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In our efforts to improve the efficacy of taxane-based microtubule (MT) stabilizing agents against tumor drug resistance mediated by multiple mechanisms, two clinically relevant factors were focused: i.e., P-glycoprotein and βIII-tubulin overexpression. Based on the structure of C-seco taxoid 1 m (IDN5390) which was believed to more selectively interact with βIII-tubulin than paclitaxel, we prepared a series of C-seco taxoids bearing various 7,9- O -linkages and/or different substituents at C2 and C3′ positions. Some of them exhibited much more potent binding affinity to MTs and cytotoxicity than their C-seco parent compounds in drug resistant cells with both mechanisms. SAR analysis indicated that C2 modifications significantly enhanced MT binding but brought ambiguous influence to cytotoxicity whereas 7,9-linkage and C3′ modifications enhance cytotoxicity more efficiently than improve MT binding. These observations illustrate a better translation of molecular binding effect to cellular activity by C ring closure and C3′ modification than C2 modification in C-seco taxoids. [ABSTRACT FROM AUTHOR]

Oil and gold are considered as the most vigor influencer for any economy. In this research volatility spillover networking among the oil (energy), gold, and Asian leading emerging stock markets are constructed by the coalescence of two approaches BEKK-GARCH and complex networking. The data consists of the daily return of sixteen Asian countries' stock markets, an index of the Asia Pacific, and future prices of oil and gold contracts for the period of 01–01-2010 to 31-05-2020. It covers all the recent shocks of the current decade to study the impact of these crises. The data is further divided into four sub-periods as well for this research. The results of our total period detect that commodities of oil and gold receive more volatility spillover than transfer it to stock indices of Asia Pacific countries. Moreover, it is also observed that, as compared to oil, gold had more strong significant spillover linkages. Among all Asian economies, the Chinese stock markets had more influence on the price movement of oil and gold. Whereas, India had more significant correlations with other neighboring stock indices. The results of this research not only provide the facts about the interconnection of oil, gold, and Asian Pacific countries in the current scenarios but also give very useful directions for future researchers, investors, and hedgers, as well as for policymakers interested in the Asian region. • highlights spillover networking among oil, gold, and Asian stock markets. • applies the coalescence of two approaches BEKK-GARCH and complex networking. • employs the daily returns of sixteen stock markets and future prices. • shows the oil and gold receive more volatility spillover than transfer to stock. • illustrates that compared to oil, gold had more strong spillover linkages. [ABSTRACT FROM AUTHOR]

• Dynamic and static experiments are performed to simulate multi-cycle gas injection and production of the UGS. • Impact of salt deposition caused by water evaporation on petrophysical properties and pore structure are analyzed. • Salt deposition mechanism caused by water evaporation in porous media are presented. • Water evaporation helps UGS to improve gas storage capacity without formation water supplement. During the production process of underground gas storage (UGS) with high-salinity formation water, salt deposition has been observed due to formation water evaporation. This work aims at understanding the effect of salt deposition on petrophysical properties and pore structure. Firstly, dynamic and static experiments are carried out to simulate the multi-cycle gas injection and production of the UGS based on the core plugs, rock debris and water from Wen23 gas field. Secondly, Nuclear magnetic resonance (NMR), scan electron microscope (SEM) and energy dispersive spectrum (EDS) are applied to investigate the change of pore structure and salt-crystal morphology. Results indicate that the core permeability and porosity after water evaporation are averagely increased by 39 % to 68 % and 42 % to 66 % respectively compared with the initial water saturation conditions under different water salinity. Salt crystals in the reservoir are mainly deposited in large pores. The dispersed and aggregated salt crystals are observed and most salt crystals are between 1 μm and 5 μm in size. Thus, formation water evaporation is beneficial to the improvement of reservoir petrophysical properties without formation water supplement. This work provides an effective method to understand the impact of salt deposition caused by formation water evaporation on the petrophysical properties, fluid flow ability, and gas storage capacity of the UGS and CO 2 geological storage. [ABSTRACT FROM AUTHOR]

Although LEDs have been widely studied using optical simulations, there is no optical model considering the effect of micro-roughness surface (MRS) on the optical performance for packaged LEDs. In this work, we employ the finite-difference time-domain method and the direction-sensitive bidirectional scattering distribution function to characterize the optical properties of the MRS upon the n-GaN layer. The MRS is generated by the Weierstrass–Mandelbrot fractal function. Furthermore, thin-film LEDs (TFLEDs), blue TFLED devices, and white TFLED devices considering the MRS are investigated using the ray-tracing (RT) method. The results show that the MRS has different optical properties when the light propagates out and in the n-GaN layer. In turn, the difference in the scattering ability of various MRS causes a significant effect on the optical performance of packaged TFLEDs, including radiant efficacy, luminous efficacy, intensity pattern and spectrum, as well as the correlated color temperature. [ABSTRACT FROM AUTHOR]

In this paper, a classical of virus dynamics model with intracellular delay and humoral immunity is introduced. By using suitable Lyapunov functionals and the Lasalle invariant principle, the global stability of the equilibria is proved. Numerical simulations are presented to illustrate our results. The effect of delay and humoral immunity is also discussed. [ABSTRACT FROM AUTHOR]

In this work, we investigate the compositional, structural, morphological properties of CIGS film obtained from a plasma-assisted Se vapor selenization process (PASVS) coupled with a pre-alloying treatment. For comparison, a thermal-assisted Se vapor selenization process (TASVS) is also tested. A higher annealing temperature is more able to enhance the element interdiffusion of precursor film, which helps reduce the indium loss and also improve the crystallinity of CIGS film. However, the TASVS-based film exhibits an asymmetric CIGS phase with a broad shoulder due to adverse phase separation of CuInSe 2 and CuGaSe 2 . Through the use of the PASVS process, the improved film achieves uniform depth distribution of Ga through the CIGS film, resulting in a pure CIGS phase with moderate Ga concentration at the surface region. Results also indicate that the PASVS process causes more indium losses with the increase of selenization plasma power. From device performance point of view, the PASVS process and higher temperature pre-alloying treatment both are more feasible to yield an enhanced open circuit voltage and efficiency of the device. [ABSTRACT FROM AUTHOR]

