The Role of Astrocytes in Tumor Growth and Progression

Current research is continually implicating the importance of astrocytes as active participants in neurological injury, disease, and tumor progression. This chapter will discuss some of these emerging concepts, especially as they relate to tumor biology. Astrocytes themselves can become tumorigenic, such as the case in gliomas, which often have aberrant signaling in key regulating genes of astrocyte development. Astrocytes secrete factors that maintain the tight junctions of the blood brain barrier (BBB), which in turn regulates the success or failure of metastatic cells extravasating into the brain. This astrocytic association with the brain vasculature also promotes brain tumor stem cell characteristics, which are known to be necessary for tumor initiation. Tumor cells within the brain make direct contacts with astrocytes through gap junctions, which subsequently lead to increased chemoresistance of the tumor cells. Astrocytes have also been shown to effect tumors cells via secretion of degradative enzymes, cytokines, chemokines, and growth factors, all of which have been shown to promote tumor cell proliferation, survival, and invasion. Thus, research in astrocyte biology and the role of astrocytes in the tumor microenvironment has and will likely continue to reveal novel targets for cancer intervention

Screening Cellular Feature Measurements for Image-Based Assay Development

The typical “design” approach to image-based assay development involves choosing measurements that are likely to correlate with the phenotype of interest, based on the researcher’s intuition and knowledge of image analysis. An alternate “screening” approach is to measure a large number of cellular features and systematically test each feature to identify those that are best able to distinguish positive and negative controls while taking precautions to avoid overfitting the available data. The cell measurement software the authors previously developed, CellProfiler, makes both approaches straightforward, easing the process of assay development. Here, they demonstrate the use of the screening approach to image assay development to select the best measures for scoring publicly available image sets of 2 cytoplasm-to-nucleus translocation assays and 2 Transfluor assays. The authors present the resulting assay quality measures as a baseline for future algorithm comparisons, and all software, methods, and images they present are freely available

Sustained Activation of Lyn Tyrosine Kinase In Vivo Leads to Autoimmunity

Genetic ablation of the Lyn tyrosine kinase has revealed unique inhibitory roles in B lymphocyte signaling. We now report the consequences of sustained activation of Lyn in vivo using a targeted gain-of-function mutation (Lynup/up mice). Lynup/up mice have reduced numbers of conventional B lymphocytes, down-regulated surface immunoglobulin M and costimulatory molecules, and elevated numbers of B1a B cells. Lynup/up B cells are characterized by the constitutive phosphorylation of negative regulators of B cell antigen receptor (BCR) signaling including CD22, SHP-1, and SHIP-1, and display attributes of lymphocytes rendered tolerant by constitutive engagement of the antigen receptor. However, exaggerated positive signaling is also apparent as evidenced by the constitutive phosphorylation of Syk and phospholipase Cγ2 in resting Lynup/up B cells. Similarly, Lynup/up B cells show a heightened calcium flux in response to BCR stimulation. Surprisingly, Lynup/up mice develop circulating autoreactive antibodies and lethal autoimmune glomerulonephritis, suggesting that enhanced positive signaling eventually overrides constitutive negative signaling. These studies highlight the difficulty in maintaining tolerance in the face of chronic stimulation and emphasize the pivotal role of Lyn in B cell signaling

The Registry and Follow-Up of Complex Pediatric Therapies Program of Western Canada: A Mechanism for Service, Audit, and Research after Life-Saving Therapies for Young Children

Newly emerging health technologies are being developed to care for children with complex cardiac defects. Neurodevelopmental and childhood school-related outcomes are of great interest to parents of children receiving this care, care providers, and healthcare administrators. Since the 1970s, neonatal follow-up clinics have provided service, audit, and research for preterm infants as care for these at-risk children evolved. We have chosen to present for this issue the mechanism for longitudinal follow-up of survivors that we have developed for western Canada patterned after neonatal follow-up. Our program provides registration for young children receiving complex cardiac surgery, heart transplantation, ventricular assist device support, and extracorporeal life support among others. The program includes multidisciplinary assessments with appropriate neurodevelopmental intervention, active quality improvement evaluations, and outcomes research. Through this mechanism, consistently high (96%) follow-up over two years is maintained

Ecological implications of a flower size/number trade-off in tropical forest trees

Peer reviewedPublisher PD

Are categorical deniers different? Understanding demographic, personality, and psychological differences between denying and admitting sex offenders

The purpose of this study was to establish whether there were demographic, personality, or psychological differences between a sample of 40 incarcerated sex offenders in categorical denial and 37 sex offenders admitting responsibility in an Australian minimum-security unit. Categorical deniers had lower IQs, were older, and were more likely to be child molesters. Criminogenically, there were no differences between categorical deniers and those who admitted their offences in relation to Static-99 risk scores. Psychologically, offenders denying their offences were significantly more shame-prone, and likely to use externalization as a method of impression-management. They were also more compulsive than those admitting their offences, but less antisocial and sadistic, when compared on personality indices. The study is limited by the small sample size however implications for further research and the treatment of categorical deniers are discussed

Search for the Standard Model Higgs Boson with the OPAL Detector at LEP

This paper summarises the search for the Standard Model Higgs boson in e+e- collisions at centre-of-mass energies up to 209 GeV performed by the OPAL Collaboration at LEP. The consistency of the data with the background hypothesis and various Higgs boson mass hypotheses is examined. No indication of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure

Search for Higgs Bosons in e+e- Collisions at 183 GeV

The data collected by the OPAL experiment at sqrts=183 GeV were used to search for Higgs bosons which are predicted by the Standard Model and various extensions, such as general models with two Higgs field doublets and the Minimal Supersymmetric Standard Model (MSSM). The data correspond to an integrated luminosity of approximately 54pb-1. None of the searches for neutral and charged Higgs bosons have revealed an excess of events beyond the expected background. This negative outcome, in combination with similar results from searches at lower energies, leads to new limits for the Higgs boson masses and other model parameters. In particular, the 95% confidence level lower limit for the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA > 72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European Physical Journal

A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays

The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL detector at LEP. Lambda_b are selected by the presence of energetic Lambda particles in bottom events tagged by the presence of displaced secondary vertices. A fit to the momenta of the Lambda particles separates signal from B meson and fragmentation backgrounds. The measured product branching ratio is f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))% Combined with a previous OPAL measurement, one obtains f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European Physical Journal

Search for R-Parity Violating Decays of Scalar Fermions at LEP

A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.