Summary
Background
Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine‐metabolic disorder associated with insulin resistance (IR). In IR states, non–insulin‐mediated glucose uptake ...(NIMGU) may increase to compensate for declining insulin‐mediated glucose uptake (IMGU), although this does not appear to be the case in PCOS. The underlying molecular mechanisms for this deficiency remain unclear.
Objectives
To compare adipocyte glucose transporter 1 and 4 (GLUT‐1 and GLUT‐4) gene expression in PCOS women and matched controls, and to determine whether changes in GLUT‐1 and GLUT‐4 are associated with concomitant alterations in whole‐body glucose uptake.
Research design and methods
In this prospective cross‐sectional study, 23 women with PCOS (by NIH 1990 criteria) and 23 matched controls were studied for subcutaneous abdominal adipocyte GLUT‐1 and GLUT‐4 mRNA expression (by real‐time PCR), and basal whole‐body IR (by HOMA‐IR) and insulin secretion (by HOMA‐β%). A subset of six PCOS women and six matched controls also underwent a mFSIVGTT to determine dynamic state glucose uptake (by insulin sensitivity index Si and glucose effectiveness Sg) and insulin secretion (by the acute insulin response to glucose AIRg and the disposition index Di).
Results
For similar adiposity (BMI and waist‐hip ratio), PCOS women tended to have higher HOMA‐IR and lower Di and Si, and higher HOMA‐β% and lower GLUT‐4 than controls, while GLUT‐1 was similar. GLUT‐1 was positively associated with Sg (reflecting NIMGU) and GLUT‐4 positively with Si (reflecting IMGU). GLUT‐4 was associated negatively with HOMA‐IR and HOMA‐β% and positively with Di for the entire cohort but not with AIRg. Both GLUT‐1 and GLU‐4 were negatively associated with BMI, but not with each other.
Conclusion
Our results suggest that IR secondary to a lower IMGU and enhanced insulin secretion in PCOS is in part attributable to a reduction in adipocyte GLUT‐4 expression that is not accompanied by a compensatory increase in GLUT‐1 expression.
Abstract
We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. ...We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding ...to the largest fluctuations in the cosmic density field. Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far. Here we report observations of a far-infrared-luminous object at redshift 6.900 (less than 800 million years after the Big Bang) that was discovered in a wide-field survey. High-resolution imaging shows it to be a pair of extremely massive star-forming galaxies. The larger is forming stars at a rate of 2,900 solar masses per year, contains 270 billion solar masses of gas and 2.5 billion solar masses of dust, and is more massive than any other known object at a redshift of more than 6. Its rapid star formation is probably triggered by its companion galaxy at a projected separation of 8 kiloparsecs. This merging companion hosts 35 billion solar masses of stars and has a star-formation rate of 540 solar masses per year, but has an order of magnitude less gas and dust than its neighbour and physical conditions akin to those observed in lower-metallicity galaxies in the nearby Universe. These objects suggest the presence of a dark-matter halo with a mass of more than 100 billion solar masses, making it among the rarest dark-matter haloes that should exist in the Universe at this epoch.
The life extension of current pressurized water reactors and the design of reliable next-generation nuclear reactors call for advanced structural steels that can sustain radiation up to several ...hundred displacements per atom (dpa) at elevated temperatures. Here we performed Fe ion irradiation to 150dpa at 450°C on bulk coarse-grained (CG, with a grain size of ∼2μm) and ultrafine-grained (UFG, with grain size of ∼320nm) T91 steels. Extensive microscopy studies show that fine grains in UFG T91 reduced the density of nanocavities and dislocation loops. The swelling rate in UFG steel is three times lower than that of CG T91 due to the existence of abundant defect sinks, such as high angle grain boundaries and dislocations. A strong surface effect with size dependence was noted during heavy ion irradiation studies. The large deviation of swelling rate from neutron irradiated specimens implies the significance of He concentration and presumably dose rate on swelling in nuclear reactors.
We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five ...center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrts=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1) MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.
The use of recombinant protein for therapeutic applications has increased significantly in the last three decades. The heterogeneity of these proteins, often caused by the complex biosynthesis ...pathways and the subsequent PTMs, poses a challenge for drug characterization to ensure its safety, quality, integrity, and efficacy. CE, with its simple instrumentation, superior separation efficiency, small sample consumption, and short analysis time, is a well‐suited analytical tool for therapeutic protein characterization. Different separation modes, including CIEF, SDS‐CGE, CZE, and CE‐MS, provide complementary information of the proteins. The CE applications for recombinant therapeutic proteins from the year 2000 to June 2013 are reviewed and technical concerns are discussed in this article.
