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Showing papers by "University of California, Irvine published in 1993"


Journal ArticleDOI
26 Mar 1993-Cell
TL;DR: In this article, the authors used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect, which is expanded and unstable on HD chromosomes.

7,224 citations


Journal ArticleDOI
TL;DR: A formulation of numerical real-space renormalization groups for quantum many-body problems is presented and several algorithms utilizing this formulation are outlined, which can be applied to almost any one-dimensional quantum lattice system, and can provide a wide variety of static properties.
Abstract: A formulation of numerical real-space renormalization groups for quantum many-body problems is presented and several algorithms utilizing this formulation are outlined. The methods are presented and demonstrated using S=1/2 and S=1 Heisenberg chains as test cases. The key idea of the formulation is that rather than keep the lowest-lying eigenstates of the Hamiltonian in forming a new effective Hamiltonian of a block of sites, one should keep the most significant eigenstates of the block density matrix, obtained from diagonalizing the Hamiltonian of a larger section of the lattice which includes the block. This approach is much more accurate than the standard approach; for example, energies for the S=1 Heisenberg chain can be obtained to an accuracy of at least ${10}^{\mathrm{\ensuremath{-}}9}$. The method can be applied to almost any one-dimensional quantum lattice system, and can provide a wide variety of static properties.

2,532 citations


Journal ArticleDOI
TL;DR: The 1993 Special Research Forum on Configurations as discussed by the authors was dedicated to the proposition that configurational theory and research can significantly advance understanding of people, groups, and organizations, and thus can be used to improve organizational analysis.
Abstract: The 1993 Special Research Forum on Configurations is dedicated to the proposition that configurational theory and research can significantly advance understanding of people, groups, and organizations. In this introductory essay, we define configurational approaches to organizational analysis, trace the history of configurational thinking, distinguish the contingency approach from the configurational approach, and highlight key contributions of the five empirical articles that make up the special research forum. Most of these articles report research conducted at the organizational level of analysis, but we argue that the configurational perspective has unrealized potential at other levels as well and suggest some configurational approaches to revitalizing theory and research at the individual and group levels.

1,729 citations


Journal ArticleDOI
01 Jul 1993-Genetics
TL;DR: A genotypic screen was developed that permitted identification of a heterozygous recessive mutation at the URA3 locus that was introduced by targeted mutagenesis, homologous integration of transforming DNA, to avoid introduction of extraneous mutations.
Abstract: Genetic manipulation of Candida albicans is constrained by its diploid genome and asexual life cycle. Recessive mutations are not expressed when heterozygous and undesired mutations introduced in the course of random mutagenesis cannot be removed by genetic back-crossing. To circumvent these problems, we developed a genotypic screen that permitted identification of a heterozygous recessive mutation at the URA3 locus. The mutation was introduced by targeted mutagenesis, homologous integration of transforming DNA, to avoid introduction of extraneous mutations. The ura3 mutation was rendered homozygous by a second round of transformation resulting in a Ura- strain otherwise isogenic with the parental clinical isolate. Subsequent mutation of the Ura- strain was achieved by targeted mutagenesis using the URA3 gene as a selectable marker. URA3 selection was used repeatedly for the sequential introduction of mutations by flanking the URA3 gene with direct repeats of the Salmonella typhimurium hisG gene. Spontaneous intrachromosomal recombination between the flanking repeats excised the URA3 gene restoring a Ura- phenotype. These Ura- segregants were selected on 5-fluoroorotic acid-containing medium and used in the next round of mutagenesis. To permit the physical mapping of disrupted genes, the 18-bp recognition sequence of the endonuclease I-SceI was incorporated into the hisG repeats. Site-specific cleavage of the chromosome with I-SceI revealed the position of the integrated sequences.

1,627 citations


Journal ArticleDOI
TL;DR: Aggregation properties of an overlapping series of synthetic beta-amyloid peptides were investigated and compared with beta AP neurotoxic properties in vitro, finding that few beta APs assembled into aggregates immediately after solubilization, but that over time peptides containing the highly hydrophobic beta 29–35 region formed stable aggregations.
Abstract: The progressive neurodegeneration of Alzheimer9s disease has been hypothesized to be mediated, at least in part, by beta-amyloid protein. A relationship between the aggregation state of beta-amyloid protein and its ability to promote degeneration in vitro has been previously suggested. To evaluate this hypothesis and to define a structure- activity relationship for beta-amyloid, aggregation properties of an overlapping series of synthetic beta-amyloid peptides (beta APs) were investigated and compared with beta AP neurotoxic properties in vitro. Using light microscopy, electrophoresis, and ultracentrifugation assays, we found that few beta APs assembled into aggregates immediately after solubilization, but that over time peptides containing the highly hydrophobic beta 29–35 region formed stable aggregations. In short-term neuronal cultures, toxicity was associated specifically with those beta APs that also exhibited significant aggregation. Further, upon the partial reversal of beta 1–42 aggregation, a concomitant loss of toxicity was observed. A synthetic peptide derived from a different amyloidogenic protein, islet amyloid polypeptide, exhibited aggregation but not toxicity, suggesting that beta AP-induced neurotoxicity in vitro is not a nonspecific reaction to aggregated protein. The correlation between beta AP aggregation and neurotoxicity was also observed in long-term neuronal cultures but not in astrocyte cultures. These data are consistent with the hypothesis that beta-amyloid protein contributes to neurodegeneration in Alzheimer9s disease.

1,460 citations


Journal ArticleDOI
TL;DR: A detailed investigation of the factors involved in the software-related overdoses and attempts by users, manufacturers, and government agencies to deal with the accidents is presented.
Abstract: Between June 1985 and January 1987, the Therac-25 medical electron accelerator was involved in six massive radiation overdoses. As a result, several people died and others were seriously injured. A detailed investigation of the factors involved in the software-related overdoses and attempts by users, manufacturers, and government agencies to deal with the accidents is presented. The authors demonstrate the complex nature of accidents and the need to investigate all aspects of system development and operation in order to prevent future accidents. The authors also present some lessons learned in terms of system engineering, software engineering, and government regulation of safety-critical systems containing software components. >

1,307 citations


Journal ArticleDOI
14 Oct 1993-Nature

1,092 citations


Journal ArticleDOI
TL;DR: It is reported that synthetic A beta Ps trigger the degeneration of cultured neurons through activation of an apoptotic pathway, suggesting that apoptosis may play a role in the neuronal loss associated with Alzheimer disease.
Abstract: The molecular mechanism responsible for the neurodegeneration in Alzheimer disease is not known; however, accumulating evidence suggests that beta-amyloid peptide (A beta P) contributes to this degeneration. We now report that synthetic A beta Ps trigger the degeneration of cultured neurons through activation of an apoptotic pathway. Neurons treated with A beta Ps exhibit morphological and biochemical characteristics of apoptosis, including membrane blebbing, compaction of nuclear chromatin, and internucleosomal DNA fragmentation. Aurintricarboxylic acid, an inhibitor of nucleases, prevents DNA fragmentation and delays cell death. Our in vitro results suggest that apoptosis may play a role in the neuronal loss associated with Alzheimer disease.

1,080 citations


Journal ArticleDOI
TL;DR: This article explored the differences between the representations of objects and places in English and other languages, and suggested that there is a tendency for languages to level out geometric detail from both object and place representations, leading to a non-linguistic disparity between representations of what and where.
Abstract: Fundamental to spatial knowledge in all species are the representations underlying object recognition, object search, and navigation through space. But what sets humans apart from other species is our ability to express spatial experience through language. This target article explores the language of objects and places, asking what geometric properties are preserved in the representations underlying object nouns and spatial prepositions in English. Evidence from these two aspects of language suggests there are significant differences in the geometric richness with which objects and places are encoded. When an object is named (i.e., with count nouns), detailed geometric properties – principally the object's shape (axes, solid and hollow volumes, surfaces, and parts) – are represented. In contrast, when an object plays the role of either “figure” (located object) or “ground” (reference object) in a locational expression, only very coarse geometric object properties are represented, primarily the main axes. In addition, the spatial functions encoded by spatial prepositions tend to be nonmetric and relatively coarse, for example, “containment,” “contact,” “relative distance,” and “relative direction.” These properties are representative of other languages as well. The striking differences in the way language encodes objects versus places lead us to suggest two explanations: First, there is a tendency for languages to level out geometric detail from both object and place representations. Second, a nonlinguistic disparity between the representations of “what” and “where” underlies how language represents objects and places. The language of objects and places converges with and enriches our understanding of corresponding spatial representations.

