A Simple High Performance Liquid Chromatography Method for Determination of Rebamipide in Rat Urine

Rebamipide is a mucoprotective agent commonly used to prevent nonsteriodal anti-inflammatory drug-induced gastrointenstinal side effects [1]. Human plasma and urine analysis of rebamipide utilizing high performance liquid chromatography (HPLC) have been reported [2]. Recently, we reported on the plasma levels of rebamipide in presense or absence of celecoxib or diclofenac in rats [3] using a modified HPLC method of detection developed by Jeoung et al. [4]. To tailor the method towards use in urinary rebamipide extraction and analysis, the following modifications were made:To compensate for high concentrations of rebamipide found in urine, a new rebamipide stock solution was prepared with a final concentration of 50,000 ng/mL.Rat urine calibration standards were obtained within the range of 50-1000 ng/mL and 1000-50,000 ng/mL.Plasma samples were replaced with urine samples

A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies

A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data. We also quantitatively describe the parameter space in which binding occurs. Our results point toward mechanisms relating epitope immobility to cell adhesion and offer insight into the activity of an important class of drugs.Comment: 13 pages, 5 figure

Subglacial roughness of the Greenland Ice Sheet: relationship with contemporary ice velocity and geology

The subglacial environment of the Greenland Ice Sheet (GrIS) is poorly constrained both in its bulk properties, for example geology, the presence of sediment, and the presence of water, and interfacial conditions, such as roughness and bed rheology. There is, therefore, limited understanding of how spatially heterogeneous subglacial properties relate to ice-sheet motion. Here, via analysis of 2 decades of radio-echo sounding data, we present a new systematic analysis of subglacial roughness beneath the GrIS. We use two independent methods to quantify subglacial roughness: first, the variability in along-track topography – enabling an assessment of roughness anisotropy from pairs of orthogonal transects aligned perpendicular and parallel to ice flow and, second, from bed-echo scattering – enabling assessment of fine-scale bed characteristics. We establish the spatial distribution of subglacial roughness and quantify its relationship with ice flow speed and direction. Overall, the beds of fast-flowing regions are observed to be rougher than the slow-flowing interior. Topographic roughness exhibits an exponential scaling relationship with ice surface velocity parallel, but not perpendicular, to flow direction in fast-flowing regions, and the degree of anisotropy is correlated with ice surface speed. In many slow-flowing regions both roughness methods indicate spatially coherent regions of smooth beds, which, through combination with analyses of underlying geology, we conclude is likely due to the presence of a hard flat bed. Consequently, the study provides scope for a spatially variable hard- or soft-bed boundary constraint for ice-sheet models

Self-affine subglacial roughness:consequences for radar scattering and basal water discrimination in northern Greenland

Subglacial roughness can be determined at a variety of length scales from radio-echo sounding (RES) data either via statistical analysis of topography or inferred from basal radar scattering. Past studies have demonstrated that subglacial terrain exhibits self-affine (power law) roughness scaling behaviour, but existing radar scattering models do not take this into account. Here, using RES data from northern Greenland, we introduce a self-affine statistical framework that enables a consistent integration of topographicscale roughness with the electromagnetic theory of radar scattering. We demonstrate that the degree of radar scattering, quantified using the waveform abruptness (pulse peakiness), is topographically controlled by the Hurst (roughness power law) exponent. Notably, specular bed reflections are associated with a lower Hurst exponent, with diffuse scattering associated with a higher Hurst exponent. Abrupt waveforms (specular reflections) have previously been used as a RES diagnostic for basal water, and to test this assumption we compare our radar scattering map with a recent prediction for the basal thermal state. We demonstrate that the majority of thawed regions (above pressure melting point) exhibit a diffuse scattering signature, which is in contradiction to the prior approach. Self-affine statistics provide a generalised model for subglacial terrain and can improve our understanding of the relationship between basal properties and ice-sheet dynamics.</p

Using Dark Energy Explorers and Machine Learning to Enhance the Hobby-Eberly Telescope Dark Energy Experiment

