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At least 109 records · Page 6

Immunocytochemical localization of latent transforming growth factor-beta1 activation by stimulated macrophages

Transforming growth factor-beta1 (TGF-beta) is secreted in a latent form consisting of mature TGF-beta noncovalently associated with its amino-terminal propeptide, which is called latency associated peptide (LAP). Biological activity depends upon the release of TGF-beta from the latent complex following extracellular activation, which appears to be the key regulatory mechanism controlling TGF-beta action. We have identified two events associated with latent TGF-beta (LTGF-beta) activation in vivo: increased immunoreactivity of certain antibodies that specifically detect TGF-beta concomitant with decreased immunoreactivity of antibodies to LAP. Macrophages stimulated in vitro with interferon-gamma and lipopolysaccharide reportedly activate LTGF-beta via cell membrane-bound protease activity. We show through dual immunostaining of paraformaldehyde-fixed macrophages that such physiological TGF-beta activation is accompanied by a loss of LAP immunoreactivity with concomitant revelation of TGF-beta epitopes. The induction of TGF-beta immunoreactivity colocalized with immunoreactive betaglycan/RIII in activated macrophages, suggesting that LTGF-beta activation occurs on the cell surface. Confocal microscopy of metabolically active macrophages incubated with antibodies to TGF-beta and betaglycan/RIII prior to fixation supported the localization of activation to the cell surface. The ability to specifically detect and localize LTGF-beta activation provides an important tool for studies of its regulation.

NASA Discipline Radiation Health↗

Parameter degeneracy in models of the quadruple lens system Q2237+0305

The geometry of the quadruple lens system Q2237+0305 is modeled with a simple astigmatic lens: a power-law mass distribution: m approximately r(exp beta) with an external shear gamma. The image positions can be reproduced with an accuracy better than 0.01 arcsec for any 0.0 less than or = beta less than or = 1.85 and the corresponding value of gamma = 0.1385-0.0689 beta. This is a factor of approximately 4 more precise than what can be achieved by the best constant stellar mass/L lens models. The image intensity ratios and the time delay ratios are almost constant along our one parameter family of models, but the total magnification varies from 8 to greater than 1000, and the maximum time delay (between leading image B and trailing image C) for H(sub 0) of 75 km/s (Mpc) varies from more than 20 h to about 1.5 h, while beta increases from 0.0 to 1.85.

Wambsganss, Joachim↗

Non-LTE hydrogen-line formation in moving prominences

The behavior of hydrogen-line brightness variations, depending on the prominence-velocity changes were investigated. By solving the NON-Local thermodynamic equilibrium (LTE) problem for hydrogen researchers determine quantitatively the effect of Doppler brightening and/or Doppler dimming (DBE, DDE) in the lines of Lyman and Balmer series. It is demonstrated that in low-density prominence plasmas, DBE in H alpha and H beta lines can reach a factor of three for velocities around 160 km/sec, while the L alpha line exhibits typical DDE. L beta brightness variations follow from a combined DBE in the H alpha and DDE in L alpha and L beta itself, providing that all relevant multilevel interlocking processes are taken into account.

Heinzel, P.↗

PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer

Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) plays important roles in inflammation and anaphylaxis. However, its primary function in pancreatic cancer remains unclear. In the current study, we report that PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlated inversely with patient survival. PAFAH1B2 overexpression induced epithelial–mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo. Conversely, silencing PAFAH1B2 inhibited these aggressive phenotypes. Moreover, PAFAH1B2 overexpression in PDAC cells was directly mediated by HIF1a. PAFAH1B2 expression in PDAC clinical specimens correlated positively with HIF1a expression. Overall, our results defined PAFAH1B2 as a target gene of HIF1a and a critical driver of PDAC metastatic behaviors.

