Middle Power Measurement in Semi-tethered Swimming using Ergometer Attachment

The purposes of this study weie to measure middle power, energy which had been supplied mainly from the lactic acid system, during swimming using an ergometer attachment and to evaluate swimming performance by this middle power To perform these purposes, a middle power measurement test in semi-tethered swimming (STS33) using an ergometer attachment was developed In STS33, the load of the ergometer attachment was set to 7.0kg and the power measurement interval was set at 5.0 seconds The subject was instructed to swim at full strength for 33.0 seconds Power measurements using the ergometer attachment were taken 3 times during the 33.0 seconds at the end of 10s, 20s and 30s respectively The first measurement (1st measured phase) was taken between 5 and 10 seconds from the start of the swim The second measurement (2nd measured phase) was taken between 15 and 20 seconds of the swim, and the third measuiement (3rd measured phase) was taken between 25 and 30 seconds from the start of the swim by the present investigators As in preliminary experiments, the exercise intensity of the STS33 was measured as the average blood lactate concentration produced by the work rate After each STS33, a blood sample was taken by a licensed nurse under supervision of a medical doctor Subjects were 5 junior elite swimmers designated to tram by the N prefecture Swim Association The group mean post exercise blood lactate concentration was 10 5mM/l These concentration of blood lactate was greater than the OBLA measurement of 4mM for lactate accumulation developing in the middle phase of a swim trial This result led to the conclusion that the STS33 test could be used to evaluate the middle power In a main experiment, 21 male elite junior swimmers were measured Middle power in swimming in each subject was measured by the above-mentioned STS33 and the relationship between the group mean middle power and group mean total swim time was analyzed The relationship between the average power (P watt) of the 3 measured phases in STS33 and swimming velocity (V m/sec) in 50m event was P =-134.53 + 87.02 V (r = 0.880, p≦0.001) The relationship between the average power (P) of the 3 phases in STS33 and swimming velocity (V) in 100m event was given by P = - 191.95 + 128.92 V ( r=0 940, p≦O.001) From these results, the middle power in STS33 is appropriate for evaluating swimming performances in 50m and 100m event

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Transcription factor 8 activates R-Ras to regulate angiogenesis

We have recently reported that transcription factor 8 (TCF8) negatively regulates pathological angiogenesis by regulating endothelial invasiveness by acting as a transcriptional attenuator of matrix metalloproteinase 1. TCF8 also modulates cell–matrix and cell–cell adhesion; however molecular mechanism of this TCF8 function remains obscure. Here, we provide evidence that TCF8 activates R-Ras, another class of angiogenic regulator, to suppress angiogenesis by a mechanism other than a transcriptional attenuator. Tube formation by human umbilical vein endothelial cells (HUVECs) facilitated by TCF8 suppression was significantly inhibited by the expression of onstitutive active mutant of R-Ras. When we examined the mRNA expression levels of R-Ras regulators, no significant changes were observed to explain the R-Ras activation by TCF8. Interestingly, we found that TCF8 bound to CalDAG-GEFIII, an R-Ras activator, in the cytosol, indicating that TCF8 emanates signaling for R-Ras activation from cytosol to regulate angiogenesis negatively

Integral Role of Transcription Factor 8 in the Negative Regulation of Tumor Angiogenesis

Angiogenesis is involved in various physiologic and pathological conditions, including tumor growth, and is tightly regulated by the orchestration of proangiogenic and antiangiogenic factors. Inhibition of vascular endothelial growth factor (VEGF), the best-established antiangiogenic treatment in cancer, has shown some effectiveness; however, the identification of novel regulators, whose function is independent of VEGF, is required to achieve better outcomes. Here, we show that transcription factor 8 (TCF8)is up-regulated in endothelial cells during angiogenesis, acting as a negative regulator. Furthermore, TCF8 is specifically expressed in the endothelium of tumor vessels. Tcf8-heterozygous knockout mice are more permissive than wildtype mice to the formation of tumor blood vessels in s.c. implanted melanoma, which seems to contribute to the more aggressive growth and the lung metastases of the tumor in mutant mice. Suppression of TCF8 facilitates angiogenesis in both in vitro and ex vivo models, and displays comprehensive cellular phenotypes, including enhanced cell invasion, impaired cell adhesion, and increased cell monolayer permeability due to, at least partly, MMP1 overexpression, attenuation of focal adhesion formation, and insufficient VE-cadherin recruitment, respectively. Taken together, our findings define a novel, integral role for TCF8 in the regulation of pathologic angiogenesis, and propose TCF8 as a target for therapeutic intervention in cancer

Review of Bumpless Build Cube (BBCube) Using Wafer-on-Wafer (WOW) and Chip-on-Wafer (COW) for Tera-Scale Three-Dimensional Integration (3DI)

Bumpless Build Cube (BBCube) using Wafer-on-Wafer (WOW) and Chip-on-Wafer (COW) for Tera-Scale Three-Dimensional Integration (3DI) is discussed. Bumpless interconnects between wafers and between chips and wafers are a second-generation alternative to the use of micro-bumps for WOW and COW technologies. WOW and COW technologies for BBCube can be used for homogeneous and heterogeneous 3DI, respectively. Ultra-thinning of wafers down to 4 μm offers the advantage of a small form factor, not only in terms of the total volume of 3D ICs, but also the aspect ratio of Through-Silicon-Vias (TSVs). Bumpless interconnect technology can increase the number of TSVs per chip due to the finer TSV pitch and the lower impedance of bumpless TSV interconnects. In addition, high-density TSV interconnects with a short length provide the highest thermal dissipation from high-temperature devices such as CPUs and GPUs. This paper describes the process platform for BBCube WOW and COW technologies and BBCube DRAMs with high speed and low IO buffer power by enhancing parallelism and increasing yield by using a vertically replaceable memory block architecture, and also presents a comparison of thermal characteristics in 3D structures constructed with micro-bumps and BBCube