Early endostatin treatment inhibits metastatic seeding of murine colorectal cancer cells in the liver and their adhesion to endothelial cells

Endostatin, a carboxy-terminal fragment of collagen XVIII, potently inhibits angiogenesis and tumour growth, presumably through induction of apoptosis in endothelial cells and/or inhibition of their migration. Here we have tested how the timing of recombinant human endostatin (rh-E) administration affects its antitumour activity in a liver metastasis model of mouse C26 colorectal carcinoma cells. The effects of rh-E treatment on hepatic tumour load and on early tumour cell seeding were evaluated. Recombinant human endostatin was most effective in reducing intrahepatic tumour growth when administered prior to tumour cell inoculation. Analysis of early tumour cell seeding by using [125I]iododeoxyuridine-labelled C26 cells or by in vivo microscopy showed that rh-E reduced tumour cell seeding in the liver sinusoids. Recombinant human endostatin did not inhibit tumour growth when administered later than 4 days after tumour injection. Pretreatment of human umbilical vein endothelial cells with rh-E in vitro reduced C26 tumour cell adhesion under flow conditions two-fold as assessed by video microscopy and multiphoton laser scanning microscopy. Our results show that rh-E, in addition to antiangiogenic effects, reduces tumour cell adhesion in the liver sinusoids during the very early phases of metastasis formation. These data point towards a previously unknown mode of action of endostatin, that is, its ability to interfere with tumour cell seeding. Such insights may be helpful in the design of trials to improve (surgical) treatment of colorectal carcinoma and liver metastases

Learning design tools

The chapter provides the first survey and description of IMS LD tooling, and also establishes a classificatory framework within which the tools discussed are situated. The chapter builds on an analysis of work carried out by the authors in the European Framework 6 UNFOLD project to coordinate the development of IMS LD tooling, as well as practical experience in the development of IMS LD compliant applications. It identifies a number of key aspects of IMS LD tooling which have been taken up in current implemenation work, in particular the provision of a rich set of interoperable services

Hybridirakennus Leppävaaraan

The thesis is a design for a new hybrid building in Leppävaara, Espoo, Finland. The work tells only a brief explanation and history of hybrid buildings, the main focus being on the design, its background and explanation. Hybrid building is a fundamentally mixed-use building in a dense urban context. Historically the origin of hybrids is thought to be the skyscrapers of Manhattan from the beginning decades of the 1900's. Mixing different uses was then largely driven by economical speculation. Nowadays the mixing is also seen as a qualitative factor, as a possibility to create a building which is active around the clock, thus being able to enliven its surroundings. Also the starting point of my design was a simple goal of making a design which could enhance its near surroundings of a slowly deteriorating old suburban centre. The ground floor is largely public, encompassing a two-part-market hall, restaurants and small shops; youth centre entrance lobby, lobby and collective spaces of offices and the entrances of the apartments. The apartments and offices are above, as is the youth centre, which also has a basement theatre. The basement consists also of parking and maintenance spaces. The roofs of the building are all accessible by the tenants of the block. With their planted balustrades, access bridges and moving people, they send a message of living to the streets below. An essential feature of the block is the new diagonal pedestrian access which cuts the ground floor in two. It is a message of urban symbiosis, of a mutually benefiting situation between the building and the city. The mixing of functions is intended to create more of Yes in My Backyard! -attitude among people as they realize how opening up your territory to the city can benefit you.Diplomityö on hybridirakennussuunnitelma Espoon Leppävaaraan. Työssä selostetaan hybridirakentamisen käsitettä ja historiaa lyhyesti, pääpainon ollessa suunnitelmalla, sen taustoittamisella ja selostuksella. Hybridirakennuksella tarkoitetaan tiiviin urbaanin ympäristön rakennusta, jossa lähtökohtaisesti sekoitetaan eri toimintoja. Historiallisesti hybridien alkuna pidetään Manhattanin pilvenpiirtäjiä 1900-luvun alussa, jolloin toimintojen sekoittaminen oli etupäässä taloudellisen spekuloinnin ajamaa. Nykyään toimintojen sekoittaminen nähdään tämän lisäksi laadullisena tekijänä, mahdollisuutena luoda rakennus, jossa on elämää vuorokauden ympäri ja joka siten voi toimia ympäristönsä elävöittäjänä. Myös suunnitelmani lähtökohtana oli yksinkertainen tavoite luoda eloa rapistuvaan lähiökeskukseen. Rakennuksen pohjakerros on pääosin julkinen, sisältäen kaksiosaisen kauppahallin, erinäisiä pieniä ravintoloita tai kahviloita, nuorisokeskuksen sisäänkäyntiaulan, toimistojen aulan ja yhteistilat, sekä asuntojen porrasaulat. Yläkerroksissa on toimistotilaa ja asuntoja. Nuorisokeskus sijaitsee sekä yläkerroksissa että esiintymissalin osalta kellarissa. Kellarissa on myös paikoitus ja huoltotoimintoja. Kaikki katot ovat asukkaiden käytössä olevia terassipihoja. Viheristutuksineen, portaineen, ihmisineen niiltä välittyy alas katutilaan asumisen viesti. Rakennuksen olennainen osa on sen halkaiseva uusi diagonaalinen kevyen liikenteen reitti. Tämä viestii rakennuksen ja kaupungin välisestä symbioottisesta suhteesta: kumpikin tarvitsee toista. Toimintojen sekoittamisella pyrin edesauttamaan Yes In My Backyard! -asenteen leviämistä ihmisten nähdessä, kuinka oman reviirin avaaminen hyödyttää heitä itseään

Annales

Crucial in any learning process are the activities that learners undertake: reading, thinking, discussing, exploring, problem solving, etc. When learners are passive you cannot expect them to learn much. The primary role of any instructional agent, whether it is a teacher, the learners themselves or a computer, is to stimulate the performance of learning activities that will gradually result in the attainment of the learning objectives. The instructional agent defines the tasks, provides the contexts and resources to perform the tasks, supports the learner during task performance and provides feedback about the results. The learning activities that are needed to obtain some learning objectives are in most cases carefully sequenced according to some pedagogical principles. This sequence of learning activities that learners undertake to attain some learning objectives, including the resources and support mechanisms required to help learners to complete these activities, is called a learning design