Development of taxane resistance in a panel of human lung cancer cell lines

Using a selection process designed to reflect clinically relevant conditions, a panel of taxane-selected variants were developed to study further the mechanisms of resistance in lung cancer. Unlike continuous or pulse exposure to high concentrations of chemotherapeutic drugs which yield high resistance and often cross resistance, most variants developed here displayed low level resistance to the selecting drug with slight cross-resistance. Pulsing with taxol resulted in more highly resistant clones (up to 51.4-fold). Analysis of taxol and taxotere in the four major lung cancer cell types showed the taxanes to be more effective against NSCLC (with the exception of SKMES-taxane selected variants) than against the SCLC. Comparison of taxol and taxotere shows that taxol induces higher levels of resistance than taxotere. Further, in taxotere-selected cell lines, the cells are more resistant to taxol than taxotere, suggesting that taxotere may be a superior taxane from a clinical view. Taxol treatment resulted in increased cross-resistance to 5-FU in all classes of lung cancer except DMS-53. The high levels of Pgp in the DMS-53 and selected variant suggests this mechanism is not related to Pgp expression. Analysis of the Pgp and MRP-1 status by combination inhibitory assays and Western blotting showed no consistent relationship between expression of the membrane pumps Pgp or MRP-1 and resistance. However, where high level resistance was seen, the parent cell line expressed Pgp or MRP-1 and was accompanied by increased levels in the variants. Overall we found that the clinically relevant models used here are useful for investigating mechanisms of taxane resistance

Ratios and Proportions [6th grade]

In this unit students will be introduced to ratios and proportions. Students will have practice identifying ratios from pictures, graphs, models and word problems. Using these skills, students will then be able to identify proportional ratios and use ratios to describe proportional situations as well as to predict outcomes. To demonstrate their knowledge of ratios and proportional reasoning, students will complete a project assessment. The students will be given a recipe and then have to calculate the amounts of ingredients needed for various numbers of servings. The students will write down new versions of the recipes to be included in a class recipe book. To ensure that the recipes do have proportional amounts of ingredients, students may bring in a sample of their recipe to share with the class

Variations in immune response as determined by MHC class 1 polymorphism in cattle

Major histocompatibility complex (MHC) class I molecules play an essential role in the defence against intracellular pathogens. CD8+ T cells recognise antigenic peptides in association with self-MHC, a process known as MHC restriction. In this study we examined bovine MHC class I genes using both molecular and cellular approaches. There is evidence for the existence of five or six classical class I loci in cattle, with the number of genes expressed varying between haplotypes. Most alleles are putatively assigned to a locus according to their grouping following phylogenetic analysis. Here we applied reference strand mediated conformational analysis (RSCA), a high resolution typing method, to four of these groups: 1, 2, 3 and 6. Using group-specific primers and two reference strands 22 potential new alleles were identified with one probable pseudoallele in group 1. Based on the results obtained and previous phylogenetic analysis, groups 1 and 3 appear to be the most polymorphic.The need for a reliable typing method for MHC class I genes in cattle can be seen through studies of CD8+ T cell responses to Theileria parva. T. parva is an intracellular parasite against which CD8+ CTL have been shown to be the principal effector cells in infected cattle. Previous studies identified a clear bias in class I restriction of CTL to either the maternal or paternal haplotype, and showed that haplotypes differ in their ability to restrict this response. We have extended these studies using animals with wellcharacterised haplotypes. We showed that the A14 and A18 haplotypes appear to be dominant over the A10 and A31 haplotypes respectively. A14 expresses three class I genes, D18.1, D18.4 and D18.5. Assays testing an A14-restricted CTL clone against D18.1 and D18.4 transfected target cells proved inconclusive indicating a need for further investigation and the inclusion of D 18.5 in any studies

Highly Luminescent Platinum Complexes for Light Emitting Devices and Bio-Imaging

Intensely luminescent cyclometallated platinum(II) complexes have been prepared containing N^C^N-coordinating ligands, based on 1,3-dipyridylbenzene. Exceptionally high quantum yields ( 0.85, degassed DCM, 298 K) are rationalised in terms of the particularly short Pt-C bond, which raises the energy of the normally deactivating d-d* state. Terdentate ligand functionalisation has been employed to obtain complexes with tuneable emission. Fluorination at the 3,5-aryl positions and/or placing electronreleasing substituents at the 4-pyridyl position gave complexes with blue-shifted emission, whilst retaining a high quantum yield. Substitution of the chloride ancillary ligand for cyanide led to further blue-shifts. In general, these complexes undergo intermolecular interactions in solutions of higher concentration to form excimers. The excimers are emissive in their own right, and display broad, structureless emission bands at lower energy than the isolated molecules (monomers). The influence of substituents in the terdentate ligand and the identity of the coligand on the energy and relative intensity of excimer emission has been elucidated. Some complexes have been used as phosphorescent dopants in the fabrication of high efficiency organic light emitting devices (OLED)s. The colour of a device depends on the monomer-to-excimer emission ratio, which is controlled by varying the dopant concentration. At intermediate concentrations, white OLEDs, with properties approaching pure white light, have been obtained. Preliminary investigations into the utility of the complexes as bio-imaging agents in live cells are reported. The complexes which contain small substituents on the terdentate ligand enter cells rapidly, retaining their phosphorescence. These Pt(II) complexes appear to localise simultaneously in both the nucleus and mitochondria of cells, where their emission characteristics differ: the application of appropriate filter sets allows separate visualisation of the two organelles. A selection of iridium(III) complexes were also investigated as bio-imaging agents. These complexes localise in cytoplasm-based organelles, and do not appear to enter the nucleus. Both classes of organometallic complexes are shown to be suitable candidates for time resolved emission imaging microscopy (TREM)

Effects of a cognitive specific imagery intervention on the soccer skill performance of young athletes aged 11--12 and 13--14: A developmental perspective.

