We have developed a new method to determine phase velocities from the vertical component of microseisms recorded with an array of seismic sensors spaced around the circumference of a circle. We calculate two different time histories by taking the average of the seismograms with differing sets of weights for the sensor stations. The spectral ratio of these two time histories contains no information on the arrival directions or on the amplitudes of the incoming waves but depends solely on the phase velocities of the arriving modes. Theoretical considerations indicate that the effects of directional aliasing caused by the use of a finite number of sensors in the field implementation of our method are small in most situations except for short wavelengths. The presence of incoherent noise limits the efficacy of our method for long wavelengths. In field tests using arrays of three seismic sensors, we obtained appropriate estimates of phase velocities in the wavelength range from 5r to 30r where r , the array radius, was on the order of a few meters.

S U M M A R YWe present a generic formulation for analysis methods that estimate phase velocities of Rayleigh and Love waves, by way of intermediary quantities called 'spectral ratios', using three-component records of microtremors from a circular array of sensors. At each time instant, the set of records are expanded in a Fourier series with respect to azimuth, so that we obtain a set of Fourier coefficients that are represented in the form of complex time histories. We then estimate power-and cross-spectral densities of those Fourier coefficients. The spectral densities, thus obtained, generally contain information on the phase velocities, powers and arrival directions of individual modes of Rayleigh and Love waves. By taking the quotient of two different sorts of such spectral densities, we can cancel out information on their powers and arrival directions, and extract information on their phase velocities alone. The spectral ratios have to be estimated, in practice, on the basis of records from a finite number of seismic sensors that are either evenly or unevenly spaced around a circumference. We describe a general procedure for their estimation, and discuss the effects of directional aliasing that the finite number of sensors and their configuration have on the estimates of spectral ratios. We also discuss biases in the estimates of spectral ratios caused by the presence of incoherent noise. By using our method, it is also possible to estimate the central arrival direction of the microtremors, the ellipticity of the Rayleigh waves, and whether the Rayleigh waves are prograde or retrograde.

ObjectiveTo evaluate the pharmacological properties of JTE-052, a novel Janus kinase (JAK) inhibitor.MethodsThe JAK inhibitory activity of JTE-052 was evaluated using recombinant human enzymes. The inhibitory effects on cytokine signaling pathways were evaluated using primary human inflammatory cells. The in vivo efficacy and potency of JTE-052 were examined in a mouse interleukin (IL)-2-induced interferon (IFN)-γ production model and a rat collagen-induced arthritis model.ResultsJTE-052 inhibited the JAK1, JAK2, JAK3, and tyrosine kinase (Tyk)2 enzymes in an adenosine triphosphate (ATP)-competitive manner and inhibited cytokine signaling evoked by IL-2, IL-6, IL-23, granulocyte/macrophage colony-stimulating factor, and IFN-α. JTE-052 inhibited the activation of inflammatory cells, such as T cells, B cells, monocytes, and mast cells, in vitro. Oral dosing of JTE-052 resulted in potent suppression of the IL-2-induced IFN-γ production in mice with an ED50 value of 0.24 mg/kg, which was more potent than that of tofacitinib (ED50 = 1.1 mg/kg). In the collagen-induced arthritis model, JTE-052 ameliorated articular inflammation and joint destruction even in therapeutic treatments where methotrexate was ineffective.ConclusionsThe present results indicate that JTE-052 is a highly potent JAK inhibitor, and represents a candidate anti-inflammatory agent for suppressing various types of inflammation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00011-014-0782-9) contains supplementary material, which is available to authorized users.

Glucose is the most abundant monosaccharide, and an essential source of energy for most living cells. Glucose transport across the cell membrane is mediated by two types of transporters: facilitative glucose transporters (gene name: solute carrier 2A) and sodiumglucose cotransporters (SGLTs; gene name: solute carrier 5A). Each transporter has its own substrate specificity, distribution, and regulatory mechanisms. Recently, SGLT1 and SGLT2 have attracted much attention as therapeutic targets for various diseases. This review addresses the basal and functional properties of glucose transporters and SGLTs, and describes the pharmaceutical potential of SGLT1 and SGLT2.

