Upgrading of Symbolic and Synthetic Knowledge Bases: Evidence from the Chinese Automotive and Construction Industries

This paper deals with the question of how upgrading of the symbolic and synthetic knowledge bases takes place and, by doing so, we contribute to the upgrading literature by linking upgrading with the concept of the differentiated knowledge bases. We discern a number of upgrading mechanisms, and based on empirical evidence from the construction industry and the automotive industry in China, we show that the main upgrading mechanisms for symbolic knowledge include “learning-by-interacting in project teams” and “monitoring”, while upgrading of synthetic knowledge takes place via “technology transfer” and “learning-by-doing and-using”. “Mobility” and “on-the-job training and learning in Transnational Corporations” are the main upgrading mechanisms contributing to the development of both knowledge bases.     

Engineering materials for artificial cells

The grand challenge of engineering a minimal artificial cell provides a controllable framework for studying the biochemical principles of life. Artificial cells contribute to an increased understanding of complex synthetic systems with life-like properties and provide opportunities to create autonomous cell-like materials. Recent efforts to develop life-like artificial cells by bottom-up approaches involve mimicking the behavior of lipid membranes to recapitulate fundamental cellular processes. This review describes the recent progress in engineering biomimetic artificial minimal cells and recently developed chemical strategies to drive de novo membrane formation from simple synthetic precursors. In the end, we briefly point out the challenges and possible future directions in the development of artificial cells.     

Guiding Cell Network Assembly using Shape-Morphing Hydrogels

Forces and relative movement between cells and extracellular matrix (ECM) are crucial to the self-organization of tissues during development. However, the spatial range over which these dynamics can be controlled in engineering approaches is limited, impeding progress toward the construction of large, structurally mature tissues. Herein, shape-morphing materials called “kinomorphs” that rationally control the shape and size of multicellular networks are described. Kinomorphs are sheets of ECM that change their shape, size, and density depending on patterns of cell contractility within them. It is shown that these changes can manipulate structure-forming behaviors of epithelial cells in many spatial locations at once. Kinomorphs are built using a new photolithographic technology to pattern single cells into ECM sheets that are >10× larger than previously described. These patterns are designed to partially mimic the branch geometry of the embryonic kidney epithelial network. Origami-inspired simulations are then used to predict changes in kinomorph shapes. Last, kinomorph dynamics are shown to provide a centimeter-scale program that sets specific spatial locations in which ≈50 µm-diameter epithelial tubules form by cell coalescence and structural maturation. The kinomorphs may significantly advance organ-scale tissue construction by extending the spatial range of cell self-organization in emerging model systems such as organoids.     

Bottom‐Up Assembly of Functional Intracellular Synthetic Organelles by Droplet‐Based Microfluidics

Bottom‐up synthetic biology has directed most efforts toward the construction of artificial compartmentalized systems that recreate living cell functions in their mechanical, morphological, or metabolic characteristics. However, bottom‐up synthetic biology also offers great potential to study subcellular structures like organelles. Because of their intricate and complex structure, these key elements of eukaryotic life forms remain poorly understood. Here, the controlled assembly of lipid enclosed, organelle‐like architectures is explored by droplet‐based microfluidics. Three types of giant unilamellar vesicles (GUVs)‐based synthetic organelles (SOs) functioning within natural living cells are procedured: (A) synthetic peroxisomes supporting cellular stress‐management, mimicking an organelle innate to the host cell by using analogous enzymatic modules; (B) synthetic endoplasmic reticulum (ER) as intracellular light‐responsive calcium stores involved in intercellular calcium signalling, mimicking an organelle innate to the host cell but utilizing a fundamentally different mechanism; and (C) synthetic magnetosomes providing eukaryotic cells with a magnetotactic sense, mimicking an organelle that is not natural to the host cell but transplanting its functionality from other branches of the phylogenetic tree. Microfluidic assembly of functional SOs paves the way for high‐throughput generation of versatile intracellular structures implantable into living cells. This in‐droplet SO design may support or expand cellular functionalities in translational nanomedicine.     

