ISO SWS Observations of H II Regions in NGC 6822 and I ZW 36: Sulfur Abundances and Temperature Fluctuations

We report ISO SWS infrared spectroscopy of the H II region Hubble V in NGC 6822 and the blue compact dwarf galaxy I Zw 36. Observations of Br alpha, [S III] at 18.7 and 33.5 microns, and [S IV] at 10.5 microns are used to determine ionic sulfur abundances in these H II regions. There is relatively good agreement between our observations and predictions of S^+3 abundances based on photoionization calculations, although there is an offset in the sense that the models overpredict the S^+3 abundances. We emphasize a need for more observations of this type in order to place nebular sulfur abundance determinations on firmer ground. The S/O ratios derived using the ISO observations in combination with optical data are consistent with values of S/O, derived from optical measurements of other metal-poor galaxies. We present a new formalism for the simultaneous determination of the temperature, temperature fluctuations, and abundances in a nebula, given a mix of optical and infrared observed line ratios. The uncertainties in our ISO measurements and the lack of observations of [S III] lambda 9532 or lambda 9069 do not allow an accurate determination of the amplitude of temperature fluctuations for Hubble V and I Zw 36. Finally, using synthetic data, we illustrate the diagnostic power and limitations of our new method.Comment: 32 Pages total, including 6 encapsulated postscript figures (one with two parts). Accepted for Publication in the 20 Dec 2002 Ap

Dust In I Zw 18 From Hubble Space Telescope Narrow Band Imaging

We present new WFPC2 narrow band imaging of the blue compact dwarf galaxy I Zw 18, which is host to the lowest-metallicity HII regions known. Images at H-alpha and H-beta are combined with archival broad band images to allow the study of the ionized gas distribution and morphology. Analysis of the H-alpha/H-beta flux ratio reveals significant enhancements in some areas of both the ``Northwest'' and ``Southeast'' regions of the galaxy, with ratios elevated to levels as high as 3.4. The H-alpha/H-beta ratio varies considerably with position throughout the galaxy. Comparing this distribution with the stellar distribution indicates that the regions of enhanced H-alpha/H-beta ratio are not due to the effects of either collisional excitation or underlying stellar absorption, and therefore are most likely interpreted as the presence of dust. This dust has an estimated mass of (2-5)x10^3 solar masses, which is consistent with the IRAS far-IR non-detection. Under the assumption that dust traces the presence of molecular gas, these results suggest that the molecular component of the ISM of I Zw 18, which is needed to fuel its active star formation, is also very clumpy. Such a distribution would be consistent with the recent FUSE non-detections of diffuse H_2.Comment: 26 pages, 3 figures. Accepted for publication in the Astrophysical Journal, Volume 56

The Metallicity-Luminosity Relation, Effective Yields, and Metal Loss in Spiral and Irregular Galaxies

I present results on the correlation between galaxy mass, luminosity, and metallicity for a sample of spiral and irregular galaxies having well-measured abundance profiles, distances, and rotation speeds. Additional data for low surface brightness galaxies from the literature are also included for comparison. These data are combined to study the metallicity-luminosity and metallicity-rotation speed correlations for spiral and irregular galaxies. The metallicity luminosity correlation shows its familiar form for these galaxies, a roughly uniform change in the average present-day O/H abundance of about a factor 100 over 11 magnitudes in B luminosity. However, the O/H - V(rot) relation shows a change in slope at a rotation speed of about 125 km/sec. At faster V(rot), there appears to be no relation between average metallicity and rotation speed. At lower V(rot), the metallicity correlates with rotation speed. This change in behavior could be the result of increasing loss of metals from the smaller galaxies in supernova-driven winds. This idea is tested by looking at the variation in effective yield, derived from observed abundances and gas fractions assuming closed box chemical evolution. The effective yields derived for spiral and irregular galaxies increase by a factor of 10-20 from V(rot) approximately 5 km/sec to V(rot) approximately 300 km/sec, asympotically increasing to approximately constant y(eff) for V(rot) > 150 km/sec. The trend suggests that galaxies with V(rot) < 100-150 km/sec may lose a large fraction of their SN ejecta, while galaxies above this value tend to retain metals.Comment: 40 pages total, including 7 encapsulated postscript figures. Accepted for publication in 20 Dec 2002 Ap

