Showing papers by "National University of Singapore published in 1996"

The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton.

Abstract: The GTPase RhoA has been implicated in various cellular activities, including the formation of stress fibers, motility, and cytokinesis. We recently reported on a p150 serine/threonine kinase (termed ROK alpha) binding RhoA only in its active GTP-bound state and on its cDNA; introduction of RhoA into HeLa cells resulted in translocation of the cytoplasmic kinase to plasma membranes, consistent with ROK alpha being a target for RhoA (T. Leung, E. Manser, L. Tan, and L. Lim, J. Biol. Chem. 256:29051-29054, 1995). Reanalysis of the cDNA revealed that ROK alpha contains an additional N-terminal region. We also isolated another cDNA which encoded a protein (ROK beta) with 90% identity to ROK alpha in the kinase domain. Both ROK alpha and ROK beta, which had a molecular mass of 160 kDa, contained a highly conserved cysteine/histidine-rich domain located within a putative pleckstrin homology domain. The kinases bound RhoA, RhoB, and RhoC but not Rac1 and Cdc42. The Rho-binding domain comprises about 30 amino acids. Mutations within this domain caused partial or complete loss of Rho binding. The morphological effects of ROK alpha were investigated by microinjecting HeLa cells with DNA constructs encoding various forms of ROK alpha. Full-length ROK alpha promoted formation of stress fibers and focal adhesion complexes, consistent with its being an effector of RhoA. ROK alpha truncated at the C terminus promoted this formation and also extensive condensation of actin microfilaments and nuclear disruption. The proteins exhibited protein kinase activity which was required for stress fiber formation; the kinase-dead ROK alpha K112A and N-terminally truncated mutants showed no such promotion. The latter mutant instead induced disassembly of stress fibers and focal adhesion complexes, accompanied by cell spreading. These effects were mediated by the C-terminal region containing Rho-binding, cysteine/histidine-rich, and pleckstrin homology domains. Thus, the multidomained ROK alpha appears to be involved in reorganization of the cytoskeleton, with the N and C termini acting as positive and negative regulators, respectively, of the kinase domain whose activity is crucial for formation of stress fibers and focal adhesion complexes.

Top Management Support, External Expertise and Information Systems Implementation in Small Businesses

Abstract: Top management support is a key recurrent factor critical for effective information systems (IS) implementation. However, the role of top management support may not be as critical as external IS expertise, in the form of consultants and vendors, in small business IS implementation due to the unique characteristics of small businesses. This paper describes an empirical study of the relative importance of top management support and external IS expertise on IS effectiveness in 114 small businesses. Partial least squares (PLS) was used for statistical testing. The results show that top management support is not as important as effective external IS expertise in small business IS implementation. While top management support is essential for IS effectiveness, high quality external IS expertise is even more critical for small businesses operating in an environment of resource poverty. These findings call for more research efforts to be directed at selecting and engaging high quality external IS expertise for IS implementation in small businesses.

The conservation value of small, isolated fragments of lowland tropical rain forest

Abstract: Deforestation is occurring at an alarming rate in the lowland tropics. In many tropical regions, rain forest is restricted to small (

Photochemical Formation of Silver Nanoparticles in Poly(N-vinylpyrrolidone)

Abstract: Silver nanoparticles have been prepared by photoreduction of silver nitrate with 254 nm UV light in the presence of poly(N-vinylpyrrolidone). The effects of PVP concentration on the particle size, the UV−vis absorption peak, and the rate of the photoreduction process were studied. The average particle size ranged from 15.2 to 22.4 nm, with the corresponding UV−vis absorption peak position at 404−418 nm in 1−0.25 wt % PVP. The rate of the photoreduction process was observed to increase with the PVP concentration. X-ray photoelectron spectroscopic studies further revealed that the polymer interacts with silver particles through the oxygen atom in the >CO group. A negative shift of binding energy in the Ag 3d5/2 for silver nanoparticles was observed.

Top Management Support, External Expertise and Information Systems Implementation in Small Businesses

Abstract: Top management support is a key recurrent factor critical for effective information systems (IS) implementation. However, the role of top management support may not be as critical as external IS expertise, in the form of consultants and vendors, in small business IS implementation due to the unique characteristics of small businesses. This paper describes an empirical study of the relative importance of top management support and external IS expertise on IS effectiveness in 114 small businesses. Partial least squares (PLS) was used for statistical testing. The results show that top management support is not as important as effective external IS expertise in small business IS implementation. While top management support is essential for IS effectiveness, high quality external IS expertise is even more critical for small businesses operating in an environment of resource poverty. These findings call for more research efforts to be directed at selecting and engaging high quality external IS expertise for IS ...

