Showing papers by "University of Southern California published in 1989"

Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.

Abstract: Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.

An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis

Abstract: A specific assay has been developed for a blood-borne non-A, non-B hepatitis (NANBH) virus in which a polypeptide synthesized in recombinant yeast clones of the hepatitis C virus (HCV) is used to capture circulating viral antibodies. HCV antibodies were detected in six of seven human sera that were shown previously to transmit NANBH to chimpanzees. Assays of ten blood transfusions in the United States that resulted in chronic NANBH revealed that there was at least one positive blood donor in nine of these cases and that all ten recipients seroconverted during their illnesses. About 80 percent of chronic, post-transfusion NANBH (PT-NANBH) patients from Italy and Japan had circulating HCV antibody; a much lower frequency (15 percent) was observed in acute, resolving infections. In addition, 58 percent of NANBH patients from the United States with no identifiable source of parenteral exposure to the virus were also positive for HCV antibody. These data indicate that HCV is a major cause of NANBH throughout the world.

Evolution and revolution as organizations grow. 1972.

Abstract: A small research company chooses too complicated and formalized an organization structure for its young age and limited size. It flounders in rigidity and bureaucracy for several years and is finally acquired by a larger company.

We Acquire Vocabulary and Spelling by Reading: Additional Evidence for the Input Hypothesis

Abstract: attention to vocabulary and spelling.' First, there are practical reasons. A large vocabulary is, of course, essential for mastery of a language. Second language acquirers know this; they carry dictionaries with them, not grammar books, and regularly report that lack of vocabulary is a major problem. Spelling, especially for treacherous languages such as English, is also a problem. Our standards in spelling are 100%; a single spelling error in public can mean humiliation. On the theoretical level, the study of the acquisition of vocabulary and spelling ability can help us understand language acquisition in general. In my view, the most promising hypothesis is that vocabulary and spelling are acquired in fundamentally the same way the rest of language is acquired. If this supposition is true, these areas can be useful laboratories for the

Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach.

Abstract: Glucose tolerance depends on a complex interaction among insulin secretion from the beta-cells, clearance of the hormone, and the actions of insulin to accelerate glucose disappearance and inhibit endogenous glucose production. An additional factor, less well recognized, is the ability of glucose per se, independent of changes in insulin, to increase glucose uptake and suppress endogenous output (glucose effectiveness). These factors can be measured in the intact organism with physiologically based minimal models of glucose utilization and insulin kinetics. With the glucose minimal model, insulin sensitivity (SI) and glucose effectiveness (SG) are measured by computer analysis of the frequently sampled intravenous glucose tolerance test. The test involves intravenous injection of glucose followed by tolbutamide or insulin and frequent blood sampling. SI varied from a high of 7.6 x 10(-4) min-1.microU-1.ml-1 in young Whites to 2.3 x 10(-4) min-1.microU-1.ml-1 in obese nondiabetic subjects; in all of the nondiabetic subjects, SG was normal. In subjects with non-insulin-dependent diabetes mellitus (NIDDM), not only was SI reduced 90% below normal (0.61 +/- 0.16 x 10(-4) min-1.microU-1.ml-1), but in this group alone, SG was reduced (from 0.026 +/- 0.008 to 0.014 +/- 0.002 min-1); thus, defects in SI and SG are synergistic in causing glucose intolerance in NIDDM. One assumption of the minimal model is that the time delay in insulin action on glucose utilization in vivo is due to sluggish insulin transport across the capillary endothelium. This was tested by comparing insulin concentrations in plasma with those in lymph (representing interstitial fluid) during euglycemic-hyperinsulinemic glucose clamps. Lymph insulin was lower than plasma insulin at basal (12 vs. 18 microU/ml) and at steady state, indicating significant loss of insulin from the interstitial space, presumably due to cellular uptake of the insulin-receptor complex. Additionally, during clamps, lymph insulin changed more slowly than plasma insulin, but the rate of glucose utilization followed a time course identical with that of lymph (r = .96) rather than plasma (r = .71). Thus, lymph insulin, which may be reflective of interstitial fluid, is the signal to which insulin-sensitive tissues are responding. These studies support the concept that, at physiological insulin levels, the time for insulin to cross the capillary endothelium is the process that determines the rate of insulin action in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Consumer Resistance to Innovations: The Marketing Problem and its solutions

Abstract: Considers why customers resist innovations even though they are considered necessary and desirable. Identifies functional barriers such as usage, value, and risk, and psychological barriers such as tradition and image. Concludes that successful innovation lies not in bowing down to consumer resistance, but in understanding the causes and developing a marketing strategy to attack them.

