Regulation of 92-kD gelatinase release in HL-60 leukemia cells

Matrix metalloproteinase 9 (MMP-9), also known as 92-kD type IV collagenase/gelatinase, is believed to play a critical role in tumor invasion and metastasis. Here, we report that MMP-9 was constitutively released from the human promyelocytic cell line HL-60 as determined by zymographic analysis. Tumor necrosis factor-alpha (TNF-alpha) enhanced the enzyme release threefold to fourfold and the protein kinase C (PKC) activator and differentiation inducer 12-O-tetradecanoylphorbol-13- acetate (TPA) eightfold to ninefold. Gelatinase induction by TNF-alpha and TPA was inhibited by actinomycin D or cycloheximide, indicating that de novo protein synthesis was required. Neutralizing monoclonal antibodies to TNF-alpha (anti-TNF-alpha) decreased the basal MMP-9 release of these cells. In addition, these antibodies also significantly interfered with the TPA-induced enzyme release. Agents that inhibit TNF-alpha expression in HL-60 cells, such as pentoxifylline and dexamethasone, completely abrogated both the constitutive and TPA-evoked MMP-9 release. Diethyldithiocarbamate, which is known to stimulate TNF-alpha production in HL-60 cells, exerted a positive effect on MMP-9 release in untreated cells but was inhibitory in TPA-treated HL-60 cells. The PKC inhibitor staurosporine at low concentrations (100 ng/mL) caused a significant augmentation of MMP-9 release in untreated cultures that was blocked by the addition of anti-TNF-alpha. High concentrations (2 mumol/L) of staurosporine completely abolished the extracellular enzyme activity both in untreated and TPA-stimulated cells. These results suggest, that TNF- alpha is required for basal and PKC-mediated MMP-9 release in HL-60 leukemia cells. Thus, MMP-9 secretion may be regulated by TNF-alpha not only in a paracrine but also in an autocrine fashion. This may potentiate the matrix degradative capacity of immature leukemic cells in the processes of bone marrow egress and the evasion of these cells into peripheral tissue

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

Potential for Liquefaction Due to Construction Blasting

A method based on laboratory cyclic triaxial and torsional tests of undisturbed soil samples has been developed to predict the potential for liquefaction due to buried charges, such as those used in construction blasting. The results of a test blasting program conducted at a construction site are presented. The case history yielded data on particle velocities and blast induced porewater pressure changes

Health Justice Partnerships: An International Comparison of Approaches to Employing Law to Promote Prevention and Health Equity

This article traces the development and growth of health justice partnerships (HJPs) in three countries: the United States, Australia and the United Kingdom

Folding Langmuir Monolayers

The maximum pressure a two-dimensional surfactant monolayer is able to withstand is limited by the collapse instability towards formation of three-dimensional material. We propose a new description for reversible collapse based on a mathematical analogy between the formation of folds in surfactant monolayers and the formation of Griffith Cracks in solid plates under stress. The description, which is tested in a combined microscopy and rheology study of the collapse of a single-phase Langmuir monolayer of 2-hydroxy-tetracosanoic acid (2-OH TCA), provides a connection between the in-plane rheology of LM's and reversible folding

Irradiation programme HFR phase IIb - SPICE. Impact testing on up to 16.3 dpa irradiated RAFM steels. Final report for task TW2-TTMS 001b-D05

