Showing papers by "University of California, San Diego published in 1992"

Determining embedding dimension for phase-space reconstruction using a geometrical construction

Abstract: We examine the issue of determining an acceptable minimum embedding dimension by looking at the behavior of near neighbors under changes in the embedding dimension from d\ensuremath{\rightarrow}d+1. When the number of nearest neighbors arising through projection is zero in dimension ${\mathit{d}}_{\mathit{E}}$, the attractor has been unfolded in this dimension. The precise determination of ${\mathit{d}}_{\mathit{E}}$ is clouded by ``noise,'' and we examine the manner in which noise changes the determination of ${\mathit{d}}_{\mathit{E}}$. Our criterion also indicates the error one makes by choosing an embedding dimension smaller than ${\mathit{d}}_{\mathit{E}}$. This knowledge may be useful in the practical analysis of observed time series.

Mortality over a Period of 10 Years in Patients with Peripheral Arterial Disease

Abstract: Background. Previous investigators have observed a doubling of the mortality rate among patients with intermittent claudication, and we have reported a fourfold increase in the overall mortality rate among subjects with large-vessel peripheral arterial disease, as diagnosed by noninvasive testing. In this study, we investigated the association of large-vessel peripheral arterial disease with rates of mortality from all cardiovascular diseases and from coronary heart disease. Methods. We examined 565 men and women (average age, 66 years) for the presence of large-vessel peripheral arterial disease by means of two noninvasive techniques — measurement of segmental blood pressure and determination of flow velocity by Doppler ultrasound. We identified 67 subjects with the disease (11.9 percent), whom we followed prospectively for 10 years. Results. Twenty-one of the 34 men (61.8 percent) and 11 of the 33 women (33.3 percent) with large-vessel peripheral arterial disease died during follow-up, as compa...

Theory of the backpropagation neural network

Abstract: Publisher Summary This chapter presents a survey of the elementary theory of the basic backpropagation neural network architecture, covering the areas of architectural design, performance measurement, function approximation capability, and learning. The survey includes a formulation of the backpropagation neural network architecture to make it a valid neural network and a proof that the backpropagation mean squared error function exists and is differentiable. Also included in the survey is a theorem showing that any L2 function can be implemented to any desired degree of accuracy with a three-layer backpropagation neural network. An appendix presents a speculative neurophysiological model illustrating the way in which the backpropagation neural network architecture might plausibly be implemented in the mammalian brain for corticocortical learning between nearby regions of cerebral cortex. One of the crucial decisions in the design of the backpropagation architecture is the selection of a sigmoidal activation function.

Boundary Integral and Singularity Methods for Linearized Viscous Flow

Abstract: 1. Preliminaries 2. Green's Functions and the Boundary Integral Equation 3. Green's Functions in domains bounded by a solid surface 4. Generalized boundary integral methods 5. Interfacial motion 6. Boundary integral methods based on the Stream Function 7. Discrete representation of a boundary 8. Numerical solution of the integral equations.

Efficient Tests for an Autoregressive Unit Root

Abstract: This paper derives the asymptotic power envelope for tests of a unit autoregressive root for various trend specifications and stationary Gaussian autoregressive disturbances. A family of tests is proposed, members of which are asymptotically similar under a general 1(1) null (allowing nonnormality and general dependence) and which achieve the Gaussian power envelope. One of these tests, which is asymptotically point optimal at a power of 50%, is found (numerically) to be approximately uniformly most powerful (UMP) in the case of a constant deterministic term, and approximately uniformly most powerful invariant (UMPI) in the case of a linear trend, although strictly no UMP or UMPI test exists. We also examine a modification, suggested by the expression for the power envelope, of the Dickey-Fuller (1979) t-statistic; this test is also found to be approximately UMP (constant deterministic term case) and UMPI (time trend case). The power improvement of both new tests is large: in the demeaned case, the Pitman efficiency of the proposed tests relative to the standard Dickey-Fuller t-test is 1.9 at a power of 50%. A Monte Carlo experiment indicates that both proposed tests, particularly the modified Dickey-Fuller t-test, exhibit good power and small size distortions in finite samples with dependent errors.