Most Silurian-Devonian granites in South China are S- or I-type granites, which are suggested to be petrogenetically related to the Wuyi-Yunkai orogeny. In this paper, we present the detailed LA-ICP-MS zircon U-Pb dating, major and trace element geochemical, and Nd-Hf isotopic data for Xiqin A-type granites in the northeastern Cathaysia Block, SE China. Zircon U-Pb dating results show that the Xiqin granites were emplaced at about 410 Ma, indicating that they were generated at the end of Wuyi-Yunkai orogeny. These granites are high in K 2 O + Na 2 O (6.31–8.79 wt%), high field strength elements (Zr + Nb + Ce + Y = 427–699 ppm), rare earth elements (total REE = 221–361 ppm) as well as high Ga/Al ratios (10,000 Ga/Al = 2.50–3.10), and show characteristics typical of A-type granites. ε Hf (t) values of the Xiqin granites mainly vary from −0.4 to −3.1 and yield Mesoproterozoic T 2DM (Hf) (mainly ranging from 1.29 to 1.45 Ga). The ε Nd (t) values are from −1.23 to −2.11 and T 2DM (Nd) vary from 1.25 to 1.32 Ga. These isotopic data suggest that the Xiqin granites were generated by partial melting of metavolcanic rocks with minor metasedimentary rocks in the lower crust. Our data on the Xiqin granites, coupled with previous studies of Silurian-Devonian magmatism, suggest that the tectonic regime had changed to a strongly post-collisional extension environment in the Wuyi-Yunkai orogen at least since 410 Ma, and that delamination, which accounts for the change in stress from the compression to extension and asthenospheric upwelling during the early Paleozoic, plays a significant role in the generation of Xiqin A-type granites. [ABSTRACT FROM AUTHOR]

Anti-gravity loop shaped heat pipe (AGLSHP) with continuous step-graded sintered wick is useful for enhancing the effective heat transfer in the anti-gravity direction. In this work, a complete steady state model has been presented to investigate in the thermal performance and hydraulic behavior of the AGLSHP. The governing equations for the heat and mass transfer are developed for the loop operation, with specific attention given to the evaporator region. By comparing the numerical simulation with the experimental data, the heat transfer mechanism is revealed. The liquid/vapor velocity and pressure distribution in the evaporator are discussed, and the temperature distribution along the transport line is also analyzed. The numerical results indicate that with the increase of the heat load, the maximum velocity and pressure value of the liquid and vapor increase as expected. The highest temperature position occurs at the outlet of evaporator surface. Providing the capillary pressure for the circulation of working fluid, the wick in the liquid line is paid more attention. Moreover, the longer condensation length is more effective in decreasing the temperature at the outlet of condenser and improving the heat transfer capacity of the AGSLHP. [ABSTRACT FROM AUTHOR]

The propellant sloshing problem is of increasing concern in aerospace engineering. Computational-fluid-dynamics simulations have been carried out to predict three-dimensional large-amplitude liquid sloshing in spherical tanks. Basically an arbitrary Lagrangian-Eulerian method is followed. The main challenges are tracking the motion of the contact line and free surface, defining the nodal velocities on the space curved wall boundary, and maintaining rational computational mesh at the same time. A novel mesh moving strategy is presented to update the mesh and meanwhile to suppress the mesh distortion. The mesh nodes on the free surface and contact line are restricted to move along prescribed orbits, and the nodes on the container wall are moved by an algebraic mesh moving algorithm. The finite element method combined with the characteristic-based split algorithm is adopted. The numerical results are compared to analytical and published experimental results for validation, and good agreement is observed. [ABSTRACT FROM AUTHOR]

We give a brief review on the interacting Dark Matter (iDM) scenario and its effects on cosmology and particle physics. If DM candidates can have strong self-interactions or interactions with other relativistic particles, we can refer them generally as iDM. IDM is an interesting possibility that is motivated both theoretically and observationally. The relativistic particles could belong to Standard Model (SM), such as photons and neutrinos, or be dark radiation (DR) in new physics. The resulting perturbed Boltzmann equations are concisely discussed and illustrations on matter power spectrum are given. [ABSTRACT FROM AUTHOR]

We propose a novel particle physics model in which vector dark matter (VDM) and dark radiation (DR) originate from the same non-Abelian dark sector. We show an illustrating example where dark S U ( 3 ) is spontaneously broken into S U ( 2 ) subgroup by the nonzero vacuum expectation value (VEV) of a complex scalar in fundamental representation of S U ( 3 ) . The massless gauge bosons associated with the residual unbroken S U ( 2 ) constitute DR and help to relieve the tension in Hubble constant measurements between Planck and Hubble Space Telescope. In the meantime, massive dark gauge bosons associated with the broken generators are VDM candidates. Intrinsically, this non-Abelian VDM can interact with non-Abelian DR in the cosmic background, which results in a suppressed matter power spectrum and leads to a smaller σ 8 for structure formation. [ABSTRACT FROM AUTHOR]

The Nanping pegmatite deposit is a large Ta-Nb-Sn deposit in the northeastern Cathaysia Block, SE China. Columbite-group minerals from zone I in the Nanping No. 31 pegmatite vein belong to columbite-(Fe). The compositions and texture features of zircon grains from the same zone identify their magmatic origin. Columbite-(Fe) U-Pb age coincides well with the U-Pb age of zircon, and these age data constrain the absolute formation timing of this pegmatite vein to approximately 387 Ma. Zircon εHf(t) values from the Nanping No. 31 pegmatite range from −13.81 to −11.60 with the T DM2 model ages ranging from 2107 to 2246 Ma, implying that the Nanping pegmatite-forming melts are derived from Paleoproterozoic metasedimentary rocks. The differences in emplacement age and Hf isotopic features preclude the surrounding granites from being the parental granite of the pegmatite vein. [ABSTRACT FROM AUTHOR]

