I\u27m In Heaven When I\u27m In Your Arms

https://digitalcommons.library.umaine.edu/mmb-vp/5925/thumbnail.jp

Dysfunctional inflammation in cystic fibrosis airways: From mechanisms to novel therapeutic approaches

Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP-gated chloride channel expressed on the apical surface of airway epithelial cells. CFTR absence/dysfunction results in defective ion transport and subsequent airway surface liquid dehydration that severely compromise the airway microenvironment. Noxious agents and pathogens are entrapped inside the abnormally thick mucus layer and establish a highly inflammatory environment, ultimately leading to lung damage. Since chronic airway inflammation plays a crucial role in CF pathophysiology, several studies have investigated the mechanisms responsible for the altered inflammatory/immune response that, in turn, exacerbates the epithelial dysfunction and infection susceptibility in CF patients. In this review, we address the evidence for a critical role of dysfunctional inflammation in lung damage in CF and discuss current therapeutic approaches targeting this condition, as well as potential new treatments that have been developed recently. Traditional therapeutic strategies have shown several limitations and limited clinical benefits. Therefore, many efforts have been made to develop alternative treatments and novel therapeutic approaches, and recent findings have identified new molecules as potential anti-inflammatory agents that may exert beneficial effects in CF patients. Furthermore, the potential anti-inflammatory properties of CFTR modulators, a class of drugs that directly target the molecular defect of CF, also will be critically reviewed. Finally, we also will discuss the possible impact of SARS-CoV-2 infection on CF patients, with a major focus on the consequences that the viral infection could have on the persistent inflammation in these patients

Tests of Lorentz and CPT symmetry with hadrons and nuclei

We explore the breaking of Lorentz and CPT invariance in strong interactions at low energy in the framework of chiral perturbation theory. Starting from the set of Lorentz-violating operators of mass-dimension five with quark and gluon fields, we construct the effective chiral Lagrangian with hadronic and electromagnetic interactions induced by these operators. We develop the power-counting scheme and discuss loop diagrams and the one-pion-exchange nucleon-nucleon potential. The effective chiral Lagrangian is the basis for calculations of low-energy observables with hadronic degrees of freedom. As examples, we consider clock-comparison experiments with nuclei and spin-precession experiments with nucleons in storage rings. We derive strict limits on the dimension-five tensors that quantify Lorentz and CPT violation

The quadrupole collective model from a Cartan-Weyl perspective

The matrix elements of the quadrupole variables and canonic conjugate momenta, emerging from collective nuclear models are calculated within a $SU(1,1)\times O(5)$ basis. Using a harmonic oscillator implementation of the SU(1,1) degree of freedom, it can be shown that the matrix elements of the quadrupole phonon creation and annihilation operators can be calculated in a pure algebraic way, making use of an intermediate state method.Comment: Special issue of journal of physics for the QTS5 conferenc

The bile duct ligated rat : a relevant model to study muscle mass loss in cirrhosis

Muscle mass loss and hepatic encephalopathy (complex neuropsychiatric disorder) are serious complications of chronic liver disease (cirrhosis) which impact negatively on clinical outcome and quality of life and increase mortality. Liver disease leads to hyperammonemia and ammonia toxicity is believed to play a major role in the pathogenesis of hepatic encephalopathy. However, the effects of ammonia are not brain-specific and therefore may also affect other organs and tissues including muscle. The precise pathophysiological mechanisms underlying muscle wasting in chronic liver disease remains to be elucidated. In the present study, we characterized body composition as well as muscle protein synthesis in cirrhotic rats with hepatic encephalopathy using the 6-week bile duct ligation (BDL) model which recapitulates the main features of cirrhosis. Compared to sham-operated control animals, BDL rats display significant decreased gain in body weight, altered body composition, decreased gastrocnemius muscle mass and circumference as well as altered muscle morphology. Muscle protein synthesis was also significantly reduced in BDL rats compared to control animals. These findings demonstrate that the 6-week BDL experimental rat is a relevant model to study liver disease-induced muscle mass loss

Observation and theoretical description of the pure Fano-effect in the valence-band photo-emission of ferromagnets

The pure Fano-effect in angle-integrated valence-band photo-emission of ferromagnets has been observed for the first time. A contribution of the intrinsic spin polarization to the spin polarization of the photo-electrons has been avoided by an appropriate choice of the experimental parameters. The theoretical description of the resulting spectra reveals a complete analogy to the Fano-effect observed before for paramagnetic transition metals. While the theoretical photo-current and spin difference spectra are found in good quantitative agreement with experiment in the case of Fe and Co only a qualitative agreement could be achieved in the case of Ni by calculations on the basis of plain local spin density approximation (LSDA). Agreement with experimental data could be improved in this case in a very substantial way by a treatment of correlation effects on the basis of dynamical mean field theory (DMFT).Comment: 11 pages, 3 figures accepted by PR

