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Logic-in-memory (LIM) architecture holds great potential to break the von Neumann bottleneck. Despite the extensive research on novel devices, challenges persist in developing suitable engineering building blocks for such designs. Herein, we propose a reconfigurable strategy for efficient implementation of Boolean logics based on a hafnium oxide-based ferroelectric field effect transistor (HfO 2 -based FeFET). The logic results are stored within the device itself (in situ) during the computation process, featuring the key characteristics of LIM. The fast switching speed and low power consumption of a HfO 2 -based FeFET enable the execution of Boolean logics with an ultralow energy of lower than 8 attojoule (aJ). This represents a significant milestone in achieving aJ-level computing energy consumption. Furthermore, the system demonstrates exceptional reliability with computing endurance exceeding 10 8 cycles and retention properties exceeding 1000 s. These results highlight the remarkable potential of a FeFET for the realization of high performance beyond the von Neumann LIM computing architectures.

The intersection of mathematical cognition, metacognition, and advanced technologies presents a frontier with profound implications for human learning and artificial intelligence. This paper traces the historical roots of these concepts from the Pythagoreans and Aristotle to modern cognitive science and explores their relevance to contemporary technological applications. We examine how the Pythagoreans' view of mathematics as fundamental to understanding the universe and Aristotle's contributions to logic and categorization have shaped our current understanding of mathematical cognition and metacognition. The paper investigates the role of Boolean logic in computational processes and its relationship to human logical reasoning, as well as the significance of Bayesian inference and fuzzy logic in modelling uncertainty in human cognition and decision-making. We also explore the emerging field of Chemical Artificial Intelligence and its potential applications. We argue for unifying mathematical metacognition with advanced technologies, including artificial intelligence and robotics, while identifying the multifaceted benefits and challenges of such unification. The present paper examines essential research directions for integrating cognitive sciences and advanced technologies, discussing applications in education, healthcare, and business management. We provide suggestions for developing cognitive robots using specific cognitive tasks and explore the ethical implications of these advancements. Our analysis underscores the need for interdisciplinary collaboration to realize the full potential of this integration while mitigating potential risks., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Reconfigurable neuromorphic computing holds promise for advancing energy-efficient neural network implementation and functional versatility. Previous work has focused on emulating specific neural functions rather than an integrated approach. We propose an all two-dimensional (2D) material-based heterostructure capable of performing multiple neuromorphic operations by reconfiguring output terminals in response to stimuli. Specifically, our device can synergistically emulate the key neural elements of the synapse, neuron, and dendrite, which play important and interrelated roles in information processing. Dendrites, the branches that receive and transmit presynaptic action potentials, possess the ability to nonlinearly integrate and filter incoming signals. The proposed heterostructure allows reconfiguration between different operation modes, demonstrating its potential for diverse computing tasks. As a proof of concept, we show that the device can perform basic Boolean logic functions. This highlights its applicability to complex neural-network-based information processing problems. Our integrated neuromorphic approach may advance the development of versatile, low-power neuromorphic hardware.

A functionally complete Boolean operator is sufficient for computational circuits of arbitrary complexity. We connected YES (buffer) with NOT (inverter) and two NOT four-way junction (4J) DNA gates to obtain IMPLY and NAND Boolean functions, respectively, each of which represents a functionally complete gate. The results show a technological path towards creating a DNA computational circuit of arbitrary complexity based on singleton NOT or a combination of NOT and YES gates, which is not possible in electronic computers. We, therefore, concluded that DNA-based circuits and molecular computation may offer opportunities unforeseen in electronics., Competing Interests: The authors declare no conflicts of interest.

To support the increasingly complex circuits needed for plant synthetic biology applications, additional constitutive promoters are essential. Reusing promoter parts can lead to difficulty in cloning, increased heterogeneity between transformants, transgene silencing and trait instability. We have developed a pipeline to identify genes that have stable expression across a wide range of Arabidopsis tissues at different developmental stages and have identified a number of promoters that are well expressed in both transient ( Nicotiana benthamiana ) and stable ( Arabidopsis ) transformation assays. We have also introduced two genome-orthogonal gRNA target sites in a subset of the screened promoters, converting them into NOR logic gates. The work here establishes a pipeline to screen for additional constitutive promoters and can form the basis of constructing more complex information processing circuits in the future., Competing Interests: The authors declare no competing interests., (© The Author(s) 2023.)

