Single Building Block Research Articles

Variable cellular decision-making behavior in a constant synthetic network topology

BackgroundModules of interacting components arranged in specific network topologies have evolved to perform a diverse array of cellular functions. For a network with a constant topological structure, its function within a cell may still be tuned by changing the number of instances of a particular component (e.g., gene copy number) or by modulating the intrinsic biochemical properties of a component (e.g., binding strength or catalytic efficiency). How such perturbations affect cellular response dynamics remains poorly understood. Here, we explored these effects in a common decision-making motif, cross-antagonism with autoregulation, by synthetically constructing this network in yeast.ResultsWe employed the engineering design strategy of reuse to build this topology with a single protein building block, TetR, creating necessary components through TetR mutations and fusion partners. We then studied the impact of several topology-preserving perturbations – strength of cross-antagonism, number of operator sites in a promoter, and gene dosage – on decision-making behavior. We found that reducing TetR repression strength, which hinders cross-antagonism, resulted in a loss of mutually exclusive cell responses. Unexpectedly, increasing the number of operator sites also impeded decision-making exclusivity, which may be a consequence of the averaging effect that arises when multiple transcriptional activators and repressors are accommodated at a given locus. Stochastic simulations of this topology revealed that, even for networks with high TetR repression strength and a low number of operator sites, increasing gene dosage can reduce exclusivity in response dynamics. We further demonstrated this result experimentally by quantifying gene copy numbers in selected yeast clones with differing phenotypic responses.ConclusionsOur study illustrates how parameters that do not change the topological structure of a decision-making network can nonetheless exert significant influence on its response dynamics. These findings should further inform the study of native motifs, including the effects of topology-preserving mutations, and the robust engineering of synthetic networks.

Disulfide-mediated conversion of 8-mer bowl-like protein architecture into three different nanocages

Constructing different protein nanostructures with high-order discrete architectures by using one single building block remains a challenge. Here, we present a simple, effective disulfide-mediated approach to prepare a set of protein nanocages with different geometries from single building block. By genetically deleting an inherent intra-subunit disulfide bond, we can render the conversion of an 8-mer bowl-like protein architecture (NF-8) into a 24-mer ferritin-like nanocage in solution, while selective insertion of an inter-subunit disulfide bond into NF-8 triggers its conversion into a 16-mer lenticular nanocage. Deletion of the same intra-subunit disulfide bond and insertion of the inter-subunit disulfide bond results in the conversion of NF-8 into a 48-mer protein nanocage in solution. Thus, in the laboratory, simple mutation of one protein building block can generate three different protein nanocages in a manner that is highly reminiscent of natural pentamer building block originating from viral capsids that self-assemble into protein assemblies with different symmetries.

Topological interlocking and damage mechanisms in periodic Ti2AlC-Al building block composites

Ceramic Ti2AlC building blocks of 4 × 1.24 × 1.24 mm³ size were prepared by injection molding and assembled to brick-and-mortar structures with tetragonal, monoclinic and triclinic unit cells. The single building blocks were bonded with an Al-loaded polysiloxane adhesive, which was afterwards pyrolized. Afterwards the 3D-assemblies were infiltrated with an Al-melt to fabricate dense 0–3 ceramic-metal composites. The influence of the unit cell of the resulting Ti2AlC-Al composites was investigated regarding the mechanical properties and damage mechanisms in bending tests. The developed near-net shape fabrication process shows great potential to manufacture structured ceramic-metal composites with high toughness and complex shape. Due to their ductile behavior scaffold applications are possible. The calculated initial fracture toughness of monolithic Ti2AlC could be improved from 5.0 MPa m0.5 to 14.5 MPa m0.5 for the monoclinic assembly and 14.7 MPa m0.5 for the triclinic assembly, corresponding to an increase of 191%.

On the Division Problem for the Wave Maps Equation

We consider Wave Maps into the sphere and give a new proof of small data global well-posedness and scattering in the critical Besov space, in any space dimension $n \geq 2$. We use an adapted version of the atomic space $U^2$ as the single building block for the iteration space. Our approach to the so-called division problem is modular as it systematically uses two ingredients: atomic bilinear (adjoint) Fourier restriction estimates and an algebra property of the iteration space, both of which can be adapted to other phase functions.

