Measuring viscoelastic properties using compliant systems

An analysis of a novel indentation model has been implemented to obtain master curves describing the optimal experimental parameters necessary to achieve the highest possible accuracy in the determination of viscoelastic properties of soft materials. The indentation model is a rigid indenter driven by a compliant measurement system, such as an atomic force microscope or optical tweezers, into a viscoelastic half space. The viscoelastic material is described as a multiple relaxation Prony series. The results have been extended via an application of a viscoelastic equivalence principle to other physical models such as poroelasticity. Optimisation of the indentation parameters has been conducted over many orders of magnitude of the velocity, viscoelastic moduli, spring stiffness, relaxation times and the duration of indentation resulting in a characteristic master curve. It is shown that using sub-optimal conditions gives the appearance of a more elastic material than is actually the case. For a two term Prony series the ideal ramp duration was found to be approximately one eighth of the relaxation. Also the ideal ramp duration for a three term Prony series was determined and shown to guarantee distinct relaxation times under specific conditions

Quantum channels in nonlinear optical processes

Quantum electrodynamics furnishes a new type of representation for the characterisation of nonlinear optical processes. The treatment elicits the detailed role and interplay of specific quantum channels, information that is not afforded by other methods. Following an illustrative application to the case of Rayleigh scattering, the method is applied to second and third harmonic generation. Derivations are given of parameters that quantify the various quantum channels and their interferences; the results are illustrated graphically. With given examples, it is shown in some systems that optical nonlinearity owes its origin to an isolated channel, or a small group of channels. © 2009 World Scientific Publishing Company

Lake sedimentological and ecological response to hyperthermals : Boltysh impact crater, Ukraine

Acknowledgements Initial drilling of the Boltysh meteorite crater was funded by Natural Environment Research Council (NERC) grant NE/D005043/1. The authors are extremely grateful to the valuable scientific contributions of S. Kelley and I. Gilmour. The constructive and critical reviews by M. Schuster and an anonymous reviewer greatly helped to improve this manuscript.Peer reviewedPostprin

Clinical Guidelines Written by Residents

“Variation” is an innocent word that that can represent many levels of frustration to the clinician. Variation among patients is the least of these; the physician expects patients and their individual problems to be as diverse as the human race itself. Variation within a practice should be due to matching the specific needs of the specific patient. Other variations can mean trouble if they represent differences in understanding of the problem among clinicians and other allied health practitioners. These differences could be between institutions or even between shifts within one institution

On the interactions between molecules in an off-resonant laser beam:Evaluating the response to energy migration and optically induced pair forces

Electronically excited molecules interact with their neighbors differently from their ground-state counterparts. Any migration of the excitation between molecules can modify intermolecular forces, reflecting changes to a local potential energy landscape. It emerges that throughput off-resonant radiation can also produce significant additional effects. The context for the present analysis of the mechanisms is a range of chemical and physical processes that fundamentally depend on intermolecular interactions resulting from second and fourth-order electric-dipole couplings. The most familiar are static dipole-dipole interactions, resonance energy transfer (both second-order interactions), and dispersion forces (fourth order). For neighboring molecules subjected to off-resonant light, additional forms of intermolecular interaction arise in the fourth order, including radiation-induced energy transfer and optical binding. Here, in a quantum electrodynamical formulation, these phenomena are cast in a unified description that establishes their inter-relationship and connectivity at a fundamental level. Theory is then developed for systems in which the interplay of these forms of interaction can be readily identified and analyzed in terms of dynamical behavior. The results are potentially significant in Förster measurements of conformational change and in the operation of microelectromechanical and nanoelectromechanical devices. © 2009 American Institute of Physics

