990 research outputs found

    Density fluctuations following fuel pellet injection on the Alcator C tokamak

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    Why Your Secretary Is Really Worth a Million Dollars: Exploring the Harsh Penalty for Not Proofreading Your Fee Agreements in Anglo-Dutch Petroleum v. Greenberg Peden.

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    This Article examines the Texas Supreme Court\u27s decision in Anglo-Dutch Petroleum International, Inc. v. Greenberg Peden, P.C. Next, this Article discusses the decision in light of other cases dealing with attorney-client contract issues. Then, an explanation of why the court\u27s decision is inconsistent with other opinions is provided. This Article next analyzes the long-term effects of the Anglo-Dutch decision and the lessons to be learned from the case about drafting contracts and lawyers\u27 obligations to inform clients of material terms. Finally, this Article suggests that the court\u27s decision decreases the legal protection extended to lawyers and holds them closer to a strict-scrutiny standard regarding candor, while encouraging predatory conduct by clients

    Collapsing granular suspensions

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    A 2D contact dynamics model is proposed as a microscopic description of a collapsing suspension/soil to capture the essential physical processes underlying the dynamics of generation and collapse of the system. Our physical model is compared with real data obtained from in situ measurements performed with a natural collapsing/suspension soil. We show that the shear strength behavior of our collapsing suspension/soil model is very similar to the behavior of this collapsing suspension soil, for both the unperturbed and the perturbed phases of the material.Comment: 7 pages, 5 figures, accepted for publication in EPJ

    Sequence comparisons of cytochrome P450 aromatases from Australian animals predict differences in enzymatic activity and/or efficiency

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    Aromatase (P450arom, CYP19A1) is the terminal enzyme in the synthesis of the steroid hormone family of estrogens. Not surprisingly, this enzyme has structural similarities between the limited number of species studied thus far. This study examined the structure of aromatases from four diverse Australian species including a marsupial (tammar wallaby; Macropus eugenii), monotreme (platypus; Ornithorhynchus anatinus), ratite (emu; Dromaius novaehollandiae) and lizard (bearded dragon; Pogona vitticeps). We successfully built homology models for each species, using the only crystallographically determined structure available, human aromatase. The amino acid sequences showed high amino acid sequence identity to the human aromatase: wallaby 81%, platypus 73%, emu 75% and bearded dragon at 74%. The overall structure was highly conserved among the five species, although there were non-secondary structures (loops and bends) that were variable and flexible that may result in some differences in catalytic activity. At the N-terminal regions there were deletions and variations that suggest functional distinctions may be found. We found that the active sites of all these proteins were identical, except for a slight variation in the emu. The electrostatic potential across the surfaces of these aromatases highlighted likely variations to the protein-protein interactions of these enzymes with both redox partner cytochrome P450 reductase and possibly homodimerization in the case of the platypus, which has been postulated for the human aromatase enzyme. Given the high natural selection pressures on reproductive strategies the relatively high degree of conservation of aromatase sequence and structure across species suggests that there is biochemically very little scope for changes to have evolved without the loss of enzyme activity.Anam Fatima, Jessica K. Holien, Chandni Tiwari, Michael W. Parker, Raymond J. Rodgers and Lisandra L. Marti

    Uncertainty in Signals of Large-Scale Climate Variations in Radiosonde and Satellite Upper-Air Temperature Datasets

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    There is no single reference dataset of long-term global upper-air temperature observations, although several groups have developed datasets from radiosonde and satellite observations for climate-monitoring purposes. The existence of multiple data products allows for exploration of the uncertainty in signals of climate variations and change. This paper examines eight upper-air temperature datasets and quantifies the magnitude and uncertainty of various climate signals, including stratospheric quasi-biennial oscillation (QBO) and tropospheric ENSO signals, stratospheric warming following three major volcanic eruptions, the abrupt tropospheric warming of 1976–77, and multidecadal temperature trends. Uncertainty estimates are based both on the spread of signal estimates from the different observational datasets and on the inherent statistical uncertainties of the signal in any individual dataset. The large spread among trend estimates suggests that using multiple datasets to characterize large-scale upperair temperature trends gives a more complete characterization of their uncertainty than reliance on a single dataset. For other climate signals, there is value in using more than one dataset, because signal strengths vary. However, the purely statistical uncertainty of the signal in individual datasets is large enough to effectively encompass the spread among datasets. This result supports the notion of an 11th climate-monitoring principle, augmenting the 10 principles that have now been generally accepted (although not generally implemented) by the climate community. This 11th principle calls for monitoring key climate variables with multiple, independent observing systems for measuring the variable, and multiple, independent groups analyzing the data

    A Monolayer of Primary Colonic Epithelium Generated on a Scaffold with a Gradient of Stiffness for Drug Transport Studies

