bluuebunny/crossref_metadata_2025 huggingface dataset:
PROCESS DEPENDENCE AND THE SIVERS EFFECT IN INCLUSIVE AND SEMI-INCLUSIVE REACTIONS
Authors: GAMBERG LEONARD , KANG ZHONG-BO , PROKUDIN ALEXEI
Published: January 2014

We perform an analysis of the the spin asymmetry for single inclusive jet production in proton-proton collisions collected by AnDY experiment and the Sivers asymmetry data from semi-inclusive deep inelastic scattering experiments. In particular, we consider the role color gauge invariance plays in determining the process-dependence of the Sivers effect. We find that after carefully taking into account the initial-state and final-state interactions between the active parton and the remnant of the polarized hadron, the calculated jet spin asymmetry based on the Sivers functions extracted from HERMES and COMPASS experiments is consistent with the AnDY experimental data. This provides a first indication for the process-dependence of the Sivers effect in different processes. We also make predictions for both direct photon and Drell-Yan spin asymmetry, to further test the process-dependence of the Sivers effect in future experiments.
FLAVOR DEPENDENCE OF UNPOLARIZED TMDS FROM SEMI-INCLUSIVE PION PRODUCTION
Authors: SIGNORI ANDREA , BACCHETTA ALESSANDRO , RADICI MARCO
Published: January 2014

Recent data from semi-inclusive deep inelastic scattering collected by the HERMES collaboration allow for the first time to discuss how the transverse-momentum dependence of unpolarized distribution and fragmentation functions is affected by the flavor of the involved partons. A model built with flavor-dependent Gaussian transverse-momentum distributions fits data better than the same flavor-independent model. The current analysis is performed for totally unpolarized scattering of leptons off protons and deuterons, with detected pions in the final state. There are convincing indications of flavor dependence in the fragmentation functions, while for parton distribution functions the evidence is weaker.
MEASUREMENT OF FORWARD JETS AT RHIC
Authors:   (FOR THE ADY COLLABORATION), BLAND L. C.
Published: January 2014

We present first measurements of forward jet production from p↑ + p collisions at [Formula: see text] GeV, including transverse single spin asymmetries. These asymmetries are expected to be sensitive to spin-correlated transverse momentum in the initial state, which is particularly interesting because it is related to orbital angular momentum in the proton.
LONG-RANGE RAPIDITY CORRELATIONS IN HEAVY-LIGHT ION COLLISIONS
Authors: KOVCHEGOV YURI V. , WERTEPNY DOUGLAS E.
Published: January 2014

We study two-particle long-range rapidity correlations arising in the early stages of heavy ion collisions in the saturation/Color Glass Condensate framework, assuming for simplicity that one colliding nucleus is much larger than the other. We calculate the two-gluon production cross section while including all-order saturation effects in the heavy nucleus with the lowest-order rescattering in the lighter nucleus. We find four types of correlations in the two-gluon production cross section: (i) geometric correlations, (ii) HBT correlations accompanied by a back-to-back maximum, (iii) away-side correlations, and (iv) near-side azimuthal correlations which are long-range in rapidity. The geometric correlations (i) are due to the fact that nucleons are correlated by simply being confined within the same nucleus and may lead to long-range rapidity correlations for the produced particles without strong azimuthal angle dependence. Somewhat surprisingly, long-range rapidity correlations (iii) and (iv) have exactly the same amplitudes along with azimuthal and rapidity shapes: one centered around Δϕ = π with the other one centered around Δϕ = 0 (here Δϕ is the azimuthal angle between the two produced gluons). We thus observe that the early-time CGC dynamics in nucleus-nucleus collisions generates azimuthal non-flow correlations which are qualitatively different from jet correlations by being long-range in rapidity. If strong enough, they have the potential of mimicking the elliptic (and higher-order even-harmonic) flow in the di-hadron correlators: one may need to take them into account in the experimental determination of the flow observables.
PHYSICS OF GLUON HELICITY
Authors: JI XIANGDONG , ZHAO YONG
Published: January 2014

The total gluon helicity in a polarized proton is shown to be a matrix element of a gauge-invariant but nonlocal, frame-dependent gluon spin operator [Formula: see text] in the large momentum limit. The operator [Formula: see text] is fit for the calculation of the total gluon helicity in lattice QCD. This calculation also implies that parton physics can be studied through the large momentum limit of frame-dependent, equal-time correlation functions of quarks and gluons.
ARE THERE INFINITELY MANY DECOMPOSITIONS OF THE NUCLEON SPIN?
Authors: WAKAMATSU MASASHI
Published: January 2014

We argue against the rapidly spreading idea of gauge-invariant-extension (GIE) approach in the nucleon spin decomposition problem, which implies the existence of infinitely many gauge-invariant decomposition of the nucleon spin.
NEW MODEL FOR NUCLEON GENERALIZED PARTON DISTRIBUTIONS
Authors: RADYUSHKIN ANATOLY V.
Published: January 2014

We describe a new type of models for nucleon generalized parton distributions (GPDs) H and E. They are heavily based on the fact nucleon GPDs require to use two forms of double distribution (DD) representations. The outcome of the new treatment is that the usual "DD+D-term" construction should be amended by an extra term, [Formula: see text] which has the DD structure α/βe(β, α), with e(β, α) being the DD that generates GPD E(x, ξ). We found that this function, unlike the D-term, has support in the whole -1 ≤ x ≤ 1 region. Furthermore, it does not vanish at the border points |x| = ξ.
TRANSVERSE CHARGE AND MAGNETIZATION DENSITIES IN THE NUCLEON'S CHIRAL PERIPHERY
Authors: GRANADOS C. , WEISS C.
Published: January 2014

