A method for designing microreactors for isothermal operation with multiple highly exothermic or endothermic reactions under the conditions of fluid flow in a laminar flow state between two parallel ...plates is discussed. The formulated design procedure is based on a correlation between the fluid conditions and the heat properties; the operational conditions required for, e.g., a desired heat removal rate can be observed using the provided contour charts. The applicability of the proposed design method was verified using computational fluid dynamics simulations. In addition, the superiority of the microreactors is discussed specifically on the basis of the knowledge from the created charts.
A method is proposed for designing microreactors for isothermal operation with highly exothermic or endothermic reactions. The proposed design method is based on the relationship between the fluid conditions and the heat properties. The contour charts produced describe the required operational conditions, which were validated via computational fluid dynamics simulations.
Calorimetric X-ray detectors are very sensitive to their environment. The boundary conditions can have a profound effect on the gain including heat sink temperature, the local radiation temperature, ...bias, and the temperature of the readout electronics. Any variation in the boundary conditions can cause temporal variations in the gain of the detector and compromise both the energy scale and the resolving power of the spectrometer. Most production X-ray calorimeter spectrometers, both on the ground and in space, have some means of tracking the gain as a function of time, often using a calibration spectral line. For small gain changes, a linear stretch correction is often sufficient. However, the detectors are intrinsically non-linear and often the event analysis, i.e., shaping, optimal filters etc., add additional non-linearity. Thus for large gain variations or when the best possible precision is required, a linear stretch correction is not sufficient. Here, we discuss a new correction technique based on non-linear interpolation of the energy-scale functions. Using Astro-HSXS calibration data, we demonstrate that the correction can recover the X-ray energy to better than 1 part in 104 over the entire spectral band to above 12 keV even for large-scale gain variations. This method will be used to correct any temporal drift of the on-orbit per-pixel gain using on-board calibration sources for the SXS instrument on the Astro-H observatory.
A practical ultraviolet beamline is designed for UV circular dichroism experiment, which will be constructed at HiSOR-BL12. The beamline optics is based on a Wadsworth-type design with a normal ...incidence grating monochromator that covers a photon energy range between 2 eV and 10 eV. In the design, minimization of number of mirrors and wide acceptance angles of the optical elements contribute to high beam flux of monochromatic photons. The limiting and practical resolutions of the monochromator for 6 eV photons are 9 meV and 50 meV, respectively. The monochromator can be assembled compactly with good resolving power that is guaranteed by minimization of defocus and aberration of the grating.
The level set extended finite element method (XFEM) is applied to two-dimensional and quasi-three-dimensional crack propagation analyses using cohesive zone models (CZMs). The proposed method uses no ...asymptotic basis functions near the crack tip and uses only the Heaviside function. The crack geometry is approximated by two signed distance functions (SDFs). Elements that include a crack are then classified into several partitioned patterns according to nodal SDF values, and enriched nodes are determined. A CZM is introduced to the crack line or the surface including a discontinuous displacement field modeled by XFEM. In order to solve the discretized governing equations, the implicit method and the explicit dynamic method are used. The proposed method is applied to the crack propagation analysis of a three-point bending beam and fracture analyses of carbon fiber reinforced plastic (CFRP) laminates considering the interaction between the matrix cracks and delamination.
Monoamine oxidases A and B (MAO A and MAO B) are the major enzymes that catalyze the oxidative deamination of monoamine neurotaransmitters such as dopamine (DA), noradrenaline, and serotonin in the ...central and peripheral nervous systems. MAO B is mainly localized in glial cells. MAO B also oxidizes the xenobiotic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to a parkinsonism-producing neurotoxin, 1-methyl-4-phenyl-pyridinium (MPP+). MAO B may be closely related to the pathogenesis of Parkinson's disease (PD), in which neuromelanin-containing DA neurons in the substantia nigra projecting to the striatum in the brain selectively degenerate. MAO B degrades the neurotransmitter DA that is deficient in the nigro-striatal region in PD, and forms H2O2 and toxic aldehyde metabolites of DA. H2O2 produces highly toxic reactive oxygen species (ROS) by Fenton reaction that is catalyzed by iron and neuromelanin. MAO B inhibitors such as L-(-)-deprenyl (selegiline) and rasagiline are effective for the treatment of PD. Concerning the mechanism of the clinical efficacy of MAO B inhibitors in PD, the inhibition of DA degradation (a symptomatic effect) and also the prevention of the formation of neurotoxic DA metabolites, i.e., ROS and dopamine derived aldehydes have been speculated. As another mechanism of clinical efficacy, MAO B inhibitors such as selegiline are speculated to have neuroprotective effects to prevent progress of PD. The possible mechanism of neuroprotection of MAO B inhibitors may be related not only to MAO B inhibition but also to induction and activation of multiple factors for anti-oxidative stress and anti-apoptosis: i.e., catalase, superoxide dismutase 1 and 2, thioredoxin, Bcl-2, the cellular poly(ADP-ribosyl)ation, and binding to glyceraldehydes-3-phosphate dehydrogenase (GAPDH). Furthermore, it should be noted that selegiline increases production of neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrphic factor (GDNF), possibly from glial cells, to protect neurons from inflammatory process.
