Discrete element modelling of material non-coaxiality in simple shear flows

We investigate the quasi-static simple shear flow of a two-dimensional assembly of cohesionless particles using discrete element method (DEM) simulations. We focus on the unsteady flow regime where the solid would experience significant evolution of stresses, mobilised shear strength and dilation. We construct the DEM model using a discretised-wall confined granular cell where the apparent boundary is allowed to dilate or contract synchronously with the confined solid. A rather uniform simple shear field is achieved across the whole assembly, which benefits rheological studies in generalising constitutive laws for continuum methods. We examine two aspects of the simple shear behaviour: macroscopic stress and strain rate evolution, particularly the non-coaxiality between the principal directions of the two; and micromechanics such as evolution of fabric. For an initially anisotropic specimen sheared under constant normal pressure, the direction of principal stress rotates towards that of the principal strain rate, gradually reducing the degree of non-coaxiality from about 45° to fluctuating around 0°. The rate in approaching coaxiality is slower in samples with larger initial porosity, stress ratio and mean stress. Generally, a faster rate in approaching coaxiality in simple shear is observed in a more dilatant sample, which often shows a larger degree of mobilised fabric anisotropy, suggesting the possible important role of instantaneous internal friction angle. The evolution of principal fabric direction resembles that of the principal stress direction

Sequential Wnt Agonist then Antagonist Treatment Accelerates Tissue Repair and Minimizes Fibrosis

Tissue fibrosis compromises organ function and occurs as a potential long-term outcome in response to acute tissue injuries. Currently, lack of mechanistic understanding prevents effective prevention and treatment of the progression from acute injury to fibrosis. Here, we combined quantitative experimental studies with a mouse kidney injury model and a computational approach to determine how the physiological consequences are determined by the severity of ischemia injury, and to identify how to manipulate Wnt signaling to accelerate repair of ischemic tissue damage while minimizing fibrosis. The study reveals that Wnt-mediated memory of prior injury contributes to fibrosis progression, and ischemic preconditioning reduces the risk of death but increases the risk of fibrosis. Furthermore, we validated the prediction that sequential combination therapy of initial treatment with a Wnt agonist followed by treatment with a Wnt antagonist can reduce both the risk of death and fibrosis in response to acute injuries

Effects of central activation of serotonin 5-HT2A/2C or dopamine D-2/3 receptors on the acute and repeated effects of clozapine in the conditioned avoidance response test

Acute administration of clozapine (a gold standard of atypical antipsychotics) disrupts avoidance response in rodents, while repeated administration often causes a tolerance effect

Methyl 4-methyl­sulfonyl-2-nitro­benzoate

The title compound, C9H9NO6S, was prepared by the reaction of methanol and thionyl chloride with 4-methyl­sulfonyl-2-nitro­benzoic acid under mild conditions. The dihedral angle between the nitro group and benzene ring is 21.33 (19)° and that between the carboxyl­ate group and the benzene ring is 72.09 (17)°. The crystal structure is stabilized by weak inter­molecular bifurcated C—H⋯O inter­actions occurring in the (100) plane

Ethyl N-[3-(N,N-dimethyl­carbamo­yl)pyridin-2-ylsulfon­yl]carbamate

In the mol­ecular structure of the title compound, C11H15N3O5S, the amide group is nearly perpendicular to the pyridine ring, making a dihedral angle of 86.30 (13)°. The terminal ethyl group is disordered over two sites of equal occupancy. Inter­molecular N—H⋯O hydrogen bonding is present in the crystal structure

Outflows from active galactic nuclei: The BLR-NLR metallicity correlation

The metallicity of active galactic nuclei (AGNs), which can be measured by emission line ratios in their broad and narrow line regions (BLRs and NLRs), provides invaluable information about the physical connection between the different components of AGNs. From the archival databases of the International Ultraviolet Explorer, the Hubble Space Telescope and the Sloan Digital Sky Survey, we have assembled the largest sample available of AGNs which have adequate spectra in both the optical and ultraviolet bands to measure the narrow line ratio [N II]/H{\alpha} and also, in the same objects, the broad-line N V/C IV ratio. These permit the measurement of the metallicities in the NLRs and BLRs in the same objects. We find that neither the BLR nor the NLR metallicity correlate with black hole masses or Eddington ratios, but there is a strong correlation between NLR and BLR metallicities. This metallicity correlation implies that outflows from BLRs carry metal-rich gas to NLRs at characteristic radial distances of ~ 1.0 kiloparsec. This chemical connection provides evidence for a kinetic feedback of the outflows to their hosts. Metals transported into the NLR enhance the cooling of the ISM in this region, leading to local star formation after the AGNs turn to narrow line LINERs. This post-AGN star formation is predicted to be observable as an excess continuum emission from the host galaxies in the near infrared and ultraviolet, which needs to be further explored.Comment: 19 pages, 13 figures, 3 tables. Accepted for publication at MNRA

DNMT3a in the hippocampal CA1 is crucial in the acquisition of morphine self‐administration in rats

Drug‐reinforced excessive operant responding is one fundamental feature of long-lasting addiction‐like behaviors and relapse in animals. However, the transcriptional regulatory mechanisms responsible for the persistent drug‐specific (not natural rewards) operant behavior are not entirely clear. In this study, we demonstrate a key role for one of the de novo DNA methyltransferase, DNMT3a, in the acquisition of morphine self‐administration (SA) in rats. The expression of DNMT3a in the hippocampal CA1 region but not in the nucleus accumbens shell was significantly up‐regulated after 1‐ and 7‐day morphine SA (0.3 mg/kg/infusion) but not after the yoked morphine injection. On the other hand, saccharin SA did not affect the expression of DNMT3a or DNMT3b. DNMT inhibitor 5‐aza‐2‐deoxycytidine (5‐aza) microinjected into the hippocampal CA1 significantly attenuated the acquisition of morphine SA. Knockdown of DNMT3a also impaired the ability to acquire the morphine SA. Overall, these findings suggest that DNMT3a in the hippocampus plays an important role in the acquisition of morphine SA and may be a valid target to prevent the development of morphine addiction. Includes Supplemental informatio