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The flame spread behavior over a filter paper in opposed flow was investigated on the ISS/Kibo, and the results were compared with the flammability map predicted in advance by scale analysis for a two-dimensional flame. The on-orbit experiments were conducted in the solid combustion experimental module (SCEM) as the first combustion test of the FLARE project by JAXA. A filter paper with a length of 130 mm, a width of 40 mm or 20 mm, and a thickness of 0.12 mm was used as the specimen. The opposed flow velocity and the oxygen concentration were varied from 0 cm/s to 25 cm/s, and from 13.5% to 34%, respectively. The ambient pressure is 101.3 kPa. The predicted limiting curve reasonably agreed with the minimum limiting oxygen concentration observed. On the other hand, in extremely slow flows, very robust flames were observed beyond the limiting curve. When the condition reached the limit of two-dimensional flame, the flame front changed from a linear shape to a spherical shape (flamelet) to shorten the preheat zone length, reducing the radiative heat loss to survive. In these cases, the flamelet was sustained for a long time (> 100 s), and a large amount of decomposed gas was released at the periphery of the pyrolysis zone generating a combustible vapor cloud around the spherical flame font. The presence of a long-life robust flamelet and the accumulation of such combustible mist can be fire hazards in microgravity. [ABSTRACT FROM AUTHOR]

The flammability limits of flat materials with different moderate thickness in opposed flow were investigated to clarify the effect of sample thickness on flammability limit. Thin poly-methyl methacrylate (PMMA) sheets and polycarbonate (PC) sheets were used as samples. The thickness was varied as 0.2 mm, 0.5 mm and 1.0 mm for PMMA, and 0.1 mm, 0.2 mm, 0.5 mm and 1.0 mm for PC. The limiting oxygen concentration (LOC) of each sample was obtained by 20 s parabolic flight experiments in mild and low flow velocity condition, and by blow-off tests on ground in high flow velocity condition. The flight experiments showed that there existed significant difference in LOC according to the sample thickness especially in mild flow condition; the thicker the sample was, the larger the LOC became. We applied a hypothesis of heat penetration zone shape into the heat balance equation around the preheat zone to account the effect of sample thickness on quenching phenomena. Although the hypothesis was not confirmed by experimentally, the obtained empirical model based on the hypothesis well represented the trend of the change of LOC when the sample thickness varied not only for the PMMA and PC samples, but also for low-density polyethylene (LDPE) and high-density polyethylene (HDPE) samples with relatively thick thickness. The modified model states that increase in the sample thickness has equivalent effect to increase in the radiative heat loss and such thickness effect is amplified when the pyrolysis temperature of the material is high. [ABSTRACT FROM AUTHOR]

The flammability characteristics of materials in microgravity are some of the most important factors for fire safety in space. It has been reported that the limiting oxygen concentration (LOC) in microgravity is different from that in normal gravity (LOC1g), which is measured by downward spread tests and is often used as an index of flammability. However, it is expensive and time consuming to conduct screening flammability tests in microgravity environments. Hence, it is necessary to develop a novel procedure for predicting the flammability of a material with data measured in normal gravity. In our previous study, we developed a simplified model for flame spread tests in opposed flow by scale analysis. Here, we present the flammability maps of several flame retardant materials in opposed flow obtained by ground-based blow-off tests and parabolic flight experiments, and the trends of the flammability maps are discussed with the developed model. Materials whose LOC increased monotonically with the opposed flow velocity and whose pyrolysis temperature was less than 823 K had a lower LOC in microgravity environments than in normal gravity; the other investigated materials showed larger LOC in microgravity than that in normal gravity. These trends were well explained by the simplified model, and the predicted limiting curve agreed quantitatively with the experimental result for thermally thin materials, which indicates the usefulness of the developed model. [ABSTRACT FROM AUTHOR]

Glutathione is a key regulator of oxidative balance in all mammals, especially in the central nervous system. The first step of glutathione synthesis is catalyzed by glutamate-cysteine ligase (GCL), which is composed of catalytic and modifier subunits (GCLC and GCLM, respectively). In non-neural cells and tissues, insulin and insulin-like growth factor 1 (IGF-1) have been found to stimulate transcription of GCLC gene. Here we found that treatment of human neuroblastoma SH-SY5Y cells with insulin or IGF-1 increased mRNA level of GCLM, but not of GCLC, in a concentration- and time-dependent manner. In contrast, insulin did not increase GCL expression in rat C6 glioma cells. We also confirmed that IGF-1 increased protein level of GCLM and cellular glutathione content in SH-SY5Y cells. In addition, IGF-1 increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein in the nuclear fraction of SH-SY5Y cells. siRNA-mediated knockdown of Nrf2 protein expression abrogated IGF-1-induced up-regulation of GCLM mRNA expression. Finally, IGF-1-induced increase in nuclear Nrf2 protein and GCLM mRNA expression was abolished by LY294002, a phosphoinositide 3-kinase inhibitor. These results indicate that insulin and IGF-1 have the ability to enhance glutathione biosynthesis in neuronal cells via specific up-regulation of GCLM expression. [ABSTRACT FROM AUTHOR]

Many curious white spots of 1-10 cm diameter were found on wet snow (~10 mm thick) on the morning of 1 November 2009 in Kitami and Oketo in Hokkaido, Japan. At first glance, the white spots appeared to be made of spherically gathered snow; however, they had actually been formed by the scattering of sunlight over wet snow. Thin air bubbles enclosed in the wet snow caused a diffuse reflection of sunlight and formed the white spots. We refer to this phenomenon as white spotted wet snow. Although this type of snow has been briefly described previously, the formation process, meteorological conditions that lead to its formation, its vertical structure and the horizontal distribution of the white spots are unknown. Our study addresses these issues. In addition, three independent methods (a nearest-neighbour method, Voronoi diagram and two-dimensional correlation function) demonstrate that the white spots are not randomly distributed but tend to be surrounded by six other spots. [ABSTRACT FROM AUTHOR]

