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At least 55 records · Page 3

Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies

Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.

59 BASIC BIOLOGICAL SCIENCES↗

Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families

Broadly reactive antibodies that target sequence-diverse antigens are of interest for vaccine design and monoclonal antibody therapeutic development because they can protect against multiple strains of a virus and provide a barrier to evolution of escape mutants. Using LIBRA-seq (linking B cell receptor to antigen specificity through sequencing) data for the B cell repertoire of an individual chronically infected with human immunodeficiency virus type 1 (HIV-1), we identified a lineage of IgG3 antibodies predicted to bind to HIV-1 Envelope (Env) and influenza A Hemagglutinin (HA). Two lineage members, antibodies 2526 and 546, were confirmed to bind to a large panel of diverse antigens, including several strains of HIV-1 Env, influenza HA, coronavirus (CoV) spike, hepatitis C virus (HCV) E protein, Nipah virus (NiV) F protein, and Langya virus (LayV) F protein. We found that both antibodies bind to complex glycans on the antigenic surfaces. Antibody 2526 targets the stem region of influenza HA and the N-terminal domain (NTD) region of SARS-CoV-2 spike. A crystal structure of 2526 Fab bound to mannose revealed the presence of a glycan-binding pocket on the light chain. Antibody 2526 cross-reacted with antigens from multiple pathogens and displayed no signs of autoreactivity. These features distinguish antibody 2526 from previously described glycan-reactive antibodies. Further study of this antibody class may aid in the selection and engineering of broadly reactive antibody therapeutics and can inform the development of effective vaccines with exceptional breadth of pathogen coverage.

Microbiology↗

Impact of Insulation Strategies of Cross-Laminated Timber Assemblies on Energy Use, Peak Demand, and Carbon Emissions

Cross-Laminated Timber (CLT) panels have many structural benefits but do not have much thermal resistance. We have developed a solution to insulate CLT structures that uses high-performance insulation panels that provide R-values up to R40/inch. The CLT panels are made of layers of wood laminates (three, five, seven or more). The solution replaces some of the wood laminates in the CLT production with the insulation panels in a staggered fashion so that the wood laminates maintain contact throughout the panel, ensuring the CLT panel’s structural integrity. The insulated CLT panels have factory-installed water-resistive barriers reducing the installation time by eliminating installing insulation and water-resistive barriers on site. Per simulations, the CLT/insulation panel achieved code-required insulation levels with commonly available insulation materials. The significance of the thermal mass of CLT/insulation hybrid building envelopes was quantified by comparing the whole building energy performance and peak demand of traditional low mass and CLT wall assemblies resulting in up to 7% reduction in peak demand for cooling in Knoxville, TN, in a multifamily building. Buildings contribute over 40 percent of carbon emissions. The proposed CLT/insulation hybrid building envelope addresses both operational and embodied carbon by having high thermal resistances due to the embedded insulation sections and eliminating the use of high embodied carbon materials such as steel and concrete. The carbon benefit is estimated.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens

HIV-1 vaccine immunofocusing strategies may be able to induce broadly-reactive neutralizing antibodies (NAbs). Here, we engineered a panel of diverse, membrane-resident native HIV-1 trimers vulnerable to two broad targets—the V2 apex and fusion peptide (FP). Selection criteria included i) high expression and ii) infectious function, so that trimer neutralization sensitivity can be profiled in pseudovirus (PV) assays. Initially, we boosted the expression of 17 candidate trimers by truncating gp41 and introducing a gp120-gp41 SOS disulfide to prevent gp120 shedding. "Repairs" were made to fill glycan holes and eliminate other strain-specific aberrations. A new neutralization assay allowed PV infection when our standard assay was insufficient. Trimers with exposed V3 loops, a target of non-NAbs, were discarded. To try to increase V2-sensitivity, we removed clashing glycans and modified the C-strand. Notably, a D167N mutation improved V2-sensitivity in several cases. Glycopeptide analysis of JR-FL trimers revealed near complete sequon occupation and that filling the N197 glycan hole was well-tolerated. In contrast, sequon optimization and inserting/removing glycans at other positions frequently had global "ripple" effects on glycan maturation and sequon occupation throughout the gp120 outer domain and gp41. V2 MAb CH01 selectively bound to trimers with small high mannose glycans near the base of the V1 loop, thereby avoiding clashes. Knocking in a rare N49 glycan was found to perturb gp41 glycans, increasing FP NAb sensitivity—and sometimes improving expression. Finally, a biophysical analysis of VLPs revealed that i) ~25% of particles bear Env spikes, ii) spontaneous particle budding is high and only increases 4-fold upon Gag transfection, and iii) Env+ particles express ~30–40 spikes. Taken together, we identified 7 diverse trimers with a range of sensitivities to two targets to allow rigorous testing of immunofocusing vaccine concepts.