Automatic sleep/wake identification from wrist activity

Abstract: The purpose of this study was to develop and validate automatic scoring methods to distinguish sleep from wakefulness based on wrist activity. Forty-one subjects (18 normals and 23 with sleep or psychiatric disorders) wore a wrist actigraph during overnight polysomnography. In a randomly selected subsample of 20 subjects, candidate sleep/wake prediction algorithms were iteratively optimized against standard sleep/wake scores. The optimal algorithms obtained for various data collection epoch lengths were then prospectively tested on the remaining 21 subjects. The final algorithms correctly distinguished sleep from wakefulness approximately 88% of the time. Actigraphic sleep percentage and sleep latency estimates correlated 0.82 and 0.90, respectively, with corresponding parameters scored from the polysomnogram (p < 0.0001). Automatic scoring of wrist activity provides valuable information about sleep and wakefulness that could be useful in both clinical and research applications.

The Computational Brain

Abstract: From the Publisher: How do groups of neurons interact to enable the organism to see, decide, and move appropriately? What are the principles whereby networks of neurons represent and compute? These are the central questions probed by The Computational Brain. Churchland and Sejnowski address the foundational ideas of the emerging field of computational neuroscience, examine a diverse range of neural network models, and consider future directions of the field. The Computational Brain is the first unified and broadly accessible book to bring together computational concepts and behavioral data within a neurobiological framework. Computer models constrained by neurobiological data can help reveal how networks of neurons subserve perception and behavior--how their physical interactions can yield global results in perception and behavior, and how their physical properties are used to code information and compute solutions. The Computational Brain focuses mainly on three domains: visual perception, learning and memory, and sensorimotor integration. Examples of recent computer models in these domains are discussed in detail, highlighting strengths and weaknesses, and extracting principles applicable to other domains. Churchland and Sejnowski show how both abstract models and neurobiologically realistic models can have useful roles in computational neuroscience, and they predict the coevolution of models and experiments at many levels of organization, from the neuron to the system. The Computational Brain addresses a broad audience: neuroscientists, computer scientists, cognitive scientists, and philosophers. It is written for both the expert and novice. A basic overview of neuroscience and computational theory is provided, followed by a study of some of the most recent and sophisticated modeling work in the context of relevant neurobiological research. Technical terms are clearly explained in the text, and definitions are provided in an extensive glossary. The appendix contains a precis of

Computational methods in Lagrangian and Eulerian hydrocodes

Abstract: Explicit finite element and finite difference methods are used to solve a wide variety of transient problems in industry and academia. Unfortunately, explicit methods are rarely discussed in detail in finite element text books. This paper reviews the basic explicit finite element and finite difference methods that are currently used to solve transient, large deformation problems in solid mechanics. A special emphasis has been placed on documenting methods that have not been previously published in journals.

Characterization of three RXR genes that mediate the action of 9-cis retinoic acid.

Abstract: An understanding of the differences and similarities of the retinoid X receptor (RXR) and retinoic acid receptor (RAR) systems requires knowledge of the diversity of their family members, their patterns of expression, and their pharmacological response to ligands. In this paper we report the isolation of a family of mouse RXR genes encoding three distinct receptors (RXRa, p, and y). They are closely related to each other in their DNAand ligand-binding domains but are quite divergent from the RAR subfamily in both structure and ligand specificity. Recently, we demonstrated that all-trans retinoic acid (RA) serves as a "pro-hormone" to the isomer 9-cis RA, which is a high-affinity ligand for the human RXRa. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXRa, p, and y. Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA. Northern blot and in situ hybridization analyses define a broad spectrum of expression for the RXRs, which display unique patterns and only partially overlap themselves and the RARs. This study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology.

