We present newly discovered dwarf galaxy candidates in deep and wide-field images of NGC 1291 obtained with the Korea Microlensing Telescope Network. We identify 15 dwarf galaxy candidates by visual ...inspection. Using imaging simulations, we demonstrate that the completeness rate of our detection is greater than 70% for the central surface-brightness value of 0,R 26 mag arcsec−2 and for magnitudes MR −10 mag. The structural and photometric properties of the dwarf galaxy candidates appear to be broadly consistent with those of ordinary dwarf galaxies in nearby groups and clusters, with 0,R ∼ 22.5 to 26.5 mag arcsec−2 and effective radii of 200 pc to 1 kpc. The dwarf galaxy candidates show a concentration toward NGC 1291 and tend to be redder the closer they are to the center, possibly indicating that they are associated with NGC 1291. The dwarf candidates presented in this paper appear to be bluer than those in denser environments, revealing that the quenching of star formation in dwarf galaxies is susceptible to the environment, while the morphology shaping is not.
Abstract
We compare vertical profiles of the extraplanar H
α
emission to those of the UV emission for 38 nearby edge-on late-type galaxies. It is found that detection of the “diffuse” extraplanar ...dust (eDust), traced by the vertically extended, scattered UV starlight, always coincides with the presence of the extraplanar H
α
emission. A strong correlation between the scale heights of the extraplanar H
α
and UV emissions is also found; the scale height at H
α
is found to be ∼0.74 of the scale height at FUV. Our results may indicate the multiphase nature of the diffuse ionized gas and dust in the galactic halos. The existence of eDust in galaxies where the extraplanar H
α
emission is detected suggests that a larger portion of the extraplanar H
α
emission than that predicted in previous studies may be caused by H
α
photons that originate from H
ii
regions in the galactic plane and are subsequently scattered by the eDust. This possibility raise an advantage in studying the extraplanar diffuse ionized gas. We also find that the scale heights of the extraplanar emissions normalized to the galaxy size correlate well with the star formation rate surface density of the galaxies. The properties of eDust in our galaxies is on a continuation line of that found through previous observations of the extraplanar polycyclic aromatic hydrocarbons emission in more active galaxies known to have galactic winds.
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The aim of this study was to examine the potential of platelet-derived growth factor (PDGF)-coated decellularized meniscus scaffold in mediating integrative healing of meniscus tears ...by inducing endogenous cell migration.
Fresh bovine meniscus was chemically decellularized and covalently conjugated with heparin and PDGF-BB. In vitro PDGF release kinetics was measured. The scaffold was transplanted into experimental tears in avascular bovine meniscus explants and cultured for 2 and 4 weeks. The number migrating and proliferating cells at the borderline between the scaffold and injured explant and PDGF receptor-β (PDGFRβ) expressing cells were counted. The alignment of the newly produced ECM and collagen was analyzed by Safranin-O, picrosirius red staining, and differential interference contrast (DIC). Tensile testing of the explants was performed after culture for 2 and 4 weeks.
Heparin conjugated scaffold showed immobilization of high levels of PDGF-BB, with sustained release over 2 weeks. Insertion of the PDGF-BB treated scaffold in defects in avascular meniscus led to increased PDGFRβ expression, cell migration and proliferation into the defect zone. Safranin-O, picrosirius red staining and DIC showed tissue integration between the scaffold and injured explants. Tensile properties of injured explants treated with PDGF-BB coated scaffold were significantly higher than in the scaffold without PDGF.
In conclusion, PDGF-BB-coated scaffold increased PDGFRβ expression and promoted migration of endogenous meniscus cells to the defect area. New matrix was formed that bridged the space between the native meniscus and the scaffold and this was associated with improved biomechanical properties. The PDGF-BB-coated scaffold will be promising for clinical translation to healing of meniscus tears.
Meniscus tears are the most common injury of the knee joint. The most prevalent forms that occur in the inner third typically do not spontaneously heal and represent a major risk factor for the development of knee osteoarthritis. The goal of this project was to develop an approach that is readily applicable for clinical use.
We selected a natural and readily available decellularized meniscus scaffold and conjugated it with PDGF, which we had previously found to have strong chemotactic activity for chondrocytes and progenitor cells.
The present results show that insertion of the PDGF-conjugated scaffold in defects in avascular meniscus led to endogenous cell migration and proliferation into the defect zone with tissue integration between the scaffold and injured explants and improved tensile properties.
This PDGF-conjugated scaffold will be promising for a translational approach to healing of meniscus tears.