879 citations


Journal ArticleDOI
TL;DR: The extent of people's cultural beliefs of individualism or collectivism has been used to predict the effectiveness of many management practices as discussed by the authors, and a key aspect of those characteristics is the relati...
Abstract: The extent of people's cultural beliefs of individualism or collectivism has been used to predict the effectiveness of many management practices. A key aspect of those characteristics is the relati...

852 citations


Book
11 Feb 1993
TL;DR: In this article, the authors discuss the politics of ethnic enumeration in the United States Census and Pan-Asian American Ethnicity: Retrospect and Prospects of Pan-Asians.
Abstract: Tables and Figures Preface 1. Ethnicity and Panethnicity 2. Coming Together: The Asian American Movement 3. Electoral Politics 4. The Politics of Social Service Funding 5. Census Classification: The Politics of Ethnic Enumeration 6. Reactive Solidarity: Anti-Asian Violence 7. Pan-Asian American Ethnicity: Retrospect and Prospect Notes References Interviews Index

Journal ArticleDOI
TL;DR: Independent of biomedical risk, maternal prenatal stress factors are significantly associated with infant birth weight and with gestational age at birth.

Journal ArticleDOI
TL;DR: Findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate, likely to have serious consequences for the establishment of anormal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.
Abstract: Epidemiological and anatomical studies support the theory that disturbances of brain development may play a contributory role in the etiology of schizophrenia. Anatomical findings suggest that the normal pattern of neuronal migration during development of the cerebral cortex may be affected in the brains of schizophrenics, with the implication that cortical connectivity and associative function will be disrupted. In the present investigation in matched schizophrenic and control brains, we examined a particular population of neurons found in the prefrontal cortex and underlying white matter and characterized by histochemical staining for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase. In normal brains, these neurons are found in highest numbers in the white matter immediately deep to layer VI of the cortex where they remain from the subplate, an early formed, but transitory structure that plays a key role in cortical development and connection formation. The dorsolateral prefrontal area of schizophrenics showed a significant decline in nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in the superficial white matter and in the overlying cortex but a significant increase in these neurons in white matter deeper than 3 mm from the cortex. These findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate. These are likely to have serious consequences for the establishment of a normal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.


Journal ArticleDOI
TL;DR: In this paper, a model that blends comparative political economy with international relations was used to evaluate the European Community according to its economic performance, political salience, and role in international relations.
Abstract: Europeans evaluate the European Community (EC) according to its economic performance, political salience, and role in international relations. During the last two decades their measured attitudes toward European integration warmed especially when inflation rates fell, as the EC share of the country's trade expanded, when EC elections and referenda increased attention to the community, and to some extend during periods when East-West relations were relaxed. Europeans did not vary their support according to their countries' shares of the Brussels budget. Thus, notwithstanding Denmark's 1992 rejection of the Maastricht treaty and the end of the cold war, recent EC reforms that increase monetary stability, intra-European trade and political attention are all likely to maintain or increase citizen support for the EC. These findings result from a model that blends comparative political economy with international relations in one of the first applications of pooled cross-sectional and time-series analysis to the comparative study of public opinion.

Journal ArticleDOI
Abstract: Basic to several key issues in current urban economic theory and public policy is a presumption that local imbalances between employment and residential sites strongly influence people's commuting patterns. We examine this presumption by finding the commuting pattern for the Los Angeles region in 1980 which would minimise average commuting time or distance, given the actual spatial distributions of job and housing locations. We find that the amount of commuting required by these distributions is far less than actual commuting, and that variations in required commuting across job locations only weakly explain variations in actual commuting. We conclude that other factors must be more important to location decisions than commuting cost, and that policies aimed at changing the jobs-housing balance will have only a minor effect on commuting.

Journal ArticleDOI
TL;DR: It is suggested that the high concentration of lignans in vegetarians, by inhibiting aromatase in peripheral and/or cancer cells and lowering estrogen levels, may play a protective role as antipromotional compounds during growth of estrogen-dependent cancers.

