The brightness of an active galactic nucleus is set by the gas falling onto it from the galaxy, and the gas infall rate is regulated by the brightness of the active galactic nucleus; this feedback ...loop is the process by which supermassive black holes in the centres of galaxies may moderate the growth of their hosts. Gas outflows (in the form of disk winds) release huge quantities of energy into the interstellar medium, potentially clearing the surrounding gas. The most extreme (in terms of speed and energy) of these-the ultrafast outflows-are the subset of X-ray-detected outflows with velocities higher than 10,000 kilometres per second, believed to originate in relativistic (that is, near the speed of light) disk winds a few hundred gravitational radii from the black hole. The absorption features produced by these outflows are variable, but no clear link has been found between the behaviour of the X-ray continuum and the velocity or optical depth of the outflows, owing to the long timescales of quasar variability. Here we report the observation of multiple absorption lines from an extreme ultrafast gas flow in the X-ray spectrum of the active galactic nucleus IRAS 13224-3809, at 0.236 ± 0.006 times the speed of light (71,000 kilometres per second), where the absorption is strongly anti-correlated with the emission of X-rays from the inner regions of the accretion disk. If the gas flow is identified as a genuine outflow then it is in the fastest five per cent of such winds, and its variability is hundreds of times faster than in other variable winds, allowing us to observe in hours what would take months in a quasar. We find X-ray spectral signatures of the wind simultaneously in both low- and high-energy detectors, suggesting a single ionized outflow, linking the low- and high-energy absorption lines. That this disk wind is responding to the emission from the inner accretion disk demonstrates a connection between accretion processes occurring on very different scales: the X-ray emission from within a few gravitational radii of the black hole ionizing the disk wind hundreds of gravitational radii further away as the X-ray flux rises.
. Chang S‐N, Tsai C‐T, Wu C‐K, Lee J‐K, Lai L‐P, Huang S‐W, Huang L‐Y, Tseng C‐D, Lin J‐L, Chiang F‐T, Hwang J‐J (National Taiwan University Hospital Yun‐Lin Branch, Yun‐Lin; National Taiwan ...University Hospital, Taipei; National Taiwan University Hospital, Taipei; Institute of Pharmacology, Taipei; and Graduate Institute of Biomedical Engineering, Taipei, Taiwan). A functional variant in the promoter region regulates the C‐reactive protein gene and is a potential candidate for increased risk of atrial fibrillation. J Intern Med 2012; 272: 305–315.
Objectives. In a large population‐based cohort, the level of C‐reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown.
Methods. A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association.
Results. Three polymorphisms (T‐861C, A‐821G and C‐390A/C‐390T) were found in the 1‐kb promoter of CRP. A triallelic polymorphism (C‐390A/C‐390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The −390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L‐type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts.
Conclusion. A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.
Abstract Objective Prophylactic salpingo-oophorectomy is recommended to women who carry a BRCA1 or BRCA2 mutation to reduce the risks of breast, ovarian and fallopian tube cancer. We measured the ...impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual functioning in women with a BRCA mutation. Methods Women who underwent prophylactic salpingo-oophorectomy between October 1, 2002 and June 26, 2008 for a known BRCA1 or BRCA2 mutation were invited to participate. Participants completed questionnaires before prophylactic surgery and again one year after surgery. Measures of sexual functioning and menopausal symptoms before and after surgery were compared. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy was evaluated. Results 114 women who underwent prophylactic surgery completed questionnaires before and one year after surgery. Subjects who were premenopausal at the time of surgery ( n = 75) experienced a significant worsening of vasomotor symptoms (hot flashes, night sweats and sweating) and a decline in sexual functioning (desire, pleasure, discomfort and habit). The increase in vasomotor symptoms and the decline in sexual functioning were mitigated by HRT, but symptoms did not return to pre-surgical levels. HRT decreased vaginal dryness and dyspareunia; however, the decrease in sexual pleasure was not alleviated by HRT. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy remained high regardless of increased vasomotor symptoms and decreased sexual function. Conclusions Women who undergo prophylactic salpingo-oophorectomy prior to menopause experience an increase in vasomotor symptoms and a decrease in sexual functioning. These symptoms are improved by HRT, but not to pre-surgical levels.
