955 research outputs found

    Filler wire for aluminum alloys and method of welding

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    A weld filler wire chemistry has been developed for fusion welding 2195 aluminum-lithium. The weld filler wire chemistry is an aluminum-copper based alloy containing high additions of titanium and zirconium. The additions of titanium and zirconium reduce the crack susceptibility of aluminum alloy welds while producing good weld mechanical properties. The addition of silver further improves the weld properties of the weld filler wire. The reduced weld crack susceptibility enhances the repair weldability, including when planishing is required

    A Co-receptor-mimicking Antibody Stabilizes the Displaced V1V2 Loops in a Partially Open sCD4-bound HIV-1 Envelope Complex

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    Background: HIV-1 envelope glycoprotein (Env), a trimer of gp120-gp41 heterodimers, mediates membrane fusion after binding host receptor CD4. Receptor binding to closed Env displaces the V1V2 loops from Env‘s apex, allowing co-receptor binding and opening Env to enable gp41-mediated fusion. Methods: Using single-particle cryoEM methods, we solved the sCD4-bound structure of a clade B B41 SOSIP trimer in complex with 21c, a CD4-induced (CD4i) coreceptor-mimicking antibody, and with 8ANC195, a broadly neutralizing antibody (bNAb) that recognizes the gp120-gp41 interface, to a resolution of 4.05 Å. Results: Despite binding of the 8ANC195 Fab that partially closes the open, sCD4-bound Env conformation, our structure shows rearrangements in gp120, including displacement of V1V2, exposure of V3, formation of the 4-stranded bridging sheet, and formation of the α0 helix. In addition, unlike the V1V2 regions in similar sCD4-bound Env structures complexed with the CD4i antibody 17b, the displaced V1V2 loops in the B41-sCD4-21c-8ANC195 structure exhibited ordered density allowing the structure of the displaced V1V2 to be determined for the first time. Comparing partially- and fully-open Envs with closed Envs shows that gp41 rearrangements are independent of CD4-induced gp120 bridging sheet formation and V1V2 displacement, suggesting an order of conformational changes before co-receptor binding: (i) gp120 opening inducing side chain rearrangements and a compact gp41 central helix conformation, and (ii) bridging sheet formation, and V1V2 displacement. Conclusions: Analyses of these results further our understanding of HIV-1 Env conformational changes leading to fusion and provide templates for designing agents to disrupt HIV-1 entry into target cells

    Lem2p (LEM2) and Cmp7p (CHMP7) function in ESCRT-dependent nuclear envelope remodeling in fission yeast

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    ESCRT‐III proteins have been implicated in sealing the nuclear envelope in mammals, both during nuclear assembly and following mechanical disruption. This sealing process requires the ESCRT‐II/ESCRT‐ III hybrid protein CHMP7 and the AAA ATPase VPS4. It remains unclear, however, how CHMP7 is recruited to breaches of the nuclear envelope. The fission yeast S. pombe is an attractive genetic model system for investigating this role of the ESCRT pathway because, in fission yeast, the nuclear envelope develops fenestrations that must be closed twice per cell cycle: upon mitotic entry when duplicated spindle pole bodies (SPB) are incorporated into the nuclear envelope and after a successful cell cycle when the SPBs are ejected back to cytoplasm. Here we report that deletion of fission yeast vps4 leads to severe defects in nuclear morphology and integrity, which causes delayed segregation of duplicated SPBs, asymmetric nuclear bipartition in mitosis, and slow growth. Interestingly, these phenotypes are spontaneously suppressed by loss‐of‐function mutations that arise in cmp7 (pombe CHMP7) or lem2, a member of the LEM (Lap2‐Emerin‐Man1) family of inner nuclear membrane proteins—implying that all three function in the same pathway. Based on these observations, we hypothesize that Lem2p acts as a nuclear site‐specific adaptor to recruit Cmp7p to the nuclear envelope