In this work, we investigate the material growth of the electrodeposited Cu/In/Ga stacked layers selenized by a plasma-assisted Se vapor selenization (PASVS) process at various substrate heating temperatures. For comparison, a merely thermal-assisted Se vapor selenization (TASVS) process is also tested. The PASVS process can help enhance the decomposition of Cu-In-Ga mixed phase and also the formation of Cu-Se and In-Se binary phases when the sample is selenized at 150 °C. However, the use of PASVS process aggravates the element indium loss at the same temperature. Results also indicate that the PASVS process helps to activate the early formation of Ga-Se phase during selenization at 250 °C. The PASVS process generates a porous surface structure with certain CuGaSe 2 phase near the surface region at 350 °C. With the increase of selenization temperature, the film selenized by the PASVS process is prone to a grain structure, while it is a polygonal structure in the case of TASVS. The PASVS process is more able to yield a pure CIGS phase with moderate Ga incorporation at a temperature of 550 °C. [ABSTRACT FROM AUTHOR]

Sulindac is a nonsteroidal anti-inflammatory drug, which is clinically used for the ailments of various inflammations. This study investigated the allele frequencies of FMO3 E158K and E308G and evaluated the influences of these two genetic polymorphisms on the pharmacokinetics of sulindac and its metabolites in Chinese healthy male volunteers. Eight FMO3 wild-type (FMO3 HHDD) subjects and seven FMO3 homozygotes E158K and E308G mutant (FMO3 hhdd) subjects were recruited from 247 healthy male volunteers genotyped by PCR-RFLP method. The plasma concentrations of sulindac, sulindac sulfide, and sulindac sulfone were determined by UPLC, while the pharmacokinetic parameters of the two different FMO3 genotypes were compared with each other. The frequencies of FMO3 E158K and E308G were 20.3% and 20.1%, respectively, which were in line with Hardy-Weinberg equilibrium (D′ = 0.977, r2 = 0.944). The mean values of Cmax, AUC0–24, and AUC0–∞ of sulindac were significantly higher in FMO3 hhdd group than those of FMO3 HHDD group (P<0.05), while the pharmacokinetic parameters except Tmax of sulindac sulfide and sulindac sulfone showed no statistical difference between the two groups. The two FMO3 mutants were in close linkage disequilibrium and might play an important role in the pharmacokinetics of sulindac in Chinese healthy male volunteers. [ABSTRACT FROM AUTHOR]

An unexpected ring-contraction from benzo[b]pyrazino[1,2-d][1,4]thiazine-1,4-diones ( 6 ) to benzo[4,5]thiazolo[3,2-a]pyrazine-1,4-diones ( 7 ) has been developed. The preliminary mechanistic studies showed the transformation contained two independent steps: the first step is the formation of a Michael adduct upon the addition of the protic solvent, in the presence of base, to the C-2-C-3 double bond of compound 6 , and the second step is a ring-contraction induced by oxygen via the migration of sulfur atom from C-2 to C-3 position. And its scope is also studied. [ABSTRACT FROM AUTHOR]

Although multichip light-emitting diode (LED) modules are becoming popular in high-power lighting applications, better light extraction efficiency is always desirable in the industry. In this paper, V-grooves fabricated by the low-cost dicing process have been utilized on the top face of the multichip LED module to enhance the output power. An analytical model including the consideration of surface has been established by using a fractal theory. The combined finite difference time domain and ray tracing method has been used to simulate the light extraction enhancement considering the surface roughness scattering effects. The results show 12% enhancements in the experiments when the measured surface roughness of the V-groove has RMS roughness of 0.25~\mu \textm , which is in good agreement with the simulation result of 13.7%. The multichip LED models have been applied in indoor downlight systems and it is found that the luminous efficiency has been enhanced by 9.6% under a current of 350 mA (5.8 W) when compared with multichip LED modules without V-grooves. [ABSTRACT FROM AUTHOR]

In this work, the influences of surface-modified Mo back contacts on the morphology of Cu layers and quality of Cu(In,Ga)Se 2 (CIGS) thin films are investigated. One method of sputtering treatment to modify the Mo surface effectively improved the adhesion between the Cu and Mo layers. However, Cu layers electrodeposited on the various modified Mo surfaces created different morphological structures, which impacted the CIGS thin films. First, an alloyed Cu-In-Ga film based on the Cu layer of smooth structure would experience homogeneous element diffusion compared to the Cu layer of the rugged structure. Second, the CIGS film based on the smooth Cu-covered substrate exhibited a uniform surface profile with regular crystals, while the CIGS film based on a rugged one exhibited an uneven surface profile with several irregular crystals. Additionally, the smooth Cu-covered substrate reduced the adverse phase separation of CuInSe 2 and CuGaSe 2 more effectively. [ABSTRACT FROM AUTHOR]

• Silica coatings were enveloped on nylon mesh by the sol-gel method and endowed it with superhydrophilicity. • Superhydrophilic nylon mesh wicks (SNMWs) yielded good capillary performances. • SNMWs with the maximum volumetric flow rate of 1.19 mm3/s were promising wicks for flexible heat pipes. • SNMWs maintained good capillary performances even after 10,000 bending cycles. The rapid development of flexible electronic devices brings the demand for flexible thermal management systems. Nylon mesh with excellent flexibility is ideal for flexible thermal management systems, especially acting as wicks in flexible heat pipes (FHPs). In this study, novel superhydrophilic nylon mesh wicks (SNMWs) with enhanced capillary performance are fabricated by the sol-gel method. Silica coating is formed on the surface of nylon mesh and endowed the mesh with superhydrophilicity. Capillary rise tests and cyclic bending reliability tests are conducted to evaluate the capillary performance and bending fatigue resistance of the SNMWs. The results show that the SNMWs yield excellent capillary performance, the maximum equilibrated wicking height of the SNMWs reaches 87.38 mm and the largest wicking coefficient is 5.91 mm/s0.5. The average volumetric flow rate proportional to wicking velocity and wetted volume is taken as a comprehensive index to evaluate the feasibility of applying SNMWs in FHPs and the maximum average volumetric flow rate reaches 1.19 mm3/s. Simultaneously, the SNMWs maintain good capillary performance even after 10,000 bending cycles, which means strong bending fatigue resistance. This study provides a high-performance, high-reliability, and cost-effective flexible wick for enhancing the thermal performance of FHPs. [ABSTRACT FROM AUTHOR]

