Effects of Re substitution for Mn on the microstructure-property relationships in Mn30.4Re6.0Si63.6 thermoelectric material have been investigated in comparison with those in Mn36.4Si63.6. The rapid ...quenching using the meld spinning leads to relatively uniform distribution of Re. After sintering, the Nowotny chimney ladder phases known as the higher manganese silicide (HMS) are stabilized in both the Re-free and Re-substituted HMSs, and the chemical formulae become Mn15Si26 and Mn19Si33, respectively. The Re atoms are successfully substituted for Mn in the (Mn,Re)19Si33 HMS. The number density of the sublattice dislocation in the Re-substituted HMS is 1.6 times higher than that in the Re-free HMS, that causes a decrease in lattice thermal conductivity. Due to the impurity effect of the Re substitution, the electrical conductivity is supposed to be enhanced, resulting in the highest dimensionless figure of merit (ZT) among the investigated HMSs.
Identified microstructural difference in this study due to the Re addition. The grain sizes in both samples are equivalent (∼3 μm), but the local crystal structure, distribution of Re atoms and number of sublattice dislocations are different. The combinations of arc melting, melt spinning and PECS are important processes so as to disperse the heavy element of Re uniformly without oxides: as a consequence, the thermal conductivity decreases up to the half of that in the Mn36.4Si63.5 in addition to enhancement in electrical conductivity due to impurity effect of Re. Display omitted
•The oxides are removed by arc melting before the melt spinning.•Re elements are relatively homogeneously distributed in the as-melt spun sample.•Crystal structures of HMSs are determined by electron diffraction.•Both Re atoms and sublattice dislocations diminish lattice thermal conductivity.•Theoretical interpretation of thermal and electrical conductivity has provided.
The urinary metabolites of methylone in humans and rats were investigated by analysing urine specimens from its abuser and after administrating to rats with gas chromatography-mass spectrometry ...(GC-MS) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS), using authentic standards. The time-course excretion profiles of methylone and its three metabolites in rats were further investigated after a single intraperitoneal dosing of 5 mg kg−1 methylone hydrochloride. Two major metabolic pathways were revealed for both humans and rats as follows: (1) side-chain degradation by N-demethylation to the corresponding primary amine methylenedioxycathinone (MDC), partly conjugated; and (2) demethylenation followed by O-methylation of either a 3- or 4-OH group on the benzene ring to produce 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC), respectively, mostly conjugated. Of these metabolites, HMMC was the most abundant in humans and rats. The cumulative amount of urinary HMMC excreted within the first 48 h in rats was approximately 26% of the dose, and the amount of the parent methylone was not more than 3%. These results demonstrate that the analysis of HMMC will be indispensable for proof of the use of methylone in forensic urinalysis.
Reactive oxygen species (ROS)-generating enzyme Nox1 is important in the induction of oncogenic Ras transformation phenotypes, but it is not defined whether Nox1 is involved in Ras-induced ...upregulation of vascular endothelial growth factor (VEGF), a potent stimulator of tumor angiogenesis. Here we describe that ablation of the Nox1 activity by Nox1 small-interference RNAs (siRNAs) or diphenylene iodonium (DPI) inhibited synthesis of both VEGF proteins and VEGF mRNAs in K-Ras transformed normal rat kidney (KNRK) cells. Nox1siRNAs and DPI suppressed extracellular signal-regulated kinase (ERK)-dependent phosphorylation of a transcription factor Sp1 and Sp1 binding to a VEGF promoter. Furthermore, tumors derived from Nox1siRNA-transfected KNRK cells markedly decreased neovascularization. The Nox1 activity was required for VEGF production in human colon cancer CaCO-2 cells, as in the case of KNRK cells. However, since overexpression of Nox1 in normal rat kidney cells failed to induce VEGF, the Nox1 activity alone was not sufficient to upregulate VEGF expression, which suggests that unlike the previously proposed model, Nox1 may act in concert with other effectors integrated into the Ras network. We propose that Nox1 mediates oncogenic Ras-induced upregulation of VEGF and angiogenesis by activating Sp1 through Ras-ERK-dependent phosphorylation of Sp1.
