Copy number variations of colorectal cancer by whole exome sequencing data

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death worldwide. About 85% of the cases of CRC are known to have chromosomal instability, an allelic imbalance at several chromosomal loci, and chromosome amplification and translocation. The aim of this study is to determine the recurrent copy number variant (CNV) regions present in stage II of CRC through whole exome sequencing, a rapidly developing targeted next-generation sequencing (NGS) technology that provides an accurate alternative approach for accessing genomic variations. 42 normal-tumor paired samples were sequenced by Illumina Genome Analyzer. Data was analyzed with Varscan2 and segmentation was performed with R package R-GADA. Summary of the segments across all samples was performed and the result was overlapped with DEG data of the same samples from a previous study in the group1. Major and more recurrent segments of CNV were: gain of chromosome 7pq(13%), 13q(31%) and 20q(75%) and loss of 8p(25%), 17p(23%), and 18pq(27%). This results are coincident with the known literature of CNV in CRC or other cancers, but our methodology should be validated by array comparative genomic hybridisation (aCGH) profiling, which is currently the gold standard for genetic diagnosis of CNV.

β1 integrin regulation

Integrins are heterodimeric adhesion receptors mediating adhesion to extracellular matrix proteins and to other cells. Integrins are important in embryonic development, structural integrity of connective tissue, blood thrombus formation, and immune defense system. Integrins are transmembrane proteins whose ligand binding capacity (activity) is regulated by large conformational changes. Extracellular ligand binding or intracellular effector binding to integrin cytoplasmic face regulate integrin activity. Integrins are thus able to mediate bi-directional signaling. Integrin function is also regulated by intracellular location. Integrins are constantly recycled from endocytic vesicles to plasma membrane, and this has been shown to be important for cell migration and invasion as well. Deregulation of integrin functionality can lead to deleterious illnesses, such as bleeding or inflammatory disorders. It is also evident that integrin deregulation is associated with cancer progression. In this study, a novel Beta1 integrin associating protein, Rab21, was characterized. Rab21 binding to integrin cytoplasmic tail was shown to be important for Beta1 integrin endo- and exocytosis – intracellular trafficking. It was furher shown that this interaction has an important role in cell adhesion, migration, as well as in the final step of cell division, cytokinesis. This work showed that abrogation of Rab21 function or β1 integrin endocytic traffic, can lead to defects in cell division and results in formation of multinucleated cells. Multinucleation and especially tetraploidy can be a transient pathway to aneuploidy and tumorigenesis. This work characterized chromosomal deletions in rab21 locus in ovarian and prostate cancer samples and showed that a cell line with rab21 deletion also had impairment in cell division, which could be rescued by Rab21 re-expression. The work demonstrates an important role for Rab21 and Beta1 integrin traffic regulation in cell adhesion and division, and suggests a probable associaton with tumorigenesis. In this study, Beta1 integrin activity regulation was also addressed. A novel cell array platform for genome-scale RNAi screenings was characterized here. More than 4500 genes were knocked-down in prostate cancer cells using siRNA-mediated silencing. The effects on Beta1 integrin activity were analyzed upon knock-downs. The screen identified more that 400 putative regulators of Beta1 integrin activity in prostate cancer. In conclusion, this work will help us to understand complex regulatory pathways involved in cancer cell adhesion and migration.

Financial stress transmission in EMU sovereign bond market volatility: a connectedness analysis

This paper measures the connectedness in EMU sovereign market volatility between April 1999 and January 2014, in order to monitor stress transmission and to identify episodes of intensive spillovers from one country to the others. To this end, we first perform a static and dynamic analysis to measure the total volatility connectedness in the entire period (the system-wide approach) using a framework recently proposed by Diebold and Yılmaz (2014). Second, we make use of a dynamic analysis to evaluate the net directional connectedness for each country and apply panel model techniques to investigate its determinants. Finally, to gain further insights, we examine the timevarying behaviour of net pair-wise directional connectedness at different stages of the recent sovereign debt crisis.

