Bacterial pore-forming toxins: The (w)hole story?

Abstract.: Pore-forming toxins (PFTs) are the most common class of bacterial protein toxins and constitute important bacterial virulence factors. The mode of action of PFT is starting to be better understood. In contrast, little is known about the cellular response to this threat. Recent studies reveal that cells do not just swell and lyse, but are able to sense and react to pore formation, mount a defense, even repair the damaged membrane and thus survive. These responses involve a variety of signal-transduction pathways and sophisticated cellular mechanisms such as the pathway regulating lipid metabolism. In this review we discuss the different classes of bacterial PFTs and their modes of action, and provide examples of how the different bacteria use PFTs. Finally, we address the more recent field dealing with the eukaryotic cell response to PFT-induced damag

Resonant tunneling diodes as sources for millimeter and submillimeter wavelengths

High-quality Resonant Tunneling Diodes have been fabricated and tested as sources for millimeter and submillimeter wavelengths. The devices have shown excellent I-V characteristics with peak-to-valley current ratios as high as 6:1 and current densities in the range of 50-150 kA/cm(exp 2) at 300 K. Used as local oscillators, the diodes are capable of state of the art output power delivered by AlGaAs-based tunneling devices. As harmonic multipliers, a frequency of 320 GHz has been achieved by quintupling the fundamental oscillation of a klystron source

Absorbing boundary conditions for the Westervelt equation

The focus of this work is on the construction of a family of nonlinear absorbing boundary conditions for the Westervelt equation in one and two space dimensions. The principal ingredient used in the design of such conditions is pseudo-differential calculus. This approach enables to develop high order boundary conditions in a consistent way which are typically more accurate than their low order analogs. Under the hypothesis of small initial data, we establish local well-posedness for the Westervelt equation with the absorbing boundary conditions. The performed numerical experiments illustrate the efficiency of the proposed boundary conditions for different regimes of wave propagation

Lorenz function of Bi2_{2}Te3_{3}/Sb2_{2}Te3_{3} superlattices

Combining first principles density functional theory and semi-classical Boltzmann transport, the anisotropic Lorenz function was studied for thermoelectric Bi$_{2}$Te$_{3}$/Sb$_{2}$Te$_{3}$ superlattices and their bulk constituents. It was found that already for the bulk materials Bi$_{2}$Te$_{3}$ and Sb$_{2}$Te$_{3}$, the Lorenz function is not a pellucid function on charge carrier concentration and temperature. For electron-doped Bi$_{2}$Te$_{3}$/Sb$_{2}$Te$_{3}$ superlattices large oscillatory deviations for the Lorenz function from the metallic limit were found even at high charge carrier concentrations. The latter can be referred to quantum well effects, which occur at distinct superlattice periods

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Acoustically induced and controlled micro-cavitation bubbles as active source for transcranial adaptive focusing

The skull bone is a strong aberrating medium for ultrasound in the low MHz range. Brain treatment with High Intensity Focused Ultrasound (HIFU) can however be achieved through the skull by multichannel arrays using an adaptive focusing technique. Time-reversal is a robust adaptive technique for correction of aberrations. It achieves moreover a matched filter and then allows the optimal energy concentration for thermal therapy. Nevertheless, this method requires a reference signal sent by a source embedded in brain tissues. Acoustically generated cavitation bubbles are active acoustic sources which can be remotely generated. Therefore, they are suited for this non-invasive time reversal aberration correction. We report here in vitro experiments where micro-cavitation was induced transcranially in agar gel at targeted positions using a coarse aberration correction either obtained from CT-scan based simulations or conventional steering. The bubbles' ultrasonic signature received by the array were then successfully used to optimally focus at the designated locations.http://deepblue.lib.umich.edu/bitstream/2027.42/84308/1/CAV2009-final134.pd

Test beam performance measurements for the Phase I upgrade of the CMS pixel detector

A new pixel detector for the CMS experiment was built in order to cope with the instantaneous luminosities anticipated for the Phase I Upgrade of the LHC. The new CMS pixel detector provides four-hit tracking with a reduced material budget as well as new cooling and powering schemes. A new front-end readout chip mitigates buffering and bandwidth limitations, and allows operation at low comparator thresholds. In this paper, comprehensive test beam studies are presented, which have been conducted to verify the design and to quantify the performance of the new detector assemblies in terms of tracking efficiency and spatial resolution. Under optimal conditions, the tracking efficiency is (99.95 ± 0.05) %, while the intrinsic spatial resolutions are (4.80 ± 0.25) μm and (7.99 ± 0.21) μm along the 100 μm and 150 μm pixel pitch, respectively. The findings are compared to a detailed Monte Carlo simulation of the pixel detector and good agreement is found.Peer reviewe

The Two-State Prehensile Tail of the Antibacterial Toxin Colicin N

Intrinsically disordered regions within proteins are critical elements in many biomolecular interactions and signaling pathways. Antibacterial toxins of the colicin family, which could provide new antibiotic functions against resistant bacteria, contain disordered N-terminal translocation domains (T-domains) that are essential for receptor binding and the penetration of the Escherichia coli outer membrane. Here we investigate the conformational behavior of the T-domain of colicin N (ColN-T) to understand why such domains are widespread in toxins that target Gram-negative bacteria. Like some other intrinsically disordered proteins in the solution state of the protein, ColN-T shows dual recognition, initially interacting with other domains of the same colicin N molecule and later, during cell killing, binding to two different receptors, OmpF and TolA, in the target bacterium. ColN-T is invisible in the high-resolution x-ray model and yet accounts for 90 of the toxin’s 387 amino acid residues. To reveal its solution structure that underlies such a dynamic and complex system, we carried out mutagenic, biochemical, hydrodynamic and structural studies using analytical ultracentrifugation, NMR, and small-angle x-ray scattering on full-length ColN and its fragments. The structure was accurately modeled from small-angle x-ray scattering data by treating ColN as a flexible system, namely by the ensemble optimization method, which enables a distribution of conformations to be included in the final model. The results reveal, to our knowledge, for the first time the dynamic structure of a colicin T-domain. ColN-T is in dynamic equilibrium between a compact form, showing specific self-recognition and resistance to proteolysis, and an extended form, which most likely allows for effective receptor binding