The Stone-Campbell Movement: A Global History--Reviews and Comments

From the Stone-Campbell Journal website: Editors D. Newell Williams, Douglas A. Foster, and Paul M. Blowers offer their second substantial contribution to Stone-Campbell historiography with The Stone-Campbell Movement: A Global History (Chalice, 2013), an unprecedented global survey. (1) A core of thirteen scholars collaboratively wrote this unique narrative that highlights groups of people (women, African Americans, global Christians, and others) often neglected in traditional histories. In this review essay, three Stone-Campbell Movement historians each review roughly one-third of the volume

The Otterbein Miscellany - June 1984

https://digitalcommons.otterbein.edu/miscellany/1007/thumbnail.jp

The Otterbein Miscellany - December 1980

https://digitalcommons.otterbein.edu/miscellany/1014/thumbnail.jp

Integration of kinase and calcium signaling at the level of chromatin underlies inducible gene activation in T cells

TCR signaling pathways cooperate to activate the inducible transcription factors NF-κB, NFAT, and AP-1. In this study, using the calcium ionophore ionomycin and/or PMA on Jurkat T cells, we show that the gene expression program associated with activation of TCR signaling is closely related to specific chromatin landscapes. We find that calcium and kinase signaling cooperate to induce chromatin remodeling at ∼2100 chromatin regions, which demonstrate enriched binding motifs for inducible factors and correlate with target gene expression. We found that these regions typically function as inducible enhancers. Many of these elements contain composite NFAT/AP-1 sites, which typically support cooperative binding, thus further reinforcing the need for cooperation between calcium and kinase signaling in the activation of genes in T cells. In contrast, treatment with PMA or ionomycin alone induces chromatin remodeling at far fewer regions (∼600 and ∼350, respectively), which mostly represent a subset of those induced by costimulation. This suggests that the integration of TCR signaling largely occurs at the level of chromatin, which we propose plays a crucial role in regulating T cell activation

Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design

Requirements Definition for ORNL Trusted Corridors Project

The ORNL Trusted Corridors Project has several other names: SensorNet Transportation Pilot; Identification and Monitoring of Radiation (in commerce) Shipments (IMR(ic)S); and Southeastern Transportation Corridor Pilot (SETCP). The project involves acquisition and analysis of transportation data at two mobile and three fixed inspection stations in five states (Kentucky, Mississippi, South Carolina, Tennessee, and Washington DC). Collaborators include the State Police organizations that are responsible for highway safety, law enforcement, and incident response. The three states with fixed weigh-station deployments (KY, SC, TN) are interested in coordination of this effort for highway safety, law enforcement, and sorting/targeting/interdiction of potentially non-compliant vehicles/persons/cargo. The Domestic Nuclear Detection Office (DNDO) in the U.S. Department of Homeland Security (DHS) is interested in these deployments, as a Pilot test (SETCP) to identify Improvised Nuclear Devices (INDs) in highway transport. However, the level of DNDO integration among these state deployments is presently uncertain. Moreover, DHS issues are considered secondary by the states, which perceive this work as an opportunity to leverage these (new) dual-use technologies for state needs. In addition, present experience shows that radiation detectors alone cannot detect DHS-identified IND threats. Continued SETCP success depends on the level of integration of current state/local police operations with the new DHS task of detecting IND threats, in addition to emergency preparedness and homeland security. This document describes the enabling components for continued SETCP development and success, including: sensors and their use at existing deployments (Section 1); personnel training (Section 2); concept of operations (Section 3); knowledge discovery from the copious data (Section 4); smart data collection, integration and database development, advanced algorithms for multiple sensors, and network communications (Section 5); and harmonization of local, state, and Federal procedures and protocols (Section 6)