The Extremely Luminous Quasar Survey in the Pan-STARRS 1 Footprint (PS-ELQS)

We present the results of the Extremely Luminous Quasar Survey in the $3\pi$ survey of the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS; PS1). This effort applies the successful quasar selection strategy of the Extremely Luminous Survey in the Sloan Digital Sky Survey footprint ($\sim12,000\,\rm{deg}^2$) to a much larger area ($\sim\rm{21486}\,\rm{deg}^2$). This spectroscopic survey targets the most luminous quasars ($M_{1450}\le-26.5$; $m_{i}\le18.5$) at intermediate redshifts ($z\ge2.8$). Candidates are selected based on a near-infrared JKW2 color cut using WISE AllWISE and 2MASS photometry to mainly reject stellar contaminants. Photometric redshifts ($z_{\rm{reg}}$) and star-quasar classifications for each candidate are calculated from near-infrared and optical photometry using the supervised machine learning technique random forests. We select 806 quasar candidates at $z_{\rm{reg}}\ge2.8$ from a parent sample of 74318 sources. After exclusion of known sources and rejection of candidates with unreliable photometry, we have taken optical identification spectra for 290 of our 334 good PS-ELQS candidates. We report the discovery of 190 new $z\ge2.8$ quasars and an additional 28 quasars at lower redshifts. A total of 44 good PS-ELQS candidates remain unobserved. Including all known quasars at $z\ge2.8$, our quasar selection method has a selection efficiency of at least $77\%$. At lower declinations $-30\le\rm{Decl.}\le0$ we approximately triple the known population of extremely luminous quasars. We provide the PS-ELQS quasar catalog with a total of 592 luminous quasars ($m_{i}\le18.5$, $z\ge2.8$). This unique sample will not only be able to provide constraints on the volume density and quasar clustering of extremely luminous quasars, but also offers valuable targets for studies of the intergalactic medium.Comment: 34 pages, 10 figures, accepted to ApJ

Prognostic values of a combination of intervals between respiratory illness and onset of neurological symptoms and elevated serum IgM titers in Mycoplasma pneumoniae encephalopathy

Background/PurposeTo retrospectively analyze the clinical manifestations of Mycoplasma pneumoniae (M. pneumoniae)-associated encephalopathy in pediatric patients.MethodsPediatric patients with positive serum anti-M. pneumoniae immunoglobulin M (IgM) were enrolled in this study. Clinical signs and symptoms, laboratory data, neuroimaging findings, and electrophysiological data were reviewed.ResultsOf 1000 patients identified, 11 (1.1%; male:female ratio = 7:4) had encephalopathy and were admitted to the pediatric intensive care unit. Clinical presentation included fever, symptoms of respiratory illness, and gastrointestinal upset. Neurological symptoms included altered consciousness, seizures, coma, focal neurological signs, and personality change. Neuroimaging and electroencephalographic findings were non-specific. Specimens of cerebrospinal fluid (CSF) for M. pneumoniae polymerase chain reaction (PCR) were negative. Higher M. pneumoniae IgM titers and longer intervals between respiratory and CNS manifestations were associated with worse outcomes.ConclusionClinical manifestations of M. pneumoniae-associated encephalopathy were variable. Diagnosis of M. pneumoniae encephalopathy should not rely on CSF detection of M. pneumoniae by PCR. M. pneumoniae IgM titers and intervals between respiratory and CNS manifestations might be possibly related to the prognosis of patients with M. pneumoniae-associated encephalopathy

Serum repressing efflux pump CDR1 in Candida albicans

BACKGROUND: In the past decades, the prevalence of candidemia has increased significantly and drug resistance has also become a pressing problem. Overexpression of CDR1, an efflux pump, has been proposed as a major mechanism contributing to the drug resistance in Candida albicans. It has been demonstrated that biological fluids such as human serum can have profound effects on antifungal pharmacodynamics. The aim of this study is to understand the effects of serum in drug susceptibility via monitoring the activity of CDR1 promoter of C. albicans. RESULTS: The wild-type C. albicans cells (SC5314) but not the cdr1/cdr1 mutant cells became more susceptible to the antifungal drug when the medium contained serum. To understand the regulation of CDR1 in the presence of serum, we have constructed CDR1 promoter-Renilla luciferase (CDR1p-RLUC) reporter to monitor the activity of the CDR1 promoter in C. albicans. As expected, the expression of CDR1p-RLUC was induced by miconazole. Surprisingly, it was repressed by serum. Consistently, the level of CDR1 mRNA was also reduced in the presence of serum but not N-acetyl-D-glucosamine, a known inducer for germ tube formation. CONCLUSION: Our finding that the expression of CDR1 is repressed by serum raises the question as to how does CDR1 contribute to the drug resistance in C. albicans causing candidemia. This also suggests that it is important to re-assess the prediction of in vivo therapeutic outcome of candidemia based on the results of standard in vitro antifungal susceptibility testing, conducted in the absence of serum

Ludwigia octovalvis extract improves glycemic control and memory performance in diabetic mice

