Abstract
We searched for shocked carbon chain chemistry (SCCC) sources with C
3
S abundances surpassing those of HC
5
N toward the dark cloud L1251, using the Effelsberg telescope at the
K
band ...(18–26 GHz). L1251-1 and L1251-3 are identified as the most promising SCCC sources. The two sources harbor young stellar objects. We conducted mapping observations toward L1251-A, the western tail of L1251, at
λ
∼ 3 mm with the Purple Mountain Observatory 13.7 m and the Nobeyama Radio Observatory 45 m telescopes in lines of C
2
H, N
2
H
+
, CS, HCO
+
, SO, HC
3
N, and C
18
O as well as in CO 3–2 using the James Clerk Maxwell Telescope (JCMT). The spectral data were combined with archival data including Spitzer and Herschel continuum maps for further analysis. Filamentary substructures labeled as F1–F6 were extracted in L1251, with F1 being associated with L1251-A hosting L1251-1. The peak positions of dense gas traced by HCO
+
are misaligned relative to those of the dust clumps. Episodic outflows are common in this region. The twisted morphology of F1 and velocity distribution along L1251-A may originate from stellar feedback. SCCC in L1251-1 may have been caused by outflow activities originated from the infrared source IRS1. The signposts of ongoing SCCC and the broadened line widths of C
3
S and C
4
H in L1251-1 as well as the distribution of HC
3
N are also related to outflow activities in this region. L1251-1 (IRS1) together with the previously identified SCCC source IRS3 demonstrate that L1251-A is an excellent region to study SCCC.
We propose a new method for determining the target genes of transcriptional enhancers in specific cells and tissues. It combines global trends across many samples and sample-specific information, and ...considers the joint effect of multiple enhancers. Our method outperforms existing methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent experimental data. Requiring few types of input data, we are able to apply our method to reconstruct the enhancer-target networks in 935 samples of human primary cells, tissues and cell lines, which constitute by far the largest set of enhancer-target networks. The similarity of these networks from different samples closely follows their cell and tissue lineages. We discover three major co-regulation modes of enhancers and find defense-related genes often simultaneously regulated by multiple enhancers bound by different transcription factors. We also identify differentially methylated enhancers in hepatocellular carcinoma (HCC) and experimentally confirm their altered regulation of HCC-related genes.
We performed a carbon-chain molecule (CCM) survey toward four low-mass outflow sources, IRAS 04181+2655 (I04181), HH211, L1524, and L1598, using the 13.7 m telescope at the Purple Mountain ...Observatory (PMO) and the 65 m Tian Ma Radio telescope at the Shanghai Observatory. We observed the following hydrocarbons (C
2
H, C
4
H, c–C
3
H
2
), HC
2
n
+1
N (
n
= 1, 2), C
n
S (
n
= 2, 3), and SO, HNC, N
2
H
+
. Hydrocarbons and HC
3
N were detected in all the sources, except for L1598, which had a marginal detection of C
4
H and a non-detection of HC
3
N (
J
= 2–1). HC
5
N and CCCS were only detected in I04181 and L1524, whereas SO was only detected in HH211. L1598 exhibits the lowest detection rate of CCMs and is generally regarded to be lacking in CCMs source. The ratio of N(HC
3
N/N(N
2
H
+
)) increases with evolution in low-mass star-forming cores. I04181 and L1524 are carbon-chain-rich star-forming cores that may possibly be characterized by warm carbon-chain chemistry. In I04181 and L1524, the abundant CCCS can be explained by shocked carbon-chain chemistry. In HH211, the abundant SO suggests that SO is formed by sublimated S
+
. In this study, we also mapped HNC, C
4
H, c–C
3
H
2
, and HC
3
N with data from the PMO. We also find that HNC and NH
3
are concentrated in L1524S and L1524N, respectively. Furthermore, we discuss the chemical differences between I04181SE and I04181W. The co-evolution between linear hydrocarbon and cyanopolyynes can be seen in I04181SE.