Two-dimensional tessellation by molecular tiles constructed from halogen\u2013halogen and halogen\u2013metal networks

Molecular tessellations are often discovered serendipitously, and the mechanisms by which specific molecules can be tiled seamlessly to form periodic tessellation remain unclear. Fabrication of molecular tessellation with higher symmetry compared with traditional Bravais lattices promises potential applications as photonic crystals. Here, we demonstrate that highly complex tessellation can be constructed on Au(111) from a single molecular building block, hexakis(4-iodophenyl)benzene (HPBI). HPBI gives rise to two self-assembly phases on Au(111) that possess the same geometric symmetry but different packing densities, on account of the presence of halogen-bonded and halogen–metal coordinated networks. Sub-domains of these phases with self-similarity serve as tiles in the periodic tessellations to express polygons consisting of parallelograms and two types of triangles. Our work highlights the important principle of constructing multiple phases with self-similarity from a single building block, which may constitute a new route to construct complex tessellations.

Self‐Assembly of Polymer‐Coated Plasmonic Nanocrystals: From Synthetic Approaches to Practical Applications

Self-assembly of plasmonic nanocrystals (PNCs) and polymers provides access to a variety of functionalized metallic-polymer building blocks and higher-order hybrid plasmonic assemblies, and thus is of considerable fundamental and practical interest. The hybrid assemblies often not only inherit individual characteristics of polymers and PNCs but also exhibit distinct photophysical and catalytic properties compared to that of a single PNC building block. The tailorable plasmonic coupling between PNCs within assemblies enables the precise control over localized surface plasmon resonance, which subsequently affords a series of light-driven or photo-activated applications, such as surface-enhanced Raman scattering detection, photoacoustic imaging, photothermal therapy, and photodynamic therapy. In this review, the synthetic strategies of a library of PNC-polymer hybrid building blocks and corresponding assemblies are summarized along with the mechanisms of polymer-assisted self-assembly of PNCs and the concepts for bridging the intrinsic properties of PNC-polymer assemblies to widespread practical applications.

Colloidal Self‐Assembly Concepts for Plasmonic Metasurfaces

AbstractMetallic nanostructures exhibit strong interactions with electromagnetic radiation, known as the localized surface plasmon resonance. In recent years, there is significant interest and growth in the area of coupled metallic nanostructures. In such assemblies, short‐ and long‐range coupling effects can be tailored and emergent properties, e.g., metamaterial effects, can be realized. The term “plasmonic metasurfaces” is used for this novel class of assemblies deposited on planar surfaces. Herein, the focus is on plasmonic metasurfaces formed from colloidal particles. These are formed by self‐assembly and can meet the demands of low‐cost manufacturing of large‐area, flexible, and ultrathin devices. The advances in high optical quality of the colloidal building blocks and methods for controlling their self‐assembly on surfaces will lead to novel functional devices for dynamic light modulators, pulse sharpening, subwavelength imaging, sensing, and quantum devices. This progress report focuses on predicting optical properties of single colloidal building blocks and their assemblies, wet‐chemical synthesis, and directed self‐assembly of colloidal particles. The report concludes with a discussion of the perspectives toward expanding the colloidal plasmonic metasurfaces concept by integrating them with quantum emitters (gain materials) or mechanically responsive structures.

Modular ceramic scaffolds for individual implants

Ideal artificial bone grafts aim for multiscale porosity, high mechanical strength and ensure rapid vascularization for bone ingrowth. In this work modular ceramic arteriovenous loops (AV-loops) with a hierarchical porosity approach were designed and manufactured to meet these criteria and to exceed the poor mechanical strength of monolithic scaffolds. Bioactive building blocks (β-TCP, HAp, BCP) with dimensions of 1.5–3.0 mm were prepared by injection molding and assembled to complex AV-loop scaffolds using a customized automated assembly technology (pick and place). The building blocks were bonded with a biocompatible adhesive. Single building blocks are characterized by a compressive strength of 112.4–134.5 MPa with a residual sintering porosity of 32.2–41.5%, matching the strength of cortical bone of 100–230 MPa. The compressive strength of the modular assemblies varied between 22.3 and 47.6 MPa primary depending on the building block arrangement. The achieved compressive strengths are superior to current monolithic AV-scaffolds and sufficient for the implantation as non-load-bearing AV-loop scaffolds in isolation chambers. The modular AV-loop scaffolds provide a hierarchical interconnected pore network (P = 58.8%) combining small macropores of 4.1–4.3 µm size for possible enhanced protein absorption and large gradient macropores of 200–1700 µm size for optimum vascularization and complete bone ingrowth. The modular building block approach allows to design patient individualized scaffolds with complex hierarchical pore networks. The pore volume, size and geometry as well as the biological response can effectively be tuned by changing the dimensions, shape and placing gap of the bioactive building blocks. Statement of SignificanceGold standard of bone replacement in case of surgery or cancer is still own bone material usually taken from the hip/arm or leg in second surgery with poor mechanical properties and limited amount. To avoid a second surgery and provide mechanical strong scaffold structures for fast patient regeneration a novel modular building block approach is used. This allows complex scaffold geometry with a hierarchical interconnection porosity for blood vessel ingrowth. The pore volume, size and geometry as well as the biological response can effectively be tuned by changing the dimensions, shape and placing gap of the bioactive building blocks.

