Showing papers by "University of Pennsylvania published in 1998"

The Relational View: Cooperative Strategy and Sources of Interorganizational Competitive Advantage

Abstract: In this article we offer a view that suggests that a firm's critical resources may span firm boundaries and may be embedded in interfirm resources and routines. We argue that an increasingly important unit of analysis for understanding competitive advantage is the relationship between firms and identify four potential sources of interorganizational competitive advantage: (1) relation-specific assets, (2) knowledge-sharing routines, (3) complementary resources/capabilities, and (4) effective governance. We examine each of these potential sources of rent in detail, identifying key subprocesses, and also discuss the isolating mechanisms that serve to preserve relational rents. Finally, we discuss how the relational view may offer normative prescriptions for firm-level strategies that contradict the prescriptions offered by those with a resource-based view or industry structure view.

Matching As An Econometric Evaluation Estimator

Abstract: This paper develops the method of matching as an econometric evaluation estimator. A rigorous distribution theory for kernel-based matching is presented. The method of matching is extended to more general conditions than the ones assumed in the statistical literature on the topic. We focus on the method of propensity score matching and show that it is not necessarily better, in the sense of reducing the variance of the resulting estimator, to use the propensity score method even if propensity score is known. We extend the statistical literature on the propensity score by considering the case when it is estimated both parametrically and nonparametrically. We examine the benefits of separability and exclusion restrictions in improving the efficiency of the estimator. Our methods also apply to the econometric selection bias estimator. Matching is a widely-used method of evaluation. It is based on the intuitively attractive idea of contrasting the outcomes of programme participants (denoted Y1) with the outcomes of "comparable" nonparticipants (denoted Y0). Differences in the outcomes between the two groups are attributed to the programme. Let 1 and 11 denote the set of indices for nonparticipants and participants, respectively. The following framework describes conventional matching methods as well as the smoothed versions of these methods analysed in this paper. To estimate a treatment effect for each treated person iecI, outcome Yli is compared to an average of the outcomes Yoj for matched persons je10 in the untreated sample. Matches are constructed on the basis of observed characteristics X in Rd. Typically, when the observed characteristics of an untreated person are closer to those of the treated person ieI1, using a specific distance measure, the untreated person gets a higher weight in constructing the match. The estimated gain for each person i in the treated sample is

Cosmological imprint of an energy component with general equation of state

Abstract: We examine the possibility that a significant component of the energy density of the Universe has an equation of state different from that of matter, radiation, or cosmological constant ( $\ensuremath{\Lambda}$). An example is a cosmic scalar field evolving in a potential, but our treatment is more general. Including this component alters cosmic evolution in a way that fits current observations well. Unlike $\ensuremath{\Lambda}$, it evolves dynamically and develops fluctuations, leaving a distinctive imprint on the microwave background anisotropy and mass power spectrum.

Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17

Abstract: Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17)(1-9), historically termed Pick's disease(10) Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics(1-8,12) Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q2111; the tau gene also lies within this region We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon in The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10 (ref 13) This causes more frequent usage of the 5' splice site and an increased proportion of tan transcripts that include exon 10 The increase in exon 10(+) messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17 (refs 12, 14)

Genetic Heterogeneity and Penetrance Analysis of the BRCA1 and BRCA2 Genes in Breast Cancer Families

Abstract: The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.

The economics of small business finance: The roles of private equity and debt markets in the financial growth cycle

Abstract: This article examines the economics of financing small business in private equity and debt markets. Firms are viewed through a financial growth cycle paradigm in which different capital structures are optimal at different points in the cycle. We show the sources of small business finance, and how capital structure varies with firm size and age. The interconnectedness of small firm finance is discussed along with the impact of the macroeconomic environment. We also analyze a number of research and policy issues, review the literature, and suggest topics for future research.

Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.

Abstract: As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible factor (HIF)-1alpha helps to restore oxygen homeostasis by inducing glycolysis, erythropoiesis and angiogenesis. Here we show that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (HIF-1alpha+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1alpha genes (HIF-1alpha-/-); however, a deficiency of HIF-1alpha does not affect apoptosis induced by cytokines. We find that hypoxia/hypoglycaemia-regulated genes involved in controlling the cell cycle are either HIF-1alpha-dependent (those encoding the proteins p53, p21, Bcl-2) or HIF-1alpha-independent (p27, GADD153), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients. Loss of HIF-1alpha reduces hypoxia-induced expression of vascular endothelial growth factor, prevents formation of large vessels in ES-derived tumours, and impairs vascular function, resulting in hypoxic microenvironments within the tumour mass. However, growth of HIF-1alpha tumours was not retarded but was accelerated, owing to decreased hypoxia-induced apoptosis and increased stress-induced proliferation. As hypoxic stress contributes to many (patho)biological disorders, this new role for HIF-1alpha in hypoxic control of cell growth and death may be of general pathophysiological importance.

