Effects of Magnetic Field and Temperature on the Critical Current Hysteresis in Tl-Ca-Ba-Cu-O Thin Films

The behavior of the critical current density of Tl-Ca-Ba-Cu-O superconducting thin films in a cycling magnetic field was investigated. The hysteresis of the transport Jc manifested similar features to those found in polycrystalline Y-Ba-Cu-O and granular Nb, Al thin films in zero-field cooling. However, a novel result of the transport Jc in field-cooled samples has been observed. The results were attributed to the presence of a saturated trapped magnetic flux in the weaklink network. The effects of temperature on both the trapped flux and the transport Jc suggest the existence of various states of the trapped flux in the Tl-based superconducting thin films

Inflammatory Signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice

<p>Abstract</p> <p>Background</p> <p>Obesity and inflammation are highly integrated processes in the pathogenesis of insulin resistance, diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Molecular mechanisms underlying inflammatory events during high fat diet-induced obesity are poorly defined in mouse models of obesity. This work investigated gene activation signals integral to the temporal development of obesity.</p> <p>Methods</p> <p>Gene expression analysis in multiple organs from obese mice was done with Taqman Low Density Array (TLDA) using a panel of 92 genes representing cell markers, cytokines, chemokines, metabolic, and activation genes. Mice were monitored for systemic changes characteristic of the disease, including hyperinsulinemia, body weight, and liver enzymes. Liver steatosis and fibrosis as well as cellular infiltrates in liver and adipose tissues were analyzed by histology and immunohistochemistry.</p> <p>Results</p> <p>Obese C57BL/6 mice were fed with high fat and cholesterol diet (HFC) for 6, 16 and 26 weeks. Here we report that the mRNA levels of macrophage and inflammation associated genes were strongly upregulated at different time points in adipose tissues (6-16 weeks) and liver (16-26 weeks), after the start of HFC feeding. CD11b⁺and CD11c⁺macrophages highly infiltrated HFC liver at 16 and 26 weeks. We found clear evidence that signals for IL-1β, IL1RN, TNF-α and TGFβ-1 are present in both adipose and liver tissues and that these are linked to the development of inflammation and insulin resistance in the HFC-fed mice.</p> <p>Conclusions</p> <p>Macrophage infiltration accompanied by severe inflammation and metabolic changes occurred in both adipose and liver tissues with a temporal shift in these signals depending upon the duration of HFC feeding. The evidences of gene expression profile, elevated serum alanine aminotransferase, and histological data support a progression towards nonalcoholic fatty liver disease and steatohepatitis in these HFC-fed mice within the time frame of 26 weeks.</p

A selective and potent CXCR3 antagonist SCH 546738 attenuates the development of autoimmune diseases and delays graft rejection

<p>Abstract</p> <p>Background</p> <p>The CXCR3 receptor and its three interferon-inducible ligands (CXCL9, CXCL10 and CXCL11) have been implicated as playing a central role in directing a Th1 inflammatory response. Recent studies strongly support that the CXCR3 receptor is a very attractive therapeutic target for treating autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and psoriasis, and to prevent transplant rejection. We describe here the in vitro and in vivo pharmacological characterizations of a novel and potent small molecule CXCR3 antagonist, SCH 546738.</p> <p>Results</p> <p>In this study, we evaluated in vitro pharmacological properties of SCH 546738 by radioligand receptor binding and human activated T cell chemotaxis assays. In vivo efficacy of SCH 546738 was determined by mouse collagen-induced arthritis, rat and mouse experimental autoimmune encephalomyelitis, and rat cardiac transplantation models. We show that SCH 546738 binds to human CXCR3 with a high affinity of 0.4 nM. In addition, SCH 546738 displaces radiolabeled CXCL10 and CXCL11 from human CXCR3 with IC₅₀ranging from 0.8 to 2.2 nM in a non-competitive manner. SCH 546738 potently and specifically inhibits CXCR3-mediated chemotaxis in human activated T cells with IC₉₀about 10 nM. SCH 546738 attenuates the disease development in mouse collagen-induced arthritis model. SCH 546738 also significantly reduces disease severity in rat and mouse experimental autoimmune encephalomyelitis models. Furthermore, SCH 546738 alone achieves dose-dependent prolongation of rat cardiac allograft survival. Most significantly, SCH 546738 in combination with CsA supports permanent engraftment.</p> <p>Conclusions</p> <p>SCH 546738 is a novel, potent and non-competitive small molecule CXCR3 antagonist. It is efficacious in multiple preclinical disease models. These results demonstrate that therapy with CXCR3 antagonists may serve as a new strategy for treatment of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, and to prevent transplant rejection.</p

