401 research outputs found

    On the Second Law of thermodynamics and the piston problem

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    The piston problem is investigated in the case where the length of the cylinder is infinite (on both sides) and the ratio m/Mm/M is a very small parameter, where mm is the mass of one particle of the gaz and MM is the mass of the piston. Introducing initial conditions such that the stochastic motion of the piston remains in the average at the origin (no drift), it is shown that the time evolution of the fluids, analytically derived from Liouville equation, agrees with the Second Law of thermodynamics. We thus have a non equilibrium microscopical model whose evolution can be explicitly shown to obey the two laws of thermodynamics.Comment: 29 pages, 9 figures submitted to Journal of Statistical Physics (2003

    Inflammatory bowel disease-specific autoantibodies in HLA-B27-associated spondyloarthropathies: Increased prevalence of ASCA and pANCA

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    Aims: An association between inflammatory bowel disease (IBD) and spondyloarthropathies (SpA) has repeatedly been reported. The aim of the present study was to investigate whether serologic markers of IBD, e. g. antibodies against Saccharomyces cerevisiae (ASCA), antibodies against exocrine pancreas (PAB) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) are present in HLA-B27-associated SpA. Methods: 87 patients with HLA-B27-positive SpA and 145 controls were tested for ASCA, PAB and pANCA employing ELISA or indirect immunofluorescence, respectively. Antibody-positive patients were interviewed regarding IBD-related symptoms using a standardized questionnaire. Results/Conclusion: When compared to the controls, ASCA IgA but not ASCA IgG levels were significantly increased in patients with SpA, in particular in ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). pANCA were found in increased frequency in patients with SpA whereas PAB were not detected. The existence of autoantibodies was not associated with gastrointestinal symptoms but sustains the presence of a pathophysiological link between bowel inflammation and SpA. Copyright (C) 2004 S. Karger AG, Basel

    Recent changes in the mutational dynamics of the SARS-CoV-2 main protease substantiate the danger of emerging resistance to antiviral drugs

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    IntroductionThe current coronavirus pandemic is being combated worldwide by nontherapeutic measures and massive vaccination programs. Nevertheless, therapeutic options such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main-protease (Mpro) inhibitors are essential due to the ongoing evolution toward escape from natural or induced immunity. While antiviral strategies are vulnerable to the effects of viral mutation, the relatively conserved Mpro makes an attractive drug target: Nirmatrelvir, an antiviral targeting its active site, has been authorized for conditional or emergency use in several countries since December 2021, and a number of other inhibitors are under clinical evaluation. We analyzed recent SARS-CoV-2 genomic data, since early detection of potential resistances supports a timely counteraction in drug development and deployment, and discovered accelerated mutational dynamics of Mpro since early December 2021.MethodsWe performed a comparative analysis of 10.5 million SARS-CoV-2 genome sequences available by June 2022 at GISAID to the NCBI reference genome sequence NC_045512.2. Amino-acid exchanges within high-quality regions in 69,878 unique Mpro sequences were identified and time- and in-depth sequence analyses including a structural representation of mutational dynamics were performed using in-house software.ResultsThe analysis showed a significant recent event of mutational dynamics in Mpro. We report a remarkable increase in mutational variability in an eight-residue long consecutive region (R188-G195) near the active site since December 2021.DiscussionThe increased mutational variability in close proximity to an antiviral-drug binding site as described herein may suggest the onset of the development of antiviral resistance. This emerging diversity urgently needs to be further monitored and considered in ongoing drug development and lead optimization

    The reinvigoration of the Southern Ocean carbon sink

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    Several studies have suggested that the carbon sink in the Southern Ocean—the ocean’s strongest region for the uptake of anthropogenic CO2 —has weakened in recent decades. We demonstrated, on the basis of multidecadal analyses of surface ocean CO2 observations, that this weakening trend stopped around 2002, and by 2012, the Southern Ocean had regained its expected strength based on the growth of atmospheric CO2. All three Southern Ocean sectors have contributed to this reinvigoration of the carbon sink, yet differences in the processes between sectors exist, related to a tendency toward a zonally more asymmetric atmospheric circulation. The large decadal variations in the Southern Ocean carbon sink suggest a rather dynamic ocean carbon cycle that varies more in time than previously recognized

