Structural basis of the effect of activating mutations on the EGF receptor

Mutations within the kinase domain of the epidermal growth factor receptor (EGFR) are common oncogenic driver events in non-small cell lung cancer. Although the activation of EGFR in normal cells is primarily driven by growth-factor-binding-induced dimerization, mutations on different exons of the kinase domain of the receptor have been found to affect the equilibrium between its active and inactive conformations giving rise to growth-factor-independent kinase activation. Using molecular dynamics simulations combined with enhanced sampling techniques, we compare here the conformational landscape of the monomers and homodimers of the wild-type and mutated forms of EGFR ΔELREA and L858R, as well as of two exon 20 insertions, D770-N771insNPG, and A763-Y764insFQEA. The differences in the conformational energy landscapes are consistent with multiple mechanisms of action including the regulation of the hinge motion, the stabilization of the dimeric interface, and local unfolding transitions. Overall, a combination of different effects is caused by the mutations and leads to the observed aberrant signaling

Hidden local symmetry and color confinement

The hidden local symmetry is a successful model to describe the properties of the vector mesons in QCD. We point out that if we identify this hidden gauge theory as the magnetic picture of QCD, a linearized version of the model simultaneously describes color confinement and chiral symmetry breaking. We demonstrate that such a structure can be seen in the Seiberg dual picture of a softly broken supersymmetric QCD. The model possesses exact chiral symmetry and reduces to QCD when mass parameters are taken to be large. Working in the regime of the small mass parameters, we show that there is a vacuum where chiral symmetry is spontaneously broken and simultaneously the magnetic gauge group is Higgsed. If the vacuum we find persists in the limit of large mass parameters, one can identify the rho meson as the massive magnetic gauge boson, that is an essential ingredient for color confinement.Comment: 20 pages, 3 figure

RF plasma cleaning of optical surfaces: A study of cleaning rates on different carbon allotropes as a function of RF powers and distances

An extended study on an advanced method for the cleaning of carbon contaminations on large optical surfaces using a remote inductively coupled low pressure RF plasma source (GV10x downstream asher) is reported in this work. Technical as well as scientific features of this scaled up cleaning process are analyzed, such as the cleaning efficiency for different carbon allotropes (amorphous and diamond-like carbon) as a function of feedstock gas composition, RF power (ranging from 30 to 300W), and source-object distances (415 to 840 mm). The underlying physical phenomena for these functional dependences are discussed.Comment: 16 pages, 9 figure

Neutralino spin measurement with ATLAS detector at LHC

Minimal Supergravity (mSUGRA) [1] Supersimmetry breaking mechanism is a leading candidate for yielding new physics beyond the Standard Model (SM). Within mSUGRA framework masses, mixings and decays of all SUSY and Higgs particles are determined in terms of four input parameters and a sign: the common mass m 0 of scalar particles at the grand unification scale, the common fermion mass m 1/2, the common trilinear coupling A 0, the ratio of the Higgs vacuum expectation values tan β and the sign of the supersymmetric Higgs mass parameter μ. Once a signal of a physics beyond the Standard Model is seen at LHC, it will be fundamental to measure properties of new particles, like spin, in order to prove that they are indeed supersymmetric partners. The present work [2] is based on the spin analysis method proposed in [3] and allows the discrimination of different hypotheses for spin assignments. Some studies [4, 5] show that this method can also be used for the discrimination of SUSY from an Universal Extra Dimensions model which can mimick low energy SUSY at hadron colliders. In this report two selected points inside stau-coannihilation and bulk regions of the allowed mSUGRA parameter space are considered. Fast simulation [6] of the ATLAS detector was performed in order to investigate the feasibility of supersymmetric particles’ spin measurement