60 APPLIED LIFE SCIENCES↗

First observations of edge instabilities in strongly shaped negative triangularity plasmas on DIII-D

Throughout the 2023 DIII-D negative triangularity (NT) campaign, unexpected magnetic fluctuations indicative of an edge localized instability were observed in the majority of strongly shaped (–0.55 ≤ δ ≤ –0.45) discharges. Moreover, these same fluctuations were found to be absent in weaker NT plasma shapes. Based on a database study, three separate mode behaviors are observed based primarily on the edge safety factor and normalized plasma beta β N . The main regime is the bursty state, in which short (~5 ms) magnetic bursts occur every 5–10 ms. Each burst drives a small reduction in the edge electron temperature (T e ) as measured by electron cyclotron emissions (ECE), which then rapidly recovers between the bursts. The quiescent regime appears to have governing mechanics similar to the bursty regime, but with multiple unique mode signatures observed in the magnetics. These additional modes greatly reduce the bursty nature of the plasma. Finally, a saturated state is observed in a number of discharges, particularly at early time slices. The saturated regime is often short-lived (maximum 500 ms), but can have a large impact on the dynamics of the plasma edge region, causing significant drops in electron temperature as observed in the ECE diagnostic. 2D ECE imaging (ECE-I) is utilized, showing large kink-like perturbations localized near the last closed flux surface that extend into the SOL indicative of an external kink/peeling behavior. Additionally, evidence of phase mixing and observed tearing-parity perturbations localized near the edge rational surfaces is observed in the quiescent regime plasmas. As a result, the various modes do not appear to have a large impact on global confinement but may play a role in regulating the transport of the NT edge and the observed edge gradients.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Simultaneous access to high normalized density, current, pressure, and confinement in strongly-shaped diverted negative triangularity plasmas

Strongly-shaped diverted negative triangularity (NT) plasmas in the DIII-D tokamak demonstrate simultaneous access to high normalized density, current, pressure, and confinement. NT plasmas are shown to exist across an expansive parameter space compatible with high fusion power production, revealing surprisingly good core stability properties that compare favorably to conventional positive triangularity plasmas in DIII-D. Non-dimensionalizing the key parameters, expanded operating spaces featuring edge safety factors below 3, normalized betas above 3, Greenwald density fractions above 1, and high-confinement mode (H-mode) confinement qualities above 1 are observed, even simultaneously, and all with a robustly stable edge free from deleterious edge-localized mode instabilities. Scaling of the confinement time with engineering parameters reveals at least a linear dependence on plasma current although with significant power degradation, both in excess of expected H-mode scalings. These results increase confidence that NT plasmas are a viable approach to realize fusion power and open directions for future detailed study.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Evidence for a cytokine-sensitive network of iron-associated genes that protects pancreatic islets against ferroptosis

Background/Objectives: The micronutrient iron is closely connected to inflammation and is among the complex factors contributing to beta-cell failure in diabetes. High levels of dietary iron increase the risk of developing type 2 diabetes, and excessive iron uptake by beta-cells can cause oxidative stress and inhibit function. Elevated levels of proinflammatory cytokines in obese individuals, such as interleukin (IL)-1beta and IL-6, increase the risk of developing type 2 diabetes, and there is evidence that these low levels of circulating cytokines can lead to islet dysfunction. Methods: In this study, gene microarray and other data were analyzed for expression differences in islets treated for 48 h with 10 pg/mL IL-1beta + 20 pg/mL IL-6 as a model of low-grade inflammation versus untreated. Results: Three iron-associated genes were among the most cytokine-sensitive in the mouse genome: Hamp, Steap4, and Lcn2. These proteins are all involved with increasing/retaining cellular iron. We hypothesized that increased cellular iron would lead to increased susceptibility to ferroptosis. Surprisingly, 24 h pre-exposure to low-grade inflammation, which upregulates this iron-gene network, prevented subsequent erastin-induced ferroptosis. We also found that Steap4 overexpression reduced islet dysfunction caused by high-dose proinflammatory cytokines (10× low-dose), suggesting an overall protective effect. Steap4 overexpression also upregulated Hamp and Lcn2, suggesting Steap4 regulates these cytokine-sensitive iron genes.; in contrast, ferritin and ferroportin gene expression, which are not sensitive to cytokines, were unchanged. Conclusions: These data suggest an inflammation-induced network of genes involved in cellular iron uptake and retention plays a protective role in islets against oxidative stress and ferroptosis.

IL-1β↗

Low resolution infrared spectra of quasars

Recent observational results based on a joint infrared/optical survey of the hydrogen line spectra of a significant number of low and high redshift quasars are summarized. The spectra show that the Paschen-alpha and Balmer line ratios do not agree with the result of nominal case B recombination theory and vary widely within the quasars sampled. The range of P-alpha to H-beta ratios is a factor of roughly 6, while the range in Ly-alpha to H-alpha ratios is a factor of roughly 5. For the P-alpha:Balmer series, the deviations from case B recombination are not consistent with reddening, but appear, within large dispersions, to be consistent with optical depth effects in the Balmer lines affecting the lines ratios.