60 APPLIED LIFE SCIENCES↗

Postbuckling behavior of curved panels under combined compression and shear loads

A validated semiempirical design procedure and fatigue data were developed for curved, stiffened composite panels operating in the postbuckled regime under the action of combined compression and shear loading. A previously developed design methodology for composite panels under pure shear or pure compression loading was used as the starting point for the program. Initially, the well established interaction rules for metal panels were adopted to predict buckling under combined loading. Test data were then developed to verify these rules and suggest modifications where necessary. Postbuckling failure envelopes were developed by accounting for the failure modes possible under shear loading only, and under pure compression loading. Static failure predictions under combined loading were based on test verified interaction criteria. Fatigue tests were conducted under combined loading to determine strength degradation and the possible failure modes.

Deo, Ravi B.↗

Thermally anisotropic building envelope for thermal management: finite element model calibration using field evaluation data

The thermally anisotropic building envelope (TABE) is an active building envelope that redistributes thermal loads in response to weather conditions and building energy demand. Conductive layers throughout the TABE distribute low-grade heat among hydronic loops, altering heat flow direction and intensity. Finite element models of TABE roof and wall panels were developed and calibrated using field evaluation data. The calibration results showed that heat flux differences between the experimental data and finite element models averaged –0.42% and 3.57%, with a maximum mean square error of 1.78 and 3.96 for roof and wall panels, respectively. A reduction in heat flux from the environment to the building living space over the entire testing period (weeks in July/August) was found to be 85% for roof panels and 335% (load reversed) for wall panels. Finally, these results indicate TABE can effectively harness low-grade thermal energy sources to achieve high energy efficiency and promote demand-side management.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies

An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several HIV-1 envelope-derived germline-targeting immunogens have been designed to engage naive VRC01-class precursor B cells. However, they also present off-target epitopes that could hinder development of VRC01-class bNAbs. We characterize a panel of anti-idiotypic monoclonal antibodies (ai-mAbs) raised against inferred-germline (iGL) VRC01-class antibodies. By leveraging binding, structural, and B cell sorting data, we engineered a bispecific molecule derived from two aimAbs; one specific for VRC01-class heavy chains and one specific for VRC01-class light chains. The bispecific molecule preferentially activates iGL-VRC01 B cells in vitro and induces specific antibody responses in a murine adoptive transfer model with a diverse polyclonal B cell repertoire. This molecule represents an alternative non-envelope-derived germline-targeting immunogen that can selectively activate VRC01-class precursors in vivo.

59 BASIC BIOLOGICAL SCIENCES↗

Benefits Of Automated Construction And Energy Efficiency Measures In Modular Homes

This article builds on and adds to a Buildings XV publication that introduced the Transformative Efficiency and Automation in Modular Homes (TEAMH) project. The TEAMH project sought to develop a scalable solution for producing modular homes with 20-50% energy savings and similar cost relative to site-fabricated single-family home construction. A key aspect of the project was assessing the potential for labor cost reductions through automation-assisted construction using light gauge steel (LGS). To quantify the advantages of this approach, side-by-side comparisons were made between traditional wood-framed construction and automation-assisted LGS construction. This demonstration involved constructing one wood-framed wall and several LGS test walls, accompanied by a time-and-motion study. The results indicated that automation assistance could decrease construction time and associated labor costs by as much as 46%. High-performance envelope technologies for exterior insulation and air sealing were evaluated to compare modular homes with site-built homes that meet the International Energy Conservation Code (IECC). A key technology considered was vacuum insulation panels (VIPs) with fiberglass cores. Guarded hot box testing of multiple full-scale wall assemblies containing different combinations of exterior continuous insulation systems containing phenolic foam and VIPs. Testing on various full-scale wall assemblies revealed that, with LGS construction, cavity insulation had minimal impact on exterior wall performance. Omitting cavity insulation can reduce labor and material costs while streamlining manufacturing, as its installation is labor-intensive and not easily automated due to the need for precise placement around wiring and other internal components. Guarded hot box tests of multiple LGS test walls with foam and VIP-based exterior insulation systems achieved R-values of up to 31 hr-ft2-°F/Btu. Finally, building energy modeling of multiple modular home designs indicated that the upgraded envelope assemblies can yield heating energy savings of up to 50% and cooling energy savings of up to 30% compared to IECC 2018 standards.

