Effect of Weld Schedule on the Residual Stress Distribution of Boron Steel Spot Welds

Press-hardened boron steel has been utilized in anti-intrusion systems in automobiles, providing high strength and weight-saving potential through gage reduction. Boron steel spot welds exhibit a soft heat-affected zone which is surrounded by a hard nugget and outlying base material. This soft zone reduces the strength of the weld and makes it susceptible to failure. Additionally, different welding regimes lead to significantly different hardness distributions, making failure prediction difficult. Boron steel sheets, welded with fixed and adaptive schedules, were characterized. These are the first experimentally determined residual stress distributions for boron steel resistance spot welds which have been reported. Residual strains were measured using neutron diffraction, and the hardness distributions were measured on the same welds. Additionally, similar measurements were performed on spot welded DP600 steel as a reference material. A correspondence between residual stress and hardness profiles was observed for all welds. A significant difference in material properties was observed between the fixed schedule and adaptively welded boron steel samples, which could potentially lead to a difference in failure loads between the two boron steel welds

Characterization of Loading Responses and Failure Loci of a Boron Steel Spot Weld

Boron steel, classed as an ultra high-strength steel (UHSS), has been utilized in anti-intrusion systems in automobiles, providing high strength and weight-saving potential through gage reduction. UHSS spot welds exhibit unique hardness distributions, with a hard nugget and outlying base material, but with a soft heat-affected zone in-between these regions. This soft zone reduces the strength of the weld and makes it susceptible to failure. Due to the interaction of various weld zones that occurs during loading, there is a need to characterize the loading response of the weld for accurate failure predictions. The loading response of certain weld zones, as well as failure loci, was obtained through physical simulation of the welding process. The results showed a significant difference in mechanical behavior through the weld length. An important result is that instrumented indentation was shown to be a valid, quantitative method for verifying the accuracy with which weld microstructure has been recreated with regard to the target weld microstructure

Doxorubicin-conjugated siRNA lipid nanoparticles for combination cancer therapy

Evasion of apoptosis is a hallmark of cancer, attributed in part to overexpression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). In a variety of cancer types, including lymphoma, Bcl-2 is overexpressed. Therapeutic targeting of Bcl-2 has demonstrated efficacy in the clinic and is the subject of extensive clinical testing in combination with chemotherapy. Therefore, the development of co-delivery systems for Bcl-2 targeting agents, such as small interfering RNA (siRNA), and chemotherapeutics, such as doxorubicin (DOX), holds promise for enabling combination cancer therapies. Lipid nanoparticles (LNPs) are a clinically advanced nucleic acid delivery system with a compact structure suitable for siRNA encapsulation and delivery. Inspired by ongoing clinical trials of albumin-hitchhiking doxorubicin prodrugs, here we developed a DOX-siRNA co-delivery strategy via conjugation of doxorubicin to the surface of siRNA-loaded LNPs. Our optimized LNPs enabled potent knockdown of Bcl-2 and efficient delivery of DOX into the nucleus of Burkitts’ lymphoma (Raji) cells, leading to effective inhibition of tumor growth in a mouse model of lymphoma. Based on these results, our LNPs may provide a platform for the co-delivery of various nucleic acids and DOX for the development of new combination cancer therapies.Temple University. College of EngineeringBioengineerin

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events : results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants

Aims: Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated. Methods and results: After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8. Conclusion: The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect. [GRAPHICS]