3D sensors are used for many different applications, e.g., scene reconstruction, object detection, and mobile robots, etc. Several studies on usability and accuracy have been done for different sensors. However, all these studies have used different settings for the different sensors. For this reason we compare five 3D sensors, including the structured light sensors Microsoft Kinect and ASUS Xtion Pro Live, and the time of flight sensors Fotonic E70P, IFM O3D200 and Nippon Signal FX6, using the same settings. The sensor noise, absolute error, and point detection rates are compared for different depth values, environmental illumination, and different surfaces. Also, simple models of the noise depending on the measured depth are proposed. It is found that structured light sensors are very accurate for close ranges. The time of flight sensors have more noise, but the noise does not increase as strongly with the measured distance. Further, it is found that these sensors can be used for outdoor applications.

The discovery and SAR of a series of potent renin inhibitors possessing a novel 3,4-diarylpiperidine scaffold are described herein. The resulting compound 38 exhibit low nanomolar plasma renin IC(50), had a clean CYP 3A4 profile and displayed micromolar affinity for the hERG channel. Furthermore, it was found to be efficacious in the double transgenic rat hypertension model and show good to moderate oral bioavailability in two animal species.

We present a method of utilizing depth information as provided by RGBD sensors for robust real-time visual simultaneous localisation and mapping (SLAM) by augmenting monocular visual SLAM to take into account depth data. This is implemented based on the feely available software "Parallel Tracking and Mapping" by Georg Klein. Our modifications allow PTAM to be used as a 6D visual SLAM system even without any additional information about odometry or from an inertial measurement unit.

The design and optimization of a novel series of renin inhibitor is described herein. Strategically, by committing the necessary resources to the development of synthetic sequences and scaffolds that were most amenable for late stage structural diversification, even as the focus of the SAR campaign moved from one end of the molecule to another, highly potent renin inhibitors could be rapidly identified and profiled.

The incorporation of a carboxylic acid within in a series of 3-amido-4-aryl substituted piperidines (represented by general structure 32) led to the discovery of potent, zwitterionic, renin inhibitors with improved off-target profiles (CYP3A4 time-dependent inhibition and hERG affinity) relative to analogous non-zwitterionic inhibitors of the past (i.e., 3). Strategies to address the oral absorption of these zwitterions are also discussed within.

We present the evolution of a highly-efficient system for visually detecting number signs in real-time on a mobile robot with limited computational power. The system was designed for use on a robot participating in the 2010 SICK robot day robotics challenge, in which the robot needed to autonomously find 10 number signs and drive to all of them in a given order as fast as possible. Our most efficient method has proven to be robust and successful, since our robot won the competition using the final vision systems described in this paper.

Depth cameras, like the Microsoft Kinect system, are valuable sensors for mobile robotics since their data enables a highly detailed perception of the environmental structure. Certainly, their amount of data is often too high to be processed in real-time by the limited resources of mobile robots. One way of using these sensors is to reduce the amount of data by extracting features like planes from the raw depth images. In this work we present a method to extract planes from depth images based on the Randomized Hough Transformation, which is specially adapted to the properties of the Kinect sensor. Therefore we use a noise model of the sensor to solve the task of finding proper parameter metrics for the Randomized Hough Transform. As a result, our approach extracts the planes from a depth image in less than one millisecond on the platform of a mobile robot and is therefore real-time capable.

An oral bioavailability issue encountered during the course of lead optimization in the renin program is described herein. The low Fpo of pyridone analogs was shown to be caused by a combination of poor passive permeability and gut efflux transport. Substitution of pyridone ring for a more lipophilic moiety (logD>1.7) had minimal effect on rMdr1a transport but led to increased passive permeability (Papp>10×10−6cm/s), which contributed to overwhelm gut transporters and increase rat Fpo. LogD and in vitro passive permeability determination were found to be key in guiding SAR and improve oral exposure of renin inhibitors.

An SAR campaign aimed at decreasing the overall lipophilicity of renin inhibitors such as 1 is described herein. It was found that replacement of the northern appendage in 1 with an N-methyl pyridone and subsequent re-optimization of the benzyl amide handle afforded compounds with in vitro and in vivo profiles suitable for further profiling. An unexpected CV toxicity in dogs observed with compound 20 led to the employment of a time and resource sparing rodent model for in vivo screening of key compounds. This culminated in the identification of compound 31 as an optimized renin inhibitor.

The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar renin IC50 and good oral bioavailability in rats.

The discovery and SAR of a new series of substituted amino propanamide renin inhibitors are herein described. This work has led to the preparation of compounds with in vitro and in vivo profiles suitable for further development. Specifically, challenges pertaining to oral bioavailability, covalent binding and time-dependent CYP 3A4 inhibition were overcome thereby culminating in the identification of compound 50 as an optimized renin inhibitor with good efficacy in the hypertensive double-transgenic rat model.

Time-dependent inhibitors of CYPs have the potential to perpetrate drug-drug interactions in the clinical setting. After finding that several leading compounds in a novel series of substituted amino propanamide renin inhibitors inactivated CYP3A4 in an NADPH-dependent and time-dependent manner, a search to identify the cause of this liability was initiated. Extensive SAR revealed that the amide bridge present in compound 1 as a possible culprit. Through the installation of a metabolic soft spot distal to this moiety, potent renin inhibitors with improved CYP profile were identified.

The structure-activity relationship of a novel series of 8-biarylnaphthyridinones acting as type 4 phosphodiesterase (PDE4) inhibitors for the treatment of long-term memory loss and mild cognitive impairment is described herein. The manuscript describes a new paradigm for the development of PDE4 inhibitor targeting CNS indications. This effort led to the discovery of the clinical candidate MK-0952, an intrinsically potent inhibitor (IC(50)=0.6 nM) displaying limited whole blood activity (IC(50)=555 nM). Supporting in vivo results in two preclinical efficacy tests and one test assessing adverse effects are also reported. The comparative profiles of MK-0952 and two other Merck compounds are described to validate the proposed hypothesis.

The SAR study of a series of 6-aryloxymethyl-8-aryl substituted quinolines is described. Optimization of the series led to the discovery of compound 26b, a highly potent (IC50=0.6nM) and selective PDE4D inhibitor with a 75-fold selectivity over the A, B, and C subtypes and over 18,000-fold selectivity against other PDE family members. Rat pharmacokinetics and tissue distribution are also summarized.

Substituted 8-arylquinoline analogs bearing alkyl-linked side chain were identified as potent inhibitors of type 4 phophodiesterase. These compounds address the potential liabilities of the clinical candidate L-454560. The pharmacokinetic profile of the best analogs and the in vivo efficacy in an ovalbumin-induced bronchoconstriction assay in conscious guinea pigs are reported.

The structure-activity relationship of a novel series of 8-biarylquinolines acting as type 4 phosphodiesterase (PDE4) inhibitors is described herein. Prototypical compounds from this series are potent and non-selective inhibitors of the four distinct PDE4 (IC50 < 10 nM) isozymes (A-D). In a human whole blood in vitro assay, they inhibit (IC50 < 0.5 mu M) the LPS-induced release of the cytokine TNF-alpha. Optimized inhibitors were evaluated in vivo for efficacy in an ovalbumin-induced bronchoconstriction model in conscious guinea pigs. Their propensity to produce an emetic response was evaluated by performing pharmacokinetic studies in squirrel monkeys. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of efficacy over emesis. (c) 2008 Elsevier Ltd. All rights reserved.