Showing papers by "Northwestern University published in 2000"

The large-scale organization of metabolic networks

Abstract: In a cell or microorganism, the processes that generate mass, energy, information transfer and cell-fate specification are seamlessly integrated through a complex network of cellular constituents and reactions. However, despite the key role of these networks in sustaining cellular functions, their large-scale structure is essentially unknown. Here we present a systematic comparative mathematical analysis of the metabolic networks of 43 organisms representing all three domains of life. We show that, despite significant variation in their individual constituents and pathways, these metabolic networks have the same topological scaling properties and show striking similarities to the inherent organization of complex non-biological systems. This may indicate that metabolic organization is not only identical for all living organisms, but also complies with the design principles of robust and error-tolerant scale-free networks, and may represent a common blueprint for the large-scale organization of interactions among all cellular constituents.

Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis

Abstract: Background Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. Methods We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). Results Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed ga...

The Psychology of Survey Response

Abstract: 1. Introduction 2. Respondents' understanding of survey questions 3. The role of memory in survey responding 4. Answering questions about date and durations 5. Attitude questions 6. Factual judgments and numerical estimates 7. Attitude judgments and context effects 8. Mapping and formatting 9. Survey reporting of sensitive topics 10. Mode of data collection 11. Impact of the application of cognitive models to survey measurement.

The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction.

Abstract: Background Recent studies indicate that magnetic resonance imaging (MRI) after the administration of contrast material can be used to distinguish between reversible and irreversible myocardial ischemic injury regardless of the extent of wall motion or the age of the infarct. We hypothesized that the results of contrast-enhanced MRI can be used to predict whether regions of abnormal ventricular contraction will improve after revascularization in patients with coronary artery disease. Methods Gadolinium-enhanced MRI was performed in 50 patients with ventricular dysfunction before they underwent surgical or percutaneous revascularization. The transmural extent of hyperenhanced regions was postulated to represent the transmural extent of nonviable myocardium. The extent of regional contractility at the same locations was determined by cine MRI before and after revascularization in 41 patients. Results Contrast-enhanced MRI showed hyperenhancement of myocardial tissue in 40 of 50 patients before revascularizat...

Selection on Observed and Unobserved Variables: Assessing the Effectiveness of Catholic Schools

Abstract: We develop estimation methods that use the amount of selection on the observables in a model as a guide to the amount of selection on the unobservables. We show that if the observed variables are a random subset of a large number of factors that influence the endogenous variable and the outcome of interest, then the relationship between the index of observables that determines the endogenous variable and the index that determines the outcome will be the same as the relationship between the indices of unobservables that determine the two variables. In some circumstances this fact may be used to identify the effect of the endogenous variable. We also propose an informal way to assess selectivity bias based on measuring the ratio of selection on unobservables to selection on observables that would be required if one is to attribute the entire effect of the endogenous variable to selection bias. We use our methods to estimate the effect of attending a Catholic high school on a variety of outcomes. Our main conclusion is that Catholic high schools substantially increase the probability of graduating from high school and, more tentatively, college attendance. We do not find much evidence for an effect on test scores.

Scanometric DNA Array Detection with Nanoparticle Probes

Abstract: A method for analyzing combinatorial DNA arrays using oligonucleotide-modified gold nanoparticle probes and a conventional flatbed scanner is described here. Labeling oligonucleotide targets with nanoparticle rather than fluorophore probes substantially alters the melting profiles of the targets from an array substrate. This difference permits the discrimination of an oligonucleotide sequence from targets with single nucleotide mismatches with a selectivity that is over three times that observed for fluorophore-labeled targets. In addition, when coupled with a signal amplification method based on nanoparticle-promoted reduction of silver(I), the sensitivity of this scanometric array detection system exceeds that of the analogous fluorophore system by two orders of magnitude.

Mechanisms Linking Work and Family: Clarifying the Relationship Between Work and Family Constructs

Abstract: Work-family research emphasizes the importance of mechanisms that link work and family. However, these mechanisms typically are described in metaphoric terms poorly suited to rigorous research. In this article we translate work-family linking mechanisms into causal relationships between work and family constructs. For each relationship we explain its sign and causal structure and how it is influenced by personal intent. We show how these respecified linking mechanisms constitute theoretical building blocks for developing comprehensive models of the work-family interface.