Abstract This study was performed to investigate the incidence of and risk factors for postoperative cleft relapse and oronasal fistula after Furlow palatoplasty in infants. Sixty-two infants with ...cleft palate, aged 6–12 months (mean 8.25 months), who underwent cleft repair by Furlow double opposing Z-plasty between March 2012 and August 2014, were enrolled in the study. Risk factors for postoperative cleft relapse and oronasal fistula after Furlow palatoplasty were identified by logistic regression analysis. The incidence rates of cleft relapse at 1 week and oronasal fistula at 3 months after surgery were 24.2% (15/62) and 9.7% (6/62), respectively. Among all of the variables screened, only the width of the cleft was significantly associated with the incidence of postoperative cleft relapse ( P = 0.001) and oronasal fistula ( P = 0.011); the incidence rates were positively correlated with the width of the cleft when it exceeded 6.8 mm and 7.5 mm, respectively. Based on these findings, in order to reduce the incidence of postoperative cleft relapse and oronasal fistula, Furlow repair is not recommended for patients with wide clefts. An appropriate angle between the Z-flap incision and the central axis, use of a bilateral relaxation incision, and postoperative nursing care can help reduce the incidence of postoperative cleft relapse.
The open-cell porous Ti-6Al-4V structure, intended to be applied as replacement for human cortical and cancellous bone, are fabricated by selective laser melting (SLM). The computer aided design ...(CAD) was used to design porous structures in various porosity levels from 40% to 80% and with pore sizes from 600 to 1000 μm, in order to fit the bone-tissue in-growth. The SLM porous samples with 40% to 70% porosity matched well with the CAD structure, but the 80% porosity one was found to be difficult to achieve the design. In comparison with the CAD structures and the SLM samples, there are minor discrepancies in terms of pore size and ligament width, mainly a result of laser beam broadening. To achieve more precise SLM porous morphologies, further reduction of powder size and laser beam diameter would be necessary. The measured data on the Young's modulus and yield strength of the SLM porous samples can be roughly estimated by the Gibson and Ashby model. The sample with 67% porosity was found to match best with human bone, with Young's modulus of 15 GPa and yield stress of 129 MPa, preventing from the risk of stress shielding effect.
•The porous Ti-6Al-4V foams are prepared by selective laser melting.•Minor discrepancies between CAD and SLM are due to laser beam broadening.•The 67% porosity sample matches with human bone avoiding stress shielding effect.
High-entropy alloys (HEAs) are generally in a solid-solution state, possessing some superior properties over conventional alloys due to their microstructural homogeneity, effective multi-element ...strengthening and deformation twinning. In the present study, 10 at% Ti was added to an equiatomic AlCoCrFeNi high-entropy alloy, which increased its microstructural inhomogeneity with the formation of distinctive honeycomb-shaped interdendrites. The performances of the AlCoCrFeNi alloy and the Ti-added one, AlCoCrFeNiTi0.5, during unidirectional and bi-directional sliding wear processes were investigated. It was shown that the addition of Ti considerably enhanced the HEA against wear under both the sliding conditions mainly due to the increased hardness. The volume loss decreased during bi-directional sliding, which was further decreased as the sliding direction was reversed more frequently. The decreased wear by bi-directional sliding was attributed to the Bauschinger effect in which defect annihilation (i.e., cancellation of dislocations of opposite signs) occurred with reversal of the wearing stress. The Ti addition did not show much influence on the trend of wear variations with the wearing stress reversal except the magnitude of material loss. By performing wear tests with and without air-flow cooling, it was shown that local heating by friction promoted the Bauschinger effect, which could be ascribed to the increase in the dislocation mobility and reversibility at elevated temperatures.
•AlCoCrFeNi high-entropy alloy consists of disordered BCC and ordered BCC-B2 domains.•Adding Ti to AlCoCrFeNi forms honeycomb-shaped interdendrite and the intertwined structure.•The Ti addition enhances the wear resistance of AlCoCrFeNi due to increased hardness and the protective oxide scale on surface.•Bi-directional sliding causes less wear, which is attributed to the Bauschinger effect involving annihilation of dislocations.•Frictional heating facilitates the Bauschinger effect, due to the increases in dislocations' mobility and annihilation.
Despite improvements in the emergency treatment of myocardial infarction (MI), early mortality and morbidity remain high. The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute ...coronary syndromes without ST-segment elevation, but its effects in patients with ST-elevation MI were unclear.
45 852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated clopidogrel 75 mg daily (n=22 961) or matching placebo (n=22 891) in addition to aspirin 162 mg daily. 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 93% of patients completed it. The two prespecified co-primary outcomes were: (1) the composite of death, reinfarction, or stroke; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This trial is registered with
ClinicalTrials.gov, number NCT00222573.
Allocation to clopidogrel produced a highly significant 9% (95% CI 3–14) proportional reduction in death, reinfarction, or stroke (2121 9·2% clopidogrel
vs 2310 10·1% placebo; p=0·002), corresponding to nine (SE 3) fewer events per 1000 patients treated for about 2 weeks. There was also a significant 7% (1–13) proportional reduction in any death (1726 7·5%
vs 1845 8·1%; p=0·03). These effects on death, reinfarction, and stroke seemed consistent across a wide range of patients and independent of other treatments being used. Considering all fatal, transfused, or cerebral bleeds together, no significant excess risk was noted with clopidogrel, either overall (134 0·58%
vs 125 0·55%; p=0·59), or in patients aged older than 70 years or in those given fibrinolytic therapy.
In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events in hospital, and should be considered routinely.
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