A mechanistic study of the intestinal absorption of crypotanshinone, the major active constituent of Saliva miltiorrhiza

The nature of intestinal absorption of most herbal medicine is unknown. Cryptotanshinone (CTS) is the principal active constituent of the widely used cardiovascular herb Salvia miltiorrhiza (Danshen). We investigated the oral bioavailability of CTS in rats and the mechanism for its intestinal absorption using several in vitro and in vivo models:1) Caco-2 cell monolayers; 2) monolayers of MDCKII cells overexpressing P-glycoprotein
(PgP); and 3) single-pass rat intestinal perfusion with mesenteric vein cannulation. The systemic bioavailabilities of CTS after oral and intraperitoneal administration at 100 mg/kg were 2.05 and 10.60%, respectively. In the perfused rat intestinal model, permeability coefficients based on CTS disappearance from the luminal perfusate (P_lumen) were 6.7- to 10.3-fold higher than permeability coefficients based on drug appearance in venous blood (P_blood). P_blood significantly increased in the presence of the P-gP inhibitor, verapamil. CTS transport across Caco-2 monolayers was pH-, temperature- and ATP-dependent. The transport from the apical (AP) to the basolateral (BL) side was 3- to 9-fold lower than that from the BL to the AP side. Inclusion of verapamil (50 µM) in both AP and BL sides abolished the polarized CTS transport across Caco-2 cells. Moreover, CTS was significantly more permeable in the BL to AP than in the AP to BL direction in MDCKII and MDR1-MDCKII cells. The permeability coefficients in the BL to AP direction were significantly higher in MDCKII cells overexpressing PgP. These findings indicate that CTS is a substrate for PgP that can pump CTS into the luminal side.

Hypothesis verification using parametric models and active vision strategies

This paper proposes a methodology for determining the shape and ultimately the functionality of objects from intensity images; 2D analytic functions are used to track 3D features during known camera motions. Three analytic functions are proposed that describe the relationship between pairs of points that are either stationary or moving depending on whether the points are on occluding boundaries or otherwise. Many of the problems of correspondence are reduced by using foveation, known camera motion, and active vision methods. The three analytic functions are shown to enable hypothesis refinement of the functionality of a number of 3D objects without full 3D information about the shape.

Obtaining functional parametric models using active vision strategies

This paper addresses the problem of determining which 3D shape is present, and more importantly, the dimensions of the shape in a scene. This is performed in an active vision system because it reduces the complexity of the problem through the use of gaze stabilization, choice of foveation point, and selective processing by adaptively processing regions of interest. In our case, only a small number of equations and parameters are needed for each shape and these are incorporated into functional descriptions of the shapes.

Emerging hypothesis verification using function-based geometric models and active vision strategies

This paper describes an investigation into the use of parametric 2D models describing the movement of edges for the determination of possible 3D shape and hence function of an object. An assumption of this research is that the camera can foveate and track particular features. It is argued that simple 2D analytic descriptions of the movement of edges can infer 3D shape while the camera is moved. This uses an advantage of foveation i.e. the problem becomes object centred. The problem of correspondence for numerous edge points is overcome by the use of a tree based representation for the competing hypotheses. Numerous hypothesis are maintained simultaneously and it does not rely on a single kinematic model which assumes constant velocity or acceleration. The numerous advantages of this strategy are described.

Obtaining function models using active vision strategies

This paper addresses the problem of determening which 3D shape is present, and more importantly, the dimensions of the shape within a scene. This is performed in an active vision system because it reduces the complexity of the problem through the use of gaze stabilisation, choice of foveation point and selective processing by adaptively processing regions of interest. In our case only a small number of equations and parameters are needed for each shape. For example, a container has width and height. These are incorporated into functional descriptions of the shapes.

Models of passive and active dendrite motoneuron pools and their differences in muscle force control

Motoneuron (MN) dendrites may be changed from a passive to an active state by increasing the levels of spinal cord neuromodulators, which activate persistent inward currents (PICs). These exert a powerful influence on MN behavior and modify the motor control both in normal and pathological conditions. Motoneuronal PICs are believed to induce nonlinear phenomena such as the genesis of extra torque and torque hysteresis in response to percutaneous electrical stimulation or tendon vibration in humans. An existing large-scale neuromuscular simulator was expanded to include MN models that have a capability to change their dynamic behaviors depending on the neuromodulation level. The simulation results indicated that the variability (standard deviation) of a maintained force depended on the level of neuromodulatory activity. A force with lower variability was obtained when the motoneuronal network was under a strong influence of PICs, suggesting a functional role in postural and precision tasks. In an additional set of simulations when PICs were active in the dendrites of the MN models, the results successfully reproduced experimental results reported from humans. Extra torque was evoked by the self-sustained discharge of spinal MNs, whereas differences in recruitment and de-recruitment levels of the MNs were the main reason behind torque and electromyogram (EMG) hysteresis. Finally, simulations were also used to study the influence of inhibitory inputs on a MN pool that was under the effect of PICs. The results showed that inhibition was of great importance in the production of a phasic force, requiring a reduced co-contraction of agonist and antagonist muscles. These results show the richness of functionally relevant behaviors that can arise from a MN pool under the action of PICs.

Using performance measurement models for benefit realization with enterprise systems: The Queensland Government approach (Case Study)

A range of influences, technical and organizational, has encouraged the wide spread adaption of Enterprise Systems (ES). Nevertheless, there is a growing consensus that Enterprise Systems have in the many cases failed to provide the expected benefits to organizations. This paper presents ongoing research, which analyzes the benefits realization approach of the Queensland Government. This approach applies a modified Balance Scorecard. First, history and background of Queensland Government’s Enterprise Systems initiative is introduced. Second, the most common reasons for ES under performance are related. Third, relevant performance measurement models and the Balanced Scorecard in particular are discussed. Finally, the Queensland Government initiative is evaluated in light of this overview of current work in the area. In the current and future work, the authors aim to use their active involvement in Queensland Government’s benefits realization initiative for an Action Research based project investigating the appropriateness of the Balanced Scorecard for the purposes of Enterprise Systems benefits realization.

