Nonlinear Dynamics in the Resonance Lineshape of NbN Superconducting Resonators

In this work we report on unusual nonlinear dynamics measured in the resonance response of NbN superconducting microwave resonators. The nonlinear dynamics, occurring at relatively low input powers (2-4 orders of magnitude lower than Nb), and which include among others, jumps in the resonance lineshape, hysteresis loops changing direction and resonance frequency shift, are measured herein using varying input power, applied magnetic field, white noise and rapid frequency sweeps. Based on these measurement results, we consider a hypothesis according to which local heating of weak links forming at the boundaries of the NbN grains are responsible for the observed behavior, and we show that most of the experimental results are qualitatively consistent with such hypothesis.Comment: Updated version (of cond-mat/0504582), 16 figure

Characterization and Insulin-Mimetic Potential of Oxidovanadium(IV) Complexes Derived from Monoesters and -carboxylates of 2,5-Dipicolinic Acid

The monomethyl ester 2MeOdipicH ( 1 ) of 2,5-dipicolinic acid, characterized as its magnesium salt [Mg(H 2 O) 6 ](2MeOdipic) 2 , was converted, via the diesters 2MeO-5ROdipic and the copper complexes [Cu(5ROdipic) 2 ], to the ligands 5ROdipicH (R = i Pr 2a , ( S )-2-Bu 2b ). The proligands 2MeO-5ROdipic (with R = diisopropyl- D -galactose 2c , myo -inositol-orthoformate 2d ) and 2MeO-5R′NHdipic (where R′ represents the ethyl-protected L -amino acid residues Gly 3a , Ala 3b , Val 3c and Phe 3d ) were obtained from 2-MeO-5Cldipic and the amino acid ethyl esters. Reaction of 2 and 3 with VOSO 4 afforded the complexes [VO(H 2 O)(5ROdipic) 2 ]( 4a – d ) and [VO(H 2 O)(5R′NHdipic) 2 ], 5a – d , respectively. [Mg(H 2 O) 6 ](2MeOdipic) 2 · 4H 2 O, 2b , 3a and 4a· 0.5H 2 O were characterized by single-crystal X-ray diffraction analysis. Selected type 4 and 5 complexes were submitted to in vitro tests (fibroblasts, SV 3T3 mice fibroblasts) for their uptake kinetics and insulin-mimetic behavior. The compounds were comparable to insulin in their ability to stimulate cellular glucose uptake and metabolism. In vitro tests with rat adipocytes showed that the complexes also mimic the ability of insulin to inhibit lipolysis. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55802/1/3575_ftp.pd

DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers

Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes

GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma

Side population (SP) cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC8 SP cells showed characteristics of cancer stem cells, such as high growth rate, chemoresistance and high invasiveness. To further characterize the NEC8 SP cells, we used DNA microarrays. Among 38,500 genes, we identified 12 genes that were over-expressed in SP cells and 1 gene that was over-expressed in non-SP cells. Among these 13 genes, we focused on GADD45b. GADD45b was over-expressed in non-SP cells, but the inhibition of GADD45b had no effect on non-SP cells. Paradoxically, the inhibition of GADD45b significantly reduced the viability of NEC8 SP cells. The inhibition of ABCG2, which determines the SP phenotype, had no effect on the invasiveness of NEC8 SP cells, but the inhibition of GADD45b significantly reduced invasiveness. These results suggest that GADD45b, but not ABCG2, might determine the cancer stem cell-like phenotype, such as chemoresistance and the high invasiveness of NEC8 SP cells, and might be a good therapeutic target

Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells

The cellular ontogeny of hematopoietic stem cells (HSCs) remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC) differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs) as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+)CD41(+)CD45(−) phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner

Aesthetic pectoral muscle flap repair for refractory enterocutaneous fistula after salvage esophagectomy in a female patient

Anastomotic leakage is a severe complication of esophagectomy. Development of an enterocutaneous fistula after anastomotic leakage often occurs after subcutaneous-route reconstruction at esophagectomy. Pectoralis myocutaneous flap (PMCF) repair has recently been performed when an enterocutaneous fistula was refractory to conservative treatment. However, this procedure requires a conspicuous incision and results in deformity of the breast especially in female patient. We performed pectoralis muscle flap (PMF) repair for a 50-year-old woman with a refractory enterocutaneous fistula after salvage esophagectomy. We made an oblique incision along the inframammary crease in order to avoid a conspicuous scar and moved the PMF under the mammary gland to the site of anastomosis. This method was effective for repairing a refractory enterocutaneous fistula, with especially good aesthetic results in a female patient

Establishment of Novel High-Standard Chemiluminescent Assay for NTPase in Two Protozoans and Its High-Throughput Screening

Toxoplasma gondii is a major protozoan parasite and infects human and many other warm-blooded animals. The infection leads to Toxoplasmosis, a serious issue in AIDS patients, organ transplant recipients and pregnant women. Neospora caninum, another type of protozoa, is closely related to Toxoplasma gondii. Infections of the protozoa in animals also causes serious diseases such as Encephalomyelitis and Myositis-Polyradiculitis in dogs or abortion in cows. Both Toxoplasma gondii and Neospora caninum have similar nucleoside triphosphate hydrolases (NTPase), NcNTPase and TgNTPase-I in Neospora caninum and Toxoplasma gondii, respectively. These possibly play important roles in propagation and survival. Thus, we targeted the enzymes for drug discovery and tried to establish a novel high-standard assay by a combination of original biochemical enzyme assay and fluorescent assay to determine ADP content. We then validated whether or not it can be applied to high-throughput screening (HTS). Then, it fulfilled criterion to carry out HTS in both of the enzymes. In order to identify small molecules having inhibitory effects on the protozoan enzyme, we also performed HTS using two synthetic compound libraries and an extract library derived from marine bacteria and then, identified 19 compounds and 6 extracts. Nagasaki University collected many extracts from over 18,000 marine bacteria found in local Omura bay, and continues to compile an extensive collection of synthetic compounds from numerous drug libraries established by Japanese chemists