We examined the pancreatic islet lesions in Japanese patients with Type II diabetes mellitus to determine if the damage was related to oxidative stress.
Morphometric analyses were performed on ...immunostained sections of the tail portion of the pancreas from 14 diabetic and 15 non-diabetic patients. Amyloid deposition and oxidative stress-induced tissue damage were evaluated by Congo-red staining and immunostaining. Resistance to oxidative stress was assessed from immunostaining results for Cu, Zn-superoxide dismutase (SOD). Expression of (pro)insulin mRNA was assessed by in situ hybridisation.
The pancreas from diabetic patients had amyloid deposition in about 15 % of the islets, intensified reactions of 8-OHdG and HNE, as well as reduced expression of SOD. Islet volume density of beta cells and total beta-cell mass in the pancreas from diabetic patients were reduced by 22 % (p < 0.001) and 30 % (p < 0.05). Islet volume density and total mass of (pro)insulin mRNA-positive cells were similarly reduced in diabetic patients by 22 % (p < 0.001) and 39 % (p < 0.05), respectively. Islet volume density of A cells was increased by 20 % (p < 0.001) but total mass did not change. There were no changes in volume densities of islet, D and PP cells. Reduced beta-cell volume density correlated with increased positive staining of 8-OHdG.
Japanese Type II diabetic patients show a reduction of beta-cell mass and evidence of increased oxidative stress-related tissue damage that is correlated with the extent of the beta-cell lesions.
Intercellular movement of transcription factor proteins is essential for plant development. The R3 type MYB transcription factor protein, CAPRICE (CPC), moves from non-hair cells to root-hair cells ...where it promotes root hair formation in Arabidopsis root epidermis. In contrast, the CPC homolog of ENHANCER OF TRY AND CPC1 (ETC1) cannot move in root epidermal cells. In this work, we present protein localization data of CPC-ETC1 chimeric proteins. Localization of CPC-ETC1-GFP fusion proteins of chimera1 and chimera2 transgenic plants was observed using confocal laser scanning microscope. Insertion of ETC1-specific amino acids into CPC somewhat prevents normal protein localization of CPC in root epidermal cells. Cell-to-cell movement of chimera1 and chimera2 proteins from non-hair cells to root-hair cells was interfered. Nuclear localization was also inhibited, especially in chimera1.
•GEANT4 and PHITS are used to simulate neutron integral experiments for polyethylene and graphite materials.•Good agreement among GEANT4, PHITS and MCNP in the experimental benchmark.•Reasonable C/E ...for most of energy spectrum for the experimental benchmark with graphite sample.•GEANT4 and PHITS are suitable for 14.8 MeV neutron transport simulations.
The feasibility of GEANT4 and PHITS with ENDF/B-VIII.0, JEFF-3.3 and JENDL-4.0 evaluated nuclear data libraries in 14.8-MeV neutron transport simulation are verified by comparing with the MCNP calculations and the experimental data. The measured data are from neutron integral experiments including graphite and polyethylene samples. For 6 cm-thick polyethylene and 20 cm-thick graphite samples, the results from GEANT4 and PHITS with three evaluated nuclear data libraries agree well with the MCNP calculations. For a 2 cm-thick graphite sample, the simulated results from GEANT4 and PHITS agree with the MCNP calculations, and they all underestimate the experiment data in below 3 MeV and overestimate them in the energy range of 5–7 MeV. The difference between the simulation results and the experimental data depends on the evaluated nuclear data libraries. In overall, GEANT4 and PHITS are performing reasonable jobs for 14.8-MeV neutron transport simulations.
Machine-learning techniques have shown their capability for studying phase transitions in condensed matter physics. Here, we employ machine-learning techniques to study the nuclear liquid-gas phase ...transition. We adopt an unsupervised learning and classify the liquid and gas phases of nuclei directly from the final-state raw experimental data of heavy-ion reactions. Based on a confusion scheme which combines the supervised and unsupervised learning, we obtain the limiting temperature of the nuclear liquid-gas phase transition. Its value 9.24±0.04MeV is consistent with that obtained by the traditional caloric curve method. Our study explores the paradigm of combining machine-learning techniques with heavy-ion experimental data, and it is also instructive for studying the phase transition of other uncontrollable systems, such as QCD matter.
Although neuronal and mesenchymal stem cells exhibit multipotentiality, this property has not previously been demonstrated for muscle stem cells. We now show that muscle satellite cells of adult mice ...are able to differentiate into osteoblasts, adipocytes and myotubes. Undifferentiated muscle progenitor cells derived from a single satellite cell co-expressed multiple determination genes including those for MyoD and Runx2, which are specific for myogenic and osteogenic differentiation, respectively. Determination genes not relevant to the induced differentiation pathway were specifically downregulated in these cells. Similar multipotent progenitor cells were isolated from adult human muscle. Based on these observations, we propose a 'stock options' model for the generation of different fates from multipotent stem cells.
To replace the conventional maximum tolerated dose (MTD) approach, a paradigm for dose optimization and dose selection that relies on model‐informed drug development (MIDD) approaches has been ...proposed in oncology. Here, we report our application of an MIDD approach during phase I to inform dose selection for the late‐stage development of datopotamab deruxtecan (Dato‐DXd). Dato‐DXd is a TROP2‐directed antibody‐drug conjugate being developed for advanced/metastatic non‐small cell lung cancer (NSCLC) and other tumors. Data on pharmacokinetics (PKs), efficacy, and safety in NSCLC were collected in the TROPION‐PanTumor01 phase I dose‐expansion and ‐escalation study over a wide dose range of 0.27–10 mg/kg administered every 3 weeks. Population PK and exposure–response analyses were performed iteratively at three data cutoffs to inform dose selection. The 6 mg/kg dose was identified as the optimal dose by the second data cutoff analysis and confirmed by the subsequent third data cutoff analysis. The 6 mg/kg dose was more tolerable (i.e., lower rates of interstitial lung disease, stomatitis, and mucosal inflammation) than the MTD (8 mg/kg) and was more efficacious than 4 mg/kg (simulated mean objective response rate: 23.8% vs. 18.6%; mean hazard ratio of progression‐free survival: 0.74) – a candidate dose studied just below 6 mg/kg. Therefore, the 6 mg/kg dose was judged to afford the optimal benefit–risk balance. This case study demonstrated the utility of an MIDD approach for dose optimization and dose selection.
The symmetry energy of nuclear matter is a fundamental ingredient in the investigation of exotic nuclei, heavy-ion collisions, and astrophysical phenomena. New data from heavy-ion collisions can be ...used to extract the free symmetry energy and the internal symmetry energy at subsaturation densities and temperatures below 10 MeV. Conventional theoretical calculations of the symmetry energy based on mean-field approaches fail to give the correct low-temperature, low-density limit that is governed by correlations, in particular, by the appearance of bound states. A recently developed quantum-statistical approach that takes the formation of clusters into account predicts symmetry energies that are in very good agreement with the experimental data. A consistent description of the symmetry energy is given that joins the correct low-density limit with quasiparticle approaches valid near the saturation density.
In-medium binding energies and Mott points for d, t, 3He and α clusters in low-density nuclear matter have been determined at specific combinations of temperature and density in low-density nuclear ...matter produced in collisions of 47A MeV 40Ar and 64Zn projectiles with 112Sn and 124Sn target nuclei. The experimentally derived values of the in-medium modified binding energies are in good agreement with recent theoretical predictions based upon the implementation of Pauli blocking effects in a quantum statistical approach.
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