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)     

Intracranial and spinal dissemination of an ACTH secreting pituitary neoplasia. Case report and review of the literature

Smoking is associated with insulin resistance, dyslipidaemia and markers of the insulin resistance syndrome. This study investigated adipose tissue lipolysis in situ by subcutaneous microdialysis twice in 10 healthy, male smokers after smoking four cigarettes over 2 h and after the administration of an equal amount of nicotine given as nasal spray (NNS). Glucose and insulin levels, in situ lipolysis and adipose tissue blood flow were studied in the post-absorptive state and after a 75-g oral glucose tolerance test (OGTT). Post-absorptively, acute smoking and NNS increased neither subcutaneous adipose tissue glycerol production nor plasma free fatty acid (FFA) or glycerol levels. After the OGTT, plasma insulin and lactate levels were significantly higher after smoking, whereas FFA levels were higher after NNS. Normal smoking or the administration of a normal dose of NNS caused only minor metabolic changes. Thus, it does not seem likely that increased lipolysis is an important contributor to the dyslipidaemia seen in smokers.     

Conservative surgery for stage I ovarian carcinoma in women of childbearing age

OBJECTIVE: To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas. DESIGN: Retrospective study. PARTICIPANTS: Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere. METHODS: Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour. RESULTS: Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery. CONCLUSION: After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage JC tumours.