Context. Sagittarius B2 (north) is a chemically rich, high-mass star-forming region located within the giant molecular cloud complex Sgr B2 in the central molecular zone of our Galaxy. Dust continuum ...emission at 242 GHz, obtained at high angular resolution with the Atacama Large Millimeter Array (ALMA), reveals that it has a filamentary structure on scales of 0.1 pc. Aims. We aim to characterize the filamentary structure of Sgr B2(N) and its kinematic properties using multiple molecular dense gas tracers. Methods. We have used an unbiased, spectral line-survey that covers the frequency range from 211 to 275 GHz and obtained with ALMA (angular resolution of 0.′′4, or 3300 au) to study the small-scale structure of the dense gas in Sgr B2(N). In order to derive the kinematic properties of the gas in a chemically line-rich source like Sgr B2(N), we have developed a python-based tool that stacks all the detected line transitions of any molecular species. This allows us to increase the signal-to-noise ratio (S/N) of our observations and average out line blending effects, which are common in line-rich regions. Results. A filamentary network is visible in Sgr B2(N) in the emission maps of the molecular species CH 3 OCHO, CH 3 OCH 3 , CH 3 OH and H 2 CS. In total, eight filaments are found that converge to the central hub (with a mass of 2000 M ⊙ , assuming a temperature of 250 K) and extending for about 0.1 pc (up to 0.5 pc). The spatial structure, together with the presence of the massive central region, suggest that these filaments may be associated with accretion processes, transporting material from the outer regions to the central dense hub. We derive velocity gradients along the filaments of about 20–100 km s −1 pc −1 , which are 10–100 times larger than those typically found on larger scales (~1 pc) in other star-forming regions. The mass accretion rates of individual filaments are ≾0.05 M ⊙ yr −1 , which result in a total accretion rate of 0.16 M ⊙ yr −1 . Some filaments harbor dense cores that are likely forming stars and stellar clusters. We determine an empirical relation between the luminosity and stellar mass of the clusters. The stellar content of these dense cores is on the order of 50% of the total mass. The timescales required for the dense cores to collapse and form stars, exhausting their gas content, are compared with the timescale of their accretion process onto the central hub. We conclude that the cores may merge in the center when already forming stellar clusters but still containing a significant amount of gas, resulting in a “damp” merger. Conclusions. The high density and mass of the central region, combined with the presence of converging filaments with high mass, high accretion rates and embedded dense cores already forming stars, suggest that Sgr B2(N) may have the potential to evolve into a super stellar cluster.
We demonstrate, both theoretically and experimentally, that cation vacancy can be the origin of ferromagnetism in intrinsic dilute magnetic semiconductors. The vacancies can be controlled to tune the ...ferromagnetism. Using Li-doped ZnO as an example, we found that while Li itself is nonmagnetic, it generates holes in ZnO, and its presence reduces the formation energy of Zn vacancy, and thereby stabilizes the zinc vacancy. Room temperature ferromagnetism with p type conduction was observed in pulsed laser deposited ZnO:Li films with certain doping concentration and oxygen partial pressure.
Recent researches on the addictive manufacturing (AM) of titanium alloys have shown the significant advantages in fabricating complex constructions. Laser deposition manufacturing (LDM) and selective ...laser melting (SLM) are two representative AM technologies, Ti-6Al-4V alloy samples for the complex structure and functional integration application were fabricated by LDM-SLM hybrid manufacturing process in present research. The microstructure of LDM-SLM hybrid fabrication Ti-6Al-4V components can be divided into three regions: LDM zone mainly composed of the α laths, SLM zone which is fully α' martensitic and a large number of irregular crystals are distributed in the bonding area between the LDM zone and SLM zone, which is named heat affect zone (HAZ). The inhomogeneous microstructure leads to the discrepancy in mechanical behavior, after multiple cyclic thermal treatment at 750 °C/10min↔960 °C/10min, the original α′ martensitic is complete converted to the mixture of α-phase and β-phase and the growth of the thick α laths was restrained. The microstructure and mechanical properties of LDM zone and SLM zone tend to be equivalent at all of cycle-treatement. After cyclic thermal treatment, the strength of LDM samples and hybrid fabricated samples vary slightly, but the plasticity of LDM is improved significantly. The morphology features of α phase and evolutions of crystallographic orientation are the dominant factors of microstructure homogenizations during cyclic thermal treatments, related information was found in the EBSD investigation.
From Nitrate to Nitric Oxide Qu, X.M.; Wu, Z.F.; Pang, B.X. ...
Journal of dental research,
12/2016, Letnik:
95, Številka:
13
Journal Article
Recenzirano
The salivary glands and oral bacteria play an essential role in the conversion process from nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO) in the human body. NO is, at present, recognized as ...a multifarious messenger molecule with important vascular and metabolic functions. Besides the endogenous L-arginine pathway, which is catalyzed by complex NO synthases, nitrate in food contributes to the main extrinsic generation of NO through a series of sequential steps (NO3--NO2--NO pathway). Up to 25% of nitrate in circulation is actively taken up by the salivary glands, and as a result, its concentration in saliva can increase 10- to 20-fold. However, the mechanism has not been clearly illustrated until recently, when sialin was identified as an electrogenic 2NO3-/H+ transporter in the plasma membrane of salivary acinar cells. Subsequently, the oral bacterial species located at the posterior part of the tongue reduce nitrate to nitrite, as catalyzed by nitrate reductase enzymes. These bacteria use nitrate and nitrite as final electron acceptors in their respiration and meanwhile help the host to convert nitrate to NO as the first step. This review describes the role of salivary glands and oral bacteria in the metabolism of nitrate and in the maintenance of NO homeostasis. The potential therapeutic applications of oral inorganic nitrate and nitrite are also discussed.
