Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD

Infrared point source variability between the Spitzer and MSX surveys of the Galactic mid-plane

We present a list of 552 sources with suspected variability, based on a comparison of mid-infrared photometry from the GLIMPSE I and MSX surveys, which were carried out nearly a decade apart. We were careful to address issues such as the difference in resolution and sensitivity between the two surveys, as well as the differences in the spectral responses of the instruments. We selected only sources where the IRAC 8.0 and MSX 8.28 micron fluxes differ by more than a factor of two, in order to minimize contamination from sources where the difference in fluxes at 8 micron is due to a strong 10 micron silicate feature. We present a subset of 40 sources for which additional evidence suggests variability, using 2MASS and MIPSGAL data. Based on a comparison with the variability flags in the IRAS and MSX Point-Source Catalogs we estimate that at least a quarter of the 552 sources, and at least half of the 40 sources are truly variable. In addition, we tentatively confirm the variability of one source using multi-epoch IRAS LRS spectra. We suggest that most of the sources in our list are likely to be Asymptotic Giant Branch stars.Comment: 47 pages, 12 Figures, 3 Tables, accepted for publication in A

Absolute diffuse calibration of IRAC through mid-infrared and radio study of HII regions

We investigate the diffuse absolute calibration of the InfraRed Array Camera on the Spitzer Space Telescope at 8.0microns using a sample of 43 HII regions with a wide range of morphologies near GLON=312deg. For each region we carefully measure sky-subtracted,point-source- subtracted, areally-integrated IRAC 8.0-micron fluxes and compare these with Midcourse Space eXperiment (MSX) 8.3-micron images at two different spatial resolutions, and with radio continuum maps. We determine an accurate median ratio of IRAC 8.0-micron/MSX\8.3-micron fluxes, of 1.55+/-0.15. From robust spectral energy distributions of these regions we conclude that the present 8.0-micron diffuse calibration of the SST is 36% too high compared with the MSX validated calibration, perhaps due to scattered light inside the camera. This is an independent confirmation of the result derived for the diffuse calibration of IRAC by the Spitzer Science Center (SSC). From regression analyses we find that 843-MHz radio fluxes of HII regions and mid-infrared (MIR) fluxes are linearly related for MSX at 8.3-microns and Spitzer at 8.0 microns, confirming the earlier MSX result by Cohen & Green. The median ratio of MIR/843-MHz diffuse continuum fluxes is 600 times smaller in nonthermal than thermal regions, making it a sharp discriminant. The ratios are largely independent of morphology up to a size of ~24 arcsec. We provide homogeneous radio and MIR morphologies for all sources. MIR morphology is not uniquely related to radio structure. Compact regions may have MIR filaments and/or diffuse haloes, perhaps infrared counter- parts to weakly ionized radio haloes found around compact HII regions. We offer two IRAC colour-colour plots as quantitative diagnostics of diffuse HII regions.Comment: 29 pages, LaTeX (aastex), incl. 31 PostScript (ps,eps) figures and 5 tables. Accepted by MNRAS (main journal). Replaced an unused file and added this URL for people wishing to download a version with high-resolution images: http://www.astro.wisc.edu/sirtf/martin.hii.accepted.pd

Engagement in a Community-Based Integral Practice Program Enhances Well-being

This project examined associations between engagement in a community-based integral practice program and measures of health and well-being. In this prospective withinsubjects uncontrolled cohort study, 53 participants of Integral Transformative Practice (ITP), a program that incorporates movement, nutritional and exercise recommendations, affirmations, contemplative introspection, theory and philosophy, and group discussions and activities, were followed over one year. Participants completed online questionnaires upon enrollment, at six months, and one year later. Repeated measures analyses showed that participants reported improved overall health and reduced symptoms of ill health, as well as increased psychological well-being, vitality, and quality of life over the course of the year. Greater involvement in the practice community predicted better psychological well-being, increased quality of life, and greater self-transcendence. Self-transcendence mediated the relationship between level of ITP involvement and psychological well-being outcomes, and predicted physical health outcomes, suggesting that this construct may be important to the effectiveness of participating in wellness interventions

Reading problems of the bottom third: grades one through six

Thesis (Ed.M.)--Boston Universit

A Unified Account of the Moral Standing to Blame

Recently, philosophers have turned their attention to the question, not when a given agent is blameworthy for what she does, but when a further agent has the moral standing to blame her for what she does. Philosophers have proposed at least four conditions on having “moral standing”: 1. One’s blame would not be “hypocritical”. 2. One is not oneself “involved in” the target agent’s wrongdoing. 3. One must be warranted in believing that the target is indeed blameworthy for the wrongdoing. 4. The target’s wrongdoing must some of “one’s business”. These conditions are often proposed as both conditions on one and the same thing, and as marking fundamentally different ways of “losing standing.” Here I call these claims into question. First, I claim that conditions (3) and (4) are simply conditions on different things than are conditions (1) and (2). Second, I argue that condition (2) reduces to condition (1): when “involvement” removes someone’s standing to blame, it does so only by indicating something further about that agent, viz., that he or she lacks commitment to the values that condemn the wrongdoer’s action. The result: after we clarify the nature of the non-hypocrisy condition, we will have a unified account of moral standing to blame. Issues also discussed: whether standing can ever be regained, the relationship between standing and our "moral fragility", the difference between mere inconsistency and hypocrisy, and whether a condition of standing might be derived from deeper facts about the "equality of persons"

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