In the light–front description of nucleon structure the electromagnetic form factors are expressed in terms of frame–independent transverse densities of charge and magnetization. Recent work has studied the transverse densities at peripheral distances [Formula: see text], where they are governed by universal chiral dynamics and can be computed in a model–independent manner. Of particular interest is the comparison of the peripheral charge and magnetization densities. We summarize (a) their interpretation as spin–independent and –dependent current matrix elements; (b) the leading–order chiral effective field theory results; (c) their mechanical interpretation in the light–front formulation; (d) the large–Nc limit of QCD and the role of Δ intermediate states; (e) the connection with generalized parton distributions and peripheral high–energy scattering processes.
DOUBLE PARTON FRAGMENTATION FUNCTION AND ITS EVOLUTION IN QUARKONIUM PRODUCTION
Authors: KANG ZHONG-BO
Published: January 2014

We summarize the results of a recent study on a new perturbative QCD factorization formalism for the production of heavy quarkonia of large transverse momentum pT at collider energies. Such a new factorization formalism includes both the leading power (LP) and next-to-leading power (NLP) contributions to the cross section in the [Formula: see text] expansion for heavy quark mass mQ. For the NLP contribution, the so-called double parton fragmentation functions are involved, whose evolution equations have been derived. We estimate fragmentation functions in the non-relativistic QCD formalism, and found that their contribution reproduce the bulk of the large enhancement found in explicit NLO calculations in the color singlet model. Heavy quarkonia produced from NLP channels prefer longitudinal polarization, in contrast to the single parton fragmentation function. This might shed some light on the heavy quarkonium polarization puzzle.
THE 1-JETTINESS EVENT-SHAPE FOR DIS WITH NNLL RESUMMATION
Authors: KANG ZHONG-BO , LIU XIAOHUI , MANTRY SONNY , QIU JIANWEI
Published: January 2014

We propose the use of 1-jettiness, a global event shape, for exclusive single jet production in lepton-nucleus deep inelastic scattering (DIS). We derive a factorization formula, using the Soft-Collinear Effective Theory, differential in the transverse momentum and rapidity of the jet and the 1-jettiness event shape. It provides a quantitative measure of the shape of the final-state QCD radiation in the presence of the hard jet, providing a useful powerful probe of QCD and nuclear physics. For example, one expects differences in the observed pattern of QCD radiation between large and small nuclei and these can be quantified by the 1-jettiness event shape. Numerical results are given for this new DIS event shape at leading twist with resummation at the next-to-next-to-leading logarithmic (NNLL) level of accuracy, for a variety of nuclear targets. Such studies would be ideal at a future EIC or LHeC electron-ion collider, where a range of nuclear targets are planned.
SINGLE INCLUSIVE JET PRODUCTION IN PP COLLISION: DEPENDENCE ON JET ALGORITHM
Authors: MUKHERJEE ASMITA , VOGELSANG WERNER
Published: January 2014

We present a recent calculation of single-inclusive high-pT jet production in pp collisions at RHIC, when the initial protons are unpolarized and also when they are longitudinally polarized. We investigate the effect of the algorithm adopted to define the jets on the numerical results of cross sections and spin asymmetries.
ORBITAL ANGULAR MOMENTUM OF GAUGE FIELDS: EXCITATION OF AN ATOM BY TWISTED PHOTONS
Authors: AFANASEV ANDREI , CARLSON CARL E. , MUKHERJEE ASMITA
Published: January 2014

Twisted photon states, or photon states with large (> ℏ) angular momentum projection in the direction of motion, can photoexcite atomic final states of differing quantum numbers. If the photon symmetry axis coincides with the center of an atom, there are known selection rules that require exact matching between the quantum numbers of the photon and the photoexcited states. The more general case of arbitrarily positioned beams relaxes the selection rules but produces a distribution of quantum numbers of the final atomic states that is novel and distinct from final states produced by plane-wave photons. Numerical calculations are presented using a hydrogen atom as an example.
Divergence analysis
Authors: Sampaio Diogo , Souza Rafael Martins de , Collange Caroline , Pereira Fernando Magno Quintão
Published: January 2014

Growing interest in graphics processing units has brought renewed attention to the Single Instruction Multiple Data (SIMD) execution model. SIMD machines give application developers tremendous computational power; however, programming them is still challenging. In particular, developers must deal with memory and control-flow divergences. These phenomena stem from a condition that we call data divergence, which occurs whenever two processing elements (PEs) see the same variable name holding different values. This article introduces divergence analysis, a static analysis that discovers data divergences. This analysis, currently deployed in an industrial quality compiler, is useful in several ways: it improves the translation of SIMD code to non-SIMD CPUs, it helps developers to manually improve their SIMD applications, and it also guides the automatic optimization of SIMD programs. We demonstrate this last point by introducing the notion of a divergence-aware register spiller. This spiller uses information from our analysis to either rematerialize or share common data between PEs. As a testimony of its effectiveness, we have tested it on a suite of 395 CUDA kernels from well-known benchmarks. The divergence-aware spiller produces GPU code that is 26.21% faster than the code produced by the register allocator used in the baseline compiler.
Space perception in virtual environments
Authors: Kelly Jonathan W. , Burton Melissa , Pollock Brice , Rubio Eduardo , Curtis Michael , Cruz Julio De La , Gilbert Stephen , Winer Eliot
Published: January 2014

