403 research outputs found
Reviews
Rich and Poor in New Zealand: A Critique of Class, Politics and Ideology, Social Policy and the Welfare State in New Zealand, The Framework of Industrial Law in New Zealand, Industrial Society: Class Clevage and Control, The Control of Work, The Workless State: Studies in Umemployment, A Professional Union: the Evolution of the Institution of Professional Civil Servants, Strike
HOX transcription factors are potential targets and markers in malignant mesothelioma
YesBackground
The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos.
Methods
We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model.
Results
We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of HOX genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival.
Conclusion
HOX genes are a potential therapeutic target in mesothelioma, and HOXB4 expression correlates with overall survival.The authors gratefully acknowledge the support of the British Lung Foundation, grant number ICAPPG10-1. KJH acknowledges support from the ICR/RM NIHR Biomedical Research Centre
Membrane insertion and secretion of the Engrailed-2 (EN2) transcription factor by prostate cancer cells may induce antiviral activity in the stroma
YesEngrailed-2 (EN2) is a homeodomain-containing transcription factor that has roles in boundary formation and neural guidance in early development, but which is also expressed in a range of cancers. In addition to transcriptional regulation, it is secreted by cells and taken up by others through a mechanism that is yet to be fully elucidated. In this study, the distribution of EN2 protein in cells was evaluated using immunofluorescence with a set of antibodies raised against overlapping epitopes across the protein, and through the use of an EN2-GFP construct. MX2 expression in primary prostate tumors was evaluated using immunohistochemistry. We showed that EN2 protein is present in the cell membrane and within microvesicles that can be secreted from the cell and taken up by others. When taken up by normal cells from the stroma EN2 induces the expression of MX2 (MxB), a protein that has a key role in the innate immune response to viruses. Our findings indicate that EN2 secretion by tumors may be a means of preventing viral-mediated immune invasion of tissue immediately adjacent to the tumor.The Ringrose Family Trust supported this study through a studentship awarded to N.P
A computational analysis of lower bounds for big bucket production planning problems
In this paper, we analyze a variety of approaches to obtain lower bounds for multi-level production planning problems with big bucket capacities, i.e., problems in which multiple items compete for the same resources. We give an extensive survey of both known and new methods, and also establish relationships between some of these methods that, to our knowledge, have not been presented before. As will be highlighted, understanding the substructures of difficult problems provide crucial insights on why these problems are hard to solve, and this is addressed by a thorough analysis in the paper. We conclude with computational results on a variety of widely used test sets, and a discussion of future research
Coupled dark matter-dark energy in light of near Universe observations
Cosmological analysis based on currently available observations are unable to
rule out a sizeable coupling among the dark energy and dark matter fluids. We
explore a variety of coupled dark matter-dark energy models, which satisfy
cosmic microwave background constraints, in light of low redshift and near
universe observations. We illustrate the phenomenology of different classes of
dark coupling models, paying particular attention in distinguishing between
effects that appear only on the expansion history and those that appear in the
growth of structure. We find that while a broad class of dark coupling models
are effectively models where general relativity (GR) is modified --and thus can
be probed by a combination of tests for the expansion history and the growth of
structure--, there is a class of dark coupling models where gravity is still
GR, but the growth of perturbations is, in principle modified. While this
effect is small in the specific models we have considered, one should bear in
mind that an inconsistency between reconstructed expansion history and growth
may not uniquely indicate deviations from GR. Our low redshift constraints
arise from cosmic velocities, redshift space distortions and dark matter
abundance in galaxy voids. We find that current data constrain the
dimensionless coupling to be |xi|<0.2, but prospects from forthcoming data are
for a significant improvement. Future, precise measurements of the Hubble
constant, combined with high-precision constraints on the growth of structure,
could provide the key to rule out dark coupling models which survive other
tests. We shall exploit as well weak equivalence principle violation arguments,
which have the potential to highly disfavour a broad family of coupled models.Comment: 34 pages, 6 figures; changes to match published versio
Limit cycles in uniform isochronous centers of discontinuous differential systems with four zones
We apply the averaging theory of first order for discontinuous differential systems to study the bifurcation of limit cycles from the periodic orbits of the uniform isochronous center of the differential systems ẋ = -y+x, y = x + xy, and ẋ = -y + xy, y = x + xy, when they are perturbed inside the class of all discontinuous quadratic and cubic polynomials differential systems with four zones separately by the axes of coordinates, respectively. Using averaging theory of first order the maximum number of limit cycles that we can obtain is twice the maximum number of limit cycles obtained in a previous work for discontinuous quadratic differential systems perturbing the same uniform isochronous quadratic center at origin perturbed with two zones separately by a straight line, and 5 more limit cycles than those achieved in a prior result for discontinuous cubic differential systems with the same uniform isochronous cubic center at the origin perturbed with two zones separately by a straight line. Comparing our results with those obtained perturbing the mentioned centers by the continuous quadratic and cubic differential systems we obtain 8 and 9 more limit cycles respectively
The PHENIX Experiment at RHIC
The physics emphases of the PHENIX collaboration and the design and current
status of the PHENIX detector are discussed. The plan of the collaboration for
making the most effective use of the available luminosity in the first years of
RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program
available at http://www.rhic.bnl.gov/phenix
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