The Discovery of Phenylbenzamide Derivatives as Grb7‐Based Antitumor Agents

Grb7 is a non‐catalytic protein, the overexpression of which has been associated with the proliferative and migratory potentials of cancer cells. Virtual screening strategies involving a shape‐based similarity search, molecular docking, and 2D‐similarity searches complemented by experimental binding studies (Thermofluor and isothermal titration calorimetry) resulted in the identification of nine novel phenylbenzamide‐based antagonists of the Grb7 SH2 domain. Moderate binding affinities were observed, ranging from K_d=32.3 μM for lead phenylbenzamide NSC 104999 ( 1 ) to K_d=1.1 μM for a structurally related compound, NSC 57148 ( 2 ). Deconvolution of the affinity data into its components revealed differences in lead binding, from being entropy based (lead 1 ) to enthalpically driven (NSC 100874 ( 3 ), NSC 55158 ( 4 ), and compound 2 ). Finally, the lead compound 1 was found to decrease the growth of MDA‐MB‐468 breast cancer cells, with an IC₅₀ value of 39.9 μM . It is expected that these structures will serve as novel leads in the development of Grb7‐based anticancer therapeutics.     

In Situ Measurements of Bridged Crack Interfaces in the Scanning Electron Microscope

A device for in situ SEM examination of crack propagation during loading of compact tension specimens is described, with a specific demonstration on an alumina ceramic. The device facilitates direct qualitative observations of the inception and subsequent frictional pullout of grain-localized bridges at the crack interface. Quantitative data on the bridging mechanism are obtained from measurements of the crack-opening displacements behind the crack tip. The crack profile is found to be closer to linear than parabolic at the bridged interface. Deconvolution of these crack-opening data allow for an evaluation of the closure tractions operative at the crack walls within the bridging zone, and thence the R -curve.     

Quantitative determination of short‐chain branching content and distribution in commercial polyethylenes by thermally fractionated differential scanning calorimetry

A method for rapid quantitative analysis of the content and distribution of short chain branching (SCB) for α‐olefin/ethylene copolymers based on thermally fractionated DSC is presented. Eight commercial polyethylenes, four made with conventional Ziegler‐Natta catalysts and four made with metallocene catalysts, were analyzed by differential scanning calorimetry (DSC), after having been thermally segregated by successive nucleation annealing (SNA). The polyethylenes were also analyzed by temperature rising elution fractionation (TREF) and carbon‐13 nuclear magnetic resonance (¹³C‐NMR). The SNA‐DSC procedure segregates polyethylenes according to methylene sequence lengths (MSL). The relationship between DSC melting temperature and SCB content was obtained by calibration with linear hydrocarbons; TREF results were not used in the SNA‐DSC calibration. Deconvolution of the SNA‐DSC endotherms yielded estimates of the average SCB contents and SCB distributions. The SCB contents obtained from the SNA‐DSC for linear low density polyethylenes agreed very well with the SCB contents obtained by ¹³C‐NMR and TREF, and the SCB distributions measured by SNA‐DSC were very similar to those obtained by TREF. The SCB contents obtained by SNA‐DSC for ultra‐low density polyethylenes, made with metallocene catalysts, were about 20% lower than the values obtained by ¹³C‐NMR; the values obtained by TREF were even lower.     

Effect of substituting CaO with BaO on the viscosity and structure of CaO‐BaO‐SiO2‐MgO‐Al2O3 slags

In this study, the effect of CaO and BaO substitution on the viscosity and structure of CaO‐BaO‐SiO₂‐MgO‐Al₂O₃ slags was investigated. The results showed that the viscosity increased with an increase in the BaO substitution concentration, which was correlated to an increase in the degree of polymerization (DOP) of the slag structural units as the activation energy increased from 207.9 to 263.8 kJ/mol for viscous flow. Deconvolution and area integration of the Raman spectrum of the slag revealed that the ratio of Q³/Q² (Qⁱ, i is the number of O⁰ in a [SiO₄]‐tetrahedral unit) increased and NBO/Si (nonbridging oxygen per unit silicon atom) decreased with higher BaO content. It was also observed from the ²⁷Al magic angles pinning nuclear magnetic resonance (²⁷Al MAS‐NMR) spectrum that the relative proportion of Al^IV increased, while that of Al^V decreased because of the decrease in the percentage of nonbridging oxygen (O^?), indicating the polymerization of the slag. O_1s X‐ray photoelectron spectroscopy (XPS) was also carried out to semi‐quantitatively analyze the various types of oxygen anions present in the slag. The XPS results correlated well with the results obtained from the analysis of the Raman and ²⁷Al MAS‐NMR spectra of the slags and its viscous behavior.     