Predicting response to rtPA is essential in the era of endovascular therapy for stroke. The purpose of this study was to elucidate prognostic factors of early neurologic improvement and long-term ...outcome with respect to the development and reversion of leptomeningeal collaterals in recanalization therapy after acute ischemic stroke.
We analyzed consecutive patients with proximal MCA occlusion treated with rtPA from 2007 to 2012 at 2 hospital stroke centers. All patients routinely underwent brain MR imaging before rtPA. To assess the reversion of collateral signs, we included patients who underwent follow-up MR imaging. We assessed the development and reversion of collaterals by using a combination of 2 MR imaging collateral markers, the hyperintense vessel sign and the posterior cerebral artery laterality sign. Early neurologic improvement was defined as a decrease in the NIHSS score of ≥10 or a score of ≤2 at 24 hours of treatment.
Early neurologic improvement was observed in 22 of 48 eligible patients. The development of collaterals at arrival (15/22 versus 9/26, P = .042) was significantly associated with early neurologic improvement. Multivariate analysis adjusting for other variables showed that the development of collaterals at arrival (OR, 4.82; 95% CI, 1.34-19.98; P = .015) was independently associated with early neurologic improvement. Reversion of collaterals was significantly associated with successful recanalization (P < .001), and multivariate analysis showed that the reversion of collaterals was an independent prognostic factor of long-term functional outcome (OR, 5.07; 95% CI, 1.38-22.09; P = .013).
Our results indicate that the development of leptomeningeal collaterals plays a crucial role in achieving early neurologic improvement, and reversion of collaterals predicts a favorable outcome via arterial recanalization after rtPA treatment for acute stroke.
Abstract This is the first report on identifying the specific metabolites of the new designer drugs 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one (bk-MBDB) and ...2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one (bk-MDEA) in human urine using synthesized standards. Based on GC/MS and LC/MS, we identified N-dealkylation, demethylenation followed by O-methylation, and β-ketone reduction as their major metabolic pathways. The quantitative analyses by LC/MS revealed that both demethylenation followed by O-methylation and β-ketone reduction were superior to N-dealkylation and that both bk-MBDB and bk-MDEA were mainly metabolized into their corresponding 4-hydroxy-3-methoxy metabolites (4-OH-3MeO metabolites). After hydrolysis, the concentrations of 4-OH-3MeO metabolites and 3-hydroxy-4-methoxy metabolites of both bk-MBDB and bk-MDEA dramatically increased, suggesting that the metabolites mainly exist as their conjugates.
Pancreatic adenocarcinoma is an aggressive human malignancy and is characterized by resistance to apoptosis. Recently, NADPH oxidase (Nox) 4-mediated generation of intracellular reactive oxygen ...species (ROS) was proposed to confer antiapoptotic activity and thus a growth advantage to pancreatic cancer cells. The signaling mechanism by which Nox4 transmits cell survival signals remains unclear. Here, we show that both a flavoprotein inhibitor, diphenylene iodonium (DPI), and small interfering RNAs designed to target Nox4 mRNA (siNox4RNAs) inhibited superoxide production in PANC-1 pancreatic cancer cells, and depletion of ROS by DPI or siNox4RNAs induced apoptosis. Parallely, DPI treatment and siNox4RNA transfection blocked activation of the cell survival kinase AKT by attenuating phosphorylation of AKT. Furthermore, AKT phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) on Ser-83 was reduced by DPI and siNox4RNAs. When ASK1Ser83Ala (an AKT phosphorylation-defective ASK1 mutant) was introduced into PANC-1 cells, this mutant alone induced apoptosis. But, addition of DPI or co-transfection of siNox4RNA had no additive effect, indicating that the mutant can substitute for these reagents in apoptosis induction. Taken together, these findings suggest that ROS generated by Nox4, at least in part, transmit cell survival signals through the AKT-ASK1 pathway in pancreatic cancer cells and their depletion leads to apoptosis.
To investigate whether or not the lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation in ...the rostrocaudal direction along the spinal cord, as has been hypothesised (the 'single seed and simple propagation' hypothesis).
Subjects included 36 patients with sporadic ALS and initial symptoms in the bulbar, respiratory or upper limb regions. Abnormal spontaneous activities in needle electromyography (nEMG)-that is, fibrillation potentials, positive sharp waves (Fib/PSWs) or fasciculation potentials (FPs)-were compared among the unilateral muscles innervated by different spinal segments, especially between the T10 and L5 paraspinal muscles, and between the vastus medialis and biceps femoris. Axon length and the proportion of muscle fibre types, which are both related to motoneuronal vulnerability in ALS, are similar in the paired muscles.
