One‐Step Formulation of Protein Microparticles with Tailored Properties: Hard Templating at Soft Conditions

Formulation of therapeutic proteins into particulate forms is a main strategy for site‐specific and prolonged protein delivery as well as for protection against degradation. Precise control over protein particle size, dispersity, purity, as well as mild preparation conditions and minimal processing steps are highly desirable. It is, however, hard to fit all these criteria with conventional preparation techniques. Here a one‐step hard‐templating synthesis of microparticles composed of functional, non‐denatured protein is reported. The method is based on filling porous CaCO₃ microtemplates with the protein near to its isoelectric point (pI) followed by pH‐ or EDTA‐mediated dissolution of the tempplates. In principle, a wide variety of proteins can be converted into microparticles using this approach. The main requirement is an overlap of the protein insolubility and a template solubility for a certain parameter (here pH or EDTA). Here the formulation of insulin particles is studied in detail and it is shown that particles consisting of high molecular weight protein (catalase) can also be prepared. In this context, the synthesis of CaCO₃ templates with controlled size, the mechanism of the protein microparticle formation and mechanical properties of the microparticles are discussed. For the first time, the fabrication of mesoporous monodispersed CaCO₃ microtemplates with identical porocity but tuned diameter from 3 to 20 μm is demonstrated. The protein particle diameter can be adjusted by choosing the appropriate template size that is critical for successful pulmonary delivery of insulin. As a first step towards insulin delivery, the in vitro release of insulin at physiological conditions is studied.     

Numerical simulation of molten pool dynamics in high power disk laser welding

A single-phase problem is solved rather than a multiphase problem for numerical simplicity: and the solution is based on the assumption that the region of gas or plasma can be treated as a void because solid or liquid steel has a greater density level than gas or plasma. The volume-of-fluid method, which can calculate the free surface shape of the keyhole, is used in conjunction with a ray-tracing algorithm to estimate the multiple reflections. Fresnel's reflection model is simplified by the Hagen-Rubens relation for handling a laser beam interaction with materials. Factors considered in the simulations include buoyancy force, Marangoni force and recoil pressure; furthermore, pore generation is simulated by means of an adiabatic bubble model, which can also lead to the phenomenon of a keyhole collapse. Models of the shear stress on the keyhole surface and of the heat transfer to the molten pool via a plasma plume are introduced in simulations of the weld pool dynamics. Analysis of the temperature profile characteristics of the weld bead and molten pool flow in the molten pool is based on the results of the numerical simulations. The simulation results are used to estimate the weld fusion zone shape; and the results of the simulated fusion zone formation are compared with the results of the experimental fusion zone formation and found to be in good agreement. The effects of laser beam profile (Gaussian vs. measured), vapor shear stress, vapor heat source and sulfur content on the molten pool behavior and fusion zone shape are analyzed.     

Synergy and Subsidiarity: The Systematic Determination of Software,User, and Operating Instructions

The quality of a software product is determined by its usability; the quality of technical documentation is determined by its comprehensibility. Usability conceptualizes the person using a software product to perform a task; comprehensibility deals with the reader of operating instructions-although they are generally one and the same person. However, only rarely are the software and technical documentation part of an integrated design.

This is all the more surprising in that, on the technical level, the boundary between software and user information is becoming increasingly blurred; one need only think of the hypertext links between software and help systems, or of electronic versions of operating instructions.

We make the case for considering user, software, and operating instructions as a single system oriented toward performing a task; the operating instructions therefore are regarded as a subsidiary subsystem of a structure to be described. This is done from a linguistic perspective, with reference to the central category of knowledge available to the user or contained in the software and in the operating instructions and that we approach via an empirical analysis of authentic material (operating instructions as primary data, statements of end users concerning operating instructions).

Taking the example of creating software and operating instructions for a computer tomograph, we show how the relevant knowledge elements contribute to the accomplishment of an operating task and discuss the resultant requirements concerning the contents of software and operating instructions, particularly for handling fault and problem situations.     