Shrestha, Som [ORNL] (ORCID:0000000183993797)↗

Developing and Implementing New Waste Chemistry Controls for Hanford's Double-Shell Tanks - 20041

Waste chemistry controls for the Hanford double-shell tanks (DSTs) were established in the 1980's in response to tank failures caused by stress corrosion cracking (SCC) at the Savannah River Site (SRS). The controls were established based on a combination of SRS chemistry limits and corrosion testing results. Conditions in the Hanford DSTs have changed over time, with the temperature in the majority of the DSTs dropping below 50 deg. C. Testing indicated that the original chemistry control specification and SCC testing performed in 2010 did not protect against pitting corrosion mechanisms - what is believed to have caused the failure of tank 241-AY-102. New waste chemistry controls are necessary to protect the DSTs from both SCC and pitting corrosion. Savannah River National Laboratory (SRNL), with input from the Tank Integrity Expert Panel (TIEP) Corrosion Subgroup (CSG), performed a statistically based investigation of nitrate and halide ion induced pitting corrosion. The investigation was intended to develop a comprehensive waste chemistry envelope that minimizes the risk of both SCC and pitting caused by halide and nitrate ions. The waste chemistry envelope needed to be robust enough to address future waste retrieval and process changes which could significantly change the waste composition of the DSTs. The experimental design allowed the statistically significant ions and their effect on pitting corrosion to be determined. SRNL developed the 'pitting factor' which is an empirical relationship between the statistically significant inhibitive species (hydroxide, and nitrite), and pitting inducing species (nitrate, chloride, and fluoride). The coefficients are weighted factors that show the degree of influence the species have on the propensity for pitting. New waste chemistry control limits were recommended by SRNL, and concurred with by the TIEP CSG, that incorporated the pitting factor along with other limits. The controls developed to reduce the risk of pitting corrosion were evaluated to determine if they also protected against SCC. Hundreds of test results were reviewed and compared against the proposed limits. With the exception of one test result, instances where cracking was observed corresponded to chemistry that was outside of the proposed limits - indicating that the chemistry controls developed for pitting also adequately addressed SCC concerns. Existing tank composition estimates were evaluated against the new chemistry controls - three current tank chemistries are suspect, and may not meet the new chemistry control requirements. These included the interstitial liquid (liquid associated with solids) of DSTs 241-AN-102, 241-AN-106, 241-AN-107, and 241-AY-101. Measures are ongoing to evaluate the tanks with the suspect chemistry. These include varying combinations of: performing additional evaluations (history of use, modeling); DST specific laboratory testing; and, pursuing core samples of the DSTs. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials

The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals. The majority of viruses identified were clade B and C; with clades A, D, F and G and recombinants AC and BF detected at lower frequencies. We tested eight bnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10–1074 and 10E8v4) for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998–2010), the HVTN703/HPTN081 clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best against clade C viruses and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. Overall, the AMP placebo viruses represent a valuable resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs and highlight the need to update reference panels regularly. Our data also suggests that combining bnAbs in passive immunization trials would improve coverage of global viruses.

