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Showing papers by "University of Chicago published in 2009"


Journal ArticleDOI
08 Oct 2009-Nature
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Abstract: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

7,797 citations


Journal ArticleDOI
TL;DR: An overview of the CHARMM program as it exists today is provided with an emphasis on developments since the publication of the original CHARMM article in 1983.
Abstract: CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecu- lar simulation program. It has been developed over the last three decades with a primary focus on molecules of bio- logical interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estima- tors, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numer- ous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

7,035 citations


Journal ArticleDOI
TL;DR: In this article, the Wilkinson Microwave Anisotropy Probe (WMAP) 5-year data were used to constrain the physics of cosmic inflation via Gaussianity, adiabaticity, the power spectrum of primordial fluctuations, gravitational waves, and spatial curvature.
Abstract: The Wilkinson Microwave Anisotropy Probe (WMAP) 5-year data provide stringent limits on deviations from the minimal, six-parameter Λ cold dark matter model. We report these limits and use them to constrain the physics of cosmic inflation via Gaussianity, adiabaticity, the power spectrum of primordial fluctuations, gravitational waves, and spatial curvature. We also constrain models of dark energy via its equation of state, parity-violating interaction, and neutrino properties, such as mass and the number of species. We detect no convincing deviations from the minimal model. The six parameters and the corresponding 68% uncertainties, derived from the WMAP data combined with the distance measurements from the Type Ia supernovae (SN) and the Baryon Acoustic Oscillations (BAO) in the distribution of galaxies, are: Ω b h 2 = 0.02267+0.00058 –0.00059, Ω c h 2 = 0.1131 ± 0.0034, ΩΛ = 0.726 ± 0.015, ns = 0.960 ± 0.013, τ = 0.084 ± 0.016, and at k = 0.002 Mpc-1. From these, we derive σ8 = 0.812 ± 0.026, H 0 = 70.5 ± 1.3 km s-1 Mpc–1, Ω b = 0.0456 ± 0.0015, Ω c = 0.228 ± 0.013, Ω m h 2 = 0.1358+0.0037 –0.0036, z reion = 10.9 ± 1.4, and t 0 = 13.72 ± 0.12 Gyr. With the WMAP data combined with BAO and SN, we find the limit on the tensor-to-scalar ratio of r 1 is disfavored even when gravitational waves are included, which constrains the models of inflation that can produce significant gravitational waves, such as chaotic or power-law inflation models, or a blue spectrum, such as hybrid inflation models. We obtain tight, simultaneous limits on the (constant) equation of state of dark energy and the spatial curvature of the universe: –0.14 < 1 + w < 0.12(95%CL) and –0.0179 < Ω k < 0.0081(95%CL). We provide a set of WMAP distance priors, to test a variety of dark energy models with spatial curvature. We test a time-dependent w with a present value constrained as –0.33 < 1 + w 0 < 0.21 (95% CL). Temperature and dark matter fluctuations are found to obey the adiabatic relation to within 8.9% and 2.1% for the axion-type and curvaton-type dark matter, respectively. The power spectra of TB and EB correlations constrain a parity-violating interaction, which rotates the polarization angle and converts E to B. The polarization angle could not be rotated more than –59 < Δα < 24 (95% CL) between the decoupling and the present epoch. We find the limit on the total mass of massive neutrinos of ∑m ν < 0.67 eV(95%CL), which is free from the uncertainty in the normalization of the large-scale structure data. The number of relativistic degrees of freedom (dof), expressed in units of the effective number of neutrino species, is constrained as N eff = 4.4 ± 1.5 (68%), consistent with the standard value of 3.04. Finally, quantitative limits on physically-motivated primordial non-Gaussianity parameters are –9 < f local NL < 111 (95% CL) and –151 < f equil NL < 253 (95% CL) for the local and equilateral models, respectively.

5,904 citations


Journal ArticleDOI
TL;DR: A series of improvements to the spectroscopic reductions are described, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.
Abstract: This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11,663 deg^2 of imaging data, with most of the ~2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry on a 120° long, 2°.5 wide stripe along the celestial equator in the Southern Galactic Cap, with some regions covered by as many as 90 individual imaging runs. We include a co-addition of the best of these data, going roughly 2 mag fainter than the main survey over 250 deg^2. The survey has completed spectroscopy over 9380 deg^2; the spectroscopy is now complete over a large contiguous area of the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog, reducing the rms statistical errors at the bright end to 45 milliarcseconds per coordinate. We further quantify a systematic error in bright galaxy photometry due to poor sky determination; this problem is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.

5,665 citations


Journal ArticleDOI
30 Jul 2009-Blood
TL;DR: The classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.

4,274 citations


Journal ArticleDOI
W. B. Atwood1, A. A. Abdo2, A. A. Abdo3, Markus Ackermann4  +289 moreInstitutions (37)
TL;DR: The Large Area Telescope (Fermi/LAT) as mentioned in this paper is the primary instrument on the Fermi Gamma-ray Space Telescope, which is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV.
Abstract: (Abridged) The Large Area Telescope (Fermi/LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV. This paper describes the LAT, its pre-flight expected performance, and summarizes the key science objectives that will be addressed. On-orbit performance will be presented in detail in a subsequent paper. The LAT is a pair-conversion telescope with a precision tracker and calorimeter, each consisting of a 4x4 array of 16 modules, a segmented anticoincidence detector that covers the tracker array, and a programmable trigger and data acquisition system. Each tracker module has a vertical stack of 18 x,y tracking planes, including two layers (x and y) of single-sided silicon strip detectors and high-Z converter material (tungsten) per tray. Every calorimeter module has 96 CsI(Tl) crystals, arranged in an 8 layer hodoscopic configuration with a total depth of 8.6 radiation lengths. The aspect ratio of the tracker (height/width) is 0.4 allowing a large field-of-view (2.4 sr). Data obtained with the LAT are intended to (i) permit rapid notification of high-energy gamma-ray bursts (GRBs) and transients and facilitate monitoring of variable sources, (ii) yield an extensive catalog of several thousand high-energy sources obtained from an all-sky survey, (iii) measure spectra from 20 MeV to more than 50 GeV for several hundred sources, (iv) localize point sources to 0.3 - 2 arc minutes, (v) map and obtain spectra of extended sources such as SNRs, molecular clouds, and nearby galaxies, (vi) measure the diffuse isotropic gamma-ray background up to TeV energies, and (vii) explore the discovery space for dark matter.

3,666 citations


Journal ArticleDOI
TL;DR: In this article, the open-circuit voltage of polymer solar cells constructed based on the structure of a low-bandgap polymer, PBDTTT, can be tuned, step by step, using different functional groups.
Abstract: Following the development of the bulk heterojunction1 structure, recent years have seen a dramatic improvement in the efficiency of polymer solar cells. Maximizing the open-circuit voltage in a low-bandgap polymer is one of the critical factors towards enabling high-efficiency solar cells. Study of the relation between open-circuit voltage and the energy levels of the donor/acceptor2 in bulk heterojunction polymer solar cells has stimulated interest in modifying the open-circuit voltage by tuning the energy levels of polymers3. Here, we show that the open-circuit voltage of polymer solar cells constructed based on the structure of a low-bandgap polymer, PBDTTT4, can be tuned, step by step, using different functional groups, to achieve values as high as 0.76 V. This increased open-circuit voltage combined with a high short-circuit current density results in a polymer solar cell with a power conversion efficiency as high as 6.77%, as certified by the National Renewable Energy Laboratory. Adding electron-withdrawing groups to the backbone of the polymer PBDTTT is shown to increase the open-circuit voltage of photovoltaic cells, resulting in a polymer solar-cell that has a certified power-conversion efficiency of 6.77%.

3,029 citations


Journal ArticleDOI
TL;DR: Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli, along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.
Abstract: Mucosal surfaces are lined by epithelial cells. These cells establish a barrier between sometimes hostile external environments and the internal milieu. However, mucosae are also responsible for nutrient absorption and waste secretion, which require a selectively permeable barrier. These functions place the mucosal epithelium at the centre of interactions between the mucosal immune system and luminal contents, including dietary antigens and microbial products. Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli. Here I discuss these discoveries along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.

2,795 citations


Journal ArticleDOI
TL;DR: A strategy for whole-body rehabilitation-consisting of interruption of sedation and physical and occupational therapy in the earliest days of critical illness-was safe and well tolerated, and resulted in better functional outcomes at hospital discharge, a shorter duration of delirium, and more ventilator-free days compared with standard care.

