The Normal State Resistivity of Grain Boundaries in YBa2Cu3O7-delta

Using an optimized bridge geometry we have been able to make accurate measurements of the properties of YBa2Cu3O7-delta grain boundaries above Tc. The results show a strong dependence of the change of resistance with temperature on grain boundary angle. Analysis of our results in the context of band-bending allows us to estimate the height of the potential barrier present at the grain boundary interface.Comment: 11 pages, 3 figure

Improving high-T_c dc-SQUID performance by junction asymmetry

We study noise and noise energy of a high-T$_c$ dc SQUID fabricated on a high-$\epsilon_R$ substrate whose conduction properties are given by transmission line physics. We show that transmission line resonances greatly enhance the noise. Remarkably, resistance asymmetry enhances these resonances even more. However, as the transfer function scales the same way, the noise energy is reduced by asymmetry greatly enhancing the flexibility and performance of the SQUID.Comment: 9 pages, 4 figures. v2: published versio

Synthesis and characterization of novel chelation-free Zn(II)-azole complexes: Evaluation of antibacterial, antioxidant and DNA binding activity

589-597Here, we synthesized novel chelation-free Zn(II)-complexes (1-3) [ZnCl2L2] of monodentate ligands with L = 2-isopropylimidazole (L1), 2-methylbenzimidazole (L2), and 2-methylbenzoxazole (L3) and evaluated their antibacterial, antioxidant and DNA binding activities. The chelation-free properties of these coordination complexes were confirmed by UV-visible spectroscopy, 1H NMR spectroscopy, single X-ray crystallography and elemental analysis. Complexes 1-3 exhibited substantial antibacterial activity against all antibiotic susceptible bacteria within a concentration range of 100-200 µg/ml while free ligands L1 and L2 exhibited weak antibacterial activity considerably concentration above 200 µg/ml. Also, both complexes 2 and 3 were twice more active against methicillin-resistant Staphylococcus aureus (MRSA) than complex 1. Furthermore, we found that complexes 1-3 showed DNA binding activity with E. coli plasmid DNA and calf thymus DNA, which may be a plausible mechanism for their antibacterial activity. We also investigated the antioxidant activity of complexes 1-3 and found that complex 2 exhibited potential antioxidant activity compared to complexes 1 and 3. All these results suggest that the chelation-free Zn(II)-complexes can be the future candidates for more advance biological studies

Autologous Adipocyte Derived Stem Cells Favour Healing in a Minipig Model of Cutaneous Radiation Syndrome

Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs). For experiments, Göttingen minipigs were locally gamma irradiated using a 60Co source at the dose of 50 Gy and grafted (n = 5) or not (n = 8). ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL−1) and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50×106 ASCs each time) into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91). In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/− 28). Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS

Effects of a Ceramic Biomaterial on Immune Modulatory Properties and Differentiation Potential of Human Mesenchymal Stromal Cells of Different Origin.

The aim of this study was to assess the immune modulatory properties of human mesenchymal stromal cells obtained from bone marrow (BM-MSCs), fat (ASCs), and cord blood (CB-MSCs) in the presence of a hydroxyapatite and tricalcium-phosphate (HA/TCP) biomaterial as a scaffold for MSC delivery. In resting conditions, a short-term culture with HA/TCP did not modulate the anti-apoptotic and suppressive features of the various MSC types toward T, B, and NK cells; in addition, when primed with inflammatory cytokines, MSCs similarly increased their suppressive capacities in the presence or absence of HA/TCP. The long-term culture of BM-MSCs with HA/TCP induced an osteoblast-like phenotype with upregulation of OSTERIX and OSTEOCALCIN, similar to what was obtained with dexamethasone and, to a higher extent, with bone morphogenetic protein 4 (BMP-4) treatment. MSC-derived osteoblasts did not trigger immune cell activation, but were less efficient than undifferentiated MSCs in inhibiting stimulated T and NK cells. Interestingly, their suppressive machinery included not only the activation of indoleamine-2,3 dioxygenase (IDO), which plays a central role in T-cell inhibition, but also cyclooxygenase-2 (COX-2) that was not significantly involved in the immune modulatory effect of human undifferentiated MSCs. Since COX-2 is significantly involved in bone healing, its induction by HA/TCP could also contribute to the therapeutic activity of MSCs for bone tissue engineering

Mobile π−\pi-kinks and half-integer zero-field-like steps in highly discrete alternating 0−π0-\pi Josephson junction arrays

The dynamics of a one-dimensional, highly discrete, linear array of alternating $0-$ and $\pi-$ Josephson junctions is studied numerically, under constant bias current at zero magnetic field. The calculated current - voltage characteristics exhibit half-integer and integer zero-field-like steps for even and odd total number of junctions, respectively. Inspection of the instantaneous phases reveals that, in the former case, single $\pi-$kink excitations (discrete semi-fluxons) are supported, whose propagation in the array gives rise to the $1/2-$step, while in the latter case, a pair of $\pi-$kink -- $\pi-$antikink appears, whose propagation gives rise to the $1-$step. When additional $2\pi-$kinks are inserted in the array, they are subjected to fractionalization, transforming themselves into two closely spaced $\pi-$kinks. As they propagate in the array along with the single $\pi-$kink or the $\pi-$kink - $\pi-$antikink pair, they give rise to higher half-integer or integer zero-field-like steps, respectively.Comment: 7 pages, 8 figures, submitted to Supercond. Sci. Techno