The Deep Ecliptic Survey (DES)-a search optimized for the discovery of Kuiper belt objects (KBOs) with the Blanco and Mayall 4 m telescopes at the Cerro Tololo Inter-American Observatory and Kitt ...Peak National Observatory-has covered 550 deg2 from its inception in 1998 through the end of 2003. This survey has a mean 50% sensitivity at VR magnitude 22.5. We report here the discoveries of 320 designated KBOs and Centaurs for the period 2000 March through 2003 December and describe improvements to our discovery and recovery procedures. Our data and the data products needed to reproduce our analyses in this paper are available through the NOAO survey database. Here we present a dynamical classification scheme, based on the behavior of orbital integrations over 10 Myr. The dynamical classes, in order of testing, are 'Resonant,' 'Centaur,' 'Scattered-Near,' 'Scattered-Extended,' and 'Classical.' (These terms are capitalized when referring to our rigorous definitions.) Of the 382 total designated KBOs discovered by the DES, a subset of 196 objects have sufficiently accurate orbits for dynamical classification. Summary information is given for an additional 240 undesignated objects also discovered by the DES from its inception through the end of 2003. The number of classified DES objects (uncorrected for observational bias) are Classical, 96; Resonant, 54; Scattered-Near, 24; Scattered-Extended, 9; and Centaur, 13. We use subsets of the DES objects (which can have observational biases removed) and larger samples to perform dynamical analyses on the Kuiper belt. The first of these is a determination of the Kuiper belt plane (KBP), for which the Classical objects with inclinations less than 5° from the mean orbit pole yield a pole at R.A. = 27392 ± 062 and decl. = 6670 ± 020 (J2000), consistent with the invariable plane of the solar system. A general method for removing observational biases from the DES data set is presented and used to find a provisional magnitude distribution and the distribution of orbital inclinations relative to the KBP. A power-law model fit to the cumulative magnitude distribution of all KBOs discovered by the DES in the VR filter yields an index of 0.86 ± 0.10 (with the efficiency parameters for the DES fitted simultaneously with the population power law). With the DES sensitivity parameters fixed, we derive power-law indices of 0.74 ± 0.0,0.52 ± 0.08, and 0.74 ± 0.15, respectively, for the Classical, Resonant, and Scattered classes. Plans for calibration of the DES detection efficiency function and DES magnitudes are discussed. The inclination distribution confirms the presence of 'hot' and 'cold' populations; when the geometric sin i factor is removed from the inclination distribution function, the cold population shows a concentrated 'core' with a full width at half-maximum of approximately 46, while the hot population appears as a 'halo,' extending beyond 30°. The inclination distribution is used to infer the KBO distribution in the sky, as a function of latitude relative to the KBP. This inferred latitude distribution is reasonably consistent with the latitude distribution derived from direct observation, but the agreement is not perfect. We find no clear boundary between the Classical and Scattered classes either in their orbital inclinations with respect to the KBP or in their power-law indices in their respective magnitude distributions. This leaves open the possibility that common processes have shaped the distribution of orbital parameters for the two classes.
Rare red‐fluorescent fluorene derivatives have been designed and synthesized. The long‐wavelength red fluorescence is achieved by incorporating a di(4‐tolyl)amino or diphenylamino electron donor and ...a dicyanovinyl electron acceptor. The single‐crystal X‐ray structures of the di(4‐tolyl)amino (pTSPDCV) and diphenylamino (PhSPDCV) compounds indicate only weak non‐π van der Waals contacts in addition to long‐distance dipole–dipole interactions of the red‐emitting fluorene molecules in the solid state. The aggregation of the dipolar fluorene is largely suppressed by introducing bulky 9,9‐substituents (spiro‐fused bifluorene) as well as a non‐planar di(4‐tolyl)amino or diphenylamino group. In the solid state, these fluorene derivatives all show red fluorescence that is much brighter than with the red dopants Nile Red and DCM (4‐(dicyanomethylene)‐2‐methyl‐6‐4‐(dimethylaminostyryl)‐4H‐pyran). The unique photophysical properties of red‐emitting fluorene derivatives differ from other known red dopants and facilitate the fabrication of non‐doped red organic light‐emitting diodes (OLEDs). Authentic red (CIE, x = 0.65, y = 0.35) electroluminescence with a brightness of more than 12 000 cd m–2 (greater than 600 cd m–2 at 20 mA cm–2) and a remarkable external quantum efficiency as high as 3.6 % have been observed for the red‐emitting OLEDs with pTSPDCV or PhSPDCV as the sole emitting host.
Brilliant red‐light‐emitting fluorenes, diphenylamino‐ and dicyanovinyl‐ substituted spirobifluorenes are reported. These compounds perform far better than Nile Red and DCM in the solid state (see Figure); non‐doped light‐emitting diodes with a red‐emitting fluorene as host‐emitter show external quantum efficiencies as high as 3.6 % and electroluminescence of over 12 000 cd m–2.
