The Role of Macrophage Migration Inhibitory Factor (MIF) in the Pathogenesis of murine Chronic Lymphocytic Leukemia (CLL) - Analysis based on the TCL1 mouse model

Besides the genetic aberrations the interaction between the tumor cell and its microenvironment plays an important role in the leukemogenesis of chronic lymphocytic leukemia (CLL). Stimulation via extracellular factors is important for the survival of the CLL cell, since without this the CLL cell is driven into apoptosis when taken out of its micromilieu. Preliminary analyses showed that Macrophage Migration Inhibitory Factor (MIF), a chemokine with pro-inflammatory properties, is overexpressed in CLL. As MIF exerts regulatory control on cellular growth, -differentiation and apoptosis, this work tests the hypothesis whether MIF has a contribution in the pathomechanism of CLL development. To this end, we used the Eu-T-cell leukemia 1 (TCL1) mouse model (Bichi et al., 2002) in which B-cell specific overexpression of TCL1 leads to accumulation and organ infiltration by CD5+IgM+ mature B cells. The transgenic mice develop a CLL-like disease, which is manifested by leukemia, lymphadenopathy, hepatosplenomegaly, bone marrow infiltration as well as premature death after 8 to 15 months. The impact of MIF is tested in vivo by breeding the TCL1+/+ mouse to the MIF-/- mouse (Fingerle-Rowson et al., 2003). In this work, TCL1+/wt MIF+/+ and TCL1+/wt MIF-/- mice were compared with each other regarding the rate of leukemia development, tumor burden, hematopathological alterations, overall survival, cytogenetic changes as well as proliferative capacity and apoptosis. The known MIF cell surface receptors CD74/CD44 and CXCR2 are also expressed on the murine B cells. TCL1+/wt MIF+/+ mice show already in the pre-leukemic phase a higher number of CD5+IgM+ cells, and the development of a peripheral leukemia starts about three months earlier in TCL1+/wt MIF+/+ mice compared to TCL1+/wt MF-/- animals (p = 0.02). At the age of 12 months, organs like liver and spleen are infiltrated to a higher degree by small, mature and malignant B lymphocytes in the TCL1+/wt MIF+/+ than in the MIF-deficient mice. One reason for this could be the increased accumulation of CD68+ macrophages in the leukemia infiltrated spleens and bone marrow of the MIF wildtype mice (p < 0.0001). "nurse-like" cells (NLCs) act to protect the leukemic cells from apoptosis. This fits the observation that the rate of spontaneous apoptosis is elevated in the MIF-deficient leukemia infiltrated spleens in vivo, and that a trend towards higher rates of apoptosis can be seen in splenocytes of the TCL1+/wt MIF-/- mice ex vivo. These MIF-dependent effects even affect overall survival since in the MIF-/- mice, the overall median survival is prolonged by 80 days (TCL1+/wt MIF+/+ 380 days vs. TCL1+/wt MIF-/- 460 days, p = 0.04). An analysis of genomic aberrations by spectral karyotyping (SKY) of metaphases from leukemic splenocytes shows distinct genetic damages like trisomy, tetraploidy, translocations and deletions in both genotypes. An overexpression of the tumor suppressor p53 presumably due to an inactivating gene mutation was found in TCL1+/wt MIF+/+ mice at a higher frequency than in TCL1+/wt MIF-/- mice. Our analysis of the Eu-TCL1 mouse model shows that this is a valuable model for the validation of potential target molecules in the pathogenesis of CLL. We are able to demonstrate that MIF acts as a tumor promoter primarily by influencing the micromilieu in the early as well as in the late phase of leukemkia development. Further analyses are on the way which focus on the role of MIF in the function of the nurse-like cells in CLL and other tumor entities and which test the interaction of MIF and Akt