Accurate prediction of epileptic seizures will open novel therapeutic possibilities for patients with intractable epilepsy. We attempted to identify precursors of seizures in the functional networks of electrocorticograms by applying graph theory. Long-term electrocorticograms for periods of 39-76 h from three patients with temporal lobe epilepsy were investigated using pair-wise cross-correlations. Time-varying network properties suggested that there were several distinct brain states. Although functional networks during seizures could be characterized as having a regular topography, no consistent characteristics of functional networks were found immediately prior to seizure onsets. However, it was found that seizures under an identical state were followed by similar transients of the network properties. These results suggest that network properties themselves could not serve as reliable predictors of seizure onset. Yet, some significant pre-seizure changes in the parameters tested appear likely to depend on the brain state. To predict seizures, it may be necessary to take into consideration the states of the brain. In addition to stationary network properties we characterized in the present study, dynamic interactions of epileptic activities with the network might be taken into account to predict the spread of a seizure. [ABSTRACT FROM AUTHOR]

To clarify the behavior of the blade tip vortices of a wind turbine equipped with a brimmed-diffuser shroud, called a "Wind-Lens turbine", we conducted a three-dimensional numerical simulation using a large eddy simulation (LES). Since this unique wind turbine consists of not only rotating blades but also a diffuser shroud with a broad-ring brim at the exit periphery, the flow field around the turbine is highly complex and unsteady. Previously, our research group conducted numerical simulations using an actuator-disc approximation, in which the rotating blades were simply modeled as an external force on the fluid. Therefore, the detailed flow patterns around the rotating blades and the shroud, including the blade tip vortices, could not be simulated. Instead of an actuator-disc approximation, we used a moving boundary technique in the present CFD simulation to simulate the flow around a rotating blade in order to focus especially on blade tip vortices. The simulation results showed a pair of vortices consisting of a blade tip vortex and a counter-rotating vortex which was generated between the blade tip and the inner surface of the diffuser. Since these vortices interacted with each other, the blade tip vortex was weakened by the counter-rotating vortex. The results showed good agreement with past wind tunnel experiments. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Cordyceps militaris has the potential to suppress differentiation of pre-adipocytes. However, the active entities in the extract and the underlying mechanisms of its action are not known. Hence, we investigated whether and how cordycepin (3′-deoxyadenosine), a constituent of C. militaris, inhibits adipogenesis. EXPERIMENTAL APPROACH Differentiation of 3T3-L1 pre-adipocytes and pre-adipocytes in primary cultures was induced by Insulin, dexamethasone and IBMX, and these were used as in vitro models of adipogenesis. The effects of cordycepin on adipogenesis were examined with particular focus on the regulation of CCAAT/enhancer-binding protein β (C/EBPβ) and PPARγ. KEY RESULTS Cordycepin suppressed the lipid accumulation and induction of adipogenic markers that occurred on differentiation of pre-adipocytes and also blocked the down-regulation of a pre-adipocyte marker. This anti-adipogenic effect was reversible and mediated by an adenosine transporter, but not A1, A2 or A3 adenosine receptors. This effect of cordycepin was not reproduced by other adenosine-related substances, including ATP, ADP and adenosine. Early induction of the adipogenic C/EBPβ-PPARγ pathway was suppressed by cordycepin. Blockade of mTORC1 via inhibition of PKB (Akt) and activation of AMP kinase was identified as the crucial upstream event targeted by cordycepin. In addition to its negative effect on adipogenesis, cordycepin suppressed lipid accumulation in mature adipocytes. CONCLUSIONS AND IMPLICATIONS These results suggest that the anti-adipogenic effects of cordycepin occur through its intervention in the mTORC1-C/EBPβ-PPARγ pathway. Cordycepin, by blocking both adipogenesis and lipid accumulation, may have potential as a therapeutic agent for effective treatment of obesity and obesity-related disorders. [ABSTRACT FROM AUTHOR]

Amorphous GaF3 and GaF3–BaF2 thin films were prepared by electron cyclotron resonance microwave plasma-enhanced chemical vapor deposition. Metal β-diketonates and a NF3 gas were used as starting materials and a fluorinating reagent, respectively. Single crystals of CaF2(1 1 1) were employed as substrates. Almost contaminant-free and amorphous GaF3 and GaF3–BaF2 films were obtained on the substrates kept at 300 °C at the deposition rates of 0.8 μm h−1 and 1.1–1.8 μm h−1, respectively. In amorphous GaF3–BaF2 films, optical propagation was detected at one or two transverse electric modes. The refractive indices of GaF3–BaF2 thin films increased with the BaF2 content. Based on the measured refractive indices, moreover, the synthesis condition of single-mode planar optical waveguides were determined. Consequently, the optimum thickness of amorphous GaF3–BaF2 thin film was estimated to be approximately 0.3–1.6 μm. [Copyright &y& Elsevier]

This study conducted a shaking table test using a centrifuge model to clarify the dynamic response of the saturated soil–reinforced concrete pile–superstructure interaction under conditions of multiple earthquakes. The shaking table test was conducted under a 50-G field with multiple shaking inputs reproducing the mainshock and aftershocks to explore the interactions in terms of differences in relative soil density. The centrifuge test demonstrated the liquefaction of saturated soil during the mainshock and the simultaneous formation of plastic hinges at the pile head and base. However, the gradual compaction of the ground by repeated shaking did not promote the occurrence of liquefaction. Ground compaction caused the shear span ratio of the pile member to decrease and the inertial force acting on the superstructure to increase. It is possible that in the case of low relative soil density, the maximum inertial force during aftershock excitation exceeded that of mainshock excitation. • Experimental study of pile damage behavior during the soil liquefaction. • The centrifugal shaking table test was conducted with multiple input waves. • Gradual compaction occurred at the saturated sandy ground due to repeated shaking. • Ground compaction caused the inertial force acting on superstructure to increase. [ABSTRACT FROM AUTHOR]

Stance stability in individuals with bilateral spastic cerebral palsy (BSCP) in various standing postures including the quiet standing (QS) and limits of stability (LoS) has been widely studied. However, the relationships between the QS and LoS remain unclear. This study aimed to determine the relationships between the positions and postural sway in the QS and anteroposterior LoS in individuals with BSCP. It included 27 adolescents and young adults with BSCP (BSCP group) and 27 adolescents and young adults without disability (control group). The position of center of pressure in the anteroposterior direction (CoPy position) and the path length of center of pressure (CoP path length) during the QS and the anterior and posterior LoS (A-LoS and P-LoS, respectively) were measured using a force platform. The CoPy positions in the A-LoS and P-LoS in the BSCP group were limited compared with those in the control group. In the BSCP group, the more anterior the CoPy position in the QS, the more anterior (i.e., limited) it was in the P-LoS. Although the CoP path length in the QS was larger in the BSCP group, those in the A-LoS and P-LoS were larger in the control group. The BSCP group also showed that the more anterior the CoPy position or the longer the CoP path length in the QS, the more decreased the anteroposterior LoS range was. Therefore, assessing various standing postures, including QS and anteroposterior LoS, is important to manage balance impairments in individuals with BSCP. [ABSTRACT FROM AUTHOR]

Abstract: Tests with flames spreading over wires in microgravity were performed at external opposed flow conditions from 60 to 200mm/s to examine the influence of flow velocity on the extinction limit. In the experiments, low density polyethylene insulated Nickel–chrome and Copper wire samples were used. The experiments were conducted both in normal gravity and microgravity attained by parabolic flights. The experimental results are discussed based on non-dimensional numbers developed by Takahashi et al. This study added the heat conduction through the wire insulation to the inner core to their model, which is considered as a heat loss term arising due to the presence of the inner core. Further the effect of curvature of the sample is taken into consideration. From the results of the experiments in normal gravity, there was a low oxygen limit for Copper wire at around 125mm/s. However there was no low oxygen limit for Nickel–chrome wire; the limits of the oxygen concentration decreased monotonically with decreases in the external flow velocity. The non-dimensional number implies that the decrease in inner core temperature around the preheat zone occurring with Copper wire plays a role in the change in low oxygen limits. Further, in the external flow velocity range investigated here, there was no low oxygen limit in microgravity with the Copper wire. This might arise due to the changes in the flame shapes by gravity. The heat input from flame to the wire is supposed to increase in microgravity because the wire is surrounded by flame due to inhibited natural convection. This increased heat input might help the increase of the inner core temperature around the preheat zone. For this reason, there is a possibility that the low oxygen limit with Copper wire in microgravity exists at lower flow velocity than that in normal gravity. [Copyright &y& Elsevier]

This method is used in the preparation of pradimicinone precursor (X). [ABSTRACT FROM AUTHOR]

d- and l-Tryptophan (Trp) and d- and l-kynurenine (KYN) were derivatized with a chiral reagent, ( S)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-PyNCS), and were separated enantiomerically by high-performance liquid chromatography (HPLC) equipped with a triazole-bonded column (Cosmosil HILIC) using tandem mass spectrometric (MS/MS) detection. Effects of column temperature, salt (HCO2NH4) concentration, and pH of the mobile phase in the enantiomeric separation, followed by MS detection of ( S)-DBD-PyNCS- d, l-Trp and - d, l-KYN, were investigated. The mobile phase consisting of CH3CN/10 mM ammonium formate in H2O (pH 5.0) (90/10) with a column temperature of 50-60 °C gave satisfactory resolution ( Rs) and mass-spectrometric detection. The enantiomeric separation of d, l-Trp and d, l-KYN produced Rs values of 2.22 and 2.13, and separation factors (α) of 1.08 and 1.08, for the Trp and KYN enantiomers, respectively. The proposed LC-MS/MS method provided excellent detection sensitivity of both enantiomers of Trp and KYN (5.1-19 nM). [ABSTRACT FROM AUTHOR]

Rh(II)-catalyzed O H insertion reaction of diazonaphthoquinones with water or alocohols proceeded to yield 1,2-naphthalenediol derivatives. [ABSTRACT FROM AUTHOR]

Background: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed. Methods: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and had received radiotherapy for BM initially at the Hokkaido Cancer Center. We evaluated the effect on the prognosis of Lung-molGPA items, the expression of PD-L1 (classified as high, low, and no expression), and the treatment history. The main outcome was the survival measured from the day of the diagnosis of BM, and log-rank tests were performed to evaluate the results. Results: The median overall survival (OS) times for adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p < 0.0001), respectively. The median survival times for non-adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, and 2.5‒3.0) were 3.2, 11.0, and 16.0 months (p = 0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome (median OS: 34.2 and 17.6 months with and without osimertinib, respectively (p = 0.0164)). There was no significant difference in the OS between patients who were initially treated with tyrosine-kinase inhibitor for BM and those who initially received radiotherapy (p = 0.5337). In patients tested for PD-L1 expression, the median survival times after the diagnosis of BM were 5.6, 22.5, and 9.3 months for the high-, low- and no-expression groups (p = 0.2198), respectively. Also, in patients with high PD-L1 expressions, those with ICI had survival (median OS, 8.6 months) than those without (median OS, 3.6 months). Conclusions: We confirmed that Lung-molGPA successfully classified Japanese NSCLC patients with BM by the prognosis. Osimertinib prolonged survival of EGFR-positive NSCLC patients with BM, and ICI was effective in patients with high PD-L1 expressions. [ABSTRACT FROM AUTHOR]