60 APPLIED LIFE SCIENCES↗

Reducing the cost of home energy upgrades in the US: An industry survey

Decarbonizing the US residential building stock requires a substantial acceleration in home energy upgrades. Numerous barriers exist to accelerating adoption of efficient and electric building technologies, but foremost among these is high upfront costs. This study uses an industry survey delivered to a sample of home energy professionals to examine promising cost reduction strategies across a range of project types, including HVAC, water heating, and envelope/insulation projects. The survey included quantitative and qualitative questions to collect evidence on the estimated cost reduction potential of these strategies and their likelihood of use in the construction industry. The 167 survey respondents included contractors, energy consultants, architects, manufacturers, and others with experience in delivering energy upgrades in single-family and multifamily buildings in the US. Results show that significant cost reductions are achievable by minimizing additional infrastructure costs (such as replacing electric panels), streamlining project planning/management, and deploying innovations that simplify installation. We find that for a typical deep retrofit project, including heat pumps for space and water heating in addition to envelope upgrades, the strategies could result in a total installed cost reduction of nearly 50%, dramatically improving the customer economics of such a project. This research makes a novel contribution to the literature on strategies to reduce the costs of residential retrofits. We discuss how our study's insights on the highest-value cost reduction strategies for home energy upgrades can further accelerate their uptake in the US housing stock.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

A modified VAPEPS method for predicting vibroacoustic response of unreinforced mass loaded honeycomb panels

VAPEPS (VibroAcoustic Payload Environment Prediction System) is a computer program used to predict the vibroacoustic response of a structure. An alternate VAPEPS modeling technique, the Modified NASA Lewis Method, is an improvement for modeling unreinforced mass loaded honeycomb panels. The Modified NASA Lewis Method prediction is compared to the standard ASMS VAPEPS prediction, and the acoustic test data for three spacecraft panels. An analytical method of computing variance is presented and used to compute 95 percent confidence levels. These levels are compared to the standard VAPEPS confidence levels and to the envelope of the test data. As a result of using the new methodology suggested in the paper, both the mean prediction and the 95 percent confidence level prediction agree well with the test data in both spectral shape and magnitude. Therefore, the Modified NASA Lewis Method prediction methodology may be used to define more realistic random vibration test levels.

Mcnelis, Mark E.↗

A modified VAPEPS method for predicting vibroacoustic response of unreinforced mass loaded honeycomb panels

VAPEPS (vibroAcoustic Payload Environment Prediction System) is a computer program used to predict the vibroacoustic response of a structure. An alternate VAPEPS modeling technique, the Modified NASA Lewis Method, is an improvement for modeling unreinforced mass loaded honeycomb panels. The Modified NASA Lewis Method prediction is compared to the standard ASMS VAPEPS prediction, and the acoustic test data for three spacecraft panels. An analytical method of computing variance is presented and used to compute 95 percent confidence levels. These levels are compared to the standard VAPEPS confidence levels and to the envelope of the test data. As a result of using the new methodology suggested in the paper, both the mean prediction and the 95 percent confidence level prediction agree well with the test data in both spectral shape and magnitude. Therefore, the Modified NASA Lewis Method prediction methodology may be used to define more realistic random vibration test levels.

Mcnelis, Mark E.↗

Developing a Composite Vacuum Insulated Panel (VIP) Insulation/Vinyl Siding Composite Technology for Retrofitting Residential Walls

This paper reports on a project that has attempted to seize on an opportunity to take a giant leap forward in commercializing a technology that would address a key opportunity to achieve energy savings in the existing residential housing stock. It is typically very difficult to increase the R-value of the walls in existing residential housing as doing so from the inside is disruptive and there have not been good solutions to increase thermal envelope performance from the exterior through adding continuous insulation due to the additional work required to fit existing architectural features to the new wall thickness and to reclad the façade. A high thermal resistivity or R-value per inch product that can be used in these applications offers an excellent solution.This paper summarizes a three-year research project to a produce vacuum insulated panel (VIP)/vinyl siding that would have sufficient R-value to meet the continuous insulation requirements of the 2018 International Energy Conservation Code (IECC, 2018) in all climate zones and has a much thinner profile that will facilitate its application to existing residential homes without the need for expensive retrimming of the architectural details. The paper will supply information on the development of the technology, its thermal modelling, testing, voice of user sessions to solicit input from architects, designers, manufacturers, contractors, and installers, and a techno-economic analysis to gauge its competitiveness with existing product options.

