Age- and Strain-Related Differences in Bone Microstructure and Body Composition During Development in Inbred Male Mouse Strains

We explored age- and strain-related differences in bone microstructure and body composition in male C57BL/6J, DBA/2JRj and C3H/J mice. Bone microstructure of the femur, tibia and L4 was assessed by μCT at the age of 8, 16 and 24 weeks. The weight of several muscles and fat depots were measured at the same time points. At all timepoints, C3H/J mice had the thickest cortices followed by DBA/2JRj and C57BL/6J mice. Nevertheless, C57BL/6J mice had higher Tb.BV/TV and Tb.N, and lower Tb.Sp than DBA/2JRj and C3H/J mice at least at 24 weeks of age. Skeletal development patterns differed among strains. C57BL/6J and DBA/2JRj mice, but not C3H/J mice, experienced significant increases in the sum of the masses of 6 individual muscles by 24 weeks of age. In C57BL/6J and DBA/2JRj mice, the mass of selected fat depots reached highest values at 24 weeks, whist, in C3H/J mice, the highest values of fat depots masses were achieved at 16 weeks. Early strain differences in muscle and fat masses were largely diminished by 24 weeks of age. C3H/J and C57BL/6J mice displayed the most favorable cortical and trabecular bone parameters, respectively. Strain differences in body composition were less overt than strain specificity in bone microstructure, however, they possibly influenced aspects of skeletal development.

Cooperation between Strain-Specific and Broadly Neutralizing Responses Limited Viral Escape and Prolonged the Exposure of the Broadly Neutralizing Epitope

ABSTRACT V3-glycan-targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate the development of these antibodies can provide insights for immunogen design. We used a deep-sequencing approach, together with neutralization phenotyping, to investigate the rate and complexity of escape from V3-glycan-directed bNAbs compared to overlapping early strain-specific neutralizing antibody (ssNAb) responses to the V3/C3 region in donor CAP177. Escape from the ssNAb response occurred rapidly via an N334-to-N332 glycan switch, which took just 7.5 weeks to reach >50% frequency. In contrast, escape from the bNAbs was mediated via multiple pathways and took longer, with escape first occurring through an increase in V1 loop length, which took 46 weeks to reach 50% frequency, followed by an N332-to-N334 reversion, which took 66 weeks. Importantly, bNAb escape was incomplete, with contemporaneous neutralization observed up to 3 years postinfection. Both the ssNAb response and the bNAb response were modulated by the presence/absence of the N332 glycan, indicating an overlap between the two epitopes. Thus, selective pressure by ssNAbs to maintain the N332 glycan may have constrained the bNAb escape pathway. This slower and incomplete viral escape resulted in prolonged exposure of the bNAb epitope, which may in turn have aided the maturation of the bNAb lineage. IMPORTANCE The development of an HIV-1 vaccine is of paramount importance, and broadly neutralizing antibodies are likely to be a key component of a protective vaccine. The V3-glycan-targeting bNAb responses are among the most promising vaccine targets, as they are commonly elicited during infection. Understanding the interplay between viral evolution and the development of these antibodies provides insights that may guide immunogen design. Our work contrasted the dynamics of the early strain-specific antibodies and the later broadly neutralizing responses to a common Env target (V3C3), showing slower and more complex escape from bNAbs. Constrained bNAb escape, together with evidence of contemporaneous autologous virus neutralization, supports the proposal that prolonged exposure of the bNAb epitope enabled the maturation of the bNAb lineage.

STRENGTHENING OF RC BEAMS SUBJECTED TO CYCLIC LOAD USING ULTRA HIGH-PERFORMANCE STRAIN HARDENING CEMENTITIOUS COMPOSITES

Ultra High-Performance Strain Hardening Cementitious Composites (UHP-SHCC) is a composite material comprising a cement-based matrix and short fibers with outstanding mechanical and protective performance having advantages as large strain capacity as well as high compressive and tensile strength, which is useful for strengthening or repair concrete members. In the present study, five specimens were tested experimentally, one as a control and four strengthened with 40 mm thickness of UHP-SHCC layer attached from tension side with variable reinforcement ratios embedded in strengthening layer. Cyclic loading was applied to all specimens. The test results showed the importance of reinforcing the UHP-SHCC to eliminate the observed early strain localization and to gain adequate dissipated energy under cyclic loading. It is also proved that using an unreinforced UHP-SHCC layer for strengthening may lead to a brittle failure especially in case of cyclic load.

Local Strain Hardening and Non-Uniformity of Plastic Strain of Tinplate

During evaluation of the mechanical properties of tinplate for packaging industry by uniaxial tensile test, a non-uniform plastic strain occurs very often. This phenomenon results from the fact, that the plastic deformation is not uniformly developed throughout the measured section. There is a localization of deformation in one or more places resulting in local changes of the tinplate ́s mechanical properties. This paper deals with local strain hardening and non-uniformity of plastic strain of the tinplate temper TH415CA during uniaxial tensile test. Based on micro hardness measurements in the following locally deformed areas, local changes of mechanical properties of the tinplate were determined. The reasons of early strain localization were assumed by microstructural analysis. In the present work are considering partial aspects of the problem focusing on the properties of the local strain hardening and their consequences for stability of uniform plastic strain.