The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

Pion Excess, Nuclear Correlations, and the Interpretation of (p⃗,n⃗\vec p, \vec n) Spin Transfer Experiments

Conventional theories of nuclear interactions predict a net increase in the distribution of virtual pions in nuclei relative to free nucleons. Analysis of data from several nuclear experiments has led to claims of evidence against such a pion excess. These conclusions are usually based on a collective theory (RPA) of the pions, which may be inadequate. The issue is the energy dependence of the nuclear response, which differs for theories with strong NN correlations from the RPA predictions. In the present paper, information about the energy dependence is extracted from sum rules, which are calculated for such a correlated, noncollective nuclear theory. The results lead to much reduced sensitivity of nuclear reactions to the correlations that are responsible for the pion excess. The primary example is $(\vec p,\vec n)$ spin transfer, for which the expected effects are found to be smaller than the experimental uncertainties. The analysis has consequences for Deep Inelastic Scattering (DIS) experiments as well.Comment: 16 pages, LaTeX, no figures, submitted to Phys. Rev.

Dynamical coupled channel calculation of pion and omega meson production

A dynamical coupled channel approach is used to study $\pi$ and $\omega$--meson production induced by pions and photons scattering from the proton. Six intermediate channels including $\pi N$, $\eta N$, $\pi\Delta$, $\sigma N$, $\rho N$ and $\omega N$ are employed to describe unpolarized and polarized data. Bare parameters in an effective hadronic Lagrangian are determined in a fit to data for $\pi N \to \pi N$, $\gamma N \to \pi N$, $\pi^- p \to \omega n$, and $\gamma p \to \omega p$ reactions at center-of-mass energies from threshold to $W < 2.0$ GeV. The $T$ matrix determined in these fits is used to calculate the photon beam asymmetry for $\omega$-meson production and the $\omega N \to\omega N$ total cross section and $\omega N$ scattering lengths.Comment: 26 pages, 18 figures, submitted to Phys. Rev. C; corrected typos, added references, minor revisions, same results/fig

Shadowing, Binding and Off-Shell Effects in Nuclear Deep Inelastic Scattering

We present a unified description of nuclear deep inelastic scattering (DIS) over the whole region $0<x<1$ of the Bjorken variable. Our approach is based on a relativistically covariant formalism which uses analytical properties of quark correlators. In the laboratory frame it naturally incorporates two mechanisms of DIS: (I) scattering from quarks and antiquarks in the target and (II) production of quark-antiquark pairs followed by interactions with the target. We first calculate structure functions of the free nucleon and develop a model for the quark spectral functions. We show that mechanism (II) is responsible for the sea quark content of the nucleon while mechanism (I) governs the valence part of the nucleon structure functions. We find that the coherent interaction of $\bar qq$ pairs with nucleons in the nucleus leads to shadowing at small $x$ and discuss this effect in detail. In the large $x$ region DIS takes place mainly on a single nucleon. There we focus on the derivation of the convolution model. We point out that the off-shell properties of the bound nucleon structure function give rise to sizable nuclear effects.Comment: 29 pages (and 10 figures available as hard copies from Authors), REVTE

Positional Differences in Areal Bone Mineral Density and Body Composition in NCAA Division - I Football Athletes

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Distorted wave impulse approximation analysis for spin observables in nucleon quasi-elastic scattering and enhancement of the spin-longitudinal response

We present a formalism of distorted wave impulse approximation (DWIA) for analyzing spin observables in nucleon inelastic and charge exchange reactions leading to the continuum. It utilizes response functions calculated by the continuum random phase approximation (RPA), which include the effective mass, the spreading widths and the \Delta degrees of freedom. The Fermi motion is treated by the optimal factorization, and the non-locality of the nucleon-nucleon t-matrix by an averaged reaction plane approximation. By using the formalism we calculated the spin-longitudinal and the spin-transverse cross sections, ID_q and ID_p, of 12C, 40Ca (\vec{p},\vec{n}) at 494 and 346 MeV. The calculation reasonably reproduced the observed ID_q, which is consistent with the predicted enhancement of the spin-longitudinal response function R_L. However, the observed ID_p is much larger than the calculated one, which was consistent with neither the predicted quenching nor the spin-transverse response function R_T obtained by the (e,e') scattering. The Landau-Migdal parameter g'_N\Delta for the N\Delta transition interaction and the effective mass at the nuclear center m^*(r=0) are treated as adjustable parameters. The present analysis indicates that the smaller g'_{N\Delta}(\approx 0.3) and m^*(0) \approx 0.7 m are preferable. We also investigate the validity of the plane wave impulse approximation (PWIA) with the effective nucleon number approximation for the absorption, by means of which R_L and R_T have conventionally been extracted.Comment: RevTex 3, 29 pages, 2 tables, 8 figure

Self-consistent Green's function approaches

We present the fundamental techniques and working equations of many-body Green's function theory for calculating ground state properties and the spectral strength. Green's function methods closely relate to other polynomial scaling approaches discussed in chapters 8 and 10. However, here we aim directly at a global view of the many-fermion structure. We derive the working equations for calculating many-body propagators, using both the Algebraic Diagrammatic Construction technique and the self-consistent formalism at finite temperature. Their implementation is discussed, as well as the inclusion of three-nucleon interactions. The self-consistency feature is essential to guarantee thermodynamic consistency. The pairing and neutron matter models introduced in previous chapters are solved and compared with the other methods in this book.Comment: 58 pages, 14 figures, Submitted to Lect. Notes Phys., "An advanced course in computational nuclear physics: Bridging the scales from quarks to neutron stars", M. Hjorth-Jensen, M. P. Lombardo, U. van Kolck, Editor

Solidification of Al alloys under electromagnetic pulses and characterization of the 3D microstructures under synchrotron x-ray tomography

A novel programmable electromagnetic pulse device was developed and used to study the solidification of Al-15 pct Cu and Al-35 pct Cu alloys. The pulsed magnetic fluxes and Lorentz forces generated inside the solidifying melts were simulated using finite element methods, and their effects on the solidification microstructures were characterized using electron microscopy and synchrotron X-ray tomography. Using a discharging voltage of 120 V, a pulsed magnetic field with the peak Lorentz force of ~1.6 N was generated inside the solidifying Al-Cu melts which were showed sufficiently enough to disrupt the growth of the primary Al dendrites and the Al2Cu intermetallic phases. The microstructures exhibit a strong correlation to the characteristics of the applied pulse, forming a periodical pattern that resonates the frequency of the applied electromagnetic field

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification

A General Model for Multilocus Epistatic Interactions in Case-Control Studies

Background: Epistasis, i.e., the interaction of alleles at different loci, is thought to play a central role in the formation and progression of complex diseases. The complexity of disease expression should arise from a complex network of epistatic interactions involving multiple genes. Methodology: We develop a general model for testing high-order epistatic interactions for a complex disease in a casecontrol study. We incorporate the quantitative genetic theory of high-order epistasis into the setting of cases and controls sampled from a natural population. The new model allows the identification and testing of epistasis and its various genetic components. Conclusions: Simulation studies were used to examine the power and false positive rates of the model under different sampling strategies. The model was used to detect epistasis in a case-control study of inflammatory bowel disease, in which five SNPs at a candidate gene were typed, leading to the identification of a significant three-locus epistasis