Explore the vast range of titles available.

Protein-protein interactions (PPIs) are critical to a range of biological processes and, consequently, aberrant interactions are implicated in many disorders. The study of the complex networks of PPIs promises to elucidate undiscovered roles in cellular processes and the mechanisms of disease. To accomplish this, tools to effectively sense PPIs are necessary. Effective PPI sensors must rapidly detect interactions in real-time with high sensitivity without perturbing the proteins of interest (POIs) under study. Split fluorescent proteins have previously been used to successfully monitor PPIs, in part due to the small size of the tags. Here, we developed an optimized tripartite split GFP system based on Corynactis californica GFP (ccGFP) to detect PPIs in vitro. In this sensor system, ccGFP fragments ccGFP10 and ccGFP11 are tagged to two POIs. PPIs can then be detected via fluorescence by complementation to the third fragment, ccGFP1-9, which reconstitutes functional ccGFP. The optimized ccGFP system shows improved detection kinetics and pH and temperature stability compared to a previous system. We then validated the sensor by monitoring PPIs in two model systems: attractive/repulsive coiled-coils and rapamycin-inducible FRB/FKBP heterodimerization. Finally, we developed an anti-tripartite ccGFP single-chain variable fragment (scFv), which could enable versatile detection of identified protein-protein complexes.

Organophosphorus (OP) nerve agents are a group of lethal small molecules. Fieldable detection of nerve agents is an on-going challenge that typically relies on mass spectrometry and infrared spectroscopy but not nuclear magnetic resonance (NMR) spectroscopy because of the portability limitations of superconducting magnets. However, Earth’s field NMR (EFNMR) demonstrates a unique signature space for OP compounds and can be made into a portable detector for OP nerve agents. Here we demonstrate a systematic study to develop the EFNMR signature space of 31 nerve-agent-related OP compounds, including surrogates, simulants, synthetic precursors, decomposition products, pesticides, and threat agents identified by the National Institutes of Health. The EFNMR spectral signatures are a diagnostic fingerprint of the molecular structure, and this study establishes the structure–signature relationships of this relatively unexplored signature space. The results indicate that EFNMR is a powerful analytical capability to distinguish and identify the unique structure of OP compounds, including nerve agents. While aimed at detection of nerve agents, this study also lays the foundations of using EFNMR for detection of any OP compound in the laboratory or in the field.

Nuclear magnetic resonance (NMR) spectroscopy in portable, permanent magnet-based spectrometers is primarily limited to nuclei with higher gyromagnetic ratio, γ , such as 1 H, 19 F, and 31 P due to the limited field strength achievable in these systems. Overhauser effect dynamic nuclear polarization (O-DNP), which transfers polarization from an unpaired electron to a nucleus by saturating an electron paramagnetic resonance transition with an oscillating radio frequency magnetic field, B 1e , can increase the polarization of low γ nuclei by hundreds or even thousands, enabling detection in a portable system. We have investigated the potential for O-DNP to enhance signals using (4-amino-2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO hereafter) as a source of unpaired electrons in a homebuilt ultra-low field (ULF) O-DNP-NMR spectrometer. We have found, in general, that larger concentrations of TEMPO are required for effective O-DNP with low γ nuclei, which has a number of important effects. Spin exchange effects cause the EPR lines to overlap and ultimately merge at high concentrations of TEMPO, fundamentally increasing the maximum possible enhancement, while the electron–electron dipolar interaction reduces both longitudinal and transverse relaxation times for the electrons, dramatically increasing the required B 1e strength. The relationship between TEMPO concentration, B 1e magnitude and O-DNP enhancement is quantified, and strategies for achieving these fields are discussed.

Using a simple low-field NMR system, we monitored water content in a living tree in a greenhouse over 2 months. By continuously running the system, we observed changes in tree water content on a scale of half an hour. The data showed a diurnal change in water content consistent both with previous NMR and biological observations. Neutron imaging experiments show that our NMR signal is primarily due to water being rapidly transported through the plant, and not to other sources of hydrogen, such as water in cytoplasm, or water in cell walls. After accounting for the role of temperature in the observed NMR signal, we demonstrate a change in the diurnal signal behavior due to simulated drought conditions for the tree. These results illustrate the utility of our system to perform noninvasive measurements of tree water content outside of a temperature controlled environment.

