Molecular modeling optimization of anticoagulant pyridine derivatives

Intravascular clotting remains a major health problem in the United States, the most prominent being deep vein thrombosis, pulmonary embolism and thromboembolic stroke. Previous reports on the use of pyridine derivatives in cardiovascular drug development encourage us to pursue new types of compounds based on a pyridine scaffold. Eleven pyridine derivatives (oximes, semicarbazones, N-oxides) previously synthesized in our laboratories were tested as anticoagulants on pooled normal plasma using the prothrombin time (PT) protocol. The best anticoagulant within the oxime series was compound AF4, within the oxime N-oxide series was compound AF4-N-oxide, and within the semicarbazone series, compound MD1-30Y. We also used a molecular modeling approach to guide our efforts, and found that there was good correlation between coagulation data and computational energy scores. Molecular docking was performed to target the active site of thrombin with the DOCK v5.2 package. The results of molecular modeling indicate that improvement in anticoagulant activities can be expected by functionalization at the three-position of the pyridine ring and by N-oxide formation. Results reported here prove the suitability of DOCK in the lead optimization process.     

Characterization of virus replication

New viruses spread faster than ever and current signature based detection do not protect against these unknown viruses. Behavior based detection is the currently preferred defense against unknown viruses. The drawback of behavior based detection is the ability only to detect specific classes of viruses or have successful detection under certain conditions plus false positives. This paper presents a characterization of virus replication which is the only virus characteristic guaranteed to be consistently present in all viruses. Two detection models based on virus replication are developed, one using operation sequence matching and the other using frequency measures. Regression analysis was generated for both models. A safe list is used to minimize false positives. In our testing using operation sequence matching, over 250 viruses were detected with 43 subsequences. There were minimal false negatives. The replication sequence of just one virus detected 130 viruses, 45% of all tested viruses. Our testing using frequency measures detected all test viruses with no false negatives. The paper shows that virus replication can be identified and used to detect known and unknown viruses.     

A hierarchical, agent-based service oriented architecture for smart environments

Service Oriented Architectures, which allow for the integration of different subsystems and of applications running on different devices and platforms, may be very suitable to solve the problem of service personalization in large smart environments like cities, where the number of potential users and potentially available services is rapidly growing. Taking this into account, we have designed an agent-based service oriented architecture for smart spaces. Two of the greatest challenges in the design of such a solution are providing effective device, service and context federation and composition mechanisms and handling user mobility. For the first challenge, we have designed a hierarchical architecture and developed a set of inheritance, aggregation and access mechanisms for devices, services and context. To handle user mobility, we have followed three different strategies, using stationary, mobile or nomadic agents. In this paper, we describe the main aspects of our architecture and perform an experimental evaluation to determine the advantages and drawbacks of the different strategies.     

Lock-in amplifier error prediction and correction in frequency sweep measurements

This article proposes an analytical algorithm for predicting errors in lock-in amplifiers (LIAs) working with time-varying reference frequency. Furthermore, a simple method for correcting such errors is presented. The reference frequency can be swept in order to measure the frequency response of a system within a given spectrum. The continuous variation of the reference frequency produces a measurement error that depends on three factors: the sweep speed, the LIA low-pass filters, and the frequency response of the measured system. The proposed error prediction algorithm is based on the final value theorem of the Laplace transform. The correction method uses a double-sweep measurement. A mathematical analysis is presented and validated with computational simulations and experimental measurements.     

