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P/NP, and the quantum field computer.

The central problem in computer science is the conjecture that two complexity classes, P (polynomial time) and NP (nondeterministic polynomial time-roughly those decision problems for which a proposed solution can be checked in polynomial time), are distinct in the standard Turing model of computation: P not equal NP. As a generality, we propose that each physical theory supports computational models whose power is limited by the physical theory. It is well known that classical physics supports a multitude of implementation of the Turing machine. Non-Abelian topological quantum field theories exhibit the mathematical features necessary to support a model capable of solving all #P problems, a computationally intractable class, in polynomial time. Specifically, Witten [Witten, E. (1989) Commun. Math. Phys. 121, 351-391] has identified expectation values in a certain SU(2)-field theory with values of the Jones polynomial [Jones, V. (1985) Bull. Am. Math. Soc. 12, 103-111] that are #P-hard [Jaeger, F., Vertigen, D. & Welsh, D. (1990) Math. Proc. Comb. Philos. Soc. 108, 35-53]. This suggests that some physical system whose effective Lagrangian contains a non-Abelian topological term might be manipulated to serve as an analog computer capable of solving NP or even #P-hard problems in polynomial time. Defining such a system and addressing the accuracy issues inherent in preparation and measurement is a major unsolved problem.

Journal Article↗

Distributed model of collicular and cerebellar function during saccades.

How does the brain tell the eye where to go? Classical models of rapid eye movements are lumped control systems that compute analogs of physical signals such as desired eye displacement, instantaneous error, and motor drive. Components of these lumped models do not correspond well with anatomical and physiological data. We have developed a more brain-like, distributed model (called a neuromimetic model), in which the superior colliculus (SC) and cerebellum (CB) play novel roles, using information about the desired target and the movement context to generate saccades. It suggests that the SC is neither sensory nor motor; rather it encodes the desired sensory consequence of the saccade in retinotopic coordinates. It also suggests a non-computational scheme for motor control by the cerebellum, based on context learning and a novel spatial mechanism, the pilot map. The CB learns to use contextual information to initialize the pilot signal that will guide the saccade to its goal. The CB monitors feedback information to steer and stop the saccade, and thus replaces the classical notion of a displacement integrator. One consequence of this model is that no desired eye movement signal is encoded explicitly in the brain; rather it is distributed across activity in both the SC and CB. Another is that the transformation from spatially coded sensory information to temporally coded motor information is implicit in the velocity feedback loop around the CB. No explicit spatial-to-temporal transformation with a normalization step is needed.

Cerebellum↗

Triplet code-independent programming of living systems organisation by DNA: the link with intelligence and memory.

Previous suggestions from this laboratory (3), (a) that within its molecular electronic structure, DNA houses a computer-analog program of immense complexity, operating independently of, but complementary to, triplet coding and (b) that, inter alia, this program is the driving force for organising and executing the construction of species individuals in three dimensions, are extended in the present communication. It is now concluded that the DNA program also embodies an 'intelligence' component, which extends its organising ability both qualitatively and quantitatively beyond any of the heavily circumscribed 'self-organising' attributes claimed to be associated with naturally occurring inanimate systems. Further, that as part of the developmental process, a program component organises the fabrication of mammalian central nervous systems, including that of human beings with the associated attributes of intelligence, creativity and constructional skills. It is further suggested that the sophisticated random access memory system associated with human beings in particular may be explicable in terms of an extension of the DNA programming system: basically this involves the latter operating as computer-type 'hardware' for the storage of long-term memory and interacting with, primarily, glial cell RNA, acting as 'software' and storing short term traces. Finally, it is suggested that such an interrelationship between DNA/RNA molecular electronic structures can provide the necessary memory storage capacity and flexibility and also facilitates random access to the long-term DNA memory store.

Animals↗

Electrophysical factors influencing endoscopic sphincterotomy.

