Showing papers by "University of Pennsylvania published in 1996"

Spectral Graph Theory

Abstract: Eigenvalues and the Laplacian of a graph Isoperimetric problems Diameters and eigenvalues Paths, flows, and routing Eigenvalues and quasi-randomness Expanders and explicit constructions Eigenvalues of symmetrical graphs Eigenvalues of subgraphs with boundary conditions Harnack inequalities Heat kernels Sobolev inequalities Advanced techniques for random walks on graphs Bibliography Index.

Exploring internal stickiness: Impediments to the transfer of best practice within the firm

Abstract: The ability to transfer best practices internally is critical to a firtn's ability to build competitive advantage through the appropriation of rents from scarce internal knowledge. Just as a firm's distinctive competencies tnight be dificult for other firms to imitate, its best prczctices could be dfficult to imitate internnlly. Yet, little systematic attention has been pcrid to such internal stickiness. The author analyzes itlterrzal stickiness of knowledge transfer crnd tests the resulting model using canonical correlation analysis of a data set consisting of 271 observations of 122 best-practice transfers in eight companies. Contrary to corzverztiorzrzl wisdom that blames primarily motivational factors, the study findings show the major barriers to internal knowledge transfer to be knowledge-related factors such as the recipient's lack oj absorptive capacity, causal anzbiguity, and an arciuous relationship between the source and the recipient. The identification and transfer of best practices cally are hindered less by confidentiality and legal is emerging as one of the most important and obstacles than external transfers, they could be widespread practical management issues of the faster and initially less complicated, all other latter half of the 1990s. Armed with meaningful, things being equal. For those reasons, in an era detailed performance data, firms that use fact- when continuous organizational learning and based management methods such as TQM, bench- relentless performance improvement are needed to marking, and process reengineering can regularly remain competitive, companies must increasingly compare the performance of their units along resort to the internal transfer of capabilitie~.~ operational dimensions. Sparse but unequivocal Yet, experience shows that transferring capaevidence suggests that such comparisons often bilities within a firm is far from easy. General reveal surprising performance differences between Motors had great difficulty in transferring manuunits, indicating a need to improve knowledge facturing practices between divisions (Kerwin and utilization within the firm (e.g., Chew, Bresnahan, Woodruff, 1992: 74) and IBM had limited suc

Crystalline Ropes of Metallic Carbon Nanotubes

Abstract: The major part of this chapter has already appeared in [1], but because of the length restrictions (in Science), the discussion on why we think this form is given in only brief detail. This chapter goes into more depth to try to answer the questions of why the fullerenes form themselves. This is another example of the very special behavior of carbon. From a chemist’s standpoint, it is carbon’s ability to form multiple bonds that allows it to make these low dimensional forms rather than to produce tetrahedral forms. Carbon can readily accomplish this and it is in the mathematics and physics of the way this universe was put together, that carbon is given this property. One of the consequences of this property is that, if left to its own devices as carbon condenses from the vapor and if the temperature range is just right, above 1000°C, but lower than 1400°C, there is an efficient self-assembly process whose endpoint is C60.

Causes and Consequences of Earnings Manipulation: An Analysis of Firms Subject to Enforcement Actions by the SEC*

Abstract: . This study investigates firms subject to accounting enforcement actions by the Securities and Exchange Commission for alleged violations of Generally Accepted Accounting Principles. We investigate: (i) the extent to which the alleged earnings manipulations can be explained by extant earnings management hypotheses; (ii) the relation between earnings manipulations and weaknesses in firms' internal governance structures; and (iii) the capital market consequences experienced by firms when the alleged earnings manipulations are made public. We find that an important motivation for earnings manipulation is the desire to attract external financing at low cost. We show that this motivation remains significant after controlling for contracting motives proposed in the academic literature. We also find that firms manipulating earnings are: (i) more likely to have boards of directors dominated by management; (ii) more likely to have a Chief Executive Officer who simultaneously serves as Chairman of the Board; (iii) more likely to have a Chief Executive Officer who is also the firm's founder, (iv) less likely to have an audit committee; and (v) less likely to have an outside blockholder. Finally, we document that firms manipulating earnings experience significant increases in their costs of capital when the manipulations are made public. Resume. Les auteurs analysent les entreprises assujetties aux mesures d'execution prises par la Securities and Exchange Commission dans les cas de presomption de transgression des principes comptables generalement reconnus. Ils s'interessent aux aspects suivants de la question: i) la mesure dans laquelle les presomptions de manipulations des benefices peuvent etre expliquees par les hypotheses existantes de gestion des benefices; ii) la relation entre les manipulations de benefices et les faiblesses des structures de regie interne des entreprises; et iii) la reaction du marche financier a l'endroit des entreprises au sujet desquelles les presomptions de manipulation des benefices sont rendues publiques. Les auteurs constatent qu'un incitatif majeur a la manipulation des benefices est le desir d'obtenir du financement externe a moindre cout. Ils demontrent que cet incitatif demeure important meme apres le controle des motifs contractuels que mettent de l'avant les travaux theoriques. Ils constatent egalement que les entreprises qui manipulent les benefices sont: i) davantage susceptibles d'avoir des conseils d'administration domines par la direction; ii) davantage susceptibles d'avoir un chef de la direction qui joue simultanement le role de president du conseil; iii) davantage susceptibles d'avoir un chef de la direction qui est egalement le fondateur de l'entreprise; iv) moins susceptibles d'avoir un comite de verification; et v) moins susceptibles d'avoir un bloc de titres detenus par un actionnaire exterieur. Enfin, les auteurs etablissent le fait que le cout du capital, pour les entreprises qui manipulent les benefices, enregistre des hausses appreciables lorsque ces manipulations sont rendues publiques.

Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.

Abstract: HIV-1 and related viruses require co-receptors, in addition to CD4, to infect target cells. The chemokine receptor CCR-5 (ref.1) was recently demonstrated to be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains, and the orphan receptor LESTR (also called fusin) allows infection by strains adapted for growth in transformed T-cell lines (T-tropic strains). Here we show that a mutant allele of CCR-5 is present at a high frequency in caucasian populations (allele frequency, 0.092), but is absent in black populations from Western and Central Africa and Japanese populations. A 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains. In a cohort of HIV-1 infected caucasian subjects, no individual homozygous for the mutation was found, and the frequency of heterozygotes was 35% lower than in the general population. White blood cells from an individual homozygous for the null allele were found to be highly resistant to infection by M-tropic HIV-1 viruses, confirming that CCR-5 is the major co-receptor for primary HIV-1 strains. The lower frequency of heterozygotes in seropositive patients may indicate partial resistance.

Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours

Abstract: Apoptosis is a genetically encoded programme of cell death that can be activated under physiological conditions and may be an important safeguard against tumour development. Regions of low oxygen (hypoxia) and necrosis are common features of solid tumours. Here we report that hypoxia induces apoptosis in oncogenically transformed cells and that further genetic alterations, such as loss of the p53 tumour-suppressor gene or overexpression of the apoptosis-inhibitor protein Bcl-2, substantially reduce hypoxia-induced cell death. Hypoxia also selects for cells with defects in apoptosis, because small numbers of transformed cells lacking p53 overtake similar cells expressing wild-type p53 when treated with hypoxia. Furthermore, highly apoptotic regions strongly correlate with hypoxic regions in transplanted tumours expressing wild-type p53, whereas little apoptosis occurs in hypoxic regions of p53-deficient tumours. We propose that hypoxia provides a physiological selective pressure in tumours for the expansion of variants that have lost their apoptotic potential, and in particular for cells acquiring p53 mutations.

Foreign entry, cultural barriers and learning

Abstract: textThis paper examines the longevity of foreign entries. Hypotheses are developed on the mode (start-ups vs. acquisitions) and ownership structure (wholly owned vs. joint ventures) in relation to cultural distance. The hypotheses are tested within a framework of organizational learning, using data on 225 entries that 13 Dutch firms carried out from 1966 onwards. Results show that the presence of cultural barriers punctuates an organization's learning. Cultural distance is a prominent factor in foreign entry whenever this involves another firm, requiring the firm to engage in double layered acculturation. We also identify locational paths of learning. The longevity of acquisitions is positively influenced by prior entries of the firm in the same country. Similarly, the longevity of foreign entries, in which the firm has a majority stake, improves whenever the expanding firm engaged in prior entries in the same country and in other countries in the same cultural block.

Foreign entry, cultural barriers, and learning

Abstract: This paper examines the longevity of foreign entries. Hypotheses are developed on the mode (start-ups vs. acquisitions) and ownership structure (wholly owned vs. joint ventures) in relation to cultural distance. The hypotheses are tested within a framework of organizational learning, using data on 225 entries that 13 Dutch firms carried out from 1966 onwards. Results show that the presence of cultural barriers punctuates an organization's learning. Cultural distance is a prominent factor in foreign entry whenever this involves another firm, requiring the firm to engage in ‘double layered acculturation.’ We also identify locational ‘paths of learning.’ The longevity of acquisitions is positively influenced by prior entries of the firm in the same country. Similarly, the longevity of foreign entries, in which the firm has a majority stake, improves whenever the expanding firm engaged in prior entries in the same country and in other countries in the same cultural block.