IntroductionCancer cells escape immune system surveillance by activating molecules called ‘immune checkpoints’, of which programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are known ...representative molecules. Immune cells do not become active when the PD-1 present on their cell surface recognises the PD-L1 present on a cancer cell’s surface, allowing cancer cells to evade the immune cell’s attack. Immune checkpoint-blocking antibodies developed to target PD-1/PD-L1 have remarkable anti-cancer activity. However, the biological reasons why cancer cells activate PD-L1 remain unclear. In addition, there is an issue with cells, such as myocardial cells, with PD-L1 present on their cell surfaces also being affected by immune checkpoint-blocking antibodies. We focused on a signal peptide of PD-1 expressed on the immune cell surface. Our hypothesis was that the signal peptide produced as part of the production process that leads to mature PD-1 has an anti-tumour function. We evaluated whether an artificial peptide designed based on this PD-1 signal peptide had cell growth inhibition activity against human melanoma A2058 and non-small cell lung cancer (NSCLC) HCC-827.Material and methodsWe chemically synthesised a conjugation peptide of the human PD-1 signal peptide (MQIPQAPWPVVWAVLQLGWR) and a cell penetrating peptide TAT (RRKKRRQRRR) and named it ‘PD1SP-TAT’ (MQIPQAPWPVVWAVLQLGWRRRKKRRQRRR). PD1SP-TAT was evaluated for growth inhibitory activity against A2058 and HCC-827 by WST assay.Results and discussionsThe results were 95% of human melanoma A2058 growth and NSCLC HCC-827 growth were inhibited in cells treated with a concentration of 25 µM PD1SP-TAT for 48 hours.ConclusionFrom these surprising results, PD1SP-TAT, based on the signal peptide of PD-1, shows remarkable anti-cancer activity against human melanoma and NSCLC, and suggests that PD1SP-TAT could be a candidate for a novel anti-cancer agent.
Etoposide (VP-16) a topoisomerase II inhibitor induces apoptosis of tumor cells. The present study was designed to elucidate the mechanisms of etoposide-induced apoptosis in C6 glioma cells. ...Etoposide induced increased formation of ceramide from sphingomyelin and release of mitochondrial cytochrome c followed by activation of caspase-9 and caspase-3, but not caspase-1. In addition, exposure of cells to etoposide resulted in decreased expression of Bcl-2 with reciprocal increase in Bax protein. z-VAD.FMK, a broad spectrum caspase inhibitor, failed to suppress the etoposide-induced ceramide formation and change of the Bax/Bcl-2 ratio, although it did inhibit etoposide-induced death of C6 cells. Reduced glutathione or N-acetylcysteine, which could reduce ceramide formation by inhibiting sphingomyelinase activity, prevented C6 cells from etoposide-induced apoptosis through blockage of caspase-3 activation and change of the Bax/Bcl-2 ratio. In contrast, the increase in ceramide level by an inhibitor of ceramide glucosyltransferase-1, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol caused elevation of the Bax/Bcl-2 ratio and potentiation of caspase-3 activation, thereby resulting in enhancement of etoposide-induced apoptosis. Furthermore, cell-permeable exogenous ceramides (C2- and C6-ceramide) induced downregulation of Bcl-2, leading to an increase in the Bax/Bcl-2 ratio and subsequent activation of caspases-9 and -3. Taken together, these results suggest that ceramide may function as a mediator of etoposide-induced apoptosis of C6 glioma cells, which induces increase in the Bax/Bcl-2 ratio followed by release of cytochrome c leading to caspases-9 and -3 activation.
Background DAV‐interferon (IFN)‐β therapy is a combination chemotherapy of dacarbazine (DTIC), nimustine (ACNU) and vincristine (VCR) with local subcutaneous injection of IFN‐β that is widely ...employed as postoperative adjuvant chemotherapy to treat malignant melanoma in Japan. However, the efficacy of DAV‐IFN‐β therapy has not been confirmed by randomized controlled trials and the benefit of DAV‐IFN‐β therapy has not been established yet. This study evaluated the contribution of DAV‐IFN‐β therapy to improve survival of postoperative patients with cutaneous melanoma.
Methods Patients with stage II or III cutaneous melanoma seen at Nagoya University Hospital from January 1998 to December 2009 were eligible for this study. Disease‐free survival rates and melanoma‐specific survival rates were evaluated. A propensity score was calculated to control for the effects of variables related to decisions regarding the application of DAV‐IFN‐β therapy.
Results Eighty‐two stage II and 60 stage III melanoma patients were included. In the post‐matched stage II patients (17 matched pairs), the mean (±SE) disease‐free survival rates were 39.9±13.7% for DAV‐IFN‐β therapy and 73.1±11.7% for non‐use (hazard ratio for recurrence, 2.06; 95% CI, 0.63–6.69; P = 0.23), and the melanoma‐specific survival rates were 66.2±20.0% for DAV‐IFN‐β therapy and 86.2±9.1% for non‐use (hazard ratio for death, 1.09; 95% CI, 0.17–6.82; P = 0.93). In the post‐matched stage III patients (nine matched pairs), the disease‐free survival rates were 29.6±16.4% for DAV‐IFN‐β therapy and 33.3±15.7% for non‐use (0.69; 95% CI, 0.22–2.17; P = 0.53), and the melanoma‐specific survival rates were 55.6±16.6% for DAV‐IFN‐β therapy and 44.4±16.6% for non‐use (0.67; 95% CI, 0.18–2.50; P = 0.55).
Conclusions DAV‐IFN‐β therapy brought no significant improvement in either disease‐free survival rates or melanoma‐specific survival rates of patients with stage II or III cutaneous melanoma. A randomized controlled trial would be required to further evaluate the efficacy of DAV‐IFN‐β therapy as an adjuvant chemotherapy.
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