Showing papers by "University of California, Irvine published in 1987"

Slipped-strand mispairing: a major mechanism for DNA sequence evolution.

Abstract: Simple repetitive DNA sequences are a widespread and abundant feature of genomic DNA. The following several features characterize such sequences: (1) they typically consist of a variety of repeated motifs of 1-10 bases--but may include much larger repeats as well; (2) larger repeat units often include shorter ones within them; (3) long polypyrimidine and poly-CA tracts are often found; and (4) tandem arrangements of closely related motifs are often found. We propose that slipped-strand mispairing events, in concert with unequal crossing-over, can readily account for all of these features. The frequent occurrence of long tandem repeats of particular motifs (polypyrimidine and poly-CA tracts) appears to result from nonrandom patterns of nucleotide substitution. We argue that the intrahelical process of slipped-strand mispairing is much more likely to be the major factor in the initial expansion of short repeated motifs and that, after initial expansion, simple tandem repeats may be predisposed to further expansion by unequal crossing-over or other interhelical events because of their propensity to mispair. Evidence is presented that single-base repeats (the shortest possible motifs) are represented by longer runs in mammalian introns than would be expected on a random basis, supporting the idea that SSM may be a ubiquitous force in the evolution of the eukaryotic genome. Simple repetitive sequences may therefore represent a natural ground state of DNA unselected for coding functions.

Knowledge acquisition via incremental conceptual clustering

Abstract: Conceptual clustering is an important way of summarizing and explaining data. However, the recent formulation of this paradigm has allowed little exploration of conceptual clustering as a means of improving performance. Furthermore, previous work in conceptual clustering has not explicitly dealt with constraints imposed by real world environments. This article presents COBWEB, a conceptual clustering system that organizes data so as to maximize inference ability. Additionally, COBWEB is incremental and computationally economical, and thus can be flexibly applied in a variety of domains.

RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons.

Abstract: In initial attempts to define the molecular events responsible for the latent state of herpes simplex virus, in situ hybridization was utilized to search for virally encoded RNA transcripts in latently infected sensory neurons. The use of cloned probes representing the entire viral genome indicated that transcripts encoded within terminal repeats were present. When the alpha genes encoding ICP-0, ICP-4, and ICP-27 and the gamma 1 gene encoding VP-5 were employed, only RNA transcripts hybridizing to the ICP-0 probe were detected. In latently infected cells, the ICP-0--related transcripts were localized principally in the nucleus; this was not the case in acutely (productively) infected neurons or in neurons probed for RNA transcripts coding for actin. In Northern blotting experiments, an RNA of 2.6 kilobases was detected with the ICP-0 probe. When single-stranded DNAs from the ICP-0 region were used as probes, RNA from the strand complementary to that encoding ICP-0 messenger RNA (mRNA) was the major species detected. This RNA species may play a significant role in maintaining the latent infection.

Scientific Discovery: Computational Explorations of the Creative Processes

Abstract: Scientific discovery is often regarded as romantic and creative -- and hence unanalyzable -- whereas the everyday process of verifying discoveries is sober and more suited to analysis. Yet this fascinating exploration of how scientific work proceeds argues that however sudden the moment of discovery may seem, the discovery process can be described and modeled. Using the methods and concepts of contemporary information-processing psychology (or cognitive science) the authors develop a series of artificial-intelligence programs that can simulate the human thought processes used to discover scientific laws. The programs -- BACON, DALTON, GLAUBER, and STAHL -- are all largely data-driven, that is, when presented with series of chemical or physical measurements they search for uniformities and linking elements, generating and checking hypotheses and creating new concepts as they go along. Scientific Discovery examines the nature of scientific research and reviews the arguments for and against a normative theory of discovery; describes the evolution of the BACON programs, which discover quantitative empirical laws and invent new concepts; presents programs that discover laws in qualitative and quantitative data; and ties the results together, suggesting how a combined and extended program might find research problems, invent new instruments, and invent appropriate problem representations. Numerous prominent historical examples of discoveries from physics and chemistry are used as tests for the programs and anchor the discussion concretely in the history of science.