An LC-MS/MS-based method for determining d-serine (Ser), an endogenous co-agonist of the N-methyl- D-aspartate receptor, in human serum, was developed and validated using a triazole-bonded silica-packed column after pre-column fluorescence derivatization with a chiral labeling reagent, ( S)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-( N, N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole. Enantiomeric separation of the d- and L-Ser derivatives occurred in the triazole-bonded column ( R: 1.85) with CHCN/100 mM HCONH in HO (95.5:4.5) as the mobile phase with isocratic elution. The ln(capacity factor of d-Ser) in the van't Hoff plot gradually decreased with the inverse of temperature, suggesting enhanced hydrophilic interactions with the triazole-bonded stationary phase with increasing column temperature, owing to decrease in the partition coefficient to the mobile phase. Multiple reaction monitoring ( m/ z 457.10 > 409.00) by triple quadrupole mass spectrometry was used for quantifying d-Ser in human serum. The presence of d-Ser in the serum was confirmed by treatment with commercial d-amino acid oxidase. A linear calibration curve was constructed in the d-Ser concentration range of 0.5-5.0 μM ( r = 0.999, n = 3) using d-homoserine as the internal standard. The precision and recovery values were adequate for quantification. The detection limit for d-Ser was 1.1 fmol/injection (signal-to-noise ratio = 3), owing to the high CHCN content in the mobile phase. The proposed LC-MS/MS method showed few fluctuations in the retention times of D- and L-Ser, and R was stable until the 40th injection of serum without column washing, and thus can be useful for d-Ser determination in human serum in clinical research. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The first efficient diazo‐transfer reaction of phenols is described. o‐Quinone diazides (diazoquinones) were prepared from phenols in high yields by the diazo‐transfer reaction using 2‐azido‐1,3‐bis(2,6‐diisopropylphenyl)imidazolium hexafluorophosphate (IPrAP, 2‐PF6), which is a safe and stable crystalline. The reaction efficiently proceeded in methanol in the presence of a base. Phenols substituted with electron‐donating groups reacted more smoothly than those having electron withdrawing groups. Reactive phenols were diazotized by IPrAP with iPr2NH as a base, and low reactive phenols were diazotized with N,N‐dimethyl‐4‐aminopyridine (DMAP). Furthermore, the formed diazoquinones reacted with sodium azide in 2‐methoxyethanol and afforded the corresponding azidophenol in high yields. [ABSTRACT FROM AUTHOR]

Abstract: Proteasome inhibitor MG132 blocks activation of NF-κB by preventing degradation of IκB. In this report, we propose an alternative mechanism by which MG132 inhibits cytokine-triggered NF-κB activation. We found that MG132 induced endoplasmic reticulum (ER) stress, and attenuation of ER stress blunted the suppressive effect of MG132 on NF-κB. Through ER stress, MG132 up-regulated C/EBPβ mRNA transiently and caused sustained accumulation of its translational products liver activating protein (LAP) and liver-enriched inhibitory protein (LIP), both of which were identified as suppressors of NF-κB. Our results disclosed a novel mechanism underlying inhibition of NF-κB by MG132. [Copyright &y& Elsevier]

Abstract: We recently reported that subtilase cytotoxin (SubAB) has the potential to attenuate experimental models of inflammatory diseases . Currently, little is known about underlying mechanisms involved in this therapeutic effect. In the present report, we show that SubAB induces A20, the endogenous negative regulator of NF-κB, in vitro and in vivo. This stimulatory effect occurred at the transcriptional level, and SubAB induced activation of the A20 promoter. We found that, in the early phase, SubAB triggered activation of NF-κB in a dose-dependent manner. Blockade of NF-κB abrogated expression of A20 by SubAB. SubAB rapidly triggered the unfolded protein response (UPR), and induction of the UPR by other agents (thapsigargin and A23187) mimicked the stimulatory effects of SubAB, both on NF-κB and on A20. The induction of A20 by thapsigargin was correlated with activation of the A20 promoter, which was not observed in the κB-mutated A20 promoter. Furthermore, induction of A20 by SubAB was substantially attenuated by treatment with different chemical chaperones. These results elucidated for the first time that the anti-inflammatory SubAB has the potential to induce A20 through the UPR–NF-κB-dependent pathway. [Copyright &y& Elsevier]

A simplified analysis and data acquired in the 4.5 s drop tower in MGLAB, Japan in a quiescent oxygen/nitrogen environment are presented for the prediction of the flammability limit in a quiescent microgravity environment. In the experimental matrix the oxygen level and thickness of PMMA are treated as control parameters. Published data from quiescent microgravity experiments on thin ashless filter paper and thick PMMA are also compared with the prediction of the analysis. Based on scale analysis, it is hypothesized that all fuels—from PMMA to cellulose—behave as thermally thin fuels during steady spread of flames in a quiescent environment. An expression for the spread rate that includes radiative effects is proposed for the first time: η0 ∼ 1/2 + 1/2 1−4R0, where η0 is the spread rate non-dimensionalized by its thermal limit and R0 is the non-dimensional radiation number. For R0 > 1/4, which in dimensional terms translates to a critical thickness criterion τ > (F2/4)(ρgcg/ρscs)(λg/&epsiv;σ)[(Tv − T∞)/(Tv4 − T∞4)], flame extinction occurs irrespective of all other environmental conditions. Based on this prediction, an extinction thickness can be calculated even at 100% oxygen level. The experimental data from the MGLAB agree reasonably well with this prediction. Flammability maps with fuel half-thickness and oxygen level as coordinates are developed for PMMA and cellulosic fuels, which are shown to be consistent with the current and published data. [Copyright &y& Elsevier]

