Active Site Structures of CYP11A1 in the Presence of Its Physiological Substrates and Alterations upon Binding of Adrenodoxin

The rate-limiting step in the steroid synthesis pathway is catalyzed by CYP11A1 through three sequential reactions. The first two steps involve hydroxylations at positions 22 and 20, generating 20(R),22(R)-dihydroxycholesterol (20R,22R-DiOHCH), with the third stage leading to a C20–C22 bond cleavage, forming pregnenolone. This work provides detailed information about the active site structure of CYP11A1 in the resting state and substrate-bound ferric forms as well as the CO-ligated adducts. In addition, high-quality resonance Raman spectra are reported for the dioxygen complexes, providing new insight into the status of Fe–O–O fragments encountered during the enzymatic cycle. Results show that the three natural substrates of CYP11A1 have quite different effects on the active site structure, including variations of spin state populations, reorientations of heme peripheral groups, and, most importantly, substrate-mediated distortions of Fe–CO and Fe–O2 fragments, as revealed by telltale shifts of the observed vibrational modes. Specifically, the vibrational mode patterns observed for the Fe–O–O fragments with the first and third substrates are consistent with H-bonding interactions with the terminal oxygen, a structural feature that tends to promote O–O bond cleavage to form the Compound I intermediate. Furthermore, such spectral data are acquired for complexes with the natural redox partner, adrenodoxin (Adx), revealing protein–protein-induced active site structural perturbations. While this work shows that Adx has an only weak effect on ferric and ferrous CO states, it has a relatively stronger impact on the Fe–O–O fragments of the functionally relevant oxy complexes

Estimation of Juvenile Striped Bass Relative Abundance in the Virginia Portion of Chesapeake Bay Annual Progress Report: 2021 - 2022

The 2021 juvenile Striped Bass abundance index was 6.30 and was not significantly different than the reference mean of 7.77 for the period 1980 to 2009. Abundance indices were average in the York and Rappahannock rivers and below average in the James River in 2021 compared with the river‐specific reference means (1980‐2009). Relatively low catches of young‐of‐the‐year Striped Bass from sites upriver and downriver of core nursery areas suggest juvenile Striped Bass largely remained within core nursery areas in 2021. Juvenile abundance indices for Alewife, American Shad, Atlantic Croaker, Atlantic Silverside, and Spot were generally below their historic averages in 2021. In contrast, abundance indices for Banded Killifish, and Spottail Shiner in 2021 were generally greater than their historic averages in Virginia waters. Inland Silverside abundance in 2021 was similar to the historic average observed in Virginia waters. Juvenile White Perch abundance indices in 2021 were above historic averages in the York and Rappahannock river systems, but below historic averages in the James River. The juvenile abundance index for Blueback Herring was average in all rivers, except the Pamunkey River, where below‐average recruitment was observed. Together, these results suggest modest production of forage fish prey for piscivores in Virginia

Estimation of Juvenile Striped Bass Relative Abundance in the Virginia Portion of Chesapeake Bay Annual Progress Report: 2022 - 2023

The 2022 juvenile Striped Bass abundance index was 7.95 and was not significantly different than the reference mean of 7.77 for the period 1980 to 2009. Abundance indices were average in the York and Rappahannock rivers and below average in the James River in 2022 compared with the river-specific reference means (1980-2009). Relatively low catches of young‐of‐the‐year Striped Bass from sites upriver and downriver of core nursery areas suggest juvenile Striped Bass largely remained within core nursery areas in 2022. Indices of abundance were also calculated for three additional economically and recreationally important fishes in Virginia waters. Juvenile White Perch abundance indices in 2022 were above historic averages in the York and Rappahannock river systems, but similar to the historic average in the James River. Atlantic Croaker abundance in 2022 was similar to the historic average observed in Virginia waters. In contrast, the abundance index for Spot in 2022 was generally below the historic average in Virginia waters

Radiotherapy students' perceptions of support provided by clinical supervisors

Aim: The aim of this study was to explore the experiences of radiotherapy students on clinical placement, specifically focussing on the provision of well-being support from clinical supervisors. Materials and methods: Twenty-five students from the University of the West of England and City University of London completed an online evaluation survey relating to their experiences of placement, involving Likert scales and open-ended questions. Results: The quantitative results were generally positive; however, the qualitative findings were mixed. Three themes emerged: (1) provision of information and advice; (2) an open, inclusive and supportive working environment; and (3) a lack of communication, understanding, and consistency. Findings: Students' experiences on placement differed greatly and appeared to relate to their specific interactions with different members of staff. It is suggested that additional training around providing well-being support to students may be of benefit to clinical supervisors

