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1.
Moeck  Christian  Merk  Markus  Radny  Dirk  Auckenthaler  Adrian  Schirmer  Mario  Gabriel  Thomas 《Grundwasser》2022,27(3):187-196
Grundwasser - Eine nachhaltige Wasserversorgung in urbanen Gebieten stellt aufgrund des Nutzungsdrucks sowie vielfältiger anthropogener Einträge eine große Herausforderung dar....  相似文献   
2.
Ni  Shuna  Gernay  Thomas 《Fire Technology》2022,58(5):2691-2725
Fire Technology - Estimation of design fires and thermal exposure conditions is an important step in structural fire engineering procedures. Mass timber, as a combustible material, may contribute...  相似文献   
3.
人体大脑和身体的发育,需要从食物中摄取均衡的营养物质。人类大脑是区分人类和其他动物的特征。食物中的必需脂肪酸是机体组织结构和功能的必要组成部分。Omega-6(O6)亚油酸(LA6)是皮肤组织的组成成分,且是炎症、血栓形成、免疫和其他信号分子的前体;Omega-3(O3)α-亚麻酸(ALA3),特别是其长链代谢产物——二十二碳六烯酸(DHA3),是大脑、视网膜和部分神经组织中的关键组分。从富含LA6脂肪酸(缺乏O3脂肪酸)的植物籽中提取出的廉价而优质油脂,是20世纪的西方国家食品工业生产的主要脂肪来源。在代谢通路中,高浓度的LA6脂肪酸可拮抗O3脂肪酸代谢,造成O3脂肪酸不足,因此,在给怀孕动物的饲料中,只提供富含LA6但缺乏O3脂肪酸的油脂作为唯一的脂肪来源,会导致幼崽大脑发育不良。过去20~30年的研究表明,低含量LA6且含DHA3的油脂可改善大脑的功能。近年来的研究较多集中在营养因素对大脑发育的影响,最新研究数据表明,脂肪酸平衡对营养不良儿童的大脑发育尤为重要。世界卫生组织(WHO)越来越重视大脑的营养健康,通过其下属的食品法典委员会,建议用于治疗严重急性营养不良儿童的即食治疗食品中,使用含有均衡脂肪酸组成/构成的脂肪。同样,脂肪酸均衡对老年人可能也很重要。目前,业界已经有了调整油脂成分的方法,以确保脂肪酸均衡,从而维持人体整个生命周期的大脑健康。  相似文献   
4.
Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential.  相似文献   
5.
This study describes the first binding assay for glycine transporter 2 (GlyT2) following the concept of MS Binding Assays. The selective GlyT2 inhibitor Org25543 was employed as a reporter ligand and it was quantified with a highly sensitive and rapid LC-ESI-MS/MS method. Binding of Org25543 at GlyT2 was characterized in kinetic and saturation experiments with an off-rate of 7.07×10−3 s−1, an on-rate of 1.01×106 M−1 s−1, and an equilibrium dissociation constant of 7.45 nM. Furthermore, the inhibitory constants of 19 GlyT ligands were determined in competition experiments. The validity of the GlyT2 affinities determined with the binding assay was examined by a comparison with published inhibitory potencies from various functional assays. With the capability for affinity determination towards GlyT2 the developed MS Binding Assays provide the first tool for affinity profiling of potential ligands and it represents a valuable new alternative to functional assays addressing GlyT2.  相似文献   
6.
A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.  相似文献   
7.
Silica gel or zeolites AlPO-5 and SAPO-34 are recommended as adsorbents in water-driven heat pumps because of their selective water uptake. Secondary energy, like solar energy, can be used for regeneration of loaded adsorbers. In case of the availability of only low energy levels, the use of dealuminated Y zeolite (DAY) is the better choice because of the infinitely variation of its hydrophilic properties by tailoring of the framework Si/Al ratio. Actual data on the hydrothermal stability of DAY are lacking. Thus, we report on the long-term behavior of DAY zeolites with different Si/Al ratios.  相似文献   
8.
An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2Mal, has been synthesized and studied for in vivo 64Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [64Cu]Cu-GluCAB-2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64Cu]Cu-GluCAB-2Mal and previous-generation [64Cu]Cu-GluCAB-1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64Cu]Cu-GluCAB-2Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [64Cu]Cu-Glu-CAB-2Mal.  相似文献   
9.
CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.  相似文献   
10.
In the last eight decades, considerable modelling and computational efforts have been made to predict the strain rate during cutting with the aim of optimizing machining processes. However, the validation of these modelling approaches on a local scale remains excessively limited due to the lack of in-situ measurements and the faulty existing quick-stop tests. This work presents the in-process analysis of the strain rate and strain in the primary shear zone using high speed Digital Image Correlation (DIC) techniques. The comparison of measured and computed results shows the suitability of the DIC techniques and the robustness of the modelling approaches.  相似文献   
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