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    Animal models are frequently used for in vitro physiologic and drug transport studies of the colon, but there exists significant pressure to improve assay throughput as well as to achieve tighter control of experimental variables than can be achieved with animals. Thus, development of a primary in vitro colonic epithelium cultured as high resistance with transport protein expression and functional behavior similar to that of a native colonic would be of enormous value for pharmaceutical research. A collagen scaffold, in which the degree of collagen cross-linking was present as a gradient, was developed to support the proliferation of primary colonic cells. The gradient of cross-linking created a gradient in stiffness across the scaffold, enabling the scaffold to resist deformation by cells. mRNA expression and quantitative proteomic mass spectrometry of cells growing on these surfaces as a monolayer suggested that the transporters present were similar to those in vivo. Confluent monolayers acted as a barrier to small molecules so that drug transport studies were readily performed. Transport function was evaluated using atenolol (a substrate for passive paracellular transport), propranolol (a substrate for passive transcellular transport), rhodamine 123 (Rh123, a substrate for P-glycoprotein), and riboflavin (a substrate for solute carrier transporters). Atenolol was poorly transported with an apparent permeability (Papp) of < 5 Ă— 10-7 cm s-1, while propranolol demonstrated a Papp of 9.69 Ă— 10-6 cm s-1. Rh123 was transported in a luminal direction (Papp,efflux/Papp,influx = 7) and was blocked by verapamil, a known inhibitor of P-glycoprotein. Riboflavin was transported in a basal direction, and saturation of the transporter was observed at high riboflavin concentrations as occurs in vivo. It is anticipated that this platform of primary colonic epithelium will find utility in drug development and physiological studies, since the tissue possesses high integrity and active transporters and metabolism similar to that in vivo

    Condensate cosmology -- dark energy from dark matter

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    Imagine a scenario in which the dark energy forms via the condensation of dark matter at some low redshift. The Compton wavelength therefore changes from small to very large at the transition, unlike quintessence or metamorphosis. We study CMB, large scale structure, supernova and radio galaxy constraints on condensation by performing a 4 parameter likelihood analysis over the Hubble constant and the three parameters associated with Q, the condensate field: Omega_Q, w_f and z_t (energy density and equation of state today, and redshift of transition). Condensation roughly interpolates between Lambda CDM (for large z_t) and sCDM (low z_t) and provides a slightly better fit to the data than Lambda CDM. We confirm that there is no degeneracy in the CMB between H and z_t and discuss the implications of late-time transitions for the Lyman-alpha forest. Finally we discuss the nonlinear phase of both condensation and metamorphosis, which is much more interesting than in standard quintessence models.Comment: 13 pages, 13 colour figures. Final version with discussion of TE cross-correlation spectra for condensation and metamorphosis in light of the WMAP result

    Prevalence and 1-year incidence of frailty among women with and without HIV in the Women's Interagency HIV Study

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    A previous cross-sectional analysis of 2028 women in the Women’s Interagency HIV Study (WIHS), who were on average 39 years old, found a frailty prevalence of 17% and 10% in women with or at risk for HIV, respectively [1]. To our knowledge, the only two longitudinal studies of frailty among people with HIV were conducted in the Multicenter AIDS Cohort Study (MACS), which includes only men [2,3]. Data on the distribution of frailty components are limited, and have not been reported for HIV-seropositive people in the United State

    Overexpression of miRNA-25-3p inhibits Notch1 signaling and TGF-β-induced collagen expression in hepatic stellate cells

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    During chronic liver injury hepatic stellate cells (HSCs), the principal source of extracellular matrix in the fibrotic liver, transdifferentiate into pro-fibrotic myofibroblast-like cells - a process potentially regulated by microRNAs (miRNAs). Recently, we found serum miRNA-25-3p (miR-25) levels were upregulated in children with Cystic Fibrosis (CF) without liver disease, compared to children with CF-associated liver disease and healthy individuals. Here we examine the role of miR-25 in HSC biology. MiR-25 was detected in the human HSC cell line LX-2 and in primary murine HSCs, and increased with culture-induced activation. Transient overexpression of miR-25 inhibited TGF-β and its type 1 receptor (TGFBR1) mRNA expression, TGF-β-induced Smad2 phosphorylation and subsequent collagen1α1 induction in LX-2 cells. Pull-down experiments with biotinylated miR-25 revealed Notch signaling (co-)activators ADAM-17 and FKBP14 as miR-25 targets in HSCs. NanoString analysis confirmed miR-25 regulation of Notch- and Wnt-signaling pathways. Expression of Notch signaling pathway components and endogenous Notch1 signaling was downregulated in miR-25 overexpressing LX-2 cells, as were components of Wnt signaling such as Wnt5a. We propose that miR-25 acts as a negative feedback anti-fibrotic control during HSC activation by reducing the reactivity of HSCs to TGF-β-induced collagen expression and modulating the cross-talk between Notch, Wnt and TGF-β signaling

    Science Development

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68479/2/10.1177_107554708500600404.pd
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