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91.

In the 1870s, Carl Neumann proposed the so-called method of the arithmetic mean for solving the Dirichlet problem on convex domains. Neumann’s approach was considered at the time to be a reliable existence proof, following Weierstrass’s criticism of the Dirichlet principle. However, in 1937 H. Lebesgue pointed out a serious gap in Neumann’s proof. Curiously, the erroneous argument once again involved confusion between the notions of infimum and minimum. The objective of this paper is to show that Lebesgue’s sharp criticism of Neumann’s proof was only partially justified.

  相似文献   
92.
Automated negotiation mechanisms can be helpful in contexts where users want to reach mutually satisfactory agreements about issues of shared interest, especially for complex problems with many interdependent issues. A variety of automated negotiation mechanisms have been proposed in the literature. The effectiveness of those mechanisms, however, may depend on the characteristics of the underlying negotiation problem (e.g. on the complexity of participant’s utility functions, as well as the degree of conflict between participants). While one mechanism may be a good choice for a negotiation problem, it may be a poor choice for another. In this paper, we pursue the problem of selecting the most effective negotiation mechanism given a particular problem by (1) defining a set of scenario metrics to capture the relevant features of negotiation problems, (2) evaluating the performance of a range of negotiation mechanisms on a diverse test suite of negotiation scenarios, (3) applying machine learning techniques to identify which mechanisms work best with which scenarios, and (4) demonstrating that using these classification rules for mechanism selection enables significantly better negotiation performance than any single mechanism alone.  相似文献   
93.
Platelet extracellular vesicles (PEVs) have emerged as potential mediators in intercellular communication. PEVs exhibit several activities with pathophysiological importance and may serve as diagnostic biomarkers. Here, imaging and analytical techniques were employed to unveil morphological pathways of the release, structure, composition, and surface properties of PEVs derived from human platelets (PLTs) activated with the thrombin receptor activating peptide (TRAP). Based on extensive electron microscopy analysis, we propose four morphological pathways for PEVs release from TRAP-activated PLTs: (1) plasma membrane budding, (2) extrusion of multivesicular α-granules and cytoplasmic vacuoles, (3) plasma membrane blistering and (4) “pearling” of PLT pseudopodia. The PLT extracellular vesiculome encompasses ectosomes, exosomes, free mitochondria, mitochondria-containing vesicles, “podiasomes” and PLT “ghosts”. Interestingly, a flow cytometry showed a population of TOM20+LC3+ PEVs, likely products of platelet mitophagy. We found that lipidomic and proteomic profiles were different between the small PEV (S-PEVs; mean diameter 103 nm) and the large vesicle (L-PEVs; mean diameter 350 nm) fractions separated by differential centrifugation. In addition, the majority of PEVs released by activated PLTs was composed of S-PEVs which have markedly higher thrombin generation activity per unit of PEV surface area compared to L-PEVs, and contribute approximately 60% of the PLT vesiculome procoagulant potency.  相似文献   
94.
I present an update on the taxonomy of the filistatid genera Wandella Gray and Yardiella Gray, both endemic to Australia. Two new species are described: Wandella grayi sp. nov., known from Queensland, and Wandella infernalis sp. nov., known from a single cave in Western Australia. The male of Wandella australiensis (L. Koch) and the females of Wandella stuartensis Gray and Wandella waldockae Gray are described and illustrated for the first time. New records are given for these and other species of Australian filistatids, including the first epigeal records of Yardiella humphreysi Gray, a species so far known only from caves. Updated distribution maps are presented. Additionally, I present novel morphological data for Wandella using light and scanning electron microscopy. The cephalothorax, spinning organs, genitalia and appendages of some species are illustrated in detail. I report the presence of a putative claw extensor muscle in the male palpal cymbium, and describe interesting modifications in the clypeal region of adult males. The phylogenetic significance of these characters is briefly discussed.  相似文献   
95.
96.
The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase   总被引:1,自引:0,他引:1  
Slade D  Dunstan MS  Barkauskaite E  Weston R  Lafite P  Dixon N  Ahel M  Leys D  Ahel I 《Nature》2011,477(7366):616-620
Post-translational modification of proteins by poly(ADP-ribosyl)ation regulates many cellular pathways that are critical for genome stability, including DNA repair, chromatin structure, mitosis and apoptosis. Poly(ADP-ribose) (PAR) is composed of repeating ADP-ribose units linked via a unique glycosidic ribose-ribose bond, and is synthesized from NAD by PAR polymerases. PAR glycohydrolase (PARG) is the only protein capable of specific hydrolysis of the ribose-ribose bonds present in PAR chains; its deficiency leads to cell death. Here we show that filamentous fungi and a number of bacteria possess a divergent form of PARG that has all the main characteristics of the human PARG enzyme. We present the first PARG crystal structure (derived from the bacterium Thermomonospora curvata), which reveals that the PARG catalytic domain is a distant member of the ubiquitous ADP-ribose-binding macrodomain family. High-resolution structures of T. curvata PARG in complexes with ADP-ribose and the PARG inhibitor ADP-HPD, complemented by biochemical studies, allow us to propose a model for PAR binding and catalysis by PARG. The insights into the PARG structure and catalytic mechanism should greatly improve our understanding of how PARG activity controls reversible protein poly(ADP-ribosyl)ation and potentially of how the defects in this regulation are linked to human disease.  相似文献   
97.
98.
Introduction  ThemajorgoaloftheHongKongInstituteofEduca tion (HKIEd)Libraryistoprovidethebestservicestoli braryusersseamlesslyandefficiently.Sinceitsinception ,theHKIEdLibraryhasadoptedaninnovativedigitalli braryapproachtobuildupitsservicesandresources.Foralmostadecade,theHKIEdLibraryhasbeendevelopingitsmulti facetlibraryservicesarounditscoredigitalli brarycomponentsoftheINNOPACIntegratedLibrarySys tem ,LibraryWebsite,electronicresourcesfromvendors,andin housedevelopedknowledgeba…  相似文献   
99.
Soukup V  Epperlein HH  Horácek I  Cerny R 《Nature》2008,455(7214):795-798
The oral cavity of vertebrates is generally thought to arise as an ectodermal invagination. Consistent with this, oral teeth are proposed to arise exclusively from ectoderm, contributing to tooth enamel epithelium, and from neural crest derived mesenchyme, contributing to dentin and pulp. Yet in many vertebrate groups, teeth are not restricted only to the oral cavity, but extend posteriorly as pharyngeal teeth that could be derived either directly from the endodermal epithelium, or from the ectodermal epithelium that reached this location through the mouth or through the pharyngeal slits. However, when the oropharyngeal membrane, which forms a sharp ecto/endodermal border, is broken, the fate of these cells is poorly known. Here, using transgenic axolotls with a combination of fate-mapping approaches, we present reliable evidence of oral teeth derived from both the ectoderm and endoderm and, moreover, demonstrate teeth with a mixed ecto/endodermal origin. Despite the enamel epithelia having a different embryonic source, oral teeth in the axolotl display striking developmental uniformities and are otherwise identical. This suggests a dominant role for the neural crest mesenchyme over epithelia in tooth initiation and, from an evolutionary point of view, that an essential factor in teeth evolution was the odontogenic capacity of neural crest cells, regardless of possible 'outside-in' or 'inside-out' influx of the epithelium.  相似文献   
100.
Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.  相似文献   
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