Orthogonal Control Research Articles

Temperature- and pH-Responsive Polymeric Photocatalysts for Enhanced Control and Recovery.

The emergence of heterogeneous photocatalysis has facilitated redox reactions with high efficiency, without compromising the recyclability of the photocatalyst. Recently, stimuli-responsive heterogeneous photocatalytic materials have emerged as a powerful synthetic tool, with simple and rapid recovery, as well as an enhanced dynamic control over reactions. Stimuli-responsive polymers are often inexpensive and easy to produce. They can be switched from an active "on" state to an inert "off" state in response to external stimuli, allowing the production of photocatalyst with adaptability, recyclability, and orthogonal control on different chemical reactions. Despite this versatility, the application of artificial smart material in the field of heterogeneous photocatalysis has not yet been maximized. In this Minireview, we will examine the recent developments of this emerging class of stimuli-responsive heterogeneous photocatalytic systems. We will discuss the synthesis route of appending photoactive components into different triggerable systems and, in particular, the controlled activation and recovery of the materials.

Chemically inducible split protein regulators for mammalian cells.

Chemically inducible systems represent valuable synthetic biology tools that enable the external control of biological processes. However, their translation to therapeutic applications has been limited because of unfavorable ligand characteristics or the immunogenicity of xenogeneic protein domains. To address these issues, we present a strategy for engineering inducible split protein regulators (INSPIRE) in which ligand-binding proteins of human origin are split into two fragments that reassemble in the presence of a cognate physiological ligand or clinically approved drug. We show that the INSPIRE platform can be used for dynamic, orthogonal and multiplex control of gene expression in mammalian cells. Furthermore, we demonstrate the functionality of a glucocorticoid-responsive INSPIRE platform in vivo and apply it for perturbing an endogenous regulatory network. INSPIRE presents a generalizable approach toward designing small-molecule responsive systems that can be implemented for the construction of new sensors, regulatory networks and therapeutic applications.

Orthogonal‐ and Path‐Dependent Photo/Acidoswitching in an Eight‐State Dihydroazulene‐Spiropyran Dyad

AbstractMolecules comprised of two or more switches have potential to exist in a variety of states, which may only be accessible by a “correct” sequence of stimuli on account of the influence of the neighboring unit. Here we present a straightforward synthesis of a dyad incorporating two photoswitchable units, dihydroazulene (DHA) and spiropyran (SP). The photoswitching properties of both chromophores and the acido‐triggered switching of the SP were retained in the dyad, allowing selective switching between eight states with distinct absorption and fluorescence properties (corresponding to light‐controlled fluorescence on/off switching). Photoisomerization of DHA and protonation of SP allowed an orthogonal control of the individual sites. Conversely, photoisomerization of SP to its merocyanine (MC) isomer could not be performed without also addressing DHA‐to‐vinylheptafulvene (VHF) switching. Access to the DHA‐MC state thus appeared to be path‐dependent as it could exclusively be reached by deprotonation of the thermally stable DHA‐E‐MCH.

ABS - CaSO4 Polymer Composite: Experimental Studies On Mechanical And Tribological Properties

Objectives: The present study examines the effect of Calcium Sulphate (CaSO4) microparticles as filler materials and ABS as matrix materials on mechanical properties and wear performance of composite materials, which are injected into molds for preparation of the specimens. Methods: The CaSO4 microparticles are added at different weight fractions to the acrylonitrile butadiene styrene (ABS) polymer composites. Moreover, the reinforcement has improved tensile strength, wear properties, and hardness. Wear behavior was measured on ABS/ CaSO4 by a wear monitor (ASTM G99) and pin-ondisc type friction. As part of this experiment, the cutting speed, loading, and sliding distance of composite materials are considered and optimized for their properties. To observe and analyze the characteristics of this material, tensile strength and wear tests were conducted. By analyzing SEM images, we were able to study the fractured material’s morphology. In this study, an orthogonal array (L9) and control parameters were used to examine wear debris that explored the flacks and grooves of the content. Findings: An increase in toughness and modulus of resilience (due to an increase in filler content) and the contribution of normal load to wear rate (37.44%) constitute the most important contribution to work. Novelty : we have evaluated the various tribological and mechanical properties of polymer composite specimens using the Taguchi method. Keywords: ABS; Tensile strength; Pinondisc; SEM; Taguchi

Orthogonal Control of Neuronal Circuits and Behavior Using Photopharmacology.