A Controlled Trial of Fluconazole to Prevent Fungal Infections in Patients Undergoing Bone Marrow Transplantation

Abstract: Background and Methods. Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a doubleblind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved. Results. By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P<0.001). Systemic fungal in...

Molecular characterization of the Arabidopsis floral homeotic gene APETALA1.

Abstract: The first step in flower development is the transition of an inflorescence meristem into a floral meristem. Each floral meristem differentiates into a flower consisting of four organ types that occupy precisely defined positions within four concentric whorls. Genetic studies in Arabidopsis thaliana and Antirrhinum majus have identified early-acting genes that determine the identify of the floral meristem, and late-acting genes that determine floral organ identity. In Arabidopsis, at least two genes, APETALA1 and LEAFY, are required for the transition of an influorescence meristem into a floral meristem. We have cloned the APETALA1 gene and here we show that it encodes a putative transcription factor that contains a MADS-domain. APETALA1 RNA is uniformly expressed in young flower primordia, and later becomes localized to sepals and petals. Our results suggest that APETALA1 acts locally to specify the identity of the floral meristem, and to determine sepal and petal development.

Gating and habituation of the startle reflex in schizophrenic patients.

Abstract: • Schizophrenic patients exhibit impairments in both sensorimotor gating and habituation in a number of paradigms. Through human and animal model research, these fundamental cognitive deficits have well-described neurobiologic bases and offer insights into the neuroanatomic and neurotransmitter abnormalities that characterize patients with schizophrenic spectrum disorders. In this context, the startle response is particularly interesting, because it is a crossspecies response to strong stimuli that is plastic or alterable using experimental and neurobiologic manipulations. Thirty-nine medicated schizophrenic patients and 37 normal control subjects were studied in a new electromyography based startle response paradigm in which both prepulse inhibition (an operational measure of sensorimotor gating) and habituation (the normal decrease in response magnitude to repeated stimuli over time) can be separated and assessed in one test session. The results indicate that schizophrenic patients have extensive deficits in both intramodal and cross-modal sensorimotor gating and a trend to show acoustic startle habituation deficits. The deficit in prepulse inhibition of startle amplitude exhibited by schizophrenic patients was evident when an acoustic prepulse stimulus preceded either an acoustic or a tactile startle stimulus. No deficit was observed in the prepulseinduced facilitation of startle latencies, indicating that the failure of gating was not due to a failure of stimulus detection. These findings suggest centrally mediated deficits in sensorimotor gating in schizophrenic patients.

Chemotherapy of Advanced Hodgkin's Disease with MOPP, ABVD, or MOPP Alternating with ABVD

Abstract: Background and Methods. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) has been the standard treatment for Hodgkin's disease for almost 20 years. In a randomized, multicenter trial, we compared three regimens of primary systemic therapy for newly diagnosed advanced Hodgkin's disease in Stages IIIA2, IIIB, and IVA or IVB: (1) MOPP alone given for 6 to 8 cycles, (2) MOPP alternating with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for 12 cycles, and (3) ABVD alone for 6 to 8 cycles. Patients in a first relapse after radiation therapy were eligible. No additional radiation therapy was given. Patients who did not have a complete response or who had a relapse with either MOPP alone or ABVD alone were switched to the opposite regimen. Results. Of 361 eligible patients, 123 received MOPP, 123 received MOPP alternating with ABVD, and 115 received ABVD alone. The patients were stratified according to age, stage, previous radiation, histologic features, and performance st...

Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke

Abstract: An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.

Ozone depletion: ultraviolet radiation and phytoplankton biology in antarctic waters.