[Display omitted] The Carboniferous is the most widely distributed system in the pre-Mesozoic strata of Xinjiang, Northwest China, and they are exposed in structurally independent units within various tectonic settings across the southwest Central Asian Orogenic Belt and Tarim Craton in Northwest China. According to the lithofacies associations and biotic assemblages, the Carboniferous successions of Xinjiang can be divided into 18 stratal regions, and each of these stratal regions may be further separated into several subregions in terms of lithology, biota, and geochronologic data. The depositional succession of each region is described on the basis of the key section. The marine fossils such as foraminifers (fusulinids), brachiopods, corals, and conodonts, as well as nonmarine fossils such as plants and pollens are reviewed in this study. Combined with the geochronologic data from the volcanic rocks and ash layers, a refined scheme of the Carboniferous successions in different regions across Xinjiang, Northwest China is obtained. The detailed and newly established stratigraphic framework of the Carboniferous strata could be very helpful for the regional and global stratigraphic correlations. It can also offer a new and reliable chronostratigraphic foundation for the comprehensive understanding of the tectonic evolution and petroleum exploration in Central Asia. [ABSTRACT FROM AUTHOR]

Chronic pain is a debilitating and rather common health problem. The present shortage in analgesic drugs with a favorable spectrum but without remarkable side effects furthered the search for alternative therapeutic manipulations. Increasing evidence from both basic and clinical research on acupuncture, a main alternative therapy of traditional Chinese medicine, suggests that chronic pain is sensitive to acupuncture procedures. Clarification of the underlying mechanisms is a challenge of great theoretical and practical significance. The seminal hypothesis of Geoffrey Burnstock and the astounding findings of Maiken Nedergaard on the involvement of purinergic signaling in the beneficial effects of acupuncture fertilized the field and led to an intensification of research on acupurines. In this review, we will summarize the state-of-the-art situation and try to forecast how the field is likely to develop in the future. [ABSTRACT FROM AUTHOR]

Objective The present study aims to elucidate the role of Rho-mediated ROCK-Semaphorin3A signaling pathway in the pathogenesis of Parkinson's disease (PD) in a mouse model. Methods One-hundred twelve eight-week male C57BL/6 mice were selected. The mouse model of PD was constructed by intraperitoneal injection of MPTP. All mice were divided into four groups (28 mice in each group): Blank group, Model group, Rho knockout (Rho +/−) group and ROCK knockout (ROCK +/−) group. Changes of behavior of the mice were studied through automatic moving test and rotarod test. Immunohistochemistry (IHC) was used to detect the expressions of TH, CD11b and GFAP. High performance liquid chromatograph (HPLC) was performed for detection of dopamine and its metabolic product. The mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Results Rho and ROCK knockout improved the damage caused by MPTP on the behavior of mice and protected dopaminergic neurons from injury, along with the increases of dopamine and its metabolic product. The mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were increased in PD mice in the Model group compared with those in the Blank group. Compared to the Model group, the mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were reduced in the Rho +/− and ROCK +/− groups. Conclusion These findings indicate that Rho and ROCK knockout may improve the behavior of mice and prevent MPTP-induced dopaminergic neurons damage by regulating Sema3A, PlexinA and NRP-1 in a mouse model of PD. [ABSTRACT FROM AUTHOR]

Motivated by the tensions in the Hubble constant H 0 and the structure growth σ 8 between Planck results and other low redshift measurements, we discuss some cosmological effects of a dark sector model in which dark matter (DM) interacts with fermionic dark radiation (DR) through a light gauge boson (dark photon). Such kind of models are very generic in particle physics with a dark sector with dark gauge symmetries. The effective number of neutrinos is increased by δ N eff ∼ 0.5 due to light dark photon and fermionic DR, thereby resolving the conflicts in H 0 . The elastic scattering between DM and DR induces suppression for DM's density perturbation, but without acoustic oscillations. For weakly-interacting DM around 100 GeV , the new gauge coupling should be ∼ 10 − 4 to have sizable effect on matter power spectrum in order to relax the tension in σ 8 . [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects. In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression. [ABSTRACT FROM AUTHOR]

Normal leaf margin development is important for leaf morphogenesis and contributes to diverse leaf shapes in higher plants. We here show the crucial roles of an atypical type II phosphatidylinositol 4-kinase, PI4Kγ5, in Arabidopsis leaf margin development. PI4Kγ5 presents a dynamics expression pattern along with leaf development and a T-DNA mutant lacking PI4Kγ5, pi4kγ5–1, presents serrated leaves, which is resulted from the accelerated cell division and increased auxin concentration at serration tips. Studies revealed that PI4Kγ5 interacts with and phosphorylates a membrane-bound NAC transcription factor, ANAC078. Previous studies demonstrated that membrane-bound transcription factors regulate gene transcription by undergoing proteolytic process to translocate into nucleus, and ANAC078 undergoes proteolysis by cleaving off the transmembrane region and carboxyl terminal. Western blot analysis indeed showed that ANAC078 deleting of carboxyl terminal is significantly reduced in pi4kγ5–1, indicating that PI4Kγ5 is important for the cleavage of ANAC078. This is consistent with the subcellular localization observation showing that fluorescence by GFP-ANAC078 is detected at plasma membrane but not nucleus in pi4kγ5–1 mutant and that expression of ANAC078 deleting of carboxyl terminal, driven by PI4Kγ5 promoter, could rescue the leaf serration defects of pi4kγ5–1. Further analysis showed that ANAC078 suppresses the auxin synthesis by directly binding and regulating the expression of auxin synthesis-related genes. These results indicate that PI4Kγ5 interacts with ANAC078 to negatively regulate auxin synthesis and hence influences cell proliferation and leaf development, providing informative clues for the regulation of in situ auxin synthesis and cell division, as well as the cleavage and functional mechanism of membrane-bound transcription factors. [ABSTRACT FROM AUTHOR]

In the past decades, side arm modified chiral bisoxazoline ligands (SaBOX) have attracted considerable attention in the asymmetric catalysis field, beyond traditional Lewis acid catalysis. A number of different types of enantioselective reactions have been developed in high yield with excellent enantioselectivity by employing SaBOX as chiral ligands. In this review, recent development and prospect on the application of SaBOX ligand in organometallic catalytic asymmetric reactions are discussed. This review does not focus on Lewis acid catalyzed reactions. [Display omitted] [ABSTRACT FROM AUTHOR]

