supply chain. Theory section of the thesis presents the various forms of responsibility in general, in Alko, and in partner companies. The study examines the value and supply chains as separate entities, describes the methods of measurement and the use of the meters. The work was carried out in 2014 during summer and autumn. The study is qualitative and it was done as semi-structured expert interviews. The interviewees were chosen as they were professionals of logistics and responsibility. The experts were from Alko and its partners companies. The results showed that the customers' interest in responsibility has increased, and it brings a variety of challenges into logistics. This means a more comprehensive emission reports and urges to act on that basis. A further challenge to emission measurements is due to businesses with different reporting models that create incomparable results. In addition, the results of the study revealed a need to minimize environmental impacts of the beverage containers during their life cycle. Three potential measuring points of the study were increasing the measuring of the carbon footprint, measuring the rate of packaging materials for recovery, and the reuse rate of transport accessories

Asennuskohtaiset työturvallisuussuunnitelmat - LVI

Opinnäytetyön tavoitteena oli luoda LVI-asentajille asennuskohtaisia työturvallisuussuunnitelmia tämänhetkiselle rakennustyömaalle. Työturvallisuussuunnitelmien tarkoituksena oli ehkäistä työtapaturmien sattumisia LVI-asentajien työtehtävissä rakennustyömaalla erilaisissa kohteissa. Opinnäytetyötä toteutettiin lukemalla työturvallisuuteen liittyviä verkkoaineistoja sekä haastattelemalla yrityksen työntekijöitä. Lisäksi työssä käytettiin omaa, vuosien kokemusta LVI-alalla. Näiden tietojen pohjalta laaditut työturvallisuussuunnitelmat eri asennuskohteissa parantaa asentajien kiinnittämistä huomiota entisestään työturvallisuuteen. Opinnäytetyöllä saavutettiin asentajille ja työnjohtajille selkeät ja helposti luettavat työturvallisuutta parantavat lomakkeet, joissa tuodaan esille työ, jota tehdään, siihen liittyvät vaarat ja niiden hallitseminen. Opinnäytetyö tuo esille yksityiskohtaisemmin työturvallisuuteen liittyviä riskejä rakennustyömaalla. Opinnäytetyötä voivat hyödyntää erityisesti putki- ja ilmanvaihtoasennustöihin liittyvät urakoitsijat: LVI-asentajat, työnjohtajat, projektinhoitajat ja projektipäälliköt

Terminal Planning:The Selection of Relevant KPIs to Evaluate Operations

The European Union is highly dependent on seaports for trade with the rest of the world and within its Internal"br" Market. Approximately, 75% of goods imported and exported and 37% of exchanges within the Union transited"br" through seaports in 2013. To manage this amount of cargo in ports, smooth operations are required. The"br" performance of ports is currently evaluated by using different types of Key Performance Indicators (KPIs). How"br" the indicators are described is dependent on the stakeholders and their organizational interest."br" Ports, and the transport sector as a whole, are undergoing drastic changes. To cite a few, demand increases, ship"br" capacity enlargements, shipping line mergers and alliances lead to more concentrated flows and increase of traffic"br" in certain hub ports detrimental to medium size ones, other aspects such new requirements regarding environment"br" protection and security are also relevant. At the same time, ports are usually located in the middle of existing"br" neighborhoods, which limits possibilities to enlarge their area whilst stress is placed to improve the port-city"br" interrelation. Therefore, there is a need to invest in port infrastructure, but expansion or renovation of a port is"br" extremely difficult. The required investments are big and the planning horizon is long. Hence, if the designed"br" structures turn out to be unsuitable due to changes in needs, it is rather expensive to make changes."br" Planning tools have developed remarkably during the past 10 years. Different types of planning tools are used in"br" seaport and terminal design to model the completeness. Modelling generates digital representations of physical"br" and functional characteristics of a terminal area, buildings and other infrastructures. With the help of model-based"br" approaches and with suitable KPIs, it is easier to understand and evaluate the effects of certain design solutions"br" for terminal operations in a larger context. By using modelling tools, it is also possible to compare different design"br" options to outline how certain choices in terminal design influences on the completeness."br" There is a need to define the objectives of good terminal prior to plan the terminal and its operations. A good"br" terminal would satisfy the stakeholders’ expectations in best possible ways in the given preconditions. The"br" achievement of objectives can be evaluated by using suitable indicators. However, the indicators used to plan and"br" model terminal operations may differ from indicators used to evaluate the performance of current ports and"br" terminals. The purpose of this paper is to analyze the indicators required for terminal planning and compare them"br" with existing KPIs used for measuring the performance of ports and terminals

Hemap : An Interactive Online Resource for Characterizing Molecular Phenotypes across Hematologic Malignancies

Large collections of genome-wide data can facilitate the characterization of disease states and subtypes, permitting pan-cancer analysis of molecular phenotypes and evaluation of disease context for new therapeutic approaches. We analyzed 9,544 transcriptomes from more than 30 hematologic malignancies, normal blood cell types, and cell lines, and showed that disease types could be stratified in a data-driven manner. We then identified cluster-specific pathway activity, new biomarkers, and in silico drug target prioritization through interrogation of drug target databases. Using known vulnerabilities and available drug screens, we highlighted the importance of integrating molecular phenotype with drug target expression for in silico prediction of drug responsiveness. Our analysis implicated BCL2 expression level as an important indicator of venetoclax responsiveness and provided a rationale for its targeting in specific leukemia subtypes and multiple myeloma, linked several polycomb group proteins that could be targeted by small molecules (SFMBT1, CBX7, and EZH1) with chronic lymphocytic leukemia, and supported CDK6 as a disease-specific target in acute myeloid leukemia. Through integration with proteomics data, we characterized target protein expression for pre-B leukemia immunotherapy candidates, including DPEP1. These molecular data can be explored using our publicly available interactive resource, Hemap, for expediting therapeutic innovations in hematologic malignancies.Peer reviewe

Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans

Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-κB signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases