A dynamical model for longitudinal wave functions in light-front holographic QCD

We construct a Schrodinger-like equation for the longitudinal wave function of a meson in the valence qq-bar sector, based on the 't Hooft model for large-N two-dimensional QCD, and combine this with the usual transverse equation from light-front holographic QCD, to obtain a model for mesons with massive quarks. The computed wave functions are compared with the wave function ansatz of Brodsky and De Teramond and used to compute decay constants and parton distribution functions. The basis functions used to solve the longitudinal equation may be useful for more general calculations of meson states in QCD.Comment: 12 pages, 2 figures, RevTeX 4.1; expanded discussion, with calculation details moved to appendice

Emerging Roles for MicroRNAs in Perioperative Medicine

MicroRNAs (miRNAs) are small, non-protein-coding, single-stranded RNAs. They function as posttranscriptional regulators of gene expression by interacting with target mRNAs. This process prevents translation of target mRNAs into a functional protein. miRNAs are considered to be functionally involved in virtually all physiologic processes, including differentiation and proliferation, metabolism, hemostasis, apoptosis, and inflammation. Many of these functions have important implications for anesthesiology and critical care medicine. Studies indicate that miRNA expression levels can be used to predict the risk for eminent organ injury or sepsis. Pharmacologic approaches targeting miRNAs for the treatment of human diseases are currently being tested in clinical trials. The present review highlights the important biological functions of miRNAs and their usefulness as perioperative biomarkers and discusses the pharmacologic approaches that modulate miRNA functions for disease treatment. In addition, the authors discuss the pharmacologic interactions of miRNAs with currently used anesthetics and their potential to impact anesthetic toxicity and side effects

HIF1A reduces acute lung injury by optimizing carbohydrate metabolism in the alveolar epithelium

Background: While acute lung injury (ALI) contributes significantly to critical illness, it resolves spontaneously in many instances. The majority of patients experiencing ALI require mechanical ventilation. Therefore, we hypothesized that mechanical ventilation and concomitant stretch-exposure of pulmonary epithelia could activate endogenous pathways important in lung protection. Methods and Findings: To examine transcriptional responses during ALI, we exposed pulmonary epithelia to cyclic mechanical stretch conditions—an in vitro model resembling mechanical ventilation. A genome-wide screen revealed a transcriptional response similar to hypoxia signaling. Surprisingly, we found that stabilization of hypoxia-inducible factor 1A (HIF1A) during stretch conditions in vitro or during ventilator-induced ALI in vivo occurs under normoxic conditions. Extension of these findings identified a functional role for stretch-induced inhibition of succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization, concomitant increases in glycolytic capacity, and improved tricarboxylic acid (TCA) cycle function. Pharmacologic studies with HIF activator or inhibitor treatment implicated HIF1A-stabilization in attenuating pulmonary edema and lung inflammation during ALI in vivo. Systematic deletion of HIF1A in the lungs, endothelia, myeloid cells, or pulmonary epithelia linked these findings to alveolar-epithelial HIF1A. In vivo analysis of 13C-glucose metabolites utilizing liquid-chromatography tandem mass-spectrometry demonstrated that increases in glycolytic capacity, improvement of mitochondrial respiration, and concomitant attenuation of lung inflammation during ALI were specific for alveolar-epithelial expressed HIF1A. Conclusions: These studies reveal a surprising role for HIF1A in lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent control of alveolar-epithelial glucose metabolism function as an endogenous feedback loop to dampen lung inflammation

Regulated ion transport in mouse liver cyst epithelial cells

AbstractDerived from bile duct epithelia (BDE), secretion by liver cyst-lining epithelia is positioned to drive cyst expansion but the responsible ion flux pathways have not been characterized. Cyst-lining epithelia were isolated and cultured into high resistance monolayers to assess the ion secretory pathways. Electrophysiologic studies showed a marked rate of constitutive transepithelial ion transport, including Cl− secretion and Na+ absorption. Na+ absorption was amiloride-sensitive, suggesting the activation of epithelial sodium channels (ENaC). Further, both cAMPi and extracellular ATP induced robust secretory responses. Western blotting and immunohistologic analysis of liver cyst epithelia demonstrated expression of P2X4, a potent purinergic receptor in normal BDE. Luminometry and bioassaying measured physiologically relevant levels of ATP in a subset of liver cyst fluid samples. Liver cyst epithelia also displayed a significant capacity to degrade extracellular ATP. In conclusion, regulated ion transport pathways are present in liver cyst epithelia and are positioned to direct fluid secretion into the lumen of liver cysts and promote increases in liver cyst expansion and growth

Nucleon Decay in the Minimal Supersymmetric SU(5)SU(5) Grand Unification

We make a detailed analysis on the nucleon decay in the minimal supersymmetric $SU(5)$ grand unified model. We find that a requirement of the unification of three gauge coupling constants leads to a constraint on a mass $M_{H_C}$ of color-triplet Higgs multiplet as 2 \times 10^{13}~\GeV \leq M_{H_C} \leq 2 \times 10^{17}~\GeV, taking both weak- and GUT-scale threshold effects into account. Contrary to the results in the previous analyses, the present experimental limits on the nucleon decay turn out to be consistent with the SUSY particles lighter than 1~TeV even without a cancellation between matrix elements contributed from different generations, if one adopts a relatively large value of $M_{H_C}$ (\ge2\times 10^{16}~\GeV). We also show that the Yukawa coupling constant of color-triplet Higgs multiplet does not necessarily blow up below the gravitational scale (2.4\times10^{18}~\GeV) even with the largest possible value of $M_{H_C}$. We point out that the no-scale model is still viable, though it is strongly constrained.Comment: 45 page

