Evaluation of HFMI as a Life Extension Technique for Welded Bridge Details

Published by Elsevier B.V. In this current study, HFMI technique is used to study the possibility to extend the fatigue life of pre-fatigued flange gusset welds typically found in girder bridges. The results from the study are also compared with results found in the literature for other more conventional techniques for retrofitting, e.g. cut-outs. The study also aims to investigate if the IIW HFMI recommendations could be applied for existing steel structures and that equal fatigue strength improvement could be claimed for prefatigued structures. Furthermore, new recommendations for structural hot spot stress type B are suggested for HFMI treated welds, applicable to flange guest welds. The results indicate that the HFMI could be used for welded bridge details rehabilitation as a competing technology with conventional cut-out. Furthermore, the results indicate that the IIW recommendations for HFMI fatigue strength improvement could also be applied for pre-fatigued welded details. \ua9 2019 The Authors

Robustness of the HFMI techniques and the effect of weld quality on the fatigue life improvement of welded joints

Robustness of HFMI treatment in different weld qualities according to ISO 5817 was studied, and fatigue testing of the treated samples was carried out in order to investigate the effect of the weld quality prior treatment. The results show that HFMI-treated welds with weld quality level D shows fatigue life improvements that fall within the IIW recommendations for HFMI. No significant influence from the HFMI operator or HFMI equipment on the fatigue life was found. However, the scatter in fatigue testing results varied with HFMI operator and indicated that different HFMI operators could produce consistent treatment results. A considerable effect on fatigue life from HFMI tool radius was found, where the 2-mm tool radius showed considerably greater fatigue life compared with the 1.5-mm tool radius. According to IIW (Marquis and Barsoum 2016), for steel grade SY = 700\ua0MPa, the fatigue strength recommendation is FAT 160 (m = 5) for transverse stiffener–welded joints with as-welded quality B according to ISO 5817 (ISO/TC 44/SC 10 2011), prior to treatment. It can be observed in the current study that fatigue-tested HFMI-treated welded joints, welded with weld quality D, are in good agreement with the IIW recommendations

Effect of Lode Parameter and Stress Triaxiality on the Effective Plastic Yield Properties of Triply Periodic IWP Ligament-Based Minimal Surface

Due to the advancements in additive manufacturing and increased applications of additive manufactured structures, it is essential to fully understand both the elastic and plastic behavior of cellular materials, which include the mathematically-driven triply periodic minimal surfaces (TPMS). The elastic and plastic behaviors have been well established for many TPMS structures. These structures are however rather computationally expensive to model explicitly when used in meta-materials and hence the need to develop an accurate yield function in order to model their plastic behavior in a homogenized approach. In this study, the effect of different loading conditions is numerically investigated on the effective yield strength of IWP ligament based (IWP-L) TPMS

D2 receptor occupancy of olanzapine pamoate depot using positron emission tomography : an open-label study in patients with schizophrenia

A long-acting depot formulation of olanzapine that sustains plasma olanzapine concentrations for over a month after a single injection is currently under development. This multicenter, open-label study explored D2 receptor occupancy of a fixed dose of olanzapine pamoate (OP) depot given every 4 weeks. Patients (nine male, five female) with schizophrenia or schizoaffective disorder previously stabilized on oral olanzapine were switched to OP depot 300 mg by intramuscular injection every 4 weeks for 6 months. No visitwise within-group significant changes were found in Brief Psychiatric Rating Scale Total or Clinical Global Impressions-Severity of Illness scores, although seven patients received oral olanzapine supplementation during the first four injection cycles. To minimize impact on D2 occupancy, positron emission tomography (PET) scans were not completed during injection cycles that required supplemental oral olanzapine. Two patients reported transient injection site adverse events, which did not result in discontinuation. The most frequently reported treatment-emergent adverse events were insomnia, aggravated psychosis, and anxiety. Mean striatal D2 receptor occupancy, as measured by [11C]-raclopride PET, was 69% on oral olanzapine (5–20 mg/day) and 50% (trough) on OP depot at steady state. Following an initial decline, occupancy returned to 84% of baseline oral olanzapine occupancy after six injections. Over the study period, D2 receptor occupancy and plasma olanzapine concentrations were significantly correlated (r=0.76, Pless than or equal to0.001). OP depot resulted in mean D2 receptor occupancy of approximately 60% or higher at the end of the 6-month study period, a level consistent with antipsychotic efficacy and found during treatment with oral olanzapine. However, supplemental oral olanzapine or another dosing strategy may be necessary to maintain adequate therapeutic response during the first few injection cycles.peer-reviewe

