Targeting colorectal cancer with human anti-EGFR monoclonocal antibodies: focus on panitumumab

The human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, panitumumab, represents a significant advance in the treatment of colorectal cancer. The strategy to target this receptor is based on sound cancer biology demonstrating its essential role in colorectal carcinogenesis. Panitumumab, unlike its predecessor, cetuximab, is fully human and thus reduces the incidence of hypersensitivity reactions. But, in several clinical trials, unexpected toxicities have become more apparent, raising concerns of how readily panitumumab can succeed cetuximab. This paper reviews the development of this agent and the pivotal clinical trials that help our understanding of its optimal use in colorectal cancer treatment

Trigeminal nerve morphology in the American alligator : implications for infering sensory potential in extinct species [abstract]

Among the many adaptations of modern crocodilians, one of the most intriguing is their derived sense of face touch, in which numerous trigeminal nerve-innervated dome pressure receptors speckle the face and mandible and sense vibrations and other mechanical stimuli, directing the animal towards, or away from stimuli. However, the morphological features of this system are not well known, and it remains unclear how aspects of the trigeminal system change during ontogeny and how they scale with other cranial and nervous structures

The Influence of Acoustic Impedance Mismatch on Post-Stenotic Pulsed-Doppler Ultrasound Measurements in a Coronary Artery Model

Acoustic impedance mismatch at the fluid-wall interface was shown to affect the spectra from an intravascular Doppler device in an in vitro model with a diameter typical of human coronary arteries. Measurements were obtained first under Poiseuille flow conditions with impedance mismatches of 0%, 7% and 12%, and then under stenosed conditions for the 0% and 7% mismatch cases. For the zero mismatch case, the Doppler spectra could be readily interpreted in terms of fluid mechanical phenomena. When mismatch was present, the spectra from Poiseuille flow exhibited multiple peaks which could not be directly related to the velocity profile. Also, the spectra from stenosed flow with a mismatch of 7% were similar to those from the zero mismatch case but did not exhibit the specific flow-related features as clearly. These results indicate that the impedance mismatch alters the acoustic environment inside the model and that this causes artifact in the Doppler spectra

Molecular Hydrodynamics: Vortex Formation and Sound Wave Propagation

In the present study, quantitative feasibility tests of the hydrodynamic description of a two-dimensional fluid at the molecular level are performed, both with respect to length and time scales. Using high-resolution fluid velocity data obtained from extensive molecular dynamics simulations, we computed the transverse and longitudinal components of the velocity field by the Helmholtz decomposition and compared them with those obtained from the linearized Navier-Stokes (LNS) equations with time-dependent transport coefficients. By investigating the vortex dynamics and the sound wave propagation in terms of these field components, we confirm the validity of the LNS description for times comparable to or larger than several mean collision times. The LNS description still reproduces the transverse velocity field accurately at smaller times, but it fails to predict characteristic patterns of molecular origin visible in the longitudinal velocity field. Based on these observations, we validate the main assumptions of the mode-coupling approach. The assumption that the velocity autocorrelation function can be expressed in terms of the fluid velocity field and the tagged particle distribution is found to be remarkably accurate even for times comparable to or smaller than the mean collision time. This suggests that the hydrodynamic-mode description remains valid down to the molecular scale

Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers

Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity

Transfer matrix method for interface optical-phonon modes in multiple-interface heterostructure systems

Interactions of carriers with interface optical phonons dominate over other carrier–phonon scatterings in narrow quantum-well structures. Herein, a transfer matrix method is used to establish a formalism for determining the dispersion relations, electrostatic potentials, and Fröhlich interaction Hamiltonians of the interface optical phonons for multiple-interface heterostructure systems within the framework of the macroscopic dielectric continuum model. This method facilitates systematic calculations for complex structures where the conventional method is very difficult to implement. Several specific cases are treated to illustrate the advantages of the general formalism. © 1997 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70863/2/JAPIAU-82-7-3363-1.pd

Phonon assisted intersubband transitions in step quantum well structures

We evaluate effects of heterointerfaces on optical phonon modes and phonon assisted electron intersubband transition rates in step quantum well structures for intersubband lasers. Various phonon modes and electron–phonon interaction Hamiltonians, including the interface modes, confined longitudinal-optical modes, and half space modes in the quantum well structures are calculated based on the macroscopic dielectric continuum model and microscopic analysis. The transfer matrix method is used to calculate the interface modes. The intersubband transition rates due to electron–phonon scattering by these phonon modes are evaluated using Fermi’s golden rule, with the electron wave functions obtained by solving the Schrödinger equation for the heterostructures under investigation. Our results show that, compared with the transition rates in the same structures calculated using the bulk phonon modes and the bulk Fröhlich interaction Hamiltonian, the electron interface–phonon interactions give significantly larger transition rates up to an order of magnitude. Therefore, the effects of localized phonon modes, especially the interface modes, must be taken into consideration for optimal device design. © 1998 American Institute of Physics.  Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71224/2/JAPIAU-84-4-2155-1.pd

Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserve

Asymptotically exact mean field theory for the Anderson model including double occupancy

The Anderson impurity model for finite values of the Coulomb repulsion $U$ is studied using a slave boson representation for the empty and doubly occupied $f$-level. In order to avoid well known problems with a naive mean field theory for the boson fields, we use the coherent state path integral representation to first integrate out the double occupancy slave bosons. The resulting effective action is linearized using {\bf two-time} auxiliary fields. After integration over the fermionic degrees of freedom one obtains an effective action suitable for a $1/N_f$-expansion. Concerning the constraint the same problem remains as in the infinite $U$ case. For $T \rightarrow 0$ and $N_f \rightarrow \infty$ exact results for the ground state properties are recovered in the saddle point approximation. Numerical solutions of the saddle point equations show that even in the spindegenerate case $N_f = 2$ the results are quite good.Comment: 19, RevTeX, cond-mat/930502