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Showing papers by "University of North Carolina at Chapel Hill published in 1991"


Book
01 Feb 1991
TL;DR: In this paper, the authors defined learning theory and research functions of theory conducting research methods of assessing learning direct observations written responses Oral responses ratings by others Self-reports Precursors of Modern Learning Theories Learning theory and philosophy Learning theory was defined by Thorndike's theory in the study of learning which processes affect learning.
Abstract: Chapter 1 -- Learning: Introduction, Issues, Historical Perspectives Learning Defined Learning Theory and Research Functions of theory Conducting research Methods of Assessing Learning Direct observations Written responses Oral responses Ratings by others Self-reports Precursors of Modern Learning Theories Learning theory and philosophy Beginnings of the psychological study of learning Structuralism and functionalism Critical Issues in the Study of Learning Which processes affect learning? What is the role of memory? What is the role of motivation? How does transfer occur? Which processes are involved in self-regulation? What are the implications for instruction? Relation of Learning and Instruction Historical perspective Instructional commonalities Integration of theory and practice Three Learning Scenarios Kathy Stone's third-grade class Jim Marshall's U. S. History class Gina Brown's educational psychology class Summary Further Reading Chapter 2 -- Conditioning Theories Connectionism Trial-and-error learning Laws of exercise and effect Other principles Revisions to Thorndike's theory Instructional applications Classical Conditioning Basic processes Informational variables Biological influences Conditioned emotional reactions Watson's Behaviorism Basic processes Little Albert experiment Contiguous Conditioning Acts and movements Associative strength Rewards and punishments Habit formation and change Operant Conditioning Conceptual framework Basic processes Behavioral change Behavior modification Verbal behavior Self-regulation Self-monitoring Self-instruction Self-reinforcement Instructional Applications Behavioral objectives Programmed instruction Contingency contracts Keller Plan Summary Further Reading Chapter 3 -- Social Cognitive Theory Conceptual Framework for Learning Reciprocal interactions Enactive and vicarious learning Learning and performance Modeling Processes Theories of imitation Functions of modeling Cognitive skill learning Rule learning Influences on Learning and Performance Developmental status of learners Model prestige and competence Vicarious consequences to models Goals and Expectations Goals Outcome expectations Self-Efficacy Conceptual overview Self-efficacy in achievement situations Models and self-efficacy Motor skills Instructional self-efficacy Health and therapeutic activities Self-Regulation Conceptual framework Social cognitive processes Cyclical nature of self-regulation Instructional Applications Models Self-efficacy Self-regulation Summary Further Reading Chapter 4 -- Cognitive Information Processing Theory Cognitive Information Processing System Assumptions Two-store (dual-memory) model Critique Levels of processing Activation level Attention Theories of attention Attention and learning Attention and reading Perception Gestalt theory Sensory registers Long term memory comparisons Two-Store Memory Model Verbal learning Short-term (working) memory Long-term memory Influences on encoding Long-Term Memory: Storage Propositions Storage of declarative knowledge Storage of procedural knowledge Production Systems and Connectionist Models Production systems Connectionist models Long-Term Memory: Retrieval Retrieval strategies Encoding specificity Retrieval of declarative knowledge Retrieval of procedural knowledge Long-Term Memory: Forgetting Verbal learning Information processing Mental Imagery Representation of spatial information Imagery in LTM Individual differences Summary Further Reading Chapter 5 -- Cognitive Learning Processes Conditional Knowledge and Metacognition Conditional knowledge Metacognition and learning Variables influencing metacognition Metacognition and behavior Concept Learning The nature of concepts Concept attainment Teaching of concepts Motivational processes Problem Solving Problem solving defined Historical influences Heuristics Information processing model Problem-solving strategies Problem solving and learning Experts and novices Implications for instruction Transfer Historical views Activation of knowledge in memory Types of transfer Strategy transfer Instructional applications Self-Regulation and Motivation Model of self-regulation Learning strategies Critique of strategy instruction Academic studying Summary Further Reading Chapter 6 -- Constructivist Theory Constructivist Assumptions and Perspectives Overview Perspectives Situated cognition Contributions and applications Vygotsky's Sociocultural Theory Background Basic principles Zone of Proximal Development Applications Critique Social Processes and Private Speech Private speech Verbalization and achievement Socially mediated learning Motivation Contextual factors Implicit theories Teachers' expectations Self-Regulation Sociocultural influences Implicit theories of self-regulation Constructivist Learning Environments Key features APA Learner-Centered Principles Instructional methods Reflective teaching Summary Further Reading Chapter 7 -- Cognition and Instruction Discovery Learning The process of discovery Teaching for discovery Meaningful Reception Learning Meaningfulness and expository teaching Advance organizers Conditions of Learning Learning outcomes Learning events Learning hierarchies Phases of learning Models of Instruction Learning time Mastery learning Inquiry teaching Instruction with worked examples Cognitive load Peer-assisted learning Research on Teaching Teacher planning and decision making Instructional practices Learner Characteristics Aptitude-treatment interactions Cognitive styles Learners' resource allocations Adapting instruction Technology and Instruction Functions of technology Technological applications Future directions Summary Further Reading Chapter 8 -- Development and Learning Beginnings of the Scientific Study of Development Historical foundations Philosophical foundations The Child Study Movement Perspectives on Human Development Issues relevant to learning Types of developmental theories Structural theories Piaget's Theory of Cognitive Development Developmental processes Implications for instruction Bruner's Theory of Cognitive Growth Cognitive growth and knowledge representation Spiral curriculum Contemporary Themes in Development and Learning Developmental changes Developmentally appropriate instruction Transitions in schooling Familial Influences SES Home environment Parental involvement Motivation and Development Developmental changes Implications Development and Instruction Case's model of instruction Teacher-student interactions Summary Further Reading Chapter 9 -- Neuroscience of Learning Organization and Structures Neural organization Brain structures Localization and interconnections Brain research methods Neurophysiology of Learning Information processing system Memory networks Language learning Brain Development Influential factors Phases of development Critical periods Language development Motivation and Emotions Motivation Emotions Implications for Teaching and Learning Relevance of brain research Educational issues Brain-based educational practices Summary Further Reading Chapter 10 -- Content-Area Learning Skill Acquisition General and specific skills Novice-to-Expert Research Methodology Language Comprehension Components of comprehension Parsing Utilization Reading Decoding Comprehension Writing Composition Processes Reviewing Processes Motivation and self-regulation Mathematics Computation skills Problem-solving skills Constructivism Individual differences Science Expert-novice differences Reasoning Constructivism and scientific beliefs Social Studies History Geography Summary Further Reading Chapter 11 -- Motivation Model of Motivated Learning Pretask During task Posttask Historical Perspectives Drive theory Conditioning theory Cognitive consistency theory Humanistic theory Achievement Motivation Expectancy-value theory Familial influences Fear of success Contemporary model of achievement motivation Self-worth theory Task and ego involvement Achievement motivation training Attribution Theory Locus of control Naive analysis of action Attribution theory of achievement Attribution change programs Social Cognitive Theory Goals and expectations Social comparison Goal Theory Goal orientations Conceptions of ability Implications for teaching Perceptions of Control Control beliefs Learned helplessness Students with learning problems Self-Concept Dimensions and development Self-concept and learning Intrinsic motivation Theoretical perspectives Overjustification and reward Motivation and Self-Regulation Volition Values Self-schemas Help seeking Summary Further Reading Chapter 12 -- Next Steps Learning Questions Which processes affect learning? What is the role of memory? What is the role of motivation? How does transfer occur? Which processes are involved in self-regulation? What are the implications for instruction Learning Theories Conditioning Social cognitive Cognitive information processing Constructivist Conclusion Glossary References Author Index Subject Index

