Possible role of Krüppel-like factor 5 in the remodeling of small airways and pulmonary vessels in chronic obstructive pulmonary disease

BACKGROUND: Small airway remodeling is an important cause of the airflow limitation in chronic obstructive pulmonary disease (COPD). A large population of patients with COPD also have pulmonary hypertension. Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor that contributes to tissue remodeling in cardiovascular diseases. Here, we evaluate the possible involvement of KLF5 in the remodeling of small airways and pulmonary vessels in COPD. METHODS: Lung tissues were obtained from 23 control never-smokers, 17 control ex-smokers and 24 ex-smokers with COPD. The expression of KLF5 in the lung tissues was investigated by immunohistochemistry. We investigated whether oxidative/nitrosative stress, which is a major cause of the pathogenesis in COPD, could augment the production of KLF5. We examined the role of KLF5 in the stress-mediated tissue remodeling responses. We also investigated the susceptibility of KLF5 expression to nitrosative stress using bronchial fibroblasts isolated from the lung tissues. RESULTS: The expression of KLF5 was up-regulated in the small airways and pulmonary vessels of the COPD patients and it was mainly expressed in bronchial fibroblasts and cells of the pulmonary vessels. The extent of the KLF5 expression in the small airway of the COPD group had a significant correlation with the severity of the airflow limitation. Oxidative/nitrosative stress augmented the production of KLF5 in lung fibroblasts as well as the translocation of KLF5 into the nuclei. Silencing of KLF5 suppressed the stress-augmented differentiation into myofibroblasts, the release of collagens and metalloproteinases. Bronchial fibroblasts from the patients with COPD highly expressed KLF5 compared to those from the control subjects under basal condition and were more susceptible to the induction of KLF5 expression by nitrosative stress compared to those from the control subjects. CONCLUSION: We provide the first evidence that the expression of KLF5 is up-regulated in small airways and pulmonary vessels of patients with COPD and may be involved in the tissue remodeling of COPD

Exotic characteristics of Centauro-I: Reexamination of the Centauro event

The cosmic-ray exotic event "Centauro-I" is reexamined. Kopenkin et al. [Phys. Rev. D 68, 052007 (2003).] have recently suggested that the original correspondence of shower clusters in the upper and the lower chambers [C. M. G. Lattes, Y. Fujimoto, and S. Hasegawa, Phys. Rep. 65, 151 (1980).] is not correct, and we confirm this suggestion. By taking into account the relative position of the upper and the lower chambers exactly, we find that the event has no upper part corresponding to the observed shower cluster in the lower chamber. Our analysis shows that showers in the shower cluster in the lower chamber are likely to have originated in a bundle of target interactions (C-jets) and that they are not a simple atmospheric family as was claimed by Kopenkin et al. The event shows peculiar characteristics quite different from commonly observed cosmic-ray events.70

Phenomenological approach of multiple particle production at high energies: Energy distribution of produced particles by data of direct observation

The energy distribution of produced particles in multiple particle production is formulated empirically based on the data of direct observations by accelerator and cosmic-ray experiments at 10(12)-10(14) eV. The formulated distribution indicates violation of the Feynman scaling law, which was shown to be valid in the low energy region of less than or equal to 10(12) eV. That is, the particle density is suppressed in the forward region and enhanced in the central region, compared with the distribution of the Feynman scaling law. The consequences of the formulated distribution, such as multiplicity, inelasticity, etc., are discussed at high energies of less than or equal to 10(15) eV by extrapolation. The distribution is also compared with those of nuclear interaction models which are used widely in simulations of accelerator and cosmic-ray experiments.64

Different formation kinetics and photoisomerization behavior of self-assembled monolayers of thiols and dithiolanes bearing azobenzene moieties

Self-assembled monolayers (SAMs) containing azobenzene moieties are very attractive for a wide range of applications, including molecular electronics and photonics, bio-interface engineering and sensoring. However, very little is known about the aggregation and photoswitching behavior that azobenzene units undergo during the SAM formation process. Here, we demonstrate that the formation of thiol based SAMs containing azobenzenes (denoted as AzoSH) on gold surfaces is characterised by a two step adsorption kinetics, while a three-step assembly process has been identified for dithiolane-based SAMs containing azobenzenes (denoted AzoSS). The H-aggregation on the AzoSS SAMs was found to be remarkably dependent on the time of self-assembly, with less aggregation as a function of time. While photoisomerization of the AzoSH was suppressed for all different assembly times, the reversible trans–cis photoisomerization of AzoSS SAMs formed over 24 hours was clearly observed upon alternating UV and Vis light irradiation. We contend that detailed information on formation kinetics and related optical properties is of crucial importance for elucidating the photoswitching capabilities of azobenzene based SAMs

Inelasticity Distribution Of Hadron-pb Collisions In The Energy Region Exceeding 1014 Ev From Mountain Cosmic Ray Experiments

