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Overactivation of the mineralocorticoid receptor (MR) is involved in many diseases, such as hypertension, kidney disease, and heart failure. Thus, MR antagonists (MRAs) are expected to be beneficial to patients with these diseases. In order to identify novel nonsteroidal MRAs that overcome the issues of already marketed steroidal MRAs, we searched for new compounds guided by our hypothesis that T-shaped compounds with a hydrophobic core structure, two polar functional groups at both extremities able to interact with MR, and a bulky substituent that can interfere with the folding of the C-terminal helix 12 may exhibit antagonist activity toward MR. We discovered that the novel 1,4-benzoxazin-3-one derivative

Companion animals are in close contact with the human surroundings, and there is growing concern about the effects of harmful substances on the health of pet cats. In this study, we investigated the potential health effects of organohalogen compounds (OHCs) on thyroid hormone (TH) homeostasis and metabolomics in Japanese pet cats. There was a significant negative correlation between concentrations of several contaminants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hydroxylated PCBs (OH-PCBs), hydroxylated PBDEs (OH-PBDEs), and THs in cat serum samples. These results suggested that exposure to OHCs causes a decrease in serum TH levels in pet cats. In this metabolomics study, each exposure level of parent compounds (PCBs and PBDEs) and their hydroxylated compounds (OH-PCBs and OH-PBDEs) were associated with their own unique primary metabolic pathways, suggesting that parent and phenolic compounds exhibit different mechanisms of action and biological effects. PCBs were associated with many metabolic pathways, including glutathione and purine metabolism, and the effects were replicated in in-vivo cat PCB administration studies. These results demonstrated that OHC exposure causes chronic oxidative stress in pet cats. PBDEs were positively associated with alanine, aspartate, and glutamate metabolism. Due to the chronic exposure of cats to mixtures of these contaminants, the combination of their respective metabolic pathways may have a synergistic effect.

Background: This is the third of a series of papers on baryon-baryon (BB) interactions, where the baryons are the lowest lying baryon states with spin and parity ${J}^{P}={(1/2)}^{+}$. The paper presents the extended-soft-core (ESC) model ESC16 for BB channels with strangeness $S=\ensuremath{-}2$.Purpose: The aim is to describe the ingredients of the $S=\ensuremath{-}2$ ESC16 potentials, to apply these two-body interactions to BB scattering and via $G$-matrix calculations to hypernuclear systems, and to compare with the presently available experimental information.Methods:The potentials for $S=\ensuremath{-}2$ are based on the SU(3) extension of the ESC potentials for the strangeness $S=0$ and $S=\ensuremath{-}1$ sectors, which are fitted to experimental nucleon-nucleon ($NN$), hyperon-nucleon ($YN$), and hyperon-hyperon ($YY$) data. Flavor SU(3) symmetry is broken only `kinematically' by the masses of the baryons and the mesons. For the $S=\ensuremath{-}2$ channels almost no experimental scattering data exist, and the information from hypernuclei is also rather limited. Nevertheless, in the fit to the $S=0$ and $S=\ensuremath{-}1$ sectors information from the Nagara event and the scarce experimental results on the $\mathrm{\ensuremath{\Xi}}N$ cross sections have been used as (mild) constraints to determine the free parameters in the simultaneous fit of the deuteron and the $NN\ensuremath{\bigoplus}YN$ scattering data. Therefore, the potentials for the $S=\ensuremath{-}2$ sectors are almost completely determined by the fits to the $NN, YN$ data, and SU(3) symmetry.Results: Various properties of the $S=\ensuremath{-}2$ potentials are illustrated by giving results for scattering lengths, bound states, phase parameters, and total cross sections. The well-depth ${U}_{\mathrm{\ensuremath{\Xi}}}$ is calculated and $\mathrm{\ensuremath{\Xi}}N G$-matrix interactions are derived and applied to ${\mathrm{\ensuremath{\Xi}}}^{\ensuremath{-}}$-capture reactions. Here, a phenomenological $\mathrm{\ensuremath{\Xi}}N$ interaction is added to describe the experiments. Furthermore, the ESC16 model supplemented with phenomenological SU(3) symmetric gaussian interactions is analyzed, and attractive $\mathrm{\ensuremath{\Xi}}N$ interactions are obtained. Combined with three-body forces derived from the ESC meson-pair vertices and the Fujita-Miyazawa interaction, yields good baryon well depths.Conclusions: The ESC16 $S=\ensuremath{-}2$ potentials, with kinematically broken SU(3) symmetry, provide a basis for realistic calculations in nuclear and hypernuclear physics. For a successful description of the well depth's ${U}_{N},{U}_{\mathrm{\ensuremath{\Lambda}}},{U}_{\mathrm{\ensuremath{\Sigma}}}$, and ${U}_{\mathrm{\ensuremath{\Xi}}}$ and hypernuclear $S=\ensuremath{-}2$ reactions phenomenological additions are needed.

Background Sensory nerves regulate cutaneous local inflammation indirectly through induction of pruritus and directly by acting on local immune cells. The underlying mechanisms for how sensory nerves influence cutaneous acquired immune responses remain to be clarified. Objective This study aimed to explore the effect of peripheral nerves on cutaneous immune cells in cutaneous acquired immune responses. Methods We analyzed contact hypersensitivity (CHS) responses as a murine model of delayed-type hypersensitivity in absence or presence of resiniferatoxin-induced sensory nerve denervation. We conducted ear thickness measurements, flow cytometric analyses, and mRNA expression analyses in CHS. Results CHS responses were attenuated in mice that were denervated during the sensitization phase of CHS. By screening neuropeptides, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA expression was decreased in the dorsal root ganglia after denervation. Administration of PACAP restored attenuated CHS response in resiniferatoxin-treated mice, and pharmacological inhibition of PACAP suppressed CHS. Flow cytometric analysis of skin-draining lymph nodes showed that cutaneous dendritic cell migration and maturation were reduced in both denervated mice and PACAP antagonist-treated mice. The expression of chemokine receptors CCR7 and CXCR4 of dendritic cell s was enhanced by addition of PACAP in vitro. Conclusion These findings indicate that a neuropeptide PACAP promotes the development of CHS responses by inducing cutaneous dendritic cell functions during the sensitization phase.

