Synergistic Dual-Cure Reactions for the Fabrication of Thermosets by Chemical Heating.

Large composite structures, such as those used in wind energy applications, rely on the bulk polymerization of thermosets on an impressively large scale. To accomplish this, traditional thermoset polymerizations require both elevated temperatures (>100 °C) and extended cure durations (>5 h) for complete conversion, necessitating the use of oversize ovens or heated molds. In turn, these requirements lead to energy-intensive polymerizations, incurring high manufacturing costs and process emissions.

Elastomeric vitrimers from designer polyhydroxyalkanoates with recyclability and biodegradability.

Cross-linked elastomers are stretchable materials that typically are not recyclable or biodegradable. Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are soft and ductile, making these bio-based polymers good candidates for biodegradable elastomers. Elasticity is commonly imparted by a cross-linked network structure, and covalent adaptable networks have emerged as a solution to prepare recyclable thermosets via triggered rearrangement of dynamic covalent bonds.

Unbiased approach to identify and assess efficacy of human SARS-CoV-2 neutralizing antibodies.

Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants.

A Novel Affinity Engineered Anti-CD47 Antibody With Improved Therapeutic Index That Preserves Erythrocytes and Normal Immune Cells.

Therapeutic blockade of the CD47/SIRPα axis by small molecules or monoclonal antibodies (mAbs) is a proven strategy to enhance macrophages-mediated anti-tumor activity. However, this strategy has been hampered by elevated on-target toxicities and rapid clearance due to the extensive CD47 expression on normal cells ("antigen sink") such as red blood cells (RBCs). To address these hurdles, we report on the development of STI-6643, an affinity-engineered fully human anti-CD47 IgG antibody with negligible binding to normal cells.

SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement.

Monoclonal antibodies (mAbs) are emerging as safe and effective therapeutics against SARS-CoV-2. However, variant strains of SARS-CoV-2 have evolved, with early studies showing that some mAbs may not sustain their efficacy in the face of escape mutants. Also, from the onset of the COVID-19 pandemic, concern has been raised about the potential for Fcγ receptor-mediated antibody-dependent enhancement (ADE) of infection.

The broad-spectrum antiviral compound ST-669 restricts chlamydial inclusion development and bacterial growth and localizes to host cell lipid droplets within treated cells.

Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells.

SAR analysis of a series of acylthiourea derivatives possessing broad-spectrum antiviral activity.

A series of acylthiourea derivatives were designed, synthesized, and evaluated for broad-spectrum antiviral activity with selected viruses from Poxviridae (vaccinia virus) and two different genera of the family Bunyaviridae (Rift Valley fever and La Crosse viruses). A compound selected from a library screen, compound 1, displayed submicromolar antiviral activity against both vaccinia virus (EC(50)=0.25 μM) and La Crosse virus (EC(50)=0.

Evaluation of Lassa antiviral compound ST-193 in a guinea pig model.

Lassa virus (LASV), a member of the Arenaviridae family, causes a viral hemorrhagic fever endemic to West Africa, where as many as 300,000 infections occur per year. Presently, there are no FDA-approved LASV-specific vaccines or antiviral agents, although the antiviral drug ribavirin has shown some efficacy. A recently identified small-molecule inhibitor of arenavirus entry, ST-193, exhibits submicromolar antiviral activity in vitro.

Alternatively initiated gene 50/RTA transcripts expressed during murine and human gammaherpesvirus reactivation from latency.

In the process of characterizing the requirements for expression of the essential immediate-early transcriptional activator (RTA) encoded by gene 50 of murine gammaherpesvirus 68 (MHV68), a recombinant virus was generated in which the known gene 50 promoter was deleted (G50pKO). Surprisingly, the G50pKO mutant retained the ability to replicate in permissive murine fibroblasts, albeit with slower kinetics than wild-type MHV68. 5'-rapid amplification of cDNA ends analyses of RNA prepared from G50pKO-infected fibroblasts revealed a novel upstream transcription initiation site, which was also utilized during wild-type MHV68 infection of permissive cells.

ORF73-null murine gammaherpesvirus 68 reveals roles for mLANA and p53 in virus replication.

Gammaherpesviruses establish lifelong, latent infections in host lymphocytes, during which a limited subset of viral gene products facilitates maintenance of the viral episome. Among the gamma-2-herpesvirus (rhadinovirus) subfamily, this includes expression of the conserved ORF73-encoded LANA proteins. We previously demonstrated by loss-of-function mutagenesis that the murine gammaherpesvirus 68 (MHV68) ORF73 gene product, mLANA, is required for the establishment of latency following intranasal inoculation of mice (N.

Identification of an Rta responsive promoter involved in driving gammaHV68 v-cyclin expression during virus replication.

Among the distinguishing characteristics of members of the gamma-2 herpesvirus family is the expression of a mammalian D-type cyclin homolog, termed v-cyclin. Murine gammaherpesvirus 68 (gammaHV68) is a gamma2-herpesvirus that can infect inbred and outbred strains of mice, providing a genetic system for the study of gammaherpesvirus pathogenesis. Disruption of the v-cyclin gene of gammaHV68 results in a virus that establishes latency in infected mice to wild-type levels, but is severely attenuated for virus reactivation [van Dyk, L.

Identification of spliced gammaherpesvirus 68 LANA and v-cyclin transcripts and analysis of their expression in vivo during latent infection.

Regulation of orf73 (LANA) gene expression is critical to the establishment and maintenance of latency following infection by members of the gamma-2 herpesvirus (rhadinovirus) family. Previous studies of murine gammaherpesvirus 68 (gammaHV68) have demonstrated that loss of LANA function results in a complete failure to establish virus latency in the spleens of laboratory mice. Here we report the characterization of alternatively spliced LANA and v-cyclin (orf72) transcripts encoded by gammaHV68.

Role of B-cell proliferation in the establishment of gammaherpesvirus latency.

Murine gammaherpesvirus 68 (gammaHV68) provides a tractable small animal model with which to study the mechanisms involved in the establishment and maintenance of latency by gammaherpesviruses. Similar to the human gammaherpesvirus Epstein-Barr virus (EBV), gammaHV68 establishes and maintains latency in the memory B-cell compartment following intranasal infection. Here we have sought to determine whether, like EBV infection, gammaHV68 infection in vivo is associated with B-cell proliferation during the establishment of chronic infection.