Specialized supplier networks as a source of competitive advantage : Evidence from the auto industry

Abstract: This study examines the relationship between interfirm asset specificity and performance in the auto industry. More specifically, I examine the extent to which differences in supplier–automaker asset specialization may explain performance differences between Japanese automakers (Nissan and Toyota) and U.S. automakers (Chrysler, Ford, General Motors). The findings indicate a positive relationship between supplier–automaker specialization and performance. In particular, the data suggest a positive relationship between interfirm human asset cospecialization and both quality and new model cycle time. Moreover, site specialization is found to be positively associated with lower inventory costs. The findings suggest that in the auto industry a tightly integrated production network characterized by proximity and a high level of human cospecialization will outperform a loosely integrated production network characterized by low levels of interfirm specialization.

Explicit reversible integrators for extended systems dynamics

Abstract: Explicit reversible integrators, suitable for use in large-scale computer simulations, are derived for extended systems generating the canonical and isothermal-isobaric ensembles. The new methods are compared with the standard implicit (iterative) integrators on some illustrative example problems. In addition, modification of the proposed algorithms for multiple time step integration is outlined.

Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice

Abstract: Liver regeneration stimulated by a loss of liver mass leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Mice with targeted disruption of the interleukin-6 (IL-6) gene had impaired liver regeneration characterized by liver necrosis and failure. There was a blunted DNA synthetic response in hepatocytes of these mice but not in nonparenchymal liver cells. Furthermore, there were discrete G1 phase (prereplicative stage in the cell cycle) abnormalities including absence of STAT3 (signal transducer and activator of transcription protein 3) activation and depressed AP-1, Myc, and cyclin D1 expression. Treatment of IL-6-deficient mice with a single preoperative dose of IL-6 returned STAT3 binding, gene expression, and hepatocyte proliferation to near normal and prevented liver damage, establishing that IL-6 is a critical component of the regenerative response.

Path-goal theory of leadership: Lessons, legacy, and a reformulated theory

Abstract: In this paper I present a retrospective review of the development and history of the path-goal theory of leader effectiveness. I briefly describe the origin of the theory. The theory is then summarized. The various methodologies that have been used to test the theory and lessons learned from empirical testing are discussed. Two legacies of the theory are described: the substitutes for leadership theory and the 1976 theory of charismatic leadership. A reformulated 1996 path-goal theory of work unit leadership is presented. The reformulated theory specifies leader behaviors that enhance subordinate empowerment and satisfaction and work unit and subordinate effectiveness. It addresses the effects of leaders on the motivation and abilities of immediate subordinates and the effects of leaders on work unit performance. The reformulated theory includes 8 classes of leader behavior, individual differences of subordinates, and contingency moderator variables which are related to each other in 26 propositions. The contingency moderators of the theory specify some of the circumstances in which each of the behaviors are likely to be effective or ineffective. It is argued that the essential underlying rationale from which the propositions are derived is strikingly parsimonious. The essence of the theory is the meta proposition that leaders, to be effective, engage in behaviors that complement subordinates ' environments and abilities in a manner that compensates for deficiencies and is instrumental to subordinate satisfaction and individual and work unit performance. This meta proposition, and the specific propositions derived from it, are consistent with, and integrate, the predictions of current extant theories of leadership. Further, the propositions of the theory are consistent with empirical tests with empirical generalizations resulting from earlier task and person oriented research. It is my hope that the 1996 theory will be subjected to empirical tests and that such tests will lead to a further improved theory to be formulated at some future time.

Development and Prospective Validation of a Clinical Index to Predict Survival in Ambulatory Patients Referred for Cardiac Transplant Evaluation

Abstract: Background Risk stratification of patients with end-stage congestive heart failure is a critical component of the transplant candidate selection process. Accurate identification of individuals most likely to survive without a transplant would facilitate more efficient use of scarce donor organs. Methods and Results Multivariable proportional hazards survival models were developed with the use of data on 80 clinical characteristics from 268 ambulatory patients with advanced heart failure (derivation sample). Invasive and noninvasive models (with and without catheterization-derived data) were constructed. A prognostic score was determined for each patient from each model. Stratum-specific likelihood ratios were used to develop three prognostic-score risk groups. The models were prospectively validated on 199 similar patients (validation sample) by calculation of the area under the receiver operating characteristic curve for 1-year event-free survival, the censored c-index for event-free survival, and compar...

Mutations in the human Sonic Hedgehog gene cause holoprosencephaly.

