The consensus molecular subtypes of colorectal cancer.

Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions.

Evidence for daily and weekly rhythmicity but not lunar or seasonal rhythmicity of physical activity in a large cohort of individuals from five different countries.

Background Biological rhythmicity has been extensively studied in animals for many decades. Although temporal patterns of physical activity have been identified in humans, no large-scale, multi-national study has been published, and no comparison has been attempted of the ubiquity of activity rhythms at different time scales (such as daily, weekly, monthly, and annual). Methods Using individually worn actigraphy devices, physical activity of 2,328 individuals from five different countries (adults of African descent from Ghana, South Africa, Jamaica, Seychelles, and the United States) was measured for seven consecutive days at different times of the year. Results Analysis for rhythmic patterns identified daily rhythmicity of physical activity in all five of the represented nationalities. Weekly rhythmicity was found in some, but not all, of the nationalities. No significant evidence of lunar rhythmicity or seasonal rhythmicity was found in any of the groups. Conclusions These findings extend previous small-scale observations of daily rhythmicity to a large cohort of individuals from around the world. The findings also confirm the existence of modest weekly rhythmicity but not lunar or seasonal rhythmicity in human activity. These differences in rhythm strength have implications for the management of health hazards of rhythm misalignment. Key Messages Analysis of the pattern of physical activity of 2,328 individuals from five countries revealed strong daily rhythmicity in all five countries, moderate weekly rhythmicity in some countries, and no lunar rhythmicity or seasonal rhythmicity in any of the countries.

La integración de Internet en la educación escolar española : situación actual y perspectivas de futuro

The main objectives and findings of this first research report are presented in this chapter."The Implementation of the Internet in the Spanish Education System: State of Affairs and Future Prospects" is a large-scale research project that seeks to obtain relevant data about the introduction and dissemination of Information and Communication Technology, particularly the internet, in the practical and organizational general procedures of the Spanish schools and high schools. The project articulates the processes of ICT implementation on the primary and secondary education levels embracing a holistic approach, propped up by an empirical and analytical research methodology. Thus, our survey does not intend to detect which is the impact of ICT on school activities but how all the agents involved in the school community incorporate ICT and what use they make of it. We are especially interested in identifying the teachers' pedagogical and professional uses of ICT, how students use it in their activities and to what extent it contributes in reinforcing teamwork and participation proceedings in the institutions, as well as the relations between the latter and their context. It is also of our interest to know the factors that exert the strongest influence on the way teachers, head teachers and students make use of ICT. Finally, we intend to identify the ways ICT may contribute to the improvementof educational practices.

La integración de Internet en la educación escolar española : situación actual y perspectivas de futuro

The main objectives and findings of this first research report are presented in thischapter. "The Implementation of the Internet in the Spanish Education System: State of Affairsand Future Prospects" is a large-scale research project that seeks to obtain relevant data about the introduction and dissemination of Information and Communication Technology, particularly the internet, in the practical and organizational general procedures of the Spanish schools and high schools. The project articulates the processes of ICT implementation on the primary andsecondary education levels embracing a holistic approach, propped up by an empirical and analytical research methodology. Thus, our survey does not intend to detect which is the impact of ICT on school activities but how all the agents involved in the school community incorporate ICT and what use they make of it. We are especially interested in identifying the teachers' pedagogical and professional uses of ICT, how students use it in their activities and to what extent it contributes in reinforcing teamwork andparticipation proceedings in the institutions, as well as the relations between the latter and their context. It is also of our interest to know the factors that exert the strongest influence on the way teachers, head teachers and students make use of ICT. Finally, we intend to identify the ways ICT may contribute to the improvement of educational practices.