Thyroid hormone (TH) is a thermogenic activator with anti-obesity potential. However, systemic TH administration has no obvious clinical benefits on weight reduction. Herein we selectively delivered ...triiodothyronine (T3) to adipose tissues by encapsulating T3 in liposomes modified with an adipose homing peptide (PLT3). Systemic T3 administration failed to promote thermogenesis in brown and white adipose tissues (WAT) due to a feedback suppression of sympathetic innervation. PLT3 therapy effectively obviated this feedback suppression on adrenergic inputs, and potently induced browning and thermogenesis of WAT, leading to alleviation of obesity, glucose intolerance, insulin resistance, and fatty liver in obese mice. Furthermore, PLT3 was much more effective than systemic T3 therapy in reducing hypercholesterolemia and atherosclerosis in apoE-deficient mice. These findings uncover WAT as a viable target mediating the therapeutic benefits of TH and provide a safe and efficient therapeutic strategy for obesity and its complications by delivering TH to adipose tissue.
Dual blockade of PD-L1 and VEGF has enhanced anticancer immunity through multiple mechanisms and augmented antitumour activity in multiple malignancies. We aimed to assess the efficacy and safety of ...atezolizumab (anti-PD-L1) alone and combined with bevacizumab (anti-VEGF) in patients with unresectable hepatocellular carcinoma.
GO30140 is an open-label, multicentre, multiarm, phase 1b study that enrolled patients at 26 academic centres and community oncology practices in seven countries worldwide. The study included five cohorts, and the two hepatocellular carcinoma cohorts, groups A and F, are described here. Inclusion criteria for these two groups included age 18 years and older; histologically, cytologically, or clinically (per American Association for the Study of Liver Diseases criteria) confirmed unresectable hepatocellular carcinoma that was not amenable to curative treatment; no previous systemic treatment; and Eastern Cooperative Oncology Group performance status of 0 or 1. In group A, all patients received atezolizumab (1200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks. In group F, patients were randomly assigned (1:1) to receive intravenous atezolizumab (1200 mg) plus intravenous bevacizumab (15 mg/kg) every 3 weeks or atezolizumab alone by interactive voice-web response system using permuted block randomisation (block size of two) and stratification factors of geographical region; macrovascular invasion, extrahepatic spread, or both; and baseline α-fetoprotein concentration. Primary endpoints were confirmed objective response rate in all patients who received the combination treatment for group A and progression-free survival in the intention-to-treat population in group F, both assessed by an independent review facility according to Response Evaluation Criteria in Solid Tumors version 1.1. In both groups, safety was assessed in all patients who received at least one dose of any study treatment. This study is registered with ClinicalTrials.gov, NCT02715531, and is closed to enrolment.
In group A, 104 patients were enrolled between July 20, 2016, and July 31, 2018, and received atezolizumab plus bevacizumab. With a median follow-up of 12·4 months (IQR 8·0–16·2), 37 (36%; 95% CI 26–46) of 104 patients had a confirmed objective response. The most common grade 3–4 treatment-related adverse events were hypertension (13 13%) and proteinuria (seven 7%). Treatment-related serious adverse events occurred in 25 (24%) patients and treatment-related deaths in three (3%) patients (abnormal hepatic function, hepatic cirrhosis, and pneumonitis). In group F, 119 patients were enrolled and randomly assigned (60 to atezolizumab plus bevacizumab; 59 to atezolizumab monotherapy) between May 18, 2018, and March 7, 2019. With a median follow-up of 6·6 months (IQR 5·5–8·5) for the atezolizumab plus bevacizumab group and 6·7 months (4·2–8·2) for the atezolizumab monotherapy group, median progression-free survival was 5·6 months (95% CI 3·6–7·4) versus 3·4 months (1·9–5·2; hazard ratio 0·55; 80% CI 0·40–0·74; p=0·011). The most common grade 3–4 treatment-related adverse events in group F were hypertension (in three 5% patients in the atezolizumab plus bevacizumab group; none in the atezolizumab monotherapy group) and proteinuria (in two 3% patients in the atezolizumab plus bevacizumab group; none in the atezolizumab monotherapy group). Treatment-related serious adverse events occurred in seven (12%) patients in the atezolizumab plus bevacizumab group and two (3%) patients in the atezolizumab monotherapy group. There were no treatment-related deaths.
Our study shows longer progression-free survival with a combination of atezolizumab plus bevacizumab than with atezolizumab alone in patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy. Therefore, atezolizumab plus bevacizumab might become a promising treatment option for these patients. This combination is being compared with standard-of-care sorafenib in a phase 3 trial.
F Hoffmann-La Roche/Genentech.
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