Molecular electronic-structure theory

Abstract: Second Quantization Spin in Second Quantization Orbital Rotations Exact and Approximate Wave Functions The Standard Models Atomic Basis Functions Short-Range Interactions and Orbital Expansions Gaussian Basis Sets Molecular Integral Evaluation Hartree-Fock Theory Configuration-Interaction Theory Multiconfigurational Self-Consistent Field Theory Coupled-Cluster Theory Perturbation Theory Calibration of the Electronic-Structure Models List of Acronyms Index

Quantifying the Bullwhip Effect in a Simple Supply Chain: The Impact of Forecasting, Lead Times, and Information

Abstract: An important observation in supply chain management, known as the bullwhip effect, suggests that demand variability increases as one moves up a supply chain. In this paper we quantify this effect for simple, two-stage supply chains consisting of a single retailer and a single manufacturer. Our model includes two of the factors commonly assumed to cause the bullwhip effect: demand forecasting and order lead times. We extend these results to multiple-stage supply chains with and without centralized customer demand information and demonstrate that the bullwhip effect can be reduced, but not completely eliminated, by centralizing demand information.

Cocatalysts for Metal-Catalyzed Olefin Polymerization: Activators, Activation Processes, and Structure−Activity Relationships

Abstract: One of the most exciting developments in the areas of catalysis, organometallic chemistry, and polymer science in recent years has been the intense exploration and commercialization of new polymerization technologies based on single-site and metallocene coordination olefin polymerization catalysts.1 The vast number of specifically designed/synthesized transition metal complexes (catalyst precursors) and main-group organometallic compounds (cocatalysts) allows unprecedented control over polymer microstructure, the generation of new polymer architectures, and the development of new polymerization reactions. Commercialization of new generations of single-site and metallocene catalyst-based technologies has provided the multibillion pound per year polyolefins industry with the ability to deliver a wide range of new and innovative olefin-based polymers having improved properties.2-4 The intense industrial activity in the field and the challenges to our basic understanding that have come to light have in turn 1391 Chem. Rev. 2000, 100, 1391−1434

Economic Analysis of Social Interactions

Abstract: Economics is broadening its scope from analysis of markets to study of general social interactions. Developments in game theory, the economics of the family, and endogenous growth theory have led the way. Economists have also performed new empirical research using observational data on social interactions, but with much less to show. The fundamental problem is that observable outcomes may be generated by many different interaction processes, so empirical findings are open to a wide variety of interpretations. To make sustained progress, empirical research will need richer data, including experiments in controlled environments and subjective data on preferences and expectations.

A trust region method based on interior point techniques for nonlinear programming

Abstract: An algorithm for minimizing a nonlinear function subject to nonlinear inequality constraints is described. It applies sequential quadratic programming techniques to a sequence of barrier problems, and uses trust regions to ensure the robustness of the iteration and to allow the direct use of second order derivatives. This framework permits primal and primal-dual steps, but the paper focuses on the primal version of the new algorithm. An analysis of the convergence properties of this method is presented.

Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms

Abstract: The bacterium Pseudomonas aeruginosa permanently colonizes cystic fibrosis lungs despite aggressive antibiotic treatment. This suggests that P. aeruginosa might exist as biofilms--structured communities of bacteria encased in a self-produced polymeric matrix--in the cystic fibrosis lung. Consistent with this hypothesis, microscopy of cystic fibrosis sputum shows that P. aeruginosa are in biofilm-like structures. P. aeruginosa uses extracellular quorum-sensing signals (extracellular chemical signals that cue cell-density-dependent gene expression) to coordinate biofilm formation. Here we found that cystic fibrosis sputum produces the two principal P. aeruginosa quorum-sensing signals; however, the relative abundance of these signals was opposite to that of the standard P. aeruginosa strain PAO1 in laboratory broth culture. When P. aeruginosa sputum isolates were grown in broth, some showed quorum-sensing signal ratios like those of the laboratory strain. When we grew these isolates and PAO1 in a laboratory biofilm model, the signal ratios were like those in cystic fibrosis sputum. Our data support the hypothesis that P. aeruginosa are in a biofilm in cystic fibrosis sputum. Moreover, quorum-sensing signal profiling of specific P. aeruginosa strains may serve as a biomarker in screens to identify agents that interfere with biofilm development.

Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.

