Showing papers by "University of Pennsylvania published in 2004"

Least angle regression

Abstract: The purpose of model selection algorithms such as All Subsets, Forward Selection and Backward Elimination is to choose a linear model on the basis of the same set of data to which the model will be applied. Typically we have available a large collection of possible covariates from which we hope to select a parsimonious set for the efficient prediction of a response variable. Least Angle Regression (LARS), a new model selection algorithm, is a useful and less greedy version of traditional forward selection methods. Three main properties are derived: (1) A simple modification of the LARS algorithm implements the Lasso, an attractive version of ordinary least squares that constrains the sum of the absolute regression coefficients; the LARS modification calculates all possible Lasso estimates for a given problem, using an order of magnitude less computer time than previous methods. (2) A different LARS modification efficiently implements Forward Stagewise linear regression, another promising new model selection method; this connection explains the similar numerical results previously observed for the Lasso and Stagewise, and helps us understand the properties of both methods, which are seen as constrained versions of the simpler LARS algorithm. (3) A simple approximation for the degrees of freedom of a LARS estimate is available, from which we derive a Cp estimate of prediction error; this allows a principled choice among the range of possible LARS estimates. LARS and its variants are computationally efficient: the paper describes a publicly available algorithm that requires only the same order of magnitude of computational effort as ordinary least squares applied to the full set of covariates.

Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.

Abstract: Regulatory T (T(reg)) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by T(reg) cells; however, definitive evidence that T(reg) cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4(+)CD25(+)FOXP3(+) T(reg) cells in 104 individuals affected with ovarian carcinoma, that human tumor T(reg) cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo. We also show that tumor T(reg) cells are associated with a high death hazard and reduced survival. Human T(reg) cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T(reg) cells to the tumor. This specific recruitment of T(reg) cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T(reg) cell migration or function may help to defeat human cancer.

Cosmological parameters from SDSS and WMAP

Abstract: We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a "vanilla" flat adiabaticCDM model without tilt (ns = 1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1� constraints on the Hubble parameter from h � 0.74 +0.18 −0.07 to h � 0.70 +0.04 −0.03, on the matter density from m � 0.25 ± 0.10 to m � 0.30 ± 0.04 (1�) and on neutrino masses from < 11 eV to < 0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0 � 16.3 +2.3

A Temporal Logic of Nested Calls and Returns

Abstract: Model checking of linear temporal logic (LTL) specifications with respect to pushdown systems has been shown to be a useful tool for analysis of programs with potentially recursive procedures. LTL, however, can specify only regular properties, and properties such as correctness of procedures with respect to pre and post conditions, that require matching of calls and returns, are not regular. We introduce a temporal logic of calls and returns (CaRet) for specification and algorithmic verification of correctness requirements of structured programs. The formulas of CaRet are interpreted over sequences of propositional valuations tagged with special symbols call and ret. Besides the standard global temporal modalities, CaRet admits the abstract-next operator that allows a path to jump from a call to the matching return. This operator can be used to specify a variety of non-regular properties such as partial and total correctness of program blocks with respect to pre and post conditions. The abstract versions of the other temporal modalities can be used to specify regular properties of local paths within a procedure that skip over calls to other procedures. CaRet also admits the caller modality that jumps to the most recent pending call, and such caller modalities allow specification of a variety of security properties that involve inspection of the call-stack. Even though verifying context-free properties of pushdown systems is undecidable, we show that model checking CaRet formulas against a pushdown model is decidable. We present a tableau construction that reduces our model checking problem to the emptiness problem for a Buchi pushdown system. The complexity of model checking CaRet formulas is the same as that of checking LTL formulas, namely, polynomial in the model and singly exponential in the size of the specification.

Law, Finance, and Economic Growth in China

Abstract: China is an important counterexample to the findings in the law, institutions, finance, and growth literature: neither its legal nor financial system is well developed by existing standards, yet it has one of the fastest growing economies. We examine 3 sectors of the economy: the State Sector (state-owned firms), the Listed Sector (publicly listed firms), and the Private Sector (all other firms with various types of private and local government ownership). The law-finance-growth nexus established by existing literature applies to the State and Listed Sectors: with poor legal protections of minority and outside investors, external markets are weak, and the growth of these firms is slow or negative. However, with arguably poorer applicable legal and financial mechanisms, the Private Sector grows much faster than the State and Listed Sectors, and provides most of the economy's growth. This suggests that there exist effective alternative financing channels and governance mechanisms, such as those based on reputation and relationships, to support this growth.

Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.

Abstract: After a median follow-up of 45.9 months, the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for local or regional recurrence, 0.61; 95 percent confidence interval, 0.41 to 0.91; P=0.01). The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group, as compared with 72 percent in the radiotherapy group. Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group (hazard ratio for disease or death, 0.78; 95 percent confidence interval, 0.61 to 0.99; P=0.04), but overall survival was not (hazard ratio for death, 0.84; 95 percent confidence interval, 0.65 to 1.09; P=0.19). The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group (P<0.001). Four patients who received combined therapy died as a direct result of the treatment. conclusions Among high-risk patients with resected head and neck cancer, concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival. However, the combined treatment is associated with a substantial increase in adverse effects.

Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

Abstract: We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.

Risks for the Long Run: A Potential Resolution of Asset Pricing Puzzles

Abstract: We model consumption and dividend growth rates as containing (1) a small longrun predictable component, and (2) fluctuating economic uncertainty (consumption volatility). These dynamics, for which we provide empirical support, in conjunction with Epstein and Zin’s (1989) preferences, can explain key asset markets phenomena. In our economy, financial markets dislike economic uncertainty and better long-run growth prospects raise equity prices. The model can justify the equity premium, the risk-free rate, and the volatility of the market return, risk-free rate, and the price‐ dividend ratio. As in the data, dividend yields predict returns and the volatility of returns is time-varying.

Gesture: Visible Action as Utterance

Abstract: 1. The domain of gesture 2. Visible action as gesture 3. Western interest in gesture from classical antiquity to the eighteenth century 4. Four contributions from the nineteenth century: Andrea de Jorio, Edward Tylor, Garrick Mallery and Wilhelm Wundt 5. Gesture studies in the twentieth century: recession and return 6. Classifying gestures 7. Gesture units, gesture phrases and speech 8. Deployments of gesture in the utterance 9. Gesture and speech in semantic interaction 10. Gesture and referential meaning 11. On pointing 12. Gestures of the 'precision-grip': topic, comment and question markers 13. Two gesture families of the open hand 14. Gesture without speech: the emergence of kinesic codes 15. Gesture and sign on common ground 16. Gesture, culture and the communication economy 17. The status of gesture Appendix I. Transcription conventions Appendix II. The recordings.

The Lagrangian Relaxation Method for Solving Integer Programming Problems

Abstract: (This article originally appeared in Management Science, January 1981, Volume 27, Number 1, pp. 1-18, published by The Institute of Management Sciences.) One of the most computationally useful ideas of the 1970s is the observation that many hard integer programming problems can be viewed as easy problems complicated by a relatively small set of side constraints. Dualizing the side constraints produces a Lagrangian problem that is easy to solve and whose optimal value is a lower bound (for minimization problems) on the optimal value of the original problem. The Lagrangian problem can thus be used in place of a linear programming relaxation to provide bounds in a branch and bound algorithm. This approach has led to dramatically improved algorithms for a number of important problems in the areas of routing, location, scheduling, assignment and set covering. This paper is a review of Lagrangian relaxation based on what has been learned in the last decade.

Beyond Money Toward an Economy of Well-Being

Abstract: Policy decisions at the organizational, corporate, and governmental levels should be more heavily influenced by issues related to well-being—people’s evaluations and feelings about their lives. Domestic policy currently focuses heavily on economic outcomes, although economic indicators omit, and even mislead about, much of what society values. We show that economic indicators have many shortcomings, and that measures of well-being point to important conclusions that are not apparent from economic indicators alone. For example, although economic output has risen steeply over the past decades, there has been no rise in life satisfaction during this period, and there has been a substantial increase in depression and distrust. We argue that economic indicators were extremely important in the early stages of economic development, when the fulfillment of basic needs was the main issue. As societies grow wealthy, however, differences in well-being are less frequently due to income, and are more frequently due to factors such as social relationships and enjoyment at work.

