Longitudinal muon spin relaxation in high purity aluminum and silver

The time dependence of muon spin relaxation has been measured in high purity aluminum and silver samples in a longitudinal 2 T magnetic field at room temperature, using time-differential \musr. For times greater than 10 ns, the shape fits well to a single exponential with relaxation rates of \lambda_{\textrm{Al}} = 1.3 \pm 0.2\,(\textrm{stat.}) \pm 0.3\,(\textrm{syst.})\,\pms and \lambda_{\textrm{Ag}} = 1.0 \pm 0.2\,(\textrm{stat.}) \pm 0.2\,(\textrm{syst.})\,\pms

Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism

Background: We previously showed that the probiotic mixture, VSL#3, prevents the onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with stimulation of epithelial-derived TNF. The aim of this study was to determine the mechanism(s) of VSL#3-mediated protection on epithelial barrier function and to further investigate the "paradoxical" effects of TNF in preventing SAMP ileitis. Methods: Permeability was evaluated in SAMP mice prior to the onset of inflammation and during established disease by measuring transepithelial electrical resistance (TEER) on ex vivo-cultured ilea following exposure to VSL#3 conditioned media (CM), TNF or VSL#3-CM + anti-TNF. Tight junction (TJ) proteins were assessed by qRT-PCR, Western blot, and confocal microscopy, and TNFRI/TNFRII expression measured in freshly isolated intestinal epithelial cells (IEC) from SAMP and control AKR mice. Results: Culture with either VSL#3-CM or TNF resulted in decreased ileal paracellular permeability in pre-inflamed SAMP, but not SAMP with established disease, while addition of anti-TNF abrogated these effects. Modulation of the TJ proteins, claudin-2 and occludin, occurred with a significant decrease in claudin-2 and increase in occludin following stimulation with VSL#3-CM or TNF. TNF protein levels increased in supernatants of SAMP ilea incubated with VSL#3-CM compared to vehicle, while IEC-derived TNFR mRNA expression decreased in young, and was elevated in inflamed, SAMP versus AKR mice. Conclusions: Our data demonstrate that the previously established efficacy of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic effects of TNF on the gut epithelium, modulation of the TJ proteins, claudin-2 and occludin, and overall improvement of intestinal permeability. © 2012 Corridoni et al

A novel model of colitis-associated cancer in SAMP1/YitFc mice with Crohn's disease-like ileitis.

Patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal cancer. Evidence suggests that colonic dysplasia and colitis-associated cancer (CAC) are often linked to repeated cycles of epithelial cell injury and repair in the context of chronic production of inflammatory cytokines. Several mouse models of CAC have been proposed, including chemical induction through exposure to dextran sulfate sodium (DSS) with the genotoxic agents azoxymethane (AOM), 1,2-dymethylhydrazine (DHM) or targeted genetic mutations. However, such models are usually performed on healthy animals that usually lack the underlying genetic predisposition, immunological dysfunction and dysbiosis characteristic of IBD. We have previously shown that inbred SAMP1/YitFc (SAMP) mice develop a progressive Crohn's disease (CD)-like ileitis in the absence of spontaneous colitis. We hypothesize that SAMP mice may be more susceptible to colonic tumorigenesis due to their predisposition to IBD. To test this hypothesis, we administered AOM/DSS to IBD-prone SAMP and their non-inflamed parental control strain, AKR mice. Our results showed that AOM/DSS treatment enhanced the susceptibility of colitis in SAMP compared to AKR mice, as assessed by endoscopic and histologic inflammatory scores, daily weight loss and disease activity index (DAI), during and after DSS administration. SAMP mice also showed increased colonic tumorigenesis, resulting in the occurrence of intramucosal carcinoma and a higher incidence of high-grade dysplasia and tumor burden. These phenomena occurred even in the absence of AOM and only upon repeated cycles of DSS. Taken together, our data demonstrate a heightened susceptibility to colonic inflammation and tumorigenesis in AOM/DSS-treated SAMP mice with CD-like ileitis. This novel model represents a useful tool to investigate relevant mechanisms of CAC, as well as for pre-clinical testing of potential IBD and colon cancer therapeutics

