397 research outputs found
Static stiffness modeling and sensitivity analysis for geared system used for rotary feeding
The positioning accuracy of rotary feed system under load greatly depends on the static stiffness of mechanical transmission system. This paper proposes a unified static stiffness model of rotary feed system with geared transmission system. Taking the torsional stiffness of transmission shaft and mesh stiffness of gear pairs into account, the motion equations of the whole transmission system are presented. Based on the static equilibrium, a unified expression for the relationship between torsional angles of two adjacent elements is derived. Then a unified static stiffness model is presented. Furthermore, analytical expressions for sensitivity analysis of the static stiffness on the individual element’s stiffness and design parameters are derived. The presented model is verified by a traditional model, and a good agreement is obtained. The influence of phase angle of meshing gear pairs on the resultant static stiffness is investigated. An example transmission system is employed to perform the sensitivity analysis and the results are analyzed. The proposed model provides an essential tool for the design of rotary feed system satisfying requirement of static stiffness
Treatment with ActRIIB-mFc Produces Myofiber Growth and Improves Lifespan in the \u3cem\u3eActa1\u3c/em\u3e H40Y Murine Model of Nemaline Myopathy
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Deconstruction of plant biomass by a Cellulomonas strain isolated from an ultra-basic (lignin-stripping) spring.
Plant material falling into the ultra-basic (pH 11.5-11.9) springs within The Cedars, an actively serpentinizing site in Sonoma County, California, is subject to conditions that mimic the industrial pretreatment of lignocellulosic biomass for biofuel production. We sought to obtain hemicellulolytic/cellulolytic bacteria from The Cedars springs that are capable of withstanding the extreme alkaline conditions wherein calcium hydroxide-rich water removes lignin, making cell wall polysaccharides more accessible to microorganisms and their enzymes. We enriched for such bacteria by adding plant debris from the springs into a synthetic alkaline medium with ground tissue of the biofuel crop switchgrass (Panicum virgatum L.) as the sole source of carbon. From the enrichment culture we isolated the facultative anaerobic bacterium Cellulomonas sp. strain FA1 (NBRC 114238), which tolerates high pH and catabolizes the major plant cell wall-associated polysaccharides cellulose, pectin, and hemicellulose. Strain FA1 in monoculture colonized the plant material and degraded switchgrass at a faster rate than the community from which it was derived. Cells of strain FA1 could be acclimated through subculturing to grow at a maximal concentration of 13.4% ethanol. A strain FA1-encoded β-1, 4-endoxylanase expressed in E. coli was active at a broad pH range, displaying near maximal activity at pH 6-9. Discovery of this bacterium illustrates the value of extreme alkaline springs in the search for microorganisms with potential for consolidated bioprocessing of plant biomass to biofuels and other valuable bio-inspired products
Survival Motor Neuron (SMN) Protein Insufficiency Exacerbates Renal Ischemia/Reperfusion Injury
The survival of motor neuron (SMN) protein is ubiquitously involved in spliceosome assembly and ribonucleoprotein biogenesis. SMN protein is expressed in kidney and can affect cell death processes. However, the role of SMN in acute kidney injury (AKI) is largely unknown. In the current study, we found that the expression of SMN in the kidney was significantly reduced in both clinical ischemic AKI and a mouse model of renal ischemia-reperfusion injury (IRI). We then used SMN heterozygous knockout (SMN+/-) mice and found that the declines in renal function, tubular injury, and tubular cell apoptosis after experimental IRI were significantly more severe in SMN+/− mice than those in their wild-type littermates. Concomitantly, the canonical transcription factor nuclear factor-κb (NFκb) signaling was enhanced in ischemic SMN+/− mice. In vitro, cobalt dichloride (CoCl2) treatment reduced SMN expression in proximal tubular epithelial cells. In addition, CoCl2-induced apoptosis and activation of NFκb signaling pathway were enhanced by transient transfection of a small-interfering RNA (siRNA) against SMN while attenuated by transient transfection of a full-length SMN plasmid. Taken together, this study for the first time supported the protective role of SMN in ischemic AKI
(-)-Epigallocatechin-3-gallate ameliorates learning and memory impairments by attenuating peroxidation in APP/PS1 transgenic mice
A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen.