Inflammatory bowel disease (IBD) is characterized by multiple alterations in cytokine expression and is a risk factor for colon cancer. The Omega class glutathione transferase GSTO1-1 regulates the release of the pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) by deglutathionylating NEK7 in the NLRP3 inflammasome. When treated with azoxymethane and dextran sodium sulphate (AOM/DSS) as a model of IBD, Gsto1 − / − mice were highly sensitive to colitis and showed a significant increase in the size and number of colon tumours compared with wild-type (WT) mice. Gsto1 − / − mice treated with AOM/DSS had significantly lower serum IL-1β and IL-18 levels as well as significantly decreased interferon (IFN)-γ, decreased pSTAT1 and increased pSTAT3 levels in the distal colon compared with similarly treated WT mice. Histologically, AOM/DSS treated Gsto1 − / − mice showed increased active chronic inflammation with macrophage infiltration, epithelial dysplasia and invasive adenocarcinoma compared with AOM/DSS treated WT mice. Thus, this study shows that GSTO1-1 regulates IL-1β and IL-18 activation and protects against colorectal cancer formation in the AOM/DSS model of IBD. The data suggest that while GSTO1-1 is a new target for the regulation of the NLRP3 inflammasome-associated cytokines IL-1β and IL-18 by small molecule inhibitors, there is a possibility that anti-inflammatory drugs targeting these cytokines may potentiate colon cancer in some situations. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (CoQ10) plays a potential role in the prevention and treatment of cardiovascular disease through improved cellular bioenergetics. Critical illness in the intensive care unit has been reported to be associated with decreased circulating CoQ10 levels, and we previously demonstrated the association of low CoQ10 levels with in-hospital mortality. However, the association of CoQ10 with the acute phase of cardiovascular disease and long-term mortality remains unclear. We enrolled 242 consecutive patients with cardiovascular disease admitted to the coronary care unit of Juntendo University Hospital to investigate the association between long-term mortality and serum CoQ10 levels. During a mean follow-up of 3.2 years, 58 patients died. The mean serum CoQ10 levels were significantly lower in the non-survivors than in the survivors (0.48 ± 0.27 vs. 0.58 ± 0.38 mg/L; p = 0.035). Compared with the patients with above-median CoQ10 levels (0.46 mg/L), the cumulative incidence of all-cause mortality was significantly higher in those with lower CoQ10 levels (p = 0.025). Multivariate Cox regression analysis further demonstrated that lower CoQ10 levels were associated with poor prognosis. Low serum CoQ10 levels during the acute phase of cardiovascular diseases were associated with long-term mortality in patients, suggesting the utility of low serum CoQ10 levels as a predictor and potential therapeutic target. [ABSTRACT FROM AUTHOR]

We developed a new acetalization method of ketones and aldehydes under non‐acidic conditions using diazophenanthrenequinone and PdBr2. The formed acetals that have a phenanthrene skeleton withstand under mild acidic conditions. Removal of acetals was successfully proceeded under strong acidic or oxidation conditions using aqueous ceric ammonium nitrate (CAN) to afford corresponding ketones and aldehydes. [ABSTRACT FROM AUTHOR]

The partial photooxidation of methane by nitric oxide selectively led to methanol formation over the V-MCM-41 catalysts under UV irradiation (?>270 nm) at room temperature, while only a complete oxidation of methane could occur in the presence of oxygen. The yield of methanol corresponds with the yield of the photoluminescence of the isolated tetrahedrally coordinated V-oxides species, indicating that the charge transfer excited triplet state of these species are active sites in this photooxidation reaction. [ABSTRACT FROM AUTHOR]

Thermoplastics are melted and often dripped down during the flame spread over them in normal gravity. The flame spread behaviors, therefore, could be quite different from those in microgravity because they involve the dripping. However, no studies have addressed the flame spread over thermoplastics to be dripped in microgravity. This work then studied the opposed flame spread over polyethylene (PE) in microgravity with varying flow velocity and oxygen concentration. Two different PEs, a semi-transparent low-density polyethylene (LDPE) and an opaque high-density polyethylene (HDPE), were tested. Microgravity experiments were conducted in parabolic flights which provided a microgravity environment of 10−2 g for 20 s. Experimental results showed that the limiting oxygen concentration (LOC) of LDPE was 20% and 1% lower than that of HDPE. The flame spread of LDPE was faster than that of HDPE too. These indicate that LDPE is more flammable than HDPE, which well agrees with the literatures on the flame spread over PE-insulated wires. Flame spread rates of both LDPE and HDPE increased with flow velocity and oxygen concentration. The flame length also increased with flow velocity, but the preheating length showed an opposite dependence. The effects of flow velocity and oxygen concentration on flame spread rate, flame length, and preheating length are discussed via a simplified flame-spread model. This study's findings help ensure fire safety in spacecraft because a flame spreads without melted materials being dripped in a spacecraft environment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Formal synthesis of isoquinocyclinone is described. • Key transformation is ortho- alkoxycarbonylmethylation of poly-substituted anthranol via diazoquinone. • Key intermediate lactone was constructed from 1,2-dihydrotetracene-1-carboxylic acid derivative via epoxidation. In this study, a formal synthesis of isoquinocyclinone is reported. Synthesis of key intermediate lactone 6 , an intermediate in Koert's s total synthesis of isoquinocyclinone, was succeeded. The lactone 6 was synthesized by using our developed diazo-transfer reaction of anthranol with 2-azido-1,3-dimethylimidazolinium chloride (ADMC) and alkoxycarbonylmethylation of diazoquinone as key reactions. [ABSTRACT FROM AUTHOR]