Ethnopharmacological relevance Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes. Aim of the study We have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK). Since AMPK has become a critical target for treating diabetes, we herein investigate the anti-hyperglycemic potential of LOE. Materials and methods Differentiated C2C12 muscle cells, HepG2 hepatocellular cells, streptozotocin (STZ)-induced diabetic mice and high fat diet (HFD)-induced diabetic mice were used to investigate the anti-hyperglycemic potential of LOE. The open field test and novel object recognition test were used to evaluate spontaneous motor activity and memory performance of HFD-induced diabetic mice. Results In differentiated C2C12 muscle cells and HepG2 hepatocellular cells, treatments with LOE and its active component (β-sitosterol) induced significant AMPK phosphorylation. LOE also enhanced uptake of a fluorescent glucose derivative (2-NBDG) and inhibited glucose production in these cells. The beneficial effects of LOE were completely abolished when an AMPK inhibitor, dorsomorphin, was added to the culture system, suggesting that LOE requires AMPK activation for its action in vitro. In streptozotocin (STZ)-induced diabetic mice, we found that both LOE and β-sitosterol induced an anti-hyperglycemic effect comparable to that of metformin, a drug that is commonly prescribed to treat diabetes. Moreover, LOE also improved glycemic control and memory performance of mice fed a HFD. Conclusions These results indicate that LOE is a potent anti-diabetic intervention that may have potential for future clinical applications

A Closer Look at Two of the Most Luminous Quasars in the Universe

Ultra-luminous quasars ($M_{1450} \leq -29$) provide us with a rare view into the nature of the most massive and most rapidly accreting supermassive black holes (SMBHs). Following the discovery of two of these extreme sources, J0341${+}$1720 ($M_{1450}=-29.56$, $z=3.71$) and J2125${-}$1719 ($M_{1450}=-29.39$, $z=3.90$), in the Extremely Luminous Quasar Survey (ELQS) and its extension to the Pan-STARRS\,1 footprint (PS-ELQS), we herein present an analysis of their rest-frame UV to optical spectroscopy. Both quasars harbor very massive SMBHs with $M_{\rm{BH}}=6.73_{-0.83}^{+0.75}\times10^{9}\,M_{\odot}$ and $M_{\rm{BH}}=5.45_{-0.55}^{+0.60}\times10^{9}\,M_{\odot}$, respectively, showing evidence of accretion above the Eddington limit ($L_{\rm{bol}}/L_{\rm{Edd}}=2.74_{-0.27}^{+0.39}$ and $L_{\rm{bol}}/L_{\rm{Edd}}=3.01_{-0.30}^{+0.34}$). NOEMA 3 millimeter observations of J0341${+}$1720 reveal a highly star-forming ($\rm{SFR}\approx1500\,M_{\odot}\,\rm{yr}^{-1}$), ultra-luminous infrared galaxy ($L_{\rm{TIR}}\approx1.0\times10^{13}\,L_{\odot}$) host, which, based on an estimate of its dynamical mass, is only ${\sim}30$ times more massive than the SMBH it harbors at its center. As examples of luminous super-Eddington accretion, these two quasars provide support for theories, which explain the existence of billion solar mass SMBHs ${\sim}700$ million years after the Big Bang by moderate super-Eddington growth from standard SMBH seeds.Comment: Accepted for publication in the Astrophysical Journal (ApJ

Discovering Chromatin Motifs using FAIRE Sequencing and the Human Diploid Genome

Background: Specific chromatin structures are associated with active or inactive gene transcription. The gene regulatory elements are intrinsically dynamic and alternate between inactive and active states through the recruitment of DNA binding proteins, such as chromatin-remodeling proteins. Results: We developed a unique genome-wide method to discover DNA motifs associated with chromatin accessibility using formaldehyde-assisted isolation of regulatory elements with high-throughput sequencing (FAIRE-seq). We aligned the FAIRE-seq reads to the GM12878 diploid genome and subsequently identified differential chromatin-state regions (DCSRs) using heterozygous SNPs. The DCSR pairs represent the locations of imbalances of chromatin accessibility between alleles and are ideal to reveal chromatin motifs that may directly modulate chromatin accessibility. In this study, we used DNA 6-10mer sequences to interrogate all DCSRs, and subsequently discovered conserved chromatin motifs with significant changes in the occurrence frequency. To investigate their likely roles in biology, we studied the annotated protein associated with each of the top ten chromatin motifs genome-wide, in the intergenic regions and in genes, respectively. As a result, we found that most of these annotated motifs are associated with chromatin remodeling, reflecting their significance in biology. Conclusions: Our method is the first one using fully phased diploid genome and FAIRE-seq to discover motifs associated with chromatin accessibility. Our results were collected to construct the first chromatin motif database (CMD), providing the potential DNA motifs recognized by chromatin-remodeling proteins and is freely available at http://syslab.nchu.edu.tw/chromatin

