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To investigate whether Ccr2 inactivation in aggrecan-expressing cells induced before post-traumatic OA (PTOA) onset or during progression, improves joint structures, synovial thickness and pain.We induced a Ccr2 deletion in aggrecan-expressing cells (CCR2-AggKO) in skeletally mature mice using a tamoxifen-inducible Ccr2 inactivation. We stimulated PTOA changes (destabilization of medial meniscus, DMM) in CCR2-AggKO and CCR2+/+ mice, inducing recombination before DMM or 4 wks after DMM (early-vs late-inactivation). Joint damage was evaluated 2, 4, 8, 12 wks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous (incapacitance meter) and evoked pain (von-Frey filaments) were assessed up to 20 wks.Early aggrecan-Ccr2 inactivation in CCR2-AggKO mice (N=8) resulted in improved ACS score (8-12wk, P=0.002), AC area (4-12wk, P0.05) and Saf-O score (2wks P=0.004, 4wks P=0.02, 8-12wks P=0.002) compared to CCR2+/+. Increased subchondral bone thickness was delayed only at 2 wks and exclusively following early recombination. Osteophyte size was not affected, but osteophyte maturation (cartilage-to-bone) was delayed (4wks P=0.04; 8 wks P=0.03). Although late aggrecan-Ccr2 deletion led to some cartilage improvement, most data did not reach statistical significance; osteophyte maturity was delayed at 12wks. Early aggrecan-Ccr2 deletion led to improved pain measures of weight bearing compared to CCR2+/+ mice (N = 9, 12wks diff 0.13 [0.01, 0.26], 16wks diff 0.15 [0.05, 0.26], 20wks diff 0.23 [0.14, 0.31]). Improved mechanosensitivity in evoked pain, although less noticeable, was detected.We demonstrated that deletion of Ccr2 in aggrecan expressing cells reduces the initiation but not progression of OA.

We evaluated children with transient synovitis for serologic evidence of infection with parvovirus B-19 (PVB-19) and human herpesvirus-6 (HHV-6) by using a prospective patient series in an urban children's hospital emergency department (ED). There were 20 children enrolled, aged 15 months to 6 years, diagnosed with transient synovitis. Clinical data were collected, and acute PVB-19 and HHV-6 immunoglobulin G (IgG) and IgM serologic titers were measured on all patients. Ten patients returned in 4-6 weeks for convalescent titers. The mean age was 4.1 years. Prodromal symptoms within a week of presentation were noted in 50% of patients, most commonly fever (25%) and upper respiratory infection (20%). Mean sedimentation rate was 11 mm/h (range, 2-22 mm/h), and mean peripheral white blood count was 11,000/microl (range, 6-21,000/ microl). No patient had increased acute or convalescent IgM titers for either PVB-19 or HHV-6, and no patient who returned for follow-up had an increase in serum IgG titers for either virus. A majority of patients (80%) had increased acute HHV-6 IgG titers, reflecting prior immunity to this virus. In conclusion, there is no evidence in this series that acute infection with PVB- 19 or HHV-6 causes or precedes transient synovitis.

High critical temperature superconductors (HTS) based devices can have impact in the study of the phase dynamics of Josephson junctions (JJs) thanks to the wide range of junction parameters they offer and to their unconventional properties. Measurements of current-voltage characteristics and of switching current distributions constitute a direct way to classify different regimes of the phase dynamics and of the transport, also in nontrivial case of the moderately damped regime (MDR). MDR is going to be more and more common in JJs with advances in nanopatterning superconductors and synthesizing novel hybrid systems. Distinctive signatures of macroscopic quantum tunneling and of thermal activation in presence of different tunable levels of dissipation have been detected in YBCO grain boundary JJs. Experimental data are supported by Monte Carlo simulations of the phase dynamics, in a wide range of temperatures and dissipation levels. This allows us to quantify dissipation in the MDR and partially reconstruct a phase diagram as guideline for a wide range of moderately damped systems. (C) 2014 Elsevier B.V. All rights reserved.

The interfacial coupling of two materials with different ordered phases, such as a superconductor (S) and a ferromagnet (F) is driving new fundamental physics and innovative applications. For example, the creation of spin-filter Josephson junctions and the demonstration of triplet supercurrents have suggested the potential of a dissipationless version of spintronics based on unconventional superconductivity. Here we demonstrate evidence for active quantum applications of S-F-S junctions, through the observation of macroscopic quantum tunneling in Josephson junctions with GdN ferromagnetic insulator barriers. We prove a clear transition from thermal to quantum regime at a crossover temperature of about 100 mK at zero magnetic field in junctions which demonstrate a clear signature of unconventional superconductivity. Following previous demonstration of passive S-F-S phase shifters in a phase qubit, our result paves the way to the active use of spin filter Josephson systems in quantum hybrid circuits., Comment: 16 pages, 4 figures

We report on $\hbox{YBa}_{2}\hbox{Cu}_{3}\hbox{O}_{7-x} $ biepitaxial grain boundary Josephson junctions (JJs) demonstrating significant tunability of their circuital parameters. We show how the enhanced control of the junction properties, and particularly of the capacitance, leads to advances in the understanding of phase dynamics of high-critical-temperature superconductor JJs and potentially of their intrinsic dissipation mechanisms.

