Modulation of Serum Antinuclear Antibody Levels by Levamisole Treatment in Patients With Oral Lichen Planus

Background/PurposeSerum autoantibodies, including antinuclear antibodies (ANAs), have been found in patients with oral lichen planus (OLP). This study evaluated whether Taiwanese OLP patients had significantly higher frequencies of serum ANAs than healthy control subjects, and whether levamisole treatment could modulate the antibody levels.MethodsThis study used an indirect immunofluorescence technique to measure the baseline serum levels of ANA in a group of 583 Taiwanese OLP patients and 53 healthy control subjects. Seventy-nine ANA-positive OLP patients were treated with levamisole under a regular follow-up schedule in our dental clinic, and their serum ANA levels were measured after treatment.ResultsWe found that the frequencies of serum ANA in patients with OLP (23.2%), erosive OLP (EOLP, 23.8%), major EOLP (31.5%), and minor EOLP (18.1%) were all significantly higher than that (5.7%) in healthy control subjects. In addition, major EOLP patients had a significantly higher serum ANA positive rate than minor EOLP or non-erosive OLP patients. Of 135 ANA-positive OLP patients, 79 were treated with levamisole under a regular follow-up schedule. We found that treatment with levamisole for a period of 2–38 months (mean, 12 ± 9 months) effectively reduced the high mean serum ANA titer (557 ± 98) at baseline to an undetectable level (0) in all ANA-positive OLP patients, regardless of different high initial serum titers of ANA.ConclusionThere was a significantly higher frequency of serum ANA (23.2%) in Taiwanese OLP patients than in healthy control subjects. Treatment with levamisole for 2–38 months reduced the high serum ANA to an undetectable level, and significantly improved the signs and symptoms in all treated OLP patients

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model

The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey: tomographic BAO analysis of DR12 combined sample in configuration space

We perform a tomographic baryon acoustic oscillations analysis using the two-point galaxy correlation function measured from the combined sample of BOSS DR12, which covers the redshift range of $0.2<z<0.75$. Splitting the sample into multiple overlapping redshift slices to extract the redshift information of galaxy clustering, we obtain a measurement of $D_A(z)/r_d$ and $H(z)r_d$ at nine effective redshifts with the full covariance matrix calibrated using MultiDark-Patchy mock catalogues. Using the reconstructed galaxy catalogues, we obtain the precision of $1.3\%-2.2\%$ for $D_A(z)/r_d$ and $2.1\%-6.0\%$ for $H(z)r_d$. To quantify the gain from the tomographic information, we compare the constraints on the cosmological parameters using our 9-bin BAO measurements, the consensus 3-bin BAO and RSD measurements at three effective redshifts in \citet{Alam2016}, and the non-tomographic (1-bin) BAO measurement at a single effective redshift. Comparing the 9-bin with 1-bin constraint result, it can improve the dark energy Figure of Merit by a factor of 1.24 for the Chevallier-Polarski-Linder parametrisation for equation of state parameter $w_{\rm DE}$. The errors of $w_0$ and $w_a$ from 9-bin constraints are slightly improved when compared to the 3-bin constraint result.Comment: 14 pages, 21 figures, 7 Tables. Submitted to MNRA

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: single-probe measurements from CMASS anisotropic galaxy clustering