Metsäpolttoaineiden vesitiekuljetus proomukalustolla

Metsäpolttoaineiden käyttö kasvaa lämpö- ja voimalaitoksissa ja mahdollisissa biojalostamoissa. Metsäpolttoaineilla voidaan saavuttaa päästövähennyksiä korvaamalla päästöintensiivisempiä polttoaineita. Metsäpolttoaineen kysynnän kasvu suurkäyttöpaikoilla luo uusia vaatimuksia metsäbiomassan hankintaan. Metsäpolttoaineiden vesitiekuljetuksen sisältämiä logistiikkajärjestelmiä kehittämällä toimitusvarmuutta pystytään parantamaan ja hankintaa laajentamaan kustannustehokkaasti ja ympäristöystävällisesti. Kuljetuskokeilut antoivat uutta tietoa vesitiekuljetuksen sisältämästä hankinnasta. Lastikapasiteetti nykyisen kaltaisessa Eurooppa IIa -suurproomussa vaihtelee 1200 tonnista jopa 1800 tonniin (kosteus 40 %) riippuen tiivistymisestä ja proomun modifiointiasteesta. Metsähakkeen energiatiheys oli suurproomukuljetuksissa keskimäärin 1 MWh/i-m3, joka oli 25 % parempi kuin vertailun hakerekkakuljetuksissa. Vesitiekuljetuksen kustannukset olivat kuljetuskokeiluissa lastauksineen ja purkuineen 0,02 €/MWh/km, ollen noin 20 % ketjun kokonaiskustannuksista. Simuloinnin edullisimpien vesitiekuljetusvaihtoehtojen vaihteluvälin kustannukset olivat vastaavasti 0,013 - 0,026 €/MWh/km. Lastauksen ja purun kustannus oli 0,4 - 0,6 €/MWh ja vesitiekuljetus 0,9 - 2,0 €/MWh (100 km). Ketjun kokonaiskustannukset hakkuutähdehakkeelle vaihtelivat simuloinnin edullisimpien vaihtoehtojen perusteella välillä 10,8 - 12,1 €/MWh (30 km rekka, 100 km proomu). Kuljetusketjujen simuloinnin kustannukset osoittivat proomukuljetusketjun olevan kilpailukykyinen vaihtoehto hakerekkakuljetusketjulle kalustosta ja vuosittaisista käyttötunneista riippuen kuljetusetäisyyden ylittäessä 100 km. Kustannustehokkain ratkaisu vesitiekuljetuksessa saavutettiin pienen aluksen ja suuren kokoluokan proomuyksikön kytkyeellä. Haketus kannattaa toteuttaa ennen proomukuljetuksen osuutta metsähakkeen paremman tiiviyden ja käsiteltävyyden perusteella. Logistiikkajärjestelmiä pitää kehittää tapauskohtaisesti käyttöpaikan tarpeet ja olosuhteet huomioon ottaen. Metsäpolttoaineiden vesitiekuljetuksen sisältämän logistiikan liiketoimintamallien vertailussa arvioitiin vaihtoehtoiset ulkoistetut toimintamallit paremmaksi kuin nykyinen urakointimalli. Tämä mahdollistaa paremman metsähakkeen saatavuuden ja logistiikan tehokkuuden lastausterminaaleissa. Terminaalitoiminnot ja proomukuljetukset lisäävät uusia liiketoimintamahdollisuuksia ja mahdollistavat metsäpolttoaineiden

Visual SLAM for underwater vehicles using video velocity log and natural landmarks

A visual SLAM system has been implemented and optimised for real-time deployment on an AUV equipped with calibrated stereo cameras. The system incorporates a novel approach to landmark description in which landmarks are local sub maps that consist of a cloud of 3D points and their associated SIFT/SURF descriptors. Landmarks are also sparsely distributed which simplifies and accelerates data association and map updates. In addition to landmark-based localisation the system utilises visual odometry to estimate the pose of the vehicle in 6 degrees of freedom by identifying temporal matches between consecutive local sub maps and computing the motion. Both the extended Kalman filter and unscented Kalman filter have been considered for filtering the observations. The output of the filter is also smoothed using the Rauch-Tung-Striebel (RTS) method to obtain a better alignment of the sequence of local sub maps and to deliver a large-scale 3D acquisition of the surveyed area. Synthetic experiments have been performed using a simulation environment in which ray tracing is used to generate synthetic images for the stereo system