Measurement of the solar electron neutrino flux with the Homestake chlorine detector

Abstract: The Homestake Solar Neutrino Detector, based on the inverse beta-decay reaction νe +37Cl →37Ar + e-, has been measuring the flux of solar neutrinos since 1970. The experiment has operated in a stable manner throughout this time period. All aspects of this detector are reviewed, with particular emphasis on the determination of the extraction and counting efficiencies, the key experimental parameters that are necessary to convert the measured 37Ar count rate to the solar neutrino production rate. A thorough consideration is also given to the systematics of the detector, including the measurement of the extraction and counting efficiencies and the nonsolar production of 37Ar. The combined result of 108 extractions is a solar neutrino-induced 37Ar production rate of 2.56 ± 0.l6 (statistical) ± 0.16 (systematic) SNU.

The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment.

Abstract: This article reviews the burgeoning literature on the relationship of mood disorders and heart disease. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated in patients with cardiovascular disease (CVD). This is of particular importance because several studies have shown depression and its associated symptoms to be a major risk factor for both the development of CVD and death after an index myocardial infarction. This review of the extant literature is derived from MEDLINE searches (1966-1997) using the search terms "major depression," "psychiatry," "cardiovascular disease," and "pathophysiology." Studies investigating pathophysiological alterations related to CVD in depressed patients are reviewed. The few studies on treatment of depression in patients with CVD are also described. Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity. Recommendations for future research are proposed.

Large-scale purification of single-wall carbon nanotubes: process, product, and characterization

Abstract: We describe, in detail, a readily scalable purification process capable of handling single-wall carbon nanotube (SWNT) material in large batches. Characterization of the resulting material by SEM, TEM, XRD, Raman scattering, and TGA shows it to be highly pure. Resistivity measurements on freestanding mats of the purified tubes are also reported. We also report progress in scaling up SWNT production by the dual pulsed laser vaporization process. These successes enable the production of gram per day quantities of highly pure SWNT, which should greatly facilitate investigation of material properties intrinsic to the nanotubes.

Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer

Abstract: Background We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. Methods Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. Results Of the 440 eligible patients with adequate data, 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who u...

Encapsulated C 60 in carbon nanotubes

Abstract: Pulsed laser vaporization of graphite in the presence of certain metallic catalysts produces both carbon nanotubes and C60 molecules1. In nanotube production, most of the C60 is removed, along with other residual contaminants, by purification and annealing. It has been suggested that C60 may be trapped inside a nanotube during this elaborate sequence, but this has not been detected.

Evaluating Density Forecasts with Applications to Financial Risk Management

Abstract: Density forecasting is increasingly more important and commonplace, forexample in financial risk management, yet little attention has been given to theevaluation of density forecasts. We develop a simple and operational frameworkfor density forecast evaluation. We illustrate the framework with adetailed application to density forecasting of asset returns in environments withtime-varying volatility. Finally, we discuss several extensions.

Nuclear events in ethylene signaling: a transcriptional cascade mediated by ETHYLENE-INSENSITIVE3 and ETHYLENE-RESPONSE-FACTOR1

Abstract: Response to the gaseous plant hormone ethylene in Arabidopsis requires the EIN3/EIL family of nuclear proteins. The biochemical function(s) of EIN3/EIL proteins, however, has remained unknown. In this study, we show that EIN3 and EILs comprise a family of novel sequence-specific DNA-binding proteins that regulate gene expression by binding directly to a primary ethylene response element (PERE) related to the tomato E4-element. Moreover, we identified an immediate target of EIN3, ETHYLENE-RESPONSE-FACTOR1 (ERF1), which contains this element in its promoter. EIN3 is necessary and sufficient for ERF1 expression, and, like EIN3-overexpression in transgenic plants, constitutive expression of ERF1 results in the activation of a variety of ethylene response genes and phenotypes. Evidence is also provided that ERF1 acts downstream of EIN3 and all other components of the ethylene signaling pathway. The results demonstrate that the nuclear proteins EIN3 and ERF1 act sequentially in a cascade of transcriptional regulation initiated by ethylene gas.

