5,813 research outputs found

    Towards automation of chemical process route selection based on data mining

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    A methodology for chemical routes development and evaluation on the basis of data-mining is presented.This work was in part funded by EPSRC project “Terpene-based manufacturing for sustainable chemical feedstocks” EP/K014889

    Arsenic removal from natural groundwater using ‘green rust’: Solid phase stability and contaminant fate

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    Arsenic (As) contamination in groundwater remains a pressing global challenge. In this study, we evaluated the potential of green rust (GR), a redox-active iron phase frequently occurring in anoxic environments, to treat As contamination at a former wood preservation site. We performed long-term batch experiments by exposing synthetic GR sulfate (GRSO4) to As-free and As-spiked (6 mg L−1) natural groundwater at both 25 and 4 °C. At 25 °C, GRSO4 was metastable in As-free groundwater and transformed to GRCO3, and then fully to magnetite within 120 days; however, GRSO4 stability increased 7-fold by lowering the temperature to 4 °C, and 8-fold by adding As to the groundwater at 25 °C. Highest GRSO4 stability was observed when As was added to the groundwater at 4 °C. This stabilizing effect is explained by GR solubility being lowered by adsorbed As and/or lower temperatures, inhibiting partial GR dissolution required for transformation to GRCO3, and ultimately to magnetite. Despite these mineral transformations, all added As was removed from As-spiked samples within 120 days at 25 °C, while uptake was 2 times slower at 4 °C. Overall, we have successfully documented that GR is an important mineral substrate for As immobilization in anoxic subsurface environments

    An adaptive observer-based controller design for active damping of a DC network with a constant power load

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    This article explores a nonlinear, adaptive controller aimed at increasing the stability margin of a direct-current (dc), small-scale, electrical network containing an unknown constant power load (CPL). Due to its negative incremental impedance, this load reduces the effective damping of the network, which may lead to voltage oscillations and even to voltage collapse. To overcome this drawback, we consider the incorporation of a controlled dc-dc power converter in parallel with the CPL. The design of the control law for the converter is particularly challenging due to the existence of unmeasured states and unknown parameters. We propose a standard input-output linearization stage, to which a suitably tailored adaptive observer is added. The good performance of the controller is validated through experiments on a small-scale network

    C-type natriuretic peptide is a pivotal regulator of metabolic homeostasis

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    Thermogenesis and adipogenesis are tightly regulated mechanisms that maintain lipid homeostasis and energy balance; dysfunction of these critical processes underpins obesity and contributes to cardiometabolic disease. C-type natriuretic peptide (CNP) fulfills a multimodal protective role in the cardiovascular system governing local blood flow, angiogenesis, cardiac function, and immune cell reactivity. Herein, we investigated a parallel, preservative function for CNP in coordinating metabolic homeostasis. Global inducible CNP knockout mice exhibited reduced body weight, higher temperature, lower adiposity, and greater energy expenditure in vivo. This thermogenic phenotype was associated with increased expression of uncoupling protein-1 and preferential lipid utilization by mitochondria, a switch corroborated by a corresponding diminution of insulin secretion and glucose clearance. Complementary studies in isolated murine and human adipocytes revealed that CNP exerts these metabolic regulatory actions by inhibiting sympathetic thermogenic programming via G(i)-coupled natriuretic peptide receptor (NPR)-C and reducing peroxisome proliferator-activated receptor-γ coactivator-1α expression, while concomitantly driving adipogenesis via NPR-B/protein kinase-G. Finally, we identified an association between CNP/NPR-C expression and obesity in patient samples. These findings establish a pivotal physiological role for CNP as a metabolic switch to balance energy homeostasis. Pharmacological targeting of these receptors may offer therapeutic utility in the metabolic syndrome and related cardiovascular disorders

    Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells

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    Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification

    Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

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    Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

    Pharmacology of airways and vessels in lung slices in situ: role of endogenous dilator hormones

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    Small airway and vessels play a critical role in chronic airway and pulmonary vascular diseases, but their pharmacology has not been well characterised. We have studied airway and vascular responses in rat lung slices and separately in vitro using myography. In lung slices, under basal conditions, acetylcholine contracted airways, but had no vascular effect. The thromboxane mimetic, U46619 contracted both vessels and airways. In the presence of U46619, acetylcholine dilated vessels, but further contracted airways, an effect that was blocked by the nitric oxide synthase inhibitor L-N(G)-nitro-L-arginine or apamin plus charybdotoxin, which inhibit endothelial-derived hyperpolarising factor. Airway responses in lung slices were unaffected by L-N(G)nitro-L-arginine methyl ester, indomethacin or apamin plus charybdotoxin. By contrast, apamin plus charybdotoxin contracted bronchi studied in isolation. Our observations are the first to identify mechanisms of endothelium dependent dilations in precision cut lung slices and the potential for transverse hormonal communication between airways and vessels

    Design of a fuzzy PID controller for a MEMS tunable capacitor for noise reduction in a voltage reference source