Journal ArticleDOI
TL;DR: It is suggested that the presence of TGF-beta s in pancreatic cancer cells may contribute to disease progression and be associated with advanced tumor stage and longer postoperative survival.


Journal ArticleDOI
TL;DR: There is a potential mechanism for the plasticity of representational maps that is demonstrable in somatic sensory, motor, auditory, and visual cortex as well as in primate neocortex.
Abstract: GABA neurons and GABA receptors are conspicuous elements of cerebral cortical organization. They serve to shape the stimulus-response properties of neurons in the sensory areas and undoubtedly play a comparable role in the nonsensory areas as well. Although non-GABAergic local circuit neurons exist in the cerebral cortex, the variety of forms adopted by the GABAergic neurons and their important functional role have served to focus attention on the latter in investigations of local cortical circuitry. In primate neocortex, GABAergic neurons constitute approximately 25-30% of the neuronal population. In addition to their known or postulated functions in shaping neuronal receptive fields and response profiles, some of which are still controversial (Sillito, 1984; Ferster, 1986), their transmitter, GABA, and the major class of receptor upon which it acts are regulated in an activity-dependent manner even in the adult (Jones, 1990). In this, there is a potential mechanism for the plasticity of representational maps that is demonstrable in somatic sensory, motor, auditory, and visual cortex (Merzenich et al., 1983; Sanes et al., 1988; Robertson and Irvine, 1989; Kaas et al., 1990).

Journal ArticleDOI
TL;DR: All mutations occur in the same base pair of exon 6 and result in the substitution of an uncharged amino acid (leucine or glutamine) for Arg271 in the mature protein.
Abstract: Hereditary hyperekplexia, or familial startle disease (STHE), is an autosomal dominant neurologic disorder characterized by marked muscle rigidity of central nervous system origin and an exaggerated startle response to unexpected acoustic or tactile stimuli. Linkage analyses in several large families provided evidence for locus homogeneity and showed the disease gene was linked to DNA markers on the long arm of chromosome 5. Here we describe the identification of point mutations in the gene encoding the α1 subunit of the glycine receptor (GLRA1) in STHE patients from four different families. All mutations occur in the same base pair of exon 6 and result in the substitution of an uncharged amino acid (leucine or glutamine) for Arg271 in the mature protein.

Journal ArticleDOI
TL;DR: Alterations of cortical ontogenesis, as reflected in the distribution of NADPH-d neurons, appear to be widespread among neocortical association fields in schizophrenics and may provide a clue to the cause of the disease.
Abstract: • The distribution of neurons expressing the enzyme nicotinamide-adenine dinucleotide phosphate—diaphorase (NADPH-d) in the lateral and medial temporal lobes of schizophrenic and matched control brains was investigated in a systematic blind analysis. Schizophrenics had significantly lower numbers of NADPH-d neurons in the hippocampal formation and in the neocortex of the lateral temporal lobe but significantly greater numbers of NADPH-d neurons in the white matter of the lateral temporal lobe and a tendency toward greater numbers in parts of the parahippocampal white matter. The distorted distribution of NADPH-d neurons in the lateral temporal lobe, which may be explained by developmental disturbances, such as impaired neuronal migration or an alteration in the death cycle of transitory subcortical neurons, is similar to that found in the prefrontal cortex of schizophrenics. Alterations of cortical ontogenesis, as reflected in the distribution of NADPH-d neurons, appear to be widespread among neocortical association fields in schizophrenics and may provide a clue to the cause of the disease.

Journal ArticleDOI
TL;DR: In this article, the authors investigated differences in the psychological involvement and task assignments of labor-contractor and employee engineers and the effects of the contractors on the attitudes of their emp...
Abstract: This study investigated differences in the psychological involvement and task assignments of labor-contractor and employee engineers and the effects of the contractors on the attitudes of their emp...

Journal ArticleDOI
TL;DR: By expanding the team turnover context to include environmental and strategic dimensions, in addition to previously examined performance and heterogeneity factors, this study enhances the understanding of managerial turnover as a form of organizational adaptation.
Abstract: Based on an organizational adaptation framework, this study examines the influence of three environmental dimensions–munificence, stability, and complexity–on top management team turnover. In addition to investigating the direct influence of these environmental dimensions, indirect effects through firm performance and strategic change are also examined; the indirect effect of environmental complexity through demographic heterogeneity is also studied. Path analysis indicates that the direct effects of the three environmental dimensions predominate. Indirect effects were nonsignificant except for the effect of instability and munificence through strategic change. By expanding the team turnover context to include environmental and strategic dimensions, in addition to previously examined performance and heterogeneity factors, this study enhances our understanding of managerial turnover as a form of organizational adaptation.