Artificial Intelligence and Tutoring Systems: Computational and Cognitive Approaches to the Communication of Knowledge

Abstract: From Marie Bienkowski's review : "Upon first encountering Etienne Wenger's book, "Artificial Intelligence and Tutoring Systems: Computational and Cognitive Approaches to the Communication of Knowledge," I assumed that it was the sort of book that would serve only as a reference. To find out about the EXCHECK tutoring system, I would just look it up in the exhaustive subject index. To see what tutoring work Beverly Woolf had done, I would look up her name in the author index. But, upon further examination, Wenger's book was revealed to be a good introductory text, first laying out basic issues in Chapters 1 and 2, then covering systems from SCHOLAR and SOPHIE to GUIDON and ACTP in Chapters 3 through 13. Each review chapter ends with a summary and an excellent set of bibliographic notes, further reinforcing the utility of the book as a reference and introduction to the field. In addition, it became clear that the book had another facet. As John Seely Brown and James Greeno point out in the introduction, "... this book is no mere catalog of programs and techniques... he has also laid out a provocative framework for analyzing and comparing intelligent tutoring systems." This framework is presented in Chapters 14 through 20. Thus, Wenger's book serves three purposes: it acts as a reference, it provides a comprehensive introduction to intelligent tutoring systems, and it develops a coherent framework for thinking about issues in any intelligent system that must communicate its knowledge." (http://dl.acm.org/citation.cfm?id=1059726)

Phylogenetic studies of coadaptation: preferred temperatures versus optimal performance temperatures of lizards.

Abstract: The view that behavior and physiological performance are tightly coadapted is a central principle of physiological ecology. Here, we test this principle using a comparative study of evolutionary patterns in thermal preferences and the thermal dependence of sprinting in some Australian skinks (Lygosominae). Thermal preferences (Tp ) differ strikingly among genera (range 24° to 35°C), but critical thermal maxima (CTMax) (range 38° to 45°C) and optimal temperatures for sprinting (To , 32° to 35°C) vary less. Diurnal genera have relatively high Tp , To , and CTMax. In contrast, nocturnal genera have low Tp but have moderate to high To and CTMax. Both nonphylogenetic and phylogenetic (minimum-evolution) approaches suggest that coadaptation is tight only for genera with high Tp . Phylogenetic analyses suggest that low Tp and, thus, partial coadaptation are evolutionarily derived, indicating that low thermal preferences can evolve, even if this results in reduced performance. In one instance, thermal preferences and the thermal dependence of sprinting may have evolved in opposite directions, a phenomenon we call "antagonistic coadaptation." We speculate on factors driving partial coadaptation and antagonistic coadaptation in these skinks.

Data compression

Abstract: This paper surveys a variety of data compression methods spanning almost 40 years of research, from the work of Shannon, Fano, and Huffman in the late 1940s to a technique developed in 1986. The aim of data compression is to reduce redundancy in stored or communicated data, thus increasing effective data density. Data compression has important application in the areas of file storage and distributed systems. Concepts from information theory as they relate to the goals and evaluation of data compression methods are discussed briefly. A framework for evaluation and comparison of methods is constructed and applied to the algorithms presented. Comparisons of both theoretical and empirical natures are reported, and possibilities for future research are suggested.

Comparing the Effectiveness of Software Testing Strategies

Abstract: This study applies an experimentation methodology to compare three state-of-the-practice software testing techniques: a) code reading by stepwise abstraction, b) functional testing using equivalence partitioning and boundary value analysis, and c) structural testing using 100 percent statement coverage criteria. The study compares the strategies in three aspects of software testing: fault detection effectiveness, fault detection cost, and classes of faults detected. Thirty-two professional programmers and 42 advanced students applied the three techniques to four unit-sized programs in a fractional factorial experimental design. The major results of this study are the following. 1) With the professional programmers, code reading detected more software faults and had a higher fault detection rate than did functional or structural testing, while functional testing detected more faults than did structural testing, but functional and structural testing were not different in fault detection rate. 2) In one advanced student subject group, code reading and functional testing were not different in faults found, but were both superior to structural testing, while in the other advanced student subject group there was no difference among the techniques. 3) With the advanced student subjects, the three techniques were not different in fault detection rate. 4) Number of faults observed, fault detection rate, and total effort in detection depended on the type of software tested. 5) Code reading detected more interface faults than did the other methods. 6) Functional testing detected more control faults than did the other methods.

