Showing papers by "Dartmouth College published in 1996"

Law and Finance

Abstract: This paper examines legal rules covering protection of corporate shareholders and creditors, the origin of these rules, and the quality of their enforcement in 49 countries. The results show that common law countries generally have the best, and French civil law countries the worst, legal protections of investors, with German and Scandinavian civil law countries located in the middle. We also find that concentration of ownership of shares in the largest public companies is negatively related to investor protections, consistent with the hypothesis that small, diversified shareholders are unlikely to be important in countries that fail to protect their rights.

Trust in Large Organizations

Abstract: Several authors suggest that trust is an important determinant of cooperation between strangers in a society, and therefore of performance of social institutions. We argue that trust should be particularly important for the performance of large organizations. In a cross-section of countries, evidence on government performance, participation in civic and professional societies, importance of large firms, and the performance of social institutions more generally supports this hypothesis. Moreover, trust is lower in countries with dominant hierarchical religions, which may have deterred networks of cooperation trust hold up remarkably well on a cross-section of countries.

Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis.

Abstract: The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBF alpha 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption of one copy of the Cbfa2 gene significantly reduces the number of progenitors for erythroid and myeloid cells.

Goods Prices and Exchange Rates: What Have We Learned?

Abstract: Import prices typically change by a smaller proportion than the exchange rate between the exporting and importing country. Recent research indicates that common-currency relative prices for similar goods exported to different markets are highly correlated with exchange rates between those markets. This evidence suggests that incomplete pass-through is a consequence of third-degree price discrimination. While distance matters for market segmentation, borders have independent effects. The source of the border effect has not been clearly identified. Furthermore, there is little evidence yet to suggest substantial market power is implied by the observed price discrimination.

The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis.

Abstract: Objective. —Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. Design. —Correlative survey study of 477 MEN 2 families. Setting. —Eighteen tertiary referral centers worldwide. Patients. —A total of 477 independent MEN 2 families. Main Outcome Measures. —Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. Results. —There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B-specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. Conclusions. —This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.

Improved Survival in Stage III Non-Small-Cell Lung Cancer: Seven-Year Follow-up of Cancer and Leukemia Group B (CALGB) 8433 Trial

Abstract: Background : For many years, high-dose radiation therapy was the standard treatment for patients with locally or regionally advanced non-small-cell lung cancer (NSCLC), despite a 5-year survival rate of only 3%-10% following such therapy. From May 1984 through May 1987, the Cancer and Leukemia Group B (CALGB) conducted a randomized trial that showed that induction chemotherapy before radiation therapy improved survival during the first 3 years of follow-up. Purpose : This report provides data for 7 years of follow-up of patients enrolled in the CALGB trial. Methods : The patient population consisted of individuals who had clinical or surgical stage III, histologically documented NSCLC ; a CALGB performance status of 0-1 ; less than 5% loss of body weight in the 3 months preceding diagnosis ; and radiographically visible disease. Patients were randomly assigned to receive either 1) cisplatin (100 mg/m 2 body surface area intravenously on days 1 and 29) and vinblastine (5 mg/m 2 body surface area intravenously weekly on days 1, 8, 15, 22, and 29) followed by radiation therapy with 6000 cGy given in 30 fractions beginning on day 50 (CT-RT group) or 2) radiation therapy with 6000 cGy alone beginning on day 1 (RT group) for a maximum duration of 6-7 weeks. Patients were evaluated for tumor regression if they had measurable or evaluable disease and were monitored for toxic effects, disease progression, and date of death. Results : There were 78 eligible patients randomly assigned to the CT-RT group and 77 randomly assigned to the RT group. Both groups were similar in terms of sex, age, histologic cell type, performance status, substage of disease, and whether staging had been clinical or surgical. All patients had measurable or evaluable disease at the time of random assignment to treatment groups. Both groups received a similar quantity and quality of radiation therapy. As previously reported, the rate of tumor response, as determined radiographically, was 56% for the CT-RT group and 43% for the RT group (P =.092). After more than 7 years of follow-up, the median survival remains greater for the CT-RT group (13.7 months) than for the RT group (9.6 months) (P =.012) as ascertained by the logrank test (two-sided). The percentages of patients surviving after years 1 through 7 were 54, 26, 24, 19, 17, 13, and 13 for the CT-RT group and 40, 13, 10, 7, 6, 6, and 6 for the RT group. Conclusions : Long-term follow-up confirms that patients with stage III NSCLC who receive 5 weeks of chemotherapy with cisplatin and vinblastine before radiation therapy have a 4.1-month increase in median survival. The use of sequential chemotherapy-radiotherapy increases the projected proportion of 5-year survivors by a factor of 2.8 compared with that of radiotherapy alone. However, inasmuch as 80%-85% of such patients still die within 5 years and because treatment failure occurs both in the irradiated field and at distant sites in patients receiving either sequential chemotherapy-radiotherapy or radiotherapy alone, the need for further improvements in both the local and systemic treatment of this disease persists.

