Proteomics of breast cancer for marker discovery and signal pathway profiling

Breast cancer is the most common form of cancer among women and the identification of markers to discriminate tumorigenic from normal cells, as well as the different stages of this pathology, is of critical importance. Two-dimensional electrophoresis has been used before for studying breast cancer, but the progressive completion of human genomic sequencing and the introduction of mass spectrometry, combined with advanced bioinformatics for protein identification, have considerably increased the possibilities for characterizing new markers and therapeutic targets. Breast cancer proteomics has already identified markers of potential clinical interest (such as the molecular chaperone 14-3-3 sigma) and technological innovations such as large scale and high throughput analysis are now driving the field. Methods in functional proteomics have also been developed to study the intracellular signaling pathways that underlie the development of breast cancer. As illustrated with fibroblast growth factor-2, a mitogen and motogen factor for breast cancer cells, proteomics is a powerful approach to identify signaling proteins and to decipher the complex signaling circuitry involved in tumor growth. Together with genomics, proteomics is well on the way to molecularly characterizing the different types of breast tumor, and thus defining new therapeutic targets for future treatment.

The Napster decision : implications for copyright law in the digital age

Challenges posed to copyright law in the digital age is most evident in A and M Records Inc v Napster Inc - the various court rulings indicate that Napster is likely to be held responsible for massive copyright infringement should the case come to a full trial - implications for Australian copyright law, the recording industry and individual artists - globalisation may hinder the ability of the recording industry to prevent mass copyright infringement.

GLUT4 - At the cross roads between membrane trafficking and signal transduction

GLUT4 is a mammalian facilitative glucose transporter that is highly expressed in adipose tissue and striated muscle. In response to insulin, GLUT4 moves from intracellular storage areas to the plasma membrane, thus increasing cellular glucose uptake. While the verification of this 'translocation hypothesis' (Cushman SW. Wardzala LJ. J Biol Chem 1980;255: 4758-4762 and Suzuki K, Kono T. Proc Natl Acad Sci 1980;77: 2542-2545) has increased our understanding of insulin-regulated glucose transport, a number of fundamental questions remain unanswered. Where is GLUT4 stored within the basal cell? How does GLUT4 move to the cell surface and what mechanism does insulin employ to accelerate this process) Ultimately we require a convergence of trafficking studies with research in signal transduction. However, despite more than 30 years of intensive research we have still not reached this point. The problem is complex, involving at least two separate signal transduction pathways which feed into what appears to be a very dynamic sorting process. Below we discuss some of these complexities and highlight new data that are bringing us closer to the resolution of these questions.

Riddling and invariance for discontinuous maps preserving Lebesgue measure

In this paper we use the mixture of topological and measure-theoretic dynamical approaches to consider riddling of invariant sets for some discontinuous maps of compact regions of the plane that preserve two-dimensional Lebesgue measure. We consider maps that are piecewise continuous and with invertible except on a closed zero measure set. We show that riddling is an invariant property that can be used to characterize invariant sets, and prove results that give a non-trivial decomposion of what we call partially riddled invariant sets into smaller invariant sets. For a particular example, a piecewise isometry that arises in signal processing (the overflow oscillation map), we present evidence that the closure of the set of trajectories that accumulate on the discontinuity is fully riddled. This supports a conjecture that there are typically an infinite number of periodic orbits for this system.

Mobile digital technology: Emerging issues for marketing

The growth of direct marketing has been attributed to rapid advances in technology and the changing market context. The fundamental ability of direct marketers to communicate with consumers and to elicit a response, combined with the ubiquitous nature and power of mobile digital technology, provides a synergy that will increase the potential for the success of direct marketing. The aim of this paper is to provide an analytical framework identifying the developments in the digital environment from e-marketing to m-marketing, and to alert direct marketers to the enhanced capabilities available to them.

An action research report on the Korean national digital library

This paper presents the results of my action research. I was involved in establishing and running a digital library that was founded by the government of South Korea. The process involved understanding the relationship between the national IT infrastructure and the success factors of the digital library. In building, the national IT infrastructure, a digital library system was implemented; it combines all existing digitized university libraries and can provide overseas information, such as foreign journal articles, instantly and freely to every Korean researcher. An empirical survey was made as a part of the action research; the survey determined user satisfaction in the newly established national digital library. After obtaining the survey results, I suggested that the current way of running the nationwide government-owned digital library should be retained. (C) 2002 Elsevier Science B.V. All rights reserved.

A new joint coding and modulation scheme for channels with clipping

A major limitation in any high-performance digital communication system is the linearity region of the transmitting amplifier. Nonlinearities typically lead to signal clipping. Efficient communication in such conditions requires maintaining a low peak-to-average power ratio (PAR) in the transmitted signal while achieving a high throughput of data. Excessive PAR leads either to frequent clipping or to inadequate resolution in the analog-to-digital or digital-to-analog converters. Currently proposed signaling schemes for future generation wireless communications suffer from a high PAR. This paper presents a new signaling scheme for channels with clipping which achieves a PAR as low as 3. For a given linear range in the transmitter's digital-to-analog converter, this scheme achieves a lower bit-error rate than existing multicarrier schemes, owing to increased separation between constellation points. We present the theoretical basis for this new scheme, approximations for the expected bit-error rate, and simulation results. (C) 2002 Elsevier Science (USA).