Abstract: The cellular-stress response can mediate cellular protection through expression of heat-shock protein (Hsp) 70, which can interfere with the process of apoptotic cell death. Stress-induced apoptosis proceeds through a defined biochemical process that involves cytochrome c, Apaf-1 and caspase proteases. Here we show, using a cell-free system, that Hsp70 prevents cytochrome c/dATP-mediated caspase activation, but allows the formation of Apaf-1 oligomers. Hsp70 binds to Apaf-1 but not to procaspase-9, and prevents recruitment of caspases to the apoptosome complex. Hsp70 therefore suppresses apoptosis by directly associating with Apaf-1 and blocking the assembly of a functional apoptosome.

What controls the melting properties of DNA-linked gold nanoparticle assemblies?

Abstract: We report a series of experiments and a theoretical model designed to systematically define and evaluate the relative importance of nanoparticle, oligonucleotide, and environmental variables that contribute to the observed sharp melting transitions associated with DNA-linked nanoparticle structures. These variables include the size of the nanoparticles, the surface density of the oligonucleotides on the nanoparticles, the dielectric constant of the surrounding medium, target concentration, and the position of the nanoparticles with respect to one another within the aggregate. The experimental data may be understood in terms of a thermodynamic model that attributes the sharp melting to a cooperative mechanism that results from two key factors: the presence of multiple DNA linkers between each pair of nanoparticles and a decrease in the melting temperature as DNA strands melt due to a concomitant reduction in local salt concentration. The cooperative melting effect, originating from short-range duplex-to-duplex interactions, is independent of DNA base sequences studied and should be universal for any type of nanostructured probe that is heavily functionalized with oligonucleotides. Understanding the fundamental origins of the melting properties of DNA-linked nanoparticle aggregates (or monolayers) is of paramount importance because these properties directly impact one's ability to formulate high sensitivity and selectivity DNA detection systems and construct materials from these novel nanoparticle materials.

Resuscitating Real Business Cycles

Abstract: The Real Business Cycle (RBC) research program has grown spectacularly over the last decade, as its concepts and methods have diffused into mainstream macroeconomics. Yet, there is increasing skepticism that technology shocks are a major source of business fluctuations. This chapter exposits the basic RBC model and shows that it requires large technology shocks to produce realistic business cycles. While Solow residuals are sufficiently volatile, these imply frequent technological regress. Productivity studies permitting unobserved factor variation find much smaller technology shocks, suggesting the imminent demise of real business cycles. However, we show that greater factor variation also dramatically amplifies shocks: a RBC model with varying capital utilization yields realistic business cycles from small, nonnegative changes in technology.

Prestin is the motor protein of cochlear outer hair cells.

Abstract: The outer and inner hair cells of the mammalian cochlea perform different functions. In response to changes in membrane potential, the cylindrical outer hair cell rapidly alters its length and stiffness. These mechanical changes, driven by putative molecular motors, are assumed to produce amplification of vibrations in the cochlea that are transduced by inner hair cells. Here we have identified an abundant complementary DNA from a gene, designated Prestin, which is specifically expressed in outer hair cells. Regions of the encoded protein show moderate sequence similarity to pendrin and related sulphate/anion transport proteins. Voltage-induced shape changes can be elicited in cultured human kidney cells that express prestin. The mechanical response of outer hair cells to voltage change is accompanied by a 'gating current', which is manifested as nonlinear capacitance. We also demonstrate this nonlinear capacitance in transfected kidney cells. We conclude that prestin is the motor protein of the cochlear outer hair cell.

Nanosphere lithography: Tunable localized surface plasmon resonance spectra of silver nanoparticles

Abstract: The wavelength corresponding to the extinction maximum, λmax, of the localized surface plasmon resonance (LSPR) of silver nanoparticle arrays fabricated by nanosphere lithography (NSL) can be systematically tuned from ∼400 nm to 6000 nm. Such spectral manipulation was achieved by using (1) precise lithographic control of nanoparticle size, height, and shape, and (2) dielectric encapsulation of the nanoparticles in SiOx. These results demonstrate an unprecedented level of wavelength agility in nanoparticle optical response throughout the visible, near-infrared, and mid-infrared regions of the electromagnetic spectrum. It will also be shown that this level of wavelength tunability is accompanied with the preservation of narrow LSPR bandwidths (fwhm), Γ. Additionally, two other surprising LSPR optical properties were discovered: (1) the extinction maximum shifts by 2−6 nm per 1 nm variation in nanoparticle width or height, and (2) the LSPR oscillator strength is equivalent to that of atomic silver in gas or...

