NK105, a paclitaxel-incorporating micellar nanoparticle, is a more potent radiosensitising agent compared to free paclitaxel

NK105 is a micellar nanoparticle formulation designed to enhance the delivery of paclitaxel (PTX) to solid tumours. It has been reported to exert antitumour activity in vivo and to have reduced neurotoxicity as compared to that of free PTX. The purpose of this study was to investigate the radiosensitising effect of NK105 in comparison with that of PTX. Lewis lung carcinoma (LLC)-bearing mice were administered a single intravenous (i.v.) injection of PTX or NK105; 24 h after the drug administration, a proportion of the mice received radiation to the tumour site or lung fields. Then, the antitumour activity and lung toxicity were evaluated. In one subset of mice, the tumours were excised and specimens were prepared for analysis of the cell cycle distribution by flow cytometry. Combined NK105 treatment with radiation yielded significant superior antitumour activity as compared to combined PTX treatment with radiation (P=0.0277). On the other hand, a histopathological study of lung sections revealed no significant difference in histopathological changes between mice treated with PTX and radiation and those treated with NK105 and radiation. Flow-cytometric analysis showed that NK105-treated LLC tumour cells showed more severe arrest at the G2/M phase as compared to PTX-treated tumour cells. The superior radiosensitising activity of NK105 was thus considered to be attributable to the more severe cell cycle arrest at the G2/M phase induced by NK105 as compared to that induced by free PTX. The present study results suggest that further clinical trials are warranted to determine the efficacy and feasibility of combined NK105 therapy with radiation

Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer

Dose-escalation study was performed to evaluate the maximum tolerated dose, recommended dose and toxicity profile of weekly irinotecan with daily carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. Thirty-one previously untreated patients with unresectable stage III non-small-cell lung cancer were enrolled in this study. Patients received weekly irinotecan plus carboplatin (20 mg m−2 daily for 5 days a week) for 4 weeks and thoracic radiotherapy (60 Gy in 30 fractions). The irinotecan dose was escalated from 30 mg m−2 in increments of 10 mg m−2. Four irinotecan dose levels were given and 30 patients were assessable. Their median age was 62 years (range: 52–72 years), 28 had a performance status of 0–1 and two had a performance status of 2, 12 had stage IIIA disease and 18 had IIIB disease. There were 19 squamous cell carcinomas, 10 adenocarcinomas, and one large cell carcinoma. The dose-limiting toxicities were pneumonitis, esophagitis, thrombocytopenia and neutropenia. The maximum tolerated dose of irinotecan was 60 mg m−2, with two patients developing grade 4 pulmonary toxicity and one patient died of pneumonitis (grade 5). The recommended dose of irinotecan was 50 mg m−2. Other grade 3 or 4 toxicities were nausea and vomiting. Three patients achieved complete remission and 15 had partial remission, for an objective response rate of 60.0%. The median survival time was 14.9 months, and the 1- and 2-year survival rates were 51.6% and 34.2%, respectively. The study concluded that the major toxicity of this regimen was pneumonitis. This therapy may be active against unresectable non-small-cell lung cancer and a phase II study is warranted

Experimental study of deformable connection consisting of friction device and rubber bearings to connect floor system to lateral force resisting system

This paper presents experimental and numerical studies of a full-scale deformable connection used to connect the floor system of the flexible gravity load resisting system to the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. The purpose of the deformable connection is to limit the earthquake-induced horizontal inertia force transferred from the floor system to the LFRS and thereby to reduce the horizontal floor accelerations and the forces in the LFRS. The deformable connection that was studied consists of a friction device (FD) and carbon fiber-reinforced laminated low-damping rubber bearings (RB), denoted as the FD + RB connection. The test results show that the force-deformation responses of the FD + RB connection are stable under quasi-static sinusoidal and earthquake loading histories and dynamic sinusoidal loading histories. The FD + RB connection force-deformation response is approximated with a bilinear elastic-plastic force-deformation response with kinematic hardening. The FD is axially stiff, compact, easy-to-assemble, and able to accommodate the FD + RB connection kinematic requirements. The FD elastic stiffness controls the FD + RB connection elastic stiffness. The FD friction force controls the force when the FD + RB connection force-deformation response transitions from elastic to post elastic. The RB provide predictable and reliable post-elastic stiffness to the FD + RB connection. The machining tolerances for the FD components, the “break-in” effect, the sliding history, and the dwell time affect the FD friction force. Numerical simulation results for a 12-story reinforced concrete wall building with FD + RB connections under seismic loading show that a reduction of the FD friction force increases the FD + RB connection deformation demand