2,492 citations


Journal ArticleDOI
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Lorenzo Galluzzi3, Stuart A. Aaronson4, John M. Abrams5, Emad S. Alnemri6, David W. Andrews7, Eric H. Baehrecke8, Nicolas G. Bazan9, Mikhail V. Blagosklonny10, Klas Blomgren11, Klas Blomgren12, Christoph Borner13, Dale E. Bredesen14, Dale E. Bredesen15, Catherine Brenner16, Maria Castedo1, Maria Castedo2, Maria Castedo3, John A. Cidlowski17, Aaron Ciechanover18, Gerald M. Cohen19, V De Laurenzi20, R De Maria21, Mohanish Deshmukh22, Brian David Dynlacht23, Wafik S. El-Deiry24, Richard A. Flavell25, Richard A. Flavell26, Simone Fulda27, Carmen Garrido2, Carmen Garrido28, Pierre Golstein16, Pierre Golstein29, Pierre Golstein2, Marie-Lise Gougeon30, Douglas R. Green, Hinrich Gronemeyer2, Hinrich Gronemeyer16, Hinrich Gronemeyer31, György Hajnóczky6, J. M. Hardwick32, Michael O. Hengartner33, Hidenori Ichijo34, Marja Jäättelä, Oliver Kepp3, Oliver Kepp1, Oliver Kepp2, Adi Kimchi35, Daniel J. Klionsky36, Richard A. Knight37, Sally Kornbluth38, Sharad Kumar, Beth Levine5, Beth Levine25, Stuart A. Lipton, Enrico Lugli17, Frank Madeo39, Walter Malorni21, Jean-Christophe Marine40, Seamus J. Martin41, Jan Paul Medema42, Patrick Mehlen16, Patrick Mehlen43, Gerry Melino44, Gerry Melino19, Ute M. Moll45, Ute M. Moll46, Eugenia Morselli3, Eugenia Morselli2, Eugenia Morselli1, Shigekazu Nagata47, Donald W. Nicholson48, Pierluigi Nicotera19, Gabriel Núñez36, Moshe Oren35, Josef M. Penninger49, Shazib Pervaiz50, Marcus E. Peter51, Mauro Piacentini44, Jochen H. M. Prehn52, Hamsa Puthalakath53, Gabriel A. Rabinovich54, Rosario Rizzuto55, Cecília M. P. Rodrigues56, David C. Rubinsztein57, Thomas Rudel58, Luca Scorrano59, Hans-Uwe Simon60, Hermann Steller25, Hermann Steller61, J. Tschopp62, Yoshihide Tsujimoto63, Peter Vandenabeele64, Ilio Vitale3, Ilio Vitale2, Ilio Vitale1, Karen H. Vousden65, Richard J. Youle17, Junying Yuan66, Boris Zhivotovsky67, Guido Kroemer2, Guido Kroemer1, Guido Kroemer3 
University of Paris-Sud1, French Institute of Health and Medical Research2, Institut Gustave Roussy3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, Boston Children's Hospital11, University of Gothenburg12, University of Freiburg13, Buck Institute for Research on Aging14, University of California, San Francisco15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Howard Hughes Medical Institute25, Yale University26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, Stony Brook University45, University of Göttingen46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells

2,218 citations


ReportDOI
TL;DR: This paper measured sizable gaps in marginal products of labor and capital across plants within narrowly defined industries in China and India compared with the United States, and calculated manufacturing TFP gains of 30%-50% in China, and 40%-60% in India.
Abstract: Resource misallocation can lower aggregate total factor productivity (TFP).We use microdata on manufacturing establishments to quantify the potential extent of misallocation in China and India versus the United States. We measure sizable gaps in marginal products of labor and capital across plants within narrowly defined industries in China and India compared with the United States. When capital and labor are hypothetically reallocated to equalize marginal products to the extent observed in the United States, we calculate manufacturing TFP gains of 30%–50% in China and 40%–60% in India.

