69 research outputs found

    Semilinear mixed problems on Hilbert complexes and their numerical approximation

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    Arnold, Falk, and Winther recently showed [Bull. Amer. Math. Soc. 47 (2010), 281-354] that linear, mixed variational problems, and their numerical approximation by mixed finite element methods, can be studied using the powerful, abstract language of Hilbert complexes. In another recent article [arXiv:1005.4455], we extended the Arnold-Falk-Winther framework by analyzing variational crimes (a la Strang) on Hilbert complexes. In particular, this gave a treatment of finite element exterior calculus on manifolds, generalizing techniques from surface finite element methods and recovering earlier a priori estimates for the Laplace-Beltrami operator on 2- and 3-surfaces, due to Dziuk [Lecture Notes in Math., vol. 1357 (1988), 142-155] and later Demlow [SIAM J. Numer. Anal., 47 (2009), 805-827], as special cases. In the present article, we extend the Hilbert complex framework in a second distinct direction: to the study of semilinear mixed problems. We do this, first, by introducing an operator-theoretic reformulation of the linear mixed problem, so that the semilinear problem can be expressed as an abstract Hammerstein equation. This allows us to obtain, for semilinear problems, a priori solution estimates and error estimates that reduce to the Arnold-Falk-Winther results in the linear case. We also consider the impact of variational crimes, extending the results of our previous article to these semilinear problems. As an immediate application, this new framework allows for mixed finite element methods to be applied to semilinear problems on surfaces.Comment: 22 pages; v2: major revision, particularly sharpening of error estimates in Section

    Unital Quantum Channels - Convex Structure and Revivals of Birkhoff's Theorem

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    The set of doubly-stochastic quantum channels and its subset of mixtures of unitaries are investigated. We provide a detailed analysis of their structure together with computable criteria for the separation of the two sets. When applied to O(d)-covariant channels this leads to a complete characterization and reveals a remarkable feature: instances of channels which are not in the convex hull of unitaries can return to it when either taking finitely many copies of them or supplementing with a completely depolarizing channel. In these scenarios this implies that a channel whose noise initially resists any environment-assisted attempt of correction can become perfectly correctable.Comment: 31 page

    On the Spectral Evolution of Cool, Helium-Atmosphere White Dwarfs: Detailed Spectroscopic and Photometric Analysis of DZ Stars

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    We present a detailed analysis of a large spectroscopic and photometric sample of DZ white dwarfs based on our latest model atmosphere calculations. We revise the atmospheric parameters of the trigonometric parallax sample of Bergeron, Leggett, & Ruiz (12 stars) and analyze 147 new DZ white dwarfs discovered in the Sloan Digital Sky Survey. The inclusion of metals and hydrogen in our model atmosphere calculations leads to different atmospheric parameters than those derived from pure helium models. Calcium abundances are found in the range from log (Ca/He) = -12 to -8. We also find that fits of the coolest objects show peculiarities, suggesting that our physical models may not correctly describe the conditions of high atmospheric pressure encountered in the coolest DZ stars. We find that the mean mass of the 11 DZ stars with trigonometric parallaxes, = 0.63 Mo, is significantly lower than that obtained from pure helium models, = 0.78 Mo, and in much better agreement with the mean mass of other types of white dwarfs. We determine hydrogen abundances for 27% of the DZ stars in our sample, while only upper limits are obtained for objects with low signal-to-noise ratio spectroscopic data. We confirm with a high level of confidence that the accretion rate of hydrogen is at least two orders of magnitude smaller than that of metals (and up to five in some cases) to be compatible with the observations. We find a correlation between the hydrogen abundance and the effective temperature, suggesting for the first time empirical evidence of a lower temperature boundary for the hydrogen screening mechanism. Finally, we speculate on the possibility that the DZA white dwarfs could be the result of the convective mixing of thin hydrogen-rich atmospheres with the underlying helium convection zone.Comment: 67 pages, 32 figures, accepted for publication in Ap

    The chemerin knockout rat reveals chemerin dependence in female, but not male, experimental hypertension

