bluuebunny/crossref_metadata_2025 huggingface dataset:
Signal-to-noise ratio adaptive post-filtering method for intelligibility enhancement of telephone speech
Authors: Jokinen Emma , Yrttiaho Santeri , Pulakka Hannu , Vainio Martti , Alku Paavo
Published: December 2012

Post-filtering can be utilized to improve the quality and intelligibility of telephone speech. Previous studies have shown that energy reallocation with a high-pass type filter works effectively in improving the intelligibility of speech in difficult noise conditions. The present study introduces a signal-to-noise ratio adaptive post-filtering method that utilizes energy reallocation to transfer energy from the first formant to higher frequencies. The proposed method adapts to the level of the background noise so that, in favorable noise conditions, the post-filter has a flat frequency response and the effect of the post-filtering is increased as the level of the ambient noise increases. The performance of the proposed method is compared with a similar post-filtering algorithm and unprocessed speech in subjective listening tests which evaluate both intelligibility and listener preference. The results indicate that both of the post-filtering methods maintain the quality of speech in negligible noise conditions and are able to provide intelligibility improvement over unprocessed speech in adverse noise conditions. Furthermore, the proposed post-filtering algorithm performs better than the other post-filtering method under evaluation in moderate to difficult noise conditions, where intelligibility improvement is mostly required.
Macro parameters describing the mechanical behavior of classical guitars
Authors: Elie Benjamin , Gautier François , David Bertrand
Published: December 2012

Since the 1960s and 1970s, researchers have proposed simplified models using only a few parameters to describe the vibro-acoustical behavior of string instruments in the low-frequency range. This paper presents a method for deriving and estimating a few important parameters or features describing the mechanical behavior of classical guitars over a broader frequency range. These features are selected under the constraint that the measurements may readily be made in the workshop of an instrument maker. The computations of these features use estimates of the modal parameters over a large frequency range, made with the high-resolution subspace ESPRIT algorithm (Estimation of Signal Parameters via Rotational Invariant Techniques) and the signal enumeration technique ESTER (ESTimation of ERror). The methods are applied to experiments on real metal and wood plates and numerical simulations of them. The results on guitars show a nearly constant mode density in the mid- and high-frequency ranges, as it is found for a flat panel. Four features are chosen as characteristic parameters of this equivalent plate: Mass, rigidity, characteristic admittance, and the mobility deviation. Application to a set of 12 guitars indicates that these features are good candidates to discriminate different classes of classical guitars.
Mechanism for generating peaks and notches of head-related transfer functions in the median plane
Authors: Takemoto Hironori , Mokhtari Parham , Kato Hiroaki , Nishimura Ryouichi , Iida Kazuhiro
Published: December 2012

It has been suggested that the first spectral peak and the first two spectral notches of head-related transfer functions (HRTFs) are cues for sound localization in the median plane. Therefore, to examine the mechanism for generating spectral peaks and notches, HRTFs were calculated from four head shapes using the finite-difference time-domain method. The comparison between HRTFs calculated from the whole head and the pinna-related transfer functions calculated from the segmented pinna indicated that the pinna determines the basic peak–notch pattern of the HRTFs. An analysis of the distribution patterns of pressure nodes and anti-nodes on the pinna computed in the steady state for sinusoidal excitations confirmed that the first three peaks correspond to the first three normal modes of the pinna. The analysis also revealed that at the first spectral notch frequencies, one or two anti-nodes appeared in the cymba and the triangular fossa, and a node developed in the concha. Furthermore, according to changes in the instantaneous pressure distribution patterns on the pinna, three types of mechanisms were hypothesized for inducing the node in the concha depending on the source elevation angle.
Quantifying the effects of roughness scattering on reflection loss measurements
Authors: Isakson Marcia J. , Chotiros Nicholas P. , Abraham Yarbrough R. , Piper James N.
Published: December 2012

Seafloor reflection loss and roughness measurements were taken at the Experimental Validation of Acoustic Modeling Techniques experiment in 2006. The magnitude and phase of the reflection loss was measured at frequencies from 5 to 80 kHz and grazing angles from 7° to 77°. Approximately 1500 samples were taken for each angle. The roughness was measured with a laser profiler. Geoacoustic parameters such as water and sediment sound speed and density were measured concurrently. The reflection loss data were compared with three models: A flat interface elastic model based on geoacoustic measurements; a flat interface poro-elastic model based on the Biot/Stoll model; and a rough interface model based on the measured interface roughness power spectrum. The data were most consistent with the poro-elastic model including scattering. The elastic model consistently predicted values for the reflection loss which were higher than measured. The data exhibited more variability than the model due to layering and fluctuations in the propagating medium.
A model for ultrasound absorption and dispersion in dilute suspensions of nanometric contrast agents
Authors: Coulouvrat François , Thomas Jean-Louis , Astafyeva Ksenia , Taulier Nicolas , Conoir Jean-Marc , Urbach Wladimir
Published: December 2012