Journal ArticleDOI
TL;DR: The Wilkinson Microwave Anisotropy Probe (WMAP) is a medium-class Explorer (MIDEX) satellite aimed at elucidating cosmology through full-sky observations of the cosmic microwave background (CMB) as mentioned in this paper.
Abstract: The Wilkinson Microwave Anisotropy Probe (WMAP) is a Medium-Class Explorer (MIDEX) satellite aimed at elucidating cosmology through full-sky observations of the cosmic microwave background (CMB). The WMAP full-sky maps of the temperature and polarization anisotropy in five frequency bands provide our most accurate view to date of conditions in the early universe. The multi-frequency data facilitate the separation of the CMB signal from foreground emission arising both from our Galaxy and from extragalactic sources. The CMB angular power spectrum derived from these maps exhibits a highly coherent acoustic peak structure which makes it possible to extract a wealth of information about the composition and history of the universe. as well as the processes that seeded the fluctuations. WMAP data have played a key role in establishing ACDM as the new standard model of cosmology (Bennett et al. 2003: Spergel et al. 2003; Hinshaw et al. 2007: Spergel et al. 2007): a flat universe dominated by dark energy, supplemented by dark matter and atoms with density fluctuations seeded by a Gaussian, adiabatic, nearly scale invariant process. The basic properties of this universe are determined by five numbers: the density of matter, the density of atoms. the age of the universe (or equivalently, the Hubble constant today), the amplitude of the initial fluctuations, and their scale dependence. By accurately measuring the first few peaks in the angular power spectrum, WMAP data have enabled the following accomplishments: Showing the dark matter must be non-baryonic and interact only weakly with atoms and radiation. The WMAP measurement of the dark matter density puts important constraints on supersymmetric dark matter models and on the properties of other dark matter candidates. With five years of data and a better determination of our beam response, this measurement has been significantly improved. Precise determination of the density of atoms in the universe. The agreement between the atomic density derived from WMAP and the density inferred from the deuterium abundance is an important test of the standard big bang model. Determination of the acoustic scale at redshift z = 1090. Similarly, the recent measurement of baryon acoustic oscillations (BAO) in the galaxy power spectrum (Eisenstein et al. 2005) has determined the acoustic scale at redshift z approx. 0.35. When combined, these standard rulers accurately measure the geometry of the universe and the properties of the dark energy. These data require a nearly flat universe dominated by dark energy consistent with a cosmological constant. Precise determination of the Hubble Constant, in conjunction with BAO observations. Even when allowing curvature (Omega(sub 0) does not equal 1) and a free dark energy equation of state (w does not equal -1), the acoustic data determine the Hubble constant to within 3%. The measured value is in excellent agreement with independent results from the Hubble Key Project (Freedman et al. 2001), providing yet another important consistency test for the standard model. Significant constraint of the basic properties of the primordial fluctuations. The anti-correlation seen in the temperature/polarization (TE) correlation spectrum on 4deg scales implies that the fluctuations are primarily adiabatic and rule out defect models and isocurvature models as the primary source of fluctuations (Peiris et al. 2003).

Journal ArticleDOI
18 Jun 2009-Nature
TL;DR: It is shown that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood–brain barrier crossing and brain colonization.
Abstract: The molecular basis for breast cancer metastasis to the brain is largely unknown. Brain relapse typically occurs years after the removal of a breast tumour, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood-brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the alpha2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood-brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood-brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.

Journal ArticleDOI
TL;DR: Combining the demographic model with a previously estimated distribution of selective effects among newly arising amino acid mutations accurately predicts the frequency spectrum of nonsynonymous variants across three continental populations (YRI, CHB, CEU).
Abstract: Demographic models built from genetic data play important roles in illuminating prehistorical events and serving as null models in genome scans for selection. We introduce an inference method based on the joint frequency spectrum of genetic variants within and between populations. For candidate models we numerically compute the expected spectrum using a diffusion approximation to the one-locus, two-allele Wright-Fisher process, involving up to three simultaneous populations. Our approach is a composite likelihood scheme, since linkage between neutral loci alters the variance but not the expectation of the frequency spectrum. We thus use bootstraps incorporating linkage to estimate uncertainties for parameters and significance values for hypothesis tests. Our method can also incorporate selection on single sites, predicting the joint distribution of selected alleles among populations experiencing a bevy of evolutionary forces, including expansions, contractions, migrations, and admixture. We model human expansion out of Africa and the settlement of the New World, using 5 Mb of noncoding DNA resequenced in 68 individuals from 4 populations (YRI, CHB, CEU, and MXL) by the Environmental Genome Project. We infer divergence between West African and Eurasian populations 140 thousand years ago (95% confidence interval: 40–270 kya). This is earlier than other genetic studies, in part because we incorporate migration. We estimate the European (CEU) and East Asian (CHB) divergence time to be 23 kya (95% c.i.: 17–43 kya), long after archeological evidence places modern humans in Europe. Finally, we estimate divergence between East Asians (CHB) and Mexican-Americans (MXL) of 22 kya (95% c.i.: 16.3–26.9 kya), and our analysis yields no evidence for subsequent migration. Furthermore, combining our demographic model with a previously estimated distribution of selective effects among newly arising amino acid mutations accurately predicts the frequency spectrum of nonsynonymous variants across three continental populations (YRI, CHB, CEU).

