Metabolism of phthalates in humans

Phthalates are synthetic compounds widely used as plasticisers, solvents and additives in many consumer products. Several animal studies have shown that some phthalates possess endocrine disrupting effects. Some of the effects of phthalates seen in rats are due to testosterone lowering effects on the foetal testis and they are similar to those seen in humans with testicular dysgenesis syndrome. Therefore, exposure of the human foetus and infants to phthalates via maternal exposure is a matter of concern. The metabolic pathways of phthalate metabolites excreted in human urine are partly known for some phthalates, but our knowledge about metabolic distribution in the body and other biological fluids, including breast milk, is limited. Compared to urine, human breast milk contains relatively more of the hydrophobic phthalates, such as di-n-butyl phthalate and the longer-branched, di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP); and their monoester metabolites. Urine, however, contains relatively more of the secondary metabolites of DEHP and DiNP, as well as the monoester phthalates of the more short-branched phthalates. This differential distribution is of special concern as, in particular, the hydrophobic phthalates and their metabolites are shown to have adverse effects following in utero and lactational exposures in animal studies.     

Improving the load flexibility of industrial air separation units using a pressure-driven digital twin

Air separation units are one of the prime examples for studies on demand side management and (non-)linear model predictive control due to their high power consumption and energy storage potential. These plants separate ambient air into its main components, nitrogen, oxygen, and argon, by means of cryogenic distillation at different pressure levels. Approximately two thirds of the industrially operated air separation units consider the separation of argon either as a value product or for reasons of energy efficiency. However, most of the studies in literature neglect the separation of argon since this requires additional equipment, increases the heat and process integration and, thus, the complexity of process control. In this work, a digital twin of an air separation unit with argon system is used to analyze and to improve load change procedures. Moreover, the potential of applying the digital twin as a soft sensor is demonstrated.     

FEA evaluation of material stiffness changes for a polymer assisted 3D polycaprolactone/β-tricalcium phosphate scaffold in a mandibular defect reconstruction model

In bone regenerative engineering, the biomechanical performance of the scaffold at the bone-tissue interface is a key consideration. The evaluation of this parameter is a crucial step in designing, optimizing and manufacturing of bone substitute materials for clinical application, but is as yet comparatively unexplored. To this end, we utilized a novel polymer-assisted method to fabricate a three-dimensional (3D) Polycaprolactone/β-Tricalcium phosphate scaffold. The compressive modulus was measured and the data used to inform finite element analysis. The scaffolds achieved a maximum compressive moduli of 151 MPa, close to that of cortical bone. Further computational simulations were performed to determine the stresses and local scaffold adaptation profile, using data from computer tomography scans of the mandible. Local stresses were simulated based on the density changes in new bone forming in the scaffold at different stages of healing. The stress distribution in the mandible, scaffold center and scaffold interface were explored for a static load of 200 N, which corresponds to the load of adult mastication near the incisors. The analysis revealed that the maximum cross-sectional stress at the scaffold center and at the scaffold interface was 2.7 and 4.12 MPa respectively. The majority of the stress was localized in the bone of the mandible, with the scaffold bearing minimal loading at the start, but more over time as infiltration of more new bone progressed.     

Engineered Human Induced Pluripotent Cells Enable Genetic Code Expansion in Brain Organoids

Human induced pluripotent stem cell (hiPSC) technology has revolutionized studies on human biology. A wide range of cell types and tissue models can be derived from hiPSCs to study complex human diseases. Here, we use PiggyBac-mediated transgenesis to engineer hiPSCs with an expanded genetic code. We demonstrate that genomic integration of expression cassettes for a pyrrolysyl-tRNA synthetase (PylRS), pyrrolysyl-tRNA (PylT) and the target protein of interest enables site-specific incorporation of a non-canonical amino acid (ncAA) in response to an amber stop codon. Neural stem cells, neurons and brain organoids derived from the engineered hiPSCs continue to express the amber suppression machinery and produce ncAA-bearing reporter. The incorporated ncAA can serve as a minimal bioorthogonal handle for further modifications by labeling with fluorescent dyes. Site-directed ncAA mutagenesis will open a wide range of applications to probe and manipulate proteins in brain organoids and other hiPSC-derived cell types and complex tissue models.     

Static and dynamic Fresnel zone lenses for optical interconnections

Abstract

Static and dynamic Fresnel zone lenses were fabricated in quartz glass by means of microstructuring techniques. Two types of on-axis and offaxis lenses with different focal lengths and of different apertures were designed to operate at wavelengths of 1·52 μm and 633 nm. The blazed profile of the onaxis and off-axis lenses was approximated by up to 16 and up to four discrete levels respectively. Dynamic, that is electrically switchable, lenses have been realized by filling the structured surface with liquid crystal. The optical properties of the lenses, such as the focal spot sizes and the diffraction efficiencies, were investigated. Further the switching behaviour of the dynamic lenses was studied. The design and fabrication of the static and dynamic, on-and off-axis Fresnel zone lenses as well as their optical and switching properties will be presented.     