Gap solitons and the nonlinear optical response of superlattices.

Abstract: We study theoretically the transmission of radiation through superlattices of finite length, where the dielectric constant of one film in each unit cell contains a term linear in the local field intensity. When such a system is illuminated with radiation with frequency in a stop gap, increasing power can switch it from a state with low transmissivity to a state with transmissivity of unity. Gap solitons play a key role in the phenomenon.

Strategy and Structure in the Multiproduct Firm

Abstract: This paper focuses on three strategies for realizing economic benefits from the multiproduct firm: vertical integration, related diversification, and unrelated diversification. The paper identifies economic benefits of the strategies and links them with the organizational control requirements necessary to realize these benefits. Organizational and environmental constraints that can inhibit the realization of these benefits also are considered.

Molecular orbital theory of the properties of inorganic and organometallic compounds 5. Extended basis sets for first‐row transition metals

Abstract: A series of efficient split-valence basis sets for first-row transition metals, termed 3-21G, has been constructed based on previously-formulated minimal expansions of Huzinaga, in which each atomic orbital has been represented by a sum of three gaussians. The original Huzinaga expansions for s- and p-type orbitals (except those for 1s) have been fit by least squares to new three-gaussian combinations in which the two sets of orbitals (of the same n quantum number) share gaussian exponents. The Huzinaga three-gaussian expansions for ls and 3d atomic orbitals have been employed without alteration. The valence description of the 3-21G basis sets comprises 3d-, 4s- and 4p-type functions, each of which has been split into two- and one-gaussian parts. 4p functions, while not populated in the ground state of the free atoms, are believed to be important to the description of the bonding in molecules. The performance of the 3-21G basis sets is examined with regard to the calculation of equilibrium geometries and normalmode vibrational frequencies for a variety of inorganic and organometallic compounds containing first-row transition metals. Calculated equilibrium structures, while generally superior to those obtained at STO-3G, are not as good as those for compounds containing main-group elements only. The calculations generally underestimate the lengths of double bonds between transition metals and main-group elements, and overestimate the lengths of single linkages. Calculated normal-mode vibrational frequencies for metal-containing systems are less uniform than in those for main-group compounds.

Introduction of a normal human chromosome 11 into a Wilms' tumor cell line controls its tumorigenic expression.

Abstract: The development of Wilms' tumor, a pediatric nephroblastoma, has been associated with a deletion in the p13 region of chromosome 11. The structure and function or functions of this deleted genetic material are unknown. The role of this deletion in the process of malignant transformation was investigated by introducing a normal human chromosome 11 into a Wilms' tumor cell line by means of the microcell transfer technique. These variant cells, derived by microcell hybridization, expressed similar transformed traits in culture as the parental cell line. Furthermore, expression of several proto-oncogenes by the parental cells was unaffected by the introduction of this chromosome. However, the ability of these cells to form tumors in nude mice was completely suppressed. Transfer of other chromosomes, namely X and 13, had no effect on the tumorigenicity of the Wilms' tumor cells. These studies provide support for the existence of genetic information on chromosome 11 which can control the malignant expression of Wilms' tumor cells.

Oryzalin, a dinitroaniline herbicide, binds to plant tubulin and inhibits microtubule polymerization in vitro