    The cohesin ring concatenates sister DNA molecules

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    Sister chromatid cohesion, which is essential for mitosis, is mediated by a multi-subunit protein complex called cohesin whose Scc1, Smc1, and Smc3 subunits form a tripartite ring structure. It has been proposed that cohesin holds sister DNAs together by trapping them inside its ring. To test this, we used site-specific cross-linking to create chemical connections at the three interfaces between the ring’s three constituent polypeptides, thereby creating covalently closed cohesin rings. As predicted by the ring entrapment model, this procedure produces dimeric DNA/cohesin structures that are resistant to protein denaturation. We conclude that cohesin rings concatenate individual sister minichromosome DNAs

    The Role of Gamma-Band Activity in the Representation of Faces: Reduced Activity in the Fusiform Face Area in Congenital Prosopagnosia

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    Congenital prosopagnosia (CP) describes an impairment in face processing that is presumably present from birth. The neuronal correlates of this dysfunction are still under debate. In the current paper, we investigate high-frequent oscillatory activity in response to faces in persons with CP. Such neuronal activity is thought to reflect higher-level representations for faces.Source localization of induced Gamma-Band Responses (iGBR) measured by magnetoencephalography (MEG) was used to establish the origin of oscillatory activity in response to famous and unknown faces which were presented in upright and inverted orientation. Persons suffering from congenital prosopagnosia (CP) were compared to matched controls.Corroborating earlier research, both groups revealed amplified iGBR in response to upright compared to inverted faces predominately in a time interval between 170 and 330 ms and in a frequency range from 50-100 Hz. Oscillatory activity upon known faces was smaller in comparison to unknown faces, suggesting a "sharpening" effect reflecting more efficient processing for familiar stimuli. These effects were seen in a wide cortical network encompassing temporal and parietal areas involved in the disambiguation of homogenous stimuli such as faces, and in the retrieval of semantic information. Importantly, participants suffering from CP displayed a strongly reduced iGBR in the left fusiform area compared to control participants.In sum, these data stress the crucial role of oscillatory activity for face representation and demonstrate the involvement of a distributed occipito-temporo-parietal network in generating iGBR. This study also provides the first evidence that persons suffering from an agnosia actually display reduced gamma band activity. Finally, the results argue strongly against the view that oscillatory activity is a mere epiphenomenon brought fourth by rapid eye-movements (micro saccades)

    Consistency and Challenges in the Ocean Carbon Sink Estimate for the Global Carbon Budget

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    Based on the 2019 assessment of the Global Carbon Project, the ocean took up on average, 2.5 ± 0.6 PgC yr−1 or 23 ± 5% of the total anthropogenic CO2 emissions over the decade 2009–2018. This sink estimate is based on simulation results from global ocean biogeochemical models (GOBMs) and is compared to data-products based on observations of surface ocean pCO2 (partial pressure of CO2) accounting for the outgassing of river-derived CO2. Here we evaluate the GOBM simulations by comparing the simulated surface ocean pCO2 to observations. Based on this comparison, the simulations are well-suited for quantifying the global ocean carbon sink on the time-scale of the annual mean and its multi-decadal trend (RMSE <20 ÎŒatm), as well as on the time-scale of multi-year variability (RMSE <10 ÎŒatm), despite the large model-data mismatch on the seasonal time-scale (RMSE of 20–80 ÎŒatm). Biases in GOBMs have a small effect on the global mean ocean sink (0.05 PgC yr−1), but need to be addressed to improve the regional budgets and model-data comparison. Accounting for non-mapped areas in the data-products reduces their spread as measured by the standard deviation by a third. There is growing evidence and consistency among methods with regard to the patterns of the multi-year variability of the ocean carbon sink, with a global stagnation in the 1990s and an extra-tropical strengthening in the 2000s. GOBMs and data-products point consistently to a shift from a tropical CO2 source to a CO2 sink in recent years. On average, the GOBMs reveal less variations in the sink than the data-based products. Despite the reasonable simulation of surface ocean pCO2 by the GOBMs, there are discrepancies between the resulting sink estimate from GOBMs and data-products. These discrepancies are within the uncertainty of the river flux adjustment, increase over time, and largely stem from the Southern Ocean. Progress in our understanding of the global ocean carbon sink necessitates significant advancement in modeling and observing the Southern Ocean carbon sink including (i) a game-changing increase in high-quality pCO2 observations, and (ii) a critical re-evaluation of the regional river flux adjustment

