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Showing papers by "University of Illinois at Chicago published in 1997"


Journal ArticleDOI
10 Jan 1997-Science
TL;DR: It is suggested that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.
Abstract: Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.

4,786 citations


Journal ArticleDOI
TL;DR: This article developed and tested a model of the antecedents and consequences of perceived organizational support (POS) and leader-member exchange (LMX) based on social exchange theory and found that POS and LMX have unique antecedent and are differentially related to outcome variables, providing support for the importance of both types of exchanges.
Abstract: Employees develop exchange relationships both with organizations and immediate superiors, as evidenced by research on perceived organizational support (POS) and leader-member exchange (LMX), respectively. Despite conceptual similarities between these two constructs, theoretical development and research has proceeded independently. In an attempt to integrate these literatures, we developed and tested a model of the antecedents and consequences of POS and LMX, based on social exchange theory. Results indicated that POS and LMX have unique antecedents and are differentially related to outcome variables, providing support for the importance of both types of exchanges.

3,399 citations


Journal ArticleDOI
TL;DR: Findings in the human resemble those in rhesus monkeys, including overproduction of synaptic contacts in infancy, persistence of high levels of synaptic density to late childhood or adolescence, the absolute values of maximum and adult synaptic density, and layer specific differences.
Abstract: The formation of synaptic contacts in human cerebral cortex was compared in two cortical regions: auditory cortex (Heschl's gyrus) and prefrontal cortex (middle frontal gyrus). Synapse formation in both cortical regions begins in the fetus, before conceptual age 27 weeks. Synaptic density increases more rapidly in auditory cortex, where the maximum is reached near postnatal age 3 months. Maximum synaptic density in middle frontal gyrus is not reached until after age 15 months. Synaptogenesis occurs concurrently with dendritic and axonal growth and with myelination of the subcortical white matter. A phase of net synapse elimination occurs late in childhood, earlier in auditory cortex, where it has ended by age 12 years, than in prefrontal cortex, where it extends to midadolescence. Synaptogenesis and synapse elimination in humans appear to be heterochronous in different cortical regions and, in that respect, appears to differ from the rhesus monkey, where they are concurrent. In other respects, including overproduction of synaptic contacts in infancy, persistence of high levels of synaptic density to late childhood or adolescence, the absolute values of maximum and adult synaptic density, and layer specific differences, findings in the human resemble those in rhesus monkeys.

2,717 citations


Journal ArticleDOI
TL;DR: In vitro results support evidence that ERK-phosphorylated MLCK has an increased capacity to phosphorylate MLC and shows increased sensitivity to calmodulin, and define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix.
Abstract: Cell interaction with adhesive proteins or growth factors in the extracellular matrix initiates Ras/ mitogen-activated protein (MAP) kinase signaling. Evidence is provided that MAP kinase (ERK1 and ERK2) influences the cells' motility machinery by phosphorylating and, thereby, enhancing myosin light chain kinase (MLCK) activity leading to phosphorylation of myosin light chains (MLC). Inhibition of MAP kinase activity causes decreased MLCK function, MLC phosphorylation, and cell migration on extracellular matrix proteins. In contrast, expression of mutationally active MAP kinase kinase causes activation of MAP kinase leading to phosphorylation of MLCK and MLC and enhanced cell migration. In vitro results support these findings since ERK-phosphorylated MLCK has an increased capacity to phosphorylate MLC and shows increased sensitivity to calmodulin. Thus, we define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix.