Survival of businesses using collaborative relationships to commercialize complex goods

Abstract: Authors with many theoretical and managerial perspectives argue that businesses commercializing technologically complex goods benefit when they collaborate closely with other businesses. Collaboration is viewed as a means for businesses to overcome competency limitations and to achieve the close configuration of components required for complex goods. We predict that collaborative relationships often assist businesses to produce complex goods, but that the relationships might also cause problems for the collaborating businesses. We find that firms using development-oriented and marketing-oriented collaborative relationships in the hospital software systems industry are less likely to shut down than businesses that follow independent approaches when the environment changes gradually, but businesses using collaborative relationships are sometimes susceptible to being acquired by other firms. Following a sudden environmental shock, businesses with collaborative relationships for activities central to the shock became more likely to shut down, while businesses with collaborative relationships for activities outside the focus of the shock became more likely to survive. The study critically evaluates and tests the widely stated but little-tested argument that interfirm collaboration is usually beneficial. The results address the issue of whether organizational choices affect comparative business performance.

Role of inscuteable in orienting asymmetric cell divisions in Drosophila.

Abstract: Drosophila neuroblasts and epithelial cells in the procephalic neurogenic region divide perpendicular to the surface, and segregate the proteins Numb and Prospero into the basal daughter cell. We demonstrate here that orientation of the mitotic spindle and correct localization of Numb and Prospero in these cells require the inscuteable gene. Moreover, ectopic expression of inscuteable in other epithelial cells leads to spindle reorientation. The Inscuteable protein localizes to the apical cell cortex before mitosis, suggesting that Inscuteable functions in establishing polarity for asymmetric cell division.

Effective data mining using neural networks

Abstract: Classification is one of the data mining problems receiving great attention recently in the database community. The paper presents an approach to discover symbolic classification rules using neural networks. Neural networks have not been thought suited for data mining because how the classifications were made is not explicitly stated as symbolic rules that are suitable for verification or interpretation by humans. With the proposed approach, concise symbolic rules with high accuracy can be extracted from a neural network. The network is first trained to achieve the required accuracy rate. Redundant connections of the network are then removed by a network pruning algorithm. The activation values of the hidden units in the network are analyzed, and classification rules are generated using the result of this analysis. The effectiveness of the proposed approach is clearly demonstrated by the experimental results on a set of standard data mining test problems.

Book review: Machine Learning, Neural and Statistical Classification Edited by D. Michie, D.J. Spiegelhalter and C.C. Taylor (Ellis Horwood Limited, 1994)

Abstract: The book is based on the "StatLog" project which lasted from 1990 to 1993, and involved six academic and 6 industrial laboratories. Statisticians, AI researchers in machine learning, and neural net specialists conducted extensive, collaborative work on the task of classification. This well-edited book provides an up-to-date review of different approaches to classification, compares their performance on a wide range of challenging datasets, and draws conclusions on their applicability to realistic industrial problems.

Activation and association of Stat3 with Src in v-Src-transformed cell lines

Abstract: STAT proteins are a group of latent cytoplasmic transcription factors which function as signal transducers and activators of transcription. Stat1 and -2 were originally identified to function in interferon signaling, and Stat1 was also found to be activated by epidermal growth factor (EGF) and other cytokines. New members of the STAT gene family are identified. Among them, Stat3 has 52.5% amino acid sequence homology with Stat1 and is activated by platelet-derived growth factor (PDGF), colony-stimulating factor 1 (CSF-1), EGF, interleukin-6, and other cytokines. Treatment of cells with EGF activates Stat1 and Stat3, which become phosphorylated on tyrosine residues to form homo - or heterodimers and translocate into the nucleus, binding to the sis-inducible element (SIE) in the c-fos promoter. Somatic cell genetic analyses demonstrated that Jaks, a family of nontransmembrane protein tyrosine kinases, are required for the activation of Stat1 and Stat2 in interferon-treated cells. However, little is known about the activation of Stat3 by growth factors. Here we report that in all v-Src-transformed cell lines examined, Stat3 is constitutively activated to bind to DNA and the phosphorylation of tyrosine on Stat3 is enhanced by the induction of v-Src expression. We also report that Src is shown to be associated with Stat3 in vivo, as well as in vitro, and phosphorylates Stat3 in vitro. Stat3 is also activated by CSF-1, possibly through CSF-1 receptor-c Src association in NIH 3T3 cells overexpressing CSF-1 receptors. Together, the data suggest that Src is involved in activation of Stat3 in growth factor signal transduction.

