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Pasireotide treatment for severe congenital hyperinsulinism due to a homozygous ABCC8 mutation
Mooij Christiaan F.,Tacke Carline E.,van Albada Mirjam E.,Barthlen Winfried,Bikker Hennie,Mohnike Klaus,Oomen Matthijs W.N.,van Trotsenburg A.S. Paul,Zwaveling-Soonawala Nitash 대한소아내분비학회 2021 Annals of Pediatirc Endocrinology & Metabolism Vol.26 No.4
ABCC8 and KCJN11 mutations cause the most severe diazoxide-resistant forms of congenital hyperinsulinism (CHI). Somatostatin analogues are considered as secondline treatment in diazoxide-unresponsive cases. Current treatment protocols include the first-generation somatostatin analogue octreotide, although pasireotide, a second-generation somatostatin analogue, might be more effective in reducing insulin secretion. Herein we report the first off-label use of pasireotide in a boy with a severe therapy-resistant form of CHI due to a homozygous ABCC8 mutation. After partial pancreatectomy, hyperinsulinism persisted; in an attempt to prevent further surgery, off-label treatment with pasireotide was initiated. Short-acting pasireotide treatment caused high blood glucose level shortly after injection. Long-acting pasireotide treatment resulted in more stable glycemic control. No side effects (e.g., central adrenal insufficiency) were noticed during a 2-month treatment period. Because of recurrent hypoglycemia despite a rather high carbohydrate intake, the boy underwent near-total pancreatectomy at the age of 11 months. In conclusion, pasireotide treatment slightly improved glycemic control without side effects in a boy with severe CHI. However, the effect of pasireotide was not sufficient to prevent near-total pancreatectomy in this case of severe CHI.
Aeroelastic tailoring using crenellated skins-modelling and experiment
Francois, Guillaume,Cooper, Jonathan E.,Weaver, Paul M. Techno-Press 2017 Advances in aircraft and spacecraft science Vol.4 No.2
Aeroelastic performance controls wing shape in flight and its behaviour under manoeuvre and gust loads. Controlling the wing‟s aeroelastic performance can therefore offer weight and fuel savings. In this paper, the rib orientation and the crenellated skin concept are used to control wing deformation under aerodynamic load. The impact of varying the rib/crenellation orientation, the crenellation width and thickness on the tip twist, tip displacement, natural frequencies, flutter speed and gust response are investigated. Various wind-off and wind-on loads are considered through Finite Element modelling and experiments, using wings manufactured through polyamide laser sintering. It is shown that it is possible to influence the aeroelastic behaviour using the rib and crenellation orientation, e.g., flutter speed increased by up to 14.2% and gust loads alleviated by up to 6.4%. A reasonable comparison between numerical and experimental results was found.
Savelyev, Dmitry P.,Kamenetsky, Vadim S.,Danyushevsky, Leonid V.,Botcharnikov, Roman E.,Kamenetsky, Maya B.,Park, Jung-Woo,Portnyagin, Maxim V.,Olin, Paul,Krasheninnikov, Stepan P.,Hauff, Folkmar,Zele Mineralogical Society of America 2018 The American mineralogist Vol.103 No.6
<P><B>Abstract</B></P><P>Silicate-sulfide liquid immiscibility in mantle-derived magmas has important control on the budget of siderophile and chalcophile metals, and is considered to be instrumental in the origin orthomagmatic sulfide deposits. Data on primitive sulfide melts in natural samples, even those representing most voluminous magmatism in oceanic rifts, are very scarce due to the small size and poor preservation of incipient sulfide melt globules. Here we present the first detailed report of the crystallized sulfides melts in the oceanic picrites of the (presumably) Cretaceous age Kamchatsky Mys ophiolite complex in Eastern Kamchatka (Far East Russia). Sulfide melts are present in three forms; (1) as inclusions in olivine (87.1-89.6 mol% Fo), (2) interstitial to the groundmass minerals (clinopyroxene, plagioclase, and Ti-magnetite) of studied picrites, and (3) as daughter phases in silicate melt inclusions hosted by olivine and Cr-spinel phenocrysts. The sulfide melt inclusions in olivine and the groundmass of studied rocks are composed of several sulfide phases that correspond to the monosulfide (Fe-Ni;<I>Mss</I>) and intermediate (Fe-Cu-Ni;<I>Iss</I>) solid solutions. Several <0.5 μm Pd-Sn, Pt-Ag, and Au-Ag phases are recorded within