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.     

Triple-probe Diagnostic Measurements in Plasma of GLAST Spherical Tokamak

Triple-probe has been developed and operated successfully to characterize ECRH-assisted argon as well as hydrogen microwave plasmas in GLAST Spherical Tokamak. This technique enables to determine transient plasma parameters such as floating potential, electron temperature and electron number density in rapidly time-varying plasmas. An effective electron heating mechanism is applied to produce microwave plasma by injecting radiofrequency (RF) radiation at a frequency of 2.45 GHz in the presence of resonant toroidal magnetic field. Plasma parameters and corresponding fluctuations are measured as a function of time in different gas fill pressures for various applied magnetic fields. The results demonstrate the dependence of plasma parameters such as V _f , T _e , n _e and their fluctuations on gas fill pressure during the pre-ionization phase of the GLAST operation. Plasma behavior is observed to be closely depending on the coupling of RF power during microwave discharge. Additionally, the hydrogen plasma shows pronounced fluctuations in comparison with argon plasma with some decrease in electron temperature and densities.     

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.     

In situ high temperature FTIR studies of NOx reduction with propylene over Cu/ZSM-5 catalysts

High temperature in situ FTIR has been used to investigate the surface species present on Cu/ZSM-5 during the reduction of NO_x with propylene in a lean environment. Parallels have been observed between adsorbed surface species and catalytic activity for this reaction. Species detected at low temperatures are not representative of those detected at high temperatures where the catalyst is active. An oxidized nitrogen-containing species has been observed at 2580 cm^–1 on Cu during reaction conditions (400°C). In contrast, at low temperatures, where the catalyst is less active, coke and Cu⁺-CO predominated. The effects of Cu weight loading, C/NO ratio, reaction temperature, and catalyst deactivation by steaming have been investigated with IR.     

Chromatographic estimation of filler surface energies and correlation with photodegradation of kaolin filled polyethylene

Inverse gas chromatography (IGC) has been used to investigate the surface properties of two calcined kaolins and of polyethylene composites containing calcined kaolin. The results reveal differences in the two kaolins that were not found in XPS spectra nor in their influence on the melting behaviour of the polymer. The kaolin that had a markedly higher surface energy and stronger Lewis acid behaviour was found to shower greater photooxidative degradation in accelerated weathering tests. This novel application of IGC derived surface characterisation of solids further extends the usefulness of the method in this type of work.     

Dietary Polyphenols in Prevention and Treatment of Prostate Cancer

Prostate cancer is the most prevalent disease affecting males in many Western countries, with an estimated 29,480 deaths in 2014 in the US alone. Incidence rates for prostate cancer deaths have been decreasing since the early 1990s in men of all races/ethnicities, though they remain about 60% higher in African Americans than in any other group. The relationship between dietary polyphenols and the prevention of prostate cancer has been examined previously. Although results are sometimes inconsistent and variable, there is a general agreement that polyphenols hold great promise for the future management of prostate cancer. Various dietary components, including polyphenols, have been shown to possess anti-cancer properties. Generally considered as non-toxic, dietary polyphenols act as key modulators of signaling pathways and are therefore considered ideal chemopreventive agents. Besides possessing various anti-tumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Polyphenols have also been shown to affect post-translational modifications and microRNA expressions. This article provides a systematic review of the health benefits of selected dietary polyphenols in prostate cancer, especially focusing on the subclasses of polyphenols, which have a great effect on disease prevention and treatment.