Radanohjaimen suunnittelu leveille päällystyskoneille

Radanohjaimia käytetään radan poikkisuuntaiseen paikoitukseen sekä oskillointiin ja ne ovat osa paperinvalmistuslinjojen radanhallintajärjestelmiä. Oikein suunnitellulla ja sijoitetulla radanohjaimella voidaan estää haitallisten ratasiirtymien esiintyminen, pienentää hylkymateriaalin määrää sekä parantaa rullauksen laatua. Ohjausperiaatteet sekä niihin liittyvä laitetekniikka on tunnettu jo vuosikymmenten ajan, joskin todelliset radanohjaustarpeet ja -laitteet ovat tähän asti rajoittuneet paino-, tekstiili- ja metalliteollisuudessa käytössä oleville kapeille radoille. Tämän työn tavoitteena oli selvittää 5… 12 metriä leveälle, modernissa päällystyskoneessa kulkevalle paperiradalle soveltuvat ohjausperiaatteet sekä muodostaa radan todennäköisimpiin vauriomuotoihin perustuvat suunnittelukriteerit kahdelle erityyppiselle ohjainkonstruktiolle. Yksitelainen, taivuttava radanohjain soveltuu kohteisiin, joissa ohjainta edeltää suhteellisen pitkä vapaa ratavienti. Kaksitelainen, taittava radanohjain on puolestaan sijoitettavissa huomattavasti lyhyempään ratavientiin. Radanohjauksen teoria pohjautuu pitävän telan ja radan väliseen kohtisuoran tulokulman periaatteeseen, jonka perusteella mikä tahansa yhdensuuntaisuuspoikkeama kahden telan välillä johtaa radan poikkisuuntaiseen siirtymään. Tämän periaatteen pohjalta voidaan dynaamista ohjaustilannetta approksimoida staattisin menetelmin sekä muodostaa kireysmuutoksiin ja aaltoiluun perustuvat geometrian mitoitusperiaatteet ohjaimen ympäristön ratavienneille. Nopean ohjauksen toteutus edellyttää radanohjaimen liikkeen olevan nivelen ympäri tapahtuvaa yhdistettyä translaatio- ja rotaatioliikettä. Ohjainkonstruktiot suunnitellaan siten, että teorian mukaiset optimaaliset liikeradat toteutuvat vaaditulla ohjausnopeudella. Suunnittelua ohjaavat tuotteille asetetut lujuus- ja värähtelykriteerit sekä aiheeseen liittyvät koneturvallisuusstandardit. Konstruointi suoritetaan järjestelmällisen tuotesuunnitteluprosessin vaiheiden ja menetelmien mukaisesti.

Study of mesoscopic tunnel junctions between two normal metals

The main purpose of this work was to study different kinds of metal-based tunnel junctions at low temperatures. The problem which had to be solved was creating a junction with appropriate properties at these temperatures. The materials for junctions were found experimentally. The goal was to find an alloy material that can provide a high quality tunnel junction, which remains in the normal conductive state at low temperatures without applying magnetic field. The fabrication technology of such a device, based on an alloy of aluminium and manganese, is described in detail. In this thesis theoretical properties of tunnel junctions are considered and results of experiments with tunnel junctions are described and quantitative properties of the junctions are analyzed based on the experimental data.

The spindle assembly checkpoint as a drug target - Novel small-molecule inhibitors of Aurora kinases

Cell division (mitosis) is a fundamental process in the life cycle of a cell. Equal distribution of chromosomes between the daughter cells is essential for the viability and well-being of an organism: loss of fidelity of cell division is a contributing factor in human cancer and also gives rise to miscarriages and genetic birth defects. For maintaining the proper chromosome number, a cell must carefully monitor cell division in order to detect and correct mistakes before they are translated into chromosomal imbalance. For this purpose an evolutionarily conserved mechanism termed the spindle assembly checkpoint (SAC) has evolved. The SAC comprises a complex network of proteins that relay and amplify mitosis-regulating signals created by assemblages called kinetochores (KTs). Importantly, minor defects in SAC signaling can cause loss or gain of individual chromosomes (aneuploidy) which promotes tumorigenesis while complete failure of SAC results in cell death. The latter event has raised interest in discovery of low molecular weight (LMW) compounds targeting the SAC that could be developed into new anti-cancer therapeutics. In this study, we performed a cell-based, phenotypic high-throughput screen (HTS) to identify novel LMW compounds that inhibit SAC function and result in loss of cancer cell viability. Altogether, we screened 65 000 compounds and identified eight that forced the cells prematurely out of mitosis. The flavonoids fisetin and eupatorin, as well as the synthetic compounds termed SACi2 and SACi4, were characterized in more detail utilizing versatile cell-based and biochemical assays. To identify the molecular targets of these SAC-suppressing compounds, we investigated the conditions in which SAC activity became abrogated. Eupatorin, SACi2 and SACi4 preferentially abolished the tensionsensitive arm of the SAC, whereas fisetin lowered also the SAC activity evoked by lack of attachments between microtubules (MTs) and KTs. Consistent with the abrogation of SAC in response to low tension, our data indicate that all four compounds inhibited the activity of Aurora B kinase. This essential mitotic protein is required for correction of erratic MT-KT attachments, normal SAC signaling and execution of cytokinesis. Furthermore, eupatorin, SACi2 and SACi4 also inhibited Aurora A kinase that controls the centrosome maturation and separation and formation of the mitotic spindle apparatus. In line with the established profound mitotic roles of Aurora kinases, these small compounds perturbed SAC function, caused spindle abnormalities, such as multi- and monopolarity and fragmentation of centrosomes, and resulted in polyploidy due to defects in cytokinesis. Moreover, the compounds dramatically reduced viability of cancer cells. Taken together, using a cell-based HTS we were able to identify new LMW compounds targeting the SAC. We demonstrated for the first time a novel function for flavonoids as cellular inhibitors of Aurora kinases. Collectively, our data support the concept that loss of mitotic fidelity due to a non-functional SAC can reduce the viability of cancer cells, a phenomenon that may possess therapeutic value and fuel development of new anti-cancer drugs.