Abstract Thermally-inducing activation mechanism of titanium dioxide (TiO 2) in air was investigated using X-ray diffraction (XRD) measurement and X-ray photoelectron spectrometry (XPS) under high temperatures. TiO 2 (anatase) crystal expanded toward the c-axis direction as compared with the a-axis direction under heating. These show that the anatase crystal was distorted under high temperature, that is, the lattice vacancy generated in the crystal at high temperatures from the XRD measurement. It was recognized that Ti3+ (binding energy of 457.8 eV) in TiO 2 increased slightly with temperature rise from the XPS. The decreasing of the ratio of O/Ti with heating would indicate that the oxygen vacancy in TiO 2 increased with heating. From these results, the thermal activation of TiO 2 must be induced by the generation of oxygen vacancy and Ti3+ in TiO 2 at high temperatures followed by the formation of trapped electron. The oxidative decomposition of toluene over TiO 2 , as an application to the oxidation of organic compounds, was superior to the only thermal decomposition over SiO 2. Highlights • Thermal activation of TiO 2 is induced by the generation of oxygen vacancy and Ti3+ in TiO 2 at high temperatures followed by the formation of trapped electron. • Oxygen radical must generate from the trapped electron and air. The active radical species decompose gaseous toluene oxidatively. [ABSTRACT FROM AUTHOR]

Thermometry using two-band near-infrared (NIR) emissions less than 1.1 μm has been implemented for combustion gases formed on a flat flame burner. The gas temperature was calibrated using a SiC thin filament pyrometry (TFP) above 1500 K for H 2 /air and CH 4 /air mixtures. The emission spectra were measured with a spectrometer and a monochrome CMOS sensor with an image doubler and two bandpass filters. Two pairs of bandpass filters (850 nm/925 nm and 975 nm/925 nm) were tested to measure temperature. Results indicated that strong H 2 O emissions existed in the NIR region, and they became stronger with an increase in the temperature. The CO 2 emission spectra in the NIR region were negligible compared to that of H 2 O. Calibration temperature lines were obtained as a function of the intensity ratio of the two-band emissions in the NIR region. Using a CMOS camera, the uncertainties of temperature were 59 K for 850 nm/925 nm and 145 K for 975 nm/925 nm. The resolutions were 0.7 K for 850 nm/925 nm and 1 K for 975 nm/925 nm. Using the calibration line, two-dimensional temperature measurements were performed for H 2 /air flames, CH 4 /air flames and Bunsen flames of 13A city gas. For the high temperature region above 1500 K, a quantitative two-dimensional temperature field was measured for lean and rich combustion. In addition, temperature measurement at high pressure was conducted for combustion gas of propane/air mixture with the equivalence ratio of 0.7 using a rapid compression machine. Temperature could be estimated using the calibration line obtained for the flat flame burner. We have demonstrated the performance and the possibility of thermometry two-band H 2 O emissions in the NIR region. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (CoQ10) has a potential role in the prevention and treatment of heart failure through improved cellular bioenergetics. In addition, it has antioxidant, free radical scavenging, and vasodilatory effects that may be beneficial. Although critical illness in intensive care unit is associated with decreased circulating CoQ10 levels, the clinical significance of CoQ10 levels during acute phase in the patients of cardiovascular disease remains unclear. We enrolled 257 consecutive cardiovascular patients admitted to the coronary care unit (CCU). Serum CoQ10 levels were measured after an overnight fast within 24 h of admission. We examined the comparison of serum CoQ10 levels between survivors and in-hospital mortalities in patients with cardiovascular disease. Serum CoQ10 levels during the acute phase in patients admitted to the CCU had similar independent of the diagnosis. CoQ10 levels were significantly lower in patients with in-hospital mortalities than in survivors (0.43 ± 0.19 vs. 0.55 ± 0.35 mg/L, P = 0.04). In patients admitted to the CCU, CoQ10 levels were negatively associated with age and C-reactive protein levels, and positively associated with body mass index, total cholesterol, and high-density lipoprotein cholesterol levels. Low CoQ10 levels correlated with low diastolic blood pressure. Multivariate logistic regression analysis demonstrated that low CoQ10 levels were an independent predictor of in-hospital mortality. Low serum CoQ10 levels during acute phase are significantly associated with cardiovascular risk and in-hospital mortality in patients admitted to the CCU. [ABSTRACT FROM AUTHOR]

In this study, we show that cordycepin (3′-deoxyadenosine), a major nucleoside isolated from Cordyceps species, attenuates genotoxic stress–induced senescence. Etoposide- or doxorubicin-treated cells exhibited senescent morphology, growth arrest, and positive staining for senescence-associated β-galactosidase. The induction of the senescent phenotype was inhibited by the treatment of cordycepin. This suppression was correlated with blunted activation of the p16INK4a and p21WAF1/CIP1 gene promoters, as well as a decreased level of p21 WAF1/CIP1 mRNA. Other adenosine-related substances including ATP, ADP, and adenosine did not mimic the suppressive effect of cordycepin. The antisenescence effect of cordycepin was mediated by activation of eukaryotic translation initiation factor 2α (eIF2α) because (1) cordycepin induced phosphorylation of eIF2α, (2) selective activation of eIF2α mimicked the suppressive effect of cordycepin on senescence, and (3) functional knockdown of eIF2α reversed the effect of cordycepin. Unexpectedly, induction of p53 by etoposide was not inhibited by cordycepin, whereas (1) expression of Sp1 (required for the induction of p21WAF1/CIP1 and activation of p16INK4a by genotoxic stress) was attenuated by cordycepin, (2) DNA binding activity of Sp1 was also inhibited, and (3) selective inhibition of Sp1 reproduced the suppressive effect of cordycepin on senescence. These results suggest that cordycepin interferes with senescence signaling via activation of eIF2α and suppression of Sp1 without affecting the level of p53. [ABSTRACT FROM AUTHOR]