With the largest spectroscopic galaxy survey volume drawn from the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), we can extract cosmological constraints from the measurements of redshift and geometric distortions at quasi-linear scales (e.g. above 50 $h^{-1}$Mpc). We analyze the broad-range shape of the monopole and quadrupole correlation functions of the BOSS Data Release 12 (DR12) CMASS galaxy sample, at the effective redshift $z=0.59$, to obtain constraints on the Hubble expansion rate $H(z)$, the angular-diameter distance $D_A(z)$, the normalized growth rate $f(z)\sigma_8(z)$, and the physical matter density $\Omega_mh^2$. We obtain robust measurements by including a polynomial as the model for the systematic errors, and find it works very well against the systematic effects, e.g., ones induced by stars and seeing. We provide accurate measurements $\{D_A(0.59)r_{s,fid}/r_s$ $\rm Mpc$, $H(0.59)r_s/r_{s,fid}$ $km s^{-1} Mpc^{-1}$, $f(0.59)\sigma_8(0.59)$, $\Omega_m h^2\}$ = $\{1427\pm26$, $97.3\pm3.3$, $0.488 \pm 0.060$, $0.135\pm0.016\}$, where $r_s$ is the comoving sound horizon at the drag epoch and $r_{s,fid}=147.66$ Mpc is the sound scale of the fiducial cosmology used in this study. The parameters which are not well constrained by our galaxy clustering analysis are marginalized over with wide flat priors. Since no priors from other data sets, e.g., cosmic microwave background (CMB), are adopted and no dark energy models are assumed, our results from BOSS CMASS galaxy clustering alone may be combined with other data sets, i.e., CMB, SNe, lensing or other galaxy clustering data to constrain the parameters of a given cosmological model. The uncertainty on the dark energy equation of state parameter, $w$, from CMB+CMASS is about 8 per cent. The uncertainty on the curvature fraction, $\Omega_k$, is 0.3 per cent. We do not find deviation from flat $\Lambda$CDM.Comment: 15 pages, 11 figures. The latest version matches and the accepted version by MNRAS. A bug in the first version has been identified and fixed in the new version. We have redone the analysis with newest data (BOSS DR12

Genome structure and evolutionary history of frankincense producing \u3ci\u3eBoswellia sacra\u3c/i\u3e

Boswellia sacra Flueck (family Burseraceae) tree is wounded to produce frankincense. We report its de novo assembled genome (667.8 Mb) comprising 18,564 high-confidence protein-encoding genes. Comparing conserved single-copy genes across eudicots suggest \u3e97% gene space assembly of B. sacra genome. Evolutionary history shows B. sacra gene-duplications derived from recent paralogous events and retained from ancient hexaploidy shared with other eudicots. The genome indicated a major expansion of Gypsy retroelements in last 2 million years. The B. sacra genetic diversity showed four clades intermixed with a primary genotype—dominating most resin-productive trees. Further, the stemtranscriptome revealed that wounding concurrently activates phytohormones signaling, cell wall fortification, and resin terpenoid biosynthesis pathways leading to the synthesis of boswellic acid—a key chemotaxonomic marker of Boswellia. The sequence datasets reported here will serve as a foundation to investigate the genetic determinants of frankincense and other resin-producing species in Burseraceae

Prevalidation of Salivary Biomarkers for Oral Cancer Detection

Background: Oral cancer is the sixth most common cancer with a 5-year survival rate of approximately 60%. Presently, there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate whether the seven mRNAs and three proteins previously reported as biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)-Early Detection Research Network (EDRN)-Biomarker Reference Laboratory (BRL). Methods: Three hundred and ninety-five subjects from five independent cohorts based on case controlled design were investigated by two independent laboratories, University of California, Los Angeles (Los Angeles, CA) discovery laboratory and NCI-EDRN-BRL. Results: Expression of all sevenmRNAand three protein markers was increased in OSCC versus controls in all five cohorts. With respect to individual marker performance across the five cohorts, the increase in interleukin (IL)-8 and subcutaneous adipose tissue (SAT) was statistically significant and they remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model showed an area under the receiver operating characteristic (ROC) curve for prediction of OSCC status ranging from 0.74 to 0.86 across the cohorts. Conclusions: The validation of these biomarkers showed their feasibility in the discrimination of OSCCs from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies. Impact: Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects. ©2012 AACR

The Chinese Herbal Medicine Tien-Hsien Liquid Inhibits Cell Growth and Induces Apoptosis in a Wide Variety of Human Cancer Cells

