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Monica Archibald,1 Tara Pritchard,1 Hayley Nehoff,1 Rhonda J Rosengren,1 Khaled Greish,1,2 Sebastien Taurin1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Aljawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. Keywords: sorafenib, nilotinib, castrate-resistant prostate cancer, tyrosine kinase inhibitors, nanomedicine

For fixed m ≥ 1, we study the number of weak left-to-right maxima which occur exactly m times in words whose letters satisfy a geometric distribution. First, we find the generating function and two exact expressions for the mean. Thereafter we use Rice's integrals to derive an asymptotic formula as n tends to infinity for the average in random geometric words of length n for each fixed value of m. [ABSTRACT FROM AUTHOR]

The article discusses the changes in cross sectioning demographics in consumer panels as a result of the onset of World War II. The author writes about how it was possible to make comparisons between living standards before the attack on Pearl Harbor in 1941 and the standards after because of the traumatic impact of the event. Furthermore, he points out how income distribution has changed sin the United States has switched to a war economy. Three groups of distribution are noted as those in the military, those working in war industries, and others. From this analyzation of the new income distribution, the author feels that this new cross section will be beneficial to consumer research.

The article discusses the proceedings of the November 3, 1941 meeting of the American Marketing Association's subcommittee on descriptive classification of income levels. Discussion was held pertaining to methods of determining districts for the classification of rental units by amount charged for rent.