1,265 citations


Journal ArticleDOI
TL;DR: Findings from a sample of 32 firms competing in a wide variety of industries indicate that configurational approaches that align ESM, strategy, and environment have greater predictive power than contingency approaches, but not all high performing configurations are consistent with normative theory.
Abstract: This field study explores the nature of entrepreneurial strategy making (ESM) and its relationship with strategy, environment and performance. In the first phase, we assess the independence of entrepreneurially oriented strategy-making processes through factor analysis. The second phase, using moderated hierarchical regression anlaysis, investigates the relative predictive power of two approaches for exploring the ESM–performance relationship: contingency and configuration. Findings from a sample of 32 firms competing in a wide variety of industries indicate that configurational approaches that align ESM, strategy, and environment have greater predictive power than contingency approaches. However, not all high performing configurations are consistent with normative theory. Thus, alternate theories linking entrepreneurial strategy making to competitive advantage should be developed and tested. © 1997 John Wiley & Sons, Ltd.

1,163 citations


Journal ArticleDOI
TL;DR: The results suggest that uncoupling of survival and mitogenesis can be explained by differing abilities of distinct mitogens to efficiently induce the PI 3-kinase/Akt signaling pathway.
Abstract: Serum and certain growth factors have the ability to inhibit programmed cell death (apoptosis) and promote survival. The mechanism by which growth factors deliver an anti-apoptotic signal and the mechanism by which this survival signal is uncoupled from mitogenesis are not clear. We studied five downstream effectors of growth factor receptors--Ras, Raf, Src, phosphoinositide 3-kinase (PI 3-kinase), and Akt (PKB)--for their abilities to block apoptosis. Activated forms of Ras, Raf, and Src, although transforming, were not sufficient to deliver a survival signal upon serum withdrawal. In contrast, inhibition of PI 3-kinase accelerated apoptosis, and an activated form of the serine/threonine kinase Akt, a downstream effector of PI 3-kinase, blocked apoptosis. The ability of Akt to promote survival was dependent on and proportional to its kinase activity. In Rat1a fibroblasts, activated Akt did not alter Bcl-2 or Bcl-X(L) expression but inhibited Ced3/ICE-like activity. Thus, the PI 3-kinase/Akt (PKB) signaling pathway transduces a survival signal that ultimately blocks Ced3/ICE-like activity. These results suggest that uncoupling of survival and mitogenesis can be explained by differing abilities of distinct mitogens to efficiently induce the PI 3-kinase/Akt signaling pathway.

1,085 citations


Journal ArticleDOI
TL;DR: Analysis of cardiac development in the GATA4-/- mice demonstrated that these embryos developed splanchnic mesoderm, which differentiated into primitive cardiac myocytes that expressed contractile proteins that formed aberrant cardiac structures in the anterior and dorsolateral regions of the embryo.
Abstract: Previous studies have suggested that the GATA4 transcription factor plays an important role in regulating mammalian cardiac development In the studies described in this report we have used gene targeting to produce GATA4-deficient mice Homozygous GATA4-deficient (GATA4 -/-) mice died between 85 and 105 days post coitum (dpc) GATA4 -/- embryos displayed severe defects in both rostral-to-caudal and lateral-to-ventral folding, which were reflected in a generalized disruption of the ventral body pattern This resulted in the defective formation of an organized foregut and anterior intestinal pore, the failure to close both the amniotic cavity and yolk sac, and the uniform lack of a ventral pericardial cavity and heart tube Analysis of cardiac development in the GATA4 -/- mice demonstrated that these embryos developed splanchnic mesoderm, which differentiated into primitive cardiac myocytes that expressed contractile proteins However, consistent with the observed defect in ventral morphogenesis, these GATA4 -/procardiomyocytes failed to migrate to the ventral midline to form a linear heart tube and instead formed aberrant cardiac structures in the anterior and dorsolateral regions of the embryo The defect in ventral migration of the GATA4 -/- procardiomyocytes was not cell intrinsic because GATA4 -/- cardiac myocytes and endocardial cells populated the hearts of GATA4-/--C57BL/6 chimeric mice Taken together, these results demonstrated that GATA4 is not essential for the specification of the cardiac cell lineages However, they define a critical role for GATA4 in regulating the rostral-to-caudal and lateral-to-ventral folding of the embryo that is needed for normal cardiac morphogenesis