Reliability in Content Analysis: Some Common Misconceptions and Recommendations

Abstract: In a recent article in this journal, Lombard, Snyder-Duch, and Bracken (2002) surveyed 200 content analyses for their reporting of reliability tests, compared the virtues and drawbacks of five popular reliability measures, and proposed guidelines and standards for their use. Their discussion revealed that numerous misconceptions circulate in the content analysis literature regarding how these measures behave and can aid or deceive content analysts in their effort to ensure the reliability of their data. This article proposes three conditions for statistical measures to serve as indices of the reliability of data and examines the mathematical structure and the behavior of the five coefficients discussed by the authors, as well as two others. It compares common beliefs about these coefficients with what they actually do and concludes with alternative recommendations for testing reliability in content analysis and similar data-making efforts.

Global Mapping of the Yeast Genetic Interaction Network

Abstract: A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.

Understanding Terror Networks

Abstract: Preface 1. The Origins of the Jihad 2. The Evolution of the Jihad 3. The Mujahedin 4. Joining the Jihad 5. Social Networks and the Jihad Conclusion Appendix: Names of Terrorists Glossary of Foreign-Language Terms Bibliography Index

Mobile elements: drivers of genome evolution.

Abstract: Mobile elements within genomes have driven genome evolution in diverse ways. Particularly in plants and mammals, retrotransposons have accumulated to constitute a large fraction of the genome and have shaped both genes and the entire genome. Although the host can often control their numbers, massive expansions of retrotransposons have been tolerated during evolution. Now mobile elements are becoming useful tools for learning more about genome evolution and gene function.

The three-dimensional power spectrum of galaxies from the sloan digital sky survey

Abstract: We measure the large-scale real-space power spectrum P(k) by using a sample of 205,443 galaxies from the Sloan Digital Sky Survey, covering 2417 effective square degrees with mean redshift z ≈ 0.1. We employ a matrix-based method using pseudo-Karhunen-Loeve eigenmodes, producing uncorrelated minimum-variance measurements in 22 k-bands of both the clustering power and its anisotropy due to redshift-space distortions, with narrow and well-behaved window functions in the range 0.02 h Mpc-1 < k < 0.3 h Mpc-1. We pay particular attention to modeling, quantifying, and correcting for potential systematic errors, nonlinear redshift distortions, and the artificial red-tilt caused by luminosity-dependent bias. Our results are robust to omitting angular and radial density fluctuations and are consistent between different parts of the sky. Our final result is a measurement of the real-space matter power spectrum P(k) up to an unknown overall multiplicative bias factor. Our calculations suggest that this bias factor is independent of scale to better than a few percent for k < 0.1 h Mpc-1, thereby making our results useful for precision measurements of cosmological parameters in conjunction with data from other experiments such as the Wilkinson Microwave Anisotropy Probe satellite. The power spectrum is not well-characterized by a single power law but unambiguously shows curvature. As a simple characterization of the data, our measurements are well fitted by a flat scale-invariant adiabatic cosmological model with h Ωm = 0.213 ± 0.023 and σ8 = 0.89 ± 0.02 for L* galaxies, when fixing the baryon fraction Ωb/Ωm = 0.17 and the Hubble parameter h = 0.72; cosmological interpretation is given in a companion paper.

Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments

Abstract: Contractile myocytes provide a test of the hypothesis that cells sense their mechanical as well as molecular microenvironment, altering expression, organization, and/or morphology accordingly. Here, myoblasts were cultured on collagen strips attached to glass or polymer gels of varied elasticity. Subsequent fusion into myotubes occurs independent of substrate flexibility. However, myosin/actin striations emerge later only on gels with stiffness typical of normal muscle (passive Young's modulus, E approximately 12 kPa). On glass and much softer or stiffer gels, including gels emulating stiff dystrophic muscle, cells do not striate. In addition, myotubes grown on top of a compliant bottom layer of glass-attached myotubes (but not softer fibroblasts) will striate, whereas the bottom cells will only assemble stress fibers and vinculin-rich adhesions. Unlike sarcomere formation, adhesion strength increases monotonically versus substrate stiffness with strongest adhesion on glass. These findings have major implications for in vivo introduction of stem cells into diseased or damaged striated muscle of altered mechanical composition.