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    Measures of the adipokine chemerin are elevated in multiple cardiovascular diseases, including hypertension, but little mechanistic work has been done to implicate chemerin as being causative in such diseases. The chemerin knockout (KO) rat was created to test the hypothesis that removal of chemerin would reduce pressure in the normal and hypertensive state. Western analyses confirmed loss of chemerin in the plasma and tissues of the KO vs. wild‐type (WT) rats. Chemerin concentration in plasma and tissues was lower in WT females than in WT males, as determined by Western analysis. Conscious male and female KO rats had modest differences in baseline measures vs. the WT that included systolic, diastolic, mean arterial and pulse pressures, and heart rate, all measured telemetrically. The mineralocorticoid deoxycorticosterone acetate (DOCA) and salt water, combined with uninephrectomy as a hypertensive stimulus, elevated mean and systolic blood pressures of the male KO higher than the male WT. By contrast, all pressures in the female KO were lower than their WT throughout DOCA‐salt treatment. These results revealed an unexpected sex difference in chemerin expression and the ability of chemerin to modify blood pressure in response to a hypertensive challenge.—Watts, S. W., Darios, E. S., Mullick, A. E., Garver, H., Saunders, T. L., Hughes, E. D., Filipiak, W. E., Zeidler, M. G., McMullen, N., Sinal, C. J., Kumar, R. K., Ferland, D. J., Fink, G. D. The chemerin knockout rat reveals chemerin dependence in female, but not male, experimental hypertension. FASEB J. 32, 6596–6614 (2018). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154357/1/fsb2fj201800479.pd

    Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology

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    BACKGROUND: Dosimetry for toxicology studies involving carbon nanotubes (CNT) is challenging because of a lack of detailed occupational exposure assessments. Therefore, exposure assessment findings, measuring the mass concentration of elemental carbon from personal breathing zone (PBZ) samples, from 8 U.S.-based multi-walled CNT (MWCNT) manufacturers and users were extrapolated to results of an inhalation study in mice. RESULTS: Upon analysis, an inhalable elemental carbon mass concentration arithmetic mean of 10.6 μg/m(3) (geometric mean 4.21 μg/m(3)) was found among workers exposed to MWCNT. The concentration equates to a deposited dose of approximately 4.07 μg/d in a human, equivalent to 2 ng/d in the mouse. For MWCNT inhalation, mice were exposed for 19 d with daily depositions of 1970 ng (equivalent to 1000 d of a human exposure; cumulative 76 yr), 197 ng (100 d; 7.6 yr), and 19.7 ng (10 d; 0.76 yr) and harvested at 0, 3, 28, and 84 d post-exposure to assess pulmonary toxicity. The high dose showed cytotoxicity and inflammation that persisted through 84 d after exposure. The middle dose had no polymorphonuclear cell influx with transient cytotoxicity. The low dose was associated with a low grade inflammatory response measured by changes in mRNA expression. Increased inflammatory proteins were present in the lavage fluid at the high and middle dose through 28 d post-exposure. Pathology, including epithelial hyperplasia and peribronchiolar inflammation, was only noted at the high dose. CONCLUSION: These findings showed a limited pulmonary inflammatory potential of MWCNT at levels corresponding to the average inhalable elemental carbon concentrations observed in U.S.-based CNT facilities and estimates suggest considerable years of exposure are necessary for significant pathology to occur at that level

    Candida albicans AGE3, the Ortholog of the S. cerevisiae ARF-GAP-Encoding Gene GCS1, Is Required for Hyphal Growth and Drug Resistance

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    BACKGROUND: Hyphal growth and multidrug resistance of C. albicans are important features for virulence and antifungal therapy of this pathogenic fungus. METHODOLOGY/PRINCIPAL FINDINGS: Here we show by phenotypic complementation analysis that the C. albicans gene AGE3 is the functional ortholog of the yeast ARF-GAP-encoding gene GCS1. The finding that the gene is required for efficient endocytosis points to an important functional role of Age3p in endosomal compartments. Most C. albicans age3Delta mutant cells which grew as cell clusters under yeast growth conditions showed defects in filamentation under different hyphal growth conditions and were almost completely disabled for invasive filamentous growth. Under hyphal growth conditions only a fraction of age3Delta cells shows a wild-type-like polarization pattern of the actin cytoskeleton and lipid rafts. Moreover, age3Delta cells were highly susceptible to several unrelated toxic compounds including antifungal azole drugs. Irrespective of the AGE3 genotype, C-terminal fusions of GFP to the drug efflux pumps Cdr1p and Mdr1p were predominantly localized in the plasma membrane. Moreover, the plasma membranes of wild-type and age3Delta mutant cells contained similar amounts of Cdr1p, Cdr2p and Mdr1p. CONCLUSIONS/SIGNIFICANCE: The results indicate that the defect in sustaining filament elongation is probably caused by the failure of age3Delta cells to polarize the actin cytoskeleton and possibly of inefficient endocytosis. The high susceptibility of age3Delta cells to azoles is not caused by inefficient transport of efflux pumps to the cell membrane. A possible role of a vacuolar defect of age3Delta cells in drug susceptibility is proposed and discussed. In conclusion, our study shows that the ARF-GAP Age3p is required for hyphal growth which is an important virulence factor of C. albicans and essential for detoxification of azole drugs which are routinely used for antifungal therapy. Thus, it represents a promising antifungal drug target

