Synthesis,characterization, and electrochemical performance of the ternary layered composite (1-x-y) LiNi1/3Co1/3Mn1/3O2·xLi2MnO3·yLiCoO2

Composite ceramic cathodes represented by the formula (1-x-y) LiNi_1/3Co_1/3Mn_1/3O₂·xLi₂MnO₃·yLiCoO₂ were studied. A ternary compositional diagram was built with these ceramic materials as end-members, and selected points were chosen to represent the compositional space. Synthesized ceramic composite materials were investigated as to whether integration of structurally compatible units leads to improved electrochemical performance. Detailed structural (X-ray diffraction – XRD), elemental (X-ray photoelectron spectroscopy-XPS), microstructure (Scanning electron microscopy – SEM), and electrochemical (galvanostatic testing of half-cells) studies were performed and are presented. Within eight samples studied three compositions are found to exhibit first discharge capacity of around 230 mAh/g.     

Deployment of a cloud pipeline for real-time visual inspection using fast streaming high-definition images

We investigate the challenges of building an end-to-end cloud pipeline for real-time intelligent visual inspection system for use in automotive manufacturing. Current methods of visual detection in automotive assembly are highly labor intensive, and thus prone to errors. An automated process is sought that can operate within the real-time constraints of the assembly line and can reduce errors. Components of the cloud pipeline include capture of a large set of high-definition images from a camera setup at the assembly location, transfer and storage of the images as needed, execution of object detection, and notification to a human operator when a fault is detected. The end-to-end execution must complete within a fixed time frame before the next car arrives in the assembly line. In this article, we report the design, development, and experimental evaluation of the tradeoffs of performance, accuracy, and scalability for a cloud system.     

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cocaine is one of the most widely abused illicit drugs worldwide and has long been recognised as an agent of cardiac dysfunction in numerous cases of drug overdose. Cocaine has previously been shown to up-regulate cytoskeletal rearrangements and morphological changes in numerous tissues; however, previous literature observes such changes primarily in clinical case reports and addiction studies. An investigation into the fundamental cytoskeletal parameters of migration, adhesion and proliferation were studied to determine the cytoskeletal and cytotoxic basis of cocaine in cardiac cells. Treatment of cardiac myocytes with cocaine increased cell migration and adhesion (p < 0.05), with no effect on cell proliferation, except with higher doses eliciting (1–10 μg/mL) its diminution and increase in cell death. Cocaine downregulated phosphorylation of cofilin, decreased expression of adhesion modulators (integrin-β3) and increased expression of ezirin within three hours of 1 μg/mL treatments. These functional responses were associated with changes in cellular morphology, including alterations in membrane stability and a stellate-like phenotype with less compaction between cells. Higher dose treatments of cocaine (5–10 μg/mL) were associated with significant cardiomyocyte cell death (p < 0.05) and loss of cellular architecture. These results highlight the importance of cocaine in mediating cardiomyocyte function and cytotoxicity associated with the possible loss of intercellular contacts required to maintain normal cell viability, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.     

Autothermal hybridization and controlled production of hydrogen-rich syngas in a molten salt solar gasifier

High efficiency solar steam gasification of biomass is carried out in a prototype molten salt reactor for solar-only and solar-autothermal hybrid operation. Previous demonstration of the prototype 3-kW solar gasifier for steam gasification of cellulose at stoichiometric conditions demonstrated thermal efficiency of 44% during continuous operation at 1200 K. The present work expands the range of operating conditions to consider two challenges. Hybridization between solar and autothermal modes of operation is accomplished by adding oxygen directly to the reactor. Control of the H₂:CO ratio of the product gas is accomplished through in-situ steam shifting. Hybridization stabilized temperatures for variations in radiative input as large as a 30% reduction in power, corresponding to conditions where both sensible and chemical heat demands for the process were fully met by exothermic heat release with no significant challenges. Peak efficiencies and carbon conversion values observed are 45% and 99.5% respectively. The resulting product gas stream composition was shifted from a hydrogen and carbon monoxide ratio of 1:1 with stoichiometric steam delivery to a ratio of 1.7:1 with steam at nine times the stoichiometric amount, only slightly lower than equilibrium predictions. The results demonstrate very favorable attributes for the molten salt reactor in a continuous fuel production process.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

A lakewide survey of Asian clam (Corbicula fluminea) distribution at warmwater discharges in Lake Michigan

The Asian clam Corbicula fluminea is among the most prolific aquatic invaders in the world; but in colder mid-latitude areas, like the Laurentian Great Lakes, their population expansion has likely been limited by poor overwinter survival. In these areas, Asian clams are typically found in thermal refugia like warmwater discharges from industrial facilities. We sought to identify the current extent of Asian clam populations in Lake Michigan and waters immediately adjacent to it, specifically at locations most likely to harbor overwintering populations – industrial warmwater discharges. During April–May 2017, we surveyed 17 locations around Lake Michigan. Evidence of Asian clam populations was found at four sites, though live specimens (n?=?3) were only found at the Indiana Harbor Ship Canal in East Chicago, IN. Shells or fragments of shells were found at Green Bay, WI, Waukegan, IL, and Port Sheldon, MI. Our findings indicate that although Asian clams are present in Lake Michigan, they are relatively rare, and remain isolated to a few small pockets of over-wintering habitat.     

