61 research outputs found

    Stable configurations of entangled graphs and weaves with repulsive interactions

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    Entangled objects such as entangled graphs and weaves are often seen in nature. In the present article, two identical graphs entangled, and weaves with two different color threads are studied. A method to identify stable configurations in the three dimensional space of a given topological entangled structure, a planar graph with crossing information, is proposed by analyzing the steepest descent flow of the energy functional with repulsive interactions. The existence and uniqueness of a solution in the entangled case. In the untangled case, a weave has a unique tangle decomposition with height order, whose components are moving away each other in the order t1/3t^{1/3} as time tt goes to the infinity.Comment: 37 pages, 4 figure

    Prompt improvement of a pressure ulcer by the administration of high viscosity semi-solid nutrition via a nasogastric tube in a man with tuberculosis: a case report

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    INTRODUCTION: Semi-solid nutrition with high viscosity has the advantage of reducing gastroesophageal reflux and diarrhea and shortens the duration of administration compared with liquid nutrition. This is the first report describing the administration of semi-solid nutrition with high viscosity via a nasogastric tube, which achieved a remarkable improvement in the patient's nutritional state. CASE PRESENTATION: A 67-year-old man (mongoloid race, Japanese) with tuberculosis, a pressure ulcer and malnutrition was admitted to our hospital. He also had right hemiplegia, dysphagia and aphasia as sequelae of a cerebral hemorrhage. Before his admission, he had been treated at another hospital with 600 kcal/day of liquid nutrition via a nasogastric tube, which was insufficient and induced severe malnutrition. After he was admitted to our hospital, we increased the quantity of his liquid nutrition without success because of complications, specifically diarrhea and gastroesophageal reflux. As it was difficult to confirm whether or not he would accept gastrostomy feeding, we administered semi-solid nutrition with high viscosity (20,000 mPa x s) via a large-bore nasogastric tube (18 French). Soon after he was started on semi-solid nutrition, his pressure ulcer and malnutrition improved without diarrhea or complications accompanying the large-bore nasogastric tube. CONCLUSION: When patients have problems with liquid nutrition, such as diarrhea or gastroesophageal reflux, semi-solid nutrition via a nasogastric tube is a useful method of achieving improvements in nutritional state in a short period of time

    The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction.

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    Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment

    Validation of ozone data from the Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES)

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    The Superconducting Submillimeter-Wave Limb-Emission Sounder (SMILES) onboard the International Space Station provided global measurements of ozone profiles in the middle atmosphere from 12 October 2009 to 21 April 2010. We present validation studies of the SMILES version 2.1 ozone product based on coincidence statistics with satellite observations and outputs of chemistry and transport models (CTMs). Comparisons of the stratospheric ozone with correlative data show agreements that are generally within 10%. In the mesosphere, the agreement is also good and better than 30% even at a high altitude of 73km, and the SMILES measurements with their local time coverage also capture the diurnal variability very well. The recommended altitude range for scientific use is from 16 to 73km. We note that the SMILES ozone values for altitude above 26km are smaller than some of the correlative satellite datasets; conversely the SMILES values in the lower stratosphere tend to be larger than correlative data, particularly in the tropics, with less than 8% difference below similar to 24km. The larger values in the lower stratosphere are probably due to departure of retrieval results between two detection bands at altitudes below 28km; it is similar to 3% at 24km and is increasing rapidly down below

    Acute Insulin Stimulation Induces Phosphorylation of the Na-Cl Cotransporter in Cultured Distal mpkDCT Cells and Mouse Kidney

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    The NaCl cotransporter (NCC) is essential for sodium reabsorption at the distal convoluted tubules (DCT), and its phosphorylation increases its transport activity and apical membrane localization. Although insulin has been reported to increase sodium reabsorption in the kidney, the linkage between insulin and NCC phosphorylation has not yet been investigated. This study examined whether insulin regulates NCC phosphorylation. In cultured mpkDCT cells, insulin increased phosphorylation of STE20/SPS1-related proline-alanine-rich kinase (SPAK) and NCC in a dose-dependent manner. This insulin-induced phosphorylation of NCC was suppressed in WNK4 and SPAK knockdown cells. In addition, Ly294002, a PI3K inhibitor, decreased the insulin effect on SPAK and NCC phosphorylation, indicating that insulin induces phosphorylation of SPAK and NCC through PI3K and WNK4 in mpkDCT cells. Moreover, acute insulin administration to mice increased phosphorylation of oxidative stress-responsive kinase-1 (OSR1), SPAK and NCC in the kidney. Time-course experiments in mpkDCT cells and mice suggested that SPAK is upstream of NCC in this insulin-induced NCC phosphorylation mechanism, which was confirmed by the lack of insulin-induced NCC phosphorylation in SPAK knockout mice. Moreover, insulin administration to WNK4 hypomorphic mice did not increase phosphorylation of OSR1, SPAK and NCC in the kidney, suggesting that WNK4 is also involved in the insulin-induced OSR1, SPAK and NCC phosphorylation mechanism in vivo. The present results demonstrated that insulin is a potent regulator of NCC phosphorylation in the kidney, and that WNK4 and SPAK are involved in this mechanism of NCC phosphorylation by insulin

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

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    「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

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    「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
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