Relative Performance Evaluation for Chief Executive Officers

Abstract: Measured individual performance often depends on random factors which also affect the performances of other workers in the same firm, industry, or market. In these cases, relative performance evaluation (RPE) can provide incentives while partially insulating workers from the common uncertainty. Basing pay on relative performance, however, generates incentives to sabotage the measured performance of co-workers, to collude with co-workers and shirk, and to apply for jobs with inept co-workers. RPE contracts also are less desirable when the output of co-workers is expensive to measure or in the presence of production externalities, as in the case of team production. The purpose of this paper is to review the benefits and costs of RPE and to test for the presence of RPE in one occupation where the benefits plausibly exceed the costs: chief executive officers (CEOs). In contrast to previous research, our empirical evidence strongly supports the RPE hypothesis-CEO pay revisions and retention probabilities are positively and significantly related to firm performance, but are negatively and significantly related to industry and market performance, ceteris paribus. Our results also suggest that CEO performance is more likely to be evaluated relative to aggregate market movements than relative to industry movements.

Tumor necrosis factor identified in multiple sclerosis brain.

Abstract: Frozen brain specimens from patients with multiple sclerosis (MS) and other neurologic diseases were analyzed using immunocytochemical techniques for the presence of TNF In brain lesions in MS, and subacute sclerosing panencephalitis, TNF+ cells were demonstrated At the lesion site in MS, TNF+ staining is associated with both astrocytes and macrophages These observations were not made in Alzheimer's disease or normal brain tissue The presence of TNF in MS lesions suggests a significant role for cytokines and the immune response in disease progression

Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons

Abstract: We estimated the prevalences of Helicobacter pylori (formerly called Campylobacter pylori) infection and histologic gastritis in 113 asymptomatic persons, using endoscopic biopsy of the gastric antrum and corpus. Unsuspected lesions, mainly mucosal erosions, were revealed at endoscopy in 16 subjects (14 percent). Gastritis was found in 42 subjects (37 percent), of whom 36 (32 percent of the total) were found to be infected with H. pylori on the basis of hematoxylin-eosin staining. H. pylori was not found in any of the 71 subjects with normal histologic features. Gastritis and H. pylori were noted in both the antrum and corpus in 75 percent of those infected (n = 27). The prevalence of H. pylori infection increased from 10 percent (2 of 20 subjects) in those between the ages of 18 and 29, to 47 percent (7 of 15) in those between the ages of 60 and 69, but the effect of age did not reach statistical significance. The prevalence of gastritis increased significantly with advancing age. Stepwise logistic regression analysis revealed that the relative risk for H. pylori infection associated with recent (within six months) antibiotic use was 5.8 (95 percent confidence interval, 1.5 to 22.1), whereas the relative risk was 6.5 (95 percent confidence interval, 1.4 to 29.2) for those who had never used bismuth compounds. We conclude that histologic gastritis and H. pylori infection commonly occur in the stomach of apparently normal persons and increase in prevalence with advancing age. All the subjects with H. pylori infection had gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion.

Chief executive compensation: A study of the intersection of markets and political processes

Abstract: A model of the determinants of chief executive (CEO) compensation is presented and tested. Based on a sample from the leisure industry, the study finds that CEO pay has complex links to several factors: firm size, complexity, performance, CEO power, board vigilance, and the CEO's human capital. The study includes a separate examination of CEO salary and bonus, as well as a test of pay determination across McEachern's (1975) ownership categories.

Sparks and prairie fires: A theory of unanticipated political revolution

Abstract: A feature shared by certain major revolutions is that they were not anticipated. Here is an explanation, which hinges on the observation that people who come to dislike their government are apt to hide their desire for change as long as the opposition seems weak. Because of this prefer- ence falsification, a government that appears unshakeable might see its support crumble following a slight surge in the opposition's apparent size, caused by events insignificant in and of them- selves. Unlikely though the revolution may have appeared in foresight, it will in hindsight appear inevitable because its occurrence exposes a panoply of previously hidden conflicts.