The Role of Al in Cross‐Linking of Alkali‐Activated Slag Cements

The structural development of a calcium (sodium) aluminosilicate hydrate (C–(N‐)A–S–H) gel system, obtained through the reaction of sodium metasilicate and ground granulated blast furnace slag, is assessed by high‐resolution ²⁹Si and ²⁷Al MAS NMR spectroscopy during the first 2 yr after mixing. The cements formed primarily consist of C–(N‐)A–S–H gels, with hydrotalcite and disordered alkali aluminosilicate gels also identified in the solid product assemblages. Deconvolution of the ²⁷Al MAS NMR spectra enables the identification of three distinct tetrahedral Al sites, consistent with the ²⁹Si MAS NMR data, where Q³(1Al), Q⁴(3Al), and Q⁴(4Al) silicate sites are identified. These results suggest significant levels of cross‐linking in the C–(N‐)A–S–H gel and the presence of an additional highly polymerized aluminosilicate product. The mean chain length, extent of cross‐linking, and Al/Si ratio of the C–(N‐)A–S–H gel decrease slightly over time. The de‐cross‐linking effect is explained by the key role of Al in mixed cross‐linked/non‐cross‐linked C–(N‐)A–S–H gels, because the cross‐linked components have much lower Al‐binding capacities than the noncross‐linked components. These results show that the aluminosilicate chain lengths and chemical compositions of the fundamental structural components in C–(N‐)A–S–H gels vary in a way that is not immediately evident from the overall bulk chemistry.     

Characterization of electrosynthesized polydihaloanilines

The nucleation and growth mechanism of some homopolymers of aniline (six monomers were studied: 3,5‐dichloroaniline, 2,5‐dichloroaniline, 2,6‐dichloroaniline, 2,3‐dichloroaniline, 2,5‐dibromoaniline, and 2,6‐dibromoaniline), synthesized by potentiostatic methods, was determined with a mathematical model that considers different contributions from current–time transients with a gold‐disc electrode. Deconvolution of the transients for the dichlorinated monomers showed IN3D_ct and PN3D_dif contributions (where IN3D_ct refers to an instantaneous nucleation and three‐dimensional growth mechanism under charge‐transfer control and PN3D_dif refers to a progressive nucleation and three‐dimensional growth mechanism under diffusion control), whereas IN2D and PN3D_dif components and IN2D, IN3D_ct, and PN3D_dif components (where IN2D refers to an instantaneous nucleation and two‐dimensional growth mechanism) were needed for 2,5‐dibromoaniline and 2,6‐dibromoaniline, respectively. The percentage of the contribution of the current–time transient to the total charge was worked out for each monomer. The effect of the scan rate on the voltammetric profile during the potentiodynamic electrosynthesis of the polymers was studied too. Curves of the current versus the square root of the potential scan rate were recorded for a selected group of monomers, and the slope was considered an estimation of the diffusion coefficient of the respective monomer. Furthermore, the electrosynthesized polymers were characterized with Fourier transform infrared, ultraviolet–visible, X‐ray photoelectron spectroscopy, and scanning electron microscopy. Microanalysis, used to establish the ratio of the atomic percentages of P and N for each polymer synthesized at a constant potential, was performed for doped and undoped polymers. This parameter was a measure of the degree of electrochemical doping. The conductivity of the doped and undoped polymers was also measured. Hence, the systematic characterization of this analogue series of monomers allows, before generalization, an adequate experimental design to prepare polymers with the properties required for their use. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Comonomer effects in copolymerization of ethylene and 1‐hexene with MgCl2‐supported Ziegler‐Natta catalysts: New evidences from active center concentration and molecular weight distribution

