Showing papers by "Harvard University published in 1990"

Soft self-consistent pseudopotentials in a generalized eigenvalue formalism.

Abstract: A new approach to the construction of first-principles pseudopotentials is described. The method allows transferability to be improved systematically while holding the cutoff radius fixed, even for large cutoff radii. Novel features are that the pseudopotential itself becomes charge-state dependent, the usual norm-conservation constraint does not apply, and a generalized eigenproblem is introduced. The potentials have a separable form well suited for plane-wave solid-state calculations, and show promise for application to first-row and transition-metal systems.

In vitro selection of RNA molecules that bind specific ligands.

Abstract: Subpopulations of RNA molecules that bind specifically to a variety of organic dyes have been isolated from a population of random sequence RNA molecules. Roughly one in 10(10) random sequence RNA molecules folds in such a way as to create a specific binding site for small ligands.

Adhesion receptors of the immune system.

Abstract: The adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes, but have a central role in the functions of the immune system throughout life Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses

A bridging model for parallel computation

Abstract: The success of the von Neumann model of sequential computation is attributable to the fact that it is an efficient bridge between software and hardware: high-level languages can be efficiently compiled on to this model; yet it can be effeciently implemented in hardware. The author argues that an analogous bridge between software and hardware in required for parallel computation if that is to become as widely used. This article introduces the bulk-synchronous parallel (BSP) model as a candidate for this role, and gives results quantifying its efficiency both in implementing high-level language features and algorithms, as well as in being implemented in hardware.

Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms

Abstract: Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

A combined quantum mechanical and molecular mechanical potential for molecular dynamics simulations

Abstract: A combined quantum mechanical (QM) and molecular mechanical (MM) potential has been developed for the study of reactions in condensed phases. For the quantum mechanical calculations semiempirical methods of the MNDO and AM1 type are used, while the molecular mechanics part is treated with the CHARMM force field. Specific prescriptions are given for the interactions between the QM and MM portions of the system; cases in which the QM and MM methodology is applied to parts of the same molecule or to different molecules are considered. The details of the method and a range of test calculations, including comparisons with ab initio and experimental results, are given. It is found that in many cases satisfactory results are obtained. However, there are limitations to this type of approach, some of which arise from the AM1 or MNDO methods themselves and others from the present QM/MM implementation. This suggests that it is important to test the applicability of the method to each particular case prior to its use. Possible areas of improvement in the methodology are discussed.

Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides

Abstract: The amyloid beta protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid beta protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid beta protein caused dendritic and axonal retraction followed by neuronal death. A portion of the amyloid beta protein (amino acids 25 to 35) mediated both the trophic and toxic effects and was homologous to the tachykinin neuropeptide family. The effects of the amyloid beta protein were mimicked by tachykinin antagonists and completely reversed by specific tachykinin agonists. Thus, the amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.

The Allocation of Talent: Implications for Growth

Abstract: A country's most talented people typically organize production by others, so they can spread their ability advantage over a larger scale. When they start firms, they innovate and foster growth, but when they become rent seekers, they only redistribute wealth and reduce growth. Occupational choice depends on returns to ability and to scale in each sector, on market size, and on compensation contracts. In most countries, rent seeking rewards talent more than entrepreneurship does, leading to stagnation. Our evidence shows that countries with a higher proportion of engineering college majors grow faster; whereas countries with a higher proportion of law concentrators grow slower.

The Multinational Corporation as an Interorganizational Network

Abstract: A multinational corporation consists of a group of geographically dispersed and goal-disparate organizations that include its headquarters and the different national subsidiaries. Such an entity can be conceptualized as an interorganizational network that is embedded in an external network consisting of all other organizations such as customers, suppliers, regulators, and so on, with which the different units of the multinational must interact. Based on such a conceptualization, the present authors draw on interorganization theory to develop a model of the multinational corporation as an internally differentiated interorganizational network. They propose hypotheses that relate certain attributes of the multinational, such as resource configuration and internal distribution of power, to certain structural properties of its external network.