This study explored the downward flame spread over carbon fiber reinforced plastic (CFRP) sheets under buoyant flow in variable oxygen concentrations. Tested CFRP sheets were fabricated by laminating two unidirectional carbon fiber (CF) sheets impregnated with epoxy resins and curing them in a high-temperature furnace. The fabricated CFRP sheets were combusted in a glovebox which allowed oxygen concentration to vary. Epoxy resin sheets were also tested to investigate the effect of CFs. SEM images of burned and unburned CFRP sheets showed that the flame spread over the CFRP sheets was driven via the pyrolysis of the impregnated epoxy resins. The limiting oxygen concentration (LOC) of the CFRP sheets was 31%, while that of the epoxy resin sheets was 19%. The difference in flammability would be produced by the different thermal inertia. Contrary to the order of flammability, the flame spread rate of the CFRP sheets was higher than that of the epoxy resin sheets in more than 31% O 2. In-plane temperature distributions visualized via an IR camera suggested that the CFs conductively transferred heat from flame forward, thereby accelerating the flame spread. In other words, the CFs acted as heat conductors, such as metal cores in electrical wire fires. To predict the flame spread behaviors of the CFRP sheets, this work developed a novel simplified flame spread model that involves solid-phase heat transfer. According to the model with a simulated surface temperature profile, the analytical solution of flame spread rate was derived by formulating energy balance in each zone. When the calculated flame spread rates were compared with the measured ones, a quantitative agreement was recognized. This model would be applicable to other thermally thin high-thermal-conductivity materials as well as the CFRP sheets and therefore contribute to the fire risk assessment of such materials. [ABSTRACT FROM AUTHOR]

Abstract: Cigarette smoke triggers apoptosis through oxidative stress- and endoplasmic reticulum (ER) stress-dependent induction of CCAAT/enhancer-binding protein–homologous protein (CHOP) (Tagawa et al., 2008. Free Radic. Biol. Med. 45, 50–59). We investigated roles of individual reactive oxygen/nitrogen species in the transcriptional induction of CHOP by cigarette smoke. Exposure of bronchial epithelial cells to O2 −, ONOO− or H2O2 induced expression of CHOP, whereas NO alone did not. Induction of CHOP mRNA by cigarette smoke extract (CSE) was attenuated by scavengers for O2 −, ONOO− or NO, whereas scavenging H2O2 did not affect the induction of CHOP. Like CSE, O2 − and ONOO− caused activation of the CHOP gene promoter. Scavengers for O2 −, ONOO− or NO attenuated CSE-triggered activation of the CHOP gene promoter. CSE, O2 − and ONOO− induced phosphorylation of protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2α (eIF2α) and caused induction of downstream activating transcription factor 4 (ATF4). Scavengers for O2 −, ONOO− or NO attenuated induction of ATF4 by CSE. Furthermore, dominant-negative inhibition of the PERK–eIF2α pathway exclusively suppressed CSE-triggered induction of CHOP and consequent apoptosis. These results suggest that O2 − and ONOO− are selectively involved in CSE-triggered induction of CHOP and that the PERK–eIF2α pathway plays a crucial role in the induction of CHOP and apoptosis downstream of the particular reactive oxygen species. [Copyright &y& Elsevier]

Recent reports suggested involvement of mitogen-activated protein (MAP) kinases in the pathogenesis of Shiga toxin–induced hemolytic uremic syndrome (HUS). In the present study, we investigated a role for subtilase cytotoxin (SubAB), a possible trigger for HUS, in the regulation of MAP kinases. Treatment of cells with SubAB caused phosphorylation of c-Jun NH2-terminal kinase, extracellular signal-regulated kinase (ERK), and p38 MAP kinase. It was associated with activation of activator protein 1 (AP-1) and induction of AP-1–dependent transcription. SubAB induced the unfolded protein response (UPR) and consequently caused MAP kinase activation. SubAB led to induction of three major branches of the UPR, and the protein kinase–like endoplasmic reticulum kinase and inositol-requiring ER-to-nucleus signal kinase 1 pathways were responsible for the activation of MAP kinases. These results elucidated the potential of SubAB to trigger MAP kinase pathways via the UPR, which may contribute to the pathogenesis of Shiga toxin–induced HUS. [ABSTRACT FROM AUTHOR]

Cigarette smoking decreases body weight, whereas molecular mechanisms underlying this phenomenon have not been elucidated. In this report, we investigated regulation of adipogenesis by cigarette smoke and involvement of aryl hydrocarbon receptor (AhR) and endoplasmic reticulum (ER) stress. We found that cigarette smoke extract (CSE) inhibited differentiation of preadipocytes into adipocytes dose dependently. It was associated with a decrease in lipid accumulation, blunted expression of adipocyte markers (adiponectin, PPAR-γ, and C/EBPα), and sustained expression of a preadipocyte marker MCP-1. CSE markedly induced activation of AhR, and AhR agonists (2,3,7,8- tetrachlorodibenzo-p-dioxin, benzo[a]pyrene and 3-methylcholanthrene) reproduced the inhibitory effect of CSE on adipocyte differentiation. Furthermore, knockout of the AhR gene or blockade of AhR by a dominant-negative mutant attenuated the suppressive effects of CSE on adipocyte differentiation. We also found that CSE induced ER stress in preadipocytes, and ER stress inducers (thapsigargin, tunicamycin, and A23187) reproduced the suppressive effect of CSE on the differentiation of preadipocytes. Interestingly, AhR agonists did not cause ER stress, and ER stress inducers did not activate AhR. These results suggested that cigarette smoke has the potential to inhibit adipocyte differentiation via dual, independent mechanisms, i.e., through activation of the AhR pathway and induction of the unfolded protein response. [ABSTRACT FROM AUTHOR]

