Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance.

The identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected. We identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.

Correlação linear e espacial entre o rendimento de grãos do feijoeiro e a resistência mecânica à penetração em um Latossolo Vermelho distrófico

A resistência mecânica à penetração apresentada pelo solo exerce grande influência sobre o desenvolvimento vegetal, uma vez que o crescimento das raízes, assim como o rendimento das culturas, varia de forma inversamente proporcional ao seu valor. No ano agrícola de 2001/2002, na Fazenda Experimental de Ensino e Pesquisa da Faculdade de Engenharia/UNESP - Campus de Ilha Solteira, foram analisados o rendimento de grãos do feijoeiro (PG) e a resistência mecânica à penetração (R), de um Latossolo Vermelho distrófico. O objetivo foi apurar diretrizes relacionadas com o aumento da produtividade agrícola em questão, estudando a correlação linear e a espacial entre a PG e a R. Foi instalada uma rede geoestatística para a coleta dos dados do solo e da planta, estabelecida com espaçamentos de 5 x 5 m e 2,5 x 2,5 m, que continham 120 pontos amostrais distribuídos numa área de 1.875 m². A correlação linear entre a PG e a R foi praticamente nula, uma vez que, dependendo das profundidades estudadas do solo, apresentou coeficientes de correlação (r) menores do que 0,20. A análise geoestatística apresentou boa estrutura de dependência espacial, tanto para a PG quanto para a R, quando analisadas isoladamente. Entretanto, a análise espacial conjunta de tais atributos apresentou-se inconsistente. Assim, com o aumento da resistência mecânica à penetração, em determinada região do solo ocorreu ora aumento, ora diminuição do rendimento de grãos do feijoeiro.

Neurobiology of suicide: do biomarkers exist?

Clinical risk factors have a low predictive value on suicide. This may explain the increasing interest in potential neurobiological correlates and specific heritable markers of suicide vulnerability. This review aims to present the current neurobiological findings that have been shown to be implicated in suicide completers and to discuss how postmortem studies may be useful in characterizing these individuals. Data on the role of the main neurobiological systems in suicidality, such as the neurotransmitter families, hypothalamic-pituitary-adrenal axis, neurotrophic factors, and polyamines, are exposed at the different biochemical, genetic, and epigenetic levels. Some neuroanatomic and neuropathological aspects as well as their in vivo morphological and functional neuroimaging correlates are also described. Except for the serotoninergic system, particularly with respect to the polymorphism of the gene coding for the serotonin transporter (5-HTTLPR) and brain-derived neurotrophic factor, data did not converge to produce a univocal consensus. The possible limitations of currently published studies are discussed, as well as the scope for long-term prospective studies.

Predictive ability of severe rainfall events over Catalonia for the year 2008

This paper analyses the predictive ability of quantitative precipitation forecasts (QPF) and the so-called "poor-man" rainfall probabilistic forecasts (RPF). With this aim, the full set of warnings issued by the Meteorological Service of Catalonia (SMC) for potentially-dangerous events due to severe precipitation has been analysed for the year 2008. For each of the 37 warnings, the QPFs obtained from the limited-area model MM5 have been verified against hourly precipitation data provided by the rain gauge network covering Catalonia (NE of Spain), managed by SMC. For a group of five selected case studies, a QPF comparison has been undertaken between the MM5 and COSMO-I7 limited-area models. Although MM5's predictive ability has been examined for these five cases by making use of satellite data, this paper only shows in detail the heavy precipitation event on the 9¿10 May 2008. Finally, the "poor-man" rainfall probabilistic forecasts (RPF) issued by SMC at regional scale have also been tested against hourly precipitation observations. Verification results show that for long events (>24 h) MM5 tends to overestimate total precipitation, whereas for short events (¿24 h) the model tends instead to underestimate precipitation. The analysis of the five case studies concludes that most of MM5's QPF errors are mainly triggered by very poor representation of some of its cloud microphysical species, particularly the cloud liquid water and, to a lesser degree, the water vapor. The models' performance comparison demonstrates that MM5 and COSMO-I7 are on the same level of QPF skill, at least for the intense-rainfall events dealt with in the five case studies, whilst the warnings based on RPF issued by SMC have proven fairly correct when tested against hourly observed precipitation for 6-h intervals and at a small region scale. Throughout this study, we have only dealt with (SMC-issued) warning episodes in order to analyse deterministic (MM5 and COSMO-I7) and probabilistic (SMC) rainfall forecasts; therefore we have not taken into account those episodes that might (or might not) have been missed by the official SMC warnings. Therefore, whenever we talk about "misses", it is always in relation to the deterministic LAMs' QPFs.