Intrinsic Fluorescence of Metabolite Amyloids Allows Label-Free Monitoring of Their Formation and Dynamics in Live Cells.

The formation of apoptosis-inducing amyloidal structures by metabolites has significantly extended the "amyloid hypothesis" to include non-proteinaceous, single metabolite building blocks. However, detection of metabolite assemblies is restricted compared to their larger protein-based counterparts owing to the hindrance of external labelling and limited immunohistochemical detection tools. Herein, we present the detection of the formation, dynamics, and cellular distribution of metabolite amyloid-like structures and provide mechanistic insights into the generation of supramolecular chromophores. Moreover, the intrinsic fluorescence properties allow the detection of metabolite assemblies in living cells without the use of external dyes. Altogether, this intrinsic fluorescence of metabolite assemblies further verifies their amyloidal nature, while providing an important tool for further investigation of their pathological role in inborn error of metabolism disorders.

Intrinsic Fluorescence of Metabolite Amyloids Allows Label‐Free Monitoring of Their Formation and Dynamics in Live Cells

AbstractThe formation of apoptosis‐inducing amyloidal structures by metabolites has significantly extended the “amyloid hypothesis” to include non‐proteinaceous, single metabolite building blocks. However, detection of metabolite assemblies is restricted compared to their larger protein‐based counterparts owing to the hindrance of external labelling and limited immunohistochemical detection tools. Herein, we present the detection of the formation, dynamics, and cellular distribution of metabolite amyloid‐like structures and provide mechanistic insights into the generation of supramolecular chromophores. Moreover, the intrinsic fluorescence properties allow the detection of metabolite assemblies in living cells without the use of external dyes. Altogether, this intrinsic fluorescence of metabolite assemblies further verifies their amyloidal nature, while providing an important tool for further investigation of their pathological role in inborn error of metabolism disorders.

Multiscale Imaging Reveals the Hierarchical Organization of Fibrillin Microfibrils

Fibrillin microfibrils are evolutionarily ancient, structurally complex extracellular polymers found in mammalian elastic tissues where they endow elastic properties, sequester growth factors and mediate cell signalling; thus, knowledge of their structure and organization is essential for a more complete understanding of cell function and tissue morphogenesis. By combining multiple imaging techniques, we visualize three levels of hierarchical organization of fibrillin structure ranging from micro-scale fiber bundles in the ciliary zonule to nano-scale individual microfibrils. Serial block-face scanning electron microscopy imaging suggests that bundles of zonule fibers are bound together by circumferential wrapping fibers, which is mirrored on a shorter-length scale where individual zonule fibers are interwoven by smaller fibers. Electron tomography shows that microfibril directionality varies from highly aligned and parallel, connecting to the basement membrane, to a meshwork at the zonule fiber periphery, and microfibrils within the zonule are connected by short cross-bridges, potentially formed by fibrillin-binding proteins. Three-dimensional reconstructions of negative-stain electron microscopy images of purified microfibrils confirm that fibrillin microfibrils have hollow tubular structures with defined bead and interbead regions, similar to tissue microfibrils imaged in our tomograms. These microfibrils are highly symmetrical, with an outer ring and interwoven core in the bead and four linear prongs, each accommodating a fibrillin dimer, in the interbead region. Together these data show how a single molecular building block is organized into different levels of hierarchy from microfibrils to tissue structures spanning nano- to macro-length scales. Furthermore, the application of these combined imaging approaches has wide applicability to other tissue systems.

Catalysis-Based Total Syntheses of Pateamine A and DMDA-Pat A.

