266 research outputs found

    Time evolution of the classical and quantum mechanical versions of diffusive anharmonic oscillator: an example of Lie algebraic techniques

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    We present the general solutions for the classical and quantum dynamics of the anharmonic oscillator coupled to a purely diffusive environment. In both cases, these solutions are obtained by the application of the Baker-Campbell-Hausdorff (BCH) formulas to expand the evolution operator in an ordered product of exponentials. Moreover, we obtain an expression for the Wigner function in the quantum version of the problem. We observe that the role played by diffusion is to reduce or to attenuate the the characteristic quantum effects yielded by the nonlinearity, as the appearance of coherent superpositions of quantum states (Schr\"{o}dinger cat states) and revivals.Comment: 21 pages, 6 figures, 2 table

    Speaker- versus listener-oriented disfluency: A re-examination of arguments and assumptions from autism spectrum disorder

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    We re-evaluate conclusions about disfluency production in high-functioning forms of autism spectrum disorder (HFA). Previous studies examined individuals with HFA to address a theoretical question regarding speaker- and listener-oriented disfluencies. Individuals with HFA tend to be self-centric and have poor pragmatic language skills, and should be less likely to produce listener-oriented disfluency. However, previous studies did not account for individual differences variables that affect disfluency. We show that both matched and unmatched controls produce fewer repairs than individuals with HFA. For silent pauses, there was no difference between matched controls and HFA, but both groups produced more than unmatched controls. These results identify limitations in prior research and shed light on the relationship between autism spectrum disorders and disfluent speech

    First- and second-order contributions to depth perception in anti-correlated random dot stereograms.

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    The binocular energy model of neural responses predicts that depth from binocular disparity might be perceived in the reversed direction when the contrast of dots presented to one eye is reversed. While reversed-depth has been found using anti-correlated random-dot stereograms (ACRDS) the findings are inconsistent across studies. The mixed findings may be accounted for by the presence of a gap between the target and surround, or as a result of overlap of dots around the vertical edges of the stimuli. To test this, we assessed whether (1) the gap size (0, 19.2 or 38.4 arc min) (2) the correlation of dots or (3) the border orientation (circular target, or horizontal or vertical edge) affected the perception of depth. Reversed-depth from ACRDS (circular no-gap condition) was seen by a minority of participants, but this effect reduced as the gap size increased. Depth was mostly perceived in the correct direction for ACRDS edge stimuli, with the effect increasing with the gap size. The inconsistency across conditions can be accounted for by the relative reliability of first- and second-order depth detection mechanisms, and the coarse spatial resolution of the latter

    Association of Fidaxomicin with C. difficile spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production.

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    Background: We have previously shown that fidaxomicin instillation prevents spore recovery in an in-vitro gut model, whereas vancomycin does not. The reasons for this are unclear. Here, we have investigated persistence of fidaxomicin and vancomycin on C. difficile spores, and examined post-antibiotic exposure spore recovery, outgrowth and toxin production. Methods: Prevalent UK C. difficile ribotypes (n=10) were incubated with 200mg/L fidaxomicin, vancomycin or a non-antimicrobial containing control for 1 h in faecal filtrate or Phosphate Buffered Saline. Spores were washed three times with faecal filtrate or phosphate buffered saline, and residual spore-associated antimicrobial activity was determined by bioassay. For three ribotypes (027, 078, 015), antimicrobial-exposed, faecal filtrate-washed spores and controls were inoculated into broth. Viable vegetative and spore counts were enumerated on CCEYL agar. Percentage phase bright spores, phase dark spores and vegetative cells were enumerated by phase contrast microscopy at 0, 3, 6, 24 and 48 h post-inoculation. Toxin levels (24 and 48h) were determined by cell cytotoxicity assay. Results: Fidaxomicin, but not vancomycin persisted on spores of all ribotypes following washing in saline (mean=10.1mg/L; range= 4.0-14mg/L) and faecal filtrate (mean =17.4mg/L; 8.4-22.1mg/L). Outgrowth and proliferation rates of vancomycin-exposed spores were similar to controls, whereas fidaxomicin-exposed spores showed no vegetative cell growth after 24 and 48 h. At 48h, toxin levels averaged 3.7 and 3.3 relative units (RU) in control and vancomycin-exposed samples, respectively, but were undetectable in fidaxomicin-exposed samples. Conclusion: Fidaxomicin persists on C. difficile spores, whereas vancomycin does not. This persistence prevents subsequent growth and toxin production in vitro. This may have implications on spore viability, thereby impacting CDI recurrence and transmission rates

