Real-time patch-cram detection of intracellular cGMP reveals long-term suppression of responses to NO and muscarinic agonists

Cyclic GMP (cGMP) is a crucial intracellular messenger in neuronal, muscle, and endocrine cells. The intracellular concentration of cGMP is regulated by various neurotransmitters, including acetylcholine (ACh) and nitric oxide (NO). While much is known about the biochemical steps leading to cGMP synthesis, little is known about cGMP kinetics in intact cells. Here, we use "patch-cramming," in which an excised, inside-out membrane patch containing cyclic nucleotide-gated ion channels is used as a biosensor, to obtain the first real-time measurements of cGMP in intact cells. Patch-cramming experiments on neuroblastoma cells show that both muscarinic agonists and NO rapidly elevate cGMP. NO elicits cGMP responses repeatedly without decrement, whereas responses to muscarinic agonists exhibit a profound and prolonged desensitization. Remarkably, muscarinic agonists also cause long-term (>30 min) suppression (LTS) of cGMP responses elicited by NO. Biochemical measurements reveal that rat sympathetic neurons also exhibit LTS of cGMP, suggesting that LTS is a widespread mechanism that may contribute to synaptic plasticity.     

ODTLES: A multi-scale model for 3D turbulent flow based on one-dimensional turbulence modeling

A novel multi-scale approach for extending the one-dimensional turbulence (ODT) model of [A.R. Kerstein. One-dimensional turbulence: model formulation and application to homogeneous turbulence, shear flows, and buoyant stratified flows, J. Fluid Mech. 392 (1999) 277] to treat turbulent flow in three-dimensional (3D) domains is described. In this model, here called ODTLES, 3D aspects of the flow are captured by embedding three, mutually orthogonal, one-dimensional ODT domain arrays within a coarser 3D mesh. The ODTLES model is obtained by developing a consistent approach for dynamically coupling the different ODT line sets to each other and to the large scale processes that are resolved on the 3D mesh. The model is implemented computationally and its performance is tested by performing simulations of decaying isotropic turbulence at two different Reynolds numbers and comparing to the experimental data of [H. Kang, S. Chester, C. Meneveau. Decaying turbulence in an active-grid-generated flow and comparisons with large-eddy simulations, J. Fluid Mech. 480 (2003) 129; G. Comte-Bellot, S. Corrsin, Simple Eulerian correlation of full-and narrow band velocity signals in grid-generated ’isotropic’ turbulence, J. Fluid Mech. 48 (1971) 273].     

Low Voltage Electrowetting-on-Dielectric Platform using Multi-Layer Insulators

A low voltage, two-level-metal, and multi-layer insulator electrowetting-on-dielectric (EWD) platform is presented. Dispensing 300pl droplets from 140nl closed on-chip reservoirs was accomplished with as little as 11.4V solely through EWD forces, and the actuation threshold voltage was 7.2V with a 1Hz voltage switching rate between electrodes. EWD devices were fabricated with a multilayer insulator consisting of 135nm sputtered tantalum pentoxide (Ta(2)O(5)) and 180nm parylene C coated with 70nm of CYTOP. Furthermore, the minimum actuation threshold voltage followed a previously published scaling model for the threshold voltage, V(T), which is proportional to (t/ε(r))(1/2), where t and ε(r) are the insulator thickness and dielectric constant respectively. Device threshold voltages are compared for several insulator thicknesses (200nm, 500nm, and 1μm), different dielectric materials (parylene C and tantalum pentoxide), and homogeneous versus heterogeneous compositions. Additionally, we used a two-level-metal fabrication process, which enables the fabrication of smaller and denser electrodes with high interconnect routing flexibility. We also have achieved low dispensing and actuation voltages for scaled devices with 30pl droplets.     

