From 2-dimensional to 3-dimensional: Overcoming dilemmas in intestinal mucosal interpretation

The purpose of this review is to provide a definitive account of small intestinal mucosal structure and interpretation. The coeliac lesion has been well known, but not well described to date and this review aims to identify the interpretative difficulties which have arisen over time with the histological assessment of coeliac disease. In early coeliac interpretation, there were significant inaccuracies, particularly surrounding intraepithelial lymphocyte counts and the degree of villous flattening which occurred in the tissue. Many of these interpretive pitfalls are still encountered today, increasing the potential for diagnostic errors. These difficulties are mostly due to the fact that stained 2-dimensional sections can never truly represent the 3-dimensional framework of the intestinal tissue under investigation. Therefore, this review offers a critical account occasioned by these 2-dimensional interpretative errors and which, in our opinion, should in general be jettisoned. As a result, we leave a framework regarding the true 3-dimensional knowledge of mucosal structure accrued over the 70-year period of study, and one which is available for future reference

Measurement of an AGN Central Mass on Centiparsec Scales: Results of Long-Term Optical Monitoring of Arp 102B

The optical spectrum of the broad-line radio galaxy Arp 102B has been monitored for more than thirteen years to investigate the nature of the source of its broad, double-peaked hydrogen Balmer emission lines. The shape of the lines varied subtly; there was an interval during which the variation in the ratio of the fluxes of the two peaks appeared to be sinusoidal, with a period of 2.16 years and an amplitude of about 16% of the average value. The variable part of the broad H-alpha line is well fit by a model in which a region of excess emission (a quiescent ``hot spot'') within an accretion disk (fitted to the non-varying portion of the double-peaked line) completes at least two circular orbits and eventually fades. Fits to spectra from epochs when the hot spot is not present allow determination of the disk inclination, while fits for epochs when it is present provide a measurement of the radius of the hot spot's orbit. From these data and the period of variation, we find that the mass within the hot spot's orbit is 2.2 +0.2/-0.7 times 10^8 solar masses, within the range of previous estimates of masses of active galactic nuclei. Because this mass is determined at a relatively small distance (~1000 AU) from the central body, it is extremely difficult to explain without assuming that a supermassive black hole lies within Arp 102B. The lack of any systematic change in the velocity of the blue peak over time yields a lower limit on the combined mass of the two bodies in a binary black hole model like that of Gaskell (1983) of 10^10 solar masses.Comment: 29 pages, including 6 figures; to appear in the Astrophysical Journal 199

Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs.

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy

Seasonal variability of the warm Atlantic Water layer in the vicinity of the Greenland shelf break

The warmest water reaching the east and west coast of Greenland is found between 200?m and 600?m. Whilst important for melting Greenland's outlet glaciers, limited winter observations of this layer prohibit determination of its seasonality. To address this, temperature data from Argo profiling floats, a range of sources within the World Ocean Database and unprecedented coverage from marine-mammal borne sensors have been analysed for the period 2002-2011. A significant seasonal range in temperature (~1-2?°C) is found in the warm layer, in contrast to most of the surrounding ocean. The phase of the seasonal cycle exhibits considerable spatial variability, with the warmest water found near the eastern and southwestern shelf-break towards the end of the calendar year. High-resolution ocean model trajectory analysis suggest the timing of the arrival of the year's warmest water is a function of advection time from the subduction site in the Irminger Basin

Electronic Spectroscopy of Chloro(terpyridine)platinum(II)