3,283 citations


Journal ArticleDOI
TL;DR: In this paper, the applicability of five conventional guidelines for construct measurement is critically examined: (a) Construct indicators should be internally consistent for valid measures, (b) there are optimal magnitudes of correlations between items, (c) the validity of measures depends on the adequacy with which a specified domain is sampled, within-construct correlations must be greater than between construct correlations, and (e) linear composites of indicators can replace latent variables.
Abstract: The applicability of 5 conventional guidelines for construct measurement is critically examined: (a) Construct indicators should be internally consistent for valid measures, (b) there are optimal magnitudes of correlations between items, (c) the validity of measures depends on the adequacy with which a specified domain is sampled, (d) within-construct correlations must be greater than between-construct correlations, and (e) linear composites of indicators can replace latent variables. A structural equation perspective is used, showing that without an explicit measurement model relating indicators to latent variables and measurement errors, none of these conventional beliefs hold without qualifications. Moreover, a "causal" indicator model is presented that sometimes better corresponds to the relation of indicators to a construct than does the classical test theory "effect" indicator model.

3,268 citations


Journal ArticleDOI
04 Jul 1991-Nature
TL;DR: It is concluded that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of X-LINKED spinal and bulbar muscular atrophy.
Abstract: X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity. We have now investigated whether the androgen receptor gene on the proximal long arm of the X chromosome is a candidate gene for this disease. In patient samples we found androgen receptor gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region. These amplified repeats were absolutely associated with the disease, being present in 35 unrelated patients and none of 75 controls. They segregated with the disease in 15 families, with no recombination in 61 meioses (the maximum log likelihood ratio (lod score) is 13.2 at a recombination rate of 0). The association is unlikely to be due to linkage disequilibrium, because 11 different disease alleles were observed. We conclude that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of this disorder.

