Identification of Nonstandard Multifractional Brownian Motions under White Noise by Multiscale Local Variations of Its Sample Paths

The Hurst exponent and variance are two quantities that often characterize real-life, high-frequency observations. Such real-life signals are generally measured under noise environments. We develop a multiscale statistical method for simultaneous estimation of a time-changing Hurst exponent H(t) and a variance parameter C in a multifractional Brownian motion model in the presence of white noise. The method is based on the asymptotic behavior of the local variation of its sample paths which applies to coarse scales of the sample paths. This work provides stable and simultaneous estimators of both parameters when independent white noise is present. We also discuss the accuracy of the simultaneous estimators compared with a few selected methods and the stability of computations with regard to adapted wavelet filters

Inhibition of autophagy promotes salinomycin-induced apoptosis via reactive oxygen species-mediated PI3K/AKT/mTOR and ERK/p38 MAPK-dependent signaling in human prostate cancer cells

Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells. Cell viability assay, Western blot, annexin V/propidium iodide assay, acridine orange (AO) staining, caspase-3 activity assay, reactive oxygen species (ROS) production, and mitochondrial membrane potential were assayed. Our data showed that salinomycin alters the sensitivity of prostate cancer cells to autophagy. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, enhanced the salinomycin-induced apoptosis. Notably, salinomycin decreased phosphorylated of AKT and phosphorylated mammalian target of rapamycin (mTOR) in prostate cancer cells. Pretreatment with LY294002, an autophagy and PI3K inhibitor, enhanced the salinomycin-induced apoptosis by decreasing the AKT and mTOR activities and suppressing autophagy. However, pretreatment with PD98059 and SB203580, an extracellular signal-regulated kinases (ERK), and p38 inhibitors, suppressed the salinomycin-induced autophagy by reversing the upregulation of ERK and p38. In addition, pretreatment with N-acetyl-L-cysteine (NAC), an antioxidant, inhibited salinomycin-induced autophagy by suppressing ROS production. Our results suggested that salinomycin induces apoptosis, which was related to ROS-mediated autophagy through regulation of the PI3K/AKT/mTOR and ERK/p38 MAPK signaling pathways

Graphene Q-switched Yb:KYW planar waveguide laser

A diode-pumped Yb:KYW planar waveguide laser, single-mode Q-switched by evanescent-field interaction with graphene, is demonstrated for the first time. Few-layer graphene grown by chemical vapor deposition is transferred onto the top of a guiding layer, which initiates stable Q-switched operation in a 2.4-cm-long waveguide laser operating near 1027 nm. Average output powers up to 34 mW and pulse durations as short as 349 ns are achieved. The measured output beam profile, clearly exhibiting a single mode, agrees well with the theoretically calculated mode intensity distribution inside the waveguide. As the pump power is increased, the repetition rate and pulse energy increase from 191 to 607 kHz and from 7.4 to 58.6 nJ, respectively, whereas the pulse duration decreases from 2.09 μs to 349 ns

Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis through VEGF and S100A8

Emerging evidence indicates that myeloid cells are essential for promoting new blood vessel formation by secreting various angiogenic factors. Given that hypoxia-inducible factor (HIF) is a critical regulator for angiogenesis, we questioned whether HIF in myeloid cells also plays a role in promoting angiogenesis. To address this question, we generated a unique strain of myeloid-specific knockout mice targeting HIF pathways using human S100A8 as a myeloid-specific promoter. We observed that mutant mice where HIF-1 is transcriptionally activated in myeloid cells (by deletion of the von Hippel-Lindau gene) resulted in erythema, enhanced neovascularization in matrigel plugs, and increased production of vascular endothelial growth factor (VEGF) in the bone marrow, all of which were completely abrogated by either genetic or pharmacological inactivation of HIF-1. We further found that monocytes were the major effector producing VEGF and S100A8 proteins driving neovascularization in matrigel. Moreover, by using a mouse model of hindlimb ischemia we observed significantly improved blood flow in mice intramuscularly injected with HIF-1-activated monocytes. This study therefore demonstrates that HIF-1 activation in myeloid cells promotes angiogenesis through VEGF and S100A8 and that this may become an attractive therapeutic strategy to treat diseases with vascular defects.X1137Ysciescopu

HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling

<p>Abstract</p> <p>Background</p> <p>Androgen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained.</p> <p>Results</p> <p>In this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21^waftumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21^waf; this inhibition largely affected HOXB13-mediated promotion of E2F signaling.</p> <p>Conclusions</p> <p>Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling.</p

Gyejigachulbu-Tang Relieves Oxaliplatin-Induced Neuropathic Cold and Mechanical Hypersensitivity in Rats via the Suppression of Spinal Glial Activation

Activation of spinal glial cells plays a crucial role in the pathogenesis of neuropathic pain. An administration of oxaliplatin, an important anticancer drug, often induces acute neuropathic cold hypersensitivity and/or mechanical hypersensitivity in patients. Gyejigachulbu-tang (GBT), a herbal formula comprising Cinnamomi Cortex, Paeoniae Radix, Atractylodis Lanceae Rhizoma, Zizyphi Fructus, Glycyrrhizae Radix, Zingiberis Rhizoma, and Aconiti Tuber, has been used in East Asia to treat various pain symptoms, especially in cold patients. This study investigated whether and how GBT alleviates oxaliplatin-induced cold and mechanical hypersensitivity in rats. The behavioral signs of cold and mechanical hypersensitivity were evaluated by a tail immersion test in cold water (4°C) and a von Frey hair test, respectively. The significant cold and mechanical hypersensitivity were observed 3 days after an oxaliplatin injection (6 mg/kg, i.p.). Daily oral administration of GBT (200, 400, and 600 mg/kg) for 5 days markedly attenuated cold and mechanical hypersensitivity. Immunoreactivities of glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker) in the spinal dorsal horn were significantly increased by an oxaliplatin injection, which were restored by GBT administration. These results indicate that GBT relieves oxaliplatin-induced cold and mechanical hypersensitivity in rats possibly through the suppression of spinal glial activation

30 inch Roll-Based Production of High-Quality Graphene Films for Flexible Transparent Electrodes

We report that 30-inch scale multiple roll-to-roll transfer and wet chemical doping considerably enhance the electrical properties of the graphene films grown on roll-type Cu substrates by chemical vapor deposition. The resulting graphene films shows a sheet resistance as low as ~30 Ohm/sq at ~90 % transparency which is superior to commercial transparent electrodes such as indium tin oxides (ITO). The monolayer of graphene shows sheet resistances as low as ~125 Ohm/sq with 97.4% optical transmittance and half-integer quantum Hall effect, indicating the high-quality of these graphene films. As a practical application, we also fabricated a touch screen panel device based on the graphene transparent electrodes, showing extraordinary mechanical and electrical performances

Efficacy of switching from adefovir to tenofovir in chronic hepatitis B patients who exhibit suboptimal responses to adefovir-based combination rescue therapy due to resistance to nucleoside analogues (SATIS study)

Background/Aims It remains to be determined whether switching from adefovir (ADV) to tenofovir (TDF) provides better virological outcomes in patients exhibiting suboptimal responses to ADV plus nucleoside analogue (ADV+NA) therapy for NA-resistant chronic hepatitis B (CHB). Methods In this prospective trial, patients who showed partial responses (defined as serum hepatitis B virus [HBV] DNA >60 IU/mL) to ADV+NA therapy for NA resistance were randomly allocated to receive TDF plus NA (TDF+NA group, n=16) or to continue their current therapy (ADV+NA group, n=16). The primary end point was the proportion of patients with complete virological response (CVR, defined as serum HBV DNA 2log10 IU/mL was more likely in the TDF+NA group at both 24 and 48 weeks (68.8% vs. 56.3%, P=0.014 vs. 81.3% vs. 56.3%, P=0.001, respectively). During the follow-up, the rate of HBeAg seroconversion was higher in the TDF+NA group than the ADV+NA group (12.5% vs. 6.25%, P=0.640), as was that for the hepatitis B surface antigen (6.25% vs. 0%, P=0.080). No serious adverse events due to antiviral agents occurred. Conclusion In patients exhibiting suboptimal responses to ADV+NA therapy for NA-resistant CHB, switching from ADV to TDF might provide better virological outcomes