Abstract: The springtime stratospheric ozone (O3) layer over the Antarctic is thinning by as much as 50 percent, resulting in increased midultraviolet (UVB) radiation reaching the surface of the Southern Ocean. There is concern that phytoplankton communities confined to near-surface waters of the marginal ice zone will be harmed by increased UVB irradiance penetrating the ocean surface, thereby altering the dynamics of Antarctic marine ecosystems. Results from a 6-week cruise (Icecolors) in the marginal ice zone of the Bellingshausen Sea in austral spring of 1990 indicated that as the O3 layer thinned: (i) sea surface- and depth-dependent ratios of UVB irradiance (280 to 320 nanometers) to total irradiance (280 to 700 nanometers) increased and (ii) UVB inhibition of photosynthesis increased. These and other Icecolors findings suggest that O3-dependent shifts of in-water spectral irradiances alter the balance of spectrally dependent phytoplankton processes, including photoinhibition, photoreactivation, photoprotection, and photosynthesis. A minimum 6 to 12 percent reduction in primary production associated with O3 depletion was estimated for the duration of the cruise.

Protein folding funnels: a kinetic approach to the sequence-structure relationship.

Abstract: A lattice model of protein folding is developed to distinguish between amino acid sequences that do and do not fold into unique conformations. Although Monte Carlo simulations provide insights into the long-time processes involved in protein folding, these simulations cannot systematically chart the conformational energy surface that enables folding. By assuming that protein folding occurs after chain collapse, a kinetic map of important pathways on this surface is constructed through the use of an analytical theory of probability flow. Convergent kinetic pathways, or "folding funnels," guide folding to a unique, stable, native conformation. Solution of the probability flow equations is facilitated by limiting treatment to diffusion between geometrically similar collapsed conformers. Similarity is measured in terms of a reconfigurational distance. Two specific amino acid sequences are deemed foldable and nonfoldable because one gives rise to a single, large folding funnel leading to a native conformation and the other has multiple pathways leading to several stable conformers. Monte Carlo simulations demonstrate that folding funnel calculations accurately predict the fact of and the pathways involved in folding-specific sequences. The existence of folding funnels for specific sequences suggests that geometrically related families of stable, collapsed conformers fulfill kinetic and thermodynamic requirements of protein folding.

Characterizing nonlinearities in business cycles using smooth transition autoregressive models

Abstract: During the past few years investigators have found evidence indicating that various time-series representing business cycles, such as production and unemployment, may be nonlinear. In this paper it is assumed that if the time-series is nonlinear, then it can be adequately described by a smooth transition autoregressive (STAR) model. The paper describes the application of these models to quarterly logarithmic production indices for 13 countries and ‘Europe’. Tests reject linearity for most of these series, and estimated STAR models indicate that the nonlinearity is needed mainly to describe the responses of production to large negative shocks such as oil price shocks.

Cytokines in symptomatic asthma airways.

Abstract: To determine whether cytokines are generated in vivo in subjects with asthma, we have measured cytokine levels (tumor necrosis factor [TNF], granulocyte-macrophage-colony-stimulating factor [GM-CSF], interleukin [IL]-1 alpha, IL-1 beta, IL-2, IL-4, and IL-6) in the airways of subjects with symptomatic (N = 24) and asymptomatic (N = 9) asthma with immunoassays (GM-CSF, IL-1 alpha, IL-1 beta, IL-2, and IL-4) or bioassays (TNF and IL-6) and the polymerase chain reaction (IL-1 beta and TNF). Significant levels of TNF (578 +/- 917 pg/ml versus 24 +/- 29 pg/ml) (p = 0.01), GM-CSF (24 +/- 41 pg/ml versus less than 8 pg/ml) (p = 0.02), and IL-6 (225 +/- 327 pg/ml versus 7 +/- 12 pg/ml) (p = 0.01), but not IL-1 alpha or IL-4, were detected in the bronchoalveolar lavage fluid (BALF) of patients with symptomatic compared with BALF of patients with asymptomatic asthma. Levels of IL-1 beta (266 +/- 270 pg/ml versus less than 20 pg/ml) (p = 0.001) and IL-2 (1.4 +/- 2.8 ng/ml versus less than 0.3 ng/ml) (p = 0.05) in BALF in patients with symptomatic compared with that in BALF levels in patients with asymptomatic asthma suggested activation of alveolar macrophages and T cells. Thus, in episodes of asthma, several cytokines, including TNF, GM-CSF, IL-1 beta, IL-2, and IL-6 are detectable in BALF.

Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition.

Abstract: Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) in the periphery is commonly accepted as the primary mechanism by which these agents produce a selective attenuation of pain (analgesia). NSAIDs are now shown to exert a direct spinal action by blocking the excessive sensitivity to pain (hyperalgesia) induced by the activation of spinal glutamate and substance P receptors. These findings demonstrate that the analgesic effects of NSAIDs can be dissociated from their anti-inflammatory actions. Spinal prostanoids are thus critical for the augmented processing of pain information at the spinal level.

The diagnosis of head injury requires a classification based on computed axial tomography.

Abstract: The introduction of structural imaging of the brain by computed tomography (CT) scans and magnetic resonance imaging (MRI) has further refined classification of head injury for prognostic, diagnosis, and treatment purposes. We describe a new classification scheme to be used both as a research and a clinical tool in association with other predictors of neurologic status.

Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat.

Abstract: Subcutaneous injection of formalin into the dorsal surface of the hindpaw evoked a two-phased flinching (phase 1:0-9 min; phase 2: 10-60 min) of the injected paw. Intrathecal administration of the nonsteroidal anti-inflammatory drugs (NSAID) produced minimal effects upon phase 1, but showed a significant, though submaximal, dose-dependent suppression of the phase 2 response. Ordering of i.t. potency was (ID50 in nmol): indomethacin (1.9) > or = flurbiprofen (2.1) > ketorolac (5.2) > or = zomepirac (5.9) > S(+)ibuprofen (16) > or = ibuprofen(racemic) (19) > acetylsalicylic acid (27) > acetaminophen (250) > R(-)ibuprofen (> 270) = 0. Intraperitoneal administration also produced a dose-dependent inhibition of phase 2, but only at doses which were 100 to 1000 times higher than those required to produce similar effects after i.t. injection. Intrathecal and i.p. dose-response curves showed similar distinct plateaus of maximum achievable inhibition (intrinsic activity) of the phase 2 behavior, ranging from 20 to 50% of the control response. Varying the time of drug injection reveals that injection 9 min after formalin yielded effects the same as those observed when the agent was given 2 min before formalin. Pretreatment at longer intervals indicated that the duration of the antinociceptive effect was between 3 to 6 hr after the i.t. injection. The i.t. injection of the highest doses of the several NSAID were without significant effect upon the 52.5 degrees C hot plate test. These studies indicate that NSAID have a powerful effect upon spinal nociceptive processing evoked by the s.c. injection of formalin.

Structural refinement of superlattices from x-ray diffraction.

Abstract: We present a general procedure for quantitative structural refinement of superlattice structures. To analyze a wide range of superlattices, we derived a general kinematical diffraction formula that includes random, continuous, and discrete fluctuations from the average structure. We show that only the structure factor of one single layer of each material has to be averaged over the random variables and prove that this relation is equivalent to earlier, less general models. Implementing a nonlinear-fitting algorithm to fit the entire x-ray-diffraction profile, refined parameters that describe the average superlattice structure and deviations from this average are obtained. We compare the results of structural refinement to results obtained independently from other measurements. The roughness introduced artificially during growth in Mo/Ni and Nb/Cu superlattices is accurately reproduced by the refinement. The lattice parameters of Ag/Mn obtained from this refinement procedure are in very good agreement with the values obtained from independent extended x-ray-absorption fine-structure and x-ray photoelectron diffraction studies. The relative thicknesses of the layers can be accurately determined, as proved for Cu/Ni in comparison with chemical analysis, for W/Ni compared to the calibrated sputtering rate, and for Mo/Ni compared to the low-angle profile.