Experimental evidence exists that the Ξ-nucleus interaction is attractive. We search for NNΞ and NNNΞ bound systems on the basis of the AV8 NN potential combined with either a phenomenological Nijmegen ΞN potential or a first principles HAL QCD ΞN potential. The binding energies of the three-body and four-body systems (below the d+Ξ and ^{3}H/^{3}He+Ξ thresholds, respectively) are calculated by a high precision variational approach, the Gaussian expansion method. Although the two ΞN potentials have significantly different isospin (T) and spin (S) dependence, the NNNΞ system with quantum numbers (T=0, J^{π}=1^{+}) appears to be bound (one deep for Nijmegen and one shallow for HAL QCD) below the ^{3}H/^{3}He+Ξ threshold. Experimental implications for such a state are discussed.

Thyroid hormones (THs), which mainly consist of 3, 3', 5-triiodo-l-thyronine (T3) and L-thyroxine (T4), play a critical role in regulating biological processes such as growth and metabolism in various animal species. Thus, accurate measurement of T3 and T4, especially physiologically active free (protein-unbound) forms, in serum/plasma is needed for the evaluation of TH homeostasis. However, such high-precision determination of free THs is lacking for non-human species. The present study aimed to develop a highly sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of six free THs in serum/plasma, which is applicable to not only humans but also non-human species. Two different physical separation steps, ultrafiltration (UF) and equilibrium dialysis (ED), were examined to obtain the free TH fraction. Several experimental conditions were carefully optimized and validated for UF or ED using the commercially available bovine serum. As a result, UF at 1100 × g and 37 °C for 30 min with a 30 kDa ultrafiltration device (Centrifree YM-30, Millipore) yielded excellent precision (CV:10%). The optimized ED step also yielded high precision (CV:10%) and the measurement values were approximately equal to those of UF, but at least 16 h were required to reach equilibrium. Thus, UF combined with LC-MS/MS was finally chosen, in terms of the time needed for the measurement. Acceptable accuracy (recovery: 70%-110%) and intra- and inter-day precision (CV:10% and12%, respectively) were obtained, when triplicate analyses in three different days were conducted using the bovine serum. The developed analytical method was successfully applied to the determination of free THs in serum/plasma samples of humans, cats, and dogs. Furthermore, comparison with free T4 concentrations measured by a common immunoassay method evidently indicated that the ultrafiltration-LC-MS/MS method developed in this study can increase the specificity and accuracy of TH measurement.

The J-PARC Hadron Experimental Facility was constructed with an aim to explore the origin and evolution of matter in the universe through experiments with intense particle beams. In the past decade, many results from particle and nuclear physics experiments have been obtained at the present facility. To expand the physics programs to as yet unexplored regions, the extension project of the Hadron Experimental Facility has been extensively discussed. This contribution presents the physics of the extension of the Hadron Experimental Facility to resolve issues related to strangeness nuclear physics, hadron physics, and flavor physics.

$\Lambda N$ spin-spin and spin-orbit splittings in low-lying excitation spectra are investigated for $p$-shell $\Lambda$ hypernuclei on the basis of the microscopic structure calculation within the antisymmetrized molecular dynamics, where the $\Lambda N$ $G$-matrix interaction derived from the baryon-baryon interaction model ESC (extended soft core) is used. It is found that the ground-state spin-parity is systematically reproduced in the $p$-shell $\Lambda$ hypernuclei by tuning the $\Lambda N$ spin-spin and spin-orbit interactions so as to reproduce the experimental data of $^{4}_\Lambda$H, $^{7}_\Lambda$Li and $^9_\Lambda$Be. Furthermore, we also focus on the excitation energies of the excited doublets as well as the energy shifts of them by the addition of a $\Lambda$ particle.

Some previously reported surface acoustic wave (SAW) devices using bulk piezoelectric substrates showed higher acoustic power radiated in either forward or backward wave propagation direction depending on their crystal orientations and are called natural single-phase unidirectional transducers (NSPUDT). While these reports were based on bulk piezoelectric substrates, we report directionality in the c-axis tilted 44% scandium doped aluminum nitride thin piezoelectric film-based SAW devices on sapphire. It is worth noting that our observance of directionality is specifically in Sezawa mode. We produced a c-axis tilt up to 5.5° over the single wafer and examined the directionality by comparing the forward and backward insertion loss utilizing split finger electrodes as a receiver. The wave propagation direction and c-axis tilt angle influence on the performance of SAW devices is evaluated. Furthermore, return loss and insertion loss data are presented for various SAW propagation directions and c-axis tilt angles. Finally, the comparison for both acoustic modes, i.e., Rayleigh and Sezawa, is reported.

This hyperon-nucleon paper is part of a simultaneous treatment of all baryon-baryon systems: $N\phantom{\rule{0}{0ex}}N$, $Y\phantom{\rule{0}{0ex}}N$, and $Y\phantom{\rule{0}{0ex}}Y$. Utilizing a meson-exchange potential approach, all $8\ifmmode\times\else\texttimes\fi{}8$ baryon-baryon channels are described in a model with SU(3)-symmetric couplings consistent with the constituent quark model. A high-quality fit is achieved for the $N\phantom{\rule{0}{0ex}}N$ data (${T}_{\text{Lab}}l350$ MeV) and the available $p$-$\mathrm{\ensuremath{\Lambda}}$ and $p$-$\mathrm{\ensuremath{\Sigma}}$ data.