Predation Impacts of Invasive Blue Catfish on Blue Crabs in Estuarine Environments

Blue crab (Callinectes sapidus) is an important resource in Chesapeake Bay serving as predator and prey in the estuarine food web and supporting one of the most valuable fisheries in the region with landings in 2019 exceeding 55,501,000 lbs. and valued at more than $81,465,000 (NOAA Fisheries 2021). Fluctuations in the abundance of blue crabs in the Chesapeake Bay reflect annual changes in recruitment, fishing mortality, and natural mortality (Lipcius and Van Engel 1990). During the 1990s, blue crab abundance in Chesapeake Bay declined markedly (Lipcius and Stockhausen 2002) and management plans were subsequently enacted to rebuild blue crab stocks to former levels of abundance. Such rebuilding plans aim to protect the spawning stock to ensure recruitment and required significant reductions in fishing mortality rates. Recruitment in this stock is closely monitored, and fishing mortality is regulated through area closures, minimum size, and seasonal harvest limits, but natural mortality due to predation is not well known or estimated. Indeed, a comprehensive list of blue crab predators is lacking for Chesapeake Bay (Bromilow and Lipcius 2017). Nonetheless, predation mortality on blue crabs may contribute to notable annual fluctuations in the abundance of juvenile and harvestable blue crabs

Discrete quantum gravity in the framework of Regge calculus formalism

An approach to the discrete quantum gravity based on the Regge calculus is discussed which was developed in a number of our papers. Regge calculus is general relativity for the subclass of general Riemannian manifolds called piecewise flat ones. Regge calculus deals with the discrete set of variables, triangulation lengths, and contains continuous general relativity as a particular limiting case when the lengths tend to zero. In our approach the quantum length expectations are nonzero and of the order of Plank scale $10^{-33}cm$. This means the discrete spacetime structure on these scales.Comment: LaTeX, 16 pages, to appear in JET

Regge Calculus as a Fourth Order Method in Numerical Relativity

The convergence properties of numerical Regge calculus as an approximation to continuum vacuum General Relativity is studied, both analytically and numerically. The Regge equations are evaluated on continuum spacetimes by assigning squared geodesic distances in the continuum manifold to the squared edge lengths in the simplicial manifold. It is found analytically that, individually, the Regge equations converge to zero as the second power of the lattice spacing, but that an average over local Regge equations converges to zero as (at the very least) the third power of the lattice spacing. Numerical studies using analytic solutions to the Einstein equations show that these averages actually converge to zero as the fourth power of the lattice spacing.Comment: 14 pages, LaTeX, 8 figures mailed in separate file or email author directl

Charged-particle magnetic-quadrupole spectrometer for neutron induced reactions

A spectrometer has been developed for measuring the charged particle production cross sections and spectra in neutron-induced reactions. The spectrometer consists of a magnetic quadrupole doublet which focuses the charged particles onto a silicon surface barrier detector telescope which is 2 meters or more from the irradiated sample. Collimators, shielding, and the large source-to- detector distance reduce the background enough to use the spectrometer with a 14- MeV neutron source producing 4 . 10$sup 12$ n/s. The spectrometer has been used in investigations of proton, deuteron, and alpha particle production by 14-MeV neutrons incident on various materials. Protons with energies as low as 1.1 MeV have been measured. The good resolution of the detectors has also made possible an improved measurement of the neutron- neutron scattering length from the 0$sup 0$ proton spectrum from deuteron breakup by 14-MeV neutrons. (auth

A fully (3+1)-D Regge calculus model of the Kasner cosmology

We describe the first discrete-time 4-dimensional numerical application of Regge calculus. The spacetime is represented as a complex of 4-dimensional simplices, and the geometry interior to each 4-simplex is flat Minkowski spacetime. This simplicial spacetime is constructed so as to be foliated with a one parameter family of spacelike hypersurfaces built of tetrahedra. We implement a novel two-surface initial-data prescription for Regge calculus, and provide the first fully 4-dimensional application of an implicit decoupled evolution scheme (the ``Sorkin evolution scheme''). We benchmark this code on the Kasner cosmology --- a cosmology which embodies generic features of the collapse of many cosmological models. We (1) reproduce the continuum solution with a fractional error in the 3-volume of 10^{-5} after 10000 evolution steps, (2) demonstrate stable evolution, (3) preserve the standard deviation of spatial homogeneity to less than 10^{-10} and (4) explicitly display the existence of diffeomorphism freedom in Regge calculus. We also present the second-order convergence properties of the solution to the continuum.Comment: 22 pages, 5 eps figures, LaTeX. Updated and expanded versio