Showing papers by "University of Illinois at Chicago published in 1993"

The effect of deleterious mutations on neutral molecular variation.

Abstract: Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral sites. This is because a new neutral variant can only remain in a large population for a long period of time if it is maintained in gametes that are free of deleterious alleles, and hence are not destined for rapid elimination from the population by selection. Approximate formulas are derived for the reduction below classical neutral values resulting from such background selection against deleterious mutations, for the mean times to fixation and loss of new mutations, nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a given selection regime and mating system, the reduction is an exponential function of the total mutation rate to deleterious mutations for the section of the genome involved. Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of outcrossing. The mean time to loss of new neutral mutations and the total number of segregating neutral sites are less sensitive to background selection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical neutral result. Observed reductions in molecular variation in low recombination genomic regions of sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in highly selfing plant populations, may be partly due to background selection against deleterious mutations.

A longitudinal study on the early development of leader-member exchanges.

Abstract: The authors investigated the first 6 months that 166 newly hired employees and their immediate supervisors worked together. Expectations, perceived similarity, liking, demographic similarity, and performance were examined as determinants of leader-member exchanges (LMXs). Leader and member expectations of each other assessed in the first 5 days in the life of the dyad predicted LMXs at 2 weeks and at 6 weeks following the 1st day of the dyads' existence. Member expectations of leaders also predicted LMXs at 6 months. Following nearly the same pattern, perceived similarity and liking from both the leaders'and members' perspectives predicted LMXs at most time periods. Demographic similarity between leaders and members had no significant effects on LMX development, and subordinate performance ratings were relatively less important in predicting LMX than were affective variables

The Syndromes of Resistance to Thyroid Hormone

Abstract: I. Introduction THE syndromes of resistance to thyroid hormone are characterized by reduced clinical and biochemical manifestations of thyroid hormone action relative to the circulating hormone levels. In practice, most patients are identified by the persistent elevation of serum levels of T4 and T3 with “inappropriately” nonsuppressed TSH, in the absence of intercurrent acute illness, drugs, or alterations of thyroid hormone binding to serum proteins. More importantly, administration of supraphysiological doses of thyroid hormone fail to produce the expected suppressive effect on the secretion of pituitary TSH and/or to induce the expected metabolic responses in the peripheral tissues. Since the publication of the index cases in 1967 (1), 347 subjects have been reported who exhibit the characteristics of the syndrome (Refs. 1–129 and our personal communications and observations). In this review, we summarize all cases known to us, present their common features as well as unusual manifestations, and attem...

The 2.2 A crystal structure of transducin-alpha complexed with GTP gamma S.

Abstract: The 2.2 A crystal structure of activated rod transducin, Gtα-GTPγS, shows the bound GTPγS molecule occluded deep in a cleft between a domain structurally homologous to small GTPases and a helical domain unique to heterotrimeric G proteins. The structure, when combined with biochemical and genetic studies, suggests: how an activated receptor might open this cleft to allow nucleotide exchange; a mechanism for GTP-induced changes in effector and receptor binding surfaces; and a mechanism for GTPase activity not evident from previous data.

Joint Estimation of Model Parameters and Outlier Effects in Time Series

Abstract: Time series data are often subject to uncontrolled or unexpected interventions, from which various types of outlying observations are produced. Outliers in time series, depending on their nature, may have a moderate to significant impact on the effectiveness of the Standard methodology for time series analysis with respect to model identification, estimation, and forecasting. In this article we use an iterative outlier detection and adjustment procedure to obtain joint estimates of model parameters and outlier effects. Four types of outliers are considered, and the issues of spurious and masking effects are discussed. The major differences between this procedure and those proposed in earlier literature include (a) the types and effects of outliers are obtained based on less contaminated estimates of model parameters, (b) the outlier effects are estimated simultaneously using multiple regression, and (c) the model parameters and the outlier effects are estimated jointly. The sampling behavior of the test s...

A population-based study of dementia in 85-year-olds.