A Synthetic Protocell-Based Heparin Scavenger

Heparin is a commonly applied blood anticoagulant agent in clinical use. After treatment, excess heparin needs to be removed to circumvent side effects and recover the blood-clotting cascade. Most existing heparin antidotes rely on direct heparin binding and complexation, yet selective compartmentalization and sequestration of heparin would be beneficial for safety and efficiency. However, such systems have remained elusive. Herein, a semipermeable protein-based microcompartment (proteinosome) is loaded with a highly positively charged chitosan derivative, which can induce electrostatics-driven internalization of anionic guest molecules inside the compartment. Chitosan-loaded proteinosomes are subsequently employed to capture heparin, and an excellent heparin-scavenging performance is demonstrated under physiologically relevant conditions. Both the highly positive scavenger and the polyelectrolyte complex are confined and shielded by the protein compartment in a time-dependent manner. Moreover, selective heparin-scavenging behavior over serum albumin is realized through adjusting the localized scavenger or surrounding salt concentrations at application-relevant circumstances. In vitro studies reveal that the cytotoxicity of the cationic scavenger and the produced polyelectrolyte complex is reduced by protocell shielding. Therefore, the proteinosome-based systems may present a novel polyelectrolyte-scavenging method for biomedical applications.     

Systemic uptake of diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and reproductive and thyroid hormone levels in humans

In vitro and animal studies have reported endocrine-disrupting activity of chemicals used commonly as additives in cosmetics and skin care products. We investigated whether diethyl phthalate (DEP), dibutyl phthalate (DBP), and butyl paraben (BP) were systemically absorbed and influenced endogenous reproductive and thyroid hormone levels in humans after topical application. In a two-week single-blinded study, 26 healthy young male volunteers were assigned to daily whole-body topical application of 2 mg/cm2 basic cream formulation each without (week one) and with (week two) the three 2% (w/w) compounds. The concentrations of BP and the main phthalate metabolites monoethyl (MEP) and monobutyl phthalate (MBP) were measured in serum together with the following reproductive hormones: follicle stimulating hormone (FSH), lutenising hormone (LH), testosterone, estradiol, and inhibin B and thyroid hormones (thyroid stimulating hormone (TSH), free thyroxine (FT4), total triiodothyroxine (T3), and total thyroxine (T4)). MEP, MBP, and BP peaked in serum a few hours after application, reaching mean +/- SEM levels of 1001 +/- 81 microg/L, 51 +/- 6 microg/ L, and 135 +/- 11 microg/L, respectively. Only MEP was detectable in serum before treatment. Minor differences in inhibin B, LH, estradiol, T4, FT4, and TSH were observed between the two weeks, but these were not related to exposure. We demonstrated for the first time that DEP, DBP, and BP could be systemically absorbed in man after topical application. The systemic absorption of these compounds did not seem to have any short-term influence on the levels of reproductive and thyroid hormones in the examined young men.     

Redox Potentials of High-Valent Iron-, Cobalt-, and Nickel-Oxido Complexes: Evidence for Exchange Enhanced Reactivity

The ferrocene titration method has been employed to determine the one-electron reduction potentials of a series of oxido-iron(IV), oxido-cobalt(IV) and oxido/hydroxido-nickel(III) complexes based on the same tetradentate TMG₃tren ligand (TMG₃tren=tris[2-(N-tetramethylguanidyl)ethyl]amine). The S=2 ground state of the [(TMG₃tren)Fe^IV=O]²⁺ complex allows an exchange enhanced reactivity, which enables it to perform efficient oxygen atom transfer (OAT) and hydrogen atom abstraction (HAA) reactions with a low one-electron reduction potential of 270 mV vs. SCE. In the absence of exchange enhanced reactivity, the OAT and HAA abilities of the S=3/2 [(TMG₃tren)Co^IV−O(Sc(OTf)₃)]²⁺, S=1/2 [(TMG₃tren)Ni^III−O(H)]²⁺ and the previously reported S=1 [(TMC)(CH₃CN)Fe^IV=O]²⁺ and [(N4Py)Fe^IV=O]²⁺ complexes can be directly correlated to their reduction potentials. Notably, [(N4Py)Fe^IV=O]²⁺ and [(TMG₃tren)Fe^IV=O]²⁺ exhibit similar OAT and HAA reactivities although the reduction potential of [(N4Py)Fe^IV=O]²⁺ is 0.24 V more positive than that of [(TMG₃tren)Fe^IV=O]²⁺. The present study therefore provides experimental evidence for exchange enhanced reactivity and rationalizes nature's choice for employing S=2 oxido-iron(IV) cores to achieve difficult oxidation reactions at biologically viable potentials.     

Evaluation of a sustainable Greek vernacular settlement and its landscape: Architectural typology and building physics

Sernikaki is a Greek vernacular settlement that can be imagined as a living organism is the outcome of centuries of optimization of material use, construction techniques and climate considerations. Being mountainous and isolated, this small vernacular settlement has preserved old types of dwellings longer than other areas in Phokida, in mainland Greece, and it can, thus, provide rich material for the understanding of architectural continuity and evolution. In this study, various types of adobe dwellings are surveyed and their response to climate, in terms of site and building design, is evaluated. In addition, the techniques of creating microclimatic conditions by incorporating the existing environmental parameters into the design are considered. Bioclimatic design employs appropriate technologies and design principles based on a thoughtful approach to climate and environment. It is concerned with the layout of the buildings (orientation in relation to sun and wind, aspect ratio), the spacing (site planning), the air movement, the openings (size–position, protection), and the building envelope (walls: construction materials-thickness, roof construction detailing). This paper evaluates specific vernacular dwelling types and their response to climate, based on passive design principles that could be adapted to current architectural practice in the area, in order to optimize the relationship between site, building and climate.