Summary
In this study, label-free-based quantitative subcellular proteomics integrated with network analysis highlighted several candidate genes including P4HB, ITGB1, CD36, and ACTN1 that may be ...involved in osteoporosis. All of them are predicted as significant membrane proteins with high confidence and enriched in bone-related biological process. The results were further verified in transcriptomic and genomic levels.
Introduction
Osteoporosis is a metabolic bone disease mainly characterized by low bone mineral density (BMD). As the precursors of osteoclasts, peripheral blood monocytes (PBMs) are supported to be important candidates for identifying genes related to osteoporosis. We performed subcellular proteomics study to identify significant membrane proteins that involved in osteoporosis.
Methods
To investigate the association between monocytes, membrane proteins, and osteoporosis, we performed label-free quantitative subcellular proteomics in 59 male subjects with discordant BMD levels, with 30 high vs. 29 low BMD subjects. Subsequently, we performed integrated gene enrichment analysis, functional annotation, and pathway and network analysis based on multiple bioinformatics tools.
Results
A total of 1070 membrane proteins were identified and quantified. By comparing the proteins’ expression level, we found 36 proteins that were differentially expressed between high and low BMD groups. Protein localization prediction supported the notion that the differentially expressed proteins, P4HB (
p
= 0.0021), CD36 (
p
= 0.0104), ACTN1 (
p
= 0.0381), and ITGB1 (
p
= 0.0385), are significant membrane proteins. Functional annotation and pathway and network analysis highlighted that P4HB, ITGB1, CD36, and ACTN1 are enriched in osteoporosis-related pathways and terms including “ECM-receptor interaction,” “calcium ion binding,” “leukocyte transendothelial migration,” and “reduction of cytosolic calcium levels.” Results from transcriptomic and genomic levels provided additional supporting evidences.
Conclusion
Our study strongly supports the significance of the genes P4HB, ITGB1, CD36, and ACTN1 to the etiology of osteoporosis risk.
A sponge‐like cotton fabric autonomously collects and releases water from fogs triggered by typical day‐and‐night temperature variations. The reversible switching between ...absorbing‐superhydrophilic/releasing‐superhydrophobic states results from structural changes of a temperature‐responsive polymer grafted on the very rough fabric‐surface. This material and concept presents a breakthrough into simple and versatile solutions for collection, uni‐directional flow, and purification of water captured from the atmosphere.
We have studied 4265 giant pulses (GPs) from the millisecond pulsar B1937+21; the largest-ever sample gathered for this pulsar, in observations made with the Large European Array for Pulsars. The ...pulse energy distribution of GPs associated with the interpulse are well-described by a power law, with index α = −3.99 ± 0.04, while those associated with the main pulse are best-described by a broken power law, with the break occurring at ∼7 Jy |$\mu$|s, with power-law indices α_low = −3.48 ± 0.04 and α_high = −2.10 ± 0.09. The modulation indices of the GP emission are measured, which are found to vary by ∼0.5 at pulse phases close to the centre of the GP phase distributions. We find the frequency-resolved structure of GPs to vary significantly, and in a manner that cannot be attributed to the interstellar medium influence on the observed pulses. We examine the distribution of polarization fractions of the GPs and find no correlation between GP emission phase and fractional polarization. We use the GPs to time PSR B1937+21 and although the achievable time of arrival precision of the GPs is approximately a factor of two greater than that of the average pulse profile, there is a negligible difference in the precision of the overall timing solution when using the GPs.
•An inexact fractional energy system planning (IMIF-EP) model is developed.•IMIF-EP generates useful results for a case of sustainable energy management (SEM).•Issues related to sustainability, ...uncertainties and dynamics can be reflected.•A comparative case of economical energy management (EEM) is also considered.•Results of two cases show significant differences between SEM and EEM.
In this study, an inexact mixed-integer fractional energy system planning (IMIF-EP) model is developed for supporting sustainable energy system management under uncertainty. Based on a hybrid of interval-parameter programming (IPP), fractional programming (FP) and mixed integer linear programming (MILP) techniques, IMIF-EP can systematically reflect various complexities in energy management systems. It not only handles imprecise uncertainties and dynamic features associated with power generation expansion planning, but also optimizes the system efficiency represented as output/input ratios. An interactive transform algorithm is proposed to solve the IMIF-EP model. For demonstrating effectiveness of the developed approach, IMIF-EP is applied to support long-term planning for an energy system. The results indicate that interval solutions obtained from IMIF-EP can provide flexible schemes of resource allocations and facility expansions towards sustainable energy management (SEM) under multiple complexities. A comparative economical energy management (EEM) system is also provided. Compared with least-cost models that optimize single criterion, IMIF-EP can better characterize practical energy management problems by optimizing a ratio between criteria of two magnitudes. In application, IMIF-EP is advantageous in balancing conflicting objectives and reflecting complicated relationships among multiple system factors.