1,059 citations


Journal ArticleDOI
TL;DR: The authors found that children tended to approve more of aggression as they grew older and that this increase appeared to be correlated with increases in aggressive behavior.
Abstract: Normative beliefs have been defined as self-regulating beliefs about the appropriateness of social behaviors. In 2 studies the authors revised their scale for assessing normative beliefs about aggression, found that it is reliable and valid for use with elementary school children, and investigated the longitudinal relation between normative beliefs about aggression and aggressive behavior in a large sample of elementary school children living in poor urban neighborhoods. Using data obtained in 2 waves of observations 1 year apart, the authors found that children tended to approve more of aggression as they grew older and that this increase appeared to be correlated with increases in aggressive behavior. More important, although individual differences in aggressive behavior predicted subsequent differences in normative beliefs in younger children, individual differences in aggressive behavior were predicted by preceding differences in normative beliefs in older children.

970 citations


Journal ArticleDOI
TL;DR: The authors employ insights derived from social network analysis to describe how social structure facilitates the exchange processes through which leaders assist in incorporating some members into the inner life of an organization but exclude others.
Abstract: Theory supporting the key premise of the leader-member exchange (LMX) approach to leadership, that leaders differentiate between subordinates, has not been fully developed. We address this deficiency by (a) returning LMX research to its historical roots in exchange processes by introducing a framework for understanding relationship quality that is based on reciprocity, and (b) extending the traditional domain of LMX research beyond the formal leader-subordinate relationship in order to offer a more complete explanation of the differentiation process. We employ insights derived from social network analysis to describe how social structure facilitates the exchange processes through which leaders assist in incorporating some members into the inner life of an organization but exclude others.

934 citations


Journal ArticleDOI
TL;DR: In this article, the authors describe the progress of an international group of investigators who have commenced a coordinated effort to develop a standardized set of cognitive measures for obsessive-compulsive disorder.

872 citations


Journal ArticleDOI
23 Jan 1997-Nature
TL;DR: The three-dimensional structure of Bcl-xL, an inhibitor of apoptosis, was recently shown to be similar to the structures of the pore-forming domains of bacterial toxins, and the ion-conducting channel formed by this protein displays multiple conductance states that have identical ion selectivity.
Abstract: Bcl-2-related proteins are critical regulators of cell survival that are localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum membranes. Despite their physiological importance, the biochemical function of Bcl-2-related proteins has remained elusive. The three-dimensional structure of Bcl-xL, an inhibitor of apoptosis, was recently shown to be similar to the structures of the pore-forming domains of bacterial toxins. A key feature of these pore-forming domains is the ability to form ion channels in biological membranes. Here we demonstrate that Bcl-xL shares this functional feature. Like the bacterial toxins, Bcl-xL can insert into either synthetic lipid vesicles or planar lipid bilayers and form an ion-conducting channel. This channel is pH-sensitive and becomes cation-selective at physiological pH. The ion-conducting channel(s) formed by Bcl-xL display multiple conductance states that have identical ion selectivity. Together, these data suggest that Bcl-xL may maintain cell survival by regulating the permeability of the intracellular membranes to which it is distributed.

Journal ArticleDOI
TL;DR: The critical role of CLCNKB in renal salt reabsorption and blood–pressure homeostasis is demonstrated, and the potential role of specific C LCNKB antagonists as diuretic antihypertensive agents is demonstrated.
Abstract: Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents.

