The mass-metallicity relation (MZR) of type-2 active galactic nuclei (AGNs) at 1.2 < z < 4.0 is investigated by using high-z radio galaxies (HzRGs) and X-ray selected radio-quiet AGNs. We combine new ...rest-frame ultraviolet (UV) spectra of two radio-quiet type-2 AGNs obtained with FOCAS on the Subaru Telescope with existing rest-frame UV emission lines, i.e., C IVλ1549, He IIλ1640, and C IIIλ1909, of a sample of 16 HzRGs and 6 additional X-ray selected type-2 AGNs, whose host stellar masses have been estimated in literature. We divided our sample in three stellar mass bins and calculated averaged emission-line flux ratios of C IVλ1549/He IIλ1640 and C IIIλ1909/C IVλ1549. Comparing observed emission-line flux ratios with photoionization model predictions, we estimated narrow line region (NLR) metallicities for each mass bin. We found that there is a positive correlation between NLR metallicities and stellar masses of type-2 AGNs at z ~ 3. This is the first indication that AGN metallicities are related to their hosts, i.e., stellar mass. Since NLR metallicities and stellar masses follow a similar relation as the MZR in star-forming galaxies at similar redshifts, our results indicate that NLR metallicities are related to those of the host galaxies. This study highlights the importance of considering lower-mass X-ray selected AGNs in addition to radio galaxies to explore the metallicity properties of NLRs at high redshift.
With this study, we sought to characterise the impact of pro-inflammatory cytokines on the outcomes of gemcitabine monotherapy (GEM) in patients with pancreatic cancer (PC).
Treatment-naive patients ...with advanced PC and no obvious infections were eligible for enrolment. All of the patients were scheduled to undergo systemic chemotherapy. Serum pro-inflammatory cytokines were measured using an electro-chemiluminescence assay method before chemotherapy. High cytokine levels were defined as values greater than the median. Clinical data were collected prospectively.
Sixty patients who received GEM were included in the analysis. High IL-6 and IL-1β levels were poor prognostic factors for overall survival in a multivariate analysis (P=0.011 and P=0.048, respectively). Patients with both a high IL-6 level and a high IL-1β level exhibited shortened overall and progression-free survival, a reduction in the tumour control rate, and a high dose intensity of GEM compared with patients with low levels of both IL-6 and IL-1β.
The serum levels of IL-6 and IL-1β predict the efficacy of GEM in patients with advanced PC.
Abstract
In Japan, nearly 80% of heatstroke occurrences in recent years have involved people older than 65 years old. This study surveyed the actual use of cooling by elderly people at sleep time ...compared to those found for younger people. Results revealed the followings.
1) Ratios of cooling use at sleep time were 30.8% for elderly people and 57.4% for younger people. The respective ratios of natural ventilation use at sleep time were 39.9% and 32.4%.
2) Average wet bulb globe temperatures (WBGTs) of bed rooms during sleep were 26.9°C for elderly people and 26.4°C for younger people. 3) Elderly people feel warmer than younger people but they feel more thermally comfortable. 4) Sleep scores were 49.7 for elderly people and 48.5 for younger people. No difference was found for the frequency of night waking or the Sleep maintenance score, but the Fatigue recovery score showed the greatest difference between elderly and younger people.
ABSTRACT One of the important unsettled problems regarding active galactic nuclei (AGNs) is the major ionization mechanism of gas clouds in AGN narrow-line regions (NLRs). In order to investigate ...this issue, we present our J-band spectroscopic observations of a sample of 26 nearby Seyfert galaxies. In our study, we use the flux ratio of the following two forbidden emission lines, Fe ii1.257 m and P ii1.188 m, because it is known that this ratio is sensitive to the ionization mechanism. We obtain the Fe ii/P ii flux ratio or its lower limit for 19 objects. In addition to our data, we compile this flux ratio (or its lower limit) for 23 nearby Seyfert galaxies from the literature. Based on the collected data, we find that three Seyfert galaxies show very large lower limits of the Fe ii/P ii flux ratios ( 10): NGC 2782, NGC 5005, and Mrk 463. It is thus suggested that the contribution of the fast shock in the gas excitation is significantly large for them. However, more than half of the Seyfert galaxies in our sample show moderate Fe ii/P ii flux ratios (∼2), which is consistent with pure photoionization by power-law ionizing continuum emission. We also find that the Fe ii/P ii flux ratio shows no clear correlation with the radio loudness, suggesting that the radio jet is not the primary origin of shocks in NLRs of Seyfert galaxies.
In this study, we propose and evaluate a novel low-auto-fluorescence photoresist (SJI photoresist) for bio-application, e.g., in gene analysis and cell assay. The spin-coated SJI photoresist has a ...wide thickness range of ten to several hundred micrometers, and photoresist microstructures with an aspect ratio of over 7 and micropatterns of less than 2 μm are successfully fabricated. The emission spectrum intensity of the SJI photoresist is found to be over 80% less than that of the widely used SU-8 photoresist. To evaluate the validity of using the proposed photoresist in bio-application for fluorescence observation, we demonstrate a chromosome extension device composed of the SJI photoresist. The normalized contrast ratio of the SJI photoresist exhibits a 50% improvement over that of the SU-8 photoresist; thus, the SJI photoresist is a versatile tool for bio-application.