Volatility spillovers in EMU sovereign bond markets

We analyse volatility spillovers in EMU sovereign bond markets. First, we examine the unconditional patterns during the full sample (April 1999-January 2014) using a measure recently proposed by Diebold and Yılmaz (2012). Second, we make use of a dynamic analysis to evaluate net directional volatility spillovers for each of the eleven countries under study, and to determine whether core and peripheral markets present differences. Finally, we apply a panel analysis to empirically investigate the determinants of net directional spillovers of this kind.

Imposicions estructurals en el drenatge de la conca del riu Onyar (Girona)

The Onyar River basin is situated in the depression of la Selva. His origins are related to tectonic activity during Neogen in this region. In his evolution, we note a slowly and continuous downfall which directs the morphodinamical behaviour. In this sense, the drainage network has a directional trend towards the north, as consecuence of fault systems, and specially the N-S oriented one. A fault of this system has an important influence in the basin morphology, directs the drainage towards the north and avoids a closely drainage in the basin

Bias and standard error for social reciprocity measurements

The directional consistency and skew-symmetry statistics have been proposed as global measurements of social reciprocity. Although both measures can be useful for quantifying social reciprocity, researchers need to know whether these estimators are biased in order to assess descriptive results properly. That is, if estimators are biased, researchers should compare actual values with expected values under the specified null hypothesis. Furthermore, standard errors are needed to enable suitable assessment of discrepancies between actual and expected values. This paper aims to derive some exact and approximate expressions in order to obtain bias and standard error values for both estimators for round-robin designs, although the results can also be extended to other reciprocal designs.

Control d'una bobinadora automàtica

Un dels problemes típics de regulació en el camp de l’automatització industrial és el control de velocitat lineal d’entrada del fil a les bobines, ja que com més gruix acumulem a igual velocitat de rotació de la bobina s’augmenta notablement la velocitat lineal d’entrada del fil, aquest desajust s’ha de poder compensar de forma automàtica per aconseguir una velocitat d’entrada constant. Aquest problema de regulació de velocitats és molt freqüent i de difícil control a la indústria on intervé el bobinat d’algun tipus de material com cablejat, fil, paper, làmines de planxa, tubs, etc... Els dos reptes i objectius principals són, primer, la regulació de la velocitat de rotació de la bobina per aconseguir una velocitat lineal del fil d’entrada, i segon, mitjançant el guiatge de l’alimentació de fil a la bobina, aconseguir un repartiment uniforme de cada capa de fil. El desenvolupament consisteix amb l’automatització i control d’una bobinadora automàtica mitjançant la configuració i programació de PLC’s, servomotors i encoders. Finalment es farà el muntatge pràctic sobre una bancada per verificar i simular el seu correcte funcionament que ha de donar solució a aquests problemes de regulació de velocitats. Com a conclusions finals s’han aconseguit els objectius i una metodologia per fer una regulació de velocitats de rotació per bobines, amb accionaments de servomotors amb polsos, i a nivell de coneixements he aconseguit dominar les aplicacions d’aquest tipus d’accionaments aplicats a construccions mecàniques.

Análisis de la fiabilidad de indicadores para sistemas de seguimiento de precios en los mercados

Para este trabajo se ha desarrollado un programa en Matlab, que nos permite realizar ensayos con algunas de las herramientas fundamentales del análisis técnico. Concretamente nos hemos centrado en el “Indicador de Movimiento Direccional” de Wilder. El programa está formado por seis funciones que permiten descargar datos, hacer la simulación del indicador, ajustar automáticamente algunos de sus parámetros y presentar los resultados obtenidos en la simulación. Con los experimentos y simulaciones realizadas se ha visto la importancia de escoger adecuadamente los períodos de ±DIs (indicadores direccionales positivo y negativo) y el ADX (Average Directional Movement Index). También hemos visto que la reglas decisión apuntadas por autores de reconocido prestigio como Cava y Ortiz ,no siempre se comportan como cabría esperar. Se propone mejorar el rendimiento y la fiabilidad de este indicador Incluyendo alguna media móvil de los precios y el volumen de contratación, en los criterios de decisión. También se podría mejorar implementando un sistema para que se pudiesen autoajustar los criterios de decisión.