Journal ArticleDOI
TL;DR: A review of past and recent developments in the dynamics of flexible multibody systems is presented, and some of the basic approaches used in the computer aided kinematic and dynamic analysis of flexible mechanical systems are reviewed to identify future directions in this research area.
Abstract: In this paper, a review of past and recent developments in the dynamics of flexible multibody systems is presented. The objective is to review some of the basic approaches used in the computer aided kinematic and dynamic analysis of flexible mechanical systems, and to identify future directions in this research area. Among the formulations reviewed in this paper are the floating frame of reference formulation, the finite element incremental methods, large rotation vector formulations, the finite segment method, and the linear theory of elastodynamics. Linearization of the flexible multibody equations that results from the use of the incremental finite element formulations is discussed. Because of space limitations, it is impossible to list all the contributions made in this important area. The reader, however, can find more references by consulting the list of articles and books cited at the end of the paper. Furthermore, the numerical procedures used for solving the differential and algebraic equations of flexible multibody systems are not discussed in this paper since these procedures are similar to the techniques used in rigid body dynamics. More details about these numerical procedures as well as the roots and perspectives of multibody system dynamics are discussed in a companion review by Schiehlen [79]. Future research areas in flexible multibody dynamics are identified as establishing the relationship between different formulations, contact and impact dynamics, control-structure interaction, use of modal identification and experimental methods in flexible multibody simulations, application of flexible multibody techniques to computer graphics, numerical issues, and large deformation problem. Establishing the relationship between different flexible multibody formulations is an important issue since there is a need to clearly define the assumptions and approximations underlying each formulation. This will allow us to establish guidelines and criteria that define the limitations of each approach used in flexible multibody dynamics. This task can now be accomplished by using the “absolute nodal coordinate formulation” which was recently introduced for the large deformation analysis of flexible multibody systems.

Posted Content
TL;DR: In this article, the authors discuss the event study methodology, including hypothesis testing, the use of different benchmarks for the normal rate of return, the power of the methodology in different applications and the modeling of abnormal returns as coefficients in a (multivariate) regression framework.
Abstract: This paper discusses the event study methodology, beginning with FFJR (1969), including hypothesis testing, the use of different benchmarks for the normal rate of return, the power of the methodology in different applications and the modeling of abnormal returns as coefficients in a (multivariate) regression framework. It also focuses on frequently encountered statistical problems in event studies and their solutions.

Journal ArticleDOI
TL;DR: The Altman Self-Rating Mania Scale was completed during medication washout and after treatment by 22 schizophrenic, 13 schizoaffective, 36 depressed, and 34 manic patients to measure concurrent validity andvantages of the ASRM over other self-rating mania scales are discussed.

Journal ArticleDOI
TL;DR: It is found that chromatin is free to undergo substantial Brownian motion, but that a given chromatin segment is confined to a subregion of the nucleus, which leads to a model for the regulation of chromosome interactions by nuclear architecture.

Journal ArticleDOI
TL;DR: The authors describe social cognition and differentiate it from nonsocial cognition and describe the potential implications of a social-cognitive model of schizophrenia for the etiology and development of the disorder.
Abstract: The study of social cognition in schizophrenia may augment the understanding of clinical and behavioral manifestations of the disorder. In this article, the authors describe social cognition and differentiate it from nonsocial cognition. They garner evidence to support the role of social cognition in schizophrenia: Nonsocial information-processing models are limited to explain social dysfunction in schizophrenia, measures of social cognition may contribute greater variance to social functioning than measures of nonsocial cognition, task performance on nonsocial-cognitive measures may not parallel performance on social-cognitive tasks, and symptomatology may be best understood within a social-cognitive framework. They describe the potential implications of a social-cognitive model of schizophrenia for the etiology and development of the disorder.

Book
01 Jan 1997
TL;DR: Detailed case studies for each of the major neural network approaches and architectures with the theories are presented, accompanied with complete computer codes and the corresponding computed results.
Abstract: The book should serve as a text for a university graduate course or for an advanced undergraduate course on neural networks in engineering and computer science departments. It should also serve as a self-study course for engineers and computer scientists in the industry. Covering major neural network approaches and architectures with the theories, this text presents detailed case studies for each of the approaches, accompanied with complete computer codes and the corresponding computed results. The case studies are designed to allow easy comparison of network performance to illustrate strengths and weaknesses of the different networks.