[1] The centerless circular array (CCA) method, proposed by ourselves in an earlier work, is an algorithm of microtremor exploration which can be used to estimate phase velocities of Rayleigh waves by analyzing vertical component records of microtremors that are obtained with an array of three or five seismic sensors placed around a circumference. We have confirmed, through field tests, the applicability of our CCA method to arrays on the order of several to several hundred meters in radii and have revealed its remarkably high performance in long-wavelength ranges, the upper resolution limit extending as far as several 10 times the array radius. We have also invented a mathematical model that enables to evaluate signal-to-noise ratios in a given microtremor field. Scrutiny of field data has borne out our hypothesis that noise is the principal factor that biases the analysis results of the CCA method in long-wavelength ranges and that its longest resolvable wavelength is determined by the signal-to-noise ratio. Combined use of the CCA method and our new method of signal-to-noise ratio analysis provides a powerful methodological tool that allows one to extract maximal information from microtremor records obtained with a simple seismic array.Citation: Cho, I., T. Tada, and Y. Shinozaki (2006), Centerless circular array method: Inferring phase velocities of Rayleigh waves in broad wavelength ranges using microtremor records,

We explore the wealth of alternative methods for inferring phase velocities of Rayleigh waves using vertical-component seismograms of microtremors from a circular array of seismic sensors, which are formulable along the extension of the popularly used spatial autocorrelation (SPAC) method. Four such methods are illustrated here: the centerless circular-array (CCA) method, the Henstridge methods of the zeroth and first orders (the H0 and H1 methods, respectively), and what we tentatively call the fifth (V) method.Different methods of phase velocity estimation have different wavelength ranges of good resolution. Implementation to field data from two sites reveals that the traditional SPAC method and the H0 method are both capable of producing reasonable estimates of Rayleigh-wave phase velocities within a relatively narrow range on the short-wavelength side, whereas the H1 method is valid in a relatively narrow range on the long-wavelength side. The CCA and V methods both remain valid over a very broad range of wavelengths, the upper limit extending as far up as several 10s of times the array radius. Use of a noise-compensation technique can further prolong the maximum resolvable wavelength of the CCA method.We also illustrate the field performance of circle phase methods, which give, without recourse to the conventional frequency-wavenumber analysis, estimates for the principal arrival directions of Rayleigh waves on the basis of circular-array seismograms of microtremors.

Background/Aims: Ferric citrate hydrate (JTT-751) is being developed as a treatment for hyperphosphatemia in chronic kidney disease patients, and shows serum phosphorus-reducing effects on hyperphosphatemia in hemodialysis patients. We examined whether JTT-751 could reduce phosphorus absorption in normal rats and prevent the progression of ectopic calcification, secondary hyperparathyroidism and bone abnormalities in chronic renal failure (CRF) rats. Methods: Normal rats were fed a diet containing 0.3, 1 or 3% JTT-751 for 7 days. The effects of JTT-751 on phosphorus absorption were evaluated with fecal and urinary phosphorus excretion. Next, a CRF model simulating hyperphosphatemia was induced by feeding rats a 0.75% adenine diet. After 21 days of starting the adenine diet feeding, 1 or 3% JTT-751 was administered for 35 days by dietary admixture. The serum phosphorus levels and mineral parameters were measured. Calcification in the aorta was examined biochemically and histopathologically. Hyperparathyroidism and bone abnormalities were evaluated by histopathological analysis of the parathyroid and femur, respectively. Results: In normal rats, JTT-751 increased fecal phosphorus excretion and reduced phosphorus absorption and urinary phosphorus excretion. In CRF rats, JTT-751 reduced serum phosphorus levels, the calcium-phosphorus product and calcium content in the aorta. Serum intact parathyroid hormone levels and the incidence and severity of parathyroid hyperplasia were also decreased. JTT-751 reduced femoral bone fibrosis, porosity and osteoid formation. Conclusions: JTT-751 could bind with phosphate in the gastrointestinal tract, increase fecal phosphorus excretion and reduce phosphorus absorption. JTT-751 could prevent the progression of ectopic calcification, secondary hyperparathyroidism and bone abnormalities in rats.

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. K E Y W O R D Satopic dermatitis, corticosteroids, cytokine signalling, immunosuppressants, psoriasisThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.