Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Does High Unemployment Rate Result in a High Divorce Rate?: A Test for Japan.

El objetivo de este artículo es determinar si el incremento en la tasa de desempleo tiene algún efecto sobre la tasa de divorcios. Con este fin se utilizan series de tiempo y datos de corte transversal para Japón. También se incluyen la tasa de crimenes y el promedio de las horas trabajadas como variables explicativas. Adicionalmente se efectúa análisis de cointegración con el fin de evitar relaciones espúreas entre las series de tiempo. Los resultados sugieren que existe una correlación positiva entre la tasa de desempleo y la tasa de divorcios. También confirmamos que existe una relación cronológica cercana entre el desempleo y el divorcio.

Determination of the direct band-gap energy of InAlAs matched to InP by photoluminescence excitation spectroscopy

A series of InxAl1-xAs samples (0.51≪x≪0.55)coherently grown on InP was studied in order to measure the band-gap energy of the lattice matched composition. As the substrate is opaque to the relevant photon energies, a method is developed to calculate the optical absorption coefficient from the photoluminescence excitation spectra. The effect of strain on the band-gap energy has been taken into account. For x=0.532, at 14 K we have obtained Eg0=1549±6 meV

UV index measurement and model agreement: uncertainties and limitations

En les últimes dècades, l'increment dels nivells de radiació solar ultraviolada (UVR) que arriba a la Terra (principalment degut a la disminució d'ozó estratosfèric) juntament amb l'augment detectat en malalties relacionades amb l'exposició a la UVR, ha portat a un gran volum d'investigacions sobre la radiació solar en aquesta banda i els seus efectes en els humans. L'índex ultraviolat (UVI), que ha estat adoptat internacionalment, va ser definit amb el propòsit d'informar al públic general sobre els riscos d'exposar el cos nu a la UVR i per tal d'enviar missatges preventius. L'UVI es va definir inicialment com el valor màxim diari. No obstant, el seu ús actual s'ha ampliat i té sentit referir-se a un valor instantani o a una evolució diària del valor d'UVI mesurat, modelitzat o predit. El valor concret d'UVI està afectat per la geometria Sol-Terra, els núvols, l'ozó, els aerosols, l'altitud i l'albedo superficial. Les mesures d'UVI d'alta qualitat són essencials com a referència i per estudiar tendències a llarg termini; es necessiten també tècniques acurades de modelització per tal d'entendre els factors que afecten la UVR, per predir l'UVI i com a control de qualitat de les mesures. És d'esperar que les mesures més acurades d'UVI s'obtinguin amb espectroradiòmetres. No obstant, com que els costs d'aquests dispositius són elevats, és més habitual trobar dades d'UVI de radiòmetres eritemàtics (de fet, la majoria de les xarxes d'UVI estan equipades amb aquest tipus de sensors). Els millors resultats en modelització s'obtenen amb models de transferència radiativa de dispersió múltiple quan es coneix bé la informació d'entrada. No obstant, habitualment no es coneix informació d'entrada, com per exemple les propietats òptiques dels aerosols, la qual cosa pot portar a importants incerteses en la modelització. Sovint, s'utilitzen models més simples per aplicacions com ara la predicció d'UVI o l'elaboració de mapes d'UVI, ja que aquests són més ràpids i requereixen menys paràmetres d'entrada. Tenint en compte aquest marc de treball, l'objectiu general d'aquest estudi és analitzar l'acord al qual es pot arribar entre la mesura i la modelització d'UVI per condicions de cel sense núvols. D'aquesta manera, en aquest estudi es presenten comparacions model-mesura per diferents tècniques de modelització, diferents opcions d'entrada i per mesures d'UVI tant de radiòmetres eritemàtics com d'espectroradiòmeters. Com a conclusió general, es pot afirmar que la comparació model-mesura és molt útil per detectar limitacions i estimar incerteses tant en les modelitzacions com en les mesures. Pel que fa a la modelització, les principals limitacions que s'han trobat és la falta de coneixement de la informació d'aerosols considerada com a entrada dels models. També, s'han trobat importants diferències entre l'ozó mesurat des de satèl·lit i des de la superfície terrestre, la qual cosa pot portar a diferències importants en l'UVI modelitzat. PTUV, una nova i simple parametrització pel càlcul ràpid d'UVI per condicions de cel serens, ha estat desenvolupada en base a càlculs de transferència radiativa. La parametrització mostra una bona execució tant respecte el model base com en comparació amb diverses mesures d'UVI. PTUV ha demostrat la seva utilitat per aplicacions particulars com ara l'estudi de l'evolució anual de l'UVI per un cert lloc (Girona) i la composició de mapes d'alta resolució de valors d'UVI típics per un territori concret (Catalunya). En relació a les mesures, es constata que és molt important saber la resposta espectral dels radiòmetres eritemàtics per tal d'evitar grans incerteses a la mesura d'UVI. Aquest instruments, si estan ben caracteritzats, mostren una bona comparació amb els espectroradiòmetres d'alta qualitat en la mesura d'UVI. Les qüestions més importants respecte les mesures són la calibració i estabilitat a llarg termini. També, s'ha observat un efecte de temperatura en el PTFE, un material utilitzat en els difusors en alguns instruments, cosa que potencialment podria tenir implicacions importants en el camp experimental. Finalment, i pel que fa a les comparacions model-mesura, el millor acord s'ha trobat quan es consideren mesures d'UVI d'espectroradiòmetres d'alta qualitat i s'usen models de transferència radiativa que consideren les millors dades disponibles pel que fa als paràmetres òptics d'ozó i aerosols i els seus canvis en el temps. D'aquesta manera, l'acord pot ser tan alt dins un 0.1º% en UVI, i típicament entre menys d'un 3%. Aquest acord es veu altament deteriorat si s'ignora la informació d'aerosols i depèn de manera important del valor d'albedo de dispersió simple dels aerosols. Altres dades d'entrada del model, com ara l'albedo superficial i els perfils d'ozó i temperatura introdueixen una incertesa menor en els resultats de modelització.