Formal Power Analysis of Systems-on-Chip

The design methods and languages targeted to modern System-on-Chip designs are facing tremendous pressure of the ever-increasing complexity, power, and speed requirements. To estimate any of these three metrics, there is a trade-off between accuracy and abstraction level of detail in which a system under design is analyzed. The more detailed the description, the more accurate the simulation will be, but, on the other hand, the more time consuming it will be. Moreover, a designer wants to make decisions as early as possible in the design flow to avoid costly design backtracking. To answer the challenges posed upon System-on-chip designs, this thesis introduces a formal, power aware framework, its development methods, and methods to constraint and analyze power consumption of the system under design. This thesis discusses on power analysis of synchronous and asynchronous systems not forgetting the communication aspects of these systems. The presented framework is built upon the Timed Action System formalism, which offer an environment to analyze and constraint the functional and temporal behavior of the system at high abstraction level. Furthermore, due to the complexity of System-on-Chip designs, the possibility to abstract unnecessary implementation details at higher abstraction levels is an essential part of the introduced design framework. With the encapsulation and abstraction techniques incorporated with the procedure based communication allows a designer to use the presented power aware framework in modeling these large scale systems. The introduced techniques also enable one to subdivide the development of communication and computation into own tasks. This property is taken into account in the power analysis part as well. Furthermore, the presented framework is developed in a way that it can be used throughout the design project. In other words, a designer is able to model and analyze systems from an abstract specification down to an implementable specification.

Secure and Anonymous Multimedia Content Distribution in Peer-to-Peer Networks

Peer-reviewed

Inversion and assimilation methods with applications in geophysical remote sensing

Stratospheric ozone can be measured accurately using a limb scatter remote sensing technique at the UV-visible spectral region of solar light. The advantages of this technique includes a good vertical resolution and a good daytime coverage of the measurements. In addition to ozone, UV-visible limb scatter measurements contain information about NO2, NO3, OClO, BrO and aerosols. There are currently several satellite instruments continuously scanning the atmosphere and measuring the UVvisible region of the spectrum, e.g., the Optical Spectrograph and Infrared Imager System (OSIRIS) launched on the Odin satellite in February 2001, and the Scanning Imaging Absorption SpectroMeter for Atmospheric CartograpHY (SCIAMACHY) launched on Envisat in March 2002. Envisat also carries the Global Ozone Monitoring by Occultation of Stars (GOMOS) instrument, which also measures limb-scattered sunlight under bright limb occultation conditions. These conditions occur during daytime occultation measurements. The global coverage of the satellite measurements is far better than any other ozone measurement technique, but still the measurements are sparse in the spatial domain. Measurements are also repeated relatively rarely over a certain area, and the composition of the Earth’s atmosphere changes dynamically. Assimilation methods are therefore needed in order to combine the information of the measurements with the atmospheric model. In recent years, the focus of assimilation algorithm research has turned towards filtering methods. The traditional Extended Kalman filter (EKF) method takes into account not only the uncertainty of the measurements, but also the uncertainty of the evolution model of the system. However, the computational cost of full blown EKF increases rapidly as the number of the model parameters increases. Therefore the EKF method cannot be applied directly to the stratospheric ozone assimilation problem. The work in this thesis is devoted to the development of inversion methods for satellite instruments and the development of assimilation methods used with atmospheric models.

