An Ultra-Fast and Parallelizable Algorithm for Finding k-Mismatch Shortest Unique Substrings.

This paper revisits the k-mismatch shortest unique substring finding problem and demonstrates that a technique recently presented in the context of solving the k-mismatch average common substring problem can be adapted and combined with parts of the existing solution, resulting in a new algorithm which has expected time complexity of O(n logk n), while maintaining a practical space complexity at O(kn), where n is the string length. When , which is the hard case, our new proposal significantly improves the any-case O(n2) time complexity of the prior best method for k-mismatch shortest unique substring finding. Experimental study shows that our new algorithm is practical to implement and demonstrates significant improvements in processing time compared to the prior best solution's implementation when k is small relative to n. For example, our method processes a 200 KB sample DNA sequence with k=1 in just 0.18 seconds compared to 174.37 seconds with the prior best solution. Further, it is observed that significant portions of the adapted technique can be executed in parallel, using two different simple concurrency models, resulting in further significant practical performance improvement. As an example, when using 8 cores, the parallel implementations both achieved processing times that are less than 1/4 of the serial implementation's time cost, when processing a 10 MB sample DNA sequence with k=2. In an age where instances with thousands of gigabytes of RAM are readily available for use through Cloud infrastructure providers, it is likely that the trade-off of additional memory usage for significantly improved processing times will be desirable and needed by many users. For example, the best prior solution may spend years to finish a DNA sample of 200MB for any , while this new proposal, using 24 cores, can finish processing a sample of this size with k=1 in 206.376 seconds with a peak memory usage of 46 GB, which is both easily available and affordable on Cloud. It is expected that this new efficient and practical algorithm for k-mismatch shortest unique substring finding will prove useful to those using the measure on long sequences in fields such as computational biology. We also give a theoretical bound that the k-mismatch shortest unique substring finding problem can be solved using O(n logk n) time and O(n) space, asymptotically much better than the one we implemented, serving as a new discovery of interest.

Accuracy assessment for the co-registration between optical and VIVE head-mounted display tracking.

PURPOSE: We report on the development and accuracy assessment of a hybrid tracking system that integrates optical spatial tracking into a video pass-through head-mounted display. METHODS: The hybrid system uses a dual-tracked co-calibration apparatus to provide a co-registration between the origins of an optical dynamic reference frame and the VIVE Pro controller through a point-based registration. This registration provides the location of optically tracked tools with respect to the VIVE controller's origin and thus the VIVE's tracking system. RESULTS: The positional accuracy was assessed using a CNC machine to collect a grid of points with 25 samples per location. The positional trueness and precision for the hybrid tracking system were [Formula: see text] and [Formula: see text], respectively. The rotational accuracy was assessed through inserting a stylus tracked by all three systems into a hemispherical phantom with cylindrical openings at known angles and collecting 25 samples per cylinder for each system. The rotational trueness and precision for the hybrid tracking system were [Formula: see text] and [Formula: see text], respectively. The difference in position and rotational trueness between the OTS and the hybrid tracking system was [Formula: see text] and [Formula: see text], respectively. CONCLUSIONS: We developed a hybrid tracking system that allows the pose of optically tracked surgical instruments to be known within a first-person HMD visualization system, achieving submillimeter accuracy. This research validated the positional and rotational accuracy of the hybrid tracking system and subsequently the optical tracking and VIVE tracking systems. This work provides a method to determine the position of an optically tracked surgical tool with a surgically acceptable accuracy within a low-cost commercial-grade video pass-through HMD. The hybrid tracking system provides the foundation for the continued development of virtual reality or augmented virtuality surgical navigation systems for training or practicing surgical techniques.

Development of CXCR3 antagonists. Part 4: discovery of 2-amino-(4-tropinyl)quinolines.

The synthesis and biological evaluation of a novel series of 2-aminoquinoline substituted piperidines and tropanes incorporating a homotropene moiety is herein described. The series exhibits potent antagonism of the CXCR3 receptor and superior physicochemical properties. Compound 24d was found to be orally bioavailable, and PK/PD studies suggested it as a suitable tool for studying the role of CXCR3 in models of disease.

Development of CXCR3 antagonists. Part 3: Tropenyl and homotropenyl-piperidine urea derivatives.

The optimization of a series of 1-aryl-3-piperidinyl urea derivatives is described in which incorporation of tropenyl and homotropenyl moieties has led to significant improvements in activity and drug-like properties. Replacement of the central piperidine with an exo-tropanyl unit led to the identification of compound 15 which provides a combination of excellent potency against human and murine receptors, drug-like properties and pharmacokinetics, thus providing a valuable tool for the evaluation of CXCR3 antagonists in models of human disease.

Development of CXCR3 antagonists. Part 2: Identification of 2-amino(4-piperidinyl)azoles as potent CXCR3 antagonists.

Development of a lead series of piperidinylurea CXCR3 antagonists has led to the identification of molecules with alternative linkages which retain good potency. A novel 5-(piperidin-4-yl)amino-1,2,4-thiadiazole derivative was found to have satisfactory in vitro metabolic stability and to be orally bioavailable in mice, giving high plasma concentrations and a half life of 5.4h.

Identification and structure-activity relationships of 1-aryl-3-piperidin-4-yl-urea derivatives as CXCR3 receptor antagonists.

The synthesis and biological evaluation of a series of 1-aryl-3-piperidin-4-yl-urea derivatives as small-molecule CXCR3 antagonists is described. SAR studies resulted in significant improvement of potency and physicochemical properties and established the key pharmacophore of the series, and led to the identification of 9t, which exhibits an IC50 of 16 nM in the GTPgammaS35 functional assay.