Fourteen of 36 patients showed a non-contiguous distribution of nEMG abnormalities from the onset site, with skipping of intermediate segments. In eight of them, the non-contiguous pattern was evident between paired muscles with the same motoneuronal vulnerability. The non-contiguously affected lumbosacral lesions involved motoneuron columns horizontally or radially proximate to one another, appearing to form a cluster in four of the eight patients. FPs, known to precede Fib/PSWs, were shown more frequently than Fib/PSWs in all the lumbosacral segments but L5, suggesting that 2nd hits occur at L5 and then spread to other lumbosacral segments.
In sporadic ALS, the distribution of lower motoneuron involvement cannot be explained by the 'single seed and simple propagation' hypothesis alone. We propose a 'multifocal hits and local propagation' hypothesis instead.
Abstract The purpose of this study was to estimate the width of free margin with a significant impact on local recurrence in surgical resection of oral squamous cell carcinoma (OSCC). Clinical and ...pathological data of 127 consecutive patients who underwent radical resection of OSCC were analyzed retrospectively. The local control rate was compared between patients with clear, close, and involved surgical margins, changing the required width of free margin for the definition of ‘close surgical margin’ (from 1 to 5 mm). If a free margin of within 1, 2, or 4 mm was judged a close margin, the risk of local recurrence was significantly different among the patients with clear, close, and involved surgical margins. If the definition of close margin was within 5 mm of the resection margin, the difference between clear and close margin did not reach statistical significance. The results of this study suggest that 5 mm of clearance at the surgical resection margin should be the index of oncological surgery. More than 5 mm of histological free margin around OSCC is not justified in terms of the risk management of local recurrence and the resultant morbidity.
The AirWay Scope (AWS) is a new fibreoptic intubation device, which allows visualization of the glottic stractures without alignment of the oral, pharyngeal, and tracheal axes, and thus may be useful ...in patients with limited cervical spine (C-spine) movement. We fluoroscopically evaluated upper C-spine movement during intubation with the AWS or Macintosh or McCoy laryngoscope.
Forty-five patients, with normal C-spine, scheduled for elective surgery were randomly assigned to one of the three intubation devices. Movement of the upper C-spine was examined by measuring angles formed by adjacent vertebrae during intubation. Time to intubation was also recorded.
Median cumulative upper C-spine movement was 22.3°, 32.3°, and 36.5° with the AWS, Macintosh laryngoscope, and McCoy laryngoscope, respectively (P<0.001, AWS vs, Macintosh and McCoy). The AWS reduced maximum movement of the C-spine at C1/C2 in comparison with the Macintosh or McCoy laryngoscope (P=0.012), and at C3/C4 in comparison with the McCoy laryngoscope (P=0.019). Intubation time was significantly longer in the AWS group than in the Macintosh group (P=0.03).
Compared with the Macintosh or McCoy laryngoscope, the AWS produced less movement of upper C-spine for intubation in patients with a normal C-spine.
Abstract Only a few reports on the level of progression of extracapsular spread (ECS) have been published. The aim of this study was to evaluate the efficacy of the level of progression of ECS in ...identifying those patients with oral squamous cell carcinoma (OSCC) at a high risk of recurrence who would benefit most from the intensification of adjuvant therapy. The level of progression of ECS for cervical lymph node metastasis in OSCC was divided into three types (A–C), and their relationships with patient prognosis were examined. ECS was observed in 87 of 441 patients with OSCC. The recurrence rate in patients with type C, which was defined as macroscopic tumour invasion into perinodal fat or muscle tissue, was high (69.8%), with 13 cases of death due to distant metastasis. The 3-year disease-specific survival rate for patients with type C was 49.0% and these patients also had a significantly poorer prognosis ( P < 0.01). The results of the multivariate analysis suggested that the prognosis of ECS in OSCC patients was associated with the level of progression of ECS, especially type C ( P < 0.01). Overall, the results of this study suggest that the level of progression of ECS is a useful prognostic factor in OSCC patients.
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