Abstract: The effects of oryzalin, a dinitroaniline herbicide, on chromosome behavior and on cellular microtubules (MTs) were examined by light microscopy and immunogold staining, respectively, in endosperm cells from Haemanthus katherinae Bak. Brief treatments with 1.0·10-8 M oryzalin reduced markedly the migration rate of anaphase chromosomes and 1.0·10-7 M oryzalin stopped migration abruptly. Oryzalin (1.0·10-7 M) depolymerized MTs and prevented the polymerization of new MTs at all stages of the mitotic cycle. The chromosome condensation cycle was unaffected by oryzalin. Endothelial cells from the heart of Xenopus leavis showed no chromosomal or microtubular rearrangements after oryzalin treatment. The inhibition by oryzalin of the polymerization of tubulin isolated from cultured cells of Rosa sp. cv. Paul's scarlet was examined in vitro by turbidimetry, electron microscopy and polymer sedimentation analysis. Oryzalin inhibited the rapid phase of taxol-induced polymerization of rose MTs at 24°C with an apparent inhibition constant (K i ) of 2.59·106 M. Shorter and fewer MTs were formed with increasing oryzalin concentrations, and maximum inhibition of taxol-induced polymerization occurred at approx. 1:1 molar ratios of oryzalin and tubulin. Oryzalin partially depolymerized taxol-stabilized rose MTs. Ligand-binding experiments with [14C]oryzalin demonstrated the formation of a tubulin-oryzalin complex that was time- and pH-dependent. The tubulin-oryzalin interaction (24°C, pH 7.1) had an apparent affinity constant (K app) of 1.19·105 M-1. Oryzalin did not inhibit taxol-induced polymerization of bovinebrain MTs and no appreciable binding of oryzalin to brain tubulin or other proteins was detected. The results demonstrate pharmacological differences between plant and animal tubulins and indicate that the most sensitive mode of action of the dinitroaniline herbicides is the direct poisoning of MT dynamics in cells of higher plants.

Evaluation of pulmonary artery pressure and resistance by pulsed Doppler echocardiography

Abstract: Pulsed Doppler echocardiography was used to examine the relation between pulmonary valve motion and pulmonary artery (PA) flow velocity patterns in 39 adults. In 16 patients with normal PA pressure (mean pressure less than 20 mm Hg), PA flow velocity accelerated slowly to a peak flow velocity at midsystole (time to peak flow velocity, or acceleration time = 134 +/- 20 ms [mean +/- standard deviation]), followed by a slow deceleration to the end of ejection, producing a "dome-like" appearance. In contrast, in 23 patients with elevated PA pressure (mean pressure 20 mm Hg or more), flow velocity accelerated rapidly to a peak flow velocity in early systole (acceleration time = 88 +/- 25 ms, p less than 0.01), followed by rapid flow velocity deceleration to a nadir in midsystole. In 13 of these patients, a transient increase in flow velocity occurred in late systole, producing a "spike and dome" appearance. In patients with an acceleration time of 120 ms or less, there was a negative linear correlation with mean PA pressure, expressed by the equation: mean PA pressure = 90 - (0.62 X acceleration time). The standard error of the estimate was 8.3 mm Hg. A similar negative linear correlation was found between PA acceleration time and total pulmonary resistance. Using a PA acceleration time of 100 ms or less resulted in a 78% sensitivity and a 100% specificity for detection of elevated PA pressure. Although this Doppler method cannot precisely estimate PA pressure, it can be helpful in separating patients with normal pressure from those with elevated PA pressure.

Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry

Abstract: The performance of three commercially available pulse oximeters was assessed in five anesthetized dogs in which increasing levels of methemoglobin were induced. Hemoglobin oxygen saturation in each dog was monitored with three pulse oximeters (Nellcor N-100, Ohmeda 3700, and Novametrix 500) and a mixed venous saturation pulmonary artery catheter (Oximetrix Opticath). Arterial and mixed venous blood specimens were analyzed for PaO2, PaCO2, and pHa using standard electrodes. An IL-282 Co-oximeter was used on the same specimens to determine oxyhemoglobin and methemoglobin as percentages of total hemoglobin. Methemoglobin levels of up to 60% were induced by intratracheal benzocaine. As MetHb gradually increased while the dogs were breathing 100% inspired oxygen, the pulse oximeter saturation (SpO2) overestimated the fractional oxygen saturation (SaO2) by an amount proportional to the concentration of methemoglobin until the latter reached approximately 35%. At this level the SpO2 values reached a plateau of 84-86% and did not decrease further. When, at fixed methemoglobin levels, additional hemoglobin desaturation was induced by reducing inspired oxygen fraction, SpO2 changed by much less than did SaO2 (regression slopes from 0.16 to 0.32). Thus, at high methemoglobin levels SpO2 tends to overestimate SaO2 by larger amounts at low hemoglobin saturations. Plots of SpO2 versus functional saturation (oxyhemoglobin/reduced hemoglobin plus oxyhemoglobin) show an improved but still poor relationship (regression slopes from 0.32 to 0.46). The Oximetrix Opticath pulmonary artery catheter behaves similarly but provides somewhat better agreement with functional saturation than do the pulse oximeters in the presence of methemoglobinemia. Pulse oximetry data (SpO2) should be used with caution in patients with methemoglobinemia.

