203 research outputs found

    Regulation of DCC Localization by HTZ-1/H2A.Z and DPY-30 Does not Correlate with H3K4 Methylation Levels

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    Dosage compensation is a specialized form of gene regulation that balances sex-chromosome linked gene expression between the sexes. In C. elegans, dosage compensation is achieved by the activity of the dosage compensation complex (DCC). The DCC binds along both X chromosomes in hermaphrodites to down-regulate gene expression by half, limiting X-linked gene products to levels produced in XO males. Sequence motifs enriched on the X chromosome play an important role in targeting the DCC to the X. However, these motifs are not strictly X-specific and therefore other factors, such as the chromatin environment of the X chromosome, are likely to aid in DCC targeting. Previously, we found that loss of HTZ-1 results in partial disruption of dosage compensation localization to the X chromosomes. We wanted to know whether other chromatin components coordinated with HTZ-1 to regulate DCC localization. One candidate is DPY-30, a protein known to play a role in DCC localization. DPY-30 homologs in yeast, flies, and mammals are highly conserved members of histone H3 lysine 4 (H3K4) methyltransferase Set1/MLL complexes. Therefore, we investigated the hypothesis that the dosage compensation function of DPY-30 involves H3K4 methylation. We found that in dpy-30 animals the DCC fails to stably bind chromatin. Interestingly, of all the C. elegans homologs of Set1/MLL complex subunits, only DPY-30 is required for stable DCC binding to chromatin. Additionally, loss of H3K4 methylation does not enhance DCC mislocalization in htz-1 animals. We conclude that DPY-30 and HTZ-1 have unique functions in DCC localization, both of which are largely independent of H3K4 methylation

    The role of the most luminous, obscured AGN in galaxy assembly at z~2

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    We present HST WFC3 F160W imaging and infrared spectral energy distributions for twelve extremely luminous, obscured AGN at 1.8<z<2.71.8<z<2.7, selected via "Hot, Dust Obscured" mid-infrared colors. Their infrared luminosities span 215×10132-15\times10^{13}L_{\odot}, making them among the most luminous objects in the Universe at z2z\sim2. In all cases the infrared emission is consistent with arising at least in most part from AGN activity. The AGN fractional luminosities are higher than those in either sub-millimeter galaxies, or AGN selected via other mid-infrared criteria. Adopting the GG, M20_{20} and AA morphological parameters, together with traditional classification boundaries, infers that three quarters of the sample as mergers. Our sample do not, however, show any correlation between the considered morphological parameters and either infrared luminosity or AGN fractional luminosity. Moreover, their asymmetries and effective radii are distributed identically to those of massive galaxies at z2z\sim2. We conclude that our sample is not preferentially associated with mergers, though a significant merger fraction is still plausible. Instead, we propose that our sample are examples of the massive galaxy population at z2z\sim2 that harbor a briefly luminous, "flickering" AGN, and in which the GG and M20_{20} values have been perturbed, due to either the AGN, and/or the earliest formation stages of a bulge in an inside-out manner. Furthermore, we find that the mass assembly of the central black holes in our sample leads the mass assembly of any bulge component. Finally, we speculate that our sample represent a small fraction of the immediate antecedents of compact star-forming galaxies at z2z\sim2.Comment: ApJ, accepted. Updated to reflect the accepted versio

    Mini-Membrane Evaporator for Contingency Spacesuit Cooling

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    The next-generation Advanced Extravehicular Mobility Unit (AEMU) Portable Life Support System (PLSS) is integrating a number of new technologies to improve reliability and functionality. One of these improvements is the development of the Auxiliary Cooling Loop (ACL) for contingency crewmember cooling. The ACL is a completely redundant, independent cooling system that consists of a small evaporative cooler--the Mini Membrane Evaporator (Mini-ME), independent pump, independent feedwater assembly and independent Liquid Cooling Garment (LCG). The Mini-ME utilizes the same hollow fiber technology featured in the full-sized AEMU PLSS cooling device, the Spacesuit Water Membrane Evaporator (SWME), but Mini-ME occupies only approximately 25% of the volume of SWME, thereby providing only the necessary crewmember cooling in a contingency situation. The ACL provides a number of benefits when compared with the current EMU PLSS contingency cooling technology, which relies upon a Secondary Oxygen Vessel; contingency crewmember cooling can be provided for a longer period of time, more contingency situations can be accounted for, no reliance on a Secondary Oxygen Vessel (SOV) for contingency cooling--thereby allowing a reduction in SOV size and pressure, and the ACL can be recharged-allowing the AEMU PLSS to be reused, even after a contingency event. The first iteration of Mini-ME was developed and tested in-house. Mini-ME is currently packaged in AEMU PLSS 2.0, where it is being tested in environments and situations that are representative of potential future Extravehicular Activities (EVA's). The second iteration of Mini-ME, known as Mini-ME2, is currently being developed to offer more heat rejection capability. The development of this contingency evaporative cooling system will contribute to a more robust and comprehensive AEMU PLSS