Book
01 Mar 1997
TL;DR: In this article, an integrated treatment of the theory of nonnegative matrices and some related classes of positive matrices, concentrating on connections with game theory, combinatorics, inequalities, optimisation and mathematical economics is presented.
Abstract: This book provides an integrated treatment of the theory of nonnegative matrices (matrices with only positive numbers or zero as entries) and some related classes of positive matrices, concentrating on connections with game theory, combinatorics, inequalities, optimisation and mathematical economics. The wide variety of applications, which include price fixing, scheduling and the fair division problem, have been carefully chosen both for their elegant mathematical content and for their accessibility to students with minimal preparation. Many results in matrix theory are also presented. The treatment is rigorous and almost all results are proved completely. These results and applications will be of great interest to researchers in linear programming, statistics and operations research. The minimal prerequisites also make the book accessible to first-year graduate students.

Journal ArticleDOI
TL;DR: A proposal is put forth to create a cancer chemoprevention drug formulation for utilization on a widespread basis by the general population, and the composition of the formulation should improve over time.

Journal ArticleDOI
TL;DR: This work focuses on Alterations in 24-h Rhythmicity of Glucose Regulation in Non-Insulin-Dependent Diabetes Mellitus (NIDDM) and its implications on diabetes Mellitus patients and the role of sleep and time of day in the regulation of glucose levels.
Abstract: I. Introduction II. Characteristics and Causal Mechanisms of 24-h Rhythms of Glucose Regulation in Normal Young Subjects A. 24-h variations in glucose tolerance B. Causal mechanisms III. Alterations of 24-h Rhythms of Glucose Regulation in Normal Aging A. Daytime variations in glucose tolerance B. Nighttime variations in glucose tolerance C. Respective roles of sleep and time of day D. Significance and clinical implications IV. Diurnal Variations of Glucose Regulation in Obesity A. Daytime variations in glucose tolerance B. Nighttime variations in glucose tolerance C. Significance and clinical implications V. Alterations in 24-h Rhythmicity of Glucose Regulation in Non-Insulin-Dependent Diabetes Mellitus (NIDDM) A. Alterations in daytime variations in glucose tolerance B. Alterations in nighttime variations in glucose levels during fasting C. Significance and clinical implications VI. Alterations in 24-h Rhythmicity of Glucose Regulation in Insulin-Dependent Diabetes Mellitus (IDDM) A. Alterations in dayt...

Journal ArticleDOI
TL;DR: In perinatally infected infants, HIV-1 RNA levels are high and decline only slowly during the first two years of life, which suggests that early treatment with antiretroviral agents may be indicated for these infants.
Abstract: Background There are only limited data on human immunodeficiency virus type 1 (HIV-1) RNA in perinatally infected infants. Understanding the dynamics of HIV-1 infection and its relation to disease progression may help identify opportunities for effective antiviral treatment in infected infants. Methods We obtained plasma samples from 106 HIV-infected infants at birth; at 1, 2, 4, 6, 9, 12, 15, and 18 months of age; and subsequently every 6 months. HIV-1 RNA was assayed by means of a reverse-transcription polymerase chain reaction. The infants were born between 1990 and 1993, and only 21 percent of the infants' mothers received any treatment with zidovudine during pregnancy. Results Plasma HIV-1 RNA levels increased rapidly after birth, peaked at 1 to 2 months of age (median values at 1 and 2 months, 318,000 and 256,000 copies per milliliter, respectively), and then slowly declined to a median of 34,000 copies per milliliter at 24 months. Newborns with a first positive HIV-1 culture within 48 hours after b...