Journal ArticleDOI
TL;DR: In this paper, the authors present cosmological constraints from the Wilkinson Microwave Anisotropy Probe (WMAP) alone for both the ACDM model and a set of possible extensions.
Abstract: The Wilkinson Microwave Anisotropy Probe (WMAP), launched in 2001, has mapped out the Cosmic Microwave Background with unprecedented accuracy over the whole sky. Its observations have led to the establishment of a simple concordance cosmological model for the contents and evolution of the universe, consistent with virtually all other astronomical measurements. The WMAP first-year and three-year data have allowed us to place strong constraints on the parameters describing the ACDM model. a flat universe filled with baryons, cold dark matter, neutrinos. and a cosmological constant. with initial fluctuations described by nearly scale-invariant power law fluctuations, as well as placing limits on extensions to this simple model (Spergel et al. 2003. 2007). With all-sky measurements of the polarization anisotropy (Kogut et al. 2003; Page et al. 2007), two orders of magnitude smaller than the intensity fluctuations. WMAP has not only given us an additional picture of the universe as it transitioned from ionized to neutral at redshift z approx.1100. but also an observation of the later reionization of the universe by the first stars. In this paper we present cosmological constraints from WMAP alone. for both the ACDM model and a set of possible extensions. We also consider tlle consistency of WMAP constraints with other recent astronomical observations. This is one of seven five-year WMAP papers. Hinshaw et al. (2008) describe the data processing and basic results. Hill et al. (2008) present new beam models arid window functions, Gold et al. (2008) describe the emission from Galactic foregrounds, and Wright et al. (2008) the emission from extra-Galactic point sources. The angular power spectra are described in Nolta et al. (2008), and Komatsu et al. (2008) present and interpret cosmological constraints based on combining WMAP with other data. WMAP observations are used to produce full-sky maps of the CMB in five frequency bands centered at 23, 33, 41, 61, and 94 GHz (Hinshaw et al. 2008). With five years of data, we are now able to place better limits on the ACDM model. as well as to move beyond it to test the composition of the universe. details of reionization. sub-dominant components, characteristics of inflation, and primordial fluctuations. We have more than doubled the amount of polarized data used for cosmological analysis. allowing a better measure of the large-scale E-mode signal (Nolta et al. 2008). To this end we describe an alternative way to remove Galactic foregrounds from low resolution polarization maps in which Galactic emission is marginalized over, providing a cross-check of our results. With longer integration we also better probe the second and third acoustic peaks in the temperature angular power spectrum, and have many more year-to-year difference maps available for cross-checking systematic effects (Hinshaw et al. 2008).

Journal ArticleDOI
TL;DR: There is growing evidence that neuroticism is a psychological trait of profound public health significance, a robust correlate and predictor of many different mental and physical disorders, comorbidity among them, and the frequency of mental and general health service use.
Abstract: The personality trait of neuroticism refers to relatively stable tendencies to respond with negative emotions to threat, frustration, or loss. Individuals in the population vary markedly on this trait, ranging from frequent and intense emotional reactions to minor challenges to little emotional reaction even in the face of significant difficulties. Although not widely appreciated, there is growing evidence that neuroticism is a psychological trait of profound public health significance. Neuroticism is a robust correlate and predictor of many different mental and physical disorders, comorbidity among them, and the frequency of mental and general health service use. Indeed, neuroticism apparently is a predictor of the quality and longevity of our lives. Achieving a full understanding of the nature and origins of neuroticism, and the mechanisms through which neuroticism is linked to mental and physical disorders, should be a top priority for research. Knowing why neuroticism predicts such a wide variety of seemingly diverse outcomes should lead to improved understanding of commonalities among those outcomes and improved strategies for preventing them.