The Nijmegen extended-soft-core ESC08c model for the baryon-baryon (BB) interactions of the SU(3) flavor-octet of baryons (N, �, �, and �) is presented. In this first of a series of papers, the NN results are reported in detail. In the spirit of the Yukawa-approach to the nuclear force problem, the interactions are studied from the meson-exchange picture viewpoint, using generalized soft-core Yukawa-functions. These interactions are supplemented with (i) multiple-gluonexchange, and (ii) structural effects due to the quark-core of the baryons. The extended-soft-core (ESC) meson-exchange interactions consist of local- and non-local-potentials due to (i) One-bosonexchanges (OBE), which are the members of nonets of pseudoscalar, vector, scalar, and axial-vector mesons, (ii) diffractive (i.e. multiple-gluon) exchanges, (iii) two pseudo-scalar exchange (PS-PS), and (iv) meson-pair-exchange (MPE). The OBE- and MPE-vertices are regulated by gaussian form factors producing potentials with a soft behavior near the origin. The assignment of the cut-off masses for the BBM-vertices is dependent on the SU(3)-classification of the exchanged mesons for OBE, and a similar scheme for MPE. The ESC-models ESC08, as well as its predecessor ESC04, describe the nucleon-nucleon (NN), hyperon-nucleon (YN), and hyperon-hyperon (YY) interactions in a unified way using broken SU(3)symmetry. Important non-standard ingredients in the OBE-sector in the ESC-models are (i) the axial-vector meson potentials, and (ii) a zero in the scalar- and axial-vector meson form factors. These innovations make it possible to keep the meson coupling parameters of the model qualitatively in accordance with the predictions of the 3 P0-dominated quark-antiquark pair creation (QPC) model. SU(3)-symmetry serves to connect the NN with the Y N and the Y Y channels. In the fit to NN and YN many parameters are essentially fixed by the NN-data. A few, but severely constrained e.g. F/(F + D)-ratio’s, parameters are left for determination of the Y N-interactions and the Y Y experimental indications. In particular, the meson-baryon coupling constants are calculated via SU(3) using the coupling constants of the NN ⊕Y N-analysis as input. In ESC08 the couplings are kept SU(3)-symmetric. In establishing the parameters of the model a simultaneous fit to NN- and YN-channels has been performed. Here the information about ��, �N, and hypernuclei played an important role in the form of using constraints. In particular, the experimental indications for the ��-attraction, the �-nuclear and the �-nuclear well-depth were directive. About 25 physical coupling parameters and 8 cut-off and diffractive masses, were searched. The obtained OBE-couplings and the F/(F + D)ratio’s can be well understood in the context of the QPC-model. The simultaneous fit of the ESC-models to the NN- and YN- scattering data with a single set of parameters has achieved excellent results for the NN- and YN-data, and for the YY-data in

The most recent Nijmegen extended-soft-core ESC16 model for the baryon-baryon (BB) interactions of the SU(3) flavor-octet of baryons (N, Λ, Σ, and Ξ) is presented. The ESC model ESC16, as well as its predecessors ESC08 and ESC04, describe the nucleon-nucleon (NN), hyperon-nucleon (YN), and hyperon-hyperon (YY) interactions in a unified way using broken SU(3) symmetry. In this paper we outline the differences between ESC16 and ESC08c.The parameters of the ESC models are established in a simultaneous fit to the NN and YN data, taking into account information about ΛΛ, ΞN, and Λ-hypernuclei in the form of constraints. In particular, the experimental indications for ΛΛ-attraction, Ξ-nuclear and Σ-nuclear well-depth were taken into account as much as possible. About 25 physical coupling parameters and 8 cut-off and diffractive masses, were searched. The obtained OBE-couplings and the F/(F+D) ratios can be well understood in the context of the quark-antiquark pair creation (QPC) mechanism.The fit of the ESC-models to the NN- and YN- scattering data with a single set of parameters has achieved excellent results for the NN and YN data, and for the YY data in accordance with the experimental indications for ΛΛ. In the case of the most recent ESC model, called ESC16, the achievements are: (i) For the selected 4313 pp and np scattering data with energies 0 ≤ Tlab ≤ 350 MeV, the model reaches a fit having χ2/Ndata = 1.10. (ii) The deuteron binding energy and all of the NN scattering lengths are fitted very nicely. (iii) The YN data are described very well with χ2 /Ndata = 1.11, giving at the same time good descriptions of the Λ, Σ, and Ξ nuclear well-depths. (iv) The model has no bound states for S = −1,−2,−3,−4. (v) The nuclear saturation, and well-depths UΣ, UΞ require important contributions from three-body forces.The most recent Nijmegen extended-soft-core ESC16 model for the baryon-baryon (BB) interactions of the SU(3) flavor-octet of baryons (N, Λ, Σ, and Ξ) is presented. The ESC model ESC16, as well as its predecessors ESC08 and ESC04, describe the nucleon-nucleon (NN), hyperon-nucleon (YN), and hyperon-hyperon (YY) interactions in a unified way using broken SU(3) symmetry. In this paper we outline the differences between ESC16 and ESC08c.The parameters of the ESC models are established in a simultaneous fit to the NN and YN data, taking into account information about ΛΛ, ΞN, and Λ-hypernuclei in the form of constraints. In particular, the experimental indications for ΛΛ-attraction, Ξ-nuclear and Σ-nuclear well-depth were taken into account as much as possible. About 25 physical coupling parameters and 8 cut-off and diffractive masses, were searched. The obtained OBE-couplings and the F/(F+D) ratios can be well understood in the context of the quark-antiquark pair creation (QPC) mechanism.The fit of the ESC-mod...

Epidermal keratinocytes achieve sequential differentiation from basal to granular layers, and undergo a specific programmed cell death, cornification, to form an indispensable barrier of the body. Although elevation of the cytoplasmic calcium ion concentration ([Ca2+]i) is one of the factors predicted to regulate cornification, the dynamics of [Ca2+]i in epidermal keratinocytes is largely unknown. Here using intravital imaging, we captured the dynamics of [Ca2+]i in mouse skin. [Ca2+]i was elevated in basal cells on the second time scale in three spatiotemporally distinct patterns. The transient elevation of [Ca2+]i also occurred at the most apical granular layer at a single cell level, and lasted for approximately 40 min. The transient elevation of [Ca2+]i at the granular layer was followed by cornification, which was completed within 10 min. This study demonstrates the tightly regulated elevation of [Ca2+]i preceding the cornification of epidermal keratinocytes, providing possible clues to the mechanisms of cornification.