Ultrasound dispersion and absorption are examined in dilute suspensions of contrast agents of nanometric size, with a typical radius around 100 nm. These kinds of contrast agents are designed for targeted delivery of drugs for cancer treatment. Compared to standard contrast agents used for imaging, particles are of smaller size to pass through the endothelial barrier, their shell, made up of biocompatible polymer, is stiffer to undergo a longer lifetime, and they have a liquid core instead of a gaseous one. Ultrasound propagation in dilute suspension is modeled by combining two modes for particle oscillations. The first one is a dilatational mode assuming an incompressible shell with a rheological behavior of Kelvin–Voigt or Maxwell type. The second one is a translational mode induced by visco-inertial interaction with the ambient fluid. The relative importance of these two modes of interaction on both dispersion and absorption is quantified and analyzed for a model system and for two radii (75 and 150 nm) and the two rheological models. The influence of shell parameters (Young modulus, viscosity, and relative thickness) is finally discussed.
JNK Expression by Macrophages Promotes Obesity-Induced Insulin Resistance and Inflammation
Authors: Han Myoung Sook , Jung Dae Young , Morel Caroline , Lakhani Saquib A. , Kim Jason K. , Flavell Richard A. , Davis Roger J.
Published: December 2012

Macrophage JNK in Metabolic Disease

Inflammation is thought to be an important driver of diet-induced obesity and insulin resistance. Proinflammatory, M1 phenotype macrophages and the c-jun NH
2
terminal kinases (JNK) are central players in this process. But whether JNK expression is specifically required inside macrophages is unclear. In mice containing a macrophage-specific deletion in both
Jnk1
and
Jnk2
,

Han
et al.

(p.
218
, published online 6 December; see the Perspective by

Ferrante Jr.

) found that the mice were protected against many of the diet-induced metabolic changes, including insulin resistance, despite similar weight gain as control mice on a high-fat diet. This protection was associated with a decrease in the presence of M1 macrophages in adipose tissue.
Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine
Authors: Hackett Jamie A. , Sengupta Roopsha , Zylicz Jan J. , Murakami Kazuhiro , Lee Caroline , Down Thomas A. , Surani M. Azim
Published: December 2012

Epigenetic Controls

Germ cells in mammals give rise to sperm and eggs. During their development, germ cells undergo extensive epigenetic reprogramming, including global DNA demethylation, which is vital for the totipotency of the developing embryo.

Hackett
et al.

(p.
448
) show that the enzymes Tet1 and Tet2 are involved in the demethylation of individual genes and in imprinted gametic differentially methylated regions. The enzymes were also responsible for the global conversion of CpG methylation to 5-hydroxymethylcytosine, which then progressively declines. The findings suggest that demethylation can occur by replication-coupled dilution, although active mechanisms cannot be excluded. A small number of loci escape demethylation, providing a possible mechanistic basis for transgenerational inheritance.
Effect of electron inertia on radiative instability of rotating two-component gaseous plasma
Authors: Patidar A.K. , Pensia R.K. , Shrivastava V.
Published: December 2012

The problem of radiative instability of homogeneous rotating partially ionized plasma incorporating viscosity, porosity, and electron inertia in the presence of a magnetic field is investigated. A general dispersion relation is obtained using normal mode analysis with the help of relevant linearized perturbation equations of the problem. The modified Jeans criterion of instability is obtained. The conditions of Jeans instabilities are discussed in the different cases of interest. It is found that the simultaneous effect of viscosity, rotation, finite conductivity, and porosity of the medium does not essentially change the Jeans criterion of instability. It is also found that the presence of arbitrary radiative heat-loss function and thermal conductivity modified the conditions of Jeans instability for longitudinal propagation. It is found that, for longitudinal propagation, the conditions of radiative instability are independent of magnetic field, viscosity, rotation, finite electrical resistivity, and electron inertia, but for the transverse mode of propagation it depends upon finite electrical resistivity and strength of magnetic field and is independent of viscosity, electron inertia, and rotation. From the curves we find that viscosity has a stabilizing effect on the growth rate of instability but the thermal conductivity and density-dependent heat-loss function has a destabilizing effect on the instability growth rate.
Optomechanical effects in self-organization of a Bose–Einstein condensate in an optical cavity
Authors: Verma Priyanka , Bhattacherjee Aranya B. , Mohan Man
Published: December 2012

The influence of mirror motion on the spatial self-organization of a Bose–Einstein condensate in an optical cavity is studied. We show that mirror dynamics tends to destroy the process of self-organization. An additional external phonon pump is shown to modify the critical photon pump needed to observe the onset of self-organization.
Gravitational binding energy in charged cylindrical symmetry
Authors: Sharif M. , Bhatti M. Zaeem Ul Haq
Published: December 2012

We consider a static, cylindrically symmetric, charged, gravitating object as a perfect fluid and investigate the gravitational binding energy. It is found that only the localized part of the mass function provides the gravitational binding energy, whereas the nonlocalized part generated by the electric coupling does not contribute to it.
Characteristics of the total disintegration events of emulsion heavy target nuclei caused by O16 and 28Si nuclei at high energies
Authors: Mohery Mahmoud
Published: December 2012

The present paper deals with the interactions of 16O and 28Si nuclei with emulsion heavy target nuclei (silver (Ag) and bromine (Br)) at 4.5A GeV/c. The results have been analyzed to identify interesting characteristics of the total disintegration (TD) events produced in these interactions. Events having a number of heavily ionizing particles Nh ≥ 28 have been selected in this study. The integral multiplicity distributions for the disintegrated particles from the target nuclei have been used to separate the inelastic interactions with the free hydrogen (H), the light (CNO), and the heavy (AgBr) nuclei. The average multiplicities of the different secondary particles emitted in these interactions have been compared with the corresponding ones of different projectiles nearly at the same momentum. The average multiplicity of the grey particles is found to increase with the mass of the projectile, while the average multiplicity of the black particles is found to decrease with increasing mass of the projectile; this result agrees with the prediction of the fireball model. Also, the dependence of the shower, grey, and black particles produced in the TD events on the mass of the projectile has been studied. Moreover, the dependence of the probability of the TD for the projectile mass as well as the target fragments has also been discussed. The results show that the multiplicity distributions of the shower, grey, and black particles present a Gaussian distribution. Finally, the linear dependence of the grey and compound multiplicities on the black, heavy, and shower particles has also been observed.
Asymptotic behavior of the global chirality distribution for quantum walks on Z2 subject to decoherence
Authors: Ampadu Clement
Published: December 2012