Journal ArticleDOI
TL;DR: The authors assesses these strategies and argues that they fall short of their objectives, and presents two alternatives to curren-ture-based case studies, such as selecting respondents 'at random' for small, in-depth interview projects or identifying'representative' neighborhoods for ethnographic case studies.
Abstract: Today, ethnographers and qualitative researchers in fields such as urban poverty, immigration, and social inequality face an environment in which their work will be read, cited, and assessed by demographers, quantitative sociologists, and even economists. They also face a demand for case studies of poor, minority, or immigrant groups and neighborhoods that not only generate theory but also somehow speak to empirical conditions in other cases (not observed). Many have responded by incorporating elements of quantitative methods into their designs, such as selecting respondents `at random' for small, in-depth interview projects or identifying `representative' neighborhoods for ethnographic case studies, aiming to increase generalizability. This article assesses these strategies and argues that they fall short of their objectives. Recognizing the importance of the predicament underlying the strategies — to determine how case studies can speak empirically to other cases — it presents two alternatives to curren...

Journal ArticleDOI
TL;DR: By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.
Abstract: Purpose Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification.

Journal ArticleDOI
Yongye Liang1, Danqin Feng1, Yue Wu1, Szu Ting Tsai1, Gang Li1, Claire Ray1, Luping Yu1 
TL;DR: It was found that films with finely distributed polymer/fulleride interpenetrating network exhibited improved solar cell conversion efficiency, and the results proved that polymer solar cells have a bright future.
Abstract: This paper describes synthesis and photovoltaic studies of a series of new semiconducting polymers with alternating thieno[3,4-b]thiophene and benzodithiophene units. The physical properties of these polymers were finely tuned to optimize their photovoltaic effect. The substitution of alkoxy side chains to the less electron-donating alkyl chains or introduction of electron-withdrawing fluorine into the polymer backbone reduced the HOMO energy levels of polymers. The structural modifications optimized polymers’ spectral coverage of absorption and their hole mobility, as well as miscibility with fulleride, and enhanced polymer solar cell performances. The open circuit voltage, Voc, for polymer solar cells was increased by adjusting polymer energy levels. It was found that films with finely distributed polymer/fulleride interpenetrating network exhibited improved solar cell conversion efficiency. Efficiency over 6% has been achieved in simple solar cells based on fluorinated PTB4/PC61BM films prepared from m...

Journal ArticleDOI
TL;DR: Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery, and national and international societies should become involved in the goal of establishing training standards and credentialing.
Abstract: Objective:To summarize the current world position on laparoscopic liver surgery.Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver re

Journal ArticleDOI
TL;DR: This paper used data on bilateral trust between European countries and found that lower bilateral trust leads to less trade between two countries, less portfolio investment, and less direct investment, even after controlling for the characteristics of the two countries.
Abstract: How much do cultural biases affect economic exchange? We answer this question by using data on bilateral trust between European countries. We document that this trust is affected not only by the characteristics of the country being trusted, but also by cultural aspects of the match between trusting country and trusted country, such as their history of conflicts and their religious, genetic, and somatic similarities. We then find that lower bilateral trust leads to less trade between two countries, less portfolio investment, and less direct investment, even after controlling for the characteristics of the two countries. This effect is stronger for goods that are more trust intensive. Our results suggest that perceptions rooted in culture are important (and generally omitted) determinants of economic exchange.

Journal ArticleDOI
TL;DR: Differences in attention and cognition impact on emotions, decisions, behaviors and interpersonal interactions that can contribute to the association between loneliness and cognitive decline and betweenoneliness and morbidity more generally.