Dynamic Fracture Mechanics

Abstract: Preface List of symbols 1. Background and overview 2. Basic elastodynamic solutions for a stationary crack 3. Further results for a stationary crack 4. Asymptotic fields near a moving crack tip 5. Energy concepts in dynamic fracture 6. Elastic crack growth at constant speed 7. Elastic crack growth at nonuniform speed 8. Plasticity and rate effects during crack growth Bibliography Index.

VLA proteins in the integrin family : structures, functions and their role on leukocytes

Abstract: Article de synthese sur les roles des integrines β1 (proteines VLA) comme recepteurs dans l'adherence des leucocytes a la matrice extracellulaire et comme recepteurs dans l'adherence cellule a cellule

The Noise Trader Approach to Finance

Abstract: This paper reviews an alternative to the efficient markets approach that we and others have recently pursued. Our approach rests on two assumptions. First, some investors are not fully rational and their demand for risky assets is affected by their beliefs or sentiments that are not fully justified by fundamental news. Second, arbitrage - defined as trading by fully rational investors not subject to such sentiment - is risky and therefore limited. The two assumption together imply that changes in investors sentiment are not fully countered by arbitrageurs and so affect security returns. We argue that this approach to financial markets is in many ways superior to the efficient markets paradigm. Our case for the noise trader approach is threefold. First, theoretical models with limited arbitrage are both tractable and more plausible than models with perfect arbitrage. The efficient markets hypithesis obtains only as an extreme case of perfect riskless arbitrage that unlikely to apply in practice. Second, the investors sentiment/ limited arbitrage approach yields a more accurate description of financial markets than the efficient markets paradigm. The approach not only explains the available anomalies, but also readly explains board features of financial markets such as trading volume and actual investment strategies. Third, and most importantly, this approach yields new and testable implications about asset prices, some of which have been proved to be consistent with the data. It is absolutely not true that introducing a degree of irrationality of some investors into models of financial markets "eliminates all discipline and can explain anything".

A Dual Methodology for Case Studies: Synergistic Use of a Longitudinal Single Site with Replicated Multiple Sites

Abstract: This paper describes a case study methodology that combines a real-time longitudinal three-year study with nine retrospective case studies about the same phenomenon. These two kinds of case studies offer opportunities for complementary and synergistic data gathering and analysis. That is, specific strengths in each method compensate for some particular weakness in the other. For instance, the retrospective studies offer the opportunity to identify patterns indicative of dynamic processes and the longitudinal study provides a close-up view of those patterns as they evolve over time. The combination of the two types of case studies also enhances three kinds of validity: construct, internal and external. The author also discusses problems with and shortcomings of this dual methodology and suggests the circumstances for which the methodology is especially appropriate.

A prospective study of obesity and risk of coronary heart disease in women.

Abstract: We examined the incidence of nonfatal and fatal coronary heart disease in relation to obesity in a prospective cohort study of 115,886 U.S. women who were 30 to 55 years of age in 1976 and free of diagnosed coronary disease, stroke, and cancer. During eight years of follow-up (775,430 person-years), we identified 605 first coronary events, including 306 nonfatal myocardial infarctions, 83 deaths due to coronary heart disease, and 216 cases of confirmed angina pectoris. A higher Quetelet index (weight in kilograms divided by the square of the height in meters) was positively associated with the occurrence of each category of coronary heart disease. For increasing levels of current Quetelet index (less than 21, 21 to less than 23, 23 to less than 25, 25 to less than 29, and greater than or equal to 29), the relative risks of nonfatal myocardial infarction and fatal coronary heart disease combined, as adjusted for age and cigarette smoking, were 1.0, 1.3, 1.3, 1.8, and 3.3 (Mantel-extension chi for trend = 7.29; P less than 0.00001). As expected, control for a history of hypertension, diabetes mellitus, and hypercholesterolemia--conditions known to be biologic effects of obesity--attenuated the strength of the association. The current Quetelet index was a more important determinant of coronary risk than that at the age of 18; an intervening weight gain increased risk substantially. These prospective data emphasize the importance of obesity as a determinant of coronary heart disease in women. After control for cigarette smoking, which is essential to assess the true effects of obesity, even mild-to-moderate overweight increased the risk of coronary disease in middle-aged women.

