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Gillespie, Kevin

Publications and source records attributed to Gillespie, Kevin.

Updimensioning strategy derived from synthetic equiaxed grain structures for approximating 3D grain size distributions from 2D visualizations with 1D parameters

We generated synthetic equiaxed grain structures using computer graphics software to explore the relationship between various grain size determination methods and true three-dimensional (3D) grain diameters. Mirroring grain measurement techniques, the synthetic 3D grain structures are imaged as 2D micrographs which are measured to yield 1D grain size parameters. Synthetic grain structures provide data at a mass scale and permit exploration of both polished and fractured surface micrographs, revealing one-to-one correspondence between exposed 2D grain cross-sections and individual 3D grains. Analysis of this correspondence yielded a procedure to approximate 3D equiaxed grain size and volume distributions based on the mode of the 2D fractograph grain size distribution. The 3D approximation procedure is shown to be less susceptible to different imaging conditions that affect small, undiscernible grains compared to the standard planimetric and linear intercept methods, which by design also tend to underestimate the 3D grain diameter. The procedure requires larger sample sizes to lower variance and a deeper analysis which could become more practical with machine learning (ML) models for grain boundary segmentation, which synthetic grain structures can help train. This work lays the foundation for analyzing other grain distributions such as columnar and composite grains in similar depth.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Prevention efficacy of the broadly neutralizing antibody VRC01 depends on HIV-1 envelope sequence features

In the Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081), prevention efficacy (PE) of the monoclonal broadly neutralizing antibody (bnAb) VRC01 (vs. placebo) against HIV-1 acquisition diagnosis varied according to the HIV-1 Envelope (Env) neutralization sensitivity to VRC01, as measured by 80% inhibitory concentration (IC80). Here, we performed a genotypic sieve analysis, a complementary approach to gaining insight into correlates of protection that assesses how PE varies with HIV-1 sequence features. We analyzed HIV-1 Env amino acid (AA) sequences from the earliest available HIV-1 RNA-positive plasma samples from AMP participants diagnosed with HIV-1 and identified Env sequence features that associated with PE. The strongest Env AA sequence correlate in both trials was VRC01 epitope distance that quantifies the divergence of the VRC01 epitope in an acquired HIV-1 isolate from the VRC01 epitope of reference HIV-1 strains that were most sensitive to VRC01-mediated neutralization. In HVTN 704/HPTN 085, the Env sequence-based predicted probability that VRC01 IC80 against the acquired isolate exceeded 1 µg/mL also significantly associated with PE. In HVTN 703/HPTN 081, a physicochemical-weighted Hamming distance across 50 VRC01 binding-associated Env AA positions of the acquired isolate from the most VRC01-sensitive HIV-1 strain significantly associated with PE. These results suggest that incorporating mutation scoring by BLOSUM62 and weighting by the strength of interactions at AA positions in the epitope:VRC01 interface can optimize performance of an Env sequence-based biomarker of VRC01 prevention efficacy. Future work could determine whether these results extend to other bnAbs and bnAb combinations.

60 APPLIED LIFE SCIENCES↗