Following Romanelli and Hernandez (Physica A, 390(6), (2011)) we investigate the global chirality distribution of the quantum walk on the plane subject to decoherence.
AN IMPORTANT CLASS OF CONFORMALLY FLAT WEAK EINSTEIN FINSLER METRICS
Authors: CHEN GUANGZU , CHENG XINYUE
Published: December 2012

In this paper, we study conformally flat (α, β)-metrics in the form F = αϕ(β/α), where α is a Riemannian metric and β is a 1-form on a C∞manifold M. We prove that if ϕ = ϕ(s) is a polynomial in s, the conformally flat weak Einstein (α, β)-metric must be either a locally Minkowski metric or a Riemannian metric. Moreover, we prove that conformally flat (α, β)-metrics with isotropic S-curvature are also either locally Minkowski metrics or Riemannian metrics.
QCD EVOLUTION WORKSHOP: INTRODUCTION
Authors: PROKUDIN ALEXEI
Published: December 2012

The introduction talk given at the beginning of QCD Evolution workshop held in Thomas Jefferson National Accelerator Facility (Jefferson Lab) on May 14 -17, 2012.
OVERVIEW OF EXPERIMENTAL RESULTS FROM HERMES
Authors: CONTALBRIGO MARCO
Published: December 2012

The investigation of the partonic degrees of freedom beyond collinear approximation (3D description) has been gained increasing interest in the last decade. At the HERMES experiment, azimuthal asymmetries in hard exclusive reactions and in semi-inclusive deep-inelastic scattering of electrons and positrons off a (polarized) hydrogen and deuterium target have been measured. Such asymmetries provide new insights on crucial aspects of the parton dynamics. By measuring various hadron types in the initial and final states, flavor sensitivity is achieved. Non zero signals are reported for azimuthal asymmetries with respect the transverse target polarization in real-photon exclusive-electroproduction, which are related (still in a model dependent way) to the elusive quark orbital motion. Evidence is reported of the poorly known transversity function and of naive-T-odd transverse-momentum-dependent parton distribution functions related to spin-orbit effects. Evidence of spin-orbit effects in quark fragmentation is also observed, which are opposite in sign for favored and disfavored processes.
RECENT RESULTS FROM RHIC SPIN AND BELLE FRAGMENTATION FUNCTION MEASUREMENTS
Authors: VOSSEN ANSELM
Published: December 2012

This contribution summarizes recent results from the RHIC spin program and the measurement of light quark fragmentation functions at Belle.
LIGHT-FRONT HOLOGRAPHY AND THE LIGHT-FRONT SCHRÖDINGER EQUATION
Authors: BRODSKY STANLEY J. , DE TÉRAMOND GUY
Published: December 2012

One of the most important nonperturbative methods for solving QCD is quantization at fixed light-front time τ = t + z/c – Dirac's "Front Form". The eigenvalues of the light-front QCD Hamiltonian predict the hadron spectrum and the eigensolutions provide the light-front wavefunctions which describe hadron structure. More generally, we show that the valence Fock-state wavefunctions of the light-front QCD Hamiltonian satisfy a single-variable relativistic equation of motion, analogous to the nonrelativistic radial Schrödinger equation, with an effective confining potential U which systematically incorporates the effects of higher quark and gluon Fock states. We outline a method for computing the required potential from first principles in QCD. The holographic mapping of gravity in AdS space to QCD, quantized at fixed light-front time, yields the same light front Schrödinger equation; in fact, the soft-wall AdS/QCD approach provides a model for the light-front potential which is color-confining and reproduces well the light-hadron spectrum. One also derives via light-front holography a precise relation between the bound-state amplitudes in the fifth dimension of AdS space and the boost-invariant light-front wavefunctions describing the internal structure of hadrons in physical space-time. The elastic and transition form factors of the pion and the nucleons are found to be well described in this framework. The light-front AdS/QCD holographic approach thus gives a frame-independent first approximation of the color-confining dynamics, spectroscopy, and excitation spectra of relativistic light-quark bound states in QCD.
GENERALIZED UNIVERSALITY FOR TMD DISTRIBUTION FUNCTIONS
Authors: BUFFING M. G. A. , MULDERS P. J.
Published: December 2012

Azimuthal asymmetries in high-energy processes, most pronounced showing up in combination with single or double (transverse) spin asymmetries, can be understood with the help of transverse momentum dependent (TMD) parton distribution and fragmentation functions. These appear in correlators containing expectation values of quark and gluon operators. TMDs allow access to new operators as compared to collinear (transverse momentum integrated) correlators. These operators include nontrivial process dependent Wilson lines breaking universality for TMDs. Making an angular decomposition in the azimuthal angle, we define a set of universal TMDs of definite rank, which appear with process dependent gluonic pole factors in a way similar to the sign of T-odd parton distribution functions in deep inelastic scattering or the Drell-Yan process. In particular, we show that for a spin 1/2 quark target there are three pretzelocity functions.
GPDs AND TMDs
Authors: BURKARDT MATTHIAS
Published: December 2012

