Adenovirus endocytosis and adenoviral gene transfer in cardiovascular and dermatologic disease models

AbstractAdenoviral gene transfer is a valuable tool in molecular biology research. In order to be an efficient and safe vector, adenovirus structure and infection mechanism as well as molecular biology of the used transgene need to be well studied. The aim of this study was to evaluate the role of adenovirus as a gene transfer vector from several perspectives. Adenovirus uses receptor-mediated endocytosis in order to enter the target cell. The effect of Rab5 GTPase on adenovirus entry and gene transfer efficiency was examined first. Next, adenovirus was used as an investigatory tool in the cardiovascular research, focused on clarifying the role of adrenomedullin (AM) in heart and vascular remodeling. Finally, a model of adenoviral gene transfer into skin fibroblasts was used.The role of Rab5 GTPase in the adenovirus endocytosis was examined in HeLa cells using Cy3-labeled adenovirus, and gene transfer efficiency using β-galactosidase encoding adenovirus. Rab5 increased both adenovirus uptake and gene transfer, whereas dominant negative Rab5S34N decreased both endocytosis and gene transfer. The data indicate that Rab5 is needed in mediating the adenovirus uptake into the target cell.In the rat heart, adenovirus-mediated AM gene transfer transiently improved systolic function both in vivo and in vitro. AM caused activation of translocation of protein kinases C ε and δ, whereas phosphorylation of p38 mitogen activated protein kinase was decreased in the left ventricle. AM significantly attenuated the development of angiotensin II-induced cardiac hypertrophy. In rats with myocardial infarction, AM enhanced dilatation of left ventricle and thinning of anterior wall. The role of AM in neointima formation was evaluated in rat artery after endothelial injury. Intravascular AM gene transfer decreased neointimal growth and increased neointimal myofibroblasts apoptosis. These results show that AM regulates left ventricular systolic function and remodeling in the heart, and plays a role in pathological vascular remodeling.Adenovirus-mediated lysyl hydroxylase (LH) gene transfer into skin fibroblasts of type VI Ehlers-Danlos syndrome patient and rat skin increased functional LH production, elevated LH activity, and human LH mRNA production both in vitro and in vivo. LH gene replacement therapy may thus lead to possibilities to improve skin wound healing in Ehlers-Danlos syndrome patients.Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium of the Department of Pharmacology and Toxicology, on September 10th, 2004, at 12 noon.Abstract Adenoviral gene transfer is a valuable tool in molecular biology research. In order to be an efficient and safe vector, adenovirus structure and infection mechanism as well as molecular biology of the used transgene need to be well studied. The aim of this study was to evaluate the role of adenovirus as a gene transfer vector from several perspectives. Adenovirus uses receptor-mediated endocytosis in order to enter the target cell. The effect of Rab5 GTPase on adenovirus entry and gene transfer efficiency was examined first. Next, adenovirus was used as an investigatory tool in the cardiovascular research, focused on clarifying the role of adrenomedullin (AM) in heart and vascular remodeling. Finally, a model of adenoviral gene transfer into skin fibroblasts was used. The role of Rab5 GTPase in the adenovirus endocytosis was examined in HeLa cells using Cy3-labeled adenovirus, and gene transfer efficiency using β-galactosidase encoding adenovirus. Rab5 increased both adenovirus uptake and gene transfer, whereas dominant negative Rab5S34N decreased both endocytosis and gene transfer. The data indicate that Rab5 is needed in mediating the adenovirus uptake into the target cell. In the rat heart, adenovirus-mediated AM gene transfer transiently improved systolic function both in vivo and in vitro. AM caused activation of translocation of protein kinases C ε and δ, whereas phosphorylation of p38 mitogen activated protein kinase was decreased in the left ventricle. AM significantly attenuated the development of angiotensin II-induced cardiac hypertrophy. In rats with myocardial infarction, AM enhanced dilatation of left ventricle and thinning of anterior wall. The role of AM in neointima formation was evaluated in rat artery after endothelial injury. Intravascular AM gene transfer decreased neointimal growth and increased neointimal myofibroblasts apoptosis. These results show that AM regulates left ventricular systolic function and remodeling in the heart, and plays a role in pathological vascular remodeling. Adenovirus-mediated lysyl hydroxylase (LH) gene transfer into skin fibroblasts of type VI Ehlers-Danlos syndrome patient and rat skin increased functional LH production, elevated LH activity, and human LH mRNA production both in vitro and in vivo. LH gene replacement therapy may thus lead to possibilities to improve skin wound healing in Ehlers-Danlos syndrome patients

