Modeling of RC shear walls using shear spring and fiber elements for seismic performance assessment

Reinforced concrete shear wall is one of the most effective members during severe lateral loads especially in earthquakes and winds. Extensive researches, both analytical and experimental, have been carried out to study the behavior of reinforced concrete (RC) shear walls. Predicting inelastic response of RC walls and wall systems requires accurate, effective, and robust analytical model that incorporate important material characteristics and behavioral response features. In this study, a modeling method using fiber and spring elements is developed to capture inelastic responses of an RC shear wall. The fiber elements and the spring reflect flexural and shear behaviors of the shear wall, respectively. The fiber elements are built by inputting section data and material properties. The parameters of the shear spring that represent strength and stiffness degradation, pinching, and slip are determined based on analysis results from a detailed finite element method (FEM) model. The reliability of the FEM analysis program is verified. The applicability of the proposed modeling method is investigated by performing inelastic dynamic analyses for reference buildings with various aspect ratios of shear walls

Modeling of RC shear walls using shear spring and fiber elements for seismic performance assessment

Reinforced concrete shear wall is one of the most effective members during severe lateral loads especially in earthquakes and winds. Extensive researches, both analytical and experimental, have been carried out to study the behavior of reinforced concrete (RC) shear walls. Predicting inelastic response of RC walls and wall systems requires accurate, effective, and robust analytical model that incorporate important material characteristics and behavioral response features. In this study, a modeling method using fiber and spring elements is developed to capture inelastic responses of an RC shear wall. The fiber elements and the spring reflect flexural and shear behaviors of the shear wall, respectively. The fiber elements are built by inputting section data and material properties. The parameters of the shear spring that represent strength and stiffness degradation, pinching, and slip are determined based on analysis results from a detailed finite element method (FEM) model. The reliability of the FEM analysis program is verified. The applicability of the proposed modeling method is investigated by performing inelastic dynamic analyses for reference buildings with various aspect ratios of shear walls

Fibroblast growth factor-2, derived from cancer-associated fibroblasts, stimulates growth and progression of human breast cancer cells via FGFR1 signaling

Cancer-associated fibroblasts (CAFs) constitute a major compartment of the tumor microenvironment. In the present study, we investigated the role for CAFs in breast cancer progression and underlying molecular mechanisms. Human breast cancer MDA-MB-231 cells treated with the CAF-conditioned media manifested a more proliferative phenotype, as evidenced by enhanced messenger RNA (mRNA) expression of Cyclin D1, c-Myc, and proliferating cell nuclear antigen. Analysis of data from The Cancer Genome Atlas revealed that fibroblast growth factor-2 (FGF2) expression was well correlated with the presence of CAFs. We noticed that the mRNA level of FGF2 in CAFs was higher than that in normal fibroblasts. FGF2 exerts its biological effects through interaction with FGF receptor 1 (FGFR1). In the breast cancer tissue array, 42% estrogen receptor-negative patients coexpressed FGF2 and FGFR1, whereas only 19% estrogen receptor-positive patients exhibited coexpression. CAF-stimulated MDA-MB-231 cell migration and invasiveness were abolished when FGF2-neutralizing antibody was added to the conditioned media of CAFs. In a xenograft mouse model, coinjection of MDA-MB-231 cells with activated fibroblasts expressing FGF2 dramatically enhanced tumor growth, and this was abrogated by silencing of FGFR1 in cancer cells. In addition, treatment of MDA-MB-231 cells with FGF2 enhanced expression of Cyclin D1, a key molecule involved in cell cycle progression. FGF2-induced cell migration and upregulation of Cyclin D1 were abolished by siRNA-mediated FGFR1 silencing. Taken together, the above findings suggest that CAFs promote growth, migration and invasion of MDA-MB-231 cells via the paracrine FGF2-FGFR1 loop in the breast tumor microenvironment.