For transversely polarized nucleons the distribution of quarks in the transverse plane is transversely shifted and that shift can be described in terms of Generalized Parton Distributions (GPDs). This observation provides a 'partonic' derivation of the Ji-relation for the quark angular momentum in terms of GPDs. Wigner distributions are used to show that the difference between the Jaffe-Manohar definiton of quark orbital angular momentum and that of Ji is equal to the change of orbital angular momentum due to the final state interactions as the struck quark leaves the target in a DIS experiment.
WIGNER DISTRIBUTIONS AND QUARK ORBITAL ANGULAR MOMENTUM
Authors: LORCÉ CÉDRIC , PASQUINI BARBARA
Published: December 2012

We discuss the quark phase-space or Wigner distributions of the nucleon which combine in a single picture all the information contained in the generalized parton distributions and the transverse-momentum dependent parton distributions. In particular, we present results for the distribution of unpolarized quarks in a longitudinally polarized nucleon obtained in a light-front constituent quark model. We show how the quark orbital angular momentum can be extracted from the Wigner distributions and compare it with alternative definitions.
LOOP SPACE AND EVOLUTION OF THE LIGHT-LIKE WILSON POLYGONS
Authors: CHEREDNIKOV I. O. , MERTENS T. , VAN DER VEKEN F. F.
Published: December 2012

We address a connection between the energy evolution of the polygonal light-like Wilson exponentials and the geometry of the loop space with the gauge invariant Wilson loops of a variety of shapes being the fundamental degrees of freedom. The renormalization properties and the differential area evolution of these Wilson polygons are studied by making use of the universal Schwinger quantum dynamical approach. We discuss the appropriateness of the dynamical differential equations in the loop space to the study of the energy evolution of the collinear and transverse-momentum dependent parton distribution functions.
QCD EVOLUTION OF NAIVE-TIME-REVERSAL-ODD QUARK-GLUON CORRELATION FUNCTIONS
Authors: KANG ZHONG-BO , QIU JIAN-WEI
Published: December 2012

In this talk, we examine the existing calculations of QCD evolution kernels for the scale dependence of two sets of twist-3 quark-gluon correlation functions, Tq,F(x, x) and [Formula: see text], which are the first transverse-momentum-moment of the naive-time-reversal-odd Sivers and Boer-Mulders function, respectively. The evolution kernels at the leading order in strong coupling constant αs were derived by several groups with apparent differences. We identify the sources of discrepancies and are able to reconcile the results from various groups.
SINGLE SPIN ASYMMETRIES IN INCLUSIVE DIS AND MULTI-PARTON CORRELATIONS IN THE NUCLEON
Authors: METZ ANDREAS , PITONYAK DANIEL , SCHÄFER ANDREAS , SCHLEGEL MARC , VOGELSANG WERNER , ZHOU JIAN
Published: December 2012

Transverse single spin asymmetries in inclusive deep-inelastic lepton-nucleon scattering can be generated through multi-photon exchange between the leptonic and the hadronic part of the process. Here we consider two-photon exchange, and mainly focus on the transverse target spin asymmetry. In particular, we investigate the case where two photons couple to different quarks. Such a contribution involves a quark-photon-quark correlator in the nucleon, which has a (model-dependent) relation to the Efremov-Teryaev-Qiu-Sterman quark-gluon-quark correlator TF. Using different parameterizations for TF we compute the transverse target spin asymmetry for both a proton and a neutron target, and compare the results to recent experimental data. Potential implications on our general understanding of single spin asymmetries in hard scattering processes are discussed as well.
SIVERS ASYMMETRY IN e + p↑ → e + J/ψ + X
Authors: MUKHERJEE ASMITA
Published: December 2012

A recent investigation of the single spin asymmetry (SSA) in low virtuality electroproduction/photoproduction of J/ψ in color evaporation model is presented. It is shown that the asymmetry is sizable and can be used as a probe for the still unknown gluon Sivers function.
BESSEL-WEIGHTED ASYMMETRIES AND TRANSVERSE SPIN EFFECTS
Authors: GAMBERG LEONARD
Published: December 2012

We consider the cross section for semi-inclusive deep inelastic scattering in Fourier space, conjugate to the outgoing hadron's transverse momentum, where convolutions of transverse momentum dependent parton distribution functions and fragmentation functions become simple products. Individual asymmetric terms in the cross section can be projected out by means of a generalized set of weights involving Bessel functions. Advantages of employing these Bessel weights are that they suppress (divergent) contributions from high transverse momentum and that soft factors cancel in (Bessel-) weighted asymmetries. Also, the resulting compact expressions immediately connect to previous work on evolution equations for transverse momentum dependent parton distribution and fragmentation functions and to quantities accessible in lattice QCD. Bessel-weighted asymmetries are thus model independent observables that augment the description and our understanding of correlations of spin and momentum in nucleon structure.
RENORMALIZATION GROUP EVOLUTION OF MULTI-GLUON CORRELATORS IN HIGH ENERGY QCD
Authors: JALILIAN-MARIAN JAMAL
Published: December 2012

