Mechanisms of clostridial toxin binding and translocation

The bacterial genus Clostridium consists of over 150 species of anaerobic, fermentative, spore-forming bacilli. Clostridial species produce up to 20% of all known bacterial exotoxins, which serve as important virulence factors in the 10% of clostridial species that are highly pathogenic. The seven serotypes of botulinum neurotoxin (BoNTs A-G) and tetanus neurotoxin (TeNT) are the causative agents of the paralytic diseases botulism and tetanus, respectively. Entry of toxins into neurons is mediated through initial interactions with gangliosides, followed by binding to a protein co-receptor. Herein we aimed to understand the mechanism through which individual neurotoxins recognize the carbohydrate motif of gangliosides. Using cell-based and in vitro binding assays, in conjunction with structure-driven site-directed mutagenesis, a conserved hydrophobic residue within the BoNTs that contributes to both affinity and specificity towards Sia5-containing gangliosides was identified. We demonstrate that targeted mutations within the Sia5 binding pocket result in the generation of neurotoxins that either bind and enter cells more efficiently (BoNT/A1 and BoNT/B) or display altered ganglioside binding specificity (TeNT). These data support a model in which recognition of Sia5 is largely driven by hydrophobic interactions between the sugar and the Sia5 binding site. Another key step in intoxication by the clostridial neurotoxins (CNTs) involves translocation domain (HCT)-mediated translocation of the light chain (LC) across the endosomal membrane. Although our understanding of the translocation process has grown in recent years, the exact mechanism by which this occurs is not well defined.Includes bibliographical reference

Stacking non-BPS D-Branes

We present a candidate supergravity solution for a stacked configuration of stable non-BPS D-branes in Type II string theory compactified on T^4/Z_2. This gives a supergravity description of nonabelian tachyon condensation on the brane worldvolume.Comment: 10 pages, revte

Forcing and response in simulated 20th and 21st century surface energy and precipitation trends

A simple methodology is applied to a transient integration of the Met Office Hadley Centre Global Environmental Model version1 (UKMO-HadGEM1) fully coupled atmosphere-ocean general circulation model in order to separate forcing from climate response in simulated 20th century and future global mean surface energy and precipitation trends. Forcings include any fast responses that are caused by the forcing agent and that are independent of global temperature change. Results reveal that surface radiative forcing is dominated by shortwave forcing over the 20th and 21st centuries, which is strongly negative. However, when fast responses of surface turbulent heat fluxes are separated from climate feedbacks, and included in the forcing, net surface forcing becomes positive. The nonradiative forcings are the result of rapid surface and tropospheric adjustments and impact 20th century, as well as future, evaporation and precipitation trends. A comparison of energy balance changes in eight different climate models finds that all models exhibit a positive surface energy imbalance by the late 20th century. However, there is considerable disagreement in how this imbalance is partitioned between the longwave, shortwave, latent heat and sensible heat fluxes. In particular, all models show reductions in shortwave radiation absorbed at the surface by the late 20th century compared to the pre-industrial control state, but the spread of this reduction leads to differences in the sign of their latent heat flux changes and thus in the sign of their hydrological responses

Data Quality Assessment Methods for the Eastern Range 915 MHz Wind Profiler Network

The Eastern Range installed a network of five 915 MHz Doppler Radar Wind Profilers with Radio Acoustic Sounding Systems in the Cape Canaveral Air Station/Kennedy Space Center area to provide three-dimensional wind speed and direction and virtual temperature estimates in the boundary layer. The Applied Meteorology Unit, staffed by ENSCO, Inc., was tasked by the 45th Weather Squadron, the Spaceflight Meteorology Group, and the National Weather Service in Melbourne, Florida to investigate methods which will help forecasters assess profiler network data quality when developing forecasts and warnings for critical ground, launch and landing operations. Four routines were evaluated in this study: a consensus time period check a precipitation contamination check, a median filter, and the Weber-Wuertz (WW) algorithm. No routine was able to effectively flag suspect data when used by itself. Therefore, the routines were used in different combinations. An evaluation of all possible combinations revealed two that provided the best results. The precipitation contamination and consensus time routines were used in both combinations. The median filter or WW was used as the final routine in the combinations to flag all other suspect data points

Video summarization by group scoring

In this paper a new model for user-centered video summarization is presented. Involvement of more than one expert in generating the final video summary should be regarded as the main use case for this algorithm. This approach consists of three major steps. First, the video frames are scored by a group of operators. Next, these assigned scores are averaged to produce a singular value for each frame and lastly, the highest scored video frames alongside the corresponding audio and textual contents are extracted to be inserted into the summary. The effectiveness of this approach has been evaluated by comparing the video summaries generated by this system against the results from a number of automatic summarization tools that use different modalities for abstraction