Super-resolution of remotely sensed images with variable-pixel linear reconstruction

This paper describes the development and applications of a super-resolution method, known as Super-Resolution Variable-Pixel Linear Reconstruction. The algorithm works combining different lower resolution images in order to obtain, as a result, a higher resolution image. We show that it can make significant spatial resolution improvements to satellite images of the Earth¿s surface allowing recognition of objects with size approaching the limiting spatial resolution of the lower resolution images. The algorithm is based on the Variable-Pixel Linear Reconstruction algorithm developed by Fruchter and Hook, a well-known method in astronomy but never used for Earth remote sensing purposes. The algorithm preserves photometry, can weight input images according to the statistical significance of each pixel, and removes the effect of geometric distortion on both image shape and photometry. In this paper, we describe its development for remote sensing purposes, show the usefulness of the algorithm working with images as different to the astronomical images as the remote sensing ones, and show applications to: 1) a set of simulated multispectral images obtained from a real Quickbird image; and 2) a set of multispectral real Landsat Enhanced Thematic Mapper Plus (ETM+) images. These examples show that the algorithm provides a substantial improvement in limiting spatial resolution for both simulated and real data sets without significantly altering the multispectral content of the input low-resolution images, without amplifying the noise, and with very few artifacts.

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

AIM: Inulin clearance (Cin) is the gold standard for assessing glomerular filtration rate (GFR). Other methods are based on the plasma creatinine concentration (Pcreat), creatinine clearance (Ccreat), the Haycock-Schwartz formula and the plasma concentration of cystatin C (PcysC), a 13 kDa basic protein produced at a constant rate by all nucleated cells. The present prospective study was thus designed to evaluate the reliability of PcysC as a marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock-Schwartz formula, using Cin as the gold standard. METHODS: Ninety-nine children (51 m/48 f), with a median age of 8.3 y (1.0-17.9) were studied. Using a cut-off for Cin of 100 ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with normal GFR were comparable for age, height, weight and body mass index. RESULTS: Logistic regression, ROC analysis and linear regression all showed that Ccreat was the best parameter to discriminate between impaired and normal GFR, followed by the Haycock-Schwartz formula, PcysC, and finally Pcreat, each one being significantly more predictive than the next. CONCLUSION: GFR is better assessed by the Haycock-Schwartz formula than by PcysC or Pcreat alone. It is therefore concluded that when urine collection is not possible, simply measuring the child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

Correlação linear e espacial entre a produtividade de forragem, a porosidade total e a densidade do solo de Pereira Barreto (SP)

Em relação aos sistemas de manejo adotados pelo homem, a porosidade total e a densidade do solo são atributos ativamente alterados, refletindo decisivamente sobre a produtividade vegetal agrícola. No ano agrícola de 2005, na Fazenda Bonança, no município de Pereira Barreto, Estado de São Paulo, Brasil, foram analisadas a produtividade de forragem do milho outonal (MSF) no sistema plantio direto irrigado, a porosidade total (PT) e a densidade do solo (DS) em profundidade, em um Latossolo Vermelho distrófico. O objetivo foi estudar a variabilidade e as correlações lineares e espaciais entre os atributos da planta e do solo, visando selecionar um indicador da qualidade física do solo de boa representatividade para produtividade da forragem. Foi instalada a malha geoestatística, para coleta de dados do solo e planta, contendo 125 pontos amostrais, numa área de 2.500 m². Os atributos estudados, além de não terem variado aleatoriamente, apresentaram variabilidade dos dados entre média e baixa e seguiram padrões espaciais bem definidos, com alcance entre 6,8 e 23,7 m. Por sua vez, a correlação linear entre o atributo da planta e os do solo, em razão do elevado número de observações, foi baixa. As observações de melhor correlação com a MSF foram a DS1 e a PT1. Entretanto, do ponto de vista espacial, houve excelente correlação inversa entre a MSF e a DS1, assim como entre a DS1 e a PT1. Nos sítios onde a DS1 aumentou (1,45-1,64 kg dm-3) a MSF variou entre 11.653 e 14.552 kg ha-1; já naqueles onde diminuiu (1,35-1,45 kg dm-3) a MSF, ficou entre 14.552 e 17.450 kg ha-1. Portanto, a densidade global, avaliada na camada de 0-0,10 m (DS1), apresentou-se como satisfatório indicador da qualidade física do solo de Pereira Barreto (SP), quando destinado à produtividade de forragem do milho outonal.

Tandem repeat sequence variation as causative cis-eQTLs for protein-coding gene expression variation: the case of CSTB.