Magnetic domain wall (DW)-based logic devices offer numerous opportunities for emerging electronics applications allowing superior performance characteristics such as fast motion, high density, and nonvolatility to process information. However, these devices rely on an external magnetic field, which limits their implementation; this is particularly problematic in large-scale applications. Multiferroic systems consisting of a piezoelectric substrate coupled with ferromagnets provide a potential solution that provides the possibility of controlling magnetization through an electric field via magnetoelastic coupling. Strain-induced magnetization anisotropy tilting can influence the DW motion in a controllable way. We demonstrate a method to perform all-electrical logic operations using such a system. Ferromagnetic coupling between neighboring magnetic domains induced by the electric-field-controlled strain has been exploited to promote noncollinear spin alignment, which is used for realizing essential building blocks, including DW generation, propagation, and pinning, in all implementations of Boolean logic, which will pave the way for scalable memory-in-logic applications.

Background: The intersection of synthetic biology and biomaterials promises to enhance safety and efficacy in novel therapeutics. Both fields increasingly employ Boolean logic, which allows for specific therapeutic outputs (e.g., drug release, peptide synthesis) in response to inputs such as disease markers or bio-orthogonal stimuli. Examples include stimuli-responsive drug delivery devices and logic-gated chimeric antigen receptor (CAR) T cells. In this review, we explore recent manuscripts highlighting the potential of synthetic biology and biomaterials with Boolean logic to create novel and efficacious living therapeutics., Main Body: Collaborations in synthetic biology and biomaterials have led to significant advancements in drug delivery and cell therapy. Borrowing from synthetic biology, researchers have created Boolean-responsive biomaterials sensitive to multiple inputs including pH, light, enzymes and more to produce functional outputs such as degradation, gel-sol transition and conformational change. Biomaterials also enhance synthetic biology, particularly CAR T and adoptive T cell therapy, by modulating therapeutic immune cells in vivo. Nanoparticles and hydrogels also enable in situ generation of CAR T cells, which promises to drive down production costs and expand access to these therapies to a larger population. Biomaterials are also used to interface with logic-gated CAR T cell therapies, creating controllable cellular therapies that enhance safety and efficacy. Finally, designer cells acting as living therapeutic factories benefit from biomaterials that improve biocompatibility and stability in vivo., Conclusion: By using Boolean logic in both cellular therapy and drug delivery devices, researchers have achieved better safety and efficacy outcomes. While early projects show incredible promise, coordination between these fields is ongoing and growing. We expect that these collaborations will continue to grow and realize the next generation of living biomaterial therapeutics., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Burgeoning population growth and subsequent demand for freshwater, besides competition among irrigation, domestic, and industrial sectors, coupled with a changing climate, have necessitated prudent and effective management of water resources. Rainwater harvesting (RWH) is considered one of the most effective strategies for water management. However, the location and design of RWH structures are essential for proper implementation, operation, and maintenance. An attempt has been made in this study to locate the most suitable site for RWH structure and design using one of the robust multi-criteria decision analysis techniques, viz. analytic hierarchy process, using geospatial tools in the Gambhir watershed, Rajasthan, India. High-resolution Sentinel-2A data and a digital elevation model of the Advanced Land Observation Satellite were used in this study. Five biophysical parameters, viz. land use and land cover, slope, soil texture, surface runoff, and drainage density, were considered to identify suitable locations for RWH structures. It was observed that runoff is the prime factor in determining the location of RWH structures compared to other parameters. It was revealed that 75.54 km 2 (13% of the total area) was very highly suited for the construction of RWH structures, while 114.56 km 2 (19%) was highly suitable. A total of 43.77 km 2 (7%) of land was determined to be unsuitable for the construction of any type of RWH structure. Farm ponds, check dams, and percolation ponds were suggested for the study area. Furthermore, Boolean logic was used to target a particular type of RWH structure. The study indicated that a total of 25 farm ponds, 14 check dams, and 16 percolation ponds can be constructed at identified locations in the watershed. Water resource development maps of the watershed generated using an analytical approach would be useful for policymakers and hydrologists for targeting and implementing RWH structures in the study watershed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Living cells constantly monitor their external and internal environments for changing conditions, stresses or developmental cues. Networks of genetically encoded components sense and process these signals following pre-defined rules in such a way that specific combinations of the presence or absence of certain signals activate suitable responses. Many biological signal integration mechanisms approximate Boolean logic operations, whereby presence or absence of signals are computed as variables with values described as either true or false, respectively. Boolean logic gates are commonly used in algebra and in computer sciences, and have long been recognized as useful information processing devices in electronic circuits. In these circuits, logic gates integrate multiple input values and produce an output signal according to pre-defined Boolean logic operations. Recent implementation of these logic operations using genetic components to process information in living cells has allowed genetic circuits to enable novel traits with decision-making capabilities. Although several literature reports describe the design and use of these logic gates to introduce new functions in bacterial, yeast and mammalian cells, similar approaches in plants remain scarce, likely due to challenges posed by the complexity of plants and the lack of some technological advances, e.g., species-independent genetic transformation. In this mini review, we have surveyed recent reports describing synthetic genetic Boolean logic operators in plants and the different gate architectures used. We also briefly discuss the potential of deploying these genetic devices in plants to bring to fruition a new generation of resilient crops and improved biomanufacturing platforms., Competing Interests: Declaration of competing interest All the authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Biomolecular materials offer tremendous potential for the development of memristive devices due to their low cost of production, environmental friendliness, and, most notably, biocompatibility. Herein, biocompatible memristive devices based on amyloid-gold nanoparticle hybrids have been investigated. These memristors demonstrate excellent electrical performance, featuring an ultrahigh R off /R on ratio (>10 7 ), a low switching voltage (<0.8 V), and reliable reproducibility. Additionally, the reversible transition from threshold switching to resistive switching mode was achieved in this work. The arrangement of peptides in amyloid fibrils endows the surface polarity and phenylalanine packing, which provides channels for the migration of Ag ions in the memristors. By modulating voltage pulse signals, the study successfully imitates the synaptic behavior of excitatory postsynaptic current (EPSC), paired-pulse facilitation (PPF), and the transition from short-term plasticity (STP) to long-term plasticity (LTP). More interestingly, Boolean logic standard cells were designed and simulated using the memristive devices. The fundamental and experimental results of this study thus offer insights into the utilization of biomolecular materials for advanced memristive devices.

