Induction of apoptosis in a carp leucocyte cell line infected with turbot (Scophthalmus maximus L.) rhabdovirus

A rhabdovirus was observed from the diseased turbot (Scophthalmus maximus L.) with lethal syndrome. In this study, a carp leucocyte (CLC) cell line was used to investigate the infection process and cell death mechanism occurring during the virus infection. Strong cytopathogenic effect (CPE) and the morphological changes, such as extreme chromatin condensation, nucleus fragmentation, and apoptotic body formation, were observed under fluorescence microscopy after DAPI staining in the infected CLC cells. Transmission electron microscopy analysis showed cell shrinkage, plasma membrane blebbing, cytoplasm vacuolization, chromatin condensation, nuclear breakdown and formation of discrete apoptotic bodies. The bullet-shaped nucleocapsids were measured and ranged in size from 110 to 150 nm in length and 40 to 60 nm in diameter. And therefore the virus is called Scophthalmus maximus rhabdovirus (SMRV). Agarose gel electrophoresis analysis of the DNA extracted from infected cells showed typical DNA ladder in the course of SMRV infection. Flow cytometry analysis of SMRV infected CLC cells detected apoptotic peak in the virus infected CLC cells. Virus titre analysis and electron microscopic observation revealed that the virus replication fastigium was earlier than that of the apoptosis occurrence. No apoptosis was observed in the CLC infected with UV-inactivated SMRV. All these supported that SMRV infected CLC cells undergo apoptosis and the virus replication is necessary for apoptosis induction of CLC cells. (C) 2004 Published by Elsevier B.V.

Farnesyltransferase inhibitors induce cytochrome c release and caspase 3 activation preferentially in transformed cells

Farnesyltransferase inhibitors (FTIs) represent a new class of anticancer drugs that show promise in blocking the growth of tumors. Here, we report that FTIs are capable of inducing apoptosis of transformed but not untransformed cells. Treatment of v-K-ras-transformed normal rat kidney (KNRK) cells with FTIs leads to the induction of apoptotic cell morphology, chromatin condensation and DNA fragmentation. In addition, fluorescence-activated cell sorter analysis of FTI-treated KNRK cells shows a sub-G1 apoptotic peak (chromosome content of <2 N). This FTI-induced apoptosis is evident only when the cells are grown in low serum conditions (0.1% fetal calf serum) and is observed selectively with transformed KNRK cells and not with untransformed NRK cells. Further analysis of the mechanism underlying this apoptosis has shown that FTI treatment of KNRK cells results in the activation of caspase 3 but not caspase 1. Moreover, the addition of Z-DEVD-fmk, an agent that interferes with caspase 3 activity, can inhibit FTI-induced apoptosis in a dose-dependent manner. Introduction of the CASP-3 gene into MCF7 cells, which lack caspase 3 activity, results in a significant increase of FTI-induced apoptosis. Furthermore, FTI induces the release of cytochrome c into the cytosol. This release is an important feature of caspase 3-mediated apoptosis. These results suggest that FTIs induce apoptosis through the release of cytochrome c from the mitochondria resulting in caspase 3 activation.

Cytotoxic and pro-apoptotic effects of Abrus precatorius L. on human metastatic breast cancer cell line, MDA-MB-231

Abrus precatorius is highly regarded as a universal panacea in the herbal medicine with diverse pharmacological activity spectra. This experimental study on the mechanism of the anticancer activity of A. precatorius leaf extracts, may offer new evidence for A. precatorius in the treatment of breast cancer in clinical practice. Cell death was determined by using MTT assay. Further analyses were carried out by doing DNA laddering, PARP cleavage, FACS, semi-quantitative RT-PCR and detection of cellular reactive oxygen species (ROS) by DCFDA assay. A. precatorius showed very striking inhibition on MDA-MB-231 cells. MTT assay showed more than 75 % inhibition of the cells and treated cells indicated visible laddering pattern with thick compact band. PARP cleavage produced 89 kDa cleavage product which was associated with apoptosis. Flow cytometer exhibited a sub-G0/G1 peak as an indicative of apoptosis. mRNA expression level of apoptosis-related genes p21 and p53 was markedly increased in cells treated with the extract as compared to control. The up-regulation of p21 and p53 may be the molecular mechanisms by which A. precatorius extract which induces apoptosis. An increase in the concentration of A. precatorius extract does not generate ROS, instead it reduces ROS formation in MDA-MB-231 cells, as evident from the shift in fluorescence below untreated control. This is the first report showing that A. precatorius leaf extract exhibits a growth inhibitory effect by induction of apoptosis in MDA-MB-231 cells. Our results contribute towards validation of the A. precatorius extract as a potentially effective chemopreventive or therapeutic agent against breast cancer.

Peak-to-average power ratio of IEEE 802.11a PHY layer signals

In this chapter we propose clipping with amplitude and phase corrections to reduce the peak-to-average power ratio (PAR) of orthogonal frequency division multiplexed (OFDM) signals in high-speed wireless local area networks defined in IEEE 802.11a physical layer. The proposed techniques can be implemented with a small modification at the transmitter and the receiver remains standard compliant. PAR reduction as much as 4dB can be achieved by selecting a suitable clipping ratio and a correction factor depending on the constellation used. Out of band noise (OBN) is also reduced.