Association studies have revealed expression quantitative trait loci (eQTLs) for a large number of genes. However, the causative variants that regulate gene expression levels are generally unknown. We hypothesized that copy-number variation of sequence repeats contribute to the expression variation of some genes. Our laboratory has previously identified that the rare expansion of a repeat c.-174CGGGGCGGGGCG in the promoter region of the CSTB gene causes a silencing of the gene, resulting in progressive myoclonus epilepsy. Here, we genotyped the repeat length and quantified CSTB expression by quantitative real-time polymerase chain reaction in 173 lymphoblastoid cell lines (LCLs) and fibroblast samples from the GenCord collection. The majority of alleles contain either two or three copies of this repeat. Independent analysis revealed that the c.-174CGGGGCGGGGCG repeat length is strongly associated with CSTB expression (P = 3.14 × 10(-11)) in LCLs only. Examination of both genotyped and imputed single-nucleotide polymorphisms (SNPs) within 2 Mb of CSTB revealed that the dodecamer repeat represents the strongest cis-eQTL for CSTB in LCLs. We conclude that the common two or three copy variation is likely the causative cis-eQTL for CSTB expression variation. More broadly, we propose that polymorphic tandem repeats may represent the causative variation of a fraction of cis-eQTLs in the genome.

Correlação linear e espsacial entre a produtividade de feijão e a porosidade de um Latossolo Vermelho de Selvíria (MS)

A porosidade do solo exerce grande influência sobre o crescimento e desenvolvimento vegetal, uma vez que o crescimento das raízes, tal como a produtividade das culturas, é limitado pela profundidade que atingem. Portanto, o objetivo deste trabalho foi estudar a variabilidade espacial e as correlações lineares entre a produtividade de feijão e a porosidade do solo. No ano de 2004/2005, no município de Selvíria, MS, foram analisadas a produtividade de grãos de feijão (PG), cultivar IAC Carioca, irrigado, a macroporosidade (MA), a microporosidade (MI) e a porosidade total (PT) do solo em quatro profundidades: 1 (0,0-0,10); 2(0,10-0,20); 3(0,20-0,30) e 4(0,30-0,40 m), num Latossolo Vermelho distroférrico. As amostras de solo e planta foram coletadas em uma malha geoestatística com 75 pontos espaçados de 10 x 10 m, mais 60 pontos de quatro malhas de refinamento numa área de 50 x 150 m. Os atributos estudados, além de não terem variado aleatoriamente, apresentaram média e baixa variabilidades. Seguiram padrões espaciais bem definidos, com alcances entre 11,70 e 104,40 m. A correlação linear entre o atributo da planta e os do solo, em função do elevado número de observações, foi baixa. As de melhor correlação linear com a PG foram a MA1, MI1 e a PT3. Entretanto, do ponto de vista espacial, houve excelente correlação inversa entre a PG e a #PT2. Assim, nos sítios onde a #PT2 diminuiu (0,030-0,045 m³ m-3 ), a PG variou entre 2.173 e 3.529 kg ha-1. Já naqueles onde aumentou (0,045-0,076 m³ m-3 ), a PG ficou entre 1.630-2.173 kg ha-1. Assim, a porosidade total do solo, quando avaliada na camada de 0,10-0,20 m (#PT2), indicou a importância do contato raiz/solo e, de modo inverso, apresentou satisfatório indicador da qualidade física do solo estudado, quando destinado à produtividade de grãos de feijão irrigado.

Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.

Predictive factors in the long term outcome in gastro-oesophageal reflux disease: six years follow up of 107 patients

There is little information concerning the long term outcome of patients with gastro-oesophageal reflux disease (GORD). Thus 109 patients with reflux symptoms (33 with erosive oesophagitis) with a diagnosis of GORD after clinical evaluation and oesophageal testing were studied. All patients were treated with a stepwise approach: (a) lifestyle changes were suggested aimed at reducing reflux and antacids and the prokinetic agent domperidone were prescribed; (b) H2 blockers were added after two months when symptoms persisted; (c) anti-reflux surgery was indicated when there was no response to (b). Treatment was adjusted to maintain clinical remission during follow up. Long term treatment need was defined as minor when conservative measures sufficed for proper control, and as major if daily H2 blockers or surgery were required. The results showed that one third of the patients each had initial therapeutic need (a), (b), and (c). Of 103 patients available for follow up at three years and 89 at six years, respective therapeutic needs were minor in 52% and 55% and major in 48% and 45%. Eighty per cent of patients in (a), 67% in (b), and 17% in (c) required only conservative measures at six years. A decreasing lower oesophageal sphincter pressure (p < 0.001), radiological reflux (p = 0.028), and erosive oesophagitis (p = 0.031), but not initial clinical scores, were independent predictors of major therapeutic need as shown by multivariate analysis. The long term outcome of GORD is better than previously perceived.