    Mechanisms involved in acquisition of blaNDM genes by IncA/C2 and IncFIIY plasmids

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    blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family

    Spacesuit Water Membrane Evaporator; An Enhanced Evaporative Cooling Systems for the Advanced Extravehicular Mobility Unit Portable Life Support System

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    Spacesuit Water Membrane Evaporator - Baseline heat rejection technology for the Portable Life Support System of the Advanced EMU center dot Replaces sublimator in the current EMU center dot Contamination insensitive center dot Can work with Lithium Chloride Absorber Radiator in Spacesuit Evaporator Absorber Radiator (SEAR) to reject heat and reuse evaporated water The Spacesuit Water Membrane Evaporator (SWME) is being developed to replace the sublimator for future generation spacesuits. Water in LCVG absorbs body heat while circulating center dot Warm water pumped through SWME center dot SWME evaporates water vapor, while maintaining liquid water - Cools water center dot Cooled water is then recirculated through LCVG. center dot LCVG water lost due to evaporation (cooling) is replaced from feedwater The Independent TCV Manifold reduces design complexity and manufacturing difficulty of the SWME End Cap. center dot The offset motor for the new BPV reduces the volume profile of the SWME by laying the motor flat on the End Cap alongside the TCV

    The First Hyper-luminous Infrared Galaxy Discovered by WISE

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    We report the discovery by the Wide-field Infrared Survey Explorer (WISE) of the z = 2.452 source WISE J181417.29+341224.9, the first hyperluminous source found in the WISE survey. WISE 1814+3412 is also the prototype for an all-sky sample of ~1000 extremely luminous "W1W2-dropouts" (sources faint or undetected by WISE at 3.4 and 4.6 μm and well detected at 12 or 22 μm). The WISE data and a 350 μm detection give a minimum bolometric luminosity of 3.7 × 10^(13) L_☉, with ~10^(14) L_☉ plausible. Follow-up images reveal four nearby sources: a QSO and two Lyman break galaxies (LBGs) at z = 2.45, and an M dwarf star. The brighter LBG dominates the bolometric emission. Gravitational lensing is unlikely given the source locations and their different spectra and colors. The dominant LBG spectrum indicates a star formation rate ~300 M_☉ yr^(–1), accounting for ≲ 10% of the bolometric luminosity. Strong 22 μm emission relative to 350 μm implies that warm dust contributes significantly to the luminosity, while cooler dust normally associated with starbursts is constrained by an upper limit at 1.1 mm. Radio emission is ~10 times above the far-infrared/radio correlation, indicating an active galactic nucleus (AGN) is present. An obscured AGN combined with starburst and evolved stellar components can account for the observations. If the black hole mass follows the local M BH-bulge mass relation, the implied Eddington ratio is ≳ 4. WISE 1814+3412 may be a heavily obscured object where the peak AGN activity occurred prior to the peak era of star formation

    Predicting which children with juvenile idiopathic arthritis will not attain early remission with conventional treatment: Results from the Reacch-out cohort

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    Objective. To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD). Methods. We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcome was clinically inactive disease for ≥ 6 months starting within 1 year of JIA diagnosis in patients who did not receive early biologic agents or triple DMARD. Models were developed in 200 random splits of 75% of the cohort and tested on the remaining 25% of subjects, calculating expected and observed frequencies of remission and c-index values. Results. Our best Cox logistic model combining 18 clinical variables a median of 2 days after diagnosis had a c-index of 0.69 (95% CI 0.67-0.71), better than using JIA category alone (0.59, 95% CI 0.56-0.63). Children in the lowest probability decile had a 20% chance of remission and 21% attained remission; children in the highest decile had a 69% chance of remission and 73% attained remission. Compared to 5% of subjects identified by JIA category alone, the model identified 14% of subjects as low chance of remission (probability \u3c 0.25), of whom 77% failed to attain remission. Conclusion. Although the model did not meet our a priori performance threshold (c-index \u3e 0.70), it identified 3 times more subjects with low chance of remission than did JIA category alone, and it may serve as a benchmark for assessing value added by future laboratory/imaging biomarkers

    In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection

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    Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization
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