The skeletal phenotype of chondroadherin deficient mice

Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their a2b1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3–6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the a1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth

Gene Expression and Distribution of Key Bone Turnover Markers in the Callus of Estrogen-Deficient, Vitamin D-Depleted Rats

An experimental rat model was used to test the hypothesis that in osteoporosis (OP) the molecular composition of the extracellular matrix in the fracture callus is disturbed. OP was induced at 10 weeks of age by ovariectomy and a vitamin D3-deficient diet, and sham-operated animals fed normal diet served as controls. Three months later a closed tibial fracture was made and stabilized with an intramedullary nail. After 3 and 6 weeks of healing, the animals were killed and the fracture calluses examined with global gene expression, in situ mRNA expression, and ultrastructural protein distribution of four bone turnover markers: osteopontin, bone sialoprotein, tartrate-resistant acid phosphatase, and cathepsin K. Global gene expression showed a relatively small number of differently regulated genes, mostly upregulated and at 3 weeks. The four chosen markers were not differently regulated, and only minor differences in the in situ mRNA expression and ultrastructural protein distribution were detected. Gene expression and composition of fracture calluses are not generally disturbed in experimental OP

Anomalous Behavior Of The Complex Conductivity Of Y_{1-x}Pr_xBa_2Cu_3O_7 Observed With THz Spectroscopy

We have measured the electrodynamic properties of Y_{1-x}Pr_xBa_2Cu_3O_7 single crystal thin films as a function of temperature using coherent THz-time-domain spectroscopy. We obtain directly the complex conductivity $\sigma=\sigma_1+i\sigma_2$, the London penetration depth $\lambda_L$, the plasma frequency $\omega_p$, and the quasiparticle scattering rate $1/\tau$. We find that $1/\tau$ drops exponentially rapidly with $T$ below the critical temperature in {\em all} the superconducting samples, implying that this behavior is a {\em signature} of high-$T_c$ superconductivity. The plasma frequency decreases with increasing Pr content, providing evidence that Pr depletes carriers, leaving the CuO planes {\em underdoped}. Both the conductivity in the THz region and the dc resistivity yield evidence for the opening of a spin gap {\em above} $T_c$.Comment: 9 pages, REVTEX 3.

Electrical manipulation of spin states in a single electrostatically gated transition-metal complex

We demonstrate an electrically controlled high-spin (S=5/2) to low-spin (S=1/2) transition in a three-terminal device incorporating a single Mn2+ ion coordinated by two terpyridine ligands. By adjusting the gate-voltage we reduce the terpyridine moiety and thereby strengthen the ligand-field on the Mn-atom. Adding a single electron thus stabilizes the low-spin configuration and the corresponding sequential tunnelling current is suppressed by spin-blockade. From low-temperature inelastic cotunneling spectroscopy, we infer the magnetic excitation spectrum of the molecule and uncover also a strongly gate-dependent singlet-triplet splitting on the low-spin side. The measured bias-spectroscopy is shown to be consistent with an exact diagonalization of the Mn-complex, and an interpretation of the data is given in terms of a simplified effective model.Comment: Will appear soon in Nanoletter

Ultrafast quasiparticle relaxation dynamics in normal metals and heavy fermion materials

We present a detailed theoretical study of the ultrafast quasiparticle relaxation dynamics observed in normal metals and heavy fermion materials with femtosecond time-resolved optical pump-probe spectroscopy. For normal metals, a nonthermal electron distribution gives rise to a temperature (T) independent electron-phonon relaxation time at low temperatures, in contrast to the T^{-3}-divergent behavior predicted by the two-temperature model. For heavy fermion compounds, we find that the blocking of electron-phonon scattering for heavy electrons within the density-of-states peak near the Fermi energy is crucial to explain the rapid increase of the electron-phonon relaxation time below the Kondo temperature. We propose the hypothesis that the slower Fermi velocity compared to the sound velocity provides a natural blocking mechanism due to energy and momentum conservation laws.Comment: 10 pages, 11 figure

Observation of inhibited electron-ion coupling in strongly heated graphite

Creating non-equilibrium states of matter with highly unequal electron and lattice temperatures (Tele≠Tion) allows unsurpassed insight into the dynamic coupling between electrons and ions through time-resolved energy relaxation measurements. Recent studies on low-temperature laser-heated graphite suggest a complex energy exchange when compared to other materials. To avoid problems related to surface preparation, crystal quality and poor understanding of the energy deposition and transport mechanisms, we apply a different energy deposition mechanism, via laser-accelerated protons, to isochorically and non-radiatively heat macroscopic graphite samples up to temperatures close to the melting threshold. Using time-resolved x ray diffraction, we show clear evidence of a very small electron-ion energy transfer, yielding approximately three times longer relaxation times than previously reported. This is indicative of the existence of an energy transfer bottleneck in non-equilibrium warm dense matter

Electrophysiologic actions of high plasma concentrations of propranolol in human subjects

The authors have previously shown that 40% of patients whose ventricular arrhythmias respond to propranolol require plasma concentrations in excess of those producing substantial beta-receptor blockade (> 150 ng/ml). However, the electrophysiologic actions of propranolol have only been examined in human beings after small intravenous doses achieving concentrations of less than 100 ng/ml. In this study, the electrophysiologic effects of a wider concentration range of propranolol was examined in nine patients. Using a series of loading and maintenance infusions, measurements were made at baseline, at low mean plasma propranolol concentrations (104 ± 17 ng/ml) and at high concentrations (472 ± 68 ng/ml). Significant (p < 0.05) increases in AH interval and sinus cycle length were seen at low concentrations of propranolol, with no further prolongation at the high concentrations; these effects are typical of those produced by beta-blockade. However, progressive shortening of the endocardial monophasic action potential duration and QTc interval were seen over the entire concentration range tested (p < 0.05). At high concentrations, there was significant (p < 0.05) further shortening of both the QTc and monophasic action potential duration beyond that seen at low propranolol concentrations, along with a progressive increase in the ratio of the ventricular effective refractory period to monophasic action potential duration. No significant changes were seen in HV interval, QRS duration or ventricular effective refractory period.In summary, the concentration-response relations for atrioventricular conductivity and sinus node automat-icity were flat above concentrations of 150 ng/ml. On the other hand, the durations of the monophasic action potential and the QTc interval shortened at high concentrations. It is concluded that propranolol, in addition to blocking beta-receptors, produces other beta-receptor independent electrophysiologic effects in human beings

Spontaneous Emission in Chaotic Cavities

The spontaneous emission rate \Gamma of a two-level atom inside a chaotic cavity fluctuates strongly from one point to another because of fluctuations in the local density of modes. For a cavity with perfectly conducting walls and an opening containing N wavechannels, the distribution of \Gamma is given by P(\Gamma) \propto \Gamma^{N/2-1}(\Gamma+\Gamma_0)^{-N-1}, where \Gamma_0 is the free-space rate. For small N the most probable value of \Gamma is much smaller than the mean value \Gamma_0.Comment: 4 pages, RevTeX, 1 figur

Spontaneous emission of an atom placed near a nanobelt of elliptical cross-section

Spontaneous emission of an atom (molecule) placed near a nanocylinder of elliptical cross-section of an arbitrary composition is studied. The analytical expressions have been obtained for the radiative and nonradiative channels of spontaneous decay and investigated in details.Comment: 35 pages, 11 figure