In this article, comonomer effects in copolymerization of ethylene and 1‐hexene with four MgCl₂‐supported Ziegler‐Natta catalysts using either ethylene or 1‐hexene as the main monomer were investigated. It was found that no matter which monomer was used as the main monomer, the polymerization activity was significantly enhanced by introducing small amount of comonomer. In copolymerization with ethylene as the main monomer, the strength of comonomer effects was much stronger in active centers producing low‐molecular‐weight polymer than those producing high‐molecular‐weight polymer. In copolymerization with 1‐hexene as the main monomer, the number of active centers ([C*]/[Ti]) was determined, and the propagation rate constants (k_p) were calculated. Deconvolution of the polymer molecular weight distribution into Flory components were made to study the active center distribution. Introduction of small amount of ethylene caused marked increase in the number of active centers and decrease in average chain propagation rate constant. Introducing internal electron donor in the catalyst enhanced not only the number of active centers but also the chain propagation rate constant. In copolymerization of 1‐hexene with small amount of ethylene, the internal donor weakened the comonomer effects to some extent and changed the distribution of comonomer effects among different types of active centers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41264.     

Using Chemical Probes to Assess the Feasibility of Targeting SecA for Developing Antimicrobial Agents against Gram‐Negative Bacteria

With the widespread emergence of drug resistance, there is an urgent need to search for new antimicrobials, especially those against Gram‐negative bacteria. Along this line, the identification of viable targets is a critical first step. The protein translocase SecA is commonly believed to be an excellent target for the development of broad‐spectrum antimicrobials. In recent years, we developed three structural classes of SecA inhibitors that have proven to be very effective against Gram‐positive bacteria. However, we have not achieved the same level of success against Gram‐negative bacteria, despite the potent inhibition of SecA in enzyme assays by the same inhibitors. In this study, we use representative inhibitors as chemical probes to gain an understanding as to why these inhibitors were not effective against Gram‐negative bacteria. The results validate our initial postulation that the major difference in effectiveness against Gram‐positive and Gram‐negative bacteria is in the additional permeability barrier posed by the outer membrane of Gram‐negative bacteria. We also found that the expression of efflux pumps, which are responsible for multidrug resistance (MDR), have no effect on the effectiveness of these SecA inhibitors. Identification of an inhibitor‐resistant mutant and complementation tests of the plasmids containing secA in a secAts mutant showed that a single secA‐azi‐9 mutation increased the resistance, providing genetic evidence that SecA is indeed the target of these inhibitors in bacteria. Such results strongly suggest SecA as an excellent target for developing effective antimicrobials against Gram‐negative bacteria with the intrinsic ability to overcome MDR. A key future research direction should be the optimization of membrane permeability.     

Application of Hertzian Tests to Measure Stress–Strain Characteristics of Ceramics at Elevated Temperatures

A new method for evaluating the elastic–plastic properties of ceramics from room temperature up to the onset of creep based on Hertzian indentation testing is proposed. Indentation stress–strain curves are compiled for representative alumina and zirconia ceramics at prescribed temperatures. Deconvolution of the indentation stress–strain curves for each material provides a measure of Young's modulus, yield stress, and work-hardening coefficient as a function of temperature, enabling construction of true stress–strain curves. The stress–strain curves flatten out with increasing temperature, in accordance with an expected increased plastic response at elevated temperatures.     

A reduced‐order model for chemical species transport in a tube with a constant wall concentration

A two‐dimensional advection‐diffusion model accompanied with a parabolic velocity profile of Poiseuille flow is considered for the chemical species transport in a tube with a constant wall concentration. The Reynolds decomposition technique is applied to reduce it to an equivalent one‐dimensional model for advective‐dispersive transport in a tube through which the effective advection coefficient, the dispersion coefficient, and the effective Sherwood number are developed for the problem under study. The derived and the classical Taylor models are also compared in order to find the difference between the two arrangements. The reduced‐order model for the transport equation shows that the effective advection coefficient increases, whereas the dispersion coefficient in the tube decreases as compared to the classical Taylor equation. The effective Sherwood number for the steady state form of the developed model is found to be only a function of the Peclet number, which varies in the range of 3.215 ≤ Sh ≤ 4. These results find application in design of experiments and improve our understanding of mass transfer in microfluidic devices.     

