Deoxyribozyme-based three-input logic gates and construction of a molecular full adder

We have developed an array of seven deoxyribozyme-based molecular logic gates that behaves as a full adder in a single solution, with three oligonucleotides as inputs and two independent fluorogenic cleavage reactions as carry and sum outputs. The sum output consisted of four new deoxyribozyme-based logic gates: an ANDAND gate and three ANDNOTANDNOT gates. These gates required the design of a generic three-input deoxyribozyme-based logic gate that can use any three-way combination of activating or inactivating inputs. This generic gate design utilizes an additional inverting element that hybridizes to convert YES logic into NOT logic and vice versa. The system represents the first solution-phase, single test tube, enzymatic full adder and shows the complexity of control over molecular scale events that can be achieved with deoxyribozyme-based logic gates. Similar systems could be applied to control autonomous therapeutic and diagnostic devices.     

The Logic of Misplaced Concreteness: Paiela Body Counting and the Nature of the Primitive Mind

The paper has two goals: to demonstrate ethnographically the connection between "structure" and communication, which Lévi-Strauss has consistently alleged to exist, and to challenge the thesis of Hallpike's book , The Foundations of Primitive Thought, that primitive thought reflects an "incomplete," unsophisticated logic .
The paper focuses on the counting system of the Paiela, a highland Papua New Guinea group. It argues that Paiela counting behavior is best analyzed as an element in a complex communication process. The logic of Paiela counting behavior is then the logic of the encompassing process: a communicational logic founded on concepts such as information and pattern. According to some theorists, the relationship between this logic and the logic that informs Western science is metalogical and dualistic. Paiela thought is thus revealed to be based on a complete and sophisticated alternative logic, a science among sciences. [Papua New Guinea, counting behavior, communication]     

Multi/infinite dimensional neural networks, multi/infinite dimensional logic theory

A mathematical model of an arbitrary multi-dimensional neural network is developed and a convergence theorem for an arbitrary multi-dimensional neural network represented by a fully symmetric tensor is stated and proved. The input and output signal states of a multi-dimensional neural network/logic gate are related through an energy function, defined over the fully symmetric tensor (representing the connection structure of a multi-dimensional neural network). The inputs and outputs are related such that the minimum/maximum energy states correspond to the output states of the logic gate/neural network realizing a logic function. Similarly, a logic circuit consisting of the interconnection of logic gates, represented by a block symmetric tensor, is associated with a quadratic/higher degree energy function. Infinite dimensional logic theory is discussed through the utilization of infinite dimension/order tensors.     

Noise-Aided Logic in an Electronic Analog of Synthetic Genetic Networks

We report the experimental verification of noise-enhanced logic behaviour in an electronic analog of a synthetic genetic network, composed of two repressors and two constitutive promoters. We observe good agreement between circuit measurements and numerical prediction, with the circuit allowing for robust logic operations in an optimal window of noise. Namely, the input-output characteristics of a logic gate is reproduced faithfully under moderate noise, which is a manifestation of the phenomenon known as Logical Stochastic Resonance. The two dynamical variables in the system yield complementary logic behaviour simultaneously. The system is easily morphed from AND/NAND to OR/NOR logic.     

Enzyme logic gates for the digital analysis of physiological level upon injury

A biocomputing system composed of a combination of AND/IDENTITY logic gates based on the concerted operation of three enzymes: lactate oxidase, horseradish peroxidase and glucose dehydrogenase was designed to process biochemical information related to pathophysiological conditions originating from various injuries. Three biochemical markers: lactate, norepinephrine and glucose were applied as input signals to activate the enzyme logic system. Physiologically normal concentrations of the markers were selected as logic 0 values of the input signals, while their abnormally increased concentrations, indicative of various injury conditions were defined as logic 1 input. Biochemical processing of different patterns of the biomarkers resulted in the formation of norepi-quinone and NADH defined as the output signals. Optical and electrochemical means were used to follow the formation of the output signals for eight different combinations of three input signals. The enzymatically processed biochemical information presented in the form of a logic truth table allowed distinguishing the difference between normal physiological conditions, pathophysiological conditions corresponding to traumatic brain injury and hemorrhagic shock, and abnormal situations (not corresponding to injury). The developed system represents a biocomputing logic system applied for the analysis of biomedical conditions related to various injuries. We anticipate that such biochemical logic gates will facilitate decision-making in connection to an integrated therapeutic feedback-loop system and hence will revolutionize the monitoring and treatment of injured civilians and soldiers.     

数据噪音构建基因布尔网络模型的方法

在分析基因数据时,往往有噪音出现,因此借用基因表达谱数据中的噪音来建立卡诺图,可以得到布尔网络逻辑函数。而且利用此方法确定蛋白质与蛋白质之间的逻辑关系,建立蛋白质的逻辑网络。通过该方法可以寻找直系同源簇蛋白质数据的逻辑关系。     

Multiplexed sensing of mercury(II) and silver(I) ions: a new class of DNA electrochemiluminescent-molecular logic gates

Most of the DNA logic gates employ fluorescent or colorometric signals as their outputs, which were limited by the cumbersome handling procedures, lack of portability and lower sensitivity. To the best of our knowledge, the logic gates with electrochemiluminescent (ECL) signal as their outputs have not been reported. In response, we report here the construction of DNA molecular logic gates that produce ECL signals as their outputs, having the advantages of versatility, low background and simplified optical setup. The logic gates are based on the T-rich or C-rich oligonucleotides for the selective analysis of Hg(2+) and Ag(+) ions using energy or electron transfer-quenching path. Efficient and stable quenching of ECL of Ru bis(2,2'-bipyridine) (2,2'-bipyridine-4,4'-dicarboxylic acid) N-hydroxysuccinimide ester by oxidizing ferrocene at the Au electrode enabled us to use Hg(2+) and Ag(+) ions as inputs that activate logic gates, and to execute ECL of Ru(II) as readout signals for logic gate operations.     

Continuity and transformation of body logic

This article is concerned with two distinct corporeal logics. In the first, corporeality is founded on joints, tendons, and mobility; in the second, the envelope and its apertures are considered primordial. The first logic is extant in very few works. Although these texts (e.g. The Iliad, Beowulf) clearly share the same, very specific, conception of the body, they belong to different histories. The corporeal logic of the 'jointed body' (corps articulaire) cannot, therefore, be appraised in terms of longue durée. The texts represent, instead, a moment of transition between the psychodynamics of orality and literacy. A problem correlated to this fact is that readers (ancient and modern) no longer think using the same logic as that pertaining to the jointed body. They tend to translate information regarding the logic of the jointed body into data meaningful in their own logic.     

基因逻辑网络研究进展

海量生物数据的涌现,使得通过数据分析和理论方法探索生物机理成为理论生物学研究的重要途径．特别是对于基因的复杂的功能系统,建立基因网络这种理论方法的意义更为突出．Bowers在蛋白质相互作用的分析中引入了高阶逻辑关系,从而建立了系统发生谱数据的逻辑分析（LAPP）的系统方法．LAPP和通常建立模型的方法不同,它给出了一个从复杂网络的元素（或部件）的表达数据出发,通过逻辑分析,找到元素之间逻辑关联性的建模方法．这种方法能够从蛋白质表达谱数据出发,利用信息熵的算法发现两种蛋白质对一种蛋白质的联合作用,对于发现蛋白质之间新的作用机理有重要意义．由于涉及功能的基因组通常是一个大的群体构成的系统,因此LAPP方法也是一个生成复杂的基因逻辑网络的方法．基因逻辑网络的建立,方便实现通过逻辑调控进行基因调控的目的．这种方法可以应用在很多方面,如物种进化、肿瘤诊疗等等．系统阐述并分析了LAPP方法,并指出其在方法和应用方面的新进展以及评述．     

Reconfigurable Plasmonic Logic Gates

Reconfigurable one-, two-, and three-bit plasmonic logic gate configurations have been proposed, which work by covering a straight slot waveguide with materials with tunable dielectric constants, such as graphene. By encoding the logic states in the values of dielectric constants as opposed to different waveguides, the plasmon excitation problems are minimized and the simplified logic gate configurations could be easily implemented.

     

A Formal Representation of the WHO and UNICEF Estimates of National Immunization Coverage: A Computational Logic Approach

Production of official statistics frequently requires expert judgement to evaluate and reconcile data of unknown and varying quality from multiple and potentially conflicting sources. Moreover, exceptional events may be difficult to incorporate in modelled estimates. Computational logic provides a methodology and tools for incorporating analyst''s judgement, integrating multiple data sources and modelling methods, ensuring transparency and replicability, and making documentation computationally accessible. Representations using computational logic can be implemented in a variety of computer-based languages for automated production. Computational logic complements standard mathematical and statistical techniques and extends the flexibility of mathematical and statistical modelling. A basic overview of computational logic is presented and its application to official statistics is illustrated with the WHO & UNICEF estimates of national immunization coverage.     

Symbolic logic analysis of cause of dealth in humans: Application to 108 patients after coronary artery bypass graft surgery

Over the past two decades there has been increasing interest in the development of an objective, or formalized “medical logic”, and many authors have employed classical symbolic logic as a part of their approach. On the other hand, it has become clear that certain patterns of reasoning which are commonplace in evaluating patients clinicopathologically are awkward to handle in classical symbolic logic. The present paper proposes an extension of classical symbolic logic which addresses three problems in medical reasoning: (i) the problem of provisional diagnosis, (ii) the problem of inaccessible data, and (iii) the problem of the adequate discharge summary. It is proved mathematically that with a suitably constructed logic, the system “complains” until all questions involving threats to the patient's health are either answered or shown to be unanswerable because of inaccessibility of data. To illustrate this method, the cause of death was studied in 108 patients who had been autopsied at The Johns Hopkins Hospital after coronary artery bypass surgery. The analysis disclosed that 46% of patients suffered a fatal complication which could be attributed to events in the perioperative period; in 15% of patients the cause of death was unexplained by the analysis. Computerized symbolic logic analysis is a useful supplement to intuitive reasoning in assigning cause of death to patients with complex medical histories.     

Ring-Shaped Plasmonic Logic Gates

Ring-shaped one-, two-, and three-bit plasmonic logic gate configurations and circuits have been proposed, which, besides being compact, are also versatile and can be easily cascaded, the output logic values being controlled by both the geometry of the multi-port rings and the phase of the incident beams. This latter degree of freedom, not fully exploited up to now in plasmonic circuits, offers a high degree of flexibility of logic gate configurations.

     

Implementing conventional logic unconventionally: photochromic molecular populations as registers and logic gates

In this paper we detail experimental methods to implement registers, logic gates and logic circuits using populations of photochromic molecules exposed to sequences of light pulses. Photochromic molecules are molecules with two or more stable states that can be switched reversibly between states by illuminating with appropriate wavelengths of radiation. Registers are implemented by using the concentration of molecules in each state in a given sample to represent an integer value. The register's value can then be read using the intensity of a fluorescence signal from the sample. Logic gates have been implemented using a register with inputs in the form of light pulses to implement 1-input/1-output and 2-input/1-output logic gates. A proof of concept logic circuit is also demonstrated; coupled with the software workflow describe the transition from a circuit design to the corresponding sequence of light pulses.     

A Formalized Design Process for Bacterial Consortia That Perform Logic Computing

The concept of microbial consortia is of great attractiveness in synthetic biology. Despite of all its benefits, however, there are still problems remaining for large-scaled multicellular gene circuits, for example, how to reliably design and distribute the circuits in microbial consortia with limited number of well-behaved genetic modules and wiring quorum-sensing molecules. To manage such problem, here we propose a formalized design process: (i) determine the basic logic units (AND, OR and NOT gates) based on mathematical and biological considerations; (ii) establish rules to search and distribute simplest logic design; (iii) assemble assigned basic logic units in each logic operating cell; and (iv) fine-tune the circuiting interface between logic operators. We in silico analyzed gene circuits with inputs ranging from two to four, comparing our method with the pre-existing ones. Results showed that this formalized design process is more feasible concerning numbers of cells required. Furthermore, as a proof of principle, an Escherichia coli consortium that performs XOR function, a typical complex computing operation, was designed. The construction and characterization of logic operators is independent of “wiring” and provides predictive information for fine-tuning. This formalized design process provides guidance for the design of microbial consortia that perform distributed biological computation.     

Fuzzy logic feedback control for fed-batch enzymatic hydrolysis of lignocellulosic biomass

A fuzzy logic feedback control system was developed for process monitoring and feeding control in fed-batch enzymatic hydrolysis of a lignocellulosic biomass, dilute acid-pretreated corn stover. Digested glucose from hydrolysis reaction was assigned as input while doser feeding time and speed of pretreated biomass were responses from fuzzy logic control system. Membership functions for these three variables and rule-base were created based on batch hydrolysis data. The system response was first tested in LabVIEW environment then the performance was evaluated through real-time hydrolysis reaction. The feeding operations were determined timely by fuzzy logic control system and efficient responses were shown to plateau phases during hydrolysis. Feeding of proper amount of cellulose and maintaining solids content was well balanced. Fuzzy logic proved to be a robust and effective online feeding control tool for fed-batch enzymatic hydrolysis.     

From complexation to computation: Recent progress in molecular logic

The new thrusts in molecular logic are gathered together in this short review, while paying attention to the seeds from which these developments have arisen. The original demonstration of a few basic logic operations has now been extended to cover many of the one- and two-input varieties and even some of the three-input types. Many kinds of inputs and outputs have emerged, including various chemical species and some physical properties. The latter can include heat, light and, arguably, polarity. Reconfigurable logic has grown up to include a range of examples. Even superposable logic has proved possible with molecular systems. Numerical processors have flowered in recent years with several diverse approaches being revealed in recent years. Photochemical concepts such as photoinduced electron transfer (PET), internal charge transfer (ICT) and electronic energy transfer (EET) can be discerned among the designs in the field.     

Fluorescence for biological logic gates

Biological logic gates are smart probes able to respond to biological conditions in behaviors similar to computer logic gates, and they pose a promising challenge for modern medicine. Researchers are creating many kinds of smart nanostructures that can respond to various biological parameters such as pH, ion presence, and enzyme activity. Each of these conditions alone might be interesting in a biological sense, but their interactions are what define specific disease conditions. Researchers over the past few decades have developed a plethora of stimuli‐responsive nanodevices, from activatable fluorescent probes to DNA origami nanomachines, many explicitly defining logic operations. Whereas many smart configurations have been explored, in this review we focus on logic operations actuated through fluorescent signals. We discuss the applicability of fluorescence as a means of logic gate implementation, and consider the use of both fluorescence intensity as well as fluorescence lifetime.     

Ultrasensitive DNA detection by cycle isothermal amplification based on nicking endonuclease and its application to logic gates

In recent years, an intense interest has grown in the DNA logic gates having high potential for computation at literally the “nano-size” level. A limitation of traditional DNA logic gates is that each target strand hybridizes with only a single copy of the probe. This 1:1 hybridization radio limits the gain of the approach and thus its sensitivity. The exponential amplification of nucleic acids has become a core technology in medical diagnostics and has been widely used for the construction of DNA sensor, DNA nanomachine and DNA sequencing. It would be of great interest to develop DNA-based logic systems with exponential amplification for the output signal. In the present study, a series of three-input DNA logic gates with the cycle isothermal amplification based on nicking endonuclease (NEase) are designed. Very low concentrations of the analytes were sufficient to initiate an autocatalytic cascade, achieving a significant improvement of the detection limit, 100-fold improvement compared to the non-autocatalytic system. This was achieved by engineering a simple and flexible biological circuit designed to initiate a cascade of events to detect and amplify a specific DNA sequence. This procedure has the potential to greatly simplify the logic operation because amplification can be performed in “one-pot”.