ReportDOI
TL;DR: In this paper, the authors conduct a within-county analysis using detailed ZIP code-level data to document new findings regarding the origins of the biggest financial crisis since the Great Depression, finding that the sharp increase in mortgage defaults in 2007 is significantly amplified in subprime ZIP codes, or ZIP codes with a disproportionately large share of subprime borrowers as of 1996.
Abstract: We conduct a within-county analysis using detailed ZIP code—level data to document new findings regarding the origins of the biggest financial crisis since the Great Depression. The sharp increase in mortgage defaults in 2007 is significantly amplified in subprime ZIP codes, or ZIP codes with a disproportionately large share of subprime borrowers as of 1996. Prior to the default crisis, these subprime ZIP codes experience an unprecedented relative growth in mortgage credit. The expansion in mortgage credit from 2002 to 2005 to subprime ZIP codes occurs despite sharply declining relative (and in some cases absolute) income growth in these neighborhoods. In fact, 2002 to 2005 is the only period in the past eighteen years in which income and mortgage credit growth are negatively correlated. We show that the expansion in mortgage credit to subprime ZIP codes and its dissociation from income growth is closely correlated with the increase in securitization of subprime mortgages.

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TL;DR: Results suggest that Complex PTSD symptoms occur in both adult and child samples in a principled, rule-governed way and that childhood experiences significantly influenced adult symptoms.
Abstract: Exposure to multiple traumas, particularly in childhood, has been proposed to result in a complex of symptoms that includes posttraumatic stress disorder (PTSD) as well as a constrained, but variable group of symptoms that highlight self-regulatory disturbances. The relationship between accumulated exposure to different types of traumatic events and total number of different types of symptoms (symptom complexity) was assessed in an adult clinical sample (N = 582) and a child clinical sample (N = 152). Childhood cumulative trauma but not adulthood trauma predicted increasing symptom complexity in adults. Cumulative trauma predicted increasing symptom complexity in the child sample. Results suggest that Complex PTSD symptoms occur in both adult and child samples in a principled, rule-governed way and that childhood experiences significantly influenced adult symptoms.

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TL;DR: This PCO addresses the utility of KRAS gene mutation testing in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MoAb) therapy with cetuximab or panitumumab with a systematic review of the relevant literature.
Abstract: Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO), offers timely clinical direction to ASCO’s oncologists following publication or presentation of potentially practicechanging data from major studies. This PCO addresses the utility of KRAS gene mutation testing in patients with metastatic colorectal carcinoma to predict response to anti–epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MoAb) therapy with cetuximab or panitumumab (see Note). Clinical Context Recent results from phase II and III clinical trials demonstrate that patients with metastatic colorectal cancer benefit from therapy with monoclonal antibodies directed against the EGFR, when used either as monotherapy or combined with chemotherapy. Retrospective subset analyses of the data from these trials strongly suggest that patients who have KRAS mutations detected in codon 12 or 13 do not benefit from this therapy. Recent Data

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16 Jul 2009-Blood
TL;DR: It is reported that reduction of tumor burden after ablative RT depends largely on T-cell responses, and the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity is emphasized.

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TL;DR: It is demonstrated that cortical volume measures combine at least 2 distinct sources of genetic influences, and using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.
Abstract: Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.