    Papers in New Guinea Linguistics No. 11

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    Cryo-EM Structures of HIV-1 trimer bound to CD4-mimetics M48U1 and BNM-III-170 adopt a CD4-bound open conformation

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    Human Immunodeficiency Virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host receptor CD4, which triggers conformational changes allowing binding to a coreceptor and subsequent membrane fusion. Small molecule or peptide CD4-mimetic drugs mimic CD4’s Phe43 interaction with Env by inserting into the conserved Phe43 pocket on Env subunit gp120. Here, we present single-particle cryo-EM structures of CD4-mimetics BNM-III-170 and M48U1 bound to a BG505 native-like Env trimer plus the CD4-induced antibody 17b at 3.7Å and 3.9Å resolution, respectively. CD4-mimetic-bound BG505 exhibits canonical CD4-induced conformational changes including trimer opening, formation of the 4-stranded gp120 bridging sheet, displacement of the V1V2 loop, and formation of a compact and elongated gp41 HR1C helical bundle. We conclude that CD4-induced structural changes on both gp120 and gp41 Env subunits are induced by binding to the gp120 Phe43 pocket

    Blobs in Wolf-Rayet Winds: Random Photometric and Polarimetric Variability

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    Some isolated Wolf-Rayet stars present random variability in their optical flux and polarization. We make the assumption that such variability is caused by the presence of regions of enhanced density, i.e. blobs, in their envelopes. In order to find the physical characteristics of such regions we have modeled the stellar emission using a Monte Carlo code to treat the radiative transfer in an inhomogeneous electron scattering envelope. We are able to treat multiple scattering in the regions of enhanced density as well as in the envelope itself. The finite sizes of the source and structures in the wind are also taken into account. Most of the results presented here are based on a parameter study of models with a single blob. The effects due to multiple blobs in the envelope are considered to a more limited extent. Our simulations indicate that the density enhancements must have a large geometric cross section in order to produce the observed photopolarimetric variability. The sizes must be of the order of one stellar radius and the blobs must be located near the base of the envelope. These sizes are the same inferred from the widths of the sub-peaks in optical emission lines of Wolf-Rayet stars. Other early-type stars show random polarimetric fluctuations with characteristics similar to those observed in Wolf-Rayet stars, which may also be interpreted in terms of a clumpy wind. Although the origin of such structures is still unclear, the same mechanism may be working in different types of hot stars envelopes to produce such inhomogeneities.Comment: Accepted to ApJ. 17 pages + 6 figure

    Fast ray-tracing algorithm for circumstellar structures (FRACS). II. Disc parameters of the B[e] supergiant CPD-57° 2874 from VLTI/MIDI data

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    B[e] supergiants are luminous, massive post-main sequence stars exhibiting non-spherical winds, forbidden lines, and hot dust in a disc-like structure. The physical properties of their rich and complex circumstellar environment (CSE) are not well understood, partly because these CSE cannot be easily resolved at the large distances found for B[e] supergiants (typically \ga 1~kpc). From mid-IR spectro-interferometric observations obtained with VLTI/MIDI we seek to resolve and study the CSE of the Galactic B[e] supergiant CPD-57\degr\,2874. For a physical interpretation of the observables (visibilities and spectrum) we use our ray-tracing radiative transfer code (FRACS), which is optimised for thermal spectro-interferometric observations. Thanks to the short computing time required by FRACS (<10<10~s per monochromatic model), best-fit parameters and uncertainties for several physical quantities of CPD-57\degr\,2874 were obtained, such as inner dust radius, relative flux contribution of the central source and of the dusty CSE, dust temperature profile, and disc inclination. The analysis of VLTI/MIDI data with FRACS allowed one of the first direct determinations of physical parameters of the dusty CSE of a B[e] supergiant based on interferometric data and using a full model-fitting approach. In a larger context, the study of B[e] supergiants is important for a deeper understanding of the complex structure and evolution of hot, massive stars
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