Intratumoral Administration of Secondary Lymphoid Chemokine and Unmethylated Cytosine-phosphorothioate-guanine Oligodeoxynucleotide Synergistically Inhibits Tumor Growth in Vivo

Secondary lymphoid tissue chemokine (SLC), which is expressed in T cell zones of secondary lymphoid organs, including the spleen and lymph nodes, strongly recruits both T lymphocytes and mature dendritic cells. As appropriate interaction of tumor-specific T cells and mature dendritic cells, equipped with tumor antigens, is a prerequisite for effective T cell immunity against established tumors, we mobilized lymphocytes and dendritic cells to tumor sites by intratumoral injection of secondary lymphoid tissue chemokine-Fc (SLC-Fc) fusion protein using the B16F10 murine melanoma model. Activation of dendritic cells, another prerequisite for the effective activation of naïve tumor-specific T cells, was achieved by the addition of immunostimulatory cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG-ODN) into the tumor site. Intratumoral administration of SLC-Fc or CpG-ODN revealed antitumor effects against B16F10 murine melanoma grown in the subcutaneous space. Co-treatment of SLC-Fc and CpG-ODN displayed synergistic effects in reducing the tumor size. The synergistic antitumor effect in co-treatment group was correlated with the synergistic/additive increase in the infiltration of CD4+ T cells and CD11c+ dendritic cells in the tumor mass compared to the single treatment groups. These results suggest that the combined use of chemokines and adjuvant molecules may be a possible strategy in clinical tumor immunotherapy

Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet

The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO) model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/ 0.12% cholesterol (HF/CH) or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM). Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF), stromal vascular fraction (SVF), and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg) for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6

Scanned Probe Oxidation onp-GaAs(100) Surface with an Atomic Force Microscopy

Locally anodic oxidation has been performed to fabricate the nanoscale oxide structures onp-GaAs(100) surface, by using an atomic force microscopy (AFM) with the conventional and carbon nanotube (CNT)-attached probes. The results can be utilized to fabricate the oxide nanodots under ambient conditions in noncontact mode. To investigate the conversion of GaAs to oxides, micro-Auger analysis was employed to analyze the chemical compositions. The growth kinetics and the associated mechanism of the oxide nanodots were studied under DC voltages. With the CNT-attached probe the initial growth rate of oxide nanodots is in the order of ~300 nm/s, which is ~15 times larger than that obtained by using the conventional one. The oxide nanodots cease to grow practically as the electric field strength is reduced to the threshold value of ~2 × 107 V cm−1. In addition, results indicate that the height of oxide nanodots is significantly enhanced with an AC voltage for both types of probes. The influence of the AC voltages on controlling the dynamics of the AFM-induced nanooxidation is discussed

Nanogrids and Beehive-Like Nanostructures Formed by Plasma Etching the Self-Organized SiGe Islands

A lithography-free method for fabricating the nanogrids and quasi-beehive nanostructures on Si substrates is developed. It combines sequential treatments of thermal annealing with reactive ion etching (RIE) on SiGe thin films grown on (100)-Si substrates. The SiGe thin films deposited by ultrahigh vacuum chemical vapor deposition form self-assembled nanoislands via the strain-induced surface roughening (Asaro-Tiller-Grinfeld instability) during thermal annealing, which, in turn, serve as patterned sacrifice regions for subsequent RIE process carried out for fabricating nanogrids and beehive-like nanostructures on Si substrates. The scanning electron microscopy and atomic force microscopy observations confirmed that the resultant pattern of the obtained structures can be manipulated by tuning the treatment conditions, suggesting an interesting alternative route of producing self-organized nanostructures