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Brian Yanny1, Constance M. Rockosi2, Heidi Jo Newberg3, Gillian R. Knapp4, Jennifer K. Adelman-McCarthy1, Bonnie Alcorn1, S. Allam1, Carlos Allende Prieto5, Carlos Allende Prieto6, Deokkeun An7, K. S. J. Anderson8, K. S. J. Anderson9, Scott F. Anderson10, Coryn A. L. Bailer-Jones11, Steve Bastian1, Timothy C. Beers12, Eric F. Bell11, Vasily Belokurov13, Dmitry Bizyaev9, Norm Blythe9, John J. Bochanski10, William N. Boroski1, Jarle Brinchmann14, J. Brinkmann9, Howard Brewington9, Larry N. Carey10, Kyle M. Cudworth15, Michael L. Evans10, Nick Evans13, Evalyn Gates15, Boris T. Gänsicke16, Bruce Gillespie9, G. F. Gilmore13, Ada Nebot Gomez-Moran, Eva K. Grebel17, Jim Greenwell10, James E. Gunn4, Cathy Jordan9, Wendell Jordan9, Paul Harding18, Hugh C. Harris, John S. Hendry1, Diana Holder9, Inese I. Ivans4, Željko Ivezić10, Sebastian Jester11, Jennifer A. Johnson7, Stephen M. Kent1, S. J. Kleinman9, Alexei Y. Kniazev11, Jurek Krzesinski9, Richard G. Kron15, Nikolay Kuropatkin1, Svetlana Lebedeva1, Young Sun Lee12, R. French Leger1, Sébastien Lépine19, Steve Levine, Huan Lin1, Dan Long9, Craig P. Loomis4, Robert H. Lupton4, O. Malanushenko9, Viktor Malanushenko9, Bruce Margon2, David Martínez-Delgado11, P. M. McGehee20, Dave Monet, Heather L. Morrison18, Jeffrey A. Munn, Eric H. Neilsen1, Atsuko Nitta9, John E. Norris21, Daniel Oravetz9, Russell Owen10, Nikhil Padmanabhan22, Kaike Pan9, R. S. Peterson1, Jeffrey R. Pier, Jared Platson1, Paola Re Fiorentin11, Paola Re Fiorentin23, Gordon T. Richards24, Hans-Walter Rix11, David J. Schlegel22, Donald P. Schneider25, Matthias R. Schreiber26, Axel Schwope, Valena C. Sibley1, Audrey Simmons9, Stephanie A. Snedden9, J. Allyn Smith27, Larry Stark10, Fritz Stauffer9, Matthias Steinmetz, Christopher Stoughton1, Mark SubbaRao15, Mark SubbaRao28, Alexander S. Szalay29, Paula Szkody10, Aniruddha R. Thakar29, Sivarani Thirupathi12, Douglas L. Tucker1, A. Uomoto30, Daniel E. Vanden Berk25, S. Vidrih17, Yogesh Wadadekar4, Yogesh Wadadekar31, S. Watters9, R. Wilhelm32, Rosemary F. G. Wyse29, Jean Yarger9, Daniel B. Zucker13 
TL;DR: The Sloan Extension for Galactic Understanding and Exploration (SEGUE) Survey as mentioned in this paper obtained approximately 240,000 moderate-resolution spectra from 3900 to 9000 of fainter Milky Way stars (14.0 10 per resolution element).
Abstract: The Sloan Extension for Galactic Understanding and Exploration (SEGUE) Survey obtained {approx}240,000 moderate-resolution (R {approx} 1800) spectra from 3900 {angstrom} to 9000 {angstrom} of fainter Milky Way stars (14.0 10 per resolution element, stellar atmospheric parameters are estimated, including metallicity, surface gravity, and effective temperature. SEGUE obtained 3500 deg{sup 2} of additional ugriz imaging (primarily at low Galactic latitudes) providing precise multicolor photometry ({sigma}(g, r, i) {approx} 2%), ({sigma}(u, z) {approx} 3%) and astrometry ({approx}0.1) for spectroscopic target selection. The stellar spectra, imaging data, and derived parameter catalogs for this survey are publicly available as part of Sloan Digital Sky Survey Data Release 7.

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TL;DR: This document and the conference recommendations it includes builds upon prior literature, the National Consensus Project Guidelines, and the National Quality Forum Preferred Practices and Conference proceedings.
Abstract: A Consensus Conference sponsored by the Archstone Foundation of Long Beach, California, was held February 17–18, 2009, in Pasadena, California. The Conference was based on the belief that spiritual care is a fundamental component of quality palliative care. This document and the conference recommendations it includes builds upon prior literature, the National Consensus Project Guidelines, and the National Quality Forum Preferred Practices and Conference proceedings.

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TL;DR: In this paper, the authors reviewed data from controlled studies investigating different measures of impulsive behaviors, including delay discounting, behavioral inhibition and a newly proposed measure of inattention, and found that drugs of abuse alter performance across independent behavioral measures of impulsivity.
Abstract: Impulsive behaviors are closely linked to drug use and abuse, both as contributors to use and as consequences of use. Trait impulsivity is an important determinant of drug use during development, and in adults momentary ‘state’ increases in impulsive behavior may increase the likelihood of drug use, especially in individuals attempting to abstain. Conversely, acute and chronic effects of drug use may increase impulsive behaviors, which may in turn facilitate further drug use. However, these effects depend on the behavioral measure used to assess impulsivity. This article reviews data from controlled studies investigating different measures of impulsive behaviors, including delay discounting, behavioral inhibition and a newly proposed measure of inattention. Our findings support the hypothesis that drugs of abuse alter performance across independent behavioral measures of impulsivity. The findings lay the groundwork for studying the cognitive and neurobiological substrates of impulsivity, and for future studies on the role of impulsive behavior as both facilitator and a result of drug use.