98 research outputs found
A convenient category of locally preordered spaces
As a practical foundation for a homotopy theory of abstract spacetime, we
extend a category of certain compact partially ordered spaces to a convenient
category of locally preordered spaces. In particular, we show that our new
category is Cartesian closed and that the forgetful functor to the category of
compactly generated spaces creates all limits and colimits.Comment: 26 pages, 0 figures, partially presented at GETCO 2005; changes:
claim of Prop. 5.11 weakened to finite case and proof changed due to problems
with proof of Lemma 3.26, now removed; Eg. 2.7, statement before Lem. 2.11,
typos, and other minor problems corrected throughout; extensive rewording;
proof of Lem. 3.31, now 3.30, adde
Functional and genetic analysis of regulatory regions of coliphage H-19B: location of shiga-like toxin and lysis genes suggest a role for phage functions in toxin release
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74784/1/j.1365-2958.1998.00890.x.pd
Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines
Background: EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and
Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and
in combination with EGF.
Methods: Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was
conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression
and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene
expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40
K array A.
Results: Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this
level of cell cycle distribution after treatment, suggesting a predominantly differentiated state.
Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their
viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important
reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating
microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and
showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane
reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes
upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the
2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment.
In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological
effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes
appeared to be less stimulated than for single drug cases.
Conclusion: This is the first study to have systematically investigated the effect of cetuximab or
gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors
have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an
expression pattern that inversely correlates with EGF treatment. We found interesting cytomorphological
features closely relating to gene expression profile. Both drugs have an effect on
differentiation towards cellular death
Exploring Cosmic Origins with CORE: Survey requirements and mission design
Future observations of cosmic microwave background (CMB) polarisation havethe potential to answer some of the most fundamental questions of modernphysics and cosmology. In this paper, we list the requirements for a future CMBpolarisation survey addressing these scientific objectives, and discuss thedesign drivers of the CORE space mission proposed to ESA in answer to the "M5"call for a medium-sized mission. The rationale and options, and themethodologies used to assess the mission's performance, are of interest toother future CMB mission design studies. CORE is designed as a near-ultimateCMB polarisation mission which, for optimal complementarity with ground-basedobservations, will perform the observations that are known to be essential toCMB polarisation scienceand cannot be obtained by any other means than adedicated space mission
Exploring cosmic origins with CORE: Survey requirements and mission design
Future observations of cosmic microwave background (CMB) polarisation have
the potential to answer some of the most fundamental questions of modern
physics and cosmology. In this paper, we list the requirements for a future CMB
polarisation survey addressing these scientific objectives, and discuss the
design drivers of the CORE space mission proposed to ESA in answer to the "M5"
call for a medium-sized mission. The rationale and options, and the
methodologies used to assess the mission's performance, are of interest to
other future CMB mission design studies. CORE is designed as a near-ultimate
CMB polarisation mission which, for optimal complementarity with ground-based
observations, will perform the observations that are known to be essential to
CMB polarisation scienceand cannot be obtained by any other means than a
dedicated space mission.Comment: 79 pages, 14 figure
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