BACKGROUND: Analog computer techniques were used to measure electrosurgical power during sphincterotomy in experimental models and patients. METHODS: Total energy and transient changes in power were measured during sphincterotomy of bile ducts in the livers of pigs, ampullae of humans post mortem, and during clinical sphincterotomy. The effect of waveform on hemostasis was studied in experiments on canine mesenteric arteries. RESULTS: Electrosurgical waveforms (CUT, COAG, BLEND) were measured. Halving wire contact length halved energy needed to initiate cutting. The CUT waveform rarely initiated cutting at lower power settings than the BLEND waveform. With CUT, BLEND, and COAG waveforms, approximately the same energy initiated cutting. Efficiency of cutting increased linearly with power. The COAG waveform required higher power settings than BLEND or CUT to initiate cutting (p < 0.05). Force and wire diameter influenced cutting. BLEND was more effectively hemostatic than CUT (p < 0.05). COAG was significantly more hemostatic than BLEND and CUT. Cutting efficiency during clinical sphincterotomy was poor. CONCLUSIONS: This work has practical implications. Shortening wire contact length was effective in starting a cut at suboptimal settings, whereas changing from BLEND to CUT made little difference. Increasing power setting may help if cutting does not start. BLEND stops bleeding better than CUT. COAG stops bleeding better than BLEND but cuts poorly. Cutting during clinical sphincterotomy is inefficient and can be improved.

Analog-Digital Conversion↗

A comparison of intravenous and subarachnoid lidocaine pharmacokinetics in the rhesus monkey.

A comparative study between intravenous and subarachnoid lidocaine in the rhesus monkey was conducted in an effort to compare the kinetics of lidocaine in the monkey with reported intravenous human data, and to determine the rate and extent of systemic absorption of lidocaine following subarachnoid injection. Each animal received an intravenous and subarachnoid treatment in an effort to determine the fraction of drug absorbed. Pharmacokinetic parameters were calculated for each animal based on arterial blood concentrations of lidocaine. In the case of the intravenous data, a standard two-compartment model was used. Subarachnoid injections were evaluated by fitting data to an extravascular one-compartment model and by analog computer fitting of the blood level data to an extravascular two-compartment model. Data for both intravenous and subarachnoid injection were also analysed independent of compartment model. The intravascular parameters, alpha and beta, were in excellent agreement with those reported for man.

Anesthesia, Spinal↗

Acute phenytoin and primidone intoxication: a pharmacokinetic analysis.

Serial plasma levels of phenytoin, primidone, and phenobarbital were determined in a patient following massive overdose of phenytoin and primidone. The patient's neurologic status improved slowly over a period of 10 days and correlated best with the rise and fall of phenytoin plasma concentrations. The pharmacokinetics of all three agents were characterized by nonlinear regression analysis of their respective plasma concentration-time profiles during the elimination phase, followed by analog computer simulations of their entire plasma concentration-time profile closely resembled the observed values. Average values of Km and Vmax obtained from patients undergoing chronic therapy were used in the simulation and appear to adequately describe phenytoin elimination in this overdose situation. The elimination half-lives of primidone and phenobarbital of 6.2 and 83.5 hours, respectively, were within the "normal range" for patients on chronic therapy. Two distinct absorption phases for primidone and three for phenytoin were noted. The marked decrease in the estimated absorption rate constant between phases 1 and 2 for each drug may have been due to slow dissolution of a large congealed mass of phenytoin and primidone in the gut. The analysis of serial plasma samples following a massive overdose is recommended to provide a reliable data base for therapeutic decisions.

Adult↗

Molecules and cognition: the latterday lessons of levels, language, and lac. Evolutionary overview of brain structure and function in some vertebrates and invertebrates.

The characteristics of the nervous systems of a number of organisms in different phyla are examined at the recombinant DNA, protein, neuroanatomic, neurophysiological, and cognitive levels. Among the invertebrates, special attention is paid to the advantages as well as the shortcomings of the fly Drosophila melanogaster, the worm Caenorhabditis elegans, the honey bee Apis mellifera, the sea hare Aplysia californica, the octopus Octopus vulgaris, and the squid Loligo pealei. Among vertebrates, the focus is on Homo sapiens, the mouse Mus musculus, the rat Rattus norvegicus, the cat Felis catus, the macaque monkey Macaca fascicularis, the barn owl Tyto alba, and the zebrafish Brachydanio rerio. Vertebrate nervous systems have also been compared in fossil vs. extant organisms. I conclude that complex nervous systems arose in the Early Cambrian via a big bang that was underpinned by a modular method of construction involving massive pleiotropy of gene circuits. This rapidity of construction had enormous implications for the degrees of freedom that were subsequently available to evolving nervous systems. I also conclude that at the level of neuronal populations and interactions of neuropiles there is no model system between phyla except at the basic macromolecular level. Further, I argue that to achieve a significant understanding of the functions of extant nervous systems we need to concentrate on fewer organisms in greater depth and manipulate genomes via transgenic technologies to understand the behavioral outputs that are possible from an organism. Finally, I analyze the concepts of "perceptual categorization" and "information processing" and the difficulties involved in the extrapolation of computer analogies to sophisticated nervous systems.

