Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium

Background: Loss of CFTR-dependent anion and fluid secretion in the ducts of the exocrine pancreas is thought to contribute to the development of pancreatitis, but little is known about the impact of inflammation on ductal CFTR function. Here we used adult stem cell-derived cell cultures (organoids) obtained from porcine pancreas to evaluate the effects of pro-inflammatory cytokines on CFTR function. Methods: Organoids were cultured from porcine pancreas and used to prepare ductal epithelial monolayers. Monolayers were characterized by immunocytochemistry. Epithelial bicarbonate and chloride secretion, and the effect of IL-1β, IL-6, IFN-γ, and TNF-α on CFTR function was assessed by electrophysiology. Results:Immunolocalization of ductal markers, including CFTR, keratin 7, and zonula occludens 1, demonstrated that organoid-derived cells formed a highly polarized epithelium. Stimulation by secretin or VIP triggered CFTR-dependent anion secretion across epithelial monolayers, whereas purinergic receptor stimulation by UTP, elicited CFTR-independent anion secretion. Most of the anion secretory response was attributable to bicarbonate transport. The combination of IL-1β, IL-6, IFN-γ, and TNF-α markedly enhanced CFTR expression and anion secretion across ductal epithelial monolayers, whereas these cytokines had little effect when tested separately. Although TNF-α triggered apoptotic signaling, epithelial barrier function was not significantly affected by cytokine exposure. Conclusions: Pro-inflammatory cytokines enhance CFTR-dependent anion secretion across pancreatic ductal epithelium. We propose that up-regulation of CFTR in the early stages of the inflammatory response, may serve to promote the removal of pathogenic stimuli from the ductal tree, and limit tissue injury.</p

Structure Factors and Their Distributions in Driven Two-Species Models

We study spatial correlations and structure factors in a three-state stochastic lattice gas, consisting of holes and two oppositely ``charged'' species of particles, subject to an ``electric'' field at zero total charge. The dynamics consists of two nearest-neighbor exchange processes, occuring on different times scales, namely, particle-hole and particle-particle exchanges. Using both, Langevin equations and Monte Carlo simulations, we study the steady-state structure factors and correlation functions in the disordered phase, where density profiles are homogeneous. In contrast to equilibrium systems, the average structure factors here show a discontinuity singularity at the origin. The associated spatial correlation functions exhibit intricate crossovers between exponential decays and power laws of different kinds. The full probability distributions of the structure factors are universal asymmetric exponential distributions.Comment: RevTex, 18 pages, 4 postscript figures included, mistaken half-empty page correcte

Wound healing and hyper-hydration - a counter intuitive model

Winters seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model ‘hyper-hydration’ of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration

Determination of the Strange Quark Content of the Nucleon from a Next-to-Leading-Order QCD Analysis of Neutrino Charm Production

We present the first next-to-leading-order QCD analysis of neutrino charm production, using a sample of 6090 $\nu_\mu$- and $\bar\nu_\mu$-induced opposite-sign dimuon events observed in the CCFR detector at the Fermilab Tevatron. We find that the nucleon strange quark content is suppressed with respect to the non-strange sea quarks by a factor \kappa = 0.477 \: ^{+\:0.063}_{-\:0.053}, where the error includes statistical, systematic and QCD scale uncertainties. In contrast to previous leading order analyses, we find that the strange sea $x$-dependence is similar to that of the non-strange sea, and that the measured charm quark mass, $m_c = 1.70 \pm 0.19 \:{\rm GeV/c}^2$, is larger and consistent with that determined in other processes. Further analysis finds that the difference in $x$-distributions between $xs(x)$ and $x\bar s(x)$ is small. A measurement of the Cabibbo-Kobayashi-Maskawa matrix element $|V_{cd}|=0.232 ^{+\:0.018}_{-\:0.020}$ is also presented. uufile containing compressed postscript files of five Figures is appended at the end of the LaTeX source.Comment: Nevis R#150

Pyrochlore Photons: The U(1) Spin Liquid in a S=1/2 Three-Dimensional Frustrated Magnet