Managing professional intellect: making the most of the best.

Abstract: In the postindustrial era, the success of a corporation lies more in its intellectual and systems capabilities than in its physical assets. The capacity to manage human intellect—and to convert it into useful products and services—is fast becoming the critical executive skill of the age. As a result, there has been a flurry of interest in intellectual capital, creativity, innovation, and the learning organization, but surprisingly little attention has been given to managing professional intellect.

OVERVIEW AND EVALUATION OF FUEL ETHANOL FROM CELLULOSIC BIOMASS: Technology, Economics, the Environment, and Policy

Abstract: ▪ Abstract Ethanol is a high performance fuel in internal combustion engines. It is a liquid, which is advantageous in terms of storage, delivery, and infrastructural compatability. Ethanol burns relatively cleanly, especially as the amount of gasoline with which it is blended decreases. Evaporative and toxicity-weighted air toxics emissions are consistently lower for ethanol than for gasoline. It is likely that vehicles can be configured so that exhaust emissions of priority pollutants are very low for ethanol-burning engines, although the same can probably be said for most other fuels under consideration. Recent work suggests that ethanol may be more compatible with fuel cell—powered vehicles than has generally been assumed. Research and development—driven advances have clear potential to lower the price of cellulosic ethanol to a level competitive with bulk fuels. Process areas with particular potential for large cost reductions include biological processing (with consolidated bioprocessing particularl...

Immune regulation by cd40 and its ligand gp39

Abstract: Over the past three years, CD40 and its ligand (gp39, CD40L, TBAM) have been shown to be essential for humoral immune responses to thymus-dependent antigens. However, as the tissue distribution widens for those cells that express CD40 and gp39, we can now show that this ligand-receptor pair also plays an important role in the selection of self-reactive T cells in the thymus (central tolerance) and the regulation of tolerance in mature T cells (peripheral tolerance). Advances in our understanding of the molecular basis for CD40 biology is based in two areas of research. First, a major breakthrough in our understanding of how CD40 transduces biological events centers on the identification of a novel protein that binds to the cytoplasmic tail of CD40 and may act as a signal transducing molecule. Secondly, advances in molecular modeling and mutagenesis of this ligand-receptor pair have helped to identify the critical receptor/ligand contacts in the gp39/CD40 complex. Advances in each of these areas are discussed.

Executive Compensation, Strategic Competition, and Relative Performance Evaluation: Theory and Evidence

Abstract: We argue that strategic interactions between firms in an oligopoly can explain the puzzling lack of high-powered incentives in executive compensation contracts written by shareholders whose objective is to maximize the value of their shares. We derive the optimal compensation contracts for managers and demonstrate that the use of high-powered incentives will be limited by the need to soften product market competition. In particular, when managers can be compensated based on their own and their rivals' performance, we show that there will be an inverse relationship between the magnitude of high-powered incentives and the degree of competition in the industry. More competitive industries are characterized by weaker pay-performance incentives. Empirically, we find strong evidence of this inverse relationship in the compensation of executives in the United States. Our econometric results are not consistent with alternative theories of the effect of competition on executive compensation. We conclude that strategic considerations can preclude the use of high-powered incentives, in contrast to the predictions of the standard principal-agent model.

CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis

Abstract: We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Activated helper T cells expressing CD40L (gp39) surface protein were found in MS patient brain sections, but not in brain tissue sections of normal controls or patients with other neurological disease. CD40L-positive cells were co-localized with CD40-bearing cells in active lesions (perivascular infiltrates). Most of these CD40-bearing cells proved to be of the monocytic lineage (macrophages or microglial cells), and relatively few were B cells. To functionally evaluate CD40-CD40L interactions, EAE was elicited in mice by means of proteolipid-peptide immunization. Treatment with anti-CD40L monoclonal antibody completely prevented the development of disease. Furthermore, administration of anti-CD40L monoclonal antibody, even after disease onset, shortly before maximum disability score was reached led to dramatic disease reduction. The presence of helper T cells expressing CD40L in brain tissue of MS patients and EAE animals, together with the functional evidence provided by successful experimental prevention and therapy in an animal model, indicates that blockade of CD40-CD40L-mediated cellular interactions may be a method for interference in active MS.