We present analysis using a citizen science campaign to improve the cosmological measures from the Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). The goal of HETDEX is to measure the Hubble expansion rate, $H(z)$, and angular diameter distance, $D_A(z)$, at $z =$ 2.4, each to percent-level accuracy. This accuracy is determined primarily from the total number of detected Lyman-$\alpha$ emitters (LAEs), the false positive rate due to noise, and the contamination due to [O II] emitting galaxies. This paper presents the citizen science project, Dark Energy Explorers, with the goal of increasing the number of LAEs, decreasing the number of false positives due to noise and the [O II] galaxies. Initial analysis shows that citizen science is an efficient and effective tool for classification most accurately done by the human eye, especially in combination with unsupervised machine learning. Three aspects from the citizen science campaign that have the most impact are 1) identifying individual problems with detections, 2) providing a clean sample with 100% visual identification above a signal-to-noise cut, and 3) providing labels for machine learning efforts. Since the end of 2022, Dark Energy Explorers has collected over three and a half million classifications by 11,000 volunteers in over 85 different countries around the world. By incorporating the results of the Dark Energy Explorers we expect to improve the accuracy on the $D_A(z)$ and $H(z)$ parameters at $z =$ 2.4 by 10 - 30%. While the primary goal is to improve on HETDEX, Dark Energy Explorers has already proven to be a uniquely powerful tool for science advancement and increasing accessibility to science worldwide.Comment: 14 pages, 6 figures, accepted for publication in The Astrophysical Journa

Exacerbation of Celecoxib-Induced Renal Injury by Concomitant Administration of Misoprostol in Rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 μg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters were measured during the study period. Hearts and kidneys were harvested on final day. Day 2 urinary electrolyte samples revealed significant reductions in sodium excretion in misoprostol (0.12±0.05 μmol/min/100 g) and misoprostol+celecoxib groups (0.07±0.02 μmol/min/100 g). At day 3, all treatment groups showed significantly reduced sodium excretion. Potassium excretion diminished significantly in vehicle+celecoxib and misoprostol+celecoxib groups from day 3 onward. Urinary kidney injury molecule-1 levels were significantly increased in vehicle+celecoxib (0.65±0.02 vs. 0.35±0.07 ng/mL, p = 0.0002) and misoprostol+celecoxib (0.61±0.06 vs. 0.37±0.06 ng/mL, p = 0.0015) groups when compared to baseline; while plasma levels of cardiac troponin I increased significantly in vehicle+celecoxib (p = 0.0040) and misoprostol+misoprostol (p = 0.0078) groups when compared to vehicle+vehicle. Blood pressure parameters increased significantly in all misoprostol treated groups. Significant elevation in diastolic (p = 0.0071) and mean blood pressure (p = 0.0153) was noted in misoprostol+celecoxib compared to vehicle+celecoxib. All treatments produced significant tubular dilatation/necrosis compared to control. No significant myocardial changes were noticed; however, three animals presented with pericarditis. Kidney, heart, and plasma celecoxib levels revealed no significant change between vehicle+celecoxib and misoprostol+celecoxib. Concomitant misoprostol administration did not prevent celecoxib renal toxicity, and instead exacerbated renal side effects. Misoprostol did not alter plasma or tissue celecoxib concentrations suggesting no pharmacokinetic interaction between celecoxib and misoprostol

The Active Galactic Nuclei in the Hobby-Eberly Telescope Dark Energy Experiment Survey (HETDEX). III. A Red Quasar with Extremely High Equivalent Widths Showing Powerful Outflows

We report an active galactic nucleus (AGN) with an extremely high equivalent width (EW), EWLyα+N V,rest ≳921 Å, in the rest frame, at z ∼ 2.24 in the Hobby-Eberly Telescope Dark Energy Experiment Survey (HETDEX), as a representative case of the high-EW AGN population. The continuum level is a nondetection in the HETDEX spectrum; thus the measured EW is a lower limit. The source is detected with significant emission lines (>7σ) at Lyα + N v λ1241, C iv λ1549, and a moderate emission line (∼4σ) at He ii λ1640 within the wavelength coverage of HETDEX (3500-5500 Å). The r-band magnitude is 24.57 from the Hyper Suprime-Cam-HETDEX joint survey with a detection limit of r = 25.12 at 5σ. The Lyα emission line spans a clearly resolved region of ∼10″ (85 kpc) in diameter. The Lyα line profile is strongly double peaked. The spectral decomposed blue gas and red gas Lyα emission are separated by ∼1.″2 (10.1 kpc) with a line-of-sight velocity offset of ∼1100 km s−1. This source is probably an obscured AGN with powerful winds

