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PubMed2004

BioLogic gates enable logical transcription control in mammalian cells.

The architecture of gene regulatory networks is reminiscent of electronic circuits. Modular building blocks that respond in a logical way to one or several inputs are connected to perform a variety of complex tasks. Gene circuit engineers have pioneered the construction of artificial gene regulatory networks with the intention to pave the way for the construction of therapeutic gene circuits for next-generation gene therapy approaches. However, due to the lack of a critical amount of eukaryotic cell-compatible gene regulation systems, the field has so far been limited to prokaryotes. Recent development of several mammalian cell-compatible expression control systems laid the foundations for the assembly of transcription control modules that can respond to several inputs. Herein, three approaches to evoke combinatorial transcription control have been followed: (i) construction of artificial promoters with up to three operator sites for regulatory proteins, and (ii) parallel and (iii) serial linking of two gene regulation systems. We have combined tetracycline-, streptogramin-, macrolide-, and butyrolactone transcription control systems to engineer BioLogic gates of the NOT IF-, AND-, NOT IF IF-, NAND-, OR-, NOR-, and INVERTER-type in mammalian cells, which are able to respond to up to three different small molecule inputs. BioLogic gates enable logical transcriptional control in mammalian cells and, in combination with modern transduction technologies, could serve as versatile tools for regulated gene expression and as building blocks for complex artificial gene regulatory networks for applications in gene therapy, tissue engineering, and biotechnology.

Animals↗

PubMed1975

Use of logic-based flow patterns in the investigation and management of surgical disorders.

The principles used in the development of logic-based flow charts for use by computer have been applied to the decision-making processes encountered in surgical disorders. Such charts do not attempt to alter one's decisions, but rather present a more logical approach to a given problem, based on past experience. It has been shown that the use of flow charts may be of material benefit to the patient, as well as having other advantages.

Catheters, Indwelling↗

PubMed2006

Relative risk of a shuffled deck: a generalizable logical consistency criterion for sample selection in health state valuation studies.

In a health state valuation study, respondents may be asked to rank a deck of cards, with each card representing a particular health state. A logical inconsistency occurs when a more severe health state card is ranked higher than a less severe card. Occasional inconsistencies may be justified by errors in judgment or measurement. However, when respondents return shuffled decks, their responses must be removed from the sample; otherwise, valuation estimates will be biased toward the median. In this paper, we present a logical consistency criterion for sample selection in health state valuation studies. This statistical criterion is based on the relative risk of a shuffled deck and generalizable to all health state classification systems, subsets (or decks) of health states, and valuation techniques. We applied the criterion to secondary data collected from 4048 United States and 3395 United Kingdom respondents. In both studies, respondents evaluated 12-card decks of EQ-5D health states using time trade-off and visual analog scale techniques. Among the UK respondents, a small portion (approximately 5%) did not satisfy the criterion; their exclusion significantly changed the sample characteristics and the mean value estimates of the EQ-5D health states. Similar results were found among the US respondents.

Consumer Behavior↗

PubMed2002

(Physio)logical circuits: the intellectual origins of the McCulloch-Pitts neural networks.

This article examines the intellectual and institutional factors that contributed to the collaboration of neuropsychiatrist Warren McCulloch and mathematician Walter Pitts on the logic of neural networks, which culminated in their 1943 publication, "A Logical Calculus of the Ideas Immanent in Nervous Activity." Historians and scientists alike often refer to the McCulloch-Pitts paper as a landmark event in the history of cybernetics, and fundamental to the development of cognitive science and artificial intelligence. This article seeks to bring some historical context to the McCulloch-Pitts collaboration itself, namely, their intellectual and scientific orientations and backgrounds, the key concepts that contributed to their paper, and the institutional context in which their collaboration was made. Although they were almost a generation apart and had dissimilar scientific backgrounds, McCulloch and Pitts had similar intellectual concerns, simultaneously motivated by issues in philosophy, neurology, and mathematics. This article demonstrates how these issues converged and found resonance in their model of neural networks. By examining the intellectual backgrounds of McCulloch and Pitts as individuals, it will be shown that besides being an important event in the history of cybernetics proper, the McCulloch-Pitts collaboration was an important result of early twentieth-century efforts to apply mathematics to neurological phenomena.

Biology↗

PubMed1997

Establishement of the dorso-ventral pattern during embryonic development of drosophila melanogasater: a logical analysis

This report focuses on dorso-ventral patterning in the segmented region of the Drosophila melanogaster embryo. According to the concept of positional information, this pattern results from the different response of cells to the Dorsal-protein morphogen. This protein shows a distribution gradient along the dorso-ventral axis, with the highest concentration on the ventral side. Using the generalized logical formalism developed by R. Thomas and co-workers, the different cellular responses were analysed in terms of the intracellular loops between the regulatory genes. Two positive loops were found to be involved, each constituting a switch which can be acted upon by the Dorsal morphogen to determine the different cell types that make up the embryonic dorso-ventral pattern. The novelty in this use of generalized logical formalism is the employment of a multilevel variable to represent a morphogen gradient. The proposed model accounts for the essential qualitative effects of the Dorsal gradient in the dorso-ventral determination process. Three main conclusions may be drawn. Firstly, the gene twist needs to have two functional threshold concentrations, one for autoactivation and the other for activation of the gene snail. Secondly, the autoactivation threshold must be smaller than that which activates snail. Thirdly, the action of the gene snail on the maintenance function of the gene twist is crucial for cells to be able to choose between the mesoderm or neuroectoderm developmental pathways. Furthermore, it is predicted that if the gene snail shows autoregulation, this will not be crucial for the determination of the embryonic D-V pattern. Copyright 1997 Academic Press Limited Copyright 1997 Academic Press Limited

Journal Article↗

PubMed1980

Logical relations and comprehension in conversation.

This study examines how logical relations (e.g., causality and identity) in spoken discourse affect comprehension. Research on cohesion, which shows that specific unit template structures link discourse and text together, is used to build a model of language comprehension that places template structures at the base of a context comparison operation. Subjects were engaged in ordinary conversation with a confederate trained to produce specific types of logical utterances unobtrusively. The comprehension model predicted that systematically different latencies, topical response, and remedial response of subjects would follow the test items produced by the confederate. The data support the predictions. It is shown that comprehension occurs via one processing path if there is a direct tie between the target item and the immediately prior item in discourse, and a separate processing path if the tie is between the target item and the earlier context. Subject response in conversation is shown to display useful evidence on the nature of comprehension achieved. The findings specify and extend the recent research on the integration of new information into a textual structure.

Adult↗

PubMed1978

The logical analysis of the electroenterogram.

Simple--and inexpensive--logic circuitry is described which will discriminate three types of spike activity in the canine electroenterogram. Used during high-speed replay of tape-recorded myoelectric activity, it provides a numerical analysis of the duration and spike content of the three types of activity, without the need for sophisticated (and costly) computer analysis. The ability of the analyzer to detect types of activity is illustrated by the analysis of the effects of a peptide hormone infusion on the canine electroenterogram. The device might also serve as the prototype for other applications in which simple digital logic could be used to detect different patterns in continous analog signals.

Animals↗

PubMed2003

Logical checking function increases the accuracy of data entry in the patterns of care study.

BACKGROUND: For clinical studies, the use of a databases combined with a computer is becoming popular for data capturing. Commercially available database software has a logical checking function, which can restrict the type of data and their range. The study presented here quantitatively and prospectively evaluated the effectiveness for data management with this function using the database of Patterns of Care Study (PCS) in Japan. PATIENTS AND METHODS: The first external audit was performed from September 1998 to March 1999 using the PCS database without the function, and the second from April to September 1999 with the function. We analyzed the numbers and patterns of erroneous data for these two periods obtained with and without the function. RESULTS: In the database without the function, the number of incorrect data was 2,812 out of 596,186 (0.47%), while the corresponding number with the function was significantly reduced to 161 out of 533,656 (0.03%, p < 0.0001). CONCLUSIONS: The data accuracy was improved by using the computer database more extensively than the conventional case report form. By adding the logical checking function to the PCS database, significant improvement in the accuracy of data entry was accomplished. This indicates the potential for increasing the accuracy of data capturing with the aid of a computer.

Data Collection↗

PubMed2006

Representation of molecular structure using quantum topology with inductive logic programming in structure-activity relationships.

The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.

Mutagenesis, Site-Directed↗

PubMed1994

Writing Arden Syntax Medical Logic Modules.

The Arden Syntax for Medical Logic Modules is a language for encoding medical knowledge bases that consist of independent modules. The Arden Syntax has been used to generate clinical alerts, diagnostic interpretations, management messages, and screening for research studies and quality assurance. An Arden Syntax knowledge base consists of rules called Medical Logic Modules (MLMs), which are stored as simple ASCII files that can be written on any text editor. An MLM is made of slots grouped into three categories: maintenance information, library information, and the actual medical knowledge. Most MLMs are triggered by clinical events, evaluate medical criteria, and, if appropriate, perform an action such as sending a message to a health care provider. This paper provides a detailed tutorial on how to write MLMs.

Artificial Intelligence↗

PubMed1977

General-purpose timer from transistor logic to auxiliary equipment.

This paper describes a low-cost circuit for the control and timing of auxiliary experimental equipment by a variety of signals from 5 V, integrated-circuit logic. The circuit is designed for variable timing and switching up to 240 AC V at 3 A, with two independent timing parameters, delay and duration, in response to positive-going or to negative-going logic signal transitions.

Electronics, Medical↗

PubMed1994

DILEMMA: logic engineering in primary care, shared care and oncology (AIM Project A2005).

The aim of DILEMMA is to provide tools for the development of decision support systems for use in general medical practice, hospital-based cancer care, and shared care of cancer and cardiology patients. In primary care, the project intends to provide aids to clinical performance in prescribing, referral and the use of clinical guidelines. The demonstrator applications involve telematics and knowledge-based methodology, using an approach termed logic engineering which combines logic programming and software lifecycle methods. DILEMMA will demonstrate systems to assist shared care and home care which should help reduce pressure on secondary health resources and, by disseminating best practice knowledge, improve patient care and patient quality of life.

Artificial Intelligence↗

PubMed1992

Challenges to understanding spatial patterns of disease: philosophical alternatives to logical positivism.

Most studies of disease distribution, in medical geography and other related disciplines, have been empirical in nature and rooted in the assumptions of logical positivism. However, some of the more newly articulated philosophies of the social sciences, and of social theory, have much to add in the understanding of the processes and mechanisms underlying disease distribution. This paper represents a plea for creative synthesis between logical positivism and realism or structuration, and uses specific examples to suggest how disease distribution, as a surface phenomenon, can be explained using deeper analysis.

Cross-Cultural Comparison↗

PubMed2005

Molecular interaction map of the p53 and Mdm2 logic elements, which control the Off-On switch of p53 in response to DNA damage.

The molecular network that controls responses to genotoxic stress is centered at p53 and Mdm2. Recent findings have shown this network to be more complex than previously envisioned. Using a notation specifically designed for circuit diagram-like representations of bioregulatory networks, we have prepared an updated molecular interaction map of the immediate connections of p53 and Mdm2, which are described as logic elements of the network. We use the map as the basis for a comprehensive review of current concepts of signal processing by these logic elements (an interactive version of the maps-eMIMs can be examined at ). We also used molecular interaction maps to propose a p53 Off-On switch in response to DNA damage.

Apoptosis↗

PubMed2006

SideLink: automated side-chain assignment of biopolymers from NMR data by relative-hypothesis-prioritization-based simulated logic.

Previously we published the development of AutoLink, a program to assign the backbone resonances of macromolecules. The primary limitation of this program has proven to be its inability to directly recognize spectral data, relying on the user to define peak positions in its input. Here, we introduce a new program for the assignment of side-chain resonances. Like AutoLink, this new program, called SideLink, uses Relative Hypothesis Prioritization to emulate "human" logic. To address the higher complexity of side-chain assignment problems, the RHP algorithm has itself been advanced, making it capable of processing almost any combinatorial logic problem. Additionally, SideLink directly examines spectral data, overcoming the need and limitations of prior data interpretation by users.

Algorithms↗

PubMed2005

The evolution of the human mind and logic--mathematics structures.

The evolution of the human mind is discussed based on: (i) the fact that living beings interchange matter, energy and information with their environment, (ii) an ontological interpretation of the "reality" of the quantum world, of which logic-mathematics structures are considered constitutive parts, (iii) recent theories according to which living beings are considered as dynamic complex systems organized by information, and (iv) the fact that the evolution of living beings is guided by information about the environment and by intrinsic information on living systems (auto-organization). Assuming the evolution of vision as a model we observe that the driving forces that directed the evolution of the eyes, as dynamic complex systems, are the information about the environment supplied by sunlight and the intrinsic information-gaining mechanism of living organisms. Thus, there exists a convergence toward a visual system with the greatest ability to obtain light information, like the human eye, and also a divergence that leads to the development of specific qualities in some species. As in the case of vision the evolution of the human mind-brain cannot be a consequence of factors unrelated to the object of its own functioning. The human mind was structured for the acquisition from reality of the logic-mathematics structures that underlie the whole universe and consequently of an internal representation of the external world and of its own self. Thus, these structures are, together with the intrinsic capacity for auto-organization of the human brain, the predominant driving force of the human mind evolution. Both factors are complementary.

Biological Evolution↗

PubMed2005

The functional COMT polymorphism, Val 158 Met, is associated with logical memory and the personality trait intellect/imagination in a cohort of healthy 79 year olds.

A polymorphism (Val 158 Met) in the gene for catechol-O-methyl transferase (COMT) was previously associated with differences in cognitive ability and personality. Here we examine associations between this polymorphism and cognitive ability, cognitive aging, personality and mood in 460 relatively healthy people born in 1921. All had cognitive ability measured at age 11 in the Scottish Mental Survey of 1932, and again at age 79. COMT genotype was not associated with childhood IQ. At age 79, COMT genotype was significantly related to differences in verbal declarative memory (scores on the Logical Memory test; p=0.028) and to scores on the personality trait of intellect/imagination (p=0.023), adjusted for sex and childhood IQ. In both cases the Val/Met heterozygotes had higher scores than both homozygous groups. There were trends toward the heterozygotes having higher scores on the personality traits of agreeableness and conscientiousness. The effect of COMT genotype on Logical Memory scores was independent of the effect of APOE genotype, and similar in effect size. Therefore, COMT genotype may contribute to differences in normal cognitive aging and to differences in some of the major personality traits in old age.

Aged↗

PubMed2006

Biological pattern generation: the cellular and computational logic of networks in motion.

In 1900, Ramón y Cajal advanced the neuron doctrine, defining the neuron as the fundamental signaling unit of the nervous system. Over a century later, neurobiologists address the circuit doctrine: the logic of the core units of neuronal circuitry that control animal behavior. These are circuits that can be called into action for perceptual, conceptual, and motor tasks, and we now need to understand whether there are coherent and overriding principles that govern the design and function of these modules. The discovery of central motor programs has provided crucial insight into the logic of one prototypic set of neural circuits: those that generate motor patterns. In this review, I discuss the mode of operation of these pattern generator networks and consider the neural mechanisms through which they are selected and activated. In addition, I will outline the utility of computational models in analysis of the dynamic actions of these motor networks.

Animals↗