Knuckling Down on Predictive Factors for Early Relapse after Posterolateral Percutaneous Endoscopic Lumbar Discectomy

Objective Percutaneous endoscopic lumbar discectomy (PELD) has several advantages, but it is not used routinely due to early relapse and steep learning curve. We have studied the factors associated with early relapse in patients who underwent posterolateral PELD at or above the L4-5 level. Methods In this retrospective study, we have enrolled 200 cases and divided them into 4 groups (A, B, C, and D) with 50 patients in each group, that had undergone PELD by 2 different techniques (inside-out and outside-in with or without anti-adhesive agent) and operated by 2 different surgeons between May 2009 and November 2010. The factors studied were - Age, gender, disc (degeneration grade, location, level), associated adjacent level herniated nucleus pulposus (HNP), episode (first or recurrent), anti-adhesive agent, annulus preservation, approach, disc height and segmental dynamic motion (discrepancy in flexion and extension). Statistical analysis was done by Pearson’s chi-square test and p value (significance). The clinical results were evaluated by visual analogue scale (VAS). Results The mean age and mean follow-up period was comparable in all four groups. The overall recurrence rate was 9.5% (19/200). Average early relapse time was 3.26 months. Factors like Age of the patient, multilevel HNP and degeneration grade showed significant correlation with relapse rate. The change in VAS pre-operatively to post-operatively was significant across all groups (p<0.001). Conclusion Based on the results of this study, high grade disc degeneration, multilevel disc herniation, and early postoperative activity are significantly associated with early relapse after PELD

Improvements of motion vector in variational echo tracking technique by correction of initial guess

Póster presentado en: 3rd European Nowcasting Conference, celebrada en la sede central de AEMET en Madrid del 24 al 26 de abril de 2019

Spontaneous Spinal Canal Remodeling after Postural Pillow Reduction and Lordotic Posterior Column Compressive Percutaneous Transpedicular Screw Fixation in Neurologically Intact Thoracolumbar Burst Fractures

Objective The optimal treatment methods for thoracolumbar burst fracture with intact neurology are not established yet. Spinal canal integrity, sagittal balance and anterior column intactness are very important for successful outcome in this type of injury. There is no study analyzing restoration of these parameters by low pressure restoration using postural pillow reduction and lordotic posterior column compressive percutaneous transpedicular screw fixation and this study analyzes canal remodeling, spinal balance and anterior column intactness after this procedure. Methods The surgical procedure included three different elements: (1) preoperative postural pillow reduction for 1-2 days, (2) augmentation of fractured vertebra by polymethylmethacrylate (PMMA) in osteoporotic bone or by non-PMMA materials in non-osteoporotic bone, and (3) lordotic, posterior column compressive, percutaneous transpedicular screw fixation. We measured anterior vertebral height, canal size and lordotic angle preoperatively, immediate postoperatively and after 6 months in 34 patients treated with this technique and were analyzed. Results Of 34 patients 17 were male. The mean age was 52.03±12.51 years. They were followed for 30.68±11.67 months on average. At 6 months, preoperative canal stenosis of 44% remodeled to 12%, preoperative anterior vertebral height of 44% increased to 77% and preoperative average kyphosis of 14 degrees corrected to 3.4 degrees No neurological deterioration noted. Functionally all patients returned to their previous status. Conclusion The postural pillow reduction and lordotic posterior column compressive percutaneous screw fixation in patients with neurologically intact thoracolumbar burst fracture is effective and safe

Exploratory, cognitive, and depressive-like behaviors in adult and pediatric mice exposed to controlled cortical impact

Objective Sequelae of behavioral impairments associated with human traumatic brain injury (TBI) include neurobehavioral problems. We compared exploratory, cognitive, and depressive-like behaviors in pediatric and adult male mice exposed to controlled cortical impact (CCI). Methods Pediatric (21 to 25 days old) and adult (8 to 12 weeks old) male C57Bl/6 mice underwent CCI at a 2-mm depth of deflection. Hematoxylin and eosin staining was performed 3 to 7 days after recovery from CCI, and injury volume was analyzed using ImageJ. Neurobehavioral characterization after CCI was performed using the Barnes maze test (BMT), passive avoidance test, open-field test, light/dark test, tail suspension test, and rotarod test. Acutely and subacutely (3 and 7 days after CCI, respectively), CCI mice showed graded injury compared to sham mice for all analyzed deflection depths. Results Time-dependent differences in injury volume were noted between 3 and 7 days following 2-mm TBI in adult mice. In the BMT, 2-mm TBI adults showed spatial memory deficits compared to sham adults (P<0.05). However, no difference in spatial learning and memory was found between sham and 2-mm CCI groups among pediatric mice. The open-field test, light/dark test, and tail suspension test did not reveal differences in anxiety-like behaviors in both age groups. Conclusion Our findings revealed a graded injury response in both age groups. The BMT was an efficient cognitive test for assessing spatial/non-spatial learning following CCI in adult mice; however, spatial learning impairments in pediatric mice could not be assessed

