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1.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
2.
Alison Willette Benjamin Fallen Hem Bhandari Carl Sams Feng Chen Virginia Sykes Chris Smallwood Kristin Bilyeu Zenglu Li Vincent Pantalone 《Journal of the American Oil Chemists' Society》2021,98(8):861-869
Soybean oil hydrogenation alters the linolenic acid molecule to prevent the oil from becoming rancid, however, health reports have indicated trans-fat caused by hydrogenation, is not generally regarded as safe. Typical soybeans contain approximately 80 g kg−1 to 120 g kg−1 linolenic acid and 240 g kg−1 of oleic acid. In an effort to accommodate the need for high-quality oil, the United Soybean Board introduced an industry standard for a high oleic acid greater than 750 g kg−1 and linolenic acid less than 30 g kg−1 oil. By combing mutations in the soybean plant at four loci, FAD2-1A and FAD2-1B, oleate desaturase genes and FAD3A and FAD3C, linoleate desaturase genes, and seed oil will not require hydrogenation to prevent oxidation and produce high-quality oil. In 2017 and 2018, a study comparing four near-isogenic lines across multiple Tennessee locations was performed to identify agronomic traits associated with mutations in FAD3A and FAD3C loci, while holding FAD2-1A and FAD2-1B constant in the mutant (high oleic) state. Soybean lines were assessed for yield and oil quality based on mutations at FAD2-1 and FAD3 loci. Variations of wild-type and mutant genotypes were compared at FAD3A and FAD3C loci. Analysis using a generalized linear mixed model in SAS 9.4, indicated no yield drag or other negative agronomic traits associated with the high oleic and low linolenic acid genotype. All four mutations of fad2-1A, fad2-1B, fad3A, and fad3C were determined as necessary to produce a soybean with the new industry standard (>750 g kg−1 oleic and <30 g kg−1 linolenic acid) in a maturity group-IV-Late cultivar for Tennessee growers. 相似文献
3.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
4.
Effects of breed and age at slaughter on degradation of muscle lipids during processing of dry‐cured hams
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Linda Storrustløkken Hanne Marie Devle Lars Erik Gangsei Carl Fredrik Naess‐Andresen Bjørg Egelandsdal Ole Alvseike Dag Ekeberg 《International Journal of Food Science & Technology》2015,50(8):1933-1943
Hams from Landrace, Duroc and Hampshire pigs slaughtered at ages 6, 7.5 and 9 months were processed to generate Norwegian Parma‐style hams. Lipid contents and the compositions of fatty acid classes (ΣSFA, ΣMUFA, ΣPUFA) within neutral lipids, phospholipids and free fatty acids were determined. Small differences in lipid degradation and composition of the classes were revealed. However, significant sensory differences related to lipids were observed. Breed was more important than age. Dry‐cured Hampshire hams gave a more intense mature odour that may be associated with higher overall lipid degradation. Unexpectedly, these hams also demonstrated high juiciness and tenderness, which could be related to the melting characteristics of the fat. Dry‐cured Duroc hams showed a higher susceptibility towards rancidity, presumably associated with preferential oxidation of n‐6 fatty acids relative to C18:1 n‐9. Dry‐cured Landrace hams showed the lowest juiciness and tenderness, likely due to their lower fat content (marbling). 相似文献
5.
CarlScharrer 《世界电子元器件》2006,(5):72-75
主要半导体生产商最近承认,开发和生产先进IC卡迫切需要晶片级射频测量。在某种程度上,这一直是 ITRS建模与仿真技术工作组所倡导的:射频紧凑型模型的参数提取更适合将射频测量降到最少。如有必要, 相似文献
6.
Sheldon H. Jacobson Julie L. Virta Jon M. Bowman John E. Kobza John J. Nestor 《IIE Transactions》2003,35(3):259-269
Aviation security protects vital national interests, as well as passengers and aircraft. Key components of an aviation security system include baggage and passenger screening devices and operations. Determining how and where to assign (deploy) such devices can be quite challenging. Moreover, even after such systems are in place, it can be difficult to measure their effectiveness. This paper describes how discrete optimization models can be used to address these questions, based on three performance measures that quantify the effectiveness of airport baggage screening security device systems. These models are used to solve for optimal airport baggage screening security device deployments considering the number of passengers on a set of flights who have not been cleared using a security risk assessment system in use by the Federal Aviation Administration (i.e., passengers whose baggage is subjected to screening), the number of flights in this set, and the size of the aircraft for such flights. Several examples are provided to illustrate these results, including an example that uses data available from the Official Airline Guide. 相似文献
7.
The phospholipids of the spongePolymastia gleneni contain saturated long chain (C22–30)-acetoxy fatty acids. Their structures were assigned based on chromatographic and spectrometric data as well as comparison
with a synthetic sample. The use of capillary gas chromatography combined with chemical ionization and electron impact mass
spectrometry was instrumental in the eludication of structures, since only a very small amount of crude lipids was available.
Part 10 of “Phospholipids in Marine Organisms.” For Part 9 in this series, see reference 12. 相似文献
8.
Jon T. Carter Paul E. Krajewski Ravi Verma 《JOM Journal of the Minerals, Metals and Materials Society》2008,60(11):77-81
The hot blow forming of magnesium sheet offers significant opportunity for forming complex, lightweight parts for automotive
applications. This paper characterizes the elevated-temperature formability of AZ31 magnesium sheet materials and the effect
of processing conditions on the performance of these materials. In addition, magnesium sheet application development at General
Motors Corporation is reviewed. 相似文献
9.
This paper presents a methodology whereby the payload weight of a serial manipulator can be determined from a minimum set of sensor data, i.e., joint angle and joint torque measurements. The particular manipulator geometry that is analyzed is a four degree‐of‐freedom serial chain that is commonly used in excavator systems. It was quite remarkable that a relatively simple solution was obtained for the payload weight considering that there are a total of nine unknown moments and cross moments of inertia of the payload together with the unknown location of the center of mass. Example calculations are presented. © 2003 Wiley Periodicals, Inc. 相似文献
10.
Jānis Bārzdiņš Rūsiņš Freivalds Carl H. Smith 《Journal of Computer and System Sciences》2008,74(4):527-545
We study learning of predicate logics formulas from “elementary facts,” i.e. from the values of the predicates in the given model. Several models of learning are considered, but most of our attention is paid to learning with belief levels. We propose an axiom system which describes what we consider to be a human scientist's natural behavior when trying to explore these elementary facts. It is proved that no such system can be complete. However we believe that our axiom system is “practically” complete. Theorems presented in the paper in some sense confirm our hypothesis. 相似文献