A Farewell to Flat Biology. Three-dimensional Cell Culture Models in Cancer Drug Target Identification and Validation

Cells of epithelial origin, e.g. from breast and prostate cancers, effectively differentiate into complex multicellular structures when cultured in three-dimensions (3D) instead of conventional two-dimensional (2D) adherent surfaces. The spectrum of different organotypic morphologies is highly dependent on the culture environment that can be either non-adherent or scaffold-based. When embedded in physiological extracellular matrices (ECMs), such as laminin-rich basement membrane extracts, normal epithelial cells differentiate into acinar spheroids reminiscent of glandular ductal structures. Transformed cancer cells, in contrast, typically fail to undergo acinar morphogenic patterns, forming poorly differentiated or invasive multicellular structures. The 3D cancer spheroids are widely accepted to better recapitulate various tumorigenic processes and drug responses. So far, however, 3D models have been employed predominantly in the Academia, whereas the pharmaceutical industry has yet to adopt a more widely and routine use. This is mainly due to poor characterisation of cell models, lack of standardised workflows and high throughput cell culture platforms, and the availability of proper readout and quantification tools. In this thesis, a complete workflow has been established entailing well-characterised 3D cell culture models for prostate cancer, a standardised 3D cell culture routine based on high-throughput-ready platform, automated image acquisition with concomitant morphometric image analysis, and data visualisation, in order to enable large-scale high-content screens. Our integrated suite of software and statistical analysis tools were optimised and validated using a comprehensive panel of prostate cancer cell lines and 3D models. The tools quantify multiple key cancer-relevant morphological features, ranging from cancer cell invasion through multicellular differentiation to growth, and detect dynamic changes both in morphology and function, such as cell death and apoptosis, in response to experimental perturbations including RNA interference and small molecule inhibitors. Our panel of cell lines included many non-transformed and most currently available classic prostate cancer cell lines, which were characterised for their morphogenetic properties in 3D laminin-rich ECM. The phenotypes and gene expression profiles were evaluated concerning their relevance for pre-clinical drug discovery, disease modelling and basic research. In addition, a spontaneous model for invasive transformation was discovered, displaying a highdegree of epithelial plasticity. This plasticity is mediated by an abundant bioactive serum lipid, lysophosphatidic acid (LPA), and its receptor LPAR1. The invasive transformation was caused by abrupt cytoskeletal rearrangement through impaired G protein alpha 12/13 and RhoA/ROCK, and mediated by upregulated adenylyl cyclase/cyclic AMP (cAMP)/protein kinase A, and Rac/ PAK pathways. The spontaneous invasion model tangibly exemplifies the biological relevance of organotypic cell culture models. Overall, this thesis work underlines the power of novel morphometric screening tools in drug discovery.

Large scale solar power plant flat roof and carport installation in Finland

This work focuses on the 159.5 kW solar photovoltaic power plant project installed at the Lappeenranta University of Technology in 2013 as an example of what a solar plant project could be in Finland. The project consists of a two row carport and a flat roof installation on the roof of the university laboratories. The purpose of this project is not only its obvious energy savings potential but also to serve as research and teaching laboratory tool. By 2013, there were not many large scale solar power plants in Finland. For this reason, the installation and data experience from the solar power plant at LUT has brought valuable information for similar projects in northern countries. This work includes a first part for the design and acquisition of the project to continue explaining about the components and their installation. At the end, energy produced by this solar power plant is studied and calculated to find out some relevant economical results. For this, the radiation arriving to southern Finland, the losses of the system in cold weather and the impact of snow among other aspects are taken into account.

An investigation into the physical and psychological stress factors that elementary teachers experience : recommendations to boards and personal calming strategies /

The prlmaiy objective of this study was to Identify and describe the physical and psychological stress factors that elementary school teachers experience and how teachers cope with stress. A secondary objective was to offer boards and teachers potential coping strategies counteracting stress and the effects of stress. The sample consisted of 120 elementaiy teachers from southern Ontario. Ten elementaiy schools were randomly chosen. The Teacher Stress Inventory questionnaire (Flmian, 1989) was used. Data were analyzed using a variety of statistics. Test norms and interpretations were performed based on standard results obtained from the author of the questionnaire (Flmian, 1988). Overall, the results indicated that work-related stressors were the main factor for teacher stress. This Included such factors as caseload/class is too big, too much administrative paperwork, and having little time to prepare lessons. Implications for further research and practical suggestions for further reseairch are discussed. Also a variety of recommendations to boards and for individual use are discussed. Some recommendations are having counselling available for teachers, workshops on how to handle stress, and learning how to breathe and using calm visualization.

