Dynamic simulations of water at constant chemical potential

The grand molecular dynamics (GMD) method has been extended and applied to examine the density dependence of the chemical potential of a three-site water model. The method couples a classical system to a chemical potential reservoir of particles via an ansatz Lagrangian. Equilibrium properties such as structure and thermodynamics, as well as dynamic properties such as time correlations and diffusion constants, in open systems at a constant chemical potential, are preserved with this method. The average number of molecules converges in a reasonable amount of computational effort and provides a way to estimate the chemical potential of a given model force field

Lumped mass modelling for the dynamic analysis of aircraft structures

Aircraft structures may be modelled by lumping the masses at particular strategic points and the flexibility or stiffness of the structure is obtained with reference to these points. Equivalent moments of inertia for the section at these positions are determined. The lumped masses are calculated based on the assumption that each point will represent the mass spread on one half of the space on each side. Then these parameters are used in the differential equation of motion and the eigen characteristics are determined. A comparison is made with results obtained by other established methods. The lumped mass approach in the dynamic analysis of complicated structures provides an easier means of predicting the dynamic characteristics of these structures. It involves less computer time and avoids computational errors that are inherent in the numerical solution of complicated systems

Lignin biomarkers as tracers of mercury sources in lakes water column

This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems

The effectiveness of anaerobic digestion in removing estrogens and nonylphenol ethoxylates

This is the post-print version of the final paper published in Journal of Hazardous Materials. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2011 Elsevier B.V.The fate and behaviour of two groups of endocrine disrupting chemicals, steroid estrogens and nonylphenol ethoxylates, have been evaluated during the anaerobic digestion of primary and mixed sewage sludge under mesophilic and thermophilic conditions. Digestion occurred over six retention times, in laboratory scale reactors, treating sludges collected from a sewage treatment works in the United Kingdom. It has been established that sludge concentrations of both groups of compounds demonstrated temporal variations and that concentrations in mixed sludge were influenced by the presence of waste activated sludge as a result of transformations during aerobic treatment. The biodegradation of total steroid estrogens was >50% during primary sludge digestion with lower removals observed for mixed sludge, which reflected bulk organic solids removal efficiencies. The removal of nonylphenol ethoxylates was greater in mixed sludge digestion (>58%) compared with primary sludge digestion and did not reflect bulk organic removal efficiencies. It is apparent that anaerobic digestion reduces the concentrations of these compounds, and would therefore be expected to confer a degree of protection against exposure and transfer of both groups of compounds to the receiving/re-use environment.Thames Water, Yorkshire Water, and EPSRC

HDAC1 regulates pluripotency and lineage specific transcriptional networks in embryonic and trophoblast stem cells

Epigenetic regulation of gene expression is important in maintaining self-renewal of embryonic stem (ES) and trophoblast stem (TS) cells. Histone deacetylases (HDACs) negatively control histone acetylation by removing covalent acetylation marks from histone tails. Because histone acetylation is a known mark for active transcription, HDACs presumably associate with inactive genes. Here, we used genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES and TS cells. Through evaluation of genes associated with acetylated histone H3 marks, and global expression analysis of Hdac1 knockout ES and trichostatin A-treated ES and TS cells, we found that HDAC1 occupies mainly active genes, including important regulators of ES and TS cells self-renewal. We also observed occupancy of methyl-CpG binding domain protein 3 (MBD3), a subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex, at a subset of HDAC1-occupied sequences in ES cells, including the pluripotency regulators Oct4, Nanog and Kfl4. By mapping HDAC1 targets on a global scale, our results describe further insight into epigenetic mechanisms of ES and TS cells self-renewal

Atmospheric chemosynthesis is phylogenetically and geographically widespread and contributes significantly to carbon fixation throughout cold deserts

