Tetracaine reports a conformational change in the pore of cyclic nucleotide-gated channels

Local anesthetics are a diverse group of clinically useful compounds that act as pore blockers of both voltage- and cyclic nucleotide-gated (CNG) ion channels. We used the local anesthetic tetracaine to probe the nature of the conformational change that occurs in the pore of CNG channels during the opening allosteric transition. When applied to the intracellular side of wild-type rod CNG channels expressed in Xenopus oocytes from the alpha subunit, the local anesthetic tetracaine exhibits state-dependent block, binding with much higher affinity to closed states than to open states. Here we show that neutralization of a glutamic acid in the conserved P region (E363G) eliminated this state dependence of tetracaine block. Tetracaine blocked E363G channels with the same effectiveness at high concentrations of cGMP, when the channel spent more time open, and at low concentrations of cGMP, when the channel spent more time closed. In addition, Ni2+, which promotes the opening allosteric transition, decreased the effectiveness of tetracaine block of wild-type but not E363G channels. Similar results were obtained in a chimeric CNG channel that exhibits a more favorable opening allosteric transition. These results suggest that E363 is accessible to internal tetracaine in the closed but not the open configuration of the pore and that the conformational change that accompanies channel opening includes a change in the conformation or accessibility of E363.     

Planetary exploration by robotic aerovehicles

Planetary aerobots are a new type of telerobotic science platform that can fly and navigate in a dynamic 3-dimensional atmospheric environment, thus enabling the global in situ exploration of planetary atmospheres and surfaces. Aerobots are enabled by a new concept in planetary balloon altitude control, developed at JPL, which employs reversible-fluid changes to permit repeated excursions in altitude. The essential physics and thermodynamics ofreversible-fluid altitude control have been demonstrated in a series of altitude-control experiments conducted in the Earth's atmosphere, which are described. Aerobot altitude-control technology will be important in the exploration of seven planets and satellites in our solar system. Three of these objects—Venus, Mars, and the Saturnian satellite Titan—have accessible solid surfaces and atmospheres dominated by the dense gases nitrogen or carbon dioxide. They will be explored with aerobots using helium or hydrogen as their primary means of buoyancy. The other four planets—Jupiter, Saturn, Uranus, and Neptune—have deep atmospheres that are predominantly hydrogen. It may be possible to explore these atmospheres with aerobots inflated with atmospheric gas that is then radiatively heated from the hotter gaseous depths below. To fulfill their potential, aerobots to explore the planets will need autonomous state estimators to guide their observations and provide information to the altitude-control systems. The techniques of acquiring these data remotely are outlined. Aerobots will also use on board altitude control and navigation systems to execute complex flight paths including descent to the surface and exploiting differential wind velocities to access different latitude belts. Approaches to control of these systems are examined. The application of aerobots to Venus exploration is explored in some detail: The most ambitious mission described, the Venus Flyer Robot (VFR), would have the capability to make repeated short excursions to the high-temperature surface environment of Venus to acquire data and then return to the Earth-like upper atmosphere to communicate and recool its electronic systems. Finally a Planetary Aerobot Testbed is discussed which will conduct Earth atmospheric flights to validate autonomous-state-estimator techniques and flight-path-control techniques needed for future planetary missions.     

News: "Greener" dry-cleaning alternative pushed by industry, environmental groups

Technology.     

CAL delivery selection criteria and authoring systems

Abstract  In the past, authoring systems have been used to generate computer-assisted learning materials that have often followed the rather restrictive programmed learning format. A number of innovative ways of using recently developed systems to develop CAL packages that include a wider range of learning activities (access to data bases, simulations, interactive video, etc.) are described. Analogous to the concept of a media selection model, a computer delivery mode selection model is presented as an aid to decision making for designers. This increase in flexibility should broaden the applicability of computerassisted learning (CAL) to a wider range of educational objectives and raise the level of the cognitive emphasis in learning packages, as well as facilitate the implementation of visually appealing materials. The paper also implies a standard of acceptability for authoring systems.     

Locus heterogeneity in autosomal dominant congenital external ophthalmoplegia (CFEOM)

An autopsy case of retroperitoneal leiomyosarcoma of a centenarial male is described. He complained of abdominal pain in his left side 1 month before his death. Ultrasonography and computed tomography revealed a large mass in the left abdominal cavity. At autopsy, a circumscribed mass, 15 cm in diameter, was found in the left-upper abdominal cavity, and seemed to be derived from the retroperitoneum in an exophytic manner. Histologically, spindle cells with slight eosinophilic cytoplasm and blunt-ended nuclei showed interwoven fascicular growth, and mitotic figures were easily encountered. Immunohistochemically, the tumor cells were labeled by alpha-smooth muscle actin and vimentin. To our knowledge, this case of leiomyosarcoma has presented in the oldest patient ever reported. The rarity of soft tissue sarcomas in the extremely elderly is also discussed.     

