Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer

Driver-directed therapeutics have revolutionized cancer treatment, presenting similar or better efficacy compared to traditional chemotherapy and substantially improving quality of life. Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition. PKC isoforms α, ε, η, ι, ζ upregulation has been reported in lung cancer, and overexpression correlates with worse prognosis in NSCLC patients. Most importantly, PKC isozymes have been established as mediators of resistance to tyrosine kinase inhibitors in NSCLC. Unfortunately, however, PKC-directed therapeutics have yielded unsatisfactory results, likely due to a lack of specific evaluation for PKC. To achieve satisfactory results in clinical trials, predictive biomarkers of PKC activity must be established and screened for prior to patient enrollment. Furthermore, tandem inhibition of PKC and molecular drivers may be a potential therapeutic strategy to prevent the emergence of resistance in NSCLC.     

Further experimental evidences of the compatibility of poly(vinyl acetate) with poly(ethyl methacrylate) and its dependence on the ratio of the molecular weight of the two homopolymers

Using various fractions of poly(ethyl methacrylate) (PEMA) and poly(vinyl acetate) (PVAc) of very narrow molecular weight distribution, a very wide range of 2–120 of molecular weight ratio M¯_ν PEMA/M¯_ν PVAc, (M¯_ν)_r was obtained. Studies of some tensile mechanical properties of films of the blends produced from solution on mercury confirmed strong dependence of the improvements of PVAc properties for blend with 18% PEMA on (M¯_ν)_r, especially in the range 5 ≤ (M¯_ν)_r < 100. The density of the films of the blend was much higher than those of the individual polymers and increased monotonically with (M¯_ν)_r. Optical micrographs of the films of the blends showed interactions between the two polymers with 18% PEMA composition, which appears to be more intimate as (M¯_ν)_r increases, as further evidence of compatibility and miscibility of the two polymers.     

Comparative study of a variety of ATRP systems with high oxidation state metal catalyst system

MMA (methyl methacrylate) was polymerized in different ATRP systems using the different ligands of HMTETA (1, 1, 4, 7, 10, 10, hexamethyltriethylenetetraamine), TMEDA (N,N,N′,N′-Tetramethylethylenediamine) with copper salts (CuBr/CuBr₂) and EBriB was used as an initiator in toluene at a reaction temperature of 80 °C. Both conventional and a low catalyst to initiator ratios ranging from 1/1 to 0.01/1 were compared in this study. All four of the ATRP methods, such as normal, reverse, AGET and ATRP using a high oxidation state metal complex without any additives, were evaluated at different conditions. The ATRP using a high oxidation state metal system in the absence of a conventional radical initiator like AIBN, which is used in reverse ATRP, or reducing agents such as Sn (EH)₂ in AGET ATRP was a better controlled system in terms of both the catalytic activity and controllability (PDI ∼ 1.2).     

Deposition and Characterization of Si Substituted Cu2ZnSnS4 Thin Films

Silicon - The influence of the Si substitution ratio on the structural, morphological, and optical properties of Cu2ZnSnS4 (CZTS) thin films was examined. The Cu2Zn(SixSn1–x)S4 thin films...     

Evaluation of machining performance in cryogenic machining of Inconel 718 and comparison with dry and MQL machining

There has been significant work on establishing relationships between machining performance and the cutting parameters for various work materials. Recent trends in machining research show that major efforts are being made to understand the impact of various cooling/lubrication methods on machining performance and surface integrity characteristics, all aimed at improving process and product performance. This study presents the experimental results of cryogenic machining of Inconel 718, a high-temperature aerospace alloy, and comparison of its performance in dry and minimum quantity lubrication machining. Experimental data on force components, progressive tool wear parameters such as flank wear, notch wear, crater wear, cutting temperature, chip morphology, and surface roughness/topography of machined samples are presented. New findings show that cryogenic machining is a promising research direction for machining of high-temperature aerospace alloy, Inconel 718, as it offers improved machining performance in terms of reduced tool wear, temperature, and improved surface quality. It was also found that the number of nozzles in cryogenic machining plays a vital role in controlling cutting forces and power consumption in cryogenic machining of Inconel 718.     

Surveillance and prevention of hepatitis B virus transmission

We have demonstrated a microfabricated single-molecule DNA sizing device. This device does not depend on mobility to measure molecule size, is 100 times faster than pulsed-field gel electrophoresis, and has a resolution that improves with increasing DNA length. It also requires a million times less sample than pulsed-field gel electrophoresis and has comparable resolution for large molecules. Here we describe the fabrication and use of the single-molecule DNA sizing device for sizing and sorting DNA restriction digests and ladders spanning 2-200 kbp.     

DWAM — A WAM model extension for disjunctive logic programming

Answering queries in disjunctive logic programming requires the use of ancestry-resolution. The resulting complication makes it difficult to implement a Prolog-type query answering procedure for disjunctive logic programs. However, SLO-resolution provides a mechanism which is similar to SLD-resolution and hence offers a solution to this problem. The Warren Abstract Machine has been a very effective model for implementing Prolog. In this paper, we extend the WAM model of Prolog and adapt it for DISLOG — a language for disjunctive logic programming. We describe the extensions and additional instructions needed to make WAM viable for modeling and executing DISLOG. The extension is made in such a way that the original architecture is not disturbed and a Prolog program will execute as efficiently as it does in the original WAM.This work was done while the author was at the University of Kentucky.