Spin Hamiltonian Parameters for Cu(II)−Prion Peptide Complexes from L-Band Electron Paramagnetic Resonance Spectroscopy

Cu(II) is an essential element for life but is also associated with numerous and serious medical conditions, particularly neurodegeneration. Structural modeling of crystallization-resistant biological Cu(II) species relies on detailed spectroscopic analysis. Electron paramagnetic resonance (EPR) can, in principle, provide spin Hamiltonian parameters that contain information on the geometry and ligand atom complement of Cu(II). Unfortunately, EPR spectra of Cu(II) recorded at the traditional X-band frequency are complicated by (i) strains in the region of the spectrum corresponding to the g∥ orientation and (ii) potentially very many overlapping transitions in the g⊥ region. The rapid progress of density functional theory computation as a means to correlate EPR and structure, and the increasing need to study Cu(II) associated with biomolecules in more biologically and biomedically relevant environments such as cells and tissue, have spurred the development of a technique for the extraction of a more complete set of spin Hamiltonian parameters that is relatively straightforward and widely applicable. EPR at L-band (1−2 GHz) provides much enhanced spectral resolution and straightforward analysis via computer simulation methods. Herein, the anisotropic spin Hamiltonian parameters and the nitrogen coordination numbers for two hitherto incompletely characterized Cu(II)-bound species of a prion peptide complex are determined by analysis of their L-band EPR spectra

EPR Methods for Biological Cu(II): L-Band CW and NARS

Abstract: Copper has many roles in biology that involve the change of coordination sphere and/or oxidation state of the copper ion. Consequently, the study of copper in heterogeneous environments is an important area in biophysics. EPR is a primary technique for the investigation of paramagnetic copper, which is usually the isolated Cu(II) ion, but sometimes as Cu(II) in different oxidation states of multitransition ion clusters. The gross geometry of the coordination environment of Cu(II) can often be determined from a simple inspection of the EPR spectrum, recorded in the traditional X-band frequency range (9–10 GHz). Identification and quantitation of the coordinating ligand atoms, however, is not so straightforward. In particular, analysis of the superhyperfine structure on the EPR spectrum, to determine the number of coordinated nitrogen atoms, is fraught with difficulty at X-band, despite the observation that the overwhelming number of EPR studies of Cu(II) in the literature have been carried out at X-band. Greater reliability has been demonstrated at S-band (3–4 GHz), using the low-field parallel (gz) features. However, analysis relies on clear identification of the outermost superhyperfine line, which has the lowest intensity of all the spectral features. Computer simulations have subsequently indicated that the much more intense perpendicular region of the spectrum can be reliably interpreted at L-band (2 GHz). The present work describes the development of L-band EPR of Cu(II) into a routine method that is applicable to biological samples

Venus Lander Design

The students designed an Entry, Descent, and Landing (EDL) system for a lander to reach the surface of Venus. The students used a combination of 3D modelling and programming to design the EDL within given constraints under specific tolerances. An EDL takes into consideration entry flight dynamics, aeroheating, and landing systems. The EDL was divided into three stages (see below). The separation of stages was designed to address unique challenges found at different points throughout the EDL. The primary objective of the first stage was to minimize the heat associated with the entry velocity to the payload. The second stage implemented a parachute to reduce velocity such that the descent time criteria could be met. The third stage involved landing design. Through the use of six simultaneous differential equations, the flight of the vehicle was determined. The system was optimized by modifying craft parameters and initial conditions to meet objectives. After optimization, the revised values of position and velocity were obtained at every time step during descent. The vehicle velocity was used to calculate the heat rate to the heat shield of the entry vehicle. Through the use of a parachute, drag was increased to extend the time of flight and to slow the vehicle for landing. Designs were implemented to minimize impact force to the lander and maintain proper orientation during landing.https://scholarscompass.vcu.edu/capstone/1204/thumbnail.jp

Formal Compiler Implementation in a Logical Framework

The task of designing and implementing a compiler can be a difficult and error-prone process. In this paper, we present a new approach based on the use of higher-order abstract syntax and term rewriting in a logical framework. All program transformations, from parsing to code generation, are cleanly isolated and specified as term rewrites. This has several advantages. The correctness of the compiler depends solely on a small set of rewrite rules that are written in the language of formal mathematics. In addition, the logical framework guarantees the preservation of scoping, and it automates many frequently-occurring tasks including substitution and rewriting strategies. As we show, compiler development in a logical framework can be easier than in a general-purpose language like ML, in part because of automation, and also because the framework provides extensive support for examination, validation, and debugging of the compiler transformations. The paper is organized around a case study, using the MetaPRL logical framework to compile an ML-like language to Intel x86 assembly. We also present a scoped formalization of x86 assembly in which all registers are immutable

Moving Difference (MDIFF) Non-adiabatic Rapid Sweep (NARS) EPR of Copper(II)

Non-adiabatic rapid sweep (NARS) EPR spectroscopy has been introduced for application to nitroxide-labeled biological samples (Kittell et al., 2011). Displays are pure absorption, and are built up by acquiring data in spectral segments that are concatenated. In this paper we extend the method to frozen solutions of copper-imidazole, a square planar copper complex with four in-plane nitrogen ligands. Pure absorption spectra are created from concatenation of 170 5-gauss segments spanning 850 G at 1.9 GHz. These spectra, however, are not directly useful since nitrogen superhyperfine couplings are barely visible. Application of the moving difference (MDIFF) algorithm to the digitized NARS pure absorption spectrum is used to produce spectra that are analogous to the first harmonic EPR. The signal intensity is about four times higher than when using conventional 100 kHz field modulation, depending on line shape. MDIFF not only filters the spectrum, but also the noise, resulting in further improvement of the SNR for the same signal acquisition time. The MDIFF amplitude can be optimized retrospectively, different spectral regions can be examined at different amplitudes, and an amplitude can be used that is substantially greater than the upper limit of the field modulation amplitude of a conventional EPR spectrometer, which improves the signal-to-noise ratio of broad lines