Virtual reality systems commonly include both monocular and binocular depth cues, which have the potential to provide viewers with a realistic impression of spatial properties of the virtual environment. However, when multiple viewers share the same display, only one viewer typically receives the projectively correct images. All other viewers experience the same images despite displacement from the center of projection (CoP). Three experiments evaluated perceptual distortions caused by displacement from the CoP and compared those percepts to predictions of models based on monocular and binocular viewing geometry. Leftward and rightward displacement from the CoP caused virtual angles on the ground plane to be judged as larger and smaller, respectively, compared to judgments from the CoP. Backward and forward displacement caused rectangles on the ground plane to be judged as larger and smaller in depth, respectively, compared to judgments from the CoP. Judgment biases were in the same direction as cue-based model predictions but of smaller magnitude. Displacement from the CoP had asymmetric effects on perceptual judgments, unlike model predictions. Perceptual distortion occurred with monocular cues alone but was exaggerated when binocular cues were added. The results are grounded in terms of practical implications for multiuser virtual environments.
Mondrian tree
Authors: Doo Myungcheol , Liu Ling
Published: January 2014

With ubiquitous wireless connectivity and technological advances in mobile devices, we witness the growing demands and increasing market shares of mobile intelligent systems and technologies for real-time decision making and location-based knowledge discovery. Spatial alarms are considered as one of the fundamental capabilities for intelligent mobile location-based systems. Like time-based alarms that remind us the arrival of a future time point, spatial alarms remind us the arrival of a future spatial point. Existing approaches for scaling spatial alarm processing are focused on computing Alarm-Free Regions (A
fr
) and Alarm-Free Period (A
fp
) such that mobile objects traveling within an A
fr
can safely hibernate the alarm evaluation process for the computed A
fp
, to save battery power, until approaching the nearest alarm of interest. A key technical challenge in scaling spatial alarm processing is to efficiently compute A
fr
and A
fp
such that mobile objects traveling within an A
fr
can safely hibernate the alarm evaluation process during the computed A
fp
, while maintaining high accuracy. In this article we argue that on-demand computation of A
fr
is expensive and may not scale well for dense populations of mobile objects. Instead, we propose to maintain an index for both spatial alarms and empty regions (A
fr
) such that for a given mobile user's location, we can find relevant spatial alarms and whether it is in an alarm-free region more efficiently. We also show that conventional spatial indexing methods, such as R-tree family,
k
-d tree, Quadtree, and Grid, are by design not well suited to index empty regions. We present Mondrian Tree – a region partitioning tree for indexing both spatial alarms and alarm-free regions. We first introduce the Mondrian Tree indexing algorithms, including index construction, search, and maintenance. Then we describe a suite of Mondrian Tree optimizations to further enhance the performance of spatial alarm processing. Our experimental evaluation shows that the Mondrian Tree index, as an intelligent technology for mobile systems, outperforms traditional index methods, such as R-tree, Quadtree, and
k
-d tree, for spatial alarm processing.
Monitoring business constraints with the event calculus
Authors: Montali Marco , Maggi Fabrizio M. , Chesani Federico , Mello Paola , Aalst Wil M. P. van der
Published: January 2014

Today, large business processes are composed of smaller, autonomous, interconnected subsystems, achieving modularity and robustness. Quite often, these large processes comprise software components as well as human actors, they face highly dynamic environments and their subsystems are updated and evolve independently of each other. Due to their dynamic nature and complexity, it might be difficult, if not impossible, to ensure at design-time that such systems will always exhibit the desired/expected behaviors. This, in turn, triggers the need for runtime verification and monitoring facilities. These are needed to check whether the actual behavior complies with expected business constraints, internal/external regulations and desired best practices. In this work, we present Mobucon EC, a novel monitoring framework that tracks streams of events and continuously determines the state of business constraints. In Mobucon EC, business constraints are defined using the declarative language Declare. For the purpose of this work, Declare has been suitably extended to support quantitative time constraints and non-atomic, durative activities. The logic-based language
Event Calculus
(EC) has been adopted to provide a formal specification and semantics to Declare constraints, while a light-weight, logic programming-based EC tool supports dynamically reasoning about partial, evolving execution traces. To demonstrate the applicability of our approach, we describe a case study about maritime safety and security and provide a synthetic benchmark to evaluate its scalability.
LAKE
Authors: Bicakci Kemal , Crispo Bruno , Oligeri Gabriele
Published: January 2014

Server-side authenticated key-establishment protocols are characterized by placing a heavy workload on the server. We propose LAKE: a new protocol that enables amortizing servers’ workload peaks by moving most of the computational burden to the clients. We provide a formal analysis of the LAKE protocol under the Canetti-Krawczyk model and prove it to be secure. To the best of our knowledge, this is the most computationally efficient authenticated key-establishment ever proposed in the literature.
Autocrine regulation of glioma cell proliferation via pHe-sensitive K+ channels
Authors: Honasoge Avinash , Shelton Katherine A. , Sontheimer Harald
Published: January 2014

Since the seminal studies of Otto Warburg in the 1920s, it has been widely recognized that cancers grow glycolytically, even in the presence of oxygen. This generates an abundance of protons in a gradient across most solid tumors with an acidic core and an alkaline rim. Whether and how this proton gradient may also serve in an autocrine fashion in these tumors is unclear. We demonstrate that human glioma cells form spheroids that act as a viable three-dimensional tumor model, forming physiologically relevant extracellular pH (pHe) and cell proliferation gradients. Using fluorescent cell cycle trackers, we determined that the rate of cell proliferation is directly dependent on pHe and that cells adjust their growth rate according to their position within the pH gradient. We further show that glioma cells sense pH via H+-sensitive K+ channels, which translate changes in pH into changes in membrane voltage. These channels are tonically active and blocked by acidic pHe, quinine, and ruthenium red. Blockade of this K+ conductance by acidic pHe or drug inhibition depolarized glioma cells and tumor spheroids and prevented their passage through the hyperpolarization-dependent G1-to-S phase cell cycle checkpoint, thereby inhibiting cell division. In this way, pHe directly determines the proliferative state of glioma cells.
Cx46 hemichannels contribute to the sodium leak conductance in lens fiber cells
Authors: Ebihara Lisa , Korzyukov Yegor , Kothari Sorabh , Tong Jun-Jie
Published: January 2014