Styles of stance in English: Lexical and grammatical marking of evidentiality and affect

Abstract: The present paper identifies anddescribes various speech styles of English äs marked by stance. By stance we mean the lexical and grammatical expression of attitudes, feelings, judgments, or commitment concerning the propositional content of a message. In an earlier paper (Biber and Finegan, 1988), we limited our investigation to the adverbial marking of stance; here we extend the analysis to include adjectival, verbal, and modal markers of stance. All occurrences of a large sei of stance markers are identified in 500 texts, drawn principally from the LOB and London-Lund corpora (of written and spoken British English). The stance markers are divided into 12 categories basedon semantic and grammatical criteria, and thefrequency of occurrence for each category in each text is computed. The twelve categories are (1) affect markers (adverbs, verbs, and adjectives); (2) certainty adverbs; (3) certainty verbs; (4) certainty adjectives; (5) doubt adverbs; (6) doubt verbs; (7) doubt adjectives; (8) hedges; (9) emphatics; (10) possibility modals; (11) necessity modals; and (12) predictive modals. Using a statistical technique called düster analysis, texts that are maximally similar in their exploitation of stance markers are sorted into clusters. We Interpret each düster äs a stance style by consideration of the predominant stance jeatwes in the düster, the situational characteristics of the texts constituting the düster, and a functional analysis of individual texts. Overall, six stance styles are identified, among which are 'Emphatic Expression of Affect', 'Expository Expression of Doubt', and 'Faceless'.

A generalized EM algorithm for 3-D Bayesian reconstruction from Poisson data using Gibbs priors

Abstract: A generalized expectation-maximization (GEM) algorithm is developed for Bayesian reconstruction, based on locally correlated Markov random-field priors in the form of Gibbs functions and on the Poisson data model. For the M-step of the algorithm, a form of coordinate gradient ascent is derived. The algorithm reduces to the EM maximum-likelihood algorithm as the Markov random-field prior tends towards a uniform distribution. Three different Gibbs function priors are examined. Reconstructions of 3-D images obtained from the Poisson model of single-photon-emission computed tomography are presented. >

Dealer Dependence Levels and Reciprocal Actions in a Channel of Distribution in a Developing Country

Abstract: The primary purpose of this article is to expand our understanding of the dependence and reciprocal action constructs in distribution channel relationships. The authors develop a conceptual framewo...

A simple method for site-directed mutagenesis using the polymerase chain reaction

Abstract: We have developed a general and simple method for directing specific sequence changes in a plasmid using primed amplification by the polymerase chain reaction (PCR). The method is based on the amplification of the entire plasmid using primers that include the desired changes. The method is rapid, simple in its execution, and requires only minute amounts of plasmid template DNA. It is significant that there are no special requirements for appropriately placed restriction sites in the sequence to be manipulated. In our system the yield of transformants was high and the fraction of them harboring plasmids with only the desired change was consistently about 80%. The generality of the method should make it useful for the direct alteration of most cloned genes. The only limitation may be the total length of the plasmid to be manipulated. During the study we found that the Taq DNA polymerase used for PCR adds on a single extra base (usually an A) at the end of a large fraction of the newly synthesized chains. These had to be removed by the Klenow fragment of DNA polymerase to insure restoration of the gene sequence.

A Schur method for balanced-truncation model reduction

Abstract: It is shown that a not-necessarily-balanced state-space realization of the Moore reduced model can be computed directly without balancing via projections defined in terms of arbitrary bases for the left and right eigenspaces associated with the large eigenvalues of the product PQ of the reachability and controllability Grammians Two specific methods for computing these bases are proposed, one based on the ordered Schur decomposition of PQ and the other based on the Cholesky factors of P and Q The algorithms perform reliably even for nonminimal models >

A Multicommunity Trial for Primary Prevention of Adolescent Drug Abuse: Effects on Drug Use Prevalence