The marine natural product pateamine A (1) and its somewhat simplified designer analogue DMDA-Pat A (2) (DMDA = desmethyl-desamino) are potently cytotoxic compounds; most notably, 2 had previously been found to exhibit a promising differential in vivo activity in xenograft melanoma models, even though the ubiquitous eukaryotic initiation factor 4A (eIF4A) constitutes its primary biological target. In addition, 1 had also been identified as a possible lead in the quest for medication against cachexia, an often lethal muscle wasting syndrome affecting many immunocompromised or cancer patients. The short supply of these macrodiolides, however, rendered a more detailed biological assessment difficult. Therefore, a new synthetic approach to 1 and 2 has been devised, which centers on an unorthodox strategy for the formation of the highly isomerization-prone but essential Z, E-configured dienoate substructure embedded into the macrocyclic core. This motif was encoded in the form of a 2-pyrone ring and unveiled only immediately before macrocyclization by an unconventional iron-catalyzed ring opening/cross-coupling reaction, in which the enol ester entity of the pyrone gains the role of a leaving group. Since the required precursor was readily available by gold catalysis, this strategy rendered the overall sequence short, robust, and scalable. A surprisingly easy protecting group management together with a much improved end game for the formation of the trienyl side chain via a modern Stille coupling protocol also helped to make the chosen route practical. Change of a single building block allowed the synthesis to be redirected from the natural lead compound 1 toward its almost equipotent analogue 2. Isolation and reactivity profiling of pyrone tricarbonyliron complexes provide mechanistic information as well as insights into the likely origins of the observed chemoselectivity.

Software for Peak Finding and Elemental Composition Assignment for Glycosaminoglycan Tandem Mass Spectra

Glycosaminoglycans (GAGs) covalently linked to proteoglycans (PGs) are characterized by repeating disaccharide units and variable sulfation patterns along the chain. GAG length and sulfation patterns impact disease etiology, cellular signaling, and structural support for cells. We and others have demonstrated the usefulness of tandem mass spectrometry (MS2) for assigning the structures of GAG saccharides; however, manual interpretation of tandem mass spectra is time-consuming, so computational methods must be employed. In the proteomics domain, the identification of monoisotopic peaks and charge states relies on algorithms that use averagine, or the average building block of the compound class being analyzed. Although these methods perform well for protein and peptide spectra, they perform poorly on GAG tandem mass spectra, because a single average building block does not characterize the variable sulfation of GAG disaccharide units. In addition, it is necessary to assign product ion isotope patterns to interpret the tandem mass spectra of GAG saccharides. To address these problems, we developed GAGfinder, the first tandem mass spectrum peak finding algorithm developed specifically for GAGs. We define peak finding as assigning experimental isotopic peaks directly to a given product ion composition, as opposed to deconvolution or peak picking, which are terms more accurately describing the existing methods previously mentioned. GAGfinder is a targeted, brute force approach to spectrum analysis that uses precursor composition information to generate all theoretical fragments. GAGfinder also performs peak isotope composition annotation, which is typically a subsequent step for averagine-based methods. Data are available via ProteomeXchange with identifier PXD009101.

Contribution of Building Façades to Attractive Streetscapes: Study of Two Main Streets in Kuala Lumpur City

Building facades contribute to attractive urban streetscapes. In between, physical elements and visual qualities of building faA§ades play the most important role. This study seeks to identify the impact of building facades on creating attractive streetscapes in the city of Kuala Lumpur. In achieving this, a self-administered questionnaire survey was conducted to gather peoples' evaluation of building facades in Kuala Lumpur where combination of modern and traditional architecture creates worth-study urban landscapes. The researcher randomly surveyed 330 respondents, 18 to 50 years old, from the passers-by who just visit the area and those who reside and work there, using the time interval sampling method. The results demonstrate that consistency of colors and details of building facades, simplicity, unity, conformity of store lots in a single building block, large windows, transparency of the function of buildings, and display items of store-fronts determine visual richness of streetscapes in the study areas. The findings contribute to visual identity of cities through creating attractive streetscapes.

Voltage difference transresistance amplifier and its application: floating FDNR simulator circuit

ABSTRACTIn this article, a new active building component with electronically tunable transresistive block, voltage difference transresistance amplifier, and its floating frequency dependent negative resistor simulator circuit application is presented. The simulator circuit is shown to operate using single active building block with two grounded passive components, to be electronically tunable over its value which is controlled by an independent current source, not to require any conditions of component matching and to have good sensitivity performance with respect to tracking errors. To examine functionality of the design, a CRD band-pass filter example is given.Numerous simulation program with integrated circuit emphasis (SPICE) simulations are performed and depicted through the article to verify validity of the study. Taiwan semiconductor manufacturing company (TSMC) 0.18 µm complementary metal oxide semiconductor technology parameters are used through simulations.