Relações patofisiológicas entre estresse oxidativo e arteriosclerose

Oxidative stress is the result of an imbalance between oxidant and antioxidant species, with predominance of oxidative species with harmful action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) on cells. Changes in the levels of nitric oxide (NO•) can be the cause and/ or a result of various pathophysiological processes. The main objective of this review is to address the relationship between oxidative stress and atherosclerosis in order to better understand the main features of this disease.

Improving and User Interface to E-Procurement Software Used in Asset Accounting and Investigating Effects to Efficiency

This diploma thesis has been done to international organization which takes care from the accounting actions of two major companies. In this organization are used three different purchasing tools which are used when new asset master data is wanted to input to SAP R/3- system. The aim of this thesis is to find out how much changing the user interface of one of these three e-procurement programs will affect to overall efficiency in asset accounting. As an addition will be introduced project framework which can be used in future projects and which help to avoid certain steps in the development process. At the moment data needs to be inputted manually with many useless mouse clicks and data needs to be searched from many various resources which slow down the process. Other organization has better tools at the moment than the myOrders system which is under investigation Research was started by exploring the main improvement areas. After this possible defects were traced. Suggested improvements were thought by exploring literature which has been written from usability design and research. Meanwhile also directional calculations from the benefits of the project were done alongside with the analysis of the possible risks and threats. After this NSN IT approved the changes which they thought was acceptable. The next step was to program them into tool and test them before releasing to production environment. The calculations were made also from implemented improvements and compared them to planned ones From whole project was made a framework which can be utilized also to other similar projects. The complete calculation was not possible because of time schedule of the project. Important observation in the project was that efficiency is not improved not only by changing the GUI but also improving processes without any programming. Feedback from end user should be also listened more in development process. End-user is after all the one who knows the best how the program should look like.

Holocene Varved Lake Sediments as Records of Palaeoenvironmental Change and Geomagnetic Palaeosecular Variation in Eastern Finland

This dissertation discusses Holocene palaeoenvironmental and palaeomagnetic secular variation (PSV) records reconstructed from sediments preserved in Lake Lehmilampi (63º37´N, 29º06´E) and Lake Kortejärvi (63º37´N, 28º56´E) in eastern Finland. Several piston and freeze cores were obtained from both lakes for varve and magnetic analyses. Sediment samples were impregnated in low-viscosity epoxy and physical parameters of varves, including varve thickness and relative grey-scale values, were recorded using x-ray densitometry combined with semiautomatic digital image analysis. On average, varve records of Lehmilampi and Kortejärvi cover 5122 and 3902 years, respectively. Past solar activity, as estimated by residual ₁₄C data, compares favourably with varve thicknesses from Lehmilampi during the last 2000 years. This indicates the potential of clastic-organic varves to record sensitively climatic variations. Bulk magnetic parameters, including magnetic susceptibility together with natural, anhysteretic and isothermal remanent magnetizations, were measured to describe mineral magnetic properties and geomagnetic palaeosecular variation recorded in the sediments. Main stages in the development of the investigated lakes are reflected in the variations in the mineral magnetic records, sediment lithology and composition. Similar variations in magnetic parameters and sediment organic matter suggest contribution of bacterial magnetite in the magnetic assemblages of Lehmilampi. Inclination and relative declination records yielded largely consistent results, attesting to the great potential of these sediments to preserve directional palaeosecular variation in high resolution. The PSV data from Lehmilampi and Kortejärvi were stacked into North Karelian PSV stack, which may be used for dating homogenous lake sediments in the same regional context. Reconstructed millennial variations in relative palaeointensity results are approximately in agreement with those seen in the absolute palaeointensity data from Europe. Centennial variations in the relative palaeointensity, however, are influenced by environmental changes. Caution is recommended when using varved lake sediments in reconstructing relative palaeointensity.