2,704 citations


Journal ArticleDOI
TL;DR: A randomized clinical trial to test the hypothesis that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer and the clinical implications.
Abstract: Background. Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. Methods. Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, <1.0×l09 per liter, with a temperature ≥38.2°C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21 -day cycle. Results. The safety of the study treatment could be evaluated in 207 of the 211 pa...

1,314 citations


Journal ArticleDOI
TL;DR: The autosomal recessive lpr and gld genes induce in mice multiple autoantibodies and the progressive accumulation of large numbers of non-malignant CD4- CD8- T lymphocytes, and the mechanism whereby these two genes induce autoimmunity and lymphoproliferation remains obscure.
Abstract: The autosomal recessive lpr and gld genes induce in mice multiple autoantibodies and the progressive accumulation of large numbers of non-malignant CD4- CD8- T lymphocytes. The clinical syndromes and immune abnormalities associated with these two nonallelic genes are nearly identical and are also highly dependent on background genes. MRL/lpr mice are particularly severely affected, and they develop a syndrome that is serologically and pathologically similar to human systemic lupus erythematosus (SLE). Abnormal cell marker expression in the aberrant lpr T lymphocytes includes surface antigens normally associated with activated T cells or even with B cells, and it occurs along with enhanced expression of certain oncogenes. The lpr gene results in intrinsic abnormalities of both T and B lymphocytes, yet its location and product are unknown. The gld gene is located on chromosome 1; its product is also unknown. Although many immunological abnormalities are known, the mechanism whereby these two genes induce au...

1,214 citations


Journal ArticleDOI
TL;DR: Multiple regression analysis is one of the most widely used statistical procedures for both scholarly and applied marketing research as discussed by the authors. Yet, correlated predictor variables, and potential collinearity of correlated predictors have not yet been explored.
Abstract: Multiple regression analysis is one of the most widely used statistical procedures for both scholarly and applied marketing research. Yet, correlated predictor variables—and potential collinearity ...

1,159 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examined several hypotheses on how the survival and success of small businesses headed by men and women are related to industry differences, organizational structures, and attribu...
Abstract: In this study, we examined several hypotheses on how the survival and success of small businesses headed by men and women are related to industry differences, organizational structures, and attribu...

1,094 citations


Journal ArticleDOI
TL;DR: A theory of accommodation processes is advanced, and the results of 6 studies are reported as discussed by the authors, and it is shown that self-reports of accommodation are related to relevant behavioral measures, such as commitment, commitment, investment size, centrality of relationship, psychological femininity, and partner perspective taking.
Abstract: A theory of accommodation processes is advanced, and the results of 6 studies are reported. Accommodation refers to the willingness, when a partner has engaged in a potentially destructive act, to inhibit impulses to react destructively and instead react constructively. Studies 1 and 2 demonstrated that accommodation is lower under conditions of reduced social concern and lower interdependence. Studies 3,4, and 5 revealed that accommodation is associated with greater satis- faction, commitment, investment size, centrality of relationship, psychological femininity, and partner perspective taking and with poorer quality alternatives. Commitment plays a fairly strong role in mediating willingness to accommodate. Study 6 showed that couple functioning is asso- ciated with greater joint and mutual tendencies to inhibit destructive reactions. Study 6 also demon- strated that self-reports of accommodation are related to relevant behavioral measures. All partners in close relationships eventually behave badly. It is inevitable that in responding to the irritations and dissatisfac- tions of everyday life, one or the other partner eventually will engage in a potentially destructive act (e.g., being thoughtless, yelling at the partner, or not spending adequate time at home). How are people likely to react to such breaches of good behav- ior? Are they likely to exacerbate the problem by reacting de- structively in turn, or are they more likely to soothe ruffled feelings by reacting constructively? What makes them more willing to react constructively and inhibit destructive impulses? Do partners typically share equally in dealing with destructive content? Does feeling less involved than the partner lead to reduced willingness to react constructively? Our work ad- dresses such questions, and concerns a phenomenon that we term accommodation.' Accommodation refers to an individ- ual's willingness, when a partner has engaged in a potentially destructive behavior, to (a) inhibit tendencies to react destruc- tively in turn and (b) instead engage in constructive reactions. This article advances a general model of accommodation and presents preliminary empirical evidence regarding this phe- nomenon. We begin with a discussion of the response typology used in our model—the exit, voice, loyalty, and neglect typol- ogy Then we explore the implications of conceptualizing ac- commodation using an interdependen ce analysis (Kelley & Thibaut, 1978). Finally, we advance several hypotheses regard- ing the causes and dynamics of accommodation and review the results of six studies that serve as preliminary empirical tests of our model. Exit, Voice, Loyalty, and Neglect Our theory of accommodation processes emerged from re- search on Rusbult's exit-voice-loyalty-neglect typology of re- sponses to dissatisfaction in close relationships (Rusbult, Zem- brodt, & Gunn, 1982). The typology is based on the writings of Hirschman (1970), who discussed three reactions to decline in formal organizations: (a) exit—actively destroying the relation- ship; (b) voice—actively and constructively attempting to im- prove conditions; and (c) loyalty—passively but optimistically waiting for conditions to improve. To assess the comprehen- siveness of this model, Rusbult and Zembrodt (1983) performed multidimensional scaling studies of couple responses to dissat- isfaction. They found that Hirschman's categories character- ized responses to dissatisfaction in close relationships, and they

