Showing papers by "Cornell University published in 2003"

Maximizing the spread of influence through a social network

Abstract: Models for the processes by which ideas and influence propagate through a social network have been studied in a number of domains, including the diffusion of medical and technological innovations, the sudden and widespread adoption of various strategies in game-theoretic settings, and the effects of "word of mouth" in the promotion of new products. Recently, motivated by the design of viral marketing strategies, Domingos and Richardson posed a fundamental algorithmic problem for such social network processes: if we can try to convince a subset of individuals to adopt a new product or innovation, and the goal is to trigger a large cascade of further adoptions, which set of individuals should we target?We consider this problem in several of the most widely studied models in social network analysis. The optimization problem of selecting the most influential nodes is NP-hard here, and we provide the first provable approximation guarantees for efficient algorithms. Using an analysis framework based on submodular functions, we show that a natural greedy strategy obtains a solution that is provably within 63% of optimal for several classes of models; our framework suggests a general approach for reasoning about the performance guarantees of algorithms for these types of influence problems in social networks.We also provide computational experiments on large collaboration networks, showing that in addition to their provable guarantees, our approximation algorithms significantly out-perform node-selection heuristics based on the well-studied notions of degree centrality and distance centrality from the field of social networks.

Nonlinear magic: multiphoton microscopy in the biosciences

Abstract: Multiphoton microscopy (MPM) has found a niche in the world of biological imaging as the best noninvasive means of fluorescence microscopy in tissue explants and living animals. Coupled with transgenic mouse models of disease and 'smart' genetically encoded fluorescent indicators, its use is now increasing exponentially. Properly applied, it is capable of measuring calcium transients 500 microm deep in a mouse brain, or quantifying blood flow by imaging shadows of blood cells as they race through capillaries. With the multitude of possibilities afforded by variations of nonlinear optics and localized photochemistry, it is possible to image collagen fibrils directly within tissue through nonlinear scattering, or release caged compounds in sub-femtoliter volumes.

A Framework to Quantitatively Assess and Enhance the Seismic Resilience of Communities

Abstract: This paper presents a conceptual framework to define seismic resilience of communities and quantitative measures of resilience that can be useful for a coordinated research effort focusing on enhancing this resilience. This framework relies on the complementary measures of resilience: ‘‘Reduced failure probabilities,’’ ‘‘Reduced consequences from failures,’’ and ‘‘Reduced time to recovery.’’ The framework also includes quantitative measures of the ‘‘ends’’ of robustness and rapidity, and the ‘‘means’’ of resourcefulness and redundancy, and integrates those measures into the four dimensions of community resilience—technical, organizational, social, and economic—all of which can be used to quantify measures of resilience for various types of physical and organizational systems. Systems diagrams then establish the tasks required to achieve these objectives. This framework can be useful in future research to determine the resiliency of different units of analysis and systems, and to develop resiliency targets and detailed analytical procedures to generate these values. [DOI: 10.1193/1.1623497]

Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients with Non-Small Cell Lung Cancer: A Randomized Trial

Abstract: ContextMore persons in the United States die from non–small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib.ObjectiveTo assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib.Design, Setting, and PatientsDouble-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens.InterventionDaily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo).Main Outcome MeasuresImprovement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies).ResultsOf 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P = .26), radiographic tumor regression (P = .51), and projected 1-year survival (P = .54). The 500-mg dose was associated more frequently with transient acne-like rash (P = .04) and diarrhea (P = .006).ConclusionsGefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.

Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo

Abstract: The use of semiconductor nanocrystals (quantum dots) as fluorescent labels for multiphoton microscopy enables multicolor imaging in demanding biological environments such as living tissue. We characterized water-soluble cadmium selenide-zinc sulfide quantum dots for multiphoton imaging in live animals. These fluorescent probes have two-photon action cross sections as high as 47,000 Goeppert-Mayer units, by far the largest of any label used in multiphoton microscopy. We visualized quantum dots dynamically through the skin of living mice, in capillaries hundreds of micrometers deep. We found no evidence of blinking (fluorescence intermittency) in solution on nanosecond to millisecond time scales.

Nineteen Dubious Ways to Compute the Exponential of a Matrix, Twenty-Five Years Later ⁄

Abstract: In principle, the exponential of a matrix could be computed in many ways. Methods involving approximation theory, differential equations, the matrix eigenvalues, and the matrix characteristic polyn...