The extended-soft-core model ESC08 is presented. The ESC-models are at present the most complete meson-exchange models for the baryon–baryon interactions. The ESC-model describes the nucleon–nucleon (NN), hyperon–nucleon (YN), and hyperon–hyperon (YY), in terms of meson-exchanges using (broken) SU(3)f-symmetry. In this approach to baryon-baryon (BB) the dynamics is derived from (i) one-boson-exchanges (OBE), (ii) two-meson-exchanges (TME), and (iii) meson-pair-exchanges (MPE), (iv) gluon-exchanges in the form of the pomeron and odderon potentials, and (v) quark-core effects. In the OBE-sector, special features are: (a) the inclusion of a zero in the scalar- and axial- meson form-factors, (b) the odderon-exchage representing the exchange of the odd-number gluons-exchange, whereas the pomeron represents the even-number gluon-exchange, and (c) special pronounced effects of the appearance of forbidden six-quark configurations. With these ingredients a rather flexible dynamical framework is constructed. Namely, it appeared feasible to keep the parameters of the model in reasonable accordance with the predictions of the ^3P_0 quark-pair-creation model (QPC), although in ESC08a,b,c an admixture of ^3S_1 quark-pair creation is present. This is the case for the meson- and meson-pair-baryon coupling constants and the F/(F+D)-ratio’s as well. The NN, YN, and YY results for this model are excellent. This is marked in particularly by the NN-results, namely \(\chi _{p.d.p.}^{2} = 1.08\) for ESC08a,b,c. Also, we improved the ΛN spin–orbit interaction greatly by the inclusion of (a) the Brown, Downs, and Iddings anti-symmetric spin–orbit potentials, and (b) new corrections to the MPE-potentials. Also, the special quark-core effects provide extra repulsion in the Σ^+p(^3S_1, T = 3/2)- and ΣN(^1S_0, T = 1/2)-channels, although the strength is constrained by SU(3) symmetry and the Σ^+p experimental X-sections. In the S = −2 sector the ΛΛ-interaction is weak, which is in accordance with the NAGARA-event. Furthermore, in the ΞN(^3S_1, I = 1) there occurs a “strange-deuteron” D^* with binding-energy \(E_{B}^{*} \approx 2.0 - 1.5\) MeV. A very notable consequence of the MPE-vertices are the related three-body forces (TBF). In this conference we report on the predictions of these TBF’s for (i) the triton binding energy, and (ii) the charge-symmetry-breaking (CSB) effects. The first results are encouraging.

This paper reports, for the first time, the sensitivity deterioration phenomenon of surface acoustic wave (SAW) sensors for distortion, load, or pressure monitoring. Assuming that the acoustoelastic effect causes this phenomenon and that the effect can be characterized with two coefficients for stress components parallel and perpendicular to SAW propagation direction, we developed a method to quantify these coefficients. We found that the coefficient for the stress parallel to the propagation direction causes sensitivity deterioration for Sc doped AlN (ScAlN) film on 6H-silicon carbide (6H-SiC) substrate structures. This result also indicates the possibility of effectively improving the sensitivity by taking advantage of the effect.

The angular distributions of differential cross sections of $^{12}\mathrm{C}+^{12}\mathrm{C}$ elastic and inelastic scattering populating the ground and excited states in $^{12}\mathrm{C}$ up to 15 MeV excitation energy are precisely measured for the first time at an incident energy of $100A$ MeV to study the effect of repulsive three-body forces. Using the high-resolution spectrometer Grand Raiden at the Research Center for Nuclear Physics (RCNP), Osaka University, we have obtained the differential cross sections for the ground state (${0}_{1}^{+}$) and 4.44 MeV (${2}_{1}^{+}$) excited state, as well as the summed differential cross sections for the states between 4.44 and 15 MeV in the angular range of $1.{0}^{\ensuremath{\circ}}--7.{5}^{\ensuremath{\circ}}$. The results are compared with microscopic coupled-channel calculations. The potential between the colliding nuclei is determined by the double folding method with three different complex $G$-matrix interactions, the ESC, CEG07b, and MPa interactions. The CEG07b and MPa interactions, which include repulsive three-body forces, describe the data well, whereas the ESC interaction, which does not include repulsive three-body forces, fails to reproduce the data. The results provide evidence of repulsive three-body forces in $^{12}\mathrm{C}$ and demonstrate the possible sensitivity of elastic scattering to three-body forces.

Janus kinases (JAKs) are required for several inflammatory cytokine signalling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis. JTE-052 inhibited the Th1-, Th2- and Th17-type inflammatory responses of human T cells and mast cells in vitro. Oral administration of JTE-052 inhibited skin inflammation in hapten-induced chronic dermatitis in mice, associated with reduced levels of inflammatory cytokines in the skin and immunoglobulin (Ig) E in serum. In contrast, although ciclosporin partly inhibited skin inflammation, it did not reduce interleukin (IL)-4 production in skin, and enhanced IgE production in serum. Oral administration of JTE-052 also inhibited skin inflammation in mouse models of atopic dermatitis and psoriasis induced by a mite extract, thymic stromal lymphopoietin or IL-23. The maximal efficacy of JTE-052 in these dermatitis models was superior to the conventional therapeutic agents, ciclosporin and methotrexate. Topical application of JTE-052 ointment ameliorated hapten-induced chronic dermatitis in rats more effectively than tacrolimus ointment. Furthermore, JTE-052 ointment did not cause the thinning of normal skin associated with topical corticosteroids. These results indicate that JTE-052 is a promising candidate as an anti-inflammatory drug for various types of chronic dermatitis, with a distinctly different profile from conventional therapy following either oral or topical application.

We have investigated the excitation-power dependence of polarization-entangled photon pairs generated from a CuCl single crystal using biexciton resonant hyper-parametric scattering. The two-photon polarization density matrix of photon pairs generated from a CuCl single crystal maintained at 10 K was measured under different excitation powers. The measured two-photon polarization density matrix, which corresponds to the two-photon polarization state, changes with an increase in the excitation power. The evaluations of the tangle and the linear entropy obtained from the measured density matrix indicate that the two-photon polarization density matrix can be expressed as the mixed state of an ideal state and a totally mixed state, and the mixture ratio of the totally mixed state increases as the excitation density increases. The variations of the density matrix and the mixture ratio with the excitation power originate from the generation of the multiple photon pairs. Furthermore, a numerical calculation considering simultaneous detection efficiency was able to reproduce the experimental results.