An I 2 -DMSO promoted remote difunctionalization reaction of anthranils is reported. This cross-coupling process realizes simultaneous N1- and C5-dicarbonylation of anthranils with a highly atom- and step-economy. The mechanism involves the copper-catalyzed N–O bond cleavage of anthranils and the construction of a new C–C and a C–N bond respectively. The transformation proceeds smoothly in gram-scale, and the product of the reaction could be transformed into other valuable heterocyclic structures. [Display omitted] [ABSTRACT FROM AUTHOR]

Pyroptosis, characterized by activation of the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and its downstream effector inflammatory factors, has been shown to play a crucial role in atherosclerosis development. Long noncoding RNAs (lncRNAs) are involved in the progression of pyroptosis. However, the role and mechanism of the novel lncRNA gastric adenocarcinoma associated, positive CD44 regulator (Gaplinc), in endothelial cell pyroptosis during atherosclerosis development remain unexplored. Bioinformatics was performed to evaluate dysregulated lncRNAs in atherosclerotic mice fed a high-fat diet. The effect of Gaplinc on atherosclerosis progression in vivo was assessed via Oil Red O staining and fluorescence in situ hybridization. Its function in oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis of endothelial cells was determined through ectopic expression. Additionally, RNA pull-down and immunoprecipitation (RIP) assays were performed to determine Gaplinc and transcription factor SP1 interactions. Then the pyroptosis pathway proteins were analyzed via immunofluorescence and western blotting. We found that lncRNA Gaplinc was highly expressed in ox-LDL-induced endothelial cells as well as in the plaque and plasma of high-fat diet-treated ApoE−/− mice. Gaplinc silencing significantly inhibited endothelial cell pyroptosis and atherosclerotic plaque formation. Mechanistically, Gaplinc could interact with SP1 to bind to the NLRP3 promoter and upregulate the target gene expression of NLRP3, facilitating endothelial cell pyroptosis and atherosclerotic plaque enlargement in high- fat diet-fed mice. In conclusion, our results revealed the underlying mechanism of the lncRNA Gaplinc /SP1/NLRP3 axis in endothelial cell pyroptosis, which may provide new potential targets for the treatment of atherosclerosis. • Gaplinc is upregulated in human plasma and mice with atherosclerosis. • Gaplinc promotes the pyroptosis of vascular endothelial cells, exacerbating the progression of atherosclerosis. • The Gaplinc /SP1/NLRP3 axis plays key role in endothelial cell pyroptosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: The incidence rate of degenerative spinal deformity (DSD) has gradually increased in the elderly. Currently, the relationship between the functional status of trunk muscle and the spinal-pelvic parameters of DSD patients remains unclear. OBJECTIVE: This paper aims to explore the relationship between the two factors and provide new clues for exploring the mechanism of the occurrence and development of DSD. METHODS: A total of 41 DSD patients treated in our hospital (DSD group) and 35 healthy volunteers (control group) were selected. Muscle strength was evaluated using an IsoMed-2000 isokinetic dynamometer, and the trunk flexor and extensor peak torque (PT) of subjects was measured at a low, medium, and high angular velocity of 30 ∘ /s, 60 ∘ /s, and 120 ∘ /s, respectively. Hand grip strength (HGS) was assessed using an electronic grip dynamometer and Surgimap software was used to measure the spinal-pelvic parameters, including the sagittal vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence rate (PI), and PI-LL, and the relationship between trunk muscle function and various parameters was analyzed. RESULTS: Under the three angular velocities, the flexor and extensor PT values in the DSD group were lower than those in the control group, and only the extensor PT showed a statistically significant difference (P < 0.05). There was no significant difference in HGS between the two groups (P > 0.05). In the DSD group, the extensor PT at 30 ∘ /s was significantly negatively correlated with SVA (P < 0.05). At 60 ∘ /s and 120 ∘ /s, the extensor PT was significantly negatively correlated with SVA and PT (P < 0.05). CONCLUSION: Trunk extensor strength is significantly lower in DSD patients than in normal controls. The decline in trunk extensor strength in DSD patients is a type of local muscle dysfunction more closely related to the deformity, which is likely involved in the compensatory mechanism of DSD and may reflect the overall imbalance of the trunk. [ABSTRACT FROM AUTHOR]

Etrasimod (APD334) is an investigational, once‐daily, oral, selective sphingosine 1‐phosphate receptor 1,4,5 modulator (S1P1,4,5) in development for treatment of various immune‐mediated inflammatory disorders. The disposition and mass balance of a single 2‐mg [14C]etrasimod dose were evaluated in 8 healthy males. An in vitro study was also conducted to identify etrasimod's oxidative metabolizing enzymes. Peak concentrations of etrasimod and total radioactivity in plasma and whole blood were typically reached 4–7 hours postdose. Etrasimod constituted 49.3% of total radioactivity plasma exposure, with multiple minor/trace metabolites making up the remainder. Etrasimod was slowly cleared mainly via biotransformation, predominantly by oxidative metabolism, with unchanged etrasimod recovered in feces accounting for only 11.2% of the dose and none in urine. The mean apparent terminal half‐lives of etrasimod and total radioactivity in plasma were 37.8 and 89.0 hours, respectively. Mean cumulative recovery of radioactivity in excreta over 336 hours was 86.9% of the dose, mostly in feces. The prevalent metabolites eliminated in feces were M3 (hydroxy‐etrasimod) and M36 (oxy‐etrasimod sulfate), accounting for 22.1% and 18.9% of the dose, respectively. From in vitro reaction phenotyping, the predominant enzymes involved in the oxidation of etrasimod were CYP2C8, CYP2C9, and CYP3A4, with minor contributions from CYP2C19 and CYP2J2. [ABSTRACT FROM AUTHOR]

