Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors

Mammals express the sialic acids ​N-acetylneuraminic acid (​Neu5Ac) and ​N-glycolylneuraminic acid (​Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). ​Neu5Gc is synthesized from ​Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). In humans, this enzyme is inactive and only ​Neu5Ac is produced. Ferrets are susceptible to human-adapted IAV strains and have been the dominant animal model for IAV studies. Here we show that ferrets, like humans, do not synthesize ​Neu5Gc. Genomic analysis reveals an ancient, nine-exon deletion in the ferret CMAH gene that is shared by the Pinnipedia and Musteloidia members of the Carnivora. Interactions between two human strains of IAV with the sialyllactose receptor (sialic acid—α2,6Gal) confirm that the type of terminal sialic acid contributes significantly to IAV receptor specificity. Our results indicate that exclusive expression of ​Neu5Ac contributes to the susceptibility of ferrets to human-adapted IAV strains

Spin-orbital gapped phase with least symmetry breaking in the one-dimensional symmetrically coupled spin-orbital model

To describe the spin-orbital energy gap formation in the one-dimensional symmetrically coupled spin-orbital model, we propose a simple mean field theory based on an SU(4) constraint fermion representation of spins and orbitals. A spin-orbital gapped phase is formed due to a marginally relevant spin-orbital valence bond pairing interaction. The energy gap of the spin and orbital excitations grows extremely slowly from the SU(4) symmetric point up to a maximum value and then decreases rapidly. By calculating the spin, orbital, and spin-orbital tensor static susceptibilities at zero temperature, we find a crossover from coherent to incoherent magnetic excitations as the spin-orbital coupling decreasing from large to small values.Comment: 10 pages, Revtex file, 5 figure

Stability of the Minimal Heterotic Standard Model Bundle

The observable sector of the "minimal heterotic standard model" has precisely the matter spectrum of the MSSM: three families of quarks and leptons, each with a right-handed neutrino, and one Higgs-Higgs conjugate pair. In this paper, it is explicitly proven that the SU(4) holomorphic vector bundle leading to the MSSM spectrum in the observable sector is slope-stable.Comment: LaTeX, 19 page

Classification of Atretic Small Antral Follicles in the Human Ovary

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition. Our findings revealed that atresia spreads in the follicle with wave-like dynamics, initiating away from the cumulus granulosa cells. We also observed an enrichment of CD68+ macrophages in the antrum during the progression of follicular atresia. This work not only provides criteria for classifying three stages of follicular atresia in small antral follicles in the human ovary but also serves as a foundation for understanding follicular degeneration and ultimately preventing or treating premature ovarian failure. Understanding follicular remodeling in the ovary could provide a means to increase the number of usable follicles and delay the depletion of the follicular reserve, increasing the reproductive lifespan.</p

Extremal Bundles on Calabi-Yau Threefolds

We study constructions of stable holomorphic vector bundles on Calabi–Yau threefolds, especially those with exact anomaly cancellation which we call extremal. By going through the known databases we find that such examples are rare in general and can be ruled out for the spectral cover construction for all elliptic threefolds. We then introduce a general Hartshorne–Serre construction and use it to find extremal bundles of general ranks and study their stability, as well as computing their Chern numbers. Based on both existing and our new constructions, we revisit the DRY conjecture for the existence of stable sheaves on Calabi–threefolds, and provide theoretical and numerical evidence for its correctness. Our construction can be easily generalized to bundles with no extremal conditions imposed

Nonequilibrium Josephson effect in mesoscopic ballistic multiterminal SNS junctions

We present a detailed study of nonequilibrium Josephson currents and conductance in ballistic multiterminal SNS-devices. Nonequilibrium is created by means of quasiparticle injection from a normal reservoir connected to the normal part of the junction. By applying a voltage at the normal reservoir the Josephson current can be suppressed or the direction of the current can be reversed. For a junction longer than the thermal length, $L\gg\xi_T$, the nonequilibrium current increases linearly with applied voltage, saturating at a value equal to the equilibrium current of a short junction. The conductance exhibits a finite bias anomaly around $eV \sim \hbar v_F/L$. For symmetric injection, the conductance oscillates $2\pi$-periodically with the phase difference $\phi$ between the superconductors, with position of the minimum ($\phi=0$ or $\pi$) dependent on applied voltage and temperature. For asymmetric injection, both the nonequilibrium Josephson current and the conductance becomes $\pi$-periodic in phase difference. Inclusion of barriers at the NS-interfaces gives rise to a resonant behavior of the total Josephson current with respect to junction length with a period $\sim \lambda_F$. Both three and four terminal junctions are studied.Comment: 21 pages, 19 figures, submitted to Phys. Rev.