Sweet Taste Signaling Functions as a Hypothalamic Glucose Sensor

Brain glucosensing is essential for normal body glucose homeostasis and neuronal function. However, the exact signaling mechanisms involved in the neuronal sensing of extracellular glucose levels remain poorly understood. Of particular interest is the identification of candidate membrane molecular sensors that would allow neurons to change firing rates independently of intracellular glucose metabolism. Here we describe for the first time the expression of the taste receptor genes Tas1r1, Tas1r2 and Tas1r3, and their associated G-protein genes, in the mammalian brain. Neuronal expression of taste genes was detected in different nutrient-sensing forebrain regions, including the paraventricular and arcuate nuclei of the hypothalamus, the CA fields and dentate gyrus of the hippocampus, the habenula, and cortex. Expression was also observed in the intra-ventricular epithelial cells of the choroid plexus. These same regions were found to express the corresponding gene products that form the heterodimeric T1R2/T1R3 and T1R1/T1R3 sweet and l-amino acid taste G-protein coupled receptors, respectively, along with the taste G-protein α-gustducin. Moreover, in vivo studies in mice demonstrated that the hypothalamic expression of taste-related genes is regulated by the nutritional state of the animal, with food deprivation significantly increasing expression levels of Tas1r1 and Tas1r2 in hypothalamus, but not in cortex. Furthermore, exposing mouse hypothalamic cells to a low-glucose medium, while maintaining normal l-amino acid concentrations, specifically resulted in higher expression levels of the sweet-associated gene Tas1r2. This latter effect was reversed by adding the non-metabolizable artificial sweetener sucralose to the low-glucose medium, indicating that taste-like signaling in hypothalamic neurons does not require intracellular glucose oxidation. Taken together, our findings suggest that the heterodimeric G-protein coupled sweet receptor T1R2/T1R3 is a candidate membrane-bound brain glucosensor

Stopping Light on a Defect

Gap solitons are localized nonlinear coherent states which have been shown both theoretically and experimentally to propagate in periodic structures. Although theory allows for their propagation at any speed $v$, $0\le v\le c$, they have been observed in experiments at speeds of approximately 50% of $c$. It is of scientific and technological interest to trap gap solitons. We first introduce an explicit multiparameter family of periodic structures with localized defects, which support linear defect modes. These linear defect modes are shown to persist into the nonlinear regime, as {\it nonlinear defect modes}. Using mathematical analysis and numerical simulations we then investigate the capture of an incident gap soliton by these defects. The mechanism of capture of a gap soliton is resonant transfer of its energy to nonlinear defect modes. We introduce a useful bifurcation diagram from which information on the parameter regimes of gap soliton capture, reflection and transmission can be obtained by simple conservation of energy and resonant energy transfer principles.Comment: 45 pages, Submitted to Journal of the Optical Society

A sabre-tooth felid from Coopers Cave (Gauteng, South Africa) and its implications for Megantereon (Felidae: Machairodontinae) taxonomy

Metrical and morphological analysis of a new sabre-tooth felid mandible recovered from the Plio-Pleistocene hominid-bearing site of Coopers, South Africa, indicates that it can be assigned to the genus Megantereon, though it is by some measures the smallest individual of this taxon yet described. Comparison of morphological variability within this genus to that found within four extant, medium-sized felid species (Acinonyx jubatus, Neofelis nebulosa, Panthera pardus and P. uncia) and the extinct genus Smilodon (sister taxon of Megantereon) provides confirmation of the suggestion by Martínez-Navarro&Palmqvist (1995, 1996) that Megantereon is a geographically polymorphic genus comprised of at least two species: M. cultridens (Cuvier, 1824) of North America and Europe and M. whitei (Broom, 1937) of Africa and Europe.Duke University’s Undergraduate Research Support Office, Howard Hughes Program and Department of Biological Anthropology and Anatomy; the Palaeo-Anthropology Scientific Trust (PAST); the National Geographic Society; and the Wenner-Gren Foundation (grant 6914 to D.J.D.

Mach's principle: Exact frame-dragging via gravitomagnetism in perturbed Friedmann-Robertson-Walker universes with K=(±1,0)K = (\pm 1, 0)

We show that the dragging of the axis directions of local inertial frames by a weighted average of the energy currents in the universe is exact for all linear perturbations of any Friedmann-Robertson-Walker (FRW) universe with K = (+1, -1, 0) and of Einstein's static closed universe. This includes FRW universes which are arbitrarily close to the Milne Universe, which is empty, and to the de Sitter universe. Hence the postulate formulated by E. Mach about the physical cause for the time-evolution of the axis directions of inertial frames is shown to hold in cosmological General Relativity for linear perturbations. The time-evolution of axis directions of local inertial frames (relative to given local fiducial axes) is given experimentally by the precession angular velocity of gyroscopes, which in turn is given by the operational definition of the gravitomagnetic field. The gravitomagnetic field is caused by cosmological energy currents via the momentum constraint. This equation for cosmological gravitomagnetism is analogous to Ampere's law, but it holds also for time-dependent situtations. In the solution for an open universe the 1/r^2-force of Ampere is replaced by a Yukawa force which is of identical form for FRW backgrounds with $K = (-1, 0).$ The scale of the exponential cutoff is the H-dot radius, where H is the Hubble rate, and dot is the derivative with respect to cosmic time. Analogous results hold for energy currents in a closed FRW universe, K = +1, and in Einstein's closed static universe.Comment: 23 pages, no figures. Final published version. Additional material in Secs. I.A, I.J, III, V.H. Additional reference