Over the last decades, photopharmacology has gone far beyond its proof-of-concept stage to become a bona fide approach to study neural systems in vivo. Indeed, photopharmacological control has expanded over a wide range of endogenous targets, such as receptors, ion channels, transporters, kinases, lipids, and DNA transcription processes. In this review, we provide an overview of the recent progresses in the in vivo photopharmacological control of neuronal circuits and behavior. In particular, the use of small aquatic animals for the in vivo screening of photopharmacological compounds, the recent advances in optical modulation of complex behaviors in mice, and the development of adjacent techniques for light and drug delivery in vivo are described.

Controlling forward and backward rotary molecular motion on demand

Synthetic molecular machines hold tremendous potential to revolutionize chemical and materials sciences. Their autonomous motion controlled by external stimuli allows to develop smart materials whose properties can be adapted on command. For the realisation of more complex molecular machines, it is crucial to design building blocks whose properties can be controlled by multiple orthogonal stimuli. A major challenge is to reversibly switch from forward to backward and again forward light-driven rotary motion using external stimuli. Here we report a push-pull substituted photo-responsive overcrowded alkene whose function can be toggled between that of a unidirectional 2nd generation rotary motor and a molecular switch depending on its protonation and the polarity of its environment. With its simplicity in design, easy preparation, outstanding stability and orthogonal control of distinct forward and backward motions, we believe that the present concept paves the way for creating more advanced molecular machines.

Orthogonal control of gene expression in plants using synthetic promoters and CRISPR-based transcription factors

BackgroundThe construction and application of synthetic genetic circuits is frequently improved if gene expression can be orthogonally controlled, relative to the host. In plants, orthogonality can be achieved via the use of CRISPR-based transcription factors that are programmed to act on natural or synthetic promoters. The construction of complex gene circuits can require multiple, orthogonal regulatory interactions, and this in turn requires that the full programmability of CRISPR elements be adapted to non-natural and non-standard promoters that have few constraints on their design. Therefore, we have developed synthetic promoter elements in which regions upstream of the minimal 35S CaMV promoter are designed from scratch to interact via programmed gRNAs with dCas9 fusions that allow activation of gene expression.ResultsA panel of three, mutually orthogonal promoters that can be acted on by artificial gRNAs bound by CRISPR regulators were designed. Guide RNA expression targeting these promoters was in turn controlled by either Pol III (U6) or ethylene-inducible Pol II promoters, implementing for the first time a fully artificial Orthogonal Control System (OCS). Following demonstration of the complete orthogonality of the designs, the OCS was tied to cellular metabolism by putting gRNA expression under the control of an endogenous plant signaling molecule, ethylene. The ability to form complex circuitry was demonstrated via the ethylene-driven, ratiometric expression of fluorescent proteins in single plants.ConclusionsThe design of synthetic promoters is highly generalizable to large tracts of sequence space, allowing Orthogonal Control Systems of increasing complexity to potentially be generated at will. The ability to tie in several different basal features of plant molecular biology (Pol II and Pol III promoters, ethylene regulation) to the OCS demonstrates multiple opportunities for engineering at the system level. Moreover, given the fungibility of the core 35S CaMV promoter elements, the derived synthetic promoters can potentially be utilized across a variety of plant species.

Molecular Approaches to Protein Dimerization: Opportunities for Supramolecular Chemistry.

