A
bstract
Utilizing 7
.
33 fb
−
1
of
e
+
e
−
collision data taken at the center-of-mass energies of 4.128, 4.157, 4.178, 4.189, 4.199, 4.209, 4.219, and 4.226 GeV with the BESIII detector, the ...branching fraction of the leptonic decay
D
s
+
→ τ
+
ν
τ
via
τ
+
→ μ
+
ν
μ
ν
¯
τ
is measured to be
B
D
s
+
→
τ
+
ν
τ
= (5
.
37
±
0
.
17
stat
±
0
.
15
syst
)%. Combining this branching fraction with the world averages of the measurements of the masses of
τ
+
and
D
s
+
as well as the lifetime of
D
s
+
, we extract the product of the decay constant of
D
s
+
and the
c → s
Cabibbo-Kobayashi-Maskawa matrix element to be
f
D
s
+
|V
cs
|
= (246
.
7
±
3
.
9
stat
±
3
.
6
syst
) MeV. Taking
|V
cs
|
from a global fit in the standard model we obtain
f
D
s
+
= (253
.
4
±
4
.
0
stat
±
3
.
7
syst
) MeV. Conversely, taking
f
D
s
+
from lattice quantum chromodynamics calculations, we obtain
|V
cs
|
= 0
.
987
±
0
.
016
stat
±
0
.
014
syst
.
Background
Premedication in upper gastrointestinal endoscopy for higher lesions detection rate has not been well studied so far. This study aimed to confirm whether premedication could improve the ...detection rate of early cancer or precancerous lesions and mucosal visibility.
Method
From July 2015 to December 2015, 7200 participants from 6 centers were screened by endoscopy with one of the 4 following premedications randomly: (1) water (group D); (2) pronase (group A); (3) simethicone (group B); (4) pronase and simethicone (group C). Early cancer and precancerous lesions detection rates were taken as the primary endpoints, and mucosal visibility was taken as the secondary endpoint. They were compared among four groups to determine different premedication effects in terms of different anatomical sites. Trial was registered at Chinese Clinical Trial Registry; the registration number is ChiCTR-IOR-17010985.
Results
The upper gastrointestinal overall precancerous lesion detection rates among four groups were 8.7, 8.4, 10.0, and 10.3%, the overall early cancer detection rates were 1.3, 1.4%, 1.5, and 1.6%, both without significant difference (
p
= 0.138 and 0.878). However, the visibility score distributions between control group (D) and premedication groups (A, B, and C) were all statistically significant, with all anatomical sites
p
values < 0.001. Subgroup analyses, from 2 centers without screening before, also showed significant difference in esophageal (3.9, 3.3, 4.5, and 8.4% with
p
= 0.004) and overall (7.0, 5.5, 7.3, and 12.0% with
p
= 0.004) precancerous lesion detection rate.
Conclusions
Premedication with pronase and simethicone may not increase lesion detection rates but could significantly increase the upper gastrointestinal mucosal visibility.
A potential factor dominating the obstacle strength of second phase precipitate particles in dispersion strengthening is the crystallographic mismatch between the matrix phase and the second phase; ...however, yet this concept has not been fully assessed by experiments and simulations. In the present study, we experimentally investigated the obstacle strength of body centered cubic (bcc) Nb particles and nanometric Nb clusters embedded in hexagonal close packed (hcp) Zr matrix. The bcc Nb is softer than the hcp Zr in terms of shear modulus, whereas from a crystallographic viewpoint, the bcc Nb particles can be nonshearable, strong obstacles because the slip plane inside the particles is not parallel with that in the matrix. Although the bcc Nb is thermodynamically the stable configuration for Nb atoms precipitating from the Zr matrix, in the very early stage of solute agglomeration, the crystal structure of Nb nanoclusters is possibly hcp rather than bcc. The obstacle strength (α) was no greater than 0.5 for the Nb nanoclusters, whereas 0.85 ≤ α ≤ 1 for the coarse bcc Nb particles; α = 1 was obtained with the Taylor factor (M) of 5.5 and α = 0.85 with M = 6.5, respectively. These results indicate that the bcc Nb particles are strong obstacles, and that the Nb nanoclusters are weak obstacles.
Display omitted
Information about the specific regulatory environment of orphan drugs is scarce and inconsistent. Uncertainties surrounding the postmarketing long-term safety of orphan drugs remain. This study aimed ...to evaluate the labelling changes of orphan drugs and to identify postmarketing safety-associated approval factors.
This retrospective cohort study includes all drugs with orphan drug designation approved by the Center for Drug Evaluation and Research of the US Food and Drug Administration between 1999 and 2018. Main outcomes are safety-related labelling changes up to 31 December 2019. We defined any safety-related labelling changes as postmarketing safety events (PMSE). Safety-related withdrawals, suspensions, and boxed warnings were further categorised as severe postmarketing safety events (SPSE). Outcome measurements include frequencies of PMSE, SPSE, and association between approval factors and the occurrence of safety events.
Amongst the 214 drugs identified with orphan drug designation (25.7% biologics), 83.6% were approved through at least one expedited programme, and 29.4% were approved with boxed warnings. During a median follow-up of 6.74 years since approval, 69.2% and 14.5% of the analysed orphan drugs had PMSE and SPSE, respectively. Safety-related withdrawal (0%, 0/214), suspended marketing (0.46%, 1/214) and new boxed warnings are uncommon (3.7%, 8/214). The safety-related labelling changes were more frequent in the drugs approved with boxed warnings Incidence rate ratio (IRR): 1.95 (1.02-3.73) and approved for long-term use IRR: 2.76 (1.52-5.00).
In this long-term postmarketing analysis, approximately 70% of FDA-approved orphan drugs had safety-related labelling changes although severe safety events were rare. While maintaining early access to orphan drugs, the drug regulatory body has taken timely regulatory action with postmarketing surveillance to ensure patient safety.
Patterning and phenotypic variations of appendages in insects provide important clues on developmental genetics. In the silkworm Bombyx mori, morphological variations associated with the E complex, ...an analogue of the Drosophila melanogaster bithorax complex, mainly determine the shape and number of prolegs on abdominal segments. Here, we report the identification and characterization of the allele responsible for the supernumerary crescents and legs‐like (ECs‐l) mutant, a model derived from spontaneous mutation of the E complex, with supernumerary legs and extra crescents. Fine mapping with 1605 individuals revealed a ∼68 kb sequence in the upstream intergenic region of B. mori abdominal‐A (Bmabd‐A) clustered with the ECs‐l locus. Quantitative real‐time PCR (qRT‐PCR) and Western blotting analyses disclosed a marked increase in Bmabd‐A expression in the ECs‐l mutant at both the transcriptional and translational levels, compared to wild‐type Dazao. Furthermore, we observed ectopic expression of the Bmabd‐A protein in the second abdominal segment (A2) of the ECs‐l mutant. Our results collectively suggest that the 68 kb region contains important regulatory elements of the Bmabd‐A gene, and provide evidence that the gene is required for limb development in abdominal segments in the silkworm.
In order to enhance the corrosion resistance of the Ca65Mg15Zn20 bulk metallic glass, which has too fast a degradation rate for biomedical applications, we fabricated the Ca20Mg20Zn20Sr20Yb20 ...high-entropy bulk metallic glass because of the unique properties of high-entropy alloys. Our results showed that the mechanical properties and corrosion behavior were enhanced. The in vitro tests showed that the Ca20Mg20Zn20Sr20Yb20 high-entropy bulk metallic glass could stimulate the proliferation and differentiation of cultured osteoblasts. The in vivo animal tests showed that the Ca20Mg20Zn20Sr20Yb20 high-entropy bulk metallic glass did not show any obvious degradation after 4weeks of implantation, and they can promote osteogenesis and new bone formation after 2weeks of implantation. The improved mechanical properties and corrosion behavior can be attributed to the different chemical composition as well as the formation of a unique high-entropy atomic structure with a maximum degree of disorder.
