Showing papers by "University of Southern California published in 1999"

Pooled Mean Group Estimation of Dynamic Heterogeneous Panels

Abstract: It is now quite common to have panels in which both T, the number of time series observations, and N, the number of groups, are quite large and of the same order of magnitude. The usual practice is either to estimate N separate regressions and calculate the coefficient means, which we call the mean group (MG) estimator, or to pool the data and assume that the slope coefficients and error variances are identical. In this article we propose an intermediate procedure, the pooled mean group (PMG) estimator, which constrains long-run coefficients to be identical but allows short-run coefficients and error variances to differ across groups. We consider both the case where the regressors are stationary and the case where they follow unit root processes, and for both cases derive the asymptotic distribution of the PMG estimators as T tends to infinity. We also provide two empirical applications: Aggregate consumption functions for 24 Organization for Economic Cooperation and Development economies over th...

Web caching and Zipf-like distributions: evidence and implications

Abstract: This paper addresses two unresolved issues about Web caching. The first issue is whether Web requests from a fixed user community are distributed according to Zipf's (1929) law. The second issue relates to a number of studies on the characteristics of Web proxy traces, which have shown that the hit-ratios and temporal locality of the traces exhibit certain asymptotic properties that are uniform across the different sets of the traces. In particular, the question is whether these properties are inherent to Web accesses or whether they are simply an artifact of the traces. An answer to these unresolved issues will facilitate both Web cache resource planning and cache hierarchy design. We show that the answers to the two questions are related. We first investigate the page request distribution seen by Web proxy caches using traces from a variety of sources. We find that the distribution does not follow Zipf's law precisely, but instead follows a Zipf-like distribution with the exponent varying from trace to trace. Furthermore, we find that there is only (i) a weak correlation between the access frequency of a Web page and its size and (ii) a weak correlation between access frequency and its rate of change. We then consider a simple model where the Web accesses are independent and the reference probability of the documents follows a Zipf-like distribution. We find that the model yields asymptotic behaviour that are consistent with the experimental observations, suggesting that the various observed properties of hit-ratios and temporal locality are indeed inherent to Web accesses observed by proxies. Finally, we revisit Web cache replacement algorithms and show that the algorithm that is suggested by this simple model performs best on real trace data. The results indicate that while page requests do indeed reveal short-term correlations and other structures, a simple model for an independent request stream following a Zipf-like distribution is sufficient to capture certain asymptotic properties observed at Web proxies.

Exploring the Black Box: An Analysis of Work Group Diversity, Conflict and Performance

Abstract: In this paper we present an integrative model of the relationships among diversity, conflict, and performance, and we test that model with a sample of 45 teams. Findings show that diversity shapes conflict and that conflict, in turn, shapes performance, but these linkages have subtleties. Functional background diversity drives task conflict, but multiple types of diversity drive emotional conflict. Race and tenure diversity are positively associated with emotional conflict, while age diversity is negatively associated with such conflict. Task routineness and group longevity moderate these relationships. Results further show that task conflict has more favorable effects on cognitive task performance than does emotional conflict. Overall, these patterns suggest a complex link between work group diversity and work group functioning.

Cancer-epigenetics comes of age

Abstract: The discovery of numerous hypermethylated promoters of tumour-suppressor genes, along with a better understanding of gene-silencing mechanisms, has moved DNA methylation from obscurity to recognition as an alternative mechanism of tumour-suppressor inactivation in cancer. Epigenetic events can also facilitate genetic damage, as illustrated by the increased mutagenicity of 5-methylcytosine and the silencing of the MLH1 mismatch repair gene by DNA methylation in colorectal tumours. We review here current mechanistic understanding of the role of DNA methylation in malignant transformation, and suggest Knudson's two-hit hypothesis should now be expanded to include epigenetic mechanisms of gene inactivation.

Two-Dimensional Photonic Band-Gap Defect Mode Laser

Abstract: A laser cavity formed from a single defect in a two-dimensional photonic crystal is demonstrated. The optical microcavity consists of a half wavelength–thick waveguide for vertical confinement and a two-dimensional photonic crystal mirror for lateral localization. A defect in the photonic crystal is introduced to trap photons inside a volume of 2.5 cubic half-wavelengths, approximately 0.03 cubic micrometers. The laser is fabricated in the indium gallium arsenic phosphide material system, and optical gain is provided by strained quantum wells designed for a peak emission wavelength of 1.55 micrometers at room temperature. Pulsed lasing action has been observed at a wavelength of 1.5 micrometers from optically pumped devices with a substrate temperature of 143 kelvin.