ABSTRACT Objective: Tien-Hsien liquid (THL) is a commercially available Chinese herbal mixture that has been used as an anticancer dietary supplement for more than 10 years. We recently showed that THL has strong immunomodulatory effects on peripheral blood mononuclear cells (PBMC) and T cells. To investigate the antitumor activity of THL further, we sought to test whether THL could induce apoptosis in various human cancer cell lines based on the fact that THL contains several components with tumor killing functions. Design: The growth inhibitory effect of THL on human cervical carcinoma C-33A cells, human lung carcinoma H1299 cells, and human PBMC was assessed by counting viable cells using the trypan blue dye exclusion method. The apoptosis-inducing activity of THL in H1299 cells was assessed by analyzing the cells with four assays: (1) Hoechst 33258 nuclear DNA staining; (2) the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay; (3) the nucleosomal DNA fragment ladder assay; and (4) the sub-G 1 cell analysis. The activities of caspase-8, -9, and -3 in H1299 cells treated with or without THL were also measured to elucidate the possible mechanism underlying THL apoptosis-inducing effect. Finally, the apoptotic effect of THL on fifteen human cancer cell lines and normal human cells were analyzed by the TUNEL assay. Results: THL could induce apoptosis in all human cancer cell lines tested but not in normal human cells. THL treatment of H1299 cancer cells resulted in activation of caspase-8, -9, and -3 and the inhibitors of these caspases could partially block THL-induced apoptosis. Conclusions: THL has been used by numerous patients with cancer for many years with no known adverse effect. Our present study showing that THL had a broad-range tumor killing function has provided a molecular basis underlying THL therapeutic activity. Furthermore, because THL had apoptotic effects only on cancer cells but not on normal cells, this selectivity suggests that THL could be a potential cancer therapeutic agent. 24

The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey : tomographic BAO analysis of DR12 combined sample in Fourier space

We perform a tomographic baryon acoustic oscillations (BAO) analysis using the monopole, quadrupole and hexadecapole of the redshift-space galaxy power spectrum measured from the pre-reconstructed combined galaxy sample of the completed Sloan Digital Sky Survey Baryon Oscillation Spectroscopic Survey (BOSS) Data Release12 covering the redshift range of 0.20 < z < 0.75. By allowing for overlap between neighbouring redshift slices, we successfully obtained the isotropic and anisotropic BAO distance measurements within nine redshift slices to a precision of 1.5–3.4 per cent for DV/rd, 1.8–4.2 per cent for DA/rd and 3.7–7.5 per cent for H rd, depending on effective redshifts. We provide our BAO measurement of DA/rd and H rd with the full covariance matrix, which can be used for cosmological implications. Our measurements are consistent with those presented in Alam et al., in which the BAO distances are measured at three effective redshifts. We constrain dark energy parameters using our measurements and find an improvement of the Figure-of-Merit of dark energy in general due to the temporal BAO information resolved. This paper is a part of a set that analyses the final galaxy clustering data set from BOSS.PostprintPeer reviewe

Nanoscale waveguiding methods

While 32 nm lithography technology is on the horizon for integrated circuit (IC) fabrication, matching the pace for miniaturization with optics has been hampered by the diffraction limit. However, development of nanoscale components and guiding methods is burgeoning through advances in fabrication techniques and materials processing. As waveguiding presents the fundamental issue and cornerstone for ultra-high density photonic ICs, we examine the current state of methods in the field. Namely, plasmonic, metal slot and negative dielectric based waveguides as well as a few sub-micrometer techniques such as nanoribbons, high-index contrast and photonic crystals waveguides are investigated in terms of construction, transmission, and limitations. Furthermore, we discuss in detail quantum dot (QD) arrays as a gain-enabled and flexible means to transmit energy through straight paths and sharp bends. Modeling, fabrication and test results are provided and show that the QD waveguide may be effective as an alternate means to transfer light on sub-diffraction dimensions

The genome sequence of the orchid Phalaenopsis equestris

Orchidaceae, renowned for its spectacular flowers and other reproductive and ecological adaptations, is one of the most diverse plant families. Here we present the genome sequence of the tropical epiphytic orchid Phalaenopsis equestris, a frequently used parent species for orchid breeding. P. equestris is the first plant with crassulacean acid metabolism (CAM) for which the genome has been sequenced. Our assembled genome contains 29,431 predicted protein-coding genes. We find that contigs likely to be underassembled, owing to heterozygosity, are enriched for genes that might be involved in self-incompatibility pathways. We find evidence for an orchid-specific paleopolyploidy event that preceded the radiation of most orchid clades, and our results suggest that gene duplication might have contributed to the evolution of CAM photosynthesis in P. equestris. Finally, we find expanded and diversified families of MADS-box C/D-class, B-class AP3 and AGL6-class genes, which might contribute to the highly specialized morphology of orchid flowers. (Résumé d'auteur