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Experimental Study of the Nonlinear Flow Characteristics of Fluid in 3D Rough-Walled Fractures During Shear Process
No full textTo understand the influence of shear on the hydraulic properties of rock fractures, shear-flow tests were carried out on rock fractures with different surface roughnesses. Each rough-walled fracture was replicated in four specimens, which were sheared at different displacements under normal stresses that varied from 0.5 to 2.0 MPa. At each shear displacement, a series of hydraulic tests with different hydraulic gradients were performed, and the nonlinear flow regimes of the fluid within the fractures were investigated. The results show that Forchheimer’s law can well describe the nonlinear relationship between the flow rate and the hydraulic gradient in rough-walled fractures. Both the linear coefficient and nonlinear coefficient decrease during shearing but increase as the normal stress increases. The critical hydraulic gradient increases with an increase in the shear displacement and normal stress. With an increase in the joint roughness coefficient, the critical hydraulic gradient decreases. The normalized transmissivity exhibits a strong correlation with the Reynolds number. As the shear displacement increases, the fitted curves of the normalized transmissivity versus the Reynolds number shift upward but the curves shift downward with an increase in normal stress. Additionally, the Forchheimer coefficient decreases with an increase in the shear displacement but increases with an increase in the applied normal stress. Visualization tests show that the number of flow paths is large when the shear displacement is small due to various distributions of the contact areas and that the flow of dyed water over the entire fracture decreases. As the shear displacement increases, the flow resistance decreases due to the shear dilation-induced increase in the aperture, and the advantage channel flow is distinct in the fracture. The contact ratio rapidly decreases as the shear displacement increases from 1 to 3 mm and then slightly varies with a continuously increasing maximum shear displacement of 9 mm
A case of thrombomodulin mutation causing defective thrombin binding with absence of protein C and TAFI activation
Get PDFThrombomodulin functions as an anticoagulant through thrombin binding and protein C activation. We herein report the first case of hereditary functional thrombomodulin deficiency presenting with recurrent subcutaneous hemorrhage and old cerebral infarction. The patient had a homozygous substitution of glycine by aspartate at amino acid residue 412 (Gly412Asp) in the thrombin-binding domain of the thrombomodulin gene (designated thrombomodulin-Nagasaki). In vitro assays using a recombinant thrombomodulin with the same mutation as the patient showed a total lack of thrombin binding and activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI). Marked clinical and laboratory improvement was obtained with recombinant human soluble thrombomodulin therapy
Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
Get PDFBACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. METHODS/DESIGN: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. DISCUSSION: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057
Evaluation of Poly Lactic-co-Glycolic Acid-Coated β-Tricalcium Phosphate Bone Substitute as a Graft Material for Ridge Preservation after Tooth Extraction in Dog Mandible: A Comparative Study with Conventional β-Tricalcium Phosphate Granules
Get PDFThis study aims to evaluate the safety and efficacy of a poly lactic-co-glycolic acid (PLGA)-coated β-tricalcium phosphate (β-TCP)
with N-methyl-2-pyrrolidone (NMP) liquid activator (PLGA/β-TCP) on alveolar ridge preservation after tooth extraction in dog mandible. Thirty-two extraction sites were prepared in eight dog mandibles. A distal root of the mandibular premolar was extracted and randomly grafted with one of the following bone substitutes: (1) PLGA/β-TCP, (2) β-TCP, or (3) left empty as a control, and wounds were closed
with keratinized mucosa graft. Post-operative wound healing was observed and scored to evaluate safety. After 12 and 24 weeks, the bone regeneration was evaluated with micro-computed tomography (CT) images and histomorphometric analyses. Gingival epithelization progressed over time without complication or infection. Micro-CT images and histological observation revealed that both PLGA/β-TCP and β-TCP granules supported sufficient new bone formation. Although bone formation and substrate resorption were delayed slightly with the PLGA and the NMP-containing plasticizer as compared to those treated with conventional β-TCP, it can be concluded that the PLGA and the NMP-containing plasticizer that facilitated the in situ hardening properties of the material had no negative influence on the biocompatibility of the material
Study on quantitative evaluation method of large deformation characteristics of vibration-isolated laminated rubber bearing for bridge
Get PDFLaminated rubber bearings are widely used as vibration isolation bearings for bridges. The purpose of this study is to quantitatively evaluate the large deformation
characteristics of laminated rubber bearings experimentally and analytically. In the experiment, strain measurement and strain distribution were visualized using digital image correlation method, and simulation analysis by FEM was performed
Prevalence and risk factors of Schistosoma mansoni infection among children under two years of age in Mbita, Western Kenya
Get PDFDespite growing evidence that infants and very young children can be infected with schistosomes, the epidemiological
features and risk factors are not well described in this age group. We aimed to assess the prevalence of S. mansoni
infection in children under two years of age from a population with a known high burden of infection in school-aged children and adults and thus inform the need for interventions in this potentially vulnerable age group. In a cross-sectional study in Mbita Sub-county, along the east coast of Lake Victoria, Western Kenya, we enrolled
361 children aged 6-23 months. The prevalence of S. mansoni infection was detected using the Kato-Katz stool
examination and a point-of-care test for urinary circulating cathodic antigen (POC-CCA) (Rapid Medical Diagnostics, Pretoria, South Africa). Three-hundred and five (305) children had complete data of whom 276 (90.5%, 95%CI: 86.6-93.5)children were positive for S. mansoni by the POC-CCA test, while 11 (3.6%, 95%CI: 1.8-6.4) were positive by the Kato-Katz method. All Kato-Katz positive cases were also positive by the POC-CCA test. In multivariable analysis,
only geographical area, Rusinga West (AOR = 7.1, 95%CI: 1.4-35.2, P = 0.02), was associated with S. mansoni infection
using Kato-Katz test. Independent associations for POC-CCA positivity included age, (12-17 months vs 6-11 months;AOR = 7.8, 95%CI: 1.8-32.6, P = 0.002) and breastfeeding in the previous 24 hours (AOR = 3.4, 95%CI: 1.3-9.0, P = 0.009). We found a potentially very high prevalence of S. mansoni infection among children under two years of age based on POC-CCA test results in Mbita Sub-county, Kenya, which if confirmed strongly supports the need
to include infants in public health strategies providing universal prophylactic treatment in high burden settings.Further research is required to determine the accuracy of diagnostic tools to detect light infection among very young children and possible long-term health impacts