We have identified anomalous behavior of the escape rate out of the zero-voltage state in Josephson junctions with a high critical current density Jc. For this study we have employed YBa2Cu3O7-x grain boundary junctions, which span a wide range of Jc and have appropriate electrodynamical parameters. Such high Jc junctions, when hysteretic, do not switch from the superconducting to the normal state following the expected stochastic Josephson distribution, despite having standard Josephson properties such as a Fraunhofer magnetic field pattern. The switching current distributions (SCDs) are consistent with nonequilibrium dynamics taking place on a local rather than a global scale. This means that macroscopic quantum phenomena seem to be practically unattainable for high Jc junctions. We argue that SCDs are an accurate means to measure nonequilibrium effects. This transition from global to local dynamics is of relevance for all kinds of weak links, including the emergent family of nanohybrid Josephson junctions. Therefore caution should be applied in the use of such junctions in, for instance, the search for Majorana fermions., Comment: 8 pages, 4 figures

We have developed a fabrication process that allows us to realize pure YBCO nanowires displaying robust superconductivity at widths w as low as 160 nm. We can modify the process in order to maintain a Au protective layer. This allows us to scale our nanowires even further to widths as low as 50 nm. We have studied how the presence of vortices and the occurrence of phase slips affect the transport properties of nanowires in the width range xi < w < lambda, being xi the coherence length and lambda the magnetic penetration depth. Magnetoresistance curves present features which are related to the effect of screening currents. Vortex entry barrier is found to scale with the width. Our findings confirm that for widths xi < w < lambda nanowires are better protected against phase slips and vortex flow. (C) 2014 Elsevier B.V. All rights reserved.

We investigate the phase dynamics of moderately damped NbN/AlN/NbN Josephson junctions and we present experimental results on detailed aspects of phase diffusion processes. We measure both single escape and multiple escape and retrapping events obtaining a crossover temperature T* from Kramers to phase diffusion switching. We observe a clear dependence of the crossover temperature T* by the bias current ramp rate, while the damping factor Q remains the same. The measured effect is in strong agreement with theoretical predictions reported by Fenton and Warburton. © 2014 AIP Publishing LLC.

Gliadin is a heterogeneous group of alcohol-soluble wheat storage proteins, comprising ≈50% of the gluten proteins (Campbell et al 1987; Fido et al 1997). Gliadin influences important baking properties of wheat, in particular loaf volume (Weegels et al 1994; Khatkar et al 2002) and water absorption (Dong et al 1992). Gliadin has been used also as a tool for wheat varietal identification (Bietz et al 1984). More importantly, gliadin, along with the prolamins of rye, barley and possibly of spelta wheat (Kasarda and D’Ovidio 1999), is responsible for the pathogenesis of the celiac disease. This food intolerance has a prevalence of 1/200 to 1/300 (Hin et al 1999) and is strongly associated with DQ2 and DQ8 HLA class II haplotypes (Sollid 2000). The symptoms of the disease disappear when patients follow a strict gluten-free diet and reappear when gluten is introduced again. Thus, treatment of celiac disease relies exclusively on a gluten-free diet. At present, ELISA is used frequently to ascertain the absence of toxic prolamins in gluten-free foods (Sorell et al 1998). We investigated the possibility of using ELISA for flow cytometry. The applications of this technique are becoming increasingly numerous. However, flow cytometry can only analyze single cells. To mimic a cell population in this study, the gliadin in test samples was extracted with 70% ethanol, adsorbed on latex particles, coated with rat anti-gliadin antibodies, labeled with fluoresceinated goat antirat immunoglobulins, and finally measured by flow cytometry. The same approach has been used before to detect toxins (Evidente et al 1997), antibodies (Presani et al 1989; Iannelli et al 1998), and viruses (Iannelli et al 1996), which are all not visible to the laser in their natural state. The method described in this study can detect all cereal prolamins (gliadin, secalin, hordein, and avenin) potentially toxic to the celiac patient with a sensitivity of 5 ppm (5 ng of gliadin added to 1 mg of maize flour), introducing the condition to further reduce the amount of gluten allowed in gluten-free foods.

The moderately damped regime in a Josephson junction (JJ) is quite common in devices characterized by low critical currents and therefore by low Josephson energies. Measurements of switching current distribution (SCD) are a direct way of discriminating the phase dynamics also in the nontrivial case of moderate damping, which is going to be more and more common with advances in nanopatterning superconductors and in materials science finalized to build hybrid systems. We report on measurements of SCDs, both in thermal and quantum regime, on moderately damped YBaCuO grain boundary biepitaxial JJs. A direct transition from phase diffusion regime to macroscopic quantum tunnelling occurs at about 130 mK. The crossover to the quantum regime is tuned by the magnetic field and phase dynamics is described by a fully consistent set of junction parameters derived through numerical simulations.

