Pure magnesium (Mg) develops a strong basal texture after conventional processing of hot rolling or extrusion. Consequently, it exhibits anisotropic mechanical properties and is difficult to form at ...room temperature. Adding appropriate alloying elements can weaken the basal texture or even change it, but the improvement in formability and mechanical properties is still far from expectations. Over the past 20 years, considerable efforts have been made and significant progress has been made on wrought Mg alloys at the fundamental and technological levels. At the fundamental level, textures formed in sheets and extrusions of different alloy compositions and produced under different strain paths or thermomechanical processing conditions are relatively well established, with the assistance of the advanced characterization technique of electron backscatter diffraction. At the technological level, room temperature formability of sheet has been significantly improved, and tension–compression yield asymmetry of extrusion is also remarkably reduced or eliminated. This paper starts with an overview of dislocations, stacking faults and twins, and deformation of single crystals of pure Mg along different orientations and under different loading conditions, followed by a review of microstructure (texture and grain size) and deformation of polycrystalline pure Mg with different textures, grain sizes, and loading conditions. With this information as a base, texture, grain size, and deformation of polycrystalline Mg alloy sheets and extrusions produced under different processing conditions are systematically examined and compared. Remaining and emerging scientific and technology issues are then highlighted and discussed in the context of texture and grain size. The need for better-resolution diffraction and spectroscopy techniques is also discussed in the relationship between texture change and grain boundary solute segregation.
Aims
Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE‐EPS), a lactic acid bacteria isolated from Kimchi (a Korean fermented vegetable product), was preliminary characterized and its ...immunostimulating effects were analysed.
Methods and Results
In this study, we used interferon‐γ (IFN‐γ)‐primed RAW 264·7 macrophages and CD3/CD28‐stimulated splenocytes to determine the immunotimulatory activities of PE‐EPS. Upon exposure to PE‐EPS, IFN‐γ‐primed RAW 264·7 macrophages showed significant increases in the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6 and IL‐1β. Molecular data using reporter gene assay and electrophoretic mobility shift assay (EMSA) revealed that PE‐EPS upregulated transcriptional activity, DNA binding and the nuclear translocation of nuclear factor‐κB (NF‐κB). Furthermore, PE‐EPS enhanced anti‐CD3/CD28‐specific proliferation and the productions of IL‐2 and IFN‐γ in primary splenocytes. In cyclophosphamide‐induced immunosuppressed mice, pretreatment with PE‐EPS (5, 15 or 45 mg kg−1 day−1, p.o.) increased thymus and spleen indices, and improved lymphocyte and neutrophil counts.
Conclusion
PE‐EPS stimulated the IFN‐γ‐primed macrophages and primary splenocytes to induce immune responses and improved the cyclophosphamide‐induced immunosuppression in mice.
Significance and Impact of the Study
The results in this study improved our understanding of immunostimulating activity of PE‐EPS and supported its potential treatment option as a natural immunostimulant.
The presence of a di-unsaturated highly branched isoprenoid (HBI) lipid biomarker (diene II) in Southern Ocean sediments has previously been proposed as a proxy measure of palaeo Antarctic sea ice. ...Here we show that a source of diene II is the sympagic diatom Berkeleya adeliensis Medlin. Furthermore, the propensity for B. adeliensis to flourish in platelet ice is reflected by an offshore downward gradient in diene II concentration in >100 surface sediments from Antarctic coastal and near-coastal environments. Since platelet ice formation is strongly associated with super-cooled freshwater inflow, we further hypothesize that sedimentary diene II provides a potentially sensitive proxy indicator of landfast sea ice influenced by meltwater discharge from nearby glaciers and ice shelves, and re-examination of some previous diene II downcore records supports this hypothesis. The term IPSO25-Ice Proxy for the Southern Ocean with 25 carbon atoms-is proposed as a proxy name for diene II.
Abstract
We report on the discovery of FRB 20200120E, a repeating fast radio burst (FRB) with a low dispersion measure (DM) detected by the Canadian Hydrogen Intensity Mapping Experiment FRB project. ...The source DM of 87.82 pc cm
−3
is the lowest recorded from an FRB to date, yet it is significantly higher than the maximum expected from the Milky Way interstellar medium in this direction (∼50 pc cm
−3
). We have detected three bursts and one candidate burst from the source over the period 2020 January–November. The baseband voltage data for the event on 2020 January 20 enabled a sky localization of the source to within ≃14 arcmin
2
(90% confidence). The FRB localization is close to M81, a spiral galaxy at a distance of 3.6 Mpc. The FRB appears on the outskirts of M81 (projected offset ∼20 kpc) but well inside its extended H
i
and thick disks. We empirically estimate the probability of a chance coincidence with M81 to be <10
−2
. However, we cannot reject a Milky Way halo origin for the FRB. Within the FRB localization region, we find several interesting cataloged M81 sources and a radio point source detected in the Very Large Array Sky Survey. We search for prompt X-ray counterparts in Swift Burst Alert Telescope and Fermi/GBM data, and, for two of the FRB 20200120E bursts, we rule out coincident SGR 1806−20-like X-ray bursts. Due to the proximity of FRB 20200120E, future follow-up for prompt multiwavelength counterparts and subarcsecond localization could be constraining of proposed FRB models.