Innovations in Performance Measurement: Trends and Research Implications

Abstract: The objective of this paper is to foster research on recent innovations in performance measurement by providing a rich description of emerging measurement practices and suggesting directions for future research. Using survey data collected by consulting firms and government organizations, we examine three measurement trends: (1) economic value measures, (2) non-financial performance measures and the balanced scorecard, and (3) performance measurement initiatives in government agencies. Existing research on these topics is reviewed and research opportunities are highlighted.

Beyond the productivity paradox

Abstract: of output produced per unit of input. While it is easy to define, it is notoriously difficult to measure, especially in the modern economy. In particular, there are two aspects of productivity that have increasingly defied precise measurement: output and input. Properly measured, output should include not just the number of widgets coming out of a factory, or the lines of code produced by a programming team, but rather the value created for consumers. Fifty years ago, tons of steel or bushels of corn were a reasonable proxy for the value of output. In today’s economy, value depends increasingly on product quality, timeliness, customization, convenience, variety, and other intangibles. Why Should We Care About Productivity?

Structure of the amide i band of peptides measured by femtosecond nonlinear-infrared spectroscopy

Abstract: Femtosecond infrared (IR) pump probe and dynamic hole burning experiments were used to examine the ultrafast response of the modes in the 1600−1700 cm-1 region (the so-called amide I modes) of N-methylacetamide (NMA) and three small globular peptides, apamin, scyllatoxin, and bovine pancreatic trypsin inhibitor (BPTI). A value of 16 cm-1 was found for the anharmonicity of the amide I vibration. Vibrational relaxation of the amide I modes of all investigated peptides occurs in ca. 1.2 ps. An even faster value of 450 fs is obtained for NMA, a model for the peptide unit. The vibrational relaxation is dominated by intramolecular energy redistribution (IVR) and reflects an intrinsic property of the peptide group in any environment. Dynamic hole burning experiments with a narrow band pump pulse which selectively excites only a subset of the amide I eigenstates reveal that energy migration between different amide I states is slow compared with vibrational relaxation. Two-dimensional pump−probe (2D-IR) spectra th...

National Cultural Distance and Cross-Border Acquisition Performance

Abstract: Previous theoretical research has argued that national cultural distance hinders cross-border acquisition performance by increasing the costs of integration This article tests the alternative hypothesis that national cultural distance enhances cross-border acquisition performance by providing access to the target's and/or the acquirer's diverse set of routines and repertoires embedded in national culture Using a multi-dimensional measure of national cultural distance and controlling for other effects, we examine a sample of 52 cross-border acquisitions that took place between 1987 and 1992, and find a positive association between national cultural distance and cross-border acquisition performance

Optimal Financial Crises

Abstract: Empirical evidence suggests that banking panics are related to the business cycle and are not simply the result of "sunspots." Panics occur when depositors perceive that the returns on bank assets are going to be unusually low. We develop a simple model of this. In this setting, bank runs can be first-best efficient: they allow efficient risk sharing between early and late withdrawing depositors and they allow banks to hold efficient portfolios. However, if costly runs or markets for risky assets are introduced, central bank intervention of the right kind can lead to a Pareto improvement in welfare. FROM THE EARLIEST TIMES, banks have been plagued by the problem of bank runs in which many or all of the bank's depositors attempt to withdraw their funds simultaneously. Because banks issue liquid liabilities in the form of deposit contracts, but invest in illiquid assets in the form of loans, they are vulnerable to runs that can lead to closure and liquidation. A financial crisis or banking panic occurs when depositors at many or all of the banks in a region or a country attempt to withdraw their funds simultaneously. Prior to the twentieth century, banking panics occurred frequently in Europe and the United States. Panics were generally regarded as a bad thing and the development of central banks to eliminate panics and ensure financial stability has been an important feature of the history of financial systems. It has been a long and involved process. The first cerntral bank, the Bank of Sweden, was established more than 300 years ago. The Bank of England played an especially important role in the development of effective stabilization policies in the eighteenth and nineteenth centuries. By the end of the nineteenth century, banking panics had been eliminated in Europe. The last true panic in England was the Overend, Gurney & Company Crisis of 1866.

Mutation-Specific Functional Impairments in Distinct Tau Isoforms of Hereditary FTDP-17

Abstract: Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms. Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.