Protein dimerization plays a key role in many biological processes. Most cellular events such as enzyme activation, transcriptional cofactor recruitment, signal transduction, and even pathogenic pathways are significantly regulated via protein-protein interactions. Understanding and controlling the molecular mechanisms that regulate protein dimerization is crucial for biomedical applications. The limitations of engineered protein dimerization provide an opportunity for molecular chemistry to induce dimerization of protein in biological events. In this review, molecular control over dimerization of protein and activation in this respect are discussed. The well known molecule glue-based approaches to induced protein dimerization provide powerful tools to modulate the functionality of dimerized proteins and are shortly highlighted. Subsequently metal ion, nucleic acid and host-guest chemistry are brought forward as novel approaches for orthogonal control over dimerization of protein. The specific focus of the review will be on host-guest systems as novel, robust and versatile supramolecular approaches to modulate the dimerization of proteins, using functional proteins as model systems.

Circularly Polarized Light Can Override and Amplify Asymmetry in Supramolecular Helices.

Circularly polarized light (CPL) is an inherently chiral entity and is considered one of the possible deterministic signals that led to the evolution of homochirality. While accumulating examples indicate that chirality beyond the molecular level can be induced by CPL, not much is yet known about circumstances where the spin angular momentum of light competes with existing molecular chiral information during the chirality induction and amplification processes. Here we present a light-triggered supramolecular polymerization system where chiral information can both be transmitted and nonlinearly amplified in a "sergeants-and-soldiers" manner. While matching handedness with CPL resulted in further amplification, we determined that opposite handedness could override molecular information at the supramolecular level when the enantiomeric excess was low. The presence of a critical chiral bias suggests a bifurcation point in the homochirality evolution under random external chiral perturbation. Our results also highlight opportunities for the orthogonal control of supramolecular chirality decoupled from molecular chirality preexisting in the system.

Retraction notice: Application of a V-belt continuously variable transmission system by using a composite recurrent Laguerre orthogonal polynomial neural network control system and modified particle swarm optimization

Retraction notice: Application of a V-belt continuously variable transmission system by using a composite recurrent Laguerre orthogonal polynomial neural network control system and modified particle swarm optimization

Orthogonal control of DNA nanoswitches with mixed physical and biochemical cues

Nanoscale devices that can respond to external stimuli have potential applications in drug delivery, biosensing, and molecular computation. Construction using DNA has provided many such devices that can respond to cues such as nucleic acids, proteins, pH, light, or temperature. However, simultaneous control of molecular devices is still limited. Here, we present orthogonal control of DNA nanoswitches using physical (light) and biochemical (enzyme and nucleic acid) triggers. Each one of these triggers controls the reconfiguration of specific nanoswitches from locked to open states within a mixture and can be used in parallel to control a combination of nanoswitches.

Orthogonal Design-Based Control Vector Parameterization Combined With Improved Seagull Optimization Algorithm for Dynamic Optimization Problems

Orthogonal Design-Based Control Vector Parameterization Combined With Improved Seagull Optimization Algorithm for Dynamic Optimization Problems

Electronically Tunable Universal Filter and Quadrature Oscillator Using Low-Voltage Differential Difference Transconductance Amplifiers

This paper presents a new electronically tunable universal filter and quadrature oscillator for low frequency biomedical and biosensor applications employing low-voltage differential difference transconductance amplifier (DDTA). The DDTA CMOS structure uses 0.5 V of supply voltage and consumes 277 nW of power. Unlike the previous universal filters, the proposed filter provides many transfer functions of the standard five transfer functions such as low-pass, high-pass, band-pass, band-stop and all-pass with both unity and controlled voltage gains as well as both inverting and non-inverting transfer functions. The natural frequency and the voltage gain of the five standard transfer functions can be controlled electronically. For the band-pass filter, the third intermodulation distortion (IMD₃) was 0.37&#x0025; for 20 mV_pp input signal while the output integrated noise was 61.37 <inline-formula> <tex-math notation="LaTeX">$\mu \text{V}$ </tex-math></inline-formula>. The dynamic range (DR) was 53.27 dB for 1&#x0025; IMD₃. The quadrature oscillator has electronically and orthogonal control of the condition and frequency of oscillation. The proposed circuit and its applications were designed and verified via Cadence simulator tool using 0.13 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> UMC CMOS technology. Further, the circuit was evaluated by PSPICE simulation and experiment test using commercial OTA LM13700.