1,019 citations


Journal ArticleDOI
TL;DR: Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene, which predisposes heterozygotes to cancer, particularly breast cancer in women.
Abstract: Background. Ataxia—telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age—matched subjects. Retrospective studies have shown that persons heterozygous for the ataxia—telangiectasia gene, who make up about 1 percent of the general population, also have an excess risk of cancer, particularly breast cancer in women. Patients with ataxia—telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation. Methods. Cancer incidence and mortality, mortality from ischemic heart disease, and mortality from all causes were compared prospectively for a mean of 6.4 years in 1599 adult blood relatives of patients with ataxia—telangiectasia and 821 of their spouses, who served as controls, in 161 families affected by ataxia—telangiectasia. In a case–control substudy, we compared documented occupational and fluoroscopic diagnostic exposures to radiation in th...

898 citations


Journal ArticleDOI
TL;DR: Multivariable-adjusted odds ratios point to differences of considerable magnitude in the risk of carotid atherosclerosis between groups defined by clinical and public health-oriented risk factor cut-points.
Abstract: To assess whether carotid atherosclerosis measured by B-mode ultrasound is related to cardiovascular risk factors, 386 cases with carotid artery wall thickening and an equal number of controls free of arterial intima-media thickening were drawn from the cohort of the Atherosclerosis Risk in Communities (ARIC) Study examined in four communities in the United States between 1988 and 1990. Cases and controls were individually matched on sex, race, age group, study center, and date of examination. The mean values of total cholesterol, low density lipoprotein (LDL) cholesterol, total triglyceride, blood pressure, and pack-years of cigarette smoking were higher in cases than controls. Mean high density lipoprotein (HDL) cholesterol was lower in cases than controls. Case-control differences were all statistically significant. Multivariable-adjusted odds ratios point to differences of considerable magnitude in the risk of carotid atherosclerosis between groups defined by clinical and public health-oriented risk factor cut-points.

864 citations


Journal ArticleDOI
TL;DR: These measurements represent time-resolved observation of quantal secretion of catecholamine and provide direct evidence for the exocytotic hypothesis.
Abstract: Secretion of catecholamines from single bovine chromaffin cells in culture was elicited by brief pressure ejections from a micropipette containing nicotine, carbamoylcholine, or potassium ions or by mechanical stimulation. Release was monitored electrochemically with a carbon-fiber microelectrode placed adjacent to the cell. Cyclic voltammetry was used to identify secreted species, whereas constant potential amperometry was used for improved temporal resolution (millisecond range) of catecholamine detection. During secretion, brief current spikes were observed, which were shown to be due to detection of catecholamines by electrooxidation. The spikes have the physical characteristics of multimolecular packets of catecholamines released at random times and locations from the surface of the single cell. The half-width of the spikes was found to increase with an increase in cell-electrode spacing. The properties of the catecholamine spikes correlate well with expectations based on secretion from individual storage vesicles. Spikes do not occur in the absence of Ca2+ in the buffer, and the majority of spikes are found to be distributed between 0.2 and 2 picocoulombs, corresponding to 1-10 attomoles of catecholamine detected. The frequency of the spikes increases with the intensity of the stimulus, but the average quantity of catecholamine in each spike is independent of the stimulus. Thus, these measurements represent time-resolved observation of quantal secretion of catecholamines and provide direct evidence for the exocytotic hypothesis.

Journal ArticleDOI
TL;DR: This paper presents narrative as a framework for understanding the subject and interview data in qualitative research and examples of narrative approaches are offered, narrative analyses are contrasted with other kinds of qualitative analyses, and truth in narratives is considered.
Abstract: There is a new attention across disciplines to narrative knowing--the impulse to story life events into order and meaning. In this paper, narrative is presented as a framework for understanding the subject and interview data in qualitative research. Examples of narrative approaches are offered, narrative analyses are contrasted with other kinds of qualitative analyses, and truth in narratives is considered.