A new approach to the minimum cut problem

Abstract: This paper present a new approach to finding minimum cuts in undirected graphs. The fundamental principle is simple: the edges in a graph's minimum cut form an extremely small fraction of the graph's edges. Using this idea, we give a randomized, strongly polynomial algorithm that finds the minimum cut in an arbitrarily weighted undirected graph with high probability. The algorithm runs in O(n2log3n) time, a significant improvement over the previous O˜(mn) time bounds based on maximum flows. It is simple and intuitive and uses no complex data structures. Our algorithm can be parallelized to run in RNC with n2 processors; this gives the first proof that the minimum cut problem can be solved in RNC. The algorithm does more than find a single minimum cut; it finds all of them.With minor modifications, our algorithm solves two other problems of interest. Our algorithm finds all cuts with value within a multiplicative factor of a of the minimum cut's in expected O˜(n2a) time, or in RNC with n2a processors. The problem of finding a minimum multiway cut of graph into r pieces is solved in expected O˜(n2(r-1)) time, or in RNC with n2(r-1) processors. The “trace” of the algorithm's execution on these two problems forms a new compact data structure for representing all small cuts and all multiway cuts in a graph. This data structure can be efficiently transformed into the more standard cactus representing for minimum cuts.

UCN-01: a Potent Abrogator of G2 Checkpoint Function in Cancer Cells With Disrupted p53

Abstract: Background: Arrest of the cell cycle in G2 phase following DNA damage helps protect cell viability by allowing time for DNA repair before entry into mitosis (M phase). Abrogation of G 2 arrest sensitizes cells to the effects of DNA-damaging agents. UCN-01 (7-hydroxystaurosporine), a protein kinase C inhibitor that may block G2 checkpoint regulation, has been reported to enhance the cytotoxicity of mitomycin C, a known DNA-damaging agent. Purpose: We studied the effect of UCN-01 on G 2 checkpoint control in human lymphoma CA46 cells, whose sensitivity to various DNA-damaging agents and G2 response to DNA damage have been characterized. We also assessed the ability of UCN-01 to enhance the cytotoxicity of y irradiation in CA46 cells and human colon carcinoma HT-29 cells, both of which are mutant for p53 function. The influence of p53 function on UCN-01mediated abrogation of the G2 checkpoint and enhancement of DNA-damaging agent cytotoxicity was studied in transfected human breast carcinoma MCF-7 cells that either expressed or did not express the human papillomavirus type-16 E6 protein. MCF-7 cells have normal p53 function, and the E6 protein binds p53 protein and promotes its destruction. Methods: The effect of UCN-01 on cell cycle arrest induced by y irradiation was studied in CA46 cells and in transfected MCF-7 cells by use of flow cytometry. A histone HI phosphorylati on assay was employed to measure cyclin Bl/Cdc2 kinase activity in extracts derived from irradiated and nonirradiated CA46 cells that had been either treated or not treated with UCN-01; the phosphorylation status of Cdc2 kinase protein in the same extracts was determined by use of western blotting. The effect of UCN-01 on the cytotoxicity of y irradiation in CA46 and HT-29 cells was determined by use of MTT (thiazolyl blue) and clonogenic (colony-forming) assays, respectively; a clonogenic assay was also used to measure the effect of UCN-01 on the cytotoxicity of cisplatin in transfected and nontransfected MCF-7 cells. Results: G2 arrest induced in CA46 cells by y irradiation was inhibited by treatment with UCN-01 in a dose-dependent manner; arrest in G2 was completely abrogated by exposure to 300 nAf UCN-01. Biochemical markers indicative of the G2/M transition, including the activation of cyclin Bl/Cdc2 kinase and the suppression of Cdc2 threonine-14 and tyrosine-15 phosphorylation, were detected in irradiated cells treated with UCN-01. UCN-01 enhanced the cytotoxicity of y irradiation in CA46 and HT-29 cells. MCF7 cells with functional p53 protein were more resistant to G2 checkpoint abrogation by UCN-01 than MCF-7 cells with disrupted p53 function. UCN-01 markedly enhanced the cell-killing activity of cisplatin in MCF-7 cells defective for p53 function. Conclusions and Implications: UCN-01 is a potent abrogator of G 2 checkpoint control in cancer cells with disrupted p53 function. UCN-01 might be capable of enhancing the effectiveness of DNA-damaging agents in the treatment of tumors with cells lacking normal p53 function. [J Natl Cancer Inst 1996;88:956-65]

Basic epidemiology of fractures of the upper and lower limb among Americans over 65 years of age.

