Discovery of Mono‐ and Disubstituted 1H‐Pyrazolo[3,4]pyrimidines and 9H‐Purines as Catalytic Inhibitors of Human DNA Topoisomerase IIα

Human DNA topoisomerase IIα (htIIα) is a validated target for the development of anticancer agents. Based on structural data regarding the binding mode of AMP‐PNP (5′‐adenylyl‐β,γ‐imidodiphosphate) to htIIα, we designed a two‐stage virtual screening campaign that combines structure‐based pharmacophores and molecular docking. In the first stage, we identified several monosubstituted 9H‐purine compounds and a novel class of 1H‐pyrazolo[3,4]pyrimidines as inhibitors of htIIα. In the second stage, disubstituted analogues with improved cellular activities were discovered. Compounds from both classes were shown to inhibit htIIα‐mediated DNA decatenation, and surface plasmon resonance (SPR) experiments confirmed binding of these two compounds on the htIIα ATPase domain. Proposed complexes and interaction patterns between both compounds and htIIα were further analyzed in molecular dynamics simulations. Two compounds identified in the second stage showed promising anticancer activities in hepatocellular carcinoma (HepG2) and breast cancer (MCF‐7) cell lines. The discovered compounds are suitable starting points for further hit‐to‐lead development in anticancer drug discovery.     

Supply-chain transparency within industrialized construction projects

This paper addresses those issues relating to the integration of information flows in relation to material management throughout the construction industry supply-chain. Based on a case study, it shows how to bridge any gaps between those information systems used within the design, prefabrication, and on-site construction processes.     

Image processing and machine learning for fully automated probabilistic evaluation of medical images

The paper presents results of our long-term study on using image processing and data mining methods in a medical imaging. Since evaluation of modern medical images is becoming increasingly complex, advanced analytical and decision support tools are involved in integration of partial diagnostic results. Such partial results, frequently obtained from tests with substantial imperfections, are integrated into ultimate diagnostic conclusion about the probability of disease for a given patient. We study various topics such as improving the predictive power of clinical tests by utilizing pre-test and post-test probabilities, texture representation, multi-resolution feature extraction, feature construction and data mining algorithms that significantly outperform medical practice. Our long-term study reveals three significant milestones. The first improvement was achieved by significantly increasing post-test diagnostic probabilities with respect to expert physicians. The second, even more significant improvement utilizes multi-resolution image parametrization. Machine learning methods in conjunction with the feature subset selection on these parameters significantly improve diagnostic performance. However, further feature construction with the principle component analysis on these features elevates results to an even higher accuracy level that represents the third milestone. With the proposed approach clinical results are significantly improved throughout the study. The most significant result of our study is improvement in the diagnostic power of the whole diagnostic process. Our compound approach aids, but does not replace, the physician's judgment and may assist in decisions on cost effectiveness of tests.     

Dual-task performance in multimodal human-computer interaction: a psychophysiological perspective

This paper examines the psychophysiological effects of mental workload in single-task and dual-task human-computer interaction. A mental arithmetic task and a manual error correction task were performed both separately and concurrently on a computer using verbal and haptic input devices. Heart rate, skin conductance, respiration and peripheral skin temperature were recorded in addition to objective performance measures and self-report questionnaires. Analysis of psychophysiological responses found significant changes from baseline for both single-task and dual-task conditions. There were also significant psychophysiological differences between the mental arithmetic task and the manual error correction task, but no differences in questionnaire results. Additionally, there was no significant psychophysiological difference between performing only the mental arithmetic task and performing both tasks at once. These findings suggest that psychophysiological measures respond differently to different types of tasks and that they do not always agree with performance or with participants’ subjective feelings.     

Extensions of sweep surface constructions

Sweeping is a very important, powerful, and widespread method in geometric modelling. In this paper, we consider only sweep surfaces, generated by sweeping one curve (cross-section) along the other curve (trajectory), and their existing construction methods: the Frenet frame method, the discrete approach, the offset method, and the projection technique. All these methods are extended so that they now include non-homogeneous scaling and twisting of the cross-section, which enable the generation of complex twisted-profiled sweep surfaces.     

Unusual magnetic properties of NiO nanoparticles embedded in a silica matrix

We have observed unusual magnetic properties of NiO (nickel oxide) nanoparticles embedded in a silica matrix. The sample was synthesized by a method based on the contribution of sol-gel and combustion processes. X-ray powder diffraction (XRPD) of the sample shows the formation of the nanocrystalline NiO phase whereas transmission electron microscope (TEM) reveals spherical-shaped nanoparticles of about 4 nm diameter. Moreover, HRTEM images show lattice fringes of the nanoparticles and defects in the crystal structure. The temperature and field dependence of the magnetization are also measured. The zero-field-cooled (ZFC) measurements show two maximums, one sharp and narrow at low temperatures ∼6.5 K and an other broad one at higher temperature ∼64 K. The FC magnetization shows a continuous increase upon lowering the temperature. The M(H) measurements reveal that NiO nanoparticles display anomalous hysteretic behaviors at low temperatures (below the low temperature maximum in the ZFC curve, 2 K and 5 K) showing that the magnetization initial curve lies below the hysteresis loop for a certain field range. Moreover, jump of the magnetization at low temperatures (2 K and 5 K) are also observed. These features represent novel magnetic properties for nanosized NiO which may be attributed to the surface spins. Moreover, these results indicate that the NiO nanoparticle consists of magnetically disorder shell and antiferromagnetically order core with an uncompensated magnetic moment.     

