Development and operation of Digital Twins for technical systems and services

Digital Twins are new solution elements to enable ongoing digital monitoring and active functional improvement of interconnected products, devices and machines. In addition, benefits of horizontal and vertical integration in manufacturing are targeted by the introduction of Digital Twins. Using the test environment of smart factory cells, this paper investigates methodological, technological, operative, and business aspects of developing and operating Digital Twins. The following Digital Twin dimensions are considered in scientific and application oriented analysis: (1) integration breadth, (2) connectivity modes, (3) update frequency, (4) CPS intelligence, (5) simulation capabilities, (6) digital model richness, (7) human interaction, and (8) product lifecycle. From this, design elements for the development of Digital Twins are derived and presented.     

Effect of recycled content and rPET quality on the properties of PET bottles,part II: Migration

Polyethylene terephthalate (PET) bottles were produced from three types of recycled PET (rPET) with four levels of recycled content. The migration of substances from these bottles to water was studied. Several migrated substances were detected. The migrated amounts of acetaldehyde and ethylene glycol complied with the limits given in the food contact material (FCM) legislation. Migration of 2-methyl-1,3-dioxolane was below the limit of 10 μg·L⁻¹, which is conventionally applied for non-intentionally added substances (NIAS) not classified as ‘carcinogenic’, ‘mutagenic’ or ‘toxic to reproduction’ (CMR). Limonene, acetone, butanone and furan were also detected as migrants, of which limonene is a natural fragrant, and the other three are probably residues from solvents used to clean and protect the mould at the small-scale production facility. Finally, benzene and styrene were also found as migrants from rPET. These migrants appear to originate from heat-induced reactions within the PET matrix, which involve contaminants. The formation of benzene in rPET is attributed to polyvinylchloride as contaminant. The migrated amounts of benzene from the PET bottles with recycled content to the water simulant are relatively small (0.03–0.44 μg·L⁻¹) after 10 days at 40°C. Consequently, the margin of exposure is 3.10⁵–8.10⁶. Hence, the level of concern for the public health is low, and the migrated amount represents a low priority for risk management. The FCM legislation demands a risk assessment for migrating NIAS. Depending on the underlying data and exposure scenario, different threshold limits in the food can be derived which can still be considered as safe.     

Maxsim2—Real-time interactive simulations for computer-assisted teaching of pharmacokinetics and pharmacodynamics

We developed a computer program for use in undergraduate and graduate courses in pharmacology, pharmacokinetics and pharmacodynamics. This program can also be used in environmental and toxicological studies and preclinical simulation, to facilitate communication between modeling pharmacokineticists and project leaders or other decision-makers in the pharmaceutical industry. The program simulates the drug delivery and transport by means of (I) a six-compartment physiological pharmacokinetic flow model, (II) a system of traditional compartment models, or (III) a target-mediated drug disposition system. The program also can be used to simulate instantaneous equilibria between concentration and pharmacodynamic response, or as temporal delays between concentration and response. The latter is done by means of turnover models (indirect response models). Drug absorption, distribution, and elimination are represented by differential equations, which are described by organ and tissue volumes or other volumes of distribution, blood flows, clearance terms, and tissue-to-blood partition coefficients. The user can control and adjust these parameters by means of a slider in real time. By interactively changing the parameter values and simultaneously displaying the resulting concentration–time and/or response–time profiles, users can understand the major mechanisms that govern the disposition or the pharmacological response of the drug in the organism in real time. Schedule dependence is typically seen in clinical practice with a non-linear concentration–response relationship, and is difficult to communicate except via simulations. Here, we sought to illustrate the potential advantages of this approach in teaching pharmacology, pharmacokinetics, and pharmacodynamics to undergraduate pharmacy-, veterinary-, and medical students or to project teams in drug discovery/development.     