Coherent passage of Cooper pairs in a Josephson junction (JJ) above the liquid nitrogen temperature has been the first impressive revolutionary effect induced by high critical temperature superconductors (HTS) in the domain of the study of Josephson effect (JE). But this has been only the start. A d-wave order parameter has lead to significant novel insights in the physics of the JE turning into a device the notion of a ?-junction. Spontaneous currents in a frustrated geometry, Andreev bound states, long-range proximity effect have rapidly become standard terms in the study of the JE, standing as a reference bench for conventional systems based on low critical temperature superconductors (LTS) and inspiring analogies for junctions based on novel superconductors discovered in the meantime. The extreme richness of the physics of HTS JJs has not been adequately supported by the expected impact in the applications, the main reason lying in the complexity of these materials and in the consequent unsatisfactory yield and reproducibility of the performances of the JJs within the required limits. The continuous progress in material science, and specifically in the realization of oxide multi-layers, and in nanotechnologies applied to superconductors, accompanied by the advances in a better understanding of the properties of HTS and of HTS devices, has as a matter of fact opened possible novel scenarios and interest in the field. We intend to give a brief overview on interesting new problems concerning HTS JJs of inspiration also for other systems. We also review some ideas and experimental techniques on macroscopic quantum decay phenomena occurring in Josephson structures. The attention is mainly addressed to intermediate levels of dissipation, which characterize a large majority of low critical current Josephson devices and are therefore an unavoidable consequence of nanotechnology applied more and more to Josephson devices.

The moderately damped regime (MDR) in a Josephson junction (JJ) is quite distinct from the well-known case of underdamped systems and quite common in devices characterized by low critical currents. Measurements of switching current distribution (SCD) are a direct way of discriminating the phase dynamics and the transport also in nontrivial cases of moderate damping. MDR is going to be more and more common with advances in nanopatterning superconductors and in materials science finalized to build hybrid devices. We report on measurements of SCDs, both in the thermal and quantum regime, on moderately damped NbN/MgO/NbN JJs. A transition from the Thermal Activation (TA) regime to Macroscopic Quantum Tunnelling (MQT) occurs at about 90 mK, while above 1.6 K a phase diffusive dynamics is clearly observed. The combined analysis of these regimes through numerical simulations allowed us to extract the fundamental parameters, which completely characterize the phase dynamics of such moderately damped JJs.

We report on the study of the phase dynamics of high critical temperature superconductor Josephson junctions. We realized YBa$_2$Cu$_3$O$_{7-x}$ (YBCO) grain boundary (GB) biepitaxial junctions in the submicron scale, using low loss substrates, and analyzed their dissipation by comparing the transport measurements with Monte Carlo simulations. The behavior of the junctions can be fitted using a model based on two quality factors, which results in a frequency dependent damping. Moreover, our devices can be designed to have Josephson energy of the order of the Coulomb energy. In this unusual energy range, phase delocalization strongly influences the device's dynamics, promoting the transition to a quantum phase diffusion regime. We study the signatures of such a transition by combining the outcomes of Monte Carlo simulations with the analysis of the device's parameters, the critical current and the temperature behavior of the low voltage resistance $R_0$., Comment: 8 pages, 4 figures

Dissipation encodes the interaction of a quantum system with the environment and regulates the activation regimes of a Brownian particle. We have engineered grain boundary biepitaxial YBaCuO junctions to drive a direct transition from a quantum activated running state to a phase diffusion regime. The crossover to the quantum regime is tuned by the magnetic field and dissipation is described by a fully consistent set of junction parameters. To unravel phase dynamics in moderately damped systems is of general interest for advances in the comprehension of retrapping phenomena and in view of quantum hybrid technology.

YBaCuO nanowires were reproducibly fabricated down to widths of 50 nm. A Au/Ti cap layer on YBCO yielded high electrical performance up to temperatures above 80 K in single nanowires. Critical current density of tens of MA/cm2 at T = 4.2 K and of 10 MA/cm2 at 77 K were achieved that survive in high magnetic fields. Phase-slip processes were tuned by choosing the size of the nanochannels and the intensity of the applied external magnetic field. Data indicate that YBCO nanowires are rather attractive system for the fabrication of efficient sensors, supporting the notion of futuristic THz devices., 8 pages, 3 figures. Accepted for publication in Superconductor Science and Technology

We have extended the off-axis biepitaxial technique to produce YBCO grain boundary junctions on low loss substrates. Excellent transport properties have been reproducibly found, with remarkable values of the quality factor I(c)R(n) (with I(c) the critical current and R(n) the normal state resistance) above 10 mV, far higher than the values commonly reported in the literature for high temperature superconductor (HTS) based Josephson junctions. The outcomes are consistent with a picture of a more uniform grain boundary region along the current path. This work supports a possible implementation of grain boundary junctions for various applications including terahertz sensors and HTS quantum circuits in the presence of microwaves.