Cherenkov Phase Matched Monochromatic Tunable Terahertz Wave Generation

Non

Multicascade-linked synthetic wavelength digital holography using an optical-comb-referenced frequency synthesizer

Digital holography (DH) is a promising method for non-contact surface topography because the reconstructed phase image can visualize the nanometer unevenness in a sample. However, the axial range of this method is limited to the range of the optical wavelength due to the phase wrapping ambiguity. Although the use of two different wavelengths of light and the resulting synthetic wavelength, i.e., synthetic wavelength DH, can expand the axial range up to a few tens of microns, this method is still insufficient for practical applications. In this article, a tunable external cavity laser diode phase-locked to an optical frequency comb, namely, an optical-comb-referenced frequency synthesizer, is effectively used for multiple synthetic wavelengths within the range of 32 um to 1.20 m. A multiple cascade link of the phase images among an optical wavelength (= 1.520 um) and 5 different synthetic wavelengths (= 32.39 um, 99.98 um, 400.0 um, 1003 um, and 4021 um) enables the shape measurement of a reflective millimeter-sized stepped surface with the axial resolution of 34 nm. The axial dynamic range, defined as the ratio of the maximum axial range (= 0.60 m) to the axial resolution (= 34 nm), achieves 1.7*10^8, which is much larger than that of previous synthetic wavelength DH. Such a wide axial dynamic range capability will further expand the application field of DH for large objects with meter dimensions.Comment: 19 pages, 7 figure

CD226 (DNAM-1) Is Involved in Lymphocyte Function–associated Antigen 1 Costimulatory Signal for Naive T Cell Differentiation and Proliferation

Upon antigen recognition by the T cell receptor, lymphocyte function–associated antigen 1 (LFA-1) physically associates with the leukocyte adhesion molecule CD226 (DNAM-1) and the protein tyrosine kinase Fyn. We show that lentiviral vector-mediated mutant (Y-F322) CD226 transferred into naive CD4+ helper T cells (Ths) inhibited interleukin (IL)-12–independent Th1 development initiated by CD3 and LFA-1 ligations. Moreover, proliferation induced by LFA-1 costimulatory signal was suppressed in mutant (Y-F322) CD226-transduced naive CD4+ and CD8+ T cells in the absence of IL-2. These results suggest that CD226 is involved in LFA-1–mediated costimulatory signals for triggering naive T cell differentiation and proliferation. We also demonstrate that although LFA-1, CD226, and Fyn are polarized at the immunological synapse upon stimulation with anti-CD3 in CD4+ and CD8+ T cells, lipid rafts are polarized in CD4+, but not CD8+, T cells. Moreover, proliferation initiated by LFA-1 costimulatory signal is suppressed by lipid raft disruption in CD4+, but not CD8+, T cells, suggesting that the LFA-1 costimulatory signal is independent of lipid rafts in CD8+ T cells

Effect of the Tokyo 2020 Summer Olympic Games on COVID-19 incidence in Japan: A synthetic control approach

BACKGROUND: The Tokyo 2020 Summer Olympic Games (23 July-8 August 2021) were held in the middle of Japan\u27s fifth wave of COVID-19, when the number of cases was on the rise, and coincided with the fourth state of emergency implemented by the host city, Tokyo. AIM: This study aimed to assess whether the hosting of the Games was associated with a change in the number of COVID-19 cases in Japan using a synthetic control method. METHODS: A weighted average of control countries with a variety of predictors was used to estimate the counterfactual trajectory of daily COVID-19 cases per 1 000 000 population in the absence of the Games in Japan. Outcome and predictor data were extracted using official and open sources spanning several countries. The predictors comprise the most recent country-level annual or daily data accessible during the Games, including the stringency of the government\u27s COVID-19 response, testing capacity and vaccination capacity; human mobility index; electoral democracy index and demographic, socioeconomic, health and weather information. After excluding countries with missing data, 42 countries were ultimately used as control countries. RESULTS: The number of observed cases per 1 000 000 population on the last day of the Games was 109.2 (7-day average), which was 115.7% higher than the counterfactual trajectory comprising 51.0 confirmed cases per 1 000 000 population. During the Olympic period (since 23 July), the observed cumulative number of cases was 61.0% higher than the counterfactual trajectory, comprising 143 072 and 89 210 confirmed cases (p=0.023), respectively. The counterfactual trajectory lagged 10 days behind the observed trends. CONCLUSIONS: Given the increasing likelihood that new emerging infectious diseases will be reported in the future, we believe that the results of this study should serve as a sentinel warning for upcoming mega-events during COVID-19 and future pandemics