Language-based information-flow security

Abstract: Current standard security practices do not provide substantial assurance that the end-to-end behavior of a computing system satisfies important security policies such as confidentiality. An end-to-end confidentiality policy might assert that secret input data cannot be inferred by an attacker through the attacker's observations of system output; this policy regulates information flow. Conventional security mechanisms such as access control and encryption do not directly address the enforcement of information-flow policies. Previously, a promising new approach has been developed: the use of programming-language techniques for specifying and enforcing information-flow policies. In this paper, we survey the past three decades of research on information-flow security, particularly focusing on work that uses static program analysis to enforce information-flow policies. We give a structured view of work in the area and identify some important open challenges.

Intellectual Impairment in Children with Blood Lead Concentrations below 10 μg per Deciliter

Abstract: background Despite dramatic declines in children’s blood lead concentrations and a lowering of the Centers for Disease Control and Prevention’s level of concern to 10 µg per deciliter (0.483 µmol per liter), little is known about children’s neurobehavioral functioning at lead concentrations below this level. methods We measured blood lead concentrations in 172 children at 6, 12, 18, 24, 36, 48, and 60 months of age and administered the Stanford–Binet Intelligence Scale at the ages of 3 and 5 years. The relation between IQ and blood lead concentration was estimated with the use of linear and nonlinear mixed models, with adjustment for maternal IQ, quality of the home environment, and other potential confounders. results The blood lead concentration was inversely and significantly associated with IQ. In the linear model, each increase of 10 µg per deciliter in the lifetime average blood lead concentration was associated with a 4.6-point decrease in IQ (P=0.004), whereas for the subsample of 101 children whose maximal lead concentrations remained below 10 µg per deciliter, the change in IQ associated with a given change in lead concentration was greater. When estimated in a nonlinear model with the full sample, IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 µg per deciliter. conclusions Blood lead concentrations, even those below 10 µg per deciliter, are inversely associated with children’s IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated.

Microwave oscillations of a nanomagnet driven by a spin-polarized current

Abstract: The recent discovery that a spin-polarized electrical current can apply a large torque to a ferromagnet, through direct transfer of spin angular momentum, offers the possibility of manipulating magnetic-device elements without applying cumbersome magnetic fields. However, a central question remains unresolved: what type of magnetic motions can be generated by this torque? Theory predicts that spin transfer may be able to drive a nanomagnet into types of oscillatory magnetic modes not attainable with magnetic fields alone, but existing measurement techniques have provided only indirect evidence for dynamical states. The nature of the possible motions has not been determined. Here we demonstrate a technique that allows direct electrical measurements of microwave-frequency dynamics in individual nanomagnets, propelled by a d.c. spin-polarized current. We show that spin transfer can produce several different types of magnetic excitation. Although there is no mechanical motion, a simple magnetic-multilayer structure acts like a nanoscale motor; it converts energy from a d.c. electrical current into high-frequency magnetic rotations that might be applied in new devices including microwave sources and resonators.

Predominant Autoantibody Production by Early Human B Cell Precursors

Abstract: During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.

Nutrient availability and leaching in an archaeological Anthrosol and a Ferralsol of the Central Amazon basin: fertilizer, manure and charcoal amendments

Abstract: Soil fertility and leaching losses of nutrients were compared between a Fimic Anthrosol and a Xanthic Ferralsol from Central Amazonia The Anthrosol was a relict soil from pre-Columbian settlements with high organic C containing large proportions of black carbon It was further tested whether charcoal additions among other organic and inorganic applications could produce similarly fertile soils as these archaeological Anthrosols In the first experiment, cowpea (Vigna unguiculata (L) Walp) was planted in pots, while in the second experiment lysimeters were used to quantify water and nutrient leaching from soil cropped to rice (Oryza sativa L) The Anthrosol showed significantly higher P, Ca, Mn, and Zn availability than the Ferralsol increasing biomass production of both cowpea and rice by 38–45% without fertilization (P<005) The soil N contents were also higher in the Anthrosol but the wide C-to-N ratios due to high soil C contents led to immobilization of N Despite the generally high nutrient availability, nutrient leaching was minimal in the Anthrosol, providing an explanation for their sustainable fertility However, when inorganic nutrients were applied to the Anthrosol, nutrient leaching exceeded the one found in the fertilized Ferralsol Charcoal additions significantly increased plant growth and nutrition While N availability in the Ferralsol decreased similar to the Anthrosol, uptake of P, K, Ca, Zn, and Cu by the plants increased with higher charcoal additions Leaching of applied fertilizer N was significantly reduced by charcoal, and Ca and Mg leaching was delayed In both the Ferralsol with added charcoal and the Anthrosol, nutrient availability was elevated with the exception of N while nutrient leaching was comparatively low

Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation

Abstract: Multicolor nonlinear microscopy of living tissue using two- and three-photon-excited intrinsic fluorescence combined with second harmonic generation by supermolecular structures produces images with the resolution and detail of standard histology without the use of exogenous stains. Imaging of intrinsic indicators within tissue, such as nicotinamide adenine dinucleotide, retinol, indoleamines, and collagen provides crucial information for physiology and pathology. The efficient application of multiphoton microscopy to intrinsic imaging requires knowledge of the nonlinear optical properties of specific cell and tissue components. Here we compile and demonstrate applications involving a range of intrinsic molecules and molecular assemblies that enable direct visualization of tissue morphology, cell metabolism, and disease states such as Alzheimer's disease and cancer.

Defining cultural competence: a practical framework for addressing racial/ethnic disparities in health and health care.

Abstract: OBJECTIVES: Racial/ethnic disparities in health in the U.S. have been well described. The field of "cultural competence" has emerged as one strategy to address these disparities. Based on a review of the relevant literature, the authors develop a definition of cultural competence, identify key components for intervention, and describe a practical framework for implementation of measures to address racial/ethnic disparities in health and health care. METHODS: The authors conducted a literature review of academic, foundation, and government publications focusing on sociocultural barriers to care, the level of the health care system at which a given barrier occurs, and cultural competence efforts that address these barriers. RESULTS: Sociocultural barriers to care were identified at the organizational (leadership/workforce), structural (processes of care), and clinical (provider-patient encounter) levels. A framework of cultural competence interventions--including minority recruitment into the health professions, development of interpreter services and language-appropriate health educational materials, and provider education on cross-cultural issues--emerged to categorize strategies to address racial/ethnic disparities in health and health care. CONCLUSIONS: Demographic changes anticipated over the next decade magnify the importance of addressing racial/ethnic disparities in health and health care. A framework of organizational, structural, and clinical cultural competence interventions can facilitate the elimination of these disparities and improve care for all Americans.

Gossip-based computation of aggregate information

Abstract: Over the last decade, we have seen a revolution in connectivity between computers, and a resulting paradigm shift from centralized to highly distributed systems. With massive scale also comes massive instability, as node and link failures become the norm rather than the exception. For such highly volatile systems, decentralized gossip-based protocols are emerging as an approach to maintaining simplicity and scalability while achieving fault-tolerant information dissemination. In this paper, we study the problem of computing aggregates with gossip-style protocols. Our first contribution is an analysis of simple gossip-based protocols for the computation of sums, averages, random samples, quantiles, and other aggregate functions, and we show that our protocols converge exponentially fast to the true answer when using uniform gossip. Our second contribution is the definition of a precise notion of the speed with which a node's data diffuses through the network. We show that this diffusion speed is at the heart of the approximation guarantees for all of the above problems. We analyze the diffusion speed of uniform gossip in the presence of node and link failures, as well as for flooding-based mechanisms. The latter expose interesting connections to random walks on graphs.

Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration.

Abstract: Emerging evidence suggests that bone marrow-derived endothelial, hematopoietic stem and progenitor cells contribute to tissue vascularization during both embryonic and postnatal physiological processes. Recent preclinical and pioneering clinical studies have shown that introduction of bone marrow-derived endothelial and hematopoietic progenitors can restore tissue vascularization after ischemic events in limbs, retina and myocardium. Corecruitment of angiocompetent hematopoietic cells delivering specific angiogenic factors facilitates incorporation of endothelial progenitor cells (EPCs) into newly sprouting blood vessels. Identification of cellular mediators and tissue-specific chemokines, which facilitate selective recruitment of bone marrow-derived stem and progenitor cells to specific organs, will open up new avenues of research to accelerate organ vascularization and regeneration. In addition, identification of factors that promote differentiation of the progenitor cells will permit functional incorporation into neo-vessels of specific tissues while diminishing potential toxicity to other organs. In this review, we discuss the clinical potential of vascular progenitor and stem cells to restore long-lasting organ vascularization and function.

