Short SULF1/SULF2 splice variants predominate in mammary tumours with a potential to facilitate receptor tyrosine kinase-mediated cell signalling

The relative roles of SULF1 and SULF2 enzymes in tumour growth are controversial, but short SULF1/SULF2 splice variants predominate in human mammary tumours despite their non-detectable levels in normal mammary tissue. Compared with the normal, the level of receptor tyrosine kinase (RTK) activity was markedly increased in triple-positive mammary tumours during later stages of tumour progression showing increased p-EGFR, p-FGFR1 and p-cMet activity in triple-positive but not in triple-negative tumours. The abundance of catalytically inactive short SULF1/SULF2 variants permits high levels of HS sulphation and thus growth driving RTK cell signalling in primary mammary tumours. Also observed in this study, however, was increased N-sulphation detected by antibody 10E4 indicating that not only 6-O sulphation but also N-sulphation may contribute to increased RTK cell signalling in mammary tumours. The levels of such increases in not only SULF1/SULF2 but also in pEGFR, pFGFR1, p-cMet and Smad1/5/8 signalling were further enhanced following lymph node metastasis. The over-expression of Sulf1 and Sulf2 variants in mammary tumour-derived MDA-MB231 and MCF7 cell lines by transfection further confirms Sulf1-/Sulf2-mediated differential modulation of growth. The short variants of both Sulf1 and Sulf2 promoted FGF2-induced MDA-MB231 and MCF7 in vitro growth while full-length Sulf1 inhibited growth supporting in vivo mammary tumour cell signalling patterns of growth. Since a number of mammary tumours become drug resistant to hormonal therapy, Sulf1/Sulf2 inhibition could be an alternative therapeutic approach to target such tumours by down-regulating RTK-mediated cell signalling

A study of the application of singular perturbation theory

A hierarchical real time algorithm for optimal three dimensional control of aircraft is described. Systematic methods are developed for real time computation of nonlinear feedback controls by means of singular perturbation theory. The results are applied to a six state, three control variable, point mass model of an F-4 aircraft. Nonlinear feedback laws are presented for computing the optimal control of throttle, bank angle, and angle of attack. Real Time capability is assessed on a TI 9900 microcomputer. The breakdown of the singular perturbation approximation near the terminal point is examined Continuation methods are examined to obtain exact optimal trajectories starting from the singular perturbation solutions

A simple sandpile model of active-absorbing state transitions

We study a simple sandpile model of active-absorbing state transitions in which a particle can hop out of a site only if the number of particles at that site is above a certain threshold. We show that the active phase has product measure whereas nontrivial correlations are found numerically in the absorbing phase. It is argued that the system relaxes to the latter phase slower than exponentially. The critical behavior of this model is found to be different from that of the other known universality classes.Comment: Revised version. To appear in Phys. Rev.

Rural Library Professionals as Change Agents in the 21st Century: Integrating Information Technology Competencies in the Southern and Central Appalachian Region (ITRL)

Rural Library Professionals as Change Agents in the 21st Century: Integrating Information Technology Competencies in the Southern and Central Appalachian Region (ITRL) ($567,660). Institute of Museum and Library Services, Laura Bush 21st Century Librarian Program, October 2009 – September 2012. Principal Investigators: B. Mehra, K. Black, and V. Singh. Project Partners: Clinch-Powell Regional Library (Clinton, Tennessee: S. Simmons, Director), Nolichucky Regional Library (Morristown, Tennessee: D. Reynolds, Director), Sevier County Public Library System (Sevierville, Tennessee: K. C. Williams, System Director), and the Watauga Regional Library (Johnson City, Tennessee: N. Renfro, Director)

A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein.

Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10-kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae-specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection

Perfectly Translating Lattices on a Cylinder

We perform molecular dynamics simulations on an interacting electron gas confined to a cylindrical surface and subject to a radial magnetic field and the field of the positive background. In order to study the system at lowest energy states that still carry a current, initial configurations are obtained by a special quenching procedure. We observe the formation of a steady state in which the entire electron-lattice cycles with a common uniform velocity. Certain runs show an intermediate instability leading to lattice rearrangements. A Hall resistance can be defined and depends linearly on the magnetic field with an anomalous coefficient reflecting the manybody contributions peculiar to two dimensions.Comment: 13 pages, 5 figure

Temperature effect in the Casimir attraction of a thin metal film

The Casimir effect for conductors at arbitrary temperatures is theoretically studied. By using the analytical properties of the Green functions and applying the Abel-Plan formula to Lifshitz's equation, the Casimir force is presented as sum of a temperature dependent and vacuum contributions of the fluctuating electromagnetic field. The general results are applied to the system consisting of a bulk conductor and a thin metal film. It is shown that a characteristic frequency of the thermal fluctuations in this system is proportional to the square root of a thickness of the metal film. For the case of the sufficiently high temperatures when the thermal fluctuations play the main role in the Casimir interaction, this leads to the growth of the effective dielectric permittivity of the film and to a disappearance of the dependence of Casimir's force on the sample thickness.Comment: LaTeX 2.09, 8 pages, no figure

Trapping of a random walk by diffusing traps

We present a systematic analytical approach to the trapping of a random walk by a finite density rho of diffusing traps in arbitrary dimension d. We confirm the phenomenologically predicted e^{-c_d rho t^{d/2}} time decay of the survival probability, and compute the dimension dependent constant c_d to leading order within an eps=2-d expansion.Comment: 16 pages, to appear in J. Phys.