A Knowledge Accessing Theory of Strategic Alliances

Abstract: The emerging knowledge-based view of the firm offers new insight into the causes and management of interfirm alliances. However, the development of an effective knowledge-based theory of alliance formation has been inhibited by a simplistic view of alliances as vehicles for organizational learning in which strategic alliances have presumed to be motivated by firms' desire to acquire knowledge from one another. We argue that the primary advantage of alliances over both firms and markets is in rather than knowledge. Building upon the distinction between the knowledge generation ('exploration') and knowledge application ('exploitation'), we show that alliances contribute to the efficiency in the application of knowledge; first, by improving the efficiency with which knowledge is integrated into the production of complex goods and services, and second, by increasing the efficiency with which knowledge is utilized. These static efficiency advantages of alliances are enhanced where there is uncertainty over future knowledge requirements and where new products offer early-mover advantages. Compared with alternative learning-based approaches to alliance formation, our proposed knowledge-accessing theory of alliances offers the advantages of greater theoretical rigour and consistency with general trends in alliance activity and corporate strategy.

AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus

Abstract: AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus

Liver regeneration: from myth to mechanism

Abstract: The unusual regenerative properties of the liver are a logical adaptation by organisms, as the liver is the main detoxifying organ of the body and is likely to be injured by ingested toxins. The numerous cytokine- and growth-factor-mediated pathways that are involved in regulating liver regeneration are being successfully dissected using molecular and genetic approaches. So what is known about this process at present and which questions remain?

Akt stimulates aerobic glycolysis in cancer cells

Abstract: Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival.

Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes.

Abstract: Programmed cell death can be divided into several categories including type I (apoptosis) and type II (autophagic death). The Bcl-2 family of proteins are well-characterized regulators of apoptosis, and the multidomain pro-apoptotic members of this family, such as Bax and Bak, act as a mitochondrial gateway where a variety of apoptotic signals converge. Although embryonic fibroblasts from Bax/Bak double knockout mice are resistant to apoptosis, we found that these cells still underwent a non-apoptotic death after death stimulation. Electron microscopic and biochemical studies revealed that double knockout cell death was associated with autophagosomes/autolysosomes. This non-apoptotic death of double knockout cells was suppressed by inhibitors of autophagy, including 3-methyl adenine, was dependent on autophagic proteins APG5 and Beclin 1 (capable of binding to Bcl-2/Bcl-x(L)), and was also modulated by Bcl-x(L). These results indicate that the Bcl-2 family of proteins not only regulates apoptosis, but also controls non-apoptotic programmed cell death that depends on the autophagy genes.

Strengths of character and well-being

Abstract: We investigated the relationship between various character strengths and life satisfaction among 5,299 adults from three Internet samples using the Values in Action Inventory of Strengths. Consistently and robustly associated with life satisfaction were hope, zest, gratitude, love, and curiosity. Only weakly associated with life satisfaction, in contrast, were modesty and the intellectual strengths of appreciation of beauty, creativity, judgment, and love of learning. In general, the relationship between character strengths and life satisfaction was monotonic, indicating that excess on any one character strength does not diminish life satisfaction.

Advanced anodes for high-temperature fuel cells

Abstract: Fuel cells will undoubtedly find widespread use in this new millennium in the conversion of chemical to electrical energy, as they offer very high efficiencies and have unique scalability in electricity-generation applications. The solid-oxide fuel cell (SOFC) is one of the most exciting of these energy technologies; it is an all-ceramic device that operates at temperatures in the range 500–1,000 °C. The SOFC offers certain advantages over lower temperature fuel cells, notably its ability to use carbon monoxide as a fuel rather than being poisoned by it, and the availability of high-grade exhaust heat for combined heat and power, or combined cycle gas-turbine applications. Although cost is clearly the most important barrier to widespread SOFC implementation, perhaps the most important technical barriers currently being addressed relate to the electrodes, particularly the fuel electrode or anode. In terms of mitigating global warming, the ability of the SOFC to use commonly available fuels at high efficiency, promises an effective and early reduction in carbon dioxide emissions, and hence is one of the lead new technologies for improving the environment. Here, we discuss recent developments of SOFC fuel electrodes that will enable the better use of readily available fuels.

What Are the Effects of Induction and Mentoring on Beginning Teacher Turnover

Abstract: In recent years there has been an increase in the number of programs offering support, guidance, and orientation for beginning teachers during the transition into their first teaching job. This study examines whether such programs—collectively known as induction—have a positive effect on the retention of beginning teachers. The data used in the analysis are from the nationally representative 1999–2000 Schools and Staffing Survey. The results indicate that beginning teachers who were provided with mentors from the same subject field and who participated in collective induction activities, such as planning and collaboration with other teachers, were less likely to move to other schools and less likely to leave the teaching occupation after their first year of teaching.