Abstract: Background The aim of this study was to investigate the causes, severity, and prevalence of dementia in a representative sample of 494 85-year-olds living in Gothenburg, Sweden. Methods The study included a psychiatric interview, neuropsychological and physical examinations, comprehensive laboratory tests, electrocardiography, chest radiography, computed tomography (CT) of the head, and analysis of cerebrospinal fluid. A person close to each subject was also interviewed. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to recently proposed criteria that incorporate information from CT scanning and the patient's neurologic history. Results The prevalence of dementia was 29.8 percent (147 subjects...

A Twin Study of Genetic and Environmental Contributions to Liability for Posttraumatic Stress Symptoms

Abstract: • We studied 4042 Vietnam era veteran monozygotic and dizygotic male twin pairs to determine the effects of heredity, shared environment, and unique environment on the liability for 15 self-reported posttraumatic stress disorder symptoms included in the symptom categories of reexperiencing the trauma, avoidance of stimuli related to the trauma, and increased arousal. Quantitative genetic analysis reveals that inheritance has a substantial influence on liability for all symptoms. Symptoms in the reexperiencing cluster and one symptom in the avoidance and numbing cluster are strongly associated with combat exposure, and monozygotic pairs are more highly concordant for combat exposure than dizygotic pairs. By fitting a bivariate genetic model, we show that there are significant genetic influences on symptom liability, even after adjusting for differences in combat exposure; genetic factors account for 13% to 30% of the variance in liability for symptoms in the reexperiencing cluster, 30% to 34% for symptoms in the avoidance cluster, and 28% to 32% for symptoms in the arousal cluster. There is no evidence that shared environment contributes to the development of posttraumatic stress disorder symptoms.

What’s Wrong with Empowerment

Abstract: Although it has stimulated useful and important research and theory in community psychology, the concept of empowerment is problematic. This article criticizes two assumptions and values underlying the concept of empowerment: (a) individualism, leading potentially to unmitigated competition and conflict among those who are empowered; and (b) a preference for traditionally masculine concepts of mastery, power, and control over traditionally feminine concerns of communion and cooperation. The challenge to community psychology is to develop a vision that incorporates both empowerment and community, despite the paradoxical nature of these two phenomena.

Automatic and effortful processing in depression.

Abstract: Automatic processes require few attentional resources, but effortful processes use attentional capacity. Research on cognitive processing by depressed individuals is reviewed and the following is concluded: (a) Depression interferes with effortful processing. The degree of interference is determined by the degree of effortfulness of the task, the severity of depression, and the valence of the stimulus material to be processed. (b) Depression interferes only minimally with automatic processes. Hypothetical causal mechanisms for interference in effortful processes by depression, whether interference in effortful processing is unique to depression or characteristic of psychopathology in general, and whether negative automatic thoughts are associated with current depression or depression proneness are also addressed. The effortful-automatic perspective has implications for understanding depressive clinical features, treating depression, and conducting future research.

Religion as a Determinant of Marital Stability

Abstract: This paper develops hypotheses about the effects of husbands’ and wives’ religious affiliations on fertility. The hypotheses are based on two central ideas. First, religions differ in their fertility norms and corresponding tradeoffs between the quality and quantity of children; differences in religious beliefs between husband and wife may thus lead to conflict regarding fertility decisions and possible resolution through bargaining. Second, a low level of religious compatibility between the spouses may raise the expected probability of marital dissolution and thereby decrease the optimal amount of investments in spouse-specific human capital. Analyses of data from the 1987—1988 National Survey of Families and Households conducted in the United States suggest that both of these effects play important roles in explaining the observed linkages between the religious composition of unions and fertility behavior.