Concatenated enzyme-based Boolean logic gates activated with 5 chemical input signals were analyzed with a smartphone photo camera. Simultaneous detection of 32 input combinations was conveniently performed using enzyme-modified fiberglass sensing spots generating fluorescence with different intensities for the 0 and 1 binary outputs. The developed technology offers an easy readout method for multi-channel logic systems., (© 2022 Wiley-VCH GmbH.)

The advent of modern single-cell biology has revealed the striking molecular diversity of cell populations once thought to be more homogeneous. This newly appreciated complexity has made intersectional genetic approaches essential to understanding and probing cellular heterogeneity at the functional level. Here, we build on previous knowledge to develop a simple adeno-associated virus (AAV)-based approach to define specific subpopulations of cells by Boolean exclusion logic (AND NOT). This expression by Boolean exclusion (ExBoX) system encodes for a gene of interest that is turned on by a particular recombinase (Cre or FlpO) and turned off by another. ExBoX allows for the specific transcription of a gene of interest in cells expressing only the activating recombinase, but not in cells expressing both. We show the ability of the ExBoX system to tightly regulate expression of fluorescent reporters in vitro and in vivo, and further demonstrate the adaptability of the system by achieving expression of a variety of virally delivered coding sequences in the mouse brain. This simple strategy will expand the molecular toolkit available for cell- and time-specific gene expression in a variety of systems., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Synthetic biology aims to harness natural and synthetic biological parts and engineering them in new combinations and systems, producing novel therapies, diagnostics, bioproduction systems, and providing information on the mechanism of function of biological systems. Engineering cell function requires the rewiring or de novo construction of cell information processing networks. Using natural and synthetic signal processing elements, researchers have demonstrated a wide array of signal sensing, processing and propagation modules, using transcription, translation, or post-translational modification to program new function. The toolbox for synthetic network design is ever-advancing and has still ample room to grow. Here, we review the diversity of synthetic gene networks, types of building modules, techniques of regulation, and their applications., (© 2020 Federation of European Biochemical Societies.)

Isothermal nucleic acid amplification tests (iNATs), such as loop-mediated isothermal amplification (LAMP), are good alternatives to PCR-based amplification assays, especially for point-of-care and low-resource use, in part because they can be carried out with relatively simple instrumentation. However, iNATs can often generate spurious amplicons, especially in the absence of target sequences, resulting in false-positive results. This is especially true if signals are based on non-sequence-specific probes, such as intercalating dyes or pH changes. In addition, pathogens often prove to be moving, evolving targets and can accumulate mutations that will lead to inefficient primer binding and thus false-negative results. Multiplex assays targeting different regions of the analyte and logical signal readout using sequence-specific probes can help to reduce both false negatives and false positives. Here, we describe rapid conversion of three previously described SARS-CoV-2 LAMP assays that relied on a non-sequence-specific readout into individual and multiplex one-pot assays that can be visually read using sequence-specific oligonucleotide strand exchange (OSD) probes. We describe both fluorescence-based and Boolean logic-gated colorimetric lateral flow readout methods and demonstrate detection of SARS-CoV-2 virions in crude human saliva. IMPORTANCE One of the key approaches to treatment and control of infectious diseases, such as COVID-19, is accurate and rapid diagnostics that is widely deployable in a timely and scalable manner. To achieve this, it is essential to go beyond the traditional gold standard of quantitative PCR (qPCR) that is often faced with difficulties in scaling due to the complexity of infrastructure and human resource requirements. Isothermal nucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), have been long pursued as ideal, low-tech alternatives for rapid, portable testing. However, isothermal approaches often suffer from false signals due to employment of nonspecific readout methods. We describe general principles for rapidly converting nonspecifically read LAMP assays into assays that are read in a sequence-specific manner by using oligonucleotide strand displacement (OSD) probes. We also demonstrate that inclusion of OSD probes in LAMP assays maintains the simplicity of one-pot assays and a visual yes/no readout by using fluorescence or colorimetric lateral-flow dipsticks while providing accurate sequence-specific readout and the ability to logically query multiplex amplicons for redundancy or copresence. These principles not only yielded high-surety isothermal assays for SARS-CoV-2 but might also aid in the design of more sophisticated molecular assays for other analytes., (Copyright © 2021 Bhadra et al.)

Plant immunity is a highly dynamic process and requires dynamic modeling to capture the events of complexity mediated by the interaction between plant host and the attacking pathogen. The events of recognition are invoked by pathogen-based epitopes, while the subversion of host defenses are orchestrated by pathogen-originated effector molecules. The pathogen constitutes an immune signaling network inside the host cells. We model plant immune dynamics by using JIMENA-package, which is a java-based genetic regulatory network (GRN) simulation framework. It can efficiently compute network behavior and system states mediated by pathogenic perturbations. Here, we describe a step-by-step protocol to introduce the application of JIMENA-package to quantify immune dynamics in plant-pathogen interaction networks., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The assessment of rainwater-harvesting demand (RWHD) map and the identification of appropriate priority-based locations for rainwater-harvesting (RWH) and groundwater recharge structures are very crucial for the water managers, particularly in irrigation commands. This study addresses this challenge by using multi-criteria decision-making (MCDM) and geospatial techniques to present a novel and robust approach for generating RWHD map and identifying sites/zones for distinct RWH and groundwater recharge on a priority basis. Primary thematic layers such as existing irrigation water supply, irrigation demand, and groundwater potential were considered in this study for delineating RWHD zones. Further, sites suitable for RWH and groundwater recharge were identified using soil, slope, drainage network, and lineament thematic layers of the study area and they were prioritized. Four zones of rainwater demand were identified for the prioritization of RWH and groundwater structures: (a) "low" rainwater-harvesting demand zone (covering 3% of the total study area), (b) "moderate" rainwater-harvesting demand zone (40%), (c) "high" rainwater-harvesting demand zone (42%), and (d) "very high" rainwater-harvesting demand zone (15%). Moreover, 46 sites for check dams and 145 suitable sites for percolation tanks were identified, together with 253 ha area for groundwater recharge based on the priority of rainwater-harvesting demand. Integration of geospatial and MCDM techniques in conjunction with suitable thematic layers provides a helpful and realistic tool for large-scale planning and management of rainwater conservation measures.

The enzyme system mimicking Implication (IMPLY) and Inhibition (INHIB) Boolean logic gates has been designed. The same enzyme system was used to operate as the IMPLY or INHIB gate simply by reformulating the input signals. The optical analysis of the logic operation confirmed the output generation as expected for the studied logic gates. The conceptual approach to the IMPLY and INHIB logic gates allows their construction with many other enzymes operating in a similar way., (© 2020 Wiley-VCH GmbH.)

The flow of data between processing and memory units in contemporary computing systems is their main performance and energy-efficiency bottleneck, often referred to as the 'von Neumann bottleneck' or 'memory wall'. Emerging resistance switching memories (memristors) show promising signs to overcome the 'memory wall' by enabling computation in the memory array. Majority logic is a type of Boolean logic, and in many nanotechnologies, it has been found to be an efficient logic primitive. In this paper, a technique is proposed to implement a majority gate in a memory array. The majority gate is realised in an energy-efficient manner as a memory R E A D operation. The proposed logic family disintegrates arithmetic operations to majority and NOT operations which are implemented as memory R E A D and W R I T E operations. A 1-bit full adder can be implemented in 6 steps (memory cycles) in a 1T-1R array, which is faster than I M P L Y , N A N D , N O R and other similar logic primitives.

The ability to integrate biological signals and execute a functional response when appropriate is critical for sophisticated cell engineering using synthetic biology. Although the CRISPR-Cas system has been harnessed for synthetic manipulation of the genome, it has not been fully utilized for complex environmental signal sensing, integration, and actuation. Here, we develop a split dCas12a platform and show that it allows for the construction of multi-input, multi-output logic circuits in mammalian cells. The system is highly programmable and can generate expandable AND gates with two, three, and four inputs. It can also incorporate NOT logic by using anti-CRISPR proteins as an OFF switch. By coupling the split dCas12a design to multiple tumor-relevant promoters, we provide a proof of concept that the system can implement logic gating to specifically detect breast cancer cells and execute therapeutic immunomodulatory responses., Competing Interests: Declaration of Interests The authors filed a provisional patent related to this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Herein, we present an approach that integrates molecular logic functions using surface-confined metallo-organic assemblies. These assemblies are electrochromic and mimic the behaviour of logic elements. The logic elements are addressed individually by electrochemical methods, and their outputs are simultaneously read-out optically by UV/Vis absorption spectroscopy. The versatility of our setup is demonstrated by the integration of two multi-component assemblies; each acting as ternary logic elements. We used also a laminated cell configuration to demonstrate color-to-color and color-to-transparent transitions. This concept offers a route for the future development of devices with multiple logic states., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Rhodococcus opacus PD630 ( R. opacus ) is a nonmodel, Gram-positive bacterium that holds promise as a biological catalyst for the conversion of lignocellulosic biomass to value-added products. In particular, it demonstrates both a high tolerance for and an ability to consume inhibitory lignin-derived aromatics, generates large quantities of lipids, exhibits a relatively rapid growth rate, and has a growing genetic toolbox for engineering. However, the availability of genetic parts for tunable, high-activity gene expression is still limited in R. opacus . Furthermore, genetic logic circuits for sophisticated gene regulation have never been demonstrated in Rhodococcus spp. To address these shortcomings, two inducible T7 RNA polymerase-based expression systems were implemented for the first time in R. opacus and applied to the construction of AND and NAND genetic logic gates. Additionally, three isopropyl β-d-1-thiogalactopyranoside (IPTG)-inducible promoters were created by inserting LacI binding sites into newly characterized constitutive promoters. Furthermore, four novel aromatic sensors for 4-hydroxybenzoic acid, vanillic acid, sodium benzoate, and guaiacol were developed, expanding the gene expression toolbox. Finally, the T7 RNA polymerase platform was combined with a synthetic IPTG-inducible promoter to create an IMPLY logic gate. Overall, this work represents the first demonstration of a heterologous RNA polymerase system and synthetic genetic logic in R. opacus , enabling complex and tunable gene regulation in this promising nonmodel host for bioproduction.

The controlled presentation of proteins from and within materials remains of significant interest for many bioengineering applications. Though "smart" platforms offer control over protein release in response to a single external cue, no strategy has been developed to trigger delivery in response to user-specified combinations of environmental inputs, nor to independently control the release of multiple species from a homogenous material. Here, a modular semisynthetic scheme is introduced to govern the release of site-specifically modified proteins from hydrogels following Boolean logic. A sortase-mediated transpeptidation reaction is used to generate recombinant proteins C-terminally tethered to gels through environmentally sensitive degradable linkers. By varying the connectivity of multiple stimuli-labile moieties within these customizable linkers, YES/OR/AND control of protein release is exhaustively demonstrated in response to one and two-input combinations involving enzyme, reductant, and light. Tethering of multiple proteins each through a different stimuli-sensitive linker permits their independent and sequential release from a common material. It is expected that these methodologies will enable new opportunities in tissue engineering and therapeutic delivery., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present a potential new mode of natural computing in which simple, heat-driven fluid flows perform Boolean logic operations. The system comprises a two-dimensional single-phase fluid that is heated from below and cooled from above, with two obstacles placed on the horizontal mid-plane. The obstacles remove all vertical momentum that flows into them. The horizontal momentum extraction of the obstacles is controlled in a binary fashion, and constitutes the 2-bit input. The output of the system is a thresholded measure of the energy extracted by the obstacles. Due to the existence of multiple attractors in the phase space of this system, the input-output relationships are equivalent to those of the OR, XOR or NAND gates, depending on the threshold and obstacle separation. The ability to reproduce these logical operations suggests that convective flows might have the potential to perform more general computations, despite the fact that they do not involve electronics, chemistry or multiple fluid phases., Competing Interests: We declare we have no competing interests.

Biocomputing uses molecular biology parts as the hardware to implement computational devices. By following pre-defined rules, often hard-coded into biological systems, these devices are able to process inputs and return outputs-thus computing information. Key to the success of any biocomputing endeavor is the availability of a wealth of molecular tools and biological motifs from which functional devices can be assembled. Synthetic biology is a fabulous playground for such purpose, offering numerous genetic parts that allow for the rational engineering of genetic circuits that mimic the behavior of electronic functions, such as logic gates . A grand challenge, as far as biocomputing is concerned, is to expand the molecular hardware available beyond the realm of genetic parts by tapping into the host metabolism. This objective requires the formalization of the interplay of genetic constructs with the rest of the cellular machinery. Furthermore, the field of metabolic engineering has had little intersection with biocomputing thus far, which has led to a lack of definition of metabolic dynamics as computing basics. In this perspective article, we advocate the conceptualization of metabolism and its motifs as the way forward to achieve whole-cell biocomputations . The design of merged transcriptional and metabolic circuits will not only increase the amount and type of information being processed by a synthetic construct, but will also provide fundamental control mechanisms for increased reliability.

Research in the area of molecular computing systems, in the general framework of unconventional computing, has received high attention and resulted in rapid progress in formulating signal-controlled switchable molecules capable to perform Boolean logic operations and basic arithmetic functions. Extension of this research to biomolecular systems allowed sophisticated computational functions much easier than using synthetic molecular and supramolecular species. The advantage of biomolecular systems comparing with synthetic molecular systems is in their complementarity and compatibility allowing easy assembling multi-component systems from various biomolecules, thus increasing their functional complexity. While DNA-based computing systems are promising faster computing than Si-based electronics, at least for solving some combinatorial problems, due to massive parallel operation, enzyme-based logic systems are less promising for computational applications in their narrow definition. However, they offer novel biosensing and bioactuation features operating in binary Yes/No format. The present review article overviews different kinds of enzyme logic gates exemplified with specific enzymatic reactions/cascades. Motivation for this research and its possible applications are discussed. The review will be helpful to researchers working in this specific area to see the comprehensive collection of logic operations performed by the enzyme reactions. The newcomers to the reviewed area will benefit from the example systems representing various logic functions systematically., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The municipal waste management has always been one of the most challenging environmental concerns. Today, although different strategies have been developed, sanitary disposal of municipal waste is still considered as one of the most widely used alternatives, especially in developing countries such as Iran. To investigate the land capability of Pishva, for landfill sitting, the important criteria were categorized in two groups of ecological and socioeconomic and then a multi-criteria decision-making model was used with decision-making trial and evaluation decision-making trial and evaluation (DEMATEL)-analytical network process (ANP) approach. First and foremost, the interaction of criteria was determined implementing DEMATEL. It was found that the soil depth criterion not only is the most effective but also is the most influenced one. Moreover, ANP structure was developed to weigh the criteria. In comparison to socioeconomic criteria, ecological ones play a more significant role. Afterwards, factor maps and constraints were standardized using fuzzy and Boolean logic, respectively, and all layers were combined to generate the final capability map of Pishva applying WLC method. The capability map showed that 71% of the area is not capable of landfilling, and only 5% of Pishva has a high capability. The results proved the great effectiveness of the methods proposed in this study.

Rho GTPases such as the canonical Rac1 and RhoA are embedded within complex networks requiring the precise spatiotemporal balance of GEFs, GAPs, upstream regulators, growth factors, and downstream effectors. A modeling approach based on Boolean logical networks is becoming an increasingly relied-upon tool to harness this complexity and elucidate further details regarding Rho GTPase signaling. In this methods chapter we describe how to initially create appropriately sized networks based on literature evidence; formalize these networks with reactions based on Boolean logical operators; implement the network into appropriate simulation software (CellNetAnalyzer); and finally perform simulations and make novel, testable predictions via in silico knockouts. Given this predictive power, the Boolean approach may ultimately help to highlight potential future avenues of experimental research.

Nonvolatile stateful logic computing in memristors is a promising paradigm with which to realize the unity of information storage and processing in the same physical location that has shown great feasibility for breaking the von Neumann bottleneck in traditional computing architecture. How to reduce the computational complexity of memristor-based logic functions is a matter of concern. Here, based on a general logic expression, we proposed a method to implement the arbitrary logic of complete 16 Boolean logic in two steps with one memristor in the crossbar architecture. A representative functional complete NAND logic is successfully experimentally demonstrated in the filamentary Ag-AgGeTe-Ta memristors to prove the validity of our method. We believe our work may promote the development of the revolutionary logic in memory architectures.

Metastasis, initially driven by cells migrating and invading through the local environment, leads to most cancer-associated deaths. Cells can use a variety of modes to move in vitro, all of which depend on Rho GTPases at some level. While traditionally it was thought that Rac1 activity drives protrusive lamellipodia at the leading edge of a polarised cell while RhoA drives rear retraction, more recent work in 3D microenvironments has revealed a much more complicated picture of GTPase dynamics. In particular, RhoA activity can dominate the leading edge polymerisation of actin to form filopodial actin-spike protrusions that drive more invasive cell migration. We recently described a potential mechanism to abrogate this pro-invasive localised leading edge Rac1 to RhoA switch via manipulation of a negative feedback loop that was revealed by adopting a logical modelling approach. Both challenging dogma and taking a formal, mathematical approach to understanding signalling involved in motility may be vital to harnessing harmful cell migration and preventing metastasis in future research., (© 2016 The Author(s).)

Biocomputing nanoplatforms are designed to detect and integrate single or multiple inputs under defined algorithms, such as Boolean logic gates, and generate functionally useful outputs, such as delivery of therapeutics or release of optically detectable signals. Using sensing modules composed of small molecules, polymers, nucleic acids, or proteins/peptides, nanoplatforms have been programmed to detect and process extrinsic stimuli, such as magnetic fields or light, or intrinsic stimuli, such as nucleic acids, enzymes, or pH. Stimulus detection can be transduced by the nanomaterial via three different mechanisms: system assembly, system disassembly, or system transformation. The increasingly sophisticated suite of biocomputing nanoplatforms may be invaluable for a multitude of applications, including medical diagnostics, biomedical imaging, environmental monitoring, and delivery of therapeutics to target cell populations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Diploid budding yeast ( Saccharomyces cerevisiae ) can adopt one of several alternative differentiation fates in response to nutrient limitation, and each of these fates provides distinct biological functions. When different strain backgrounds are taken into account, these various fates occur in response to similar environmental cues, are regulated by the same signal transduction pathways, and share many of the same master regulators. I propose that the relationships between fate choice, environmental cues and signaling pathways are not Boolean, but involve graded levels of signals, pathway activation and master-regulator activity. In the absence of large differences between environmental cues, small differences in the concentration of cues may be reinforced by cell-to-cell signals. These signals are particularly essential for fate determination within communities, such as colonies and biofilms, where fate choice varies dramatically from one region of the community to another. The lack of Boolean relationships between cues, signaling pathways, master regulators and cell fates may allow yeast communities to respond appropriately to the wide range of environments they encounter in nature.

The ability to map environmental signals onto distinct internal physiological states or programmes is critical for single-celled microbes. A crucial systems dynamics feature underpinning such ability is multistability. While unlimited multistability is known to arise from multi-site phosphorylation seen in the signalling networks of eukaryotic cells, a similarly universal mechanism has not been identified in microbial signalling systems. These systems are generally known as two-component systems comprising histidine kinase (HK) receptors and response regulator proteins engaging in phosphotransfer reactions. We develop a mathematical framework for analysing microbial systems with multi-domain HK receptors known as hybrid and unorthodox HKs. We show that these systems embed a simple core network that exhibits multistability, thereby unveiling a novel biochemical mechanism for multistability. We further prove that sharing of downstream components allows a system with n multi-domain hybrid HKs to attain 3n steady states. We find that such systems, when sensing distinct signals, can readily implement Boolean logic functions on these signals. Using two experimentally studied examples of two-component systems implementing hybrid HKs, we show that bistability and implementation of logic functions are possible under biologically feasible reaction rates. Furthermore, we show that all sequenced microbial genomes contain significant numbers of hybrid and unorthodox HKs, and some genomes have a larger fraction of these proteins compared with regular HKs. Microbial cells are thus theoretically unbounded in mapping distinct environmental signals onto distinct physiological states and perform complex computations on them. These findings facilitate the understanding of natural two-component systems and allow their engineering through synthetic biology.

Engineering biological cells to perform computations has a broad range of important potential applications, including precision medical therapies, biosynthesis process control, and environmental sensing. Implementing predictable and effective computation, however, has been extremely difficult to date, due to a combination of poor composability of available parts and of insufficient characterization of parts and their interactions with the complex environment in which they operate. In this paper, the author argues that this situation can be improved by quantitative signal-to-noise analysis of the relationship between computational abstractions and the variation and uncertainty endemic in biological organisms. This analysis takes the form of a ΔSNRdB function for each computational device, which can be computed from measurements of a device's input/output curve and expression noise. These functions can then be combined to predict how well a circuit will implement an intended computation, as well as evaluating the general suitability of biological devices for engineering computational circuits. Applying signal-to-noise analysis to current repressor libraries shows that no library is currently sufficient for general circuit engineering, but also indicates key targets to remedy this situation and vastly improve the range of computations that can be used effectively in the implementation of biological applications.

We discuss the role and importance of dynamics in the brain and biological neural networks and argue that dynamics is one of the main missing elements in conventional Boolean logic and circuits. We summarize a simple dynamics based computing method, and categorize different techniques that we have introduced to realize logic, functionality, and programmability. We discuss the role and importance of coupled dynamics in networks of biological excitable cells, and then review our simple coupled dynamics based method for computing. In this paper, for the first time, we show how dynamics can be used and programmed to implement computation in any given base, including but not limited to base two.

A promising application of DNA self-assembly is the fabrication of chromophore-based excitonic devices. DNA brick assembly is a compelling method for creating programmable nanobreadboards on which chromophores may be rapidly and easily repositioned to prototype new excitonic devices, optimize device operation, and induce reversible switching. Using DNA nanobreadboards, we have demonstrated each of these functions through the construction and operation of two different excitonic AND logic gates. The modularity and high chromophore density achievable via this brick-based approach provide a viable path toward developing information processing and storage systems.

Physarum polycephalum is a large single amoeba cell, which in its plasmodial phase, forages and connects nearby food sources with protoplasmic tubes. The organism forages for food by growing these tubes towards detected foodstuff, this foraging behaviour is governed by simple rules of photoavoidance and chemotaxis. The electrical activity of the tubes oscillates, creating a peristaltic like action within the tubes, forcing cytoplasm along the lumen; the frequency of this oscillation controls the speed and direction of growth. External stimuli such as light and food cause changes in the oscillation frequency. We demonstrate that using these stimuli as logical inputs we can approximate logic gates using these tubes and derive combinational logic circuits by cascading the gates, with software analysis providing the output of each gate and determining the input of the following gate. Basic gates OR, AND and NOT were correct 90%, 77.8% and 91.7% of the time respectively. Derived logic circuits XOR, half adder and full adder were 70.8%, 65% and 58.8% accurate respectively. Accuracy of the combinational logic decreases as the number of gates is increased, however they are at least as accurate as previous logic approximations using spatial growth of P. polycephalum and up to 30 times as fast at computing the logical output. The results shown here demonstrate a significant advancement in organism-based computing, providing a solid basis for hybrid computers of the future., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Surface electrical potential and observational growth recordings were made of a protoplasmic tube of the slime mould Physarum polycephalum in response to a multitude of stimuli with regards to sensory fusion or multisensory integration. Each stimulus was tested alone and in combination in order to evaluate for the first time the effect that multiple stimuli have on the frequency of streaming oscillation. White light caused a decrease in frequency whilst increasing the temperature and applying a food source in the form of oat flakes both increased the frequency. Simultaneously stimulating P. polycephalum with light and oat flake produced no net change in frequency, while combined light and heat stimuli showed an increase in frequency smaller than that observed for heat alone. When the two positive stimuli, oat flakes and heat, were combined, there was a net increase in frequency similar to the cumulative increases caused by the individual stimuli. Boolean logic gates were derived from the measured frequency change., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Memristors, namely hysteretic devices capable of changing their resistance in response to applied electrical stimuli, may provide new opportunities for future memory and computation, thanks to their scalable size, low switching energy and nonvolatile nature. We have developed a functionally complete set of logic functions including NOR, NAND and NOT gates, each utilizing a single phase-change memristor (PCM) where resistance switching is due to the phase transformation of an active chalcogenide material. The logic operations are enabled by the high functionality of nanoscale phase change, featuring voltage comparison, additive crystallization and pulse-induced amorphization. The nonvolatile nature of memristive states provides the basis for developing reconfigurable hybrid logic/memory circuits featuring low-power and high-speed switching., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Based on known anatomy and physiology, we present a hypothesis where the basal ganglia motor loop is hierarchically organized in two main subsystems: the arbitration system and the extension system. The arbitration system, comprised of the subthalamic nucleus, globus pallidus, and pedunculopontine nucleus, serves the role of selecting one out of several candidate actions as they are ascending from various brain stem motor regions and aggregated in the centromedian thalamus or descending from the extension system or from the cerebral cortex. This system is an action-input/action-output system whose winner-take-all mechanism finds the strongest response among several candidates to execute. This decision is communicated back to the brain stem by facilitating the desired action via cholinergic/glutamatergic projections and suppressing conflicting alternatives via GABAergic connections. The extension system, comprised of the striatum and, again, globus pallidus, can extend the repertoire of responses by learning to associate novel complex states to certain actions. This system is a state-input/action-output system, whose organization enables it to encode arbitrarily complex Boolean logic rules using striatal neurons that only fire given specific constellations of inputs (Boolean AND) and pallidal neurons that are silenced by any striatal input (Boolean OR). We demonstrate the capabilities of this hierarchical system by a computational model where a simulated generic "animal" interacts with an environment by selecting direction of movement based on combinations of sensory stimuli, some being appetitive, others aversive or neutral. While the arbitration system can autonomously handle conflicting actions proposed by brain stem motor nuclei, the extension system is required to execute learned actions not suggested by external motor centers. Being precise in the functional role of each component of the system, this hypothesis generates several readily testable predictions.