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

Introduction

Introduction to the assessing, planning and adapting to climate change Impacts in Skagit River watershed session of the Salish Sea Conference

Alternatively spliced variants of the cell adhesion molecule CD44 and tumour progression in colorectal cancer.

Increased expression of alternatively spliced variants of the CD44 family of cell adhesion molecules has been associated with tumour metastasis. In the present study, expression of alternatively spliced variants of CD44 and their cellular distribution have been investigated in human colonic tumours and in the corresponding normal mucosa, in addition to benign adenomatous polyps. The expression of CD44 alternatively spliced variants has been correlated with tumour progression according to Dukes' histological stage. CD44 variant expression was determined by immunohistochemisty using monoclonal antibodies directed against specific CD44 variant domains together with RT-PCR analysis of CD44 variant mRNA expression in the same tissue specimens. We demonstrate that as well as being expressed in colonic tumour cells, the full range of CD44 variants, CD44v2-v10, are widely expressed in normal colonic crypt epithelium, predominantly in the crypt base. CD44v6, the epitope which is most commonly associated with tumour progression and metastasis, was not only expressed by many benign colonic tumours, but was expressed as frequently in normal basal crypt epithelium as in malignant colonic tumour cells, and surprisingly, was even absent from some metastatic colorectal tumours. Expression of none of the CD44 variant epitopes was found to be positively correlated with tumour progression or with colorectal tumour metastasis to the liver, results which are inconsistent with a role for CD44 variants as indicators of colonic cancer progression

Extensions of tempered representations

Let $\pi, \pi'$ be irreducible tempered representations of an affine Hecke algebra H with positive parameters. We compute the higher extension groups $Ext_H^n (\pi,\pi')$ explicitly in terms of the representations of analytic R-groups corresponding to $\pi$ and $\pi'$. The result has immediate applications to the computation of the Euler-Poincar\'e pairing $EP(\pi,\pi')$, the alternating sum of the dimensions of the Ext-groups. The resulting formula for $EP(\pi,\pi')$ is equal to Arthur's formula for the elliptic pairing of tempered characters in the setting of reductive p-adic groups. Our proof applies equally well to affine Hecke algebras and to reductive groups over non-archimedean local fields of arbitrary characteristic. This sheds new light on the formula of Arthur and gives a new proof of Kazhdan's orthogonality conjecture for the Euler-Poincar\'e pairing of admissible characters.Comment: This paper grew out of "A formula of Arthur and affine Hecke algebras" (arXiv:1011.0679). In the second version some minor points were improve

Cochlear Implants in the Workplace: A Nationwide Survey

A nation wide survey of cochlear implant recipients was conducted to study how implants may impact people at work. Using a self-reporting questionnaire, recipients using four cochlear implant designs were surveyed about spoken communication on the job, overall job performance, job satisfaction, confidence in job retention and in seeking new employment, job promotion, and income. Of the implant recipients using their implants at work (106 people), the majority used their implants during all work hours and reported positive changes in their job situations. The survey results suggest that cochlear implants may help in mitigating functional limitations in the workplace resulting from profound hearing loss

Examining racial variation in antiemetic use and post-chemotherapy health care utilization for nausea and vomiting among breast cancer patients

Racial minority cancer patients may experience underuse of antiemetic medications to prevent chemotherapy-induced nausea and vomiting (CINV). In addition to its adverse implications for quality of life, antiemetic underuse may contribute to observed disparities in acute illness during chemotherapy. To understand the potential contribution of CINV prophylaxis to breast cancer disparities, we assessed racial variation in potent antiemetic use and post-chemotherapy utilization related to CINV, and the relationship between the two

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.

Half Life of the Doubly-magic r-Process Nucleus 78Ni

Nuclei with magic numbers serve as important benchmarks in nuclear theory. In addition, neutron-rich nuclei play an important role in the astrophysical rapid neutron-capture process (r-process). 78Ni is the only doubly-magic nucleus that is also an important waiting point in the r-process, and serves as a major bottleneck in the synthesis of heavier elements. The half-life of 78Ni has been experimentally deduced for the first time at the Coupled Cyclotron Facility of the National Superconducting Cyclotron Laboratory at Michigan State University, and was found to be 110 (+100 -60) ms. In the same experiment, a first half-life was deduced for 77Ni of 128 (+27 -33) ms, and more precise half-lives were deduced for 75Ni and 76Ni of 344 (+20 -24) ms and 238 (+15 -18) ms respectively.Comment: 4 pages, 3 figure

Initial Results from the CHOOZ Long Baseline Reactor Neutrino Oscillation Experiment

Initial results are presented from CHOOZ, a long-baseline reactor-neutrino vacuum-oscillation experiment. Electron antineutrinos were detected by a liquid scintillation calorimeter located at a distance of about 1 km. The detector was constructed in a tunnel protected from cosmic rays by a 300 MWE rock overburden. This massive shielding strongly reduced potentially troublesome backgrounds due to cosmic-ray muons, leading to a background rate of about one event per day, more than an order of magnitude smaller than the observed neutrino signal. From the statistical agreement between detected and expected neutrino event rates, we find (at 90% confidence level) no evidence for neutrino oscillations in the electron antineutrino disappearance mode for the parameter region given approximately by deltam**2 > 0.9 10**(-3) eV**2 for maximum mixing and (sin(2 theta)**2) > 0.18 for large deltam**2.Comment: 13 pages, Latex, submitted to Physics Letters