We present a new architecture level unified reliability evaluation methodology for chip multiprocessors (CMPs). The proposed reliability estimation (REST) is based on a Monte Carlo algorithm. What distinguishes REST from the previous work is that both the computational and communication components are considered in a unified manner to compute the reliability of the CMP. We utilize REST tool to develop a new dynamic reliability management (DRM) scheme to address time-dependent dielectric breakdown and negative-bias temperature instability aging mechanisms in network-on-chip (NoC) based CMPs. Designed as a control loop, the proposed DRM scheme uses an effective neural network based reliability estimation module. The neural-network predictor is trained using the REST tool. We investigate how system's lifetime changes when the NoC as the communication unit of the CMP is considered or not during the reliability evaluation process and find that differences can be as high as 60%. Full-system based simulations using a customized GEM5 simulator show that reliability can be improved by up to 52% using the proposed DRM scheme in a best-effort scenario with 2-9% performance penalty (using a user set target lifetime of 7years) over the case when no DRM is employed.

The structure of heavy hyperhydrogen 6 Λ H is studied within the framework of a t n n Λ four-body cluster model. Interactions among the constituent subunits are determined so as to reproduce reasonably well the observed low energy properties of the t n , t Λ and tnn subsystems. As long as we reproduce the energy and width of 5 H within the error bar, the ground state of 6 Λ H is obtained as a resonant state.

The G-matrices are derived on the basis of meson-theoretical hyperon-nucleon and hyperon-hyperon potentials from the Nijmegen group (model-D. model-F. soft-core model) and the Jiilich group (version-A, version-B). In order to make easy applications to hypernu· clei, they are parametrized to express in terms of three· range Gaussian radial functions with the density dependence being in the quadratic form of the Fermi momentum. Through the structure calculations of A-, 1:-, AAand ,S-hypernuclei, properties of these G-matrix interactions have been investigated in the AN, l:N, AA and EN channels, respectively.

The stiff equation of state (EoS) giving the neutron-star mass of $2{M}_{\ensuremath{\bigodot}}$ suggests the existence of strongly repulsive many-body effects (MBE) not only in nucleon channels but also in hyperonic ones. As a specific model for MBE, the repulsive multi-Pomeron exchange potential (MPP) is added to the two-body interaction together with the phenomenological three-body attraction. For various versions of the Nijmegen interaction models, the MBE parts are determined so as to reproduce the observed data of ${B}_{\mathrm{\ensuremath{\Lambda}}}$. The mass dependence of ${B}_{\mathrm{\ensuremath{\Lambda}}}$ values is shown to be reproduced well by adding MBE to the strong MPP repulsion, assuring the stiff EoS of hyperon-mixed neutron-star matter, in which $P$-state components of the adopted interaction model lead to almost vanishing contributions. The nuclear matter $\mathrm{\ensuremath{\Lambda}}N\phantom{\rule{4pt}{0ex}}G$-matrix interactions are derived and used in $\mathrm{\ensuremath{\Lambda}}$ hypernuclei on the basis of the averaged-density approximation (ADA). The ${B}_{\mathrm{\ensuremath{\Lambda}}}$ values of hypernuclei with $9\ensuremath{\le}A\ensuremath{\le}59$ are analyzed in the framework of antisymmetrized molecular dynamics with use of the two types of $\mathrm{\ensuremath{\Lambda}}N\phantom{\rule{4pt}{0ex}}G$-matrix interactions including strong and weak MPP repulsions. The calculated values of ${B}_{\mathrm{\ensuremath{\Lambda}}}$ reproduce the experimental data well within a few hundred keV. The values of ${B}_{\mathrm{\ensuremath{\Lambda}}}$ in $p$ states also can be reproduced well, when the ADA is modified to be suitable also for weakly bound $\mathrm{\ensuremath{\Lambda}}$ states.

The existence of neutron stars with $2M_\odot$ requires the strong stiffness of the equation of state (EoS) of neutron-star matter. We introduce a multi-pomeron exchange potential (MPP) working universally among 3- and 4-baryons to stiffen the EoS. Its strength is restricted by analyzing the nucleus-nucleus scattering with the G-matrix folding model. The EoSs are derived using the Brueckner-Hartree-Fock (BHF) and the cluster variational method (CVM) with the nuclear interactions ESC and AV18. The mass-radius relations are derived by solving the Tolmann-Oppenheimer-Volkoff (TOV) equation, where the maximum masses over $2M_\odot$ are obtained on the basis of the terrestrial data. Neutron-star radii $R$ at a typical mass $1.5M_\odot$ are predicted to be $12.3\!\sim\!13.0$ km. The uncertainty of calculated radii is mainly from the ratio of 3- and 4-pomeron coupling constants, which cannot be fixed by any terrestrial experiment. Though values of $R(1.5M_\odot)$ are not influenced by hyperon-mixing effects, finely-observed values for them indicate degrees of EoS softening by hyperon mixing in the region of $M\!\sim\!2M_\odot$. If $R(1.5M_\odot)$ is less than about 12.4 km, the softening of EoS by hyperon mixing has to be weak. Useful information can be expected by the space mission NICER offering precise measurements for neutron-star radii within $\pm 5\%$., Comment: 8 pages, 7 figures

We review the extended-soft-core models ESC08, which at present are the most complete meson-exchange models for the baryon–baryon (BB) interactions. The ESC-model describes the nucleon–nucleon (NN), hyperon–nucleon (YN), and hyperon–hyperon (YY), in terms of meson-exchanges using (broken) SU(3,F)-symmetry. In this approach to baryon-baryon the dynamics is derived from (1) one-boson-exchanges (OBE), (2) two-meson-exchanges, and (3) meson-pair-exchanges, (4) multiple gluon-exchanges (MGE), and (5) quark-core effects. In the OBE-sector, special features are (a) the axial-vector meson potentials, and (b) the inclusion of a zero in the scalar- and axial- meson form-factors. Novel for the ESC08-versions is (a) the inclusion in MGE next to the pomeron the odderon-exchange, and (b) the analysis of possible (pronounced) effects of the appearance of forbidden six-quark configurations. With these ingredients a rather flexible dynamical model is constructed for the description of all BB-channels in the {8} × {8} SU(3,F)-representation. Namely, it appeared feasible to keep the meson coupling parameters of the model in accordance with the predictions of the quark-pair-creation model, with a clear dominance of the 3 P 0-mechanism. This is the case for the meson- and meson-pair-baryon coupling constants and the F/(F + D)-ratio’s as well. The NN, YN, and YY results for this model are excellent. This is marked in particular by the NN-results, namely $${\chi^2_{p.d.p.}}$$ = 1.180, 1.135, and 1.085 for, respectively, ESC08a, ESC08b, and ESC08c. These fits were achieved with partial-wave independent meson-coupling parameters in a combined fit of the $${NN \oplus YN}$$ -data, supplemented with information from G-matrix calculations of hypernuclei, e.g. $${B_\Lambda(^{6}_{\Lambda\Lambda}He)}$$ from the Nagara-event, and an attractive Ξ-nucleus interaction. The special quark-core effects provide ample repulsion in the Σ + p(3 S 1, T = 3/2)- and ΣN(1 S 0, T = 1/2)-channels, in particular for ESC08a,b. The well depths (U Λ , U Σ , U Ξ ) correspond rather well with expectations from hypernuclei. Here, in ESC08c a universal repulsion, which we derived from multiple pomeron-exchange, is necessary. This at the same time gives both a very satisfactory nuclear saturation point as well as a description of the neutron star matter in the presence of hyperons for all ESC08-models. The requirement of a sizable Ξ-nucleus attraction leads to the prediction of an S = −2 deuteron-state in ΞN(3 S 1, T = 1) with E B ≈ 8.3 MeV. Also possible/likely are similar bound states for Ξ N(3 S 1, T = 0), Λ Ξ, Σ Ξ(3 S 1, T = 1/2, 3/2), and Ξ Ξ(1 S 0, T = 1).