Continuous appearance-based trajectory SLAM

This paper describes a novel probabilistic approach to incorporating odometric information into appearance-based SLAM systems, without performing metric map construction or calculating relative feature geometry. The proposed system, dubbed Continuous Appearance-based Trajectory SLAM (CAT-SLAM), represents location as a probability distribution along a trajectory, and represents appearance continuously over the trajectory rather than at discrete locations. The distribution is evaluated using a Rao-Blackwellised particle filter, which weights particles based on local appearance and odometric similarity and explicitly models both the likelihood of revisiting previous locations and visiting new locations. A modified resampling scheme counters particle deprivation and allows loop closure updates to be performed in constant time regardless of map size. We compare the performance of CAT-SLAM to FAB-MAP (an appearance-only SLAM algorithm) in an outdoor environment, demonstrating a threefold increase in the number of correct loop closures detected by CAT-SLAM.

3D ellipsoid fitting for multi-view gait recognition

Gait recognition approaches continue to struggle with challenges including view-invariance, low-resolution data, robustness to unconstrained environments, and fluctuating gait patterns due to subjects carrying goods or wearing different clothes. Although computationally expensive, model based techniques offer promise over appearance based techniques for these challenges as they gather gait features and interpret gait dynamics in skeleton form. In this paper, we propose a fast 3D ellipsoidal-based gait recognition algorithm using a 3D voxel model derived from multi-view silhouette images. This approach directly solves the limitations of view dependency and self-occlusion in existing ellipse fitting model-based approaches. Voxel models are segmented into four components (left and right legs, above and below the knee), and ellipsoids are fitted to each region using eigenvalue decomposition. Features derived from the ellipsoid parameters are modeled using a Fourier representation to retain the temporal dynamic pattern for classification. We demonstrate the proposed approach using the CMU MoBo database and show that an improvement of 15-20% can be achieved over a 2D ellipse fitting baseline.

Higher-Order spectra of nonlinear polynomial models for Chua's circuit

Polynomial models are shown to simulate accurately the quadratic and cubic nonlinear interactions (e.g. higher-order spectra) of time series of voltages measured in Chua's circuit. For circuit parameters resulting in a spiral attractor, bispectra and trispectra of the polynomial model are similar to those from the measured time series, suggesting that the individual interactions between triads and quartets of Fourier components that govern the process dynamics are modeled accurately. For parameters that produce the double-scroll attractor, both measured and modeled time series have small bispectra, but nonzero trispectra, consistent with higher-than-second order nonlinearities dominating the chaos.

Intelligent computing and sensing for active safety on construction sites

On obstacle-cluttered construction sites where heavy equipment is in use, safety issues are of major concern. The main objective of this paper is to develop a framework with algorithms for obstacle avoidance and path planning based on real-time three-dimensional job site models to improve safety during equipment operation. These algorithms have the potential to prevent collisions between heavy equipment vehicles and other on-site objects. In this study, algorithms were developed for image data acquisition, real-time 3D spatial modeling, obstacle avoidance, and shortest path finding and were all integrated to construct a comprehensive collision-free path. Preliminary research results show that the proposed approach is feasible and has the potential to be used as an active safety feature for heavy equipment.

CAT-SLAM : probabilistic localisation and mapping using a continuous appearance-based trajectory

This paper describes a new system, dubbed Continuous Appearance-based Trajectory Simultaneous Localisation and Mapping (CAT-SLAM), which augments sequential appearance-based place recognition with local metric pose filtering to improve the frequency and reliability of appearance-based loop closure. As in other approaches to appearance-based mapping, loop closure is performed without calculating global feature geometry or performing 3D map construction. Loop-closure filtering uses a probabilistic distribution of possible loop closures along the robot’s previous trajectory, which is represented by a linked list of previously visited locations linked by odometric information. Sequential appearance-based place recognition and local metric pose filtering are evaluated simultaneously using a Rao–Blackwellised particle filter, which weights particles based on appearance matching over sequential frames and the similarity of robot motion along the trajectory. The particle filter explicitly models both the likelihood of revisiting previous locations and exploring new locations. A modified resampling scheme counters particle deprivation and allows loop-closure updates to be performed in constant time for a given environment. We compare the performance of CAT-SLAM with FAB-MAP (a state-of-the-art appearance-only SLAM algorithm) using multiple real-world datasets, demonstrating an increase in the number of correct loop closures detected by CAT-SLAM.

The active site residue V266 of Chlamydial HtrA is critical for substrate binding during both in vitro and in vivo conditions

HtrA is a complex, multimeric chaperone and serine protease important for the virulence and survival of many bacteria. Chlamydia trachomatis is an obligate, intracellular bacterial pathogen that is responsible for severe disease pathology. C. trachomatis HtrA (CtHtrA) has been shown to be highly expressed in laboratory models of disease. In this study, molecular modelling of CtHtrA protein active site structure identified putative S1-S3 subsite residues I242, I265, and V266. These residues were altered by site-directed mutagenesis, and these changes were shown to considerably reduce protease activity on known substrates and resulted in a narrower and distinct range of substrates compared to wild type. Bacterial two-hybrid analysis revealed that CtHtrA is able to interact in vivo with a broad range of protein sequences with high affinity. Notably, however, the interaction was significantly altered in 35 out of 69 clones when residue V266 was mutated, indicating that this residue has an important function during substrate binding.