Anderson localization for Bernoulli and other singular potentials

Abstract: We prove exponential localization in the Anderson model under very weak assumptions on the potential distribution. In one dimension we allow any measure which is not concentrated on a single point and possesses some finite moment. In particular this solves the longstanding problem of localization for Bernoulli potentials (i.e., potentials that take only two values). In dimensions greater than one we prove localization at high disorder for potentials with Holder continuous distributions and for bounded potentials whose distribution is a convex combination of a Holder continuous distribution with high disorder and an arbitrary distribution. These include potentials with singular distributions. We also show that for certain Bernoulli potentials in one dimension the integrated density of states has a nontrivial singular component.

Interpretation of Statistical Evidence in Criminal Trials : The Prosecutor’s Fallacy and the Defense Attorney’s Fallacy*

Abstract: In criminal cases where the evidence shows a match between the defendant and the perpetrator on some characteristic, the jury often receives statistical evidence on the incidence rate of the “matching” characteristic. Two experiments tested undergraduates' ability to use such evidence appropriately when judging the probable guilt of a criminal suspect based on written descriptions of evidence. Experiment 1 varied whether incidence rate statistics were presented as conditional probabilities or as percentages, and found the former promoted inferential errors favoring the prosecution while the latter produced more errors favoring the defense. Experiment 2 exposed subjects to two fallacious arguments on how to interpret the statistical evidence. The majority of subjects failed to detect the error in one or both of the arguments and made judgments consistent with fallacious reasoning. In both experiments a comparison of subjects' judgments to Bayesian norms revealed a general tendency to underutilize the statistical evidence. Theoretical and legal implications of these results are discussed.

Trophic Stimulation of Cultured Neurons from Neonatal Rat Brain by Epidermal Growth Factor

Abstract: Epidermal growth factor (EGF) is a potent polypeptide mitogen originally isolated from the adult male mouse submaxillary gland. It also acts as a gastrointestinal hormone. EGF-immunoreactive material has recently been identified within neuronal fibers and terminals in rodent brain. In the present study, EGF was found to enhance survival and process outgrowth of primary cultures of subneocortical telencephalic neurons of neonatal rat brain in a dose-dependent manner. This effect was observed with EGF concentrations as low as 100 picograms per milliliter (0.016 nanomolar) and was dependent on the continuous presence of EGF in the medium. Similar effects were observed with basic fibroblast growth factor, but several other growth-promoting substances, including other mitogens for glial elements, were without effect. Thus EGF, in addition to its mitogenic and hormonal activities, may act as a neurite elongation and maintenance factor for select neurons of the rodent central nervous system.

Terminal arbors of axons projecting to the somatosensory cortex of the adult rat. I. The normal morphology of specific thalamocortical afferents

Abstract: A characteristic feature of the rat somatosensory neocortex is a discrete topographic representation of the facial whiskers. Afferent fibers projecting to this vibrissae representation were "bulk-labeled" by injecting horseradish peroxidase into the white matter. Terminal arbors with the morphological characteristics of Lorente de No's (1949) "specific" thalamocortical afferents were then reconstructed through serial sections. These terminal arbors, characterized by the discrete organization of their dense plexus in layer IV, have a laminar distribution of boutons that parallels the laminar pattern of terminal degeneration resulting from lesions of the ventral posterior nucleus of the thalamus. The regional distribution of different-sized arbors corresponds to the distribution of vibrissae-related clusters of different sizes. Larger arbors were found in the posteromedial region corresponding to the mystacial vibrissae representation, while smaller arbors were found in the anterolateral region corresponding to the representation of the anterior sinus hairs. Terminal arbors were also reconstructed from sections stained simultaneously to demonstrate the pattern of vibrissae-related clusters. The greatest concentration of boutons on these axons occurred within a single vibrissae-related cluster. Furthermore, when 2 fibers terminated within a single cluster, their terminal arbors appeared to be largely coextensive. The morphology, size, and distribution of these terminal arbors support the hypothesis that the layer IV plexus of a single specific thalamocortical afferent tends to fill a vibrissae-related cluster. Thus, the organization of specific thalamocortical afferents may be responsible for clustered organization within the somatotopic map of the rodent neocortex.