Journal ArticleDOI
TL;DR: Using a sensitive transfection-tumorigenicity assay, a novel transforming gene from the DNA of two patients with chronic myelogenous leukemia is isolated and sequence analysis indicates that the product of this gene, axl, is a receptor tyrosine kinase.
Abstract: Using a sensitive transfection-tumorigenicity assay, we have isolated a novel transforming gene from the DNA of two patients with chronic myelogenous leukemia. Sequence analysis indicates that the product of this gene, axl, is a receptor tyrosine kinase. Overexpression of axl cDNA in NIH 3T3 cells induces neoplastic transformation with the concomitant appearance of a 140-kDa axl tyrosine-phosphorylated protein. Expression of axl cDNA in the baculovirus system results in the expression of the appropriate recombinant protein that is recognized by antiphosphotyrosine antibodies, confirming that the axl protein is a tyrosine kinase. The juxtaposition of fibronectin type III and immunoglobulinlike repeats in the extracellular domain, as well as distinct amino acid sequences in the kinase domain, indicate that the axl protein represents a novel subclass of receptor tyrosine kinases.

Journal ArticleDOI
TL;DR: The reference values and charts presented here have two major advantages over the current Swedish ones: the sample size used is now sufficiently large at the lower gestational ages, so that empirically found variations can be used, and the skewness of the birth weight distribution has been taken into account.
Abstract: An update of the Swedish reference standards for weight, length, and head circumference at birth, for each week of gestational age, is presented It is based on the total Swedish cohorts of infants born 1977-1981 (n = 475,588) A "healthy population" (79%) was extracted, using prospectively collected data Weekly (28-42 weeks) grouped data for length and head circumference were well approximated by the normal distribution, but the distributions for birthweight were positively skewed The original skewed distributions for birthweight were transformed, using the square root, resulting in distributions close to the Gaussian For smoothing purposes, the weakly values for the mean and the standard deviation were both fitted by a third degree polynomial function These functions also make possible the calculation of the continuous variable, standard deviation score, for individual newborn infants as well as a comparison of distributions between groups of infants The reference values and charts presented here have two major advantages over the current Swedish ones: the sample size used is now sufficiently large at the lower gestational ages, so that empirically found variations can be used, and the skewness of the birth weight distribution has been taken into account The use of the reference standards presented here improves and facilitates evaluation of size deviation at birth

Journal ArticleDOI
TL;DR: It is postulated that the integrin-stimulated tyrosine phosphorylation of pp130 may reflect part of an important signal transduction process between the extracellular matrix and the cell interior.
Abstract: The integrin family of cell adhesion receptors mediates many of the interactions between cells and the extracellular matrix. Because the extracellular matrix has profound influences on cell behavior, it seems likely that integrins transduce biochemical signals across the cell membrane. The nature of these putative signals has, thus far, remained elusive. Antibody-mediated clustering of integrin receptors was used to mimic the integrin clustering process that occurs during formation of adhesive contacts. Human epidermal carcinoma (KB) cells were incubated with an anti-beta 1 integrin monoclonal antibody for 30 min on ice followed by incubation at 37 degrees C with anti-rat IgG. This treatment, which induced integrin clustering, stimulated the phosphorylation on tyrosine residues of a 115- to 130-kDa complex of proteins termed pp130. When integrins were clustered in the presence of the phosphatase inhibitor sodium orthovanadate, pp130 showed a substantial increase in phosphorylation compared to the case in which integrins were clustered in the absence of vanadate. Maximal pp130 phosphorylation was observed 10-20 min after initiation of integrin clustering in the absence of vanadate or after 5-10 min in its presence. These time courses roughly parallel the formation of integrin clusters on the cell surface as observed by fluorescence microscopy. pp130 phosphorylation depended on the amount of anti-integrin antibody present. Additionally, the tyrosine phosphorylation of pp130 showed specificity since it was stimulated by antibodies to the integrin alpha 3 and beta 1 subunits but not by antibodies to other integrin alpha subunits or to nonintegrin cell surface proteins. Immunoprecipitation experiments clearly demonstrated that pp130 is not itself a beta 1 integrin. It is postulated, therefore, that the integrin-stimulated tyrosine phosphorylation of pp130 may reflect part of an important signal transduction process between the extracellular matrix and the cell interior.

Journal ArticleDOI
28 Jun 1991-Cell
TL;DR: The cloned MAD-3 cDNA encodes an I kappa B-like protein that is likely to be involved in regulation of transcriptional responses to NF-kappa B, including adhesion-dependent pathways of monocyte activation.