Closing in on the link between apoptosis and autophagy

While there is a clear connection between apoptosis and autophagy, the mechanisms that regulate the interaction have been difficult to identify. The initial clue to the link was the observation that Bcl-2 was located at the endoplasmic reticulum (ER), where it could prevent some forms of apoptosis and also bind to the autophagy regulatory protein Beclin-1. However, both of these enigmatic observations have been united with the discovery of the nutrient-deprivation autophagy factor-1 (NAF-1) protein. As an ER-localized protein that enhances the interaction of Bcl-2 and Beclin-1 and that also binds to the pro-apoptotic protein Bik, NAF-1 is perfectly placed to be a central regulator of the switch between autophagy and apoptosis

Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line

We demonstrated that a subclone of an Abelson murine leukemia virus-transformed B-lymphoid cell line switched from mu to gamma 2b expression in vitro, by the classical recombination-deletion mechanism. In this line, the expressed VHDJH region and the C gamma 2b constant region gene were juxtaposed by a recombination event which linked the highly repetitive portions of the S mu and S gama 2b regions and resulted in the loss of the C mu gene from the intervening region. An additional recombination event in this subclone involved an internal deletion in the S mu region of the expressed (switched) allele. One end of this deletion occurred very close to the switch recombination point. Despite the recombination-deletion mechanism of switching, the gamma 2b-producing line retained two copies of the C mu gene and two copies of the sequence just 5' to the S gamma 2b recombination point. The possible significance of the retention of these sequences to the mechanism of class switching is discussed

Removing bias against membrane proteins in interaction networks

<p>Abstract</p> <p>Background</p> <p>Cellular interaction networks can be used to analyze the effects on cell signaling and other functional consequences of perturbations to cellular physiology. Thus, several methods have been used to reconstitute interaction networks from multiple published datasets. However, the structure and performance of these networks depends on both the quality and the unbiased nature of the original data. Due to the inherent bias against membrane proteins in protein-protein interaction (PPI) data, interaction networks can be compromised particularly if they are to be used in conjunction with drug screening efforts, since most drug-targets are membrane proteins.</p> <p>Results</p> <p>To overcome the experimental bias against PPIs involving membrane-associated proteins we used a probabilistic approach based on a hypergeometric distribution followed by logistic regression to simultaneously optimize the weights of different sources of interaction data. The resulting less biased genome-scale network constructed for the budding yeast <it>Saccharomyces cerevisiae </it>revealed that the starvation pathway is a distinct subnetwork of autophagy and retrieved a more integrated network of unfolded protein response genes. We also observed that the centrality-lethality rule depends on the content of membrane proteins in networks.</p> <p>Conclusions</p> <p>We show here that the bias against membrane proteins can and should be corrected in order to have a better representation of the interactions and topological properties of protein interaction networks.</p

Phase 1 Trial of Vaccination with Autologous Tumor Cells and Antisense Directed Against the Insulin Growth Factor Type 1 Receptor (IGF-1R AS ODN) in Patients with Recurrent Glioblastoma

Background: Extending a previous Phase I study, we report the results of a second Phase I autologous tumor cell vaccination trial for patients with recurrent glioblastomas (IND 14379-101, NCT01550523). Methods: Following surgery, subjects were treated by 24 hour implantation in the rectus sheath of ten biodiffusion chambers containing irradiated autologous tumor cells and IGF-1R AS ODN with the objective of stimulating tumor immunity. Patients were monitored for safety, clinical and radiographic as well as immune responses. Results: There were no Grade 3 toxicities related to protocol treatment and overall median survival from initial diagnosis was 91.4 weeks. Two protocol survival cohorts with median survivals of 48.2 and 10 weeks were identified and predicted by our pre-treatment assessments of immune function, corroborated by post-vaccination pro-inflammatory cytokine profiles. Longer survival subjects had imaging findings including transient elevations in cerebral blood volume (rCBV) and sustained elevations of apparent diffusion coefficient (ADC) interpreted as transient hyperemia and cell loss. Conclusions: The vaccine paradigm was well-tolerated with a favorable median survival. Our data support this as a novel treatment paradigm that promotes anti-tumor immunity