Using Gauge Coupling Unification and Proton Decay to Test Minimal Supersymmetric SU(5)

We derive a one-loop expression, including all thresholds, for the mass of the proton decay mediating color triplets, $M_{D^c}$, in minimal supersymmetric SU(5). The result for $M_{D^c}$ does not depend on other heavy thresholds or extra representations with SU(5) invariant masses which might be added to the minimal model. We numerically correct our result to two-loop accuracy. Choosing inputs to maximize $M_{D^c}$ and $\tau_P$, within experimental limits on the inputs and a $1~TeV$ naturalness bound, we derive a strict bound $\alpha_3>0.117$. We discuss how this bound will change as experimental limits improve. Measurements of $\alpha_3$ from deep inelastic scattering and the charmonium spectrum are below the bound $\alpha_3>0.117$ by more than $3\sigma$. We briefly review several ideas of how to resolve the discrepancy between these low values of $\alpha_3$ and the determinations of $\alpha_3$ from LEP event shapes.Comment: 10 pages (2 figures not included, available upon request), MIU-THP-94/6

Light-front holographic QCD and emerging confinement

In this report we explore the remarkable connections between light-front dynamics, its holographic mapping to gravity in a higher-dimensional anti-de Sitter (AdS) space, and conformal quantum mechanics. This approach provides new insights into the origin of a fundamental mass scale and the physics underlying confinement dynamics in QCD in the limit of massless quarks. The result is a relativistic light-front wave equation for arbitrary spin with an effective confinement potential derived from a conformal action and its embedding in AdS space. This equation allows for the computation of essential features of hadron spectra in terms of a single scale. The light-front holographic methods described here give a precise interpretation of holographic variables and quantities in AdS space in terms of light-front variables and quantum numbers. This leads to a relation between the AdS wave functions and the boost-invariant light-front wave functions describing the internal structure of hadronic bound-states in physical space-time. The pion is massless in the chiral limit and the excitation spectra of relativistic light-quark meson and baryon bound states lie on linear Regge trajectories with identical slopes in the radial and orbital quantum numbers. In the light-front holographic approach described here currents are expressed as an infinite sum of poles, and form factors as a product of poles. At large q(2) the form factor incorporates the correct power-law fall-off for hard scattering independent of the specific dynamics and is dictated by the twist. At low q2 the form factor leads to vector dominance. The approach is also extended to include small quark masses. We briefly review in this report other holographic approaches to QCD, in particular top-down and bottom-up models based on chiral symmetry breaking. We also include a discussion of open problems and future applications. (C)) 2015 Elsevier B.V. All rights reserved

Hypoxia-inducible factor 2-alpha-dependent induction of amphiregulin dampens myocardial ischemia- reperfusion injury

Myocardial ischemia-reperfusion injury (IRI) leads to the stabilization of the transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and hypoxia-inducible factor 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, the role of HIF2-alpha remains elusive. Here we show that HIF2-alpha induces the epithelial growth factor amphiregulin (AREG) to elicit cardioprotection in myocardial IRI. Comparing mice with inducible deletion of Hif1a or Hif2a in cardiac myocytes, we show that loss of Hif2-alpha increases infarct sizes. Microarray studies in genetic models or cultured human cardiac myocytes implicate HIF2-alpha in the myocardial induction of AREG. Likewise, AREG increases in myocardial tissues from patients with ischemic heart disease. Areg deficiency increases myocardial IRI, as does pharmacologic inhibition of Areg signaling. In contrast, treatment with recombinant Areg provides cardioprotection and reconstitutes mice with Hif2a deletion. These studies indicate that HIF2-alpha induces myocardial AREG expression in cardiac myocytes, which increases myocardial ischemia tolerance

Quality control in oocytes by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level.

Mammalian oocytes are arrested in the dictyate stage of meiotic prophase I for long periods of time, during which the high concentration of the p53 family member TAp63α sensitizes them to DNA damage-induced apoptosis. TAp63α is kept in an inactive and exclusively dimeric state but undergoes rapid phosphorylation-induced tetramerization and concomitant activation upon detection of DNA damage. Here we show that the TAp63α dimer is a kinetically trapped state. Activation follows a spring-loaded mechanism not requiring further translation of other cellular factors in oocytes and is associated with unfolding of the inhibitory structure that blocks the tetramerization interface. Using a combination of biophysical methods as well as cell and ovary culture experiments we explain how TAp63α is kept inactive in the absence of DNA damage but causes rapid oocyte elimination in response to a few DNA double strand breaks thereby acting as the key quality control factor in maternal reproduction

Bremsstrahlung Suppression due to the LPM and Dielectric Effects in a Variety of Materials

The cross section for bremsstrahlung from highly relativistic particles is suppressed due to interference caused by multiple scattering in dense media, and due to photon interactions with the electrons in all materials. We present here a detailed study of bremsstrahlung production of 200 keV to 500 MeV photons from 8 and 25 GeV electrons traversing a variety of target materials. For most targets, we observe the expected suppressions to a good accuracy. We observe that finite thickness effects are important for thin targets.Comment: 52 pages, 13 figures (incorporated in the revtex LaTeX file