Abstract: The entire early adolescent population of the 15 communities that constitute the Kansas City (Kansas and Missouri) metropolitan area has participated in a community-based program for prevention of drug abuse since September 1984. The Kansas City area is the first of two major metropolitan sites being evaluated in the Midwestern Prevention Project, a longitudinal trial for primary prevention of cigarette, alcohol, and marijuana use in adolescents. The project includes mass media programming, a school-based educational program for youths, parent education and organization, community organization, and health policy components that are introduced sequentially into communities during a 6-year period. Effects of the program are determined through annual assessments of adolescent drug use in schools that are assigned to immediate intervention or delayed intervention control conditions. In the first 2 years of the project, 22 500 sixth- and seventh-grade adolescents received the school-based educational program component, with parental involvement in homework and mass media coverage. Analyses of 42 schools indicate that the prevalence rates of use for all three drugs are significantly lower at 1-year follow-up in the intervention condition relative to the delayed intervention condition, with or without controlling for race, grade, socioeconomic status, and urbanicity (17% vs 24% for cigarette smoking, 11% vs 16% for alcohol use, and 7% vs 10% for marijuana use in the last month), and the net increase in drug use prevalence among intervention schools is half that of delayed intervention schools. (JAMA. 1989;261:3259-3266)

Lymphocytes bearing antigen-specific γδ T-cell receptors accumulate in human infectious disease lesions

Abstract: THE majority of T cells bear the T-cell receptor (TCR) αβ complex which recognizes foreign antigen peptides only in the context of self major histocompatibility complex (MHC) molecules1. Such T cells function in a variety of effector roles and secrete cytokines that mediate the activation and differentiation of other cells in the immune system. Recently, a small subpopulation T cells was found to bear a distinct TCR composed of γ and δ subunits2. In man, TCR γδ+ cells are distributed as ~5 per cent of the CD3+ cells in all organized lymphoid organs as well as in the skin- and gut-associated lymphoid tissues3. Although a limited number of germ-line genes encode the TCR γ and δ subunits, extensive junctional variation particularly in the δ gene, results in unprecedented diversity for this receptor4,5 The nature of the specificity and immunological functions of these T cells remains enigmatic. We report here that in contrast to the normal low frequency of γδ-bearing cells in lymphoid tissues, peripheral blood, or normal skin, the frequency is increased five to eightfold in particular granulomatous reactions of leprosy. TCR γδ+lymphocyte lines from these leprosy skin lesions proliferate in vitro specifically to mycobacterial antigens. This reactivity to foreign antigens appears to require presentation in the context of self-molecules. Moreover, culture supernatants from activated γδT lymphocytes induce adhesion and aggregation of bone-marrow monocytes in the presence of granulocyte monocyte-colony stimulating factor (CSF), suggesting that products of γδ-bearing T cells may play a role in the immune response, possibly by stimulating granuloma formation.

Software Risk Management

Abstract: In mature engineering disciplines, risk management has been de rigeur for centuries. When Michelangelo set out to raise the dome of St. Peters in 1547, he was well aware of the potential collapse zones under the staging, the possibility of materials failure, and the human capacity for error. For each of these major risks he prepared a mitigation plan: a fallback, a safety factor, or an alternative. Today, we routinely practice risk management in our stewardship of the environment, in planning financial strategy, in construction engineering, and in medicine. But how do we apply it to the ultimate risky business, software development?

Factors influencing infection rate in open fracture wounds.

Abstract: Seventy-seven infections in 1104 open fracture wounds were evaluated to identify those factors that predisposed to infection. Factors could be placed into three categories: (1) increased risk, (2) no effect, and (3) inconclusive. The single most important factor in reducing the infection rate was the early administration of antibiotics that provide antibacterial activity against both gram-positive and gram-negative microorganisms. In this study, surgical debridement was performed on all open fracture wounds.

A Framework for Analyzing Customer Service Orientations in Manufacturing

Abstract: The proposed framework first clarifies the concept of customer service in a manufacturing context. Then the key strategic choices associated with emphasizing a customer service–oriented strategy are specified. Next, the organizational arrangements necessary to implement these strategic choices are described. Finally, alternative effective configurations of the strategic choices, organizational arrangements, and customer service activities are proposed. Research propositions are presented that focus on the relationship between central contingencies in the strategic management literature and customer service in manufacturing.

