Gyrase ATPase Domain as an Antitubercular Drug Discovery Platform: Structure‐Based Design and Lead Optimization of Nitrothiazolyl Carboxamide Analogues

In this study, we explored the pharmaceutically underexploited mycobacterial gyrase ATPase (GyrB) domain as a template for a structure‐based virtual screening of our in‐house (BITS Pilani) compound collection to discover new inhibitors targeting Mycobacterium tuberculosis (M.tb.) The hit identified was further customized by using a combination of molecular docking and medicinal chemistry strategies to obtain an optimized analogue displaying considerable in vitro enzyme efficacy and bactericidal properties against the M.tb. H₃₇Rv strain. The binding affinity of the ligand toward the GyrB domain was reascertained by differential scanning fluorimetry experiments. Further evaluation of the hERG toxicity (a major limitation among the previously reported N‐linked aminopiperidine analogues) indicated these molecules to be completely devoid of cardiotoxicity, a significant achievement within this class.     

Optimal route planning for stochastic time-dependent hitchhiker’s problem

ABSTRACT

Hitchhiking is a travel mode characterised by unpredictable travel times involving several possible combinations of lifts on roads. In this paper, we formulate a hitchhiker’s problem and develop a time-dependent stochastic route planning algorithm for hitchhikers. Namely, we introduce a concept of the stochastic time-dependent hitchhiking graph to find hitchhiking strategies with the least expected travel time or maximised reliability. We introduce various heuristics to prune the original hitchhiking graph to improve computational efficiency. We provide a complexity analysis of the problem and evaluate the proposed solution on real-world networks of several countries.     

An Innovative Master's Program in Distributed Computing

Distributed computing systems and applications are not only changing the face of computing, they're also continually changing the way we live, work, and interact as a society. In recent years, the demand for educational courses in advanced computing and networking has expanded rapidly. This has led to a huge demand for Internet-based distributed computing technologies (such as Web and grid services) and applications that virtualize geographically distributed resources to enable the creation of virtual enterprises, marketplaces, and service-oriented computing industries. Because current academic programs don't yet address the skill set required to meet these demands, we launched a Master of Engineering in distributed computing program at the University of Melbourne     

Join algorithm costs revisited

A method of analysing join algorithms based upon the time required to access, transfer and perform the relevant CPU-based operations on a disk page is proposed. The costs of variations of several of the standard join algorithms, including nested block, sort-merge, GRACE hash and hybrid hash, are presented. For a given total buffer size, the cost of these join algorithms depends on the parts of the buffer allocated for each purpose. For example, when joining two relations using the nested block join algorithm, the amount of buffer space allocated for the outer and inner relations can significantly affect the cost of the join. Analysis of expected and experimental results of various join algorithms show that a combination of the optimal nested block and optimal GRACE hash join algorithms usually provide the greatest cost benefit, unless the relation size is a small multiple of the memory size. Algorithms to quickly determine a buffer allocation producing the minimal cost for each of these algorithms are presented. When the relation size is a small multiple of the amount of main memory available (typically up to three to six times), the hybrid hash join algorithm is preferable. Edited by Masaru Kitsuregawa. Received April 26, 1993 / Revised March 3, 1994 / Accepted October 13, 1994     

The Bauschinger effect’s influence on the SIFs of multiple longitudinal coplanar cracks in autofrettaged pressurized cylinders

The influence of the Bauschinger effect (BE) on the three-dimensional, Mode I, stress intensity factor (SIF) distributions for arrays of longitudinal coplanar, surface cracks emanating from the bore of a fully or partially autofrettaged thick-walled cylinder is investigated. The SIFs for both “realistic” - Bauschinger effect dependent autofrettage (BEDA) and “ideal” - Bauschinger effect independent autofrettage (BEIA) are obtained and compared. The 3D analysis is performed via the finite element (FE) method and the submodeling technique, employing singular elements along the crack front. Both autofrettage residual stress fields, BEDA and BEIA, are simulated using an equivalent temperature field. The Bauschinger effect (BE) is found to significantly lower the beneficial stress intensity factor due to autofrettage, K_IA, by up to 52%, as compared to the “ideal” autofrettage case. The reduction in K_IA varies along the crack front with the maximum determined by the crack ellipticity, crack depth and crack separation distance. The detrimental influence of the BE increases as the crack density decreases and as crack depth decreases. For a partially autofrettaged cylinder, the influence of the BE is considerably reduced as the level of overstrain becomes smaller. Furthermore, the results indicate that in certain situations crack density and crack ellipticity have opposing effects on the autofrettage SIF.     