Community violence and children on Chicago's southside

Abstract: This report summarizes a program of study on African-American children and violence conducted by a comprehensive community mental health center on the southside of Chicago. The research, which looked at exposure to violence, self-reports of aggression, and possible interventions, grew out of: (1) an awareness of the enormous amount of familial and extrafamilial violence in the black community; (2) clinical experiences that indicated that victimization and covictimization (i.e., victimization of close others) were often significant factors in the lives of the mentally ill; (3) a growing uneasiness, and indeed curiosity, over the extent to which children were witnessing these events and the impact of this witnessing, particularly on their own levels of aggression; and (4) a belief that the integrity of the black community was being threatened by the violence and that solutions must be sought.

Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage.

Abstract: In Saccharomyces cerevisiae, telomeres repress transcription of genes located nearby. This region-specific gene inactivation is thought to involve the packaging of telomeric domains into silent chromatin. To gain insight into the mechanism of telomeric silencing, a genetic assay to examine the spread of silencing along the distal right arm of chromosome V was developed. The frequency of silencing a telomere-adjacent URA3 gene decreased with increasing distance of the gene's promoter from the telomere, irrespective of transcriptional orientation. The distance over which telomeric silencing of URA3 was observed was extended by weakening the gene's promoter--specifically, by deleting PPR1, the trans-activator of URA3. The silent telomeric domain was extended even farther by increasing the gene dosage of SIR3. These results suggest that a gene's promoter is a key determinant in controlling silencing on that gene and that SIR3 is a crucial component of the silent chromatin domain that initiates at the telomere and is assembled inwardly along the yeast chromosome. Finally, silencing is not observed on the centromeric side of an actively transcribed telomeric gene, demonstrating that the repressed telomeric domain is propagated continuously along the DNA. Taken together, these data reflect the complex and dynamic organization of eukaryotic genomes into functionally distinct regions.

Lacunarity indices as measures of landscape texture

Abstract: Lacunarity analysis is a multi-scaled method of determining the texture associated with patterns of spatial dispersion (i.e., habitat types or species locations) for one-, two-, and three-dimensional data. Lacunarity provides a parsimonious analysis of the overall fraction of a map or transect covered by the attribute of interest, the degree of contagion, the presence of self-similarity, the presence and scale of randomness, and the existence of hierarchical structure. For self-similar patterns, it can be used to determine the fractal dimension. The method is easily implemented on the computer and provides readily interpretable graphic results. Differences in pattern can be detected even among very sparsely occupied maps.

Symmetry and Model Checking

Abstract: We show how to exploit symmetry in model checking for concurrent systems containing many identical or isomorphic components. We focus in particular on those composed of many isomorphic processes. In many cases we are able to obtain significant, even exponential, savings in the complexity of model checking.

The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene

Abstract: Modification of specific intracellular proteins by ubiquitin targets them for degradation We describe a yeast enzyme, Doa4, that is integral to the degradation of ubiquitinated proteins and is required in diverse physiological processes Doa4 appears to function late in the proteolytic pathway by cleaving ubiquitin from substrate remnants still bound to protease The human tre-2 oncogene encodes a deubiquitinating enzyme similar to Doa4, indicating a role for the ubiquitin system in mammalian growth control

The Effects of Leader-Member Exchange on Employee Citizenship and Impression Management Behavior

Abstract: A field study was conducted to examine the relationship between leader-member exchange (LMX) and two types of employee behavior: citizenship behavior and impression management. One form of citizenship behavior, altruism, and one form of impression management, other-focused were significantly related to LMX. Implications of the results are discussed.

Induction of Multidrug Resistance in Human Cells by Transient Exposure to Different Chemotherapeutic Drugs

