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Cross-Section Measurements of Lambda(1405) Photoproduction from CLAS G12 Data

The nature of the Λ(1405) state remains an unsolved puzzle despite being predicted in 1959 and experimentally confirmed soon thereafter in 1961. It has an unusual line shape that deviates from a Breit-Wigner form, typically associated with resonances. Theoretical explanations of this first, excited Λ hyperon range from it being a three-quark state (uds) to being a dynamically generated, quasi-bound KN¯ molecule to consisting of a two-pole (two resonances) structure. None of these descriptions of Λ(1405) are universally accepted. Thus, there is a need for additional data on this notoriously cryptic state to help guide theoretical models. Measurements such as cross sections can assist to elucidate our understanding of resonances and how they’re produced. In this analysis, data from the CLAS g12 experiment were studied and differential cross-section measurements for Λ(1405) photoproduction were extracted. The results contained within this work are in relatively good agreement with prior photoproduction measurements (CLAS g11). Moreover, the energy range over which the existing measurements extend is expanded to higher values with these new results. These higher energy cross-section measurements should prove to be beneficial for subsequent analyses of Λ(1405).

Reed, Trevor↗

Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils

The self-assembly of the Nucleocapsid protein (NCAP) of SARS-CoV-2 is crucial for its function. Computational analysis of the amino acid sequence of NCAP reveals low-complexity domains (LCDs) akin to LCDs in other proteins known to self-assemble as phase separation droplets and amyloid fibrils. Previous reports have described NCAP’s propensity to phase-separate. Here we show that the central LCD of NCAP is capable of both, phase separation and amyloid formation. Within this central LCD we identified three adhesive segments and determined the atomic structure of the fibrils formed by each. Those structures guided the design of G12, a peptide that interferes with the self-assembly of NCAP and demonstrates antiviral activity in SARS-CoV-2 infected cells. Our work, therefore, demonstrates the amyloid form of the central LCD of NCAP and suggests that amyloidogenic segments of NCAP could be targeted for drug development.

60 APPLIED LIFE SCIENCES↗

Hydrophobic interactions dominate the recognition of a KRAS G12V neoantigen

Specificity remains a major challenge to current therapeutic strategies for cancer. Mutation associated neoantigens (MANAs) are products of genetic alterations, making them highly specific therapeutic targets. MANAs are HLA-presented (pHLA) peptides derived from intracellular mutant proteins that are otherwise inaccessible to antibody-based therapeutics. Here, we describe the cryo-EM structure of an antibody-MANA pHLA complex. Specifically, we determine a TCR mimic (TCRm) antibody bound to its MANA target, the KRAS G12V peptide presented by HLA-A*03:01. Hydrophobic residues appear to account for the specificity of the mutant G12V residue. We also determine the structure of the wild-type G12 peptide bound to HLA-A*03:01, using X-ray crystallography. Based on these structures, we perform screens to validate the key residues required for peptide specificity. These experiments led us to a model for discrimination between the mutant and the wild-type peptides presented on HLA-A*03:01 based exclusively on hydrophobic interactions.

36 MATERIALS SCIENCE↗

Photoproduction of Lambda* Resonances using the CLAS Detector

This thesis presents the study of the reaction yp -> K^+Lambda* using the photo production data from the CLAS-g12 experiment performed in Hall B of Jefferson Laboratory. The decay of Lambda* resonances, Lambda(1520), Lambda(1670), and Lambda(1690), into two exclusive channels, Sigma+pi?and Sigma-pi+, is studied from the detected K+,pi+, and pi?particles. This work aims at understanding photoproduction mechanism to excited state baryons, and to facilitate phenomenological model predictions using precision experimental measurements. A good agreement is established for the Lambda(1520) differential cross sections with the previous CLAS measurements. The differential cross sections as a function of CM angle are extended to higher photon energies. Newly added are the differential cross sections as a function of invariant 4-momentum transfer, which is the natural variable to use for a theoretical model based on a Regge-exchange reaction mechanism. No new N* resonances decaying into the K+Lambda(1520) final state are found. The higher mass resonances, Lambda(1670)1/2- and Lambda(1690)3/2-, are studied for the first time using photoproduction. This work provides a model dependent preliminary cross sections for these excited states.

Shrestha, Utsav↗