150 research outputs found

    Classical and Quantum Equations of Motion for a BTZ Black String in AdS Space

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    We investigate gravitational collapse of a (3+1)(3+1)-dimensional BTZ black string in AdS space in the context of both classical and quantum mechanics. This is done by first deriving the conserved mass per unit length of the cylindrically symmetric domain wall, which is taken as the classical Hamiltonian of the black string. In the quantum mechanical context, we take primary interest in the behavior of the collapse near the horizon and near the origin (classical singularity) from the point of view of an infalling observer. In the absence of radiation, quantum effects near the horizon do not change the classical conclusions for an infalling observer, meaning that the horizon is not an obstacle for him/her. The most interesting quantum mechanical effect comes in when investigating near the origin. First, quantum effects are able to remove the classical singularity at the origin, since the wave function is non-singular at the origin. Second, the Schr\"odinger equation describing the behavior near the origin displays non-local effects, which depend on the energy density of the domain wall. This is manifest in that derivatives of the wavefunction at one point are related to the value of the wavefunction at some other distant point.Comment: 9 pages, 1 figure. Minor Clarification and corrections. Accepted for Publication in JHE

    A Conserved PHD Finger Protein and Endogenous RNAi Modulate Insulin Signaling in Caenorhabditis elegans

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    Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16–dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes.Leukemia & Lymphoma Society of America (3260-07 Special Fellow Award)Arnold and Mabel Beckman Foundation (Young Investigator Award)United States. National Institutes of Health (Director's New Innovator Award (1 DP2 OD006412-01))United States. National Institutes of Health (grant GM66269)modENCODE (grant U01 HG004270)United States. National Institutes of Health (training grant 5T32 GM07088-34

    Exploring wettability difference-driven wetting by utilizing electrospun chimeric Janus microfiber comprising cellulose acetate and polyvinylpyrrolidone

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    In exploring the difference in the wettability of fibers with various structures, three inner constructions of fibers, namely, uniaxial, Janus and chimeric Janus, have been fabricated by electrospinning. In electrospun fibers, polyvinyl pyrrolidone and cellulose acetate were used as a polymer matrix and ketoprofen was used as a model drug. Morphologies and inner structures were respectively investigated by scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). Physical states and compatibilities of materials were detected by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Water contact angle (WCA) tests were conducted to determine the difference between wettability and wetting time among assorted fiber membranes. Results showed that the wettability gradient could drive water movement and wetting, which resulted in the rapid decrease of the WCA, to prepare Janus and chimeric Janus fiber membranes compared with uniaxial fiber membranes. Otherwise, in vitro drug release experiments were carried out and four fitting models were applied in matching release profiles. The results showed that electrospun fiber membranes belonged to sustained-release systems and such membranes were influenced by drug diffusion and backbone corrosion effects. In this study, whether electrospun multilayer Janus fibers could affect wettability and drug release was investigated

    A heterozygous moth genome provides insights into herbivory and detoxification

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    How an insect evolves to become a successful herbivore is of profound biological and practical importance. Herbivores are often adapted to feed on a specific group of evolutionarily and biochemically related host plants1, but the genetic and molecular bases for adaptation to plant defense compounds remain poorly understood2. We report the first whole-genome sequence of a basal lepidopteran species, Plutella xylostella, which contains 18,071 protein-coding and 1,412 unique genes with an expansion of gene families associated with perception and the detoxification of plant defense compounds. A recent expansion of retrotransposons near detoxification-related genes and a wider system used in the metabolism of plant defense compounds are shown to also be involved in the development of insecticide resistance. This work shows the genetic and molecular bases for the evolutionary success of this worldwide herbivore and offers wider insights into insect adaptation to plant feeding, as well as opening avenues for more sustainable pest management.Minsheng You … Simon W Baxter … et al

    Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension

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    BACKGROUND: Aldosterone dysregulation plays an important pathogenic role in hard-to-control hypertension. In several studies, baxdrostat, an aldosterone synthase inhibitor, reduced the seated systolic blood pressure of patients with uncontrolled or resistant hypertension. METHODS: In this phase 3, multinational, double-blind, randomized, placebo-controlled trial, we recruited patients with a seated systolic blood pressure of between 140 mm Hg and less than 170 mm Hg despite the receipt of stable treatment with two antihypertensive medications (uncontrolled hypertension) or three or more such medications (resistant hypertension), including a diuretic. After a 2-week placebo run-in period, we randomly assigned patients with a seated systolic blood pressure of 135 mm Hg or more in a 1:1:1 ratio to receive baxdrostat at a dose of 1 mg, baxdrostat at a dose of 2 mg, or placebo once daily for 12 weeks. The primary end point was the change in seated systolic blood pressure from baseline to week 12. RESULTS: A total of 796 patients underwent randomization and 794 received 1-mg baxdrostat (264 patients), 2-mg baxdrostat (266 patients), or placebo (264 patients) in addition to background therapy. At 12 weeks, the change from baseline in the least-squares mean seated systolic blood pressure was -14.5 mm Hg (95% confidence interval [CI], -16.5 to -12.5) with 1-mg baxdrostat, -15.7 mm Hg (95% CI, -17.6 to -13.7) with 2-mg baxdrostat, and -5.8 mm Hg (95% CI, -7.9 to -3.8) with placebo. The estimated difference from placebo (placebo-corrected difference) was -8.7 mm Hg (95% CI, -11.5 to -5.8) with 1-mg baxdrostat and -9.8 mm Hg (95% CI, -12.6 to -7.0) with 2-mg baxdrostat (P<0.001 for both comparisons). A potassium level of more than 6.0 mmol per liter was reported in 6 patients (2.3%) with 1-mg baxdrostat, in 8 patients (3.0%) with 2-mg baxdrostat, and in 1 patient (0.4%) with placebo. CONCLUSIONS: Among patients with uncontrolled or resistant hypertension, the addition of baxdrostat to background therapy resulted in a significantly lower seated systolic blood pressure at 12 weeks than placebo. (Funded by AstraZeneca and others; BaxHTN ClinicalTrials.gov number, NCT06034743.)

    Hypoglycemia and Death in Mice Following Experimental Exposure to an Extract of Trogia venenata Mushrooms

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    BACKGROUND: Clusters of sudden unexplained death (SUD) in Yunnan Province, China, have been linked to eating Trogia venenata mushrooms. We evaluated the toxic effect of this mushroom on mice. METHODS: We prepared extracts of fresh T. venenata and Laccaria vinaceoavellanea mushrooms collected from the environs of a village that had SUD. We randomly allocated mice into treatment groups and administered mushroom extracts at doses ranging from 500 to 3500 mg/kg and water (control) via a gavage needle. We observed mice for mortality for 7 days after a 3500 mg/kg dose and for 24 hours after doses from 500 to 3000 mg/kg. We determined biochemical markers from serum two hours after a 2000 mg/kg dose. RESULTS: Ten mice fed T. venenata extract (3500 mg/kg) died by five hours whereas all control mice (L. vinaceoavellanea extract and water) survived the seven-day observation period. All mice died by five hours after exposure to single doses of T. venenata extract ranging from 1500 to 3000 mg/kg, while the four mice exposed to a 500 mg/kg dose all survived. Mice fed 2000 mg/kg of T. venenata extract developed profound hypoglycemia (median= 0.66 mmol/L) two hours after exposure. DISCUSSION: Hypoglycemia and death within hours of exposure, a pattern unique among mushroom toxicity, characterize T. venenata poisoning

    Preparation and Characterization of Fluorescence Probe from Assembly Hydroxyapatite Nanocomposite

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    A new nanocomposite fluorescence probe with thioglycolic acid (TA) functional layers embedded inside the hydroxyapatite nanoribbon spherulites has been synthesized. The fluorescence intensity of the novel probe is about 1.5–3.3-fold increase compared with the probe containing no TA. When used to detect cadmium ion, the most of original assembly nanoribbon spherulites structure in the novel probe is found to have been damaged to new flake structures. The mechanism of determining cadmium ion in alcohol solution has been studied. The present systematic study provides significant information on the effect of assembly nanostructure on the metal-enhanced fluorescence phenomenon

    Brown Adipose Tissue in Humans Is Activated by Elevated Plasma Catecholamines Levels and Is Inversely Related to Central Obesity

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    BACKGROUND: Recent studies have shown that adult human possess active brown adipose tissue (BAT), which might be important in controlling obesity. It is known that ß-adrenoceptor-UCP1 system regulates BAT in rodent, but its influence in adult humans remains to be shown. The present study is to determine whether BAT activity can be independently stimulated by elevated catecholamines levels in adult human, and whether it is associated with their adiposity. METHODOLOGY/PRINCIPAL FINDINGS: We studied 14 patients with pheochromocytoma and 14 normal subjects who had performed both ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and plasma total metanephrine (TMN) measurements during 2007-2010. The BAT detection rate and the mean BAT activity were significantly higher in patients with elevated TMN levels (Group A: 6/8 and 6.7±2.1 SUVmean· g/ml) than patients with normal TMN concentrations (Group B: 0/6 and 0.4±0.04 SUVmean· g/ml) and normal subjects (Group C: 0/14 and 0.4±0.03 SUVmean·g/ml). BAT activities were positively correlated with TMN levels (R = 0.83, p<0.0001) and were inversely related to body mass index (R = -0.47, p = 0.010), visceral fat areas (R = -0.39, p = 0.044), visceral/total fat areas (R = -0.52, p = 0.0043) and waist circumferences (R = -0.43, p = 0.019). Robust regression revealed that TMN (R = 0.81, p<0.0001) and waist circumferences (R = -0.009, p = 0.009) were the two independent predictors of BAT activities. CONCLUSIONS/SIGNIFICANCE: Brown adipose tissue activity in adult human can be activated by elevated plasma TMN levels, such as in the case of patients with pheochromocytoma, and is negatively associated with central adiposity

    Comparison of sterols and fatty acids in two species of Ganoderma

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    <p>Abstract</p> <p>Background</p> <p>Two species of <it>Ganoderma, G. sinense </it>and <it>G. lucidum</it>, are used as <it>Lingzhi </it>in China. Howerver, the content of triterpenoids and polysaccharides, main actives compounds, are significant different, though the extracts of both <it>G. lucidum </it>and <it>G. sinense </it>have antitumoral proliferation effect. It is suspected that other compounds contribute to their antitumoral activity. Sterols and fatty acids have obvious bioactivity. Therefore, determination and comparison of sterols and fatty acids is helpful to elucidate the active components of <it>Lingzhi</it>.</p> <p>Results</p> <p>Ergosterol, a specific component of fungal cell membrane, was rich in <it>G. lucidum </it>and <it>G. sinense</it>. But its content in <it>G. lucidum </it>(median content 705.0 μg·g<sup>-1</sup>, range 189.1-1453.3 μg·g<sup>-1</sup>, n = 19) was much higher than that in <it>G. sinense </it>(median content 80.1 μg·g<sup>-1</sup>, range 16.0-409.8 μg·g<sup>-1</sup>, n = 13). Hierarchical clustering analysis based on the content of ergosterol showed that 32 tested samples of <it>Ganoderma </it>were grouped into two main clusters, <it>G. lucidum </it>and <it>G. sinense</it>. Hierarchical clustering analysis based on the contents of ten fatty acids showed that two species of <it>Ganoderma </it>had no significant difference though two groups were also obtained. The similarity of two species of <it>Ganoderma </it>in fatty acids may be related to their antitumoral proliferation effect.</p> <p>Conclusions</p> <p>The content of ergosterol is much higher in <it>G. lucidum </it>than in <it>G. sinense</it>. Palmitic acid, linoleic acid, oleic acid, stearic acid are main fatty acids in <it>Ganoderma </it>and their content had no significant difference between <it>G. lucidum </it>and <it>G. sinense</it>, which may contribute to their antitumoral proliferation effect.</p

    Purification and Characterization of Enterovirus 71 Viral Particles Produced from Vero Cells Grown in a Serum-Free Microcarrier Bioreactor System

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    [[abstract]]Background: Enterovirus 71 (EV71) infections manifest most commonly as a childhood exanthema known as hand-foot-and-mouth disease (HFMD) and can cause neurological disease during acute infection. Principal Finding: In this study, we describe the production, purification and characterization of EV71 virus produced from Vero cells grown in a five-liter serum-free bioreactor system containing 5 g/L Cytodex 1 microcarrier. The viral titer was >106 TCID50/mL by 6 days post infection when a MOI of 10?5 was used at the initial infection. Two EV71 virus fractions were separated and detected when the harvested EV71 virus concentrate was purified by sucrose gradient zonal ultracentrifugation. The EV71 viral particles detected in the 24–28% sucrose fractions had an icosahedral structure 30–31 nm in diameter and had low viral infectivity and RNA content. Three major viral proteins (VP0, VP1 and VP3) were observed by SDS-PAGE. The EV71 viral particles detected in the fractions containing 35–38% sucrose were 33–35 nm in size, had high viral infectivity and RNA content, and were composed of four viral proteins (VP1, VP2, VP3 and VP4), as shown by SDS-PAGE analyses. The two virus fractions were formalin-inactivated and induced high virus neutralizing antibody responses in mouse immunogenicity studies. Both mouse antisera recognized the immunodominant linear neutralization epitope of VP1 (residues 211–225). Conclusion:These results provide important information for cell-based EV71 vaccine development, particularly for the preparation of working standards for viral antigen quantification
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