A meta-analysis of physical activity in the prevention of coronary heart disease

Abstract: Evidence for an independent role of increased physical activity in the primary prevention of coronary heart disease has grown in recent years. The authors apply the techniques of meta-analysis to data extracted from the published literature by Powell et al. (Ann Rev Public Health 1987;8:253-87), as well as more recent studies addressing this relation, in order to make formal quantitative statements and to explore features of study design that influence the observed relation between physical activity and coronary heart disease risk. They find, for example, a summary relative risk of death from coronary heart disease of 1.9 (95% confidence interval 1.6-2.2) for sedentary compared with active occupations. The authors also find that methodologically stronger studies tend to show a larger benefit of physical activity than less well-designed studies.

Assessing the political landscape: Structure, cognition, and power in organizations.

Abstract: David Krackhardt Comell University This paper argues that an accurate cognition of informal networks can itself be a base of power, above and beyond power attributable to informal and formal structural positions. To explore this claim, a small entrepreneurial firm was studied. Perceptions of the friendship and advice networks were compared to \"actual\" networte. Those who had more accurate cognitions of the advice network were rated as more powerful by others in the organization, although accuracy of the friendship network was not related to reputational power.*

The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation.

Abstract: Background Nonrheumatic atrial fibrillation increases the risk of stroke, presumably from atrial thromboemboli. There is uncertainty about the efficacy and risks of long-term warfarin therapy to prevent stroke. Methods We conducted an unblinded, randomized, controlled trial of long-term, low-dose warfarin therapy (target prothrombin-time ratio, 1.2 to 1.5) in patients with nonrheumatic atrial fibrillation. The control group was not given warfarin but could choose to take aspirin. Results A total of 420 patients entered the trial (212 in the warfarin group and 208 in the control group) and were followed for an average of 2.2 years. Prothrombin times in the warfarin group were in the target range 83 percent of the time. Only 10 percent of the patients assigned to receive warfarin discontinued the drug permanently. There were 2 strokes in the warfarin group (incidence, 0.41 percent per year) as compared with 13 strokes in the control group (incidence, 2.98 percent per year), for a reduction of 86 percent in the risk of stroke (warfarin:control incidence ratio = 0.14; 95 percent confidence interval, 0.04 to 0.49; P = 0.0022). There were 37 deaths altogether. The death rate was markedly lower in the warfarin group than in the control group: 2.25 percent as compared with 5.97 percent per year, for an incidence ratio of 0.38 (95 percent confidence interval, 0.17 to 0.82; P = 0.005). There was one fatal hemorrhage in each group. The frequency of bleeding events that led to hospitalization or transfusion was essentially the same in both groups. The warfarin group had a higher rate of minor hemorrhage than the control group (38 vs. 21 patients). Conclusions Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation, and can be quite safe with careful monitoring.

A Positive Theory of Fiscal Deficits and Government Debt

Abstract: This paper considers an economy in which policymakers with different preferences alternate in office as a result of elections. Government debt is used strategically by each policymaker to influence the choices of his successors. If different policymakers disagree about the desired composition of government spending between two public goods, the economy exhibits a deficits bias; that is, debt accumulation is higher than it would be with a social planner. The equilibrium level of debt is larger the larger is the degree of polarization between alternating governments and the less likely it is that the current government will be re-elected.

Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping

Abstract: Cytogenetic analysis has identified chromosome 11p13 as the smallest overlap region for deletions found in individuals with WAGR syndrome, which includes Wilms tumour (a recessive childhood nephroblastoma), aniridia, genito-urinary abnormalities and mental retardation. The underlying loci have since been resolved into an aniridia (AN2) locus at a telomeric position, and a locus of closely spaced genes or a single pleiotropic gene involved in genito-urinary tract abnormalities and Wilms tumour at a more centromeric position. Pulsed-field gel analysis of the 11p13 region has revealed the presence of several putative CpG islands, structures which are frequently associated with the 5' ends of expressed sequences, mainly housekeeping genes and some tissue-specific genes. Starting from a CpG island, we have now isolated four neighbouring CpG islands, all within 650 kilobases (kb), by means of two consecutive bidirectional jumps in rare-cutting restriction-enzyme jumping libraries. In two instances, flanking sequences were conserved in other species and RNA transcripts were identified. A complementary DNA clone isolated for one of them derives from an RNA highly expressed in fetal kidney, and is predicted to encode a Kruppel-like zinc-finger protein that is probably a transcription factor. The entire cDNA region is included in two partially overlapping homozygous deletions found in Wilms tumour DNA samples. Cloning of the breakpoints in one tumour revealed a deletion size of 170 kb, one-third of which is covered by the cDNA. The expression pattern and sequence of this cDNA could point to an important role for its corresponding gene in the normal development of the renal system as well as in Wilms tumour.

Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women.

Abstract: Background The rates of colon cancer in various countries are strongly correlated with the per capita consumption of red meat and animal fat and, to a lesser degree, inversely associated with the consumption of fiber. Methods We conducted a prospective study among 88,751 women 34 to 59 years old and without a history of cancer, inflammatory bowel disease, or familial polyposis who completed a dietary questionnaire in 1980. By 1986, during 512,488 person-years of follow-up, 150 incident cases of colon cancer had been documented. Results After adjustment for total energy intake, animal fat was positively associated with the risk of colon cancer (P for trend = 0.01); the relative risk for the highest as compared with the lowest quintile was 1.89 (95 percent confidence interval, 1.13 to 3.15). No association was found for vegetable fat. The relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 (95 percent confidence interval, 1.24 to 5.03), as compared with those reporting consumption less than once a month. Processed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk. The ratio of the intake of red meat to the intake of chicken and fish was particularly strongly associated with an increased incidence of colon cancer (P for trend = 0.0005); the relative risk for women in the highest quintile of this ratio as compared with those in the lowest quintile was 2.49 (95 percent confidence interval, 1.50 to 4.13). A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but this relation was not statistically independent of meat intake. Conclusions These prospective data provide evidence for the hypothesis that a high intake of animal fat increases the risk of colon cancer, and they support existing recommendations to substitute fish and chicken for meats high in fat.

Why change programs don't produce change.

Abstract: Faced with changing markets and tougher competition, more and more companies realize that to compete effectively they must transform how they function. But while senior managers understand the necessity of change, they often misunderstand what it takes to bring it about. They assume that corporate renewal is the product of company-wide change programs and that in order to transform employee behavior, they must alter a company's formal structure and systems. Both these assumptions are wrong, say these authors. Using examples drawn from their four-year study of organizational change at six large corporations, they argue that change programs are, in fact, the greatest obstacle to successful revitalization and that formal structures and systems are the last thing a company should change, not the first. The most successful change efforts begin at the periphery of a corporation, in a single plant or division. Such efforts are led by general managers, not the CEO or corporate staff people. And these general managers concentrate not on changing formal structures and systems but on creating ad hoc organizational arrangements to solve concrete business problems. This focuses energy for change on the work itself, not on abstractions such as "participation" or "culture." Once general managers understand the importance of this grass-roots approach to change, they don't have to wait for senior management to start a process of corporate renewal. The authors describe a six-step change process they call the "critical path."