MicroRNA-375 plays a dual role in prostate carcinogenesis

Background: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. Results: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, aswellaswithregionallymph nodesmetastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. Conclusions: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.

An integrated model for simulation of construction phasing of arch concrete dams

Dissertação de mestrado integrado em Civil Engineering

Superhydrophobic surfaces as a tool for the fabrication of hierarchical spherical polymeric carriers

Hierarchical polymeric carriers with high encapsulation efficiencies are fabricated via a biocompatible strategy developed using superhydrophobic (SH) surfaces. The carries are obtained by the incorporation of cell/BSA-loaded dextran-methacrylate (DEXT-MA) microparticles into alginate (ALG) macroscopic beads. Engineered devices like these are expected to boost the development of innovative and customizable systems for biomedical and biotechnological purposes.

Role of sirtuin 3 on mitochondrial dynamics in Huntington's disease striatal cells

Dissertação de mestrado em Genética Molecular

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Diagnóstico precoce do câncer de mama e colo uterino em mulheres do município de Guarapuava, PR, Brasil

O objetivo desta pesquisa é identificar a freqüência com que é realizado o diagnóstico precoce do câncer de mama e de colo uterino no município de Guarapuava, Paraná. Realizou-se estudo transversal de base populacional, incluindo 885 mulheres com idade mínima de 18 anos, no período de outubro a dezembro de 2006. Considerou-se nível de confiança de 95% e margem de erro de 3% para cálculo amostral. Utilizou-se o software Statistica versão 7.1 para a análise dos dados, considerando nível de significância de 5%. O auto-exame das mamas foi realizado por 63% das entrevistadas e o exame clínico em 49%. A mamografia foi realizada por menos de um quarto da amostra. A prevenção do câncer de colo uterino foi praticada pela maioria das mulheres (80%). Conclui-se que as mulheres da amostra estudada realizam exames preventivos de câncer de mama com menos freqüência, se comparado ao exame preventivo de colo de útero.

Maintaining dendritic cell viability in culture.

When mouse dendritic cells (DCs) are isolated from tissues, purified and placed in a nutritive culture they die more rapidly than would be expected from their normal turnover in vivo. This can distort culture assays of DC function. We therefore tested several approaches to prolonging DC survival in culture. Of several cytokines tested granulocyte-macrophage colony stimulating factor was most effective at preserving the viability of conventional DCs (cDCs) but was ineffective for plasmacytoid DCs (pDCs). Surprisingly, Fms-like tyrosine kinase 3 ligand, crucial for DC development, produced only a marginal improvement in DC survival in culture, and interleukin-3, reported to prevent apoptosis of human pDCs, produced only a minor improvement in survival of mouse DCs. Genetic manipulation of cell death pathways was also tested, to avoid activation effects exerted by cytokine signalling. The isolation of DCs from mice overexpressing Bcl-2 was especially effective in maintaining pDC viability but gave a lesser improvement in cDC viability. DCs isolated from Bim(-/-)Noxa(-/-) mice also showed improved culture survival, but in this case with pDCs showing the least improvement.

BAFF, APRIL and their receptors: structure, function and signaling.

BAFF, APRIL and their receptors play important immunological roles, especially in the B cell arm of the immune system. A number of splice isoforms have been described for both ligands and receptors in this subfamily, some of which are conserved between mouse and human, while others are species-specific. Structural and mutational analyses have revealed key determinants of receptor-ligand specificity. BAFF-R has a strong selectivity for BAFF; BCMA has a higher affinity for APRIL than for BAFF, while TACI binds both ligands equally well. The molecular signaling events downstream of BAFF-R, BCMA and TACI are still incompletely characterized. Survival appears to be mediated by upregulation of Bcl-2 family members through NF-kappaB activation, degradation of the pro-apototic Bim protein, and control of subcellular localization of PCKdelta. Very little is known about other signaling events associated with receptor engagement by BAFF and APRIL that lead for example to B cell activation or to CD40L-independent Ig switch.

Mouse hepatic oval cells require Met-dependent PI3K to impair TGF-β-Induced oxidative stress and apoptosis.