Soifer, B. T.↗

Dust extinction of the stellar continua in starburst galaxies: The ultraviolet and optical extinction law

We analyze the International Ultraviolet Explorer (IUE) UV and the optical spectra of 39 starburst and blue compact galaxies in order to study the average properties of dust extinction in extended regions of galaxies. The optical spectra have been obtained using an aperture which matches that of IUE, so comparable regions within each galaxy are sampled. The data from the 39 galaxies are compared with five models for the geometrical distribution of dust, adopting as extinction laws both the Milky Way and the Large Magellanic Cloud laws. The commonly used uniform dust screen is included among the models. We find that none of the five models is in satisfactory agreement with the data. In order to understand the discrepancy between the data and the models, we have derived an extinction law directly from the data in the UV and optical wavelength range. The resulting curve is characterized by an overall slope which is more gray than the Milky Way extinction law's slope, and by the absence of the 2175 A dust feature. Remarkably, the difference in optical depth between the Balmer emission lines H(sub alpha) and H(sub beta) is about a factor of 2 larger than the difference in the optical depth between the continuum underlying the two Balmer lines. We interpret this discrepancy as a consequence of the fact that the hot ionizing stars are associated with dustier regions than the cold stellar population is. The absence of the 2175 A dust feature can be due either to the effects of the scattering and clumpiness of the dust or to a chemical composition different from that of the Milky Way dust grains. Disentangling the two interpretations is not easy because of the complexity of the spatial distribution of the emitting regions. The extinction law of the UV and optical spectral continua of extended regions can be applied to the spectra of medium- and high-redshift galaxies, where extended regions of a galaxy are, by necessity, sampled.

Calzetti, Daniela↗

Comparison of large-scale structures and velocities in the local universe

Comparison of the large-scale density and velocity fields in the local universe shows detailed agreement, strengthening the standard paradigm of the gravitational origin of these structures. Quantitative analysis can determine the cosmological density parameter, Omega, and biasing factor, b; there is virtually no sensitivity in any local analyses to the cosmologial constant, lambda. Comparison of the dipole anisotropy of the cosmic microwave background with the acceleration due to the Infrared Astronomy Satellite (IRAS) galaxies puts the linear growth factor in the range beta approximately equals Omega (exp 0.6)/b = 0.6(+0.7/-0.3) (95% confidence). A direct comparison of the density and velocity fields of nearby galaxies gives beta = 1.3 (+0.7/-0.6), and from nonlinear analysis the weaker limit (Omega greater than 0.45 for b greater than 0.5 (again 95% confidence). A tighter limit (Omega greater than 0.3 (4-6 sigma)), is obtained by a reconstruction of the probability distribution function of the initial fluctuations from which the structures observed today arose. The last two methods depend critically on the smooth velocity field determined from the observed velocities of nearby galaxies by the POTENT method. A new analysis of these velocities, with more than three times the data used to obtain the above quoted results, is now underway and promises to tighten the uncertainties considerably, as well as reduce systematic bias.

Yahil, Amos↗

Identification and Quantification of Beta-Emitters in Waste Packages by Segmented Gamma-Scanning - 20114

