Dose-related effects of Ampligen (poly(I).poly(C12U)), a mismatched double-stranded RNA, in a bleomycin-mouse model of pulmonary fibrosis

The antifibrotic effect of the mismatched double-stranded RNA, Ampligen (poly(I).poly(C12U)), was evaluated in a bleomycin-mouse model of pulmonary fibrosis. Mice received a single intratracheal dose of bleomycin (0.125 U/mouse) or saline (50 microL) at the beginning of the experiment, followed by 5 or 6 intraperitoneal injections of Ampligen (1.0, 5.0, 10.0, 15.0, or 25.0 mg/kg) or saline at regular intervals for 2 weeks. Ampligen did not produce increased mortality or weight loss by itself. However, it produced varying degrees of mortality in combination with bleomycin. Five injections of 10 mg/kg Ampligen or three injections of 25 mg/kg Ampligen plus three injections of 10 mg/kg Ampligen in combination with bleomycin .produced significant reductions in lung collagen accumulation as indicated by lung hydroxyproline content compared to the bleomycin control group. Animals receiving bleomycin plus Ampligen at all dosages had significantly reduced prolyl hydroxylase activity compared to the bleomycin control group. Lipid peroxidation and bronchoalveolar lavage fluid (BALF)-supernatant protein content for the groups receiving bleomycin plus Ampligen were not reduced compared to the bleomycin control group. In the BALF-supernatant, the activity of acid phosphatase, a lysosomal enzyme produced by neutrophils, monocytes, and macrophages, was significantly decreased in the group receiving bleomycin plus 10 mg/kg Ampligen. Also, selected BALF differential immune cell counts were reduced in some of the groups receiving bleomycin plus Ampligen, but not in a consistent or dose-dependent manner. The results of this study indicate that Ampligen can significantly reduce the bleomycin-induced increased collagen accumulation and may be therapeutically useful in the management of lung fibrosis in humans.     

Temperature-regulated expression of the tac/lacl system for overproduction of a fungal xylanase in Escherichia coli

Temperature-regulated expression of recombinant proteins in the tac promoter (Ptac) system was investigated. Expression levels of fungal xylanase and cellulase from N. patriciarum in E. coli strains containing the natural lacI gene under the control of the Ptac markedly increased with increasing cultivation temperature in the absence of a chemical inducer. The specific activities (units per milligram protein of crude enzyme) of the fungal xylanase and cellulase produced from recombinant E. coli strain pop2136 grown at 42 degrees C were about 4.5 times higher than those of the cells grown at 23 degrees C and were even slightly higher when compared with cells grown in the presence of the inducer isopropyl beta-D-thiogalactopyranoside. The xylanase expression level in the temperature-regulated Ptac system was about 35% of total cellular protein. However, this system can not be applied to E. coli strains containing lacIq, which confers over production of the lac repressor, for high-level expression of recombinant proteins. In comparison with the lambda PL system, the Ptac-based xylanase plasmid in E. coli pop2136 gave a considerably higher specific activity of the xylanase than did the best lambda PL-based construct using the same thermal induction procedure. The high-level expression of the xylanase using the temperature-regulated Ptac system was also obtained in 10-litre fermentation studies using a fed-batch process. These results unambiguously demonstrated that the temperature-modulated Ptac system can be used for overproduction of some non-toxic recombinant proteins.     

Switching to Directional Antennas with Constant Increase in Radius and Hop Distance

For any angle α<2π, we show that any connected communication graph that is induced by a set P of n transceivers using omni-directional antennas of radius 1, can be replaced by a strongly connected communication graph, in which each transceiver in P is equipped with a directional antenna of angle α and radius r _dir, for some constant r _dir=r _dir(α). Moreover, the new communication graph is a c-spanner of the original graph, for some constant c=c(α), with respect to number of hops.     

Perceiving,learning, and exploiting object affordances for autonomous pile manipulation

Autonomous manipulation in unstructured environments will enable a large variety of exciting and important applications. Despite its promise, autonomous manipulation remains largely unsolved. Even the most rudimentary manipulation task—such as removing objects from a pile—remains challenging for robots. We identify three major challenges that must be addressed to enable autonomous manipulation: object segmentation, action selection, and motion generation. These challenges become more pronounced when unknown man-made or natural objects are cluttered together in a pile. We present a system capable of manipulating unknown objects in such an environment. Our robot is tasked with clearing a table by removing objects from a pile and placing them into a bin. To that end, we address the three aforementioned challenges. Our robot perceives the environment with an RGB-D sensor, segmenting the pile into object hypotheses using non-parametric surface models. Our system then computes the affordances of each object, and selects the best affordance and its associated action to execute. Finally, our robot instantiates the proper compliant motion primitive to safely execute the desired action. For efficient and reliable action selection, we developed a framework for supervised learning of manipulation expertise. To verify the performance of our system, we conducted dozens of trials and report on several hours of experiments involving more than 1,500 interactions. The results show that our learning-based approach for pile manipulation outperforms a common sense heuristic as well as a random strategy, and is on par with human action selection.     