Uncertainties in annual riverine phosphorus load estimation: Impact of load estimation methodology, sampling frequency, baseflow index and catchment population density

Models developed to identify the rates and origins of nutrient export from land to stream require an accurate assessment of the nutrient load present in the water body in order to calibrate model parameters and structure. These data are rarely available at a representative scale and in an appropriate chemical form except in research catchments. Observational errors associated with nutrient load estimates based on these data lead to a high degree of uncertainty in modelling and nutrient budgeting studies. Here, daily paired instantaneous P and flow data for 17 UK research catchments covering a total of 39 water years (WY) have been used to explore the nature and extent of the observational error associated with nutrient flux estimates based on partial fractions and infrequent sampling. The daily records were artificially decimated to create 7 stratified sampling records, 7 weekly records, and 30 monthly records from each WY and catchment. These were used to evaluate the impact of sampling frequency on load estimate uncertainty. The analysis underlines the high uncertainty of load estimates based on monthly data and individual P fractions rather than total P. Catchments with a high baseflow index and/or low population density were found to return a lower RMSE on load estimates when sampled infrequently than those with a tow baseflow index and high population density. Catchment size was not shown to be important, though a limitation of this study is that daily records may fail to capture the full range of P export behaviour in smaller catchments with flashy hydrographs, leading to an underestimate of uncertainty in Load estimates for such catchments. Further analysis of sub-daily records is needed to investigate this fully. Here, recommendations are given on load estimation methodologies for different catchment types sampled at different frequencies, and the ways in which this analysis can be used to identify observational error and uncertainty for model calibration and nutrient budgeting studies. (c) 2006 Elsevier B.V. All rights reserved.

For better or for worse, till the human development index do us part?

This paper describes the results of research intended to explore the volatility inherent in the United Nations Development Programme's (UNDP) Human Development Index (HDI). The HDI is intended to be a simple and transparent device for comparing progress in human development, and is an aggregate of life expectancy, education and GDP per capita. Values of the HDI for each country are presented in the Human Development Reports (HDRs), the first being published in 1990. However, while the methodology is consistent for all countries in each year there are notable differences between years that make temporal comparisons of progress difficult. The paper presents the results of recalculating the HDI for a simplified sample of 114 countries using various methodologies employed by the UNDP. The results are a set of deviations of recalculated HDI ranks compared to the original ranks given in the HDRs. The volatility that can result from such recalculation is shown to be substantial (+/-10-15 ranks), yet reports in the popular press are frequently sensitive to movements of only a few ranks. Such movement can easily be accounted for by changes in the HDI methodology rather than genuine progress in human development. While the HDRs often carry warnings about the inadvisability of such year-on-year comparisons, it is argued that the existence of such a high-profile index and the overt presentation within league tables do encourage such comparison. Assuming that the HDI will be retained as a focal point within the HDRs, then it is suggested that greater focus be upon more meaningful and robust categories of human development (e.g. low, medium and high) rather than league tables where shifts of a few places, perhaps as a result of nothing more than a methodological or data artefact, may be highlighted in the press and by policy makers. (C) 2003 Elsevier Science B.V. All rights reserved.

