Reconfigurable aJ-Level Ferroelectric Transistor-Based Boolean Logic for Logic-in-Memory.

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 (HfO2-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 HfO2-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 108 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.

Bi-Directional and Operand-Controllable In-Memory Computing for Boolean Logic and Search Operations with Row and Column Directional SRAM (RC-SRAM).

The von Neumann architecture is no longer sufficient for handling large-scale data. In-memory computing has emerged as the potent method for breaking through the memory bottleneck. A new 10T SRAM bitcell with row and column control lines called RC-SRAM is proposed in this article. The architecture based on RC-SRAM can achieve bi-directional and operand-controllable logic-in-memory and search operations through different signal configurations, which can comprehensively respond to various occasions and needs. Moreover, we propose threshold-controlled logic gates for sensing, which effectively reduces the circuit area and improves accuracy. We validate the RC-SRAM with a 28 nm CMOS technology, and the results show that the circuits are not only full featured and flexible for customization but also have a significant increase in the working frequency. At VDD = 0.9 V and T = 25 °C, the bi-directional search frequency is up to 775 MHz and 567 MHz, and the speeds for row and column Boolean logic reach 759 MHz and 683 MHz.

Advanced technologies and mathematical metacognition: The present and future orientation.

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.

Reconfigurable Neuromorphic Computing with 2D Material Heterostructures for Versatile Neural Information Processing.

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.

Challenges and innovations in CAR-T cell therapy: a comprehensive analysis.

Recent years have seen a marked increase in research on chimeric antigen receptor T (CAR-T) cells, with specific relevance to the treatment of hematological malignancies. Here, the structural principles, iterative processes, and target selection of CAR-T cells for therapeutic applications are described in detail, as well as the challenges faced in the treatment of solid tumors and hematological malignancies. These challenges include insufficient infiltration of cells, off-target effects, cytokine release syndrome, and tumor lysis syndrome. In addition, directions in the iterative development of CAR-T cell therapy are discussed, including modifications of CAR-T cell structures, improvements in specificity using multi-targets and novel targets, the use of Boolean logic gates to minimize off-target effects and control toxicity, and the adoption of additional protection mechanisms to improve the durability of CAR-T cell treatment. This review provides ideas and strategies for the development of CAR-T cell therapy through an in-depth exploration of the underlying mechanisms of action of CAR-T cells and their potential for innovative modification.

Genetically encoded Boolean logic operators to sense and integrate phenylpropanoid metabolite levels in plants.

Synthetic biology has the potential to revolutionize biotechnology, public health, and agriculture. Recent studies have shown the enormous potential of plants as chassis for synthetic biology applications. However, tools to precisely manipulate metabolic pathways for bioproduction in plants are still needed. We used bacterial allosteric transcription factors (aTFs) that control gene expression in a ligand-specific manner and tested their ability to repress semi-synthetic promoters in plants. We also tested the modulation of their repression activity in response to specific plant metabolites, especially phenylpropanoid-related molecules. Using these aTFs, we also designed synthetic genetic circuits capable of computing Boolean logic operations. Three aTFs, CouR, FapR, and TtgR, achieved c. 95% repression of their respective target promoters. For TtgR, a sixfold de-repression could be triggered by inducing its ligand accumulation, showing its use as biosensor. Moreover, we designed synthetic genetic circuits that use AND, NAND, IMPLY, and NIMPLY Boolean logic operations and integrate metabolite levels as input to the circuit. We showed that biosensors can be implemented in plants to detect phenylpropanoid-related metabolites and activate a genetic circuit that follows a predefined logic, demonstrating their potential as tools for exerting control over plant metabolic pathways and facilitating the bioproduction of natural products.

Single-cell multi-omics analysis identifies context-specific gene regulatory gates and mechanisms.

There is a growing interest in inferring context specific gene regulatory networks from single-cell RNA sequencing (scRNA-seq) data. This involves identifying the regulatory relationships between transcription factors (TFs) and genes in individual cells, and then characterizing these relationships at the level of specific cell types or cell states. In this study, we introduce scGATE (single-cell gene regulatory gate) as a novel computational tool for inferring TF-gene interaction networks and reconstructing Boolean logic gates involving regulatory TFs using scRNA-seq data. In contrast to current Boolean models, scGATE eliminates the need for individual formulations and likelihood calculations for each Boolean rule (e.g. AND, OR, XOR). By employing a Bayesian framework, scGATE infers the Boolean rule after fitting the model to the data, resulting in significant reductions in time-complexities for logic-based studies. We have applied assay for transposase-accessible chromatin with sequencing (scATAC-seq) data and TF DNA binding motifs to filter out non-relevant TFs in gene regulations. By integrating single-cell clustering with these external cues, scGATE is able to infer context specific networks. The performance of scGATE is evaluated using synthetic and real single-cell multi-omics data from mouse tissues and human blood, demonstrating its superiority over existing tools for reconstructing TF-gene networks. Additionally, scGATE provides a flexible framework for understanding the complex combinatorial and cooperative relationships among TFs regulating target genes by inferring Boolean logic gates among them.

Singleton {NOT} and Doubleton {YES; NOT} Gates Act as Functionally Complete Sets in DNA-Integrated Computational Circuits.

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.

Multicolor Fluorescent Inks Based on Lanthanide Hybrid Organogels for Anticounterfeiting and Logic Circuit Design.

With the rapid development of information technology, the encrypted storage of information is becoming increasingly important for human life. The luminescent materials with a color-changed response under physical or chemical stimuli are crucial for information coding and anticounterfeiting. However, traditional fluorescent materials usually face problems such as a lack of tunable fluorescence, insufficient surface-adaptive adhesion, and strict synthesis conditions, hindering their practical applications. Herein, a series of luminescent lanthanide hybrid organogels (Ln-MOGs) were rapidly synthesized using a simple method at room temperature through the coordination between lanthanide ions and 2,6-pyridinedicarboxylic acid and 5-aminoisophthalic acid. And the multicolor fluorescent inks were also prepared based on the Ln-MOG and hyaluronic acid, with the advantages of being easy to write, color-adjustable, and water-responsive discoloration, which has been applied to paper-based anticounterfeiting technology. Inspired by the responsiveness of the fluorescent inks to water, we designed a logic system that can realize single-input logic operations (NOT and PASS1) and double-input logic operations (NAND, AND, OR, NOR, XOR). The encryption of a binary code can be actualized utilizing different luminescent response modes based on the logic circuit system. By adjusting the energy sensitization and luminescence mechanism of lanthanide ions in the gel structure, the information reading and writing ability of the fluorescent inks were verified, which has great potential in the field of multicolor pattern anticounterfeiting and information encryption.

Building a pipeline to identify and engineer constitutive and repressible promoters.

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.

Cronología / Chronology

Esta cronología es una idea del psicoanalista e investigador francés Théo Lucciardi y fue publicada originalmente en el número 3 de la revista LAPSUS NUMÉRIQUE. Su autor ha preparado esta versión actualizada a 2023 especialmente para este número de Aesthethica. La secuencia, que va desde la invención de la rueda hasta la IA generativa, permite detenernos en los grandes hitos del desarrollo científico tecnológico y a la vez advertir ve el grado de aceleración de la última década. Se pueden reconocer allí varios de los temas que integran la agenda contemporánea en materia de bioética y que están presentes en este número de la revista. Algunos de ellos son cruciales para la lectura ético-analítica que proponemos, como la vigencia de la lógica booleana, la actualización del Test de Turing o el porvenir de la IA y el Chat GPT

This chronology is an initiative of the French psychoanalyst and researcher Théo Lucciardi and was originally published in number 3 of the LAPSUS NUMÉRIQUE magazine. Its author has prepared this updated version to 2023 especially for this issue of Aesthethica. The sequence, which goes from the invention of the wheel to generative AI, allows us to stop at the great milestones of technological scientific development and at the same time notice the degree of acceleration of the last decade. Several of the issues that make up the contemporary agenda in bioethics and that are present in this issue of the magazine can be recognized there. Some of them are crucial for the ethical-analytical reading that we propose, such as the validity of Boolean logic, the updating of the Turing Test or the future of AI and Chat GPT

Energy Efficient All-Electric-Field-Controlled Multiferroic Magnetic Domain-Wall Logic.

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.

Boolean logic in synthetic biology and biomaterials: Towards living materials in mammalian cell therapeutics.

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.

Amyloid-Gold Nanoparticle Hybrids for Biocompatible Memristive Devices.

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 Roff/Ron ratio (>107), 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.

Targeting of rainwater harvesting structures using geospatial tools and analytical hierarchy process (AHP) in the semi-arid region of Rajasthan (India).

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 km2 (13% of the total area) was very highly suited for the construction of RWH structures, while 114.56 km2 (19%) was highly suitable. A total of 43.77 km2 (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.

A logical way to reprogram plants.

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.

Advances in plant synthetic biology approaches to control expression of gene circuits.

The applications of synthetic biology range from creating simple circuits to monitor an organism's state to complex circuits capable of reconstructing aspects of life. The latter has the potential to be used in plant synthetic biology to address current societal issues by reforming agriculture and enhancing production of molecules of increased demand. For this reason, development of efficient tools to precisely control gene expression of circuits must be prioritized. In this review, we report the latest efforts towards characterization, standardization and assembly of genetic parts into higher-order constructs, as well as available types of inducible systems to modulate their transcription in plant systems. Subsequently, we discuss recent developments in the orthogonal control of gene expression, Boolean logic gates and synthetic genetic toggle-like switches. Finally, we conclude that by combining different means of controlling gene expression, we can create complex circuits capable of reshaping plant life.

Self-powered logically operated fluorescent detection of hepatitis B virus (HBV).

In this study, a novel sensing strategy based on double sensing/actuating pathway is demonstrated, being capable to trigger the DNA-based AND gate for the sensitive and selective detection of hepatitis B virus DNA (HBV-DNA). Such an approach encompasses an enzymatic machinery logically operated using the variation of physiologically relevant biomarkers for liver dysfunctions. Alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) are used as inputs of an AND gate generating an output signal, namely lactate. In particular, lactate is oxidized back to pyruvate at the anodic electrode by lactate oxidase connected in mediated electron transfer through ferrocene moieties (creating an amplifying recycling mechanism). The anodic electrode is further connected with a Myrothecium verrucaria bilirubin oxidase (MvBOx) based biocathode modified with SiO2 nanoparticles (SiO2NPs) functionalized with phenyl boronic acid and trigonelline, triggering the release of quenching DNA (qDNA) upon local pH change at the electrode surface (notably, modified SiONPs gets negatively recharged upon local pH gradient releasing negatively charged DNA). Next, the released qDNA labeled with BHQ2 and detecting DNA (dDNA, labeled with FAM) are detecting HBV-DNA. The proposed biosensor can discriminate between the absence and presence of HBV-DNA setting the threshold at 0.05 fM in model buffer solutions and 1 fM in human serum. This enzymatic/DNA logic network can be of particular interest for future biomedical applications (e.g., early detection of liver cancer disease etc.). In the future development this technology could be easily integrated with a smartphone camera, allowing more user-friendly applications.

Terbium-based metal-organic frameworks through energy transfer modulation for visual logical sensing zinc and fluorine ions.

Zinc is the second most abundant trace element in the human central nervous system, which is closely related to various physiological activities in the human body. Fluoride ion is one of the most harmful elements in drinking water. Excessive intake of F- may cause dental fluorosis, renal failure, or DNA damage. Therefore, it is urgent to develop sensors with high sensitivity and selectivity for the detection of Zn2+ and F- ions at the same time. In this work, a series of mixed lanthanide metal-organic frameworks (Ln-MOFs) probes are synthesized using a simple method of in situ doping. The luminous color can be finely modulated by changing the molar ratio of Tb3+ and Eu3+ during synthesis. Benefiting from the unique energy transfer modulation mechanism, the probe has the continuous detection capability of zinc ions and fluoride ions. The detection of Zn2+ and F- in a real environment shows that the probe has a good practical application prospect. The as-designed sensor at 262 nm excitation can sequentially detect Zn2+ concentrations ranging from 10-8 to 10-3 M (LOD = 4.2 nM) and F- levels ranging from 10-5 to 10-3 M (LOD = 3.6 µM) with high selectivity. Based on different output signals, a simple Boolean logic gate device is constructed to realize intelligent visualization of Zn2+ and F- monitoring.

Modular, Synthetic Boolean Logic Gates Enabled in Saccharomyces cerevisiae through T7 Polymerases/CRISPR dCas9 Designs.

Synthetic control of gene expression, whether simply promoter selection or higher-order Boolean-style logic, is an important tool for metabolic engineering and synthetic biology. This work develops a suite of orthogonal T7 RNA polymerase systems capable of exerting AND/OR switchlike control over transcription in the yeastSaccharomyces cerevisiae. When linked with CRISPR dCas9-based regulation systems, more complex circuitry is possible including AND/OR/NAND/NOR style control in response to combinations of extracellular copper and galactose. Additionally, we demonstrate that these T7 system designs are modular and can accommodate alternative stimuli sensing as demonstrated through blue light induction. These designs should greatly reduce the time and labor necessary for developing Boolean gene circuits in yeast with novel applications including metabolic pathway control in the future.