Forward rapidity di-hadron azimuthal angular correlations in high energy proton-nucleus and proton-proton collisions are sensitive to quadrupoles; traceless correlator of 4 Wilson lines whereas single inclusive particle production iNVOLVES only dipoles, traceless correlator of 2 Wilson lines. We discuss the progress made in understanding the energy (rapidity) evolution of the quadrupole as well as its various limits.
RELATIONS BETWEEN TRANSVERSE MOMENTUM DISTRIBUTIONS AND CHIRAL ODD GENERALIZED PARTON DISTRIBUTIONS
Authors: LIUTI SIMONETTA , GOLDSTEIN GARY R. , GONZALEZ HERNANDEZ J. OSVALDO , KATHURIA KUNAL
Published: December 2012

We discuss the information on the spin structure of the proton that one can access by studying transverse momentum distributions, generalized parton distributions and their connection through generalized transverse momentum distributions. A "flexible" parametrization is proposed to extract this information from deeply virtual exclusive experiments.
BASICS OF GENERALIZED PARTON DISTRIBUTIONS
Authors: RADYUSHKIN ANATOLY V.
Published: December 2012

A brief review of the theory of generalized parton distributions (GPDs) is given. We discuss the basic concepts of the GPD theory and relationship between GPDs and simpler phenomenological functions, viz. form factors, parton densities and distribution amplitudes. A special emphasis is given to the formulation of GPDs in terms of double distributions.
NONPERTURBATIVE CONTRIBUTIONS TO A RESUMMED LEPTONIC ANGULAR DISTRIBUTION IN INCLUSIVE Z/γ* BOSON PRODUCTION
Authors: GUZZI MARCO , NADOLSKY PAVEL M.
Published: December 2012

We summarize a new analysis of the distribution [Formula: see text] of charged leptons produced in decays of Z and γ* bosons in the Collins-Soper-Sterman (CSS) formalism for transverse momentum resummation. By comparing the [Formula: see text] distribution measured at the Tevatron with the resummed CSS cross section with approximate [Formula: see text] Wilson coefficients, we constrain the magnitude of the nonperturbative Gaussian smearing factor and analyze its uncertainty caused by variations in scale parameters. We find excellent agreement between the [Formula: see text] data and our theoretical prediction, provided by the RESBOS resummation program. The nonperturbative factor that we obtained can be used to update resummed QCD predictions for precision measurements in inclusive W and Z production and for comparisons to various models of nonperturbative dynamics.
NHE8 plays important roles in gastric mucosal protection
Authors: Xu Hua , Li Jing , Chen Huacong , Wang Chunhui , Ghishan Fayez K.
Published: December 2012

Sodium/hydrogen exchanger (NHE) 8 is an apically expressed membrane protein in the intestinal epithelial cells. It plays important roles in sodium absorption and bicarbonate secretion in the intestine. Although NHE8 mRNA has been detected in the stomach, the precise location and physiological role of NHE8 in the gastric glands remain unclear. In the current study, we successfully detected the expression of NHE8 in the glandular region of the stomach by Western blotting and located NHE8 protein at the apical membrane in the surface mucous cells by a confocal microscopic method. We also identified the expression of downregulated-in-adenoma (DRA) in the surface mucous cells in the stomach. Using NHE8−/−mice, we found that NHE8 plays little or no role in basal gastric acid production, yet NHE8−/−mice have reduced gastric mucosal surface pH and higher incidence of developing gastric ulcer. DRA expression was reduced significantly in the stomach in NHE8−/−mice. The propensity for gastric ulcer, reduced mucosal surface pH, and low DRA expression suggest that NHE8 is indirectly involved in gastric bicarbonate secretion and gastric mucosal protection.
Truncated dystrophins reduce muscle stiffness in the extensor digitorum longus muscle of mdx mice
Authors: Hakim Chady H. , Duan Dongsheng
Published: December 2012

Muscle stiffness is a major clinical feature in Duchenne muscular dystrophy (DMD). DMD is the most common lethal inherited muscle-wasting disease in boys, and it is caused by the lack of the dystrophin protein. We recently showed that the extensor digitorum longus (EDL) muscle of mdx mice (a DMD mouse model) exhibits disease-associated muscle stiffness. Truncated micro- and mini-dystrophins are the leading candidates for DMD gene therapy. Unfortunately, it has never been clear whether these truncated genes can mitigate muscle stiffness. To address this question, we examined the passive properties of the EDL muscle in transgenic mdx mice that expressed a representative mini- or micro-gene (ΔH2-R15, ΔR2-15/ΔR18-23/ΔC, or ΔR4-23/ΔC). The passive properties were measured at the ages of 6 and 20 mo and compared with those of age-matched wild-type and mdx mice. Despite significant truncation of the gene, surprisingly, the elastic and viscous properties were completely restored to the wild-type level in every transgenic strain we examined. Our results demonstrated for the first time that truncated dystrophin genes may effectively treat muscle stiffness in DMD.
Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists
Authors: Lin Yu-Jung , Lin You Shuei , Lai Ching Jung , Yuan Zung Fan , Ruan Ting , Kou Yu Ru
Published: December 2012

