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1.
Franois Ancien Fabrizio Pucci Marianne Rooman 《International journal of molecular sciences》2021,22(9)
Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality. 相似文献
2.
A Poblet S Andrade M Scagliola C Vodopivez A Curtosi A Pucci J Marcovecchio 《Canadian Metallurgical Quarterly》1997,207(2-3):187-194
Trace-metal contents were recorded for the epilithic antarctic lichens Usnea aurantiacoatra and U. antartica, sampled close to the Argentine scientific station 'Jubany' on '25 de Mayo' (King George) Island, in the Southern Shetland Archipelago (Antarctica). The corresponding heavy-metal levels have been measured through atomic absorption spectrophotometry, following internationally accepted analytical methods. The results obtained support the hypothesis that an atmospheric circulation of trace metals exists on the assessed area, and the activities developed at the different scientific stations located on this island would be a potential source of heavy metals to the evaluated environment. The geographical distribution of trace metals atmospherically transported in the area close to 'Jubany Station' was studied through the corresponding metal contents of the assessed lichens. Finally, the suitability of both analyzed lichen species, Usnea aurantiacoatra and U. antartica, as biological indicators for quantitative monitoring of airborne metals for this antarctic environment was recognized. 相似文献
3.
Köhler K Lellouch AC Vollmer S Stoevesandt O Hoff A Peters L Rogl H Malissen B Brock R 《Chembiochem : a European journal of chemical biology》2005,6(1):152-161
Cellular signal transduction proceeds through a complex network of molecular interactions and enzymatic activities. The timing of these molecular events is critical for the propagation of a signal and the generation of a specific cellular response. To define the timing of signalling events, we introduce the combination of high-resolution confocal microscopy with the application of small-molecule inhibitors at various stages of signal transduction in T cells. Inhibitors of Src-family tyrosine kinases and actin dynamics were employed to dissect the role of the lymphocyte-specific tyrosine kinase Lck in the formation and maintenance of T cell receptor/CD3-dependent contacts. Anti-CD3epsilon-coated coverslips served as a highly defined stimulus. The kinetics of the recruitment of the yellow fluorescent protein-tagged signalling protein ZAP-70 were detected by high-resolution confocal microscopy. The analysis revealed that at 5 min after receptor engagement, Lck activity was required for maintenance of contacts. In contrast, after 20 min of receptor engagement, the contacts were Lck-independent. The relevance of the timing of inhibitor application provides a pharmacological concept for the maturation of T cell-substrate contacts. 相似文献
4.
The Alder ene functionalization reaction of double bonds containing macromolecules such as polyisobutene oligomer (PIB) and a styrene-butadiene-styrene triblock copolymer (SBS) samples with maleic anhydride (MAH) or diethyl maleate (DEM) as enophiles is described. The analysis of the products by means of different techniques assesses the addition of the polar molecules to the reactive vinylidene units of the polymer with functional degrees (FD) depending on the type of enophile and polymer reactivity. The role of the reaction conditions and the use as Lewis acids as catalysts are discussed in terms of their influence on the addition reaction extent and on the polymer molecular weight. 相似文献
5.
MODIS Collection 5 global land cover: Algorithm refinements and characterization of new datasets 总被引:28,自引:0,他引:28
Mark A. Friedl Damien Sulla-Menashe Annemarie Schneider Adam Sibley 《Remote sensing of environment》2010,114(1):168-182
Information related to land cover is immensely important to global change science. In the past decade, data sources and methodologies for creating global land cover maps from remote sensing have evolved rapidly. Here we describe the datasets and algorithms used to create the Collection 5 MODIS Global Land Cover Type product, which is substantially changed relative to Collection 4. In addition to using updated input data, the algorithm and ancillary datasets used to produce the product have been refined. Most importantly, the Collection 5 product is generated at 500-m spatial resolution, providing a four-fold increase in spatial resolution relative to the previous version. In addition, many components of the classification algorithm have been changed. The training site database has been revised, land surface temperature is now included as an input feature, and ancillary datasets used in post-processing of ensemble decision tree results have been updated. Further, methods used to correct classifier results for bias imposed by training data properties have been refined, techniques used to fuse ancillary data based on spatially varying prior probabilities have been revised, and a variety of methods have been developed to address limitations of the algorithm for the urban, wetland, and deciduous needleleaf classes. Finally, techniques used to stabilize classification results across years have been developed and implemented to reduce year-to-year variation in land cover labels not associated with land cover change. Results from a cross-validation analysis indicate that the overall accuracy of the product is about 75% correctly classified, but that the range in class-specific accuracies is large. Comparison of Collection 5 maps with Collection 4 results show substantial differences arising from increased spatial resolution and changes in the input data and classification algorithm. 相似文献
6.