Spray‐Drying and Atomic Layer Deposition: Complementary Tools toward Fully Orthogonal Control of Bulk Composition and Surface Identity of Multifunctional Supraparticles (Small Methods 1/2022)

Inside Back Cover In article number 2101296, Thommes, Barr, Mandel, and co-workers used spray-drying as a scalable process that enables one to assemble freely chosen nanoparticles into supraparticles, i.e., microparticles with adjustable nanostructure, in combination with atomic layer deposition to deposit controlled thin films of different materials onto and within supraparticles. The combination of these two techniques allows for the independent adjustment of properties determined by bulk and surface composition.

Orthogonal manipulations of phase and phase dispersion in realization of azimuthal angle-resolved focusings

In conventional achromatic metasurfaces configurations where the engineering paths of phase and phase dispersion are the same, limited phase dispersion control range inevitably imposes a restriction on the broadband device size, which otherwise can be arranged in a periodic manner to achieve infinite size at a single wavelength. In addition to this, the adoption of geometric-phase structures imparts the orthogonal circular polarization conversion, whereas the birefringent propagation-phase structures bring an uncertain polarization state, thus resulting in an incomplete polarization conversion. In this study, we propose an azimuthal angle-resolved beam-deflection metasurface at the same polar angle with orthogonal phase and phase dispersion control paths. Periodic expansion is implemented to achieve unlimited device size along the phase control path and the broadband light is monotonously and azimuthally deflected to the designated polar angle with the delicate design along the dispersion path. In addition, the non-crossed polarized light arising from the incomplete geometric phase control would naturally separate from the cross-polarized light when adjusting the planar geometric parameters of the birefringent metaatoms to realize dispersion control. This design scenario may find applications in phased-array detection applications where beams are azimuthally swept to search targets at one polar angle.

Spray-Drying and Atomic Layer Deposition: Complementary Tools toward Fully Orthogonal Control of Bulk Composition and Surface Identity of Multifunctional Supraparticles.

Spray-drying is a scalable process enabling one to assemble freely chosen nanoparticles into supraparticles. Atomic layer deposition (ALD) allows for controlled thin film deposition of a vast variety of materials including exotic ones that can hardly be synthesized by wet chemical methods. The properties of coated supraparticles are defined not only by the nanoparticle material chosen and the nanostructure adjusted during spray-drying but also by surface functionalities modified by ALD, if ALD is capable of modifying not only the outer surfaces but also surfaces buried inside the porous supraparticle. Simultaneously, surface accessibility in the porous supraparticles must be ensured to make use of all functionalized surfaces. In this work, iron oxide supraparticles are utilized as a model substrate as their magnetic properties enable the use of advanced magnetic characterization methods. Detailed information about the structural evolution upon individual ALD cycles of aluminium oxide, zinc oxide and titanium dioxide are thereby revealed and confirmed by gas sorption analyses. This demonstrates a powerful and versatile approach to freely designing the functionality of future materials by combination of spray-drying and ALD.

Design of a digital control system of disk gyroscope with orthogonal control circuit

This paper introduces a gyro control system with the quadrature control circuit. The control system realizes the automatic decoupling of driving mode and sensing mode. The quadrature control circuit eliminates the quadrature signal in the sensitive mode by applying a voltage to the quadrature control electrode. The time needed to adjust the voltage can be changed by adjusting the parameters of the controller. The control system is realized by a digital circuit. The feasibility of the design is verified by the test.

Artificial Transcription Factors for Tuneable Gene Expression in Pichia pastoris.

The non-conventional yeast Pichia pastoris (syn. Komagataella phaffii) has become a powerful eukaryotic expression platform for biopharmaceutical and biotechnological applications on both laboratory and industrial scales. Despite the fundamental role that artificial transcription factors (ATFs) play in the orthogonal control of gene expression in synthetic biology, a limited number of ATFs are available for P. pastoris. To establish orthogonal regulators for use in P. pastoris, we characterized ATFs derived from Arabidopsis TFs. The plant-derived ATFs contain the binding domain of TFs from the plant Arabidopsis thaliana, in combination with the activation domains of yeast GAL4 and plant EDLL and a synthetic promoter harboring the cognate cis-regulatory motifs. Chromosomally integrated ATFs and their binding sites (ATF/BSs) resulted in a wide spectrum of inducible transcriptional outputs in P. pastoris, ranging from as low as 1- to as high as ∼63-fold induction with only small growth defects. We demonstrated the application of ATF/BSs by generating P. pastoris cells that produce β-carotene. Notably, the productivity of β-carotene in P. pastoris was ∼4.8-fold higher than that in S. cerevisiae, reaching ∼59% of the β-carotene productivity obtained in a S. cerevisiae strain optimized for the production of the β–carotene precursor, farnesyl diphosphate, by rewiring the endogenous metabolic pathways using plant-derived ATF/BSs. Our data suggest that plant-derived regulators have a high degree of transferability from S. cerevisiae to P. pastoris. The plant-derived ATFs, together with their cognate binding sites, powerfully increase the repertoire of transcriptional regulatory modules for the tuning of protein expression levels required in metabolic engineering or synthetic biology in P. pastoris.

Designing 2D and 3D Non-Orthogonal Frame Fields

We present a method for direction field design on surface and volumetric meshes supporting non-orthogonality. Our approach is a generalization of the representation of 3D cross fields in spherical harmonic basis. As such it induces a geometrically meaningful measure of smoothness, allows orthogonality control by a simple parameter and enables orientation constraints of a single direction. To the best of our knowledge this is the first work to propose non-orthogonal 3D frame field design. We demonstrate the applicability of our method to generate anisotropic quadrangular and hexahedral meshes which are particularly useful for remeshing CAD models.

Impact of Microdevice Geometry on Transit and Retention in the Murine Gastrointestinal Tract.

Oral protein delivery technologies often depend on encapsulating or enclosing the protein cargo to protect it against pH-driven degradation in the stomach or enzymatic digestion in the small intestine. An emergent methodology is to encapsulate therapeutics in microscale, asymmetric, planar microparticles, referred to as microdevices. Previous work has shown that, compared to spherical particles, planar microdevices have longer residence times in the GI tract, but it remains unclear how specific design choices (e.g., material selection, particle diameter) impact microdevice behavior in vivo. Recent advances in microdevice fabrication through picoliter printing have expanded the range of device sizes that can be fabricated in a rapid manner. However, relatively little work has explored how device size governs their behavior in the intestinal environment. In this study, we probe the impact of geometry of planar microdevices on their transit and accumulation in the murine GI tract. Additionally, we present a strategy to label, image, and quantify these distributions in intact tissue in a continuous manner, enabling a more detailed understanding of device distribution and transit kinetics than previously possible. We show that smaller particles (194.6 ± 7 μm.diameter) tend to empty from the stomach faster than midsize (293.2 ± 7 μm.diameter) and larger devices (440.9 ± 9 μm.diameter) and that larger devices distribute more broadly in the GI tract and exit slower than other geometries. In general, we observed an inverse correlation between device diameter and GI transit rate. These results inform the future design of drug delivery systems, using particle geometry as an engineering design parameter to control device accumulation and distribution in the GI tract. Additionally, our image analysis process provides greater insight into the tissue level distribution and transit of particle populations. Using this technique, we demonstrate that microdevices act and translocate independently, as opposed to transiting in one homogeneous mass, meaning that target sites will likely be exposed to devices multiple times over the course of hours post administration. This imaging technique and associated findings enable data-informed design of future particle delivery systems, allowing orthogonal control of transit and distribution kinetics in vivo independent of material and cargo selection.