Abstract: BACKGROUND The MDR1 (multidrug resistance) gene (also known as PGY1), which encodes the transmembrane efflux pump P-glycoprotein (Pgp), confers resistance to Pgp-transported cytotoxic drugs in tissue culture. The increase in MDR1 expression in tumors after chemotherapy is usually attributed to selection of pre-existing multidrug-resistant cells by Pgp-transported drugs. MDR1 expression in tissue culture can be increased by several types of stress-inducing treatment, including agents that activate protein kinase C (PKC). Previous studies, however, failed to demonstrate that short-term exposure to any chemotherapeutic drug can induce the expression of the resident MDR1 gene in drug-sensitive human cells. PURPOSE This study was designed to utilize highly sensitive assays to determine if transient exposure to chemotherapeutic drugs would have an effect on MDR1 expression in human cells and to assess if PKC inhibitors would influence such an effect. METHODS We analyzed the MDR1 gene expression in several human cell lines derived from leukemias or solid tumors, after treatment with different cytotoxic drugs, in the presence or absence of PKC inhibitors. Pgp function and expression were studied by flow cytometric assays, and MDR1 messenger RNA (mRNA) was assayed by polymerase chain reaction. RESULTS Transient exposure to chemotherapeutic drugs, including agents that are not transported by Pgp, induced Pgp and MDR1 mRNA expression in subpopulations of treated cells in most of the tested cell lines. This induction was observed along with microscopically detectable cell damage. The drug-induced MDR1 expression and the associated twofold to threefold increase in resistance to vinblastine were sustained in K562 leukemia cells for at least several weeks after the removal of the drug. Drug-mediated MDR1 induction was blocked by nonspecific protein kinase inhibitors that are active against PKC, but not by a protein kinase inhibitor ineffective against PKC. CONCLUSIONS Expression of the human MDR1 mRNA and Pgp can be induced in response to cellular damage by cytotoxic drugs regardless of whether the drugs are transported by Pgp. This induction can be prevented by protein kinase inhibitors. IMPLICATIONS Induction of MDR1 expression in response to cellular damage may account for increased MDR1 expression in treated human tumors. Protein kinase inhibitors may be useful in preventing the emergence of multidrug resistance during cancer chemotherapy.

Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a multidrug efflux transporter.

Abstract: The gene of the Staphylococcus aureus fluoroquinolone efflux transporter protein NorA confers resistance to a number of structurally dissimilar drugs, not just to fluoroquinolones, when it is expressed in Bacillus subtilis. NorA provides B. subtilis with resistance to the same drugs and to a similar extent as the B. subtilis multidrug transporter protein Bmr does. NorA and Bmr share 44% sequence similarity. Both the NorA- and Bmr-conferred resistances can be completely reversed by reserpine.

Cloning and expression of a human Ah receptor cDNA

Abstract: In this report, we describe the cloning and expression of a cDNA encoding a human Ah receptor, a basic/helix-loop-helix protein that mediates the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin. A comparison of this human cDNA with a murine homologue (Ahb1 allele) indicates that the molecular mass variation observed between the receptors found in these two species results from hypervariability of amino acid sequences in the carboxyl termini (< 60% conserved over 450 amino acids). Differential usage of stop codons generates proteins with molecular masses that differ by 6 kDa. In contrast, the amino-terminal halves of these proteins are highly conserved and show 90% amino acid sequence identity. Northern blot analysis indicates that the human Ah receptor mRNA is expressed at its highest levels in placenta and is also highly expressed in lung, heart, pancreas, and liver, with lower levels of expression found in brain, kidney, and skeletal muscle. Expression of the human cDNA in a rabbit reticulocyte lysate system allowed functional analysis of ligand binding, agonist-induced and Ah receptor nuclear translocator-dependent DNA binding, and receptor stabilization by sodium molybdate.

Measuring Normative Beliefs and Shared Behavioral Expectations in Organizations: The Reliability and Validity of the Organizational Culture Inventory:

Abstract: The Organizational Culture Inventory measures 12 sets of normative beliefs or shared behavioral expectations associated with three general types of cultures, Constructive, Passive-Defensive, and Ag...

Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53

Abstract: The p53 protein is apparently central to the development of human cancers because both alleles are often found to be mutated in different tumour types. In addition, wild-type p53 can inhibit transformation by viral and cellular oncogenes in vitro, so p53 has been classified as a tumour suppressor. Investigations of the normal function of p53 have indicated that at least one of its functions could involve the activation of gene expression through the binding of specific DNA-regulatory sequences. Also, overexpression of p53 can mediate growth arrest and repress transcription from a variety of promoters. We demonstrate here both in vivo and in vitro that expression of wild-type p53 specifically represses the activity of promoters whose initiation is dependent on the presence of a TATA box. Promoters whose accurate transcription is directed by a pyrimidine-rich initiator element, however, are immune to the effects of p53. Furthermore, we observe that repression is mediated by an interaction of p53 with basal transcription factor(s). Thus, p53 appears to repress the activity of certain promoters through direct communication with TATA box-dependent basal transcription machinery.

Modeling of the deformation of a liquid droplet impinging upon a flat surface

Abstract: This article presents a theoretical study of the deformation of a spherical liquid droplet impinging upon a flat surface. The study accounts for the presence of surface tension during the spreading process. The theoretical model is solved numerically utilizing deforming finite elements and grid generation to simulate accurately the large deformations, as well as the domain nonuniformities characteristic of the spreading process. The results document the effects of impact velocity, droplet diameter, surface tension, and material properties on the fluid dynamics of the deforming droplet. Two liquids with markedly different thermophysical properties, water and liquid tin, are utilized in the numerical simulations because of their relevance in the industrial processes of spray cooling and spray deposition, respectively. The occurrence of droplet recoiling and mass accumulation around the splat periphery are standout features of the numerical simulations and yield a nonmonotonic dependence of the maximum splat radius on time.

On Model-Checking for Fragments of µ-Calculus

Abstract: In this paper we considered two different fragments of μ-calculus, logics L1 and L2 We gave model checking algorithms for logics L1 and L2 which are of complexity O(m2n) where m is the length of the formula and n is the size of the structure We have shown that the logic L2 is as expressive as ECTL* given in [13] In additions to these results, we have shown that the model checking problem for the μ-calculus is equivalent to the non-emptiness problem of parity tree automata

Numerical integration of ordinary differential equations on manifolds

Abstract: This paper is concerned with the problem of developing numerical integration algorithms for differential equations that, when viewed as equations in some Euclidean space, naturally evolve on some embedded submanifold. It is desired to construct algorithms whose iterates also evolve on the same manifold. These algorithms can therefore be viewed as integrating ordinary differential equations on manifolds. The basic method “decouples” the computation of flows on the submanifold from the numerical integration process. It is shown that two classes of single-step and multistep algorithms can be posed and analyzed theoretically, using the concept of “freezing” the coefficients of differential operators obtained from the defining vector field. Explicit third-order algorithms are derived, with additional equations augmenting those of their classical counterparts, obtained from “obstructions” defined by nonvanishing Lie brackets.

Consequences of Intravascular Catheter Sepsis

Abstract: Intravascular (IV) catheter sepsis is a widely recognized complication of IV therapy or monitoring, but little emphasis has been placed on the morbidity and cost associated with this infection. To assess the consequences of IV catheter sepsis, we examined the medical records of 94 patients with 102 episodes of IV catheter sepsis due to percutaneously inserted catheters. Major complications occurred in 33 (32%) of the episodes and included septic shock (12 episodes), sustained sepsis (12), suppurative thrombophlebitis (7), metastatic infection (5), endocarditis (2), and arteritis (2). One patient died due to sepsis, and hospital stay was clearly prolonged in 15 episodes. The risk of major complications was highest in episodes of IV catheter sepsis caused by Candida, Pseudomonas aeruginosa, Staphylococcus aureus, or multiple pathogens, and the most severe complications were usually caused by S. aureus. The hospital cost of IV catheter sepsis was assessed by reviewing medical and billing records to identify extra medical care and then multiplying charges for that care by the appropriate cost-to-charge ratio. The average cost per episode, adjusted to 1991 dollars, was $3,707 for all episodes and $6,064 for episodes caused by S. aureus. The morbidity and cost associated with IV catheter sepsis warrant substantial efforts to minimize the incidence of this complication and especially to prevent cases due to S. aureus.