Abstract: Holoprosencephaly (HPE) is a common developmental defect of the forebrain and frequently the midface in humans, with both genetic and environmental causes HPE has a prevalence of 1:250 during embryogenesis and 1:16,000 newborn infants, and involves incomplete development and septation of midline structures in the central nervous system (CNS) with a broad spectrum of clinical severity Alobar HPE, the most severe form which is usually incompatible with postnatal life, involves complete failure of division of the forebrain into right and left hemispheres and is characteristically associated with facial anomalies including cyclopia, a primitive nasal structure (proboscis) and/or midfacial clefting At the mild end of the spectrum, findings may include microcephaly, mild hypotelorism, single maxillary central incisor and other defects (Fig 1) This phenotypic variability also occurs between affected members of the same family The molecular basis underlying HPE is not known, although teratogens, non-random chromosomal anomalies and familial forms with autosomal dominant and recessive inheritance have been described HPE3 on chromosome 7q36 is one of at least four different loci implicated in HPE Here, we report the identification of human Sonic Hedgehog (SHH) as HPE3-the first known gene to cause HPE Analyzing 30 autosomal dominant HPE (ADHPE) families, we found five families that segregate different heterozygous SHH mutations Two of these mutations predict premature termination of the SHH protein, whereas the others alter highly conserved residues in the vicinity of the alpha-helix-1 motif or signal cleavage site

Perception as Bayesian Inference

Abstract: 1. Introduction D. C. Knill, D. Kersten and A. Yuille 2. Pattern theory: a unifying perspective D. Mumford 3. Modal structure and reliable inference A. Jepson, W. Richards and D. C. Knill 4. Priors, preferences and categorical percepts W. Richards, A. Jepson and J. Feldman 5. Bayesian decision theory and psychophysics A. L. Yuille and H. H. Bulthoff 6. Observer theory, Bayes theory, and psychophysics B. M. Bennett, D. D. Hoffman, C. Prakash and S. N. Richman 7. Implications of a Bayesian formulation D. C. Knill, D. Kersten and P. Mamassian 8. Shape from texture: ideal observers and human psychophysics A. Blake, H. H. Bulthoff and D. Sheinberg 9. A computational theory for binocular stereopsis P. N. Belhumeur 10. The generic viewpoint assumption in a Bayesian framework W. T. Freeman 11. Experiencing and perceiving visual surfaces K. Nakayama and S. Shimojo 12. The perception of shading and reflectance E. H. Adelson and A. P. Pentland 13. Banishing the Homunculus H. Barlow.

Reducing the Cost of Demand Uncertainty Through Accurate Response to Early Sales

Abstract: Traditionally, fashion products have incurred high losses due to stockouts and inventory obsolence because long lead times coupled with a concentrated selling season force all or at least most production to be committed before demand information is available. Under a Quick Response system, lead times are shortened sufficiently to allow a greater portion of production to be scheduled in response to initial demand. We model and analyze the decisions required under Quick Response and give a method for estimating the demand probability distributions needed in our model. We applied these procedures with a major fashion skiwear firm and found that cost relative to the current informal response system was reduced by enough to increase profits by 60%. Relative to the cost that would have been incurred if no response were used, optimized response reduces cost by enough to roughly quadruple profits.

The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.

Abstract: Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds. BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds, and then identified four years later by a positional cloning strategy. BRCA2 was mapped to chromosomal 13q at about the same time. Just fifteen months later, Wooster et al. reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DMA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease.

Abstract: We sequenced the prion protein gene and studied the biochemical characteristics and the intracerebral distribution of protease-resistant prion protein with Western blot and immunohistochemistry in 19 cases of sporadic Creutzfeldt-Jakob disease. We identified four groups of subjects defined by the genotype at codon 129 of the prion protein gene, the site of a common methionine/valine polymorphism, and two types of protease-resistant prion proteins that differed in size and glycosylation. The four Creutzfeldt-Jakob disease groups showed distinct clinicopathological features that corresponded to previously described variants. The typical Creutzfeldt-Jakob disease phenotype or myoclonic variant and the Heidenhain variant were linked to methionine homozygosity at codon 129 and to "type 1" protease-resistant prion protein. The atypical and rarer variants such as that with dementia of long duration, the ataxic variant, and the variant with kuru plaques were linked to different genotypes at codon 129 and shared the "type 2" protease-resistant prion protein. Our data indicate that the sporadic form of Creutzfeldt-Jakob disease comprises a limited number of variants. The methionine/valine polymorphism at codon 129 of the prion protein gene and two types of protease-resistant prion proteins are the major determinants of these variants. These findings suggest the existence of prion strains in humans and provide the molecular basis for a novel classification of sporadic Creutzfeldt-Jakob disease.