Direct evidence for two-neutrino double-beta decay in 82Se.

Abstract: The two-neutrino mode of double-beta decay in $^{82}\mathrm{Se}$ has been observed in a time-projection chamber at a half-life of ${(1.1}_{\mathrm{\ensuremath{-}}0.3}^{+0.8}$)\ifmmode\times\else\texttimes\fi{}${10}^{20}$ yr (68% confidence level). This result from direct counting confirms the earlier geochemical measurements and helps provide a standard by which to test the double-beta-decay matrix elements of nuclear theory. It is the rarest natural decay process ever observed directly in the laboratory.

Time course of soleus muscle myosin expression during hindlimb suspension and recovery

Abstract: This study examined the time course of adult rodent soleus muscle myofibril and myosin isoform protein expression after 4, 8, 16, 28, and 56 days of hindlimb unweighting by tail suspension (S). The time course of soleus muscle recovery (R) was also examined after 28 days of hindlimb unweighting with an additional 4, 8, 16, and 28 days of unrestricted cage activity. During suspension, soleus muscle myofibril protein rapidly decreased from 34.3 +/- 3.1 (1.96SE) mg/pair in the control (C) group to 6.9 +/- 1.4 (1.96SE) mg/pair in S (t = 56 days). The calculated first-order degradation rate constant for this loss was kd = 0.17 days-1 [half time (t1/2) = 4.1 days]. The estimated slow myosin (SM) isoform content decreased from 13.4 +/- 2.0 (1.96SE) mg/pair in C to 2.1 +/- 0.2 (1.96SE) mg/pair in S (kd = 0.19 days-1, t1/2 = 3.6 days). The relative proportion of other myosin isoforms was increased at 28 and 56 days of suspension, reflecting an apparent de novo synthesis and the loss of SM. Recovery of contractile protein after 28 days of suspension was slower for both the myofibril protein and the SM isoform (kd = 0.07 days-1, t1/2 = 10 days). These data suggest that loss of weight bearing specifically affected the mechanisms of contractile protein expression reflected in soleus muscle protein degradation processes. In addition, the expression of the myosin isoforms were apparently differentially affected by the loss of weight-bearing activity.

GABAergic neurons and axon terminals in the brainstem auditory nuclei of the gerbil.

Abstract: The anatomical localization of glutamic acid decarboxylase (GAD), the synthesizing enzyme for GABA, was analyzed in the brainstem auditory nuclei of the adult gerbil. GAD-positive terminals and somata were present in the cochlear nucleus, superior olivary complex, lateral lemniscus, and inferior colliculus in varying concentrations and patterns. One of the highest densities of GAD-positive terminals is found in the superficial layers of the dorsal cochlear nucleus (DCN), whereas the ventral cochlear nucleus (VCN) has somewhat fewer terminals that are arranged in pericellular plexuses. GAD-positive neurons occur mainly in the superficial and fusiform layers of the DCN and are scattered throughout the VCN. Within the superior olivary complex, the highest concentration of immunoreactive terminals and neurons occurs in the ventral and lateral nuclei of the trapezoid body. In contrast, the medial nucleus of the trapezoid body and the medial superior olive contain fewer GAD-positive puncta and probably no immunoreactive somata. The lateral superior olive and superior periolivary nucleus contain a few immunoreactive puncta but a large number of immunoreactive somata. In the midbrain, the nuclei of the lateral lemniscus contain a moderate number of GAD-positive puncta and a large number of different types of GAD-positive neurons. The inferior colliculus also contains a heterogeneous population of labeled somata, most of which are multipolar neurons. In addition, a high concentration of immunoreactive puncta occurs in this region. These data demonstrate a diverse distribution of GAD-positive neurons and puncta throughout the brainstem auditory nuclei and suggest that GABA might be an important neurotransmitter in the processing of auditory information.