The incorporation of low-substituted hydroxypropyl cellulose into solid dispersion systems

While the use of amorphous solid dispersions to improve aqueous solubility is well documented, little consideration has traditionally been given to the finished dosage form. The objective of this study was to evaluate the dissolution performance of amorphous solid dispersions containing a dispersed superdisintegrant with binding properties. KinetiSol® dispersing was used to thermally process hypromellose acetate succinate-based compositions containing the drug substance nifedipine (NIF) and a highly compressible grade of low-substituted hydroxypropyl cellulose (New Binder Disintegrants; NBD-grade). Solid-state analysis demonstrated that compositions were rendered amorphous during processing. Tablets containing intra-dispersion NBD were found to exhibit non-sink dissolution performance similar to milled intermediate, demonstrating excellent disintegration characteristics. Conversely, tablets without intra-dispersion NBD were found to release significantly less NIF during dissolution analysis due to particle agglomeration. It was determined that compressibility and particle wetting increased as the level of intra-dispersion NBD increased.     

Efficiency of removal of whey protein from sweet whey using polymeric microfiltration membranes

Our objective was to measure whey protein removal percentage from separated sweet whey using spiral-wound (SW) polymeric microfiltration (MF) membranes using a 3-stage, 3× process at 50°C and to compare the performance of polymeric membranes with ceramic membranes. Pasteurized, separated Cheddar cheese whey (1,080 kg) was microfiltered using a polymeric 0.3-μm polyvinylidene (PVDF) fluoride SW membrane and a 3×, 3-stage MF process. Cheese making and whey processing were replicated 3 times. There was no detectable level of lactoferrin and no intact α- or β-casein detected in the MF permeate from the 0.3-μm SW PVDF membranes used in this study. We found BSA and IgG in both the retentate and permeate. The β-lactoglobulin (β-LG) and α-lactalbumin (α-LA) partitioned between retentate and permeate, but β-LG passage through the membrane was retarded more than α-LA because the ratio of β-LG to α-LA was higher in the MF retentate than either in the sweet whey feed or the MF permeate. About 69% of the crude protein present in the pasteurized separated sweet whey was removed using a 3×, 3-stage, 0.3-μm SW PVDF MF process at 50°C compared with 0.1-μm ceramic graded permeability MF that removed about 85% of crude protein from sweet whey. The polymeric SW membranes used in this study achieve approximately 20% lower yield of whey protein isolate (WPI) and a 50% higher yield of whey protein phospholipid concentrate (WPPC) under the same MF processing conditions as ceramic MF membranes used in the comparison study. Total gross revenue from the sale of WPI plus WPPC produced with polymeric versus ceramic membranes is influenced by both the absolute market price for each product and the ratio of market price of these 2 products. The combination of the market price of WPPC versus WPI and the influence of difference in yield of WPPC and WPI produced with polymeric versus ceramic membranes yielded a price ratio of WPPC versus WPI of 0.556 as the cross over point that determined which membrane type achieves higher total gross revenue return from production of these 2 products from separated sweet whey. A complete economic engineering study comparison of the WPI and WPPC manufacturing costs for polymeric versus ceramic MF membranes is needed to determine the effect of membrane material selection on long-term processing costs, which will affect net revenue and profit when the same quantity of sweet whey is processed under various market price conditions.     

Rationally Designed Polypharmacology: α-Helix Mimetics as Dual Inhibitors of the Oncoproteins Mcl-1 and HDM2

Protein–protein interactions (PPIs), many of which are dominated by α-helical recognition domains, play key roles in many essential cellular processes, and the dysregulation of these interactions can cause detrimental effects. For instance, aberrant PPIs involving the Bcl-2 protein family can lead to several diseases including cancer, neurodegenerative diseases, and diabetes. Interactions between Bcl-2 pro-life proteins, such as Mcl-1, and pro-death proteins, such as Bim, regulate the intrinsic pathway of apoptosis. p53, a tumor-suppressor protein, also has a pivotal role in apoptosis and is negatively regulated by its E3 ubiquitin ligase HDM2. Both Mcl-1 and HDM2 are upregulated in numerous cancers, and, interestingly, there is crosstalk between both protein pathways. Recently, synergy has been observed between Mcl-1 and HDM2 inhibitors. Towards the development of new anticancer drugs, we herein describe a polypharmacology approach for the dual inhibition of Mcl-1 and HDM2 by employing three densely functionalized isoxazoles, pyrazoles, and thiazoles as mimetics of key α-helical domains of their partner proteins.     

Peanut FAD2 Genotype and Growing Location Interactions Significantly Affect the Level of Oleic Acid in Seeds

The level of oleic acid is an important parameter in determining seed nutritional quality and oil stability. The level of oleic acid in peanut is genetically controlled by a pair of fatty acid desaturase genes (FAD2A and FAD2B), but the environmental conditions of the production sites can also have a significant effect. To investigate the effect of gene and environment interaction, 45 accessions were grown at three locations for 2 years. Environmental data were collected; individual plants were genotyped with functional SNP markers from FAD2A and FAD2B; and seed level of oleic acid was determined by gas chromatography. Three FAD2A/FAD2B genotypes (448G/no insertion 442A, 448A/no insertion 442A, and 448A/insertion 442A) were identified and designated as G/W, A/W, and A/A, respectively. A/A genotype averaged the highest level of oleic acid (80.0%), followed by A/W (56.0%), and then G/W (40.7%). Analysis of gene and environment interaction revealed that oleic acid phenotype plasticity could be explained by the interaction of FAD2 genotype and photothermal time, which quantified environmental conditions. The A/W genotype was the most sensitive to photothermal time changes. The oleic acid plasticity revealed in this study would be useful for breeders, farmers, and product processors.