Exemplar dynamics: Word frequency, lenition and contrast

Abstract: To appear in J. Bybee & P. Hopper (eds.), Frequency effects and emergent grammar. Amsterdam: John Benjamins. Exemplar theory was first developed as a model of similarity and classification in perception. In this paper, the theory is extended to model speech production as well as speech perception. Straightforward extension of the model provides a formal framework for thinking about the quantitative predictions of usage-based phonology, as proposed by Bybee. A model is proposed which allows us to derive the finding that leniting historical changes are more advanced in frequent words than in rarer ones. Calculations using this model are presented which reveal the interaction of production noise, lenition and entrenchment. A realistic treatment is also provided for the time course of a phonological merger which originates from lenition of a marked category.

Extended finite element method for three-dimensional crack modelling

Abstract: An extended finite element method (X-FEM) for three-dimensional crack modelling is described. A discontinuous function and the two-dimensional asymptotic crack-tip displacement fields are added to the finite element approximation to account for the crack using the notion of partition of unity. This enables the domain to be modelled by finite elements with no explicit meshing of the crack surfaces. Computational geometry issues associated with the representation of the crack and the enrichment of the finite element approximation are discussed. Stress intensity factors (SIFs) for planar three-dimensional cracks are presented, which are found to be in good agreement with benchmark solutions. Copyright © 2000 John Wiley & Sons, Ltd.

Does the "New Economy" Measure up to the Great Inventions of the Past?

Abstract: During the four years 1995-99 U.S. productivity growth experienced a strong revival and achieved growth rates exceeding that of the “golden age” of 1913-72. Accordingly many observers have declared the “New Economy” to be an Industrial Revolution even more important than the Second Industrial Revolution of 1860-1900, which made the golden age of productivity growth possible. This paper dissects the recent productivity revival, subtracts out a cyclical component, and concludes that there is no revival of the productivity growth trend in the 88 percent of the private economy lying outside of the durables manufacturing sector. The paper explains this surprising finding by pointing to limitations in computers and the internet in comparison with the great inventions of the past.

A Fluorescence-Based Method for Determining the Surface Coverage and Hybridization Efficiency of Thiol-Capped Oligonucleotides Bound to Gold Thin Films and Nanoparticles

Abstract: Using a fluorescence-based method, we have determined the number of thiol-derivatized single-stranded oligonucleotides bound to gold nanoparticles and their extent of hybridization with complementary oligonucleotides in solution. Oligonucleotide surface coverages of hexanethiol 12-mer oligonucleotides on gold nanoparticles (34 ± 1 pmol/cm2) were significantly higher than on planar gold thin films (18 ± 3 pmol/cm2), while the percentage of hybridizable strands on the gold nanoparticles (1.3 ± 0.3 pmol/cm2, 4%) was lower than for gold thin films (6 ± 2 pmol/cm2, 33%). A gradual increase in electrolyte concentration over the course of oligonucleotide deposition significantly increases surface coverage and consequently particle stability. In addition, oligonucleotide spacer sequences improve the hybridization efficiency of oligonucleotide-modified nanoparticles from ∼4 to 44%. The surface coverage of recognition strands can be tailored using coadsorbed diluent oligonucleotides. This provides a means of indire...

Role of the Heat Shock Response and Molecular Chaperones in Oncogenesis and Cell Death

Abstract: Exposure of cells to conditions of environmental stress-including heat shock, oxidative stress, heavy metals, or pathologic conditions, such as ischemia and reperfusion, inflammation, tissue damage, infection, and mutant proteins associated with genetic diseases-results in the inducible expression of heat shock proteins that function as molecular chaperones or proteases. Molecular chaperones are a class of proteins that interact with diverse protein substrates to assist in their folding, with a critical role during cell stress to prevent the appearance of folding intermediates that lead to misfolded or otherwise damaged molecules. Consequently, heat shock proteins assist in the recovery from stress either by repairing damaged proteins (protein refolding) or by degrading them, thus restoring protein homeostasis and promoting cell survival. The events of cell stress and cell death are linked, such that molecular chaperones induced in response to stress appear to function at key regulatory points in the control of apoptosis. On the basis of these observations-and on the role of molecular chaperones in the regulation of steroid aporeceptors, kinases, caspases, and other protein remodeling events involved in chromosome replication and changes in cell structure-it is not surprising that the heat shock response and molecular chaperones have been implicated in the control of cell growth. In this review, we address some of the molecular and cellular events initiated by cell stress-the interrelationships between stress signaling, cell death, and oncogenesis-and chaperones as potential targets for cancer diagnosis and treatment.