Zero-Mode Waveguides for Single-Molecule Analysis at High Concentrations

Abstract: Optical approaches for observing the dynamics of single molecules have required pico- to nanomolar concentrations of fluorophore in order to isolate individual molecules. However, many biologically relevant processes occur at micromolar ligand concentrations, necessitating a reduction in the conventional observation volume by three orders of magnitude. We show that arrays of zero-mode waveguides consisting of subwavelength holes in a metal film provide a simple and highly parallel means for studying single-molecule dynamics at micromolar concentrations with microsecond temporal resolution. We present observations of DNA polymerase activity as an example of the effectiveness of zero-mode waveguides for performing single-molecule experiments at high concentrations.

Antioxidant activity of apple peels

Abstract: Consumption of fruits and vegetables has been shown to be effective in the prevention of chronic diseases. These benefits are often attributed to the high antioxidant content of some plant foods. Apples are commonly eaten and are large contributors of phenolic compounds in European and North American diets. The peels of apples, in particular, are high in phenolics. During applesauce and canned apple manufacture, the antioxidant-rich peels of apples are discarded. To determine if a useful source of antioxidants is being wasted, the phytochemical content, antioxidant activity, and antiproliferative activity of the peels of four varieties of apples (Rome Beauty, Idared, Cortland, and Golden Delicious) commonly used in applesauce production in New York state were investigated. The values of the peels were compared to those of the flesh and flesh + peel components of the apples. Within each variety, the total phenolic and flavonoid contents were highest in the peels, followed by the flesh + peel and the flesh....

Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension

Abstract: Lipid bilayer membranes--ubiquitous in biological systems and closely associated with cell function--exhibit rich shape-transition behaviour, including bud formation and vesicle fission. Membranes formed from multiple lipid components can laterally separate into coexisting liquid phases, or domains, with distinct compositions. This process, which may resemble raft formation in cell membranes, has been directly observed in giant unilamellar vesicles. Detailed theoretical frameworks link the elasticity of domains and their boundary properties to the shape adopted by membranes and the formation of particular domain patterns, but it has been difficult to experimentally probe and validate these theories. Here we show that high-resolution fluorescence imaging using two dyes preferentially labelling different fluid phases directly provides a correlation between domain composition and local membrane curvature. Using freely suspended membranes of giant unilamellar vesicles, we are able to optically resolve curvature and line tension interactions of circular, stripe and ring domains. We observe long-range domain ordering in the form of locally parallel stripes and hexagonal arrays of circular domains, curvature-dependent domain sorting, and membrane fission into separate vesicles at domain boundaries. By analysing our observations using available membrane theory, we are able to provide experimental estimates of boundary tension between fluid bilayer domains.

Work Groups and Teams in Organizations

Abstract: Contemporary work organizations make heavy use of work teams to meet both immediate and strategic objectives. This chapter addresses the nature and dynamics of work teams. It emphasizes the types of teams that are commonly used in work settings and the processes that are key to their success. The extensive literature on work teams is reviewed and organized around the shifting demands the team's life cycle—from formation to disbanding. Special emphasis is given to research needs relative to team training and development and the role of team leadership. Keywords: composition; development; effectiveness; leadership; team life cycle; team processes; work teams

The link prediction problem for social networks

Abstract: Given a snapshot of a social network, can we infer which new interactions among its members are likely to occur in the near future? We formalize this question as the link prediction problem, and develop approaches to link prediction based on measures the "proximity" of nodes in a network. Experiments on large co-authorship networks suggest that information about future interactions can be extracted from network topology alone, and that fairly subtle measures for detecting node proximity can outperform more direct measures.

Bursty and Hierarchical Structure in Streams

Abstract: A fundamental problem in text data mining is to extract meaningful structure from document streams that arrive continuously over time. E-mail and news articles are two natural examples of such streams, each characterized by topics that appear, grow in intensity for a period of time, and then fade away. The published literature in a particular research field can be seen to exhibit similar phenomena over a much longer time scale. Underlying much of the text mining work in this area is the following intuitive premise—that the appearance of a topic in a document stream is signaled by a “burst of activity,” with certain features rising sharply in frequency as the topic emerges. The goal of the present work is to develop a formal approach for modeling such “bursts,” in such a way that they can be robustly and efficiently identified, and can provide an organizational framework for analyzing the underlying content. The approach is based on modeling the stream using an infinite-state automaton, in which bursts appear naturally as state transitionss it can be viewed as drawing an analogy with models from queueing theory for bursty network traffic. The resulting algorithms are highly efficient, and yield a nested representation of the set of bursts that imposes a hierarchical structure on the overall stream. Experiments with e-mail and research paper archives suggest that the resulting structures have a natural meaning in terms of the content that gave rise to them.

