Synthesis and SAR of Tetracyclic Inhibitors of Protein Kinase CK2 Derived from Furocarbazole W16

The serine/threonine kinase CK2 modulates the activity of more than 300 proteins and thus plays a crucial role in various physiological and pathophysiological processes including neurodegenerative disorders of the central nervous system and cancer. The enzymatic activity of CK2 is controlled by the equilibrium between the heterotetrameric holoenzyme CK2α₂β₂ and its monomeric subunits CK2α and CK2β. A series of analogues of W16 ((3aR,4S,10S,10aS)-4-{[(S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-10-(3,4,5-trimethoxyphenyl)-4,5,10,10a-tetrahydrofuro[3,4-b]carbazole-1,3(3aH)-dione ((+)- 3 a )) was prepared in an one-pot, three-component Levy reaction. The stereochemistry of the tetracyclic compounds was analyzed. Additionally, the chemically labile anhydride structure of the furocarbazoles 3 was replaced by a more stable imide ( 9 ) and N-methylimide ( 10 ) substructure. The enantiomer (−)- 3 a (K_i=4.9 μM) of the lead compound (+)- 3 a (K_i=31 μM) showed a more than sixfold increased inhibition of the CK2α/CK2β interaction (protein-protein interaction inhibition, PPII) in a microscale thermophoresis (MST) assay. However, (−)- 3 a did not show an increased enzyme inhibition of the CK2α₂β₂ holoenzyme, the CK2α subunit or the mutated CK2α′ ^C336S subunit in the capillary electrophoresis assay. In the pyrrolocarbazole series, the imide (−)- 9 a (K_i=3.6 μM) and the N-methylimide (+)- 10 a (K_i=2.8 μM) represent the most promising inhibitors of the CK2α/CK2β interaction. However, neither compound could inhibit enzymatic activity. Unexpectedly, the racemic tetracyclic pyrrolocarbazole (±)- 12 , with a carboxy moiety in the 4-position, displays the highest CK2α/CK2β interaction inhibition (K_i=1.8 μM) of this series of compounds.     

Surface modification of calcium carbonates studied by inverse gas chromatography and the effect on mechanical properties of filled polypropylene

Inverse gas chromatography (IGC) has been used to characterize the surfaces of a pure calcitic calcium carbonate as well as samples that had been treated with sodium polyacrylate and/or stearic acid. The dispersive components of the surface free energy for the pure material agreed well with related literature data. Polar contributions to the surface interactions with a range of probes were determined. The results show that the surface treatments reduced the polarities of the surfaces and that modification with stearic acid produced a non-polar, low-energy surface. Some mechanical properties of the polypropylene composites containing the modified calcium carbonates were found to correlate well with the filler surface energies. Copyright © 2004 Society of Chemical Industry     

Multi-scale Single Image Super-Resolution with Remote-Sensing Application Using Transferred Wide Residual Network

In the integrated circuit (IC) designing floorplanning is an important phase in the process of obtaining the layout of the circuit to be designed. The floorplanning determines the performance, size, yield, and reliability of VLSI ICs. The obtained results in this step are necessary for the other consecutive process of the chip designing. VLSI floorplanning from the computational point of view is a non-polynomial hard (NP-hard problem), and hence cannot be efficiently solved by the classical optimization techniques. In this paper, we have proposed a metaheuristic approach to address the problem by using the parallel particle swarm optimization (P-PSO) technique. The P-PSO uses a new greedy operation on the sequence pair (SP) to explore the search space to find an optimal solution. Experimental results on the Microelectronic Centre of North Carolina and Gigascale Systems Research Center benchmark shows that the applied parallel PSO (P-PSO) may be used to produce an optimal solution.

     

Plasma measurements in pulse discharge with resistively heated emissive probe

A resistively heated emissive probe has been developed to work in low-pressure air plasma produced by 100 Hz pulsed DC source. The evolution of the discharge and consequent rapid changes in plasma potential and electron temperature are characterized for different fill pressures at constant input voltage of 300 V. The floating point method in the strong emission regime is applied to determine the plasma potential. Emissive probe responds to rapid changes in the discharge current during different stages of the pulse cycle. The electron temperature is determined from the potential difference of hot probe in the strong emission regime and the cold one incorporating the space charge effects of the hot probe. Temporal measurements of V _p and T _e describe the development and characteristics of the emissive probe technique for fast measurements in pulsating discharges.     

Semantic tagging and linking of software engineering social content

Social online communities and platforms play a significant role in the activities of software developers either as an integral part of the main activities or through complimentary knowledge and information sharing. As such techniques become more prevalent resulting in a wealth of shared information, the need to effectively organize and sift through the information becomes more important. Top-down approaches such as formal hierarchical directories have shown to lack scalability to be applicable to these circumstanes. Light-weight bottom-up techniques such as community tagging have shown promise for better organizing the available content. However, in more focused communities of practice, such as software engineering and development, community tagging can face some challenges such as tag explosion, locality of tags and interpretation differences, to name a few. To address these challenges, we propose a semantic tagging approach that benefits from the information available in Wikipedia to semantically ground the tagging process and provide a methodical approach for tagging social software engineering content. We have shown that our approach is able to provide high quality tags for social software engineering content that can be used not only for organizing such content but also for making meaningful and relevant content recommendation to the users both within a local community and also across multiple social online communities. We have empirically validated our approach through four main research questions. The results of our observations show that the proposed approach is quite effective in organizing social software engineering content and making relevant, helpful and novel content recommendations to software developers and users of social software engineering communities.     

