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141.
Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.  相似文献   
142.
This paper considers the state‐dependent interference relay channel (SIRC) in which one of the two users may operate as a secondary user and the relay has a noncausal access to the signals from both users. For discrete memoryless SIRC, we first establish the achievable rate region by carefully merging Han‐Kobayashi rate splitting encoding technique, superposition encoding, and Gelfand‐Pinsker encoding technique. Then, based on the achievable rate region that we derive, the capacity of the SIRC is established in many different scenarios including (a) the weak interference regime, (b) the strong interference regime, and (c) the very strong interference regime. This means that our capacity results contain all available known results in the literature. Next, the achievable rate region and the associated capacity results are also evaluated in the case of additive Gaussian noise. Additionally, many numerical examples are investigated to show the value of our theoretical derivations.  相似文献   
143.
The ‐centroid problem or leader–follower problem is generalized considering different customer choice rules where a customer may use facilities belonging to different firms, if the difference in travel distance (or time) is small enough. Assuming essential goods, some particular customer choice rules are analyzed. Linear programming formulations for the generalized ‐medianoid and ‐centroid problems are presented and an exact solution approach is applied. Some computational examples are included.  相似文献   
144.
A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.  相似文献   
145.
When solving a mathematical problem, students who do not have sufficient conceptual understanding may perform poorly and exhibit misconceptions. This study was aimed to examine students' conceptual understanding and significant misconceptions when solving number sense‐related problems. An online three‐tier diagnostic test was administered to 125 fifth‐grade students with varied socio‐economic backgrounds in Hong Kong. Only 14.40% of the students exhibited high performance with high confidence, indicating that these students had a profound conceptual understanding of number sense. In addition, the majority of the students (66.40%) did not demonstrate number sense; these students exhibited several significant misconceptions and could solve the questions only by using a rule‐based method or guessing. Accordingly, most students performed unsatisfactorily on number sense‐related problems. This study is imperative in identifying early predictors and provides information for further compatible interventions in the teaching and learning of number sense in Hong Kong in particular and worldwide in general.  相似文献   
146.
147.
Lithium‐rich disordered rock‐salt oxides have attracted great interest owing to their promising performance as Li‐ion battery cathodes. While experimental and theoretical efforts are critical in advancing this class of materials, a fundamental understanding of key property changes upon Li extraction is largely missing. In the present study, single‐crystal synthesis of a new disordered rock‐salt cathode material, Li1.3Ta0.3Mn0.4O2 (LTMO), and its use as a model compound to investigate Li concentration–driven evolution of local cationic ordering, charge compensation, and chemical distribution are reported. Through the combined use of 2D and 3D X‐ray nanotomography, it is shown that Li removal accompanied by oxygen oxidation is correlated with the development of morphological defects such as particle cracking. Chemical heterogeneity, quantified by subparticle level distribution of Mn valence state, is minimal during Mn redox, which drastically increases upon the formation of cracks during oxygen redox. Density functional theory and bond valence sum mismatch calculations reveal the presence of local short‐range ordering in the pristine oxide, which gradually disappears along with the extraction of Li. The study suggests that with cycling the transformation into true cation–disordered state can be expected, which likely impacts the voltage profile and obtainable energy density of the oxide cathodes.  相似文献   
148.
High Temperature - Experimental findings suggest that a strongly ionized, arc He plasma of atmospheric pressure does not exist in the state of the local thermodynamic equilibrium (LTE) expected for...  相似文献   
149.
Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions.  相似文献   
150.
Lipoxins (LXs) are autacoids, specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)–metabolites, which direct potent cellular responses to resolve inflammation and restore tissue homeostasis. Together, these SPM activities have been intensely studied in systemic inflammation and acute injury or infection, but less is known about LX signaling and activities in the central nervous system. LXs are derived from arachidonic acid, an omega‐6 PUFA. In addition to well‐established roles in systemic inflammation resolution, they have increasingly become implicated in regulating neuroinflammatory and neurodegenerative processes. In particular, chronic inflammation plays a central role in Alzheimer's disease (AD) etiology, and dysregulated LX production and activities have been reported in a variety of AD rodent models and clinical tissue samples, yet with complex and sometimes conflicting results. In addition, reduced LX production following retinal injury has been reported recently by the authors, and an intriguing direct neuronal activity promoting survival and homeostasis in retinal and cortical neurons is demonstrated. Here, the authors review and clarify this growing literature and suggest new research directions to further elaborate the role of lipoxins in neurodegeneration.  相似文献   
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