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    This study presents a conventional Ziegler-Nichols (ZN) Proportional Integral Derivative (PID) controller, having reviewed the mathematical modeling of the Micro Electro Mechanical Systems (MEMS) Tunable Capacitors (TCs), and also proposes a fuzzy PID controller which demonstrates a better tracking performance in the presence of measurement noise, in comparison with conventional ZN-based PID controllers. Referring to importance and impact of this research, the proposed controller takes advantage of fuzzy control properties such as robustness against noise. TCs are responsible for regulating the reference voltage when integrated into Alternating Current (AC) Voltage Reference Sources (VRS). Capacitance regulation for tunable capacitors in VRS is carried out by modulating the distance of a movable plate. A successful modulation depends on maintaining the stability around the pull-in point. This distance regulation can be achieved by the proposed controller which guarantees the tracking performance of the movable plate in moving towards the pull-in point, and remaining in this critical position. The simulation results of the tracking performance and capacitance tuning are very promising, subjected to measurement noise. Article Highlights This article deals with MEMS tunable capacitor dynamics and modeling, considering measurement noise. It designs and applies fuzzy PID control system for regulating MEMS voltage reference output. This paper contributes to robustness increase in pull-in performance of the tunable capacitor

    FINAL REPORT DETERMINATION OF THE PROCESSING RATE OF RPP WTP HLW SIMULANTS USING A DURAMELTER J 1000 VITRIFICATION SYSTEM VSL-00R2590-2 REV 0 8/21/00

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    This report provides data, analysis, and conclusions from a series of tests that were conducted at the Vitreous State Laboratory of The Catholic University of America (VSL) to determine the melter processing rates that are achievable with RPP-WTP HLW simulants. The principal findings were presented earlier in a summary report (VSL-00R2S90-l) but the present report provides additional details. One of the most critical pieces of information in determining the required size of the RPP-WTP HLW melter is the specific glass production rate in terms of the mass of glass that can be produced per unit area of melt surface per unit time. The specific glass production rate together with the waste loading (essentially, the ratio of waste-in to glass-out, which is determined from glass formulation activities) determines the melt area that is needed to achieve a given waste processing rate with due allowance for system availability. As a consequence of the limited amount of relevant information, there exists, for good reasons, a significant disparity between design-base specific glass production rates for the RPP-WTP LAW and HLW conceptual designs (1.0 MT/m{sup 2}/d and 0.4 MT/m{sup 2}/d, respectively); furthermore, small-scale melter tests with HLW simulants that were conducted during Part A indicated typical processing rates with bubbling of around 2.0 MT/m{sup 2}/d. This range translates into more than a factor of five variation in the resultant surface area of the HLW melter, which is clearly not without significant consequence. It is clear that an undersized melter is undesirable in that it will not be able to support the required waste processing rates. It is less obvious that there are potential disadvantages associated with an oversized melter, over and above the increased capital costs. A melt surface that is consistently underutilized will have poor cold cap coverage, which will result in increased volatilization from the melt (which is generally undesirable) and increased plenum temperatures due to increased thermal radiation from the melt surface (which mayor may not be desirable but the flexibility to choose may be lost). Increased volatilization is an issue both in terms of the increased challenge to the off-gas system as well as for the ability to effectively close the recycle loops for volatile species that must be immobilized in the glass product, most notably technetium and cesium. For these reasons, improved information is needed on the specific glass production rates of RPP-WTP HLW streams in DuraMelterJ systems over a range of operating conditions. Unlike the RPP-WTP LAW program, for which a pilot melter system to provide large-scale throughout information is already in operation, there is no comparable HLW activity; the results of the present study are therefore especially important. This information will reduce project risk by reducing the uncertainty associated with the amount of conservatism that mayor may not be associated with the baseline RPP-WTP HLW melter sizing decision. After the submission of the first Test Plan for this work, the RPP-WTP requested revisions to include tests to determine the processing rates that are achievable without bubbling, which was driven by the potential advantages of omitting bubblers from the HLW melter design in terms of reduced maintenance. A further objective of this effort became the determination of whether the basis of design processing rate could be achieved without bubbling. Ideally, processing rate tests would be conducted on a full-scale RPP-WTP melter system with actual HLW materials, but that is clearly unrealistic during Part B1. As a practical compromise the processing rate determinations were made with HL W simulants on a DuraMelter J system at as close to full scale as possible and the DM 1000 system at VSL was selected for that purpose. That system has a melt surface area of 1.2 m{sup 2}, which corresponds to about one-third scale based on the specific glass processing rate of 0.4 MT/m{sup 2}/d assumed in the RPP-WTP HLW conceptual design, but would correspond to larger than full scale if the typical Part A test results of about 2.0 MT/m{sup 2}/d were realized. The DM 1000 system was used with the existing off-gas treatment system in order to expedite the collection of this information; while that system is somewhat different from the RPP-WTP conceptual design, that should have no effect on the processing rate measurements. Subsequent tasks supported the later modification of that off-gas system to obtain large-scale system performance information on the baseline off-gas design and those modifications are now complete. Work planned for Part B2 includes similar pilot-scale testing with the prototypical off-gas system. Three HLW simulant compositions were used in the present tests: the tank AZ-101 waste (the first B2 HLW feed to the RPP-WTP), the 106-C/AY-102 blend (the largest B2 HLW tank), and the HLW composition processed at West Valley

    Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

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    We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.Fil: Goncearenco, Alexander. National Institutes of Health; Estados UnidosFil: Li, Minghui. Soochow University; China. National Institutes of Health; Estados UnidosFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂ­micas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂ­micas de Buenos Aires; ArgentinaFil: Shoemaker, Benjamin A. National Institutes of Health; Estados UnidosFil: Panchenko, Anna R. National Institutes of Health; Estados Unido
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