An impact based mass-in-mass unit as a building block of wideband nonlinear resonating metamaterial

Vibration transmission through a mass-in-mass unit is frequency dependent due to the difference in phase between the internal resonator and the surrounding structure. Generally, the attenuation band is confined between the two-transmission bands for a linear resonating metamaterial. In the case of a linear metamaterial, the attenuation band can be widened up to a certain limit by tuning the material properties, but cannot be extended infinitely by removing the 2nd transmission band. An impacting resonator can attenuate the vibration of the metamaterial due to the counteraction of the external excitation by the resulting impulse force and due to the presence of the sub and super-harmonic and chaotic responses. This paper theoretically elucidates that an impact metamaterial can results zero averaged effective mass for the multi-periodic type impacting vibration as in these frequency ranges vibration becomes essentially out of phase. Most importantly, an impacting metamaterial has a potential to extend the attenuation bandwidth by reducing the vibration of the main structure even for the minimal mass ratio. The scope of the paper is limited to analysis of a single building block of the impacting metamaterial to provide better insight comprehension of the effect of impacting oscillation inside a metamaterial unit more systematically.

Covalent organic frameworks with lithiophilic and sulfiphilic dual linkages for cooperative affinity to polysulfides in lithium-sulfur batteries

Confining lithium polysulfides (PSs) within the cathode materials is one of effective solutions to improve cycling stability of lithium-sulfur batteries. The lithiophilicity and sulfiphilicity are two mainstreaming chemical interactions to stabilize lithium PSs, but they have been demonstrated independently in most of cathode materials with well-defined structures and chemical compositions. It is a great challenge for designing new materials to simultaneously elucidate such two types of chemical interactions at molecular level. Here, we develop a self-condensation approach of single building block to construct a covalent organic framework (COF) containing triazine and boroxine units (TB-COF). TB-COF was generated from 4-cyanophenylboronic acid through simultaneous formation of two types of reversible covalent bonds. The triazine unit chemically absorbs lithium ions through lithiophilic interaction, while boroxine unit traps PSs through sulfiphilic interaction. The amphiphilic chemisorption of lithium PSs has been elucidated by spectroscopic studies and theoretical calculations. The TB-COF/S electrode delivers a reversible capacity of 663 mA h g−1 after 800 cycles at 1 C with the average capacity decay per cycle as low as 0.023%, which outperforms those in the reported COF-based sulfur cathodes.

Modular assembling process of an in-silico protocell

The bottom-up approach of synthetic biology is driven by the need for a deepened understanding of the interaction of functional modules in living or artificial systems. The hope is that the gained knowledge will help to optimize existing systems, or, as one long-term goal of synthetic biology, to build up artificial cell-like entities from single building blocks. This article focuses on a system theoretic approach to synthetic biology, and in particular on the construction of a protocell model by the modular assembling process. Different models for an in-silico protocell are described that combines experimentally validated biological subsystems with theoretical assumptions. The in-silico protocell that is characterized consists of three different functional modules: the membrane proliferating module, the membrane contraction module, and a positioning module. Additional theoretical hypotheses are tested in order to merge the module models to one protocell model with synchronously working parts. The different approaches used here for developing a protocell model could be helpful for assembling the different modules to one system in reality. Depending on the objective one wants to achieve a more or less detailed modeling approach is appropriate.

PH mediated kinetics of assembly and disassembly of molecular and nanoscopic building blocks

Self-assembly occurs when building blocks of the system interact with one another through interactions existing between them. Proper temporal control of these interactions can lead to formation of transient self-assembled states. pH mediated self-assembly is one of the powerful tools to stabilize and destabilize structures consisting of different sized building blocks. Here we investigate the kinetics of pH triggered reversible transformation of two building blocks using a relaxation method, reversible vesicle–micelle transformation of oleic acid molecules and dispersion–aggregation of pH sensitive gold nanoparticles. We found significant differences in the characteristic times (two orders of magnitudes) between the disassembly processes—from an ordered structure to a less ordered structure (in the case of oleic acid molecules) or to single building blocks (in the case of nanoparticles)—and the self-assembly processes (bilayer formation or aggregation of nanoparticles). It can be explained by a sophisticated interplay between repulsive (electrostatic) and attractive (van der Waals) interactions.

Classification of matrix product states with a local (gauge) symmetry

Matrix Product States (MPS) are a particular type of one dimensional tensor network states, that have been applied to the study of numerous quantum many body problems. One of their key features is the possibility to describe and encode symmetries on the level of a single building block (tensor), and hence they provide a natural playground for the study of symmetric systems. In particular, recent works have proposed to use MPS (and higher dimensional tensor networks) for the study of systems with local symmetry that appear in the context of gauge theories. In this work we classify MPS which exhibit local invariance under arbitrary gauge groups. We study the respective tensors and their structure, revealing known constructions that follow known gauging procedures, as well as different, other types of possible gauge invariant states.