A semantic metrics suite for evaluating modular ontologies

Ontologies, which are formal representations of knowledge within a domain, can be used for designing and sharing conceptual models of enterprises information for the purpose of enhancing understanding, communication and interoperability. For representing a body of knowledge, different ontologies may be designed. Recently, designing ontologies in a modular manner has emerged for achieving better reasoning performance, more efficient ontology management and change handling. One of the important challenges in the employment of ontologies and modular ontologies in modeling information within enterprises is the evaluation of the suitability of an ontology for a domain and the performance of inference operations over it. In this paper, we present a set of semantic metrics for evaluating ontologies and modular ontologies. These metrics measure cohesion and coupling of ontologies, which are two important notions in the process of assessing ontologies for enterprise modeling. The proposed metrics are based on semantic-based definitions of relativeness, and dependencies between local symbols, and also between local and external symbols of ontologies. Based on these semantic definitions, not only the explicitly asserted knowledge in ontologies but also the implied knowledge, which is derived through inference, is considered for the sake of ontology assessment. We present several empirical case studies for investigating the correlation between the proposed metrics and reasoning performance, which is an important issue in applicability of employing ontologies in real-world information systems.     

Decision support for the software product line domain engineering lifecycle

Software product line engineering is a paradigm that advocates the reusability of software engineering assets and the rapid development of new applications for a target domain. These objectives are achieved by capturing the commonalities and variabilities between the applications of the target domain and through the development of comprehensive and variability-covering feature models. The feature models developed within the software product line development process need to cover the relevant features and aspects of the target domain. In other words, the feature models should be elaborate representations of the feature space of that domain. Given that feature models, i.e., software product line feature models, are developed mostly by domain analysts by sifting through domain documentation, corporate records and transcribed interviews, the process is a cumbersome and error-prone one. In this paper, we propose a decision support platform that assists domain analysts throughout the domain engineering lifecycle by: (1) automatically performing natural language processing tasks over domain documents and identifying important information for the domain analysts such as the features and integrity constraints that exist in the domain documents; (2) providing a collaboration platform around the domain documents such that multiple domain analysts can collaborate with each other during the process using a Wiki; (3) formulating semantic links between domain terminology with external widely used ontologies such as WordNet in order to disambiguate the terms used in domain documents; and (4) developing traceability links between the unstructured information available in the domain documents and their formal counterparts within the formal feature model representations. Results obtained from our controlled experimentations show that the decision support platform is effective in increasing the performance of the domain analysts during the domain engineering lifecycle in terms of both the coverage and accuracy measures.     

Initial Plasma Formation in the GLAST-II Spherical Tokamak

This paper reports the initial plasma formation in glass spherical tokamak (GLAST-II) with electron cyclotron resonance pre-ionization assisted startup. Initially, a plasma current of 3 kA has been produced for duration of about 0.5 ms after establishing optimum conditions for microwave absorption at 2.45 GHz. Plasma current is then enhanced up to 5 kA by applying a small vertical magnetic field that provides additional plasma heating and shaping. Applied vertical field is optimized experimentally and optimal value is found to be 40 Gauss for this experiment. Plasma current and loop voltage are monitored by using Rogowski coil and toroidal loop of wire. A fast framing camera (5000 fps) is used for temporal investigation of plasma during the discharge scenario. A fast photodiode (BPX-65) and USB4000 spectrometer are used to record the signature of plasma current and the impurity content (O₂, H etc.). Cross-sectional average electron temperature is also estimated from plasma resistivity and found to be 6.1 eV for maximum plasma current of 5 kA.     

我国露天煤矿无人驾驶及新能源卡车发展现状与关键技术

针对我国露天煤矿受外包运营模式影响而存在的由半连续、连续工艺向间断工艺倒退、由大型化设备向小型化设备倒退的趋势,提出采用无人驾驶矿用卡车、新能源卡车可以实现露天煤矿安全高效、节能环保运输。鉴于我国无人驾驶矿用卡车正处于试验测试阶段,适应恶劣天气及矿山恶劣环境能力差,以及我国新能源矿用卡车研发处在产业化前期,受电池重量、循环寿命、充电速度及电池性能等因素制约的现状,认为,无人驾驶矿用卡车应注重研发非结构化道路无人驾驶感知融合技术、规模化运营智能调度技术及智能协同控制技术、露天矿山时变场景匹配关键技术、高可靠性、高算力无人驾驶计算平台、大型矿用卡车关键部件、基于数字孪生的设备健康管理技术等;大型矿用新能源卡车应致力于高电量、大功率、长寿命动力电池研发关键技术、极端天气下纯电动矿用卡车研发及应用关键技术、载重100 t以上纯电动矿用卡车研发关键技术等。