The elastic-plastic behaviour of some axisymmetric pressure vessel heads and nozzles

Imperial Users onl

A genetic approach toward defining the role of Factor X in development and coagulation

Activated Factor X (FX) is a vitamin K-dependent serine protease that plays a crucial role in blood coagulation by converting prothrombin to thrombin. There are no humans with complete deficiency of FX. The overall objective of this study is to investigate the role of FX in development and coagulation by generating FX-deficient mouse models and determining the embryonic pattern of FX expression. First, a FX knock-out mouse model was engineered by eliminating FX exon 8 and its 3’ flanking sequence; this resulted in embryonic or perinatal lethality in FX -/- mice. Approximately 50% of FX -/- embryos died between days 10-12 of development. Fatal bleeding in the remaining FX(-/-) animals occurred soon after birth. The cause of embryonic lethality remains unclear. Next, a viable mouse model of FX deficiency was generated. These mice expressed a FX variant with normal antigen levels but a low level of activity (4-9% in humans carrying the analogous defect, Pro343→Ser, termed FX Friuli). Homozygous mice had FX coagulation activity of ~5.5% of normal, which was sufficient to rescue both embryonic and perinatal lethality. To generate mice with even lower FX activity, FX(F/F) and FX(+/-) mice were crossed. Their offspring, FX(-/F) mice, indeed had even lower FX activity (1-3% of normal) and nonetheless also showed complete rescue of embryonic and perinatal lethality. Therefore, while complete absence of FX is incompatible with murine and human survival, minimum FX activity as low as 1% demonstrates sufficiency in rescue of FX knockout mice from lethality. FX(-/F) mice provided an opportunity to assess the relative contributions of maternal and embryonic FX as well as FX activity and antigen to embryonic survival. FX(-/F) mice also facilitated investigation into a developmental role of FX by allowing for examination of FX(-/-) embryos born to mothers with minimal levels of FX activity. Furthermore, FX expression in multiple embryonic tissues was detected by in situ hybridization and immunostaining. Combined, these results represent an initial investigation into defining the role of FX in development.Ph.D., Biomedical Science -- Drexel University, 200

Enhanced Temperature Control Method Using ANFIS with FPGA

Temperature control in etching process is important for semiconductor manufacturing technology. However, pressure variations in vacuum chamber results in a change in temperature, worsening the accuracy of the temperature of the wafer and the speed and quality of the etching process. This work develops an adaptive network-based fuzzy inference system (ANFIS) using a field-programmable gate array (FPGA) to improve the effectiveness. The proposed method adjusts every membership function to keep the temperature in the chamber stable. The improvement of the proposed algorithm is confirmed using a medium vacuum (MV) inductively-coupled plasma- (ICP-) type etcher

Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis

The cellular apoptosis susceptibility (CSE1L/CAS) protein is highly expressed in cancer, and its expression is positively correlated with high cancer stage, high cancer grade, and worse outcomes of patients. CSE1L (or CAS) regulates chemotherapeutic drug-induced cancer cell apoptosis and may play important roles in mediating the cytotoxicities of chemotherapeutic drugs against cancer cells in cancer chemotherapy. CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression. However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells. Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer. Therefore, CSE1L may be a useful serological marker for screening, diagnosis and prognosis, assessment of therapeutic responses, and monitoring for recurrence of cancer. In this paper, we review the expression of CSE1L in cancer and discuss why CSE1L regulates the invasion and metastasis rather than the proliferation of cancer

Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA), and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc), five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group), 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second of 10, but different electric field strengths of 0 (ie, no voltage, control group), 74, 148, 296, and 592 V/cm. Before and after each extraction experiment, skin impedance was measured at 20 Hz.Results: It was found that urea could be extracted transdermally using reverse iontophoresis alone, and further enhancement of extraction could be achieved by combined use of electroporation and reverse iontophoresis. Conversely, PSA and osteopontin were found to be extracted transdermally only by use of reverse iontophoresis and electroporation with a high electrical field strength (>296 V/cm). After application of reverse iontophoresis, electroporation, or a combination of the two techniques, a reduction in skin impedance was observed.Conclusion: Simultaneous transdermal extraction of urea, PSA, and osteopontin is possible only for the condition of applying reverse iontophoresis in conjunction with high electroporation.Keywords: electroporation, reverse iontophoresis, nanochannels, noninvasive, urea, prostate-specific antigen, osteoponti

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is one of the most common malignant cancers in Southeast Asia and Southern China. Centipeda minima extract (CME) had previously demonstrated anti-cancer effects in human NPC. Brevilin A, a sesquiterpene lactone isolated from C. minima, has been reported to exhibit biological activities. In this study, we investigated its anti-NPC effect and further explored its molecular mechanisms. The effects of brevilin A were tested in the NPC cell lines CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. Effects of brevilin A on cell viability were determined by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. The molecular mechanism of cell cycle regulation and apoptosis were investigated via Western blot. Results showed that brevilin A inhibited NPC cell viability in a concentration- and time-dependent manner. Brevilin A induced cell cycle arrest at G2/M and induced apoptosis. Western blot results demonstrated that brevilin A could down-regulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, while up-regulating cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by brevilin A showed dynamic changes according to dose and time. In the tumor xenograft model, brevilin A could reduce tumor growth, at a similar magnitude to cisplatin. However, notably, whereas cisplatin treatment led to significant weight loss in treated mice, treatment with brevilin A did not, indicating its relative lack of toxicity. Taken together, brevilin A regulated cell cycle, activated the caspase signaling pathway, and inhibited PI3K/AKT/mTOR and STAT3 signaling pathways in vitro, and exhibited similar efficacy to the common chemotherapeutic cisplatin in vivo, without its associated toxicity. These findings provide a framework for the preclinical development of brevilin A as a chemotherapeutic for NPC