Activated carbons as potentially useful non-nutritive additives to prevent the effect of fumonisin B1 on sodium bentonite activity against chronic aflatoxicosis

Aflatoxin B₁ (AFB₁) and fumonisin B₁ (FB₁) are mycotoxins that often co-occur in feedstuffs. The ingestion of AFB₁ causes aflatoxicosis in humans and animals. Sodium bentonite (NaB), a cheap non-nutritive unselective sequestering agent incorporated in animal diets, can effectively prevent aflatoxicosis. Fumonisins are responsible for equine leukoencephalomalacia and porcine pulmonary oedema, and often have subclinical toxic effects in poultries. Fumonisin B₁ and aflatoxin B₁ are both strongly adsorbed in vitro on sodium bentonite. Co-adsorption studies, carried out with a weight ratio of FB₁ to AFB₁ that mimics the natural occurrence (200:1), showed that FB₁ greatly decreases the in vitro ability of NaB to adsorb AFB₁. The ability of two activated carbons to adsorb FB₁ was also investigated. Both carbons showed high affinity for FB₁. A complex behaviour of the FB₁ adsorption isotherms with pH was observed. In vitro results suggest that under natural contamination levels of AFB₁ and FB₁, a mixture of activated carbon and sodium bentonite might be potentially useful for prevention of sub-acute aflatoxicosis.     

Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.     

Basic Oxygen Furnace: Assessment of Recent Physicochemical Models

Metallurgical and Materials Transactions B - Modeling of the basic oxygen furnace (BOF) process, both for online monitoring and fundamental research, has gained importance in steelmaking industry...     

Interfacial Tension; a Stabilizing Factor for Janus Emulsions of Silicone Bixa Orellana Oils

The destabilization process was investigated for a Janus emulsion of silicone and Bixa Orellana oils stabilized by polyoxyethylene sorbitan monooleate (Tw 80) and carboxymethyl cellulose. The emulsion stabilized with Tw 80 showed significant and fast creaming, a process that was prevented by the addition of the polymer. During the extensive coalescence of the emulsions stabilized by Tw 80, the Janus topology was retained for months of storage until, finally, separation of the oils occurred. This result strongly indicates an unexpected stabilizing action of the i nterfacial free energy. This conclusion was supported by a calculation for a realistic model system of the interfacial energy difference between two cases of coalescence. In the first case, the two coalescing Janus drops united into a larger Janus drop, while in the second case two drops formed, each with only one oil. The first case gave a spontaneous reaction (reduced interfacial energy), while the second one meant an increase of energy, i.e. it cannot happen without adding energy. The authors are aware that this stabilization is a new phenomenon in emulsion science with potential ramifications in future emulsion technology. However, it is essential to realize that the stabilization is of temporary occurrence in the destabilization process, and the free energy to give a final emulsion state with separated oils is overwhelmingly dominant. In short, Janus emulsions will, in the end, separate into layers of the liquids, like all emulsions.     

Thermal properties of Sn-based solder alloys

During last few decades, emerging environmental regulations worldwide, more notably in Europe and Japan, have targeted the elimination of Pb usage in electronic assemblies due to the inherent toxicity of this element. This situation drives to the replacement of the Sn–Pb solder alloy of eutectic composition commonly used as joining material to suitable lead-free solders for microelectronic assembly. Sn-based alloys containing Ag, Cu, Bi, and Zn are potential lead-free solders, usually close to the binary or ternary eutectic composition. For this reason a great effort was directed to establish reliable thermophysical data fundamental to interpret the solidification process and fluidity of alloys belonging to these systems. In this work, an analysis of the solidification process of pure Sn, binary Sn–Ag, Sn–Cu, Sn–Bi, Sn–Zn, Sn–Pb and ternary Sn–Ag–Cu eutectic alloys was carried out using computer aided-cooling curve analysis and differential scanning calorimetry.     

Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones

A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N‐substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D ‐galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D ‐galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.     

Does sodium fluoride in bone cement affect implant fixation? Part I: Bone tissue response, implant fixation and histology in nine rabbits

The addition of sodium fluoride to poly (methyl-methacrylate) (PMMA) bone cement may theoretically improve the fixation of joint replacement. This hypothesis was tested in an animal model using nine mature healthy lop-eared rabbits. A femoral prosthesis was inserted in both knees to resurface the patellofemoral articulation. The same acrylic cement, with and without sodium fluoride, was randomised between the two sides for prosthetic fixation. Two screw shaped implants machined from cured rods of either cement were also inserted bilaterally into the proximal tibia. Qualitative and quantitative histomorphometry of the bone tissue response surrounding the cement in the femur and the intact tibial implants revealed similar results regardless of sodium fluoride addition. Six weeks after surgery removal, torque did not significantly differ between the two sides. Our findings indicate that addition of sodium fluoride to PMMA has little effect on implant stability and bone remodeling in rabbits in the short-term.