The role of hydrogen bonds in energy redistribution in the cyclic structure of a formamide–water complex has been studied with semiclassical formulations of energy transfer probabilities and ...solutions of the equations of motion. We show high efficiency of near-resonant vibrational energy from initially excited OH stretching to the first overtone of the bending vibration, which is followed by ultrafast (∼100 fs) energy redistribution in the accepting modes of the complex. A strong coupling of the OH bending vibration with the low-frequency modes generated in the hydrogen-bonding intermolecular regions, especially that formed between the water oxygen and formamide hydrogen, plays the key role of ultrafast relaxation of the overtone mode, transferring energy to the hydrogen bonds and distant functional groups in the complex.
This paper reports a multi-throughput multi-organ-on-a-chip system formed on a pneumatic pressure-driven medium circulation platform with a microplate-sized format as a novel type of ...microphysiological system. The pneumatic pressure-driven platform enabled parallelized multi-organ experiments (i.e. simultaneous operation of multiple multi-organ culture units) and pipette-friendly liquid handling for various conventional cell culture experiments, including cell seeding, medium change, live/dead staining, cell growth analysis, gene expression analysis of collected cells, and liquid chromatography-mass spectrometry analysis of chemical compounds in the culture medium. An eight-throughput two-organ system and a four-throughput four-organ system were constructed on a common platform, with different microfluidic plates. The two-organ system, composed of liver and cancer models, was used to demonstrate the effect of an anticancer prodrug, capecitabine (CAP), whose metabolite 5-fluorouracil (5-FU) after metabolism by HepaRG hepatic cells inhibited the proliferation of HCT-116 cancer cells. The four-organ system, composed of intestine, liver, cancer, and connective tissue models, was used to demonstrate evaluation of the effects of 5-FU and two prodrugs of 5-FU (CAP and tegafur) on multiple organ models, including cancer and connective tissue.
This study aimed to evaluate endogenous metabolic markers of hepatic cytochrome P450 (CYP)3A activity in healthy subjects using a metabolomics approach. Twenty‐four subjects received the following ...medication during the following three study periods: 1 mg of i.v. midazolam alone (control phase), 1 mg of i.v. midazolam after 4 days of pretreatment with 400 mg of ketoconazole once daily (CYP3A‐inhibited phase), and 2.5 mg of i.v. midazolam after 10 days of pretreatment with 600 mg of rifampicin once daily (CYP3A‐induced phase). During each study period, 24 h before and after the administration of midazolam, urine samples were collected at 12‐h intervals for metabolomic analyses. We derived an equation to predict midazolam clearance (CL) based on several of these markers. We demonstrated that a combination of the concentrations and ratios of several endogenous metabolites and the CYP3A5*3 genotype is a reliable predictive marker of hepatic CYP3A activity as assessed by i.v. administration of midazolam.
Clinical Pharmacology & Therapeutics (2013); 94 5, 601–609. doi:10.1038/clpt.2013.128
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) commonly occurs in individuals receiving bisphosphonates (BPs) with clinical manifestations of the exposed necrotic bone. Although defective ...wound healing of soft tissue is frequently, if not always, observed in BRONJ, the effects of BPs on oral soft tissue or cells remain unknown. To investigate the effects of BPs on cells of oral mucosal tissue, we studied the effect of pamidronate (PAM), one of the BPs most commonly administered to cancer patients, on the phenotypes of normal human oral keratinocytes (NHOK) and fibroblasts (NHOF). When exposed to PAM at 10 µM, NHOK, not NHOF, underwent senescence: NHOK overexpressed senescence-associated β-galactosidase (SA-β-Gal), p16INK4A, IL-6, and IL-8. When exposed to a higher level (50 µM) of PAM, NHOK maintained senescent phenotypes, but NHOF underwent apoptosis. PAM-induced senescence in NHOK is mediated, in part, via geranylgeranylation of the mevalonate pathway. Our in vitro 3D oral mucosal tissue construction studies further demonstrated that PAM induced senescence and impaired re-epithelialization of oral mucosa. Analysis of these data indicates that premature senescence of oral mucosal cells and subsequent defective soft-tissue wound healing might be partly responsible for the development of BRONJ in individuals receiving PAM or other BPs.
PDF
