1,335 research outputs found
Simulation of Flood Propagation Due to Levee Break Using the Cartesian Cut Cell Method
Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv
Tenovin-1, a selective SIRT1/2 inhibitor, attenuates high-fat diet-induced hepatic fibrosis via Inhibition of HSC activation in ZDF rats
Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-β1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 inhibitor. ZDF rats were divided into chow diet, HFD, and HFD + Tenovin-1 groups. Tenovin-1 reduced hepatic damage, inhibited inflammatory cell infiltration, micro/ macro-vesicular steatosis and prevented collagen deposition HFD-fed rats. Tenovin-1 reduced serum biochemical parameters, triglyceride (TG) and malondialdehyde (MDA) levels but increased glutathione, catalase, and superoxide dismutase levels. Tenovin-1 mitigated proinflammatory cytokines IL-6, IL-1β, TNFα and fibrosis biomarkers in HFD rats, TGF-β1-activated LX-2 and FFA treated SCC cells. Additionally, Tenovin-1 suppressed SIRT1/2 expression and inhibited JNK-1 and STAT3 phosphorylation in HFD rats and FFA-treated SCC cells. In conclusion, Tenovin-1 attenuates hepatic fibrosis by stimulating antioxidants and inhibiting inflammatory cytokines under HFD conditions in diabetic rats
Physical properties of transparent perovskite oxides (Ba,La)SnO3 with high electrical mobility at room temperature
Transparent electronic materials are increasingly in demand for a variety of
optoelectronic applications. BaSnO3 is a semiconducting oxide with a large band
gap of more than 3.1 eV. Recently, we discovered that La doped BaSnO3 exhibits
unusually high electrical mobility of 320 cm^2(Vs)^-1 at room temperature and
superior thermal stability at high temperatures [H. J. Kim et al. Appl. Phys.
Express. 5, 061102 (2012)]. Following that work, we report various physical
properties of (Ba,La)SnO3 single crystals and films including
temperature-dependent transport and phonon properties, optical properties and
first-principles calculations. We find that almost doping-independent mobility
of 200-300 cm^2(Vs)^-1 is realized in the single crystals in a broad doping
range from 1.0x10^19 to 4.0x10^20 cm^-3. Moreover, the conductivity of ~10^4
ohm^-1cm^-1 reached at the latter carrier density is comparable to the highest
value. We attribute the high mobility to several physical properties of
(Ba,La)SnO3: a small effective mass coming from the ideal Sn-O-Sn bonding,
small disorder effects due to the doping away from the SnO2 conduction channel,
and reduced carrier scattering due to the high dielectric constant. The
observation of a reduced mobility of ~70 cm^2(Vs)^-1 in the film is mainly
attributed to additional carrier-scatterings which are presumably created by
the lattice mismatch between the substrate SrTiO3 and (Ba,La)SnO3. The main
optical gap of (Ba,La)SnO3 single crystals remained at about 3.33 eV and the
in-gap states only slightly increased, thus maintaining optical transparency in
the visible region. Based on these, we suggest that the doped BaSnO3 system
holds great potential for realizing all perovskite-based, transparent
high-frequency high-power functional devices as well as highly mobile
two-dimensional electron gas via interface control of heterostructured films.Comment: 31 pages, 7 figure
Normal stress difference-driven particle focusing in nanoparticle colloidal dispersion
Colloidal dispersion has elastic properties due to Brownian relaxation process. However, experimental evidence for the elastic properties, characterized with normal stress differences, is elusive in shearing colloidal dispersion, particularly at low Peclet numbers (Pe < 1). Here, we report that single micrometer-sized polystyrene (PS) beads, suspended in silica nanoparticle dispersion (8 nm radius; 22%, v/v), laterally migrate and form a tightly focused stream by the normal stress differences, generated in pressure-driven microtube flow at low Pe. The nanoparticle dispersion was expected to behave as a Newtonian fluid because of its ultrashort relaxation time (2 mu s), but large shear strain experienced by the PS beads causes the notable non-Newtonian behavior. We demonstrate that the unique rheological properties of the nanoparticle dispersion generate the secondary flow in perpendicular to mainstream in a noncircular conduit, and the elastic properties of blood plasma-constituting protein solutions are elucidated by the colloidal dynamics of protein molecules
Nitric oxide induces MUC5AC mucin in respiratory epithelial cells through PKC and ERK dependent pathways