We have previously shown that oval cells harboring a genetically inactivated Met tyrosine kinase (Met−/− oval cells) are more sensitive to TGF-β-induced apoptosis than cells expressing a functional Met (Metflx/flx), demonstrating that the HGF/Met axis plays a pivotal role in oval cell survival. Here, we have examined the mechanism behind this effect and have found that TGF-β induced a mitochondria-dependent apoptotic cell death in Metflx/flx and Met−/− oval cells, associated with a marked increase in levels of the BH3-only proteins Bim and Bmf. Bmf plays a key role during TGF-β-mediated apoptosis since knocking down of BMF significantly diminished the apoptotic response in Met-/- oval cells. TGF-β also induced oxidative stress accompanied by NADPH oxidase 4 (Nox4) mRNA up-regulation and decreased protein levels of antioxidant enzymes. Antioxidants inhibit both TGF-β-induced caspase 3 activity and Bmf up-regulation, revealing an oxidative stress-dependent Bmf regulation by TGF-β. Notably, oxidative stress-related events were strongly amplified in Met−/− oval cells, emphasizing the critical role of Met in promoting survival. Pharmacological inhibition of PI3K did impair HGF-driven protection from TGF-β-induced apoptosis and increased sensitivity of Metflx/flx oval cells to TGF-ß by enhancing oxidative stress, reaching apoptotic indices similar to those obtained in Met−/− oval cells. Interestingly, both PI3K inhibition and/or knockdown itself resulted in caspase-3 activation and loss of viability in Metflx/flx oval cells, whereas no effect was observed in Met−/− oval cells. Altogether, results presented here provide solid evidences that both paracrine and autocrine HGF/Met signaling requires PI3K to promote mouse hepatic oval cell survival against TGF-β-induced oxidative stress and apoptosis.

Tietomallintamisen aiheuttamat muutokset ja hyödyt LVI-suunnitteluprosessissa sekä määrälaskennassa

Tässä diplomityössä tarkastellaan tietomallintamista eng. BIM (Building Information Modeling) LVI-suunnittelun näkökulmasta sekä esitellään tietomallintamisen vaikutuksia ja hyötyjä suunnitteluprosessiin. Tietomallintaminen mahdollistaa esimerkiksi LVI-suunnittelijan tuottaman määräluettelon 3D-mallista, jonka seurauksena eri toimijoiden väliset rajapinnat tulevat luultavasti kokemaan muutoksia. Työssä vertaillaan käsin laskettuja ja 3D-mallista tuotettuja määräluetteloita toisiinsa. Työhön sisällytetään myös urakoitsijoiden haastatteluja, joissa pyritään selvittämään heidän näkemyksiään suunnittelijan tuottamiin määrätietoihin.

Mobiiliavusteisen rakennusprojektin seurantajärjestelmän suunnittelu ja toteutus

In the construction industry, the role of project management and monitoring is emphasized, because the responsibilities have been carefully planned and divided. A concrete element factory manufactures the units based on construction drawings, while a transport company is responsible of transporting the elements to the worksite. At the worksite, an installation team assembles the elements according to plans. Usually, there are several manufacturers and transport companies involved in the construction process and the distances between different parties can be rather long. Therefore, the role of information exchange is critical in order to control, for example, schedules and exceptions. From the viewpoint of project management, the whole process should be controlled and monitored in realtime - in such a way that the managers are able to analyze and report the data afterwards. In this master’s thesis, a mobile-aided construction project monitoring system is designed and implemented. The monitoring system consists of three main components: mobile phone application, server software and an interface application to Tekla Structures BIM-software. Precast construction components, projects and users are identified by using 2D-barcodes that are read with the camera of a mobile phone. An option would be to use RFID tags and readers. After successful identification, the precast component can be tagged with monitoring data, including state acknowledgments and error reports that are sent and saved to the server. Collected data can be viewed through the www-pages of the monitoring system. In addition, the data can be synchronized to the Tekla Structures-software that is running the 3D-model of the whole building. Synchronization maintains and enhances the traceability of monitoring data, as well as, helps to visualize the progression of the project.