The terminals of vagal lung C fibers (VLCFs) express various types of pharmacological receptors that are important to the elicitation of airway reflexes and the development of airway hypersensitivity. We investigated the blockade of the reflex and afferent responses of VLCFs to intravenous injections of agonists using perivagal treatment with antagonists (PAT) targeting the transient receptor potential vanilloid 1, P2X, and 5-HT3receptors in anesthetized rats. Blockading these responses via perivagal capsaicin treatment (PCT), which blocks the neural conduction of C fibers, was also studied. We used capsaicin, α,β-methylene-ATP, and phenylbiguanide as the agonists, and capsazepine, iso-pyridoxalphosphate-6-azophenyl-2′,5′-disulfonate, and tropisetron as the antagonists of transient receptor potential vanilloid 1, P2X, and 5-HT3receptors, respectively. We found that each of the PATs abolished the VLCF-mediated reflex apnea evoked by the corresponding agonist, while having no effect on the response to other agonists. Perivagal vehicle treatment failed to produce any such blockade. These blockades had partially recovered at 3 h after removal of the PATs. In contrast, PCT abolished the reflex apneic response to all three agonists. Both PATs and PCT did not affect the myelinated afferent-mediated apneic response to lung inflation. Consistently, our electrophysiological studies revealed that each of the PATs prevented the VLCF responses to the corresponding agonist, but not to any other agonist. PCT inevitably prevented the VLCF responses to all three agonists. Thus these PATs selectively blocked the stimulatory action of corresponding agonists on the VLCF terminals via mechanisms that are distinct from those of PCT. PAT may become a novel intervention for studying the pharmacological modulation of VLCFs.
The specific role of gravitational accelerations for arterial adaptations
Authors: Weber Tobias , Ducos Michel , Mulder Edwin , Herrera Frankyn , Brüggemann Gert-Peter , Bloch Wilhelm , Rittweger Jörn
Published: December 2012

It is mostly agreed that arterial adaptations occur, among others, in response to changes in mechanical stimuli. Models like bed rest, spinal cord injury, or limb suspension have been applied to study vascular adaptations to unloading in humans. However, these models cannot distinguish the role of muscle contractions and the role of gravitational accelerations for arterial adaptation. The HEPHAISTOS orthosis allows normal ambulation, while it significantly reduces force generation in the lower leg muscles. Eleven subjects wore HEPHAISTOS unilaterally for 56 days and were followed up for another 4 wk. Arterial diameters, intima media thickness (IMT), flow-mediated dilation (FMD), and resting blood flow (BFrest) were measured using high-frequency ultrasonography. Arterial adaptations were investigated in the superficial femoral artery (SFA), the brachial artery (BA), and the carotid artery (CA). Mean SFA resting diameter was decreased from 6.57 mm (SD = 0.74 mm) at baseline to 5.77 mm (SD = 0.87 mm) at the end of the intervention ( P < 0.001), whereas SFA wall-to-lumen ratio, SFA BFrest, and SFA FMD remained unaffected throughout the study. The application of HEPHAISTOS had no effect on structure and function of the systemic control sites, the BA, and the CA. Our findings highlight the importance of muscular contractions for arterial diameter adaptations. Moreover, we propose that FMD and wall-to-lumen ratio are unaffected by ambulating with the HEPHAISTOS orthosis, which is suggestive of habitual acceleration profiles in the lower leg constituting an important stimulus for the maintenance of FMD and wall-to-lumen ratio.
Biomechanical interaction between the transverse carpal ligament and the thenar muscles
Authors: Shen Zhilei Liu , Li Zong-Ming
Published: December 2012

The transverse carpal ligament (TCL) serves as the origin of the thenar muscles and is integral to thenar muscle contraction anatomically and biomechanically. TCL hypertrophy has been observed in patients with carpal tunnel syndrome and is potentially caused by repetitive hand use. The purpose of this study was to investigate the biomechanical interaction between the TCL and the thenar muscles. Specifically, the morphological changes of the carpal arch, formed by the TCL, in response to thenar muscle contractions were examined during isometric tip pinch between the thumb and index finger. Ultrasound videos of the carpal tunnel were recorded from 13 healthy subjects and were synchronized with the forces measured by a pinch dynamometer. The thenar muscles' ulnar point, trapezium, and hamate were tracked by a pattern-matching program. The pinch force significantly affected the carpal arch height, width, and area ( P < 0.005). As the pinch force increased from 0 to 100% maximum voluntary contraction force, the carpal arch height increased from 1.8 ± 1.0 to 2.3 ± 1.3 mm, the carpal arch width decreased from 23.9 ± 2.4 to 23.1 ± 2.4 mm, and the carpal arch area increased from 22.2 ± 13.6 to 27.3 ± 16.3 mm2. The TCL was pulled volarly during thenar muscle contractions, providing evidence for the biomechanical interaction between the ligament and muscles. Repetitive biomechanical stimulation on the TCL from thenar muscle contractions could lead to tissue remodeling and then TCL hypertrophy. This study sheds light on the potential cause of TCL hypertrophy, which may be an etiological factor for carpal tunnel syndrome.
A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non–Small Cell Lung Cancer with a KRAS Mutation
Authors: Dingemans Anne-Marie C. , Mellema Wouter W. , Groen Harry J.M. , van Wijk Atie , Burgers Sjaak A. , Kunst Peter W.A. , Thunnissen Erik , Heideman Danielle A.M. , Smit Egbert F.
Published: December 2012

Purpose: Sorafenib inhibits the Ras/Raf pathway, which is overactive in cancer patients with a KRAS mutation. We hypothesized that patients with non–small cell lung cancer (NSCLC) with KRAS mutation will benefit from treatment with sorafenib.

Experimental Design: In this phase II study, patients with KRAS-mutated, stage IIIb or IV NSCLC that progressed after at least one platinum-containing regimen were treated with sorafenib. Treatment consisted of sorafenib 400 mg twice daily until disease progression or unacceptable toxicity. Pretreatment serum from each patient was obtained to predict outcome using a proteomic assay (VeriStrat). Primary endpoint was disease control rate (DCR) at 6 weeks.

