MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale.

A considerable proportion of mammalian gene expression undergoes circadian oscillations. Post-transcriptional mechanisms likely make important contributions to mRNA abundance rhythms. We have investigated how microRNAs (miRNAs) contribute to core clock and clock-controlled gene expression using mice in which miRNA biogenesis can be inactivated in the liver. While the hepatic core clock was surprisingly resilient to miRNA loss, whole transcriptome sequencing uncovered widespread effects on clock output gene expression. Cyclic transcription paired with miRNA-mediated regulation was thus identified as a frequent phenomenon that affected up to 30% of the rhythmic transcriptome and served to post-transcriptionally adjust the phases and amplitudes of rhythmic mRNA accumulation. However, only few mRNA rhythms were actually generated by miRNAs. Overall, our study suggests that miRNAs function to adapt clock-driven gene expression to tissue-specific requirements. Finally, we pinpoint several miRNAs predicted to act as modulators of rhythmic transcripts, and identify rhythmic pathways particularly prone to miRNA regulation.DOI: http://dx.doi.org/10.7554/eLife.02510.001.

Magnetic susceptibility to identify landscape segments on a detailed scale in the region of Jaboticabal, São Paulo, Brazil

The agricultural potential is generally assessed and managed based on a one-dimensional vision of the soil profile, however, the increased appreciation of sustainable production has stimulated studies on faster and more accurate evaluation techniques and methods of the agricultural potential on detailed scales. The objective of this study was to investigate the possibility of using soil magnetic susceptibility for the identification of landscape segments on a detailed scale in the region of Jaboticabal, São Paulo State. The studied area has two slope curvatures: linear and concave, subdivided into three landscape segments: upper slope (US, concave), middle slope (MS, linear) and lower slope (LS, linear). In each of these segments, 20 points were randomly sampled from a database with 207 samples forming a regular grid installed in each landscape segment. The soil physical and chemical properties, CO2 emissions (FCO2) and magnetic susceptibility (MS) of the samples were evaluated represented by: magnetic susceptibility of air-dried fine earth (MS ADFE), magnetic susceptibility of the total sand fraction (MS TS) and magnetic susceptibility of the clay fraction (MS Cl) in the 0.00 - 0.15 m layer. The principal component analysis showed that MS is an important property that can be used to identify landscape segments, because the correlation of this property within the first principal component was high. The hierarchical cluster analysis method identified two groups based on the variables selected by principal component analysis; of the six selected variables, three were related to magnetic susceptibility. The landscape segments were differentiated similarly by the principal component analysis and by the cluster analysis using only the properties with higher discriminatory power. The cluster analysis of MS ADFE, MS TS and MS Cl allowed the formation of three groups that agree with the segment division established in the field. The grouping by cluster analysis indicated MS as a tool that could facilitate the identification of landscape segments and enable the mapping of more homogeneous areas at similar locations.

Spatial correlations and cross sections of clusters in the A + B -> 0 reaction

We consider the distribution of cross sections of clusters and the density-density correlation functions for the A+B¿0 reaction. We solve the reaction-diffusion equations numerically for random initial distributions of reactants. When both reactant species have the same diffusion coefficients the distribution of cross sections and the correlation functions scale with the diffusion length and obey superuniversal laws (independent of dimension). For different diffusion coefficients the correlation functions still scale, but the scaling functions depend on the dimension and on the diffusion coefficients. Furthermore, we display explicitly the peculiarities of the cluster-size distribution in one dimension.

Preserved capillary density of dorsal finger skin in treated hypertensive patients with or without type 2 diabetes.

OBJECTIVES: Capillary rarefaction is a hallmark of untreated hypertension. Recent data indicate that rarefaction may be reversed by antihypertensive treatment in nondiabetic hypertensive patients. Despite the frequent association of diabetes with hypertension, nothing is known on the capillary density of treated diabetic patients with hypertension. METHODS: We enrolled 21 normotensive healthy, 25 hypertensive only, and 21 diabetic (type 2) hypertensive subjects. All hypertensive patients were treated with a blocker of the renin-angiotensin system, and a majority had a home blood pressure ≤135/85 mmHg. Capillary density was assessed with videomicroscopy on dorsal finger skin and with laser Doppler imaging on forearm skin (maximal vasodilation elicited by local heating). RESULTS: There was no difference between any of the study groups in either dorsal finger skin capillary density (controls 101 ± 11 capillaries/mm(2) , nondiabetic hypertensive 99 ± 16, diabetic hypertensive 96 ± 18, p > 0.5) or maximal blood flow in forearm skin (controls 666 ± 114 perfusion units, nondiabetic hypertensive 612 ± 126, diabetic hypertensive 620 ± 103, p > 0.5). CONCLUSIONS: Irrespective of the presence or not of type 2 diabetes, capillary density is normal in hypertensive patients with reasonable control of blood pressure achieved with a blocker of the renin-angiotensin system.