The Ontario Municipal Freedom of Information and Protection of Individual Privacy Act: an analysis of its application to school boards

In Canada freedom of information must be viewed in the context of governing -- how do you deal with an abundance of information while balancing a diversity of competing interests? How can you ensure people are informed enough to participate in crucial decision-making, yet willing enough to let some administrative matters be dealt with in camera without their involvement in every detail. In an age when taxpayers' coalition groups are on the rise, and the government is encouraging the establishment of Parent Council groups for schools, the issues and challenges presented by access to information and protection of privacy legislation are real ones. The province of Ontario's decision to extend freedom of information legislation to local governments does not ensure, or equate to, full public disclosure of all facts or necessarily guarantee complete public comprehension of an issue. The mere fact that local governments, like school boards, decide to collect, assemble or record some information and not to collect other information implies that a prior decision was made by "someone" on what was important to record or keep. That in itself means that not all the facts are going to be disclosed, regardless of the presence of legislation. The resulting lack of information can lead to public mistrust and lack of confidence in those who govern. This is completely contrary to the spirit of the legislation which was to provide interested members of the community with facts so that values like political accountability and trust could be ensured and meaningful criticism and input obtained on matters affecting the whole community. This thesis first reviews the historical reasons for adopting freedom of information legislation, reasons which are rooted in our parliamentary system of government. However, the same reasoning for enacting such legislation cannot be applied carte blanche to the municipal level of government in Ontario, or - ii - more specifially to the programs, policies or operations of a school board. The purpose of this thesis is to examine whether the Municipal Freedom of Information and Protection of Privacy Act, 1989 (MFIPPA) was a neccessary step to ensure greater openness from school boards. Based on a review of the Orders made by the Office of the Information and Privacy Commissioner/Ontario, it also assesses how successfully freedom of information legislation has been implemented at the municipal level of government. The Orders provide an opportunity to review what problems school boards have encountered, and what guidance the Commissioner has offered. Reference is made to a value framework as an administrative tool in critically analyzing the suitability of MFIPPA to school boards. The conclusion is drawn that MFIPPA appears to have inhibited rather than facilitated openness in local government. This may be attributed to several factors inclusive of the general uncertainty, confusion and discretion in interpreting various provisions and exemptions in the Act. Some of the uncertainty is due to the fact that an insufficient number of school board staff are familiar with the Act. The complexity of the Act and its legalistic procedures have over-formalized the processes of exchanging information. In addition there appears to be a concern among municipal officials that granting any access to information may be violating personal privacy rights of others. These concerns translate into indecision and extreme caution in responding to inquiries. The result is delay in responding to information requests and lack of uniformity in the responses given. However, the mandatory review of the legislation does afford an opportunity to address some of these problems and to make this complex Act more suitable for application to school boards. In order for the Act to function more efficiently and effectively legislative changes must be made to MFIPPA. It is important that the recommendations for improving the Act be adopted before the government extends this legislation to any other public entities.

J. McDonagh's Saw and Plaining Mills - Vignette

A vignette of J. McDonagh's Saw and Plaining Mills, Welland Canal, Thorold.

What I saw in california : being the journal of a tour... in the year 1846-1847

UANL

Impuesto de tasa fija (Flat Tax) en sustitución de los impuestos federales directos al ingreso (ISR y IETU). Estudio teórico-comparado y análisis empírico aplicado a México.

Tesis (Doctor en Contaduría) UANL, 2012.

Analyse ludique de la franchise Saw

La saga Saw est une franchise qui a marqué le cinéma d’horreur des années 2000. Le présent mémoire tâchera d’en faire une étude détaillée et rigoureuse en utilisant la notion de jeu. En élaborant tout d’abord un survol du cinéma d’horreur contemporain et en observant la réception critique de la saga à travers l’étude de différents articles, ce travail tentera en majeure partie d’analyser la franchise Saw en rapport avec l’approche ludique du cinéma en général et celle adoptée par Bernard Perron. Cette étude, qui s’élaborera tant au niveau diégétique que spectatoriel, aura pour but de montrer l’importance de la place qu’occupe la notion de jeu dans cette série de films.

Assessing locomotion in cats trained on a flat treadmill and on a ladder treadmill before and after spinal cord injury (SCI)

Les effets des lésions de la moelle épinière sur la locomotion sont souvent évalués sur un tapis roulant avec une surface plane, ce qui demande peu d’implication active des structures supraspinales. L’objectif du présent travail est d’évaluer si un type d’entraînement nécessitant une plus grande part de contrôle volontaire (c.-à-d. supraspinal) pourrait améliorer la récupération de la marche chez le chat après une hémilésion unilatérale spinale au niveau thoracique (T10). Pour ce faire, pendant 6 semaines les chats ont été entrainés sur un tapis roulant conventionnel ou sur un tapis-échelle roulante, tâche requérant un placement des pattes plus précis. Les paramètres de la marche ont été évalués par cinématique et électromyographie (EMG) avant et une fois par semaine pendant 6 semaines après lésion. Nos résultats comparant la marche sur tapis conventionnel à celle sur échelle roulante montrent des différences dans les excursions angulaires et les couplages entre les membres. On observe aussi des différences dans l’amplitude des EMG notamment une augmentation de la deuxième bouffée du muscle Semitendineux (St) sur l’échelle roulante. Après l’hémilésion spinale cette bouffée disparait du côté de la lésion tandis qu’elle est maintenue du côté intact. Après l’entrainement sur échelle roulante, on observe des changements de trajectoire de la patte et une disparition du pied tombant (foot drag) qui suggèrent une amélioration du contrôle de la musculature distale. Nos résultats montrent que le patron locomoteur observé sur tapis conventionnel est influencé par le type d’entraînement procuré. De plus, certains paramètres de la locomotion suggèrent que l’entraînement sur échelle roulante, qui requiert plus de contrôle supraspinal, favorise une meilleure récupération de la marche après lésion spinale.