A commonly applied method for the non-destructive characterization of the radioactive inventory of waste packages (e.g. 200-l drums) is segmented gamma-scanning. The gamma-emitting inventory is identified via their characteristic lines in the measured spectra. The corresponding net peak areas allow for quantification applying appropriate models. The identification and quantification of beta-emitters present in the waste package require further evaluation. While some of them emit gamma-rays, too, which can be used for identification and quantification, pure beta-emitters contribute to the gamma-spectra only by their Bremsstrahlung-spectra. {sup 32}P, {sup 90}Sr and {sup 90}Y are typical representatives of these isotopes. A method is developed for identification and quantification of these pure beta-emitters in radioactive waste packages. Origin of the procedure is the evaluation of the measured gamma-spectrum. After the identification of all lines present in the spectrum (characteristic gamma-lines, single- and double-escape-lines, X-ray-lines, annihilation peak etc.) this information is used together with calibration data of the detection system and further a-priori information like matrix composition, cross-section data from databases etc. to simulate the spectra without the Bremsstrahlung-components by an appropriate method. This may be Monte Carlo simulations or, like in our case, a computer code taking into account mathematical descriptions of the physical effects like photo effect, (multiple) Compton scattering, backscattering etc. and the attenuation effects of the waste matrix. In any case, the resulting spectrum must simulate the real spectrum without its Bremsstrahlung-component as good as possible. Subtracting the simulated from the measured spectrum then results in the Bremsstrahlung-components caused by the beta-emitters. Prior to evaluation, a set of Bremsstrahlung-spectra is calculated and stored for different beta-emitters in different matrices using the Bethe-Heitler equation. This data set can be extended for new conditions, if necessary, and is allocated in a data base for future application. Applying a non-linear optimization using the generalized reduced gradient method for comparing the calculated with the derived Bremsstrahlung-spectra results in the identification of the beta-emitter and a factor, which is proportional to its activity. The proportionality is determined by previous calibration measurements. The application of the method is demonstrated by measurements on a 200-l mock-up drum and a real waste package. (authors)

07 ISOTOPE AND RADIATION SOURCES↗

Alpha/beta-gated gamma–gamma spectroscopy of mixed fission products for trace analysis

This experiment demonstrated that some hard-to-detect fission products can be quantified directly from mixed fission product samples using advanced radio-emission spectroscopy techniques. A gamma/gamma coincidence detector was combined with a custom liquid scintillation counter to evaluate the benefits of alpha and beta coincident and anti-coincident analysis of mixed fission product samples. Reduction factors in the minimum detectable activity (MDA) relative to traditional gamma counting were quantified for a set of radionuclides. For isotopes like 91Y, 144Ce, 147Nd, and 153Sm MDA reductions of factors of 1-2 were observed using optimized beta thresholds. Using beta anti-coincidence counting reductions of factors 3-5 were observed for isotopes like 89Sr, 95mNb, 115Cd, and 137Cs and factors of 5-7 for isotopes like 235U using alpha coincidence counting. The selectivity of gamma/gamma coincidence and reduction in backgrounds using beta gating were also demonstrated with 136Cs and 153Sm. The improvements observed in the detection sensitivity of fission products and actinides achieved by combining time-correlated radiation signatures is significant and of value to applications such as nuclear fission physics, environmental monitoring for nuclear waste, reactor accidental releases, and nuclear forensics.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Beta-adrenoceptor dysfunction after inhibition of NO synthesis

G(s) protein-coupled beta-adrenoceptors rapidly desensitize on exposure to agonists in reconstituted membrane preparations, whereas rapid tachyphylaxis to beta-adrenoceptor-mediated vasodilation does not readily occur in vivo. This study examined the possibility that endothelium-derived nitrosyl factors prevent the rapid desensitization of beta-adrenoceptors in the vascular smooth muscle of resistance arteries in pentobarbital-anesthetized rats. The fall in mean arterial blood pressure and in hindquarter vascular resistance produced by the beta-adrenoceptor agonist isoproterenol (ISO, 0.1 to 10 microg/kg IV) was slightly but significantly smaller in rats treated with the NO synthase inhibitor N:(G)-nitro-L-arginine methyl ester (L-NAME, 100 micromol/kg IV) than in saline-treated rats. The ISO-induced fall in mesenteric resistance was similar in L-NAME-treated and in saline-treated rats. The fall in hindquarter vascular resistance and in mesenteric resistance produced by ISO (8 x 10 microg/kg IV) was subject to tachyphylaxis on repeated injection in rats treated with L-NAME (100 micromol/kg IV) but not in rats treated with saline. Injections of L-S:-nitrosocysteine (1200 nmol/kg IV), a lipophobic S:-nitrosothiol, before each injection of ISO (10 microg/kg IV) prevented tachyphylaxis to ISO in L-NAME-treated rats. The vasodilator effects of ISO (0.1 to 10 microg/kg IV) in L-NAME-treated rats that received 8 injections of ISO (10 microg/kg IV) were markedly smaller than in L-NAME-treated rats that received 8 injections of saline. These results indicate that (1) the vasodilator actions of ISO in pentobarbital-anesthetized rats only minimally involve the release of endothelium-derived nitrosyl factors, (2) the effects of ISO are subject to development of tachyphylaxis in L-NAME-treated rats, and (3) tachyphylaxis to ISO is prevented by L-S:-nitrosocysteine. These findings suggest that endothelium-derived nitrosyl factors may prevent desensitization of beta-adrenoceptors in vivo.