Characterizing Selection Bias Using Experimental Data

Abstract: This paper develops and applies semiparametric econometric methods to estimate the form of selection bias that arises from using nonexperimental comparison groups to evaluate social programs and to test the identifying assumptions that justify three widely-used classes of estimators and our extensions of them: (a) the method of matching; (b) the classical econometric selection model which represents the bias solely as a function of the probability of participation; and (c) the method of difference-in-differences. Using data from an experiment on a prototypical social program combined with unusually rich data from a nonexperimental comparison group, we reject the assumptions justifying matching and our extensions of that method but find evidence in support of the index-sufficient selection bias model and the assumptions that justify application of a conditional semiparametric version of the method of difference-in-difference. Fa comparable people and to appropriately weight participants and nonparticipants a sources of selection bias as conveniently measured. We present a rigorous defin bias and find that in our data it is a small component of conventially meausred it is still substantial when compared with experimentally-estimated program impa matching participants to comparison group members in the same labor market, givi same questionnaire, and making sure they have comparable characteristics substan the performance of any econometric program evaluation estimator. We show how t analysis to estimate the impact of treatment on the treated using ordinary obser

Entry of Alphaherpesviruses Mediated by Poliovirus Receptor-Related Protein 1 and Poliovirus Receptor

Abstract: A human member of the immunoglobulin superfamily was shown to mediate entry of several alphaherpesviruses, including herpes simplex viruses (HSV) 1 and 2, porcine pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1). This membrane glycoprotein is poliovirus receptor-related protein 1 (Prr1), designated here as HveC. Incubation of HSV-1 with a secreted form of HveC inhibited subsequent infection of a variety of cell lines, suggesting that HveC interacts directly with the virus. Poliovirus receptor (Pvr) itself mediated entry of PRV and BHV-1 but not of the HSV strains tested. HveC was expressed in human cells of epithelial and neuronal origin; it is the prime candidate for the coreceptor that allows both HSV-1 and HSV-2 to infect epithelial cells on mucosal surfaces and spread to cells of the nervous system.

A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.

Abstract: Epileptic disorders affect about 20-40 million people worldwide, and 40% of these are idiopathic generalized epilepsies (IGEs; ref. 1). Most of the IGEs that are inherited are complex, multigenic diseases. To address basic mechanisms for epilepsies, we have focused on one well-defined class of IGEs with an autosomal-dominant mode of inheritance: the benign familial neonatal convulsions (BFNC; refs 2,3). Genetic heterogeneity of BFNC has been observed. Two loci, EBN1 and EBN2, have been mapped by linkage analysis to chromosome 20q13 (refs 5,6) and chromosome 8q24 (refs 7,8), respectively. By positional cloning, we recently identified the gene for EBN1 as KCNQ2 (ref. 9). This gene, a voltage-gated potassium channel, based on homology, is a member of the KQT-like family. Here we describe an additional member, KCNQ3. We mapped this new gene to chromosome 8, between markers D8S256 and D8S284 on a radiation hybrid map. We screened KCNQ3 for mutations in the large BFNC family previously linked to chromosome 8q24 in the same marker interval. We found a missense mutation in the critical pore region in perfect co-segregation with the BFNC phenotype. The same conserved amino acid is also mutated in KVLQT1 (KCNQ1) in an LQT patient. KCNQ2, KCNQ3 and undiscovered genes of the same family of K+ channels are strong candidates for other IGEs.

Cluster Abundance Constraints for Cosmological Models with a Time-varying, Spatially Inhomogeneous Energy Component with Negative Pressure

Abstract: The abundance of rich clusters is a strong constraint on the mass power spectrum. The current constraint can be expressed in the form ? -->8 ?${γ}m$ -->=0.5?0.1, where ?8 is the rms mass fluctuation on 8 h-1 Mpc scales, ?m is the ratio of matter density to the critical density, and ? is model dependent. In this paper, we determine a general expression for ? that applies to any models with a mixture of cold dark matter plus cosmological constant or quintessence (a time-evolving, spatially inhomogeneous component with negative pressure) including dependence on the spectral index n, the Hubble constant h, and the equation of state of the quintessence component w. The cluster constraint is combined with COBE measurements to identify a range of best-fitting models. The constraint from the evolution of rich clusters is also discussed.

A new classification for HIV-1

Abstract: The phenotype of HIV-1 isolates is defined by the cells in which they replicate in vitro, but these phenotypes can change in vivo with profound implications for viral transmission, pathogenesis and disease progression. Here we propose a new classification system based on co-receptor use, providing a more accurate description of viral phenotype than the present imprecise and often misleading classification schemes.