Tofogliflozin is an oral hypoglycemic agent with a novel mechanism of action that reduces blood glucose levels by promoting glucose excretion in urine, achieved by selectively inhibiting ...sodium-glucose co-transporter 2 (SGLT2). We evaluated the effects of several selected anti-type 2 diabetes mellitus (T2DM) drugs-glimepiride, metformin, sitagliptin, pioglitazone, miglitol, nateglinide, and voglibose-on the pharmacokinetics and pharmacodynamics of tofogliflozin, and the effects of tofogliflozin on the pharmacokinetics of these anti-T2DM drugs in healthy male volunteers.
A single dose of either tofogliflozin alone, one of the anti-T2DM drugs alone, or co-administration of tofogliflozin and the anti-T2DM drug was administered to 108 healthy men. Cmax, AUCinf, and cumulative urine glucose excretion after co-administration of tofogliflozin and each of the anti-T2DM drugs was evaluated relative to the values of those parameters after administration of each drug alone.
None of the anti-T2DM drugs had any effect on tofogliflozin exposure. Tofogliflozin had no or little effect on the exposure of any anti-T2DM drug. No anti-T2DM drug had any major effect on the cumulative urine glucose excretion induced by tofogliflozin. There were no safety concerns evident after administration of any drug alone or in co-administration.
Neither the pharmacokinetics nor the pharmacodynamics of tofogliflozin was affected by any of the anti-T2DM drugs evaluated in this study, nor was the pharmacokinetics of any of the anti-T2DM drugs affected by tofogliflozin in healthy male volunteers.
A palm-sized optical measurement device capable of polarisation rotation and single-wavelength absorption measurements is presented. The device is equipped with a polarisation-analysing CMOS image ...sensor with an on-chip multi-angular polariser array. The volume of the device is as small as 51 cm3, which is smaller than both 1/1000 of a conventional desktop polarimeter and 1/10 of the previous device. The capability of the proposed device to perform simultaneous polarisation rotation/single-wavelength absorption measurements is experimentally verified through in situ monitoring of a photochemical reaction performed in a microflow reactor.
Abstract Recombinant adeno-associated viral (rAAV) vector-mediated overexpression of α-synuclein (αSyn) protein has been shown to cause neurodegeneration of the nigrostriatal dopaminergic pathway in ...rodents and primates. Using serotype-2 rAAV vectors, we recently reported the protective effect of Parkin on αSyn-induced nigral dopaminergic neurodegeneration in a rat model. Here we investigated the neuronal specificity of αSyn toxicity and the effect of Parkin co-expression in a primate model. We used another serotype (type-1) of AAV vector that was confirmed to deliver genes of interest anterogradely and retrogradely to neurons in rats. The serotype-1 rAAV (rAAV1) carrying α Syn cDNA (rAAV1-αSyn), and a cocktail of rAAV1-αSyn and rAAV1 carrying parkin cDNA (rAAV1-parkin) were unilaterally injected into the striatum of macaque monkeys, resulting in protein expression in striatonigral GABAergic and nigrostriatal dopaminergic neurons. Injection of rAAV1-αSyn alone decreased tyrosine hydroxylase immunoreactivity in the striatum compared with the contralateral side injected with a cocktail of rAAV1-αSyn and rAAV1-parkin. Immunostaining of striatonigral GABAergic neurons was similar on both sides. Overexpression of Parkin in GABAergic neurons was associated with less accumulation of αSyn protein and/or phosphorylation at Ser129 residue. Our results suggest that the toxicity of accumulated αSyn is not induced in non-dopaminergic neurons and that the αSyn-ablating effect of Parkin is exerted in virtually all neurons in primates.
One potential strategy for gene therapy of Parkinson's disease (PD) is the local production of dopamine (DA) in the striatum induced by restoring DA-synthesizing enzymes. In addition to tyrosine ...hydroxylase (TH) and aromatic-L-amino-acid decarboxylase (AADC), GTP cyclohydrolase I (GCH) is necessary for efficient DA production. Using adeno-associated virus (AAV) vectors, we previously demonstrated that expression of these three enzymes in the striatum resulted in long-term behavioral recovery in rat models of PD. We here extend the preclinical exploration to primate models of PD. Mixtures of three separate AAV vectors expressing TH, AADC, and GCH, respectively, were stereotaxically injected into the unilateral putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys. Coexpression of the enzymes in the unilateral putamen resulted in remarkable improvement in manual dexterity on the contralateral to the AAV-TH/-AADC/-GCH-injected side. Behavioral recovery persisted during the observation period (four monkeys: 48 days, 65 days, 50 days, and >10 months, each). TH-immunoreactive (TH-IR), AADC-IR, and GCH-IR cells were present in a large region of the putamen. Microdialysis demonstrated that concentrations of DA in the AAV-TH/-AADC/-GCH-injected putamen were increased compared with the control side. Our results show that AAV vectors efficiently introduce DA-synthesizing enzyme genes into the striatum of primates with restoration of motor functions. This triple transduction method may offer a potential therapeutic strategy for PD.
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