Desjarlais, Andre Omer↗

Developing a Composite Vacuum Insulated Panel (VIP) Insulation/Vinyl Siding Composite Technology for Retrofitting Residential Walls

This paper reports on a project that has attempted to seize on an opportunity to take a giant leap forward in commercializing a technology that would address a key opportunity to achieve energy savings in the existing residential housing stock. It is typically very difficult to increase the R-value of the walls in existing residential housing as doing so from the inside is disruptive and there have not been good solutions to increase thermal envelope performance from the exterior through adding continuous insulation due to the additional work required to fit existing architectural features to the new wall thickness and to reclad the facade. A high thermal resistivity or R-value per inch product that can be used in these applications offers an excellent solution. This paper summarizes a three-year research project to a produce vacuum insulated panel (VIP)/vinyl siding that would have sufficient R-value to meet the continuous insulation requirements of the 2018 International Energy Conservation Code (IECC, 2018) in all climate zones and has a much thinner profile that will facilitate its application to existing residential homes without the need for expensive retrimming of the architectural details. The paper will supply information on the development of the technology, its thermal modelling, testing, voice of user sessions to solicit input from architects, designers, manufacturers, contractors, and installers, and a techno-economic analysis to gauge its competitiveness with existing product options.

Desjarlais, Andre↗

Flight Test Measurements From The Tu- 144LL Structure/Cabin Noise Experiment

During the period September 1997 to February 1998, the Tupolev 144 Supersonic Flyine Laboratory was used to obtain data for the purpose of enlarging the data base used by models for the prediction of cabin noise in supersonic passenger airplanes. Measured were: turbulent boundary layer pressure fluctuations on the fuselage in seven instrumented window blanks distributed over the length of the fuselage; structural response with accelerometers on skin panels close to those window blanks-, interior noise with microphones at the same fuselage bay stations as those window blanks. Flight test points were chosen to cover much of the TU- 144's flight envelope, as well as to obtain as large a unit Reynolds number range as possible at various Mach numbers: takeoff, landing, six subsonic cruise conditions, and eleven supersonic conditions up to Mach 2. Engine runups and reverberation times were measured with a stationary aircraft. The data in the form of time histories of the acoustic signals, together with auxiliary data and basic MATLAB processing modules, are available on CD-R disks.

Rizzi, Stephen A.↗

Failure Maps for Rectangular 17-4PH Stainless Steel Sandwiched Foam Panels

A new and innovative concept is proposed for designing lightweight fan blades for aircraft engines using commercially available 17-4PH precipitation hardened stainless steel. Rotating fan blades in aircraft engines experience a complex loading state consisting of combinations of centrifugal, distributed pressure and torsional loads. Theoretical failure plastic collapse maps, showing plots of the foam relative density versus face sheet thickness, t, normalized by the fan blade span length, L, have been generated for rectangular 17-4PH sandwiched foam panels under these three loading modes assuming three failure plastic collapse modes. These maps show that the 17-4PH sandwiched foam panels can fail by either the yielding of the face sheets, yielding of the foam core or wrinkling of the face sheets depending on foam relative density, the magnitude of t/L and the loading mode. The design envelop of a generic fan blade is superimposed on the maps to provide valuable insights on the probable failure modes in a sandwiched foam fan blade.

Raj, S. V.↗

Experimental apparatus and methodology to test and quantify thermal performance of micro and macro-encapsulated phase change materials in building envelope applications

Thermal energy storage (TES) is used as a viable technology to shift peak electricity demand caused by the space cooling requirements in buildings. Passive TES is implemented in building envelope via micro and macroencapsulation methods. This study describes the use of a state-of-the-art laboratory to test different PCM inclusions in simplified building walls. A microencapsulated PCM and two macroencapsulated PCMs are tested in a controlled environment to gather data for validation purposes of PCM modelling algorithms in building energy modelling programs. Data indicates that the chamber environment and the heating and cooling system can conduct full-cycle tests of wall panels with PCM inclusions. This study also generates data from parallel tests on 4 wall panels which can be used in building energy modelling programs to validate the PCM modelling algorithms. The cyclic tests also capture the thermal effects of PCMs and complex PCM behaviors like sub-cooling in PCM hydrate-salts.

25 ENERGY STORAGE↗