Transport Use Case Trials of 5G-HEART Project

5G-HEART (5G HEalth AquacultuRe and Transport validation trials) project focuses on realising 5G trials and validating 5G Key Performance Indicators (KPIs) on the vital vertical use-cases of healthcare, transport and aquaculture. In the health area, 5G-HEART validates pillcams for automatic detection in screening of colon cancer and vital-sign patches with advanced geo-localization as well as 5G Augmented/Virtual Reality (AR/VR) paramedic services. In the transport area, 5G-HEART validates autonomous/ assisted/ remote driving and vehicle data services. In the aquaculture area, 5G-HEART validates 5G-based fish farm monitoring systems. Among them, transport sector connected with fifth generation (5G) mobile communications systems will drive transformational changes while bringing social, economic and industrial benefits to the economies that take the lead in its adoption. 5G-enabled industry digitisation for automotive and public transport represents 10% and 8% of the overall $1.3T market in 2026, respectively. In this paper, transport use case trials of 5G-HEART project are introduced

Transport Use Case Trials of 5G-HEART Project

5G-HEART (5G HEalth AquacultuRe and Transport validation trials) project focuses on realising 5G trials and validating 5G Key Performance Indicators (KPIs) on the vital vertical use-cases of healthcare, transport and aquaculture. In the health area, 5G-HEART validates pillcams for automatic detection in screening of colon cancer and vital-sign patches with advanced geo-localization as well as 5G Augmented/Virtual Reality (AR/VR) paramedic services. In the transport area, 5G-HEART validates autonomous/ assisted/ remote driving and vehicle data services. In the aquaculture area, 5G-HEART validates 5G-based fish farm monitoring systems. Among them, transport sector connected with fifth generation (5G) mobile communications systems will drive transformational changes while bringing social, economic and industrial benefits to the economies that take the lead in its adoption. 5G-enabled industry digitisation for automotive and public transport represents 10% and 8% of the overall $1.3T market in 2026, respectively. In this paper, transport use case trials of 5G-HEART project are introduced

Repensar el desarrollo. Un aporte para las políticas públicas de nueva generación desde la perspectiva del Pensamiento Complejo

Frente a la actual crisis del desarrollo y la dificultad de alcanzar los Objetivos del Milenio propuestos por las Naciones Unidas, el propósito de este proyecto ha sido explorar y describir las teorías acerca del concepto desarrollo y vincular las mismas con la propuesta de Edgar Morin de repensar esta idea desde el enfoque del pensamiento complejo.Al comienzo de la investigación, el estudio del término desde las teorías clásicas reveló que su definición conceptual es reduccionista y unidimensional. En la siguiente etapa indagamos el pensamiento de Morin, y al relacionar estas reflexiones con las teorías clásicas, obtuvimos los siguientes resultados parciales: a) la idea occidental de desarrollo se conformó en base a una idea humanista, racionalista y unidimensional del hombre, que estaría asentada sobre la base del mito de la sociedad industrial y el reduccionismo de carácter económico y burocrático, es decir, la creencia de que el crecimiento económico conduciría inevitablemente a todas las formas de desarrollo; b) la idea que elaboró Morin transgrede esta propuesta clásica y ofrece una novedosa forma de pensar el desarrollo como un metaconcepto destinado al autodesarrollo del hombre.Así, como resultado final, podemos esbozar un acercamiento a la noción compleja del desarrollo, que supone la construcción de un futuro inédito en tanto es una aventura de carácter errante e incierto; es un medio y un fin del sistema auto organizador que selecciona lo que debe crecer y lo que debe decrecer; finalmente, comporta avances, ganancias y construcciones tanto como regresiones, pérdidas y destrucciones.El producto fueron dos artículos titulados “Subdesarrollo, desarrollo y crisis”, 1ª y 2ª parte, publicados en la Revista Complejidad números 23 y 24; también presentado en la XII Jornada de Investigación del IDICSO 2014.Facing up to the current development crises and the impossibility to rise up the Millennium Development Goals proposed by the United Nations, the purpose of this project had been explore and describe the theories of development concept and connect them to Edgar Morin’s proposal to rethink this idea from the perspective of complex thought.At the beginning of the research, the study of the term from the classical theories revealed that its conceptual definition is reductionist and unidimensional. In the next step we investigate the thought of Morin, and to relate these reflections with the classical theories, obtained the following partial results: a) The Western idea of development was formed based on a humanist, rationalistand one-dimensional idea of man, which would established on the basis of the myth of industrialsociety and the economic reductionism and bureaucratic, that is, the belief that economic growthwould inevitably lead to all forms of development; b) More in developed the idea that violates thisclassic proposal offers a new way of thinking development metaconcept intended as a self of manand not the mere industrial growth.Thus, through the proposal of the intellectual, we can outline an approach to the complex notionof development, which tends to building an unprecedented futureas it is an adventure of wanderingand uncertain character; it is a means and an end to the self-organizing system which select whatto grow and what should decrease; finally, behaves progress, profit and buildings as well as regressions,loss and destruction.The product was two articles entitled “Underdevelopment, development and crisis,” parts 1and 2, published in the journal Complexity numbers 23 and 24; Also presented at the XII IDICSOResearch Day 2014. The accompanying research continues the theme of research in his Master’sthesis in International Relations