Relativistic mean-field interaction with density-dependent meson-nucleon vertices based on microscopical calculations

Although ab initio calculations of relativistic Brueckner theory lead to large scalar isovector fields in nuclear matter, at present, successful versions of covariant density functional theory neglect the interactions in this channel. A new high-precision density functional DD-MEδ is presented which includes four mesons, σ, ω, δ, and ρ, with density-dependent meson-nucleon couplings. It is based to a large extent on microscopic ab initiocalculations in nuclear matter. Only four of its parameters are determined by adjusting to binding energies and charge radii of finite nuclei. The other parameters, in particular the density dependence of the meson-nucleon vertices, are adjusted to nonrelativistic and relativistic Brueckner calculations of symmetric and asymmetric nuclear matter. The isovector effective mass mp*−mn* derived from relativistic Brueckner theory is used to determine the coupling strength of the δ meson and its density dependence.

Density matrices and momentum distributions in 3He-4He mixtures

We report variational calculations, in the hypernetted-chain (HNC)-Fermi-HNC scheme, of one-body density matrices and one-particle momentum distributions for 3He-4He mixtures described by a Jastrow correlated wave function. The 4He condensate fractions and the 3He strength poles are examined and compared with the Monte Carlo available results. The agreement has been found to be very satisfactory. Their density dependence is also studied.

A large-scale genetic validation study coupled with in vitro analyses reveal a role for vitamin Dsignaling in the pathogenesis and response to treatment of hepatitis C virus infection

Background and Aims: Vitamin D is an important modulatorof numerous cellular processes. Some of us recently observedan association of the 1a-hydroxylase promoter polymorphismCYP27B1-1260 rs10877012 with sustained virologic response (SVR)in a relatively small number of German patients with chronichepatitis C. In the present study, we aimed to validate thisassociation in a large and well characterized patient cohort, theSwiss Hepatitis C Cohort Study (SCCS). In addition, we examinedthe effect of vitamin D on the hepatitis C virus (HCV) life cyclein vitro.Methods: CYP27B1-1260 rs10877012 and IL28B rs12979860 singlenucleotide polymorphisms (SNPs) were genotyped in 1049 patientswith chronic hepatitis C from the SCCS, of whom 698 were treatedwith pegylated interferon-a (PEG-IFN-a) and ribavirin. In addition,112 patients with spontaneous clearance of HCV were examined.SNPs were correlated with variables reflecting the natural courseand treatment outcome of chronic hepatitis C. The effect of1,25-(OH)2D3 (calcitriol) on HCV replication and viral particleproduction was investigated in vitro using human hepatoma celllines (Huh-7.5) harbouring subgenomic replicons and cell culturederivedHCV.Results: The CYP27B1-1260 rs10877012 genotype was notassociated with SVR in patients with the good-response IL28Brs1279860 CC genotype. However, in patients with poor-responseIL28B rs1279860 genotype CT and TT, CYP27B1-1260 rs10877012was a significant independent predictor of SVR (15% difference inSVR between rs10877012 genotype AA vs. CC, p = 0.030, OR = 1.495,95% CI = 1.038-2.152). The CYPB27-1260 rs10877012 genotype wasneither associated with spontaneous clearance of HCV, nor withliver fibrosis progression rate, inflammatory activity of chronichepatitis C, or HCV viral load. Physiological doses of 1,25-(OH)2D3did not significantly affect HCVRNA replication or infectiousparticle production in vitro.Conclusions: The results of this large-scale genetic validationstudy reveal a role of vitamin D metabolism in the responseto treatment in chronic hepatitis C, but 1,25-(OH)2D3 does notexhibit a significant direct inhibitory antiviral effect. Thus, theability of vitamin D to modulate immunity against HCV shouldbe investigated.

Accelerated Microstructure Imaging via Convex Optimization (AMICO) from diffusion MRI data.

Microstructure imaging from diffusion magnetic resonance (MR) data represents an invaluable tool to study non-invasively the morphology of tissues and to provide a biological insight into their microstructural organization. In recent years, a variety of biophysical models have been proposed to associate particular patterns observed in the measured signal with specific microstructural properties of the neuronal tissue, such as axon diameter and fiber density. Despite very appealing results showing that the estimated microstructure indices agree very well with histological examinations, existing techniques require computationally very expensive non-linear procedures to fit the models to the data which, in practice, demand the use of powerful computer clusters for large-scale applications. In this work, we present a general framework for Accelerated Microstructure Imaging via Convex Optimization (AMICO) and show how to re-formulate this class of techniques as convenient linear systems which, then, can be efficiently solved using very fast algorithms. We demonstrate this linearization of the fitting problem for two specific models, i.e. ActiveAx and NODDI, providing a very attractive alternative for parameter estimation in those techniques; however, the AMICO framework is general and flexible enough to work also for the wider space of microstructure imaging methods. Results demonstrate that AMICO represents an effective means to accelerate the fit of existing techniques drastically (up to four orders of magnitude faster) while preserving accuracy and precision in the estimated model parameters (correlation above 0.9). We believe that the availability of such ultrafast algorithms will help to accelerate the spread of microstructure imaging to larger cohorts of patients and to study a wider spectrum of neurological disorders.

