Parenteral Drug Association

Quality culture as an enabler of high-quality performance and subsequently as a source of competitive advantage is increasingly discussed among operational excellence (OPEX) and quality executives. Research studies indicate an impact of quality culture on performance, especially on the success of quality improvement programs, such as Total Quality Management initiatives. A continual challenge in quality culture research, however, remains the lack of practical and accepted metrics to assess culture. In 2014, the Parental Drug Association (PDA) conducted a quality culture survey within the pharmaceutical industry. The results indicate a positive and significant correlation between quality (culture) behavior of a production site's employees and quality (system) maturity, which represents the maturity of the quality system in place. As the maturity of the quality system is more comfortable to assess by objective criteria, the positive correlation between quality (culture) behavior and quality (system) maturity may be exploited by using the latter as an indicator for quality culture. This paper confirms this positive relationship by exploring the comprehensive St. Gallen OPEX database for pharmaceutical production plants. Furthermore, data analysis shows that high-performing production sites, regarding timely provision of high-quality drugs, reveal a higher level of both quality (system) maturity and quality (culture) behavior than low-performing sites.

Kilroy Springs are cantilever spring auxiliaries that have been added to orthodontic armamentarium to provide forces to maxillary impacted teeth so as to direct their eruption downward and toward the dental arch. Dr. Bowman had designed and developed these orthodontic auxiliaries to assist in the correction of impacted maxillary canines, one of the most problematic dilemmas in our specialty. The key to dealing with impacted maxillary canines is to provide specific directional forces to insure that these teeth are moved down into the dental arch from the point where they are stuck in the jaw. These auxiliaries provide a versatile and predictable biomechanics for the correction of a very complex problem of canine impaction. This article describes three cases to highlight the efficacy of these springs.

Abstract VPS34 is a phosphatidylinositol 3-kinase (PI3K) that catalyzes phosphorylation of phosphatidylinositol. In response to nutrients, VPS34 contributes to the activation of mTOR/S6K1 signaling which regulates proliferation, protein synthesis, and cell survival. Intracellular mechanisms leading to VPS34 activation are just beginning to be elucidated. Src is a non-receptor tyrosine kinase that signals downstream of numerous pathways to regulate cell proliferation, survival, and cancer metastasis. Here, we report that Src directly phosphorylates VPS34 leading to activation of VPS34 lipid kinase activity, and that VPS34 lipid kinase activity is required for Src-mediated cellular transformation. Silencing VPS34 specifically inhibits Src-Y527F-induced colony formation in soft agar, but not Ras-G12V-induced colony formation. We have identified two novel VPS34 mutations, which either eliminate lipid kinase activity (KD mutant) or reduce tyrosine phosphorylation (Y231F mutant) by Src-Y527F. When VPS34-KD is stably expressed in Src-Y527F-transformed cells, proliferation and anchorage independent growth are significantly inhibited. Additionally, stable expression of VPS34-KD causes an increased number of binucleate and multinucleate cells, suggesting that VPS34 kinase activity is also required for cytokinesis. Stable expression of VPS34-Y231F in Src-Y527F transformed cells also reduces colony formation. We additionally found that VPS34 protein levels and tyrosine phosphorylation correlate with the tumorigenic activity of breast cancer cell lines. Together these data suggest that Src to VPS34 signaling may contribute to the development and progression of human cancers. Citation Format: Dianne S. Hirsch, Yi Shen, Milos Dokmanovic, Wen Jin Wu. VPS34 lipid kinase activity is positively regulated by Src phosphorylation and is required for Src-mediated cellular transformation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-38. doi:10.1158/1538-7445.AM2013-LB-38

The IL‐4 receptor is a central mediator of Th2‐mediated diseases and associates with either the common gamma chain (type‐I IL‐4R) or IL‐13Rα1 (type‐II IL‐4R) to form two receptor complexes. Here, using IL‐13Rα1−/− mice, we characterized the distinct functions of the type‐II IL‐4R. In contrast to IL‐4Rα−/− mice that display weak Th2 responses, IL‐13Rα1−/− mice developed Th2 responses stronger than WT. Nevertheless, they displayed significantly reduced fibrosis and mortality following S. mansoni infection and markedly increased susceptibility to N. brasiliensis. The IL‐13Rα1 also controlled allergen‐induced airway hyperreactivity and mucus hypersecretion but not alternative‐macrophage activation or arginase‐1 expression, for which the type‐I IL‐4R was sufficient. Hence therapeutics that selectively target the type‐II IL‐4R might prove the best strategy to regulate Th2‐driven disease.

This paper presents an efficient procedure for the design of interpolated FIR (IFIR) filters with linear phase. The algorithm uses the uniform B-spline function as an interpolator and solves the optimal Chebyshev approximation problem on the optimal subinterval. The technique can be used for the design of general lowpass, highpass and bandpass filters. While the number of multiplications of the IFIR filter is dependent on the bandwidth and the center frequency of the desired filter, it provides the minimum number of multiplications achievable and nearly always provides a substantial reduction when compared to Parks-McClellan designs.