    Small molecule receptor tyrosine kinase inhibitor of platelet-derived growth factor signaling (SU9518) modifies radiation response in fibroblasts and endothelial cells

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    BACKGROUND: Several small receptor tyrosine kinase inhibitors (RTKI) have entered clinical cancer trials alone and in combination with radiotherapy or chemotherapy. The inhibitory spectrum of these compounds is often not restricted to a single target. For example Imatinib/Gleevec (primarily a bcr/abl kinase inhibitor) or SU11248 (mainly a VEGFR inhibitor) are also potent inhibitors of PDGFR and other kinases. We showed previously that PDGF signaling inhibition attenuates radiation-induced lung fibrosis in a mouse model. Here we investigate effects of SU9518, a PDGFR inhibitor combined with ionizing radiation in human primary fibroblasts and endothelial cells in vitro, with a view on utilizing RTKI for antifibrotic therapy. METHODS: Protein levels of PDGFR-α/-β and phosphorylated PDGFR in fibroblasts were analyzed using western and immunocytochemistry assays. Functional proliferation and clonogenic assays were performed (i) to assess PDGFR-mediated survival and proliferation in fibroblasts and endothelial cells after SU9518 (small molecule inhibitor of PDGF receptor tyrosine kinase); (ii) to test the potency und selectivity of the PDGF RTK inhibitor after stimulation with PDGF isoforms (-AB, -AA, -BB) and VEGF+bFGF. In order to simulate in vivo conditions and to understand the role of radiation-induced paracrine PDGF secretion, co-culture models consisting of fibroblasts and endothelial cells were employed. RESULTS: In fibroblasts, radiation markedly activated PDGF signaling as detected by enhanced PDGFR phosphorylation which was potently inhibited by SU9518. In fibroblast clonogenic assay, SU9518 reduced PDGF stimulated fibroblast survival by 57%. Likewise, SU9518 potently inhibited fibroblast and endothelial cell proliferation. In the co-culture model, radiation of endothelial cells and fibroblast cells substantially stimulated proliferation of non irradiated fibroblasts and vice versa. Importantly, the RTK inhibitor significantly inhibited this paracrine radiation-induced fibroblast and endothelial cell activation. CONCLUSION: Radiation-induced autocrine and paracrine PDGF signaling plays an important role in fibroblast and endothelial cell proliferation. SU9518, a PDGFR tyrosine kinase inhibitor, reduces radiation-induced fibroblast and endothelial cell activation. This may explain therapeutic anticancer effects of Imatinib/Gleevec, and at the same time it could open a way of attenuating radiation-induced fibrosis

    Presence of Antibodies Against Coxiella burnetii and Risk of Spontaneous Abortion: A Nested Case-Control Study