Self-healing through microencapsulated agents for protective coatings

The use of microcapsules containing healing agents, which can serve as source of self-healing for coatings, was investigated. The appropriate self-repairing coatings are designed to be used for heavy-duty corrosion protection or for the protection of moisture-sensitive substrates like wood. Microcapsules based on thermoset resins (urea–formaldehyde and melamine–formaldehyde) which contained components of different chemical natures (resins or inhibitors) were fabricated using emulsion techniques. The subsequent characterization included optical, fluorescence, and electron microscopy as well as adapted microindentation techniques to determine capsule break forces. Different model coatings were formulated making use of varying amounts of healing agent-charged microcapsules. The coated samples were then injured under controlled conditions (by Erichsen cupping in the case of steel, by simulated hail in the case of wood) and then subjected to salt spray testing (natural and accelerated), weathering, or even real-life exposure, always in comparison with a blank. The results obtained demonstrate the superiority of microcapsule-based self-healing coatings compared to classical protection formulations, and appropriate coating systems have in the meantime been successfully brought to the market.     

Ecological reflections in unbounded architecture

For many years, the environmental effort in Scandinavian residential building has taken the form of construction-related improvements and technical renewal. For example, the standard in insulation has been improved and, to an increasing extent, the supply of energy is being covered by alternative energy sources. However, 'green' accounts reveal that the building and its environmental standards are not the most important factors in the residence's consumption of resources. The most crucial factors are the residents and their behaviour. Resource consumption in the residence is thus entirely dependent on the residents' habits, on their behaviour and life style. In the final analysis, it is our culture that becomes the topic for debate, as a direct consequence of environmental problems. Question marks are being placed alongside the consumption society and concomitantly alongside the entire occidental culture. The upshot of this is that, sooner or later, environmental problems will eventually come to influence the architectonic design, which reflects the culture and the societal values from which such modelling originates. The environmentally oriented work can, in this way, be discussed in an architectonic context. This is the aim of the present paper: to describe urban ecological endeavours in a wide cultural perspective. This ought to make it possible to look at this work in conjunction with current tendencies in contemporary design. In order to understand the present day, however, it is necessary to start at some distance from it - with the Renaissance.     

Behavior of internal stakeholders in project portfolio management and its impact on success

Stakeholder behavior and stakeholder management are key success factors within project portfolio management (PPM). This empirical study of 197 project portfolios investigates the effect of the intensity of engagement (IoE) of portfolio-internal stakeholders on project portfolio success. We show that the effect of stakeholders is phase-specific and that role clarity as a measure of PPM maturity affects the nature of the relationship between the IoE of stakeholders and portfolio success. The effects of the IoE of senior managers on success are not clearly positive with regard to strategic portfolio structuring and are even negative in operative portfolio steering in established PPM systems. In immature PPM systems, line managers tend to take advantage of their position in resource management. Surprisingly, the influence of portfolio managers in portfolio steering is insignificant. Altogether, this paper shows the diverse effect of the IoE of stakeholders on portfolio success. This study enriches project research by applying stakeholder theory to the project portfolio context and offers practical guidance for further professionalizing PPM.     

Purification of Biorefinery Lignin with Alcohols

After hydrothermal pretreatment and enzymatic hydrolysis of wheat straw, a slurry rich in lignin but with a high content of inorganic substances, especially silica, and residual carbohydrates is produced. This slurry was used to develop an ethanol organosolv separation method to produce silica-free lignin fractions. The addition of para toluene sulphonic acid (PTSA) and the use of two alternative long-chain alcohols, oleyl alcohol or nonylphenol, were tested. In every reaction, two lignin fractions were produced and their molecular size and elemental composition were characterized. The yield of each fraction and the change in MWD were studied as a function of temperature and solid to liquid ratio. At 100, 150, and 200°C and with the use of PTSA, high-purity lignin fractions were obtained. After lignin fractionation with nonylphenol, a liquid silica-free product with high lignin content was obtained in yields between 17 and 72%.     

SMART-Reactors: Tailoring Gas Holdup Distribution by Additively Manufactured Lattice Structures

In chemical process engineering, fast gas-liquid reactions often suffer from an inefficient distribution of gas and therefore mixing and mass transfer performance. This study deals with the possibility of influencing the local gas holdup and bubble size distribution in a gas-liquid process using additively manufactured lattice structures (AMLS). The used measuring technique to study bubble size, velocity, and the local gas holdup is a photo-optical needle probe. By using AMLS, a significant radial homogenization of the local gas holdup and the mean bubble size is achieved. Furthermore, it can be demonstrated that the bubble size can be tailored by the geometry of the inserted structure. It is illustrated that the mean bubble velocities are lowered within the lattice resulting in a higher residence time of the dispersed phase with an impact on the mass transfer performance within the AMLS.     

Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.