We explored the impact of professional experience and personality on police officers’ shooting performance under pressure. We recruited: (1) regular officers, (2) officers wanting to join a specialised arrest unit (AU) (expected to possess more stress-resistant traits; pre-AU) and (3) officers from this unit (expected to also possess more professional experience; AU) (all male). In Phase 1, we determined personality traits and experience. In Phase 2, state anxiety, shot accuracy, decision-making (shoot/don’t shoot), movement speed and gaze behaviour were measured while officers performed a shooting test under low and high pressure. Results indicate minimal differences in personality among groups and superior performance of AU officers. Regression analyses showed that state anxiety and shooting performance under high pressure were first predicted by AU experience and second by certain personality traits. Results suggest that although personality traits attenuate the impact of high pressure, it is relevant experience that secures effective performance under pressure.
Practitioner Summary: To obtain information for police selection and training purposes, we let officers who differed in personality and experience execute a shooting test under low and high pressure. Outcomes indicate that experience affected anxiety and performance most strongly, while personality traits of thrill- and adventure-seeking and self-control also had an effect. 相似文献
7.
We study the complexity of routing a set of messages with multiple destinations (multicast routing) on an n-node square mesh under the store-and-forward model. A standard argument proves that
time is required to route n messages, where each message is generated by a distinct node and at most c messages are to be delivered to any individual node. The obvious approach of simply replicating each message into the appropriate
number of unicast (single-destination) messages and routing these independently does not yield an optimal algorithm. We provide
both randomized and deterministic algorithms for multicast routing, which use constant-size buffers at each node. The randomized
algorithm attains optimal performance, while the deterministic algorithm is slower by a factor of O( log 2
n). We also describe an optimal deterministic algorithm that, however, requires large buffers of size O(c).
A preliminary version of this paper appeared in Proceedings of the 13th Annual ACM Symposium on Parallel Algorithms and Architectures,
Crete, Greece, 2001. This work was supported, in part, by MIUR under project ALGO-NEXT. 相似文献
8.
Diana Nanova Sebastian Beck Andreas Fuchs Tobias Glaser Christian Lennartz Wolfgang Kowalsky Annemarie Pucci Michael Kroeger 《Organic Electronics》2012,13(7):1237-1244
The degree of charge transfer in thin films of organic charge transfer (CT)-complexes, which are deposited via thermal evaporation, is examined via infrared-spectroscopy. We demonstrate a linear relationship between the shift in the excitation energy of the CN-stretching mode of CT-complexes with the acceptor 7,7,8,8-tetracyanoquinodimethane (TCNQ) and the charge transfer. The measured correlation corresponds very well with DFT calculations. For Na-TCNQ we observe a splitting in the peak of the CN-stretching mode, which can be explained by the coupling of two modes and was confirmed by the calculations. In CT-complexes with partial charge transfer the appearance of an electronic excitation is demonstrated. 相似文献
9.
10.
Variation in household CO2 emissions between and within countries may have important consequences for the equity dimension of climate policies. In this study we aim to identify some determinants of national household CO2 emissions and their distribution across income groups. For that purpose, we quantify the CO2 emissions of households in the Netherlands, UK, Sweden and Norway around the year 2000 by combining a hybrid approach of process analysis and input–output analysis with data on household expenditures. Our results show that average households in the Netherlands and the UK give rise to higher amounts of CO2 emissions than households in Sweden and Norway. Moreover, CO2 emission intensities of household consumption decrease with increasing income in the Netherlands and the UK, whereas they increase in Sweden and Norway. A comparison of the national results at the product level points out that country characteristics, like energy supply, population density and the availability of district heating, influence variation in household CO2 emissions between and within countries. 相似文献