The inelasticity distribution of hadron-lead collisions in the energy region exceeding 1014 eV is estimated on the basis of 66 events, induced by cosmic ray hadrons and detected at high mountain altitudes at Pamir (4300 m, 595 g/cm2). The distribution of the best fitting is approximated as g(K)dK=[α(1-K)m1-1 + βKm2-1]dK, where m1=0.5, m2=1.125, α=0.26, β=0.55, giving 〈K〉=0.60. The errors of the parameters are discussed in the text. The distribution is compared with those which are based on theoretical models. ©1999 The American Physical Society.611110Frichter, G.M., Gaisser, T.K., Stanev, T., (1997) Phys. Rev. D, 56, p. 3135Fowler, G.N., Weiner, R.M., Wilk, G., (1985) Phys. Rev. Lett., 55, p. 173Fowler, G.N., Vourdas, A., Weiner, R.M., Wilk, G., (1987) Phys. Rev. D, 35, p. 870Fowler, G.N., Navarra, F.S., Plümer, M., Voudras, A., Weiner, R.M., Wilk, G., (1989) Phys. Rev. C, 40, p. 1219Shabelski, Yu.M., Weiner, R.M., Wilk, G., Włodarczyk, Z., (1992) J. Phys. G, 18, p. 1281Włodarczyk, Z., (1995) J. Phys. G, 21, p. 281Chou, T.T., Yang, C.N., (1985) Phys. Rev. D, 32, p. 1692Gaisser, T.K., Stanev, T., (1989) Phys. Lett. B, 219, p. 375Kaǐdalov, A.B., Ter-Martirosyan, K.A., (1987) Proceedings of the 20th International Cosmic Ray Conference, 5, p. 139(1984) Sov. J. Nucl. Phys., 40, p. 135Nazareth, R.A.M.S., Kodama, T., Portes Jr., D.A., (1992) Phys. Rev. D, 46, p. 2896Schatz, G., Thouw, T., Werner, K., Oehlschläger, J., Bekk, K., (1994) J. Phys. G, 20, p. 1267Gaisser, T.K., Protheroe, R.J., Turver, K.E., McComb, T.J.L., (1978) Rev. Mod. Phys., 50, p. 859Van Hove, L., Pokorski, S., (1975) Nucl. Phys., B86, p. 243Akashi, M., (1964) Prog. Theor. Phys. Suppl., 32, p. 1Feynman, R., (1969) Phys. Rev. Lett., 23, p. 1415Taylor, F.E., Carey, D.C., Johnson, J.R., Kammerud, R., Ritchie, D.J., Roberts, A., Sauer, J.R., Walker, J.K., (1976) Phys. Rev. D, 14, p. 1217Ohsawa, A., (1994) Prog. Theor. Phys., 92, p. 1005Arata, N., (1983) Nucl. Phys., B211, p. 189Tabuki, T., (1983) Prog. Theor. Phys. Suppl., 76, p. 40Chinellato, J.A., (1983) Prog. Theor. Phys. Suppl., 76, p. 1Alner, G.L., (1987) Phys. Rep., 5-6, p. 247Nishimura, J., (1967) Handbuch der Physik, 46 (2), p. 1. , Springer, BerlinArisawa, T., Fujimoto, Y., Hasegawa, S., Honda, K., Ito, H., Kopenkin, V.V., Semba, H., Strogova, O.P., (1994) Nucl. Phys., B424, p. 241Baradzei, L.T., (1992) Nucl. Phys. B, B370, p. 365Kopenkin, V., Fujimoto, Y., (1996) Nuovo Cimento C, 19, p. 1017Moriya, M., (1997), Master thesis, Waseda UniversityBarroso, S.L.C., Fujimoto, Y., Kopenkin, V., Moriya, M., Navia, C., Ohsawa, A., Shibuya, E.H., Tamada, M., (1997) Nucl. Phys. B (Proc. Suppl.), 52 B, p. 201(1997) Proceedings of the 25th International Cosmic Ray Conference, 6, p. 41Hama, Y., Paiva, S., (1997) Phys. Rev. Lett., 78, p. 3070Tamada, M., (1995) J. Phys. G, 21, p. 1387Knapp, J., Heck, D., Schatz, G., (1996) Report of Institut für Kernphysik, Forschungszentrum Karlsruhe, , Wissenchafteliche Berichte FZKA 5828Harr, R., Liapis, C., Karchin, P., Biino, C., Erhan, S., Hofmann, W., Kreuzer, P., Zweizig, J., (1997) Phys. Lett. B, 401, p. 176Tamada, M., Kopenkin, V.V., (1997) Nucl. Phys., B494, p. 3Ohsawa, A., (1971) Prog. Theor. Phys. Suppl., 47, p. 180Gaisser, T.K., (1990) Cosmic Rays and Particle Physics, , Cambridge University Press, Cambridge, Englan

Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale

The detection of sound begins when energy derived from acoustic stimuli deflects the hair bundles atop hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors stabilize the structure, further reducing the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.Comment: 21 pages, including 3 figures. For supplementary information, please see the online version of the article at http://www.nature.com/natur

Oscillatory oblique stagnation-point flow toward a plane wall

Two-dimensional oscillatory oblique stagnation-point flow toward a plane wall is investigated. The problem is a eneralisation of the steady oblique stagnation-point flow examined by previous workers. Far from the wall, the flow is composed of an irrotational orthogonal stagnation-point flow with a time-periodic strength, a simple shear flow of constant vorticity, and a time-periodic uniform stream. An exact solution of the Navier-Stokes equations is sought for which the flow streamfunction depends linearly on the coordinate parallel to the wall. The problem formulation reduces to a coupled pair of partial differential equations in time and one spatial variable. The first equation describes the oscillatory orthogonal stagnation-point flow discussed by previous workers. The second equation, which couples to the first, describes the oblique component of the flow. A description of the flow velocity field, the instantaneous streamlines, and the particle paths is sought through numerical solutions of the governing equations and via asymptotic analysis