5G Vertical Use Cases and Trials of Transportation

The 5G networks are still being deployed in many countries creating new business opportunities. 5G networks allow us to include new features and deliver new levels of system capacity and efficiency such as higher speed connectivity, ultra low latency connectivity, improved security, distributed networks, virtualizednetworks and so on. They enable us to have new use cases and scenarios such as automated vehicles, smart city, eHealth, and so on. In this paper, 5G vertical use cases and large scale trials of transportation undertaken at the EU 5G-HEART project trial sites across Europe are introduced. Four representative transport use cases are validated in the 5G-HEART project. They are as follows: (1) Platooning that drives a group of vehicles together, (2) Autonomous driving that avoids collision and achieves safer driving and better traffic efficiency, (3) Remote driving support that allows an user or cloud software to control vehicles remotely, and (4) Vehicle data services that provides us with a better vehicle services byinterconnecting various third-party data to autonomous vehicles using5G networks. User requirements and KPIs are analyzed for 5G transportation use cases. The selected results of 5G-HEART transportation vertical trials are presented

Maatutkaprofiilien syvyyskalibrointi CMP-luotauksella esimerkkikohteissa Helsingissä ja Hollolassa

Tässä tutkimuksessa perehdytään CMP-luotauksen teoriaan ja käytäntöön maatutkaluotausten profiililinjojen syvyyskalibroinnissa. CMP-luotaus on Suomessa harvoin käytetty nopeusanalyysimenetelmä ja tutkimuksessa haluttiin selvittää CMP-luotauksen tuomia mahdollisuuksia. Tutkimuskohteet sijaitsevat Etelä-Suomessa, Helsingissä ja Hollolassa. Tutkimuskohteet valikoitiin toisistaan poikkeavan geologian vuoksi. Patolassa metsässä maakerrokset olivat pääosin moreenia ja kalliomaata. Tattarisuon pohjavesialueella kerroksissa vaihtelivat hiekkaiset ja saviset kerrosrakenteet. Hollolan deltamuodostumalla maakerrokset vaihtelivat karkeasta sorasta hiekkaan. Sekä Tattarisuolla että Hollolassa saatiin myös aineistoa pohjavesikerroksesta. Kohteissa tehtiin sekä profiililuotaukset että CMP-luotaukset. Tutkimuksissa hyödynnettiin Malå:n ja GSSI:n maatutkalaitteistoja, joita käyttökokemuksen perusteella vertailtiin myös keskenään. CMP-luotauksella saatuja kerrosnopeuksia verrattiin kohteiden referenssiaineistoihin, keskiarvoiseen 0,1 m/ns:n nopeuteen, taulukkoarvoihin sekä Patolassa hyperbelianalyysin tuottamaan tulokseen. Tulokset olivat rohkaisevia, joskin myös poikkeavia arvoja löytyi. Patolassa haasteena oli moreenin ja rikkonaisen kallionpinnan tunnistaminen profiililuotauksista. Tämä aiheutti hajontaa CMP-luotauksella ja muilla referenssiaineistolla saatujen tulosten välillä. Osa tuloksista oli hyvinkin lähellä referenssiaineistoja, mutta moreeni-kallio-rajapinnan tulkinnan haasteellisuuden vuoksi myös huomattavia poikkeamia saatiin. Tattarisuolla tulkinnan haasteena oli monimutkainen kerrosrakenne ja paikoin profiililuotauslinjoja häiritsevät heijasteet. CMP-luotauksen kerrosnopeudet vastasivat hyvin hiekkaisten kerrosten nopeuksia. Lisäksi CMP-luotauksella voitiin varmistaa luotauslinjalla 2 oleva pohjavesikerros ja että luotauslinjalla 1 pohjavettä ei CMP-luotauksella saatujen nopeuksien perusteella ollut. Hollolassa CMP-luotausaineisto kärsi päällisin puolin huomattavasti häiriösignaaleista. Aineiston prosessoinnin jälkeen saadut kerrosnopeudet vastasivat kuitenkin erinomaisesti referenssiaineistojen kerrossyvyyksiä. Kahden maatutkalaitteiston ja useamman antennikonfiguraation hyödyntäminen profiililuotauslinjoissa mahdollistivat hyvän luotausresoluution niin matalammilla kuin paksummilla kerrospaksuuksilla. Malå:n ja GSSI:n luotauslaitteistot toimivat pääosin hyvin eikä kumpikaan laitteisto ollut selkeästi toista parempi. Tässä tutkimuksessa saadun kokemuksen perusteella CMP-luotauksella voidaan saada merkittävää hyötyä maatutkalinjojen tulkintaan. Kun CMP-luotauksen heikkoudet osataan tunnistaa ja aineiston tulkitsija omaa riittävän hyvän kokemuksen, voidaan CMP-luotauksen avulla tehdyillä syvyyskalibroinneilla saada luotettavia tuloksia tutkimusalueen kerrospaksuuksista