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    BACKGROUND AND AIMS: Q fever is a bacterial zoonosis caused by infection with Coxiella burnetii. It is well established that Q fever causes fetal loss in small ruminants. The suspicion has been raised that pregnant women may also experience adverse pregnancy outcome when the infection is acquired or reactivated during pregnancy. The purpose of this study was to assess the potential association between serologic markers of infection with C. burnetii and spontaneous abortion. METHODS: A nested case-control study within the Danish National Birth Cohort, a cohort of 100,418 pregnancies recruited from 1996-2002. Women were recruited in first trimester of pregnancy and followed prospectively. Median gestational age at enrolment was 8 weeks (25 and 75 percentiles: 7 weeks; 10 weeks). During pregnancy, a blood sample was collected at gestational week 6-12 and stored in a bio bank. For this study, a case sample of 218 pregnancies was drawn randomly among the pregnancies in the cohort which ended with a miscarriage before 22 gestational weeks, and a reference group of 482 pregnancies was selected in a random fashion among all pregnancies in the cohort. From these pregnancies, serum samples were screened for antibodies against C. burnetii in a commercial enzyme-linked immunosorbent assay (ELISA). Samples that proved IgG or IgM antibody positive were subsequently confirmatory tested by an immunofluorescence (IFA) test. RESULTS: Among cases, 11 (5%) were C. burnetii positive in ELISA of which one was confirmed in the IFA assay compared to 29 (6%) ELISA positive and 3 IFA confirmed in the random sample. CONCLUSIONS: We found no evidence of a higher prevalence of C. burnetii antibodies in serum samples from women who later miscarried and the present study does not indicate a major association between Q fever infection and spontaneous abortion in humans. Very early first trimester abortions were, however, not included in the study

    Genomic Analysis of Parent-of-Origin Allelic Expression in Arabidopsis thaliana Seeds

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    Differential expression of maternally and paternally inherited alleles of a gene is referred to as gene imprinting, a form of epigenetic gene regulation common to flowering plants and mammals. In plants, imprinting primarily occurs in the endosperm, a seed tissue that supports the embryo during its growth and development. Previously, we demonstrated that widespread DNA demethylation at remnants of transposable elements accompanies endosperm development and that a subset of these methylation changes are associated with gene imprinting. Here we assay imprinted gene expression genome-wide by performing high-throughput sequencing of RNA derived from seeds of reciprocal intraspecific crosses. We identify more than 200 loci that exhibit parent-of-origin effects on gene expression in the endosperm, including a large number of transcription factors, hormone biosynthesis and response genes, and genes that encode regulators of epigenetic information, such as methylcytosine binding proteins, histone methyltransferases, and chromatin remodelers. The majority of these genes are partially, rather than completely, imprinted, suggesting that gene dosage regulation is an important aspect of imprinted gene expression

    A redox switch in angiotensinogen modulates angiotensin release.

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    Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 Å resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 Å structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child

    LCA of greywater management within a water circular economy restorative thinking framework

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    Greywater reuse is an attractive option for the sustainable management of water under water scarcity circumstances, within a water circular economy restorative thinking framework. Its successful deployment relies on the availability of low cost and environmentally friendly technologies. The life cycle assessment (LCA) approach provides the appropriate methodological tool for the evaluation of alternative treatments based on environmental decision criteria and, therefore, it is highly useful during the process conceptual design. This methodology should be employed in the early design phase to select those technologies with lower environmental impact. This work reports the comparative LCA of three scenarios for greywater reuse: photocatalysis, photovoltaic solar-driven photocatalysis and membrane biological reactor, in order to help the selection of the most environmentally friendly technology. The study has been focused on the removal of the surfactant sodium dodecylbenzenesulfonate, which is used in the formulation of detergents and personal care products and, thus, widely present in greywater. LCA was applied using the Environmental Sustainability Assessment methodology to obtain two main environmental indicators in order to simplify the decision making process: natural resources and environmental burdens. Energy consumption is the main contributor to both indicators owing to the high energy consumption of the light source for the photocatalytic greywater treatment. In order to reduce its environmental burdens, the most desirable scenario would be the use of solar light for the photocatalytic transformation. However, while the technological challenge of direct use of solar light is approached, the environmental suitability of the photovoltaic solar energy driven photocatalysis technology to greywater reuse has been demonstrated, as it involves the smallest environmental impact among the three studied alternatives.Financial support from the Spanish Ministry of Economy and Competitiveness and from FEDER funds for projects CTM2013-43539-R, CTM2015-69845-R and CTQ2015-66078-R(MINECO/FEDER, UE) is gratefully acknowledged. Sara Dominguez and Jara Laso would also like to express their gratitude for the FPI postgraduate research grants (BES-2013-064055 and BES-2014-069368)

    Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

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    Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO
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