Hepatic and intestinal biotransformation gene expression and drug disposition in a dextran sulfate sodium-induced colitis mouse model

We examined the impact of gut inflammation on the expression of cytochrome P450 (P450) and other biotransformation genes in male mice using a dextran sulfate sodium (DSS)-induced colitis model. Several P450 isoforms, including CYP1A, CYP2B, CYP2C, and CYP3A, were down-regulated, accompanied by decreases in microsomal metabolism of diclofenac and nifedipine, in the liver and small intestine. The impact of the colitis on in vivo clearance of oral drugs varied for four different drugs tested: a small decrease for nifedipine, a relatively large decrease for lovastatin, but no change for pravastatin, and a large decrease in the absorption of cyclosporine A. To further assess the scope of influence of gut inflammation on gene expression, we performed genome-wide expression analysis using RNA-seq, which showed down-regulation of many CYPs, non-CYP phase-I enzymes, phase-II enzymes and transporters, and up-regulation of many other members of these gene families, in both liver and intestine of adult C57BL/6 mice, by DSS-induced colitis. Overall, our results indicate that gut inflammation suppresses the expression of many P450s and other biotransformation genes in the intestine and liver, and alters the pharmacokinetics for some but not all drugs, potentially affecting therapeutic efficacy or causing adverse effects in a drug-specific fashion.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

An Efficient Certificateless Encryption for Secure Data Sharing in Public Clouds

We propose a mediated certificateless encryption scheme without pairing operations for securely sharing sensitive information in public clouds. Mediated certificateless public key encryption (mCL-PKE) solves the key escrow problem in identity based encryption and certificate revocation problem in public key cryptography. However, existing mCL-PKE schemes are either inefficient because of the use of expensive pairing operations or vulnerable against partial decryption attacks. In order to address the performance and security issues, in this paper, we first propose a mCL-PKE scheme without using pairing operations. We apply our mCL-PKE scheme to construct a practical solution to the problem of sharing sensitive information in public clouds. The cloud is employed as a secure storage as well as a key generation center. In our system, the data owner encrypts the sensitive data using the cloud generated users’ public keys based on its access control policies and uploads the encrypted data to the cloud. Upon successful authorization, the cloud partially decrypts the encrypted data for the users. The users subsequently fully decrypt the partially decrypted data using their private keys. The confidentiality of the content and the keys is preserved with respect to the cloud, because the cloud cannot fully decrypt the information. We also propose an extension to the above approach to improve the efficiency of encryption at the data owner. We implement our mCL-PKE scheme and the overall cloud based system, and evaluate its security and performance. Our results show that our schemes are efficient and practical

Magnetic field-modulated exciton generation in organic semiconductors: an intermolecular quantum correlation effect

Magnetoelectroluminescence (MEL) of organic semiconductor has been experimentally tuned by adopting blended emitting layer consisting of both hole and electron transporting materials. A theoretical model considering intermolecular quantum correlation is proposed to demonstrate two fundamental issues: (1) two mechanisms, spin scattering and spin mixing, dominate the two different steps respectively in the process of the magnetic field modulated generation of exciton; (2) the hopping rate of carriers determines the intensity of MEL. Calculation successfully predicts the increase of singlet excitons in low field with little change of triplet exciton population.Comment: 16 pages, 4 figure

The impacts of environmental regulation on regional green productivity growth in China: from the perspective of local-neighborhood effects

It is of great theoretical and practical implications for developing countries to achieve the win-win for economic growth and environmental performance. Extant studies focus on the local effect of environmental regulation, but ignore the neighborhood effect. This study tries to fill the gap from both the theoretical analysis and empirical test. We construct the theoretical framework of the localneighborhood effect of environmental regulation on regional green productivity growth (GPG). Based on the panel data of 237 cities in China from 2011 to 2020, we employ the spatial panel models to empirically examine the local-neighborhood effects of environmental regulation on regional GPG. We further use the mediating effect models to examine the mechanism of environmental regulation affecting neighborhood GPG. The results demonstrate that both the local and neighborhood effect on regional GPG are U-shaped. The difference is that the inflection point of neighborhood effect is larger than that of local effect. The stringency of environmental regulations implemented by most cities in China is on the left side of the inflection point of the U-shaped curve, which leads to the inhibition of local and neighborhood GPG. Moreover, both green technology spillover mechanism and pollution transfer mechanism play a significant mediating role in the neighborhood effect of environmental regulation. The competition between these two mechanisms determines the U-shaped feature of neighborhood effect of environmental regulation. Finally, we put forward policy suggestions for the GPG from the perspective of local-neighborhood effect of environmental regulation