The Koala component model for consumer electronics software

Most consumer electronics today contain embedded software. In the early days, developing CE software presented relatively minor challenges, but in the past several years three significant problems have arisen: size and complexity of the software in individual products; the increasing diversity of products and their software; and the need for decreased development time. The question of handling diversity and complexity in embedded software at an increasing production speed becomes an urgent one. The authors present their belief that the answer lies not in hiring more software engineers. They are not readily available, and even if they were, experience shows that larger projects induce larger lead times and often result in greater complexity. Instead, they believe that the answer lies in the use and reuse of software components that work within an explicit software architecture. The Koala model, a component-oriented approach detailed in this article, is their way of handling the diversity of software in consumer electronics. Used for embedded software in TV sets, it allows late binding of reusable components with no additional overhead     

Morphing active contours

A method for deforming curves in a given image to a desired position in a second image is introduced. The algorithm is based on deforming the first image toward the second one via a partial differential equation (PDE), while tracking the deformation of the curves of interest in the first image with an additional, coupled PDE; both the images and the curves on the frame/slices of interest are used for tracking. The technique can be applied to object tracking and sequential segmentation. The topology of the deforming curve can change without any special topology handling procedures added to the scheme. This permits, for example, the automatic tracking of scenes where, due to occlusions, the topology of the objects of interest changes from frame to frame. In addition, this work introduces the concept of projecting velocities to obtain systems of coupled PDEs for image analysis applications. We show examples for object tracking and segmentation of electronic microscopy     

A Cost-Based Approach to Adaptive Resource Management in Data Stream Systems

Data stream management systems need to adaptively control their resources, since stream characteristics and query workload may vary over time. In this paper, we investigate an approach to adaptive resource management for continuous sliding-window queries that adjusts window sizes and time granularities to keep resource usage within bounds. These two novel techniques differ from standard load shedding approaches based on sampling, as they ensure exact query answers for given user-defined quality of service specifications, even under query reoptimization. In order to quantify the effects of both techniques on the various operations in a query plan, we develop an appropriate cost model for estimating operator resource allocation in terms of memory usage and processing costs. A thorough experimental study not only validates the accuracy of our cost model but also demonstrates the efficacy and scalability of the proposed techniques.     

Influence of age and proximity warning devices on collision avoidance in simulated driving

OBJECTIVE: We conducted a set of experiments to examine the utility of several different uni- and multimodal collision avoidance systems (CASs) on driving performance of young and older adult drivers in a high-fidelity simulator. BACKGROUND: Although previous research has examined the efficacy of different CASs on collision avoidance, there has been a dearth of studies that have examined such devices in different driving situations with different populations of drivers. METHOD: Several different CAS warnings were examined in varying traffic and collision configurations both without (Experiment 1a) and with (Experiment 2) a distracting in-vehicle task. RESULTS: Overall, collision avoidance performance for both potential forward and side object collisions was best for an auditory/visual CAS, which alerted drivers using both modalities. Interestingly, older drivers (60-82 years of age) benefited as much as younger drivers from the CAS, and sometimes they benefited more. CONCLUSION: These data suggest that CASs can be beneficial across a number of different driving scenarios, types of collisions, and driver populations. APPLICATION: These results have important implications for the design and implementation of CASs for different driver populations and driving conditions.     

An Approach for Recovering Distributed System Architectures

Reasoning about software systems at the architectural level is key to effective software development, management, evolution and reuse. All too often, though, the lack of appropriate documentation leads to a situation where architectural design information has to be recovered directly from implemented software artifacts. This is a very demanding process, particularly when involving recovery of runtime abstractions (clients, servers, interaction protocols, etc.) that are typical to the design of distributed software systems. This paper presents an exploratory reverse engineering approach, called X-ray, to aid programmers in recovering architectural runtime information from a distributed system's existing software artifacts. X-ray comprises three domain-based static analysis techniques, namely component module classification, syntactic pattern matching, and structural reachability analysis. These complementary techniques can facilitate the task of identifying a distributed system's implemented executable components and their potential runtime interconnections. The component module classification technique automatically distinguishes source code modules according to the executables components they implement. The syntactic pattern matching technique in turn helps to recognise specific code fragments that may implement typical component interaction features. Finally, the structural reachability analysis technique aids in the association of those features to the code specific for each executable component. The paper describes and illustrates the main concepts underlying each technique, reports on their implementation as a suit of new and off-the-shelf tools, and, to give evidence of the utility of the approach, provides a detailed account of a successful application of the three techniques to help recover a static approximation of the runtime architecture for Field, a publicly-available distributed programming environment.