The lens is proposed to have an internal microcirculation system consisting of continuously circulating ionic fluxes that play an essential role in maintaining lens transparency. One of the key components of this system is the sodium leak conductance. Here we investigate the contribution of Cx46 hemichannels to the basal membrane permeability of peripheral fiber cells isolated from transgenic mouse lenses lacking Cx50 or both Cx50 and Cx46 (dKO) using the whole cell patch-clamp technique. Our results show that Cx46 hemichannels were largely closed at a resting voltage of −60 mV in the presence of millimolar divalent cation concentrations. However, even though the vast majority of these channels were closed at −60 mV, a small, persistent, inward current could still be detected. This current could be mostly blocked by exposure to 1 mM La3+ and was not observed in fiber cells isolated from dKO mouse lenses suggesting that it was due to Cx46 hemichannels. In addition, Cx50−/− fiber cells showed increased open channel noise and a depolarized resting potential compared with dKO fiber cells. Exposure of Cx50−/− fiber cells to La3+ hyperpolarized the resting potential to −58 mV, which is similar to the value of resting potential measured in dKO fiber and significantly reduced the open channel noise. In conclusion, these results suggest that Cx46 hemichannels may contribute to the sodium leak conductance in lens fiber cells.
Role of adiponectin in the metabolic effects of cannabinoid type 1 receptor blockade in mice with diet-induced obesity
Authors: Tam Joseph , Godlewski Grzegorz , Earley Brian J. , Zhou Liang , Jourdan Tony , Szanda Gergö , Cinar Resat , Kunos George
Published: January 2014

The adipocyte-derived hormone adiponectin promotes fatty acid oxidation and improves insulin sensitivity and thus plays a key role in the regulation of lipid and glucose metabolism and energy homeostasis. Chronic cannabinoid type 1 (CB1) receptor blockade also increases lipid oxidation and improves insulin sensitivity in obese individuals or animals, resulting in reduced cardiometabolic risk. Chronic CB1blockade reverses the obesity-related decline in serum adiponectin levels, which has been proposed to account for the metabolic effects of CB1antagonists. Here, we investigated the metabolic actions of the CB1inverse agonist rimonabant in high-fat diet (HFD)-induced obese adiponectin knockout (Adipo−/−) mice and their wild-type littermate controls (Adipo+/+). HFD-induced obesity and its hormonal/metabolic consequences were indistinguishable in the two strains. Daily treatment of obese mice with rimonabant for 7 days resulted in significant and comparable reductions in body weight, serum leptin, free fatty acid, cholesterol, and triglyceride levels in the two strains. Rimonabant treatment improved glucose homeostasis and insulin sensitivity to the same extent in Adipo+/+and Adipo−/−mice, whereas it reversed the HFD-induced hepatic steatosis, fibrosis, and hepatocellular damage only in the former. The adiponectin-dependent, antisteatotic effect of rimonabant was mediated by reduced uptake and increased β-oxidation of fatty acids in the liver. We conclude that reversal of the HFD-induced hepatic steatosis and fibrosis by chronic CB1blockade, but not the parallel reduction in adiposity and improved glycemic control, is mediated by adiponectin.
Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice
Authors: Wang Ying , Liu Limei , Du Hanze , Nagaoka Yoshiko , Fan Winnie , Lutfy Kabirullah , Friedman Theodore C. , Jiang Meisheng , Liu Yanjun
Published: January 2014

The prereceptor activation of glucocorticoid production in adipose tissue by NADPH-dependent 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has emerged as a potential mechanism in the pathogenesis of visceral obesity and metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) is an endoplasmic reticulum lumen-resident enzyme that generates cofactor NADPH and thus mediates 11β-HSD1 activity. To determine the role of adipose H6PDH in the prereceptor modulation of 11β-HSD1 and metabolic phenotypes, we generated a transgenic (Tg) mouse model overexpressing H6PDH under the control of the enhancer-promoter region of the adipocyte fatty acid-binding protein (aP2) gene (aP2/H6PDH Tg mice). Transgenic aP2/H6PDH mice exhibited relatively high expression of H6PDH and elevated corticosterone production with induction of 11β-HSD1 activity in adipose tissue. This increase in corticosterone production in aP2-H6PDH Tg mice resulted in mild abdominal fat accumulation with induction of C/EBP mRNA expression and slight weight gain. Transgenic aP2/H6PDH mice also exhibited fasting hyperglycemia and glucose intolerance with insulin resistance. In addition, the aP2/H6PDH Tg mice have elevated circulating free fatty acid levels with a concomitant increased adipose lipolytic action associated with elevated HSL mRNA and Ser660HSL phosphorylation within abdominal fat. These results suggest that increased H6PDH expression specifically in adipose tissue is sufficient to cause intra-adipose glucocorticoid production and adverse metabolic phenotypes. These findings suggest that the aP2/H6PDH Tg mice may provide a favorable model for studying the potential impact of H6PDH in the pathogenesis of human metabolic syndrome.
Exercise training boosts eNOS-dependent mitochondrial biogenesis in mouse heart: role in adaptation of glucose metabolism
Authors: Vettor Roberto , Valerio Alessandra , Ragni Maurizio , Trevellin Elisabetta , Granzotto Marnie , Olivieri Massimiliano , Tedesco Laura , Ruocco Chiara , Fossati Andrea , Fabris Roberto , Serra Roberto , Carruba Michele O. , Nisoli Enzo
Published: January 2014