The electronic spectrum of [Pt(tpy)Cl]^+ (tpy = 2,2':6',2"-terpyridine) is influenced dramatically by intermolecular stacking interactions in solution and in the solid state. The crystal structure of [Pt(tpy)Cl]ClO_4 (monoclinic, P2_1/c (No. 14); a = 7.085(2), b = 17.064(5), c = 26.905(8) Å; β = 90.0(1) °; Z = 8) consists of discrete Pt_2 units (Pt-Pt = 3.269(1) Å) arranged along an infinite tpy-π stack (spacing ~ 3.35 Å). Variable-temperature and concentration studies of the absorption and emission spectra of [Pt(tpy)Cl]^+ suggest that similar metal-metal and ligand-ligand interactions persist in the solution phase. The high concentration, low-temperature emission spectrum (5:5:1 ethanol:methanol:DMF) reveals a 740-nm band indicative of M-M oligomerization, a 650-nm band attributable to tpy π-π interactions, and a 470-nm band characteristic of mononuclear [Pt(tpy)Cl]^+ π-π* emission. Concentration-dependent absorption spectra were fit to a "two-dimer" model, yielding equilibrium constants for the formation of Pt-Pt-, and tpy-tpy-bound dimers of 1.3(1) x 10^3 and 1.0(1) x 10^3 M^(-1), respectively, in 0.1 M aqueous NaCl. The low temperature solid-state luminescence of [Pt(tpy)Cl]^+ is assigned to a ^3(MMLCT) (MMLCT = metal-metal-to-ligand charge transfer) transition. The energy of this band is highly dependent on the counterion (PF_6^-, ClO_4^- , C1^-, CF_3SO_3^-), in line with the different colors of these various salts. In contrast, the room-temperature solid-state emission spectra are more difficult to interpret. While the red perchlorate salt exhibits a relatively narrow emission band at 725 nm (red-shifted from the 77-K maximum at 695 nm), consistent with a 3(MMLCT) transition, the orange (Cl^-, ClO_4^-, CF_3SO_3^-) and yellow (PF6^-) salts have extremely broad room-temperature emission bands that all appear at nearly the same energy (λ_(max) ~ 640 nm). We assign this luminescence to an eximeric intraligand transition resulting from π- π interactions and propose that the temperature dependent emissions from the orange and yellow solid materials originate from multiple electronic states

The First Ultra-cool Brown Dwarf Discovered by the Wide-field Infrared Survey Explorer

We report the discovery of the first new ultra-cool brown dwarf (BDs) found with the Wide-field Infrared Survey Explorer (WISE). The object’s preliminary designation is WISEPC J045853.90+643451.9. Follow-up spectroscopy with the LUCIFER instrument on the Large Binocular Telescope indicates that it is a very late-type T dwarf with a spectral type approximately equal to T9. Fits to an IRTF/SpeX 0.8–2.5 μm spectrum to the model atmospheres of Marley and Saumon indicate an effective temperature of approximately 600 K as well as the presence of vertical mixing in its atmosphere. The new BD is easily detected by WISE, with a signal-to-noise ratio of ~36 at 4.6 μm. Current estimates place it at a distance of 6–10 pc. This object represents the first in what will likely be hundreds of nearby BDs found by WISE that will be suitable for follow-up observations, including those with the James Webb Space Telescope. One of the two primary scientific goals of the WISE mission is to find the coolest, closest stars to our Sun; the discovery of this new BD proves that WISE is capable of fulfilling this objective

The Post-Common Envelope and Pre-Cataclysmic Binary PG 1224+309

We have made extensive spectroscopic and photometric observations of PG 1224+309, a close binary containing a DA white dwarf primary and an M4+ secondary. The H alpha line is in emission due to irradiation of the M-star by the hot white dwarf and is seen to vary around the orbit. From the radial velocities of the H alpha line we derive a period of P = 0.258689 +/- 0.000004 days and a semi-amplitude of K_Halpha = 160 +/- 8 km/s. We estimate a correction Delta_K = 21 +/- 2 km/s, where K_M = K_Halpha + Delta_K. Radial velocity variations of the white dwarf reveal a semi-amplitude of K_WD = 112 +/- 14 km/s. The blue spectrum of the white dwarf is well fit by a synthetic spectrum having T_eff = 29,300 K and log(g) = 7.38. The white dwarf contributes 97% of the light at 4500 Angstroms and virtually all of the light blueward of 3800 Angstroms. No eclipses are observed. The mass inferred for the white dwarf depends on the assumed mass of the thin residual hydrogen envelope: 0.40 < M_WD < 0.45 solar masses for hydrogen envelope masses of 0 < M_H < 4.0E-4 solar masses. We argue that the mass of the white dwarf is closer to 0.45 solar masses, hence it appears that the white dwarf has a relatively large residual hydrogen envelope. The mass of the M-star is then M_M = 0.28 +/- 0.05 solar masses, and the inclination is i = 77 +/- 7 degrees. We discuss briefly how PG 1224+309 may be used to constrain theories of close binary star evolution, and the past and future histories of PG 1224+309 itself. The star is both a ``post-common envelope'' star and a ``pre-cataclysmic binary'' star. Mass transfer by Roche-lobe overflow should commence in about 10 Gyr.Comment: 17 pages, 8 figures, AAS LaTeX, to appear in AJ, March 199

Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain

Aim: A deficit in parvalbumin neurons is found in schizophrenia and several animal models of the disease. In this preliminary study, we determined whether one such model, phencyclidine (PCP) administration, results in changes in DNA methylation in the rat Pvalb promoter. Materials & methods: DNA from hippocampus and prefrontal cortex from rats, which 6 weeks previously received either 2 mg/kg PCP or vehicle for 7 days, underwent bisulphite pyrosequencing to determine methylation. Results: PCP administration induced significantly greater methylation at one of two Pvalb CpG sites in both prefrontal cortex and hippocampus, while no significant difference was found in long interspersed nucleotide element-1, a global measure of DNA methylation. Conclusion: Subchronic PCP administration results in a specific hypermethylation in the Pvalb promoter which may contribute to parvalbumin deficits in this animal model of psychosis

A Catalog of Spectroscopically Confirmed White Dwarfs from the Sloan Digital Sky Survey Data Release 4

We present a catalog of 9316 spectroscopically confirmed white dwarfs from the Sloan Digital Sky Survey Data Release 4. We have selected the stars through photometric cuts and spectroscopic modeling, backed up by a set of visual inspections. Roughly 6000 of the stars are new discoveries, roughly doubling the number of spectroscopically confirmed white dwarfs. We analyze the stars by performing temperature and surface gravity fits to grids of pure hydrogen and helium atmospheres. Among the rare outliers are a set of presumed helium-core DA white dwarfs with estimated masses below 0.3 Msun, including two candidates that may be the lowest masses yet found. We also present a list of 928 hot subdwarfs.Comment: Accepted by the Astrophysical Journal Supplements, 25 pages, 24 figures, LaTeX. The electronic catalog, as well as diagnostic figures and links to the spectra, is available at http://das.sdss.org/wdcat/dr4

Physiological concentrations of bile acids down-regulate agonist induced secretion in colonic epithelial cells

In patients with bile acid malabsorption, high concentrations of bile acids enter the colon and stimulate Cl− and fluid secretion, thereby causing diarrhoea. However, deoxycholic acid (DCA), the predominant colonic bile acid, is normally present at lower concentrations where its role in regulating transport is unclear. Thus, the current study set out to investigate the effects of physiologically relevant DCA concentrations on colonic epithelial secretory function. Cl− secretion was measured as changes in short-circuit current across voltage-clamped T84 cell monolayers. At high concentrations (0.5–1 mM), DCA acutely stimulated Cl− secretion but this effect was associated with cell injury, as evidenced by decreased transepithelial resistance (TER) and increased lactate dehydrogenase (LDH) release. In contrast, chronic (24 hrs) exposure to lower DCA concentrations (10–200 μM) inhibited responses to Ca2+ and cAMP-dependent secretagogues without altering TER, LDH release, or secretagogue-induced increases in intracellular second messengers. Other bile acids – taurodeoxycholic acid, chenodeoxycholic acid and cholic acid – had similar antisecretory effects. DCA (50 μM) rapidly stimulated phosphorylation of the epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen-activated protein kinases). The EGFr inhibitor, AG1478, and the protein synthesis inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the MAPK inhibitors, PD98059 and SB203580, did not. In summary, our studies suggest that, in contrast to its acute prosecretory effects at pathophysiological concentrations, lower, physiologically relevant, levels of DCA chronically down-regulate colonic epithelial secretory function. On the basis of these data, we propose a novel role for bile acids as physiological regulators of colonic secretory capacity