Organofluorine Hydrazone Derivatives as Multifunctional Anti-Alzheimer's Agents with CK2 Inhibitory and Antioxidant Features

A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4-N(CH₃)₂ residue or perfluorinated phenyl rings showed high activity in the radical-scavenging assays and possess nanomolar IC₅₀ values in the kinase assays.     

Effects of upholstery materials on the burning behavior of real‐scale residential upholstered furniture mock‐ups

Fire spread and growth on real‐scale four cushion mock‐ups of residential upholstered furniture (RUF) were investigated with the goal of identifying whether changes in five classes of materials (barrier, flexible polyurethane foam, polyester fiber wrap, upholstery fabric, and sewing thread), referred to as factors, resulted in statistically significant changes in burning behavior. A fractional factorial experimental design plus practical considerations yielded a test matrix with 20 material combinations. Experiments were repeated a minimum of two times. Measurements included fire spread rates derived from video recordings and heat release rates (HRRs). A total of 13 experimental parameters (3 based on the videos and 10 on the HRR results), referred to as responses, characterized the measurements. Statistical analyses based on Main Effects Plots (main effects) and Block Plots (main effects and factor interactions) were used. The results showed that three of the factors resulted in statistically significant effects on varying numbers of the 13 responses. The Barrier and Fabric factors had the strongest main effects with roughly comparable magnitudes. Foam was statistically significant for fewer of the responses and its overall strength was weaker than for Barrier and Fabric. No statistically significant main effects were identified for Wrap or Thread. Multiple two‐term interactions between factors were identified as being statistically significant. The Barrier*Fabric interaction resulted in the highest number of and strongest statistically significant effects. The existence of two‐term interactions means that it will be necessary to consider their effects in approaches designed to predict the burning behavior of RUF.     

An integrated dimensionality reduction and surrogate optimization approach for plant-wide chemical process operation

With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data-driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large-scale industrial chemical systems.     

Sustainable ammonia production through process synthesis and global optimization

Current ammonia production technologies have a significant carbon footprint. In this study, we present a process synthesis and global optimization framework to discover the efficient utilization of renewable resources in ammonia production. Competing technologies are incorporated in a process superstructure where biomass, wind, and solar routes are compared with the natural gas-based reference case. A deterministic global optimization-based branch-and-bound algorithm is used to solve the resulting large-scale nonconvex mixed-integer nonlinear programming problem (MINLP). Case studies for Texas, California, and Iowa are conducted to examine the effects of different feedstock prices and availabilities. Results indicate that profitability of ammonia production is highly sensitive to feedstock and electricity prices, as well as greenhouse gas (GHG) restrictions. Under strict 75% GHG reductions, biomass to ammonia route is found to be competitive with natural gas route, whereas wind and solar to ammonia routes require further improvement to compete with those two routes. © 2018 American Institute of Chemical Engineers AIChE J, 65: e16498 2019     

Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

Classic and inverse compositional Gauss-Newton in global DIC

Today, effective implementations of digital image correlation (DIC) are based on iterative algorithms with constant linear operators. A relevant idea of the classic finite element (or, more generally, global) DIC solver consists in replacing the gradient of the deformed state image with that of the reference image, so as to obtain a constant operator. Different arguments (small strains, small deformations, equality of the two gradients close to the solution, etc) have been given in the literature to justify this approximation, but none of them are fully accurate. Indeed, the convergence of the optimization algorithm has to be investigated from its ability to produce descent directions. Through such a study, this paper attempts to explain why this approximation works and what is its domain of validity. Then, an inverse compositional Gauss-Newton implementation of finite element DIC is proposed as a cost-effective and mathematically sound alternative to this approximation.     

Epigenetic Targets for Oligonucleotide Therapies of Pulmonary Arterial Hypertension

Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.     

Relative expression and regulation by short-term fasting of lysophosphatidic acid receptors and autotaxin in white and brown adipose tissue depots

Lysophosphatidic acid (lysoPtdOH) levels have previously been reported to decrease in rodents with short-term fasting. We investigated whether a 16 h fast would change expression of autotaxin, the predominant phospholipase D responsible for adipose-derived lysoPtdOH synthesis, or any of the lysophosphatidic acid receptors (1–6) in four white adipose tissue (WAT) depots and interscapular brown adipose tissue (BAT) in male C57Bl/6J mice fed ad libitum, or fasted for 16 h. Aside from small inductions of Lpar1 in epididymal WAT and Lpar2 in epididymal and inguinal WAT, no significant changes were observed in expression of the Lpar family members, or autotaxin in perirenal, retroperitoneal, epididymal, or inguinal WAT or BAT with fasting. Comparison of the relative expression of Lpar1-6 in various depots showed that Lpar6 was the predominant Lpar in both WAT and BAT, and suggests that further work on the adipose-specific role of Lpar6 is warranted.