Games in urban planning – a comparative study

The purpose of this paper is to show and discuss the results of a comparative study of games for urban planning. We provide an overview of the selected games available on the market. Because of the variety of offered games, we decided to group them in categories distinguishing among non-digital/traditional, digital and pervasive. The group of non-digital/traditional games includes some well-known, but also some recently developed games: Broken Cities, CLUG, Ginkgopolis, Masterplan, Neue Heimat, Pop-up Pest, Stadtspieler and The Harbour Game. In the category of digital games we considered: Anno, City One, Civilisation, Community PlanIt, Green Sight City, Minecraft/Block by block, Plasticity, Securing Sydney´s Urban Planning, SimCity and Surfing Global Change. The category of pervasive games included: Mogi, PacManhattan and REXplorer. We compared them according to the predefined criteria including participation, interaction, realistic visualization, learning effect and knowledge transfer. One of the positive aspects comprehended that there are some games used for integrating people in urban planning processes. The critical aspects included that there are many games focusing on urban planning issues, but only little were used for integrating people in active urban planning processes. We conclude our paper with a critical discussion of the results of our study and a reflection about further research on games for urban planning

Investigating sex differences in fingerprint minutiae density of the core region utilizing the minutiae: ridge-length ratio

In an attempt to develop a statistical model for fingerprint analysis, the Minutiae:Ridge-Length Ratio (MRLR) was used to examine differences between the different sexes, hands, fingers, ridge patterns, and racial groups. In regards to sex, statistically significant MRLR differences (α=0.05) were found between males and females when analyzing both individual prints (p<0.001) and entire ten-print cards (p=0.025). Further examination of the data revealed more specific differences within separate subcategories. The MRLR was significantly different (p<0.001) between males and females with both right and left hands. With respect to sex and individual finger differences, the thumb (p<0.001), index finger (p<0.001), and middle finger (p=0.015) were statistically significant. For ridge pattern, whorls (p<0.001) and ulnar loops (p<0.001) had significant differences between the sexes. Racially, males and females had statistically significant differences from one another within the Caucasian (p<0.001) and African American (p<0.001) racial groups. Further investigation of variables independent of sex highlighted other statistically significant MRLR relationships. Within the fingers, the thumb was found to be significantly different than the middle (p<0.001), ring (p<0.001), and little fingers (p<0.001); the index finger also differed from the little finger significantly (p=0.001). Comparison of level one detail demonstrated the whorl pattern was statistically different than the arch (p<0.001), radial loop (p=0.002), and ulnar loop patterns (p<0.001). No statistically significant difference was found between the right and left hands of the sample population (p=0.160). The racial subdivisions produced more complex relationships. Caucasians had statistically significant MRLR differences to African Americans (p=0.036), Hispanics (p=0.003), and Asians (p=0.046). African Americans had additional significant differences from Hispanics (p<0.001), Asians (p<0.001), and Native Americans (p=0.036). Finally, Native Americans and Hispanics shared a significant difference as well (p<0.036). However, due to the uncertainty of racial demographic data, the extrapolation of these findings to the general population may not be appropriate for forensic investigation purposes

Associations of the FKBP5 gene C/T polymorphism and stressful life experiences with symptoms of attention-deficit/hyperactivity disorder and aggressiveness in ages 9, 15 and 18

Aktiivsus- ja tähelepanuhäire (ATH) sümptomaatika ja agressiivsuse geneetiliste ning keskkondlike aluste paremaks mõistmiseks on käesolevas töös uuritud ATH sümptomite ja agressiivsuse seoseid geeni FKBP5 C/T polümorfismi (rs1360780) ja stressikogemustega. Kasutatud on Eesti laste isiksuse ja käitumise longituuduuringu noorema kohordi andmeid vanustes 9 (n=583), 15 (n=483) ja 18 (n=457) eluaastat. ATH sümptomid on mõõdetud af Klintebergi skaalal ning stressikogemused enesekohaste raportitega. Tulemustest selgus, et koolikiusamise all kannatanud T-alleeliga 9-aastastel tüdrukutel ilmnes rohkem ATH sümptomeid, eelkõige keskendumisraskusi, võrreldes mitte-kiusatud ja CC genotüübiga tüdrukutega. Hilisemas vanuses eelmainitud seos enam ei ilmnenud. Poistel ei ilmnenud sarnast seost üheski uuritud vanuseastmetes. Tulemustest järeldub, et FKBP5 C/T polümorfismi seos ATH sümptomitega sõltub stressitasemest, soost ja vanusest

Proposta de um Sistema de Desenvolvimento de Pesquisa de Marketing (SDPM) para a metodologia Quality Function Deployment (QFD) no processo de informação

