Low-Frequency Optical Conductivity in Inhomogeneous d-wave Superconductors

Motivated by the recent optical conductivity experiments on Bi_2Sr_2CaCu_2O_{8+delta} films, we examine the possible origin of low-frequency dissipation in the superconducting state. In the presence of spatial inhomogeneity of the local phase stiffness rho_s, it is shown that some spectral weight is removed from omega=0 to finite frequencies and contribute to dissipation. A case where both rho_s and the local normal fluid density are inhomogeneous is also considered. We find an enhanced dissipation at low frequency if the two variations are anti-correlated.Comment: To appear in Phys. Rev.

Generation of functional cardiomyocytes from the synoviocytes of patients with rheumatoid arthritis via induced pluripotent stem cells

Cardiovascular disease is a leading cause of morbidity in rheumatoid arthritis (RA) patients. This study aimed to generate and characterise cardiomyocytes from induced pluripotent stem cells (iPSCs) of RA patients. Fibroblast-like synoviocytes (FLSs) from patients with RA and osteoarthritis (OA) were successfully reprogrammed into RA-iPSCs and OA-iPSCs, respectively. The pluripotency of iPSCs was confirmed by quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining. Established iPSCs were differentiated into cardiomyocytes using a small molecule-based monolayer differentiation protocol. Within 12 days of cardiac differentiation from patient-specific and control-iPSCs, spontaneously beating cardiomyocytes (iPSC-CMs) were observed. All iPSC-CMs exhibited a reliable sarcomeric structure stained with antibodies against cardiac markers and similar expression profiles of cardiac-specific genes. Intracellular calcium signalling was recorded to compare calcium-handling properties among cardiomyocytes differentiated from the three groups of iPSCs. RA-iPSC-CMs had a lower amplitude and a shorter duration of calcium transients than the control groups. Peak tangential stress and the maximum contractile rate were also decreased in RA-iPSC-CMs, suggesting that contractility was reduced. This study demonstrates the successful generation of functional cardiomyocytes from pathogenic synovial cells in RA patients through iPSC reprogramming. Research using RA-iPSC-CMs might provide an opportunity to investigate the pathophysiology of cardiac involvement in RA

The in vitro effects of dehydroepiandrosterone on human osteoarthritic chondrocytes

AbstractObjective: To investigate the in vitro effects of dehydroepiandrosterone (DHEA) on human osteoarthritic chondrocytes.Design: Chondrocytes isolated from human osteoarthritic knee cartilage were three-dimensionally cultured in alginate beads, except for cell proliferation experiment. Cells were treated with DHEA in the presence or absence of IL-1β. The effects on chondrocytes were analyzed using a 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay (for chondrocyte proliferation), a dimethylmethylene blue (DMB) assay (for glycosaminoglycan (GAG) synthesis), and an indole assay (for DNA amount). Gene expressions of type I and II collagen, metalloproteinase-1 and -3 (MMP-1 and -3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) as well as the IL-1β-induced gene expressions of MMP-1 and -3 were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The protein synthesis of MMP-1 and -3 and TIMP-1 was determined by Western blotting.Results: The treatment of chondrocytes with DHEA did not affect chondrocyte proliferation or GAG synthesis up to 100μM of concentration. The gene expression of type II collagen increased in a dose-dependent manner, while that of type I decreased. DHEA suppressed the expression of MMP-1 significantly at concentrations exceeding 50μM. The gene expression of MMP-3 was also suppressed, but this was without statistical significance. The expression of TIMP-1 was significantly increased by DHEA at concentrations exceeding 10μM. The effects of DHEA on the gene expressions of MMP-1 and -3 were more prominent in the presence of IL-1β, in which DHEA suppressed not only MMP-1, but also MMP-3 at the lower concentrations, 10 and 50μM, respectively. Western blotting results were in agreement with RT-PCR, which indicates that DHEA acts at the gene transcription level.Conclusions: Our study demonstrates that DHEA has no toxic effect on chondrocytes up to 100μM of concentration and has an ability to modulate the imbalance between MMPs and TIMP-1 during OA at the transcription level, which suggest that it has a protective role against articular cartilage loss

Chemical Accident Hazard Assessment by Spatial Analysis of Chemical Factories and Accident Records in South Korea

This study identified the potential chemical accident occurrence in Korea by analyzing the spatial distribution of chemical factories and accidents. The number of chemical factories and accidents in 25-km2 grids were used as the attribute value for spatial analysis. First, semi-variograms were conducted to examine spatial distribution patterns and to identify spatial autocorrelation of chemical factories and accidents. Semi-variograms explained that the spatial distribution of chemical factories and accidents were spatially autocorrelated. Second, the results of the semi-variograms were used in Ordinary Kriging to estimate chemical hazard levels. The level values were extracted from the Ordinary Kriging result and their spatial similarity was examined by juxtaposing the two values with respect to their location. Six peaks were identified in both the factory hazard and accident hazard estimation result, and the peaks correlated with major cities in Korea. Third, the estimated two hazard levels were classified with geometrical interval and could be classified into four quadrants: Low Factory and Low Accident (LFLA), High Factory and Low Accident (HFLA), Low Factory and High Accident(LFHA), and High Factory and High Accident (HFHA). The 4 groups identified different chemical safety management issues in Korea; safe LFLA group, many chemical reseller factories were found in HFLA group, chemical transportation accidents were in the LFHA group, and an abundance of factories and accidents were in the HFHA group. Each quadrant represented different safety management obstacles in Korea, and studying spatial differences can support the establishment of an efficient risk management plan

A Geometric Fractal Growth Model for Scale Free Networks

We introduce a deterministic model for scale-free networks, whose degree distribution follows a power-law with the exponent $\gamma$. At each time step, each vertex generates its offsprings, whose number is proportional to the degree of that vertex with proportionality constant m-1 (m>1). We consider the two cases: first, each offspring is connected to its parent vertex only, forming a tree structure, and secondly, it is connected to both its parent and grandparent vertices, forming a loop structure. We find that both models exhibit power-law behaviors in their degree distributions with the exponent $\gamma=1+\ln (2m-1)/\ln m$. Thus, by tuning m, the degree exponent can be adjusted in the range, $2 <\gamma < 3$. We also solve analytically a mean shortest-path distance d between two vertices for the tree structure, showing the small-world behavior, that is, $d\sim \ln N/\ln {\bar k}$, where N is system size, and $\bar k$ is the mean degree. Finally, we consider the case that the number of offsprings is the same for all vertices, and find that the degree distribution exhibits an exponential-decay behavior

Mucociliary Transit Assessment Using Automatic Tracking in Phase Contrast X-Ray Images of Live Mouse Nasal Airways

Purpose The rate of mucociliary transit (MCT) is an indicator of the hydration and health of the airways for cystic fibrosis (CF). To determine the effectiveness of cystic fibrosis respiratory therapies, we have developed a novel method to noninvasively quantify the local rate and patterns of MCT behaviour in vivo by using synchrotron phase contrast X-ray imaging (PCXI) to visualise the MCT motion of micron-sized spherical particles deposited onto the airway surfaces of live mice. Methods In this study the baseline MCT behaviour was assessed in the nasal airways of CFTR-null and normal mice which were then treated with hypertonic saline (HS) or mannitol. To assess MCT, the particle motion was tracked throughout the synchrotron PCXI sequences using fully-automated custom image analysis software. Results There was no significant difference in the MCT rate between normal and CFTR-null mice, but the analysis of MCT particle tracking showed that HS may have a longer duration of action in CFTR-null mice than in the normal mice. Conclusion This study demonstrated that changes in MCT rate in CF and normal mouse nasal airways can be measured using PCXI and customised tracking software and used for assessing the effects of airway rehydrating pharmaceutical treatments.Hye-Won Jung, Ivan Lee, Sang, Heon Lee, Kaye Morgan, David Parsons, Martin Donnelle

DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load

Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation in precision immunotherapy