Endurance exercise training increases cardiac energy metabolism through poorly understood mechanisms. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) in cardiomyocytes contributes to cardiac adaptation. Here we demonstrate that the NO donor diethylenetriamine-NO (DETA-NO) activated mitochondrial biogenesis and function, as assessed by upregulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (Tfam) expression, and by increased mitochondrial DNA content and citrate synthase activity in primary mouse cardiomyocytes. DETA-NO also induced mitochondrial biogenesis and function and enhanced both basal and insulin-stimulated glucose uptake in HL-1 cardiomyocytes. The DETA-NO-mediated effects were suppressed by either PGC-1α or Tfam small-interference RNA in HL-1 cardiomyocytes. Wild-type and eNOS−/− mice were subjected to 6 wk graduated swim training. We found that eNOS expression, mitochondrial biogenesis, mitochondrial volume density and number, and both basal and insulin-stimulated glucose uptake were increased in left ventricles of swim-trained wild-type mice. On the contrary, the genetic deletion of eNOS prevented all these adaptive phenomena. Our findings demonstrate that exercise training promotes eNOS-dependent mitochondrial biogenesis in heart, which behaves as an essential step in cardiac glucose transport.
A validation of the application of D2O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans
Authors: Wilkinson Daniel J. , Franchi Martino V. , Brook Matthew S. , Narici Marco V. , Williams John P. , Mitchell William K. , Szewczyk Nathaniel J. , Greenhaff Paul L. , Atherton Philip J. , Smith Kenneth
Published: January 2014

Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control of muscle mass. Traditional [13C]amino acid tracer methodologies necessitate sustained bed rest and intravenous cannulation(s), restricting studies to ∼12 h, and thus cannot holistically inform on diurnal MPS. This limits insight into the regulation of habitual muscle metabolism in health, aging, and disease while querying the utility of tracer techniques to predict the long-term efficacy of anabolic/anticatabolic interventions. We tested the efficacy of the D2O tracer for quantifying MPS over a period not feasible with13C tracers and too short to quantify changes in mass. Eight men (22 ± 3.5 yr) undertook one-legged resistance exercise over an 8-day period (4 × 8–10 repetitions, 80% 1RM every 2nd day, to yield “nonexercised” vs. “exercise” leg comparisons), with vastus lateralis biopsies taken bilaterally at 0, 2, 4, and 8 days. After day 0 biopsies, participants consumed a D2O bolus (150 ml, 70 atom%); saliva was collected daily. Fractional synthetic rates (FSRs) of myofibrillar (MyoPS), sarcoplasmic (SPS), and collagen (CPS) protein fractions were measured by GC-pyrolysis-IRMS and TC/EA-IRMS. Body water initially enriched at 0.16–0.24 APE decayed at ∼0.009%/day. In the nonexercised leg, MyoPS was 1.45 ± 0.10, 1.47 ± 0.06, and 1.35 ± 0.07%/day at 0–2, 0–4, and 0–8 days, respectively (∼0.05–0.06%/h). MyoPS was greater in the exercised leg (0–2 days: 1.97 ± 0.13%/day; 0–4 days: 1.96 ± 0.15%/day, P < 0.01; 0–8 days: 1.79 ± 0.12%/day, P < 0.05). CPS was slower than MyoPS but followed a similar pattern, with the exercised leg tending to yield greater FSRs (0–2 days: 1.14 ± 0.13 vs. 1.45 ± 0.15%/day; 0–4 days: 1.13 ± 0.07%/day vs. 1.47 ± 0.18%/day; 0–8 days: 1.03 ± 0.09%/day vs. 1.40 ± 0.11%/day). SPS remained unchanged. Therefore, D2O has unrivaled utility to quantify day-to-day MPS in humans and inform on short-term changes in anabolism and presumably catabolism alike.
Identification of HnRNP M as a novel biomarker for colorectal carcinoma by quantitative proteomics
Authors: Chen Shuijiao , Zhang Jie , Duan Lunxi , Zhang Yu , Li Cui , Liu Deliang , Ouyang Chunhui , Lu Fanggen , Liu Xiaowei
Published: January 2014

Colorectal carcinoma (CRC) is one of the most common cancers in the world, and identification of new CRC biomarkers will be helpful for the diagnosis and treatment of CRC. For isobaric tags for relative and absolute quantitation (iTRAQ) analysis, fresh CRC and adjacent, colonic adenoma, ulcerative colitis, Crohn's disease, and noncancerous colonic epithelial tissue were obtained from patients at the 2nd Xiangya Hospital of Central South University, China. The function of heterogeneous nuclear ribonucleoprotein M (HnRNP M) during the proliferation, invasion, and metastasis of CRC cells in vitro was evaluated. One hundred and twenty-six differentially expressed proteins were identified by iTRAQ analysis. The expression of HnRNP M exhibited progressive changes during the carcinogenic process and was validated by Western blot. The upregulation of HnRNP M correlated with cancer recurrence and regional lymph node metastasis. Furthermore, biological role exploration suggests that HnRNP M positively regulates cell cycle progression, promotes cell growth and invasion in vitro, and increases the colony-forming ability of LS174T cells. The present data demonstrate that the upregulation of HnRNP M is involved in human colorectal epithelial carcinogenesis and may serve as a carcinoma biomarker for CRC.
Ostα−/−mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity
Authors: Wheeler Sadie G. , Hammond Christine L. , Jornayvaz François R. , Samuel Varman T. , Shulman Gerald I. , Soroka Carol J. , Boyer James L. , Hinkle Patricia M. , Ballatori Nazzareno
Published: January 2014

