Direct Patterning of Ceramic Circuit Board with Q-Switched Nd:YAG Laser

Direct patterning of copper coated ceramic circuit board is experimentally investigated with Q-switched Nd:YAG laser in order to shorten the time of the trial manufacture of electronic circuit board and to adapt the flexible design change. It is pointed out that the fast direct patterning the speed of which reaches about 100 mm/s is possible if the repetition frequency and the average power are selected properly. Furthermore cutting off and/or drilling of ceramic board are also possible under the condition that the repetition frequency is less than 3kHz. This technique makes it possible the mask1ess patterning of ceramic circuit board which has been widely used recently in place of conventional glass-epoxy or phenolic resin circuit board, and it leads to the shorter time limit of delivery as compared with the conventional end-milling method

Scribing of Ceramie Circuit Board with Q-Switched Nd：YAG Laser

Scribing of copper coated alumina ceramic board with Q-switched YAG laser used for the maskless direct patterning of circuit　board is experimentally investigated, which leads to efficient production of trial circuit board. Better dividing of alumina circuit board 655μm in thickness can be attained by the scribing of about 100μm depth. Higher repetition frequency of laser irradiation leads to smaller notch angle and lower breaking load

PD-L1 expression combined with microsatellite instability/CD8+tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer

While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cance

Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody

The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs

The respiratory microbiome associated with chronic obstructive pulmonary disease comorbidity in non‐small cell lung cancer

博士（医学）甲日本医科大学202

The Conformal Transformation in General Single Field Inflation with Non-Minimal Coupling

The method of a conformal transformation is applied to a general class of single field inflation models with non-minimal coupling to gravity and non-standard kinetic terms, in order to reduce the cosmological perturbative calculation to the conventional minimal coupling case to all orders in perturbation theory. Our analysis is made simple by the fact that all perturbation variables in the comoving gauge are conformally invariant to all orders. The structure of the vacuum, on which cosmological correlation functions are evaluated, is also discussed. We show how quantization in the Jordan frame for non-minimally coupled inflation models can be equivalently implemented in the Einstein frame. It is thereafter argued that the general N-point cosmological correlation functions (of the curvature perturbation) are independent of the conformal frame.Comment: 15 pages, no figure, references adde

Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities

Purpose: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsufficiency. Methods: Three individuals with intellectual disability and iris anomalies and truncating de novo PRR12 variants were described previously. We add 21 individuals with similar PRR12 variants identified via matchmaking platforms, bringing the total number to 24. Results: We observed 12 frameshift, 6 nonsense, 1 splice-site, and 2 missense variants and one patient with a gross deletion involving PRR12. Three individuals had additional genetic findings, possibly confounding the phenotype. All patients had developmental impairment. Variable structural eye defects were observed in 12/24 individuals (50%) including anophthalmia, microphthalmia, colobomas, optic nerve and iris abnormalities. Additional common features included hypotonia (61%), heart defects (52%), growth failure (54%), and kidney anomalies (35%). PrediXcan analysis showed that phecodes most strongly associated with reduced predicted PRR12 expression were enriched for eye- (7/30) and kidney- (4/30) phenotypes, such as wet macular degeneration and chronic kidney disease. Conclusion: These findings support PRR12 haploinsufficiency as a cause for a novel disorder with a wide clinical spectrum marked chiefly by neurodevelopmental and eye abnormalities. Graphic Abstract: [Figure not available: see fulltext.

Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities

PURPOSE: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsufficiency. METHODS: Three individuals with intellectual disability and iris anomalies and truncating de novo PRR12 variants were described previously. We add 21 individuals with similar PRR12 variants identified via matchmaking platforms, bringing the total number to 24. RESULTS: We observed 12 frameshift, 6 nonsense, 1 splice-site, and 2 missense variants and one patient with a gross deletion involving PRR12. Three individuals had additional genetic findings, possibly confounding the phenotype. All patients had developmental impairment. Variable structural eye defects were observed in 12/24 individuals (50%) including anophthalmia, microphthalmia, colobomas, optic nerve and iris abnormalities. Additional common features included hypotonia (61%), heart defects (52%), growth failure (54%), and kidney anomalies (35%). PrediXcan analysis showed that phecodes most strongly associated with reduced predicted PRR12 expression were enriched for eye- (7/30) and kidney- (4/30) phenotypes, such as wet macular degeneration and chronic kidney disease. CONCLUSION: These findings support PRR12 haploinsufficiency as a cause for a novel disorder with a wide clinical spectrum marked chiefly by neurodevelopmental and eye abnormalities

Time-resolved Fourier-transform infrared reflection study on photoinduced phase transition of tetrathiafulvalene-p-chloranil crystal

We have measured temporal change of infrared reflection spectrum of ionic phase of tetrathiafulvalene-p-chloranil (TTF-CA) crystal induced by 10 ns pulsed laser excitation at 2.35 eV with using a step-scan Fourier-transform infrared spectrometer. The excitation reduced the magnitude of the ag-mode bands around 980 cm-1 and 1380 cm-1 and enhanced reflection intensity at 1630 cm-1. The time evolution of both the ag-mode changes and the enhancement at 1630 cm-1 are described by the sum of two decay components: one decayed within 2 μs and the other showed very gradual decay within the time range used in the present study. The fractional changes of reflectivity for the fast decay components were almost identical for all ag modes. The 1630 cm-1 enhancement can be ascribed to the carbonyl stretching vibration of CA. The position of this peak shifts slightly to low-wavenumber side from the CA peak of the neutral phase in thermal equilibrium. Consequently, the fast decay component is ascribed to the photoinduced phase. The slow decay component is conceivably due to the metastable center formed by the excitation, because we could not resolve the spectral change corresponding to the slow component in the range between 1595 and 1660 cm-1, where the carbonyl stretching vibration of TTF-CA is observed. The degree of charge transfer of the photoinduced phase is evaluated to 0.52 ± 0.08 by comparing the peak position of the transient enhancement with those of the carbonyl stretching vibration modes in ionic and neutral phases in thermal equilibrium