Experimental study of deformable connection consisting of buckling-restrained brace and rubber bearings to connect floor system to lateral force resisting system

This paper presents experimental and numerical studies of a full-scale deformable connection used to connect the floor system of the flexible gravity load resisting system to the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. The purpose of the deformable connection is to limit the earthquake-induced horizontal inertia force transferred from the floor system to the LFRS and, thereby, to reduce the horizontal floor accelerations and the forces in the LFRS. The deformable connection that was studied consists of a buckling-restrained brace (BRB) and steel-reinforced laminated low-damping rubber bearings (RB). The test results show that the force–deformation responses of the connection are stable, and the dynamic force responses are larger than the quasi-static force responses. The BRB+RB force–deformation response depends mainly on the BRB response. A detailed discussion of the BRB experimental force–deformation response is presented. The experimental results show that the maximum plastic deformation range controls the isotropic hardening of the BRB. The hardened BRB force–deformation responses are used to calculate the overstrength adjustment factors. Details and limitations of a validated, accurate model for the connection force–deformation response are presented. Numerical simulation results for a 12-story reinforced concrete wall building with deformable connections show the effects of including the RB in the deformable connection and the effect of modeling the BRB isotropic hardening on the building seismic response. Copyright © 2016 John Wiley & Sons, Ltd

Experimental study of deformable connection consisting of friction device and rubber bearings to connect floor system to lateral force resisting system

This paper presents experimental and numerical studies of a full-scale deformable connection used to connect the floor system of the flexible gravity load resisting system to the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. The purpose of the deformable connection is to limit the earthquake-induced horizontal inertia force transferred from the floor system to the LFRS and thereby to reduce the horizontal floor accelerations and the forces in the LFRS. The deformable connection that was studied consists of a friction device (FD) and carbon fiber-reinforced laminated low-damping rubber bearings (RB), denoted as the FD + RB connection. The test results show that the force-deformation responses of the FD + RB connection are stable under quasi-static sinusoidal and earthquake loading histories and dynamic sinusoidal loading histories. The FD + RB connection force-deformation response is approximated with a bilinear elastic-plastic force-deformation response with kinematic hardening. The FD is axially stiff, compact, easy-to-assemble, and able to accommodate the FD + RB connection kinematic requirements. The FD elastic stiffness controls the FD + RB connection elastic stiffness. The FD friction force controls the force when the FD + RB connection force-deformation response transitions from elastic to post elastic. The RB provide predictable and reliable post-elastic stiffness to the FD + RB connection. The machining tolerances for the FD components, the “break-in” effect, the sliding history, and the dwell time affect the FD friction force. Numerical simulation results for a 12-story reinforced concrete wall building with FD + RB connections under seismic loading show that a reduction of the FD friction force increases the FD + RB connection deformation demand

Development of deformable connection for earthquake-resistant buildings to reduce floor accelerations and force responses

This paper presents the development of a deformable connection that is used to connect each floor system of the flexible gravity load resisting system (GLRS) with the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. It is shown that the deformable connection acts as a seismic response modification device, which limits the lateral forces transferred from each floor to the LFRS and allows relative motion between the GLRS and LFRS. In addition, the floor accelerations and the LFRS story shears related to the higher-mode responses are reduced. The dispersion of peak responses is also significantly reduced. Numerical simulations of the earthquake response of a 12-story reinforced concrete shear wall example building with deformable connections are used to define an approximate feasible design space for the deformable connection. The responses of the example building model with deformable connections and the example building model with rigid-elastic connections are compared. Two configurations of the deformable connection are studied. In one configuration, a buckling restrained brace is used as the limited-strength load-carrying hysteretic component of the deformable connection, and in the other configuration, a friction device is used. Low damping laminated rubber bearings are used in both configurations to ensure the out-of-plane stability of the LFRS and to provide post-elastic stiffness to the deformable connection. Important experimental results from full-scale tests of the deformable connections are presented and used to calibrate numerical models of the connections. Copyright © 2016 John Wiley & Sons, Ltd

