The BRAF–MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells

The mitogen-activated protein kinase (MAPK) pathway is frequently activated in human cancers, leading to malignant phenotypes such as autonomous cellular proliferation. Here, we demonstrate a novel role of the activated MAPK pathway in immune evasion by melanoma cells with the mutation of BRAF, which encodes a MAPKKs, (BRAFV600E). MEK inhibitor U0126 or RNA interference (RNAi) for BRAFV600E decreased production of the immunosuppressive soluble factors interleukin (IL)-10, VEGF, or IL-6 from melanoma cells to levels comparable to those after signal transducer and activator of transcription (STAT)3 inactivation. The suppressive activity of the culture supernatants from the melanoma cells on the production of inflammatory cytokines IL-12 and tumor necrosis factor α by dendritic cells upon lipopolysaccharide stimulation was markedly reduced after transduction with BRAFV600E RNAi, comparable to the effects observed with STAT3 RNAi transduction. No additive or synergistic effects were observed by the simultaneous transduction of RNAi for both BRAFV600E and STAT3. Furthermore, specific DNA binding and transcriptional activity of STAT3 were not affected by down-regulation of the MAPK signaling with the BRAF RNAi. These results indicate that the MAPK signal, along with the STAT3 signal, is essential for immune evasion by human melanomas that have constitutively active MAPK signaling and is a potential molecular target for overcoming melanoma cell evasion of the immune system

RAISE-3 for Agile On-Orbit Demonstration of Innovative Satellite Technologies: Mission Definition and Conceptual Design

The Japan Aerospace Exploration Agency (JAXA) has selected on-orbit demonstration missions for the Innovative Satellite Technology Demonstration-3 project in May 2020, as part of the Innovative Satellite Technology Demonstration Program. Seven on-orbit demonstration missions were selected in a category of parts, components and subsystems and those missions will be demonstrated onboard the RApid Innovative payload demonstration SatellitE-3 (RAISE-3). This 100kg-class satellite developed by JAXA is a flagship of the Innovative Satellite Technology Demonstration-3 fleet. This paper describes an overview of the demonstration missions and system specifications of RAISE-3, as well as results of conceptual design of the satellite and a partial application of digital development process to an initial phase of the project. Further, project plan and technical challenges to be studied in a project implementation phase are also discussed

RAISE-2 for Agile On-Orbit Demonstration of Innovative Satellite Technologies: Program Strategy, Mission Definition, and Preliminary Design

The Japan Aerospace Exploration Agency (JAXA) has provided the second demonstration opportunity of the Innovative Satellite Technology Demonstration Program. In this second mission, JAXA develops the Rapid Innovative Payload Demonstration Satellite-2 (RAISE-2) that carries six components and parts as on-orbit demonstration themes. This paper presents an overview of the RAISE-2’s demonstration themes, mission definition including standard platform specifications, results of Phase-A study and preliminary design

The Luminosity Function of Lyman Alpha Emitters at Redshift z~5.7

We report results of a deep wide-field narrowband survey for redshift z~5.7 Ly alpha emitters carried out with SuprimeCam on Subaru 8.3-m telescope. Deep narrowband imaging of the SSA22 field through a 120 A bandpass filter centered at 8150 A was combined with deep multicolor RIz' SuprimeCam broadband imaging, and BVRZ imaging taken with CFHT's CFH12K camera to select high-redshift galaxy candidates. Spectroscopic observations were made using the new wide-field multi-object DEIMOS spectrograph on Keck for 22 of the 26 candidate objects. Eighteen objects were identified as z~5.7 Lyman alpha emitters, and a further nineteenth candidate was identified based on an LRIS spectrum. At the 3.3 A resolution of the DEIMOS spectra the asymmetric profile for Ly alpha emission with its steep blue fall-off can be clearly seen. We use this to describe the distribution of equivalent widths and the continuum color break properties for z~5.7 Ly alpha galaxies compared with foreground objects. The large majority (>75%) of Ly alpha lines have rest frame equivalent widths less than 240 A and can be understood in terms of young star forming galaxies with a Salpeter initial mass function for the stars. With narrowband selection criteria of I-N > 0.7 and N<25.05 (AB mags) we find a surface density of Ly alpha emitters of 0.03 per square arcminute per (deltaz=0.1) to a limiting flux just under 2e-17 erg/cm2/s. The luminosity function of the Ly alpha emitters is similar to that at lower redshifts to the lowest measurable luminosity of 1e43 ergs/s as is the universal star formation rate based on their continuum properties. We note that the objects are highly structured in both spatial and spectral properties on the angular scale of the fields (~60 Mpc), and that multiple fields will have to be averaged to accurately measure their ensemble properties.Comment: 12 pages, 20 figures, emulateapj, to appear in the Astronomical Journal (February 2004), version with higher quality figures available at http://www.ifa.hawaii.edu/publications/preprints/Hu_03-95.pdf Fixed problem with cited papers appearing as numbered hypertex links instead of text (only affected astro-ph pdf file