Journal Article
TL;DR: Findings suggest that coexpression of EGFR and its ligands may contribute to the aggressiveness of human pancreatic cancer.
Abstract: Immunohistochemical analysis for the epidermal growth factor receptor (EGFR), EGF and transforming growth factor-alpha (TGF-alpha) was performed in 87 human pancreatic carcinomas. Expression frequencies for EGFR, EGF, and TGF-alpha were 43%, 46% and 54%, respectively. Coexpression of the receptor and at least one of its ligands occurred in 38% of the tumors, and correlated with large tumor size, advanced clinical staging, and decreased survival period. In situ hybridization revealed that the respective mRNAs were also overexpressed in the carcinomas. These findings suggest that coexpression of EGFR and its ligands may contribute to the aggressiveness of human pancreatic cancer.

Journal ArticleDOI
TL;DR: The tumescent technique for local anesthesia improves the safety of large-volume liposuction by virtually eliminating surgical blood loss and by completely eliminating the risks of general anesthesia.
Abstract: The tumescent technique for local anesthesia improves the safety of large-volume liposuction (≥1500 ml of'fat) by virtually eliminating surgical blood loss and by completely eliminating the risks of general anesthesia. Results of two prospective studies of large-volume liposuction using the tumescent technique are reported. In 112 patients, the mean lidocaine dosage was 33.3 mg/kg, the mean volume of aspirated material was 2657 ml, and the mean volume of supranatant fat was 1945 ml. The mean volume of whole blood aspirated by liposuction was 18.5 ml. For each 1000 ml of fat removed, 9. 7 ml of whole blood was suctioned. In 31 large-volume liposuction patients treated in 1991, the mean difference between preoperative and 1-week postoperative hematocrits was -1.9 percent

Journal ArticleDOI
TL;DR: The combination of environmental manipulation with evolutionary divergence provides valuable information about the biological connections between life‐history, caloric reserves, and reproductive physiology in Drososphila.
Abstract: Earlier experiments have shown that the evolution of postponed senescent populations can be achieved by selection on either demographic or stress resistance characters. Both types of selection have produced results in which survival characters (stress resistance and longevity) have apparently traded-off against early-life fecundity. Here we present the results of a series of experiments in which an environmental variable — the level of live yeast inoculate applied to the substrate — produces a qualitatively similar phenotypic response: longevity and starvation resistance are enhanced by lower yeast levels, at the expense of fecundity. For the starvation resistance versus fecundity experiments we show a negative and linear relationship between the norms of reaction for each character across a gradient of yeast levels. This phenotypic trade-off is stable across the 20 populations and 4 selection treatments reported on here, and its general agreement with earlier selection results suggests that the evolutionary response and the phenotypically plastic response may share a common physiological basis. However, an important discrepancy in the lifetime fecundity data between the selection response and the dietary manipulations preclude strict analogy. The results broadly conform to a simple “Y-model” of allocation, in which a limited resource is divided between survival and reproduction; here the characters are starvation resistance and longevity versus fecundity.

Journal ArticleDOI
TL;DR: A new family of cysteine-rich antimicrobial peptides from bovine neutrophils was identified and characterized in this paper, and the peptides are characterized by a highly cationic 38-42-residue chain which includes 6 invariantly spaced cysteines which form three disulfides.

Journal ArticleDOI
TL;DR: The authors investigates the much discussed phenomenon of postmodernity as it relates to and influences marketing, and the major conditions of post-modernity are discussed as hyperreality, fragmentation, reversal of consumption and production, decentering of the subject, and paradoxical juxtapositions (of opposites), with the caution that marketing may already be a postmodern institution.

Journal ArticleDOI
TL;DR: In this paper, the degree of separation of the d and l enantiomers of PheNHPh (α value) is used to establish the influence of polymer morphology on polymer performance.