Construction Plan Image Service for Mobile Devices

The forthcoming media revolution of exchanging paper documents to digital media in construction engineering requires new tools to be developed. The basis of this bachelor’s thesis was to explore the preliminary possibilities of exporting imagery from a Building Information Modelling –software to a mobile phone on a construction yard. This was done by producing a Web Service which uses the design software’s Application Programming Interface to interact with a structures model in order to produce the requested imagery. While mobile phones were found lacking as client devices, because of limited processing power and small displays, the implementation showed that the Tekla Structures API can be used to automatically produce various types of imagery. Web Services can be used to transfer this data to the client. Before further development the needs of the contractor, benefits for the building master and inspector and the full potential of the BIM-software need to be mapped out with surveys.

LVI-suunnittelun ohjaus IPD-projekteissa

Tässä diplomityössä on tutkittu LVI-suunnittelun ohjaamista ja sen kehittämistä integroiduissa rakennushankkeissa. Tutkimuksen tavoitteena on löytää kehitysehdotuksia LVI-suunnittelun eteenpäinviemiseksi integroiduissa hankkeissa. Tutkimus on tehty hyödyntäen kirjallisia lähteitä ja haastattelemalla integroiduissa projekteissa mukana ollutta henkilöstöä. Perinteisessä rakennushankkeessa eri suunnittelualat toimitetaan useasta yrityksestä. Tässä työssä lähtökohtana on, että merkittävimmät suunnittelualat kuten arkkitehti-, rakenne- ja talotekninensuunnittelu tulevat samalta toimittajalta. Toimituslaajuuteen voidaan lisätä myös mm. rakennuttajakonsultointi- ja kiinteistönkehitysprosessi. Tutkimuksen tuloksena saatiin määritettyä kehitysehdotukset integroituihin hankkeisiin yleiseltä ja LVI-suunnittelun kannalta. Kehitystyössä tulee panostaa tietomallintamiseen, aikataulutukseen ja yhteistyöhön. Tietomallintamista voidaan parantaa koulutuksen, Yleisten tietomallivaatimusten 2012 ja tietomallien tarkasteluohjelmistojen avulla. Aikataulutus paranee, kun suunnittelijat saadaan hankkeeseen mukaan riittävän aikaisessa vaiheessa ja kun suunnittelijat pyrkivät aktiivisesti vaikuttamaan hankkeen tarjouksen- ja sopimuksentekoon. Yhteistyötä voidaan parantaa avoimen ilmapiirin korostamisella ja projektiorganisaation tiivistämisellä.

Potential benefits of building information modeling for building material supplier

This thesis investigated building information modeling (BIM) from a material supplier’s point of view. The objective was to gain understanding about how a building material supplier could benefit from the growing use of BIM in the AEC (architectural, engineering and construction) industry. Increasing amount of inquiries related to BIM from customers and other interest groups had awoken target company’s interest towards BIM. This thesis acts as a pre-study for the target company related to potential of BIM. First of all BIM and its meaning from a material supplier’s point of view was defined based on a literature review. To reveal the potential benefits of BIM for a material supplier a questionnaire survey and in total of 11 interviews were conducted. Based on the literature review and analyzed results it came clear that BIM offers benefits also for material suppliers. Product libraries and material databases for BIM tools can act as an important marketing channel for material suppliers. Material suppliers could also utilize the information from the BIM models to schedule their deliveries more precisely and potentially even to schedule their own production. All this needs deeper cooperation between material suppliers, contractors and other stakeholders in the AEC industry. Based on the results also first steps for the target company to utilize the growing use of BIM were defined.

Customer Need Assessment for Differentiation in Building Information Modeling

Building Information Modeling – BIM is widely spreading in the Architecture, Engineering, and Construction (AEC) industries. Manufacturers of building elements are also starting to provide more and more objects of their products. The ideal availability and distribution for these models is not yet stabilized. Usual goal of a manufacturer is to get their model into design as early as possible. Finding the ways to satisfy customer needs with a superior service would help to achieve this goal. This study aims to seek what case company’s customers want out of the model and what they think is the ideal way to obtain these models and what are the desired functionalities for this service. This master’s thesis uses a modified version of lead user method to gain understanding of what the needs are in a longer term. In this framework also benchmarking of current solutions and their common model functions is done. Empirical data is collected with survey and interviews. As a result this thesis provides understanding that what is the information customer uses when obtaining a model, what kind of model is expected to be achieved and how is should the process optimally function. Based on these results ideal service is pointed out.