As a base structural unit, 1,4-dihydropyridines (DHPs) containing benzosultams widely exist in bioactive molecules and drugs. These compounds are generally synthesized by organic-base catalyzed methods that require specifically functionalized substrates or harsh conditions. Herein, a [3+3] annulation reaction of cyclic N-sulfonyl ketimine with various substituted isatylidene malononitrile or benzylidene malononitriles was documented. This biocatalytic strategy provides a green route for synthesis of 1,4-DHPs containing benzosultams, with good functional groups compatibility and yields. Under optimal conditions, lipase leads to the formation of 1,4-DHPs containing benzosultams in up to 87% yield. [ABSTRACT FROM AUTHOR]

• Weak horizontal and vertical transmission channels are defined. • A power flow adjustment strategy that can fasten the adjustment processing is formulated. • The prior probability of action is given to improve learning efficiency. • A deep reinforcement learning model suitable for power flow adjustment is established. To solve the problem of human resources and time consumption caused by unsolvable power flow of weak power grid, an adjustment method for unsolvable power flow based on weak transmission channels and deep reinforcement learning (DRL) is proposed. Weak horizontal and vertical channels are defined, and their relationship with unsolvable power flow is demonstrated. Then, based on the idea of reducing the load level first and then gradually recovering it, actionable device and action margin are determined based on transmission channel positioning, adjustment sensitivity and solvability degree, so as to form a power flow adjustment strategy. Next, the Markov decision-making process of power flow adjustment is constructed, the prior probability of action is given by adjustment sensitivity of the actionable device, and the action is mapped to the adjustment amounts of generators and capacitors/reactors. Based on soft actor-critic, a DRL model suitable for power flow adjustment is established. Finally, the simulation results show that the proposed method performs well both in the New England 39-bus standard system and an actual power grid of China. Compared with the results obtained by other methods, the superiority of the proposed method is verified. [ABSTRACT FROM AUTHOR]

In the practical application of nanofiltration (NF) membrane, regular chemical cleaning is necessary to eliminate the membrane fouling and ensure the normal operation of the system. Generally, the commercial NF membranes can be divided into MPD-TMC membranes and PIP-TMC membranes of which the permeability and pH resistance cannot be balanced. In this work, the ultra-low concentration monomers of MPD and TMC were used to fabricate the dense polyamide layer of NF membrane through a conventional interfacial polymerization reaction. The newly prepared membrane exhibited a smooth surface with very low roughness. Besides, the pore size distribution and desalination performance including water permeability and salt rejection of our membrane were comparable to the lab-made and commercial PIP-TMC membranes. The membrane was also confirmed to have an excellent separation efficiency to SO 4 2−/Cl− anions and good resistance to extreme pH conditions. Overall, this study presents a new insight for the preparation of high-performance NF membrane with good chemical stability. [Display omitted] • NF membrane fabricated by interfacial polymerization of low concentration MPD and TMC. • Separation degree changed from RO to NF with the decreasing monomer concentration. • MPD-based NF membrane presented high permeability and good selectivity to Cl−/SO 4 2-. • Higher acid and alkali resistance than a lab-made PIP-based NF membrane. [ABSTRACT FROM AUTHOR]

To bridge the performance gap between network and storage, performance tuning of file systems according to different workloads has become an important work on the Internet of Things (IoT). However, existing methods on file system tuning mainly focused on tailoring the file system kernel codes, or cannot scope to high dimensional parameters and dynamically changing workloads. In this paper, we propose an automatic I/O performance tuning system FSbrain that recommends reasonable and performance-efficient configurations for file systems by using machine learning. It makes the configuration recommendations based on current workloads within an acceptable time, however, without any manual interventions or kernel code modifications. In specific, FSbrain mainly consists of two phases which are model training and configuration tuning. Since tuning attempts will cause frequent remounting on target file systems, we deploy FSbrain and conduct the tuning sessions on an experimental node called "shadow server". We evaluate FSbrain on three representative file systems (namely, Ext4, F2FS, and PMFS). The experimental results show that the configuration recommended by FSbrain can improve the I/O performance by up to 1.28 × averagely than the default configuration. Besides, FSbrain reduces the overall tuning time by 90% compared to manual tuning. [ABSTRACT FROM AUTHOR]

This paper presents the numerical investigation and optimization of the operating parameters of the in situ generated CO2 Huff-n-Puff method with compound surfactant on the performance of enhanced oil recovery. First, we conducted experiments of in situ generated CO2 and surfactant flooding. Next, we constructed a single-well radial 3D numerical model using a thermal recovery chemical flooding simulator to simulate the process of CO2 Huff-n-Puff. The activation energy and reaction enthalpy were calculated based on the reaction kinetics and thermodynamic models. The interpolation parameters were determined through history matching a series of surfactant core flooding results with the simulation model. The effect of compound surfactant on the Huff-n-Puff CO2 process was demonstrated via a series of sensitivity studies to quantify the effects of a number of operation parameters including the injection volume and mole concentration of the reagent, the injection rate, the well shut-in time, and the oil withdrawal rate. Based on the daily production rate during the period of Huff-n-Puff, a desirable agreement was shown between the field applications and simulated results. [ABSTRACT FROM AUTHOR]

In this study, we investigate a scenario that dark matter (DM) has only gravitational interaction. In the framework of effective field theory of gravity, we find that DM is still stable at tree level even if there is no symmetry to protect its longevity, but could decay into standard model particles due to gravitational loop corrections. The radiative corrections can lead to both higher- and lower-dimensional effective operators. We also first explore how DM can be produced in the early universe. Through gravitational interaction at high temperature, DM is then found to have mass around TeV ≲ m X ≲ 10 11 GeV to get the right relic abundance. When DM decays, it mostly decays into gravitons, which could be tested by current and future CMB experiments. We also estimate the resulting fluxes for cosmic rays, gamma-ray and neutrino. [ABSTRACT FROM AUTHOR]