The Neutron Electric Dipole Moment (nEDM) experiment that will take place at the Spallation Neutron Source (SNS) in Oak Ridge, Tennessee will measure the electric dipole moment (EDM) of the neutron with a precision of order 10-28 e-cm, utilizing spin-polarized 3He in bulk liquid 4He to detect neutron precession in a 10 mG magnetic field and 50 kV/cm electric field. Since depolarized 3He will produce a background, relaxation of the polarized 3He, characterized by the probability of depolarization per bounce, Pd, was measured for materials that will be in contact with polarized 3He. Depolarization probabilities were determined from measurements of the longitudinal relaxation time of polarized 3He in bulk liquid 4He inside an acrylic cell coated with the wavelength shifter deuterated tetraphenyl butadiene (d-TPB), which will be used to coat the nEDM measurement cell. Relaxation measurements were also performed while rods, made from plumbing material Torlon and valve bellows material BeCu, were present in the cell. The BeCu was coated with Pyralin resin prior to relaxation measurements, while relaxation measurements were performed both before and after the Torlon rod was coated with Pyralin resin. The depolarization probabilities were found to be [special characters omitted] The relaxation rates extrapolated from the observed values of Pd for d-TPB, coated Torlon, and coated BeCu in the nEDM apparatus were found to be consistent with design goals.

We investigate some of the mechanical design factors of wafers and the effect on strength. Thin, solid, pre-stressed films are proposed as a means to improve the bulk mechanical properties of a wafer. Three-point bending was used to evaluate the laser scribe density and chemical processing effect on wafer strength. Drop and strike tests were employed to investigate the edge bevel profile effect on the mechanical properties of the wafer. To characterize the effect of thin films on strength, one-micron ceramic films were deposited on wafers using PECVD. Coated samples were prepared by cleaving and were tested using four-point bending. Film adhesion was characterized by notched four-point bending. RBS and FTIR were used to obtain film chemistry, and nanoindentation was used to investigate thin film mechanical properties. A stress measurement gauge characterized residual film stress. Mechanical properties of the wafers correlated to the residual stress in the film.

\"The Fire of Liberty in Their Hearts: The Diary of Jacob E. Yoder of the Freedmen's Bureau School, Lynchburg, Virginia, 1866-1870\" edited by Samuel L. Horst is reviewed.

Per- and polyfluoroalkyl substances (PFASs) are used in a multitude of processes and products, including nonstick coatings, food wrappers, and fire-fighting foams. These chemicals are environmentally-persistent, ubiquitous, and can be detected in the serum of 98% of Americans. Despite evidence that PFASs alter adaptive immunity, few studies have investigated their effects on innate immunity. The report here presents results of studies that investigated the impact of nine environmentally-relevant PFASs [e.g. perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na)] on one component of the innate immune response, the neutrophil respiratory burst. The respiratory burst is a key innate immune process by which microbicidal reactive oxygen species (ROS) are rapidly induced by neutrophils in response to pathogens; defects in the respiratory burst can increase susceptibility to infection. The study here utilized larval zebrafish, a human neutrophil-like cell line, and primary human neutrophils to ascertain whether PFAS exposure inhibits ROS production in the respiratory burst. It was observed that exposure to PFHxA and GenX suppresses the respiratory burst in zebrafish larvae and a human neutrophil-like cell line. GenX also suppressed the respiratory burst in primary human neutrophils. This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function.

Founded in part on a rejection of \"worldly\" power and the use of force, Anabaptism carried with it the promise of redemptive power. Yet the attempt to banish worldly power to the margins of the Christian community has been fraught with dilemmas, contradictions, and, at times, blatant abuses of authority. In this groundbreaking book, Benjamin W. Redekop, Calvin W. Redekop, and their coauthors draw on classic and contemporary thinking to confront the issue of power and authority in the Anabaptist-Mennonite community. From the power relationships of the sixteenth-century Peasants' War to issues of contemporary sexuality, the topics of Power, Authority, and the Anabaptist Tradition are sure to interest a wide audience. Contributors: Stephen C. Ainlay, College of the Holy Cross • J. Lawrence Burkholder, President Emeritus, Goshen College • Lydia Neufeld Harder, Toronto School of Theology • Joel Hartman, University of Missouri • Jacob A. Loewen, missionary, retired • Dorothy Yoder Nyce, Writer and former Assistant Professor, Goshen College • Lynda Nyce, Bluffton College • Wesley Prieb (deceased), former dean, Tabor College • Benjamin W. Redekop, Kettering University • Calvin W. Redekop, Conrad Grebel College, emeritus • James M. Stayer, Queen's University, Ontario