Stability of switched systems with average dwell-time

Abstract: It is shown that switching among stable linear systems results in a stable system provided that switching is "slow-on-the-average". In particular, it is proved that exponential stability is achieved when the number of switches in any finite interval grows linearly with the length of the interval, and the growth rate is sufficiently small. Moreover, the exponential stability is uniform over all switchings with the above property. For switched systems with inputs this guarantees that several input-to-state induced norms are bounded uniformly over all slow-on-the-average switchings. These results extend to classes of nonlinear switched systems that satisfy suitable uniformity assumptions. In this paper it is also shown that, in a supervisory control context, scale-independent hysteresis can produce switching that is slow-on-the-average and therefore the results mentioned above can be used to study the stability of hysteresis-based adaptive control systems.

Marine viruses and their biogeochemical and ecological effects

Abstract: Viruses are the most common biological agents in the sea, typically numbering ten billion per litre. They probably infect all organisms, can undergo rapid decay and replenishment, and influence many biogeochemical and ecological processes, including nutrient cycling, system respiration, particle size-distributions and sinking rates, bacterial and algal biodiversity and species distributions, algal bloom control, dimethyl sulphide formation and genetic transfer. Newly developed fluorescence and molecular techniques leave the field poised to make significant advances towards evaluating and quantifying such effects.

Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma

Abstract: Background Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. Methods Women with bulky stage IB cervical cancers (tumor, ≥4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external...

Type-2 fuzzy logic systems

Abstract: We introduce a type-2 fuzzy logic system (FLS), which can handle rule uncertainties. The implementation of this type-2 FLS involves the operations of fuzzification, inference, and output processing. We focus on "output processing," which consists of type reduction and defuzzification. Type-reduction methods are extended versions of type-1 defuzzification methods. Type reduction captures more information about rule uncertainties than does the defuzzified value (a crisp number), however, it is computationally intensive, except for interval type-2 fuzzy sets for which we provide a simple type-reduction computation procedure. We also apply a type-2 FLS to time-varying channel equalization and demonstrate that it provides better performance than a type-1 FLS and nearest neighbor classifier.

BIRDSONG AND HUMAN SPEECH: Common Themes and Mechanisms

Abstract: Human speech and birdsong have numerous parallels. Both humans and songbirds learn their complex vocalizations early in life, exhibiting a strong dependence on hearing the adults they will imitate, as well as themselves as they practice, and a waning of this dependence as they mature. Innate predispositions for perceiving and learning the correct sounds exist in both groups, although more evidence of innate descriptions of species-specific signals exists in songbirds, where numerous species of vocal learners have been compared. Humans also share with songbirds an early phase of learning that is primarily perceptual, which then serves to guide later vocal production. Both humans and songbirds have evolved a complex hierarchy of specialized forebrain areas in which motor and auditory centers interact closely, and which control the lower vocal motor areas also found in nonlearners. In both these vocal learners, however, how auditory feedback of self is processed in these brain areas is surprisingly unclear. Finally, humans and songbirds have similar critical periods for vocal learning, with a much greater ability to learn early in life. In both groups, the capacity for late vocal learning may be decreased by the act of learning itself, as well as by biological factors such as the hormones of puberty. Although some features of birdsong and speech are clearly not analogous, such as the capacity of language for meaning, abstraction, and flexible associations, there are striking similarities in how sensory experience is internalized and used to shape vocal outputs, and how learning is enhanced during a critical period of development. Similar neural mechanisms may therefore be involved.

Intermittent Administration of Inhaled Tobramycin in Patients with Cystic Fibrosis

Abstract: Background and Methods We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection. A total of 520 patients (mean age, 21 years) were randomly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks, followed by four weeks with no study drug. Patients received treatment or placebo in three on–off cycles for a total of 24 weeks. The end points included pulmonary function, the density of P. aeruginosa in sputum, and hospitalization. Results The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001). In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from w...

Exploring Expression Data: Identification and Analysis of Coexpressed Genes

Abstract: Analysis procedures are needed to extract useful information from the large amount of gene expression data that is becoming available. This work describes a set of analytical tools and their application to yeast cell cycle data. The components of our approach are (1) a similarity measure that reduces the number of false positives, (2) a new clustering algorithm designed specifically for grouping gene expression patterns, and (3) an interactive graphical cluster analysis tool that allows user feedback and validation. We use the clusters generated by our algorithm to summarize genome-wide expression and to initiate supervised clustering of genes into biologically meaningful groups.