Summary Objective Invasive pulmonary aspergillosis (IPA) and Pneumocystis pneumonia (PCP) are two types of pulmonary fungal infection that are not easy to differentiate. The purpose of this study was to investigate the role of inflammatory cytokines in the differential diagnosis of IPA and PCP. Methods A total of 227 pediatric oncology patients diagnosed with acute pneumonia were enrolled. They were divided into three groups: IPA, PCP, and ‘others’. The cytokine levels in these groups were compared, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, IL-4, and IL-2. Results Of the six cytokines, only IL-6 and IFN-γ levels were elevated in patients with acute pneumonia. IL-6 was comparable between patients with IPA and PCP (52.0 pg/ml vs. 25.8 pg/ml, p = 0.092), while IFN-γ was much higher in patients with PCP (19.9 pg/ml vs. 8.9 pg/ml, p = 0.001). The accuracy of IL-6 and the ratio of IL-6/IFN-γ in predicting IPA were 69.0% and 72.0%, respectively, while the accuracy of IFN-γ to predict PCP was 67.2%. IL-6 >140 pg/ml and IL-6/IFN-γ >9.0 presented specificities of 90% in predicting IPA, while IFN-γ >40 pg/ml presented specificity of 90% in predicting PCP. Conclusions IL-6 is predominantly elevated in IPA, while IFN-γ is significantly increased in PCP. These are helpful tools for the differential diagnosis of IPA and PCP. [ABSTRACT FROM AUTHOR]

An interconnected microchannel net (IMN) was developed using microfabrication technique for flow boiling heat transfer enhancement. The flow boiling experiments were conducted using deionized water as the working fluid with variation in the heat flux and mass flux ( G = 100, 180 and 250 kg m −2 s −1 ) and a comparison with conventional rectangular microchannels (RMC) was investigated. The results indicated that the IMN yielded higher heat transfer coefficient and lower pressure drop at G = 100 and 180 kg m −2 s −1 than that of the RMC. However, a reverse trend was observed at G = 250 kg m −2 s −1 . A transition of boiling mechanism from the nucleate boiling region to the convective boiling region occurred with increase of vapor quality for both samples at G = 180 and 250 kg m −2 s −1 accompanied with the flow pattern changing from the bubbly flow to annular flow, which didn’t occur at G = 100 kg m −2 s −1 . Further study revealed that the advantage of mitigating the two-phase flow instability for the IMN diminished as mass flux increased to G = 250 kg m −2 s −1 . Such phenomenon may account for the lower heat transfer rate and higher pressure drop for the IMN than that for the RMC at high mass flux. [ABSTRACT FROM AUTHOR]

We investigate possible cosmological effects of interacting scalar radiation and dark matter. After its decoupling, scalar radiation can stream freely as neutrinos or self-interact strongly as perfect fluid, highly depending on the magnitude of its self-couplings. We obtain the general and novel structure for self-scattering rate and compare it with the expansion rate of our Universe. If its trilinear/cubic coupling is non-zero, scalar radiation can be eventually treated as perfect fluid. Possible effects on CMB are also discussed. When this scalar also mediates interaction among dark matter particles, the linear matter power spectrum for large scale structure can be modified differently from other models. We propose to use Debye shielding to avoid the singularity appearing in the scattering between scalar radiation and dark matter. [ABSTRACT FROM AUTHOR]

Donor-acceptor (DA) cyclopropanes are particularly useful synthetic building blocks, which have been widely applied in the total synthesis of natural products and important chiral molecules in organic synthesis. The asymmetric ring-opening reactions of racemic DA cyclopropanes and cyclobutanes, for example, aryl-substituted 1,1-cyclopropane diesters and aryl-substituted 1,1-cyclobutane diesters, with nucleophiles provides versatile access to optically active γ- and δ-functionalized carbon skeletons, as well as the kinetic resolution of racemic DA cyclopropanes, which are useful chiral skeletons in organic synthesis. Recently, we have developed a series of highly enantioselective ring-opening and annulation reactions of DA cyclopropanes and cyclobutanes with various nucleophiles, such as amines, alcohols, nitrones, azomethine imines, enol silyl ethers, and indoles, by employing nickel and copper catalysts with TOX and SaBOX as ligands. The reactions worked smoothly with excellent diastereoselectivities and enantioselectivities (up to >99/1 dr and up to 99 % ee) over broad substrate scopes. [ABSTRACT FROM AUTHOR]

Novel high-flux thin film composite (TFC) nanofiltration (NF) membranes were fabricated by the sodium hypochlorite (NaClO) pre-oxidation of the mixed diamine monomers of piperazine (PIP) and 2,2′-bis(1-hydroxyl-1-trifluoromethyl-2,2,2-triflutoethyl)-4,4′-methylenedianiline (BHTTM) in the aqueous phase solution, and via interfacial polymerization (IP) with trimesoyl chloride (TMC) on the polysulfone (PSF) ultrafiltration (UF) membrane. The chemical change of the pre-oxidation aqueous phase solution was characterized by LC-MS. By optimizing the NaClO and NaOH content in the aqueous phase solution, the pure water flux was improved greatly and the salt rejection kept on a high level (>90%). The properties of NF membranes were characterized by XPS, SEM, AFM and contact angle. Through the NaClO pre-oxidation of the mixed diamine monomers of PIP and BHTTM in the aqueous phase solution, the active layer of NF membrane became thinner and the pore size of NF membrane was enlarged. Besides, after oxidation treatment by 3000 ppm active chlorine solution for 1 h, the NF membrane exhibited pure water flux (PWF) with 161 (LMH) and Na 2 SO 4 rejection of 92.1% under 0.6 MPa. The molecular weight cut-off (MWCO) of the NF membrane was greater than 500, which was calculated from the carbohydrates rejection. The good performance and the satisfactory stability of the novel high-flux NF membrane demonstrated its good potential in the practical application. [ABSTRACT FROM AUTHOR]

Porous interconnected microchannel nets were developed using microfabrication techniques for pool boiling heat transfer enhancement with both subcooled and saturated deionized water as working fluid at atmospheric pressure. The effects of varying the powder morphology, powder size and channel width on the pool boiling heat transfer were studied. Experimental results showed that these structures exhibited a lower wall-superheat at the onset of nucleate boiling (ONB) and a higher nucleate boiling heat transfer coefficient (HTC) than the solid interconnected microchannel net. The sample of medium size powders (50–75 μm) yielded a maximum heat transfer coefficient while the powder morphology has little influence on the boiling heat transfer performance. At the low heat flux, the HTC was found to increase with decrease of the channel width while at the high heat flux, a reverse trend was observed. High speed visualization (2000 frames/s) revealed that the bubble growth was governed by the heat transfer regime at q a = 225 kW/m 2 and no waiting phase was observed due to the overlap of the next bubble expulsion in the same vertical channel. [ABSTRACT FROM AUTHOR]