We study the S=1/2 Heisenberg antiferromagnet on the pyrochlore lattice in the limit of strong easy-axis exchange anisotropy. We find, using only standard techniques of degenerate perturbation theory, that the model has a U(1) gauge symmetry generated by certain local rotations about the z-axis in spin space. Upon addition of an extra local interaction in this and a related model with spins on a three-dimensional network of corner-sharing octahedra, we can write down the exact ground state wavefunction with no further approximations. Using the properties of the soluble point we show that these models enter the U(1) spin liquid phase, a novel fractionalized spin liquid with an emergent U(1) gauge structure. This phase supports gapped S^z = 1/2 spinons carrying the U(1) ``electric'' gauge charge, a gapped topological point defect or ``magnetic'' monopole, and a gapless ``photon,'' which in spin language is a gapless, linearly dispersing S^z = 0 collective mode. There are power-law spin correlations with a nontrivial angular dependence, as well as novel U(1) topological order. This state is stable to ALL zero-temperature perturbations and exists over a finite extent of the phase diagram. Using a convenient lattice version of electric-magnetic duality, we develop the effective description of the U(1) spin liquid and the adjacent soluble point in terms of Gaussian quantum electrodynamics and calculate a few of the universal properties. The resulting picture is confirmed by our numerical analysis of the soluble point wavefunction. Finally, we briefly discuss the prospects for understanding this physics in a wider range of models and for making contact with experiments.Comment: 22 pages, 14 figures. Further minor changes. To appear in Phys. Rev.

Association between body mass index and risk of total knee replacement, the Singapore Chinese Health Study

SummaryPurposeData on the association between body mass index (BMI) and risk of knee osteoarthritis (KOA) are sparse for Asian populations who are leaner than Western populations. We evaluated the association between BMI and risk of total knee replacement (TKR) due to severe KOA among Chinese in Singapore.MethodsWe used data from the Singapore Chinese Health Study (SCHS), a population-based prospective cohort of 63,257 Chinese men and women, aged 45–74 years at enrollment from 1993 to 1998. Information on height, weight, diet and lifestyle factors were obtained via in-person interviews. TKR cases for severe KOA were identified via linkage with the nationwide hospital discharge database through 2011. Cox regression and weighted least squares regression were used in the analysis.ResultsThe mean BMI among cohort participants was 23.1 kg/m2, and more than two-thirds had BMI below 25 kg/m2. A total of 1649 had TKR attributable to severe KOA. Risk of TKR increased in a strong dose-dependent manner with increasing BMI throughout the 15–32 kg/m2 range and became less clear at BMI >32 kg/m2. In the BMI range 16–27 kg/m2, there was a 27% increase in TKR risk for each unit increase in BMI (P for trend < 0.001). Compared to BMI 19–20 kg/m2, the risk estimates of TKR were all statistically significant with increasing unit of BMI ≥21 kg/m2. Results were similar for men and women.ConclusionOur results provided evidence for a constant mechanical mechanism underlying BMI and KOA initiation and/or progression

Possible Z2 phase and spin-charge separation in electron doped cuprate superconductors

The SU(2) slave-boson mean-field theory for the tt'J model is analyzed. The role of next-nearest-neighbor hopping t' on the phase-diagram is studied. We find a pseudogap phase in hole-doped materials (where t'<0). The pseudo-gap phase is a U(1) spin liquid (the staggered-flux phase) with a U(1) gauge interaction and no fractionalization. This agrees with experiments on hole doped samples. The same calculation also indicates that a positive t' favors a Z2 state with true spin-charge separation. The Z2 state that exists when t' > 0.5J can be a candidate for the pseudo-gap phase of electron-doped cuprates (if such a phase exists). The experimental situation in electron-doped materials is also addressed.Comment: 6 pages, 2 figures, RevTeX4. Homepage http://dao.mit.edu/~wen

Multiband tight-binding theory of disordered ABC semiconductor quantum dots: Application to the optical properties of alloyed CdZnSe nanocrystals

Zero-dimensional nanocrystals, as obtained by chemical synthesis, offer a broad range of applications, as their spectrum and thus their excitation gap can be tailored by variation of their size. Additionally, nanocrystals of the type ABC can be realized by alloying of two pure compound semiconductor materials AC and BC, which allows for a continuous tuning of their absorption and emission spectrum with the concentration x. We use the single-particle energies and wave functions calculated from a multiband sp^3 empirical tight-binding model in combination with the configuration interaction scheme to calculate the optical properties of CdZnSe nanocrystals with a spherical shape. In contrast to common mean-field approaches like the virtual crystal approximation (VCA), we treat the disorder on a microscopic level by taking into account a finite number of realizations for each size and concentration. We then compare the results for the optical properties with recent experimental data and calculate the optical bowing coefficient for further sizes