The synthesis and structure-activity relationship (SAR) of thiophene-C-glucosides have been explored, and the human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitory activities and rat urinary glucose excretion (UGE) effects of 3a-f were evaluated. As a result, they showed good hSGLT2 inhibitory activities and rat UGE effects. In particular, the chlorothiophene derivative 3f showed remarkable inhibitory activity against hSGLT2.

The features of the new interaction model ESC08c in \({\Lambda N}\), \({\Sigma N}\) and \({\Xi N}\) channels are demonstrated single hyperon potentials \({U_Y(Y=\Lambda, \Sigma, \Xi)}\) in nuclear matter on the basis of the G-matrix theory. (K−, K+) productions of \({\Xi}\) hypernuclei are studied with \({\Xi}\)-nucleus folding potentials.

We investigate the property of the high-density nuclear matter probed by the nucleus-nucleus elastic scattering in the framework of the double-folding (DF) model with the complex $G$-matrix interaction. The medium effect including three-body-force (TBF) effect is investigated with present two methods based on the frozen density approximation (FDA). The medium effect is clearly seen on the potential and the elastic cross section for the $^{16}$O + $^{16}$O system at $E/A =$ 70 MeV. The crucial role of the medium effect is also confirmed with other effective nucleon-nucleon ($NN$) interactions. In addition, the present methods are applied to other heavy-ion elastic scattering systems. Again, the medium effect is clearly seen in the heavy-ion elastic cross section. The medium effect on the elastic cross section becomes invisible with the increase of the target mass and the incident energy (up to $E/A =$ 200 MeV). However, the medium effect is again important to fix the heavy-ion scattering over $E/A =$ 200 MeV. Finally, we make clear the crucial role of the TBF effect up to $k_F =$ 1.6 fm$^{-1}$ in the nucleus-nucleus elastic scattering., 29 pages, 11 figures, accepted in Physical Review C. arXiv admin note: substantial text overlap with arXiv:1406.3718

Classic glucocorticoids that have outstanding anti-inflammatory effects are still widely prescribed for the treatment of various inflammatory and autoimmune diseases. Conversely, glucocorticoids cause numerous unwanted side effects, particularly systemically dosed glucocorticoids. Therefore, selective glucocorticoid receptor modulator (SGRM), which maintains beneficial anti-inflammatory effects while reducing the occurrence of side effects, is one of the most anticipated drugs. However, there have been no SGRMs marketed to date. The assumption is that there are two major mechanisms of action of glucocorticoids via glucocorticoid receptors, transrepression (TR) and transactivation (TA). In general, the anti-inflammatory effects of glucocorticoids are mostly mediated through TR, while the side effects associated with glucocorticoids are largely caused by TA. We started to evaluate novel orally available SGRMs that maintain anti-inflammatory effects while minimizing adverse effects by favoring TR over TA. Based on this evaluation, we discovered JTP-117968, (4b'S,7'R,8a'S)-4b'-benzyl-7'-hydroxy-N-(2-methylpyridin-3-yl)-7'-(trifluoromethyl)-4b',6',7',8',8a',10'-hexahydro-5'H-spiro[cyclopropane-1,9'-phenanthrene]-2'-carboxamide, a non-steroidal SGRM. JTP-117968 has partial TR activity, but exhibits extremely low TA activity. The maximum TR efficacy of JTP-117968 was comparable to its structural analogue, PF-802, (4bS,7R,8aR)-4b-Benzyl-7-hydroxy-N-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-2-carboxamide, which is the active form of Fosdagrocorat that has been developed clinically as a first-in-class orally available SGRM. Remarkably, the TA activity of JTP-117968 was much weaker than PF-802 not only in in vitro assays, but also in in vivo mice experiments. These findings indicate that JTP-117968 exhibits improved TR/TA dissociation because the compound has significantly lower TA activity compared with an already reported SGRM. Therefore, JTP-117968 is expected to be a useful compound for evaluating ideal SGRMs in the future.

Competitive effects of nuclear deformation and density dependence of $\mathrm{\ensuremath{\Lambda}}N$ interaction in $\mathrm{\ensuremath{\Lambda}}$ binding energies ${B}_{\mathrm{\ensuremath{\Lambda}}}$ of hypernuclei are studied systematically on the basis of the baryon-baryon interaction model ESC (extended soft core) including many-body effects. By using the $\mathrm{\ensuremath{\Lambda}}N$ $G$-matrix interaction derived from ESC, we perform microscopic calculations of ${B}_{\mathrm{\ensuremath{\Lambda}}}$ in $\mathrm{\ensuremath{\Lambda}}$ hypernuclei within the framework of the antisymmetrized molecular dynamics under the averaged-density approximation. The calculated values of ${B}_{\mathrm{\ensuremath{\Lambda}}}$ reproduce experimental data within a few hundred keV in the wide mass regions from 9 to 51. It is found that competitive effects of nuclear deformation and density dependence of $\mathrm{\ensuremath{\Lambda}}N$ interaction work decisively for fine-tuning of ${B}_{\mathrm{\ensuremath{\Lambda}}}$ values.