Biology of Flat Toadfish,Colletteichthys dussumieri(Valenciennes,1837) of Cochin Estuary

Dept.of Marine Biology,Microbiology and Biochemistry,Cochin University of Science and Technology

Punching Shear Behavior of UHPC Flat Slabs

At the Institute of Structural Engineering of the Faculty of Civil Engineering, Kassel University, series tests of slab-column connection were carried out, subjected to concentrated punching load. The effects of steel fiber content, concrete compressive strength, tension reinforcement ratio, size effect, and yield stress of tension reinforcement were studied by testing a total of six UHPC slabs and one normal strength concrete slab. Based on experimental results; all the tested slabs failed in punching shear as a type of failure, except the UHPC slab without steel fiber which failed due to splitting of concrete cover. The post ultimate load-deformation behavior of UHPC slabs subjected to punching load shows harmonic behavior of three stages; first, drop of load-deflection curve after reaching maximum load, second, resistance of both steel fibers and tension reinforcement, and third, pure tension reinforcement resistance. The first shear crack of UHPC slabs starts to open at a load higher than that of normal strength concrete slabs. Typically, the diameter of the punching cone for UHPC slabs on the tension surface is larger than that of NSC slabs and the location of critical shear crack is far away from the face of the column. The angle of punching cone for NSC slabs is larger than that of UHPC slabs. For UHPC slabs, the critical perimeter is proposed and located at 2.5d from the face of the column. The final shape of the punching cone is completed after the tension reinforcement starts to yield and the column stub starts to penetrate through the slab. A numerical model using Finite Element Analysis (FEA) for UHPC slabs is presented. Also some variables effect on punching shear is demonstrated by a parametric study. A design equation for UHPC slabs under punching load is presented and shown to be applicable for a wide range of parametric variations; in the ranges between 40 mm to 300 mm in slab thickness, 0.1 % to 2.9 % in tension reinforcement ratio, 150 MPa to 250 MPa in compressive strength of concrete and 0.1 % to 2 % steel fiber content. The proposed design equation of UHPC slabs is modified to include HSC and NSC slabs without steel fiber, and it is checked with the test results from earlier researches.

PowerPoint Teaching Template - UoS blue flat.ppt

This PowerPoint file can be used as a template for teaching presentations. This version has a solid blue background and pale grey text on the title slide and all subsequent content slides.

School Boards in Kenya

Los consejos de administración de las escuelas secundarias públicas en Kenia son nombrados por las autoridades públicas a las que les deben rendir cuenta a pesar de que los padres pagan por todos los gastos de las escuelas, excepto los sueldos de los profesores. Esta tesis doctoral es una investigación histórica y sociológica sobre la naturaleza y evolución de estos consejos de administración escolar.. Después de analizar los consejos de administración escolar como estructuras intermedias, organizaciones no-gubernamentales y organizaciones quasi no-gubernamentales, se estudia el impacto de cuatro acontecimientos políticos en la naturaleza y rol de estos consejos: la independencia de Gran Bretaña, el 'Sessional Paper'* no. 10 de 1965 sobre el Socialismo Africano y su aplicación en el planeamiento de Kenia, la ley de educación de 1968 que nacionalizó el sistema educativo, y el 'Sessional Paper'* no. 6 de 1988 sobre el manejo de las finanzas públicas para renovar el crecimiento económico en Kenia. Se continua con el estudio de la normativa que controla los consejos de administración escolar, la influencia de los grupos de interés (asociaciones de padres y maestros, 'sponsors' y el Ministerio de Educación) y el principio de subsidiariedad. Finalmente se describe un relevamiento postal a escala nacional de escuelas secundarias públicas. El análisis del relevamiento provee un perfil de las escuelas, de sus consejos de administración y del trabajo que éstos desempeñan, mostrando los posibles efectos de su falta de autonomía. La tesis concluye con algunas propuestas para el diseño de consejos de administración eficientes, y algunas estrategias para aumentar su importancia que tratan sobre la influencia de los consejos escolares, la calidad de los servicios escolares, participación y subsidariedad .