Journal ArticleDOI
TL;DR: A concerted interplay among the domains of the AR protein in regulating gene transcription is demonstrated, with androgen-dependent nuclear uptake and inhibition of wild type AR by coexpression with an inactive NH2-terminal fragment suggested competition for nuclear factors required for transcriptional regulation.

Journal ArticleDOI
TL;DR: The development of specific mechanisms to effect release from the endosome in combination with gene transfer by the receptor-mediated endocytosis pathway will increase the utility of this delivery system by allowing high levels of gene expression in target cells.
Abstract: Gene transfer may be accomplished by the receptor-mediated endocytosis pathway using transferrin-polylysine conjugates. For some target cells, however, gene transfer by this vector is extremely limited, despite the presence of the appropriate surface receptors, a phenomenon attributed to lysosomal degradation of endosome-internalized conjugate-DNA complexes. To enhance DNA escape from the cell vesicle system and thus augment gene transfer by this route, we have used the capacity of adenoviruses to disrupt endosomes as part of their entry mechanism. Adenoviral infection augmented levels of gene transfer by transferrin-polylysine conjugates in a dose-dependent manner: levels of gene transfer of greater than 2000-fold above baseline were achieved. Use of the adenovirus in this context allowed enhanced levels of gene transfer in a variety of target cells, including cell lines otherwise refractory to gene transfer by transferrin-polylysine conjugates. This augmentation was based on adenoviral-mediated vesicle disruption, a process independent of viral gene expression. Thus, the development of specific mechanisms to effect release from the endosome in combination with gene transfer by the receptor-mediated endocytosis pathway will increase the utility of this delivery system by allowing high levels of gene expression in target cells.

Proceedings ArticleDOI
04 Dec 1991
TL;DR: It is proved that the problem of deciding schedulability of a set of concrete periodic tasks is intractable.
Abstract: A fundamental problem in the theory of real-time scheduling is examined: scheduling a set of periodic or sporadic tasks on a uniprocessor without preemption and without inserted idle time. The authors give a necessary and sufficient set of conditions C for a set of periodic or sporadic tasks to be schedulable for arbitrary release times of the tasks. They show that any set of periodic or sporadic tasks that satisfies C can be scheduled with an earliest-deadline-first (EDF) scheduling algorithm. The authors present the scheduling model, briefly review the literature in real-time scheduling, prove that the non-preemptive EDF algorithm is universal for sets of tasks, whether periodic or sporadic, and demonstrate the absence of a universal algorithm for periodic tasks with specified release times. It is proved that the problem of deciding schedulability of a set of concrete periodic tasks is intractable. >

Journal ArticleDOI
29 Mar 1991-Science
TL;DR: After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nocICEptors to tissue-damaging stimulation.
Abstract: The mechanisms by which peripheral nerve injuries sometimes lead to causalgia, aberrant burning pain peripheral to the site of nerve damage, are uncertain, although the sympathetic nervous system is known to be involved. Whether such syndromes could be the result of the development of responsiveness by some cutaneous pain receptors (C-fiber nociceptors) to sympathetic efferent activity as a consequence of the nerve injury was tested in an animal model. After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nociceptors to tissue-damaging stimulation. These effects were demonstratable within days after nerve lesions, occurred at the cutaneous receptive terminal region, were manifest in sensory fibers that had not degenerated after the injury, and were mediated by alpha 2-adrenergic-like receptors.

Journal ArticleDOI
TL;DR: In this paper, healthy male volunteers were hospitalized and fed a semisynthetic diet devoid of choline supplemented with 500 mg/day choline for 1 wk, and were randomly divided into two groups, one that continued to receive choline (control), and the other that received no choline(deficient) for three additional wk.
Abstract: Choline is required to make essential membrane phospholipids. It is a precursor for the biosynthesis of the neurotransmitter acetylcholine and also is an important source of labile methyl groups. Mammals fed a choline-deficient diet develop liver dysfunction; however, choline is not considered an essential nutrient in humans. Healthy male volunteers were hospitalized and fed a semisynthetic diet devoid of choline supplemented with 500 mg/day choline for 1 wk. Subjects were randomly divided into two groups, one that continued to receive choline (control), and the other that received no choline (deficient) for three additional wk. During the 5th wk of the study all subjects received choline. The semisynthetic diet contained adequate, but no excess, methionine. In the choline-deficient group, plasma choline and phosphatidylcholine concentrations decreased an average of 30% during the 3-wk period when a choline-deficient diet was ingested; plasma and erthrocyte phosphatidylcholine decreased 15%; no such changes occurred in the control group. In the choline-deficient group, serum alanine aminotransferase activity increased steadily from a mean of 0.42 mukat/liter to a mean of 0.62 mukat/liter during the 3-wk period when a choline-deficient diet was ingested; no such change occurred in the control group. Other tests of liver and renal function were unchanged in both groups during the study. Serum cholesterol decreased an average of 15% in the deficient group and did not change in the control group. Healthy humans consuming a choline-deficient diet for 3 wk had depleted stores of choline in tissues and developed signs of incipient liver dysfunction. Our observations support the conclusion and choline is an essential nutrient for humans when excess methionine and folate are not available in the diet.