UNIDROIT-periaatteiden hardship sopimusriskien hallinnan välineenä

Tutkielman tarkoituksena on tutkia, miten hardship-ehdon käyttö ennakoivan sopimussuunnittelun välineenä kansainvälisiä kauppasopimuksia solmittaessa parantaa sopimuksellista riskienhallintaa. Tähän sisältyy myös ehdot sopimuksen uudelleenneuvottelusta, joihin sopimusosapuolten tulee ryhtyä, jos hardshipin osoittama taloudellinen liikavaikeus on todella sopimuksessa tapahtuneen muutoksen syynä. Lisäksi tarkoituksena on selvittää, miten sopimuskäsityksen muutos ennakoivaan suuntaan on luonut sopimusosapuolille mahdollisuuksia suunnitella sopimuksiaan paremmin. Tutkimuksessa käytetään lainopillista lähestymistapaa. Tarkoituksena on löytää vastaus käsillä olevaan kysymykseen voimassa olevan lainsäädännön avulla sekä saatavilla olevaan kirjallisuuteen perehtyen. Hardship-ehdon voidaan nähdä parantavan sopimuksellista riskienhallintaa tehokkaasti. Ehto on toimiva varsinkin liike-elämän pitkäkestoisissa sopimuksissa, joissa sopimuksen sitovuus on korostuneessa asemassa. Hardship-ehto dynaamisena välineenä takaa sopimuksen sitovuuden tarjoamalla muuttuneiden olosuhteiden korjaamiseen uudelleenneuvotteluja ja näin ollen mahdollisuuden tasapainottaa sopimuksessa vallitseva epätasapaino.

Coaching agile methods in research and development projects

Agile coaching of a project team is one way to aid learning of the agile methods. The objective of this thesis is to present the agile coaching plan and to follow how complying the plan affects to the project teams. Furthermore, the agile methods are followed how they work in the projects. Two projects are used to help the research. From the thesis point of view, the task for the first project is to coach the project team and two new coaches. The task for the second project is also to coach the project team, but this time so that one of the new coaches acts as the coach. The agile methods Scrum process and Extreme programming are utilized by the projects. In the latter, the test driven development, continuous integration and pair programming are concentrated more precisely. The results of the work are based on the observations from the projects and the analysis derived from the observations. The results are divided to the effects of the coaching and to functionality of the agile methods in the projects. Because of the small sample set, the results are directional. The presented plan, to coach the agile methods, needs developing, but the results of the functionality of the agile methods are encouraging.

In pursuit of an intercultural dimension in EFL-teaching : exploring cognitions among Finland-Swedish comprehensive school teachers