Job Insecurity and Its Outcomes: Moderating Effects of Work-Based and Nonwork-Based Social Support

Abstract: The moderating effects of work-based support on the relationship between job insecurity and several work-related outcomes, namely (i) job dissatisfaction, (ii) proactive job search, (iii) noncompliant job behaviors; and nonwork based support on the relationship between job insecurity and a nonwork-related outcome, (iv) life dissatisfaction, were examined. Data were gathered through a mail survey to MBA graduates of a large northeastern university in the U.S. The findings of this study suggested that support derived from others at the workplace can contribute significantly in buffering individuals against job dissatisfaction, proactive job search, and noncompliant job behaviors when their job security is at stake. Equally important is support provided by family and friends which may buffer individuals against negative outcomes such as life dissatisfaction associated with job insecurity. Implications of the study are discussed.

Regulation of phosphorylation pathways by p21 GTPases. The p21 Ras-related Rho subfamily and its role in phosphorylation signalling pathways.

Abstract: The oncogenic Ras p21 GTPases regulate phosphorylation pathways that underlie a wealth of activities, including growth and differentiation, in organisms ranging from yeast to human. In metazoa, growth factors trigger conversion of Ras from an inactive GDP-bound form to an active GTP-bound form. This activation of Ras leads to activation of Raf. Raf is one of the initial kinases in the cytoplasmic mitogen-activated protein kinase (MAPK) cascade, involving extracellular-signal-regulated kinases (ERK), which culminates in nuclear transcription. The Ras-related subfamily of Rho p21s, including Rho, Rac and Cdc42 are similarly active in their GTP-bound forms. These p21s mediate growth-factor-induced morphological changes involving actin-based cellular structures. For example, in mammalian fibroblasts, Rho mediates the formation of cytoskeletal stress fibres induced by lysophosphatidic acid, while Rac mediates the formation of membrane ruffles induced by platelet-derived growth factor, and Cdc42 mediates the formation of peripheral filopodia by bradykinin. In some cases, factor-induced Rac activation results in Rho activation, and factor-induced Cdc42 activation leads to Rac activation, as determined by specific morphological changes. Although separate Cdc42/Rac and Rac/Rho hierarchies exist, these might not extend into a linear form (i.e. Cdc42→Rac→Rho) since Cdc42 and Rho activities may be competitive or even antagonistic. Thus Cdc42-mediated formation of filopodia is accompanied by loss of stress fibres (whose formation is mediated by Rho). Recently, mammalian kinases that bind to the GTP-bound forms of Rho p21s have been isolated. These kinases include the p21-activated serine/threonine kinase (PAK), which is stimulated by binding to Cdc42 and Rac, and the Rho-binding serine/threonine kinase (ROK), which is not as strongly stimulated by binding. These kinases act as effectors for their p21 partners since they can directly affect the reorganization of the relevant actin-containing structures. ROK promotes the formation of Rho-induced actin-containing stress fibres and focal-adhesion complexes, to which the ends of the stress fibres attach. PAK stimulates the disassembly of stress fibres, which has been shown to accompany formation of Cdc42-induced peripheral-actin-containing structures, including filopodia, which with Rac-induced membrane ruffles play a role in cell movement. PAK also fosters loss of focal-adhesion complexes. Thus, there is cooperation between different Rho p21s as well as antagonism, with their associated kinases having a role in the integration of the reorganization of the actin cytoskeleton. The similarity of PAK to the Saccharomyces cerevisiae kinase Ste20p, which initiates the yeast mating/pheromone MAPK cascade, led to experiments showing that Cdc42 regulates Ste20p in this MAPK pathway. This similarity has also led to the demonstration that mammalian Cdc42 and Rac can signal to the nucleus through MAPK pathways. However, c-Jun N-terminal kinase (JNK, stress-activated protein kinase) rather than ERK, is involved. PAK have been implicated in the JNK pathway, but their exact roles are uncertain. Thus members of the Rho subfamily, and kinases that bind to these p21s are intimately involved in immediate morphological processes as well as long-term transcriptional events.

The frequency of chimeric molecules as a consequence of PCR co-amplification of 16S rRNA genes from different bacterial species.