The Stars of the HETDEX Survey. I. Radial Velocities and Metal-Poor Stars from Low-Resolution Stellar Spectra

The Hobby-Eberly Telescope Dark Energy Experiment (HETDEX) is an unbiased, massively multiplexed spectroscopic survey, designed to measure the expansion history of the universe through low-resolution (R∼750) spectra of Lyman-Alpha Emitters. In its search for these galaxies, HETDEX will also observe a few 105 stars. In this paper, we present the first stellar value-added catalog within the internal second data release of the HETDEX Survey (HDR2). The new catalog contains 120,571 low-resolution spectra for 98,736 unique stars between 10∘) Galactic latitudes. With these spectra, we measure radial velocities (RVs) for ∼42,000 unique FGK-type stars in the catalog and show that the HETDEX spectra are sufficient to constrain these RVs with a 1σ precision of 28.0 km/s and bias of 3.5 km/s with respect to the LAMOST surveys and 1σ precision of 27.5 km/s and bias of 14.0 km/s compared to the SEGUE survey. Since these RVs are for faint (G≥16) stars, they will be complementary to Gaia. Using t-Distributed Stochastic Neighbor Embedding (t-SNE), we also demonstrate that the HETDEX spectra can be used to determine a star's Teff, and log g and its [Fe/H]. With the t-SNE projection of the FGK-type stars with HETDEX spectra we also identify 416 new candidate metal-poor ([Fe/H] <−1~dex) stars for future study. These encouraging results illustrate the utility of future low-resolution stellar spectroscopic surveys

The HETDEX Survey: Emission Line Exploration and Source Classification

The Hobby-Eberly Telescope Dark Energy Experiment (HETDEX) is an untargeted spectroscopic survey that aims to measure the expansion rate of the Universe at $z \sim 2.4$ to 1% precision for both $H(z)$ and $D_A(z)$. HETDEX is in the process of mapping in excess of one million Lyman Alpha emitting (LAE) galaxies and a similar number of lower-z galaxies as a tracer of the large-scale structure. The success of the measurement is predicated on the post-observation separation of galaxies with Ly$\alpha$ emission from the lower-$z$ interloping galaxies, primarily [OII], with low contamination and high recovery rates. The Emission Line eXplorer (ELiXer) is the principal classification tool for HETDEX, providing a tunable balance between contamination and completeness as dictated by science needs. By combining multiple selection criteria, ELiXer improves upon the 20 Angstrom rest-frame equivalent width cut commonly used to distinguish LAEs from lower-$z$ [OII] emitting galaxies. Despite a spectral resolving power, R $\sim800$, that cannot resolve the [OII] doublet, we demonstrate the ability to distinguish LAEs from foreground galaxies with 98.1% accuracy. We estimate a contamination rate of Ly$\alpha$ by [OII] of 1.2% and a Ly$\alpha$ recovery rate of 99.1% using the default ELiXer configuration. These rates meet the HETDEX science requirements.Comment: 38 pages, 11 figure

HETDEX Public Source Catalog 1 -- Stacking 50K Lyman Alpha Emitters

We describe the ensemble properties of the $1.9 < z < 3.5$ Lyman Alpha Emitters (LAEs) found in the HETDEX survey's first public data release, HETDEX Public Source Catalog 1 (Mentuch Cooper et al. 2023). Stacking the low-resolution ($R \sim$ 800) spectra greatly increases the signal-to-noise ratio, revealing spectral features otherwise hidden by noise, and we show that the stacked spectrum is representative of an average member of the set. The flux limited, Ly$\alpha$ signal-to-noise ratio restricted stack of 50K HETDEX LAEs shows the ensemble biweight ``average" $z \sim 2.6$ LAE to be a blue (UV continuum slope $\sim -2.4$ and E(B-V) $< 0.1$), moderately bright (M$_{\text{UV}} \sim -19.7$) star forming galaxy with strong Ly$\alpha$ emission (log $L_{Ly\alpha}$ $\sim$ 42.8 and $W_{\lambda}$(Ly$\alpha$) $\sim$ 114\AA), and potentially significant leakage of ionizing radiation. The restframe UV light is dominated by a young, metal poor stellar population with an average age 5-15 Myr and metallicity of 0.2-0.3 Z$_{\odot}$.Comment: 17 pages, 11 figures, 2 data files (ApJ Accepted