    Deceleration during 'real life' motor vehicle collisions – a sensitive predictor for the risk of sustaining a cervical spine injury?

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    <p>Abstract</p> <p>Background</p> <p>The predictive value of trauma impact for the severity of whiplash injuries has mainly been investigated in sled- and crash-test studies. However, very little data exist for real-life accidents. Therefore, the predictive value of the trauma impact as assessed by the change in velocity of the car due to the collision (ΔV) for the resulting cervical spine injuries were investigated in 57 cases after real-life car accidents.</p> <p>Methods</p> <p>ΔV was determined for every car and clinical findings related to the cervical spine were assessed and classified according to the Quebec Task Force (QTF).</p> <p>Results</p> <p>In our study, 32 (56%) subjects did not complain about symptoms and were therefore classified as QTF grade 0; 25 (44%) patients complained of neck pain: 8 (14%) were classified as QTF grade I, 6 (10%) as QTF grade II, and 11 (19%) as QTF grade IV. Only a slight correlation (r = 0.55) was found between the reported pain and ΔV. No relevant correlation was found between ΔV and the neck disability index (r = 0.46) and between ΔV and the QTF grade (r = 0.45) for any of the collision types. There was no ΔV threshold associated with acceptable sensitivity and specificity for the prognosis of a cervical spine injury.</p> <p>Conclusion</p> <p>The results of this study indicate that ΔV is not a conclusive predictor for cervical spine injury in real-life motor vehicle accidents. This is of importance for surgeons involved in medicolegal expertise jobs as well as patients who suffer from whiplash-associated disorders (WADs) after motor vehicle accidents.</p> <p>Trial registration</p> <p>The study complied with applicable German law and with the principles of the Helsinki Declaration and was approved by the institutional ethics commission.</p

    Active Suppression of Early Immune Response in Tobacco by the Human Pathogen Salmonella Typhimurium

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    The persistence of enteric pathogens on plants has been studied extensively, mainly due to the potential hazard of human pathogens such as Salmonella enterica being able to invade and survive in/on plants. Factors involved in the interactions between enteric bacteria and plants have been identified and consequently it was hypothesized that plants may be vectors or alternative hosts for enteric pathogens. To survive, endophytic bacteria have to escape the plant immune systems, which function at different levels through the plant-bacteria interactions. To understand how S. enterica survives endophyticaly we conducted a detailed analysis on its ability to elicit or evade the plant immune response. The models of this study were Nicotiana tabacum plants and cells suspension exposed to S. enterica serovar Typhimurium. The plant immune response was analyzed by looking at tissue damage and by testing oxidative burst and pH changes. It was found that S. Typhimurium did not promote disease symptoms in the contaminated plants. Live S. Typhimurium did not trigger the production of an oxidative burst and pH changes by the plant cells, while heat killed or chloramphenicol treated S. Typhimurium and purified LPS of Salmonella were significant elicitors, indicating that S. Typhimurium actively suppress the plant response. By looking at the plant response to mutants defective in virulence factors we showed that the suppression depends on secreted factors. Deletion of invA reduced the ability of S. Typhimurium to suppress oxidative burst and pH changes, indicating that a functional SPI1 TTSS is required for the suppression. This study demonstrates that plant colonization by S. Typhimurium is indeed an active process. S. Typhimurium utilizes adaptive strategies of altering innate plant perception systems to improve its fitness in the plant habitat. All together these results suggest a complex mechanism for perception of S. Typhimurium by plants

    A Predictive Model of Intein Insertion Site for Use in the Engineering of Molecular Switches

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    Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch
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