Low voltage to high voltage level shifter and related methods

A shifter circuit comprises a high and low voltage buffer stages and an output buffer stage. The high voltage buffer stage comprises multiple transistors arranged in a transistor stack having a plurality of intermediate nodes connecting individual transistors along the stack. The transistor stack is connected between a voltage level being shifted to and an input voltage. An inverter of this stage comprises multiple inputs and an output. Inverter inputs are connected to a respective intermediate node of the transistor stack. The low voltage buffer stage has an input connected to the input voltage and an output, and is operably connected to the high voltage buffer stage. The low voltage buffer stage is connected between a voltage level being shifted away from and a lower voltage. The output buffer stage is driven by the outputs of the high voltage buffer stage inverter and the low voltage buffer stage

The role of PAR1 autoantibodies in patients with primary epithelial ovarian cancer

AIM: This study aimed to analyze the predictive, prognostic and diagnostic value of autoantibodies to coagulation factor II thrombin receptor (F2R; protease-activated receptor 1, PAR1) (PAR1-AB) in patients with primary epithelial ovarian cancer (EOC). MATERIALS AND METHODS: A total of 197 patients with primary EOC and 200 healthy female blood donors were included in the study. Enzyme-linked immunosorbent assay was applied to determine PAR1-AB levels in blood sera taken preoperatively. Correlation of PAR1-AB with clinicopathological outcome, progression-free (PFS) and overall (OS) survival was analyzed and patients were compared with controls. RESULTS: PAR1-AB was significantly negatively correlated with histological grading (p=0.008) and was significantly lower in the patient group compared to healthy controls (p<0.001). There was no significant correlation of PAR1-AB level with PFS or OS. CONCLUSION: This study showed PAR1-AB to significantly decrease in patients with primary EOC and with histological high-grade carcinoma. The relevance of PAR1-AB in early detection of ovarian cancer and follow-up for EOC should be further investigated

HIF1&alpha; is an independent prognostic factor for overall survival in advanced primary epithelial ovarian cancer &ndash; a study of the OVCAD Consortium

Elena Ioana Braicu,1 Hrvoje Luketina,1 Rolf Richter,1 Dan Cacsire Castillo-Tong,2 Sandrina Lambrechts,4 Sven Mahner,5 Nicole Concin,6 Monika Mentze,1 Robert Zeillinger,2,3 Ignace Vergote,4 Jalid Sehouli1 1Department of Gynecology, European Competence Center for Ovarian Cancer, Charit&eacute; &ndash; Universit&auml;tsmedizin Berlin, Berlin, Germany; 2Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 3Ludwig Boltzmann Cluster Translational Oncology, General Hospital of Vienna, Vienna, Austria; 4Department of Obstetrics and Gynecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Leuven, Belgium; 5Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 6Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, AustriaPurpose: Hypoxia is a common phenomenon encountered in solid cancers, leading to chemotherapy resistance and therefore to aggressiveness of the disease. The homeostatic response to hypoxia is mediated by hypoxia-inducible factor-1 (HIF-1). The aim of this study was to investigate the impact of HIF1&alpha; in patients with primary epithelial ovarian cancer.Methods: In this multicentric study, 275 patients with advanced primary epithelial ovarian cancer were included. All patients underwent cytoreductive surgery with maximal surgical effort and adjuvant platinum-based chemotherapy. HIF1&alpha; expression was analyzed in tissue lysates, using an enzyme-linked immunosorbent assay.Results: HIF1&alpha; was detected in 79.3% of the tissue samples. Patients with increased HIF1&alpha; expression (cutoff: 80 pg/mg protein) in tumoral tissue lysates were more likely to have less favorable survival. HIF1&alpha; (P=0.009, hazard ratio [HR] 2.505, 95% confidence interval [95% CI] 1.252&ndash;5.013) together with International Federation of Gynecology and Obstetrics (III versus IV) (P=0.013, HR 0.540, 95% CI 0.332&ndash;0.878), histology (P=0.007, HR 2.748, 95% CI 1.315&ndash;5.743), presence of peritoneal carcinomatosis (P=0.014, HR 2.176, 95% CI 1.170&ndash;4.046), residual tumor mass (P=0.017, HR 1.641, 95% CI 1.091&ndash;2.468), and response to platinum-based chemotherapy (P&lt;0.001, HR 8.131, 95% CI 5.13&ndash;12.88) were independent prognosis factors for overall survival. The independent prognostic factors for progression-free survival were International Federation of Gynecology and Obstetrics stage (P=0.01), histological subtypes (P=0.016), and presence of peritoneal carcinomatosis (P&lt;0.05).Conclusion: HIF1&alpha; overexpression in ovarian cancer is associated with poor overall survival, underlining the importance of hypoxia in this angiogenesis driven disease.Keywords: HIF1&alpha;, surgical outcome, platinum response, survival, primary epithelial ovarian cancer, predictive factor