Unique symmetric (66,26,10) design admitting an automorphism of order 55

We have proved that the first known symmetric (66,26,10) design, constructed by Tran van Trung, is up to isomorphism the only symmetric (66,26,10) design admitting an automorphism of order 55. A full automorphism group of that design is isomorphic to Frob_{55}times D_{10}

New examples of self-dual near-extremal ternary codes of length 48 derived from 2-(47,23,11) designs

In a recent paper [M. Araya, M. Harada, Some restrictions on the weight enumerators of near-extremal ternary self-dual codes and quaternary Hermitian self-dual codes, Des. Codes Cryptogr., 91 (2023), 1813--1843], Araya and Harada gave examples of self-dual near-extremal ternary codes of length 48 for $145$ distinct values of the number $A_{12}$ of codewords of minimum weight 12, and raised the question about the existence of codes for other values of $A_{12}$. In this note, we use symmetric 2-$(47,23,11)$ designs with an automorphism group of order 6 to construct self-dual near-extremal ternary codes of length 48 for $150$ new values of $A_{12}$.Comment: 7 page

Symmetric 2−-(36,15,6) designs with an automorphism of order two

The parameters 2-(36,15,6) are the smallest parameters of symmetric designs for which a complete classification up to isomorphism is yet unknown. Bouyukliev, Fack and Winne classified all 2-$(36,15,6)$ designs that admit an automorphism of odd prime order, and gave a partial classification of such designs that admit an automorphism of order 2. In this paper, we give the classification of all symmetric 2-$(36,15,6)$ designs that admit an automorphism of order two. It is shown that there are exactly $1 547 701$ nonisomorphic such designs, $135 779$ of which are self-dual designs. The ternary linear codes spanned by the incidence matrices of these designs are computed. Among these codes, there are near-extremal self-dual codes with previously unknown weight distributions.Comment: 20 page

On symmetric 2-(70,24,8) designs with an automorphism of order 6

In this paper we analyze possible actions of an automorphism of order six on a $2$-$(70, 24, 8)$ design, and give a complete classification for the action of the cyclic automorphism group of order six $G= \langle \rho \rangle \cong Z_6 \cong Z_2 \times Z_3$ where $\rho^3$ fixes exactly $14$ points (blocks) and $\rho^2$ fixes $4$ points (blocks). Up to isomorphism, there are $3718$ such designs. This result significantly increases the number of known $2$-$(70,24,8)$ designs.Comment: 10 page

The involvement of CD14 in the activation of human monocytes by peptidoglycan monomers.

BACKGROUND: Cell-wall components of Gram-positive and Gram-negative bacteria induce the production of cytokines in human peripheral blood mononuclear cells. These cytokines are the main mediators of local or systemic inflammatory reaction that can contribute to the development of innate immunity. AIMS: This study was performed to analyze the involvement of CD14 molecule in the activation of human monocytes by peptidoglycan monomer (PGM) obtained by biosynthesis from culture fluid of penicillin-treated Brevibacterium divaricatum NRLL-2311. METHODS: Cytokine release of interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha from human monocytes via soluble CD14 (sCD14) or membrane-associated (mCD14) receptor using anti-CD14 monoclonal antibody (MEM-18) or lipid A structure (compound 406) was measured in bioassays. RESULTS: The results demonstrated that PGM in the presence of human serum might induce the monokine release in a dose-dependent manner. The addition of sCD14 at physiologic concentrations enhanced the PGM-induced monokine release, while the monokine inducing capacity of PGM in the presence of sCD14 was inhibited by MEM-18. Effects of PGM were also blocked by glycolipid, compound 406, suggesting the involvement of binding structures similar to those for lipopolysaccharide. CONCLUSION: Activation of human monocytes by PGM involves both forms of CD14 molecule, sCD14 and mCD14

Targeted protein degradation via intramolecular bivalent glues

Targeted protein degradation is a pharmacological modality that is based on the induced proximity of an E3 ubiquitin ligase and a target protein to promote target ubiquitination and proteasomal degradation. This has been achieved either via proteolysis-targeting chimeras (PROTACs)—bifunctional compounds composed of two separate moieties that individually bind the target and E3 ligase, or via molecular glues that monovalently bind either the ligase or the target 1–4. Here, using orthogonal genetic screening, biophysical characterization and structural reconstitution, we investigate the mechanism of action of bifunctional degraders of BRD2 and BRD4, termed intramolecular bivalent glues (IBGs), and find that instead of connecting target and ligase in trans as PROTACs do, they simultaneously engage and connect two adjacent domains of the target protein in cis. This conformational change ‘glues’ BRD4 to the E3 ligases DCAF11 or DCAF16, leveraging intrinsic target–ligase affinities that do not translate to BRD4 degradation in the absence of compound. Structural insights into the ternary BRD4–IBG1–DCAF16 complex guided the rational design of improved degraders of low picomolar potency. We thus introduce a new modality in targeted protein degradation, which works by bridging protein domains in cis to enhance surface complementarity with E3 ligases for productive ubiquitination and degradation.</p

Targeted protein degradation via intramolecular bivalent glues

Targeted protein degradation is a pharmacological modality that is based on the induced proximity of an E3 ubiquitin ligase and a target protein to promote target ubiquitination and proteasomal degradation. This has been achieved either via proteolysis-targeting chimeras (PROTACs)—bifunctional compounds composed of two separate moieties that individually bind the target and E3 ligase, or via molecular glues that monovalently bind either the ligase or the target 1–4. Here, using orthogonal genetic screening, biophysical characterization and structural reconstitution, we investigate the mechanism of action of bifunctional degraders of BRD2 and BRD4, termed intramolecular bivalent glues (IBGs), and find that instead of connecting target and ligase in trans as PROTACs do, they simultaneously engage and connect two adjacent domains of the target protein in cis. This conformational change ‘glues’ BRD4 to the E3 ligases DCAF11 or DCAF16, leveraging intrinsic target–ligase affinities that do not translate to BRD4 degradation in the absence of compound. Structural insights into the ternary BRD4–IBG1–DCAF16 complex guided the rational design of improved degraders of low picomolar potency. We thus introduce a new modality in targeted protein degradation, which works by bridging protein domains in cis to enhance surface complementarity with E3 ligases for productive ubiquitination and degradation.</p