179 research outputs found

    Wait-Learning: Leveraging Wait Time for Second Language Education

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    Competing priorities in daily life make it difficult for those with a casual interest in learning to set aside time for regular practice. In this paper, we explore wait-learning: leveraging brief moments of waiting during a person's existing conversations for second language vocabulary practice, even if the conversation happens in the native language. We present an augmented version of instant messaging, WaitChatter, that supports the notion of wait-learning by displaying contextually relevant foreign language vocabulary and micro-quizzes just-in-time while the user awaits a response from her conversant. Through a two week field study of WaitChatter with 20 people, we found that users were able to learn 57 new words on average during casual instant messaging. Furthermore, we found that users were most receptive to learning opportunities immediately after sending a chat message, and that this timing may be critical given user tendency to multi-task during waiting periods.Quanta Computer (Firm)Lincoln Laborator

    Propane on Titan

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    We present the first observations of propane (C3_3H8_8) on Titan that unambiguously resolve propane features from other numerous stratospheric emissions. This is accomplished using a R=Ξ»/Ξ΄Ξ»β‰ˆ105R=\lambda/\delta\lambda\approx10^5 spectrometer (TEXES) to observe propane's Ξ½26\nu_{26} rotation-vibration band near 748 cmβˆ’1^{-1}. We find a best-fit fractional abundance of propane in Titan's stratosphere of (6.2Β±1.2)Γ—10βˆ’7(6.2\pm1.2)\times10^{-7} in the altitude range to which we are sensitive (90-250 km or 13-0.24 mbar).Comment: accepted to ApJL 18 September 2003; See also: http://www.gps.caltech.edu/~hroe/propane2003

    Principles of meiotic chromosome assembly revealed in S. cerevisiae

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    During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

    Small intestinal mucosa expression of putative chaperone fls485

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    <p>Abstract</p> <p>Background</p> <p>Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. <it>fls485 </it>coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze <it>fls48</it>5 expression in human small intestinal mucosa.</p> <p>Methods</p> <p><it>fls485 </it>expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several <it>in situ </it>techniques and usage of newly synthesized mouse monoclonal antibodies.</p> <p>Results</p> <p>fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.</p> <p>Conclusions</p> <p>Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.</p

    Gene expression profiling in sinonasal adenocarcinoma

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    <p>Abstract</p> <p>Background</p> <p>Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers.</p> <p>Methods</p> <p>To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors.</p> <p>Results</p> <p>Among the genes with significant differential expression we selected <it>LGALS4, ACS5, CLU, SRI and CCT5 </it>for further exploration. The overexpression of <it>LGALS4, ACS5, SRI</it>, <it>CCT5 </it>and the downregulation of <it>CLU </it>were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type.</p> <p>Conclusion</p> <p>Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers.</p

    Adaptive Optics Spectroscopy of the [Fe II] Outflows from HL Tauri and RW Aurigae

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    We present new results of [Fe II] 1.644-micron spectroscopy toward the jets from HL Tau and RW Aur carried out with the Subaru Telescope combined with the adaptive optics system. We observed the regions within 2" - 3" from the stars with the sub-arcsecond resolutions of 0."5 and 0."2 for HL Tau and RW Aur, respectively. In addition to the strong, high velocity emission extended along each jet, we detected a blueshifted low velocity emission feature seen as a wing or shoulder of the high velocity emission at each stellar position. Detailed analysis shows that the position-velocity diagrams (PVDs) of HL Tau and RW Aur show a characteristic similar to those of the cold disk wind and X-wind models in that the [Fe II] line width is broad in the vicinity of the stellar position and is narrower at the extended jet. A closer comparison suggests, however, that the disk wind model tends to have too large line width at the jet while the X-wind model has excess emission on the redshifted side at the stellar position. The narrow velocity width with symmetric line profiles of the observed high velocity emission supports an X-wind type model where the launching region is localized in a small radial range, while the low velocity emission located away from the star favors the presence of a disk wind. The [Fe II] emission from the HL Tau jet shows a gap of 0."8 between the redshifted jet and the star, indicating the presence of an optically thick disk of ~ 160 AU in radius. The [Fe II] emission from the RW Aur jet shows a marked drop from the redshifted peak at Y ~ -0."2 toward the star, suggesting that its disk radius is smaller than 40 AU.Comment: Accepted in the ApJ (October 2006, v649n2), AAS LaTEX macros v 5.2, Total 25 pages with 7 figure

    Reduction in podocyte density as a pathologic feature in early diabetic nephropathy in rodents: Prevention by lipoic acid treatment