CCL2 as a potential therapeutic target for clear cell renal cell carcinoma

We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration. For functional analysis of CCL2 in ccRCC cells, we generated subclones of WT8 cells that overexpressed CCL2 and subclones 786-O cells in which CCL2 expression was knocked down. Although CCL2 expression did not affect cell proliferation in vitro, CCL2 overexpression enhanced and CCL2 knockdown suppressed tumor growth, angiogenesis, and macrophage infiltration in vivo. We then depleted macrophages from tumor xenografts by administration of clodronate liposomes to confirm the role of macrophages in ccRCC. Depletion of macrophages suppressed tumor growth and angiogenesis. To examine the effect of inhibiting CCL2 activity in ccRCC, we administered CCL2 neutralizing antibody to primary RCC xenografts established from patient surgical specimens. Inhibition of CCL2 activity resulted in significant suppression of tumor growth, angiogenesis, and macrophage infiltration. These results suggest that CCL2 is involved in angiogenesis and macrophage infiltration in ccRCC, and that CCL2 could be a potential therapeutic target for ccRCC

Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial

TRIAL DESIGN: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. METHODS: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. RESULTS: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. CONCLUSIONS: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study

大腸癌患者における術前血清インターロイキン6 が全身性炎症反応に与える影響についての検討

背景：全身性炎症反応は担癌患者における免疫応答を反映し，予後と関連することが報告されている．目的：血清インターロイキン6（IL-6）と臨床背景因子，とりわけ全身炎症性反応との関連について大腸癌患者を対象として検討すること．方法：大腸癌患者20 人の術前IL-6 濃度を測定し，L 群（低IL-6 群，11 人；IL-6＜10 pg/ml）とH 群（高IL-6 群，9 人；IL-6 ≥ 10 pg/ml）の2 群に分けて臨床背景因子との関連について検討した．結果：血清C-reactive protein（CRP）値＞1.0 mg/dl（P＝0.038），血沈；9±7 versus 31±24（mm/ hr , P＝0.031）が2 群間で有意差を認めたが，血小板数・血清アルブミン値・Glasgow Prognostic Score・好中球リンパ比に2 群間で有意差は認めなかった．2 群間の生存曲線による解析は，H 群はL 群に比べて予後不良の傾向を認めたが，統計学的な有意差は認められなかった．結論：高IL-6 血症は大腸癌術前患者における高CRP 値，血沈の亢進といった全身性炎症反応と相関し，予後との関連を示唆するものであった．Purpose：To investigate the relationship between preoperative serum interleukin-6（IL-6）level and clinical characteristics, including systemic inflammatory response（SIR）related characteristics, in colorectal cancer（CRC）patients undergoing surgery. Patients and methods：Twenty CRC patients who had undergone curative surgery were divided into two groups as follows：Group A（n＝9）；patients with low serum IL-6 level（＜10 pg/ml）and Group B（n＝11）；patients with high serum IL-6 level（≥ 10 pg/ml）. Chi squared test and Mann-Whitney test were performed to compare the clinical characteristics of two groups. Kaplan-Meier analysis and log rank test were used to compare the two groups in relation to overall survival. Results：Among a lot of clinical characteristics, there were significant differences between the two groups in serum C-reactive protein（CRP）level（0.2±0.1 versus 2.9 ±4.9 mg/dl, mean± SD, P＝0.016）and erythrocyte sedimentation rate（ESR）（9±7 versus 31±24 mm/hr, mean ± SD, P＝0.031）. However, there was no significant difference between the two groups in overall survival. Conclusion：There is a close relationship between preoperative serum IL-6 level and SIR related clinical characteristics such as serum CRP level and ESR in CRC patients

Multicascade-linked synthetic wavelength digital holography using an optical-comb-referenced frequency synthesizer

Digital holography (DH) is a promising method for non-contact surface topography because the reconstructed phase image can visualize the nanometer unevenness in a sample. However, the axial range of this method is limited to the range of the optical wavelength due to the phase wrapping ambiguity. Although the use of two different wavelengths of light and the resulting synthetic wavelength, i.e., synthetic wavelength DH, can expand the axial range up to several hundreds of millimeters, its axial precision does not reach sub-micrometer. In this article, we constructed a tunable external cavity laser diode phase-locked to an optical frequency comb, namely, an optical-comb-referenced frequency synthesizer, enabling us to generate multiple synthetic wavelengths within the range of 32 μm to 1.20 m. A multiple cascade link of the phase images among an optical wavelength ( = 1.520 μm) and 5 different synthetic wavelengths ( = 32.39 μm, 99.98 μm, 400.0 μm, 1003 μm, and 4021 μm) enables the shape measurement of a reflective millimeter-sized stepped surface with the axial resolution of 34 nm. The axial dynamic range, defined as the ratio of the axial range ( = 2.0 mm) to the axial resolution ( = 34 nm), achieves 5.9 × 105, which is larger than that of previous synthetic wavelength DH. Such a wide axial dynamic range capability will further expand the application field of DH for large objects with meter dimensions