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71.
MOTIVATION: Several kernel-based methods have been recently introduced for the classification of small molecules. Most available kernels on molecules are based on 2D representations obtained from chemical structures, but far less work has focused so far on the definition of effective kernels that can also exploit 3D information. RESULTS: We introduce new ideas for building kernels on small molecules that can effectively use and combine 2D and 3D information. We tested these kernels in conjunction with support vector machines for binary classification on the 60 NCI cancer screening datasets as well as on the NCI HIV data set. Our results show that 3D information leveraged by these kernels can consistently improve prediction accuracy in all datasets. AVAILABILITY: An implementation of the small molecule classifier is available from http://www.dsi.unifi.it/neural/src/3DDK. 相似文献
72.
Claudio Milanesi Franco Baldi Sara Borin Lorenzo Brusetti Fabrizio Ciampolini Fabrizio Iacopini Mauro Cresti 《International biodeterioration & biodegradation》2009,63(7):844-850
Painted surfaces in the Chapel of the Holy Nail in the medieval ex-hospital of Siena show five areas of oxidation and blackening. Most were treated with Paraloid B72 acrylic resin 40 years ago. To study deterioration of the painted surfaces by scanning microscopy with X-ray dispersion microanalysis, fragments obtained from the five areas were analyzed directly and after hydration. Hydrated fragments treated with Paraloid showed a compact, shiny, impermeable surface. The acrylic resin forms a layer that inhibits interaction of the painting with the environment, including transpiration and gaseous exchange. Element composition of paint layers of different colours revealed gold, iron (oxides in ochre) and lead (oxide) tempered with lime and/or gypsum. A few microbial cells were found on all fragments. To study biological deterioration in the five areas, fragments were hydrated and incubated in minimal culture medium without added carbon source to select bacteria capable of using carbon sources in the medieval fresco. Analysis did not reveal any spores or hyphae, and excluded physical and mechanical damage. Bacteria of the genus Bacillus were isolated only from untreated samples. Paraloid resin forms an inert film over the mural, preventing access to microbes able to use nutrient sources in the painted layer. The screening of 16S rRNA libraries from enrichment cultures showed wide phylogenetic diversity. Forty-four percent of the clones retrieved from the clone library were affiliated with the order Firmicutes, confirming the prevalence of aerobic spore-formers among the colonizing microflora. Firmicutes therefore presumably produced extracellular material which made water available to other bacteria which may have converted thiosulphate in the medieval tempera to sulphur globules. Sulphur is a known oxidant of metallic pigments, in this case aluminium, which may explain the blackening of the untreated sample. 相似文献
73.
Land abandonment is causing woodland expansion and loss of open habitats in the Alps, coupled with a shift in forestry practices
from coppice management to high forest. Despite such rapid large-scale changes, there has been very little investigation of
the environmental predictors of biodiversity in the Alpine landscape. We assessed the richness of amphibians, reptiles and
breeding birds (n = 189 species), used as a surrogate of biodiversity, in 58 quadrats of 100 km2, located within a well surveyed area of the province of Trento (central-eastern Italian Alps). The surrogates were then related
to a series of environmental variables by means of stepwise multiple regression. Depending on the surrogate analysed, species
richness declined linearly or quadratically with elevation, and increased with habitat heterogeneity and the availability
of grassland and arid-rocky habitats. The same results were obtained when incorporating a measure of species threat into the
biodiversity estimates. Different surrogates were positively inter-correlated, probably because of a common response to the
same factor, namely elevation, which was the only variable to enter all models. Such elevational gradient produced a clear
biodiversity peak in low-elevation areas, generating potential conflict between efficient biodiversity conservation and economic
interests linked to human development, a scenario which probably applies to many mountain regions worldwide. The current network
of protected areas was quite satisfactory in terms of area covered but biased towards high-elevation areas, of high scenic
beauty but relatively low in animal biodiversity value. Low-elevation reserves were small and isolated. Proposed conservation
targets include the establishment of corridors increasing the connectivity of low-elevation reserves and the promotion of
incentives for the extensive management of grassland, an agro-ecosystem of high historical and biological value. 相似文献
74.
Paul R. J. Ames Tommaso Bucci Mira Merashli Marta Amaral Alessia Arcaro Fabrizio Gentile 《Free radical research》2013,47(10):1063-1082
AbstractSystemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future. 相似文献
75.
