The calpastatin-derived calpain inhibitor CP1B reduces mRNA expression of matrix metalloproteinase-2 and-9 and invasion by leukemic THP-1 cells

The ubiquitous proteases μ- and m-calpain are Ca2+-dependent cysteine endopeptidases. Besides involvement in a variety of physio(patho)logical processes, recent studies suggest a pivotal role of calpains in differentiation of hematopoietic cells and tumor cell invasion. However, the precise actions of calpains and their endogenous inhibitor, calpastatin, in these processes are only partially understood. Here we have studied the role of the calpain/calpastatin system in the invasion of leukemic cells under basal and differentiationstimulating conditions. To further differentiate the human leukaemic cell line THP-1 (monocytic), the cells were treated for 24 hours with the differentiationstimulating reagents phorbol 12-myristate 13-acetate (PMA) and dimethyl sulfoxide (DMSO). Macrophage and granulocytelike differentiation was confirmed by induction of vimentin expression as well as by microscopic and fluorescence assisted cytometric analysis. Extracellular matrix (ECM) invasion of both the basal and differentiation stimulated cells in a Matrigel assay was inhibited by preincubation of the cells with the specific calpain inhibitor CP1B for 24 hours. Inhibition of invasiveness correlated with decreased mRNA expression and secretion of the matrix metalloproteinases MMP-2 and MMP-9. In contrast, addition of CP1B only during the invasion process did neither influence transmigration nor MMP release. This is the first report showing that the calpain/calpastatin system mediates MMPmRNA expression of the leukemic THP-1 cells and as a consequence their invasiveness

The Physics of Miniature Worlds

This excerpt from a book length work on the history of the methodology of experimental physical models (physically similar systems) interwoven in Ludwig Wittgenstein's life begins in 1913-1914. It also discusses works by physicists around the same time that were thematically related to the philosophical topics he was working on: Ludwig Boltzmann, Wilhelm Ostwald, Edgar Buckingham, James Thomson, D'Arcy Wentworth Thompson, Henry Crew (and his new translation of Galileo's Two New Sciences during this period), Heike Kamerlingh Onnes, Van Der Waals, and Rayleigh (following up on the work of Gabriel Stokes), and Richard C Tolman. The landmark work at Britain's National Physical Laboratory in 1914 on Similar Motions by Stanton and Pannell, following up on Osborne Reynolds' work in Manchester, is also described and discussed. Connections between physics and the history of flight are mentioned, too: Penuad's successes, Boltzmann's relationship with engineer Otto Lilienthal, and the significance that Hermann von Helmholtz's landmark paper in meteorology which addressed the problem of steering aircraft, took on during this period

Nowhere minimal CR submanifolds and Levi-flat hypersurfaces

A local uniqueness property of holomorphic functions on real-analytic nowhere minimal CR submanifolds of higher codimension is investigated. A sufficient condition called almost minimality is given and studied. A weaker necessary condition, being contained a possibly singular real-analytic Levi-flat hypersurface is studied and characterized. This question is completely resolved for algebraic submanifolds of codimension 2 and a sufficient condition for noncontainment is given for non algebraic submanifolds. As a consequence, an example of a submanifold of codimension 2, not biholomorphically equivalent to an algebraic one, is given. We also investigate the structure of singularities of Levi-flat hypersurfaces.Comment: 21 pages; conjecture 2.8 was removed in proof; to appear in J. Geom. Ana

Development of a generic activities model of command and control

This paper reports on five different models of command and control. Four different models are reviewed: a process model, a contextual control model, a decision ladder model and a functional model. Further to this, command and control activities are analysed in three distinct domains: armed forces, emergency services and civilian services. From this analysis, taxonomies of command and control activities are developed that give rise to an activities model of command and control. This model will be used to guide further research into technological support of command and control activities

The effects of a plant proteinase inhibitor from Enterolobium contortisiliquum on human tumor cell lines

Supplementary to the efficient inhibition of trypsin, chymotrypsin, plasma kallikrein, and plasmin already described by the EcTI inhibitor from Enterolobium contortisiliquum, it also blocks human neutrophil elastase (K(iapp)=4.3 nM) and prevents phorbol ester (PMA)-stimulated activation of matrix metalloproteinase (MMP)-2 probably via interference with membrane-type 1 (MT1)-MMP. Moreover, plasminogen-induced activation of proMMP-9 and processing of active MMP-2 was also inhibited. Furthermore, the effect of EcTI on the human cancer cell lines HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), K562 and THP-1 (leukemia), as well as on human primary fibroblasts and human mesenchymal stem cells (hMSCs) was studied. EcTI inhibited in a concentration range of 1.0-2.5 mu M rather specifically tumor cell viability without targeting primary fibroblasts and hMSCs. Taken together, our data indicate that the polyspecific proteinase inhibitor EcTI prevents proMMP activation and is cytotoxic against tumor cells without affecting normal tissue remodeling fibroblasts or regenerative hMSCs being an important tool in the studies of tumor cell development and dissemination

Distributed situation awareness in dynamic systems: Theoretical development and application of an ergonomics methodology

The purpose of this paper is to propose foundations for a theory of situation awareness based on the analysis of interactions between agents (i.e., both human and non-human) in subsystems. This approach may help promote a better understanding of technology-mediated interaction in systems, as well as helping in the formulation of hypotheses and predictions concerning distributed situation awareness. It is proposed that agents within a system each hold their own situation awareness which may be very different from (although compatible with) other agents. It is argued that we should not always hope for, or indeed want, sharing of this awareness, as different system agents have different purposes. This view marks situation awareness as a 1 dynamic and collaborative process that binds agents together on tasks on a moment-by-moment basis. Implications of this viewpoint for development of a new theory of, and accompanying methodology for, distributed situation awareness are offered

Chirality-Selective Excitation of Coherent Phonons in Carbon Nanotubes

Using pre-designed trains of femtosecond optical pulses, we have selectively excited coherent phonons of the radial breathing mode of specific-chirality single-walled carbon nanotubes within an ensemble sample. By analyzing the initial phase of the phonon oscillations, we prove that the tube diameter initially increases in response to ultrafast photoexcitation. Furthermore, from excitation profiles, we demonstrate that an excitonic absorption peak of carbon nanotubes periodically oscillates as a function of time when the tube diameter undergoes radial breathing mode oscillations.Comment: 4 pages, 4 figure