Statistical and machine learning approaches predict drug-to-target relationships from 2D small-molecule topology patterns. One might expect 3D information to improve these calculations. Here we apply ...the logic of the extended connectivity fingerprint (ECFP) to develop a rapid, alignment-invariant 3D representation of molecular conformers, the extended three-dimensional fingerprint (E3FP). By integrating E3FP with the similarity ensemble approach (SEA), we achieve higher precision-recall performance relative to SEA with ECFP on ChEMBL20 and equivalent receiver operating characteristic performance. We identify classes of molecules for which E3FP is a better predictor of similarity in bioactivity than is ECFP. Finally, we report novel drug-to-target binding predictions inaccessible by 2D fingerprints and confirm three of them experimentally with ligand efficiencies from 0.442–0.637 kcal/mol/heavy atom.
El artículo analiza la regulación jurídica de la calidad del agua en la provincia de Buenos Aires. La calidad del agua reviste un papel crítico por la incidencia que tiene en la salud de la población ...y las condiciones de vida digna. Su prestación mediante el servicio público es la forma más segura de acceso y reduce la explotación de los acuíferos por parte de particulares de forma directa. La selección de la provincia como caso de estudio se vincula con dos motivos: por un lado, la presencia de distintas empresas que prestan el servicio y un entramado que atraviesa regulaciones de la nación y la provincia; y, por otro, la jurisprudencia que ha tenido lugar a partir de demandas por la calidad. El trabajo hace un análisis de la normativa vigente a nivel nacional y provincial de forma comparada, y de los fallos jurisprudenciales relativos a la calidad del agua. El análisis permite observar las tensiones que se presentan por la adecuación de valores de elementos contaminantes a las recomendaciones de la Organización Mundial de la Salud y la relevancia que ha tenido el Poder Judicial en materia de reconocimiento del derecho humano al agua.
In plants, the oxidative cleavage of carotenoid substrates produces volatile apocarotenoids, including α-ionone, β-ionone, and dihydro-β-ionone, compounds that are important in herbivore-plant ...communication. For example, β-ionone is part of an induced defense in canola, Brassica napus, and is released following wounding by herbivores. The objectives of the research were to evaluate whether these volatile compounds would: 1) be released in higher quantities from plants through the over-expression of the carotenoid cleavage dioxygenase1 (CCD1) gene and 2) cause herbivores to be repelled or attracted to over-expressing plants relative to the wild-type. In vivo dynamic headspace collection of volatiles coupled with gas chromatography–mass spectrometry was used to determine volatile organic compounds (VOC) in the headspace of the Arabidopsis thaliana ecotype Columbia-0 (L.) over-expressing the AtCCD1 gene. The analytical method allowed the detection of β-ionone in the Arabidopsis headspace where emission rates ranged between 2 and 5-fold higher compared to the wild type, thus corroborating the in vivo enhancement of gene expression. A two chamber choice test between wild type and AtCCD1 plants revealed that crucifer flea beetle Phyllotreta cruciferae (Goeze) adults were repelled by the AtCCD1 plants with the highest transcription and β-ionone levels. α-Ionone and dihydro-β-ionone were not found in the headspace analysis, but solutions of the three compounds were tested in the concentration range of β-ionone found in the Arabidopsis headspace (0.05 to 0.5 ng/μl) in order to assess their biological activity with crucifer flea beetle, two spotted spider mite Tetranychus urticae (Koch), and silverleaf whiteflies Bemisia tabaci (Gennadius). Choice bioassays demonstrated that β-ionone has a strong repellent effect toward both the flea beetle and the spider mite, and significant oviposition deterrence to whiteflies. In contrast, dihydro-β-ionone had attractant properties, especially to the crucifer flea beetle, while α-ionone did not show any significant activity. These findings demonstrate how regulating genes of the carotenoid pathway can increase herbivore deterrent volatiles, a novel tool for insect pest management.