BACKGROUND: Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts. METHODS: We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses. RESULTS: We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested. CONCLUSIONS: Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans
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Retrogressive thaw slumps along the Qinghai-Tibet Engineering Corridor: a comprehensive inventory and their distribution characteristics
The important Qinghai–Tibet Engineering Corridor (QTEC) covers the part of the Highway and Railway underlain by permafrost. The permafrost on the QTEC is sensitive to climate warming and human disturbance and suffers accelerating degradation. Retrogressive thaw slumps (RTSs) are slope failures due to the thawing of ice-rich permafrost. They typically retreat and expand at high rates, damaging infrastructure, and releasing carbon preserved in frozen ground. Along the critical and essential corridor, RTSs are commonly distributed but remain poorly investigated. To compile the first comprehensive inventory of RTSs, this study uses an iteratively semi-automatic method built on deep learning to delineate thaw slumps in the 2019 PlanetScope CubeSat images over a ∼ 54 000 km2 corridor area. The method effectively assesses every image pixel using DeepLabv3+ with limited training samples and manually inspects the deep-learning-identified thaw slumps based on their geomorphic features and temporal changes. The inventory includes 875 RTSs, of which 474 are clustered in the Beiluhe region, and 38 are near roads or railway lines. The dataset is available at https://doi.org/10.5281/zenodo.6397029 (Xia et al., 2021a), with the Chinese version at DOI: https://doi.org/10.11888/Cryos.tpdc.272672 (Xia et al. 2021b). These RTSs tend to be located on north-facing slopes with gradients of 1.2–18.1∘ and distributed at medium elevations ranging from 4511 to 5212 m a.s.l. They prefer to develop on land receiving relatively low annual solar radiation (from 2900 to 3200  kWh m−2), alpine meadow covered, and loam underlay. Our results provide a significant and fundamental benchmark dataset for quantifying thaw slump changes in this vulnerable region undergoing strong climatic warming and extensive human activities.
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Inducible Depletion of Satellite Cells in Adult, Sedentary Mice Impairs Muscle Regenerative Capacity without Affecting Sarcopenia
A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and strength. Although the etiology of sarcopenia is unknown, the correlation during aging between the loss of activity of satellite cells, which are endogenous muscle stem cells, and impaired muscle regenerative capacity has led to the hypothesis that the loss of satellite cell activity is also a cause of sarcopenia. We tested this hypothesis in male sedentary mice by experimentally depleting satellite cells in young adult animals to a degree sufficient to impair regeneration throughout the rest of their lives. A detailed analysis of multiple muscles harvested at various time points during aging in different cohorts of these mice showed that the muscles were of normal size, despite low regenerative capacity, but did have increased fibrosis. These results suggest that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis
Clinical biomarkers for thyroid immune-related adverse events in patients with stage III and IV gastrointestinal tumors
BackgroundThyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs.MethodsWe retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: “thyroid irAEs” group and “no thyroid irAEs” group. We compared continuous variables using Mann–Whitney U and Kruskal–Wallis tests and categorical variables using Pearson’s chi–square test. Survival curves were generated using the Kaplan–Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model.ResultsA total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, p = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, p = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index (p = 0.005), increased eosinophil count (p = 0.014), increased lactate dehydrogenase (p = 0.008), higher baseline thyroid stimulating hormone (TSH) (p = 0.001), HCC (p = 0.001) and increased adenosine deaminase (ADA) (p = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, p = 0.032] was independently associated with thyroid irAEs occurrence.ConclusionsIncreased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs
Bleeding complications related to external ventricular drainage placement in patients with ruptured intracranial aneurysms: a single-center study
ObjectiveAcute aneurysmal rupture can be treated with endovascular therapy or surgical clipping. For patients with concurrent acute hydrocephalus, the placement of an external ventricular drainage (EVD) is required. This study aims to investigate the impact of pre-treatment EVD placement on rebleeding in ruptured aneurysms and to examine the influence of dual antiplatelet therapy and the sequencing of dual antiplatelet therapy with EVD placement on EVD-related hematomas.MethodsWe reviewed the clinical data of 83 patients with ruptured aneurysms who underwent EVD placement from a total of 606 aneurysm patients consecutively admitted between January 2018 and January 2023. The analysis focused on the impact of pre-treatment EVD placement on aneurysmal rebleeding and the effect of dual antiplatelet therapy and its sequencing with EVD placement on EVD-related hematomas.ResultsAmong the 503 patients with ruptured aneurysms, 83 required EVD placement. EVD was placed before aneurysm treatment in 63 patients and after treatment in 20 patients. The number of aneurysmal rebleeding cases in the pre-treatment EVD group and non-EVD group was 1 (1.6%) and 20 (4.8%), respectively (p = 0.406). 31 patients (37.3%) underwent stent-assisted embolization or flow diversion requiring dual antiplatelet therapy, while 52 patients (62.7%) underwent simple embolization or surgical clipping without antiplatelet therapy. EVD-related hematomas occurred in 14 patients (16.9%), with 10 cases (32.3%) in those receiving dual antiplatelet therapy and 4 cases (7.7%) in those not receiving antiplatelet therapy (p = 0.01). Among 16 patients who had EVD placed before dual antiplatelet therapy, 4 (25%) developed EVD-related hematomas. Of the 15 patients who had EVD placed after dual antiplatelet therapy, 6 (40%) developed EVD-related hematomas (p = 0.458).ConclusionIn patients with aneurysmal subarachnoid hemorrhage (aSAH) and acute hydrocephalus, the placement of EVD before aneurysm treatment does not increase the risk of rebleeding. However, dual antiplatelet therapy increases the risk of EVD-related hematoma, and the sequence of EVD placement relative to dual antiplatelet therapy does not appear to significantly affect the outcome of EVD-related hematoma
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