The COMPASS Experiment at CERN

The COMPASS experiment makes use of the CERN SPS high-intensitymuon and hadron beams for the investigation of the nucleon spin structure and the spectroscopy of hadrons. One or more outgoing particles are detected in coincidence with the incoming muon or hadron. A large polarized target inside a superconducting solenoid is used for the measurements with the muon beam. Outgoing particles are detected by a two-stage, large angle and large momentum range spectrometer. The setup is built using several types of tracking detectors, according to the expected incident rate, required space resolution and the solid angle to be covered. Particle identification is achieved using a RICH counter and both hadron and electromagnetic calorimeters. The setup has been successfully operated from 2002 onwards using a muon beam. Data with a hadron beam were also collected in 2004. This article describes the main features and performances of the spectrometer in 2004; a short summary of the 2006 upgrade is also given.Comment: 84 papes, 74 figure

A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts

Patients with follicular lymphoma (FL) have heterogeneous outcomes. Predictor models able to distinguish, at diagnosis, patients at high versus low risk of progression are still needed. A training set of fresh-frozen tumour biopsies was prospectively obtained from 160 untreated patients with high-tumour-burden follicular lymphoma enrolled in the phase 3 randomised PRIMA trial, in which rituximab maintenance was evaluated after rituximab plus chemotherapy induction (median follow-up 6·6 years [IQR 6·0-7·0]). RNA of sufficient quality was obtained for 149 of 160 cases, and Affymetrix U133 Plus 2.0 microarrays were used for gene-expression profiling. We did a multivariate Cox regression analysis to identify genes with expression levels associated with progression-free survival independently of maintenance treatment in a subgroup of 134 randomised patients. Expression levels from 95 curated genes were then determined by digital expression profiling (NanoString technology) in 53 formalin-fixed paraffin-embedded samples of the training set to compare the technical reproducibility of expression levels for each gene between technologies. Genes with high correlation (>0·75) were included in an L2-penalised Cox model adjusted on rituximab maintenance to build a predictive score for progression-free survival. The model was validated using NanoString technology to digitally quantify gene expression in 488 formalin-fixed, paraffin-embedded samples from three independent international patient cohorts from the PRIMA trial (n=178; distinct from the training cohort), the University of Iowa/Mayo Clinic Lymphoma SPORE project (n=201), and the Barcelona Hospital Clinic (n=109). All tissue samples consisted of pretreatment diagnostic biopsies and were confirmed as follicular lymphoma grade 1-3a. The patients were all treated with regimens containing rituximab and chemotherapy, possibly followed by either rituximab maintenance or ibritumomab-tiuxetan consolidation. We determined an optimum threshold on the score to predict patients at low risk and high risk of progression. The model, including the multigene score and the threshold, was initially evaluated in the three validation cohorts separately. The sensitivity and specificity of the score for the prediction of the risk of lymphoma progression at 2 years were assessed on the combined validation cohorts. FINDINGS: In the training cohort, the expression levels of 395 genes were associated with a risk of progression. 23 genes reflecting both B-cell biology and tumour microenvironment with correlation coefficients greater than 0·75 between the two technologies and sample types were retained to build a predictive model that identified a population at an increased risk of progression (p<0·0001). In a multivariate Cox model for progression-free survival adjusted on rituximab maintenance treatment and Follicular Lymphoma International Prognostic Index 1 (FLIPI-1) score, this predictor independently predicted progression (adjusted hazard ratio [aHR] of the high-risk group compared with the low-risk group 3·68, 95% CI 2·19-6·17 [p<0·0001]). The 5-year progression-free survival was 26% (95% CI 16-43) in the high-risk group and 73% (64-83) in the low-risk group. The predictor performances were confirmed in each of the individual validation cohorts (aHR comparing high-risk to low-risk groups 2·57 [95% CI 1·65-4·01] in cohort 1; 2·12 [1·32-3·39] in cohort 2; and 2·11 [1·01-4·41] in cohort 3). In the combined validation cohort, the median progression-free survival was 3·1 years (95% CI 2·4-4·8) in the high-risk group and 10·8 years (10·1-not reached) in the low-risk group (p<0·0001). The risk of lymphoma progression at 2 years was 38% (95% CI 29-46) in the high-risk group and 19% (15-24) in the low-risk group. In a multivariate analysis, the score predicted progression-free survival independently of anti-CD20 maintenance treatment and of the FLIPI score (aHR for the combined cohort 2·30, 95% CI 1·72-3·07). INTERPRETATION: We developed and validated a robust 23-gene expression-based predictor of progression-free survival that is applicable to routinely available formalin-fixed, paraffin-embedded tumour biopsies from patients with follicular lymphoma at time of diagnosis. Applying this score could allow individualised therapy for patients according to their risk category