A novel nuclear structure containing the survival of motor neurons protein.

Abstract: Spinal muscular atrophy (SMA) is a common, often fatal, autosomal recessive disease leading to progressive muscle wasting and paralysis as a result of degeneration of anterior horn cells of the spinal cord. A gene termed survival of motor neurons (SMN), at 5q13, has been identified as the determining gene of SMA (Lefebvre et al., 1995). The SMN gene is deleted in > 98% of SMA patients, but the function of the SMN protein is unknown. In searching for hnRNP-interacting proteins we found that SMN interacts with the RGG box region of hnRNP U, with itself, with fibrillarin and with several novel proteins. We have produced monoclonal antibodies to the SMN protein, and we report here on its striking cellular localization pattern. Immunolocalization studies using SMN monoclonal antibodies show several intense dots in HeLa cell nuclei. These structures are similar in number (2-6) and size (0.1-1.0 micron) to coiled bodies, and frequently are found near or associated with coiled bodies. We term these prominent nuclear structures gems, for Gemini of coiled bodies.

Classifying political regimes

Abstract: This study presents a classification of political regimes as democracies and dictatorships for a set of 141 countries between 1950 or the year of independence and 1990. It improves existing classifications by a better grounding in political theory, an exclusive reliance on observables rather than on subjective judgements, an explicit distinction between systematic and random errors, and a more extensive coverage.

Reduced Transit-Time Sensitivity in Noninvasive Magnetic Resonance Imaging of Human Cerebral Blood Flow

Abstract: Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.

Atrial fibrillation following coronary artery bypass graft surgery: Predictors, outcomes, and resource utilization

Abstract: Objective. —To determine the incidence, predictors, and cost of atrial fibrillation and flutter (AFIB) following coronary artery bypass graft (CABG) surgery. Design. —Prospective observational study (MultiCenter Study of Perioperative Ischemia). Setting. —Twenty-four university-affiliated hospitals in the United States from 1991 to 1993. Subjects. —A total of 2417 patients undergoing CABG with or without concurrent valvular surgery selected using a systematic sampling interval. Measurements. —Detailed preoperative, intraoperative, and postoperative data collected on standardized reporting forms. Results. —The overall incidence of postoperative AFIB was 27%. Independent predictors of postoperative AFIB included advanced age (odds ratio [OR], 1.24 per 5-year increase; 95% confidence interval [CI], 1.18-1.31); male sex (OR, 1.41; 95% CI, 1.09-1.81); a history of AFIB (OR, 2.28; 95% CI, 1.74-3.00); a history of congestive heart failure (OR, 1.31; 95% CI, 1.04-1.64); and a precardiopulmonary bypass heart rate of more than 100 beats per minute (OR, 1.59; 95% CI, 1.00-.00-2.55). Surgical practices such as pulmonary vein venting (OR, 1.44; 95% CI, 1.13-1.83); bicaval venous cannulation (OR, 1.40; 95% CI, 1.04-1.89); postoperative atrial pacing (OR, 1.27; 95% CI, 1.00-1.62); and longer cross-clamp times (OR, 1.06 per 15 minutes; 95% CI, 1.00-1.11) also were identified as independent predictors of postoperative AFIB. Patients with postoperative AFIB remained an average of 13 hours longer in the intensive care unit and 2.0 days longer in the ward when compared with patients without AFIB. Conclusion. —Postoperative AFIB is common after CABG surgery and has a significant effect on both intensive care unit and overall hospital length of stay. In addition to expected demographic factors, certain surgical practices increase the risk of postoperative AFIB. Randomized controlled trials are necessary to determine if modification of these surgical practices, especially in patients at high risk, would decrease the incidence of postoperative AFIB.

Crystal structure of the lactose operon repressor and its complexes with DNA and inducer.

Abstract: The lac operon of Escherichia coli is the paradigm for gene regulation. Its key component is the lac repressor, a product of the lacI gene. The three-dimensional structures of the intact lac repressor, the lac repressor bound to the gratuitous inducer isopropyl-β-D-1-thiogalactoside (IPTG) and the lac repressor complexed with a 21-base pair symmetric operator DNA have been determined. These three structures show the conformation of the molecule in both the induced and repressed states and provide a framework for understanding a wealth of biochemical and genetic information. The DNA sequence of the lac operon has three lac repressor recognition sites in a stretch of 500 base pairs. The crystallographic structure of the complex with DNA suggests that the tetrameric repressor functions synergistically with catabolite gene activator protein (CAP) and participates in the quaternary formation of repression loops in which one tetrameric repressor interacts simultaneously with two sites on the genomic DNA.