Some previously reported surface acoustic wave (SAW) devices using bulk piezoelectric substrates showed higher acoustic power radiated in either forward or backward wave propagation direction depending on their crystal orientations and are called natural single-phase unidirectional transducers (NSPUDT). While these reports were based on bulk piezoelectric substrates, we report directionality in the c-axis tilted 44% scandium doped aluminum nitride thin piezoelectric film-based SAW devices on sapphire. It is worth noting that our observance of directionality is specifically in Sezawa mode. We produced a c-axis tilt up to 5.5° over the single wafer and examined the directionality by comparing the forward and backward insertion loss utilizing split finger electrodes as a receiver. The wave propagation direction and c-axis tilt angle influence on the performance of SAW devices is evaluated. Furthermore, return loss and insertion loss data are presented for various SAW propagation directions and c-axis tilt angles. Finally, the comparison for both acoustic modes, i.e., Rayleigh and Sezawa, is reported.

Optical properties in (C4H9NH3)2PbBr4 single crystals under high density excitation have been investigated by photoluminescence (PL) spectroscopy. The PL bands associated with the Γ1, Γ2 and Γ5 excitons and the biexcitons have been observed. While the Γ2 exciton and biexciton PL intensities are proportional to the 0.9 and 1.7 power of the excitation density, respectively, the Γ5 exciton PL intensity shows the nonlinear dependence on the excitation density. The excitation-density dependence of the PL bands is calculated by taking account of the dynamical change of the exciton and biexciton populations in an exciton-biexciton system consisting of two exciton states and a biexciton state. The calculated results well explain the nonlinear dependence of the Γ5 exciton PL intensity on the excitation density. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The structure of the isodoublet hypernuclei, $^{10}_��$B and $^{10}_��$Be within the framework of an $��+��+��+N$ four-body cluster model is studied. Interactions between the constituent subunits are determined so as to reproduce reasonably well the observed low-energy properties of the $����$, $��N$, $����$, $������$ and $����N$ subsystems. Furthermore, the two-body $��N$ interaction is adjusted so as to reproduce the $0^+$-$1^+$ splitting of $^4_��$H. The $��$ binding energies of $^{10}_��$B and $^{10}_��$Be are 8.76 MeV and 8.94 MeV, respectively. The energy splitting of the $1^-$-$2^-$ levels in $^{10}_��$B is 0.08 MeV, which does not contradict the experimental report in BNL-E930. An even-state $��N$ charge symmetry breaking (CSB) interaction determined from the A=4 systems works repulsively by +0.1 MeV (attractively by -0.1 MeV) in $^{10}_��$Be ($^{10}_��$B). We discuss a possibility that an odd-state CSB interaction improves the fitting to the experimental data of A=10 double $��$ hypernuclei., 20 pages and 7 fugures, To be published in Progress of Theoretical Physics

The features of the new interaction model ESC08 in ΛN, ΣN, ΛΛ and ΞN channels are demonstrated on the basis of the G-matrix theory.

In the G-matrix approach, two topics are discussed. One is the spin-dependent components of ΛN interactions. The other is the derivation of Σ-nucleus interactions.

We present and discuss the most recent version of the extended-soft-core (ESC) interactions. The ESC-model describes the nucleon-nucleon ( NN ), hyperon-nucleon ( YN ), and hyperon-hyperon ( YY ), in terms of meson-exchanges using (broken) SUF(3)-symmetry. In this approach to baryon-baryon ( BB ) the dynamics is derived from (i) one-boson-exchanges (OBE), (ii) two-meson-exchanges (TME), and (iii) meson-pair-exchanges (MPE), (iv) gluon-exchanges, and (v) quark-core effects. In the OBE-sector, a special feature is the importance of the axial-vector meson potentials, and the inclusion of a zero in the scalar- and axial- meson form-factors. Novelties are the inclusion of (a) odderon-exchange, and (b) special pronounced effects of the appearance of forbidden six-quark configurations. With these ingredients, a rather flexible dynamical framework is constructed. Namely, it appeared feasible to keep the parameters of the model in reasonable accordance with the predictions of the 3P0 quark-pair-creation model (QPC). This is the case for the meson- and meson-pair-baryon coupling constants and the F/(F + D)-ratio's as well. The NN , YN , and YY results for this model are rather promising. In particular, we improved the ΛN spin-orbit interaction greatly by the inclusion of (a) the Brown, Downs, and Iddings anti-symmetric spin-orbit potentials, and (b) new corrections to the MPE-potentials. Also, the special quark-core effects provide ample repulsion in the Σ+p(3S1,T = 3/2)- and ΣN(1S0,T = 1/2)-channels. The new version of the ESC-model reported here will be referred to as ESC07 henceforth.

We have constructed the hyperon-nucleus optical potential based on the complex G -matrix folding model. The complex G -matrix interactions are derived from the extended-soft core (ESC) model interactions, ESC04a and ESC08. The elastic cross sections and analyzing powers are calculated using the folding-model potentials (FMPs) based on the complex G -matrix interactions. The strength functions for the ( π − , K + ) reaction are also obtained using the FMPs and are compared with the result calculated with a phenomenological repulsive optical potential. The ESC08 interaction gives a better result than does ESC04a.

The features of the new YN interaction model ESC08 are studied on the basis of the G-matrix theory.

