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        Joint Strength in High Speed Friction Stir Spot Welded DP 980 Steel

        Nathan Saunders,Michael Miles,Trent Hartman,Yuri Hovanski,Sung-Tae Hong,Russell Steel 한국정밀공학회 2014 International Journal of Precision Engineering and Vol. No.

        High speed friction stir spot welding was applied to 1.2 mm thick DP 980 steel sheets under different welding conditions, using PCBNtools. The range of vertical feed rates used during welding was 2.5~102 mm per minute, while the range of spindle speeds was 2500~6000 rpm. Extended testing was carried out for five different sets of welding conditions, until tool failure. These welding conditionsresulted in vertical welding loads of 3.6~8.2 kN and lap shear tension failure loads of 8.9~11.1 kN. PCBN tools were shown, in thebest case, to provide lap shear tension failure loads at or above 9 kN for 900 spot welds, after which tool failure caused a rapid dropin joint strength. Joint strength was shown to be strongly correlated to bond area, which was measured from weld cross sections. Failure modes of the tested joints were a function of bond area and softening that occurred in the heat-affected zone.

      • Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial

        Easterhoff, David,Moody, M. Anthony,Fera, Daniela,Cheng, Hao,Ackerman, Margaret,Wiehe, Kevin,Saunders, Kevin O.,Pollara, Justin,Vandergrift, Nathan,Parks, Rob,Kim, Jerome,Michael, Nelson L.,O’Connell, Public Library of Science 2017 PLoS pathogens Vol.13 No.2

        <▼1><P>The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1-uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 in the RV305 trial. Env-specific post-RV144 and RV305 boost memory B cell V<SUB>H</SUB> mutation frequencies increased from 2.9% post-RV144 to 6.7% post-RV305. The vaccine was well tolerated with no adverse events reports. While post-boost plasma did not have bnAb activity, the vaccine boosts expanded a pool of envelope CD4 binding site (bs)-reactive memory B cells with long third heavy chain complementarity determining regions (HCDR3) whose germline precursors and affinity matured B cell clonal lineage members neutralized the HIV-1 CRF01 AE tier 2 (difficult to neutralize) primary isolate, CNE8. Electron microscopy of two of these antibodies bound with near-native gp140 trimers showed that they recognized an open conformation of the Env trimer. Although late boosting of RV144 vaccinees expanded a novel pool of neutralizing B cell clonal lineages, we hypothesize that boosts with stably closed trimers would be necessary to elicit antibodies with greater breadth of tier 2 HIV-1 strains.</P><P><B>Trial Registration:</B> ClinicalTrials.gov NCT01435135</P></▼1><▼2><P><B>Author summary</B></P><P>Developing a successful HIV-1 vaccine remains a high global health priority. Several HIV-1 vaccine trials have been performed with only the RV144 vaccine trial showing vaccine efficacy, albeit modest. No broadly neutralizing antibody activity was identified in RV144 and inducing sterilizing immunity against a complex pathogen like HIV-1 remains a major challenge. Here we characterize the B cell responses after RV144 vaccine-recipients received two additional boosts severals years after the conclusion of the RV144 vaccine trial. Delayed and repetitive boosting of RV144 vaccine-recipients was capable of increasing somatic hypermutation of the Env-reactive antibodies and expanding subdominant pools of neutralizing B cell clonal lineages. These data are pertinent to HIV-1 vaccine-regimen design.</P></▼2>

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