Normal Mannesmann-Mulag kardanvagn

kuv., 24 x 16 cm

M.A.N. normal 2-2 1/2 tons lastvagn

kuv., 23 x 16 cm

Normal Mannesmann-Mulag kedjevagn

kuv., 23 x 16 cm

Normal Mannesmann-Mulag 5-tons lastvagn

kuv., 23 x 16 cm

Spin Polarization and Normal Reflection at Nanoscale Point Contacts

This thesis presents point-contact measurements between superconductors (Nb, Ta, Sn,Al, Zn) and ferromagnets (Co, Fe, Ni) as well as non-magnetic metals (Ag, Au, Cu, Pt).The point contacts were fabricated using the shear method. The differential resistanceof the contacts was measured either in liquid He at 4.2 K or in vacuum in a dilutionrefrigerator at varying temperature down to 0.1 K. The contact properties were investigatedas function of size and temperature. The measured Andreev-reflection spectrawere analysed in the framework of the BTK model – a three parameter model that describescurrent transport across a superconductor - normal conductor interface. Theoriginal BTK model was modified to include the effects of spin polarization or finitelifetime of the Cooper pairs. Our polarization values for the ferromagnets at 4.2 K agree with the literature data, but the analysis was ambiguous because the experimental spectra both with ferromagnets and non-magnets could be described equally well either with spin polarization or finite lifetime effects in the BTK model. With the polarization model the Z parametervaries from almost 0 to 0.8 while the lifetime model produces Z values close to 0.5. Measurements at lower temperatures partly lift this ambiguity because the magnitude of thermal broadening is small enough to separate lifetime broadening from the polarization. The reduced magnitude of the superconducting anomalies for Zn-Fe contacts required an additional modification of the BTK model which was implemented as a scaling factor. Adding this parameter led to reduced polarization values. However, reliable data is difficult to obtain because different parameter sets produce almost identical spectra.

Formin proteins in normal tissues and cancer

The actin cytoskeleton is a dynamic structure that determines cell shape. Actin turnover is mandatory for migration in normal and malignant cells. In epithelial cancers invasion is frequently accompanied by epithelial to mesenchymal transition (EMT). In EMT, cancer cells acquire a migratory phenotype through transcriptional reprogramming. EMT requires substantial re-organization of actin. During the past decade, new actin regulating proteins have been discovered. Among these are members of the formin family. To study formin expression in tissues and cells, antibodies for detection of formin proteins FMNL1 (Formin-like protein 1), FMNL2 (Formin-like protein 2) and FHOD1 (Formin homology 2 domain containing protein 1) were used. The expression of formins was characterized in normal tissues and selected cancers using immunohistochemistry. The functional roles of formins were studied in cancer cell lines. We found that FMNL2 is widely expressed. It is a filopodial component in cultured melanoma cells. In clinical melanoma, FMNL2 expression has prognostic significance. FHOD1 is a formin expressed in mesenchymal cell types. FHOD1 expression is increased in oral squamous cell carcinoma (SCC) EMT. Importantly, FHOD1 participates in invasion of cultured oral SCC cells. FMNL1 expression is low in normal epithelia, but high in leukocytes and smooth muscle cells. Expression of FMNL1 can be found in carcinoma; we detected FMNL1 expressing cells in basal type of breast cancer. Our results indicate that formins are differentially expressed in normal tissues and that their expression may shift in cancer. Functionally FMNL2 and FHOD1 participate in processes related to cancer progression. Studying formins is increasingly important since they are potential drug targets.