Journal ArticleDOI
TL;DR: Depending on your perspective, demographers either have become quite aggressive in enlarging the territory considered to be part of population studies or have become more realistic in recognizing the complexity of human behavior.
Abstract: An understanding of fertility behavior is improved by consideration of roles and behavior by those of childbearing age. This perspective is consistent with the changes taking place in demography to expand the range of behavior under examination. The focus is on the young adult years (18-30 years) which represent a demographically dense period of multiple transitions which may occur as similarity or diversity staged in a mandated order or not or appear ambiguous or clear cut. The data used for discussion are from the US National Longitudinal Study of the High School Class of 1972 (senior year) with followup data from 1973747679 and 86 (NLS72). This population of baby boomers with separate family activities and work/school activities which impact on one another is diverse in many ways. The demographic density of the young adult years is characterized by fertility and migration which reaches a peak magnitude during these years; i.e. age specific fertility begins to decline after age 27 and 66% of all births in 1987 were to women 18-29 versus 76% in 1975. Mortality is the only core demographic variable which shows a trough unless one considers mortality specific causes such as motor vehicle accidents which peak during the young adult years. Other variables such as 1st marriage peak in the mid 20s for women and the late 20s for men and divorces and remarriage rates are also highest in the 20s. Leaving school and unemployment rates are also concentrated in these years to add to the density. The sparsity of activity in the midlife years may account for the crisis; young adults have the most positive view of life and provide the engines of social change with the least resources (28% of households with 8% of the assets) with relatively little power. The substantial number of demographic events for young adults is coupled with their diverse roles and activities. The sequencing of roles is examined with the NLS72 data and 75% of combinations of work school other are unique to 1 person and only 10% worked all 12 years. Gender differences reflect females experiencing more diversity. Across societies the US offers greater opportunity to drop in and out of education. In the work and family sphere there are consequences of the diverse and demographically dense years where order is the exception. A fixed set of reproductive norms and operating in a changing context. Little empirical work has been done to examine the extent to which transitions are blurred or crisp. American fertility trends may not follow the pattern of decline due to changes in the evolving relationships among the roles of father mother spouse worker student. With the changes in choices child rearing will be very different in the future.

Journal ArticleDOI
TL;DR: Women with suspicious abnormal mammograms exhibited significantly elevated levels of mammography-related anxiety and breast cancer worries that interfered with their moods and functioning, despite the fact that diagnostic work-ups had ruled out breast cancer.
Abstract: Evaluated the impact of receiving abnormal mammogram results on women's anxiety and breast cancer worries and on their breast self-examination (BSE) frequency and intentions to obtain subsequent mammograms. A telephone survey was conducted with 308 women 50 years old and older approximately 3 months following a screening mammogram. Subjects included women with suspicious abnormal mammograms, nonsuspicious abnormal mammograms, and normal mammograms. Women with suspicious abnormal mammograms exhibited significantly elevated levels of mammography-related anxiety and breast cancer worries that interfered with their moods and functioning, despite the fact that diagnostic work-ups had ruled out breast cancer. Women with moderate levels of impairment in mood or functioning were more likely to practice monthly BSE than women with either high or low levels of impairment. Breast cancer worries, perceived susceptibility to breast cancer, and physician encouragement to get mammograms all exhibited independent positive relationships to mammogram intentions.

Journal ArticleDOI
TL;DR: At least in some patients with cystic fibrosis, respiratory syncytial virus may be important in predisposing to subsequent bacterial infections, and other bacteria appear to play a secondary role in airway infection.
Abstract: Individuals with cystic fibrosis have abbreviated life spans primarily due to chronic airway infection. A limited number of types of organisms are responsible for these infections, with Staphylococcus aureus and Pseudomonas aeruginosa being of primary importance. In the pre-antibiotic era, greater than 90% of deaths due to infection were caused by S. aureus and death usually occurred in the first 2 years of life. With the advent of effective antistaphylococcal therapy, life spans increased and P. aeruginosa became the pathogen of primary importance. P. aeruginosa isolates recovered from patients with cystic fibrosis have a unique phenotypic characteristic referred to as "mucoid." The mucoid phenotype is due to the production of a mucoid exopolysaccharide. A mucoid exopolysaccharide is believed to play a central role in the establishment of chronic pseudomonal lung infection in these patients. A third organism, Pseudomonas cepacia, has recently been detected in the airways of older patients with cystic fibrosis and is associated with increased mortality. The virulence of P. cepacia is not understood, but the organism is extremely refractory to antimicrobial therapy. Other bacteria, including Haemophilus influenzae and members of the family Enterobacteriaceae, appear to play a secondary role in airway infection. Aspergillus fumigatus is the most important fungal agent causing allergic bronchopulmonary disease. The role of viruses has only recently been examined. At least in some patients with cystic fibrosis, respiratory syncytial virus may be important in predisposing to subsequent bacterial infections.