Mycelial extracts have a wide range of biological activities that modulate functions of mammalian cells. In this report, we sought to identify antiadipogenic mycelia with the use of 3T3-L1 cells and found that the extract of Cordyceps militaris exclusively suppressed differentiation of 3T3-L1 preadipocytes into mature adipocytes without affecting cell viability. This inhibitory effect was dose dependent, reversible, and associated with 1) a decrease in lipid accumulation, 2) blunted induction of adipocyte markers including adiponectin, peroxisome proliferator-activated receptor-γ, and CCAAT/enhancer binding protein-α, and 3) sustained expression of a preadipocyte marker, monocyte chemoattractant protein-1. C. militaris also significantly decreased accumulation of lipid and hypertrophy in mature adipocytes and preserved their response to insulin (phosphorylation of Akt) during prolonged culture. Subsequent experiments revealed that C. militaris has the potential to activate the aryl hydrocarbon receptor (AhR). In 3T3-L1 cells, treatment with AhR agonists including benzo[a]pyrene and 3-methylchol-anthrene reproduced the antiadipogenic effect of C. militaris. Furthermore, dominant-negative inhibition of AhR abrogated the suppressive effect of C. militaris on adipocyte differentiation. These results suggest that C. militaris has the potential to interfere with adipocyte differentiation through activation of AhR. [ABSTRACT FROM AUTHOR]

This work studied flame spread over polyethylene (PE)-insulated wires at high pressure with an emphasis on the effect of ambient pressure. Laboratory simulated wires were used as a tested wire, which consisted of semi-transparent low-density PE (LDPE) tube as an insulation and copper (Cu) rod or stainless-steel (SS) tube as a core. Increasing ambient pressure produced much soot, leading to an intensively yellow luminous flame. Flame spread rate for Cu rod increased with ambient pressure, whereas that for SS tube decreased. A qualitative analysis via a simplified flame spread model shows that the flame heat flux increases with ambient pressure, but consequently the flame heating decreases due to the decreased flame heating length. Therefore, the flame spread rate for SS tube decreased with increasing ambient pressure. For Cu rod, however, the core heating is dominant enough to compensate the decreased flame heating, and thus the ambient pressure positively affected the flame spread. During the flame spread, melted insulations were often dripped down, but it reduced with increasing ambient pressure. For Cu rod, no dripping occurred when further increasing ambient pressure, which indicates that there is the dripping limit at a high-pressure region. These findings should contribute to electrical fire safety in elevated pressure environments. • Flame spread over polyethylene-insulated copper (Cu) and stainless-steel (SS) wires was studied at high pressure. • Much soot was produced with increased ambient pressuredue to high flame temperature, resulting in a yellow luminous flame. • Flame spread rate for Cu rod linearly increased with ambient pressure, whereas that for SS tube decreased. • Increasing ambient pressure reduced the dripping of melted insulations regardless of core materials. • The effects of ambient pressure on flame spread and dripping are discussed via a simplified flame spread model. [ABSTRACT FROM AUTHOR]

Background: Delirium frequently occurs in patients admitted to intensive care unit and is associated with poor clinical outcome. Although the brain is an organ with high metabolic activity and nutritional demands, little is known regarding nutrients and nutritional status. Polyunsaturated fatty acids (PUFAs) are related to cognitive disorders, whereas whether PUFA levels affect the development of delirium in patients with acute cardiovascular disease remains unclear. Hypothesis: We assessed the hypothesis that malnutrition and imbalance in PUFA levels may be associated with the development of delirium. Methods: We enrolled 589 consecutive patients with acute cardiovascular disease (mean age: 70 ± 14 y) admitted to the coronary care unit of our hospital from January 2015 to December 2016. We calculated three nutritional indices, including geriatric nutritional risk index, prognostic nutritional index (PNI), and controlling nutritional index (CONUT). Fasting serum PUFA levels were measured within 24 h of admission. Delirium was defined as patients with a delirium score ≥4 using the Intensive Care Delirium Screening Checklist. Results: Delirium developed in 54 patients, and all nutritional indices were negatively associated with its development (p < 0.001). Furthermore, a negative association was observed between the severity of each nutritional index and the delirium scores (p < 0.001). The levels of dihomo-gamma-linolenic acid (DGLA) and the ratio of DGLA/arachidonic acid (DGLA/AA) were significantly lower in patients with delirium than those in patients without delirium (Figure), whereas AA and omega 3 PUFA levels were similar between the two groups. The levels of DGLA, AA, and the ratio of DGLA/AA, but not of omega 3 PUFA, were negatively associated with the delirium scores (DGLA: p < 0.001; AA: p = 0.002; DGLA/AA: p < 0.001). Multivariate analysis confirmed that PNI, CONUT, the DGLA levels, and DGLA/AA ratio were significant predictors of delirium development. Conclusions: In conclusion, malnutrition and low omega 6 PUFA levels on admission were significantly correlated with the development of delirium. The evaluation of nutritional status and low omega 6 PUFA levels on admission may identify patients who are at a high risk of developing delirium. [ABSTRACT FROM AUTHOR]

Schwannomas are rarely located in the pelvis. A 54-year-old woman was found incidentally to have a tumor in the abdomen. Abdominal computed tomography and magnetic resonance imaging revealed a well-defined, heterogeneous tumor, 5 cm in diameter, in the pelvic cavity. With a diagnosis of a mesenteric tumor, a laparoscopic procedure was performed. Intra-operatively, an elastic tumor was identified in the pelvis adjacent to the right internal iliac vein and ureter. The tumor was dissected free from adjacent structures using Liga-Sure and blunt maneuvers. A complete laparoscopic excision was performed. Histopathological examination revealed a benign schwannoma. The patient had an uneventful post-operative course, and was discharged on the fourth post-operative day. Laparoscopic treatment is useful and feasible for retroperitoneal pelvic schwannoma, with minimal invasiveness and an early post-operative recovery. Thus, this procedure may be the first-choice surgical procedure for retroperitoneal pelvic schwannomas. [ABSTRACT FROM AUTHOR]