Study of second lightest neutralino spin measurement with ATLAS detector at LHC

One of the goals of the ATLAS experiment at the CERN Large Hadron Collider is to search for evidence of Supersymmetry (SUSY) signals. If SUSY would be discovered, it will be fundamental to measure the spin of the new particles in order to prove that they are indeed supersymmetric partners. Left-handed squark cascade decay to second lightest neutralino which further decays to slepton can represent a good opportunity for SUSY particles' spin measurement. Assuming the neutralino spin to be 1/2, the invariant mass distributions of some detectable final products of the reactions have to be charge asymmetric. In the present work the detectability of this charge asymmetry is analysed in the stau-coannihilation region and in the bulk region of the minimal Supergravity parameter space allowed by the latest experimental constraints. The criteria used to isolate the decay chain of interest and to reject the background, coming from both Standard Model and different SUSY decay channels, are described as obtained by suitable optimizations on Monte Carlo samples produced with the ATLAS fast simulation. The estimates of the residual contributions to background and of the applied cut efficiencies are presented. Results on charge asymmetry are then shown and discussed

Combination Therapy of Brain Natriuretic Peptide and Sildenafil Attenuates Pulmonary Hypertension in Rats [abstract]

Abstract only availableFaculty Mentor: Dr. Vincent DeMarco, Child HealthBackground: Pulmonary arterial hypertension (PAH) is a lethal disease characterized by changes in pulmonary vascular structure and function. We tested the hypothesis that Sildenafil, a phosphodiesterase 5 inhibitor, and brain natriuretic peptide (BNP), a guanosine cyclase stimulator, in combination synergistically attenuates PAH when compared to individual therapy in rats through different mechanisms to increase cGMP while minimizing systemic side effects. Methods: Adult male Sprague-Dawley rats were subcutaneously injected with monocrotaline (n=30, 50 mg/kg). After approximately 5 weeks, rats were anesthetized and instrumented to measure systemic pressure (MAP) and right ventricular systolic pressure (RVSP) during infusions of vehicle solution (n=5), intravenous Sildenafil (84 mg/kg/min; n=8), and intravenous BNP (100 ng/kg/min; n=7) alone and a combination of Sildenafil and BNP (n=10). Results: Sildenafil alone decreased RVSP (-17 ±13.2 mmHg) and had a relatively minimal effect on MAP (-4±9.9 mmHg). BNP decreased RVSP (-19±14 mmHg) but also significantly effected MAP (-11±15.3mmHg). Combination therapy with Sildenafil and BNP lowered RVSP (-20±18.7 mmHg), however it also induced the greatest systemic hypotensive effect (MAP = -19±9.9 mmHg). Conclusion: The combination of Sildenafil and BNP, at these doses, significantly attenuates monocrotaline-induced pulmonary hypertension. However, compared with individual treatment, there is no significant difference in effect on RVSP. Furthermore, additive systemic side effects are too significant to consider combination therapy safe. With a different dosing regime, this combination is a potentially viable option in the treatment of patients with PAH

Comments on orientifold projection in the conifold and SO x USp duality cascade

We study the O3-plane in the conifold. On the D3-brane world-volume we obtain SO x USp gauge theory that exhibits a duality cascade phenomenon. The orientifold projection is determined on the type IIB string side, and corresponds to that of O4-plane on the dual type IIA side. We show that SUGRA solutions of Klebanov-Tseytlin and Klebanov-Strassler survive under the projection. We also investigate the orientifold projection in the generalized conifolds, and verify desired features of the O4-projection in the type IIA picture.Comment: 1+27 pages, 9 figures, references added; version to appear in Phys. Rev.

European Headache Federation recommendations for placebo and nocebo terminology

Background and aim Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. Methods The working group identified relevant questions and agreed upon recommendations. Because no data were required to ans

Productivity and convergence in European agriculture

In the paper we investigate relative productivity levels and decompose productivity change for European agriculture between 2004 and 2013. More specifically (1) we contribute to the debate whether agricultural Total Factor Productivity (TFP) has declined or not in the European Union (EU); (2) we compare the relative TFP level across EU member states and investigate the difference between 'old' member states (OMS, i.e. the EU-15) and 'new' member states (NMS) and (3) we test whether TFP is converging or not among member states. The empirical analysis applies the aggregate quantity framework developed in O'Donnell (2008), using country level panel data from the Economic Accounts for Agriculture for 23 EU member states. The results imply that TFP has slightly decreased in the EU over the analysed period; however there are significant differences in this respect between the OMS and NMS and across member states. Finally, our estimations support the productivity convergence hypothesis across the member states