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Jianan Wang Guorui Yang Jie Chen Yunpeng Liu Yuankun Wang Cheng‐Yen Lao Kai Xi Duowen Yang Christopher J. Harris Wei Yan Shujiang Ding Ramachandran Vasant Kumar 《Liver Transplantation》2019,9(38)
Lithium–sulfur batteries are appealing as high‐energy storage systems and hold great application prospects in wearable and portable electronics. However, severe shuttle effects, low sulfur conductivity, and especially poor electrode mechanical flexibility restrict sulfur utilization and loading for practical applications. Herein, high‐flux, flexible, electrospun fibrous membranes are developed, which succeed in integrating three functional units (cathode, interlayer, and separator) into an efficient composite. This structure helps to eliminate negative interface effects, and effectively drives synergistic boosts to polysulfide confinement, electron transfer, and lithium‐ion diffusion. It delivers a high initial capacity of 1501 mA h g?1 and a discharge capacity of 933 mA h g?1 after 400 cycles, with slow capacity attenuation (0.069% per cycle). Even under high sulfur loading (13.2 mg cm?2, electrolyte/sulfur ratio = 6 mL g?1) or in an alternative folded state, this three‐in‐one membrane still exhibits high areal capacity (11.4 mA h cm?2) and exceptional application performance (powering an array of over 30 light‐emitting diodes (LEDs)), highlighting its huge potential in high‐energy flexible devices. 相似文献
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Sreekanth A. Ramachandran Pradeep S. Jadhavar Sandeep K. Miglani Manvendra P. Singh Deepak P. Kalane Anil K. Agarwal Balaji D. Sathe Kakoli Mukherjee Ashu Gupta Srijan Haldar Mohd Raja Siddhartha Singh Son M. Pham Sarvajit Chakravarty Kevin Quinn Sebastian Belmar Ivan E. Alfaro Christopher Higgs Roopa Rai 《Bioorganic & medicinal chemistry letters》2017,27(10):2153-2160
Signaling via the receptor tyrosine kinase CSF1R is thought to play an important role in recruitment and differentiation of tumor-associated macrophages (TAMs). TAMs play pro-tumorigenic roles, including the suppression of anti-tumor immune response, promotion of angiogenesis and tumor cell metastasis. Because of the role of this signaling pathway in the tumor microenvironment, several small molecule CSF1R kinase inhibitors are undergoing clinical evaluation for cancer therapy, either as a single agent or in combination with other cancer therapies, including immune checkpoint inhibitors. Herein we describe our lead optimization effort that resulted in the identification of a potent, cellular active and orally bioavailable bis-amide CSF1R inhibitor. Docking and biochemical analysis allowed the removal of a metabolically labile and poorly permeable methyl piperazine group from an early lead compound. Optimization led to improved metabolic stability and Caco2 permeability, which in turn resulted in good oral bioavailability in mice. 相似文献
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Adam N. Spierer Jim A. Mossman Samuel Pattillo Smith Lorin Crawford Sohini Ramachandran David M. Rand 《PLoS genetics》2021,17(3)
The winged insects of the order Diptera are colloquially named for their most recognizable phenotype: flight. These insects rely on flight for a number of important life history traits, such as dispersal, foraging, and courtship. Despite the importance of flight, relatively little is known about the genetic architecture of flight performance. Accordingly, we sought to uncover the genetic modifiers of flight using a measure of flies’ reaction and response to an abrupt drop in a vertical flight column. We conducted a genome wide association study (GWAS) using 197 of the Drosophila Genetic Reference Panel (DGRP) lines, and identified a combination of additive and marginal variants, epistatic interactions, whole genes, and enrichment across interaction networks. Egfr, a highly pleiotropic developmental gene, was among the most significant additive variants identified. We functionally validated 13 of the additive candidate genes’ (Adgf-A/Adgf-A2/CG32181, bru1, CadN, flapper (CG11073), CG15236, flippy (CG9766), CREG, Dscam4, form3, fry, Lasp/CG9692, Pde6, Snoo), and introduce a novel approach to whole gene significance screens: PEGASUS_flies. Additionally, we identified ppk23, an Acid Sensing Ion Channel (ASIC) homolog, as an important hub for epistatic interactions. We propose a model that suggests genetic modifiers of wing and muscle morphology, nervous system development and function, BMP signaling, sexually dimorphic neural wiring, and gene regulation are all important for the observed differences flight performance in a natural population. Additionally, these results represent a snapshot of the genetic modifiers affecting drop-response flight performance in Drosophila, with implications for other insects. 相似文献