Timing the ancestor of the HIV-1 pandemic strains.

Abstract: HIV-1 sequences were analyzed to estimate the timing of the ancestral sequence of the main group of HIV-1, the strains responsible for the AIDS pandemic. Using parallel supercomputers and assuming a constant rate of evolution, we applied maximum-likelihood phylogenetic methods to unprecedented amounts of data for this calculation. We validated our approach by correctly estimating the timing of two historically documented points. Using a comprehensive full-length envelope sequence alignment, we estimated the date of the last common ancestor of the main group of HIV-1 to be 1931 (1915-41). Analysis of a gag gene alignment, subregions of envelope including additional sequences, and a method that relaxed the assumption of a strict molecular clock also supported these results.

Perspective-taking: decreasing stereotype expression, stereotype accessibility, and in-group favoritism.

Abstract: Using 3 experiments, the authors explored the role of perspective-taking in debiasing social thought. In the 1st 2 experiments, perspective-taking was contrasted with stereotype suppression as a possible strategy for achieving stereotype control. In Experiment 1, perspective-taking decreased stereotypic biases on both a conscious and a nonconscious task. In Experiment 2, perspective-taking led to both decreased stereotyping and increased overlap between representations of the self and representations of the elderly, suggesting activation and application of the self-concept in judgments of the elderly. In Experiment 3, perspective-taking reduced evidence of in-group bias in the minimal group paradigm by increasing evaluations of the out-group. The role of self-other overlap in producing prosocial outcomes and the separation of the conscious, explicit effects from the nonconscious, implicit effects of perspective-taking are discussed.

Portfolio Choice and Asset Prices: The Importance of Entrepreneurial Risk

Abstract: Using cross-sectional data from the SCF and Tax Model, we show that entrepreneurial income risk has a significant inf luence on portfolio choice and asset prices. We find that households with high and variable business income hold less wealth in stocks than other similarly wealthy households, although they constitute a significant fraction of the stockholding population. Similarly for nonentrepreneurs, holding stock in the firm where one works reduces the portfolio share of other common stocks. Finally, we show that adding proprietary income to a linear asset pricing model improves its performance over a similar model that includes only wage income. IN CONSTRUCTING INVESTMENT PORTFOLIOS, it appears that many if not most households fail to behave in a manner consistent with simple economic theory. Even among relatively wealthy households, the share of financial assets held in different asset classes varies widely, and there is evidence that among those who hold common stock, there is often little diversification ~e.g., King and Leape ~1987!, Blume and Zeldes ~1994!!. We begin this paper with an empirical investigation into some of the risk factors and demographic variables that might explain these cross-sectional differences in portfolio composition. A number of previous studies focus on the level and variability of wage income growth as one of the largest sources of undiversifiable income risk. Here we present evidence that, for the subset of the population that has significant stockholdings, income from entrepreneurial ventures ~which we refer to as proprietary business income) represents a large source of undiversifiable risk that is more highly correlated with common stock returns. These findings motivate the investigation in the second part of the paper of a linear asset pricing model that incorporates proprietary income from pri

HIV-1 Nomenclature Proposal

Abstract: A clear and consistent genetic classification of human immunodeficiency virus-type 1 (HIV-1) strains continues to be of great utility in epidemiological tracking of the AIDS pandemic and in vaccine design. It also provides a foundation for detecting any biological differences that may have evolved

Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1

Abstract: Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that limits vessel density in normal tissues and curtails tumor growth. Here, we show that the inhibition of angiogenesis in vitro and in vivo and the induction of apoptosis by thrombospondin-1 all required the sequential activation of CD36, p59fyn, caspase-3 like proteases and p38 mitogen-activated protein kinases. We also detected increased endothelial cell apoptosis in situ at the margins of tumors in mice treated with thrombospondin-1. These results indicate that thrombospondin-1, and possibly other broad-spectrum natural inhibitors of angiogenesis, act in vivo by inducing receptor-mediated apoptosis in activated microvascular endothelial cells.