Using Polysulfone (PSF) ultrafiltration (UF) membrane as porous support, a chlorine-tolerant nanofiltration (NF) membrane was prepared by interfacial polymerization of piperazine (PIP) and 2,2'-bis(1-hydroxyl-1-trifluoromethyl-2,2,2-triflutoethyl)-4,4'-methylenedianiline (BHTTM) mixture with trimesoyl chloride (TMC). The XPS, SEM, AFM and contact angle methods were employed to characterize the physicochemical properties and morphology of the prepared NF membranes. The effects of preparation conditions such as reaction time, monomers mixing ratio and oxidation treatment on NF membrane performance were investigated. The salt rejection of the NF membrane met the order of Na 2 SO 4 >MgSO 4 >NaCl, indicating the membrane possessed a negative surface charge. The results showed the NF membrane prepared under the optimum conditions exhibited pure water flux (PWF) with 79.1 (L/m 2 h) and Na 2 SO 4 rejection of 99.5% under 0.6 MPa. The optimized post oxidation condition was treated by 3000 ppm NaClO solution for 1 h. The best NF membrane had a molecular weight cut-off (MWCO) less than 300 Da, corresponding to the pore size of 1 nm, which was calculated from the rejection of carbohydrates. The robustness of the NF membrane was proven by showing satisfactory stability in the long time running. [ABSTRACT FROM AUTHOR]

The recently observed IceCube PeV events could be due to heavy dark matter (DM) decay. In this paper, we propose a simple DM model with extra U ( 1 ) X gauge symmetry and bridge it with standard model particles through heavy right-handed neutrino. The Dirac fermion DM χ with mass ∼ 5 PeV can dominantly decay into a dark Higgs ( ϕ ), the SM Higgs ( h ) and a neutrino ( ν ). If the lifetime of χ is ∼ O ( 10 28 ) s , the resulting neutrino flux can fit data consistently. The neutrino flux from χ → ϕ h ν in our model is softer than the one predicted from χ → ν h , for example. We also discuss a possible mechanism to produce DM with the right relic abundance. [ABSTRACT FROM AUTHOR]

It is generally expected that adding light sterile species would increase the effective number of neutrinos, N eff . In this paper we discuss a scenario that N eff can actually decrease due to the neutrino oscillation effect if sterile neutrinos have self-interactions. We specifically focus on the eV mass range, as suggested by the neutrino anomalies. With large self-interactions, sterile neutrinos are not fully thermalized in the early Universe because of the suppressed effective mixing angle or matter effect. As the Universe cools down, flavor equilibrium between active and sterile species can be reached after big bang nucleosynthesis (BBN) epoch, but leading to a decrease of N eff . In such a scenario, we also show that the conflict with cosmological mass bounds on the additional sterile neutrinos can be relaxed further when more light species are introduced. To be consistent with the latest Planck results, at least 3 sterile species are needed. [ABSTRACT FROM AUTHOR]

CXCR2 plays a key role in protecting the integrity of the endothelium. Emerging evidence has demonstrated that the long ncRNAs (lncRNA) Human metastasis associated lung adenocarcinoma transcript 1 (MALAT1) participates in the regulation of the pathophysiological processes. However, whether there is crosstalk between CXCR2 and MALAT1 remains unknown. In this study, we demonstrated that MALAT1 was upregulated in patients with unstable angina. MALAT1 silencing significantly downregulated the expression of the miR-22-3p target gene CXCR2 via reversing the effect of the miR-22-3p, resulting in the aggravation of Oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury; this process was associated with the AKT pathway. Thus, MALAT1 protects the endothelium from ox-LDL-induced endothelial dysfunction partly through competing with miR-22-3p for endogenous RNA. [ABSTRACT FROM AUTHOR]

The SWI/SNF (SWItch/Sucrose NonFermentable or BAF, Brg/Brahma-associated factors) complexes are epigenetic modifiers of chromatin structure and undergo progressive changes in subunit composition during cellular differentiation. For example, in embryonic stem cells, esBAF contains Brg1 and Baf155, while their homologs, Brm and Baf170, are present in BAF of somatic cells. In this study, we sought to determine whether Brm and Baf170 play any roles in induced pluripotent stem cell (iPSC) reprogramming by using shRNA-mediated knockdown studies in the mouse model. We found that knocking down Brm during early, mid, and late stages (days 3, 6, and 9 after initial iPSC induction) and knocking down Baf170 during late-stage (day 9) reprogramming improve the numbers of iPSC colonies formed. We further showed that inhibition of these somatic BAF components also promotes complete reprogramming of partially reprogrammed somatic cells (pre-iPSCs). Finally, we found that the expression of Brm and Baf170 during reprogramming was regulated by Jak/Stat3 activity. Taken together, these data suggest that inhibiting somatic BAF improves complete reprogramming by facilitating the activation of the pluripotency circuitry. [ABSTRACT FROM AUTHOR]

Coronary artery disease is a major cause of morbidity and mortality worldwide. Impaired endothelial function and integrity are major contributory factors to coronary artery disease. Micro RNAs have been proposed to play an important role in coronary artery disease pathogenesis. In the present study, the expression of miR-206 was found to be significantly upregulated in peripheral blood endothelial progenitor cells from patients with coronary artery disease compared to healthy donors. MiR-206 was found to regulate endothelial progenitor cell activities by targeting the protein kinase PIK3C2α, which showed decreased expression in coronary artery disease endothelial progenitor cells. Knockdown of miR-206 in coronary artery disease endothelial progenitor cells rescued their angiogenic and vasculogenic abilities both in vitro and in vivo in a mouse ischemic hindlimb model. Furthermore, knockdown of miR-206 activated not only PIK3C2α, but also the angiogenic signal modulators Akt and endothelial nitric oxide synthase. It is therefore proposed that repression of the phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase signal transduction pathway by miR-206 downregulates angiogenesis contributing to the pathophysiology of coronary artery disease. [ABSTRACT FROM AUTHOR]