Activation cross sections of \alpha-induced reactions on nat^{nat}Zn for Ge and Ga production

The production cross sections of $^{68,69}$Ge and $^{66,67}$Ga by \alpha-induced reactions on $^{nat}$Zn have been measured using the stacked-foil activation method and off-line \gamma-ray spectrometry from their threshold energies to 50.7 MeV. The derived cross sections were compared with the previous experimental data and the calculated values in the TENLD-2017 library. Our result shows a slightly larger amplitude than the previous data at the peak, though the peak energy is consistent with them.Comment: 12 pages, 6 figure

Evaluation of intramuscular lateral distribution profile of topically administered acetaminophen in rats

&#65279;To clarify to what extent topically administered drug molecules horizontally permeate into tissues surrounding the administration site, the intramuscular lateral concentration profile of acetaminophen was investigated in vivo using the microdialysis method in rats. When acetaminophen was intramuscularly administered for 6 hr in a pinpoint manner at a constant rate of 3 &#956;g/min, it was clearly detected in the muscle surrounding the administration site, being 17.5 &#956;g/ml when measured at a 2 mm distance from the administration site. The concentration in the muscle was decreased as the distance increased, and those measured at 5 mm and 40 mm were 0.35 &#956;g/ml and 0.09 &#956;g/ml, respectively. In addition, it was shown that the concentration in the muscle at 40 mm reflected the compound’s concentration in plasma, but not the compound’s horizontal permeation from the administration site. With these observations, the intramuscular distribution profile of acetaminophen was numerically characterized according to Fick’s law. As a result, it was revealed that horizontal permeation is the primary process accountable for the increased intramuscular concentration only in the area adjacent to the administration site, and the radius of the adjacent area was calculated to be 5.80 mm for acetaminophen. </p

Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice

Runt-related transcription factor 2 (Runx2)-deficient mice can be used to model congenital tooth agenesis in humans. Conversely, uterine sensitization-associated gene-1 (Usag-1)-deficient mice exhibit supernumerary tooth formation. Arrested tooth formation can be restored by crossing both knockout-mouse strains; however, it remains unclear whether topical inhibition of Usag-1 expression can enable the recovery of tooth formation in Runx2-deficient mice. Here, we tested whether inhibiting the topical expression of Usag-1 can reverse arrested tooth formation after Runx2 abrogation. The results showed that local application of Usag-1 Stealth small interfering RNA (siRNA) promoted tooth development following Runx2 siRNA-induced agenesis. Additionally, renal capsule transplantation of siRNA-loaded cationized, gelatin-treated mouse mandibles confirmed that cationized gelatin can serve as an effective drug-delivery system. We then performed renal capsule transplantation of wild-type and Runx2-knockout (KO) mouse mandibles, treated with Usag-1 siRNA, revealing that hindered tooth formation was rescued by Usag-1 knockdown. Furthermore, topically applied Usag-1 siRNA partially rescued arrested tooth development in Runx2-KO mice, demonstrating its potential for regenerating teeth in Runx2-deficient mice. Our findings have implications for developing topical treatments for congenital tooth agenesis

Superheavy element nuclear chemistry at RIKEN

金沢大学理工研究域物質化学系A gas-jet transport system has been coupled to the RIKEN gas-filled recoil ion separator GARIS to startup superheavy element (SHE) chemistry at RIKEN. The performance of the system was appraised using an isotope of element 104, 261Rf, produced in the 248Cm(18O,5n) 261Rf reaction. Alpha-particles of 261Rf separated with GARIS and extracted to a chemistry laboratory were successfully identified with a rotating wheel apparatus for α spectrometry. The setting parameters such as the magnetic field of the separator and the gas-jet conditions were optimized. The present results suggest that the GARIS/gas-jet system is a promising approach for exploring new frontiers in SHE chemistry: (i) the background radioactivities of unwanted reaction products are strongly suppressed, (ii) the intense beam is absent in the gas-jet chamber and hence high gas-jet efficiency is achieved, and (iii) the beam-free condition also allows for investigations of new chemical systems. © 2010 American Institute of Physics

Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation

Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Pparγ2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Pparγ2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis

In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Human hepatocellular carcinoma (HCC) cells express WT1 and/or carcinoembryonic antigen (CEA) as potential targets for the induction of antitumor immunity. In this study, generation of cytotoxic T lymphocytes (CTL) and regulatory T cells (Treg) by fusions of dendritic cells (DCs) and HCC cells was examined.</p> <p>Methods</p> <p>HCC cells were fused to DCs either from healthy donors or the HCC patient and investigated whether supernatants derived from the HCC cell culture (HCCsp) influenced on the function of DCs/HCC fusion cells (FCs) and generation of CTL and Treg.</p> <p>Results</p> <p>FCs coexpressed the HCC cells-derived WT1 and CEA antigens and DCs-derived MHC class II and costimulatory molecules. In addition, FCs were effective in activating CD4⁺and CD8⁺T cells able to produce IFN-γ and inducing cytolysis of autologous tumor or semiallogeneic targets by a MHC class I-restricted mechanism. However, HCCsp induced functional impairment of DCs as demonstrated by the down-regulation of MHC class I and II, CD80, CD86, and CD83 molecules. Moreover, the HCCsp-exposed DCs failed to undergo full maturation upon stimulation with the Toll-like receptor 4 agonist penicillin-inactivated <it>Streptococcus pyogenes</it>. Interestingly, fusions of immature DCs generated in the presence of HCCsp and allogeneic HCC cells promoted the generation of CD4⁺CD25^highFoxp3⁺Treg and inhibited CTL induction in the presence of HCCsp. Importantly, up-regulation of MHC class II, CD80, and CD83 on DCs was observed in the patient with advanced HCC after vaccination with autologous FCs. In addition, the FCs induced WT1- and CEA-specific CTL that were able to produce high levels of IFN-γ.</p> <p>Conclusion</p> <p>The current study is one of the first demonstrating the induction of antigen-specific CTL and the generation of Treg by fusions of DCs and HCC cells. The local tumor-related factors may favor the generation of Treg through the inhibition of DCs maturation; however, fusion cell vaccination results in recovery of the DCs function and induction of antigen-specific CTL responses in vitro. The present study may shed new light about the mechanisms responsible for the generation of CTL and Treg by FCs.</p

Online chemical adsorption studies of Hg, Tl, and Pb on SiO2 and Au surfaces in preparation for chemical investigations on Cn, Nh, and Fl at TASCA

Online gas-solid adsorption studies with single-atom quantities of Hg, Tl, and Pb, the lighter homologs of the superheavy elements (SHE) copernicium (Cn, Z =112), nihonium (Nh, Z =113), and flerovium (Fl, Z =114), were carried out using short-lived radioisotopes. The interaction with Au and SiO 2 surfaces was studied and the overall chemical yield was determined. Suitable radioisotopes were produced in fusion-evaporation reactions, isolated in the gas-filled recoil separator TASCA, and flushed rapidly to an adjacent setup of two gas chromatography detector arrays covered with SiO 2 (first array) and Au (second array). While Tl and Pb adsorbed on the SiO 2 surface, Hg interacts only weakly and reached the Au-covered array. Our results contribute to elucidating the influence of relativistic effects on chemical properties of the heaviest elements by providing experimental data on these lighter homologs