Consequence Management Assessment Method Synthesis for Combatant Commands

One of the most important roles that the US fulfills in the global war on terror and their integration with Partner Nations (PNs) is minimizing the threats and effects  of weapons of mass destruction (WMD) as well as Chemical, Biological, Radiological, Nuclear and Explosive (CBRNE) attacks by enemy nations, rogue elements, or terrorist groups around the world. The Defense Threat Reduction Agency (DTRA) currently implements an assessment framework for determining a PN’s state of CBRNE readiness, but it is unable to conceptualize that assessment at a regional or Combatant Command (CCMD) level. This research uses the Systems Decision Process (SDP) to create an assessment metric that is capable of synchronizing PN CBRNE readiness across a CCMD into a single assessment. This research is focused on developing an effective and flexible Microsoft Access database, which evaluates all global PNs across a wide array of metrics and then synthesizes them through multi-purpose objectives in order to develop an encompassing assessment framework at the CCMD level

Probing the Large Faraday Rotation Measure Environment of Compact Active Galactic Nuclei

Knowing how the ambient medium in the vicinity of active galactic nuclei (AGNs) is shaped is crucial to understanding generally the evolution of such cosmic giants as well as AGN jet formation and launching. Thanks to the new broadband capability now available at the Jansky Very Large Array (JVLA), we can study changes in polarization properties, fractional polarization, and polarization angles, together with the total intensity spectra of a sample of 14 AGNs, within a frequency range from 1 to 12 GHz. Depolarization modeling has been performed by means of so-called "qu-fitting" to the polarized data, and a synchrotron self absorption model has been used for fitting to the total intensity data. We found complex behavior both in the polarization spectra and in the total intensity spectra, and several Faraday components with a large rotation measure (RM) and several synchrotron components were needed to represent these spectra. Here, results for three targets are shown. This new method of analyzing broadband polarization data through qu-fitting successfully maps the complex surroundings of unresolved objects

Classicalization and Unitarity

We point out that the scenario for UV completion by "classicalization", proposed recently is in fact Wilsonian in the classical Wilsonian sense. It corresponds to the situation when a field theory has a nontrivial UV fixed point governed by a higher dimensional operator. Provided the kinetic term is a relevant operator around this point the theory will flow in the IR to the free scalar theory. Physically, "classicalization", if it can be realized, would correspond to a situation when the fluctuations of the field operator in the UV are smaller than in the IR. As a result there exists a clear tension between the "classicalization" scenario and constraints imposed by unitarity on a quantum field theory, making the existence of classicalizing unitary theories questionable.Comment: Some clarifications and refs added. Accepted as a JHEP publication; 12 page

Volume 42, Number 4, December 2022 OLAC Newsletter

Digitized December 2022 issue of the OLAC Newsletter

Volume 43, Number 3, September 2023 OLAC Newsletter

Digitized September 2023 issue of the OLAC Newsletter

A proofreading mutation with an allosteric effect allows a cluster of SARS-CoV-2 viruses to rapidly evolve

The RNA-dependent RNA polymerase of the severe acute respiratory syndrome coronavirus 2 virus is error prone, with errors being corrected by the exonuclease (NSP14) proofreading mechanism. However, the mutagenesis and subsequent evolutionary trajectory of the virus is mediated by the delicate interplay of replicase fidelity and environmental pressures. Here, we have shown that a single, distal mutation (F60S) in NSP14 can have a profound impact upon proofreading with an increased accumulation of mutations and elevated evolutionary rate being observed. Understanding the implications of these changes is crucial, as these underlying mutational processes may have important implications for understanding the population-wide evolution of the virus. This study underscores the urgent need for continued research into the replicative mechanisms of this virus to combat its continued impact on global health, through the re-emergence of immuno-evasive variants

Volume 43, Number 1, March 2023 OLAC Newsletter

Digitized March 2023 issue of the OLAC Newsletter

Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease

Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4+ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4+ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4+ T cells specific for these ligands in all HLA-DP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4+ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD

CD4\u3csup\u3e+\u3c/sup\u3e T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope

Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3–restricted manner. Using ELISPOT analysis, a greater number of IFN-γ– and IL-2–secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS