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Unmet needs in the treatment of psoriasis call for novel therapeutic strategies. Pustular psoriasis and psoriatic arthritis often represent a therapeutic challenge. Focus on IL-36 cytokines offers an interesting approach, as the IL-36 axis has been appointed a critical driver of the autoinflammatory responses involved in pustular psoriasis. Two IL-36R blocking antibodies, imsidolimab and spesolimab, are currently undergoing phase II and III clinical trials, with promising results. 相似文献
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Software is a central component in the modern world and vastly affects the environment’s sustainability. The demand for energy and resource requirements is rising when producing hardware and software units. Literature study reveals that many studies focused on green hardware; however, limited efforts were made in the greenness of software products. Green software products are necessary to solve the issues and problems related to the long-term use of software, especially from a sustainability perspective. Without a proper mechanism for measuring the greenness of a particular software product executed in a specific environment, the mentioned benefits will not be attained. Currently, there are not enough works to address this problem, and the green status of software products is uncertain and unsure. This paper aims to identify the green measurements based on sustainable dimensions in a software product. The second objective is to reveal the relationships between the elements and measurements through empirical study. The study is conducted in two phases. The first phase is the theoretical phase, where the main components, measurements and practices that influence the sustainability of a software product are identified. The second phase is the empirical study that involved 103 respondents in Malaysia investigating current practices of green software in the industrial environment and further identifying the main sustainability dimensions and measurements and their impact on achieving green software products. This study has revealed seven green measurements of software product: Productivity, Usability, Cost Reduction, Employee Support, Energy Efficiency, Resource Efficiency and Tool Support. The relationships are statistically significant, with a significance level of less than 0.01 (p = 0.000). Thus, the hypothesised relationships were all accepted. The contributions of this study revolve around the research perspectives of the measurements to attain a green software product. 相似文献
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Amanat Ali Elizabeth K. M. Johnstone Bincy Baby Heng B. See Angela Song K. Johan Rosengren Kevin D. G. Pfleger Mohammed Akli Ayoub Ranjit Vijayan 《International journal of molecular sciences》2021,22(1)
Hemorphins are known for their role in the control of blood pressure. Recently, we revealed the positive modulation of the angiotensin II (AngII) type 1 receptor (AT1R) by LVV-hemorphin-7 (LVV-H7) in human embryonic kidney (HEK293) cells. Here, we examined the molecular binding behavior of LVV-H7 on AT1R and its effect on AngII binding using a nanoluciferase-based bioluminescence resonance energy transfer (NanoBRET) assay in HEK293FT cells, as well as molecular docking and molecular dynamics (MD) studies. Saturation and real-time kinetics supported the positive effect of LVV-H7 on the binding of AngII. While the competitive antagonist olmesartan competed with AngII binding, LVV-H7 slightly, but significantly, decreased AngII’s kD by 2.6 fold with no effect on its Bmax. Molecular docking and MD simulations indicated that the binding of LVV-H7 in the intracellular region of AT1R allosterically potentiates AngII binding. LVV-H7 targets residues on intracellular loops 2 and 3 of AT1R, which are known binding sites of allosteric modulators in other GPCRs. Our data demonstrate the allosteric effect of LVV-H7 on AngII binding, which is consistent with the positive modulation of AT1R activity and signaling previously reported. This further supports the pharmacological targeting of AT1R by hemorphins, with implications in vascular and renal physiology. 相似文献
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Deniz Caylioglu Rieke Johanna Meyer Dana Hellmold Carolin Kubelt Michael Synowitz Janka Held-Feindt 《International journal of molecular sciences》2021,22(7)
Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences. 相似文献
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针对常见泥石流防治结构被冲击破坏的问题,基于“柔性消能”理念,结合张弦梁结构和竖向预应力锚杆技术,提出一种既能改善结构受力性能、增加结构整体抗冲击能力、保证结构安全可靠,又能减小结构构件截面尺寸、节约成本、便于现场施工组装和后期运营维护的新型地锚张弦梁式泥石流格栅坝,并阐述其技术原理。根据泥石流荷载分布和新型地锚张弦梁式泥石流格栅坝的受力特征,给出其简化的内力计算方法;并利用SAP2000建立新结构有限元模型,分析了结构的整体受力,验证了构件简化计算方法的合理性;结合Python语言和Qt De? signer软件开发了相应的设计计算软件,对新型地锚张弦梁式泥石流格栅坝的内力进行求解。结果表明:提出的新结构抗冲击性能好,构件受力均匀;以后设计中应关注竖杆的剪切脆性破坏和立柱偏心受力情况,保证结构安全;变形协调仅使底层张弦梁与竖杆内力偏大,实际工程应用时,应着重验算底层构件,防止其破坏;文中提出的简化计算方法能较准确的反映结构的受力特性,具有一定的合理性,研究可为新型地锚张弦梁式泥石流格栅坝的设计计算和推广应用提供理论依据和技术支持。 相似文献
9.
《Ceramics International》2022,48(2):2377-2384
Bi2O3, Y2O3 and MgO co-doped BaTiO3 (BT)-based X8R ceramics were synthesized successfully for the first time. The effects of the sintering temperature and Bi2O3, Y2O3 and MgO dopants on the dielectric properties were investigated systematically. Bi2O3 doping can increase the Curie temperature (Tc), but reduces the overall dielectric permittivity. On the other hand, Y2O3 doping is beneficial to the formation of core-shell microstructure and the increase of Tc, whereas MgO can prevent excessive Y2O3 from diffusing into grain core, and thereby further contributes to the generation of the core–shell microstructure. The generation of the typical core-shell microstructure was confirmed and investigated in detail by using transmission electron microscopy (TEM). It is argued that the synergistic effects of Bi2O3, Y2O3 and MgO co-doping in terms of the formation of the core-shell structure and the increase of Tc, can help improve the temperature stability of the dielectric permittivity effectively. Increasing the sintering temperature leads to an increase in the grain size, which in turn leads to an increase in the overall dielectric permittivity due to the grain size effect. 相似文献
10.
M.S. AlBuriahi H.H. Hegazy Faisal Alresheedi I.O. Olarinoye H. Algarni H.O. Tekin H.A. Saudi 《Ceramics International》2021,47(5):5951-5958
This research article aims to study the effect of CdO addition on the radiation shielding characteristics of boro-tellurite glasses in the composition of 50B2O3 - (50-x) TeO2- xCdO, where x = 0, 10, 20, 30, 40 and 50 mol%. These glasses were exposed to gamma radiation and the transmitted gamma photons were evaluated for energies varying from 15 keV to 15 MeV using Geant4 simulation toolkit. The number of transmitted photons was then used to characterize the gamma shielding for the studied glasses in terms of linear/mass attenuation coefficients, MFP, Zeff, and HVL. The simulation outcomes were theoretically confirmed by using Phy-X software. The beta (electron) shielding characterization of the involved glasses was also investigated by determining the projectile range and stopping power using ESTAR software. Additionally, the fast neutron shielding characterization of the glasses was achieved by evaluating removal cross-section (ΣR). The results reveal that the CdO has a small influence on the shielding performance of the boro-tellurite glasses against gamma, beta, and neutron radiations. The shielding performance of the boro-tellurite glasses was compared with that of common shielding materials in terms of MFP. It can be concluded that the boro-tellurite glasses regardless of the concentration of CdO content have promising shielding performance to be used for radiation applications. 相似文献