Active paper for active learning

Recent research into distance learning and the virtual campus has focused on the use of electronic documents and computer‐based demonstrations to replace or reinforce traditional learning material. We show how a computer‐augmented desk, the DigitalDesk, can provide the benefits of both paper and electronic documents using a natural interface based on real paper documents. Many electronic documents, particularly those created using the guidelines produced by the Text Encoding Initiative (TEI), include detailed semantic and linguistic information that can be used to good effect in learning material. We discuss potential uses of TEI texts, and describe one simple application that allows a student's book to become an active part of a grammar lesson when placed on the DigitalDesk. The book is integrated into an interactive point‐and‐click interface, and feedback is related to the currently visible pages of the boo

Oct-4 expression in equine embryonic cells

The Oct-4 transcription factor is believed to co-regulate early embryonic development of mammals due to the correlation of its presence with the maintenance of pluripotency. It is commonly used as a marker for the identification of embryonic stem (ES) cells for this reason. Until 1999, Oct-4 studies were limited to in vivo-produced embryos; equine embryos have not been studied for their Oct-4 expression patterns. In addition, equine stem-like cells (defined by marker expression, induced differentiation, passage survival, and morphology) have recently been isolated from in vivo-produced embryos, but no work has been performed in horses to isolate ES cells from in vitroproduced embryos. This study investigated the expression of Oct-4 transcription factor using immunocytochemistry in 42 in vitro-produced embryos aged 1-10 days and in 5 in vivoproduced blastocysts aged 7-10 days. Effective conditions for rapid establishment of a feeder layer of equine fetal fibroblasts were established, and this feeder layer was used to grow isolated equine inner cell mass (ICM) cells from in vitro-produced embryos. The expression of Oct-4 was examined in resultant cell growths. In vitro-produced embryos less than 6 days of age showed variable staining within blastomeres of the same embryo, and the peak of variability correlated with maternal-zygotic transition. After Oct-4 staining of in vitro-produced blastocysts, no cells could be identified as an ICM based on a difference in fluorescent intensity from the other cells of the blasyocysts. However, in vitro-produced blastocysts that were subsequently cultured in vivo contained a presumptive ICM, visible based on greater fluorescent intensity of Oct-4 stain. The trophoblast of all blastocysts also stained positively for Oct-4 protein. Fibroblasts were successfully isolated from equine feti. Treatment with 20 õg/ml of Mitomycin C arrested cell growth without causing excessive death. Fibroblasts were inactivated and frozen, then thawed as needed to establish a confluent monolayer for ICM isolation overnight. ICMs from in vitro-produced embryos formed outgrowths, but none that could be identified morphologically as ES cells. Outgrowth cells contained about 20% Oct-4 expressing cells in sporadic groupings. Assuming appropriate binding of the Oct-4 antibody, Oct-4 expressing cells (potentially indicating pluripotency) are found throughout the embryo in early development and in the feeder layer after co-culture

Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response

Stress-induced eukaryotic translation initiation factor 2 (eIF2) α phosphorylation paradoxically increases translation of the metazoan activating transcription factor 4 (ATF4), activating the integrated stress response (ISR), a pro-survival gene expression program. Previous studies implicated the 5′ end of the ATF4 mRNA, with its two conserved upstream ORFs (uORFs), in this translational regulation. Here, we report on mutation analysis of the ATF4 mRNA which revealed that scanning ribosomes initiate translation efficiently at both uORFs and ribosomes that had translated uORF1 efficiently reinitiate translation at downstream AUGs. In unstressed cells, low levels of eIF2α phosphorylation favor early capacitation of such reinitiating ribosomes directing them to the inhibitory uORF2, which precludes subsequent translation of ATF4 and represses the ISR. In stressed cells high levels of eIF2α phosphorylation delays ribosome capacitation and favors reinitiation at ATF4 over the inhibitory uORF2. These features are common to regulated translation of GCN4 in yeast. The metazoan ISR thus resembles the yeast general control response both in its target genes and its mechanistic details

Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-γ

I*nterferon-γ (IFN-γ) is believed to contribute to immune-mediated demyelinating disorders by targeting the myelin-producing oligodendrocyte, a cell known to be highly sensitive to the disruption of protein synthesis and to the perturbation of the secretory pathway. We found that apoptosis induced by IFN-γ in cultured rat oligodendrocytes was associated with endoplasmic reticulum (ER) stress. ER stress also accompanied oligodendrocyte apoptosis and hypomyelination in transgenic mice that inappropriately expressed IFN-γ in the central nervous system (CNS). Compared with a wild-type genetic background, the enforced expression of IFN-γ in mice that were heterozygous for a loss of function mutation in pancreatic ER kinase (PERK) dramatically reduced animal survival, promoted CNS hypomyelination, and enhanced oligodendrocyte loss. PERK encodes an ER stress–inducible kinase that phosphorylates eukaryotic translation initiation factor 2α and specifically maintains client protein homeostasis in the stressed ER. Therefore, the hypersensitivity of PERK+/− mice to IFN-γ implicates ER stress in demyelinating disorders that are induced by CNS inflammation

Star Clusters in M31: II. Old Cluster Metallicities and Ages from Hectospec Data

We present new high signal-to-noise spectroscopic data on the M31 globular cluster system, obtained with the Hectospec multifiber spectrograph on the 6.5m MMT. More than 300 clusters have been observed at a resolution of 5A. The primary focus of this paper is the determination of mean cluster metallicities, ages and reddenings. Metallicities were estimated using a calibration of Lick indices with [Fe/H] provided by Galactic GCs. The metallicity distribution is not generally bimodal, in strong distinction with the bimodal Galactic globular distribution. Rather, the M31 distribution shows a broad peak, centered at [Fe/H]=-1, suggesting that the cluster systems of M31 and the Milky Way had different formation histories. Ages for clusters with [Fe/H] > -1 were determined using the automatic stellar population analysis program EZ_Ages. We find no evidence for massive clusters in M31 with intermediate ages. Moreover, we find that the mean ages of the old GCs are remarkably constant over about a decade in metallicity (-0.95 < [Fe/H] < 0.0). (abridged)Comment: 25 pages, 24 figures, 3 table

Dephosphorylation of Translation Initiation Factor 2α Enhances Glucose Tolerance and Attenuates Hepatosteatosis in Mice

SummaryThe molecular mechanisms linking the stress of unfolded proteins in the endoplasmic reticulum (ER stress) to glucose intolerance in obese animals are poorly understood. In this study, enforced expression of a translation initiation factor 2α (eIF2α)-specific phosphatase, GADD34, was used to selectively compromise signaling in the eIF2(αP)-dependent arm of the ER unfolded protein response in liver of transgenic mice. The transgene resulted in lower liver glycogen levels and susceptibility to fasting hypoglycemia in lean mice and glucose tolerance and diminished hepatosteatosis in animals fed a high-fat diet. Attenuated eIF2(αP) correlated with lower expression of the adipogenic nuclear receptor PPARγ and its upstream regulators, the transcription factors C/EBPα and C/EBPβ, in transgenic mouse liver, whereas eIF2α phosphorylation promoted C/EBP translation in cultured cells and primary hepatocytes. These observations suggest that eIF2(αP)-mediated translation of key hepatic transcriptional regulators of intermediary metabolism contributes to the detrimental consequences of nutrient excess

Mapping the Galactic Halo. V. Sgr dSph Tidal Debris 60 degrees from the Main Body

As part of the Spaghetti Project Survey (SPS) we have detected a concentration of giant stars well above expectations for a smooth halo model. The position (l~350, b~50) and distance (~50 kpc) of this concentration match those of the Northern over-density detected by SDSS (Yanny et al. 2000, Ivezic et al. 2000). We find additional evidence for structure at ~80 kpc in the same direction. We present radial velocities for many of these stars, including the first published results from the 6.5m Magellan telescope. The radial velocities for stars in these structures are in excellent agreement with models of the dynamical evolution of the Sgr dwarf tidal debris, whose center is 60 degrees away. The metallicity of stars in these streams is lower than that of the main body of the Sgr dwarf, which may indicate a radial metallicity gradient prior to disruption.Comment: 10 pages, 3 figures accepted in Astrophysical Journal Letter