The primary purpose of the present study was to examine the effects of a cognitive specific imagery intervention on the soccer skill performance of young athletes aged 11--12 and 13--14 years and determine if such performances vary with age and gender. A secondary purpose was to determine if such performances are a result of imagery function. Participants were 68 soccer athletes belonging to eight different teams. Teams were randomly assigned to either a CS or MG-A imagery group. Athletes were administered the SIQ-C and tested on the soccer skill to determine baseline performance. Following the intervention, athletes were tested on the same soccer skill, and completed the SIQ-C. Athletes in the current study did not increase their frequency of imagery use, nor did they improve their performance. Performances varied with respect to gender however, no significant age group differences were present. Reasons for these findings are discussed.Dept. of Human Kinetics. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2006 .M87. Source: Masters Abstracts International, Volume: 45-01, page: 0487. Thesis (M.H.K.)--University of Windsor (Canada), 2006

Digital Document Interactions: What Knowledge Workers Do Every Day

Much knowledge in today\u27s organizations is explicit — in data bases, in expert systems, in procedures, and in knowledge management systems. One of the most common forms in which organizational knowledge resides is as documents (Paepcke, 1996; Ruggles, 1998). And today, those documents are most likely to have been created and exist digitally (Orlikowski & Yates, 1994). This paper presents pretest results from research in progress about what knowledge workers do with digital documents in organizations and briefly discusses the implications and directions for future research. Results from a larger sample will be available at the conference

Childhood Obesity: The Role of Health Policy

This first policy report from the CPRC and the NICHQ Childhood Obesity Action Network was released on March 18, 2008 in Miami Florida as part of the Second Childhood Obesity Congress

The Climate Impact of the Messinian Salinity Crisis

This study uses an atmospheric general circulation model to examine the regional and global climate response to the Messinian Salinity Crisis (MSC) roughly 6 Ma. During this time, the tectonic collision of the African and European plates isolated the Mediterranean Sea (MedSea) from the Atlantic Ocean. MedSea level is estimated to have fallen between 1000-2000 m and desiccation may have lasted for 90 kyr. Our results show that the substantial MedSea depression generates planetary-scale atmospheric waves responsible for significant climate effects throughout the Northern Hemisphere. A notable deepening of the Aleutian Low and a significant equator-ward shift in the Atlantic jet stream are evident. Cyclical patterns in Messinian sediments suggest alternating wet and dry climate during the MSC. These cycles have been attributed to variations in the Earth's precession. This is the first study to detail how reduced MedSea level alters orbitally-driven climate change during the Late Miocene. Reduced MedSea level results in wetter conditions to the Northeast, in particular the Alps, consistent with proxy data. This signal is robust under all precession signals and is supported by evidence of greater weathering of the Alps during the MSC. Desiccation and lowered MedSea level results in greater precipitation over the Guinea Coast region of North Africa. Greater runoff from this region is supported by proxy evidence of higher monsoon intensity and enhanced total organic carbon accumulation throughout the Messinian. We couple our model to an online aerosol model to examine the response of dust to varying orbital parameters and to MedSea desiccation. Modeling dust source and transport changes in response to decreased dustiness during precession minimum shows that warmer tropical North Atlantic SSTs, attributed to increased insolation in the absence of dust, enhances evaporation and favors more precipitation over the western tropical North Atlantic. This stresses the importance of allowing dust to respond to climate change and including prognostic dust in paleo-simulations that examine changes in the West African monsoon. Enhanced dust loading over the tropical North Atlantic Ocean occurs when the Mediterranean is desiccated. This reduces the net radiative flux at the surface, which cools SSTs north of the Equator and shifts the ITCZ towards the Southern Hemisphere, consistent with theories that link African dust with extended Sahel droughts. Greater ocean productivity results from nutrient rich iron-laden dust waters, which is consistent with increased benthic foraminiferal accumulation rates off the African coast between 5.8 Ma and 5.25 Ma. The dustier Northern Hemisphere inhibits convective precipitation in the tropical North Atlantic and large-scale precipitation over Eastern Europe and into Central Asia, in agreement with proxy evidence of greater aridity in these regions between 6.2 and 5 Ma. Our results show that a desiccated Mediterranean has a significant impact on Northern Hemisphere sea-ice formation during precession maximum, which agrees with &delta18O proxies. Sea ice growth spreads southward, especially in the Labrador and Bering Seas. Interestingly, proxy data studies show discontinuous sea-ice in the Labrador Sea and south of Greenland, as well as concurrent ice-rafting in both the northwest Pacific and Gulf of Alaska sites in the late Miocene, a few million years prior to Northern Hemisphere glaciation