Analysis of the residual safety level in R/C slabs with severe joist corrosion

An analysis until the failure on a series of one-way slabs with severe corrosion at the lower reinforcement of the R/C joists is presented. Different positions in the slab and number of damaged joists have been studied, obtaining the residual safety assessment in cases of slabs damaged by flexural failure mechanisms. Since the boundary conditions have proved decisive for obtaining the behavior, the damaged slab has been evaluated as part of the entire building, as precisely as possible, taking into account the different phases of the construction process and deterioration in time, and the complex behavior of concrete, steel and masonry. The results of the proposed methodology are consistent with the pathology of the observed cases. As a result of this study the authors propose practical recommendations to help in making decisions about the magnitude of the intervention, always necessary in this type of pathology.Vercher Sanchis, JM.; Gil Benso, E.; Mas Tomas, MDLA.; Cubel Arjona, FJ. (2014). Analysis of the residual safety level in R/C slabs with severe joist corrosion. Journal of Performance of Constructed Facilities. 1-14. doi:10.1061/(ASCE)CF.1943-5509.0000608S11

Growth of {Tb₃}[Sc_2−<i>x</i>Lu_<i>x</i>](Al₃)O₁₂ Single Crystals for Visible-Infrared Optical Isolators

{Tb3}[Sc2−xLux](Al3)O12 crystals have been grown and investigated for the first time for magneto-optical applications. Tb3Al5O12 exhibits the best magneto-optical features; however, its incongruent melting nature has led to the industrial use of Tb3Ga5O12. Tb3Sc2Al3O12 had been proposed as an alternative to Tb3Al5O12, but unfortunately its growth also presents several drawbacks. The present investigation shows that by the isovalent substitution of Sc3+ by Lu3+ in the octahedral site of the garnet structure, it is possible to improve the growth characteristics while preserving the superior magneto-optical properties. We demonstrate that {Tb3}[Sc2−xLux](Al3)O12 crystals show a higher visible transparency and a larger Faraday rotation than Tb3Ga5O12 crystals. {Tb3}[Sc2−xLux](Al3)O12 is therefore a very promising material in particular for new magneto-optical applications in the visible-near IR wavelength region

Exposure and Tumor Fn14 Expression as Determinants of Pharmacodynamics of the Anti-TWEAK Monoclonal Antibody RG7212 in Patients with Fn14-Positive Solid Tumors

PURPOSE: The TWEAK-Fn14 pathway represents a novel anticancer target that is being actively investigated. Understanding the relationship between pharmacokinetics of anti-TWEAK therapeutics and tumor pharmacodynamics is critical. We investigated exposure-response relationships of RG7212, an anti-TWEAK mAb, in patients with Fn14-expressing tumors. EXPERIMENTAL DESIGN: Patients with Fn14-positive tumors (IHC ≥ 1+) treated in a phase I first-in-human study with ascending doses of RG7212 were the basis for this analysis. Pharmacokinetics of RG7212 and dynamics of TWEAK were determined, as were changes in tumor TWEAK-Fn14 signaling in paired pre- and posttreatment tumor biopsies. The objectives of the analysis were to define exposure-response relationships and the relationship between pretreatment tumor Fn14 expression and pharmacodynamic effect. Associations between changes in TWEAK-Fn14 signaling and clinical outcome were explored. RESULTS: Thirty-six patients were included in the analysis. RG7212 reduced plasma TWEAK to undetectable levels at all observed RG7212 exposures. In contrast, reductions in tumor Fn14 and TRAF1 protein expression were observed only at higher exposure (≥ 300 mg*h/mL). Significant reductions in tumor Ki-67 expression and early changes in serum concentrations of CCL-2 and MMP-9 were observed exclusively in patients with higher drug exposure who had high pretreatment tumor Fn14 expression. Pretreatment tumor Fn14 expression was not associated with outcome, but a trend toward longer time on study was observed with high versus low RG7212 exposure. CONCLUSIONS: RG7212 reduced tumor TWEAK-Fn14 signaling in a systemic exposure-dependent manner. In addition to higher exposure, relatively high Fn14 expression might be required for pharmacodynamic effect of anti-TWEAK monoclonal antibodies

A Phase I Monotherapy Study of RG7212, a First-in-Class Monoclonal Antibody Targeting TWEAK Signaling in Patients with Advanced Cancers

PURPOSE: Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible molecule 14 (Fn14) are a ligand-receptor pair frequently overexpressed in solid tumors. TWEAK: Fn14 signaling regulates multiple oncogenic processes through MAPK, AKT, and NFκB pathway activation. A phase I study of RG7212, a humanized anti-TWEAK IgG1κ monoclonal antibody, was conducted in patients with advanced solid tumors expressing Fn14. EXPERIMENTAL DESIGN: Dose escalations, over a 200- to 7,200-mg range, were performed with patients enrolled in weekly (QW), bi-weekly (Q2W), or every-three-week (Q3W) schedules. Primary objectives included determination of dose and safety profile. Secondary endpoints included assessments related to inhibition of TWEAK: Fn14 signaling, tumor proliferation, tumor immune cell infiltration, and pharmacokinetics. RESULTS: In 192 treatment cycles administered to 54 patients, RG7212 was well-tolerated with no dose-limiting toxicities observed. More than 95% of related adverse events were limited to grade 1/2. Pharmacokinetics were dose proportional for all cohorts, with a t1/2 of 11 to 12 days. Pharmacodynamic changes included clearance of free and total TWEAK ligand and reductions in tumor Ki-67 and TRAF1. A patient with BRAF wild-type melanoma who received 36 weeks of RG7212 therapy had tumor regression and pharmacodynamic changes consistent with antitumor effects. Fifteen patients (28%) received 16 or more weeks of RG7212 treatment. CONCLUSION: RG7212 demonstrated excellent tolerability and favorable pharmacokinetics. Pharmacodynamic endpoints were consistent with reduced TWEAK: Fn14 signaling. Tumor regression was observed and prolonged stable disease was demonstrated in multiple heavily pretreated patients with solid tumors. These encouraging results support further study of RG7212. Clin Cancer Res; 21(2); 258-66. ©2014 AACR