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Transforming growth factor (TGF)-β is known to promote tumor invasion and metastasis. Although bone morphogenetic proteins (BMPs), members of the TGF-β family, are expressed in a variety of human carcinoma cell lines, their roles in tumor progression have not been fully clarified. In this study, we sought to determine the roles of BMPs in the progression of breast cancer bone metastasis using human breast cancer samples and a mouse xenograft model. Immunohistochemical analysis of samples from breast cancer patients as well as a mouse xenograft model of MDA-231-D, highly metastatic human breast cancer cells, revealed phospho-Smad2 and phospho-Smad1/5/8 staining in the nuclei of cancer cells in primary tumor and/or bone metastasis. Using a functional in vivo bioluminescence imaging system, we showed that TGF-β- and BMP-induced transcriptional pathways are active in bone metastatic lesions in vivo . In addition, both TGF-β3 and BMP-2 promoted the motility and invasiveness of the MDA-231-D cells in vitro . Moreover, expression of dominant-negative receptors for TGF-β and/or BMPs in the MDA-231-D cells inhibited invasiveness in vitro and bone metastasis in the xenograft model. These results suggest that BMPs as well as TGF-β promote invasion and bone metastasis of breast cancer.

The high current density of HTS material allows electromagnet to induce sufficiently strong magnetic field without relying on any iron core. This permits the design of air-cored cyclotron, where the absence of iron core brings the properties of light-weight and high field reproducibility, making it an ideal medical cyclotron to be installed inside hospitals. However, the cyclotron coil system need to induce highly accurate field while satisfying the engineering restriction from the HTS coil. Compact size, small fringe field and minimum fabrication cost are also desirable at the same time. A HTS coil system of air-cored cyclotron is designed with the above restrictions taken into consideration. Multiple beam type accelerations that are required for medical RI production are simulated, in order to verify the usefulness of this design. In this work, the coil system design, the magnetic field and the HTS coil properties are presented. The feasibility of actual fabrication and in-hospital installation is discussed.

Background. Diagnosis of malaria relies on parasite detection by microscopy or antigen detection; both fail to detect low-density infections. New tests providing rapid, sensitive diagnosis with minimal need for training would enhance both malaria diagnosis and malaria control activities. We determined the diagnostic accuracy of a new loop-mediated amplification (LAMP) kit in febrile returned travelers. Methods. The kit was evaluated in sequential blood samples from returned travelers sent for pathogen testing to a specialist parasitology laboratory. Microscopy was performed, and then malaria LAMP was performed using Plasmodium genus and Plasmodium falciparum-speciñc tests in parallel. Nested polymerase chain reaction (PCR) was performed on all samples as the reference standard. Primary outcome measures for diagnostic accuracy were sensitivity and specificity of LAMP results, compared with those of nested PCR. Results. A total of 705 samples were tested in the primary analysis. Sensitivity and specificity were 98.4% and 98.1%, respectively, for the LAMP P. falciparum primers and 97.0% and 99.2%, respectively, for the Plasmodium genus primers. Post hoc repeat PCR analysis of all 15 tests with discrepant results resolved 4 results in favor of LAMP, suggesting that the primary analysis had underestimated diagnostic accuracy. Conclusions. Malaria LAMP had a diagnostic accuracy similar to that of nested PCR, with a greatly reduced time to result, and was superior to expert microscopy.

Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite the extensive research, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. Loss of GABAergic tone may have an important role in the neuropathic pain state. Glutamic acid decarboxylase 67 (GAD67) is one of the isoforms that catalyze GABA synthesis. Here, we used recombinant herpes simplex virus (HSV-1) vectors that encode gad1 gene to evaluate the therapeutic potential of GAD67 in peripheral HIV gp120-induced neuropathic pain in rats. We found that (1) subcutaneous inoculation of the HSV vectors expressing GAD67 attenuated mechanical allodynia in the model of HIV gp120-induced neuropathic pain, (2) the anti-allodynic effect of GAD67 was reduced by GABA-A and-B receptors antagonists, (3) HSV vectors expressing GAD67 reversed the lowered GABA-IR expression and (4) the HSV vectors expressing GAD67 suppressed the upregulated mitochondrial superoxide and Wnt5a in the spinal dorsal horn. Taken together, our studies support the concept that recovering GABAergic tone by the HSV vectors may reverse HIV-associated neuropathic pain through suppressing mitochondrial superoxide and Wnt5a. Our studies provide validation of HSV-mediated GAD67 gene therapy in the treatment of HIV-related neuropathic pain.