カン focal nodular hyperplasia ニ タイスル フククウキョウカ カン セツジョジュツ

Recently, laparoscopic hepatectomy of the liver has been reported to be safe, with possible advantages to the patients such as reduced postoperative pain and shorter hospital stay. We report successful laparoscopic partial liver resections for two cases of focal nodular hyperplasia. Two cases of 43-year-old male and 69-year-old male, with chronic hepatitis C and without any symptoms, presented in each other a solitary mass 1.5 and 1.0 cm in size at the edge of the liver on diagnostic imagings. The patients underwent laparoscopic partial hepatectomy to rule out well differentiated hepatocellular carcinoma. The histopathological diagnosis was focal nodular hyperplasia. Each patient had an uneventful postoperative recovery and had been free from recurrence during the 6 years follow-up period. Laparoscopic partial hepatectomy is indicated in patients with benign solid mass located at the edge of the liver

Subaru Deep Survey V. A Census of Lyman Break Galaxies at z=4 and 5 in the Subaru Deep Fields: Photometric Properties

(abridged) We investigate photometric properties of Lyman Break Galaxies (LBGs) at z=3.5-5.2 based on large samples of 2,600 LBGs detected in deep (i'~27) and wide-field (1,200 arcmin^2) images taken in the Subaru Deep Field (SDF) and the Subaru/XMM Deep Field (SXDF). The selection criteria for the LBG samples are examined with 85 spectroscopically identified objects and by Monte Carlo simulations. We find in the luminosity functions of LBGs (i) that the number density of bright galaxies (M_{1700}<-22; corresponding to SFR_{corr}>100 Msolar yr^{-1}) decreases significantly from z=4 to 5 and (ii) that the faint-end slope of the luminosity function may become steeper towards higher redshifts. We estimate dust extinction of z=4 LBGs with M<M^* from UV slopes, and obtain E(B-V)=0.15+/-0.03 as the mean value. The dust extinction remains constant with apparent luminosity, but increases with intrinsic luminosity. We find no evolution in dust extinction between LBGs at z=3 and 4. We investigate the evolution of UV-luminosity density at 1700A, rho, and find that rho does not significantly change from z=3 to z=5, i.e., rho(z=4)/rho(z=3)=1.0+/-0.2 and rho(z=5)/rho(z=3)=0.8+/-0.4, thus the cosmic star-formation rate (SFR) density remains constant. We find that the stellar mass density estimated from the cosmic SFR is consistent with those derived directly from the stellar mass function at z=0-1, but exceeds those at z~3 by a factor of 3. We find that the ratio of the UV-luminosity density of Ly-a emitters (LAEs) to that of LBGs is ~60% at z=5, and thus about a half of the star formation at z=5 probably occurs in LAEs. We obtain a constraint on the escape fraction of UV-ionizing photons produced by LBGs, f_{esc}>~0.13.Comment: 41 pages, 22 figures, ApJ in press. Paper with high resolution figures is available at http://hikari.astron.s.u-tokyo.ac.jp/~ouchi/work/astroph/SDS_V_VI/SDS_V.pdf (PDF

スイ カセイ ノウホウ ニ タイスル フククウキョウカ ノホウ イ フンゴウジュツ : イヘキ トノ ユチャク オ ゼンテイ ト シナイ アンゼンナ ジュツシキ

A forty seven-year-old male who had been in clinical follow-up for a pancreatic pseudocystunderwent a laparoscopic cystogastrostomy through the lesser peritoneal sac in 1996. Thisprocedure is performed by creating a cystotomy and posterior gastrotomy through whichan Endo GIATM is applied. The mouth of cystogastrostomy is closed using continuous suturesby Endo STITCHTM. This approach does not rely on adhesions between the pseudocyst andposterior wall of the stomach, and offers clear advantages over previously described techniquesin the management of pancreatic pseudocyst

A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis

In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high clinical efficacy shortly after the subcutaneous injection. To elucidate the mechanism underlying the rapid onset of the effects of ozoralizumab, we compared the biodistribution kinetics of ozoralizumab and adalimumab after subcutaneous injection in an animal model of arthritis. Alexa Fluor 680-labeled ozoralizumab and adalimumab were administered by subcutaneous injection once (2 mg/kg) at five weeks after induction of collagen-induced arthritis (CIA) in an animal arthritis model. The time-course of changes in the fluorescence intensities of the two compounds in the paws and serum were evaluated. The paws of the CIA mice were harvested at four and eight hours after the injection for fluorescence microscopy. Biofluorescence imaging revealed better distribution of ozoralizumab to the joint tissues than of adalimumab, as early as at four hours after the injection. Fluorescence microscopy revealed a greater fluorescence intensity of ozoralizumab in the joint tissues than that of adalimumab at eight hours after the injection. Ozoralizumab showed a significantly higher absorption rate constant as compared with adalimumab. These results indicate that ozoralizumab enters the systemic circulation more rapidly and is distributed to the target tissues earlier and at higher levels than conventional IgG antibodies. Our investigation provides new insight into the mechanism underlying the rapid onset of the effects of ozoralizumab in clinical practice.Oyama S., Ebina K., Etani Y., et al. A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis. Scientific Reports 12, 18102 (2022); https://doi.org/10.1038/s41598-022-23152-6