The organic solute transporter OSTα-OSTβ is a key transporter for the efflux of bile acids across the basolateral membrane of ileocytes and the subsequent return of bile acids to the liver. Ostα−/−mice exhibit reduced bile acid pools and impaired lipid absorption. In this study, wild-type and Ostα−/−mice were characterized at 5 and 12 mo of age. Ostα−/−mice were resistant to age-related weight gain, body fat accumulation, and liver and muscle lipid accumulation, and male Ostα−/−mice lived slightly longer than wild-type mice. Caloric intake and activity levels were similar for Ostα−/−and wild-type male mice. Fecal lipid excretion was increased in Ostα−/−mice, indicating that a defect in lipid absorption contributes to decreased fat accumulation. Analysis of genes involved in intestinal lipid absorption revealed changes consistent with decreased dietary lipid absorption in Ostα−/−animals. Hepatic expression of cholesterol synthetic genes was upregulated in Ostα−/−mice, showing that increased cholesterol synthesis partially compensated for reduced dietary cholesterol absorption. Glucose tolerance was improved in male Ostα−/−mice, and insulin sensitivity was improved in male and female Ostα−/−mice. Akt phosphorylation was measured in liver and muscle tissue from mice after acute administration of insulin. Insulin responses were significantly larger in male and female Ostα−/−than wild-type mice. These findings indicate that loss of OSTα-OSTβ protects against age-related weight gain and insulin resistance.
Sarcoplasmic reticulum Ca2+ release is both necessary and sufficient for SK channel activation in ventricular myocytes
Authors: Terentyev Dmitry , Rochira Jennifer A. , Terentyeva Radmila , Roder Karim , Koren Gideon , Li Weiyan
Published: January 2014

SK channels are upregulated in human patients and animal models of heart failure (HF). However, their activation mechanism and function in ventricular myocytes remain poorly understood. We aim to test the hypotheses that activation of SK channels in ventricular myocytes requires Ca2+ release from sarcoplasmic reticulum (SR) and that SK currents contribute to reducing triggered activity. SK2 channels were overexpressed in adult rat ventricular myocytes using adenovirus gene transfer. Simultaneous patch clamp and confocal Ca2+ imaging experiments in SK2-overexpressing cells demonstrated that depolarizations resulted in Ca2+-dependent outward currents sensitive to SK inhibitor apamin. SR Ca2+ release induced by rapid application of 10 mM caffeine evoked repolarizing SK currents, whereas complete depletion of SR Ca2+ content eliminated SK currents in response to depolarizations, despite intact Ca2+ influx through L-type Ca2+ channels. Furthermore, voltage-clamp experiments showed that SK channels can be activated by global spontaneous SR Ca2+ release events Ca2+ waves (SCWs). Current-clamp experiments revealed that SK overexpression reduces the amplitude of delayed afterdepolarizations (DADs) resulting from SCWs and shortens action potential duration. Immunolocalization studies showed that overexpressed SK channels are distributed both at external sarcolemmal membranes and along the Z-lines, resembling the distribution of endogenous SK channels. In summary, SR Ca2+ release is both necessary and sufficient for the activation of SK channels in rat ventricular myocytes. SK currents contribute to repolarization during action potentials and attenuate DADs driven by SCWs. Thus SK upregulation in HF may have an anti-arrhythmic effect by reducing triggered activity.
Pivotal role of IL-6 in the hyperinflammatory responses to subacute ozone in adiponectin-deficient mice
Authors: Kasahara David I. , Kim Hye Y. , Mathews Joel A. , Verbout Norah G. , Williams Alison S. , Wurmbrand Allison P. , Ninin Fernanda M. C. , Neto Felippe L. , Benedito Leandro A. P. , Hug Christopher , Umetsu Dale T. , Shore Stephanie A.
Published: January 2014

Adiponectin is an adipose-derived hormone with anti-inflammatory activity. Following subacute ozone exposure (0.3 ppm for 24–72 h), neutrophilic inflammation and IL-6 are augmented in adiponectin-deficient ( Adipo−/−) mice. The IL-17/granulocyte colony-stimulating factor (G-CSF) axis is required for this increased neutrophilia. We hypothesized that elevated IL-6 in Adipo−/−mice contributes to their augmented responses to ozone via effects on IL-17A expression. Therefore, we generated mice deficient in both adiponectin and IL-6 ( Adipo−/−/IL-6−/−) and exposed them to ozone or air. In ozone-exposed mice, bronchoalveolar lavage (BAL) neutrophils, IL-6, and G-CSF, and pulmonary Il17a mRNA expression were greater in Adipo−/−vs. wild-type mice, but reduced in Adipo−/−/IL-6−/−vs. Adipo−/−mice. IL-17A+F4/80+cells and IL-17A+γδ T cells were also reduced in Adipo−/−/IL-6−/−vs. Adipo−/−mice exposed to ozone. Only BAL neutrophils were reduced in IL-6−/−vs. wild-type mice. In wild-type mice, IL-6 was expressed in Gr-1+F4/80−CD11c−cells, whereas in Adipo−/−mice F4/80+CD11c+cells also expressed IL-6, suggesting that IL-6 is regulated by adiponectin in these alveolar macrophages. Transcriptomic analysis identified serum amyloid A3 ( Saa3), which promotes IL-17A expression, as the gene most differentially augmented by ozone in Adipo−/−vs. wild-type mice. After ozone, Saa3 mRNA expression was markedly greater in Adipo−/−vs. wild-type mice but reduced in Adipo−/−/IL-6−/−vs. Adipo−/−mice. In conclusion, our data support a pivotal role of IL-6 in the hyperinflammatory condition observed in Adipo−/−mice after ozone exposure and suggest that this role of IL-6 involves its ability to induce Saa3, IL-17A, and G-CSF.
Involvement of the calcium-sensing receptor in calcium homeostasis in larval zebrafish exposed to low environmental calcium
Authors: Kwong Raymond W. M. , Auprix Dan , Perry Steve F.
Published: January 2014

