In vivo regulation of the Vi antigen in Salmonella and induction of immune responses with an in vivo-inducible promoter.

Salmonella enterica serovar Typhi, the agent of typhoid fever in humans, expresses the surface Vi polysaccharide antigen that contributes to virulence. However, Vi expression can also be detrimental to some key steps of S. Typhi infectivity, for example, invasion, and Vi is the target of protective immune responses. We used a strain of S. Typhimurium carrying the whole Salmonella pathogenicity island 7 (SPI-7) to monitor in vivo Vi expression within phagocytic cells of mice at different times after systemic infection. We also tested whether it is possible to modulate Vi expression via the use of in vivo-inducible promoters and whether this would trigger anti-Vi antibodies through the use of Vi-expressing live bacteria. Our results show that Vi expression in the liver and spleen is downregulated with the progression of infection and that the Vi-negative population of bacteria becomes prevalent by day 4 postinfection. Furthermore, we showed that replacing the natural tviA promoter with the promoter of the SPI-2 gene ssaG resulted in sustained Vi expression in the tissues. Intravenous or oral infection of mice with a strain of S. Typhimurium expressing Vi under the control of the ssaG promoter triggered detectable levels of all IgG subclasses specific for Vi. Our work highlights that Vi is downregulated in vivo and provides proof of principle that it is possible to generate a live attenuated vaccine that induces Vi-specific antibodies after single oral administration.

Design and optimization of a 250nm SOI LDMOSFET

This work is aimed at optimising the static performance of a high voltage SOI LDMOSFET. Starting with a conventional LDMOSFET, 2D and 3D numerical simulation models, able to accurately match datasheet values, have been developed. Moving from the original device, several design techniques have been investigated with the target of improving the breakdown voltage and the ON-state resistance. The considered design techniques are based on the modification of the doping profile of the drift region and the Superjunction design technique. The paper shows that a single step doping within the drift region is the best design choice for the considered device and is found to give a 24% improvement in the breakdown voltage and a 17% reduction of the ON-state resistance. © 2011 IEEE.

The temporal evolution of feedback gains rapidly update to task demands.

Recent theoretical frameworks such as optimal feedback control suggest that feedback gains should modulate throughout a movement and be tuned to task demands. Here we measured the visuomotor feedback gain throughout the course of movements made to "near" or "far" targets in human subjects. The visuomotor gain showed a systematic modulation over the time course of the reach, with the gain peaking at the middle of the movement and dropping rapidly as the target is approached. This modulation depends primarily on the proportion of the movement remaining, rather than hand position, suggesting that the modulation is sensitive to task demands. Model-predictive control suggests that the gains should be continuously recomputed throughout a movement. To test this, we investigated whether feedback gains update when the task goal is altered during a movement, that is when the target of the reach jumped. We measured the visuomotor gain either simultaneously with the jump or 100 ms after the jump. The visuomotor gain nonspecifically reduced for all target jumps when measured synchronously with the jump. However, the visuomotor gain 100 ms later showed an appropriate modulation for the revised task goal by increasing for jumps that increased the distance to the target and reducing for jumps that decreased the distance. We conclude that visuomotor feedback gain shows a temporal evolution related to task demands and that this evolution can be flexibly recomputed within 100 ms to accommodate online modifications to task goals.

Energy scattering in weakly non-linear systems.

The Chinese Tam-Tam exhibits non-linear behavior in its vibro-acoustic response. The frequency content of the response during free, unforced vibration smoothly changes, with energy being progressively smeared out over a greater bandwidth with time. This is used as a motivating case for the general study of the phenomenon of energy cascading through weak nonlinearity. Numerical models based upon the Fermi-Pasta-Ulam system of non-linearly coupled oscillators, modified with the addition of damping, have been developed. These were used to study the response of ensembles of systems with randomized natural frequencies. Results from simulations will be presented here. For un-damped systems, individual ensemble members exhibit cyclical energy exchange between linear modes, but the ensemble average displays a steady state. For the ensemble response of damped systems, lightly damped modes can exhibit an effective damping which is higher than predicated by linear theory. The presence of a non-linearity provides a path for energy flow to other modes, increasing the apparent damping spectrum at some frequencies and reducing it at others. The target of this work is a model revealing the governing parameters of a generic system of this type and leading to predictions of the ensemble response.