Iodine occurs in multiple oxidation states in aquatic systems in the form of organic and inorganic species. This feature leads to complex biogeochemical cycling of stable iodine and its long-lived ...isotope, 129I. In this study, we investigated the sorption, transport, and interconversion of iodine species by comparing their mobility in groundwaters at ambient concentrations of iodine species (10–8 to 10–7 M) to those at artificially elevated concentrations (78.7 μM), which often are used in laboratory analyses. Results demonstrate that the mobility of iodine species greatly depends on, in addition to the type of species, the iodine concentration used, presumably limited by the number of surface organic carbon binding sites to form covalent bonds. At ambient concentrations, iodide and iodate were significantly retarded (K d values as high as 49 mL g–1), whereas at concentrations of 78.7 μM, iodide traveled along with the water without retardation. Appreciable amounts of iodide during transport were retained in soils due to iodination of organic carbon, specifically retained by aromatic carbon. At high input concentration of iodate (78.7 μM), iodate was found to be reduced to iodide and subsequently followed the transport behavior of iodide. These experiments underscore the importance of studying iodine geochemistry at ambient concentrations and demonstrate the dynamic nature of their speciation during transport conditions.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and is highly correlated with hepatitis virus infection. Our previous report shows that a DEAD box RNA helicase, ...DDX3, is targeted and regulated by hepatitis C virus (HCV) core protein, which implicates the involvement of DDX3 in HCV-related HCC development. In this study, the potential role of DDX3 in hepatocarcinogenesis is investigated by examining its expression in surgically excised human HCC specimens. Here we report the differential deregulation of DDX3 expression in hepatitis virus-associated HCC. A significant downregulation of DDX3 expression is found in HCCs from hepatitis B virus (HBV)-positive patients, but not from HCV-positive ones, compared to the corresponding nontumor tissues. The expression of DDX3 is differentially regulated by the gender and, moreover, there is a tendency that the downregulation of DDX3 expression in HCCs is more frequent in males than in females. Genetic knockdown of DDX3 with small interfering RNAs (siRNA) in a nontransformed mouse fibroblast cell line, NIH-3T3, results in a premature entry to S phase and an enhancement of cell growth. This enhanced cell cycle progression is linked to the upregulation of cyclin D1 and the downregulation of p21(WAF1) in the DDX3 knockdown cells. In addition, constitutive reduction of DDX3 expression increases the resistance of NIH-3T3 cells to serum depletion-induced apoptosis and enhances the ras-induced anchorage-independent growth, indicating the involvement of DDX3 in cell growth control. These findings together with the previous study suggest that the deregulation of DDX3, a DEAD box RNA helicase with cell growth-regulatory functions, is involved in HBV- and HCV-associated pathogenesis.
ABSTRACT
We report the detection of radio recombination line (RRL) H40α towards 75 sources, with data obtained from ACA (Atacama Compact 7 m Array) observations in the ATOMS (ALMA Three-millimeter ...Observations of Massive Star-forming regions) survey of 146 active Galactic star-forming regions. We calculated ionized gas mass and star formation rate (SFR) with H40α line emission. The mass of ionized gas is significantly smaller than molecular gas mass, indicating that ionized gas is negligible in the star-forming clumps of the ATOMS sample. The SFR estimated with RRL H40α agrees well with that calculated with the total bolometric luminosity (Lbol) when SFR ≥ 5 M⊙ Myr−1, suggesting that millimetre RRLs could well sample the upper part of the initial mass function and thus be good tracers of SFR. We also study the relationships between Lbol and the molecular line luminosities (L$^{^{\prime }}_{\rm mol}$) of CS J = 2–1 and HC3N J = 11–10 for all the 146 ATOMS sources. The $L_{\rm bol} \!-\! L^{\prime }_{\rm mol}$ correlations of both the CS J = 2–1 and HC3N J = 11–10 lines appear approximately linear and these transitions have success in predicting Lbol similar to that of more commonly used transitions. The Lbol-to-$L^{\prime }_{\rm mol}$ ratios or SFR-to-mass ratios (star formation efficiency) do not change with galactocentric distances (RGC). Sources with H40α emission (or H ii regions) show higher Lbol-to-$L^{\prime }_{\rm mol}$ ratios than those without H40α emission, which may be an evolutionary effect.
The Levant constitutes an important region for assessing linkages between climate and societal changes throughout the course of human history. However, large uncertainties remain in our understanding ...of the region's hydroclimate variability under varying boundary conditions. Here we present a new high‐resolution, precisely dated speleothem oxygen‐carbon isotope and Sr/Ca records, spanning the last 20 ka from Jeita Cave, northern Levant. Our record reveals a higher (lower) precipitation‐evaporation (P‐E) balance during the Last Glacial Maximum and Bølling interstadial (Heinrich stadial 1). The early‐middle Holocene is characterized by a trend toward higher P‐E state, culminating between ~7 and 6 ka. The middle‐late Holocene is characterized by two millennial‐length drier periods during 5.3–4.2 and 2.8–1.4 ka. On submillennial time scale, the northern Levant climate variability is dominated by 500 year periodicity. Comparisons with the regional proxy records suggest persistent out‐of‐phase climate variability between the northern and southern Levant on a wide range of timescales.
Key Points
High‐resolution speleothem record is established in northern Levant in the last 20 ka
The Climate variability on various timescales in northern Levant is characterized
Climate variations are out of phase between northern and southern Levant
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