Discovery of a proto-white dwarf with a massive unseen companion

We report the discovery of SDSS~J022932.28+713002.7, a nascent extremely low-mass (ELM) white dwarf (WD) orbiting a massive ($> 1\,M_\odot$ at 2$\sigma$ confidence) companion with a period of 36 hours. We use a combination of spectroscopy, including data from the ongoing SDSS-V survey, and photometry to measure the stellar parameters for the primary pre-ELM white dwarf. The lightcurve of the primary WD exhibits ellipsoidal variation, which we combine with radial velocity data and $\tt{PHOEBE}$ binary simulations to estimate the mass of the invisible companion. We find that the primary WD has mass $M_1$ = $0.18^{+0.02}_{-0.02}$ M$_\odot$ and the unseen secondary has mass $M_2$ = $1.19^{+0.21}_{-0.14}$ M$_\odot$. The mass of the companion suggests that it is most likely a near-Chandrasekhar mass white dwarf or a neutron star. It is likely that the system recently went through a Roche lobe overflow from the visible primary onto the invisible secondary. The dynamical configuration of the binary is consistent with the theoretical evolutionary tracks for such objects, and the primary is currently in its contraction phase. The measured orbital period puts this system on a stable evolutionary path which, within a few Gyrs, will lead to a contracted ELM white dwarf orbiting a massive compact companion.Comment: 21 Pages, 8 Figure

Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism

Background: We previously showed that the probiotic mixture, VSL#3, prevents the onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with stimulation of epithelial-derived TNF. The aim of this study was to determine the mechanism(s) of VSL#3-mediated protection on epithelial barrier function and to further investigate the "paradoxical" effects of TNF in preventing SAMP ileitis. Methods: Permeability was evaluated in SAMP mice prior to the onset of inflammation and during established disease by measuring transepithelial electrical resistance (TEER) on ex vivo-cultured ilea following exposure to VSL#3 conditioned media (CM), TNF or VSL#3-CM + anti-TNF. Tight junction (TJ) proteins were assessed by qRT-PCR, Western blot, and confocal microscopy, and TNFRI/TNFRII expression measured in freshly isolated intestinal epithelial cells (IEC) from SAMP and control AKR mice. Results: Culture with either VSL#3-CM or TNF resulted in decreased ileal paracellular permeability in pre-inflamed SAMP, but not SAMP with established disease, while addition of anti-TNF abrogated these effects. Modulation of the TJ proteins, claudin-2 and occludin, occurred with a significant decrease in claudin-2 and increase in occludin following stimulation with VSL#3-CM or TNF. TNF protein levels increased in supernatants of SAMP ilea incubated with VSL#3-CM compared to vehicle, while IEC-derived TNFR mRNA expression decreased in young, and was elevated in inflamed, SAMP versus AKR mice. Conclusions: Our data demonstrate that the previously established efficacy of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic effects of TNF on the gut epithelium, modulation of the TJ proteins, claudin-2 and occludin, and overall improvement of intestinal permeability

Measuring The Mass-Radius Relation of White Dwarfs Using Wide Binaries

Measuring the mass-radius relation of individual white dwarfs is an empirically challenging task that has been performed for only a few dozen stars. We measure the white dwarf mass-radius relation using gravitational redshifts and radii of 137 white dwarfs in wide binaries with main sequence companions. We obtain the space velocities to these systems using the main sequence companion, and subtract these Doppler redshifts from the white dwarfs' apparent motions, isolating their gravitational redshifts. We use Gaia data to calculate the surface temperatures and radii of these white dwarfs, thereby deriving an empirical gravitational redshift-radius relation. This work demonstrates the utility of low-resolution Galactic surveys to measure the white dwarf equation of state. Our results are consistent with theoretical models, and represent the largest sample of individual white dwarf gravitational redshift measurements to date.Comment: 12 pages, 9 figure

B-NMR of 8Li+ in rutile TiO2

We report preliminary low-energy B-NMR measurements of 8Li+ implanted in single crystal rutile TiO2 at an applied field of 6.55 T and 300 K. We observe a broad 12 kHz wide quadrupole split resonance with unresolved features and a sharp component at the Larmor frequency. The line broadening may be caused by overlapping multi-quantum transitions or motion of 8Li+ on the scale of its lifetime (1.21 s). We also find spin-lattice relaxation that is relatively fast compared to other wide band gap insulators. The origin of this fast relaxation is also likely quadrupolar and may be due to anisotropic 8Li+ diffusion

Spin depolarization of muonium in mesoporous silica

We report muon spin rotation/relaxation measurements of muonium in mesoporous silica (SBA-15) with a high specific surface area of 600 m2/g. Up to 70 percent of the incoming muons form muonium and escape efficiently into the open pores at all temperatures between 3 and 300K. We present evidence that the interaction with the silica surfaces involves both spin exchange and a transition to a diamagnetic state, possibly due to dangling bonds on the surface. At very low temperatures, below 20K, the interaction between muonium and the silica surfaces is suppressed due to a He film coating the surfaces. These results indicate that it should be possible to use muonium to probe the surfaces of uncapped nanoparticles supported in silica

A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia in patients receiving multicycle chemotherapy

Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg−1wk−1) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose–response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg−1wk−1cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl−1respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing. © 2001 Cance Cancer Research Campaig