Revealing two radio active galactic nuclei extremely near PSR J0437−-4715

Newton's gravitational constant $G$ may vary with time at an extremely low level. The time variability of $G$ will affect the orbital motion of a millisecond pulsar in a binary system and cause a tiny difference between the orbital period-dependent measurement of the kinematic distance and the direct measurement of the annual parallax distance. PSR J0437$-$4715 is the nearest millisecond pulsar and the brightest at radio. To explore the feasibility of achieving a parallax distance accuracy of one light-year, comparable to the recent timing result, with the technique of differential astrometry, we searched for compact radio sources quite close to PSR J0437$-$4715. Using existing data from the Very Large Array and the Australia Telescope Compact Array, we detected two sources with flat spectra, relatively stable flux densities of 0.9 and 1.0 mJy at 8.4 GHz and separations of 13 and 45 arcsec. With a network consisting of the Long Baseline Array and the Kunming 40-m radio telescope, we found that both sources have a point-like structure and a brightness temperature of $\geq$10$^7$ K. According to these radio inputs and the absence of counterparts in the other bands, we argue that they are most likely the compact radio cores of extragalactic active galactic nuclei rather than Galactic radio stars. The finding of these two radio active galactic nuclei will enable us to achieve a sub-pc distance accuracy with the in-beam phase-referencing very-long-baseline interferometric observations and provide one of the most stringent constraints on the time variability of $G$ in the near future.Comment: 9 pages, 3 tables, 3 figures. Accepted for publication in MNRA

Cerebral vasomotor reactivity predicts the development of acute stroke in patients with internal carotid artery stenosis

Objective To investigate the relationship between cerebral vasomotor reactivity (VMR) and acute stroke in patients with internal carotid artery stenosis. Methods 54 patients with internal carotid artery stenosis were enrolled. VMR was calculated by transcranial Doppler monitoring of the velocity of blood flow. 3-Dimensional dynamic contrast enhanced magnetic resonance angiography was used to detect stenosis, and diffusion weighted imaging was used to detect infarction. Results VMR value was significantly lower in patients with carotid artery stenosis than in control group (T=3.112, P=0.002), and significantly lower in patients with aortic atherosclerotic stroke than in non-infarct group (T=10.930, P=0.000). However, VMR value was significantly higher in patients with new-onset small-artery occlusion stroke than in non-infarction group (T=−2.538, P=0.013). Scatter plots showed that aortic atherosclerotic stroke occurred mainly in patients with severe internal carotid artery stenosis, and VMR value in cerebral artery significantly decreased. Conclusion Decreased VMR value is an important prognostic factor for the occurrence of aortic atherosclerotic stroke, and can be used as a reference for preoperative hemodynamic evaluation in patients with internal carotid artery stenosis

Chat-PM: A Class of Composite Hybrid Aerial/Terrestrial Precise Manipulator

This paper concentrates on the development of Chat-PM, a class of composite hybrid aerial/terrestrial manipulator, in concern with composite configuration design, dynamics modeling, motion control and force estimation. Compared with existing aerial or terrestrial mobile manipulators, Chat-PM demonstrates advantages in terms of reachability, energy efficiency and manipulation precision. To achieve precise manipulation in terrestrial mode, the dynamics is analyzed with consideration of surface contact, based on which a cascaded controller is designed with compensation for the interference force and torque from the arm. Benefiting from the kinematic constraints caused by the surface contact, the position deviation and the vehicle vibration are effectively decreased, resulting in higher control precision of the end gripper. For manipulation on surfaces with unknown inclination angles, the moving horizon estimation (MHE) is exploited to obtain the precise estimations of force and inclination angle, which are used in the control loop to compensate for the effect of the unknown surface. Real-world experiments are performed to evaluate the superiority of the developed manipulator and the proposed controllers