Autoantibodies to the insulin receptor. Effect on the insulin-receptor interaction in IM-9 lymphocytes

The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of (125)I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins. The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as unique probes of insulin receptor structure and function.     

Experimental automobile-pedestrian injuries

Fifteen fresh cadaver impacts were conducted in simulation of pedestrian-automobile accidents. The test sled configuration simulated an automobile bumper and hood in "standard" and "nosedive" situations as well as "hard" and "soft" impact surfaces. Instrumentation and film demonstrated large axial compression forces in the struck leg and considerable angular velocity of the torso in all modes. Dissection revealed primary injury at the impact site at low velocities with added remote injury at high velocities. Fracture of the lateral tibial plateau was most common. Lowering the bumper height offered the greatest protection against injury at moderate impact velocities.     

Project proposal for the investigation of particle-stabilised emulsions and foams by microgravity experiments

The utilisation of particle-surfactants nanostructures as stabilising agents represents today the technologic and scientific frontier in the stabilisation of liquid films in emulsion and foams. This topic will be addressed by the proposal STEFAN (STabilisation of Emulsions and FoAms by Nanoparticles), proposed by European groups in the framework of the ESA AO-2004 for Life and Physical Sciences and Applied Research projects Similarly to what can be observed for surfactant-stabilised emulsions and foams, microgravity provides ideal conditions for the investigation of the hierarchy of involved objects: interfacial layer, liquid film, dispersed systems foam or emulsion. Microgravity experiments are planned by refurbishing the Experimental Container FASES for the ISS Fluid Science Laboratory and the facility FASTER for the European Drawer Rack, already under development in existing research programmes. Here the scientific guidelines of the project are presented together with examples and preliminary results on the effect of nano-particle-surfactant structures adsorbed at liquid interfaces. First experimental results have been achieved for particle monolayers at the water/air interface and a thermodynamic model was derived to describe the obtained surface pressure-area isotherms.     

Rheological studies with spherically shaped thin liquid films

The present work shows the first experimental and theoretical results for investigations on the rheology of liquid films. The experiments are planned to be performed under microgravity conditions. This environment will allow forming films of different thickness, which is impossible under ground conditions due to drainage. Then the films are forced to harmonic oscillations of the film area so that the film elasticity can be measured as a function of frequency. The presented theoretical model demonstrates the main relationships to be solved under corresponding boundary conditions     

Automatic multiscale meshing through HRBF networks

A procedure for the real-time construction of three-dimensional (3-D) multiscale meshes from not evenly sampled 3-D points is described and discussed in this paper. The process is based on the connectionist model named hierarchical radial basis functions network (HRBF), which has been proved effective in the reconstruction of smooth surfaces from sparse noisy data points. The network goal is to achieve a uniform reconstruction error, equal to measurement error, by stacking noncomplete grids of Gaussians at decreasing scales. It is shown here how the HRBF properties can be used to develop a configuration algorithm, which produces a continuous surface in real time. In addition, the model is extended to automatically convert the continuous surface into a 3-D mesh according to an adequate error measure.     

Surface Segregation Mechanisms in Ferroelectric Thin Films

Reliability issues have hampered the adoption of ferroelectric thin films by the microelectronics industry. One of these is imprint, an important problem affecting the performance of ferroelectric non-volatile memories. This paper presents the effects of the low temperature pyrolysis step on the chemical and physical properties of SrBi₂Ta₂O₉ films. A comparison of the hysteretic properties and composition profiles shows that control of the oxidising conditions during pyrolysis is critical to the dielectric properties. Data from this work and from the literature have been used to construct a model that explains the origin of surface depletion and segregation, self poling and as-grown imprint in ferroelectric films.     

Multirobot motion coordination in space and time

This paper describes a solution to the multirobot motion planning problem based on a decoupled analysis in the space domain and in the time domain. It investigates the practical use of the notion of motion plan quality and of the motion plan robustness measures for computing safe motions. The use of anytime algorithms allows one to evaluate the opportunity of looking for alternative solution paths by generating small variations of robot motions affecting both its geometrical path and its scheduled velocity. By using the concept of plan robustness, several alternative paths are generated and evaluated through various performance indices and impact factors, using heuristic rules. These indices allow one to know how much a variation affects a given plan. Finally, some recent experiments are outlined.     

Multiscale approximation with hierarchical radial basis functions networks

An approximating neural model, called hierarchical radial basis function (HRBF) network, is presented here. This is a self-organizing (by growing) multiscale version of a radial basis function (RBF) network. It is constituted of hierarchical layers, each containing a Gaussian grid at a decreasing scale. The grids are not completely filled, but units are inserted only where the local error is over threshold. This guarantees a uniform residual error and the allocation of more units with smaller scales where the data contain higher frequencies. Only local operations, which do not require any iteration on the data, are required; this allows to construct the network in quasi-real time. Through harmonic analysis, it is demonstrated that, although a HRBF cannot be reduced to a traditional wavelet-based multiresolution analysis (MRA), it does employ Riesz bases and enjoys asymptotic approximation properties for a very large class of functions. HRBF networks have been extensively applied to the reconstruction of three-dimensional (3-13) models from noisy range data. The results illustrate their power in denoising the original data, obtaining an effective multiscale reconstruction of better quality than that obtained by MRA.     

Pleurotusostreatus and Agaricus subrufescens: investigation of chemical composition and antioxidant properties of these mushrooms cultivated with different handmade and commercial supplements

In this study, the chemical composition, total phenolic content and antioxidant activity (DPPH, ORAC and FRAP assays) of A. subrufescens and P. ostreatus, cultivated with handmade and commercials supplements, were compared. Additionally, the compounds ergosterol, saccharopine, and hexitol were identified in A. subrufescens by HPLC-MS/MS. The antioxidant compound p-coumaric acid and dihexoses was found in both mushroom species. A. subrufescens presented higher total phenolic content (73.8 ± 0.6 mg GAE 100 g⁻¹) and antioxidant activity than P. ostreatus (16.6 ± 0.5 mg GAE 100 g⁻¹). The handmade supplement based on the waste of noble grains presented statistically similar phenolic content to the mushrooms cultivated with commercial ones Spawn Mate II SE (86.1 ± 1.4 and 92.9 ± 0.3 mg GAE 100 g⁻¹, respectively). Therefore, the results support the use of handmade supplements based on agro-wastes as a viable alternative to the use of high-cost commercial ones.     

Intrinsic Fluorescence of the Active and the Inactive Functional Forms of Human Thymidylate Synthase

The observables associated with protein intrinsic fluorescence – spectra, time decays, anisotropies – offer opportunities to monitor in real time and non-invasively a protein‘s functional form and its interchange with other forms with different functions. We employed these observables to sketch the fluorometric profiles of two functional forms of human thymidylate synthase (hTS), a homodimeric enzyme crucial for cell proliferation and thus targeted by anticancer drugs. The protein takes an active and an inactive form. Stabilization of the latter by peptides that, unlike classical hTS inhibitors, bind it at the monomer/monomer interface offers an alternative inhibition mechanism that promises to avoid the onset of drug resistance in anticancer therapy. The fluorescence features depicted herein can be used as tools to identify and quantify each of the two protein forms in solution, thus making it possible to investigate the kinetic and thermodynamic aspects of the active/inactive conformational interchange. Two examples of fluorometrically monitored interconversion kinetics are provided.