the matrix sulfides, commonly along phase boundaries and fractures. Major elements (S, Fe, Cu, Ni, Co), platinum group elements (PGE), and gold analyzed in the homogenized olivine-hosted sulfide melt inclusions, and phases identified in the matrix sulfides record the range of magmatic sulfide compositions. The most primitive sulfide liquids are notably enriched in Ni and Cu [(Ni+Cu)/Fe, at% > 0.5], continuously evolve with crystallization of (e.g., increasing Cu/Ni and Au/PGE) and demonstrate metal fractionation between<I>Mss</I>and<I>Iss</I>. Although the compositional systematics found in this study are consistent with those previously recorded, the compositions of individual sulfide phases are strongly affected by the noble metal (PGE, Au) “nuggets” that exsolve at subsolidus temperatures and form during serpentinization of the rocks. We conclude that the budget of noble metals in the studied picrites is controlled by sulfides, but the abundances of Pt and Au are influenced by mobility in post-magmatic alteration. Our data can be also used for modeling sulfide saturation at crustal pressures and understanding behavior of the noble metals in primitive oceanic magmas.</P>
Ideals and Practicality: The Reorientation of US Foreign Policy
( Paul E Gallis ) 한국국방연구원 1991 The Korean Journal of Defense Analysis Vol.3 No.2
The declining Soviet threat is leading to a reformulation of US foreign policy. During the Cold War, US foreign policy was Euro- centric, and NATO was the centerpiece of US security. The Soviet Union presented a clear threat to the United States. Ideology and ideals played a major role in the US-Soviet competition. US leaders could describe the threat as one poised to undermine democracy and a free market system, and by doing so could often strengthen domestic and allied support for US policy. In the wake of Soviet retrenchment in Eastern Europe and US- Soviet cooperation in several areas of the world, US foreign policy is slowly moving towards a new course. Ideology will play a dimin-ished role in Was) ington`s effort to gain the support of American citizens and of other nations for US policy. During the 199Os, NATO will likely wane in importance to US security interests, in part because of the decline of the Soviet threat, in part because the European allies will increasingly seek to express their interest through other institutions, such as the European Com- munity or the Conference on Security and Cooperation in Europe. The united Germany will play an important role in shaping European opinion and policy towards the United States. US influence over NATO and with the EC nations will likely diminish, with attendant differences more sharply evident between the United States and its European allies over security interests outside the European theater and over global trade. US foreign policy may reflect more practical concerns in the 1990s. Foreign assistance to such nations as Greece and Israel has been tied closely to the effort to counter Soviet power and influence in the world. Such a rationale for foreign assistance has now been weakened. The Persian Gulf War demonstrated the need to seek support from a broader range of nations and multilateral institutions in order to protect US interests abroad. The implication inherent in this turn in policy is that the United States will loosen its ties to a number of traditional friends and allies and seek to strengthen bonds with nations and regions more able to contribute to US interests in the post-Cold War period.
Preferential Trade Agreements, Market Power, and Product Differentiation
( Paul E. Jensen ),( Vibhas Madan ) 세종대학교 경제통합연구소 (구 세종대학교 국제경제연구소) 2004 Journal of Economic Integration Vol.19 No.1
Preferential trade agreements (PTAs) usually result in increased trade amongst member countries and lower prices within the PTA. Thus the markets are assumed to be “more competitive” because lower prices are taken to imply “decreased market power” due to a reduction in price-cost margins. In this paper we empirically examine the relationship between changes in market power and product differentiation within the context of a duopoly framework with restricted entry. Using industry level trade data from the EEC we show that the formation of a PTA may increase the market power of PTA-exporters and lower the market power of non-PTA exporters. In addition, we show that these market power effects are more pronounced for less differentiated products.