GLIMPSE: I. A SIRTF Legacy Project to Map the Inner Galaxy

GLIMPSE (Galactic Legacy Infrared Mid-Plane Survey Extraordinaire), a SIRTF Legacy Science Program, will be a fully sampled, confusion-limited infrared survey of the inner two-thirds of the Galactic disk with a pixel resolution of \~1.2" using the Infrared Array Camera (IRAC) at 3.6, 4.5, 5.8, and 8.0 microns. The survey will cover Galactic latitudes |b| <1 degree and longitudes |l|=10 to 65 degrees (both sides of the Galactic center). The survey area contains the outer ends of the Galactic bar, the Galactic molecular ring, and the inner spiral arms. The GLIMPSE team will process these data to produce a point source catalog, a point source data archive, and a set of mosaicked images. We summarize our observing strategy, give details of our data products, and summarize some of the principal science questions that will be addressed using GLIMPSE data. Up-to-date documentation, survey progress, and information on complementary datasets are available on the GLIMPSE web site: www.astro.wisc.edu/glimpse.Comment: Description of GLIMPSE, a SIRTF Legacy project (Aug 2003 PASP, in press). Paper with full res.color figures at http://www.astro.wisc.edu/glimpse/glimpsepubs.htm

Policy Recommendations for Meeting the Grand Challenge to Achieve Equal Opportunity and Justice

This brief was created forSocial Innovation for America’s Renewal, a policy conference organized by the Center for Social Development in collaboration with the American Academy of Social Work & Social Welfare, which is leading theGrand Challenges for Social Work initiative to champion social progress. The conference site includes links to speeches, presentations, and a full list of the policy briefs

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Surveying the Agents of Galaxy Evolution in the Tidally-Stripped, Low Metallicity Small Magellanic Cloud (SAGE-SMC) II. Cool Evolved Stars

We investigate the infrared (IR) properties of cool, evolved stars in the Small Magellanic Cloud (SMC), including the red giant branch (RGB) stars and the dust-producing red supergiant (RSG) and asymptotic giant branch (AGB) stars using observations from the Spitzer Space Telescope Legacy program entitled: "Surveying the Agents of Galaxy Evolution in the Tidally-stripped, Low Metallicity SMC", or SAGE-SMC. The survey includes, for the first time, full spatial coverage of the SMC bar, wing, and tail regions at infrared (IR) wavelengths (3.6 - 160 microns). We identify evolved stars using a combination of near-IR and mid-IR photometry and point out a new feature in the mid-IR color-magnitude diagram that may be due to particularly dusty O-rich AGB stars. We find that the RSG and AGB stars each contribute ~20% of the global SMC flux (extended + point-source) at 3.6 microns, which emphasizes the importance of both stellar types to the integrated flux of distant metal-poor galaxies. The equivalent SAGE survey of the higher-metallicity Large Magellanic Cloud (SAGE-LMC) allows us to explore the influence of metallicity on dust production. We find that the SMC RSG stars are less likely to produce a large amount of dust (as indicated by the [3.6]-[8] color). There is a higher fraction of carbon-rich stars in the SMC, and these stars appear to able to reach colors as red as their LMC counterparts, indicating that C-rich dust forms efficiently in both galaxies. A preliminary estimate of the dust production in AGB and RSG stars reveals that the extreme C-rich AGB stars dominate the dust input in both galaxies, and that the O-rich stars may play a larger role in the LMC than in the SMC.Comment: Accepted for publication in AJ. 25 pages, 36 figures, Table 4 will be available electronically from A

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1–4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1–4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including γ-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and l-lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCT-mediated detoxification strategies in GHB overdose

Cluster K Mycobacteriophages: Insights into the Evolutionary Origins of Mycobacteriophage TM4

Five newly isolated mycobacteriophages –Angelica, CrimD, Adephagia, Anaya, and Pixie – have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them – with the exception of TM4 – form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species

Speech Communication

Contains table of contents for Part IV, table of contents for Section 1, an introduction, reports on seven research projects and a list of publications.C.J. Lebel FellowshipDennis Klatt Memorial FundNational Institutes of Health Grant T32-DC00005National Institutes of Health Grant R01-DC00075National Institutes of Health Grant F32-DC00015National Institutes of Health Grant R01-DC00266National Institutes of Health Grant P01-DC00361National Institutes of Health Grant R01-DC00776National Science Foundation Grant IRI 89-10561National Science Foundation Grant IRI 88-05680National Science Foundation Grant INT 90-2471