A Thermo-Mechanical Study of Some Epoxy Adhesives Subjected to Combined Dynamic and Static Stresses

The object of the present study was to investigate the effect of superimposed dynamic and static stresses on mechanical and thermal properties of some epoxy adhesives. It was found that combinations of shear creep and torsional oscillations, applied simultaneously to adhesive joints at temperatures within the glassy range of the adhesive, led to strengthening of the joints in shear and to an increase in the glass transition temperature of the adhesive. Similar loading stresses applied at temperatures close to the T_g of the adhesive, led to opposite effects on the above mentioned properties of the joints. The width of the glassy-rubbery transition of the adhesives increased, in the whole range of temperatures used in this study and for all epoxy compositions, as a result of subjecting the joints to superimposed dynamic and static stresses. The broadening of the glass transition was interpreted as a result of the stiffening of polymer network during the combined stressing experiments. A linear relationship was found between the area of endothermal peaks in the first DSC scan of specimens subjected prior to test to superimposed dynamic and static stresses at temperatures below T_g, and the shear strength of the joints. In agreement with this observation and with literature data, a linear relationship was revealed also between the glass transition temperature of the resins (measured in the first DSC scan) and the shear strength of the joints. Based on experimental observations and on some literature information, it was suggested that the strengthening of the joint, as well as the changes in thermal properties of the adhesives, are mainly due to physical processes, such as short-range orientation of network chains and an increase in intermolecular interaction between highly polar sites of the network. The possibility that superimposed stressing led to changes in chemical crosslinking was discussed but it seems that no such reactions occurred.     

Optimally Adaptive Integration of Univariate Lipschitz Functions

We consider the problem of approximately integrating a Lipschitz function f (with a known Lipschitz constant) over an interval. The goal is to achieve an additive error of at most ε using as few samples of f as possible. We use the adaptive framework: on all problem instances an adaptive algorithm should perform almost as well as the best possible algorithm tuned for the particular problem instance. We distinguish between and , the performances of the best possible deterministic and randomized algorithms, respectively. We give a deterministic algorithm that uses samples and show that an asymptotically better algorithm is impossible. However, any deterministic algorithm requires samples on some problem instance. By combining a deterministic adaptive algorithm and Monte Carlo sampling with variance reduction, we give an algorithm that uses at most samples. We also show that any algorithm requires samples in expectation on some problem instance (f,ε), which proves that our algorithm is optimal.     

Multisensory VR interaction for protein-docking in the CoRSAIRe project

Proteins take on their function in the cell by interacting with other proteins or biomolecular complexes. To study this process, computational methods, collectively named protein docking, are used to predict the position and orientation of a protein ligand when it is bound to a protein receptor or enzyme, taking into account chemical or physical criteria. This process is intensively studied to discover new biological functions for proteins and to better understand how these macromolecules take on these functions at the molecular scale. Pharmaceutical research also employs docking techniques for a variety of purposes, most notably in the virtual screening of large databases of available chemicals to select likely molecular candidates for drug design. The basic hypothesis of our work is that Virtual Reality (VR) and multimodal interaction can increase efficiency in reaching and analysing docking solutions, in addition to fully a computational docking approach. To this end, we conducted an ergonomic analysis of the protein–protein current docking task as it is carried out today. Using these results, we designed an immersive and multimodal application where VR devices, such as the three-dimensional mouse and haptic devices, are used to interactively manipulate two proteins to explore possible docking solutions. During this exploration, visual, audio, and haptic feedbacks are combined to render and evaluate chemical or physical properties of the current docking configuration.     

Striate cortex extracts higher-order spatial correlations from visual textures

Spatial correlations define the statistical structure of any visual image. Two-point correlations inform the visual system about the spatial frequency content of an image. Higher-order correlations can capture salient features such as object contours. We studied "isodipole" texture discrimination in V1 to determine if higher-order spatial correlations can be extracted by early stages of cortical processing. We made epicortical, local field potential, and single-cell recordings of responses elicited by isodipole texture interchange in anesthetized monkeys. Our studies demonstrate that single neurons in V1 can signal the presence of higher-order spatial correlations in visual textures. This places a computational mechanism, which may be essential for form vision at the earliest stage of cortical processing.     

Neutrophil apoptosis is associated with a reduction in CD16 (Fc gamma RIII) expression

Resolution of inflammation involves removal of recruited neutrophils from inflamed sites via a noninflammatory mechanism, possibly involving neutrophil apoptosis and engulfment/phagocytosis by macrophages. In this study, we describe the reduction in surface expression (> 90%) of the neutrophil molecule Fc gamma RIII (CD16) during in vitro culture at 37 degrees C, which was found to be temporally associated with the appearance of neutrophils with apoptotic morphology during in vitro culture and inhibitable by granulocyte-macrophage colony-stimulating factor (GM-CSF), which postpones apoptosis in the neutrophil. By using dual fluorescence analysis, CD16 "low" expressing neutrophils showed reduced staining with the DNA-binding dye propidium iodide, suggesting that CD16 low expressing neutrophils were apoptotic. Separation of CD16 "high" and CD16 "low" expressing neutrophils by fluorescence-activated cell sorting revealed that morphologically apoptotic cells exhibited the CD16 low phenotype. We did not observe similar marked changes in expression of other neutrophil surface molecules (including other phosphatidylinositol (PI)-linked molecules), indicating that generalized loss of surface molecules does not occur during apoptosis. We believe this to be the first reported cell type-specific membrane alteration in a surface glycoprotein associated with apoptosis, suggesting that the program of cell death in the neutrophil, in addition to morphologic and nuclear changes, includes alterations in expression of surface receptors.