    A statistical gap-filling method to interpolate global monthly surface ocean carbon dioxide data

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    We have developed a statistical gap-ïŹlling method adapted to the speciïŹc coverage and prop-erties of observed fugacity of surface ocean CO2(fCO2). We have used this method to interpolate the Sur-face Ocean CO2Atlas (SOCAT) v2 database on a 2.5832.58 global grid (south of 708N) for 1985–2011 atmonthly resolution. The method combines a spatial interpolation based on a ‘‘radius of inïŹ‚uence’’ to deter-mine nearby similar fCO2values with temporal harmonic and cubic spline curve-ïŹtting, and also ïŹts long-term trends and seasonal cycles. Interannual variability is established using deviations of observations fromthe ïŹtted trends and seasonal cycles. An uncertainty is computed for all interpolated values based on thespatial and temporal range of the interpolation. Tests of the method using model data show that it performsas well as or better than previous regional interpolation methods, but in addition it provides a near-globaland interannual coverage

    Evaluation of the third- and fourth-generation GOCE Earth gravity field models with Australian terrestrial gravity data in spherical harmonics

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    In March 2013 the fourth generation of ESA’s (European Space Agency) global gravity field models, DIR4 (Bruinsma et al, 2010b) and TIM4 (Pail et al, 2010), generated from the GOCE (Gravity field and steady-state Ocean Circulation Explorer) gravity observation satellite were released. We evaluate the models using an independent ground truth data set of gravity anomalies over Australia. Combined with GRACE (Gravity Recovery and Climate Experiment) satellite gravity, a new gravity model is obtained that is used to perform comparisons with GOCE models in spherical harmonics. Over Australia, the new gravity model proves to have significantly higher accuracy in the degrees below 120 as compared to EGM2008 and seems to be at least comparable to the accuracy of this model between degree 150 and degree 260. Comparisons in terms of residual quasi-geoid heights, gravity disturbances, and radial gravity gradients evaluated on the ellipsoid and at approximate GOCE mean satellite altitude (h=250 km) show both fourth generation models to improve significantly w.r.t. their predecessors.Relatively, we find a root-mean-square improvement of 39 % for the DIR4 and 23 % for TIM4 over the respective third release models at a spatial scale of 100 km (degree 200). In terms of absolute errors TIM4 is found to perform slightly better in the bands from degree 120 up to degree 160 and DIR4 is found to perform slightly better than TIM4 from degree 170 up to degree 250. Our analyses cannot confirm the DIR4 formal error of 1 cm geoid height (0.35 mGal in terms of gravity) at degree 200. The formal errors of TIM4, with 3.2 cm geoid height (0.9 mGal in terms of gravity) at degree 200, seem to be realistic. Due to combination with GRACE and SLR data, the DIR models, at satellite altitude, clearly show lower RMS values compared to TIM models in the long wavelength part of the spectrum (below degree and order 120). Our study shows different spectral sensitivity of different functionals at ground level and at GOCE satellite altitude and establishes the link among these findings and the Meissl scheme (Rummel and van Gelderen in Manuscripta Geodaetica 20:379–385, 1995)
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