NASA Discipline Regulatory Physiology↗

Far-ultraviolet observations of the Delta-Scuti variable Beta Cassiopeiae

FUV (115-200-nm) observations of Beta Cas, obtained at resolutions 5 and 0.15 A by the IUE during September 1984, are reported and analyzed. The data are presented graphically and compared with results for Procyon, a sharp-lined F star similar in temperature to Beta Cas. A sharp factor-of-two increase in H I Ly-alpha flux on a time scale comparable to its Delta Sct pulsation period was observed, but the data were insufficient to determine whether the increase was flarelike or pulsation-related. The outer edges of the Beta Cas emission are shown to be significantly wider than those of Procyon.

Ayres, Thomas R.↗

Neutrons, gamma rays, and beta particles interactions with IIaO films flown on Astro I and Astro II and comparison with IIaO flown on the get-away-special STS-7

The current requirements for the Laboratory for Astronomy and Solar Physics, sends rocket satellites and in the near future will involve flights in the shuttle to the upper reaches of the Earth's atmosphere where they will be subjected to the atomic particles and electromagnetic radiation produced by the Sun and other cosmic radiation. It is therefore appropriate to examine the effect of neutrons, gamma rays, beta particles, and X-rays on the film currently being used by the Laboratory for current and future research requirements. It is also hoped by examining these particles in their effect that we will have simulated the space environment of the rockets, satellites, and shuttles. Several samples of the IIaO film were exposed to a neutron howitzer with a source energy of approximately 106 neutrons/steradians. We exposed several samples of the film to a 10 second blast of neutrons in both metal and plastic containers which exhibited higher density readings which indicated the possibility of some secondary nuclear interactions between neutrons and the aluminum container. The plastic container showed some variations at the higher densities. Exposure of the samples of IIaO film to a neutron beam of approximately 10 neutrons per steradians for eight minutes produces approximately a 13% difference in the density readings of the dark density grids. It is not noticeable that at the lighter density grid the neutrons have minimal effects, but on a whole the trend of the eight minute exposed IIaO film density grids at the darker end had a 7.1% difference than the control. Further analysis is anticipated by increasing the exposure time. Two sets of film were exposed to a beta source in a plastic container. The beta source was placed at the bottom so that the cone of rays striking the film would be conical for a period of seven days. It was observed in the films, designated 4a and 4b, a dramatic increase in the grid densities had occurred. The attenuation of beta particles due to the presence of air were observed. The darker density grids, whose positions were the furthest from the beta source, displayed minimal fluctuations as compared with the control. It is suspected that the orientation of the film in the cansister with the beta source is the key factor responsible for the dramatic increases of the lighter density grids. Emulsions 3a and 3b exposed for a period of six days with the grid orientation reserved produced substantial differences in the darker grids as shown in the graphs. There is a great deal of fluctuations in this sample between the beta exposed density grids and the control density grids. The lighter density grids whose orientations were reversed displays minimal fluctuations due to the presence of this beta source and the attenuation that is taking place.

Hammond, Ernest C., Jr.↗

Improving the chi-squared approximation for bivariate normal tolerance regions

Let X be a two-dimensional random variable distributed according to N2(mu,Sigma) and let bar-X and S be the respective sample mean and covariance matrix calculated from N observations of X. Given a containment probability beta and a level of confidence gamma, we seek a number c, depending only on N, beta, and gamma such that the ellipsoid R = (x: (x - bar-X)'S(exp -1) (x - bar-X) less than or = c) is a tolerance region of content beta and level gamma; i.e., R has probability gamma of containing at least 100 beta percent of the distribution of X. Various approximations for c exist in the literature, but one of the simplest to compute -- a multiple of the ratio of certain chi-squared percentage points -- is badly biased for small N. For the bivariate normal case, most of the bias can be removed by simple adjustment using a factor A which depends on beta and gamma. This paper provides values of A for various beta and gamma so that the simple approximation for c can be made viable for any reasonable sample size. The methodology provides an illustrative example of how a combination of Monte-Carlo simulation and simple regression modelling can be used to improve an existing approximation.

Feiveson, Alan H.↗