Polysorbate identity and quantity dictate the extensional flow properties of protein-excipient solutions

While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of high-concentration formulations. Here, the extensional flow properties of protein-excipient solutions are examined via dripping-onto-substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior. Undesirable elasticity is observed in ultra-concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein-excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein-excipient formulations.     

Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

A simple model for the semicontinuous heterophase polymerization: Ethyl methacrylate as a case example

A simple but comprehensive model considering homogeneous and micellar nucleation, coagulation, entry of radicals to particles and to micelles and radicals' exit from particles, is presented. The model is validated, in a starved semicontinuous heterophase polymerization of ethyl methacrylate, at three monomer addition rates. The model accurately describes the overall and instantaneous conversion, the average particle density and diameter, and the number and weight average molar masses evolutions over time. It is found that even though the average number of radicals is much smaller than 0.5, the system is not 0-1. An empirical function was used to describe the gel effect. The homogeneous nucleation was the prevailing mechanism for particle formation and large exit rates of radicals were observed. POLYM. ENG. SCI., 60: 223–232, 2019. © 2019 Society of Plastics Engineers     

Algorithmic Fairness in Mortgage Lending: from Absolute Conditions to Relational Trade-offs

Minds and Machines - To address the rising concern that algorithmic decision-making may reinforce discriminatory biases, researchers have proposed many notions of fairness and corresponding...     

Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis

Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination.     

Impact of Reaction Conditions on MnO2 Genesis during Permanganate Oxidation

To enhance the understanding of the behavior and effects of the precipitation of MnO2 particles in the subsurface generated during in situ chemical oxidation (ISCO) using permanganate, laboratory batch experiments were completed to examine the influence that varied reaction matrix conditions have on the generation and properties of manganese oxides. The conditions examined include organic material type and concentration, permanganate concentration, pH, and the presence of calcium (as a representative divalent cation) in solution. Experimental studies included: (1) spectrophotometric examination of permanganate depletion and manganese oxides generation over time during reactions with trichloroethene; (2) scanning electron microscopy analyses of manganese particle morphology; (3) particle size distribution (filtration) characterization studies; and (4) optical particle sizing and numeration studies. Bench-scale, batch experiments were conducted to focus on fundamental chemical properties affecting particle development under varied potential environmental conditions. The amount of manganese oxides particles that develop, grow, and potentially settle as a result of permanganate ISCO of organic contaminants is a function of the particle size and concentration, the time allowed for particle development, and the impact of matrix conditions on the ability of particles to agglomerate.     

市场观察:向H.264过渡将推动视频IC快速增长

数字视频编码和解码芯片目前需求量很大.在未来几年里,这种芯片的市场将更加强劲地增长.推动这个市场增长的因素有三个:一个是全球范围的从模拟电视向数字电视的过渡,这种过渡将刺激数字接收机和基础设施设备的需求;另一个因素是手机、便携式播放机和汽车内的移动视频功能日益流行;第三个因素是数字视频标准的持续发展将推动对提供高性能芯片的新需求.