Ian P. Holmes Richard J. Blunt Olivier E. Lorthioir Stephen M. Blowers Andy Gribble Andrew H. Payne Ian G. Stansfield Martyn Wood Patrick M. Woollard Charlie Reavill Claire M. Howes Fabrizio Micheli Romano Di Fabio Daniele Donati Silvia Terreni Dieter Hamprecht Luca Arista Angela Worby Steve P. Watson 《Bioorganic & medicinal chemistry letters》2010,20(6):2013-2016
The identification of a highly selective D2 partial agonist, D3 antagonist tool molecule which demonstrates high levels of brain exposure and selectivity against an extensive range of dopamine, serotonin, adrenergic, histamine, and muscarinic receptors is described. 相似文献
76.
77.
Bismuto E Nucci R Febbraio F Tanfani F Gentile F Briante R Scirè A Bertoli E Amodeo P 《European biophysics journal : EBJ》2004,33(1):38-49
The perturbation induced by mono- and divalent cations on the thermophilicity and thermostability of Solfolobus solfataricus -glycosidase, a hyperthermophilic tetrameric enzyme, has been investigated by spectroscopic and computational simulation methods to ascertain the Hofmeister effects on two strategic protein regions identified previously. Specifically, (1) an extra segment (83–124), present only in the sequence of hyperthermophilic glycosidases and recognized as an important thermostability determinant for the enzyme structure; and (2) a restricted area of the subunit interface responsible for the quaternary structure maintenance. Mono- and divalent cations inhibit to a different extent the -glycosidase activity, whose kinetic constants show an apparent competitive inhibition of the catalytic process that reflects the Hofmeister order. The thermostability is also affected by the nature and charge of the cations, reaching maximal effects for the case of Mg2+. Fourier transform infrared spectroscopy has revealed very small changes in the protein secondary structure in the presence of the investigated cations at 20 °C, while large effects on the protein melting temperatures are observed. Computational analysis of the enzyme structure has identified negative patches on the accessible surface of the two identified regions. Following the Hofmeister series, cations weaken the existing electrostatic network that links the extra segment to the remaining protein matrix. In particular, the perturbing action of cations could involve the ionic pair interactions E107–R245 and E109–R185, thus leading to a local destructuring of the extra segment as a possible starting event for thermal destabilization. A detailed investigation of the electrostatic network at the A–C intermolecular interface of Sgly after energy minimization suggests that cations could cause a strong attenuation of the ion pair interactions E474–K72 and D473–R402, with consequent partial dissociation of the tetrameric structure.Abbreviations Amide I
amide I band in a 2H2O medium
- EM
energy minimization
- ONPG
o-nitrophenyl--d-galactopyranoside
- Sgly
Escherichia coli expressed Sulfolobus solfataricus -glycosidase 相似文献
78.
The two-faced nature of protozoa allowed us to study the relationship between cell cycle and behaviour in Euplotes crassus; the former represents one of the most typical cellular traits, the latter is one of the most significant characteristics of an organism. Dividing cells of E. crassus were isolated on a slide and recorded for 11 h: the classic ethographic parameters were calculated every 60 min. The percentage of mobile cells went from 0-100% in the first 2.5 h. This value was maintained for 6.5 h, but from 9 h the value began to drop, reaching 0% at 11 h. The relative frequency of leftward arcs was very high in the first hour, the radius and length of the arcs increased from 1-7 h; velocity showed a similar trend, peaking at 7 h. All our results showed that the behaviour of this ciliate is heavily affected by its cell-division cycle. 相似文献
79.
Carnevali S Petruzzelli S Longoni B Vanacore R Barale R Cipollini M Scatena F Paggiaro P Celi A Giuntini C 《American journal of physiology. Lung cellular and molecular physiology》2003,284(6):L955-L963
Cigarette smoke is a mixture of chemicals having direct and/or indirect toxic effects on different lung cells. We investigated the effect of cigarette smoke on human lung fibroblasts (HFL-1) oxidation and apoptosis. Cells were exposed to various concentrations (1, 5, and 10%) of cigarette smoke extract (CSE) for 3 h, and oxidative stress and apoptosis were assessed by fluorescence-activated cell sorting and confocal laser fluorescence microscopy. Both oxidative stress and apoptosis exhibited a dose-response relationship with CSE concentrations. Lung fibroblasts also showed marked DNA fragmentation at the Comet assay after exposure to 10% CSE. Coincubation of HLF-1 cells with N-acetylcysteine (1 mM) during CSE exposure significantly reduced oxidative stress, apoptosis, and DNA fragmentation, whereas preincubation (3 h) with the glutathione-depleting agent buthionine sulfoximine (125 microM) produced a significant increase of oxidative stress. Cigarette smoke is a potent source of oxidative stress, DNA damage, and apoptosis for HFL-1 cells, and we speculate that this could contribute to the development of pulmonary emphysema in the lungs of smokers. 相似文献
80.