Various factors influence each other in an ion source. Therefore, when operating an ion source, it is necessary to optimize and adjust various parameters. This time, we performed an experiment to automize adjustment that maximizes the brightness of the beam using machine learning. By automatically adjusting 4 parameters, we succeeded in finding a point with a beam brightness of 4.32 × 10 -6 mA/(imm mrad) 2 in 25 steps. This shows that automatic adjustment using Bayesian optimization is feasible.

We report the realization of an ultraviolet light-emitting diode with the use of a diamond pn junction. The pn junction was formed from a boron-doped p-type diamond layer and phosphorus-doped n-type diamond layer grown epitaxially on the {111} surface of single crystalline diamond. The pn junction exhibited good diode characteristics, and at forward bias of about 20 volts strong ultraviolet light emission at 235 nanometers was observed and was attributed to free exciton recombination.

Colorectal cancer metastasis to the retroperitoneum, especially solitary metastasis allowing curative resection, is rare. We report a case of complete resection of retroperitoneal metachronous solitary metastasis from caecal cancer without distant metastasis. An 80-year-old woman with caecal cancer underwent laparoscopic ileocaecal resection with regional lymph node dissection. According to the eighth edition of the TNM classification, the pathological diagnosis was stage IIA (T3N0M0). Six months following the surgery, computed tomography revealed a solitary mass of 2cm diameter, dorsal to the right kidney. A second procedure for the removal of the tumour was performed. The lesion was pathologically diagnosed as a metachronous solitary retroperitoneal metastasis from caecal cancer. The patient is surviving and free from recurrence 17 months following the second procedure.

Abstract We performed a novel Σ+p scattering experiment at the J-PARC Hadron Experimental Facility. Approximately 2400 Σ+p elastic scattering events were identified from 4.9 × 107 tagged Σ+ particles in the Σ+ momentum range 0.44–0.80 GeV/c. The differential cross sections of the Σ+p elastic scattering were derived with much better precision than in previous experiments. The obtained differential cross sections were approximately 2 mb/sr or less, which were not as large as those predicted by the fss2 and FSS models based on the quark cluster model in the short-range region. By performing phase-shift analyses for the obtained differential cross sections, we experimentally derived the phase shifts of the 3S1 and 1P1 channels for the first time. The phase shift of the 3S1 channel, where a large repulsive core was predicted owing to the Pauli effect between quarks, was evaluated as $20^\\circ \\lt |\\delta _{^3S_1}|\\lt 35^\\circ$. If the sign of $\\delta _{^3S_1}$ is assumed to be negative, the interaction in this channel is moderately repulsive, as the Nijmegen extended-sort-core models predicted.

The pepper-pot emittance monitor is a device that can measure the phase space distribution of the beam rapidly. We have introduced one at the ion source test stand of Gunma University. We confirmed that the phase space distribution can be measured accurately comparing to the existing wire-slit type emittance monitor.

Abstract The hadron spectrum at finite density is an important observable for exploring the origin of hadron masses. In the KEK-PS E325 experiment, the di-electron decays of $\\phi$ mesons inside and outside nuclei were measured using $12 \\,\\mathrm{G}\\mathrm{e\\mathrm{V}}$ pA reactions. In the previous analysis, a significant excess was observed on the low-mass side of the $\\phi$ meson peak in the data for slow-moving $\\phi$ mesons ($\\beta \\gamma =p_{\\phi }/m_{\\phi }<1.25$) with the copper target, and in-medium vector meson spectral modification was verified. We used, for the first time, the PHSD transport approach to take into account the time evolution of the spatial density distribution of the target nuclei. Consistent with the previous analysis, a significant excess was observed in the present analysis as well. It was found that incorporating momentum dependence into the spectral modification leads to better agreement with the experimental results. For the slow-moving $\\phi$ mesons with the copper target, the newly obtained modification parameters are consistent with those from the previous analysis within the uncertainties.