ABSTRACT
We present the first large sample of scintillation arcs in millisecond pulsars (MSPs), analysing 12 sources observed with the Large European Array for Pulsars (LEAP), and the Effelsberg ...100-m telescope. We estimate the delays from multipath propagation, measuring significant correlated changes in scattering time-scales over a 10 yr time span. Many sources show compact concentrations of power in the secondary spectrum, which in PSRs J0613−0200 and J1600−3053 can be tracked between observations, and are consistent with compact scattering at fixed angular positions. Other sources such as PSRs J1643−1224 and J0621+1002 show diffuse, asymmetric arcs which are likely related to phase-gradients across the scattering screen. PSR B1937+21 shows at least three distinct screens which dominate at different times and evidence of varying screen axes or multiscreen interactions. We model annual and orbital arc curvature variations in PSR J0613−0200, providing a measurement of the longitude of ascending node, resolving the sense of the orbital inclination, where our best-fit model is of a screen with variable axis of anisotropy over time, corresponding to changes in the scattering of the source. Unmodelled variations of the screen’s axis of anisotropy are likely to be a limiting factor in determining orbital parameters with scintillation, requiring careful consideration of variable screen properties, or independent very long baseline interferometry (VLBI) measurements. Long-term scintillation studies such as this serve as a complementary tool to pulsar timing, to measure a source of correlated noise for pulsar timing arrays, solve pulsar orbits, and to understand the astrophysical origin of scattering screens.
The aim of the present study was to authenticate the involvement of DNA methyltransferases (DNMTs) and methyl-CpG binding domain protein 2 (MBD2) in the process of HBx induced p16(INK4A) promoter ...hypermethylation in HBV-related hepatocellular carcinoma (HCC) and their corresponding noncancerous liver tissues. Eighty-eight fresh tissue specimens of surgically resected HBV-associated HCC and their corresponding noncancerous liver tissues were studied. The methylation status of the p16(INK4A) promoter was determined by methylation-specific polymerase chain reaction (MSP). Reverse transcription and real-time polymerase chain reaction (RT-PCR) showed the expression of DNMTs, MBD2 and HBx. Western blot and immunohistochemistry were used for the protein analysis of HBx, DNMT1, DNMT3A and P16. Tissue HBV-DNA levels were determined by RT-PCR. HBV genotype was examined by nested PCR and restriction fragment length polymorphism (RFLP). In the corresponding noncancerous liver tissues, higher HBx expression was associated with the hypermethylation of the p16(INK4A) promoter. HBx was positively correlated with the DNMT1 and DNMT3A at both the mRNA and protein level. Furthermore, HBx, DNMT1 and DNMT3A protein expression were negatively correlated with p16 protein expression. In HCC tissues, HBx was positively correlated with DNMT1 and DNMT3A at both mRNA and protein level, but HBx expression did not correlate with hypermethylation of the p16(INK4A) promoter or p16 protein expression. The methylation status of the p16(INK4A) promoter did not correlate with clinicopathological characteristics. DNMT1 and DNMT3A may play important roles in the process of HBx inducing hypermethylation of the p16(INK4A) promoter in the early stages of HBV-associated HCC. HBx-DNMTs-p16(INK4A) promoter hypermethylation may constitute a mechanism for tumorigenesis during HBV-associated hepatocarcinogenesis.
Processing Al alloys by combining aging and deformation have attracted considerable interests recently. However, contrary to the well defined precipitation-hardening in Al alloys obtained by ...conventional artificial aging, the strengthening mechanism in these alloys is still poorly understood. In this report, a thermo-mechanical route proceeding by solution treatment, water quenching, natural aging, cold-rolling and post-annealing was implemented to produce an Al–Mg–Si alloy sheet with significant improvement in strength and a comparable ductility to conventional T6 treated alloy. A relatively complete physical metallurgical picture of this Al–Mg–Si sheet alloy processed by deformation and aging was established based on electron microscopy. During post-annealing, the deformed structures underwent a considerable decrease in dislocation density and extensive sub-grains as well as nano-grains formed. At the same time, nano-sized wall-like precipitates that were rather different with those in traditionally aged Al–Mg–Si alloys formed with the mediation of lattice defects. Observing in the longitudinal plane, the sheet possessed a banded microstructure consisted of sub-lamellas with a thickness of about 100–200nm. The hierarchical nanostructures achieved by deformation and aging due to concurrent precipitation and defects annihilation can enhance the capacity of the alloy to accommodate dislocations under tension deformation and thus led to a ductile failure. The combination of strength and ductility in our hierarchically nanostructured Al–Mg–Si alloy was discussed.