Multistimuli Sensing Adhesion Unit for the Self‐Positioning of Minimal Synthetic Cells

Cells have the ability to sense different environmental signals and position themselves accordingly in order to support their survival. Introducing analogous capabilities to the bottom‐up assembled minimal synthetic cells is an important step for their autonomy. Here, a minimal synthetic cell which combines a multistimuli sensitive adhesion unit with an energy conversion module is reported, such that it can adhere to places that have the right environmental parameters for ATP production. The multistimuli sensitive adhesion unit senses light, pH, oxidative stress, and the presence of metal ions and can regulate the adhesion of synthetic cells to substrates in response to these stimuli following a chemically coded logic. The adhesion unit is composed of the light and redox responsive protein interaction of iLID and Nano and the pH sensitive and metal ion mediated binding of protein His‐tags to Ni²⁺‐NTA complexes. Integration of the adhesion unit with a light to ATP conversion module into one synthetic cell allows it to adhere to places under blue light illumination, non‐oxidative conditions, at neutral pH and in the presence of metal ions, which are the right conditions to synthesize ATP. Thus, the multistimuli responsive adhesion unit allows synthetic cells to self‐position and execute their functions.     

Surface and Interface Properties in Thin‐Film Solar Cells: Using Soft X‐rays and Electrons to Unravel the Electronic and Chemical Structure

Thin‐film solar cells have great potential to overtake the currently dominant silicon‐based solar cell technologies in a strongly growing market. Such thin‐film devices consist of a multilayer structure, for which charge‐carrier transport across interfaces plays a crucial role in minimizing the associated recombination losses and achieving high solar conversion efficiencies. Further development can strongly profit from a high‐level characterization that gives a local, electronic, and chemical picture of the interface properties, which allows for an insight‐driven optimization. Herein, the authors' recent progress of applying a “toolbox” of high‐level laboratory‐ and synchrotron‐based electron and soft X‐ray spectroscopies to characterize the chemical and electronic properties of such applied interfaces is provided. With this toolbox in hand, the activities are paired with those of experts in thin‐film solar cell preparation at the cutting edge of current developments to obtain a deeper understanding of the recent improvements in the field, e.g., by studying the influence of so‐called “post‐deposition treatments”, as well as characterizing the properties of interfaces with alternative buffer layer materials that give superior efficiencies on large, module‐sized areas.     

Strategic Advances in Formation of Cell‐in‐Shell Structures: From Syntheses to Applications

Single‐cell nanoencapsulation, forming cell‐in‐shell structures, provides chemical tools for endowing living cells, in a programmed fashion, with exogenous properties that are neither innate nor naturally achievable, such as cascade organic‐catalysis, UV filtration, immunogenic shielding, and enhanced tolerance in vitro against lethal factors in real‐life settings. Recent advances in the field make it possible to further fine‐tune the physicochemical properties of the artificial shells encasing individual living cells, including on‐demand degradability and reconfigurability. Many different materials, other than polyelectrolytes, have been utilized as a cell‐coating material with proper choice of synthetic strategies to broaden the potential applications of cell‐in‐shell structures to whole‐cell catalysis and sensors, cell therapy, tissue engineering, probiotics packaging, and others. In addition to the conventional “one‐time‐only” chemical formation of cytoprotective, durable shells, an approach of autonomous, dynamic shellation has also recently been attempted to mimic the naturally occurring sporulation process and to make the artificial shell actively responsive and dynamic. Here, the recent development of synthetic strategies for formation of cell‐in‐shell structures along with the advanced shell properties acquired is reviewed. Demonstrated applications, such as whole‐cell biocatalysis and cell therapy, are discussed, followed by perspectives on the field of single‐cell nanoencapsulation.     

Membrane Tension–Mediated Growth of Liposomes

Recent years have seen a tremendous interest in the bottom‐up reconstitution of minimal biomolecular systems, with the ultimate aim of creating an autonomous synthetic cell. One of the universal features of living systems is cell growth, where the cell membrane expands through the incorporation of newly synthesized lipid molecules. Here, the gradual tension‐mediated growth of cell‐sized (≈10 µm) giant unilamellar vesicles (GUVs) is demonstrated, to which nanometer‐sized (≈30 nm) small unilamellar vesicles (SUVs) are provided, that act as a lipid source. By putting tension on the GUV membranes through a transmembrane osmotic pressure, SUV–GUV fusion events are promoted and substantial growth of the GUV is caused, even up to doubling its volume. Thus, experimental evidence is provided that membrane tension alone is sufficient to bring about membrane fusion and growth is demonstrated for both pure phospholipid liposomes and for hybrid vesicles with a mixture of phospholipids and fatty acids. The results show that growth of liposomes can be realized in a protein‐free minimal system, which may find useful applications in achieving autonomous synthetic cells that are capable of undergoing a continuous growth–division cycle.     

Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical Applications

The design of advanced functional materials with nanometer‐ and micrometer‐scale control over their properties is of considerable interest for both fundamental and applied studies because of the many potential applications for these materials in the fields of biomedical materials, tissue engineering, and regenerative medicine. The layer‐by‐layer deposition technique introduced in the early 1990s by Decher, Moehwald, and Lvov is a versatile technique, which has attracted an increasing number of researchers in recent years due to its wide range of advantages for biomedical applications: ease of preparation under “mild” conditions compatible with physiological media, capability of incorporating bioactive molecules, extra‐cellular matrix components and biopolymers in the films, tunable mechanical properties, and spatio‐temporal control over film organization. The last few years have seen a significant increase in reports exploring the possibilities offered by diffusing molecules into films to control their internal structures or design “reservoirs,” as well as control their mechanical properties. Such properties, associated with the chemical properties of films, are particularly important for designing biomedical devices that contain bioactive molecules. In this review, we highlight recent work on designing and controlling film properties at the nanometer and micrometer scales with a view to developing new biomaterial coatings, tissue engineered constructs that could mimic in vivo cellular microenvironments, and stem cell “niches.”     

Engineering Functional Membrane–Membrane Interfaces by InterSpy

Engineering synthetic interfaces between membranes has potential applications in designing non-native cellular communication pathways and creating synthetic tissues. Here, InterSpy is introduced as a synthetic biology tool consisting of a heterodimeric protein engineered to form and maintain membrane–membrane interfaces between apposing synthetic as well as cell membranes through the SpyTag/SpyCatcher interaction. The inclusion of split fluorescent protein fragments in InterSpy allows tracking of the formation of a membrane–membrane interface and reconstitution of functional fluorescent protein in the space between apposing membranes. First, InterSpy is demonstrated by testing split protein designs using a mammalian cell-free expression (CFE) system. By utilizing co-translational helix insertion, cell-free synthesized InterSpy fragments are incorporated into the membrane of liposomes and supported lipid bilayers with the desired topology. Functional reconstitution of split fluorescent protein between the membranes is strictly dependent on SpyTag/SpyCatcher. Finally, InterSpy is demonstrated in mammalian cells by detecting fluorescence reconstitution of split protein at the membrane–membrane interface between two cells each expressing a component of InterSpy. InterSpy demonstrates the power of CFE systems in the functional reconstitution of synthetic membrane interfaces via proximity-inducing proteins. This technology may also prove useful where cell-cell contacts and communication are recreated in a controlled manner using minimal components.     

Recent Advances in Nanotechnology for Autophagy Detection

Autophagy is closely related to various diseases, and is a diagnostic and therapeutic target for some diseases. In recent years, tremendous efforts have been made to develop excellent probes for detection of autophagy. Nanostructure‐based probes are interesting and promising approaches for in vivo biological imaging due to their unique structural and functional characteristics, e.g., modulating pharmacokinetics property by biocompatible coatings, multimodality capacity by delivering multiple imaging agents and highly specific targeting by antibody ligands. In this Review, we first introduce recent advancements in the development of nanostructure‐based probes for detection of autophagy, including inorganic hybrid nanomaterials and self‐assembled peptide polymeric nanoparticles. Meanwhile, a nanoprobe based on a “in vivo self‐assembly” strategy is highlighted. The “in vivo self‐assembly” endows nanoprobes with higher accumulation, and longer and better signal stability for in vivo detection of autophagy. Furthermore, this novel strategy could be widely used for biomedical imaging/diagnostics and therapeutics, which would attract more attention to this research area.     

A synthetic double sampling control chart for process mean using auxiliary information

A control chart is a simple yet powerful tool that is extensively adopted to monitor shifts in the process mean. In recent years, auxiliary‐information–based (AIB) control charts have received considerable attention as these control charts outperform their counterparts in monitoring changes in the process parameter(s). In this article, we integrate the conforming run length chart with the existing AIB double sampling (AIB DS) chart to propose an AIB synthetic DS chart for the process mean. The AIB synthetic DS chart also encompasses the existing synthetic DS chart. A detailed discussion on the construction, optimization, and evaluation of the run length profiles is provided for the proposed control chart. It is found that the optimal AIB synthetic DS chart significantly outperforms the existing AIB Shewhart, optimal AIB synthetic, and AIB DS charts in detecting various shifts in the process mean. An illustrative example is given to demonstrate the implementation of the existing and proposed AIB control charts.     