Observed trends and teleconnections of the Siberian high: A recently declining center of action

This study investigates variability in the intensity of the wintertime Siberian high (SH) by defining a robust SH index (SHI) and correlating it with selected meteorological fields and teleconnection indices. A dramatic trend of -2.5 hPa decade(-1) has been found in the SHI between 1978 and 2001 with unprecedented (since 1871) low values of the SHI. The weakening of the SH has been confirmed by analyzing different historical gridded analyses and individual station observations of sea level pressure (SLP) and excluding possible effects from the conversion of surface pressure to SLP. SHI correlation maps with various meteorological fields show that SH impacts on circulation and temperature patterns extend far outside the SH source area extending from the Arctic to the tropical Pacific. Advection of warm air from eastern Europe has been identified as the main mechanism causing milder than normal conditions over the Kara and Laptev Seas in association with a strong SH. Despite the strong impacts of the variability in the SH on climatic variability across the Northern Hemisphere, correlations between the SHI and the main teleconnection indices of the Northern Hemisphere are weak. Regression analysis has shown that teleconnection indices are not able to reproduce the interannual variability and trends in the SH. The inclusion of regional surface temperature in the regression model provides closer agreement between the original and reconstructed SHI.

Inter-simple sequence repeat and aggressiveness analyses revealed high genetic diversity, recombination and long-range dispersal in Fusarium culmorum

Inter-simple sequence repeat (ISSR) analysis and aggressiveness assays were used to investigate genetic variability within a global collection of Fusarium culmorum isolates. A set of four ISSR primers were tested, of which three primers amplified a total of 37 bands out of which 30 (81%) were polymorphic. The intraspecific diversity was high, ranging from four to 28 different ISSR genotypes for F. culmorum depending on the primer. The combined analysis of ISSR data revealed 59 different genotypes clustered into seven distinct clades amongst 75 isolates of F. culmorum examined. All the isolates were assayed to test their aggressiveness on a winter wheat cv. 'Armada'. A significant quantitative variation for aggressiveness was found among the isolates. The ISSR and aggressiveness variation existed on a macro- as well as micro-geographical scale. The data suggested a long-range dispersal of F. culmorum and indicated that this fungus may have been introduced into Canada from Europe. In addition to the high level of intraspecific diversity observed in F. culmorum, the index of multilocus association calculated using ISSR data indicated that reproduction in F. culmorum cannot be exclusively clonal and recombination is likely to occur.

The chemistry of intrinsically chiral surfaces

Intrinsically chiral metal and mineral surfaces show enantioselective behaviour without modifiers. Examples are artificial high-Miller-index surfaces of metal single crystals with cubic bulk lattice symmetry, which have no mirror planes and are therefore chiral, or surfaces of naturally occurring crystallites of some common minerals, such as alpha-quartz or calcite. Recent findings with regards to the surface geometry, reactivity and thermal stability of intrinsically chiral surfaces are discussed. A number of enantioselective effects have been reported in connection with the adsorption of small chiral molecules (e.g. alanine, cysteine) on intrinsically chiral surfaces under well-defined conditions. From a combination of experimental surface science techniques and theoretical ab initio model calculations it emerges that these effects are due to a combination of attractive and repulsive adsorbate-substrate and inter-adsorbate interactions.