Efficient recursive aggregation and negation in deductive databases

We present an efficient evaluation technique for modularly stratified deductive database programs for which the local strata level mappings are known at compile time. We present an important subclass of these programs (called EMS-programs) in which one can easily express problems, such as shortest distance, company ownership, bill of materials, and preferential vote counting. Programs written in this style have an easy-to-understand semantics and can be efficiently computed. Another important virtue of these programs is that their modular-stratification properties are independent of the extensional database     

A call quality performance measure for handoff algorithms

This paper proposes a new approach for performance evaluation and comparison between existing handoff algorithms taking into consideration signal levels, call dropping, and handoff cost. Using the new approach, existing handoff algorithms are then compared in terms of signal quality and number of handoffs required to achieve a desired overall signal quality. We also provide in this paper a method to estimate handoff cost and to optimize handoff sequences for retrial (where repeated call attempts are made after a call is lost) and non‐retrial models based on the proposed approach. We observe that the Threshold with Hysteresis method performs better than other known methods including the one used in the GSM standard. Our results indicate that the Threshold with 4 dB Hysteresis method performs well for urban areas although with a high dropping probability, whereas the Threshold with 6 dB Hysteresis method suits for suburban areas with a low dropping probability. We find that handoff sequences obtained by existing handoff methods are less efficient than the optimal handoff sequence given in the paper by a margin of 29–45% for retrial model, and by 34–77% for non‐retrial model. The paper also suggests some specific parameter values to improve the performance of currently used handoff methods based on our findings. Copyright © 2010 John Wiley & Sons, Ltd.     

Data Mining: How Research Meets Practical Development?

At the 2001 IEEE International Conference on Data Mining in San Jose, California, on November 29 to December 2, 2001, there was a panel discussion on how data mining research meets practical development. One of the motivations for organizing the panel discussion was to provide useful advice for industrial people to explore their directions in data mining development. Based on the panel discussion, this paper presents the views and arguments from the panel members, the Conference Chair and the Program Committee Co-Chairs. These people as a group have both academic and industrial experiences in different data mining related areas such as databases, machine learning, and neural networks. We will answer questions such as (1) how far data mining is from practical development, (2) how data mining research differs from practical development, and (3) what are the most promising areas in data mining for practical development.     

A backtracking algorithm for the stream AND-parallel execution of logic programs

We present the first backtracking algorithm for stream AND-parallel logic programs. It relies on compile-time knowledge of the dataflow graph of each clause to let it figure out efficiently which goals to kill or restart when a goal fails. This crucial information, which we derive from mode declarations, was not available at compile-time in any previous stream AND-parallel system. We show that modes can increase the precision of the backtracking algorithm, though our algorithm allows this precision to be traded off against overhead on a procedure-by-procedure and call-by-call basis. The modes also allow our algorithm to handle efficiently programs that manipulate partially instantiated data structures and an important class of programs with circular dependency graphs. On code that does not need backtracking, the efficiency of our algorithm approaches that of the committed-choice languages; on code that does need backtracking its overhead is comparable to that of the independent AND-parallel backtracking algorithms.     

An Efficient Evaluation Technique for Non-Stratified Programs by Transformation to Explicitly Locally Stratified Programs

We give a simple transformation from normal programs with no stratification (local, weak, modular, etc.) into a subclass of the locally stratified programs, called Explicitly Locally Stratified (ELS) programs, for which there are efficient evaluation techniques. One set of predicates are generated for the true tuples and a different set of predicate are generated for the true and undefined tuples. A similar transformation is given that incorporates a magic sets like transformation. Previous approaches to magic sets transformations of unstratified programs either restricted the class of sips used or generated a program that required special treatment of the magic sets predicates. Our transformation does not suffer from these flaws.