Regulation of transcription by a protein methyltransferase.

Abstract: The p160 family of coactivators, SRC-1, GRIP1/TIF2, and p/CIP, mediate transcriptional activation by nuclear hormone receptors. Coactivator-associated arginine methyltransferase 1 (CARM1), a previously unidentified protein that binds to the carboxyl-terminal region of p160 coactivators, enhanced transcriptional activation by nuclear receptors, but only when GRIP1 or SRC-1a was coexpressed. Thus, CARM1 functions as a secondary coactivator through its association with p160 coactivators. CARM1 can methylate histone H3 in vitro, and a mutation in the putative S-adenosylmethionine binding domain of CARM1 substantially reduced both methyltransferase and coactivator activities. Thus, coactivator-mediated methylation of proteins in the transcription machinery may contribute to transcriptional regulation.

Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients.

Abstract: We identified circulating CD8+ T-cell populations specific for the tumor-associated antigens (TAAs) MART-1 (27-35) or tyrosinase (368-376) in six of eleven patients with metastatic melanoma using peptide/HLA-A*0201 tetramers. These TAA-specific populations were of two phenotypically distinct types: one, typical for memory/effector T cells; the other, a previously undescribed phenotype expressing both naive and effector cell markers. This latter type represented more than 2% of the total CD8+ T cells in one patient, permitting detailed phenotypic and functional analysis. Although these cells have many of the hallmarks of effector T cells, they were functionally unresponsive, unable to directly lyse melanoma target cells or produce cytokines in response to mitogens. In contrast, CD8+ T cells from the same patient were able to lyse EBV-pulsed target cells and showed robust allogeneic responses. Thus, the clonally expanded TAA-specific population seems to have been selectively rendered anergic in vivo. Peptide stimulation of the TAA-specific T-cell populations in other patients failed to induce substantial upregulation of CD69 expression, indicating that these cells may also have functional defects, leading to blunted activation responses. These data demonstrate that systemic TAA-specific T-cell responses can develop de novo in cancer patients, but that antigen-specific unresponsiveness may explain why such cells are unable to control tumor growth.

A Theory of Political Transitions

Abstract: We develop a theory of political transitions inspired in part by the experiences of Western Europe and Latin America. Nondemocratic societies are controlled by a rich elite. The initially disenfranchised poor can contest power by threatening social unrest or revolution and this may force the elite to democratize. Democracy may not consolidate because it is more redistributive than a nondemocratic regime, and this gives the elite an incentive to mount a coup. Because inequality makes democracy more costly for the elite, highly unequal societies are less likely to consolidate democracy and may end up oscillating between regimes or in a nondemocratic repressive regime. An unequal society is likely to experience fiscal volatility, but the relationship between inequality and redistribution is nonmonotonic; societies with intermediate levels of inequality consolidate democracy and redistribute more than both very equal and very unequal countries. We also show that asset redistribution, such as educational and land reform, may be used to consolidate both democratic and nondemocratic regimes.

Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene.

Abstract: The recessive autosomal disorder known as ICF syndrome (for immunodeficiency, centromere instability and facial anomalies; Mendelian Inheritance in Man number 242860) is characterized by variable reductions in serum immunoglobulin levels which cause most ICF patients to succumb to infectious diseases before adulthood. Mild facial anomalies include hypertelorism, low-set ears, epicanthal folds and macroglossia. The cytogenetic abnormalities in lymphocytes are exuberant: juxtacentromeric heterochromatin is greatly elongated and thread-like in metaphase chromosomes, which is associated with the formation of complex multiradiate chromosomes. The same juxtacentromeric regions are subject to persistent interphase self-associations and are extruded into nuclear blebs or micronuclei. Abnormalities are largely confined to tracts of classical satellites 2 and 3 at juxtacentromeric regions of chromosomes 1, 9 and 16. Classical satellite DNA is normally heavily methylated at cytosine residues, but in ICF syndrome it is almost completely unmethylated in all tissues. ICF syndrome is the only genetic disorder known to involve constitutive abnormalities of genomic methylation patterns. Here we show that five unrelated ICF patients have mutations in both alleles of the gene that encodes DNA methyltransferase 3B (refs 5, 6). Cytosine methylation is essential for the organization and stabilization of a specific type of heterochromatin, and this methylation appears to be carried out by an enzyme specialized for the purpose.

