It’s an Illusion that Border Restrictions Help to Deal With a Global Outbreak

Clare Wenham 동아시아재단 2020 Global Asia Vol.15 No.1

A GPS Positioning Method for Underwater Targets Using Dual Acoustic Devices

Lili Ai,Wenham Xu,Yancheng Liu,Youtao Zhao 보안공학연구지원센터 2016 International Journal of Future Generation Communi Vol.9 No.1

Since the existing underwater GPS positioning technology can only position underwater targets equipped with acoustic transponders, this study proposed a method of positioning underwater combining targets based on an ultra short baseline forward-looking sonar acoustic device. The mathematical model of the obtaining longitude and latitude coordinates of the underwater target in the WGS84 ellipsoidal coordinate system was established. A group of data was given based on the measuring state, and Monte Carlo simulation was carried out to study the effects of the random errors in the indirect measurements in the algorithm on the positioning accuracy and the combined effect of the random errors in the indirect measurements in the algorithm on the positioning accuracy at different geological locations. The preset target was measured in the offshore waters of Dalian, confirming the validity of the proposed algorithm.

Photovoltaics and Renewable Energy Education and Research at the University of New South Wales

R. Corkish,S.R. Wenham,A.B. Sproul,J. Cotter,C.B. Honsberg,M.A. Green,A.G. Aberle,G. Conibeer,J. Zhao 한국태양에너지학회 2004 한국태양에너지학회 학술대회논문집 Vol.- No.-

BCL2 antagonist of cell death kinases, phosphatases, and ovarian cancer sensitivity to cisplatin

Nisha Bansal,Douglas C. Marchion,Elona Bicaku,Yin Xiong,Ning Chen,Xiaomang B. Stickles,Entidhar Al Sawah,Robert M. Wenham,Sachin M. Apte,Jesus Gonzalez-Bosquet,Patricia L. Judson,Ardeshir Hakam,Johnat 대한부인종양학회 2012 Journal of Gynecologic Oncology Vol.23 No.1

Objective: The BCL2 family proteins are critical mediators of cellular apoptosis and, as such, have been implicated as determinants of cancer cell chemo-sensitivity. Recently, it has been demonstrated that the phosphorylation status of the BCL2 antagonist of cell death (BAD) protein may influence ovarian cancer (OVCA) cell sensitivity to cisplatin. Here, we sought to evaluate how kinase and phosphatase components of the BAD apoptosis pathway influence OVCA chemo-sensitivity. Methods: Protein levels of cyclin-dependent kinase 1 (CDK1) and protein phosphatase 2C (PP2C) were measured by immunofluorescence in a series of 64 primary advanced-stage serous OVCA patient samples. In parallel, levels of cAMP-dependent protein kinase (PKA), AKT, and PP2C were quantified by Western blot analysis in paired mother/daughter platinum-sensitive/resistant OVCA cell lines (A2008/C13, A2780S/A2780CP, Chi/ChiR). BAD pathway kinase CDK1 was depleted using siRNA transfection, and the influence on BAD phosphorylation and cisplatin-induced apoptosis was evaluated. Results: OVCA patient samples that demonstrated complete responses to primary platinum-based therapy demonstrated 4-fold higher CDK1 (p<0.0001) and 2-fold lower PP2C (p=0.14) protein levels than samples that demonstrated incomplete responses. Protein levels of PP2C were lower in the platinum-resistant versus that shown in the platinum-sensitive OVCA cell line sub-clones. Levels of PKA were higher in all platinum-resistant than in platinum-sensitive OVCA cell line sub-clones. Selective siRNA depletion of CDK1 increased sensitivity to cisplatin-induced apoptosis (p<0.002). Conclusion: BAD pathway kinases and phosphatases, including CDK1 and PP2C, are associated with OVCA sensitivity to platinum and may represent therapeutic opportunities to enhance cytotoxic efficacy. Objective: The BCL2 family proteins are critical mediators of cellular apoptosis and, as such, have been implicated as determinants of cancer cell chemo-sensitivity. Recently, it has been demonstrated that the phosphorylation status of the BCL2 antagonist of cell death (BAD) protein may influence ovarian cancer (OVCA) cell sensitivity to cisplatin. Here, we sought to evaluate how kinase and phosphatase components of the BAD apoptosis pathway influence OVCA chemo-sensitivity. Methods: Protein levels of cyclin-dependent kinase 1 (CDK1) and protein phosphatase 2C (PP2C) were measured by immunofluorescence in a series of 64 primary advanced-stage serous OVCA patient samples. In parallel, levels of cAMP-dependent protein kinase (PKA), AKT, and PP2C were quantified by Western blot analysis in paired mother/daughter platinum-sensitive/resistant OVCA cell lines (A2008/C13, A2780S/A2780CP, Chi/ChiR). BAD pathway kinase CDK1 was depleted using siRNA transfection, and the influence on BAD phosphorylation and cisplatin-induced apoptosis was evaluated. Results: OVCA patient samples that demonstrated complete responses to primary platinum-based therapy demonstrated 4-fold higher CDK1 (p<0.0001) and 2-fold lower PP2C (p=0.14) protein levels than samples that demonstrated incomplete responses. Protein levels of PP2C were lower in the platinum-resistant versus that shown in the platinum-sensitive OVCA cell line sub-clones. Levels of PKA were higher in all platinum-resistant than in platinum-sensitive OVCA cell line sub-clones. Selective siRNA depletion of CDK1 increased sensitivity to cisplatin-induced apoptosis (p<0.002). Conclusion: BAD pathway kinases and phosphatases, including CDK1 and PP2C, are associated with OVCA sensitivity to platinum and may represent therapeutic opportunities to enhance cytotoxic efficacy.

Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial

Vergote, Ignace,Scambia, Giovanni,O'Malley, David M,Van Calster, Ben,Park, Sang-Yoon,del Campo, Josep M,Meier, Werner,Bamias, Aristotelis,Colombo, Nicoletta,Wenham, Robert M,Covens, Al,Marth, Christia Elsevier 2019 LANCET ONCOLOGY Vol.20 No.6

<P><B>Summary</B></P> <P><B>Background</B></P> <P>Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial.</P> <P><B>Methods</B></P> <P>TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m<SUP>2</SUP>) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete.</P> <P><B>Findings</B></P> <P>Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7–34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0–17·6]) and the placebo group (15·0 months [12·6–16·1]) groups (hazard ratio 0·93 [95% CI 0·79–1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] <I>vs</I> placebo 126 [38%]) anaemia (76 [11%] <I>vs</I> 40 [12%]), and leucopenia (81 [12%] <I>vs</I> 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group.</P> <P><B>Interpretation</B></P> <P>Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population.</P> <P><B>Funding</B></P> <P>Amgen.</P>