BACKGROUND: Nitric oxide (NO) is generally increased during inflammatory airway diseases. This increased NO stimulates the secretion of mucin from the goblet cell and submucosal glands but the mechanism is still unknown precisely. In this study, we investigated potential signaling pathways involving protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) in the NO-induced MUC5AC mucin gene and protein expression in A549 cells. METHODS: Nitric oxide was donated to the A549 cells by NOR-1. MUC5AC mucin levels were assayed by enzyme-linked immunosorbent assay (ELISA). MUC5AC promoter activity was determined by measuring luciferase activity after the lysing the transfected cells. Activation of PKC isoforms were measured by assessing the distribution of the enzyme between cytosolic and membrane fractions using immunoblotting. Immunoblotting experiments using a monoclonal antibody specific to PKC isoforms were performed in the cytosol and membrane fractions from A549 cells. Western blot analysis for pERK and p38 were performed using the corresponding antibodies from the cell lysates after donating NO to the A549 cells by NOR-1. RESULTS: The transcriptional activity of MUC5AC promoter was maximal at the concentration of 0.1 mM NOR-1 for 1 hour incubation in transfected A549 cells. (±)-(E)-methyl-2-((E)-hydroxyimino)-5-nitro-6-methoxy-3-hexenamide (NOR-1) markedly displaced the protein kinase C (PKC)α and PKCδ from the cytosol to the membrane. Furthermore, the PKC-α,βinhibitors, GÖ6976 (10 nM) and PKCδ inhibitors, rottlerin (4 μM) inhibited the NOR-1 induced migration of PKCα and PKCδ respectively. NOR-1 also markedly increased the MUC5AC promoter activity and mRNA expression, mucin synthesis and ERK1/2 phosphorylation. The PKC inhibitors also inhibited the NOR-1 induced MUC5AC mRNA and MUC5AC protein synthesis by inhibiting the activation of PKCα and PKCδ with ERK1/2 pathways. CONCLUSION: Exogenous NO induced the MUC5AC mucin gene and protein through the PKCα and PKCδ – ERK pathways in A549 cells. Inhibition of PKC attenuated NO-mediated MUC5AC mucin synthesis. In view of this findings, PKC inhibitors might be useful in the treatment of bronchial asthma and chronic bronchitis patients where NO and mucus are increased in the bronchial airways
WSPMaker: a web tool for calculating selection pressure in proteins and domains using window-sliding
Complete response to FOLFOX4 therapy in a patient with advanced urothelial cancer: a case report
No standard has been established for salvage therapy in gemcitabine refractory advanced urothelial cancer. We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was still showing a complete response after 4 months. Clinical trials using the FOLFOX regimen as salvage therapy for gemcitabine-refractory advanced urothelial cancer are warranted
Intra- and inter-hemispheric effective connectivity in the human somatosensory cortex during pressure stimulation
Background: Slow-adapting type I (SA-I) afferents deliver sensory signals to the somatosensory cortex during low-frequency (or static) mechanical stimulation. It has been reported that the somatosensory projection from SA-I afferents is effective and reliable for object grasping and manipulation. Despite a large number of neuroimaging studies on cortical activation responding to tactile stimuli mediated by SA-I afferents, how sensory information of such tactile stimuli flows over the somatosensory cortex remains poorly understood. In this study, we investigated tactile information processing of pressure stimuli between the primary (SI) and secondary (SII) somatosensory cortices by measuring effective connectivity using dynamic causal modeling (DCM). We applied pressure stimuli for 3 s to the right index fingertip of healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. Results: DCM analysis revealed intra-hemispheric effective connectivity between the contralateral SI (cSI) and SII (cSII) characterized by both parallel (signal inputs to both cSI and cSII) and serial (signal transmission from cSI to cSII) pathways during pressure stimulation. DCM analysis also revealed inter-hemispheric effective connectivity among cSI, cSII, and the ipsilateral SII (iSII) characterized by serial (from cSI to cSII) and SII-level (from cSII to iSII) pathways during pressure stimulation. Conclusions: Our results support a hierarchical somatosensory network that underlies processing of low-frequency tactile information. The network consists of parallel inputs to both cSI and cSII (intra-hemispheric), followed by serial pathways from cSI to cSII (intra-hemispheric) and from cSII to iSII (inter-hemispheric). Importantly, our results suggest that both serial and parallel processing take place in tactile information processing of static mechanical stimuli as well as highlighting the contribution of callosal transfer to bilateral neuronal interactions in SII.open1
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