The Effects of Pedometers on Body Weight and Metabolic Factors in Patients with Prediabetes

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Arvon yhteisluonti kiinteistökehityshankkeen tarveselvitysvaiheessa: Mahdollisuudet ja edellytykset

Tutkimuksessa selvitettiin, mitä arvo ja arvon yhteisluonti ovat kiinteistökehityshankkeessa. Aihetta tutkittiin yrityksen ja asiakkaan välisellä rajapinnalla, ja yhteiskunnallinen näkökulma rajattiin pois tutkimuksen aihepiiristä. Tavoitteena oli selvittää, miten arvon yhteisluontia voidaan hyödyntää tarveselvitysvaiheessa ja mitä sen onnistuminen edellyttää. Lisäksi perehdyttiin siihen, miten osapuolet hyötyvät arvon yhteisluonnista tarveselvitysvaiheessa. Tutkimuksessa havaittiin, että yrityksen ja asiakkaan välinen yhteistyö tarveselvitysvaiheessa parantaa hankkeen onnistumismahdollisuuksia. Sen lisäksi yritys saa esimerkiksi uutta tietoa markkinasta ja asiakas saa asiantuntevaa näkemystä päätöksentekonsa tueksi. Toisaalta aikaisessa vaiheessa alkava yhteistyö myös mahdollistaa osapuolten välisen suhteen syvenemisen, mikä parantaa yhteistyön edellytyksiä myös hankkeen myöhemmissä vaiheissa

Repensar el desarrollo. Un aporte para las políticas públicas de nueva generación desde la perspectiva del Pensamiento Complejo

Las experiencias de las crisis y el fracaso de las políticas de Desarrollo muestran la actual necesidad de elaborar una nueva propuesta que tenga en cuenta la complejidad de las sociedades. La revisión del término Desarrollo, en esta etapa de la investigación, revela que su definición conceptual es reduccionista, unidimensional e inconsistente.Los estudios realizados sobre la cuestión fueron abordados inicialmente por las Ciencias Económicas en la década de 1930. Aquellas primeras teorías concebían al Desarrollo como una fase evolutiva lineal de los Estados hacia la modernización. Luego, frente a la diferencia entre los países desarrollados y quienes no podían alcanzarlo, a partir de 1960, la definición se vinculó a los movimientos sociales y el ordenamiento internacional. De esta manera, la intervención estatal asumió un rol importante dentro del pensamiento científico para el Desarrollo nacional.Al analizar estos postulados se arribó al siguiente resultado parcial: numerosos autores consideransólo las variables económicas, tales como el Producto Bruto Interno o el nivel de Inversión, de las Naciones y olvidan cuestiones esenciales como la identidad, solidaridad y cultura de las mismas al pensar en el Desarrollo.En la próxima etapa indagaremos las líneas principales del pensamiento de Edgar Morin. Dentrode este marco, el objetivo de la presente investigación es profundizar en aquellos aspectos de la obra de Edgar Morin relacionados con su propuesta de repensar la idea de Desarrollo, desde el enfoque del Pensamiento Complejo. En consecuencia, a partir de estos resultados avanzar en el análisis de la condiciones de posibilidad de una idea de Desarrollo alternativa desde una visión compleja de la participación social y a la medida de los riesgos y la escala de los desafíos planetarios con la finalidad de enriquecer los diseños de las políticas públicas.Para alcanzar este objetivo, la metodología empleada es la lectura y análisis de textos como también entrevistas con expertos. Hasta el momento se avanzó con la selección de la bibliografía y gran parte de su lectura. Además, se está trabajando en la elaboración de un artículo titulado “Subdesarrollo, desarrollo y crisis” para ser presentado al comité evaluador de la Revista Complejidad