We review the Nijmegen extended-soft-core (ESC) models for the baryon-baryon (BB) interactions of the SU(3) flavor-octet of baryons (N, Lambda Sigma and Xi). The interactions are basically studied from the meson-exchange point of view, in the spiri t of the Yukawa-approach to the nuclear force problem [H. Yukawa, 'On the interaction of Elementary Particles I' Proceedings of the Physico-Mathematical Society of Japan 17 (1935), 48], using generalized soft-core Yukawa-functions. These interactions are supplemented with (i) multiple-gluon-exchange, and (ii) structural effects due to the quark-core of the baryons. We present in some detail the most recent extended-soft-core model, henceforth referred to as ESC08, which is the most complete, sophisticated , and successful interaction-model. Furthermore, we discuss briefly its predecessor the ESC04-model [Th. A. Rijken and Y. Yamamoto, Phys. Rev. C 73 (2006), 044007, Th. A. Rijken and Y. Yamamoto, Phys. Rev. C 73 (2006), 044008, Th. A. Rijken and Y. Yamamot o, nucl-th/0608074]. For the soft-core one-boson-exchange (OBE) models we refer to the literature [Th. A. Rijken, in Proceedings of the International Conference on Few-Body Problems in Nuclear and Particle Physics, Quebec, 1974, ed. R. J. Slobodrian, B. C uec and R. Ramavataram (Presses Universite Laval, Quebec, 1975), p. 136, Th. A. Rijken, Ph. D. thesis, University of Nijmegen, 1975, M. M. Nagels, Th. A. Rijken and J. J. de Swart, Phys. Rev. D 17 (1978), 768, P. M. M. Maessen, Th. A. Rijken and J. J. de Swart, Phys. Rev. C 40 (1989), 2226, Th. A. Rijken, V. G. J. Stoks and Y. Yamamoto, Phys. Rev. C 59 (1999), 21, V. G. J. Stoks and Th. A. Rijken, Phys. Rev. C 59 (1999), 3009]. All ingredients of these latter models are also part of ESC08, and so a descri ption of ESC08 comprises all models so far in principle. The extended-soft-core (ESC) interactions consist of local- and non-local-potentials due to (i) one-boson-exchanges (OBE), which are the members of nonets of pseudo-scalar-, vector-, scalar-, and ax ial-mesons, (ii) diffractive (i.e. multiple-gluon) exchanges, (iii) two pseudo-scalar exchange (PS-PS), and (iv) meson-pair-exchange (MPE). The OBE- and pair-vertices are regulated by gaussian form factors producing potentials with a soft behavior near th e origin. The assignment of the cutoff masses for the BBM-vertices is dependent on the SU(3)-classification of the exchanged mesons for OBE, and a similar scheme for MPE. The ESC-models ESC04 and ESC08 describe the nucleon-nucleon (NN), hyperon-nucleon (Y N), and hyperon-hyperon (YY) interactions in a unified way using broken SU(3)-symmetry. Novel ingredients in the OBE-sector in the ESC-models are the inclusion of (i) the axial-vector meson potentials, (ii) a zero in the scalar- and axial-vector meson for m factors. These innovations made it possible for the first time to keep the meson coupling parameters of the model qualitatively in accordance with the predictions of the (3)P0 quark-antiquark creation (QPC) model. This is also the case for the F/(F+D)-r atios. Furthermore, the introduction of the zero helped to avoid the occurrence of unwanted bound states in LambdaN. Broken SU(3)-symmetry serves to connect the NN and the YN channels, which leaves after fitting NN only a few free parameters for the deter mination of the YN-interactions. In particular, the meson-baryon coupling constants are calculated via SU(3) using the coupling constants of the NN+YN-analysis as input. In ESC04 medium strong flavor-symmetry-breaking (FSB) of the coupling constants was i nvestigated, using the (3)P0-model with a Gell-Mann-Okubo hypercharge breaking for the BBM-coupling. In ESC08 the couplings are kept SU(3)-symmetric. The charge-symmetry-breaking (CSB) in the Lambdap and Lambdan channels, which is an SU(2) isospin breakin g, is included in the OBE-, TME-, and MPE-potentials. In ESC04 and ESC08 simultaneous fits to the NN- and the YN- scattering data have been achieved, using different options for the ESC-model. In particularly in ESC08 with single-sets of parameters excell ent fits were obtained for the NN- and YN-data. For example, in the case of ESC08a' we have: (i) For the selected 4233 NN-data with energies 0 Tlab Ndata = 1.094. (ii) For the usual set of 35 YN-data and 3 Sigma+p cross-sections from a recent KEK-experime nt E289 [H. Kanda et al., AIP Conf. Proc. 842 (2006), 501, H. Kanda, Measurement of the cross sections of Sigma(=)p elastic scattering, Ph. D. thesis, Department of Physics, Faculty of Science, Kyoto University, March 2007] the fit has chi(2)/YNdata appro x.0.83. (iii) For YY there is a weak LambdaLambda-interaction, which successfully matches with the Nagara-event [H. Takahashi et al., Phys. Rev. Lett. 87 (2001), 212502]. (iv) The nuclear Sigma and Xi well-dephts satisfy USigma > 0 and UXi The predictions for the S = -2 (LambdaLambda XiN, LambdaSigma SigmaSigma)-channels are the occurrences of an S = -2 bound states in the XiN((3)S1-(3)D1, I = 0,1)-channels.

We analyze and discuss the extended-soft-core models ESC04 and ESC08, which at present are the most complete meson-exchange models for the baryon-baryon interactions. The ESC-model describes the nucleon-nucleon (NN), hyperon-nucleon (YN), and hyperon-hyperon (YY), in terms of meson-exchanges using (broken) S U F ( 3 ) -symmetry. In this approach to baryon-baryon (BB) the dynamics is derived from (i) one-boson-exchanges (OBE), (ii) two-meson-exchanges (TME), and (iii) meson-pair-exchanges (MPE), (iv) gluon-exchanges, and (v) quark-core effects. In the OBE-sector, special features are the importance of the axial-vector meson potentials, and the inclusion of a zero in the scalar- and axial-meson form-factors. Novel for the ESC08-versions is the inclusion of (a) odderon-exchange, and (b) special pronounced effects of the appearance of forbidden six-quark configurations. With these ingredients a rather flexible dynamical framework is constructed. Namely, it appeared feasible to keep the parameters of the model in reasonable accordance with the predictions of the P 0 3 quark-pair-creation model (QPC), although in ESC08a,b a certain admixture of S 1 3 quark-pair creation is present. This is the case for the meson- and meson-pair-baryon coupling constants and the F / ( F + D ) -ratio's as well. The NN, YN, and YY results for this model are excellent. This is marked in particularly by the NN-results, namely χ p . d . p . 2 = 1.180 and 1.135 for respectively ESC08a and ESC08b. Also, we improved the ΛN spin-orbit interaction greatly by the inclusion of (a) the Brown, Downs, and Iddings anti-symmetric spin-orbit potentials, and (b) new corrections to the MPE-potentials. Also, the special quark-core effects provide ample repulsion in the Σ + p ( S 1 3 , T = 3 / 2 ) - and Σ N ( S 0 1 , T = 1 / 2 ) -channels.