An Engineering Process model for managing a digitalised life-cycle of products in the Industry 4.0

The Internet of Things (IoT), and more specifically the industrial IoT, is revolutionising industry. This technology has catalyzed the fourth industrial revolution and inspired movements such as Industry 4.0, the Industrial Internet Consortium and Society 5.0. Morphing an industrial process or assembly line to aggregate Internet-connected devices and systems does not complete the picture. The concept penetrates all aspects of the engineering process (EP) which encompasses the full lifecycle of the product/solution. Phases of the EP traditionally tended to be sequential but, with the IoT, can now evolve and influence other phases throughout the product/solution lifecycle. The EU-funded Arrowhead Tools project aims to promote a service-oriented architecture (SOA) to allow tools within each phase of the engineering process to interact with each other. This paper, applies the proposed EP model to a real value chain composed of multiple stakeholders adopting different EPs for the life-cycle management of a Smart Boiler System

Release of Soluble Receptors for Tumor Necrosis Factor in Clinical Sepsis and Experimental Endotoxemia

To assess the role of tumor necrosis factor (TNF) in the appearance of soluble TNF receptors (sTNFRs), 20 consecutive patients with a clinical diagnosis of sepsis were studied as were 7 chimpanzees after administration of endotoxin (4 ng/kg) with or without pentoxifylline. The patients had markedly elevated serum levels of sTNFR-p55 and sTNFR-p75 compared with healthy controls (P < .0001 for both receptors). The levels of both soluble receptors correlated with simultaneously measured immunoreactive TNF concentrations (p55: r = .63, P < .01; p75: r = .69, P < .001). In the chimpanzees, endotoxin induced subsequent rises in the serum concentrations ofTNF and sTNFRs. Although pentoxifylline reduced the TNF response to intravenous endotoxin to 20% (P < .05), the appearance of sTNFRs was only moderately inhibited (sTNFR-p55 to 79% on average, P < .05; sTNFR-p75 to 77%, P = .12). These results indicate that TNF either does not play an important role in the appearance of sTNFRs in systemic infection or that a small amount ofTNF remaining in the circulation after some bacterial challenges is sufficient to preserve the secretion of its soluble receptor

Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants

BACKGROUND: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. CONCLUSIONS: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection

Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

Background: The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings: Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions: The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens

A History of Universalism: Conceptions of the Internationality of Science from the Enlightenment to the Cold War

That science is fundamentally universal has been proclaimed innumerable times. But the precise geographical meaning of this universality has changed historically. This article examines conceptions of scientific internationalism from the Enlightenment to the Cold War, and their varying relations to cosmopolitanism, nationalism, socialism, and 'the West'. These views are confronted with recent tendencies to cast science as a uniquely European product

An ultrasonic density measurement technique : performance, thermal effects, experimental validations, and modeling

This licentiate thesis addresses the idea of measurement of the density of liquids using sound. The thesis can be dived into three sections: 1. An introduction that presents the need for the research and its future application into an ultrasonic mass flow meter. 2. Experimental results of an ultrasonic density probe (paper 1 and 2) which evaluate the probe's concept with liquids ranging from 750 to 1300 kg/m over temperatures extending form 0 to 40°C. Thermodynamic measurements are also presented. 3. Comparisons of experimental versus theoretically based simulation of ultrasonic systems (paper 3). The theory allows the simulation tool to predict sound generation, propagation and reception as a function of frequency and temperature. Within the thesis are three papers: 1. An Ultrasonic Density Probe. (published in IEEE Ultrasonic symposium) 2. Thermostatic and dynamic performance of a Density Probe. (submitted to IEEE Transactions on UFFC) 3. PSpice simulation of Ultrasonic Systems. (submitted to IEEE Transactions on UFFC)Godkänd; 1999; 20070403 (ysko)</p

Material investigations and simulation tools towards a design strategy for an ultrasonic densitometer

The purpose of the research described in the thesis has been to improve the accuracy, precision and reliability of an ultrasonic densitometer for liquids in general. Its practical application is a stand-alone device or, in combination with an ultrasonic volumetric flow meter, an all-ultrasonic mass flow meter. The work shows that the densitometer is reliable at different though steady temperatures. Changes in temperature alter the characteristics of the densitometer. Recognition of one of these alterations enables one to compensate for the thermal influence. The presence of thermal gradients in the densitometer due to thermal transients can be recognized and handled properly. A simulation tool is refined to aid in the design of the densitometer to include spectral and thermal dependencies of the sensor materials. The model described by the simulation tool is compared successfully with actual ultrasonic systems. The simulation tool is used to predict the received electrical signal of a two-transducer ultrasonic mass flow meter. The simulation tool is also used to investigate the effects of transducer variations on flow measurement errors in a volumetric flow meter. When the two transducers are not identical, there is a difference in the times of flight of the ultrasonic pulses used to calculate the flow velocity, which should not occur when the fluid is stationary. The simulation tool is based on the electronic simulation software SPICE, which aids in the design of the associated electronics. To incorporate the spectral and thermal dependencies of polymers used in the densitometer into the simulation tool, their characteristics have been explored. The superposition of frequency and temperature of their characteristics is used and parametric surfaces are proposed. The problem however is that those characteristics are not commonly found for most polymers. Signal processing techniques are applied to two densitometers for solids to illustrate the extraction of information from the measured signals as well as their drawbacks. The same signal processing methods provide the densitometer for liquids a means to achieve better accuracy, precision and reliability.Godkänd; 2001; 20061113 (haneit)</p

Detection of, and compensation for error inducing thin layer deposits on an ultrasonic densitometer for liquids

A pulse echo ultrasonic densitometer can measure the acoustic impedance of a liquid by listening to the echo of an acoustic pulse reflected from the densitometer probe and liquid interface. The density of the liquid Is obtained by dividing the acoustic impedance of the liquid and the speed of sound through the liquid. However, thin layer deposits, also known as fouling, on the probe at the liquid interface Introduce errors in the assessment of the liquid's acoustic Impedance and hence in the density estimation. In this paper, we simulate the situation with different types of contaminations at different fouling layer thickness and show that when performing a discrete Fourier transform (DFT) on the echo, the presence of the contaminating layer can be detected while the correct liquid density can be estimatedGodkänd; 2003; 20061005 (ysko)</p

Introduction of a 2 transducer ultrasonic mass flow meter

This article presents a new ultrasonic massflow meter that has only two transducers. The mass flow is inferred from volumetric flow and density. Each of the transducers is an ultrasonic densitometer based on a design by Lynnworth. The flow is estimated by the transit time difference of the sound pulse between the up and down-stream acoustic propagation. Beyond presenting the meter, this article does looks at its signal at zero flow to address the issue of reciprocity in transit time flow meters which is in contradiction with the theory of transit time flow meters.Godkänd; 2005; 20060922 (ysko)</p