Looking for orders of magnitude : five essays in trade and the environment and economic geography

General Summary Although the chapters of this thesis address a variety of issues, the principal aim is common: test economic ideas in an international economic context. The intention has been to supply empirical findings using the largest suitable data sets and making use of the most appropriate empirical techniques. This thesis can roughly be divided into two parts: the first one, corresponding to the first two chapters, investigates the link between trade and the environment, the second one, the last three chapters, is related to economic geography issues. Environmental problems are omnipresent in the daily press nowadays and one of the arguments put forward is that globalisation causes severe environmental problems through the reallocation of investments and production to countries with less stringent environmental regulations. A measure of the amplitude of this undesirable effect is provided in the first part. The third and the fourth chapters explore the productivity effects of agglomeration. The computed spillover effects between different sectors indicate how cluster-formation might be productivity enhancing. The last chapter is not about how to better understand the world but how to measure it and it was just a great pleasure to work on it. "The Economist" writes every week about the impressive population and economic growth observed in China and India, and everybody agrees that the world's center of gravity has shifted. But by how much and how fast did it shift? An answer is given in the last part, which proposes a global measure for the location of world production and allows to visualize our results in Google Earth. A short summary of each of the five chapters is provided below. The first chapter, entitled "Unraveling the World-Wide Pollution-Haven Effect" investigates the relative strength of the pollution haven effect (PH, comparative advantage in dirty products due to differences in environmental regulation) and the factor endowment effect (FE, comparative advantage in dirty, capital intensive products due to differences in endowments). We compute the pollution content of imports using the IPPS coefficients (for three pollutants, namely biological oxygen demand, sulphur dioxide and toxic pollution intensity for all manufacturing sectors) provided by the World Bank and use a gravity-type framework to isolate the two above mentioned effects. Our study covers 48 countries that can be classified into 29 Southern and 19 Northern countries and uses the lead content of gasoline as proxy for environmental stringency. For North-South trade we find significant PH and FE effects going in the expected, opposite directions and being of similar magnitude. However, when looking at world trade, the effects become very small because of the high North-North trade share, where we have no a priori expectations about the signs of these effects. Therefore popular fears about the trade effects of differences in environmental regulations might by exaggerated. The second chapter is entitled "Is trade bad for the Environment? Decomposing worldwide SO2 emissions, 1990-2000". First we construct a novel and large database containing reasonable estimates of SO2 emission intensities per unit labor that vary across countries, periods and manufacturing sectors. Then we use these original data (covering 31 developed and 31 developing countries) to decompose the worldwide SO2 emissions into the three well known dynamic effects (scale, technique and composition effect). We find that the positive scale (+9,5%) and the negative technique (-12.5%) effect are the main driving forces of emission changes. Composition effects between countries and sectors are smaller, both negative and of similar magnitude (-3.5% each). Given that trade matters via the composition effects this means that trade reduces total emissions. We next construct, in a first experiment, a hypothetical world where no trade happens, i.e. each country produces its imports at home and does no longer produce its exports. The difference between the actual and this no-trade world allows us (under the omission of price effects) to compute a static first-order trade effect. The latter now increases total world emissions because it allows, on average, dirty countries to specialize in dirty products. However, this effect is smaller (3.5%) in 2000 than in 1990 (10%), in line with the negative dynamic composition effect identified in the previous exercise. We then propose a second experiment, comparing effective emissions with the maximum or minimum possible level of SO2 emissions. These hypothetical levels of emissions are obtained by reallocating labour accordingly across sectors within each country (under the country-employment and the world industry-production constraints). Using linear programming techniques, we show that emissions are reduced by 90% with respect to the worst case, but that they could still be reduced further by another 80% if emissions were to be minimized. The findings from this chapter go together with those from chapter one in the sense that trade-induced composition effect do not seem to be the main source of pollution, at least in the recent past. Going now to the economic geography part of this thesis, the third chapter, entitled "A Dynamic Model with Sectoral Agglomeration Effects" consists of a short note that derives the theoretical model estimated in the fourth chapter. The derivation is directly based on the multi-regional framework by Ciccone (2002) but extends it in order to include sectoral disaggregation and a temporal dimension. This allows us formally to write present productivity as a function of past productivity and other contemporaneous and past control variables. The fourth chapter entitled "Sectoral Agglomeration Effects in a Panel of European Regions" takes the final equation derived in chapter three to the data. We investigate the empirical link between density and labour productivity based on regional data (245 NUTS-2 regions over the period 1980-2003). Using dynamic panel techniques allows us to control for the possible endogeneity of density and for region specific effects. We find a positive long run elasticity of density with respect to labour productivity of about 13%. When using data at the sectoral level it seems that positive cross-sector and negative own-sector externalities are present in manufacturing while financial services display strong positive own-sector effects. The fifth and last chapter entitled "Is the World's Economic Center of Gravity Already in Asia?" computes the world economic, demographic and geographic center of gravity for 1975-2004 and compares them. Based on data for the largest cities in the world and using the physical concept of center of mass, we find that the world's economic center of gravity is still located in Europe, even though there is a clear shift towards Asia. To sum up, this thesis makes three main contributions. First, it provides new estimates of orders of magnitudes for the role of trade in the globalisation and environment debate. Second, it computes reliable and disaggregated elasticities for the effect of density on labour productivity in European regions. Third, it allows us, in a geometrically rigorous way, to track the path of the world's economic center of gravity.