Interleaved PC-OFDM to reduce peak-to-average power ratio

Parallel combinatory orthogonal frequency division multiplexing (PC-OFDM yields lower maximum peak-to-average power ratio (PAR), high bandwidth efficiency and lower bit error rate (BER) on Gaussian channels compared to OFDM systems. However, PC-OFDM does not improve the statistics of PAR significantly. In this chapter, the use of a set of fixed permutations to improve the statistics of the PAR of a PC-OFDM signal is presented. For this technique, interleavers are used to produce K-1 permuted sequences from the same information sequence. The sequence with the lowest PAR, among K sequences is chosen for the transmission. The PAR of a PC-OFDM signal can be further reduced by 3-4 dB by this technique. Mathematical expressions for the complementary cumulative density function (CCDF)of PAR of PC-OFDM signal and interleaved PC-OFDM signal are also presented.

Peak power demand reduction under moving block signalling using an expert system

The concept of moving block signallings (MBS) has been adopted in a few mass transit railway systems. When a dense queue of trains begins to move from a complete stop, the trains can re-start in very close succession under MBS. The feeding substations nearby are likely to be overloaded and the service will inevitably be disturbed unless substations of higher power rating are used. By introducing starting time delays among the trains or limiting the trains’ acceleration rate to a certain extent, the peak energy demand can be contained. However, delay is introduced and quality of service is degraded. An expert system approach is presented to provide a supervisory tool for the operators. As the knowledge base is vital for the quality of decisions to be made, the study focuses on its formulation with a balance between delay and peak power demand.

A novel load transfer scheme for peak load management in rural areas

This paper proposes a novel peak load management scheme for rural areas. The scheme transfers certain customers onto local nonembedded generators during peak load periods to alleviate network under voltage problems. This paper develops and presents this system by way of a case study in Central Queensland, Australia. A methodology is presented for determining the best location for the nonembedded generators as well as the number of generators required to alleviate network problems. A control algorithm to transfer and reconnect customers is developed to ensure that the network voltage profile remains within specification under all plausible load conditions. Finally, simulations are presented to show the performance of the system over a typical maximum daily load profile with large stochastic load variations.

Demand side response to mitigate electrical peak demand in Eastern and Southern Australia

The aim of this work is to develop a Demand-Side-Response (DSR) model, which assists electricity end-users to be engaged in mitigating peak demands on the electricity network in Eastern and Southern Australia. The proposed innovative model will comprise a technical set-up of a programmable internet relay, a router, solid state switches in addition to the suitable software to control electricity demand at user's premises. The software on appropriate multimedia tool (CD Rom) will be curtailing/shifting electric loads to the most appropriate time of the day following the implemented economic model, which is designed to be maximizing financial benefits to electricity consumers. Additionally the model is targeting a national electrical load be spread-out evenly throughout the year in order to satisfy best economic performance for electricity generation, transmission and distribution. The model is applicable in region managed by the Australian Energy Management Operator (AEMO) covering states of Eastern-, Southern-Australia and Tasmania.

p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.

Obtaining peak performance in the transition to Higher Education: Support for the worried well, acutely anxious and seriously sluggish student

Research suggests that students in their late teens and early twenties have not reached "identity formation" (James Marcia, 1969, 1980). The heightened anxiety and uncertainty about themselves and their future contribute to sometimes crippling fears emanating as anxiety, clinical depression and other mood disorders. This paper will explore some issues and suggest healthy ways of helping young people safely through these chaotic years and into a fulfilling career.

A practical signal processing approach for condition monitoring of low speed machinery using Peak-Hold-Down-Sample algorithm

A simple and effective down-sample algorithm, Peak-Hold-Down-Sample (PHDS) algorithm is developed in this paper to enable a rapid and efficient data transfer in remote condition monitoring applications. The algorithm is particularly useful for high frequency Condition Monitoring (CM) techniques, and for low speed machine applications since the combination of the high sampling frequency and low rotating speed will generally lead to large unwieldy data size. The effectiveness of the algorithm was evaluated and tested on four sets of data in the study. One set of the data was extracted from the condition monitoring signal of a practical industry application. Another set of data was acquired from a low speed machine test rig in the laboratory. The other two sets of data were computer simulated bearing defect signals having either a single or multiple bearing defects. The results disclose that the PHDS algorithm can substantially reduce the size of data while preserving the critical bearing defect information for all the data sets used in this work even when a large down-sample ratio was used (i.e., 500 times down-sampled). In contrast, the down-sample process using existing normal down-sample technique in signal processing eliminates the useful and critical information such as bearing defect frequencies in a signal when the same down-sample ratio was employed. Noise and artificial frequency components were also induced by the normal down-sample technique, thus limits its usefulness for machine condition monitoring applications.