1,033 research outputs found
Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway
This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel
Coracoid Abnormalities and Their Relationship with Glenohumeral Deformities in Children with Obstetric Brachial Plexus Injury
<p>Abstract</p> <p>Background</p> <p>Patients with incomplete recovery from obstetric brachial plexus injury (OBPI) usually develop secondary muscle imbalances and bone deformities at the shoulder joint. Considerable efforts have been made to characterize and correct the glenohumeral deformities, and relatively less emphasis has been placed on the more subtle ones, such as those of the coracoid process. The purpose of this retrospective study is to determine the relationship between coracoid abnormalities and glenohumeral deformities in OBPI patients. We hypothesize that coracoscapular angles and distances, as well as coracohumeral distances, diminish with increasing glenohumeral deformity, whereas coracoid overlap will increase.</p> <p>Methods</p> <p>39 patients (age range: 2-13 years, average: 4.7 years), with deformities secondary to OBPI were included in this study. Parameters for quantifying coracoid abnormalities (coracoscapular angle, coracoid overlap, coracohumeral distance, and coracoscapular distance) and shoulder deformities (posterior subluxation and glenoid retroversion) were measured on CT images from these patients before any surgical intervention. Paired Student t-tests and Pearson correlations were used to analyze different parameters.</p> <p>Results</p> <p>Significant differences between affected and contralateral shoulders were found for all coracoid and shoulder deformity parameters. Percent of humeral head anterior to scapular line (PHHA), glenoid version, coracoscapular angles, and coracoscapular and coracohumeral distances were significantly lower for affected shoulders compared to contralateral ones. Coracoid overlap was significantly higher for affected sides compared to contralateral sides. Significant and positive correlations were found between coracoscapular distances and glenohumeral parameters (PHHA and version), as well as between coracoscapular angles and glenohumeral parameters, for affected shoulders. Moderate and positive correlations existed between coracoid overlap and glenohumeral parameters for affected shoulders. On the contrary, all correlations between the coracoid and glenohumeral parameters for contralateral shoulders were only moderate or relatively low.</p> <p>Conclusions</p> <p>These results indicate that the spatial orientation of the coracoid process differs significantly between affected and contralateral shoulders, and it is highly correlated with the glenohumeral deformity. With the progression of glenohumeral deformity, the coracoid process protrudes more caudally and follows the subluxation of the humeral head which may interfere with the success of repositioning the posteriorly subluxed humeral head anteriorly to articulate with the glenoid properly.</p
Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays
We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using
360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector.
The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ)
charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which
the pions are from Rho0 decay. The latter case also encompasses exotic
interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho
hypotheses are compatible with our data. Since 3S1 is untenable on other
grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872).
Models for different J/Psi-Rho angular momenta L are considered. Flexibility in
the models, especially the introduction of Rho-Omega interference, enable good
descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let
Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA
Correlations between charged particles in deep inelastic ep scattering have
been studied in the Breit frame with the ZEUS detector at HERA using an
integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in
terms of the angular separation between current-region particles within a cone
centred around the virtual photon axis. Long-range correlations between the
current and target regions have also been measured. The data support
predictions for the scaling behaviour of the angular correlations at high Q2
and for anti-correlations between the current and target regions over a large
range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations
and Monte Carlo models correctly describe the trends of the data at high Q2,
but show quantitative discrepancies. The data show differences between the
correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C
Search for Pair Production of Scalar Top Quarks Decaying to a tau Lepton and a b Quark in ppbar Collisions at sqrt{s}=1.96 TeV
We search for pair production of supersymmetric top quarks (~t_1), followed
by R-parity violating decay ~t_1 -> tau b with a branching ratio beta, using
322 pb^-1 of ppbar collisions at sqrt{s}=1.96 TeV collected by the CDF II
detector at Fermilab. Two candidate events pass our final selection criteria,
consistent with the standard model expectation. We set upper limits on the
cross section sigma(~t_1 ~tbar_1)*beta^2 as a function of the stop mass
m(~t_1). Assuming beta=1, we set a 95% confidence level limit m(~t_1)>153
GeV/c^2. The limits are also applicable to the case of a third generation
scalar leptoquark (LQ_3) decaying LQ_3 -> tau b.Comment: 7 pages, 2 eps figure
Search for Higgs Boson Decaying to b-bbar and Produced in Association with W Bosons in p-pbar Collisions at sqrt{s}=1.96 TeV
We present a search for Higgs bosons decaying into b-bbar and produced in
association with W bosons in p-pbar collisions at sqrt{s}=1.96 TeV. This search
uses 320 pb-1 of the dataset accumulated by the upgraded Collider Detector at
Fermilab. Events are selected that have a high-transverse momentum electron or
muon, missing transverse energy, and two jets, one of which is consistent with
a hadronization of a b quark. Both the number of events and the dijet mass
distribution are consistent with standard model background expectations, and we
set 95% confidence level upper limits on the production cross section times
branching ratio for the Higgs boson or any new particle with similar decay
kinematics. These upper limits range from 10 pb for mH=110 GeV/c2 to 3 pb for
mH=150 GeV/c2.Comment: 7 pages, 3 figures; updated title to published versio
Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties
The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse
Double Diffraction Dissociation at the Fermilab Tevatron Collider
We present results from a measurement of double diffraction dissociation in
collisions at the Fermilab Tevatron collider. The production cross
section for events with a central pseudorapidity gap of width
(overlapping ) is found to be [] at [630]
GeV. Our results are compared with previous measurements and with predictions
based on Regge theory and factorization.Comment: 10 pages, 4 figures, using RevTeX. Submitted to Physical Review
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