Solar Intranetwork Magnetic Elements: bipolar flux appearance

The current study aims to quantify characteristic features of bipolar flux appearance of solar intranetwork (IN) magnetic elements. To attack such a problem, we use the Narrow-band Filter Imager (NFI) magnetograms from the Solar Optical Telescope (SOT) on board \emph{Hinode}; these data are from quiet and an enhanced network areas. Cluster emergence of mixed polarities and IN ephemeral regions (ERs) are the most conspicuous forms of bipolar flux appearance within the network. Each of the clusters is characterized by a few well-developed ERs that are partially or fully co-aligned in magnetic axis orientation. On average, the sampled IN ERs have total maximum unsigned flux of several 10^{17} Mx, separation of 3-4 arcsec, and a lifetime of 10-15 minutes. The smallest IN ERs have a maximum unsigned flux of several 10^{16} Mx, separations less than 1 arcsec, and lifetimes as short as 5 minutes. Most IN ERs exhibit a rotation of their magnetic axis of more than 10 degrees during flux emergence. Peculiar flux appearance, e.g., bipole shrinkage followed by growth or the reverse, is not unusual. A few examples show repeated shrinkage-growth or growth-shrinkage, like magnetic floats in the dynamic photosphere. The observed bipolar behavior seems to carry rich information on magneto-convection in the sub-photospheric layer.Comment: 26 pages, 14 figure

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Collisionless and hydrodynamic excitations of trapped boson-fermion mixtures

Within a scaling ansatz formalism plus Thomas-Fermi approximation, we investigate the collective excitations of a harmonically trapped boson-fermion mixture in the collisionless and hydrodynamic limit at low temperature. Both the monopole and quadrupole modes are considered in the presence of spherical as well as cylindrically symmetric traps. In the spherical traps, the frequency of monopole mode coincides in the collisionless and hydrodynamic regime, suggesting that it might be undamped in all collisional regimes. In contrast, for the quadrupole mode, the frequency differs largely in these two limits. In particular, we find that in the hydrodynamic regime the quadrupole oscillations with equal bosonic and fermionic amplitudes generate an exact eigenstate of the system, regardless of the boson-fermion interaction. This resembles the Kohn mode for the dipole excitation. We discuss in some detail the behavior of monopole and quadrupole modes as a function of boson-fermion coupling at different boson-boson interaction strength. Analytic solutions valid at weak and medium fermion-boson coupling are also derived and discussed.Comment: 29 pages + 7 figures, resubmitted to Physical Review

Simplified phenotyping of CYP2D6 for tamoxifen treatment using the N-desmethyl-tamoxifen/ endoxifen ratio

Introduction: CYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (NDMT) to endoxifen (E). CYP2D6 polymorphisms are common and can affect CYP2D6 protein activity and E level. Some retrospective studies indicate that E < 16 nM may relate to worse outcome. Materials and methods: A target NDMT/E ratio was defined as associated with an E level of 15 nM in the 161 patient Test cohort of tamoxifen-treated patients, dichotomizing them into ‘Normal’ (NM) and ‘Slow’ (SM) CYP2D6 metabolizer groups. This ratio was then tested on a validation cohort of 52 patients. Patients were phenotyped based on the standard method (ultrarapid/extensive, intermediate or poor metabolizers; UM/EM, IM, PM) or a simplified system based on whether any variant allele (V) vs wildtype (wt) was present (wt/wt, wt/V, V/V). Comprehensive CYP2D6 genotyping was undertaken on germline DNA. Results: A target NDMT/E ratio of 35 correlated with the 15 nM E level, dichotomizing patients into NM (35; N ¼ 44) groups. The ratio was independently validated by a validation cohort. The simplified system was better in predicting patients without slow metabolism, with specificity and sensitivity of 96% and 44% respectively, compared with the standard method - sensitivity 81% and specificity 83%. Conclusions: The simplified classification system based on whether any variant was present better identified patients who were truly not CYP2D6 slow metabolizers more accurately than the current system. However, as CYP2D6 genotype is not the only determinant of endoxifen level, we recommend that direct measurement of endoxifen should also be considered