Microfluidics for Biosynthesizing: from Droplets and Vesicles to Artificial Cells

Fabrication of artificial biomimetic materials has attracted abundant attention. As one of the subcategories of biomimetic materials, artificial cells are highly significant for multiple disciplines and their synthesis has been intensively pursued. In order to manufacture robust “alive” artificial cells with high throughput, easy operation, and precise control, flexible microfluidic techniques are widely utilized. Herein, recent advances in microfluidic‐based methods for the synthesis of droplets, vesicles, and artificial cells are summarized. First, the advances of droplet fabrication and manipulation on the T‐junction, flow‐focusing, and coflowing microfluidic devices are discussed. Then, the formation of unicompartmental and multicompartmental vesicles based on microfluidics are summarized. Furthermore, the engineering of droplet‐based and vesicle‐based artificial cells by microfluidics is also reviewed. Moreover, the artificial cells applied for imitating cell behavior and acting as bioreactors for synthetic biology are highlighted. Finally, the current challenges and future trends in microfluidic‐based artificial cells are discussed. This review should be helpful for researchers in the fields of microfluidics, biomaterial fabrication, and synthetic biology.     

The new German soundproofing standard: Comparison between DIN 4109:1989 and E DIN 4109:2013 / Die neue Schallschutznorm: Vergleich DIN 4109:1989 und E DIN 4109:2013

In 2013, a new draft of a complete standard for DIN 4109 “Soundproofing in buildings” was issued in 4 parts – “Requirements”, “Method of calculation”, “Parts catalogue” and “Testing acoustics in buildings”. It includes several increases in the requirements for protection against airborne noise and impact sound by comparison to DIN 4109:1989. The increases are based on the grades from monitored buildings of standard construction periodically noted in recent years. Significant changes are also included in Part 2 “Input data for verifying the requirements by calculation”. A detailed computation of all transmission paths is carried out here, taking into account the special vibration reducing indices. For a brick wall, the specific indices for the weighted sound reduction index R’w,R are shown that arise for various formations of the joints. When compared with the calculated values according to DIN 4109:1989 there are differences of up to 10 dB.     

“All‐in‐One” Gel System for Whole Procedure of Stem‐Cell Amplification and Tissue Engineering

Microsphere (MS)‐based systems provides great advantages for cell expansion and transplantation due to their high surface‐to‐volume ratio and biomimetic environment. However, a MS‐based system that includes cell attachment, proliferation, passage, harvest, cryopreservation, and tissue engineering together has not been realized yet. An “all‐in‐one” gel MS‐based system is established for human adipose‐derived mesenchymal stem cells (hADSCs), realizing real 3D culture with enhanced expansion efficiency and simplified serial cell culture operations, and construction of macrotissues with uniform cell distribution and specific function. A 3D digital light‐processing technology is developed to fabricate gel MSs in an effective way. The printed MSs present a suitable environment with rough surface architecture and the mechanical properties of soft tissues, leading to high cell viability, attachment, proliferation, activity, and differentiation potential. Further, convenient standard operation procedures, including cell passage, detachment, and cryopreservation, are established for cell culture on the gel MSs. Finally, hADSCs‐loaded gel MSs form macrotissues through a “bottom‐up” approach, which demonstrates the potential applications for tissue engineering. These findings exhibit the feasibility and beauty of “all‐in‐one” stem cell culture and tissue engineering system.     

Biocompatibilty of starch-based films from starch of Andean crops for biomedical applications

In this communication we report the use of starch films as cell substrates. To the best of our knowledge it is the first time that films prepared from native Andean starches are studied as biomaterials. For the present study 3T3 fibroblast cells were seeded in seventeen novel starch based films from different Andean crops. In order to analyze the use of these types of starch as biomedical materials, biocompatibility, viability and cell adhesion studies were performed at the third day of incubation on supplemented DMEM medium. After cultured, films made from starch of “tunta”, “muro-huayro” potato and white carrot showed the highest level of living cells and cell viability. These results indicate that native starches from Andean crops can be used for biomedical applications.     

Chemical analysis of a single basic cell of porous anodic aluminium oxide templates

We prepared anodic aluminium oxide (AAO) templates with “honeycomb” geometry, i.e. hexagonally ordered circular pores. The structures were extensively studied and characterized by EPMA coupled with FEG-SEM and FEG-TEM coupled with EDX at meso and nanoscopic scales, in other words, at the scale of a single basic cell making up the highly ordered porous anodic film. The analyses allowed the identification of the chemical compounds present and the evaluation of their levels in the different parts of each cell. Of note was the absence of phosphates inside the “skeleton” and their high content in the “internal part”. Various models of porous anodic film growth are discussed on the basis of the results, contributing to a better understanding of AAO template preparation and self-nanostructuring phenomena.