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Mario Cano-Muoz Julie Lucas Li-Yun Lin Samuele Cesaro Christiane Moog Francisco Conejero-Lara 《International journal of molecular sciences》2022,23(5)
Inhibition of the HIV-1 fusion process constitutes a promising strategy to neutralize the virus at an early stage before it enters the cell. In this process, the envelope glycoprotein (Env) plays a central role by promoting membrane fusion. We previously identified a vulnerability at the flexible C-terminal end of the gp41 C-terminal heptad repeat (CHR) region to inhibition by a single-chain miniprotein (named covNHR-N) that mimics the first half of the gp41 N-terminal heptad repeat (NHR). The miniprotein exhibited low stability, moderate binding to its complementary CHR region, both as an isolated peptide and in native trimeric Envs, and low inhibitory activity against a panel of pseudoviruses. The addition of a disulfide bond stabilizing the miniprotein increased its inhibitory activity, without altering the binding affinity. Here, to further study the effect of conformational stability on binding and inhibitory potency, we additionally stabilized these miniproteins by engineering a second disulfide bond stapling their N-terminal end, The new disulfide-bond strongly stabilizes the protein, increases binding affinity for the CHR target and strongly improves inhibitory activity against several HIV-1 strains. Moreover, high inhibitory activity could be achieved without targeting the preserved hydrophobic pocket motif of gp41. These results may have implications in the discovery of new strategies to inhibit HIV targeting the gp41 CHR region. 相似文献
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1986年,一对来自意大利南部的年轻的兄弟, Ennio与Carlo Capasa,在米兰工作很长时间之后, 创立一个新的时装店——Costume National。在短短几年之后,这个服装品牌迅速成为五光十色的意大利时尚界最为著名的品牌之一。Costume National与其他成熟品牌一样崇尚自然存在主义精神,这种精神也深深扎根在两位创立者的血液中。但又有所不同, Costume National受到了非意大利传统的影响。因此,它的形象很难与常规的民族风尚联系在一起。很多人并不知道Capasa兄弟来自Lecce(位于意大利东南沿海),这个名字很容易让人联想到这可能是起源于日本,例如由Rei Kawakubo创立的 commes des Garcons品牌就是如此。这个结论是有根据的:Ennio Capasa曾经在东京与Yohji Ya- mamoto一起工作过很多年,在他的作品中有明显的日式风格。然而,Costume National的服装并不与日本趋同,在服装的款式上有自己的独到之处。与 Yohji Yamamoto所树立的样式不同,Capasa的设计与意大利传统的裁缝业密切联系,这样做并没有约束到品牌的发展,反而提高了自身的品质。 相似文献
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HPLC is applied and assessed as an effective tool to investigate both the production of PLA by polycondensation and its corresponding degradation. A new HPLC calibration procedure, through which it is possible to fully characterize LMW PLA samples by determining the concentration of each individual oligomer, is developed. A comparison between HPLC, 1H NMR spectroscopy and non‐aqueous solution titration is also reported in order to confirm the reliability of the proposed method. Finally, the proposed analytical technique is applied to monitor the development of a polycondensation reaction performed at 150 °C and 133.3 mbar for 12 h.
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Samuele Martelli 《中国室内装饰装修天地》2008,(4):124-129
在经过多年品牌形象的发展后,意大利国家航空公司(Alitatia)决定聘请著名的设计师马西莫伊欧萨·吉尼(Massimo losa Ghini)为该品牌设计一种新型的现代形象。马西莫伊欧萨·吉尼本人与Ferrari形象品牌的合作在近年取得了巨大的成功。 相似文献
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Giuseppe Grazzini Adriano Milazzo Samuele Piazzini 《International Journal of Refrigeration》2011,34(7):1641-1648
An experimental refrigeration system based on a two-stage steam ejector was set-up in the Thermodynamics and Heat Transfer Laboratory of our Department. The system optimization and realization have been described elsewhere (
[Grazzini and Mariani, 1998]
and
[Grazzini and Rocchetti, 2008]
). In both stages, primary flows are highly supersonic and reach low pressure and temperature levels. As usual in the literature, an ideal gas model was used during the design process. This paper is intended to check the validity of this assumption. In order to understand the actual working condition of our system, several models have been compared. The presence of high flow speed suggests the existence of metastable conditions. To set the border for the metastable region, the spinodal curve has been drawn. Isentropic expansion of vapour through the nozzle, modelled as ideal gas, seems well within the metastable zone. However, the Classic Nucleation Theory shows that the Wilson line is crossed at the nozzle throat. Condensation produces a marked difference in the conditions at the nozzle exit. Results coming from the present analysis will be used in further optimization of the experimental ejector design. 相似文献