Journal ArticleDOI
TL;DR: Extracellular nucleotides are effective in vivo chloride secretagogues in the nasal epithelia of patients with cystic fibrosis and the equipotency of ATP and UTP suggests that the effect is mediated by P2 nucleotide receptors.
Abstract: Background. Cystic fibrosis is characterized by abnormal electrolyte transport across the epithelia of the airways. In particular, there is excessive sodium absorption and de..cient chloride secretion. Drugs that block excessive sodium absorption may provide clinical benefit in cystic fibrosis, but there are no available therapeutic agents to improve chloride secretion. In vitro studies in cultured human-airway epithelia indicate that triphosphate nucleotides (ATP and UTP) induce chloride secretion through apical-membrane purinergic receptors. Methods. We tested the ability of nucleotides to induce chloride secretion in vivo in 9 normal subjects and 12 patients with cystic fibrosis by measuring responses of nasal transepithelial potential difference (PD) to superfusion of nucleotides. Changes in transepithelial bioelectric properties and the permeability of the apical membrane to chloride in response to extracellular (apical) UTP were determined with ion-selective microelectrodes in cultured nasa...

Journal ArticleDOI
TL;DR: The effectiveness of written advance directives is limited by inattention to them and by decisions to place priority on considerations other than the patient's autonomy.
Abstract: Background The use of advance directives is recommended so that people can determine the medical care they will receive when they are no longer competent, but the effectiveness of such directives is not clear. Methods. In a prospective study conducted over a two-year period, 126 competent residents of a nursing home and 49 family members of incompetent patients were interviewed to determine their preferences with respect to hospitalization, intensive care, cardiopulmonary resuscitation, artificial ventilation, surgery, and tube feeding in the event of critical illness, terminal illness, or permanent unconsciousness. Advance directives, consisting of signed statements of treatment preferences, were placed in the medical record to assist in care in the nursing home and to be forwarded to the hospital if necessary. Results. In an analysis of 96 outcome events (hospitalization or death in the nursing home), care was con

Journal ArticleDOI
TL;DR: In this paper, a pulsed-field-gradient NMR experiment that permits accurate measurements of diffusion and flow rates in the presence of eddy currents is presented, which is useful for the study of systems exhibiting fast transverse relaxation or homonuclear scalar coupling.

Journal ArticleDOI
TL;DR: A substantial proportion of women with suspicious mammograms have psychological difficulties, even after learning that they do not have cancer, and sequelae do not appear to interfere with subsequent adherence.
Abstract: Objective: To evaluate women's psychological responses to abnormal mammograms and the effect on mammography adherence. To identify psychological responses and other factors that predict mammography...

Proceedings ArticleDOI
01 Jul 1991
TL;DR: In this paper, a biologically motivated method of texture synthesis called reaction-diffusion is described and shown how these textures can be generated in a manner that directly matches the geometry of a given surface.
Abstract: This paper describes a biologically motivated method of texture synthesis called reaction-diffusion and demonstrates how these textures can be generated in a manner that directly matches the geometry of a given surface. Reaction-diffusion is a process in which two or more chemicals diffuse at unequal rates over a surface and react with one another to form stable patterns such as spots and stripes. Biologists and mathematicians have explored the patterns made by several reaction-diffusion systems. We extend the range of textures that have previously been generated by using a cascade of multiple reaction-diffusion systems in which one system lays down an initial pattern and then one or more later systems refine the pattern. Examples of patterns generated by such a cascade process include the clusters of spots on leopards known as rosettes and the web-like patterns found on giraffes. In addition, this paper introduces a method which reaction-diffusion textures are created to match the geometry of an arbitrary polyhedral surface. This is accomplished by creating a mesh over a given surface and then simulating the reaction-diffusion process directly on this mesh. This avoids the often difficult task of assigning texture coordinates to a complex surface. A mesh is generated by evenly distributing points over the model using relaxation and then determining which points are adjacent by constructing their Voronoi regions. Textures are rendered directly from the mesh by using a weighted sum of mesh values to compute surface color at a given position. Such textures can also be used as bump maps.

Journal ArticleDOI
01 Jun 1991-Cancer
TL;DR: Multi‐variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI.
Abstract: Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characterisitcs and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant.