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PubMed1991

Application of metabolic-control logic to fuel utilization and its significance in tumor cells.

The importance and the value of applying metabolic-control logic to the question of fuels, their rates of utilization and their significance to the process of proliferation are presented. Application of the recently developed quantitative theory of metabolic control of branched pathways provides a hypothesis to account for the high rate of both glycolysis and glutaminolysis in lymphocytes, macrophages and, in particular, in tumor cells. Both glycolysis and glutaminolysis provide metabolic intermediates for biosynthetic pathways: for example, glucose-6-phosphate for the formation of ribose-5-phosphate, and glutamine, ammonia and aspartate which are required for the synthesis of purine and pyrimidine nucleotides. However, the rates of both glycolysis and glutaminolysis are greatly in excess (greater than 400-fold) of the requirements for the biosynthetic processes. If energy formation per se was the major reason for the high rate of glutamine utilization, why is the oxidation only partial? The ability of the cell to divide will require the synthesis of all the DNA, RNA, phospholipids, etc., at precise times in the cell cycle. Hence very high and accurate sensitivity of the processes that provide the precursors for these compounds to their specific regulators will be expected. Maintenance of high rates of glycolysis and glutaminolysis at all times can be seen therefore as a device to allow intermediates to be "tapped off" at the precise rate required whenever they are needed for biosynthesis. Maximal activities of some key enzymes of glycolysis, the tricarboxylic acid cycle and glutaminolysis from a variety of normal, neoplastic and suppressed cells are presented. The relative activities of hexokinase and 6-phosphofructokinase suggest that, particularly in neoplastic cells, in which the capacity for glucose transport is high, hexokinase could approach saturation in respect to intracellular glucose; consequently, hexokinase and phosphofructokinase could play an important role in the regulation of glycolytic flux in these cells. The activity of pyruvate kinase is considerably higher in tumorigenic cells than in nontumorigenic cells and higher in metastatic cells than in tumorigenic cells: for nontumorigenic cells the activities range from 28.4 to 574, for tumorigenic cells from 899 to 1280, and for metastatic cells from 1590 to 1627 nmol/min per mg of protein. The ratio of pyruvate kinase activity to 2 x phosphofructokinase activity is very high in neoplastic cells. The mean is 22.4 for neoplastic cells, whereas for muscle from 60 different animals it is only 3.8.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Division↗
PubMed1977

A logic circuit for identifying and reinforcing operant response durations.

A simple circuit useful for the study of response duration and timing response in operant behavior in rats was described. Important features of the circuit include: a logic function to identify respondings with the preregistered duration, elimination of the premature reinforcement by the feeder operation during lever-pressing behavior, reinforcement after the complete release of the lever, simple design and inexpensive construction. Experimental results with and without the present circuit were also given.

Animals↗
PubMed1992

A fuzzy logic controller.

This paper describes a fuzzy sets method which is very useful for handling uncertainties and essential for knowledge acquisition of a human expert. Kinetics of a reactor is often complex and not trivial to describe by mathematical equations. Reactor control by traditional control technology is therefore difficult. A novel technology is presented. In the following a fuzzy inference (approximate reasoning) is used for decision making in analogy to human thinking, facilitating a more sophisticated control. Readers of this paper do not need any advanced mathematics beyond the four basic operations in arithmetic (+, -, x, divided by) and using the maximum and minimum values. This fuzzy inference is introduced to construct a fuzzy logic controller which is suitable for a nonlinear, multivariable and time variant system applied to a bioreactor.

Biotechnology↗
PubMed1989

Querying medical databases in an environment offering logical data independence.

Medical information systems are becoming popular. Furthermore, their use is expected to be expanded in future. In order to easily extract information from the underlying databases, easy to use man-machine interfaces are required. This paper concerns the doctor interface of the ARPIA medical information system based on a relational database management system. The whole system is currently used inside the Outpatient Pediatric Clinic of the Catholic University of Rome, Italy. The interface provides logical data independence towards the underlying relational database. The paper contains some background about this kind of interfaces, and also, it sketches the software architecture of the implemented prototype.

Database Management Systems↗
PubMed1989

The logic of a controversy: the case of Agent Orange in Australia.

Since 1979 the Vietnam Veterans' Association of Australia (VVAA) has claimed that exposure to the herbicide Agent Orange in Vietnam has adversely affected the health of Vietnam veterans and their families. A campaign for government recognition of diseases and disabilities caused by herbicide exposure led in 1983 to the appointment of the Evatt Royal Commission which, after a 2-year inquiry, comprehensively rejected the VVAA's claim. The Evatt Commission's findings have not been accepted by the VVAA and the claim continues to be defended, albeit in a highly qualified form. This controversy exemplifies the way in which a claim can attract public support, and persist despite rejections by Committees of Inquiry. An understanding of the reasons for the persistence of controversy requires an understanding of the logic of rejecting causal claims, the psychology of everyday inductive reasoning, and the interaction between politics and science.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1991

The Risk Approach: unassailable logic?

The Risk Approach (RA) is a framework for selective provision of health care services advocated by the World Health Organization (WHO). Although the potential utility of RA is stressed in the WHO literature, the framework remains largely untested as a basis for resource deployment. Despite this, advocates claim the logic of RA is 'theoretically unassailable'. The purpose of this paper is to challenge this claim by critically examining some of the assumptions and proposed methods contained in the WHO literature concerning RA. Two areas of concern are discussed, relating to (i) prediction and the nature of relations between markers and outcomes, and (ii) marker measurement and scoring.

Calibration↗
PubMed1992

The cultural logic of Indian medicine: prognosis and etiology in Rajasthani popular therapeutics.

This paper considers certain ways of describing and treating sickness in rural Rajasthan, and the representations of sickness and of the body on which they are based. Two indigenous medical or 'ethnomedical' perspectives on illness and its treatment emerge from the analysis of ethnographic material collected during field research in northern India. In the first part of the paper various characterizations of South Asian medicine are discussed, and I suggest that Western preconceptions about the nature and purpose of 'medicine' itself has led one of these perspectives to be highlighted in anthropological considerations at the expense of the other. A further dimension of ethnomedicine emerges through discussions of local therapeutic rituals and discourses about sickness and the body. This consideration of one domain of local therapeutics reveals its underlying cultural logic and highlights ethnomedical formulations that have heretofore been analytically neglected. It does not address the formal or textually based Indian medical traditions to any extent. It is concerned with the cultural construction of sickness and medicine among Hindu lay people and folk healers and employs folkloric material that, though rarely considered in anthropological writings on South Asia, may be fruitful guide to the meanings which sickness has for those experiencing and treating it.

Culture↗
PubMed1985

The next logical step in the emergency radiographic evaluation of cervical spine trauma: the five-view trauma series.

The five-view standard series is considered the golden standard in the radiographic evaluation of the cervical spine. Although the three-view trauma series has proved significantly more accurate than the cross-table lateral view in the emergency evaluation of patients with cervical spine trauma, this series does not deal with questionable findings. The introduction of a five-view trauma series, with the inclusion of supine oblique views, is the next logical step in the emergency evaluation of these patients. An algorithm for the emergency radiographic evaluation of patients with suspected cervical spine trauma is proposed.

Cervical Vertebrae↗
PubMed1990

Logic of the Escherichia coli cell cycle.

The logic of Escherichia coli's responses to environmental changes gives hope that its cell cycle will be equally well designed. During growth in a constant environment, internal signals trigger cell-cycle events such as replication initiation and cell division. Internal signals must also provide the cell with information about its present state, enabling it to coordinate the synthesis of cytoplasm, DNA and cell wall and maintain proper cell shape and composition. How the cell regulates these aspects of its growth is a fascinating--and as yet unfinished--story.

Cell Cycle↗
PubMed2006

The logic of the Membrane, Magnesium, Mitosis (MMM) model for the regulation of animal cell proliferation.

The addition of animal serum or specific protein growth factors to quiescent, serum-deprived vertebrate cells in culture activates a wide variety of biochemical responses within minutes, which are followed in 5-10h by the initiation of DNA synthesis and then by mitosis. The quintessential early and continuing activation step for the increase in DNA synthesis is the increased initiation rate of protein synthesis, which must be continuously maintained throughout the G1 phase for advancement into S. The aggregate of biochemical reactions to growth factors is called the coordinate response, to indicate that many related and unrelated processes are orchestrated to repetitively reproduce cells. It is, however, crucial to recognize that the coordinate response can be induced for one or more rounds of replication by a variety of non-specific and quasi-specific membrane effectors. The logic of considering this framework of events in growth control implied that a single multi-target second messenger plays a central role in coordinating the events of the overall response. The same reasoning suggested that free Mg(2+) is the unifying regulatory element in that response which includes protein kinase pathways, and that the cytoplasmic activity of Mg(2+) increases with the binding of growth factors to their receptors in the cell membrane, or of less specific perturbations of the membrane. Experimental support of this conclusion is presented here and is represented in the MMM model of cell proliferation control.

Animals↗
PubMed2005

Logical networks inferred from highly specific discovery of transcriptionally regulated genes predict protein states in cultured gliomas.

Cultured glioma cells are motile and invasive. The phenotype of tumor cell motility is likely created by a complex system of molecular interactions because it requires the orchestration of molecular and physical events that modify the cytoskeleton, cell membrane, extracellular matrix, and signaling. Recent reports have described an algorithm for microarray data analysis that generates highly specific genome-scale discovery; these methods identify states of differential gene expression that are true to a high degree of certainty. Here, highly specific discovery of transcriptionally regulated genes combined with logical networks inferred from the functions of known genes predicts states of protein activation, which are validated in cultured glioma cells by independent laboratories. Highly specific discovery of transcriptionally regulated genes facilitates functional genomics of complex molecular systems.

Actins↗
PubMed2005

The scrambling theorem: a simple proof of the logical possibility of spectrum inversion.

The possibility of spectrum inversion has been debated since it was raised by and is still discussed because of its implications for functionalist theories of conscious experience (e.g., Palmer, 1999). This paper provides a mathematical formulation of the question of spectrum inversion and proves that such inversions, and indeed bijective scramblings of color in general, are logically possible. Symmetries in the structure of color space are, for purposes of the proof, irrelevant. The proof entails that conscious experiences are not identical with functional relations. It leaves open the empirical possibility that functional relations might, at least in part, be causally responsible for generating conscious experiences. Functionalists can propose causal accounts that meet the normal standards for scientific theories, including numerical precision and novel prediction; they cannot, however, claim that, because functional relationships and conscious experiences are identical, any attempt to construct such causal theories entails a category error.

Consciousness↗
PubMed2006

ERK2: a logical AND gate critical for drug-induced plasticity?

Drug addiction results in part from the distortion of dopamine-controlled plasticity, and extracellular signal-regulated kinase (ERK) plays an important role in the underlying molecular mechanisms of this process. ERK is activated by drugs of abuse in a subset of neurons in reward-related brain regions. This activation, necessary for the expression of immediate early genes, depends upon dopamine D1 and glutamate receptors. Blockade of ERK activation prevents long-lasting behavioral changes, including psychomotor sensitization and conditioned place preference. It also interferes with drug craving and drug-associated memory reconsolidation. By contrast, ERK1 mutation enhances the effects of morphine and cocaine. We suggest that the ERK2 pathway acts as a logical AND gate, permissive for plasticity, in neurons on which dopamine-mediated reward signals and glutamate-mediated contextual information converge.

Animals↗
PubMed2004

Bacterial chemosensing: cooperative molecular logic.

Bacterial chemotaxis is mediated by transmembrane receptors that bind attractant and repellent chemicals and control an intracellular protein kinase. Each cell contains thousands of receptor subunits that form a tightly packed array at one pole. Recent studies of bacterial behavior have begun to reveal the molecular logic of this sensory architecture.

Bacterial Physiological Phenomena↗
PubMedDate not supplied

Representing nursing assessments in clinical information systems using the logical observation identifiers, names, and codes database.

In recent years, the Logical Observation Identifiers, Names, and Codes (LOINC) Database has been expanded to include assessment items of relevance to nursing and in 2002 met the criteria for "recognition" by the American Nurses Association. Assessment measures in LOINC include those related to vital signs, obstetric measurements, clinical assessment scales, assessments from standardized nursing terminologies, and research instruments. In order for LOINC to be of greater use in implementing information systems that support nursing practice, additional content is needed. Moreover, those implementing systems for nursing practice must be aware of the manner in which LOINC codes for assessments can be appropriately linked with other aspects of the nursing process such as diagnoses and interventions. Such linkages are necessary to document nursing contributions to healthcare outcomes within the context of a multidisciplinary care environment and to facilitate building of nursing knowledge from clinical practice. The purposes of this paper are to provide an overview of the LOINC database, to describe examples of assessments of relevance to nursing contained in LOINC, and to illustrate linkages of LOINC assessments with other nursing concepts.

Computational Biology↗
PubMed2005

Modeling a description logic vocabulary for cancer research.

The National Cancer Institute has developed the NCI Thesaurus, a biomedical vocabulary for cancer research, covering terminology across a wide range of cancer research domains. A major design goal of the NCI Thesaurus is to facilitate translational research. We describe: the features of Ontylog, a description logic used to build NCI Thesaurus; our methodology for enhancing the terminology through collaboration between ontologists and domain experts, and for addressing certain real world challenges arising in modeling the Thesaurus; and finally, we describe the conversion of NCI Thesaurus from Ontylog into Web Ontology Language Lite. Ontylog has proven well suited for constructing big biomedical vocabularies. We have capitalized on the Ontylog constructs Kind and Role in the collaboration process described in this paper to facilitate communication between ontologists and domain experts. The artifacts and processes developed by NCI for collaboration may be useful in other biomedical terminology development efforts.

Animals↗
PubMedDate not supplied

The exploded hand syndrome: logical evaluation and comprehensive treatment of the severely crushed hand.

Severe compressive trauma to the hand presents with multiple soft-tissue and osseous manifestations that often appear unrelated, leading to underrecognition and potential undertreatment of the complex injuries. Approaching the crushed hand with a logical and systematic diagnostic plan allows surgeons to recognize the location and severity of the injury portfolio and direct comprehensive treatment. Both for emphasis and for the purpose of describing the hydraulic mechanism of tissue failure, the term exploded hand syndrome is proposed. The exploded hand connotes the compendium of clinical findings that include skin failure at the webspaces or glabrous border, atypical (usually longitudinal) fracture patterns of the tubular bones, and axial carpal dissociations. These are accompanied by extensive compromise of the interosseous musculature that is extruded or may exhibit evolving compartment syndrome. Understanding the trauma mechanism and patterns of injury in the exploded hand will maximize awareness and guide surgical reconstruction and rehabilitation.

Bone Nails↗
PubMed2005

Quantum logical operations for spin 3/2 quadrupolar nuclei monitored by quantum state tomography.

This article presents the realization of many self-reversible quantum logic gates using two-qubit quadrupolar spin 3/2 systems. Such operations are theoretically described using propagation matrices for the RF pulses that include the effect of the quadrupolar evolution during the pulses. Experimental demonstrations are performed using a generalized form of the recently developed method for quantum state tomography in spin 3/2 systems. By doing so, the possibility of controlling relative phases of superimposed pseudo-pure states is demonstrated. In addition, many aspects of the effect of the quadrupolar evolution, occurring during the RF pulses, on the quantum operations performance are discussed. Most of the procedures presented can be easily adapted to describe selective pulses of higher spin systems (>3/2) and for spin 1/2 under J couplings.

Journal Article↗