Results: Fifty-nine patients were entered between May 2010 and February 2011. Fifty-seven patients started sorafenib. Mean age was 58.5 (SD = ±8.1) years, 16 male/41 female, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0/1/2 24/30/3. At 6 weeks, 5 partial response, 25 stable disease, and 27 progressive disease were observed; DCR was 52.6%. Median duration of treatment was 9 weeks. The median progression-free survival (PFS) was 2.3 months and median overall survival (OS) was 5.3 months. Patients with a prediction of good prognosis according to VeriStrat serum proteomics assay showed a significantly superior PFS [HR, 1.4; 95% confidence interval (CI), 1.0–1.9] but not OS (HR, 1.3; 95% CI, 0.9–1.7). Sorafenib-related grade III/IV toxicity was reported in 10 patients (17.5%); all but one patient experienced grade III skin toxicity (14.0%) or grade III gastrointestinal toxicity (8.8%).

Conclusion: Treatment with sorafenib has relevant clinical activity in patients with NSCLC harboring KRAS mutations. Further randomized study with this agent is warranted as single-agent or combination therapy. Clin Cancer Res; 19(3); 743–51. ©2012 AACR.
Clinical and Safety Profile of High-Dose Interleukin-2 Treatment in Elderly Patients with Metastatic Melanoma and Renal Cell Carcinoma
Authors: Clark James M. , Kelley Benjamin , Titze Jill , Fung Henry , Maciejewski John , Nathan Sunita , Rich Elizabeth , Basu Sanjib , Kaufman Howard L.
Published: December 2012

Objective: High-dose interleukin-2 (IL-2) is effective immunotherapy for the treatment of metastatic melanoma and renal cell carcinoma (RCC) but has been contraindicated in elderly patients. This study assessed the safety and therapeutic efficacy of high-dose IL-2 in patients ≥65 years of age with metastatic melanoma and RCC. Methods: A prospectively collected clinical database of 104 consecutive melanoma or RCC patients treated with high-dose IL-2 between 2009 and 2012 was used to compare clinical outcomes and adverse events in patients ≥65 years of age with those of younger patients. Results: There were 22 (21%) patients ≥65 years and 82 (79%) patients <65 years of age. The mean number of IL-2 doses was lower in older patients during cycle 1 of treatment (7.2 vs. 8.6, p = 0.012). There were no other differences in dosing pattern by age group. There was a higher rate of selected cardiac, constitutional, hematologic, metabolic and renal toxicities in younger patients (p < 0.05). Overall, objective responses and survival were not affected by age, though older patients had a higher partial response rate (p = 0.04). Conclusions: IL-2 is safe and has comparable therapeutic effectiveness in patients ≥65 years. Age should not be considered a contraindication to treatment with IL-2 in otherwise eligible patients.
Downregulation of CDH13 Expression Promotes Invasiveness of Bladder Transitional Cell Carcinoma
Authors: Lin Ying-Li , He Zheng-Kai , Li Zhi-Gang , Guan Tong-Yu
Published: December 2012

Objective: To investigate the association of downregulated CDH13 expression with invasiveness of bladder transitional cell carcinoma (TCC). Materials and Methods: CDH13 and matrix metalloproteinase-2 (MMP2) expression was detected in 23 normal bladder epithelial tissues and 71 bladder TCC tissues. RNA interference was used to inhibit CDH13 expression in bladder TCC 5637 cells and then analyzed its effects on migration, invasion, adhesion, and proliferation of 5637 cells, as well as MMP2 expression in 5637 cells. Results: The CDH13 expression in bladder TCC tissues was significantly lower than that in normal bladder epithelial tissues. Moreover, the expression of CDH13 from the muscle-invasive group was significantly lower than that from the non-muscle-invasive group. In addition, the MMP2 expression was increased in bladder TCC, especially in muscle-invasive tumors. After the transfection of CDH13 siRNA into 5637 cells, CDH13 expression was significantly decreased, and the migration, invasion, adhesion of 5637 cells, as well as MMP2 expression in 5637 cells was significantly promoted compared with blank and negative controls. Conclusions: Downregulated expression of CDH13 is associated with increased invasion of bladder TCC, and may be due to the enhancement of cell-extracellular matrix adhesion and increased MMP2 expression.
Aquaglyceroporin-7 Overexpression in Women with the Polycystic Ovary Syndrome
Authors: Seow Kok-Min , Lin Yu-Hung , Wang Peng-Hui , Hwang Jiann-Loung , Ho Low-Tone , Juan Chi-Chang
Published: December 2012