Researching corporate social responsibility in the Middle East - the current state and future directions

Corporate social responsibility (CSR) has the potential to yield economic and social value in the Middle East (ME), especially given the current high environmental flux in the region. Although much scholarly has been paid to CSR issues, a key question remains about how to operate responsibly in the ME, particularly since institutional environments and stakeholders’ needs vary across ME states. The purpose of this paper is to provide a systematic review of the current state of CSR in the ME. We identify thirty-eight articles that are most pertinent to CSR in the ME and examine the main theoretical frameworks, methodologies, trajectories for further conceptual development, gaps where new research pathways need to be created and also future research questions. From the systematic review, we reveal how attention on CSR in the ME is slowly gaining traction. A snapshot of the gaps identified include the collaboration between business and NGOs, the impact of stakeholders and institutions on CSR, the impact of political and economic crisis on CSR and the influence of individualistic characteristics shaping managers’ CSR behaviour. In addition to such gaps, we present an agenda for future research

Phase I Evaluation of STA-1474, a Prodrug of the Novel HSP90 Inhibitor Ganetespib, in Dogs with Spontaneous Cancer

The novel water soluble compound STA-1474 is metabolized to ganetespib (formerly STA-9090), a potent HSP90 inhibitor previously shown to kill canine tumor cell lines in vitro and inhibit tumor growth in the setting of murine xenografts. The purpose of the following study was to extend these observations and investigate the safety and efficacy of STA-1474 in dogs with spontaneous tumors.This was a Phase 1 trial in which dogs with spontaneous tumors received STA-1474 under one of three different dosing schemes. Pharmacokinetics, toxicities, biomarker changes, and tumor responses were assessed. Twenty-five dogs with a variety of cancers were enrolled. Toxicities were primarily gastrointestinal in nature consisting of diarrhea, vomiting, inappetence and lethargy. Upregulation of HSP70 protein expression was noted in both tumor specimens and PBMCs within 7 hours following drug administration. Measurable objective responses were observed in dogs with malignant mast cell disease (n = 3), osteosarcoma (n = 1), melanoma (n = 1) and thyroid carcinoma (n = 1), for a response rate of 24% (6/25). Stable disease (>10 weeks) was seen in 3 dogs, for a resultant overall biological activity of 36% (9/25).This study provides evidence that STA-1474 exhibits biologic activity in a relevant large animal model of cancer. Given the similarities of canine and human cancers with respect to tumor biology and HSP90 activation, it is likely that STA-1474 and ganetespib will demonstrate comparable anti-cancer activity in human patients

Comparison of KI calculation methods

This paper compares different numerical methods for mode I stress intensity factor (SIF) calculations. Both 2D and 3D models are used to calculate KI for the compact tension specimens. J-integral and interaction integral provide relatively accurate results. The analysis of a reactor pressure vessel subjected to pressurized thermal shock is performed using the finite element method (FEM) and extended finite element method (XFEM). XFEM method shows advantages in modeling cracks but oscillations in 3D problems due to extraction domains for J and interaction integrals. The best results are obtained with domain integrals using a FEM with a refined mesh.The authors are grateful for the financial support of the PISA Project provided by the Swiss Federal Nuclear Safety Inspectorate (ENSI) (DIS-Vertrag Nr. H-100668). Guian Qian is also grateful for the visiting invitation provided by Key Laboratory of Pressurized Systems and Safety (East China University of Science and Technology), Ministry of Education, China.Qian, G.; González Albuixech, VF.; Niffenegger, M.; Giner Maravilla, E. (2016). Comparison of KI calculation methods. Engineering Fracture Mechanics. 156:52-67. https://doi.org/10.1016/j.engfracmech.2016.02.014S526715

Targeting the hypoxic fraction of tumours using hypoxia activated prodrugs

The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high priority target and one therapeutic strategies designed to eradicate hypoxic cells in tumours are a group of compounds known collectively as hypoxia activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (i) the ability of oxygen to either reverse or inhibit the activation process and (ii) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples