Functionally Optimized Neuritogenic Farinosone C Analogs: SAR-Study and Investigations on Their Mode of Action

Several natural products derived from entomopathogenic fungi have been shown to initiate neuronal differentiation in the rat pheochromocytoma PC12 cell line. After the successful completion of the total synthesis program, the reduction of structural complexity while retaining biological activity was targeted. In this study, farinosone C served as a lead structure and inspired the preparation of small molecules with reduced complexity, of which several were able to induce neurite outgrowth. This allowed for the elaboration of a detailed structure-activity relationship. Investigations on the mode of action utilizing a computational similarity ensemble approach suggested the involvement of the endocannabinoid system as potential target for our analogs and also led to the discovery of four potent new endocannabinoid transport inhibitors.

Graphics Processor Unit Based Parallelization of Optimized Baseline Wander Filtering Algorithms for Long-term Electrocardiography

Long-term electrocardiogram (ECG) often suffers from relevant noise. Baseline wander in particular is pronounced in ECG recordings using dry or esophageal electrodes, which are dedicated for prolonged registration. While analog high-pass filters introduce phase distortions, reliable offline filtering of the baseline wander implies a computational burden that has to be put in relation to the increase in signal-to-baseline ratio (SBR). Here we present a graphics processor unit (GPU) based parallelization method to speed up offline baseline wander filter algorithms, namely the wavelet, finite, and infinite impulse response, moving mean, and moving median filter. Individual filter parameters were optimized with respect to the SBR increase based on ECGs from the Physionet database superimposed to auto-regressive modeled, real baseline wander. A Monte-Carlo simulation showed that for low input SBR the moving median filter outperforms any other method but negatively affects ECG wave detection. In contrast, the infinite impulse response filter is preferred in case of high input SBR. However, the parallelized wavelet filter is processed 500 and 4 times faster than these two algorithms on the GPU, respectively, and offers superior baseline wander suppression in low SBR situations. Using a signal segment of 64 mega samples that is filtered as entire unit, wavelet filtering of a 7-day high-resolution ECG is computed within less than 3 seconds. Taking the high filtering speed into account, the GPU wavelet filter is the most efficient method to remove baseline wander present in long-term ECGs, with which computational burden can be strongly reduced.

Cutaneous Collagenous Vasculopathy: A Rare Form of Microangiopathy Successfully Treated with a Combination of Multiplex Laser and Optimized Pulsed Light with a Review of the Literature.

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy of the cutaneous vasculature characterized histologically by the presence of dilated small blood vessels with flat endothelial cells and thickened walls containing hyaline material in the upper dermis. We report an elderly patient presenting with an extensive form of CCV involving the trunk, upper and lower limbs. She was treated with Multiplex PDL 595-nm/Nd:YAG 1,064-nm laser and optimized pulsed light. This approach, which has never been reported for CCV so far, resulted in a striking and almost complete clearance of the widespread lesions. We here review our knowledge about CCV and therapeutic options available with a survey of the literature.

Optimized on-line enantioselective capillary electrophoretic method for kinetic and inhibition studies of drug metabolism mediated by cytochrome P450 enzymes.

Pharmacokinetic and pharmacodynamic properties of a chiral drug can significantly differ between application of the racemate and single enantiomers. During drug development, the characteristics of candidate compounds have to be assessed prior to clinical testing. Since biotransformation significantly influences drug actions in an organism, metabolism studies represent a crucial part of such tests. Hence, an optimized and economical capillary electrophoretic method for on-line studies of the enantioselective drug metabolism mediated by cytochrome P450 enzymes was developed. It comprises a diffusion-based procedure, which enables mixing of the enzyme with virtually any compound inside the nanoliter-scale capillary reactor and without the need of additional optimization of mixing conditions. For CYP3A4, ketamine as probe substrate and highly sulfated γ-cyclodextrin as chiral selector, improved separation conditions for ketamine and norketamine enantiomers compared to a previously published electrophoretically mediated microanalysis method were elucidated. The new approach was thoroughly validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. The determined parameters were found to be comparable to literature data obtained with different techniques. The presented method constitutes a miniaturized and cost-effective tool, which should be suitable for the assessment of the stereoselective aspects of kinetic and inhibition studies of cytochrome P450-mediated metabolic steps within early stages of the development of a new drug.

Enhanced iron gettering by short, optimized low-temperature annealing after phosphorus emitter diffusion for industrial silicon solar cell processing

The introduction of a low-temperature (LT) tail after P emitter diffusion was shown to lead to considerable improvements in electron lifetime and solar cell performance by different researchers. So far, the drawback of the investigated extended gettering treatments has been the lack of knowledge about optimum annealing times and temperatures and the important increase in processing time. In this manuscript, we calculate optimum annealing temperatures of Fe-contaminated Si wafers for different annealing durations. Subsequently, it is shown theoretically and experimentally that a relatively short LT tail of 15 min can lead to a significant reduction of interstitial Fe and an increase in electron lifetime. Finally, we calculate the potential improvement of solar cell efficiency when such a short-tail extended P diffusion gettering is included in an industrial fabrication process.

Optimized edge appearance probability for cooperative localization based on tree-reweighted nonparametric belief propagation

Nonparametric belief propagation (NBP) is a well-known particle-based method for distributed inference in wireless networks. NBP has a large number of applications, including cooperative localization. However, in loopy networks NBP suffers from similar problems as standard BP, such as over-confident beliefs and possible nonconvergence. Tree-reweighted NBP (TRW-NBP) can mitigate these problems, but does not easily lead to a distributed implementation due to the non-local nature of the required so-called edge appearance probabilities. In this paper, we propose a variation of TRWNBP, suitable for cooperative localization in wireless networks. Our algorithm uses a fixed edge appearance probability for every edge, and can outperform standard NBP in dense wireless networks.

Optimized algorithms for the incremental analysis of logic programs

Global analysis of logic programs can be performed effectively by the use of one of several existing efficient algorithms. However, the traditional global analysis scheme in which all the program code is known in advance and no previous analysis information is available is unsatisfactory in many situations. Incrementa! analysis of logic programs has been shown to be feasible and much more efficient in certain contexts than traditional (non-incremental) global analysis. However, incremental analysis poses additional requirements on the fixpoint algorithm used. In this work we identify these requirements, present an important class of strategies meeting the requirements, present sufficient a priori conditions for such strategies, and propose, implement, and evalúate experimentally a novel algorithm for incremental analysis based on these ideas. The experimental results show that the proposed algorithm performs very efficiently in the incremental case while being comparable to (and, in some cases, considerably better than) other state-of-the-art analysis algorithms even for the non-incremental case. We argüe that our discussions, results, and experiments also shed light on some of the many tradeoffs involved in the design of algorithms for logic program analysis.

Accelerating FPGA-based evolution of wavelet transform filters by optimized task scheduling

Adaptive embedded systems are required in various applications. This work addresses these needs in the area of adaptive image compression in FPGA devices. A simplified version of an evolution strategy is utilized to optimize wavelet filters of a Discrete Wavelet Transform algorithm. We propose an adaptive image compression system in FPGA where optimized memory architecture, parallel processing and optimized task scheduling allow reducing the time of evolution. The proposed solution has been extensively evaluated in terms of the quality of compression as well as the processing time. The proposed architecture reduces the time of evolution by 44% compared to our previous reports while maintaining the quality of compression unchanged with respect to existing implementations. The system is able to find an optimized set of wavelet filters in less than 2 min whenever the input type of data changes.

An optimized QoS scheme for IMS-NEMO in heterogeneous networks

The network mobility (NEMO) is proposed to support the mobility management when users move as a whole. In IP Multimedia Subsystem (IMS), the individual Quality of Service (QoS) control for NEMO results in excessive signaling cost. On the other hand, current QoS schemes have two drawbacks: unawareness of the heterogeneous wireless environment and inefficient utilization of the reserved bandwidth. To solve these problems, we present a novel heterogeneous bandwidth sharing (HBS) scheme for QoS provision under IMS-based NEMO (IMS-NEMO). The HBS scheme selects the most suitable access network for each session and enables the new coming non-real-time sessions to share bandwidth with the Variable Bit Rate (VBR) coded media flows. The modeling and simulation results demonstrate that the HBS can satisfy users' QoS requirement and obtain a more efficient use of the scarce wireless bandwidth.

See-and-avoid quadcopter using fuzzy control optimized by cross-entropy

In this work we present an optimized fuzzy visual servoing system for obstacle avoidance using an unmanned aerial vehicle. The cross-entropy theory is used to optimise the gains of our controllers. The optimization process was made using the ROS-Gazebo 3D simulation with purposeful extensions developed for our experiments. Visual servoing is achieved through an image processing front-end that uses the Camshift algorithm to detect and track objects in the scene. Experimental flight trials using a small quadrotor were performed to validate the parameters estimated from simulation. The integration of crossentropy methods is a straightforward way to estimate optimal gains achieving excellent results when tested in real flights.

Analysis and optimized design of a distributed multi-stage EMC filter for an interleaved three-phase PWM-rectifier system for aircraft applications

Different possible input filter configurations for a modular three-phase PWM rectifier system consisting of three interleaved converter cells are studied. The system is designed for an aircraft application where MIL-STD-461E conducted EMI standards have to be met and system weight is a critical design issue. The importance of a LISN model on the simulated noise levels and the effect of interleaving and power unbalance between the different converter modules is discussed. The effect of the number of filter stages and the degree of distribution of the filter stages among the individual converter modules on the weight and losses of the input filter is studied and optimal filter structures are proposed.