The air distribution index as an indicator for energy consumption and performance of ventilation systems

This paper deals with the energy consumption and the evaluation of the performance of air supply systems for a ventilated room involving high- and low-level supplies. The energy performance assessment is based on the airflow rate, which is related to the fan power consumption by achieving the same environmental quality performance for each case. Four different ventilation systems are considered: wall displacement ventilation, confluent jets ventilation, impinging jet ventilation and a high level mixing ventilation system. The ventilation performance of these systems will be examined by means of achieving the same Air Distribution Index (ADI) for different cases. The widely used high-level supplies require much more fan power than those for low-level supplies for achieving the same value of ADI. In addition, the supply velocity, hence the supply dynamic pressure, for a high-level supply is much larger than for low-level supplies. This further increases the power consumption for high-level supply systems. The paper considers these factors and attempts to provide some guidelines on the difference in the energy consumption associated with high and low level air supply systems. This will be useful information for designers and to the authors' knowledge there is a lack of information available in the literature on this area of room air distribution. The energy performance of the above-mentioned ventilation systems has been evaluated on the basis of the fan power consumed which is related to the airflow rate required to provide equivalent indoor environment. The Air Distribution Index (ADI) is used to evaluate the indoor environment produced in the room by the ventilation strategy being used. The results reveal that mixing ventilation requires the highest fan power and the confluent jets ventilation needs the lowest fan power in order to achieve nearly the same value of ADI.

Predictions of some product parameters based on the processing conditions of ultra-high-temperature milk plants

The temperature-time profiles of 22 Australian industrial ultra-high-temperature (UHT) plants and 3 pilot plants, using both indirect and direct heating, were surveyed. From these data, the operating parameters of each plant, the chemical index C*, the bacteriological index B* and the predicted changes in the levels of beta-lactoglobulin, alpha-lactalbumin, lactulose, furosine and browning were determined using a simulation program based on published formulae and reaction kinetics data. There was a wide spread of heating conditions used, some of which resulted in a large margin of bacteriological safety and high chemical indices. However, no conditions were severe enough to cause browning during processing. The data showed a clear distinction between the indirect and direct heating plants. They also indicated that degree of denaturation of alpha-lactalbumin varied over a wide range and may be a useful discriminatory index of heat treatment. Application of the program to pilot plants illustrated its value in determining processing conditions in these plants to simulate the conditions in industrial UHT plants. (C) 2008 Elsevier Ltd. All rights reserved.

Effects of high pressure on functional properties of soy protein

Simultaneous measurement of the effects of low soy protein concentration, pH and high pressure treatment at room temperature on solubility, emulsifying properties and rheological properties (loss modulus, G '') of soy protein isolate (SPI) were evaluated. Central composite rotatable designs (2(3)) were employed over two pH ranges (2.66-4.34 and 5.16-6.84) with SPI concentration (0.32-3.68%) and pressure (198-702 MPa) as the other independent variables. The surface responses were obtained for protein solubility, emulsifying activity index (EAI) and G ''. The samples with the highest effect on protein solubility, EAI and G '' values were evaluated, as well, by electrophoresis and free sulphydryl determination. The pH was the main factor that affected protein solubility, with solubility at a maximum at pH < 3 or pH > 6. Increasing SPI concentration and decreasing/increasing the pH away from the isoelectric point both caused a reduction in EAI. Loss modulus (G '') was found to increase with SPI concentration in both pH ranges. (c) 2006 Elsevier Ltd. All rights reserved.

Random number generation as an index of controlled processing

Random number generation (RNG) is a functionally complex process that is highly controlled and therefore dependent on Baddeley's central executive. This study addresses this issue by investigating whether key predictions from this framework are compatible with empirical data. In Experiment 1, the effect of increasing task demands by increasing the rate of the paced generation was comprehensively examined. As expected, faster rates affected performance negatively because central resources were increasingly depleted. Next, the effects of participants' exposure were manipulated in Experiment 2 by providing increasing amounts of practice on the task. There was no improvement over 10 practice trials, suggesting that the high level of strategic control required by the task was constant and not amenable to any automatization gain with repeated exposure. Together, the results demonstrate that RNG performance is a highly controlled and demanding process sensitive to additional demands on central resources (Experiment 1) and is unaffected by repeated performance or practice (Experiment 2). These features render the easily administered RNG task an ideal and robust index of executive function that is highly suitable for repeated clinical use.

The temperature-dependent spectral properties of filter substrate materials in the far-infrared (6-40 mu m)

This paper presents the experimental results on the low temperature absorption and dispersion properties for a variety of frequently used infrared filter substrate materials. Index of refraction (n) and transmission spectra are presented for a range of temperatures 300-50 K for the Group IV materials silicon (Si) and germanium (Ge), and Group II-VI materials zinc selenide (ZnSe), zinc sulphide (ZnS) and cadmium telluride (CdTe). (C) 2003 Elsevier B.V. All rights reserved.