Statistical theory of selectivity and conductivity in biological channels

We present an equilibrium statistical-mechanical theory of selectivity in biological ion channels. In doing so, we introduce a grand canonical ensemble for ions in a channel's selectivity filter coupled to internal and external bath solutions for a mixture of ions at arbitrary concentrations, we use linear response theory to find the current through the filter for small gradients of electrochemical potential, and we show that the conductivity of the filter is given by the generalized Einstein relation. We apply the theory to the permeation of ions through the potassium selectivity filter, and are thereby able to resolve the long-standing paradox of why the high selectivity of the filter brings no associated delay in permeation. We show that the Eisenman selectivity relation follows directly from the condition of diffusion-limited conductivity through the filter. We also discuss the effect of wall fluctuations on the filter conductivity

Relation between selectivity and conductivity in narrow ion channels

To establish the general statistical mechanical properties of highly conductive but selective nano-filters we develop an equilibrium statistical-mechanical theory of the KcsA filter, find the probabilities for the filter to bind ions from the mixed intra- and extra-cellular solutions, and evaluate the conductivity of the filter in its linear response regime. The results provide first principles analytical resolution of the long-standing paradox - how can narrow filter conduct potassium ions at nearly the rate of free diffusion while strongly selecting them over sodium ions - and are applicable to a wide range of biological and artificial channels

The O/OREOS Mission - Astrobiology in Low Earth Orbit

The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small- Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cu.cm) modules: (i) a control bus, (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment, and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for micro-organisms at 3 times during the 6-month mission. We will report on the spacecraft characteristics, payload capabilities and first operational phase of the O/OREOS mission. The science and technology rationale of O/OREOS supports NASAs scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development

The O/OREOS Mission - Astrobiology in Low Earth Orbit

The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small- Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cu.cm) modules: (i) a control bus, (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment, and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for micro-organisms at 3 times during the 6-month mission. We will report on the spacecraft characteristics, payload capabilities and first operational phase of the O/OREOS mission. The science and technology rationale of O/OREOS supports NASAs scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities

Holographic Optical Data Storage

Although the basic idea may be traced back to the earlier X-ray diffraction studies of Sir W. L. Bragg, the holographic method as we know it was invented by D. Gabor in 1948 as a two-step lensless imaging technique to enhance the resolution of electron microscopy, for which he received the 1971 Nobel Prize in physics. The distinctive feature of holography is the recording of the object phase variations that carry the depth information, which is lost in conventional photography where only the intensity (= squared amplitude) distribution of an object is captured. Since all photosensitive media necessarily respond to the intensity incident upon them, an ingenious way had to be found to convert object phase into intensity variations, and Gabor achieved this by introducing a coherent reference wave along with the object wave during exposure. Gabor's in-line recording scheme, however, required the object in question to be largely transmissive, and could provide only marginal image quality due to unwanted terms simultaneously reconstructed along with the desired wavefront. Further handicapped by the lack of a strong coherent light source, optical holography thus seemed fated to remain just another scientific curiosity, until the field was revolutionized in the early 1960s by some major breakthroughs: the proposition and demonstration of the laser principle, the introduction of off-axis holography, and the invention of volume holography. Consequently, the remainder of that decade saw an exponential growth in research on theory, practice, and applications of holography. Today, holography not only boasts a wide variety of scientific and technical applications (e.g., holographic interferometry for strain, vibration, and flow analysis, microscopy and high-resolution imagery, imaging through distorting media, optical interconnects, holographic optical elements, optical neural networks, three-dimensional displays, data storage, etc.), but has become a prominent am advertising, and security medium as well. The evolution of holographic optical memories has followed a path not altogether different from holography itself, with several cycles of alternating interest over the past four decades. P. J. van Heerden is widely credited for being the first to elucidate the principles behind holographic data storage in a 1963 paper, predicting bit storage densities on the order of 1/lambda(sup 3) with source wavelength lambda - a fantastic capacity of nearly 1 TB/cu cm for visible light! The science and engineering of such a storage paradigm was heavily pursued thereafter, resulting in many novel hologram multiplexing techniques for dense data storage, as well as important advances in holographic recording materials. Ultimately, however, the lack of such enabling technologies as compact laser sources and high performance optical data I/O devices dampened the hopes for the development of a commercial product. After a period of relative dormancy, successful applications of holography in other arenas sparked a renewed interest in holographic data storage in the late 1980s and the early 1990s. Currently, with most of the critical optoelectronic device technologies in place and the quest for an ideal holographic recording medium intensified, holography is once again considered as one of several future data storage paradigms that may answer our constantly growing need for higher-capacity and faster-access memories

Steady-State Characterization of Bacteriorhodopsin-D85N Photocycle

An operational characterization of the photocycle of the genetic mutant D85N of bacteriorhodopsin, BR-D85N, is presented. Steady-state bleach spectra and pump-probe absorbance data are obtained with thick hydrated films containing BR-D85N embedded in a gelatin host. Simple two- and three-state models are used to analyze the photocycle dynamics and extract relevant information such as pure-state absorption spectra, photochemical-transition quantum efficiencies, and thermal lifetimes of dominant states appearing in the photocycle, the knowledge of which should aid in the analysis of optical recording and retrieval of data in films incorporating this photochromic material. The remarkable characteristics of this material and their implications from the viewpoint of optical data storage and processing are discussed