Mid infrared tomography of polymer pipes

Mid-infrared signals in the 2–5 μm wavelength range have been transmitted through samples of polymer pipes, as commonly used in the water supply industry. It is shown that simple through-transmission images can be obtained using a broad spectrum source and a suitable camera. This leads to the possibility of tomography, where images are obtained as the measurement system is rotated with respect to the axis of the pipe. The unusual 3D geometry created by a source of finite size and the imaging plane of a camera, plus the fact that refraction at the pipe wall would cause significant ray bending, meant that the reconstruction of tomographic images had to be considered with some care. A result is shown for a thinning defect on the inner wall of a polymer water pipe, demonstrating that such changes can be reconstructed successfully

Broad-band X-ray spectral analysis of the Seyfert 1 galaxy GRS 1734-292

We discuss the broad-band X-ray spectrum of GRS 1734−292 obtained from non-simultaneous XMM–Newton and NuSTAR (Nuclear Spectroscopic Telescope Array) observations, performed in 2009 and 2014, respectively. GRS1734−292 is a Seyfert 1 galaxy, located near the Galactic plane at z = 0.0214. The NuSTAR spectrum (3–80 keV) is dominated by a primary power-law continuum with Γ = 1.65 ± 0.05 and a high-energy cut-off Ec=53+11−8 keV, one of the lowest measured by NuSTAR in a Seyfert galaxy. Comptonization models show a temperature of the coronal plasma of kTe=11.9+1.2−0.9 keV and an optical depth, assuming a slab geometry, τ=2.98+0.16−0.19 or a similar temperature and τ=6.7+0.3−0.4 assuming a spherical geometry. The 2009 XMM–Newton spectrum is well described by a flatter intrinsic continuum (⁠Γ=1.47+0.07−0.03⁠) and one absorption line due to Fe XXV Kα produced by a warm absorber. Both data sets show a modest iron Kα emission line at 6.4 keV and the associated Compton reflection, due to reprocessing from neutral circumnuclear material

NuSTAR observations of Mrk 766: Distinguishing reflection from absorption

We present two new NuSTAR observations of the narrow line Seyfert 1 (NLS1) galaxy Mrk 766 and give constraints on the two scenarios previously proposed to explain its spectrum and that of other NLS1s: relativistic reflection and partial covering. The NuSTAR spectra show a strong hard (> 15 keV) X-ray excess, while simultaneous soft X-ray coverage of one of the observations provided by XMM-Newton constrains the ionised absorption in the source. The pure reflection model requires a black hole of high spin (a > 0.92) viewed at a moderate inclination (i = 46 +1 −4 ). The pure partial covering model requires extreme parameters: the cut-off of the primary continuum is very low (22 +7 −5 keV) in one observation and the intrinsic X-ray emission must provide a large fraction (75%) of the bolometric luminosity. Allowing a hybrid model with both partial covering and reflection provides more reasonable absorption parameters and relaxes the constraints on reflection parameters. The fractional variability reduces around the iron K band and at high energies including the Compton hump, suggesting that the reflected emission is less variable than the continuum

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Bio-physical characteristics of gastrointestinal mucosa of celiac patients: comparison with control subjects and effect of gluten free diet-

<p>Abstract</p> <p>Background</p> <p>Intestinal mucosa is leaky in celiac disease (CD), and this alteration may involve changes in hydrophobicity of the mucus surface barrier in addition to alteration of the epithelial barrier. The aims of our study were i) to compare duodenal hydrophobicity as an index of mucus barrier integrity in CD patients studied before (n = 38) and during gluten- free diet (GFD, n = 68), and in control subjects (n = 90), and ii) to check for regional differences of hydrophobicity in the gastro-intestinal tract.</p> <p>Methods</p> <p>Hydrophobicity was assessed by measurement of contact angle (CA) (Rame Hart 100/10 goniometer) generated by a drop of water placed on intestinal mucosal biopsies.</p> <p>Results</p> <p>CA (mean ± SD) of distal duodenum was significantly lower in CD patients (56° ± 10°)) than in control subjects (69° ± 9°, p < 0.0001), and persisted abnormal in patients studied during gluten free diet (56° ± 9°; p < 0.005). CA was significantly higher (62° ± 9°) in histologically normal duodenal biopsies than in biopsies with Marsh 1-2 (58° ± 10°; p < 0.02) and Marsh 3 lesions (57° ± 10°; p < 0.02) in pooled results of all patients and controls studied. The order of hydrofobicity along the gastrointestinal tract in control subjects follows the pattern: gastric antrum > corpus > rectum > duodenum > oesophagus > ileum.</p> <p>Conclusions</p> <p>We conclude that the hydrophobicity of duodenal mucous layer is reduced in CD patients, and that the resulting decreased capacity to repel luminal contents may contribute to the increased intestinal permeability of CD. This alteration mirrors the severity of the mucosal lesions and is not completely reverted by gluten-free diet. Intestinal hydrophobicity exhibits regional differences in the human intestinal tract.</p

