Thermodynamic restrictions on evolutionary optimization of transcription factor proteins

Conformational fluctuations are believed to play an important role in the process by which transcription factor proteins locate and bind their target site on the genome of a bacterium. Using a simple model, we show that the binding time can be minimized, under selective pressure, by adjusting the spectrum of conformational states so that the fraction of time spent in more mobile conformations is matched with the target recognition rate. The associated optimal binding time is then within an order of magnitude of the limiting binding time imposed by thermodynamics, corresponding to an idealized protein with instant target recognition. Numerical estimates suggest that typical bacteria operate in this regime of optimized conformational fluctuations

A simple high-sensitivity technique for purity analysis of xenon gas

We report on the development and performance of a high-sensitivity purity-analysis technique for gaseous xenon. The gas is sampled at macroscopic pressure from the system of interest using a UHV leak valve. The xenon present in the sample is removed with a liquid-nitrogen cold trap, and the remaining impurities are observed with a standard vacuum mass-spectroscopy device. Using calibrated samples of xenon gas spiked with known levels of impurities, we find that the minimum detectable levels of N2, O2, and methane are 1 ppb, 160 ppt, and 60 ppt respectively. This represents an improvement of about a factor of 10,000 compared to measurements performed without a coldtrap.Comment: 20 pages, 5 figure

Study of a zirconium getter for purification of xenon gas

Oxygen, nitrogen and methane purification efficiencies for a common zirconium getter are measured in 1050 Torr of xenon gas. Starting with impurity concentrations near 10^{-6} g/g, the outlet impurity level is found to be less than 120*10^{-12} g/g for O2 and less than 950*10^{-12} g/g for N2. For methane we find residual contamination of the purified gas at concentrations varying over three orders of magnitude, depending on the purifier temperature and the gas flow rate. A slight reduction in the purifier's methane efficiency is observed after 13 mg of this impurity has been absorbed, which we attribute to partial exhaustion of the purifier's capacity for this species. We also find that the purifier's ability to absorb N2 and methane can be extinguished long before any decrease in O2 performance is observed, and slower flow rates should be employed for xenon purification due to the cooling effect that the heavy gas has on the getter.Comment: 14 pages, 5 figure

A Xenon Condenser with a Remote Liquid Storage Vessel

We describe the design and operation of a system for xenon liquefaction in which the condenser is separated from the liquid storage vessel. The condenser is cooled by a pulse tube cryocooler, while the vessel is cooled only by the liquid xenon itself. This arrangement facilitates liquid particle detector research by allowing easy access to the upper and lower flanges of the vessel. We find that an external xenon gas pump is useful for increasing the rate at which cooling power is delivered to the vessel, and we present measurements of the power and efficiency of the apparatus.Comment: 22 pages, 7 figures Corrected typos in authors lis

Mechanical ventilation: lessons from the ARDSNet trial

The acute respiratory distress syndrome (ARDS) is an inflammatory disease of the lungs characterized clinically by bilateral pulmonary infiltrates, decreased pulmonary compliance and hypoxemia. Although supportive care for ARDS seems to have improved over the past few decades, few studies have shown that any treatment can decrease mortality for this deadly syndrome. In the 4 May 2000 issue of New England Journal of Medicine, the results of an NIH-sponsored trial were presented; they demonstrated that the use of a ventilatory strategy that minimizes ventilator-induced lung injury leads to a 22% decrease in mortality. The implications of this study with respect to clinical practice, further ARDS studies and clinical research in the critical care setting are discussed

Interplay between geometry and flow distribution in an airway tree

Uniform fluid flow distribution in a symmetric volume can be realized through a symmetric branched tree. It is shown here, however, that the flow partitioning can be highly sensitive to deviations from exact symmetry if inertial effects are present. This is found by direct numerical simulation of the Navier-Stokes equations in a 3D tree geometry. The flow asymmetry is quantified and found to depend on the Reynolds number. Moreover, for a given Reynolds number, we show that the flow distribution depends on the aspect ratio of the branching elements as well as their angular arrangement. Our results indicate that physiological variability should be severely restricted in order to ensure uniform fluid distribution in a tree. This study suggests that any non-uniformity in the air flow distribution in human lungs should be influenced by the respiratory conditions, rest or hard exercise

APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses

SummaryAccumulation of amyloid-β peptides (Aβ), the proteolytic products of the amyloid precursor protein (APP), induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer’s disease. While depression of synaptic transmission has been extensively studied, the mechanisms underlying synaptic hyperactivity remain unknown. Here, we show that Aβ40 monomers and dimers augment release probability through local fine-tuning of APP-APP interactions at excitatory hippocampal boutons. Aβ40 binds to the APP, increases the APP homodimer fraction at the plasma membrane, and promotes APP-APP interactions. The APP activation induces structural rearrangements in the APP/Gi/o-protein complex, boosting presynaptic calcium flux and vesicle release. The APP growth-factor-like domain (GFLD) mediates APP-APP conformational changes and presynaptic enhancement. Thus, the APP homodimer constitutes a presynaptic receptor that transduces signal from Aβ40 to glutamate release. Excessive APP activation may initiate a positive feedback loop, contributing to hippocampal hyperactivity in Alzheimer’s disease

A simple radionuclide-driven single-ion source

We describe a source capable of producing single barium ions through nuclear recoils in radioactive decay. The source is fabricated by electroplating 148Gd onto a silicon {\alpha}-particle detector and vapor depositing a layer of BaF2 over it. 144Sm recoils from the alpha decay of 148Gd are used to dislodge Ba+ ions from the BaF2 layer and emit them in the surrounding environment. The simultaneous detection of an {\alpha} particle in the substrate detector allows for tagging of the nuclear decay and of the Ba+ emission. The source is simple, durable, and can be manipulated and used in different environments. We discuss the fabrication process, which can be easily adapted to emit most other chemical species, and the performance of the source

Search for Neutrinoless Double-Beta Decay in 136^{136}Xe with EXO-200

We report on a search for neutrinoless double-beta decay of $^{136}$Xe with EXO-200. No signal is observed for an exposure of 32.5 kg-yr, with a background of ~1.5 x 10^{-3} /(kg yr keV) in the $\pm 1\sigma$ region of interest. This sets a lower limit on the half-life of the neutrinoless double-beta decay $T_{1/2}^{0\nu\beta\beta}$($^{136}$Xe) > 1.6 x 10$^{25}$ yr (90% CL), corresponding to effective Majorana masses of less than 140-380 meV, depending on the matrix element calculation