Cold desert soil microbiomes thrive despite severe moisture and nutrient limitations. In Eastern Antarctic soils, bacterial primary production is supported by trace gas oxidation and the light-independent RuBisCO form IE. This study aims to determine if atmospheric chemosynthesis is widespread within Antarctic, Arctic and Tibetan cold deserts, to identify the breadth of trace gas chemosynthetic taxa and to further characterize the genetic determinants of this process. H2 oxidation was ubiquitous, far exceeding rates reported to fulfill the maintenance needs of similarly structured edaphic microbiomes. Atmospheric chemosynthesis occurred globally, contributing significantly (p < 0.05) to carbon fixation in Antarctica and the high Arctic. Taxonomic and functional analyses were performed upon 18 cold desert metagenomes, 230 dereplicated medium-to-high-quality derived metagenome-assembled genomes (MAGs) and an additional 24,080 publicly available genomes. Hydrogenotrophic and carboxydotrophic growth markers were widespread. RuBisCO IE was discovered to co-occur alongside trace gas oxidation enzymes in representative Chloroflexota, Firmicutes, Deinococcota and Verrucomicrobiota genomes. We identify a novel group of high-affinity [NiFe]-hydrogenases, group 1m, through phylogenetics, gene structure analysis and homology modeling, and reveal substantial genetic diversity within RuBisCO form IE (rbcL1E), and high-affinity 1h and 1l [NiFe]-hydrogenase groups. We conclude that atmospheric chemosynthesis is a globally-distributed phenomenon, extending throughout cold deserts, with significant implications for the global carbon cycle and bacterial survival within environmental reservoirs

Uncontrolled Self-Medication with Venlafaxine in a Patient with Major Depressive Disorder

Antidepressants are known to have no significant ability to cause addiction. However, a recent study showed many individuals with mood disorders self-medicated with antidepressants to relieve symptoms. We report here a male physician, diagnosed five years ago with major depressive disorder, with insomnia, anxiousness, and chest heaviness. He began self-medicating with 150 mg of venlafaxine daily, without any monitoring. During his most recent severe depressive episode, he was taking up to 1,500 mg of venlafaxine daily. Without this medication, he experienced discontinuation syndrome, which included severe anxiety, chest heaviness, and breathing difficulty, and which he judged as indicating a more severely depressed state. He also experienced overdose symptoms, such as hypertension and tachycardia. He attempted suicide with drugs that he possessed. In conclusion, careful monitoring is needed when treating patients with venlafaxine, because its discontinuation syndrome is similar to symptoms of major depressive disorder, and suicidality may result from an overdose

Simultaneous Colonic Obstruction and Hydroureteronephrosis due to Mesenteric Fibromatosis

Mesenteric fibromatosis (MF) is a rare benign mesenchymal lesion that can occur throughout the gastrointestinal tract, especially small bowel. Its biological behavior is intermediate between benign fibrous tissue proliferation and malignant fibrosarcoma. In previously reported cases of MF, we could find colonic obstruction or ureter obstruction, but simultaneous involvement of colon and ureter was not able to be seen. We described a patient that presented with colonic obstruction and hydroureteronephrosis due to MF at sigmoid colon which mimicked submucosal tumor such as gastrointestinal tumor. This case resulted in a positive positron emission tomography scan suggesting malignant neoplasm, but β-catenin positivity on immunohistochemical staining separated MF from gastrointestinal stromal tumor and sclerosing mesenteritis. The clinical course of the patient was improved after surgical resection

DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo.

Resistance to VEGF inhibitors is emerging as a major clinical problem. Notch signaling has been implicated in tumor angiogenesis. Therefore, to investigate mechanisms of resistance to angiogenesis inhibitors, we transduced human glioblastoma cells with retroviruses encoding Notch delta-like ligand 4 (DLL4), grew them as tumor xenografts and then treated the murine hosts with the VEGF-A inhibitor bevacizumab. We found that DLL4-mediated tumor resistance to bevacizumab in vivo. The large vessels induced by DLL4-Notch signaling increased tumor blood supply and were insensitive to bevacizumab. However, blockade of Notch signaling by dibenzazepine, a γ-secretase inhibitor, disrupted the large vessels and abolished the tumor resistance. Multiple molecular mechanisms of resistance were shown, including decreased levels of hypoxia-induced VEGF and increased levels of the VEGF receptor VEGFR1 in the tumor stroma, decreased levels of VEGFR2 in large blood vessels, and reduced levels of VEGFR3 overall. DLL4-expressing tumors were also resistant to a VEGFR targeting multikinase inhibitor. We also observed activation of other pathways of tumor resistance driven by DLL4-Notch signaling, including the FGF2-FGFR and EphB4-EprinB2 pathways, the inhibition of which reversed tumor resistance partially. Taken together, our findings show the importance of classifying mechanisms involved in angiogenesis in tumors, and how combination therapy to block DLL4-Notch signaling may enhance the efficacy of VEGF inhibitors, particularly in DLL4-upregulated tumors, and thus provide a rational base for the development of novel strategies to overcome antiangiogenic resistance in the clinic