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.     

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.     

Desire and the couch: Perspectives from both sides of the analytic encounter.

This report summarizes the panel held at the 109th Annual Convention, American Psychological Association, August 26, 2001, San Francisco. The chair was William Glover and the speakers were Samuel Gerson, Karen Maroda, and Andre Patsalides. The invited symposium was directed at discussing different perspectives related to the presence of desire in the analytic process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Individual differences in self-assessed health: An information-processing investigation of health and illness cognition.

In 2 studies, the relation between measures of self-assessed health (SAH) and automatic processing of health-relevant information was investigated. In Study 1, 84 male and 86 female undergraduate students completed a modified Stroop task. Results indicated that participants with poorer SAH showed enhanced interference effects for illness versus non-illness words. In Study 2, 27 male and 30 female undergraduate students completed a self-referent encoding task. Results offered a conceptual replication and extension of Study 1 by confirming the specificity of the relation between SAH measures and automatic processing of health (vs negative or positive general trait) information. These studies provide evidence that individual differences in SAH are reflected in schematic processing of health-relevant information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opiate users and the first years after treatment: outcome analysis of the proportion of follow up time spent in abstinence

This second report on a follow-up study of drug users focuses on changes that occurred on a number of variables between intake and follow-up and during the follow-up period. The length of abstinence from opiates was considered as a proportion of the total follow-up period. Overall there was a reduction in opiate use, in injecting and sharing equipment at follow-up. There had been, however, a high level of these risky activities during the follow-up period. Sustained abstinence from opiates was associated with increased employment, enhanced social stability and mental health. Intake drug use was strongly related to follow-up drug status. In particular, those who were injectors of multiple drugs at intake were far less likely to be long term opiate abstainers at follow-up than those who were not injectors at intake or injectors of opiates only.     

Verbal and spatial working memory in school-age children: Developmental differences in susceptibility to interference.

The development of verbal and spatial working memory was investigated with an interference paradigm. Memory spans were obtained from 3 groups (8-, 10-, and 19-yr olds) under 6 different conditions: Two primary memory tasks (1 verbal, 1 spatial) were administered in isolation and in conjunction with 2 versions of a secondary task. The primary tasks required recalling a series of visually presented digits and recalling the locations of Xs in a series of visually presented grids. The secondary tasks required reporting the color of the stimuli as they were presented using either a verbal or a spatial response. Analyses revealed that all age groups showed domain-specific interference (i.e., interference by a secondary task from the same domain as the primary task), but only the 8-yr-olds also showed nonspecific interference (i.e., interference by a secondary task from a domain different than the primary memory task), suggesting that at least some executive functions do not reach adult levels of efficiency until approximately age 10. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Constraints on benthic algal response to nutrient addition in oligotrophic mountain rivers

Nutrient availability has long been considered one of the most important factors regulating production of benthic algae in oligotrophic rivers; yet, empirical relationships do not have as wide an application as similar models derived for lentic systems. The aim of this research was to derive empirical relationships between nutrient concentrations and benthic algal abundance and to identify commonalities with other studies to improve our understanding of constraints on algae in oligotrophic rivers. Surveys of physical, chemical and biological attributes of oligotrophic mountain rivers in spring, summer and autumn for 2 years confirmed that small amounts of anthropogenic phosphorus (0.1–5.6 µg/L total phosphorus (TP)) resulted in 4‐ to 30‐fold increases in abundance of benthic algae and benthic macroinvertebrates (BMIs). Algal accrual along a gradient in nutrient availability was not masked by grazing pressure but was positively correlated with abundance of scrapers. Epilithic abundance was highest downstream of anthropogenic nutrient sources in autumn. We concluded that benthic algal abundance in these mountain rivers was weakly correlated with phosphorus availability if light was not limiting but ultimately controlled by temperature and river discharge. Therefore, we recommend more direct measures of nutrient limitation be used to predict changes in ecological integrity at the lower end of the resource gradient. Copyright © 2007 John Wiley & Sons, Ltd.