Pk-yritysten kehittäminen työllisyyden näkökulmasta

Tämän työn tarkoituksena on hahmottaa pk-yrityksien työllistämismahdollisuuksia teollisuuden rakennemuutoksen karsiessa suurteollisuuden työpaikkoja. Tutkimuksessa selvitetään työllistämistä estäviä ja vaikeuttavia tekijöitä pk-yrityksissä sekä pyritään löytämään niihin liittyviä kehittämisehdotuksia. Tutkimus on kirjallisuuspohjainen katsaus, johon liittyy haastattelututkimus, jossa kohderyhmänä ovat julkisen sektorin edustajat ja toisena osapuolena yksityisen sektorin yrittäjät. Tutkimuksen työn pääongelmana on kartoittaa työllistämisesteitä pk-yrityksissä ja etsiä kehittämistoimenpiteitä, joilla työllistämismahdollisuuksien edistämiseksi. Lisäksi etsitään keinoja edistää yrittäjyyttä erityisesti työllisyyden näkökulmasta. Yrittäjyys ja pk-yritykset ovat voimavara, jonka kasvu- ja kehitysongelmia pienentämällä voidaan merkittävästi vaikuttaa uusien työpaikkojen syntymiseen. Työn alaongelmia ovat: irtisanomissuoja, keskitetty työmarkkinajärjestelmä ja ay-liike, työaikamääräykset, työvoimakustannukset ja paikallisen sopimisen puutteellisuus. Muita työllistämisen ongelmia ovat mm. ammattitaitoisen työvoiman saanti, työttömyysturva ja ensimmäisen työntekijän palkkaaminen. Työn lopputuloksina esitetään mm. irtisanomissuojan heikentämistä, ay-liikkeen saamista mukaan paikalliseen sopimiseen ja joustoihin, työaikamääräysten joustoja, työvoimakustannuksista verotuksen kannustavammaksi rakentamista ja sova-maksujen porrastamista pk-yrityksille oikealla tavalla ja paikallisen sopimisen vahvistamista. Lisäksi työttömyys-turvaa tulee muuttaa kannustavammaksi, ammattitaitoisen työvoiman saantia edistää ja ensimmäisen työntekijän palkkaamista on tuettava.

Pk-yritysten kehittäminen työllisyyden näkökulmasta

Tämän työn tarkoituksena on hahmottaa pk-yrityksien työllistämismahdollisuuksia teollisuuden rakennemuutoksen karsiessa suurteollisuuden työpaikkoja. Tutkimuksessa selvitetään työllistämistä estäviä ja vaikeuttavia tekijöitä pk-yrityksissä sekä pyritään löytämään niihin liittyviä kehittämisehdotuksia. Tutkimus on kirjallisuuspohjainen katsaus, johon liittyy haastattelututkimus, jossa kohderyhmänä ovat julkisen sektorin edustajat ja toisena osapuolena yksityisen sektorin yrittäjät. Tutkimuksen työn pääongelmana on kartoittaa työllistämisesteitä pk-yrityksissä ja etsiä kehittämistoimenpiteitä, joilla työllistämismahdollisuuksien edistämiseksi. Lisäksi etsitään keinoja edistää yrittäjyyttä erityisesti työllisyyden näkökulmasta. Yrittäjyys ja pk-yritykset ovat voimavara, jonka kasvu- ja kehitysongelmia pienentämällä voidaan merkittävästi vaikuttaa uusien työpaikkojen syntymiseen. Työn alaongelmia ovat: irtisanomissuoja, keskitetty työmarkkinajärjestelmä ja ay-liike, työaikamääräykset, työvoimakustannukset ja paikallisen sopimisen puutteellisuus. Muita työllistämisen ongelmia ovat mm. ammattitaitoisen työvoiman saanti, työttömyysturva ja ensimmäisen työntekijän palkkaaminen. Työn lopputuloksina esitetään mm. irtisanomissuojan heikentämistä, ay-liikkeen saamista mukaan paikalliseen sopimiseen ja joustoihin, työaikamääräysten joustoja, työvoimakustannuksista verotuksen kannustavammaksi rakentamista ja sova-maksujen porrastamista pk-yrityksille oikealla tavalla ja paikallisen sopimisen vahvistamista. Lisäksi työttömyysturvaa tulee muuttaa kannustavammaksi, ammattitaitoisen työvoiman saantia edistää ja ensimmäisen työntekijän palkkaamista on tuettava.

Fosforin kierron sulkeminen systeemi-innovaationa, case: Biomeri Oy

Phosphorus is a vital raw material but there is a threat that world's phosphorus reserves will diminish. It is essential to utilize phosphorus in order to feed world's population. Nevertheless phosphorus consumption causes some severe environmental problems. To solve these problems a large-scale change such as system innovation is required. System innovation is structural transition which influence on many interest groups and their interactions. One of the most potential solutions lie on phosphorus recovery. Unfortunately recovery faces many social barriers. This study examines case -company Biomeri Oy, because this company has developed an environmental innovation which meets the same problems as phosphorus recovery.