Journal ArticleDOI
TL;DR: The ability of the beta-cell to appropriately detect and respond to an oscillatory glucose infusion improved significantly after troglitazone treatment; the normalized spectral power for the insulin secretion rate increased to 5.9 +/- 1.1 and the marked reduction in PAI-1 could be expected to improve the fibrinolytic response to thrombosis in these subjects.
Abstract: Women with polycystic ovary syndrome (PCOS) are characterized by defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis. We administered the insulin-sensitizing agent troglitazone to 13 obese women with PCOS and impaired glucose tolerance to determine whether attenuation of hyperinsulinemia ameliorates these defects. All subjects had oligomenorrhea, hirsutism, polycystic ovaries, and hyperandrogenemia. Before and after treatment with troglitazone (400 mg daily for 12 weeks), all had 1) a GnRH agonist (leuprolide) test, 2) a 75-g oral glucose tolerance test, 3) a frequently sampled iv glucose tolerance test to determine the insulin sensitivity index and the acute insulin response to glucose, 4) an oscillatory glucose infusion to assess the ability of the β-cell to entrain to glucose as quantitated by the normalized spectral power for the insulin secretion rate, and 5) measures of fibrinolytic capacity[ plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen ac...

Journal ArticleDOI
TL;DR: With the use of an external, adjustable, rigid distraction device, this technique can now treat patients with severe maxillary hypoplasia with a precise and controlled distraction process, obtaining predictable results.
Abstract: We present our technique for maxillary distraction osteogenesis in patients with severe maxillary hypoplasia. With the use of an external, adjustable, rigid distraction device, we can now treat patients with severe maxillary hypoplasia with a precise and controlled distraction process, obtaining predictable results. This technique has allowed us to treat patients in all age groups. In this report we review our indications for maxillary distraction and describe our technique using an external, adjustable, rigid midface distraction device.

Journal ArticleDOI
01 Oct 1997-Genetics
TL;DR: It is hypothesized that in addition to the [PSI+] prion-determining domain in the Sup35p N-terminus, there is another self-propagating conformational determinant in the C-proximal part of Sup 35p and that this second prion is responsible for the Pin+ phenotype.
Abstract: It has previously been shown that yeast prion [PSI + ] is cured by GuHCl, although reports on reversibility of curing were contradictory. Here we show that GuHCl treatment of both [PSI + ] and [psi – ] yeast strains results in two classes of [psi – ] derivatives: Pin + , in which [PSI + ] can be reinduced by Sup35p overproduction, and Pin – , in which overexpression of the complete SUP35 gene does not lead to the [PSI + ] appearance. However, in both Pin + and Pin – derivatives [PSI + ] is reinduced by overproduction of a short Sup35p N-terminal fragment, thus, in principle, [PSI + ] curing remains reversible in both cases. Neither suppression nor growth inhibition caused by SUP35 overexpression in Pin + [psi – ] derivatives are observed in Pin – [psi – ] derivatives. Genetic analyses show that the Pin + phenotype is determined by a non-Mendelian factor, which, unlike the [PSI + ] prion, is independent of the Sup35p N-terminal domain. A Pin – [psi – ] derivative was also generated by transient inactivation of the heat shock protein, Hsp104, while [PSI + ] curing by Hsp104 overproduction resulted exclusively in Pin + [psi – ] derivatives. We hypothesize that in addition to the [PSI + ] prion-determining domain in the Sup35p N-terminus, there is another self-propagating conformational determinant in the C-proximal part of Sup35p and that this second prion is responsible for the Pin + phenotype.

Journal ArticleDOI
TL;DR: DNA shuffling can improve the function of pathways by complex and unexpected mutational mechanisms that may be activated by point mutation, and are likely to be overlooked by rational design.
Abstract: Functional evolution of an arsenic resistance operon has been accomplished by DNA shuffling, involving multiple rounds of in vitro recombination and mutation of a pool of related sequences, followed by selection for increased resistance in vivo. Homologous recombination is achieved by random fragmentation of the PCR templates and reassembly by primerless PCR. Plasmid-determined arsenate resistance from plasmid pI258 encoded by genes arsR, arsE, and arsC was evolved in Escherichia coli. Three rounds of shuffling and selection resulted in cells that grew in up to 0.5 M arsenate, a 40-fold increase in resistance. Whereas the native plasmid remained episomal, the evolved operon reproducibly integrated into the bacterial chromosome. In the absence of shuffling, no increase in resistance was observed after four selection cycles, and the control plasmid remained episomal. The integrated ars operon had 13 mutations. Ten mutations were located in arsB, encoding the arsenite membrane pump, resulting in a fourfold to sixfold increase in arsenite resistance. While arsC, the arsenate reductase gene, contained no mutations, its expression level was increased, and the rate of arsenate reduction was increased 12–fold. These results show that DNA shuffling can improve the function of pathways by complex and unexpected mutational mechanisms that may be activated by point mutation. These mechanisms may be difficult to explain and are likely to be overlooked by rational design.

