Roles and regulation of membrane-associated serine proteases

Pericellular proteolytic activity affects many aspects of cellular behaviour, via mechanisms involving processing of the extracellular matrix, growth factors and receptors. The serine proteases have exquisitely sensitive regulatory mechanisms in this setting, involving both receptor-bound and transmembrane proteases. Receptor-bound proteases are exemplified by the uPA (urokinase plasminogen activator)/uPAR (uPAR receptor) plasminogen activation system. The mechanisms initiating the activity of this proteolytic system on the cell surface, a critical regulatory point, are poorly understood. We have found that the expression of the TTSP (type II transmembrane serine protease) matriptase is highly regulated in leucocytes, and correlates with the presence of active uPA on their surface. Using siRNA (small interfering RNA), we have demonstrated that matriptase specifically activates uPAR-associated pro-uPA. The uPA/uPAR system has been implicated in the activation of the plasminogen-related growth factor HGF (hepatocyte growth factor). However, we find no evidence for this, but instead that HGF can be activated by both matriptase and the related TTSP hepsin in purified systems. Hepsin is of particular interest, as the proteolytic cleavage sequence of HGF is an ‘ideal substrate’ for hepsin and membrane-associated hepsin activates HGF with high efficiency. Both of these TTSPs can be activated autocatalytically at the cell surface, an unusual mechanism among the serine proteases. Therefore these TTSPs have the capacity to be true upstream initiators of proteolytic activity with subsequent downstream effects on cell behaviour

A Complete Year of User Retrieval Sessions in a Social Sciences Academic Search Engine

In this paper, we present an open data set extracted from the transaction log of the social sciences academic search engine sowiport. The data set includes a filtered set of 484,449 retrieval sessions which have been carried out by sowiport users in the period from April 2014 to April 2015. We propose a description of interactions performed by the academic search engine users that can be used in different applications such as result ranking improvement, user modeling, query reformulation analysis, search pattern recognition.Comment: 6 pages, 2 figures, accepted short paper at the 21st International Conference on Theory and Practice of Digital Libraries (TPDL 2017

Neutralino Dark Matter in a Class of Unified Theories

The cosmological significance of the neutralino sector is studied for a class of models in which electroweak symmetry breaking is seeded by a gauge singlet. Extensive use is made of the renormalisation group equations to significantly reduce the parameter space, by deriving analytic expressions for all the supersymmetry-breaking couplings in terms of the universal gaugino mass $m_{1/2}$, the universal scalar mass $m_0$ and the coupling $A$. The composition of the LSP is determined exactly below the W mass, no approximations are made for sfermion masses, and all particle exchanges are considered in calculating the annihilation cross-section; the relic abundance is then obtained by an analytic approximation. We find that in these models, stable neutralinos may make a significant contribution to the dark matter in the universe.Comment: 24 Pages, OUTP-92-10

Electric Dipole Moment Constraints on Phases in the Constrained MSSM

We consider constraints on \cp-violating phases in the Constrained Minimal Supersymmetric Standard Model. We find that by combining cosmological limits on gaugino masses with experimental bounds on the neutron and electron electric dipole moments, we can constrain the phase of the Higgs mixing mass $\mu$ to be $|\theta_\mu| < \pi/10$, independent of choices of the other mass parameters in the model. The other \cp-violating phase $\theta_A$ is essentially unconstrained.Comment: 10 pages in LaTeX + 3 postscript figures, uses epsf.st

Determining tan⁡β\tan\beta at the NLC with SUSY Higgs Bosons

We examine the prospects for determining $\tan\beta$ from heavy Higgs scalar production in the minimal supersymmetric standard model at a future $e^+e^-$ collider. Our analysis is independent of assumptions of parameter unification, and we consider general radiative corrections in the Higgs sector. Bounds are presented for $\sqrt{s} = 500$ GeV and 1 TeV, several Higgs masses, and a variety of integrated luminosities. For all cases considered, it is possible to distinguish low, moderate, and high $\tan\beta$. In addition, we find stringent constraints for $3\lesssim\tan\beta\lesssim 10$, and, for some scenarios, also interesting bounds on high $\tan\beta$ through $tbH^{\pm}$ production. Such measurements may provide strong tests of the Yukawa unifications in grand unified theories and make possible highly precise determinations of soft SUSY breaking mass parameters.Comment: Talk presented by T. Moroi at the SUSY'97 Conference, May 27-31, Philadelphia, PA, US

Observation of coherent delocalized phonon-like modes in DNA under physiological conditions

Underdamped terahertz-frequency delocalized phonon-like modes have long been suggested to play a role in the biological function of DNA. Such phonon modes involve the collective motion of many atoms and are prerequisite to understanding the molecular nature of macroscopic conformational changes and related biochemical phenomena. Initial predictions were based on simple theoretical models of DNA. However, such models do not take into account strong interactions with the surrounding water, which is likely to cause phonon modes to be heavily damped and localized. Here we apply state-of-the-art femtosecond optical Kerr effect spectroscopy, which is currently the only technique capable of taking low-frequency (GHz to THz) vibrational spectra in solution. We are able to demonstrate that phonon modes involving the hydrogen bond network between the strands exist in DNA at physiologically relevant conditions. In addition, the dynamics of the solvating water molecules is slowed down by about a factor of 20 compared with the bulk

The effect of Mg location on Co-Mg-Ru/γ-Al2O3 Fischer–Tropsch catalysts

© 2016 The Author(s) Published by the Royal Society. All rights reserved.The effectiveness of Mg as a promoter of Co-Ru/γ-Al2O3 Fischer-Tropsch catalysts depends on how and when the Mg is added. When the Mg is impregnated into the support before the Co and Ru addition, some Mg is incorporated into the support in the form of MgxAl2O3+x if the material is calcined at 550°C or 800°C after the impregnation, while the remainder is present as amorphous MgO/MgCO3 phases. After subsequent Co-Ru impregnation MgxCo3-xO4 is formed which decomposes on reduction, leading to Co(0) particles intimately mixed with Mg, as shown by high-resolution transmission electron microscopy. The process of impregnating Co into an Mg-modified support results in dissolution of the amorphous Mg, and it is this Mg which is then incorporated into MgxCo3-xO4. Acid washing or higher temperature calcination after Mg impregnation can remove most of this amorphous Mg, resulting in lower values of x in MgxCo3-xO4. Catalytic testing of these materials reveals that Mg incorporation into the Co oxide phase is severely detrimental to the site-Time yield, while Mg incorporation into the support may provide some enhancement of activity at high temperature