In this paper, a method is proposed for identification of 11 position-independent geometric errors (PIGEs) of five-axis machine tools with a tilting/rotary table via single-ball measurements and ...three-dimensional (3D) geometric sensitivity analysis. Eleven PIGEs were identified, including three squareness errors between three linear axes, two offset errors, and two squareness errors for the tilting/rotary axis. The approach uses a set-up of a ball and three circular measurements involving simultaneous control of two linear axes and a tilting/rotary axis. A 3D geometric sensitivity analysis is carried out to investigate the effects of the 11 PIGEs on each of the measurement’s paths and between the measurement paths. The particular measurement paths used allow the radius of the circular path at the first measurement, and the distance between the circular paths of the second and third measurements, to be increased for accurate identification of the 11 PIGEs. The proposed method was also used to derive root-sum-square values of sensitivity coefficients, and then applied to a commercial five-axis machine tool for experimental verification. It calculates the peak-to-valley values of the positional deviations in the
x
-,
y
-, and
z
-directions along the test paths as 152.1, 118.2, and 47.1 μm, respectively, without compensation for the identified PIGEs, and as 17.6, 15.0, and 11.4 μm, respectively, with compensation. The results confirm the validity of our proposed method.
Frailty and low handgrip strength (HGS) are associated with adverse outcomes after hip fracture (HF) surgery. We aimed to compare the predictive role of frailty and HGS for adverse outcome in HF ...patients.
We included older patients (age ≥ 65 years) who underwent HF surgery to compare the predictive role of HGS and hip-multidimensional frailty score (Hip-MFS) for postoperative complications and mortality. The Hip-MFS was calculated based on comprehensive geriatric assessment (CGA), and HGS was measured with a hand dynamometer. The primary outcome was a composite of postoperative complications (e.g., pneumonia, urinary tract infection, delirium, acute pulmonary thromboembolism, and unplanned intensive care unit admission). The secondary outcomes were 6-month mortality and mortality at the end of follow-up.
The median observation time was 620.5 days (interquartile range: 367.0-784.8 days). Among the 242 patients (mean age: 81.5 ± 6.7 years, 73.1% women), 106 (43.8%) experienced postoperative complications. The 6-month mortality and mortality at the end of follow-up were 7.4% (n = 18) and 20.7% (n = 50), respectively. The Hip-MFS (odds ratio OR, 1.250; 95% confidence interval CI, 1.092-1.432) and HGS (OR, 1.147; 95% CI, 1.082-1.215) could predict postoperative complications. The Hip-MFS could predict both 6-month mortality (hazard ratio HR, 1.403; 95% CI, 1.027-1.917) and mortality at the end of follow-up (HR, 1.493; 95% CI, 1.249-1.769) after adjustment, while HGS was only associated with mortality at the end of follow-up (HR, 1.080; 95% CI, 1.024-1.139). For mortality at the end of follow-up, predictive models with the Hip-MFS were superior to those with HGS in the time-dependent receiver-operating curve analysis after adjustment (p = 0.017). Furthermore, the addition of Hip-MFS or HGS to the American Society of Anesthesiologists (ASA) classification improved its prognostic ability.
Both the Hip-MFS and HGS could predict postoperative complications and improve prognostic utility when combined with the ASA classification. The Hip-MFS was a stronger predictor of mortality than HGS after HF surgery. HGS could be a useful pre-screening tool to identify patients at a high risk of postoperative complications and those who may benefit from further CGA.
The direct method of detecting a virus with extremely low concentration is recommended for the diagnosis of viral disease. In this study, coplanar-gate graphene field-effect transistors (GFETs) were ...built on flexible polyethylene terephthalate substrates for the attomolar detection of a virus. The GFETs exhibited a very low detection limit of 47.8 aM with relatively low source/drain voltage due to aqueous dielectric media which stabilizes viruses and antibodies for specific bonding. The antibody as a probe molecule was decorated on a graphene surface using 1-pyrenebutanoic acid succinimidyl ester that had previously been immobilized on a graphene surface. The Dirac point voltage shifted downward after dropping the virus solution, due to the electrostatic gating effect of graphene in the antigen (namely, virus)-antibody complex. The virus detection platform used in this study is expected to be beneficial for direct diagnosis in saline environments, since the performances of GFETs were not significantly affected by the presence of Na
and Cl
. Furthermore, since our flexible and transparent virus sensors can be used in a wearable device, they provide a simple and fast method for diagnosing viruses.
Abstract
Aims
Previously, we reported that phosphorylation of histone deacetylase 2 (HDAC2) and the resulting activation causes cardiac hypertrophy. Through further study of the specific binding ...partners of phosphorylated HDAC2 and their mechanism of regulation, we can better understand how cardiac hypertrophy develops. Thus, in the present study, we aimed to elucidate the function of one such binding partner, heat shock protein 70 (HSP70).
Methods and results
Primary cultures of rat neonatal ventricular cardiomyocytes and H9c2 cardiomyoblasts were used for in vitro cellular experiments. HSP70 knockout (KO) mice and transgenic (Tg) mice that overexpress HSP70 in the heart were used for in vivo analysis. Peptide-precipitation and immunoprecipitation assay revealed that HSP70 preferentially binds to phosphorylated HDAC2 S394. Forced expression of HSP70 increased phosphorylation of HDAC2 S394 and its activation, but not that of S422/424, whereas knocking down of HSP70 reduced it. However, HSP70 failed to phosphorylate HDAC2 in the cell-free condition. Phosphorylation of HDAC2 S394 by casein kinase 2α1 enhanced the binding of HSP70 to HDAC2, whereas dephosphorylation induced by the catalytic subunit of protein phosphatase 2A (PP2CA) had the opposite effect. HSP70 prevented HDAC2 dephosphorylation by reducing the binding of HDAC2 to PP2CA. HSP70 KO mouse hearts failed to phosphorylate S394 HDAC2 in response to isoproterenol infusion, whereas Tg overexpression of HSP70 increased the phosphorylation and activation of HDAC2. 2-Phenylethynesulfonamide (PES), an HSP70 inhibitor, attenuated cardiac hypertrophy induced either by phenylephrine in neonatal ventricular cardiomyocytes or by aortic banding in mice. PES reduced HDAC2 S394 phosphorylation and its activation by interfering with the binding of HSP70 to HDAC2.