Despite the fact that the investigation of the structural and functional properties of hemoglobin dates back more than 150 years, the topic has not lost its relevance today. The most important ...component of these studies is the development of mathematical models that formalize and generalize the mechanisms determining the cooperative binding of ligands based on data on the structural and functional state of the protein. In this work, we review the mathematical relationships describing oxygen binding by hemoglobin, ranging from the classical Hüfner, Hill, and Adair equations to the Szabo-Karplus and tertiary two-state mathematical models based on the Monod-Wyman-Changeux and Koshland-Némethy-Filmer concepts. The generality of the considered equations as mathematical functions, bearing in their basis a power dependence, is demonstrated. The problems and possible solutions related to approximation of experimental data by the oxygenation equations with correlated fitting parameters are noted. Attention is paid to empirical equations, extended versions of the Hill equation, where the coefficient of cooperation is modulated by Gauss and Lorentz distributions as functions of partial oxygen pressure.
This Letter reports on a systematic study of β-decay half-lives of neutron-rich nuclei around doubly magic (208)Pb. The lifetimes of the 126-neutron shell isotone (204)Pt and the neighboring ...(200-202)Ir, (203)Pt, (204)Au are presented together with other 19 half-lives measured during the "stopped beam" campaign of the rare isotope investigations at GSI collaboration. The results constrain the main nuclear theories used in calculations of r-process nucleosynthesis. Predictions based on a statistical macroscopic description of the first-forbidden β strength reveal significant deviations for most of the nuclei with N<126. In contrast, theories including a fully microscopic treatment of allowed and first-forbidden transitions reproduce more satisfactorily the trend in the measured half-lives for the nuclei in this region, where the r-process pathway passes through during β decay back to stability.
There is solid observational evidence on the existence of massive, M ~ 1 M..., highly magnetized white dwarfs (WDs) with surface magnetic fields up to B ~ 10 super( 9) G. We show that, if in addition ...to these features, the star is fast rotating, it can become a rotation-powered pulsar-like WD and emit detectable high-energy radiation. We infer the values of the structure parameters (mass, radius, moment of inertia), magnetic field, rotation period and spin-down rates of a WD pulsar death-line. We show that WDs above the death-line emit blackbody radiation in the soft X-ray band via the magnetic polar cap heating by back flowing pair-created particle bombardment and discuss as an example the X-ray emission of soft gamma-repeaters and anomalous X-ray pulsars within the WD model. (ProQuest: ... denotes formulae/symbols omitted.)
Massive, highly magnetized white dwarfs with fields up to 10 super(9) G have been observed and theoretically used for the description of a variety of astrophysical phenomena. Ultramagnetized white ...dwarfs with uniform interior fields up to 10 super(18) G have been recently purported to obey a new maximum mass limit, M sub(max) approximately 2.58 M sub(middot in circle), which largely overcomes the traditional Chandrasekhar value, M sub(Ch) approximately 1.44 M sub(middot in circle). Such a larger limit would make these astrophysical objects viable candidates for the explanation of the superluminous population of Type Ia supernovae. We show that several macro and micro physical aspects such as gravitational, dynamical stability, breaking of spherical symmetry, general relativity, inverse beta decay, and pycnonuclear fusion reactions are of most relevance for the self-consistent description of the structure and assessment of stability of these objects. It is shown in this work that the first family of magnetized white dwarfs indeed satisfy all the criteria of stability, while the ultramagnetized white dwarfs are very unlikely to exist in nature since they violate minimal requests of stability. Therefore, the canonical Chandrasekhar mass limit of white dwarfs still has to be applied.
