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.     

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.     

Fractal error for detecting man-made features in aerial images

A technique is proposed for aiding photointerpreters in detecting man-made features in aerial reconnaissance images. The technique, which uses a metric called fractal error, is based on the observed propensity of natural image features to fit a fractional Brownian motion model. Man-made features usually do not fit this model well, and consequently the fractal error metric may be used as a discriminant function for detecting man-made scene features     

Juvenile competence to stand trial evaluations: A survey of current practices and test usage among psychologists.

What is the current standard of practice for evaluations of juvenile competence to stand trial (JCST)? The present study surveyed psychologists regarding the practices used when conducting JCST evaluations. Respondents rated the importance of 17 elements that might be included in a JCST evaluation report. Of these elements, 7 were considered essential by 70% or more of respondents, with 9 additional elements rated as either essential or recommended. A majority of respondents felt that the use of psychological and forensic instruments was important. A list of tests used is provided, and the implications for the development of standards and policy are discussed to provide practitioners with additional knowledge that will help to further the state of the discipline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)