Orientador : Cleverson Renan da CunhaProjeto Técnico (especialização) - Universidade Federal do Paraná, Setor de Ciências Sociais Aplicadas. Curso de Especialização em Marketing EmpresarialInclui referênciasResumo : Este trabalho de pesquisa apresenta uma proposta de um Sistema de Desenvolvimento de Pesquisa de Marketing (SDPM) para alimentar a metodologia Quality Functin Deployment (QFD) na matriz da demanda da qualidade. Neste contexto realizou-se um estudo bibliográfico das ferramentas de pesquisa de marketing e comunicação em marketing, caracterizando predominantemente a melhor ferramenta de pesquisa para ser utilizada no processo de desenvolvimento da captação de informações vindas de públicos de interesse da organização. Com o SDPM as informações dos públicos passarão por um processo de desenvolvimento em um banco de dados, onde serão transformadas em desejos e necessidades dos consumidores para serem inseridas na matriz da demanda da qualidade na metodologia QFD. O objetivo do Sistema de Desenvolvimento de Pesquisa de Marketing é estruturar melhor o processo de pesquisa na captação da voz do cliente, para obter sucesso no desenvolvimento de coleta de pesquisa, para que estas informações sejam inseridas da matriz da demanda da qualidade com eficácia. É nesta perspectiva que se desenha a arquitetura de todo este trabalho, evoluindo no processo de alimentação da demanda da qualidade na matriz do QFD, com um ganho no processo de desenvolvimento de produtos e serviços, oferecendo as organizações uma metodologia que de suporte a casa da qualidade, trazendo mais rapidez no processo das informações vindas da voz do cliente

Optical investigations of CDOM-rich coastal waters in Pärnu Bay

Pärnu Bay in the Eastern Baltic Sea was chosen for studying the spatial-temporal variability of water parameters as an optically complex and semi-enclosed coastal area. The water properties of Pärnu Bay are influenced by the town of Pärnu with its 70 000 inhabitants and by the high inflow from the Pärnu River. The in situ database was collected during the ice-free period of 2006–2007 (11 sampling stations, 10 series of field trips). According to the results, the main factor influencing the light attenuation in the water was coloured dissolved organic matter (CDOM) which overshadows the relationships between the radiation characteristics and organic/inorganic particles. In April and May, when the freshwater discharge of the Pärnu River was highest, the values of aCDOM(380) were between 4.6 and 31.8 m–1, while in September they varied only within 2.52–10.2 m–1. The concentrations of chlorophyll a (including its metabolite phaeophytin a) generally ranged from 4 to 12 mg m–3 but during algal blooms they rapidly increased to 31.8 mg m–3. The temporal and spatial irregularity of suspended matter concentrations was caused by the loading of unpacked peat at the Pärnu River mouth as well as by undulation and ship traffic in Pärnu Bay. MODIS level 1 data with 250 m resolution were used for illustrative comparison of spatial and temporal variations in the water properties in Pärnu Bay and the Gulf of Riga. An attempt to perform the quantitative analysis with the purpose of estimating the concentrations of different optically significant substances separately gave statistically incorrect results

In situ determination of the remote sensing reflectance: an inter-comparison

Inter-comparison of data products from simultaneous measurements performed with independent systems and methods is a viable approach to assess the consistency of data and additionally to investigate uncertainties. Within such a context the inter-comparison called Assessment of In Situ Radiometric Capabilities for Coastal Water Remote Sensing Applications (ARC), was carried out at the Acqua Alta Oceanographic Tower in the northern Adriatic Sea to explore the accuracy of in situ data products from various in- and above-water optical systems and methods. Measurements were performed under almost ideal conditions including: a stable deployment platform, clear sky, relatively low sun zenith angles and moderately low sea state. Additionally, all optical sensors involved in the experiment were inter-calibrated through a post-field absolute radiometric calibration performed with the same standards and methods. Inter-compared data products include: spectral water-leaving radiance Lw,above-water downward irradiance Ed(0+) and remote sensing reflectance Rrs. Data products from the various measurement systems/methods were directly compared to those from a single reference system/method. Results for Rrs indicate spectrally averaged values of relative differences comprised between -1 and +6%, while spectrally averaged absolute values of relative differences vary from approximately 6% for the above-water systems/methods to 9% for buoy-based systems/methods. The good agreement between Rrs spectral relative differences and estimates of combined uncertainties of the inter-compared systems/methods is noteworthy.JRC.H.1-Water Resource