Computational differentiation of N-terminal signal peptides and transmembrane helices

Signal peptides and transmembrane helices both contain a stretch of hydrophobic amino acids. This common feature makes it difficult for signal peptide and transmembrane helix predictors to correctly assign identity to stretches of hydrophobic residues near the N-terminal methionine of a protein sequence. The inability to reliably distinguish between N-terminal transmembrane helix and signal peptide is an error with serious consequences for the prediction of protein secretory status or transmembrane topology. In this study, we report a new method for differentiating protein N-terminal signal peptides and transmembrane helices. Based on the sequence features extracted from hydrophobic regions (amino acid frequency, hydrophobicity, and the start position), we set up discriminant functions and examined them on non-redundant datasets with jackknife tests. This method can incorporate other signal peptide prediction methods and achieve higher prediction accuracy. For Gram-negative bacterial proteins, 95.7% of N-terminal signal peptides and transmembrane helices can be correctly predicted (coefficient 0.90). Given a sensitivity of 90%, transmembrane helices can be identified from signal peptides with a precision of 99% (coefficient 0.92). For eukaryotic proteins, 94.2% of N-terminal signal peptides and transmembrane helices can be correctly predicted with coefficient 0.83. Given a sensitivity of 90%, transmembrane helices can be identified from signal peptides with a precision of 87% (coefficient 0.85). The method can be used to complement current transmembrane protein prediction and signal peptide prediction methods to improve their prediction accuracies. (C) 2003 Elsevier Inc. All rights reserved.

Transposition of first digital pad for reconstruction of a palmar antebrachial soft tissue defect in a cat

An 8-year-old female neutered Siamese cat was presented with a recent history of incomplete excision of an apocrine gland adenocarcinoma from the palmar aspect of the right antebrachium, just proximal to the carpal joint. There was no evidence of metastasis. Wide surgical excision of the previous surgery site was performed resulting in a soft tissue defect. Partial reconstruction was achieved using digital pad transposition of the first digit (dewclaw), forming a local axial pattern flap that was transposed into the adjacent defect. The remaining defect was closed by primary apposition. The skin flap healed successfully. Some breakdown of the skin closed by primary apposition necessitated open wound management. The cosmetic and functional result of the first digital pad transposition was considered excellent, rendering it a useful means to reconstruct soft tissue defects in the carpal region.

Signal trait sexual dimorphism and mutual sexual selection in Drosophila serrata

The evolution of sexual dimorphism may occur when natural and sexual selection result in different optimum trait values for males and females. Perhaps the most prominent examples of sexual dimorphism occur in sexually selected traits, for which males usually display exaggerated trait levels, while females may show reduced expression of the trait. In some species, females also exhibit secondary sexual traits that may either be a consequence of a correlated response to sexual selection on males or direct sexual selection for female secondary sexual traits. In this experiment, we simultaneously measure the intersex genetic correlations and the relative strength of sexual selection on males and females for a set of cuticular hydrocarbons in Drosophila serrata. There was significant directional sexual selection on both male and female cuticular hydrocarbons: the strength of sexual selection did not differ among the sexes but males and females preferred different cuticular hydrocarbons. In contrast with many previous studies of sexual dimorphism, intersex genetic correlations were low. The evolution of sexual dimorphism in D. serrata appears to have been achieved by sex-limited expression of traits controlled by genes on the X chromosome and is likely to be in its final stages.

An advanced method for eliminating impacts from frequency deviations in power system signal processing

Frequency deviation is a common problem for power system signal processing. Many power system measurements are carried out in a fixed sampling rate assuming the system operates in its nominal frequency (50 or 60 Hz). However, the actual frequency may deviate from the normal value from time to time due to various reasons such as disturbances and subsequent system transients. Measurement of signals based on a fixed sampling rate may introduce errors under such situations. In order to achieve high precision signal measurement appropriate algorithms need to be employed to reduce the impact from frequency deviation in the power system data acquisition process. This paper proposes an advanced algorithm to enhance Fourier transform for power system signal processing. The algorithm is able to effectively correct frequency deviation under fixed sampling rate. Accurate measurement of power system signals is essential for the secure and reliable operation of power systems. The algorithm is readily applicable to such occasions where signal processing is affected by frequency deviation. Both mathematical proof and numerical simulation are given in this paper to illustrate robustness and effectiveness of the proposed algorithm. Crown Copyright (C) 2003 Published by Elsevier Science B.V. All rights reserved.

Constitutively active signal transducer and activator of transcription 5 can replace the requirement for growth hormone in adipogenesis of 3T3-F442A preadipocytes

Although it is the best characterized in vitro model of GH action, the mechanisms used by GH to induce differentiation of murine 3T3-F442A preadipocytes remain unclear. Here we have examined the role of three transcriptional regulators in adipogenesis. These regulators are either rapidly induced in response to GH [Stra13, signal transducer and activator of transcription (Stat) 3] or of central importance to GH signaling (Stat5). Retroviral transfection of 3T3-F442A preadipocytes was used to increase expression of Stra13, Stat3, and Stat5a. Only Stat5a transfection increased the expression of adipogenic markers peroxisome proliferator-activated receptor gamma, CCAAT enhancer binding protein (C/EBP)alpha, and adipose protein 2/fatty acid-binding protein in response to GH, as determined by quantitative RT-PCR. Transfection with constitutively active Stat3 and Stat5a revealed that constitutively active Stat5a but not Stat3 was able to replace the GH requirement for adipogenesis. Constitutively active Stat5a but not Stat3 was able to increase the formation of lipid droplets and expression of alpha-glycerol phosphate dehydrogenase toward levels seen in mature adipocytes. Constitutively active Stat5a was also able to increase the expression of transcripts for C/EBPalpha to similar levels as GH, and of C/EBPbeta, peroxisome proliferator-activated receptor gamma, and adipose protein 2/fatty acid-binding protein transcripts to a lesser extent. An in vivo role for GH in murine adipogenesis is supported by significantly decreased epididymal fat depot size in young GH receptor-deleted mice, before manifestation of the lipolytic actions of GH. We conclude that Stat5 is a critical factor in GH-induced, and potentially prolactin-induced, murine adipogenesis.