Correlação linear e espacial entre a resistência do solo ao penetrômetro e a produtividade do feijoeiro irrigado

A resistência do solo ao penetrômetro exerce grande influência sobre o crescimento e desenvolvimento vegetal, uma vez que o crescimento das raízes, assim como o rendimento das culturas, varia de forma inversamente proporcional ao seu valor. Dessa forma, a análise da variabilidade espacial da resistência do solo ao penetrômetro e da produtividade, por meio da geoestatística, pode indicar alternativas de manejo para reduzir os efeitos da variabilidade do solo sobre a produtividade e também melhorar a estimativa de respostas das culturas sob determinadas práticas de manejo. Diante do exposto, o objetivo deste trabalho foi relacionar e caracterizar a variabilidade espacial da resistência do solo ao penetrômetro (RP) e a produtividade do feijoeiro irrigado em sistema de semeadura direta, em duas safras consecutivas. O experimento foi realizado em Latossolo Vermelho distroférrico típico, no campo experimental da Faculdade de Engenharia Agrícola da Unicamp, no município de Campinas-SP, cujas coordenadas geográficas são: 22 ° 48 ' 57 " de latitude sul, 47 ° 03 ' 33 " de longitude oeste e altitude média de 640 m. As avaliações foram realizadas em uma malha regular de amostragem de 3 x 3 m, totalizando 60 pontos amostrais por parcela. A análise da dependência espacial foi avaliada pela geoestatística, e os parâmetros dos semivariogramas utilizados para construir mapas de isolinhas, por meio do interpolador de krigagem do programa Surfer 8.0. A regressão linear simples entre mapas (pixel-a-pixel) mostrou correlação negativa entre os valores de RP e a produtividade; no entanto, a produtividade do feijoeiro irrigado apresentou baixa correlação com a resistência do solo ao penetrômetro em sistema semeadura direta nas duas safras.

Linear and nonlinear optical properties of Si nanocrystals in SiO2 deposited by plasma-enhanced chemical-vapor deposition

Linear and nonlinear optical properties of silicon suboxide SiOx films deposited by plasma-enhanced chemical-vapor deposition have been studied for different Si excesses up to 24¿at.¿%. The layers have been fully characterized with respect to their atomic composition and the structure of the Si precipitates. Linear refractive index and extinction coefficient have been determined in the whole visible range, enabling to estimate the optical bandgap as a function of the Si nanocrystal size. Nonlinear optical properties have been evaluated by the z-scan technique for two different excitations: at 0.80¿eV in the nanosecond regime and at 1.50¿eV in the femtosecond regime. Under nanosecond excitation conditions, the nonlinear process is ruled by thermal effects, showing large values of both nonlinear refractive index (n2 ~ ¿10¿8¿cm2/W) and nonlinear absorption coefficient (ß ~ 10¿6¿cm/W). Under femtosecond excitation conditions, a smaller nonlinear refractive index is found (n2 ~ 10¿12¿cm2/W), typical of nonlinearities arising from electronic response. The contribution per nanocrystal to the electronic third-order nonlinear susceptibility increases as the size of the Si nanoparticles is reduced, due to the appearance of electronic transitions between discrete levels induced by quantum confinement.

Quality coding by neural populations in the early olfactory pathway: analysis using information theory

In this article, we analyze the ability of the early olfactory system to detect and discriminate different odors by means of information theory measurements applied to olfactory bulb activity images. We have studied the role that the diversity and number of receptor neuron types play in encoding chemical information. Our results show that the olfactory receptors of the biological system are low correlated and present good coverage of the input space. The coding capacity of ensembles of olfactory receptors with the same receptive range is maximized when the receptors cover half of the odor input space - a configuration that corresponds to receptors that are not particularly selective. However, the ensemble's performance slightly increases when mixing uncorrelated receptors of different receptive ranges. Our results confirm that the low correlation between sensors could be more significant than the sensor selectivity for general purpose chemo-sensory systems, whether these are biological or biomimetic.

Shot noise in linear macroscopic resistors

We report on direct experimental evidence of shot noise in a linear macroscopic resistor. The origin of the shot noise comes from the fluctuation of the total number of charge carriers inside the resistor associated with their diffusive motion under the condition that the dielectric relaxation time becomes longer than the dynamic transit time. The present results show that neither potential barriers nor the absence of inelastic scattering are necessary to observe shot noise in electronic devices.