Monoamine oxidase: from genes to behavior.

Abstract: Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that these enzymes are made up of different polypeptides, and our understanding of MAO structure, regulation, and function has been significantly advanced by studies using their cDNA. MAO A and B genes are located on the X-chromosome (Xp11.23) and comprise 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene. MAO A and B knock-out mice exhibit distinct differences in neurotransmitter metabolism and behavior. MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A. In contrast, MAO B knock-out mice do not exhibit aggression and only levels of phenylethylamine are increased. Mice lacking MAO B are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine. Both MAO A and B knock-out mice show increased reactivity to stress. These knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders.

Making Use of Difference: Diversity, Debate, and Decision Comprehensiveness in Top Management Teams

Abstract: This study examined how top management team diversity variables and debate interacted to influence two measures of company financial performance. Further, it assessed the degree to which decision c...

Excitonic singlet-triplet ratio in a semiconducting organic thin film

Abstract: A technique is presented to determine the spin statistics of excitons formed by electrical injection in a semiconducting organic thin film. With the aid of selective addition of luminescent dyes, we generate either fluorescence or phosphorescence from the archetype organic host material aluminum tris (8-hydroxyquinoline) $({\mathrm{Alq}}_{3}).$ Spin statistics are calculated from the ratio of fluorescence to phosphorescence in the films under electrical excitation. After accounting for varying photoluminescent efficiencies, we find a singlet fraction of excitons in ${\mathrm{Alq}}_{3}$ of $(22\ifmmode\pm\else\textpm\fi{}3)%.$

Contesting Citizenship in Urban China: Peasant Migrants, the State, and the Logic of the Market

Abstract: Post-Mao market reforms in China have led to a massive migration of rural peasants toward the cities. Officially denied residency in the cities, the over 80 million members of this "floating population" provide labor for the economic boom in urban areas but are largely denied government benefits that city residents receive. In an incisive and original study that goes against the grain of much of the current discussion on citizenship, Dorothy J. Solinger challenges the notion that markets necessarily promote rights and legal equality in any direct or linear fashion.

Chapter 38 Executive compensation

Abstract: This chapter summarizes the empirical and theoretical research on executive compensation and provides a comprehensive and up-to-date description of pay practices (and trends in pay practices) for chief executive officers (CEOs). Topics discussed include the level and structure of CEO pay (including detailed analyses of annual bonus plans, executive stock options, and option valuation), international pay differences, the pay-setting process, the relation between CEO pay and firm performance (“pay-performance sensitivities”), the relation between sensitivities and subsequent firm performance, relative performance evaluation, executive turnover, and the politics of CEO pay.

Regulation of hepatic glutathione synthesis: current concepts and controversies

Abstract: Glutathione (GSH) is an important intracellular peptide with multiple functions ranging from antioxidant defense to modulation of cell proliferation. GSH is synthesized in the cytosol of all mammalian cells in a tightly regulated manner. The major determinants of GSH synthesis are the avail- ability of cysteine, the sulfur amino acid precursor, and the activity of the rate-limiting enzyme, g-glu- tamylcysteine synthetase (GCS). In the liver, major factors that determine the availability of cysteine are diet, membrane transport activities of the three sulfur amino acids cysteine, cystine and methionine, and the conversion of methionine to cysteine via the trans-sulfuration pathway. Many conditions alter GSH level via changes in GCS activity and GCS gene expression. These include oxidative stress, activators of Phase II detoxifying enzymes, antioxidants, drug- resistant tumor cell lines, hormones, cell prolifera- tion, and diabetes mellitus. Since the molecular cloning of GCS, much has been learned about the regulation of this enzyme. Both transcriptional and post-transcriptional mechanisms modulate the activ- ity of this critical cellular enzyme.—Lu, S. C. Regu- lation of hepatic glutathione synthesis: current con- cepts and controversies. FASEB J. 13, 1169 -1183 (1999)

The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors.