A study of combustion phenomena in circulating fluidized beds by developing and applying experimental and modelling methods for laboratory-scale reactors

The results shown in this thesis are based on selected publications of the 2000s decade. The work was carried out in several national and EC funded public research projects and in close cooperation with industrial partners. The main objective of the thesis was to study and quantify the most important phenomena of circulating fluidized bed combustors by developing and applying proper experimental and modelling methods using laboratory scale equipments. An understanding of the phenomena plays an essential role in the development of combustion and emission performance, and the availability and controls of CFB boilers. Experimental procedures to study fuel combustion behaviour under CFB conditions are presented in the thesis. Steady state and dynamic measurements under well controlled conditions were carried out to produce the data needed for the development of high efficiency, utility scale CFB technology. The importance of combustion control and furnace dynamics is emphasized when CFB boilers are scaled up with a once through steam cycle. Qualitative information on fuel combustion characteristics was obtained directly by comparing flue gas oxygen responses during the impulse change experiments with fuel feed. A one-dimensional, time dependent model was developed to analyse the measurement data Emission formation was studied combined with fuel combustion behaviour. Correlations were developed for NO, N2O, CO and char loading, as a function of temperature and oxygen concentration in the bed area. An online method to characterize char loading under CFB conditions was developed and validated with the pilot scale CFB tests. Finally, a new method to control air and fuel feeds in CFB combustion was introduced. The method is based on models and an analysis of the fluctuation of the flue gas oxygen concentration. The effect of high oxygen concentrations on fuel combustion behaviour was also studied to evaluate the potential of CFB boilers to apply oxygenfiring technology to CCS. In future studies, it will be necessary to go through the whole scale up chain from laboratory phenomena devices through pilot scale test rigs to large scale, commercial boilers in order to validate the applicability and scalability of the, results. This thesis shows the chain between the laboratory scale phenomena test rig (bench scale) and the CFB process test rig (pilot). CFB technology has been scaled up successfully from an industrial scale to a utility scale during the last decade. The work shown in the thesis, for its part, has supported the development by producing new detailed information on combustion under CFB conditions.

Tool-supported invariant-based programming

The development of correct programs is a core problem in computer science. Although formal verification methods for establishing correctness with mathematical rigor are available, programmers often find these difficult to put into practice. One hurdle is deriving the loop invariants and proving that the code maintains them. So called correct-by-construction methods aim to alleviate this issue by integrating verification into the programming workflow. Invariant-based programming is a practical correct-by-construction method in which the programmer first establishes the invariant structure, and then incrementally extends the program in steps of adding code and proving after each addition that the code is consistent with the invariants. In this way, the program is kept internally consistent throughout its development, and the construction of the correctness arguments (proofs) becomes an integral part of the programming workflow. A characteristic of the approach is that programs are described as invariant diagrams, a graphical notation similar to the state charts familiar to programmers. Invariant-based programming is a new method that has not been evaluated in large scale studies yet. The most important prerequisite for feasibility on a larger scale is a high degree of automation. The goal of the Socos project has been to build tools to assist the construction and verification of programs using the method. This thesis describes the implementation and evaluation of a prototype tool in the context of the Socos project. The tool supports the drawing of the diagrams, automatic derivation and discharging of verification conditions, and interactive proofs. It is used to develop programs that are correct by construction. The tool consists of a diagrammatic environment connected to a verification condition generator and an existing state-of-the-art theorem prover. Its core is a semantics for translating diagrams into verification conditions, which are sent to the underlying theorem prover. We describe a concrete method for 1) deriving sufficient conditions for total correctness of an invariant diagram; 2) sending the conditions to the theorem prover for simplification; and 3) reporting the results of the simplification to the programmer in a way that is consistent with the invariantbased programming workflow and that allows errors in the program specification to be efficiently detected. The tool uses an efficient automatic proof strategy to prove as many conditions as possible automatically and lets the remaining conditions be proved interactively. The tool is based on the verification system PVS and i uses the SMT (Satisfiability Modulo Theories) solver Yices as a catch-all decision procedure. Conditions that were not discharged automatically may be proved interactively using the PVS proof assistant. The programming workflow is very similar to the process by which a mathematical theory is developed inside a computer supported theorem prover environment such as PVS. The programmer reduces a large verification problem with the aid of the tool into a set of smaller problems (lemmas), and he can substantially improve the degree of proof automation by developing specialized background theories and proof strategies to support the specification and verification of a specific class of programs. We demonstrate this workflow by describing in detail the construction of a verified sorting algorithm. Tool-supported verification often has little to no presence in computer science (CS) curricula. Furthermore, program verification is frequently introduced as an advanced and purely theoretical topic that is not connected to the workflow taught in the early and practically oriented programming courses. Our hypothesis is that verification could be introduced early in the CS education, and that verification tools could be used in the classroom to support the teaching of formal methods. A prototype of Socos has been used in a course at Åbo Akademi University targeted at first and second year undergraduate students. We evaluate the use of Socos in the course as part of a case study carried out in 2007.