Abstract: Current knowledge regarding the basic epidemiology of fractures is largely limited to a few fracture sites, notably those of the hip and distal forearm. To clarify the patterns of incidence of limb fractures in the elderly, we used data from a 5% sample of the U.S. Medicare population over age 65 years during the years 1986-1990. We identified incident fractures of the proximal humerus, other parts of the humerus, proximal radius/ ulna, shaft of the radius/ulna, distal radius/ulna, pelvis, hip, other parts of the femur, patella, ankle, and other parts of the tibia/fibula from diagnoses and procedures coded on claims for inpatient services, outpatient facility use, and physician services. We used Poisson regression to investigate the relation between demographic factors and fracture risk at these sites. Fractures at the hip were the most common, accounting for 38% of the fractures identified. The proximal humerus, distal radius/ulna, and ankle also were common fracture sites. A pattern of rapidly rising rates with age was seen for fractures of the pelvis, hip, and other parts of the femur among women. Fractures distal to the elbow or knee, however, had, at most, modest increases in incidence with age over 65 years. For each of the fractures studied, women had higher rates than men of the same race, and whites generally had higher rates than blacks of the same gender. Gender-related differences in risk were larger among whites than among blacks, and racial differences in risk were more marked among women than among men.

Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues.

Abstract: The deiodination of thyroid hormones in extrathyroidal tissues plays an important role in modulating thyroid hormone action. The type II deiodinase (DII) converts thyroxine to the active hormone 3,5,3'-triiodothyronine, and in the rat is expressed in the brain, pituitary gland, and brown adipose tissue (BAT). Complementary DNAs (cDNAs) for the types I and III deiodinases (DI and DIII, respectively) have been isolated and shown to code for selenoproteins. However, information concerning the structure of the mammalian DII remains limited, and the pattern of its expression in human tissues is undefined. We report herein the identification and characterization of rat and human DII cDNAs. Both code for selenoproteins and exhibit limited regions of homology with the DI and DIII. In the rat pituitary and BAT, DII mRNA levels are altered more than 10-fold by changes in the thyroid hormone status of the animal. Northern analysis of RNA derived from human tissues reveals expression of DII transcripts in heart, skeletal muscle, placenta, fetal brain, and several regions of the adult brain. These studies demonstrate that: (a) the rat and human DII are selenoproteins, (b) DII expression in the rat is regulated, at least in part, at the pretranslational level in some tissues, and (c) DII is likely to be of considerable physiologic importance in thyroid hormone economy in the human fetus and adult.

Community, Population, and Organization Effects on Innovation: A Multilevel Perspective

Abstract: Two distinct themes emerge from the Special Research Forum on Innovation and Organizations. One group of articles develops an expanded view of the influence of context on organizations' ability to innovate. Together, the articles offer a complex multilevel view of context as including elements ranging from the dominant strategy of an organization to the social-psychological antecedents of creativity. A second group of articles provides a community and population perspective on the diffusion of innovations. We suggest the possibility of a union between the context and industry dynamics approaches. As we contemplated editing this Special Research Forum on Innovation and Organizations, we observed that a plethora of books on innovation had been written in recent years. Our collections had grown dramatically during the 1990s as the topic took on increasing practical and theoretical significance. This vibrant literature covered topics and concepts ranging from paradigm shifts, through intrapreneurship, intelligent organizations, mastering change, and time-based competition. Most of these works were in good currency, enjoying unparalleled popularity among managers and enviable citation rates among scholars. Surely such a wealth of information signaled the arrival of a dominant theoretical model of innovation in organizations. Whereas each book and article made its own valuable contribution, we were disappointed to discover that no dominant theoretical perspective had emerged to integrate the multiple streams of innovation research. Unlike other evolving fields of organizational inquiry, such as organizational economics, contingency theory, organizational ecology, and institutional theory, innovation research demonstrates little in the way of common theoretical underpinnings to guide its development. Although these other approaches are not free from internal debate, each has at its core conceptual principles and advocates that drive its theoretical and empirical development.