Language and Gender

Abstract: Language and Gender is an introduction to the study of the relation between gender and language use, written by two leading experts in the field. This new edition, thoroughly updated and restructured, brings out more strongly an emphasis on practice and change, while retaining the broad scope of its predecessor and its accessible introductions which explain the key concepts in a non-technical way. The authors integrate issues of sexuality more thoroughly into the discussion, exploring more diverse gendered and sexual identities and practices. The core emphasis is on change, both in linguistic resources and their use and in gender and sexual ideologies and personae. This book explores how change often involves conflict and competing norms, both social and linguistic. Drawing on their own extensive research, as well as other key literature, the authors argue that the connections between language and gender are deep yet fluid, and arise in social practice.

Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus

Abstract: Background Although systemic lupus erythematosus is associated with premature myocardial infarction, the prevalence of underlying atherosclerosis and its relation to traditional risk factors for cardiovascular disease and lupus-related factors have not been examined in a case–control study. Methods In 197 patients with lupus and 197 matched controls, we performed carotid ultrasonography, echocardiography, and an assessment for risk factors for cardiovascular disease. The patients were also evaluated with respect to their clinical and serologic features, inflammatory mediators, and disease treatment. Results The risk factors for cardiovascular disease were similar among patients and controls. Atherosclerosis (carotid plaque) was more prevalent among patients than the controls (37.1 percent vs. 15.2 percent, P<0.001). In multivariate analysis, only older age, the presence of systemic lupus erythematosus (odds ratio, 4.8; 95 percent confidence interval, 2.6 to 8.7), and a higher serum cholesterol level were ...

Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages Insights into the Phagosomal Environment

Abstract: Little is known about the biochemical environment in phagosomes harboring an infectious agent. To assess the state of this organelle we captured the transcriptional responses of Mycobacterium tuberculosis (MTB) in macrophages from wild-type and nitric oxide (NO) synthase 2–deficient mice before and after immunologic activation. The intraphagosomal transcriptome was compared with the transcriptome of MTB in standard broth culture and during growth in diverse conditions designed to simulate features of the phagosomal environment. Genes expressed differentially as a consequence of intraphagosomal residence included an interferon γ– and NO-induced response that intensifies an iron-scavenging program, converts the microbe from aerobic to anaerobic respiration, and induces a dormancy regulon. Induction of genes involved in the activation and β-oxidation of fatty acids indicated that fatty acids furnish carbon and energy. Induction of σE-dependent, sodium dodecyl sulfate–regulated genes and genes involved in mycolic acid modification pointed to damage and repair of the cell envelope. Sentinel genes within the intraphagosomal transcriptome were induced similarly by MTB in the lungs of mice. The microbial transcriptome thus served as a bioprobe of the MTB phagosomal environment, showing it to be nitrosative, oxidative, functionally hypoxic, carbohydrate poor, and capable of perturbing the pathogen's cell envelope.

Hedgehog signalling in the mouse requires intraflagellar transport proteins

Abstract: Intraflagellar transport (IFT) proteins were first identified as essential factors for the growth and maintenance of flagella in the single-celled alga Chlamydomonas reinhardtii. In a screen for embryonic patterning mutations induced by ethylnitrosourea, here we identify two mouse mutants, wimple (wim) and flexo (fxo), that lack ventral neural cell types and show other phenotypes characteristic of defects in Sonic hedgehog signalling. Both mutations disrupt IFT proteins: the wim mutation is an allele of the previously uncharacterized mouse homologue of IFT172; and fxo is a new hypomorphic allele of polaris, the mouse homologue of IFT88. Genetic analysis shows that Wim, Polaris and the IFT motor protein Kif3a are required for Hedgehog signalling at a step downstream of Patched1 (the Hedgehog receptor) and upstream of direct targets of Hedgehog signalling. Our data show that IFT machinery has an essential and vertebrate-specific role in Hedgehog signal transduction.