The involvement of the calcium-sensing receptor (CaSR) in Ca2+homeostasis was investigated in larval zebrafish, Danio rerio. The expression of CaSR mRNA was first observed at 3 h posfertilization (hpf) and increased with development until plateauing at ∼48 hpf. At 4 dpf, CaSR mRNA was increased in fish acclimated to low Ca2+water (25 μM vs. 250 μM in normal water). Using immunohistochemistry and confocal microscopy, we demonstrated that the CaSR is expressed in the olfactory epithelium, neuromasts, ionocytes on the yolk sac epithelium, and corpuscles of Stannius. Results of double immunohistochemistry and/or in situ hybridization indicated that the CaSR is localized to a subset of mitochondrion-rich ionocytes enriched with Na+/K+-ATPase and epithelial Ca2+channel ( ecac). Translational knockdown of the CaSR prevented 4 dpf larvae from regulating whole body Ca2+levels when exposed to a low Ca2+environment. Further, the increases in ecac mRNA expression and Ca2+influx, normally associated with exposure to low-Ca2+water, were prevented by CaSR knockdown. These findings demonstrate that larval zebrafish lacking the CaSR lose their ability to regulate Ca2+when confronted with a low-Ca2+environment. Results from real-time PCR suggested that the mRNA expression of the hypocalcemic hormone stanniocalcin ( stc-1) remained elevated in the CaSR morphants following acclimation to low-Ca2+water. Overall, the results suggest that the CaSR is critical for Ca2+homeostasis in larval zebrafish exposed to low environmental Ca2+levels, possibly owing to its modulation of stanniocalcin mRNA expression.
Inhibitor of intramembranous absorption in ovine amniotic fluid
Authors: Brace Robert A. , Cheung Cecilia Y. , Anderson Debra F.
Published: January 2014

Intramembranous absorption increases during intra-amniotic infusion of physiological saline solutions. The increase may be due partly to the concomitant elevation in fetal urine production as fetal urine contains a stimulator of intramembranous absorption. In this study, we hypothesized that the increase in intramembranous absorption during intra-amniotic infusion is due, in part, to dilution of a nonrenal inhibitor of intramembranous absorption that is present in amniotic fluid. In late-gestation fetal sheep, amniotic fluid volume and the four primary amniotic inflows and outflows were determined over 2-day intervals under three conditions: 1) control conditions when fetal urine entered the amniotic sac, 2) during intra-amniotic infusion of 2 l/day of lactated Ringer solution when urine entered the amniotic sac, and 3) during the same intra-amniotic infusion when fetal urine was continuously replaced with lactated Ringer solution. Amniotic fluid volume, fetal urine production, swallowed volume, and intramembranous absorption rate increased during the infusions independent of fetal urine entry into the amniotic sac or its replacement. Lung liquid secretion rate was unchanged during infusion. Because fetal membrane stretch has been shown not to be involved and because urine replacement did not alter the response, we conclude that the increase in intramembranous absorption that occurs during intra-amniotic infusions is due primarily to dilution of a nonrenal inhibitor of intramembranous absorption that is normally present in amniotic fluid. This result combined with our previous study suggests that a nonrenal inhibitor(s) together with a renal stimulator(s) interact to regulate intramembranous absorption rate and, hence, amniotic fluid volume.
Postmenopausal hypertension: role of the sympathetic nervous system in an animal model
Authors: Maranon Rodrigo O. , Lima Roberta , Mathbout Mohammed , do Carmo Jussara M. , Hall John E. , Roman Richard J. , Reckelhoff Jane F.
Published: January 2014

In postmenopausal women the mechanisms responsible for hypertension have not been completely elucidated, and there are no gender-specific guidelines for women despite studies showing that blood pressure is not as well controlled to goal in women as in men. In the present study we tested the hypotheses that the sympathetic nervous system and the renal sympathetic nerves contribute to hypertension in aging female rats, that sympathetic activation may be mediated by the melanocortin 3/4 receptor (MC3/4R), and that MC3/4R activation may be due to increases in leptin. α-1, β-1,2-Adrenergic blockade reduced blood pressure in both young (3–4 mo) and old (18–19 mo) female spontaneously hypertensive rats (SHR). Renal denervation attenuated the hypertension more in old females than young females. MC3/4R antagonism with SHU-9119 given intracerebroventricularly had no effect on blood pressure in either young or old females but significantly reduced blood pressure in old males. Plasma leptin levels were similar in old male and female SHR and in old versus young females. These data suggest that the hypertension in old female SHR is in part due to activation of the sympathetic nervous system, that the renal nerves contribute to the hypertension, and that the mechanism responsible for sympathetic activation in old females is independent of the MC3/4R.
Expression of mineralocorticoid and glucocorticoid receptors in preautonomic neurons of the rat paraventricular nucleus
Authors: Chen Jian , Gomez-Sanchez Celso E. , Penman Alan , May Paul J. , Gomez-Sanchez Elise
Published: January 2014