The New Hampshire study of supported employment for people with severe mental illness.

Abstract: This study compared supported employment services in 2 contrasting programs: (a) Group Skills Training, a professional rehabilitation agency outside of the mental health center that provided pre-employment skills training and support in obtaining and maintaining jobs, or (b) the Individual Placement and Support (IPS) model, which integrated clinical and vocational services within the mental health center. People with severe mental disorders who expressed interest in competitive employment (N = 143) were randomly assigned to 1 of these 2 programs. Results showed that clients in the IPS program were more likely to be competitively employed throughout most of the 18-month follow-up. Among those who obtained jobs, there were few group differences, although workers in the IPS program did work more total hours and earn more total wages during the 18-month follow-up. There were no group differences on nonvocational outcomes.

FFTs for the 2-Sphere-Improvements and Variations

Abstract: Earlier work by Driscoll and Healy has produced an efficient algorithm for computing the Fourier transform of band-limited functions on the 2-sphere. In this article we present a reformulation and variation of the original algorithm which results in a greatly improved inverse transform, and consequent improved convolution algorithm for such functions. All require at most O(N log2 N) operations where N is the number of sample points. We also address implementation considerations and give heuristics for allowing reliable and computationally efficient floating point implementations of slightly modified algorithms. These claims are supported by extensive numerical experiments from our implementation in C on DEC, HP, SGI and Linux Pentium platforms. These results indicate that variations of the algorithm are both reliable and efficient for a large range of useful problem sizes. Performance appears to be architecture-dependent. The article concludes with a brief discussion of a few potential applications.

How Retirement Saving Programs Increase Saving

Abstract: This paper summarizes the authors work on the effect of IRA and 401(k) contributions on net personal saving. They consider many different nonparametric approaches to controlling for heterogeneity in individual saving behavior and conclude that the weight of the available evidence suggests that contributions to both IRAs and 401(k)s largely represent new saving. The authors devote particular attention to reconciling their results with the findings in other studies that reach different conclusions, sometimes using the same databases that the authors analyze. Methodological limitations that undermine the reliability of results in other studies explain many of these disparities.

Promotional Elasticities and Category Characteristics

Abstract: The authors study the relationships between product category characteristics and average brand promotional elasticity within the category. They present a framework for understanding these relations...

Genetic evidence that induction of root Fe(III) chelate reductase activity is necessary for iron uptake under iron deficiency

Abstract: Reduction of Fe(III) to Fe(II) by Fe(III) chelate reductase is thought to be an obligatory step in iron uptake as well as the primary factor in making iron available for absorption by all plants except grasses. Fe(III) chelate reductase has also been suggested to play a more general role in the regulation of cation absorption. In order to experimentally address the importance of Fe(III) chelate reductase activity in the mineral nutrition of plants, three Arabidopsis thaliana mutans (frd1-1, frd1-2 and frd1-3), that do not show induction of Fe(III) chelate reductase activity under iron-deficient growth conditions, have been isolated and characterized. These mutants are still capable of acidifying the rhizosphere under iron-deficiency and accumulate more Zn and Mn in their shoots relative to wild-type plants regardless of iron status. frd1 mutants do not translocate radiolabeled iron to the shoots when roots are presented with a tightly chelated form of Fe(III). These results: (1) confirm that iron must be reduced before it can be transported, (2) show that Fe(III) reduction can be uncoupled from proton release, the other major iron-deficiency response, and (3) demonstrate that Fe(III) chelate reductase activity per se is not necessarily responsible for accumulation of cations previously observed in pea and tomato mutants with constitutively high levels of Fe(III) chelate reductase activity.

Toxin-coregulated pilus, but not mannose-sensitive hemagglutinin, is required for colonization by Vibrio cholerae O1 El Tor biotype and O139 strains.

Abstract: The relative contributions of toxin-coregulated pilus (TCP) and cell-associated mannose-sensitive hemagglutinin (MSHA) to the colonization ability of Vibrio cholerae O1 El Tor biotype strains and O139 Bengal strains was determined by using isogenic parental and in-frame deletion mutant pairs in the infant mouse cholera model. Both the El Tor and O139 tcpA mutant strains showed a dramatic defect in colonization as indicated by their competitive indices, whereas deletion of mshA had a negligible effect on colonization in either background.