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    BACKGROUND: A reduction in the number of podocytes and podocyte density has been documented in the kidneys of patients with diabetes mellitus. Additional studies have shown that podocyte injury and loss occurs in both diabetic animals and humans. However, most studies in animals have examined relatively long-term changes in podocyte number and density and have not examined effects early after initiation of diabetes. We hypothesized that streptozotocin diabetes in rats and mice would result in an early reduction in podocyte density and that this reduction would be prevented by antioxidants. METHODS: The number of podocytes per glomerular section and the podocyte density in glomeruli from rats and mice with streptozotocin (STZ)-diabetes mellitus was determined at several time points based on detection of the glomerular podocyte specific antigens, WT-1 and GLEPP1. The effect of insulin administration or treatment with the antioxidant, Ξ±-lipoic acid, on podocyte number was assessed. RESULTS: Experimental diabetes resulted in a rapid decline in apparent podocyte number and podocyte density. A significant reduction in podocytes/glomerular cross-section was found in STZ diabetes in rats at 2 weeks (14%), 6 weeks (18%) and 8 weeks (34%) following STZ injection. Similar declines in apparent podocyte number were found in STZ diabetes in C57BL/6 mice at 2 weeks, but not at 3 days after injection. Treatment with Ξ±-lipoic acid substantially prevented podocyte loss in diabetic rats but treatment with insulin had only a modest effect. CONCLUSION: STZ diabetes results in reduction in apparent podocyte number and in podocyte density within 2 weeks after onset of hyperglycemia. Prevention of these effects with antioxidant therapy suggests that this early reduction in podocyte density is due in part to increased levels of reactive oxygen species as well as hyperglycemia

    The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine

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    Intestinal epithelial cells serve as mechanical barriers and active components of the mucosal immune system. These cells migrate from the crypt to the tip of the villus, where different stimuli can differentially affect their survival. Here we investigated, using in vitro and in vivo strategies, the role of galectin-1 (Gal-1), an evolutionarily conserved glycan-binding protein, in modulating the survival of human and mouse enterocytes. Both Gal-1 and its specific glyco-receptors were broadly expressed in small bowel enterocytes. Exogenous Gal-1 reduced the viability of enterocytes through apoptotic mechanisms involving activation of both caspase and mitochondrial pathways. Consistent with these findings, apoptotic cells were mainly detected at the tip of the villi, following administration of Gal-1. Moreover, Gal-1-deficient (Lgals1βˆ’/βˆ’) mice showed longer villi compared with their wild-type counterparts in vivo. In an experimental model of starvation, fasted wild-type mice displayed reduced villi and lower intestinal weight compared with Lgals1βˆ’/βˆ’ mutant mice, an effect reflected by changes in the frequency of enterocyte apoptosis. Of note, human small bowel enterocytes were also prone to this pro-apoptotic effect. Thus, Gal-1 is broadly expressed in mucosal tissue and influences the viability of human and mouse enterocytes, an effect which might influence the migration of these cells from the crypt, the integrity of the villus and the epithelial barrier function

    Interleukin-8 Is Activated in Patients with Chronic Liver Diseases and Associated with Hepatic Macrophage Accumulation in Human Liver Fibrosis

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    BACKGROUND: Interleukin-8 (IL-8, CXCL8) is a potent chemoattractant for neutrophils and contributes to acute liver inflammation. Much less is known about IL-8 in chronic liver diseases (CLD), but elevated levels were reported from alcoholic and hepatitis C-related CLD. We investigated the regulation of IL-8, its receptors CXCR1 and CXCR2 and possible IL-8 responding cells in CLD patients. METHODOLOGY: Serum IL-8 levels were measured in CLD patients (nβ€Š=β€Š200) and healthy controls (nβ€Š=β€Š141). Intrahepatic IL-8, CXCR1 and CXCR2 gene expression was quantified from liver samples (nβ€Š=β€Š41), alongside immunohistochemical neutrophil (MPO) and macrophage (CD68) stainings. CXCR1 and CXCR2 expression was analyzed on purified monocytes from patients (nβ€Š=β€Š111) and controls (nβ€Š=β€Š31). In vitro analyses explored IL-8 secretion by different leukocyte subsets. PRINCIPAL FINDINGS: IL-8 serum levels were significantly increased in CLD patients, especially in end-stage cirrhosis. Interestingly, patients with cholestatic diseases exhibited highest IL-8 serum concentrations. IL-8 correlated with liver function, inflammatory cytokines and non-invasive fibrosis markers. Intrahepatically, IL-8 and CXCR1 expression were strongly up-regulated. However, intrahepatic IL-8 could only be associated to neutrophil infiltration in patients with primary biliary cirrhosis (PBC). In non-cholestatic cirrhosis, increased IL-8 and CXCR1 levels were associated with hepatic macrophage accumulation. In line, CXCR1, but not CXCR2 or CXCR3, expression was increased on circulating monocytes from cirrhotic patients. Moreover, monocyte-derived macrophages from CLD patients, especially the non-classical CD16⁺ subtype, displayed enhanced IL-8 secretion in vitro. CONCLUSIONS: IL-8 is strongly activated in CLD, thus likely contributing to hepatic inflammation. Our study suggests a novel role of IL-8 for recruitment and activation of hepatic macrophages via CXCR1 in human liver cirrhosis

    The Lid Domain of Caenorhabditis elegans Hsc70 Influences ATP Turnover, Cofactor Binding and Protein Folding Activity

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    Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy of ATP hydrolysis to alter the folding state of its client proteins. In contrast to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C. elegans (CeHsc70) has not been studied to date
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