Estimates for material shrinkage in molded parts caused by time‐varying cavity pressures

The phenomenology of shrinkage is established through injection molding experiments in which shrinkage was measured at 25‐mm intervals along the length and width of rectangular plaques, molded in an instrumented mold. A simple solidification model, which assumes the solidified material to be elastic, is developed for the effect of time‐varying temperature and pressure histories on part shrinkage. This model predicts a linear dependence of shrinkage on an “effective pressure,” which combines the thermal diffusivity of the material, the wall thickness, and the time‐varying cavity pressure into a single parameter that is uniquely related to the shrinkage. The effective pressure is shown to effectively correlate in‐plane shrinkage data. The solidification model characterizes two material parameters, which can be estimated from the pressure‐volume‐temperature (PVT) diagram for the material, that describe the sensitivity of the shrinkage to the local cavity pressure history. The residual stresses predicted by this model are rather crude. POLYM. ENG. SCI., 59:1648–1656 2019. © 2019 Society of Plastics Engineers     

Self‐limited crystallization‐mediated removal of hydroxyl in glass

The effective removal of hydroxyl groups (OH) is receiving the attention of scientists interested in developing high‐performance photonic glass. Previous approaches rely on stringent control of the various drying techniques which meet with limited success in silicate glass obtained by the sol‐gel method. Here, we present a novel in situ strategy to remove structural OH groups, based on the self‐limited nanocrystallization‐triggered local chemical reaction between OH and F^? in the glassy phase. The experimental data revealed that a more than 100‐fold increase in the emission intensity can be realized. Moreover, the mechanism was discussed and it can be attributed to the effective removal of structural OH with especially strong binding energy. The results suggest an innovative avenue for the development of photonic glasses with efficient luminescence, excellent optical transmission, and improved reliability.     

Experimental Investigation and Thermodynamic Modeling of Glycerin/Methanol/Organic Solvent Systems

Glycerin is an important by‐product in biodiesel production. To increase its quality to be suitable for use it in other operations, e.g., the pharmaceutical industry, it needs to be purified. Therefore, the purification of glycerin by liquid‐liquid extraction of methanol using different solvents was investigated. It was shown that, in terms of separation, petroleum ether was more effective than toluene and toluene was more effective than n‐butanol. In addition to the experimental investigations, the NRTL and UNIQUAC thermodynamic models were used to predict the compositions of ternary mixtures of glycerin + methanol + organic solvent in glycerin‐rich and organic solvent‐rich phases. The results showed the high accuracy of the presented models and their consistency with the measured data.     

SAG mill system diagnosis using multivariate process variable analysis

Semi‐autogenous grinding (SAG) of ore plays a critical role in a mineral processing plant. In SAG operations, abnormal conditions, such as overload or insufficient ore holdup, often result in inefficient production and unstable operation. It is, therefore, essential to monitor the process using effective technology so that abnormal or faulty conditions can be detected and addressed in a timely manner. In this study, investigation is focused on applying multivariate analysis in the monitoring and diagnosing of an industrial SAG operation. The results show that principal component analysis provides an effective methodology for on‐line monitoring and diagnosis. The detection and removal of faulty conditions will help to provide stable and cost‐efficient operation.     

Performance of Nozzle/Diffuser Micro‐Pumps Subject to Parallel and Series Combinations

This study numerically examines the performance of micro nozzle/diffuser pumps subject to parallel and series combinations. For a single‐chamber micro nozzle/diffuser micro‐pump, four stages are identified. For dual micro‐pumps in a parallel combination, the flow field in each chamber is symmetrical about the center line of the arrangement. For in‐phase operation, the maximum flowrate is about two times higher than that of the single‐chamber. For micro‐pumps in a series combination, it is found that the overall performance is strongly related to the phase angle. The effective flowrate can be significantly increased, decreased, or even reversed. This indicates that the flowrate can be controlled within a wide span by changing the phase angles. At a phase angle of 90°, an eight‐fold increase of effective flowrate is seen relative to that of a single‐chamber operation. The significant increase of flowrate is attributed to two effects; the first effect is due to the “active valve” effect that increases the efficiency during pump mode. The second influence is attributed to the increased pressure difference that brings in more fluid during supply mode.     

