Virtual Testing of Experimental Continuation

We present a critical advance in experimental testing of nonlinear structures. Traditional quasi-static experimental methods control the displacement or force at one or more load-introduction points on a structure. This approach is unable to traverse limit points in the control parameter, as the immediate equilibrium beyond these points is statically unstable, causing the structure to snap to another equilibrium. As a result, unstable equilibria---observed numerically---are yet to be verified experimentally. Based on previous experimental work, and a virtual testing environment developed herein, we propose a new experimental continuation method that can path-follow along unstable equilibria and traverse limit points. To support these developments, we provide insightful analogies between a fundamental building block of our technique---shape control---and analysis concepts such as the principle of virtual work and Galerkin's method. The proposed testing method will enable the validation of an emerging class of nonlinear structures that exploit instabilities for novel functionality

Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies

AA amyloidosis results from the pathologic deposition in the kidneys and other organs of fibrils composed of N-terminal fragments of serum amyloid A protein (SAA). Given that there are only limited means to visualize these deposits, we have developed a series of mAbs, 2A4, 7D8, and 8G9, that bind specifically with nanomolar affinity to a carboxy-terminal epitope generated following proteolysis of SAA that yields the predominant component of AA amyloid deposits. Notably, these antibodies do not recognize native SAA, they retain their immunoreactivity when radiolabeled with I-125 and, after injection into AA amyloidotic mice, localize, as evidenced by autoradiography and micro-single photon emission computed tomography imaging, to histologically confirmed areas of amyloid deposition; namely, spleen, liver, and pancreas. The results of our in vitro and in vivo studies demonstrate the AA fibril-selectivity of mAbs 2A4, 7D8, and 8G9 and warrant further investigation into their role as novel diagnostic agents for patients with AA amyloidosis

La villa des « Vernes » à La Boisse (Ain) : contribution des fouilles récentes à la compréhensionde l’évolution d’un établissement rural antique et de son espace funéraire

Dans le cadre de l’aménagement d’un diffuseur autoroutier sur la commune de La Boisse (Ain), à une vingtaine de kilomètres au nord-est de Lyon, une opération d’archéologie préventive, réalisée en 2005-2006, a permis d’enrichir la documentation d’une villa du Ier s. après J.-C. Si une partie de cet établissement avait déjà été explorée en 1980 lors de la construction de l’autoroute A42, la fouille a permis de compléter le plan de la pars urbana, et surtout de préciser la datation de l’occupation gallo-romaine. Cette villa de plan classique n’est en effet pas une création ex nihilo ; elle a succédé à deux ensembles architecturaux antérieurs, caractérisés par des constructions en terre et bois. La villa a été abandonnée à l’extrême fin du Ier s. ap. J.-C. ou au début du siècle suivant. Deux structures isolées à caractère funéraire qui, par leur richesse, constituent un unicum régional, sont aussi datées de cette période.As part of the construction of a motorway interchange in the municipality of La Boisse (Ain), about twenty kilometres north-east of Lyon, a preventive archaeology project carried out in 2005–2006 furnished additional information about a villa built in the 1st century AD. Whereas a section of the site had already been explored during the construction of the A42 motorway, the latter excavation not only enabled the plan of the pars urbana to be completed and, above all, it allowed the dating of the Gallo-Roman occupation to be made with precision. This classically laid out villa was not an ex nihiloconstruction: it had been built over two earlier sets of architectural buildings made from wood and mud. The villa was abandoned at the extreme end of the 1st century AD or at the start of the following century. Two isolated, apparently funerary structures – which, through the wealth of their contents, are unique for the region – have also been dated to the same period.Im Rahmen des Baus eines Autobahnverteilers auf dem Gebiet der Gemeinde La Boisse (Departement Ain) etwa 20 km nordöstlich von Lyon, konnte durch eine 2005-2006 durchgeführte Präventivgrabung die Dokumentation einer villa des 1. Jh. n. Chr. bereichert werden. Ein Teil dieses Areals war bereits 1980 anlässlich des Baus der Autobahn A42 erforscht worden, doch die neue Grabung bot Gelegenheit, den Grundriss der pars urbana zu ergänzen, und vor allem die Datierung der gallo-römischen Phase zu präzisieren. Diese villa mit klassischem Grundriss war in der Tat keine Gründung ex nihilo ; sondern sie folgte auf zwei Vorgängerbauten in Holz-Erde-Bauweise. Die villa wurde Ende des 1. Jh. n. Chr. oder Anfang des folgenden Jahrhunderts aufgegeben. Zwei isolierte Grabstrukturen, deren Reichtum in der Region einzig ist, werden ebenfalls in diese Zeit datiert

Nucleoside analogue activators of cyclic AMP-independent protein kinase A of Trypanosoma

Protein kinase A (PKA), the main effector of cAMP in eukaryotes, is a paradigm for the mechanisms of ligand-dependent and allosteric regulation in signalling. Here we report the orthologous but cAMP-independent PKA of the protozoan Trypanosoma and identify 7-deazanucleosides as potent activators (EC50 >= 6.5 nM) and high affinity ligands (K-D >= 8 nM). A co-crystal structure of trypanosome PKA with 7-cyano-7-deazainosine and molecular docking show how substitution of key amino acids in both CNB domains of the regulatory subunit and its unique C-terminal alpha D helix account for this ligand swap between trypanosome PKA and canonical cAMP-dependent PKAs. We propose nucleoside-related endogenous activators of Trypanosoma brucei PKA (TbPKA). The existence of eukaryotic CNB domains not associated with binding of cyclic nucleotides suggests that orphan CNB domains in other eukaryotes may bind undiscovered signalling molecules. Phosphoproteome analysis validates 7-cyano-7-deazainosine as powerful cell-permeable inducer to explore cAMP-independent PKA signalling in medically important neglected pathogens

Free surface flows emerging from beneath a semi-infinite plate with constant vorticity

The free surface flow past a semi-infinite horizontal plate in a finite-depth fluid is considered. It is assumed that the fluid is incompressible and inviscid and that the flow approaches a uniform shear flow downstream. Exact relations are derived using conservation of mass and momentum for the case where the downstream free surface is flat. The complete nonlinear problem is solved numerically using a boundary integral method and these waveless solutions are shown to exist only when the height of the plate above the bottom is greater than the height of the uniform shear flow. Interesting results are found for various values of the constant vorticity. Solutions with downstream surface waves are also considered, and nonlinear results of this type are compared with linear results found previously. These solutions can be used to model the flow near the stern of a (two-dimensional) ship