Engineering a Web site

The World Wide Web (WWW) is famous for weaving far-flung fans with like interests into true communities. It also puts a spin all its own on product and information delivery. Nowhere is this more apparent than in a global industry such as electrical and electronic engineering. The Web is still unmatched in its ability to receive and distribute information and software, and to encourage interaction and collaboration. These strengths stem from the Web's combination of many of the best features of existing media-audio, video, text, and graphics-to which it adds some unique new talents, such as the ability to manipulate information through software. Most corporations acknowledge the opportunities the Web presents. The paper presents some guidelines on how best to start turning them to advantage     

Effect of cation exchange on the distribution and movement of cations in soils with variable charge. I. Effect of lime on potassium and magnesium exchange equilibria

The influence of Ca(OH)₂ on K and Mg exchange equilibria in three New Zealand soils was studied. Calcium hydroxide was mixed with each soil to raise the pH to about 6 or 7. For each Ca(OH)₂ treatment, K and Mg exchange isotherms were determined, from which the equilibrium activity ratios were derived. Exchange coefficients and solution activity ratios were calculated according to the Gapon convention.The addition of Ca(OH)₂ produced varying effects in the Gapon exchange coefficient for both K and Mg. The magnitude and direction of change in the exchange coefficient were related to the cation initially dominating the exchange sites, rate of Ca(OH)₂ addition, soil colloids contributing to the CEC and specific interactions of Ca with these soil colloids.Addition of Ca(OH)₂ reduced the equilibrium activity ratio of all soils. Changes in the bonding strength of K and Mg with increasing CEC were suggested as a possible mechanism for this decrease.     

A Quantitative Analysis of Current Practices in Optical Flow Estimation and the Principles Behind Them

The accuracy of optical flow estimation algorithms has been improving steadily as evidenced by results on the Middlebury optical flow benchmark. The typical formulation, however, has changed little since the work of Horn and Schunck. We attempt to uncover what has made recent advances possible through a thorough analysis of how the objective function, the optimization method, and modern implementation practices influence accuracy. We discover that “classical” flow formulations perform surprisingly well when combined with modern optimization and implementation techniques. One key implementation detail is the median filtering of intermediate flow fields during optimization. While this improves the robustness of classical methods it actually leads to higher energy solutions, meaning that these methods are not optimizing the original objective function. To understand the principles behind this phenomenon, we derive a new objective function that formalizes the median filtering heuristic. This objective function includes a non-local smoothness term that robustly integrates flow estimates over large spatial neighborhoods. By modifying this new term to include information about flow and image boundaries we develop a method that can better preserve motion details. To take advantage of the trend towards video in wide-screen format, we further introduce an asymmetric pyramid downsampling scheme that enables the estimation of longer range horizontal motions. The methods are evaluated on the Middlebury, MPI Sintel, and KITTI datasets using the same parameter settings.     

Micro-computed tomography scanning approaches to quantify,parameterize and visualize bioturbation activity in clogged streambeds: A proof of concept

Fine particle clogging and faunal bioturbation are two key processes co-occurring in the hyporheic zone that potentially affect hyporheic exchange through modifications in the sediment structure of streambeds. Clogging results from excessive fine sediment infiltration and deposition in rivers, and it is known to decrease matrix porosity and potentially reduce permeability. Faunal bioturbation activity may compensate for the negative effect of clogging by reworking the sediment, increasing porosity, and preventing further infiltration of fines. Although both processes of clogging and bioturbation have received significant attention in the literature separately, their combined effects on streambed sediment structure are not well understood, mostly due to the lack of a standard methodology for their assessment. Here, we illustrate a novel methodology using X-ray computed tomography (CT), as proof of concept, to investigate how, together, clogging and bioturbation affect streambed porosity in a controlled flow-through flume. By visualising gallery formations of an upward conveyor macroinvertebrate; Lumbriculus variegatus as a model species, we quantified bioturbation activity in a clogged streambed, focusing on orientation, depth, and volume at downwelling and upwelling areas of the flume. Gallery creation increased the porosity of the streambed sediment, suggesting a potential improvement in permeability and a possible offset of clogging effects. We illustrate the promising use of X-ray CT as a tool to assess bioturbation in clogged streambeds, and the potential role of bioturbation activity supporting hyporheic exchange processes in streambeds, warranting further studies to understand the extent of bioturbation impacts in natural systems.     

A coherence maximisation process for solving normative inconsistencies

Norms can be used in multi-agent systems for defining patterns of behaviour in terms of permissions, prohibitions and obligations that are addressed to agents playing a specific role. Agents may play different roles during their execution and they may even play different roles simultaneously. As a consequence, agents may be affected by inconsistent norms; e.g., an agent may be simultaneously obliged and forbidden to reach a given state of affairs. Dealing with this type of inconsistency is one of the main challenges of normative reasoning. Existing approaches tackle this problem by using a static and predefined order that determines which norm should prevail in the case where two norms are inconsistent. One main drawback of these proposals is that they allow only pairwise comparison of norms; it is not clear how agents may use the predefined order to select a subset of norms to abide by from a set of norms containing multiple inconsistencies. Furthermore, in dynamic and non-deterministic environments it can be difficult or even impossible to specify an order that resolves inconsistencies satisfactorily in all potential situations. In response to these two problems, we propose a mechanism with which an agent can dynamically compute a preference order over subsets of its competing norms by considering the coherence of its cognitive and normative elements. Our approach allows flexible resolution of normative inconsistencies, tailored to the current circumstances of the agent. Moreover, our solution can be used to determine norm prevalence among a set of norms containing multiple inconsistencies.