Conclusion
These results demonstrate that HSP70 specifically binds to S394-phosphorylated HDAC2 and maintains its phosphorylation status, which results in HDAC2 activation and the development of cardiac hypertrophy. Inhibition of HSP70 has possible application as a therapeutic.
Although the clinical importance of heart failure with preserved ejection fraction has been extensively explored, most therapeutic regimens, including nitric oxide (NO) donors, lack therapeutic ...benefit. Although the clinical characteristics of heart failure with preserved ejection fraction are somewhat heterogeneous, diastolic dysfunction (DD) is one of the most important features. Here we report that neuronal NO synthase (nNOS) induces DD by S-nitrosylation of HDAC2 (histone deacetylase 2).
Two animal models of DD-SAUNA (SAlty drinking water/Unilateral Nephrectomy/Aldosterone) and mild transverse aortic constriction mice-as well as human heart samples from patients with left ventricular hypertrophy were used. Genetically modified mice that were either nNOS-ablated or HDAC2 S-nitrosylation-resistant were also challenged. N(ω)-propyl-L-arginine, an nNOS selective inhibitor, and dimethyl fumarate, an NRF2 (nuclear factor erythroid 2-related factor 2) inducer, were used. Molecular events were further checked in human left ventricle specimens.
SAUNA or mild transverse aortic constriction stress impaired diastolic function and exercise tolerance without overt systolic failure. Among the posttranslational modifications tested, S-nitrosylation was most dramatically increased in both models. Utilizing heart samples from both mice and humans, we observed increases in nNOS expression and NO production. N(ω)-propyl-L-arginine alleviated the development of DD in vivo. Similarly, nNOS knockout mice were resistant to SAUNA stress. nNOS-induced S-nitrosylation of HDAC2 was relayed by transnitrosylation of GAPDH. HDAC2 S-nitrosylation was confirmed in both DD mouse and human left ventricular hypertrophy. S-nitrosylation of HDAC2 took place at C262 and C274. When DD was induced, HDAC2 S-nitrosylation was detected in wild-type mouse, but not in HDAC2 knock-in mouse heart that expressed HDAC2 C262A/C274A. In addition, HDAC2 C262A/C274A mice maintained normal diastolic function under DD stimuli. Gene delivery with adenovirus-associated virus 9 (AAV9)-NRF2, a putative denitrosylase of HDAC2, or pharmacological intervention by dimethyl fumarate successfully induced HDAC2 denitrosylation and mitigated DD in vivo.
Our observations are the first to demonstrate a new mechanism underlying DD pathophysiology. Our results provide theoretical and experimental evidence to explain the ineffectiveness of conventional NO enhancement trials for improving DD with heart failure symptoms. More important, our results suggest that reduction of NO or denitrosylation of HDAC2 may provide a new therapeutic platform for the treatment of refractory heart failure with preserved ejection fraction.
To determine the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and DCE ultrasound (DCE-US) for predicting response to neoadjuvant chemotherapy (NAC) in ...breast cancer patients.
This Institutional Review Board-approved prospective study was performed between 2014 and 2016. Thirty-nine women with breast cancer underwent DCE-US and DCE-MRI before the NAC, follow-up DCE-US after the first cycle of NAC, and follow-up DCE-MRI after the second cycle of NAC. DCE-MRI parameters (transfer constant K
, reverse constant k
, and leakage space V
) were assessed with histograms. From DCE-US, peak-enhancement, the area under the curve, wash-in rate, wash-out rate, time to peak, and rise time (RT) were obtained. After surgery, all the imaging parameters and their changes were compared with histopathologic response using the Miller-Payne Grading (MPG) system. Data from minor and good responders were compared using Wilcoxon rank sum test, chi-square test, or Fisher's exact test. Receiver operating characteristic curve analysis was used for assessing diagnostic performance to predict good response.
Twelve patients (30.8%) showed a good response (MPG 4 or 5) and 27 (69.2%) showed a minor response (MPG 1-3). The mean, 25th, 50th, and 75th percentiles of K
and K
of post-NAC DCE-MRI differed between the two groups. These parameters showed fair to good diagnostic performance for the prediction of response to NAC (AUC 0.76-0.81,
≤ 0.007). Among DCE-US parameters, the percentage change in RT showed fair prediction (AUC 0.71,
= 0.023).
Quantitative analysis of DCE-MRI and DCE-US was helpful for early prediction of response to NAC.
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