The metal content of 46 tea samples, including green, black, and instant teas, was analyzed. Al, Ba, Ca, Cu, Fe, K, Mg, Mn, Na, Sr, Ti, and Zn were determined by ICP−AES. Potassium, with an average ...content of 15145.4 mg kg-1 was the metal with major content. Calcium, magnesium, and aluminum had average contents of 4252.4, 1978.2, and 1074.0 mg kg-1, respectively. The average amount of manganese was 824.8 mg kg-1. There were no clear differences between the metal contents of green and black teas. Pattern recognition methods such as principal component analysis (PCA), linear discriminant analysis (LDA), and artificial neural networks (ANN), were applied to differentiate the tea types. LDA and ANN provided the best results in the classification of tea varieties. These chemometric procedures were also useful for distinguishing between Asian and African teas and between the geographical origin of different Asian teas. Keywords: Tea; Camellia sinensis; atomic spectroscopy; metals; chemometrics; pattern recognition; artificial neural networks
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•The dependence between the BC-surface condition and the α-Al2O3 phase formation.•Low-temperature α-Al2O3 formation in the pre-oxidation treatments.•Influence of the grit-blasting on ...the oxidation kinetics of β-(Ni, Pt)Al System.•In the grit-blasted samples, oxidation stable-state is reached less than 2 h.•Stifle the growth of metastable θ-Al2O3 and accelerate θ- to α-Al2O3 at > 1000 °C.
The effect of surface modification by grit-blasting of β-(Ni,Pt)Al bond coats on the growth of α-Al2O3 is here presented. Thermogravimetry tests at 1000 °C, 1050 °C, 1100 °C, and 1150 °C were performed on as-aluminized and as-grit-blasted specimens under the same oxygen partial pressure (pO2 = 2.1 × 10-1 atm), where the parabolic rate constant (kp) was calculated. The oxide phase fraction was obtained from the fitting of the photo-stimulated luminescence spectroscopy (PSLS) results. A strong dependence between the surface condition of the bond coat and the α-Al2O3 phase formation was observed. The thermally treated grit-blasted samples achieved faster the steady-state (1.6 h) of the thermal growth oxide (TGO), while a treatment 2.7 times longer (4.25 h) was required for the as-aluminized specimens. This result contributes to the general understanding of the effect of the surface condition on the TGO formation during pre-oxidation treatment to promote the growth of the α-Al2O3 phase at low temperature and less time without affecting the lifetime of thermal barrier coating systems.
Glyphosate (N-phosphonometylglycine) is widely used due to its broad spectrum of activity and nonselective mode of action. In Chile it is the most used herbicide, but its adsorption behavior in the ...abundant and widespread variable charge soils is not well understood. In this study, three volcanic ash-derived soils were selected, including Andisols (Nueva Braunau and Diguillin) and Ultisols (Collipulli), to evaluate the adsorption kinetics, equilibrium isotherms, and the effect of pH in glyphosate adsorption. The influence of glyphosate on soil phosphorus retention was also studied. Glyphosate was rapidly and strongly adsorbed on the selected soils, and adsorption isotherms were well described by the Freundlich relationship with strong nonlinearity (nfads < 0.5). The nfads values were consistently higher than nfdes values, suggesting strong hysteresis. Adsorption (Kads) increased strongly when pH decreased. The presence of glyphosate (3200 μg mL-1) changed the adsorption behavior of phosphate at its maximum adsorption capacity. Andisol soils without the addition of glyphosate had similar mean Kads values for Nueva Braunau (5.68) and Diguillin (7.38). Collipulli had a mean Kads value of 31.58. During the successive desorption steps, glyphosate at the highest level increased Kads values for phosphate in the Andisol soils but had little effect in the Ultisol soil. This different behavior was probably due to the irreversible occupation of some adsorption sites by glyphosate in the Ultisol soil attributed to the dominant Kaolinite mineral. Results from this study suggest that in the two types of volcanic soils, different mechanisms are involved in glyphosate and phosphate adsorption and that long-term use of glyphosate may impose different effects on the retention and availability of phosphorus. Volcanic ash-derived soils have a particular environmental behavior in relation to the retention of organic contaminants, representing an environmental substrate that may become highly polluted over time due to intensive agronomic uses.
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