Abstract: Our understanding of microbial diversity is greatly hampered by the inability to culture as much as 99% of the microbial community in the biosphere. Development of methods for identification and determining microbial phylogenies based on gene sequences, and for recovering genes directly from diverse environmental samples has made it possible to study microbes without the need for cultivation. PCR techniques have revolutionized retrieval of conserved gene sequences. However, it is well known that co-amplification of homologous genes may generate chimeric sequences leading to descriptions of non-existent species. To quantify the frequency of chimeric sequences in PCR amplification of 16S rRNA genes, we chose several 16S rDNAs with known sequences and mixed them for PCR amplifications under various conditions. Using this model system, we detected 30% occurrence of chimeric sequences after 30 cycles of co-amplification of two nearly identical 16S rRNA genes. The frequency of chimera formation decreased to 12.9% and 14.7% for templates with 82% and 86% similarity, respectively. We also examined effects of the number of amplification cycles, length of elongation periods and presence of damaged DNA on chimera formation. The results should provide useful information for microbiologists who use PCR-based strategies to retrieve conserved genes from mixed genomes.

Specific cleavage of the retinoblastoma protein by an ICE-like protease in apoptosis.

Abstract: Interleukin 1beta-converting enzyme-like (ICE-like) proteases are important mediators of apoptosis in diverse cell types and organisms. However, the role of these proteases in apoptosis cannot be satisfactorily explained on the basis of the physiological functions of their known substrates. Here we show that the C-terminal 42 amino acid peptide of the retinoblastoma (Rb) protein, an important cell cycle regulator with a known anti-apoptotic function, is specifically cleaved off by an ICE-like protease in tumour necrosis factor (TNF)- and staurosporine-induced apoptosis. Cleavage of Rb induced by TNF was blocked in vivo and in vitro by two specific inhibitors of ICE-like proteases, and in vitro by a point mutation (Asp886 to Ala) within the ICE-like protease cleavage site of Rb, (883)DEAD(886). An antibody raised against the C-terminal 15 amino acid peptide of Rb recognized the full-length but not the cleaved form of Rb. The extent of Rb cleavage correlated directly with TNF-induced apoptosis in all tumour cell lines examined. Cleaved Rb bound cyclin D3 and inhibited the transcriptional activity of E2F-1, but failed to bind to the regulatory protein MDM2, which has been implicated in apoptosis. As Rb suppresses cell death and its C-terminus has important regulatory functions, our results suggest that Rb cleavage is an important event in apoptosis.

Quaternionic determinants

Abstract: The classical matrix groups are of fundamental importance in many parts of geometry and algebra. Some of them, like Sp.n/, are most conceptually defined as groups of quaternionic matrices. But, the quaternions not being commutative, we must reconsider some aspects of linear algebra. In particular, it is not clear how to define the determinant of a quaternionic matrix. Over the years, many people have given different definitions. In this article I will try to discuss some of these. I would like to thank Jon Berrick, P. M. Cohn, Soo Teck Lee and the referee for help with improving this paper. Let us first briefly recall some basic facts about quaternions. The quaternions were discovered on October 16 1843 by Sir William Rowan Hamilton. (For more on the history, I recommend [19, 31, 47, 48].) They form a noncommutative, associative algebra over R:

Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine

Abstract: We tested the hypothesis that the level of the DNA repair protein O6-alkylguanine-DNA alkyltransferase in brain tumors was correlated with resistance to carmustine (BCNU) chemotherapy. Alkyltransferase levels in individual cells in sections from 167 primary brain tumors treated with BCNU were quantitated with an immunofluorescence assay using monoclonal antibodies against human alkyltransferase. Patients with high levels of alkyltransferase had shorter time to treatment failure (P = 0.05) and death (P = 0.004) and a death rate 1.7 times greater than patients with low alkyltransferase levels. Furthermore, the size of the subpopulation of cells with high levels of alkyltransferase was correlated directly with drug resistance. For all tumors the variables most closely correlated with survival, in order of importance, were age, tumor grade, and alkyltransferase levels. For glioblastoma multiforme, survival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evaluate alkyltransferase levels as a method, for identifying brain tumor patients with the best likelihood of response to BCNU chemotherapy.

On The Social Networks Of Managers

Abstract: Using data from the National Opinion Research Center's General Social Survey, we compared the organizational membership networks and core discussion networks of managers and nonmanagers. For the tw...

A Drosophila homolog of the Rac- and Cdc42-activated serine/threonine kinase PAK is a potential focal adhesion and focal complex protein that colocalizes with dynamic actin structures.