Molecular modeling of asymmetric induction in heterogeneously catalyzed hydrogenation of the C=O bond

Modifiering av metallytor med starkt adsorberade kirala organiska molekyler är eventuellt den mest relevanta teknik man vet i dag för att skapa kirala ytor. Den kan utnyttjas i katalytisk produktion av enantiomeriskt rena kirala föreningar som behövs t.ex. som läkemedel och aromkemikalier. Trots många fördelar av asymmetrisk heterogen katalys jämfört med andra sätt för att få kirala föreningar, har den ändå inte blivit ett allmänt verktyg för storskaliga tillämpningar. Detta beror t.ex. på brist på djupare kunskaper i katalytiska reaktionsmekanismer och ursprunget för asymmetrisk induktion. I denna studie användes molekylmodelleringstekniker för att studera asymmetriska, heterogena katalytiska system, speciellt hydrering av prokirala karbonylföreningar till motsvarande kirala alkoholer på cinchona-alkaloidmodifierade Pt-katalysatorer. 1-Fenyl-1,2-propandion (PPD) och några andra föreningar, som innehåller en prokiral C=O-grupp, användes som reaktanter. Konformationer av reaktanter och cinchona-alkaloider (som kallas modifierare) samt vätebundna 1:1-komplex mellan dem studerades i gas- och lösningsfas med metoder som baserar sig på vågfunktionsteori och täthetsfunktionalteori (DFT). För beräkningen av protonaffiniteter användes också högst noggranna kombinationsmetoder såsom G2(MP2). Den relativa populationen av modifierarnas konformationer varierade som funktion av modifieraren, dess protonering och lösningsmedlet. Flera reaktant–modifierareinteraktionsgeometrier beaktades. Slutsatserna på riktning av stereoselektivitet baserade sig på den relativa termodynamiska stabiliteten av de diastereomeriska reaktant–modifierare-komplexen samt energierna hos π- och π*-orbitalerna i den reaktiva karbonylgruppen. Adsorption och reaktioner på Pt(111)-ytan betraktades med DFT. Regioselektivitet i hydreringen av PPD och 2,3-hexandion kunde förklaras med molekyl–yta-interaktioner. Storleken och formen av klustret använt för att beskriva Pt-ytan inverkade inte bara på adsorptionsenergierna utan också på de relativa stabiliteterna av olika adsorptionsstrukturer av en molekyl. Populationerna av modifierarnas konformationer i gas- och lösningsfas korrelerade inte med populationerna på Pt-ytan eller med enantioselektiviteten i hydreringen av PPD på Pt–cinchona-katalysatorer. Vissa modifierares konformationer och reaktant–modifierare-interaktionsgeometrier var stabila bara på metallytan. Teoretiskt beräknade potentialenergiprofiler för hydrering av kirala α-hydroxiketoner på Pt implicerade preferens för parvis additionsmekanism för väte och selektiviteter i harmoni med experimenten. De uppnådda resultaten ökar uppfattningen om kirala heterogena katalytiska system och kunde därför utnyttjas i utvecklingen av nya, mera aktiva och selektiva kirala katalysatorer.