Steroid Response in Refractory Asthmatics

Inhaled glucocorticosteroids are currently the most effective anti-inflammatory controller medications for treating persistent asthma. The efficacies of glucocorticoids include reducing asthma symptoms, reducing exacerbation frequency, improving quality of life, improving lung function, decreasing airway hyperresponsiveness, controlling airway inflammation, and reducing mortality. However, the treatment response to glucocorticosteroids in asthmatics varies, and certain subtypes of asthma, such as refractory asthma, respond poorly to high-dose inhaled glucocorticoid and systemic steroids. The medical costs of treating refractory asthmatics represent about 50% of the total healthcare cost for asthma. A thorough understanding of the mechanisms of glucocorticoid action, patient responses to glucocorticoids, and steroid resistance observed in refractory asthmatics is necessary for the targeted development of therapeutic drugs. This review discusses the characteristics of severe refractory asthmatics and the mechanisms of steroid response and resistance in asthma treatment

The Critique of the Principle of Uniformitarianism and the Analysis of High School Earth Science Textbooks

1996Although uniformitarianism is widely recognized as the basic principle upon which the structure of historical geology has been erected, a closer investigation on the basis of present scientific knowledge and the philosophy of science reveals some of its invalid aspects. The concept of uniformitarianism was developed in a dual concept in Lyellian days. Substantive uniformitarianism (a testable theory of geologic change postulating uniformity of rates or material conditions) is false, ambiguous and stifling to hypotheses formation. Methodological uniformitarianism (a procedural principle asserting that former changes of the Earth's surface may be explained by reference to causes now in operation) belongs to the definition of science and is not unique to geology. Moreover, it also has some methodological defects in forming bold and novel working hypotheses. Methodological uniformitarianism today should take the form of a much older and more general scientific principle: Occam's Razor, the principle of simplicity. Accordingly, substantive uniformitarianism, an incorrect theory, should be abandoned. Methodological uniformitarianism, now a superfluous term, should be best confined to the historical roles in geology. In this connection, the presentation of uniformitarianism in high school textbooks was analyzed. It was revealed that text books were riddled with false and misleading statements as to what uniformitarianism means. Since uniformitarianism, as presented in many textbooks, is in direct contradiction to the philosophy of Inquiry learning, it is important to rethink the direction of uniformitarianism presentation in Earth Science curriculum development

Crystal structure of Helicobacter pylori MinE, a cell division topological specificity factor

In Gram-negative bacteria, proper placement of the FtsZ ring, mediated by nucleoid occlusion and the activities of the dynamic oscillating Min proteins MinC, MinD and MinE, is required for correct positioning of the cell division septum. MinE is a topological specificity factor that counters the activity of MinCD division inhibitor at the mid-cell division site. Its structure consists of an anti-MinCD domain and a topology specificity domain (TSD). Previous NMR analysis of truncated Escherichia coli MinE showed that the TSD domain contains a long α-helix and two anti-parallel β-strands, which mediate formation of a homodimeric α/β structure. Here we report the crystal structure of full-length Helicobacter pylori MinE and redefine its TSD based on that structure. The N-terminal region of the TSD (residues 19–26), previously defined as part of the anti-MinCD domain, forms a β-strand (βA) and participates in TSD folding. In addition, H. pylori MinE forms a dimer through the interaction of anti-parallel βA-strands. Moreover, we observed serial dimer–dimer interactions within the crystal packing, resulting in the formation of a multimeric structure. We therefore redefine the functional domain of MinE and propose that a multimeric filamentous structure is formed through anti-parallel β-strand interactions

Silicon-containing dendritic tris-cyclometalated Ir(III) complex and its electrophosphorescence in a polymer host

In this paper, we present the synthesis and characterization of a new highly phosphorescent cyclometalated Ir(III) complex with a silane-based dendritic substituent. The Ir(III) complex showed 74 ± 3% of absolute phosphorescence quantum efficiency in the film state. In addition, efficient electrophosphorescence (32.8 cd A–1) employing an Ir(III) complex–poly(N-vinylcarbazole) system device is observed. Study of a series of electroluminescent, spectroscopic, and electrochemical data of the Ir(III) complex and the reference Ir(ppy)3 reveals superior performance of the new Ir(III) complex.This work was supported in parts by the Ministry of Science and Technology of Korea through a National Research Laboratory (NRL) program awarded to Prof. Soo Young Park and by Dongwoo FineChem Co., Ltd. Prof. J.-J Kim acknowledges the Ministry of Commerce, Industry and Energy of Korea through the OLED center, Center for Electro- and Photo-Responsive Molecules, and Samsung SDI Corporation for financial support