Direct electron crystallographic determination of zeolite zonal structures

The prospect for improving the success of ab initio zeolite structure investigations with electron diffraction data is evaluated. First of all, the quality of intensities obtained by precession electron diffraction at small hollow cone illumination angles is evaluated for seven representative materials: ITQ-1, ITQ-7, ITQ-29, ZSM-5, ZSM-10, mordenite, and MCM-68. It is clear that, for most examples, an appreciable fraction of a secondary scattering perturbation is removed by precession at small angles. In one case, ZSM-10, it can also be argued that precession diffraction produces a dramatically improved 'kinematical' data set. There seems to no real support for application of a Lorentz correction to these data and there is no reason to expect for any of these samples that a two-beam dynamical scattering relationship between structure factor amplitude and observed intensity should be valid. Removal of secondary scattering by the precession mode appears to facilitate ab initio structure analysis. Most zeolite structures investigated could be solved by maximum entropy and likelihood phasing via error-correcting codes when precession data were used. Examples include the projected structure of mordenite that could not be determined from selected area data alone. One anomaly is the case of ZSM-5, where the best structure determination in projection is made from selected area diffraction data. In a control study, the zonal structure of SSZ-48 could be determined from selected area diffraction data by either maximum entropy and likelihood or traditional direct methods. While the maximum entropy and likelihood approach enjoys some advantages over traditional direct methods (non-dependence on predicted phase invariant sums), some effort must be made to improve the figures of merit used to identify potential structure solutions.     

Supporting ordering and consistency in a distributed Event Heap for Ubiquitous Computing

The Stanford Event Heap has been shown to provide appropriate support for constructing interactive workspace applications. Given this success it is natural to consider the Event Heap as a platform to support other classes of Ubiquitous Computing applications. In this paper we argue that the distributed, spontaneous nature of these applications places additional demands on the Event Heap that require extensions to both the engineering and API. Suitable extensions are described and their use to support a typical Ubicomp application is discussed.

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Pulsed laser technique application to liquid and gaseous flows and the scattering power of seed materials

Mie scattering computations have been performed for light scattered by small particles from a pulsed sheet of laser illumination and collected and imaged by a camera lens. From these computations the smallest particles that can be photographed in various fluid measurement situations, including air and water, have been determined in terms of system parameters such as laser power, light sheet geometry, f/No., and photographic film properties. The particle scattering requirements of the individual particle image mode and the speckle mode are compared.     

An Initial Inventory and Indexation of Groundwater Mega-Depletion Cases

The state of groundwater systems worldwide is presently not well defined, and in particular there is little context for agencies responsible for managing water resources to evaluate occurrences of groundwater depletion against other cases globally. In this study, an initial inventory of groundwater depletion problems is compiled and ranked to identify the world’s most critical cases, i.e. situations of groundwater mega-depletion. The ranking is based on an indexed approach that considers overdraft, drawdown and subsidence, plus the importance of the resources in terms of population-dependency and rates of extraction. The five most highly ranked depleted aquifers of the world include the shallow aquifers of the Hai River Plain (China), the Altiplano region (Spain), the Mexico Basin (Mexico), the Huang River basin (China) and the California Central Valley (USA). An abridged account of modelling to assess drawdown is described for the Hai River Plain, revealing that despite recharge in the order of 13,000 GL/yr, an overdraft of about 8,000 GL/yr is occurring to support the vast population of the region. This has led to up to 100 m of drawdown in places and reports of subsidence of several metres. The Hai River situation demonstrates that falling water levels may not act to alleviate pumping stresses; a symptom of unchecked extraction and an exemplary illustration of the tragedy of the commons. The causal factors leading to mega-depletion are varying across the globe and each mega-depletion case contains unique elements, although population appears to be an important factor.     

GPGPU implementation of growing neural gas: Application to 3D scene reconstruction

Self-organising neural models have the ability to provide a good representation of the input space. In particular the Growing Neural Gas (GNG) is a suitable model because of its flexibility, rapid adaptation and excellent quality of representation. However, this type of learning is time-consuming, especially for high-dimensional input data. Since real applications often work under time constraints, it is necessary to adapt the learning process in order to complete it in a predefined time. This paper proposes a Graphics Processing Unit (GPU) parallel implementation of the GNG with Compute Unified Device Architecture (CUDA). In contrast to existing algorithms, the proposed GPU implementation allows the acceleration of the learning process keeping a good quality of representation. Comparative experiments using iterative, parallel and hybrid implementations are carried out to demonstrate the effectiveness of CUDA implementation. The results show that GNG learning with the proposed implementation achieves a speed-up of 6×$6\times$ compared with the single-threaded CPU implementation. GPU implementation has also been applied to a real application with time constraints: acceleration of 3D scene reconstruction for egomotion, in order to validate the proposal.