Development of deformable connection for earthquake‐resistant buildings to reduce floor accelerations and force responses

This paper presents the development of a deformable connection that is used to connect each floor system of the flexible gravity load resisting system (GLRS) with the stiff lateral force resisting system (LFRS) of an earthquake-resistant building. It is shown that the deformable connection acts as a seismic response modification device, which limits the lateral forces transferred from each floor to the LFRS and allows relative motion between the GLRS and LFRS. In addition, the floor accelerations and the LFRS story shears related to the higher-mode responses are reduced. The dispersion of peak responses is also significantly reduced. Numerical simulations of the earthquake response of a 12-story reinforced concrete shear wall example building with deformable connections are used to define an approximate feasible design space for the deformable connection. The responses of the example building model with deformable connections and the example building model with rigid-elastic connections are compared. Two configurations of the deformable connection are studied. In one configuration, a buckling restrained brace is used as the limited-strength load-carrying hysteretic component of the deformable connection, and in the other configuration, a friction device is used. Low damping laminated rubber bearings are used in both configurations to ensure the out-of-plane stability of the LFRS and to provide post-elastic stiffness to the deformable connection. Important experimental results from full-scale tests of the deformable connections are presented and used to calibrate numerical models of the connections. Copyright © 2016 John Wiley & Sons, Ltd

Shake-table test performance of an inertial force-limiting floor anchorage system

A new floor connecting system developed for low-damage seismic-resistant building structures is described herein. The system, termed Inertial Force-Limiting Floor Anchorage System (IFAS), is intended to limit the lateral forces in buildings during an earthquake. This objective is accomplished by providing limited-strength deformable connections between the floor system and the primary elements of the lateral force-resisting system. The connections transform the seismic demands from inertial forces into relative displacements between the floors and lateral force-resisting system. This paper presents the IFAS performance in a shake-table testing program that provides a direct comparison with an equivalent conventional rigidly anchored-floor structure. The test structure is a half-scale, 4-story reinforced concrete flat-plate shear wall structure. Precast hybrid rocking walls and special precast columns were used for test repeatability in a 22-input strong ground-motion sequence. The structure was purposely designed with an eccentric wall layout to examine the performance of the system in coupled translational-torsional response. The test results indicated a seismic demand reduction in the lateral force-resisting system of the IFAS structure relative to the conventional structure, including reduced shear wall base rotation, shear wall and column inter-story drift, and, in some cases, floor accelerations. These results indicate the potential for the IFAS to minimize damage to the primary structural and non-structural components during earthquakes

Shake-table test performance of an inertial force-limiting floor anchorage system

A new floor connecting system developed for low-damage seismic-resistant building structures is described herein. The system, termed Inertial Force-Limiting Floor Anchorage System (IFAS), is intended to limit the lateral forces in buildings during an earthquake. This objective is accomplished by providing limited-strength deformable connections between the floor system and the primary elements of the lateral force-resisting system. The connections transform the seismic demands from inertial forces into relative displacements between the floors and lateral force-resisting system. This paper presents the IFAS performance in a shake-table testing program that provides a direct comparison with an equivalent conventional rigidly anchored-floor structure. The test structure is a half-scale, 4-story reinforced concrete flat-plate shear wall structure. Precast hybrid rocking walls and special precast columns were used for test repeatability in a 22-input strong ground-motion sequence. The structure was purposely designed with an eccentric wall layout to examine the performance of the system in coupled translational-torsional response. The test results indicated a seismic demand reduction in the lateral force-resisting system of the IFAS structure relative to the conventional structure, including reduced shear wall base rotation, shear wall and column inter-story drift, and, in some cases, floor accelerations. These results indicate the potential for the IFAS to minimize damage to the primary structural and non-structural components during earthquakes