Journal ArticleDOI
TL;DR: An algorithm for dynamic replication of an object in distributed systems is presented and it is shown that the algorithm can be combined with the concurrency control and recovery mechanisms of ta distributed database management system.
Abstract: This article addresses the performance of distributed database systems. Specifically, we present an algorithm for dynamic replication of an object in distributed systems. The algorithm is adaptive in the sence that it changes the replication scheme of the object i.e., the set of processors at which the object inreplicated) as changes occur in the read-write patern of the object (i.e., the number of reads and writes issued by each processor). The algorithm continuously moves the replication scheme towards an optimal one. We show that the algorithm can be combined with the concurrency control and recovery mechanisms of ta distributed database management system. The performance of the algorithm is analyzed theoretically and experimentally. On the way we provide a lower bound on the performance of any dynamic replication algorith.

Journal ArticleDOI
TL;DR: A theoretical model articulating cognitive theory and sources of potential response bias resulting from racial or ethnic cultural experience to survey questions that deal with health behavior is described, suggesting several ways in which the validity of questions about risk behavior can be improved.

Journal ArticleDOI
TL;DR: It is concluded that the List fulfills the functions of a community, with future concerns about information control and the potential to enhance patient-provider understanding.
Abstract: Using participant-observation and discourse analysis, this study explores the communication occurring on the Breast Cancer List, an on-line discussion group which continues to grow in membership and activity. Issues discussed include the evolution of the List, who participates, what topics are discussed. Three major dimensions are identified: exchange of information, social support, and personal empowerment. Social support via computer is compared with face-to-face groups. Empowerment centers on enhanced decision-making and preparation for new illness-related experiences. The influence of gender is considered in terms of communicative style and limitations of access. It is concluded that the List fulfills the functions of a community, with future concerns about information control and the potential to enhance patient-provider understanding.

Journal ArticleDOI
TL;DR: Investigation of the relation between depressive symptoms and treatment response in acute manic episodes suggests that even a modest level of pretreatment depression-related symptoms is a robust predictor of lithium nonresponse, and is associated with better response to divalproex.
Abstract: Background: Little information exists from controlled studies about clinical characteristics that predict treatment response in mania. The presence of depressive symptoms during manic episodes may be associated with poor response to psychopharmacological treatments. This is an investigation of the relation between depressive symptoms and treatment response in acute manic episodes. Methods and Design: In a parallel-group, doubleblind study, 179 patients hospitalized for acute manic episodes were randomized to receive divalproex sodium, lithium carbonate, or placebo (ratio, 2:1:2). The study was carried out at 9 academic medical centers. Patients had comprehensive evaluations of behavior and symptoms before and during 3 weeks of treatment. The primary outcome measure, change in mania factor scores derived from the Schedule for Affective Disorders and Schizophrenia: Change Version, was compared in pa- tients with and without depressive symptoms at baseline according to nurse- or physician-rated scales. Results: Depressive symptoms were associated with poor antimanic response to lithium and with better response to divalproex. This was not due to differences in overall severity of illness, substance abuse, gender, age, or history. Conclusions: These data suggest that even a modest level of pretreatment depression-related symptoms is a robust predictor of lithium nonresponse, and is associated with better response to divalproex. Although their overall efficacy in acute mania is similar, lithium and divalproex may be most effective in clinically and biologically distinct groups of patients.