Nuclear Factor Erythroid-Derived 2-Like 2-Induced Reductive Stress Favors Self-Renewal of Breast Cancer Stem-Like Cells via the FoxO3a-Bmi-1 Axis

Aims: A subpopulation of cancer cells, termed cancer stem cells (CSCs), has stemness properties, such as self-renewal and differentiation, which drive cancer recurrence and tumor resistance. CSCs possess enhanced protection capabilities to maintain reduced intracellular levels of reactive oxygen species (ROS) compared with nonstem-like cancer cells. This study investigated whether reductive stress could regulate self-renewal activity in breast CSCs. Results: We found that manifestation of stemness in breast cancer stem-like cells was associated with an elevated production of reduced glutathione (GSH) maintained by upregulation of glutamate cysteine ligase catalytic subunit (GCLC) and consequently, lowered ROS levels. This was accompanied by upregulation of phospho-AMP-activated protein kinase, FoxO3a, and Bmi-1. Notably, expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) protein was substantially increased in cells undergoing sphere formation. We noticed that expression of Bmi-1 was inhibited after introduction of Nrf2 short interfering RNA into MCF-7 mammosphere cells. Silencing of Nrf2 expression suppressed the xenograft growth of subcutaneously or orthotopically injected human breast cancer cells. Innovation: Association between Nrf2 and self-renewal signaling in CSCs has been reported, but the underlying molecular mechanism remains largely unresolved. This study demonstrates the Nrf2-mediated signaling pathway in maintenance of reductive stress in breast CSCs. Conclusion: Nrf2 overactivation in breast CSCs upregulates GCLC expression and consequently enhances GSH biosynthesis with concurrent reduction in intracellular ROS accumulation, thereby provoking the reductive stress. The consequent upregulation of nuclear FoxO3a and its binding to the promoter of the gene encoding Bmi-1 account for the self-renewal activity of breast cancer stem-like cells and their growth in a xenograft mouse model.

Identification of HLA-A*2402-restricted HCMV immediate early-1 (IE-1) epitopes as targets for CD8+ HCMV-specific cytotoxic T lymphocytes

<p>Abstract</p> <p>Background</p> <p>To identify novel HLA-A*2402-restricted human cytomegalovirus (HCMV) immediate early-1 (IE-1) epitopes for adoptive immunotherapy, we explored 120 overlapping 15-amino acid spanning IE-1.</p> <p>Methods</p> <p>These peptides were screened by measuring the frequency of polyclonal CD8+ T cells producing intracellular interferon-γ (IFN-γ) using flow cytometry and the epitopes were validated with a HCMV-infected target Cr release cytotoxicity assay.</p> <p>Results</p> <p>Initial screening was performed with 12 mini-pools of 10 consecutive peptides made from 120 overlapping peptides15-amino acids in length that spanned IE-1. When peripheral blood mononuclear cells (PBMCs) from HLA-A*2402 HCMV-seropositive donors were sensitized with each of the 12 mini-pools, mini-pools 1 and 2 induced the highest frequency of CD8+ cytotoxic T lymphocytes (CTLs) producing IFN-γ. When PBMCs were stimulated with each of the twenty peptides belonging to mini-pools 1 and 2, peptides IE-1_1–15MESSAKRKMDPDNPD and IE-1_5–19AKRKMDPDNPDEGPS induced the greatest quantities of IFN-γ production and cytotoxicity of HLA-matched HCMV-infected fibroblasts. To determine the exact HLA-A*2402-restricted epitopes within the two IE-1 proteins, we synthesized a total of twenty-one overlapping 9- or 10 amino acid peptides spanning IE-1_1–15and IE-1_5–19. Peptide IE-1_3–12SSAKRKMDPD induced the greatest quantities of IFN-γ production and target cell killing by CD8+ CTLs.</p> <p>Conclusion</p> <p>HCMV IE-1_3–12SSAKRKMDPD is a HLA-A*2402-restricted HCMV IE-1 epitope that can serve as a common target for CD8+ HCMV-specific CTLs.</p