The addition of locust bean gum but not water delayed the gastric emptying rate of a nutrient semisolid meal in healthy subjects

BACKGROUND: Most of the previous studies regarding the effects of gel-forming fibres have considered the gastric emptying of liquid or solid meals after the addition of pectin or guar gum. The influence of locust bean gum, on gastric emptying of nutrient semisolid meals in humans has been less well studied, despite its common occurrence in foods. Using a standardised ultrasound method, this study was aimed at investigating if the gastric emptying in healthy subjects could be influenced by adding locust been gum, a widely used thickening agent, or water directly into a nutrient semisolid test meal. METHODS: The viscosity of a basic test meal (300 g rice pudding, 330 kcal) was increased by adding Nestargel (6 g, 2.4 kcal), containing viscous dietary fibres (96.5%) provided as seed flour of locust bean gum, and decreased by adding 100 ml of water. Gastric emptying of these three test meals were evaluated in fifteen healthy non-smoking volunteers, using ultrasound measurements of the gastric antral area to estimate the gastric emptying rate (GER). RESULTS: The median value of GER with the basic test meal (rice pudding) was estimated at 63 %, (range 47 to 84 %), (the first quartile = 61 %, the third quartile = 69 %). Increasing the viscosity of the rice pudding by adding Nestargel, resulted in significantly lower gastric emptying rates (p < 0.01), median GER 54 %, (range 7 to 71 %), (the first quartile = 48 %, the third quartile = 60 %). When the viscosity of the rice pudding was decreased (basic test meal added with water), the difference in median GER 65 %, (range 38 to 79 %), (the first quartile = 56 %, the third quartile = 71 %) was not significantly different (p = 0.28) compared to the GER of the basic test meal. CONCLUSIONS: We conclude that the addition of locust bean gum to a nutrient semisolid meal has a major impact on gastric emptying by delaying the emptying rate, but that the addition of water to this test meal has no influence on gastric emptying in healthy subjects

NuStar observations of WISE J1036+0449, a galaxy at z ∼ 1 obscured by hot dust

Hot dust-obscured galaxies (hot DOGs), selected from Wide-Field Infrared Survey Explorer’s all-sky infrared survey, host some of the most powerful active galactic nuclei known and may represent an important stage in the evolution of galaxies. Most known hot DOGs are located at z> 1.5, due in part to a strong bias against identifying them at lower redshift related to the selection criteria. We present a new selection method that identifies 153 hot DOG candidates at z˜ 1, where they are significantly brighter and easier to study. We validate this approach by measuring a redshift z = 1.009 and finding a spectral energy distribution similar to that of higher-redshift hot DOGs for one of these objects, WISE J1036+0449 ({L}{Bol}≃ 8× {10}46 {erg} {{{s}}}-1). We find evidence of a broadened component in Mg II, which would imply a black hole mass of {M}{BH}≃ 2× {10}8 {M}⊙ and an Eddington ratio of {λ }{Edd}≃ 2.7. WISE J1036+0449 is the first hot DOG detected by the Nuclear Spectroscopic Telescope Array, and observations show that the source is heavily obscured, with a column density of {N}{{H}}≃ (2{--}15)× {10}23 {{cm}}-2. The source has an intrinsic 2-10 keV luminosity of ˜ 6× {10}44 {erg} {{{s}}}-1, a value significantly lower than that expected from the mid-infrared/X-ray correlation. We also find that other hot DOGs observed by X-ray facilities show a similar deficiency of X-ray flux. We discuss the origin of the X-ray weakness and the absorption properties of hot DOGs. Hot DOGs at z≲ 1 could be excellent laboratories to probe the characteristics of the accretion flow and of the X-ray emitting plasma at extreme values of the Eddington ratio

Inhibition of the Intrinsic but Not the Extrinsic Apoptosis Pathway Accelerates and Drives Myc-Driven Tumorigenesis Towards Acute Myeloid Leukemia

Myc plays an important role in tumor development, including acute myeloid leukemia (AML). However, MYC is also a powerful inducer of apoptosis, which is one of the major failsafe programs to prevent cancer development. To clarify the relative importance of the extrinsic (death receptor-mediated) versus the intrinsic (mitochondrial) pathway of apoptosis in MYC-driven AML, we coexpressed MYC together with anti-apoptotic proteins of relevance for AML; BCL-XL/BCL-2 (inhibiting the intrinsic pathway) or FLIPL (inhibiting the extrinsic pathway), in hematopoietic stems cells (HSCs). Transplantation of HSCs expressing MYC into syngeneic recipient mice resulted in development of AML and T-cell lymphomas within 7–9 weeks as expected. Importantly, coexpression of MYC together with BCL-XL/BCL-2 resulted in strongly accelerated kinetics and favored tumor development towards aggressive AML. In contrast, coexpression of MYC and FLIPL did neither accelerate tumorigenesis nor change the ratio of AML versus T-cell lymphoma. However, a change in distribution of immature CD4+CD8+ versus mature CD4+ T-cell lymphoma was observed in MYC/FLIPL mice, possibly as a result of increased survival of the CD4+ population, but this did not significantly affect the outcome of the disease. In conclusion, our findings provide direct evidence that BCL-XL and BCL-2 but not FLIPL acts in synergy with MYC to drive AML development

Helicobacter pylori Counteracts the Apoptotic Action of Its VacA Toxin by Injecting the CagA Protein into Gastric Epithelial Cells

Infection with Helicobacter pylori is responsible for gastritis and gastroduodenal ulcers but is also a high risk factor for the development of gastric adenocarcinoma and lymphoma. The most pathogenic H. pylori strains (i.e., the so-called type I strains) associate the CagA virulence protein with an active VacA cytotoxin but the rationale for this association is unknown. CagA, directly injected by the bacterium into colonized epithelium via a type IV secretion system, leads to cellular morphological, anti-apoptotic and proinflammatory effects responsible in the long-term (years or decades) for ulcer and cancer. VacA, via pinocytosis and intracellular trafficking, induces epithelial cell apoptosis and vacuolation. Using human gastric epithelial cells in culture transfected with cDNA encoding for either the wild-type 38 kDa C-terminal signaling domain of CagA or its non-tyrosine-phosphorylatable mutant form, we found that, depending on tyrosine-phosphorylation by host kinases, CagA inhibited VacA-induced apoptosis by two complementary mechanisms. Tyrosine-phosphorylated CagA prevented pinocytosed VacA to reach its target intracellular compartments. Unphosphorylated CagA triggered an anti-apoptotic activity blocking VacA-induced apoptosis at the mitochondrial level without affecting the intracellular trafficking of the toxin. Assaying the level of apoptosis of gastric epithelial cells infected with wild-type CagA+/VacA+ H. pylori or isogenic mutants lacking of either CagA or VacA, we confirmed the results obtained in cells transfected with the CagA C-ter constructions showing that CagA antagonizes VacA-induced apoptosis. VacA toxin plays a role during H. pylori stomach colonization. However, once bacteria have colonized the gastric niche, the apoptotic action of VacA might be detrimental for the survival of H. pylori adherent to the mucosa. CagA association with VacA is thus a novel, highly ingenious microbial strategy to locally protect its ecological niche against a bacterial virulence factor, with however detrimental consequences for the human host