While most living kidney donors are satisfied with their decision and do not regret donating, few studies have been conducted on the determinants related to the effectiveness and regret of the ...decision. This study aims to explore the relationship between basic attributes, quality of life, positive affect, negative affect, effectiveness of decision-making, and regret in living kidney donors.
In this cross-sectional study, living kidney donors were recruited from urology and kidney transplant outpatient services. The structured questionnaire used to collect the data included the Positive and Negative Affect Schedule, Medical Outcomes Study 12-Item Short-Form Health Survey, Decision Conflict Scale, and Decision Regret Scale.
The findings indicate that living donors with better health status, 24-hour creatinine clearance, physical health-related quality of life (HRQOL), and positive affect experienced greater feelings of effective decision-making. Moreover, women and donors with better physical HRQOL, positive affect, and decision effectiveness were less regretful about the decision of kidney donation.
Health status, physical HRQOL, and positive affect are related to decision validity and regret of living donors. Therefore, clinical care providers should regularly assess the mood and health of living kidney donors. Furthermore, activities promoting their health should be encouraged, especially for men.
•The living donors who had positive affect, such as being interested, focused, confident, and optimistic, experienced greater feelings of effective decision-making.•The living donors with positive affect were less regretful about the decision of kidney donation.
The mechanisms underlying human natural killer (NK) cell phenotypic and functional heterogeneity are unknown. Here, we describe the emergence of diverse subsets of human NK cells selectively lacking ...expression of signaling proteins after human cytomegalovirus (HCMV) infection. The absence of B and myeloid cell-related signaling protein expression in these NK cell subsets correlated with promoter DNA hypermethylation. Genome-wide DNA methylation patterns were strikingly similar between HCMV-associated adaptive NK cells and cytotoxic effector T cells but differed from those of canonical NK cells. Functional interrogation demonstrated altered cytokine responsiveness in adaptive NK cells that was linked to reduced expression of the transcription factor PLZF. Furthermore, subsets of adaptive NK cells demonstrated significantly reduced functional responses to activated autologous T cells. The present results uncover a spectrum of epigenetically unique adaptive NK cell subsets that diversify in response to viral infection and have distinct functional capabilities compared to canonical NK cell subsets.
•HCMV infection induces adaptive NK cell subsets with diversified signaling potential•Adaptive NK cells share molecular features of differentiation with CTLs•Adaptive NK cells lose the ability to kill autologous, activated immune cells•Gain of adaptive NK cell functions correlates with silencing of PLZF expression
Cytomegalovirus infection can shape the NK cell receptor repertoire. Schlums, Cichocki, and colleagues dig deeper and demonstrate that cytomegalovirus infection induces a genome-wide epigenetic diversification of NK cell subsets, paralleling T cell differentiation and leading to changes in NK cell specificity and function.
Nanodiamond internalization in cells and the cell uptake mechanism Perevedentseva, E.; Hong, S.-F.; Huang, K.-J. ...
Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology,
08/2013, Letnik:
15, Številka:
8
Journal Article
Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical ...applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed.
Abstract Background and aims Abdominal aortic calcification (AC) has been reported to be associated with cardiovascular disease (CVD) in hemodialysis patients but is rarely discussed in peritoneal ...dialysis (PD) patients. We examined the independent predictors and predictive power for survival of AC in prevalent PD patients. Methods and Results AC was detected by computed tomography (CT) and represented as the percentage of the total aortic cross-section area affected by AC (%AC). The predictors of %AC ≥15 were examined by multiple logistic regression analysis. Cox proportional hazard analysis was used to determine the hazard ratios associated with high %AC. A total of 183 PD patients were recruited to receive CT scans and divided into group 1 (%AC < 15, n = 97), group 2 (%AC ≥ 15, n = 41), and group 3 (diabetic patients, n = 45). Group 1 patients had lower osteoprotegerin (OPG) levels than group 2 patients (798 ± 378 vs. 1308 ± 1350 pg/mL, p < 0.05). The independent predictors for %AC ≥ 15 included the atherogenic index, OPG, and C-reactive protein (CRP). The age-adjusted hazard ratios associated with %AC ≥15 were 3.46 ( p = 0.043) for mortality and 1.90 ( p = 0.007) for hospitalization. Conclusions %AC can predict mortality and morbidity in non-diabetic PD patients, and 15% is a good cut-off value for such predictions. There are complex associations among mineral metabolism, inflammation, and dyslipidemia in the pathogenesis of AC.
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