2-Deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAIL-R2

Background: Past studies have shown that sensitivity of melanoma cells to TRAIL-induced apoptosis is largely correlated with the expression levels of TRAIL death receptors on the cell surface. However, fresh melanoma isolates and melanoma tissue sections express generally low levels of death receptors for TRAIL. The clinical potential of TRAIL in the treatment of melanoma may therefore be limited unless given with agents that increase the cell surface expression of TRAIL death receptors. 2-Deoxy-D-glucose (2-DG) is a synthetic glucose analogue that inhibits glycolysis and glycosylation and blocks cell growth. It has been in clinical evaluation for its potential use as an anticancer agent. In this study, we have examined whether 2-DG and TRAIL interact to enhance their cytotoxicity towards melanoma cells. Results: 2-DG did not kill melanoma cells, but enhanced TRAIL-induced apoptosis in cultured melanoma cells and fresh melanoma isolates. This was associated with increased activation of the caspase cascade and mitochondrial apoptotic pathway, and was blocked by inhibition of TRAIL-R2, and to a lesser extent, inhibition of TRAIL-R1. Treatment with 2-DG up-regulated TRAIL death receptors, in particular, TRAIL-R2, on the melanoma cell surface. Up-regulation of TRAIL-R2 was due to increased transcription that was not dependent on the transcription factors, p53 and CHOP. Instead, the IRE1α and ATF6 pathways of the unfolded protein response that were activated by 2-DG appeared to be involved. Moreover, XBP-1, which is known to be transcriptionally regulated by ATF6 and functionally activated by IRE1α, was found to play an important role in 2-DG-mediated transcriptional up-regulation of TRAIL-R2 in melanoma cells. Conclusion: These results indicate that 2-DG sensitizes human melanoma cells to TRAIL-induced apoptosis by up-regulation of TRAIL-2 via the ATF6/IRE1α/XBP-1 axis of the unfolded protein response. They suggest that 2-DG is a promising agent to increase the therapeutic response to TRAIL in melanoma

The Discovery of A Luminous Broad Absorption Line Quasar at A Redshift of 7.02

Despite extensive efforts, only two quasars have been found at $z>7$ to date due to a combination of low spatial density and high contamination from more ubiquitous Galactic cool dwarfs in quasar selection. This limits our current knowledge of the super-massive black hole (SMBH) growth mechanism and reionization history. In this letter, we report the discovery of a luminous quasar at $z=7.021$, DELS J003836.10$-$152723.6 (hereafter J0038$-$1527), selected using photometric data from DESI Legacy imaging Survey (DELS), Pan-STARRS1 (PS1) imaging Survey, as well as Wide-field Infrared Survey Explore ($WISE$) mid-infrared all-sky survey. With an absolute magnitude of $M_{1450}$=$-$27.1 and bolometric luminosity of $L_{\rm Bol}$=5.6$\times$10$^{13}$ $L_\odot$, J0038$-$1527 is the most luminous quasar known at $z>7$. Deep optical to near infrared spectroscopic observations suggest that J0038-1527 hosts a 1.3 billion solar mass BH accreting at the Eddington limit, with an Eddington ratio of 1.25$\pm$0.19. The CIV broad emission line of J0038$-$1527 is blue-shifted by more than 3000 km s$^{-1}$ to the systemic redshift. More detailed investigations of the high quality spectra reveal three extremely high velocity CIV broad absorption lines (BALs) with velocity from 0.08 to 0.14 times the speed of light and total balnicity index of more than 5000 km s$^{-1}$, suggesting the presence of relativistic outflows. J0038$-$1527 is the first quasar found at the epoch of reionization (EoR) with such strong outflows and provides a unique laboratory to investigate AGN feedback on the formation and growth of the most massive galaxies in the early universe.Comment: ApJL in pres

Genetic diversity and C2-like subgenogroup strains of enterovirus 71, Taiwan, 2008

<p>Abstract</p> <p>Background</p> <p>Human enterovirus 71 (EV-71) is known of having caused numerous outbreaks of hand-foot-mouth disease, and other clinical manifestations globally. In 2008, 989 EV-71 strains were isolated in Taiwan.</p> <p>Results</p> <p>In this study, the genetic and antigenic properties of these strains were analyzed and the genetic diversity of EV-71 subgenogroups surfacing in Taiwan was depicted, which includes 3 previously reported subgenogroups of C5, B5, and C4, and one C2-like subgenogroup. Based on the phylogenetic analyses using their complete genome nucleotide sequences and neutralization tests, the C2-like subgenogroup forms a genetically distinct cluster from other subgenogroups, and the antisera show a maximum of 128-fold decrease of neutralization titer against this subgenogroup. In addition, the subgenogroup C4 isolates of 2008 were found quite similar genetically to the Chinese strains that caused outbreaks in recent years and thus they should be carefully watched.</p> <p>Conclusions</p> <p>Other than to be the first report describing the existence of C2-like subgenogroup of EV-71 in Taiwan, this article also foresees a potential of subgenogroup C4 outbreaks in Taiwan in the near future.</p