Dynamic Response Of Multistory Reinforced Concrete Buildings Having Different Types Of Isolators A Parametric Study

Approaches to isolating the base have become a crucial element in enhancing quality stability during a seismic earthquake load. In the present day, base detachment is routinely utilized as an essential arrangement technique for structures and frameworks in seismically active zones. This paper aims towards the dynamic analysis of a multi-story RCC building with various parameters. For the sake of study and verification, a model of a ten-story RCC building with a symmetrical floor plan is considered. The study was conducted using SAP 2000's time-history-based software. In this paper,72 models were studied based on various parameters such as bay width, number of bays, number of floors, and various isolators (Lead Rubber Bearings, Friction Pendulum Bearing, Fixed, and Hinge). The reaction of the structure, for example, time period, base shear, and story displacements are studied and a comparison is made. The paper showed the clear superiority of isolation methods in resisting earthquakes. The friction pendulum support has been the preferred type due to the lowest drift story of the building when it was compared with other support systems. Also, as the results showed a high time period when using the lead rubber bearings, which shows the model's ability to withstand earthquakes

Numerical Investigations Of Effective Parameters On Multi-Story Building Having Inclined Supporting Foundations

This study deals with the use of finite element analysis to study the response of an RC building that has inclined supporting leads in the foundations. Several RC buildings were studied to evaluate the seismic performance of these buildings under the influence of change in three parameters (the degree of inclination of the foundations (0°, 10°, 20° & 40°), the storey number (8, 10, 12, 16 & 20 storey), and the span length (4, 5 & 6 m)). All buildings were analyzed using the SAP2000 software using the time history analysis method under the influence of the EL-Centro N-S 1940 earthquake acceleration record. The results were shown the values of the base shear, time period and roof displacements decreased by 23%, 33% and 55% respectively, when the degree of foundation inclination of the building increased from 0° to 20°, while these values increased by 68%, 53.28% and 137.6% respectively, when the No. of stories increased by 50%. The increase of base shear due to increase the height of building, also the increase lateral displacements of the buildings. The increases in time period due to decrease the stiffness of RC building and it have more displacements at tip of buildings

Intratumoral Delivery of Interferon\u3b3-Secreting Mesenchymal Stromal Cells Repolarizes Tumor-Associated Macrophages and Suppresses Neuroblastoma Proliferation In Vivo

Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is the delivery of anti-tumor therapeutic agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely used to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune diseases, and cancer. The pro-inflammatory cytokine interferon-gamma (IFN\u3b3) has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME). Despite this, clinical trials of systemic IFN\u3b3 therapy have failed due to the high blood concentration required and associated systemic toxicities. Here, we developed an intra-adrenal model of neuroblastoma, characterized by liver and lung metastases. We then engineered MSCs to deliver IFN\u3b3 directly to the TME. In vitro, these MSCs polarized murine macrophages to the M1 phenotype. In vivo, we attained a therapeutically active TME concentration of IFN\u3b3 without increased systemic concentration or toxicity. The TME-specific IFN\u3b3 reduced tumor growth rate and increased survival in two models of T cell deficient athymic nude mice. Absence of this benefit in NOD SCID gamma (NSG) immunodeficient mouse model indicates a mechanism dependent on the innate immune system. IL-17 and IL-23p19, both uniquely M1 polarization markers, transiently increased in the tumor interstitial fluid. Finally, the MSC vehicle did not promote tumor growth. These findings reveal that MSCs can deliver effective cytokine therapy directly to the tumor while avoiding systemic toxicity. This method transiently induces inflammatory M1 macrophage polarization, which reduces tumor burden in our novel neuroblastoma murine model

Splenic macrophage phagocytosis of intravenously infused mesenchymal stromal cells attenuates tumor localization

Mesenchymal stromal cells (MSCs) possess remarkable tumor tropism, making them ideal vehicles to deliver tumor-targeted therapeutic agents; however, their value in clinical medicine has yet to be realized. A barrier to clinical utilization is that only a small fraction of infused MSCs ultimately localize to the tumor. In an effort to overcome this obstacle, we sought to enhance MSC trafficking by focusing on the factors that govern MSC arrival within the tumor microenvironment. Our findings show that MSC chemoattraction is only present in select tumors, including osteosarcoma, and that the chemotactic potency among similar tumors varies substantially. Using an osteosarcoma xenograft model, we show that human MSCs traffic to the tumor within several hours of infusion. After arrival, MSCs are observed to localize in clusters near blood vessels and MSC-associated bioluminescence signal intensity is increased, suggesting that the seeded cells expand after engraftment. However, our studies reveal that a significant portion of MSCs are eliminated en route by splenic macrophage phagocytosis, effectively limiting the number of cells available for tumor engraftment. To increase MSC survival, we transiently depleted macrophages with liposomal clodronate, which resulted in increased tumor localization without substantial reduction in tumor-associated macrophages. Our data suggest that transient macrophage depletion will significantly increase the number of MSCs in the spleen and thus improve MSC localization within a tumor, theoretically increasing the effective dose of an anti-cancer agent. This strategy may subsequently improve the clinical efficacy of MSCs as vehicles for the tumor-directed delivery of therapeutic agents

Creation of PDX-Bearing Humanized Mice to Study Immuno-oncology.

A significant obstacle to the study of human cancer biology and the testing of human specific immunotherapeutics is the paucity of translational models that recapitulate both the growth of human tumors and the functionality of human immune systems. Humanized mice engrafted with human hematopoietic stem cells (HSC) and patient-derived xenografts (PDX) enable preclinical investigation of the interactions between the human immune system and human cancer. We use immunodeficient non-obese diabetic (NOD, scid, gamma) NSG™ or NSG™-SGM3 mice as hosts for establishment of human immunity following HSC injection and for engraftment of human tumors. Here we describe a refined protocol for the subcutaneous implant of solid PDX tumors into humanized mice. Protocols to recover infiltrating immune cells from growing tumors and to evaluate the immune cell subsets by flow cytometry are also described