Abstract: DNA methylation in mammals is required for embryonic development, X chromosome inactivation and imprinting. Previous studies have shown that methylation patterns become abnormal in malignant cells and may contribute to tumorigenesis by improper de novo methylation and silencing of the promoters for growth-regulatory genes. RNA and protein levels of the DNA methyltransferase DNMT1 have been shown to be elevated in tumors, however murine stem cells lacking Dnmt1 are still able to de novo methylate viral DNA. The recent cloning of a new family of DNA methyltransferases (Dnmt3a and Dnmt3b) in mouse which methylate hemimethylated and unmethylated templates with equal efficiencies make them candidates for the long sought de novo methyltransferases. We have investigated the expression of human DNMT1, 3a and 3b and found widespread, coordinate expression of all three transcripts in most normal tissues. Chromosomal mapping placed DNMT3a on chromosome 2p23 and DNMT3b on chromosome 20q11.2. Significant overexpression of DNMT3b was seen in tumors while DNMT1 and DNMT3a were only modestly over-expressed and with lower frequency. Lastly, several novel alternatively spliced forms of DNMT3b, which may have altered enzymatic activity, were found to be expressed in a tissue-specific manner.

Calcium Supplements for the Prevention of Colorectal Adenomas

Abstract: Background and Methods Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. Results The subjects in the calcium group had a lower risk of recurrent adenomas. Among the...

EEG and MEG: forward solutions for inverse methods

Abstract: A solution of the forward problem is an important component of any method for computing the spatio-temporal activity of the neural sources of magnetoencephalography (MEG) and electroencephalography (EEG) data. The forward problem involves computing the scalp potentials or external magnetic field at a finite set of sensor locations for a putative source configuration. We present a unified treatment of analytical and numerical solutions of the forward problem in a form suitable for use in inverse methods. This formulation is achieved through factorization of the lead field into the product of the moment of the elemental current dipole source with a "kernel matrix" that depends on the head geometry and source and sensor locations, and a "sensor matrix" that models sensor orientation and gradiometer effects in MEG and differential measurements in EEG. Using this formulation and a recently developed approximation formula for EEG, based on the "Berg parameters", we present novel reformulations of the basic EEG and MEG kernels that dispel the myth that EEG is inherently more complicated to calculate than MEG. We also present novel investigations of different boundary element methods (BEMs) and present evidence that improvements over currently published BEM methods can be realized using alternative error-weighting methods. Explicit expressions for the matrix kernels for MEG and EEG for spherical and realistic head geometries are included.

Earnings Surprises, Growth Expectations, and Stock Returns: Don't Let an Earnings Torpedo Sink Your Portfolio

Abstract: It is well-established that the realized returns of ?growth? stocks have been low relative to other stocks. We show that this phenomenon is explained by a large and asymmetric response to negative earnings surprises for growth stocks. After controlling for this effect, there is no longer evidence of a stock return differential between growth stocks and other stocks. Our evidence is more consistent with investors having naively optimistic expectations about the prospects of growth stocks (e.g., Lakonishok, Shleifer, and Vishny, 1994) than with the existence of unidentified risk factors that are lower for growth stocks (e.g., Fama and French, 1992).

Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein

Abstract: Most isolates of hepatitis C virus (HCV) infections are resistant to interferon, the only available therapy, but the mechanism underlying this resistance has not been defined. Here it is shown that the HCV envelope protein E2 contains a sequence identical with phosphorylation sites of the interferon-inducible protein kinase PKR and the translation initiation factor eIF2α, a target of PKR. E2 inhibited the kinase activity of PKR and blocked its inhibitory effect on protein synthesis and cell growth. This interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of interferon.

RAP: An End-to-End Rate-Based Congestion Control Mechanism for Realtime Streams in the Internet.

Abstract: End-to-end congestion control mechanisms have been critical to the robustness and stability of the Internet. Most of today's Internet traffic is TCP, and we expect this to remain so in the future. Thus, having "TCP-friendly" behavior is crucial for new applications. However, the emergence of non-congestion-controlled realtime applications threatens unfairness to competing TCP traffic and possible congestion collapse. We present an end-to-end TCP-friendly rate adaptation protocol (RAP), which employs an additive-increase, multiplicative-decrease (AIMD) algorithm. It is well suited for unicast playback of realtime streams and other semi-reliable rate-based applications. Its primary goal is to be fair and TCP-friendly while separating network congestion control from application-level reliability. We evaluate RAP through extensive simulation, and conclude that bandwidth is usually evenly shared between TCP and RAP traffic. Unfairness to TCP traffic is directly determined by how TCP diverges from the AIMD algorithm. Basic RAP behaves in a TCP-friendly fashion in a wide range of likely conditions, but we also devised a fine-grain rate adaptation mechanism to extend this range further. Finally, we show that deploying RED queue management can result in an ideal fairness between TCP and RAP traffic.