Abstract: Changes in cell morphology are essential in the development of a multicellular organism. The regulation of the cytoskeleton by the Rho subfamily of small GTP-binding proteins is an important determinant of cell shape. The Rho subfamily has been shown to participate in a variety of morphogenetic processes during Drosophila melanogaster development. We describe here a Drosophila homolog, DPAK, of the serine/threonine kinase PAK, a protein which is a target of the Rho subfamily proteins Rac and Cdc42. Rac, Cdc42, and PAK have previously been implicated in signaling by c-Jun amino-terminal kinases. DPAK bound to activated (GTP-bound) Drosophila Rac (DRacA) and Drosophila Cdc42. Similarities in the distributions of DPAK, integrin, and phosphotyrosine suggested an association of DPAK with focal adhesions and Cdc42- and Rac-induced focal adhesion-like focal complexes. DPAK was elevated in the leading edge of epidermal cells, whose morphological changes drive dorsal closure of the embryo. We have previously shown that the accumulation of cytoskeletal elements initiating cell shape changes in these cells could be inhibited by expression of a dominant-negative DRacA transgene. We show that leading-edge epidermal cells flanking segment borders, which express particularly large amounts of DPAK, undergo transient losses of cytoskeletal structures during dorsal closure. We propose that DPAK may be regulating the cytoskeleton through its association with focal adhesions and focal complexes and may be participating with DRacA in a c-Jun amino-terminal kinase signaling pathway recently demonstrated to be required for dorsal closure.

Anti-HIV triterpene acids from Geum japonicum

Abstract: The methanol extract from the whole plant of Geum japonicum was found to inhibit the human immunodeficiency virus (HIV-1) protease. Through bioassay-directed fractionation of the extract, a new triterpene acid along with five known triterpene acids, ursolic acid, epipomolic acid, maslinic acid, euscaphic acid, and tormentic acid, were isolated. The structure of the new compound was determined by spectral means including 1H-1H COSY, HMQC, HMBC, and NOE experiments to be 2 alpha, 19 alpha-dihydroxy-3-oxo-12-ursen-28-oic acid (1). Of these compounds, 1, ursolic acid, and maslinic acid showed potent inhibitory activity against HIV-1 protease.

Clustering methods for video browsing and annotation

Abstract: The large amount of video data makes it a tedious and hard job to browse and annotate them by just fast forward and rewind. Recent works in video parsing provide a foundation for building interactive and content based video browsing systems. In this paper, a generalized top-down hierarchial clustering process, which adopts partition clustering recursively at each level of the hierarchy, is studied and used to build hierarchical views of video shots. With the clustering processes, when a list of video programs or clips is provided, a browsing system can use either key-frame and/or shot features to cluster shots into classes, each of which consists of shots of similar content. After such clustering, each class of shots can be represented by an icon, which can then be displayed at the high levels of a hierarchical browser. As a result, users can know roughly the content of video shots even without moving down to a lower level of the hierarchy.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Comparison of isotherm models for hydrocarbon adsorption on activated carbon

Abstract: A number of equilibrium isotherm models can be utilized for correlating experimental equilibrium results. Seven different isotherm models are studied using equilibrium data of methane, ethane and propane in activated carbon. Besides comparing the goodness of data fit, the limiting behaviors as well as the pressure and temperature derivatives of the equilibrium isotherm models are also investigated. Performance of multicomponent extensions of these isotherm models and their combinations with the ideal adsorbed solution theory are also compared with experimental data. This systematic evaluation of the more important equilibrium isotherm models provides the general basis for making a preliminary selection of an effective model for a given application. Although an accurate and thermodynamically consistent model is desirable, these requirements may often be compromised for computational simplicity in dynamic process modeling studies.

Symbolic representation of neural networks

Abstract: Neural networks often surpass decision trees in predicting pattern classifications, but their predictions cannot be explained. This algorithm's symbolic representations make each prediction explicit and understandable. Our approach to understanding a neural network uses symbolic rules to represent the network decision process. The algorithm, NeuroRule, extracts these rules from a neural network. The network can be interpreted by the rules which, in general, preserve network accuracy and explain the prediction process. We based NeuroRule on a standard three layer feed forward network. NeuroRule consists of four phases. First, it builds a weight decay backpropagation network so that weights reflect the importance of the network's connections. Second, it prunes the network to remove irrelevant connections and units while maintaining the network's predictive accuracy. Third, it discretizes the hidden unit activation values by clustering. Finally, it extracts rules from the network with discretized hidden unit activation values.