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Role of Specific Cytochrome P450 Isoforms in the Conversion of Phenoxypropoxybiguanide Analogs in Human Liver Microsomes to Potent Antimalarial Dihydrotriazines

ABSTRACT: Phenoxypropoxybiguanides, such as PS-15, are antimalarial prodrugs analogous to the relationship of proguanil and its active metabolite cycloguanil. Unlike cycloguanil, however, WR99210, the active metabolite of PS-15, has retained in vitro potency against newly emerging antifolate-resistant malaria parasites. Recently, in vitro metabolism of a new series of phenoxypropoxybiguanide analogs has examined the production of the active triazine metabolites by human liver microsomes. The purpose of this investigation was to elucidate the primary cytochrome P450 isoforms involved in the production of active metabolites in the current lead candidate. By using expressed human recombinant isoform preparations, specific chemical inhibitors, and isoform-specific inhibitory antibodies, the primary cytochrome P450 isoforms involved in the in vitro metabolic activation of JPC-2056 were elucidated. Unlike proguanil, which is metabolized primarily by CYP2C19, the results indicate that CYP3A4 plays a more important role in the metabolism of both PS-15 and JPC-2056. Whereas CYP2D6 appears to play a major role in the metabolism of PS-15 to WR99210, it appears less important in the conversion of JPC-2056 to JPC-2067. These results are encouraging, considering the prominence of CYP2C19 and CYP2D6 polymorphisms in certain populations at risk for contracting malaria, because the current clinical prodrug candidate from this series may be less dependent on these enzymes for metabolic activation

Pharmacokinetics, Safety, and Hydrolysis of Oral Pyrroloquinazolinediamines Administered in Single and Multiple Doses in Rats▿

Pyrroloquinazolinediamine (PQD) derivatives such as tetra-acetamide PQD (PQD-A4) and bis-ethylcarbamyl PQD (PQD-BE) were much safer (with therapeutic indices of 80 and 32, respectively) than their parent compound, PQD (therapeutic index, 10). Further evaluation of PQD-A4 and PQD-BE in single and multiple pharmacokinetic (PK) studies as well as corresponding toxicity studies was conducted with rats. PQD-A4 could be converted to two intermediate metabolites (monoacetamide PQD and bisacetamide PQD) first and then to the final metabolite, PQD, while PQD-BE was directly hydrolyzed to PQD without precursor and intermediate metabolites. Maximum tolerant doses showed that PQD-A4 and PQD-BE have only 1/12 and 1/6, respectively, of the toxicity of PQD after a single oral dose. Compared to the area under the concentration-time curve for PQD alone (2,965 ng·h/ml), values measured in animals treated with PQD-A4 and PQD-BE were one-third (1,047 ng·h/ml) and one-half (1,381 ng·h/ml) as high, respectively, after an equimolar dosage, suggesting that PQD was the only agent to induce the toxicity. Similar results were also shown in multiple treatments; PQD-A4 and PQD-BE generated two-fifths and three-fifths, respectively, of PQD concentrations, with 8.8-fold and 3.8-fold safety margins, respectively, over the parent drug. PK data indicated that the bioavailability of oral PQD-A4 was greatly limited at high dose levels, that PQD-A4 was slowly converted to PQD via a sequential three-step process of conversion, and that PQD-A4 was significantly less toxic than the one-step hydrolysis drug, PQD-BE. It was concluded that the slow and smaller release of PQD was the main reason for the reduction in toxicity and that the active intermediate metabolites can still maintain antimalarial potency. Therefore, the candidate with multiple-step hydrolysis of PQD could be developed as a safer potential agent for malaria treatment