This thesis is about the educational purpose of foreign language teaching (FLT) in an increasingly internationalised world.The past 20-30 years have witnessed a fundamental rethinking of the aims of FLT, entailing a shift in emphasis from linguistic competence over communicative competence to intercultural competence. The growing emphasis on cultural issues, called for by research and international curricular documents, places new demandson language teachers. The overall aim of this study is to deepen the knowledge about the attitudes of teachers at the upper level of the Finland-Swedish comprehensive school towards the treatment of culture in English foreign language (EFL) teaching. The questions in focus are: 1) How do teachers interpret the concept"culture" in EFL-teaching?, 2) How do they specify the cultural objectives of their teaching? and 3) What do they do to attain these objectives? The thesis strives to reveal whether or not language teaching today can be describedas intercultural, in the sense that culture is taught with the aim of promotingintercultural understanding, tolerance and empathy. This abductive and largely exploratory study is placed within a constructivist and sociocultural framework,and is inspired by both phenomenography and hermeneutics. It takes its starting-point in language didactics, and can also be regarded as a contribution to teacher cognition research. The empirical data consists of verbatim transcribed interviews with 13 Finland-Swedish teachers of English at grades 7-9. The findings are presented according to three orientations and reviewed with reference to the 2004 Finnish National Framework Curriculum. Within the cognitive orientation, "culture" is perceived as factual knowledge, and the teaching of cultureis defined in terms of the transmission of knowledge, especially about Britain and the USA (Pedagogy of Information). Within the action-related orientation, "culture" is seen as skills of a social and socio-linguistic nature, andthe teaching aims at preparing the students for contacts with people from the target language areas (Pedagogy of Preparation). Within the affective orientation, which takes a more holistic approach, "culture" is seen as a bi-directional perspective. Students are encouraged to look at their own familiar culture from another perspective, and learn to empathise with and show respect for otherness in general, not just concerning representatives of English-speaking countries (Pedagogy of Encounter). Very few of the interviewed teachers represent the third approach, which is the one that can be characterised as truly intercultural. The study indicates that many teachers feel unsure about how to teach culture in an appropriate and up-to-date manner. This is attributed to, among other things, lack of teacher insights as well as lack of time and adequate material. The thesis ends with a set of recommendations as to how EFL could be developed ina more intercultural direction.

Identifying and Characterizing New Ingredients in vitro for Prebiotic and Synbiotic use

The endogenous microbiota, constituting the microbes that live inside and on humans, is estimated to outnumber human cells by a factor of ten. This commensal microbial population has an important role in many physiological functions, with the densest microbiota population found in the colon. The colonic microbiota is a highly complex and diverse bacterial ecosystem, and a delicate balance exists between the gut microbiota and its host. An imbalance in the microbial ecosystem may lead to severe symptoms in and also beyond the gastrointestinal tract. Due to the important role of the gut microbiota in human health, means of its modification have been introduced in the dietary concepts of pro-, pre- and synbiotics. Prebiotics, which are usually carbohydrates, strive to selectively influence beneficial microbes resident in the colon with the aim of modifying the composition and functionality of the commensal microbial population towards a purportedly healthier one. The study of prebiotic effects on colonic micro-organisms is typically done by using human faecal material, though this provides relatively little information on bacterial populations and metabolic events in different parts of the colon. For this reason, several in vitro models have been developed to investigate the gut microbiota. The aim of this doctoral thesis was to screen through some of the promising prebiotic candidates, characterize their effects on the microbiota through the use of two in vitro methods (pure microbial cultures and a colon simulator model) and to evaluate their potential as emerging prebiotics or synbiotics when combined with the probiotic Bifidobacterium lactis . As a result of the screening work and subsequent colon simulation studies, several compounds with promising features were identified. Xylo-oligosaccharides (XOS), which have previously already shown promise as prebiotic compounds, were well fermented by several probiotic Bifidobacterium lactis strains in pure culture studies and in the following simulation studies utilizing the complex microbiota by endogenous B. lactis Another promising compound was panose, a trisaccharide belonging to isomalto-oligosaccharides (IMO) that also was also able to modify the microbiota in vitro by increasing the number of beneficial microbes investigated. Panose has not been widely studied previously and therefore, this thesis work provided the first data on panose fermentation in mixed colonic microbiota. Galacto-oligosaccharide (GOS) is an established prebiotic, and it was studied here in conjunction with another potential polygosaccharide polydextrose (PDX) and probiotic B. lactis Bi-07. In this final study, the synbiotics including GOS were more effective than the constituting pro- or prebiotics alone in modulating the microbiota composition, thus indicating a synergy resulting from the combination. The results obtained in this in vitro work can be, and have already been, utilized in product development aimed at the nutritional modification of the human colonic microbiota. Some of the compounds have entered the human clinical intervention phase to nvestigate in more detail the prebiotic and synbiotic properties seen in these in vitro studies.