High Quality Factor Silicon Cantilever Driven by PZT Actuator for Resonant Based Mass Detection

A high quality factor (Q-factor) piezoelectric lead zirconat titanate (PZT) actuated single crystal silicon cantilever was proposed in this paper for resonant based ultra-sensitive mass detection. Energy dissipation from intrinsic mechanical loss of the PZT film was successfully compressed by separating the PZT actuator from resonant structure. Excellent Q-factor, which is several times larger than conventional PZT cantilever, was achieved under both atmospheric pressure and reduced pressures. For a 30 micrometer-wide 100 micrometer-long cantilever, Q-factor was measured as high as 1113 and 7279 under the pressure of 101.2 KPa and 35 Pa, respectively. Moreover, it was found that high-mode vibration can be realized by the cantilever for the pursuit of great Q-factor, while support loss became significant because of the increased vibration amplitude at the actuation point. An optimized structure using node-point actuation was suggested then to suppress corresponding energy dissipation.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Assessment of chemical compositions in coral skeletons (Acropora digitifera and Porites australiensis) as temperature proxies

Although biogenic carbonates, such as foraminifera and coccolithophorids, are valuable tools for reconstructing past environments, scleractinian corals also offer environmental data from tropical to subtropical regions with a higher time resolution. For example, oxygen isotopes (δ18O) and strontium-calcium (Sr/Ca) ratios have been utilized to reconstruct sea surface temperatures and salinity, primarily through the use of massive-type Porites sp. from the Pacific, as well as corals like Diploria and Montastrea from the Atlantic. While a few types of corals other than Porites have been utilized in paleoclimate studies, comprehensive evaluations of their geochemical tracers as temperature proxies have not been thoroughly conducted. Therefore, in this study, we focused on branching-type Acropora, which are found worldwide and are often present in fossil corals. We conducted a comparison of the chemical compositions (δ18O, δ13C, Sr/Ca, U/Ca, Mg/Ca, and Ba/Ca) of Acropora digitifera and Porites australiensis through temperature-controlled culture experiments. The validity of using the chemical components of A. digitifera as temperature proxies was then evaluated. Three colonies of A. digitifera and P. australiensis were collected for culture experiments on Sesoko Island, Okinawa, Japan. We reared coral samples in seawater with five different temperature settings (18, 21, 24, 27, 30°). The calcification rate and photosynthesis efficiency (Fv/Fm) of each nubbin were measured during the experimental period. After the culture experiment for 77 days, chemical components in skeletal parts grown during the experiment were then measured. Consequently, the mean growth rates and Fv/Fm throughout the experiment were higher for A. digitifera (0.22%/d and 0.63 for growth rate and Fv/Fm) compared to those for P. australiensis (0.11%/d and 0.38 for growth rate and Fv/Fm). This suggests that the higher efficiency of photosynthesis in A. digitifera would promote greater calcification compared to P. australiensis. Regarding the potential use as temperature proxies, A. digitifera exhibited a strong negative correlation, on average, between δ18O and the water temperature (r = 0.95, p< 0.001). The temperature dependency was found to be comparable to that reported in Porites corals (-0.11 and -0.17 ‰/°C for P. australiensis and A. digitifera, respectively). Thus, the δ18O of A. digitifera appeared to be a useful temperature proxy, although it was also slightly influenced by skeletal growth rate at the same temperature. A strong negative correlation was also observed between the mean Sr/Ca ratio and temperature in A. digitifera (r = 0.61, p< 0.001) as well as P. australiensis (r = 0.56, p< 0.001), without a clear influence from the skeletal growth rate. Therefore, the skeletal Sr/Ca ratio in corals may have been primarily influenced by water temperature, although large deviations in Sr/Ca were observed in A. digitifera, even at the same temperature settings. This deviation can be reduced by subsampling an apical part of a polyp including the axis of skeletal growth. The U/Ca ratio of A. digitifera appeared to be affected by internal pH variation within the corals, especially at 30°C. Similar to U/Ca ratios, metabolic and kinetic effects on corals were observed in δ13C of A. digitifera at 18 and 30°C. In addition, considering the variation pattern of both U/Ca and δ13C of A. digitifera at 30°C, it has been suggested that respirations may overwhelm photosynthesis for coral samples at 30°C. Therefore, the U/Ca and δ13C of A. digitifera could potentially be used as proxies of biomineralization processes, whereas the δ18O and Sr/Ca displayed a high possibility of acting as temperature proxies

TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment

Background Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples. Methods We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort. Results Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT+ T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance. Conclusions The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer

Chocolate consumption and risk of gestational diabetes mellitus: the Japan Environment and Children’s Study

The association of chocolate consumption with risk of gestational diabetes has not been examined. We aimed to investigate the prospective association between chocolate consumption and risk of gestational diabetes in a large birth cohort in Japan. A total of 97 454 pregnant women with a median gestational age of 12 weeks were recruited from January 2011 to March 2014. Data on demographic information, disease history, socio-economic status, lifestyle and dietary habits were obtained at the study enrolment. Dietary intake during the past 12 months before study enrolment was assessed through a semi-quantitative FFQ. The logistic regression was used to obtain the OR of gestational diabetes in relation to chocolate consumption. Among 84 948 women eligible for the analysis, 1904 cases of gestational diabetes (2·2 %) were identified during the period of pregnancy. After controlling for potential confounding factors including age, smoking status, drinking status, education level, occupation, pre-pregnant BMI, depression, previous history of macrosomia babies, parity, physical activity and dietary factors, women in the highest quartile of chocolate consumption, compared with those in the lowest quartile, had a significantly lower risk of developing gestational diabetes (OR 0·78, 95 % CI 0·67, 0·90; P for trend = 0·002). Stratified analyses suggested that the association was not significantly modified by pre-pregnancy BMI, age, parity, smoking status or drinking status. The present prospective cohort study provided evidence that chocolate consumption was associated with a significant lower risk of gestational diabetes in Japanese women

Comparative single-cell genomics of Atribacterota JS1 in the Japan Trench hadal sedimentary biosphere

Deep-sea and subseafloor sedimentary environments host heterotrophic microbial communities that contribute to Earth’s carbon cycling. However, the potential metabolic functions of individual microorganisms and their biogeographical distributions in hadal ocean sediments remain largely unexplored. In this study, we conducted single-cell genome sequencing on sediment samples collected from six sites (7,445–8,023 m water depth) along an approximately 500 km transect of the Japan Trench during the International Ocean Discovery Program Expedition 386. A total of 1,886 single-cell amplified genomes (SAGs) were obtained, offering comprehensive genetic insights into sedimentary microbial communities in surface sediments (<1 m depth) above the sulfate-methane transition zone along the Japan Trench. Our genome data set included 269 SAGs from Atribacterota JS1, the predominant bacterial clade in these hadal environments. Phylogenetic analysis classified SAGs into nine distinct phylotypes, whereas metagenome-assembled genomes were categorized into only two phylotypes, advancing JS1 diversity coverage through a single cell-based approach. Comparative genomic analysis of JS1 lineages from different habitats revealed frequent detection of genes related to organic carbon utilization, such as extracellular enzymes like clostripain and α-amylase, and ABC transporters of oligopeptide from Japan Trench members. Furthermore, specific JS1 phylotypes exhibited a strong correlation with in situ methane concentrations and contained genes involved in glycine betaine metabolism. These findings suggest that the phylogenomically diverse and novel Atribacterota JS1 is widely distributed in Japan Trench sediment, playing crucial roles in carbon cycling within the hadal sedimentary biosphere

Recent Advancements in Cytotoxic T Lymphocyte Generation Methods Using Carbohydrate-Coated Liposomes

Both tumor-specific CD4(+) and CD8(+) T cells have been identified, and the latter is known as a major effector of adaptive antitumor immune responses. Optimal antitumor immune responses are considered to require the concomitant activation of both CD8(+) and CD4(+) T cells and the additional selective activation of CD4(+) T cells with helper, but not regulatory function. As optimal antitumor immune responses are generated by the concomitant activation of both T cell types, it is necessary for vaccine methods involving cytotoxic T-lymphocytes (CTLs) generation to possess a mechanism whereby antigen presenting cells can present administrated exogenous antigens on not only Major histocompatibility complex (MHC) class II, but also MHC class I molecules

Recent Advancements in Cytotoxic T Lymphocyte Generation Methods Using Carbohydrate-Coated Liposomes

Both tumor-specific CD4 + and CD8 + T cells have been identified, and the latter is known as a major effector of adaptive antitumor immune responses. Optimal antitumor immune responses are considered to require the concomitant activation of both CD8 + and CD4 + T cells and the additional selective activation of CD4 + T cells with helper, but not regulatory function. As optimal antitumor immune responses are generated by the concomitant activation of both T cell types, it is necessary for vaccine methods involving cytotoxic T-lymphocytes (CTLs) generation to possess a mechanism whereby antigen presenting cells can present administrated exogenous antigens on not only Major histocompatibility complex (MHC) class II, but also MHC class I molecules