Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin

Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society

On the elliptic nonabelian Fourier transform for unipotent representations of p-adic groups

In this paper, we consider the relation between two nonabelian Fourier transforms. The first one is defined in terms of the Langlands-Kazhdan-Lusztig parameters for unipotent elliptic representations of a split p-adic group and the second is defined in terms of the pseudocoefficients of these representations and Lusztig's nonabelian Fourier transform for characters of finite groups of Lie type. We exemplify this relation in the case of the p-adic group of type G_2.Comment: 17 pages; v2: several minor corrections, references added; v3: corrections in the table with unipotent discrete series of G

Impact of Grazing Management Strategies on Carbon Sequestration in a Semi-Arid Rangeland, USA

The effects of 12 years of grazing management strategies on carbon (C) distribution and sequestration were assessed on a semi-arid mixed-grass prairie in Wyoming, USA. Five grazing treatments were evaluated: non-grazed exclosures; continuous, season-long grazing at a light (22 steer-days ha-1) stocking rate; and, rotationally-deferred, short-duration rotation, and continuous, season-long grazing, all three at a heavy stocking rate (59 steer-days ha-1). Non-grazed exclosures exhibited a large buildup of dead plant material (72% of total aboveground plant matter) and forb biomass represented a large component (35%) of the plant community. Stocking rate, but not grazing strategy, changed plant community composition and decreased surface litter. Light grazing decreased forbs and increased cool-season mid-grasses, resulting in a highly diversified plant community and the highest total production of grasses. Heavy grazing increased warm-season grasses at the expense of the cool-season grasses, which decreased total forage production and opportunity for early season grazing. Compared to the exclosures, all grazing treatments resulted in significantly higher levels of C (6000-9000 kg ha-1) in the surface 15 cm of the soil. Higher levels of soil C with grazing are likely the result of faster litter decomposition and recycling, and redistribution of C within the 0-60 cm plant-soil system. Grazing at an appropriate stocking rate had beneficial effects on plant composition, forage production, and soil C sequestration. Without grazing, deterioration of the plant-soil system is indicated

Search for neutrino oscillations on a long base-line at the CHOOZ nuclear power station

This final article about the CHOOZ experiment presents a complete description of the electron antineutrino source and detector, the calibration methods and stability checks, the event reconstruction procedures and the Monte Carlo simulation. The data analysis, systematic effects and the methods used to reach our conclusions are fully discussed. Some new remarks are presented on the deduction of the confidence limits and on the correct treatment of systematic errors.Comment: 41 pages, 59 figures, Latex file, accepted for publication by Eur.Phys.J.

Insurance-Based Differences in Time to Diagnostic Follow-up after Positive Screening Mammography

Insurance may lengthen or inhibit time to follow-up after positive screening mammography. We assessed the association between insurance status and time to initial diagnostic follow-up after a positive screening mammogram

Intensive Care Unit Mortality and Length of Stay Among Critically Ill Patients With Sepsis Treated With Corticosteroids: A Retrospective Cohort Study

Objectives: Sepsis is a major cause of morbidity and mortality in critically ill patients worldwide, and corticosteroids are commonly used to treat it. However, the evidence supporting the use of corticosteroids in sepsis patients admitted to the intensive care unit (ICU) is of low certainty, with conflicting results reported in previous studies. Thus, we aimed to investigate the potential association between corticosteroid treatment and various outcomes, including 30-day ICU mortality, ICU length of stay (LOS), mechanical ventilation use, new onset of infection, and hyperglycemia in patients diagnosed with sepsis and admitted to the ICU. Materials and Methods: We conducted a cohort study utilizing data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database from 2008 to 2019. The study compared users of corticosteroids following admission to the ICU with non-users. Outcomes assessed included 30-day ICU mortality, ICU length of stay (LOS), mechanical ventilation use, new onset of infection, and hyperglycemia. Doubly robust, augmented inverse propensity weighted models were employed to control for confounders and determine the average treatment effect (ATE) of corticosteroids on study outcomes. Results: A total of 10,098 patients with a first diagnosis of sepsis were identified, of which 1,235 (12.2%) received corticosteroid treatment, and 8,863 (87.8%) did not. Corticosteroid use was associated with increased 30-day ICU mortality (ATE, 0.127; 95% CI, 0.083 to 0.171), ICU LOS (ATE, 1.773; 95% CI, 1.036 to 2.510), mechanical ventilation use (ATE, 0.181; 95% CI, 0.130 to 0.233), new onset of infection (ATE, 0.063; 95% CI, 0.032 to 0.094), and hyperglycemia (ATE, 0.024; 95% CI, 0.013 to 0.035) compared to non-use. Conclusion: The safety profile of corticosteroid therapy in sepsis patients admitted to the ICU remains a concern. Clinicians should carefully consider all available evidence and patient preferences when deciding to prescribe corticosteroids. Given the low certainty of evidence supporting the current treatment guidelines, further research is warranted to provide a more conclusive understanding of the risks and benefits associated with corticosteroid use in this patient population

Limits on Neutrino Oscillations from the CHOOZ Experiment

We present new results based on the entire CHOOZ data sample. We find (at 90% confidence level) no evidence for neutrino oscillations in the anti_nue disappearance mode, for the parameter region given by approximately Delta m**2 > 7 x 10**-4 eV^2 for maximum mixing, and sin**2(2 theta) = 0.10 for large Delta m**2. Lower sensitivity results, based only on the comparison of the positron spectra from the two different-distance nuclear reactors, are also presented; these are independent of the absolute normalization of the anti_nue flux, the cross section, the number of target protons and the detector efficiencies.Comment: 19 pages, 11 figures, Latex fil

Measurements of Charged Current Reactions of νe\nu_e on 12C^{12}C

Charged Current reactions of $\nu_e$ on $^{12}C$ have been studied using a $\mu^+$ decay-at-rest $\nu_e$ beam at the Los Alamos Neutron Science Center. The cross section for the exclusive reaction $^{12}C(\nu_e,e^-)^{12}N_{g.s.}$ was measured to be $(8.9\pm0.3\pm0.9)\times10^{-42}$ cm$^2$. The observed energy dependence of the cross section and angular distribution of the outgoing electron agree well with theoretical expectations. Measurements are also presented for inclusive transitions to $^{12}N$ excited states, $^{12}C(\nu_e,e^-)^{12}N^*$ and compared with theoretical expectations. The measured cross section, $(4.3\pm0.4\pm0.6)\times10^{-42}$ cm$^2$, is somewhat lower than previous measurements and than a continuum random phase approximation calculation. It is in better agreement with a recent shell model calculation.Comment: 34 pages, 18 figures, accepted to PRC, replaced with the accepted on

Cosmic ray results on the A dependence of multiplicity and angular distributions in proton nuclear interactions above 100 GeV

A calorimeter-spark chamber system was used to collect data on several hundred proton-nucleus interactions above 100 GeV using targets of C, Al, Fe, Sn and Pb. The average charged prong multiplicity is found to depend on atomic mass number as nc> = nc>(p-p)Ax where X = 0.129 +/- 0.004, with the dominant increase in multiplicity occuring in the backward (p-p c.m.) hemisphere. The value of x shows no significant energy dependence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22150/1/0000579.pd