Bestrahlungsprogramm HFR Phase IIb – SPICE: Kerbschlagbiegeuntersuchungen an bis 16.3 dpa bestrahlten RAFM Stählen Die Untersuchung des bestrahlungsinduzierten Versprödungsverhaltens von niedrigaktivierbaren ferritisch-martensitischen (RAFM) Stählen bildet das Ziel der vorliegenden Arbeit. Die Neutronenbestrahlung bei verschiedenen Bestrahlungstemperaturen (250-450 °C) bis zu einer Schädigung von 16,3 dpa (nominell) wurde im Hoch Fluss Reaktor („High Flux Reactor“) Petten im Rahmen des HFR Phase IIb (SPICE) Bestrahlungsprogramms durchgeführt. Die Kerbschlageigenschaften wurden an miniaturisierten Charpy-V Proben (des KLST Typs) mittels der instrumentierten Kerbschlagbiegeversuche ermittelt. Der Hauptschwerpunkt des Bestrahlungsprogramms liegt in der Untersuchung des Einflusses der Neutronenbestrahlung auf die mechanischen Eigenschaften von einem europäischen RAFM Referenzstahl für die Erste Wand des Demonstrationsreaktors (DEMO), EUROFER97, bei zwei verschiedenen Wärmebehandlungen. Die mechanischen Eigenschaften von EUROFER97 wurden mit denen von internationalen Referenzmaterialien (F82H-mod, OPTIFER-Ia, GA3X und MANET-I), welche im SPICE Projekt untersucht wurden, verglichen. Die Bestrahlungsresistenz von bis 16,3 dpa bei 250-450 °C bestrahltem EUROFER97 ist vergleichbar mit der von besten Referenz-Strukturmaterialien. Es wurde für alle untersuchten RAFM Stähle eine erhebliche Tieftemperaturversprödung (Tirr ≤ 300 °C) beobachtet. Die Wärmebehandlung von EUROFER97 bei höherer Austenisierungstemperatur führt zur wesentlichen Verbesserung des Versprödungsverhaltens bei niedrigen Bestrahlungstemperaturen (Tirr ≤ 350 °C). Bei Tirr ≥ 350 °C liegen die Sprödbruchübergangstemperaturen (DBTT) von untersuchten niedrigaktivierbaren Stählen unterhalb von -20 °C und damit weit unterhalb der Anwendungstemperatur. Die Analyse des Verfestigungs- vs. Versprödungs- Verhaltens deutet auf die verfestigungsdominierte Versprödung unterhalb von Tirr ≤ 350 °C mit 0,17≤ C100 ≤ 0,53 °C/MPa. Oxiddispersionsgehärteter ODS EUROFER Stahl mit 0,5 wt.% Y2O3 wurde bei ausgewählten Temperaturen bestrahlt. Bereits im unbestrahlten Zustand zeigte ODS EUROFER keine be- friedigende Kerbschlagbiegeeigenschaften, gekennzeichnet durch eine niedrige USE = 2,54 J und durch eine große DBTT = 135 °C. Die Zunahme von USE für Bestrahlungstemperaturen unterhalb von Tirr ≤ 350°C deutet außerdem auf ein nicht optimiertes Herstellungsverfahren. Bei Tirr = 250 °C ist die bestrahlungsinduzierte Verschiebung der Übergangstemperatur vergleichbar mit der vom EUROFER97. Bei höheren Bestrahlungstemperaturen zeigt hingegen ODS EUROFER größere Versprödung im Vergleich zum Referenzmetall. Die Rolle des Heliums in der Materialversprödung wurde an EUROFER97 basierten Stählen untersucht, welche mit verschiedenem Bor Gehalt (0,008-0,112 wt.%) dotiert wurden. Bor dotierte Proben zeigen zunehmende Versprödung und Abnahme der Zähigkeit mit der Zunahme des generierten Helium Gehalts. Bis zu einem Helium Gehalt von 84 appm ist bei Tirr = 250 °C Helium induzierte Versprödung auf Helium induzierte Verfestigung zurückzuführen. Höhere Helium Konzentrationen führten zu weiteren Versprödungsmechanismen zusätzlich zur Helium induzierten Verfestigung

How Do Software Startups Pivot? Empirical Results from a Multiple Case Study

In order to handle intense time pressure and survive in dynamic market, software startups have to make crucial decisions constantly on whether to change directions or stay on chosen courses, or in the terms of Lean Startup, to pivot or to persevere. The existing research and knowledge on software startup pivots are very limited. In this study, we focused on understanding the pivoting processes of software startups, and identified the triggering factors and pivot types. To achieve this, we employed a multiple case study approach, and analyzed the data obtained from four software startups. The initial findings show that different software startups make different types of pivots related to business and technology during their product development life cycle. The pivots are triggered by various factors including negative customer feedback.Comment: Conference publication, International Conference on Software Business (ICSOB'16), Sloveni

Microwave response near zero magnetic field in transition-metal-doped silicate glasses

A sharp microwave response centered at zero magnetic field was observed in manganese- and iron-doped Na2O-CaO-MgO-SiO2 glasses with phase opposite to the normal Mn+2 and Fe+3 paramagnetic signals. The response can be described as magneto-induced microwave conductivity in the dielectric glass that derives from spin-dependent charge migration within the first coordination sphere of the paramagnetic ion. In contrast to the spin-polarized tunneling in ferromagnets between different valence states of metals, the observed effect is due to spin-dependent tunneling that occurs in the vicinity of manganese or iron in diluted paramagnetic systems