Molecular Epidemiologic Evidence for Diabetogenic Effects of Dioxin Exposure in U.S. Air Force Veterans of the Vietnam War

BACKGROUND: One of the outcomes positively associated with dioxin exposure in humans is type 2 diabetes. OBJECTIVES: This study was conducted in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans. METHODS: We obtained 313 adipose tissue samples both from Vietnam veterans who were exposed to dioxin (Operation Ranch Hand) and from comparison veterans who served in Southeast Asia with no record of dioxin exposure. We conducted quantitative reverse-transcribed polymerase chain reaction studies on selected marker mRNAs from these samples. RESULTS: We found the most sensitive and reliable molecular indicator of dioxin-induced diabetes to be the ratio of mRNA of glucose transporter 4 (GLUT4) and nuclear transcription factor kappa B (NFκB), a marker of inflammation. This ratio showed significant correlations to serum dioxin residues and to fasting glucose among those in the Ranch Hand group and, surprisingly, even in the comparison group, who have low levels of dioxin comparable to the general public. Such a correlation in the comparison group was particularly significant among those with known risk factors such as obesity and family history of diabetes. CONCLUSIONS: These results show that the GLUT4:NFκB ratio is a reliable marker for the diabetogenic action of dioxin, particularly at very low exposure levels that are not much higher than those found in the general public, implying a need to address current exposure levels

The star-forming content of the W3 giant molecular cloud

We have surveyed a ~0.9-square-degree area of the W3 giant molecular cloud and star-forming region in the 850-micron continuum, using the SCUBA bolometer array on the James Clerk Maxwell Telescope. A complete sample of 316 dense clumps was detected with a mass range from around 13 to 2500 Msun. Part of the W3 GMC is subject to an interaction with the HII region and fast stellar winds generated by the nearby W4 OB association. We find that the fraction of total gas mass in dense, 850-micron traced structures is significantly altered by this interaction, being around 5% to 13% in the undisturbed cloud but ~25 - 37% in the feedback-affected region. The mass distribution in the detected clump sample depends somewhat on assumptions of dust temperature and is not a simple, single power law but contains significant structure at intermediate masses. This structure is likely to be due to crowding of sources near or below the spatial resolution of the observations. There is little evidence of any difference between the index of the high-mass end of the clump mass function in the compressed region and in the unaffected cloud. The consequences of these results are discussed in terms of current models of triggered star formation.Comment: 13 pages, 8 figures, 1 table (full source table available on request). Accepted for publication in Monthly Notices of the Royal Astronomical Society (Main Journal

Probing the envelopes of massive young stellar objects with diffraction limited mid-infrared imaging

Massive stars form whilst they are still embedded in dense envelopes. As a result, the roles of rotation, mass loss and accretion in massive star formation are not well understood. This study evaluates the source of the Q-band, lambda=19.5 microns, emission of massive young stellar objects (MYSOs). This allows us to determine the relative importance of rotation and outflow activity in shaping the circumstellar environments of MYSOs on 1000 AU scales. We obtained diffraction limited mid-infrared images of a sample of 20 MYSOs using the VLT/VISIR and Subaru/COMICS instruments. For these 8 m class telescopes and the sample selected, the diffraction limit, ~0.6", corresponds to approximately 1000 AU. We compare the images and the spectral energy distributions (SEDs) observed to a 2D, axis-symmetric dust radiative transfer model that reproduces VLTI/MIDI observations of the MYSO W33A. We vary the inclination, mass infall rate, and outflow opening angle to simultaneously recreate the behaviour of the sample of MYSOs in the spatial and spectral domains. The mid-IR emission of 70 percent of the MYSOs is spatially resolved. In the majority of cases, the spatial extent of their emission and their SEDs can be reproduced by the W33A model featuring an in-falling, rotating dusty envelope with outflow cavities. There is independent evidence that most of the sources which are not fit by the model are associated with ultracompact HII regions and are thus more evolved. We find that, in general, the diverse 20 micron morphology of MYSOs can be attributed to warm dust in the walls of outflow cavities seen at different inclinations. This implies that the warm dust in the outflow cavity walls dominates the Q-band emission of MYSOs. In turn, this emphasises that outflows are an ubiquitous feature of massive star formation.Comment: Accepted for publication in A&A. The images in this version have been compressed. A high resolution version is available on reques

Mid-IR imaging of the transitional disk of HD169142: Measuring the size of the gap

The disk around the Herbig Ae star HD\,169142 was imaged and resolved at 18.8 and 24.5\,$\mu$m using Subaru/COMICS. We interpret the observations using a 2D radiative transfer model and find evidence for the presence of a large gap. The MIR images trace dust that emits at the onset of the strong rise in the spectral energy distribution (SED) at 20\,$\mu$m, therefore are very sensitive to the location and characteristics of the inner wall of the outer disk and its dust. We determine the location of the wall to be 23$^{+3}_{-5}$\,AU from the star. An extra component of hot dust must exist close to the star. We find that a hydrostatic optically thick inner disk does not produce enough flux in the NIR and an optically thin geometrically thick component is our solution to fit the SED. Considering the recent findings of gaps and holes in a number of Herbig Ae/Be group I disks, we suggest that such disk structures may be common in group I sources. Classification as group I should be considered a support for classification as a transitional disk, though improved imaging surveys are needed to support this speculation.Comment: 18 pages, 5 figures, accepted to Ap

Functionalized boron nitride membranes with ultrafast solvent transport performance for molecular separation

Pressure-driven, superfast organic solvent filtration membranes have significant practical applications. An excellent filtration membrane should exhibit high selectivity and permeation in aqueous and organic solvents to meet increasing industrial demand. Here, we report an amino functionalized boron nitride (FBN) based filtration membrane with a nanochannel network for molecular separation and permeation. This membrane is highly stable in water and in several organic solvents and shows high transport performance for solvents depending on the membranes' thickness. In addition, the FBN membrane is applicable for solute screening in water as well as in organic solvents. More importantly, the FBN membranes are very stable in acidic, alkaline and oxidative media for up to one month. The fast-flow rate and good separation performance of the FBN membranes can be attributed to their stable networks of nanochannels and thin laminar structure, which provide the membranes with beneficial properties for practical separation and purification processes

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

Background: Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings: Male balb/c mice were assigned randomly to either sham burn (control) or 30 % total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression

Combination therapy with irinotecan and cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer

To evaluate the response rate and toxicity of the combination of irinotecan (CPT-11) and cisplatin in a neoadjuvant setting, a phase II study was conducted regarding the regimen of this combination in patients with locally advanced cervical cancer. Eligibility included patients with previously untreated stage Ib2, IIb, or IIIb squamous cell carcinoma with good performance status. CPT-11 (60 mg m−2) was administered intravenously on days 1, 8 and 15, followed by cisplatin (60 mg m−2) given intravenously on day 1. Treatment was repeated every 4 weeks for a total of two or three cycles. Among 23 eligible patients (median age: 59 years), three showed complete response (13%), 15 showed partial response (65%), for an overall response rate of 78% (95% confidence interval 58–90%). Stable disease was observed in four cases (17%) and progressive disease in one (4%). The median time to failure and median survival time have not yet been reached. Of the 52 treatment cycles administered, diarrhoea and grade 3 or 4 neutropenia were observed in 10% and 75% respectively. There were no therapy-related deaths. The combination of CPT-11 with cisplatin is a promising regimen for neoadjuvant chemotherapy in locally advanced cervical cancer. The toxicities of this regimen are well tolerated. © 1999 Cancer Research Campaig