Identification of nonminimum phase systems using higher order statistics

Abstract: A method is presented for identification of linear, time-variant, nonminimum phase systems when only output data are available. The input sequence need not be independent, but it must be non-Gaussian, with some special properties described in the test. The authors model a finite-dimensional system as an ARMA (autoregressive moving-average) rational function of known orders, but the special cases of AR, MA, and all-pass models are also considered. To estimate the parameters of their model, the authors utilize both second- and higher-order statistics of the output, which may be contaminated by additive, zero-mean, Gaussian white noise of unknown variance. The parameter estimators obtained are proved, under mild conditions, to be consistent. Simulations verify the performance of the proposed method in the case of relatively low signal-to-noise ratios, and when there is a model-order mismatch. >

Organization and Customer: Managing Design and Coordination of Services

Abstract: Customer participation in the operations of service organizations can be a major source of input uncertainty. A framework for analyzing service organizations is presented in which different conditions of input uncertainty are matched with the design of different interdependence patterns which, in turn, are matched to different portfolios of coordination mechanisms. The composition of portfolios draws on both the conventional organizational literature and recent work on control mechanisms at the client/service firm interface.

Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus.

Abstract: A group of rats was trained to escape low-intensity shock in a shuttle-box test, while another group of yoked controls could not escape but was exposed to the same amount and regime of shock. After 1 week of training, long-term potentiation (LTP) was measured in vitro in hippocampal slices. Exposure to uncontrollable shock massively impaired LTP relative to exposure to the same amount and regime of controllable shock. These results provide evidence that controllability modulates plasticity at the cellular-neuronal level.

Hair analysis for drugs of abuse

Abstract: Hair analysis for drugs of abuse by radioimmunoassay and gas chromatography/mass spectrometry (GC/MS) is an effective means for identifying drug abusers. Hair can be collected under close supervision without embarrassment and is not subject to evasive maneuvers (false negatives) such as temporary abstention, excessive fluid intake, and substitution or adulteration of specimens. Hair analysis has a wide window of detection ranging from months to years and provides information concerning the severity and pattern of an individual's drug use. Hair analysis is also not subject to evidential false positives, such as those caused by poppy seed ingestion, spiking of drinks or food, and mix-up or contamination of specimens. In part, these problems can be avoided because hair analysis can always be repeated with a newly collected specimen. The results of animal experiments and of various clinical, forensic, and criminal justice applications are described.

How do serine proteases really work

Abstract: Recent advances in genetic engineering have led to a growing acceptance of the fact that enzymes work like other catalysts by reducing the activation barriers of the corresponding reactions. However, the key question about the action of enzymes is not related to the fact that they stabilize transition states but to the question to how they accomplish this task. This work considers the catalytic reaction of serine proteases and demonstrates how one can use a combination of calculations and experimental information to elucidate the key contributions to the catalytic free energy. Recent reports about genetic modifications of the buried aspartic group in serine proteases, which established the large effect of this group (but could not determine its origin), are analyzed. Two independent methods indicate that the buried aspartic group in serine proteases stabilizes the transition state by electrostatic interactions rather than by alternative mechanisms. Simple free energy considerations are used to eliminate the double proton-transfer mechanism (which is depicted in many textbooks as the key catalytic factor in serine proteases). The electrostatic stabilization of the oxyanion side of the transition state is also considered. It is argued that serine proteases and other enzymes work by providing electrostatic complementarity to the changes in charge distribution occurring during the reactions they catalyze.

Sexual abuse histories and sequelae in female psychiatric emergency room patients.

Abstract: The charts of 100 nonpsychotic female patients in a psychiatric emergency room were reviewed to locate references to history of sexual molestation: 50 charts were selected at random from emergency room files, and 50 charts had been written by clinicians asked to query abuse history. A substantially higher rate of sexual abuse was found for patients who had been directly asked about sexual molestation (70%) than for the random sample (6%). Further analysis linked molestation history to suicidality, substance abuse, sexual difficulties, multiple psychiatric diagnoses, and axis II traits or disorders--especially borderline personality. Severe abuse and multiple abusers best predicted psychiatric sequelae. Language: en