Thermovision Method for Diagnostics of Local Characteristics of Natural Draft Cooling Towers

Abstract

Increased and more rigorous demands for power station operation in order to minimize both the cost of electrical energy production and environment pollution, addressed the necessity for optimisation of all segments of the process. As a consequence, there are certain needs for the introduction of new experimental methods which would ensure effective diagnostics.

A newly developed experimental method for thermovisional detection of the temperature field in natural draft cooling towers is presented in this paper. The method is adapted to the real conditions that are present inside cooling towers and enables spatial‐ and time‐dependent detection of local temperatures in the region of drift eliminators of natural draft cooling towers. Combined with the previously developed methods for detection of velocity and temperature fields, the thermovision method enables quick detection of the local efficiency of cooling towers. Results of the method can be used for diagnostics of local and integral characteristics of cooling tower operation. Apart from this, they enable prediction of local corrections in order to increase the cooling tower efficiency.     

Polyurethane coatings from liquefied wood containing remains of a copper‐, chromium‐, and boron‐based wood preservative

Preparation of polyurethane wood coatings based on copper‐, chromium‐, and boron (CCB) containing liquefied wood was performed, as an alternative way to manage postconsumed preservative‐contaminated wood. Additionally, we examined the possibility of improvement of selected properties of the liquefied wood‐based coatings by an addition of silica nanoparticles. The constituents of the CCB wood preservative do not exhibit an influence on a liquefaction process and on composition of the liquefied mixture. CCB also does not affect curing of the formulations containing liquefied wood and an isocyanate‐type hardener. Furthermore, influence of CCB on adhesion strength of liquefied wood‐based coatings on a wooden substrate, their hardness, and resistance to scratching and to water, acetone, and alcohol, is not exhibited. However, apart from these, from the applicative point of view, positive results, any improvement of the coating properties by the addition of silica nanoparticles is not shown. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40865.     

Impact of test-driven development on productivity, code and tests: A controlled experiment

Context

Test-driven development is an approach to software development, where automated tests are written before production code in highly iterative cycles. Test-driven development attracts attention as well as followers in professional environment; however empirical evidence of its superiority regarding its effect on productivity, code and tests compared to test-last development is still fairly limited. Moreover, it is not clear if the supposed benefits come from writing tests before code or maybe from high iterativity/short development cycles.

Objective

This paper describes a family of controlled experiments comparing test-driven development to micro iterative test-last development with emphasis on productivity, code properties (external quality and complexity) and tests (code coverage and fault-finding capabilities).

Method

Subjects were randomly assigned to test-driven and test-last groups. Controlled experiments were conducted for two years, in an academic environment and in different developer contexts (pair programming and individual programming contexts). Number of successfully implemented stories, percentage of successful acceptance tests, McCabe’s code complexity, code coverage and mutation score indicator were measured.

Results

Experimental results and their selective meta-analysis show no statistically significant differences between test-driven development and iterative test-last development regarding productivity (χ²(6) = 4.799, p = 1.0, r = .107, 95% CI (confidence interval): −.149 to .349), code complexity (χ²(6) = 8.094, p = .46, r = .048, 95% CI: −.254 to .341), branch coverage (χ²(6) = 13.996, p = .059, r = .182, 95% CI: −.081 to .421), percentage of acceptance tests passed (one experiment, Mann-Whitney U = 125.0, p = .98, r = .066) and mutation score indicator (χ²(4) = 3.807, p = .87, r = .128, 95% CI: −.162 to .398).

Conclusion

According to our findings, the benefits of test-driven development compared to iterative test-last development are small and thus in practice relatively unimportant, although effects are positive. There is an indication of test-driven development endorsing better branch coverage, but effect size is considered small.     

Two-level control strategy of an eight link biped walking model

This paper presents an adaptive two-level control strategy for a biped walking model and demonstrates its performance in a wide range of walking modes with considerably diverse model and control parameter settings. Proposed control strategy inherits a push off that resembles considerably to forceful extension of the trailing leg during push off in human locomotion and represents a very important source of forward propulsion. Extensive simulations have shown that adjustments in the push off related parameter on higher between-step control level after each step enable evolution of various walking modes of the biped walker at selected walking speeds and distinctive gait patterns. It also allows us to investigate the changes in gait kinematics and kinetics of the biped walking model due to changes in gait velocity, torso inclination and propulsion distribution profiles.