Activation of mineralocorticoid receptors (MR) of the hypothalamic paraventricular nucleus (PVN) increases sympathetic excitation. To determine whether MR and glucocorticoid receptors (GR) are expressed in preautonomic neurons of the PVN and how they relate to endogenous aldosterone levels in healthy rats, retrograde tracer was injected into the intermediolateral cell column at T4 to identify preautonomic neurons in the PVN. Expression of MR, GR, 11-β hydroxysteroid dehydrogenase1 and 2 (11β-HSD1, 2), and hexose-6-phosphate dehydrogenase (H6PD) required for 11β-HSD1 reductase activity was assessed by immunohistochemistry. RT-PCR and Western blot analysis were used to determine MR gene and protein expression. Most preautonomic neurons were in the caudal mediocellular region of PVN, and most expressed MR; none expressed GR. 11β-HSD1, but not 11β-HSD2 nor H6PD immunoreactivity, was detected in the PVN. In rats with chronic low or high sodium intakes, the low-sodium diet was associated with significantly higher plasma aldosterone, MR mRNA and protein expression, and c-Fos immunoreactivity within labeled preautonomic neurons. Plasma corticosterone and sodium and expression of tonicity-responsive enhancer binding protein in the PVN did not differ between groups, suggesting osmotic adaptation to the altered sodium intake. These results suggest that MR within preautonomic neurons in the PVN directly participate in the regulation of sympathetic nervous system drive, and aldosterone may be a relevant ligand for MR in preautonomic neurons of the PVN under physiological conditions. Dehydrogenase activity of 11β-HSD1 occurs in the absence of H6PD, which regenerates NADP+ from NADPH and may increase MR gene expression under physiological conditions.
Descending vasa recta endothelial cells and pericytes form mural syncytia
Authors: Zhang Zhong , Lin Hai , Cao Chunhua , Payne Kristie , Pallone Thomas L.
Published: January 2014

Using patch clamp, we induced depolarization of descending vasa recta (DVR) pericytes or endothelia and tested whether it was conducted to distant cells. Membrane potential was measured with the fluorescent voltage dye di-8-ANEPPS or with a second patch-clamp electrode. Depolarization of an endothelial cell induced responses in other endothelia within a millisecond and was slowed by gap junction blockade with heptanol. Endothelial response to pericyte depolarization was poor, implying high-resistance myo-endothelial coupling. In contrast, dual patch clamp of neighboring pericytes revealed syncytial coupling. At high sampling rate, the spread of depolarization between pericytes and endothelia occurred in 9 ± 2 or 12 ± 2 μs, respectively. Heptanol (2 mM) increased the overall input resistance of the pericyte layer to current flow and prevented transmission of depolarization between neighboring cells. The fluorescent tracer Lucifer yellow (LY), when introduced through ruptured patches, spread between neighboring endothelia in 1 to 7 s, depending on location of the flanking cell. LY diffused to endothelial cells on the ipsilateral but not contralateral side of the DVR wall and minimally between pericytes. We conclude that both DVR pericytes and endothelia are part of individual syncytia. The rate of conduction of membrane potential exceeds that for diffusion of hydrophilic molecules by orders of magnitude. Gap junction coupling of adjacent endothelial cells may be spatially oriented to favor longitudinal transmission along the DVR axis.
Residual chemosensitivity to ventilatory challenges in genotyped congenital central hypoventilation syndrome
Authors: Carroll Michael S. , Patwari Pallavi P. , Kenny Anna S. , Brogadir Cindy D. , Stewart Tracey M. , Weese-Mayer Debra E.
Published: January 2014

Congenital central hypoventilation syndrome (CCHS) is a neurodevelopmental disorder characterized by life-threatening hypoventilation, possibly resulting from disruption of central chemosensory integration. However, animal models suggest the possibility of residual chemosensory function in the human disease. Cardioventilatory function in a large cohort with CCHS and verified paired-like homeobox 2B ( PHOX2B) mutations was assessed to determine the extent and genotype dependence of any residual chemosensory function in these patients. As part of inpatient clinical care and evaluation, 64 distinct studies from 32 infants, children, and young adults with the disorder were evaluated for physiological response to three different inspired steady-state gas exposures of 3 min each: hyperoxia [100% oxygen (O2)]; hyperoxic hypercapnia [95% O2and 5% carbon dioxide (CO2)]; and hypoxic hypercapnia [14% O2and 7% CO2balanced with nitrogen (N2)]. These were followed by a hypoxia challenge consisting of five or seven breaths of N2(100% N2). In addition, a control group of 15 young adults was exposed to all but the hypoxic challenge. Comprehensive monitoring was used to derive breath-to-breath and beat-to-beat measures of ventilatory, cardiovascular, and cerebrovascular function. On average, patients showed a residual awake ventilatory response to chemosensory challenge, independent of the specific patient PHOX2B genotype. Graded dysfunction in cardiovascular regulation was found to associate with genotype, suggesting differential effects on different autonomic subsystems. In addition, differences between cases and controls in the cerebrovascular response to chemosensory challenge may indicate alterations in cerebral autoregulation. Thus residual cardiorespiratory responses suggest partial preservation of central nervous system networks that could provide a fulcrum for potential pharmacological interventions.