In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

Sustainability performance measurement : a preliminary classification framework of models and indicators

In this position paper we focus on the diversity of sustainability measurements. Based on existing research on performance measurement, we propose a preliminary classification framework summarizing sustainability models and indicators. By describing illustrative examples, we claim that several models and indicators can be distinguished with their own peculiarities. Having such a framework is interesting for both academia and business to structure the range of models and indicators and to ultimately select the appropriate sustainability measurement approach. The proposed framework should be validated by further research

Introduction

This is the author accepted manuscript. The final version is available from Bristol Record Society via the DOI in this record Archived with permission of the Bristol Record SocietyBristol Record Society's publications vol. 6

Digitisation of manual composite layup task knowledge using gaming technology

Increased market demand for composite products and shortage of expert laminators is compelling the composite industry to explore ways to acquire layup skills from experts and transfer them to novices and eventually to machines. There is a lack of holistic methods in literature for capturing composite layup skills especially involving complex moulds. This research aims to develop an informatics-based method, enabled by consumer-grade gaming technology and machine learning, to capture and digitise manufacturing task knowledge from skill-intensive hand layup. The digitisation is underpinned by the proposed human-workpiece interaction theory and implemented to automatically extract and decode key knowledge constituents such as layup strategies, ply manipulation techniques, motion mechanics and problem-solving during hand layup, collectively categorised as layup skills. The significance of this research is its potential to facilitate cost-effective transfer of skills from experts to novices, real-time automated supervision of hand layup and automation of layup tasks in the future

Partner selection for reverse logistics centres in green supply chains: a fuzzy artificial immune optimisation approach

The design of reverse logistics networks has now emerged as a major issue for manufacturers, not only in developed countries where legislation and societal pressures are strong, but also in developing countries where the adoption of reverse logistics practices may offer a competitive advantage. This paper presents a new model for partner selection for reverse logistic centres in green supply chains. The model offers three advantages. Firstly, it enables economic, environment, and social factors to be considered simultaneously. Secondly, by integrating fuzzy set theory and artificial immune optimization technology, it enables both quantitative and qualitative criteria to be considered simultaneously throughout the whole decision-making process. Thirdly, it extends the flat criteria structure for partner selection evaluation for reverse logistics centres to the more suitable hierarchy structure. The applicability of the model is demonstrated by means of an empirical application based on data from a Chinese electronic equipment and instruments manufacturing company

Hand layup: understanding the manual process

© 2015, © 2015 The Author(s). Published by Taylor & Francis. The hand layup of pre-impregnated woven materials is still a large part of the composite manufacturing industry, requiring the skills and experience of a human workforce to form flat plies into complex shapes. It is capable of producing high performance and complex parts, but can be an expensive and variable process. Despite its importance, there appears to have been very little research into the actual methods and techniques used by workers to manipulate flat sheets of composite material into shape during layup. This work presents the first known detailed study of the approach and techniques used by laminators. Four participants laid up onto 15 different shaped molds that replicated features commonly found on composite components. The actions used in layup were grouped into eight distinct techniques. Use of these techniques across tasks of different geometry, ramp angles, radii and drape path was identified using video analysis techniques from the ergonomics field. This revealed strong links between specific features and techniques, revealing a systematic approach to layup. This has enabled the first step toward producing a design for manufacture knowledge base surrounding hand layup. This could then be used to inform the development of the layup process, improve training methods and assist in the design of future automated solutions

Science Goals and Overview of the Radiation Belt Storm Probes (RBSP) Energetic Particle, Composition, and Thermal Plasma (ECT) Suite on NASA’s Van Allen Probes Mission

The Radiation Belt Storm Probes (RBSP)-Energetic Particle, Composition, and Thermal Plasma (ECT) suite contains an innovative complement of particle instruments to ensure the highest quality measurements ever made in the inner magnetosphere and radiation belts. The coordinated RBSP-ECT particle measurements, analyzed in combination with fields and waves observations and state-of-the-art theory and modeling, are necessary for understanding the acceleration, global distribution, and variability of radiation belt electrons and ions, key science objectives of NASA’s Living With a Star program and the Van Allen Probes mission. The RBSP-ECT suite consists of three highly-coordinated instruments: the Magnetic Electron Ion Spectrometer (MagEIS), the Helium Oxygen Proton Electron (HOPE) sensor, and the Relativistic Electron Proton Telescope (REPT). Collectively they cover, continuously, the full electron and ion spectra from one eV to 10’s of MeV with sufficient energy resolution, pitch angle coverage and resolution, and with composition measurements in the critical energy range up to 50 keV and also from a few to 50 MeV/nucleon. All three instruments are based on measurement techniques proven in the radiation belts. The instruments use those proven techniques along with innovative new designs, optimized for operation in the most extreme conditions in order to provide unambiguous separation of ions and electrons and clean energy responses even in the presence of extreme penetrating background environments. The design, fabrication and operation of ECT spaceflight instrumentation in the harsh radiation belt environment ensure that particle measurements have the fidelity needed for closure in answering key mission science questions. ECT instrument details are provided in companion papers in this same issue. In this paper, we describe the science objectives of the RBSP-ECT instrument suite on the Van Allen Probe spacecraft within the context of the overall mission objectives, indicate how the characteristics of the instruments satisfy the requirements to achieve these objectives, provide information about science data collection and dissemination, and conclude with a description of some early mission results

Condom Use Trajectories in Adolescence and the Transition to Adulthood: The Role of Mother and Father Support

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92028/1/jora775.pd

Electric and magnetic radial diffusion coefficients using the Van Allen probes data

ULF waves are a common occurrence in the inner magnetosphere and they contribute to particle motion, significantly, at times. We used the magnetic and the electric field data from the Electric and Magnetic Field Instrument Suite and Integrated Sciences (EMFISIS) and the Electric Field and Waves instruments (EFW) on board the Van Allen Probes to estimate the ULF wave power in the compressional component of the magnetic field and the azimuthal component of the electric field, respectively. Using L∗, Kp, and magnetic local time (MLT) as parameters, we conclude that the noon sector contains higher ULF Pc-5 wave power compared with the other MLT sectors. The dawn, dusk, and midnight sectors have no statistically significant difference between them. The drift-averaged power spectral densities are used to derive the magnetic and the electric component of the radial diffusion coefficient. Both components exhibit little to no energy dependence, resulting in simple analytic models for both components. More importantly, the electric component is larger than the magnetic component by one to two orders of magnitude for almost all L∗ and Kp; thus, the electric field perturbations are more effective in driving radial diffusion of charged particles in the inner magnetosphere. We also present a comparison of the Van Allen Probes radial diffusion coefficients, including the error estimates, with some of the previous published results. This allows us to gauge the large amount of uncertainty present in such estimates