Spatial reaction engineering approach as an alternative for nonequilibrium multiphase mass‐transfer model for drying of food and biological materials

Drying is a complex process which involves simultaneous heat and mass transfer. Complicated structure and heterogeneity of food and biological materials add to the complexity of drying. Drying models are important for improving dryer design and for evaluating dryer performance. The lumped reaction engineering approach (L‐REA) has been shown to be an accurate and robust alternative for cost‐effective simulations of challenging drying systems. However, more insightful physics has to be shown spatially. In this study, the REA is coupled with the standard mechanistic drying models to yield the spatial‐REA (S‐REA) as nonequilibrium multiphase mass‐transfer model. The S‐REA consists of a system of equations of conservation with the REA representing the local evaporation and wetting rate. Results of the modeling using the S‐REA match well with the experimental data reported previously. This is the first comprehensive REA approach to model the profiles of water vapor concentration during drying of food and biological materials. This study indicates that the S‐REA can be an accurate nonequilibrium multiphase mass‐transfer model with appropriate account of the local evaporation rate. The overall REA concept is expected to contribute substantially for better and cost‐effective representation of transport phenomena of drying process. © 2012 American Institute of Chemical Engineers AIChE J, 59: 55–67, 2013     

Untersuchungen zum Hochdruck‐Permeationsverhalten reiner Gase durch mikroporöse keramische Membranen Teil 2. Analyse der Stofftransportmechanismen

The determined behaviour of a TiO₂‐membrane with an effective pore diameter below 1 nm cannot be described comprehensively by the transport mechanisms known at present. The transport mechanism is dominated by adsorption effects. The demonstrated results give an impetus for a new transport model approach termed MAT‐Model (Micro‐porous Adsorption and Transport‐Model).     

On‐line measurement of polymer orientation using ultrasonic technology

The propagation velocity of an ultrasonic shear wave can be used to detect anisotropic behavior in the mechanical properties of a solid. Thus, an ultrasonic shear transducer imbedded in an injection mold produces a signal that is sensitive to polymer orientation. This results in a non‐invasive, on‐line technique for monitoring the orientation of polymer in an injection mold cavity during part cooling and solidification. The technique is shown to be quite sensitive for semicrystalline polymers, but much less effective for amorphous polymers. Sensor results are compared to mechanical tests.     

Performance Characteristics of a Suspended‐Catalyst Oscillatory Membrane Photocatalytic Reactor

The performance characteristics of an oscillatory membrane photocatalytic reactor were investigated using dye degradation over a suspended ZnO catalyst as a model reaction. Both flat‐surface membranes and ones with transverse turbulence promoters (TP) were used. Application of oscillatory motion can be effective in enhancing the performance of suspended‐catalyst membrane photocatalytic reactors. The eddy formation and vortex shedding when using membranes with TP gave rise to several synergistic effects by providing effective removal of catalyst deposits from the membrane surface, which enhanced the flux and increased the suspended‐catalyst fraction in solution, which consequently enhanced the reaction rate. The effective mixing in the reaction channel minimized particles sedimentation and agglomeration which further enhanced the catalyst suspension and increased its effective reaction area. The specific energy consumption favorably compared to a membrane cross‐flow filtration system.     

PVC/wood‐flour composites compatibilized with chlorinated polyethylene

Chlorinated polyethylene has been demonstrated to be an effective compatibilizer for dissimilar materials in various mixed‐polymer or recycled‐polymer systems. In this paper the use of chlorinated polyethylene to compatibilize polymer/natural‐fiber composites is discussed. Examples of applications in PVC/wood‐flour composites are given.