27 research outputs found
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Pulse shaping effects on weld porosity in laser beam spot welds : contrast of long- & short- pulse welds.
Weld porosity is being investigated for long-pulse spot welds produced by high power continuous output lasers. Short-pulse spot welds (made with a pulsed laser system) are also being studied but to a much small extent. Given that weld area of a spot weld is commensurate with weld strength, the loss of weld area due to an undefined or unexpected pore results in undefined or unexpected loss in strength. For this reason, a better understanding of spot weld porosity is sought. Long-pulse spot welds are defined and limited by the slow shutter speed of most high output power continuous lasers. Continuous lasers typically ramp up to a simmer power before reaching the high power needed to produce the desired weld. A post-pulse ramp down time is usually present as well. The result is a pulse length tenths of a second long as oppose to the typical millisecond regime of the short-pulse pulsed laser. This study will employ a Lumonics JK802 Nd:YAG laser with Super Modulation pulse shaping capability and a Lasag SLS C16 40 W pulsed Nd:YAG laser. Pulse shaping will include square wave modulation of various peak powers for long-pulse welds and square (or top hat) and constant ramp down pulses for short-pulse welds. Characterization of weld porosity will be performed for both pulse welding methods
Platelet function is disturbed by the angiogenesis inhibitors sunitinib and sorafenib, but unaffected by bevacizumab
Introduction: At the clinical introduction of antiangiogenic agents as anticancer agents, no major toxicities were expected as merely just endothelial cells (ECs) in tumors would be affected. However, several (serious) toxicities became apparent, of which underlying mechanisms are largely unknown. We investigated to what extent sunitinib (multitargeted antiangiogenic tyrosine kinase inhibitor (TKI)), sorafenib (TKI) and bevacizumab [specific antibody against vascular endothelial growth factor (VEGF)] may impair platelet function, which might explain treatment-related bleedings. Materials and methods: In vitro, the influence of sunitinib, sorafenib, and bevacizumab on platelet aggregation, P-selectin expression and fibrinogen binding, platelet–EC interaction, and tyrosine phosphorylation of c-Src was studied by optical aggregation, flow cytometry, real-time perfusion, and western blotting. Ex vivo, platelet aggregation was analyzed in 25 patients upon sunitinib or bevacizumab treatment. Concentrations of sunitinib, VEGF, and platelet and EC activation markers were measured by LC–MS/MS and ELISA. Results: In vitro, sunitinib and sorafenib significantly inhibited platelet aggregation (20 μM sunitinib: 71.3%, p < 0.001; 25 μM sorafenib: 55.8%, p = 0.042). Sorafenib and sunitinib significantly inhibited P-selectin expression on platelets. Exposure to both TKIs resulted in a reduced tyrosine phosphorylation of c-Src. Ex vivo, within 24 h sunitinib impaired platelet aggregation (83.0%, p = 0.001, N = 8). Plasma concentrations of sunitinib, VEGF, and platelet/EC activation markers were not correlated with disturbed aggregation. In contrast, bevacizumab only significantly impaired platelet aggregation in vitro at high c
Physicochemical properties of novel protein kinase inhibitors in relation to their substrate specificity for drug transporters
Cell Cycle Effects and Increased Adduct Formation by Temozolomide Enhance the Effect of Cytotoxic and Targeted Agents in Lung Cancer Cell Lines
Inhibition of thymidylate synthase by 2 ',2 '-difluoro-2 '-deoxycytidine (Gemcitabine) and its metabolite 2 ',2 '-difluoro-2 '-deoxyuridine
Pharmacological Aspects of the Enzastaurin-Pemetrexed Combination in Non-Small Cell Lung Cancer (NSCLC)
Role of pharmacodynamic, pharmacogenetic and pharmacogenomic biomarkers of cancer chemotherapy with antifolates
Optimal treatment scheduling of ionizing radiation and sunitinib improves the antitumor activity and allows dose reduction
The prognostic impact of circulating miRNAs in patients with advanced esophagogastric cancer during palliative chemotherapy
The prognosis of patients with advanced oesophageal cancer (EC) and gastric cancer (GC) is poor. Circulating microRNAs (ci-miRNAs) may have prognostic and predictive value to improve patient selection for palliative treatment. The purpose of this study is to assess the prognostic and predictive value of specific ci-miRNAs in plasma of patients with EC and GC treated with first-line palliative gemcitabine and cisplatin. Droplet digital PCR (ddPCR) was used to quantify miR-200c-3p, miR-375, miR-21-5p, miR-148a-3p, miR-146a-5p, miR-141-3p and miR-218-5p in plasma from 68 patients. ci-miRNA expression was analyzed in relation to overall survival (OS), progression-free survival (PFS), and response to chemotherapy. ci-miRNA levels were detectable in 36 baseline (71%) samples and in 14 (47%) follow-up samples. Increased circulating miR-200c-3p in GC showed a trend (p = 0.06) towards a shorter OS. High circulating miR-375 was associated with a longer OS (p = 0.02) in patients with esophageal adenocarcinoma (EAC). No significant difference was observed in ci-miRNA expression between paired pre- and on-treatment samples. ci-miRNA expression was not associated with response to chemotherapy. ci-miRNAs can be measured in plasma samples of patients treated with first-line palliative chemotherapy using ddPCR despite prolonged storage in heparin. Elevated circulating miR-375 might be a prognostic marker for patients with EAC