Animals↗

The rates of saxitoxin action and of saxitoxin-tetrodotoxin interaction at the node of Ranvier.

Voltage clamp experiments were done on single nodes of Ranvier of Rana esculenta. Equilibrium effects were obtained from INa-V curves, the rates of action from changes in INa on changing solutions during repetitive depolarizing pulses. 2. Saxitoxin (STX) exclusively and reversibly blocked Na channels, the effect being fully described by a one-to-one reaction between STX and a receptor at the channel with an equilibrium dissociation constant, Ks, of 1.4 nM; the mean offset rate constant k2s, was 1.76 X 10(-2) sec-1 (16 +/- 1 degree C;pH 7.2), 1.7 times the value for tetrodotoxin (TTX). 3. At pH 5.6, K2S WAs increased by a factor of 1.33 while the equilibrium STX effects was decreased in a way suggesting competition between STX and protons. 4. After pretreatment of nodes with 3.1 nM TTX the extra block on adding 9.0 nM STX as well as its relief on taking out STX of the TTX-STX mixture revealed transients in the time course of receptor occupation. 5. These non-monotonic time courses are incompatible with the idea of two independent blocking sites (for STX and TTX) per channel but could be quantitatively fitted by analog-computed curves assuming competition between STX and TTX for the same site.

Animals↗

[Management of second stage of labour: observations, reflections, advices (author's transl)].

All vaginal deliveries of the Department of Obstetrics and Gynecology of the University Basel (N = 4081) during the year 74/73 and of the University Tübingen (N = 3249) 75/74 were analysed using an IBM-system 370/135 Only alive singletons beyond the 28th week of gestation were analysed. Clinical management was quite different in the two departments; the incidence of vaginal operations (Basal 11.2%, Tübingen 12.6%), however, as well as the distribution of pH-values and Apgar-scores after 1 min were quite similar. Basel: Acidotic risk (i.e. pHUA less than 7.200) 13.5%, severe acidotic risk (i.e. pHUA less than 7.100) 1.55%, low Apgar-scores (1--3) 0.7%. Tübingen: :12.3%, 2.11%, 1.6%. 3.5% of all parturients (Basel) had duration of second stage of labour with active maternal pressure support lasting more than 30 min. In two highly selected samples differing only with regard to the occurrence of cord-entanglements at birth (N1 = 1755, N2 = 1098) the association (rank correlation method according to Kendall) between the parameters of the fetal acid-base balance and the duration of second stage of labour as well as duration of the period with "active bearing down" was studied. Without cord encirclements pH in the umbilical artery fall --0.087 and in the umbilical vein --0.115 units and with cord complications the values amounted to --0.062 (UA) and --0.120 (UV) respectively pro 60 min duration of second stage with "bearing down efforts". Analogous computations for pCO2, pO2 and HbO2 are presented. Apgar-scores in these samples showed a very loose connection with the time variables. From these data the conclusion is drawn that the indication to perform vaginal operations for termination of delivery should not primarily be governed by the factor time but rather by the whole obstetrical situation i.e. the possible fetal risk of the intervention. This holds only if maternal welfare is established and fetal well being is monitored continuously.

Acidosis↗

[Serum proteins of growing Gunn rats. Quantitative analysis with agarose gel electrophoresis (author's transl)].

Microprocesses of quantitative agarose gel electrophoresis and biuret total protein evaluation were used for the quantitative estimation of the serum proteins of homozygous and heterozygous Gunn rats. For the analyses carried out in the course of hyperbilirubinemia, 6 microliter of serum were necessary in each case, of which 50-80 microgram were used for electrophoresis. The quantitative evaluation of the phoretogram curves plotted at two wavelengths was carried out with the aid of an analog computer. Eleven fractions were quantitatively covered by the process. Age-related concentration shifts were observed for a number of fractions, especially for albumin, transferrin, and IgG. The results obtained from a large number of animals in longitudinal and cross-sectional examination corroborate various reports found in the relevant literature.

Animals↗

Digital simulation of pulmonary microvascular exchange.

A previously published analog computer simulation of blood to lymph fluid and protein transport in the human lung [Microvascular Research 27, 51-70 (1984)] has been converted to a digital program. Comparisons have been made between the predictions of the two programs for both transient and steady state responses to perturbations. The advantages of each program are discussed. The FORTRAN simulation, including the input and output files are explained. Copies of the program will be made for anyone who wishes to use it.

Body Fluids↗