Animated movie genre detection using symbolic fusion of text and image descriptors

International audienceThis paper addresses the automatic movie genre classification in the specific case of animated movies. Two types of information are used. The first one are movie synopsis. For each genre, a symbolic representation of a thematic intensity is extracted from synopsis. Addressed visually, movie content is described with symbolic representations of different mid-level color and activity features. A fusion between the text and image descriptions is performed using a set of symbolic rules conveying human expertise. The approach is tested on a set of 107 animated movies in order to estimate their "drama" character. It is observed that the text-image fusion achieves a precision up to 78% and a recall of 44%

Space Station Freedom automation and robotics: An assessment of the potential for increased productivity

This report presents the results of a study performed in support of the Space Station Freedom Advanced Development Program, under the sponsorship of the Space Station Engineering (Code MT), Office of Space Flight. The study consisted of the collection, compilation, and analysis of lessons learned, crew time requirements, and other factors influencing the application of advanced automation and robotics, with emphasis on potential improvements in productivity. The lessons learned data collected were based primarily on Skylab, Spacelab, and other Space Shuttle experiences, consisting principally of interviews with current and former crew members and other NASA personnel with relevant experience. The objectives of this report are to present a summary of this data and its analysis, and to present conclusions regarding promising areas for the application of advanced automation and robotics technology to the Space Station Freedom and the potential benefits in terms of increased productivity. In this study, primary emphasis was placed on advanced automation technology because of its fairly extensive utilization within private industry including the aerospace sector. In contrast, other than the Remote Manipulator System (RMS), there has been relatively limited experience with advanced robotics technology applicable to the Space Station. This report should be used as a guide and is not intended to be used as a substitute for official Astronaut Office crew positions on specific issues

Evaluating Rigid and Semiflexible Fiber Orientation Evolution Models in Simple Flows

As American vehicle fuel efficiency requirements have become more stringent due to the CAFE standards, the auto industry has turned to fiber reinforced polymer composites as replacements for metal parts to reduce weight while simultaneously maintaining established safety standards. Furthermore, these composites may be easily processed using established techniques such as injection molding and compression molding. The mechanical properties of these composites are dependent on, among other variables, the orientation of the fibers within the part. Several models have been proposed to correlate fiber orientation with the kinematics of the polymer matrix during processing, each using various strategies to account for fiber interactions and fiber flexing. However, these all require the use of empirical fitting parameters. Previous work has obtained these parameters by fitting to orientation data at a specific location in an injection-molded part. This ties the parameters to the specific mold design used. Obtaining empirical parameters is not a trivial undertaking and adds significant time to the entire mold design process. Considering that new parameters must be obtained any time some aspect of the part or mold is changed, an alternative technique that obtains model parameters independent of the mold design could be advantageous. This paper continues work looking to obtain empirical parameters from rheological tests. During processing, the fiber-polymer suspension is subjected to a complex flow with both shear and extensional behavior. Rather than use a complex flow, this study seeks to isolate and compare the effects of shear and extension on two orientation models. To this end, simple shear and planar extension are employed, and the evolution of orientation from a planar random initial condition is tracked as a function of strain. Simple shear was imparted using a sliding plate rheometer designed and fabricated in-house. A novel rheometer tool was developed and fabricated in-house to impart planar extension using a lubricated squeeze flow technique, where a lowviscosity Newtonian lubricant is applied to the solid boundaries to minimize the effect of shearing due to the no-slip boundary condition. The Folgar-Tucker model with a strain reduction factor is used as a rigid fiber model and compared against a bead-rod model (a semiflexible model) proposed by Ortman. Both models are capable of predicting the data, with the bead-rod model performing slightly better. Orientation occurs at a much faster rate under startup of planar extension and also attains a much higher degree of flow alignment when compared with startup of steady shear

AGRICULTURAL VALUE ADDED: PROSPECTS FOR NORTH DAKOTA

Introduction: This report provides an overview of the important factors affecting investments in agricultural value-added ventures. The introductory section outlines current research on factors important in the location of economic activity. Research applied to specific agricultural value-added ventures, such as food manufacturing and livestock feeding and finishing operations, are discussed. A listing of resources available to entrepreneurs considering value-added investments concludes the introductory section. Following the introductory section are short overviews of industries that already have, or may have, potential for increasing economic activity in the state. All are based on the important foundation of agriculture in the state's economy or upon the natural resource base giving the state a comparative advantage in investments in alternative energy or resource-based recreation.Agribusiness,