Background: Aquaglyceroporin-7 (AQP7) is an adipose glycerol channel protein that has been suggested to be involved in whole-body glucose homeostasis and insulin sensitivity. The aim of this study was to investigate the expression of AQP7 in visceral adipose tissues from women with the polycystic ovary syndrome (PCOS). Methods:AQP7 mRNA and protein levels were measured in omental adipose tissue from 5 women with the PCOS and 4 healthy controls matched for body mass index and age; this was done by the real-time polymerase chain reaction (PCR) and Western blotting. -Results: The women with the PCOS had significantly higher homeostasis model insulin resistance indices (HOMAIR) and their quantitative insulin sensitivity check indices were significantly lower compared to the controls (p < 0.05). No significant difference was noted between the two groups for the plasma glycerol concentration. AQP7 mRNA expression and protein levels in omental adipose tissue from women with the PCOS were significantly higher than those of the controls (p = 0.007). AQP7 expression showed a positive correlation with fasting insulin levels, insulin levels at 2 h after glucose loading and HOMAIR in women with the PCOS. Conclusion:AQP7 overexpression may be related to insulin sensitivity and glucose homeostasis in women with the PCOS.
Quantitative Determination of Lattice Fluoride Effects on the Solubility and Crystallinity of Carbonated Apatites with Incorporated Fluoride
Authors: Yan G. , Moribe K. , Otsuka M. , Papangkorn K. , Higuchi W.I.
Published: December 2012

The purpose of this study was to evaluate quantitatively the effects of fluoride on the solubility and crystallinity of carbonated apatites (CAPs) after its incorporation into the crystal lattice using the metastable equilibrium solubility (MES) distribution method. Fluoride-incorporated CAPs (F-CAPs) of two different carbonate levels (3 and 5%) and fluoride contents from 0 to 20,000 µg/g were synthesized. X-ray diffraction experiments and Rietveld analysis were conducted to obtain crystallite microstrain and unit cell parameters. Acetate buffer MES solution media were prepared at two solution fluoride concentrations (0.2 and 2.0 mg/l) and at two pHs (5.0 and 5.7). The unit cell a-axis values of the F-CAPs were found to decrease as the fluoride content increased, consistent with the fluoride being incorporated into the crystal lattice. The fluoride concentrations in the MES solution media were high enough to provide a ‘swamping’ effect such that the fluoride released from the F-CAPs during dissolution was minimal in changing the solution fluoride concentration. Employing the MES distribution superposition method, it was shown that the surface complex possessing the fluorapatite (FAP) stoichiometry [Ca10(PO4)6F2] accounted for the MES distribution behavior of all experiments. In addition, the mean pIFAP [the value of –log(aCa10aPO46aF2) calculated from the ionic activity product based on FAP stoichiometry of the MES dissolution media in which 50% of the F-CAPs had dissolved] correlated well with the crystallite microstrain parameters of the F-CAPs. The incorporated fluoride in the F-CAPs showed only modest effects on F-CAP crystallinity and solubility.
Different Protocols to Produce Artificial Dentine Carious Lesions in vitro and in situ: Hardness and Mineral Content Correlation
Authors: Moron B.M. , Comar L.P. , Wiegand A. , Buchalla W. , Yu H. , Buzalaf M.A.R. , Magalhães A.C.
Published: December 2012

This study compared dentine demineralization induced by in vitro and in situ models, and correlated dentine surface hardness (SH), cross-sectional hardness (CSH) and mineral content by transverse microradiography (TMR). Bovine dentine specimens (n = 15/group) were demineralized in vitro with the following: MC gel (6% carboxymethylcellulose gel and 0.1 m lactic acid, pH 5.0, 14 days); buffer I (0.05 m acetic acid solution with calcium, phosphate and fluoride, pH 4.5, 7 days); buffer II (0.05 m acetic acid solution with calcium and phosphate, pH 5.0, 7 days), and TEMDP (0.05 m lactic acid with calcium, phosphate and tetraethyl methyl diphosphonate, pH 5.0, 7 days). In an in situ study, 11 volunteers wore palatal appliances containing 2 bovine dentine specimens, protected with a plastic mesh to allow biofilm development. The volunteers dripped a 20% sucrose solution on each specimen 4 times a day for 14 days. In vitro and in situ lesions were analyzed using TMR and statistically compared by ANOVA. TMR and CSH/SH were submitted to regression and correlation analysis (p < 0.05). The in situ model produced a deep lesion with a high R value, but with a thin surface layer. Regarding the in vitro models, MC gel produced only a shallow lesion, while buffers I and II as well as TEMDP induced a pronounced subsurface lesion with deep demineralization. The relationship between CSH and TMR was weak and not linear. The artificial dentine carious lesions induced by the different models differed significantly, which in turn might influence further de- and remineralization processes. Hardness analysis should not be interpreted with respect to dentine mineral loss.
An Improved Method of Renal Tissue Engineering, by Combining Renal Dissociation and Reaggregation with a Low-Volume Culture Technique, Results in Development of Engineered Kidneys Complete with Loops of Henle
Authors: Chang C-Hong , Davies Jamie A.
Published: December 2012

Background: Tissue engineering of functional kidney tissue is an important goal for clinical restoration of renal function in patients damaged by infectious, toxicological, or genetic disease. One promising approach is the use of the self-organizing abilities of embryonic kidney cells to arrange themselves, from a simply reaggregated cell suspension, into engineered organs similar to fetal kidneys. The previous state-of-the-art method for this results in the formation of a branched collecting duct tree, immature nephrons (S-shaped bodies) beside and connected to it, and supportive stroma. It does not, though, result in the significant formation of morphologically detectable loops of Henle – anatomical features of the nephron that are critical to physiological function. Methods: We have combined the best existing technique for renal tissue engineering from cell suspensions with a low-volume culture technique that allows intact kidney rudiments to make loops of Henle to test whether engineered kidneys can produce these loops. Results: The result is the formation of loops of Henle in engineered cultured ‘fetal kidneys’, very similar in both morphology and in number to those formed by intact organ rudiments. Conclusion: This brings the engineering technique one important step closer to production of a fully realistic organ.