On the determination of the interface density of states in a-Si:H/a-SiC:H multilayers

This paper deals with the determination of the interface density of states in amorphous silicon-based multilayers. Photothermal deflection spectroscopy is used to characterize two series of aSi:H/aSi1-xCx:H multilayers, and a new approach in the treatment of experimental dada is used in order to obtain accurate results. From this approach, an upper limit of 10^10 cm-2 is determined for the interface density of states.

Effects of traffic control on the soil physical quality and the cultivation of sugarcane

The cultivation of sugarcane with intensive use of machinery, especially for harvest, induces soil compaction, affecting the crop development. The control of agricultural traffic is an alternative of management in the sector, with a view to preserve the soil physical quality, resulting in increased sugarcane root growth, productivity and technological quality. The objective of this study was to evaluate the physical quality of an Oxisol with and without control traffic and the resulting effects on sugarcane root development, productivity and technological quality. The following managements were tested: no traffic control (NTC), traffic control consisting of an adjustment of the track width of the tractor and sugarcane trailer (TC1) and traffic control consisting of an adjustment of the track width of the tractor and trailer and use of an autopilot (TC2). Soil samples were collected (layers 0.00-0.10; 0.10-0.20 and 0.20-0.30 m) in the plant rows, inter-row center and seedbed region, 0.30 m away from the plant row. The productivity was measured with a specific weighing scale. The technological variables of sugarcane were measured in each plot. Soil cores were collected to analyze the root system. In TC2, the soil bulk density and compaction degree were lowest and total porosity and macroporosity highest in the plant row. Soil penetration resistance in the plant row, was less than 2 MPa in TC1 and TC2. Soil aggregation and total organic carbon did not differ between the management systems. The root surface and volume were increased in TC1 and TC2, with higher productivity and sugar yield than under NTC. The sugarcane variables did not differ between the managements. The soil physical quality in the plant row was preserved under management TC1 and TC2, with an improved root development and increases of 18.72 and 20.29 % in productivity and sugar yield, respectively.

Hydrological processes obtained on the plot scale under four simulated rainfall tests during the cycle of different crop systems

The cropping system influences the interception of water by plants, water storage in depressions on the soil surface, water infiltration into the soil and runoff. The aim of this study was to quantify some hydrological processes under no tillage cropping systems at the edge of a slope, in 2009 and 2010, in a Humic Dystrudept soil, with the following treatments: corn, soybeans, and common beans alone; and intercropped corn and common bean. Treatments consisted of four simulated rainfall tests at different times, with a planned intensity of 64 mm h-1 and 90 min duration. The first test was applied 18 days after sowing, and the others at 39, 75 and 120 days after the first test. Different times of the simulated rainfall and stages of the crop cycle affected soil water content prior to the rain, and the time runoff began and its peak flow and, thus, the surface hydrological processes. The depth of the runoff and the depth of the water intercepted by the crop + soil infiltration + soil surface storage were affected by the crop systems and the rainfall applied at different times. The corn crop was the most effective treatment for controlling runoff, with a water loss ratio of 0.38, equivalent to 75 % of the water loss ratio exhibited by common bean (0.51), the least effective treatment in relation to the others. Total water loss by runoff decreased linearly with an increase in the time that runoff began, regardless of the treatment; however, soil water content on the gravimetric basis increased linearly from the beginning to the end of the rainfall.