This study evaluated the effects of dietary guanidinoacetic acid (GAA) supplementation on growth performance, plasma variables, muscle energy status, glycolytic potential, and meat quality of ...broilers experiencing transport stress during the summer. A total of 320 28-day-old male Arbor Acres broilers were randomly allotted to 3 dietary treatments, including a GAA-free basal control diet (160 birds) and basal diet supplementation with 600 (80 birds) or 1,200 mg/kg (80 birds) GAA for 14 D. On the morning of day 42, after an 8-h fast, the birds fed basal diets were divided into 2 equal groups, and all birds in the 4 groups of 80 birds were transported according to the following protocols: 1) a 0.5-h transport of birds on basal diets (as a lower-stress control group), 2) a 3-h transport of birds on basal diets, and a 3-h transport of birds on basal diets supplemented with either 3) 600 or 4) 1,200 mg/kg GAA. The results revealed that dietary supplementation with GAA at 600 and 1,200 mg/kg for 14 D prior to slaughter did not affect growth performance, carcass traits, and most textural characteristics and chemical composition of the pectoralis major (PM) muscle (P > 0.05). In the GAA-free group, a 3-h transport increased the broiler live weight loss, elevated the plasma corticosterone concentration, decreased the plasma glucose concentration, muscle concentrations of ATP, creatine and energy charge value, increased the muscle AMP concentration and AMP/ATP ratio, and accelerated glycolysis metabolism, which resulted in inferior meat quality (lower pH and higher drip loss, P < 0.05). However, dietary addition of GAA at 1,200 mg/kg increased the mRNA expression of S-adenosyl-l-methionine: N-guanidino-acetate methyltransferase in the liver and creatine transporter in both the liver and PM muscle. It also elevated muscle concentrations of creatine and phosphocreatine (P < 0.05), which helps improve meat quality by ameliorating the 3-h transport-induced muscle energy expenditure and delaying anaerobic glycolysis of broilers.
The purpose of present work is to obtain a further understanding of rail corrugation on tight curved tracks. The stability of a wheelset-track system is studied using the finite element complex ...eigenvalue method. Based on the viewpoint of friction-coupling self-excited vibration causing rail corrugation, an elastic vibration model of the leading wheelset-track system is established. It is assumed that the creep forces at the inner and outer wheels of the leading wheelset are saturated when a vehicle negotiates a tight curved track, so the tangential forces are equal to the normal forces times the dynamic coefficient of friction. The simulation results demonstrate that the saturated creep force can induce self-excited vibration of the wheelset-track system, which is able to cause rail corrugation. The effects of the contact angle and the direction of the saturated creep force on the self-excited vibration of the leading wheelset-track system are studied. Parameter sensitivity analysis shows that the contact angle and the direction of the saturated creep force have significant effects on self-excited vibration of the leading wheelset-track system. Rail corrugation easily occurs when the contact angle is small. The saturated creep force in the lateral direction more easily produces rail corrugation than the saturated creep force in the longitudinal direction of the track does.
The timing of the Jiufotang Formation remains speculative despite recent progress in the study of the Jehol Biota. In this paper we contribute to this topic with 40Ar/39Ar dating on K‐feldspar ...(sanidine and orthoclase) from tuffs interbedded within the fossil‐bearing shales of the Jiufotang Formation, from the upper part of the Jehol Group in Chaoyang, Liaoning, northeastern China. 40Ar/39Ar step heating analyses of K‐feldspar and the SHRIMP U‐Pb zircon data indicate that tuffs at the Shangheshou section erupted at 120.3 ± 0.7 million years ago. This result confirms an Aptian age for the Jiufotang Formation that was mainly based on biostratigraphic evidence. It also places stringent controls on the age of the fossils from the formation, providing a minimum age (120 Ma) for the four‐winged dinosaur, Microraptor, and the seed‐eating bird, Jeholornis.