Últimos itens adicionados do Acervo: Harvard University

A Universidade de Harvard (em inglês: Harvard University) é uma universidade privada membro da Ivy League, localizada em Cambridge, Massachusetts, Estados Unidos, e cuja história, influência e riqueza tornam-a uma das mais prestigiadas universidades do mundo.

Página 6 dos resultados de 27340 itens digitais encontrados em 0.006 segundos

‣ Book Review

Zittrain, Jonathan L.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Commentary or Review
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‣ The Web's Dark Energy

Zittrain, Jonathan L.
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Newspaper or Magazine article
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‣ Roberts's Real Long Game?

Elhauge, Einer Richard
Fonte: Atlantic Monthly Co. Publicador: Atlantic Monthly Co.
Tipo: Newspaper or Magazine article
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‣ The Killer Precedent for Today's Decision

Elhauge, Einer Richard
Fonte: New Republic Publicador: New Republic
Tipo: Newspaper or Magazine article
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‣ What's So Darned Special about Church Friends?

Putnam, Robert David
Fonte: American Sociological Association Publicador: American Sociological Association
Tipo: Newspaper or Magazine article
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‣ The Growth of Executive Pay

Bebchuk, Lucian Arye; Grinstein, Yaniv
Fonte: Oxford University Press (OUP) Publicador: Oxford University Press (OUP)
Tipo: Artigo de Revista Científica
Português
This paper examines both empirically and theoretically the growth of US executive pay during the period 1993–2003. During this period, pay has grown much beyond the increase that could be explained by changes in firm size, performance, and industry classification. Had the relationship of compensation to size, performance, and industry classification remained the same in 2003 as it was in 1993, mean compensation in 2003 would have been only about half of its actual size. During the 1993–2003 period, equity-based compensation has increased considerably in both new-economy and old-economy firms, but this growth has not been accompanied by a substitution effect, i.e. a reduction in non-equity compensation. The aggregate compensation paid by public companies to their top-five executives during the considered period added up to about $350 billion, and the ratio of this aggregate top-five compensation to the aggregate earnings of these firms increased from 5 per cent in 1993–5 to about 10 per cent in 2001–3. After presenting evidence about the growth of pay, we discuss alternative explanations for it. We examine how this growth could be explained under either the arm's-length bargaining model of executive compensation or the managerial-power model. Among other things...

‣ Homologous recombination-deficient tumors are hyper-dependent on POLQ-mediated repair

Ceccaldi, Raphael; Liu, Jessica C.; Amunugama, Ravindra; Hajdu, Ildiko; Primack, Benjamin; Petalcorin, Mark I.R.; O'Connor, Kevin W.; Konstantinopoulos, Panagiotis A.; Elledge, Stephen J.; Boulton, Simon J.; Yusufzai, Timur; D'Andrea, Alan D.
Fonte: Harvard University Publicador: Harvard University
Tipo: Artigo de Revista Científica
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‣ Van Gogh's Physician

Khoshbin, Shahram; Katz, Joel T.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português

‣ The impact of private provision of public education: Empirical evidence from Bogota's concession schools

Barrera-Osorio, Felipe
Fonte: Harvard University Publicador: Harvard University
Tipo: Research Paper or Report
Português
In 1999, the city of Bogotá, Colombia launched the Concession School program designed to broaden the coverage and quality of basic education. It consists of a contract between a group of private schools and the public educational system such that private agents provide education for low-income students. This paper tests three main hypotheses concerning the impact of concessions on the quality of education: first, dropout rates are lower in concession schools than in similar public schools; second, other public schools nearby the concession schools have lower dropout rates in comparison with other public schools outside the area of influence; third, test scores from concession schools are higher than scores in similar public schools. The paper presents evidence in favor of the three hypotheses, using propensity score and matching estimators.

‣ Non-specific chemical inhibition of the Fanconi anemia pathway sensitizes cancer cells to cisplatin

Jacquemont, Céline; Simon, Julian A; D'Andrea, Alan David; Taniguchi, Toshiyasu
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Português
Background: Platinum compounds such as cisplatin and carboplatin are DNA crosslinking agents widely used for cancer chemotherapy. However, the effectiveness of platinum compounds is often tempered by the acquisition of cellular drug resistance. Until now, no pharmacological approach has successfully overcome cisplatin resistance in cancer treatment. Since the Fanconi anemia (FA) pathway is a DNA damage response pathway required for cellular resistance to DNA interstrand crosslinking agents, identification of small molecules that inhibit the FA pathway may reveal classes of chemicals that sensitize cancer cells to cisplatin. Results: Through a cell-based screening assay of over 16,000 chemicals, we identified 26 small molecules that inhibit ionizing radiation and cisplatin-induced FANCD2 foci formation, a marker of FA pathway activity, in multiple human cell lines. Most of these small molecules also compromised ionizing radiation-induced RAD51 foci formation and homologous recombination repair, indicating that they are not selective toward the regulation of FANCD2. These compounds include known inhibitors of the proteasome, cathepsin B, lysosome, CHK1, HSP90, CDK and PKC, and several uncharacterized chemicals including a novel proteasome inhibitor (Chembridge compound 5929407). Isobologram analyses demonstrated that half of the identified molecules sensitized ovarian cancer cells to cisplatin. Among them...

‣ A Portable Chemotaxis Platform for Short and Long Term Analysis

Xu, Chenjie; Poh, Yuk Kee C.; Roes, Isaac; O'Cearbhaill, Eoin D.; Matthiesen, Mads Emil; Mu, Luye; Yang, Seung Yun; Miranda-Nieves, David; Irimia, Daniel; Karp, Jeffrey Michael
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
Flow-based microfluidic systems have been widely utilized for cell migration studies given their ability to generate versatile and precisely defined chemical gradients and to permit direct visualization of migrating cells. Nonetheless, the general need for bulky peripherals such as mechanical pumps and tubing and the complicated setup procedures significantly limit the widespread use of these microfluidic systems for cell migration studies. Here we present a simple method to power microfluidic devices for chemotaxis assays using the commercially available ALZET® osmotic pumps. Specifically, we developed a standalone chemotaxis platform that has the same footprint as a multiwell plate and can generate well-defined, stable chemical gradients continuously for up to 7 days. Using this platform, we validated the short-term (24 hours) and long-term (72 hours) concentration dependent PDGF-BB chemotaxis response of human bone marrow derived mesenchymal stem cells.

‣ Loss of Effector and Anti-Inflammatory Natural Killer T Lymphocyte Function in Pathogenic Simian Immunodeficiency Virus Infection

Rout, Namita; Greene, Justin; Yue, Simon C.; O'Connor, David; Johnson, R. Paul; Else, James G.; Exley, Mark Adrian; Kaur, Amitinder
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
Chronic immune activation is a key determinant of AIDS progression in HIV-infected humans and simian immunodeficiency virus (SIV)-infected macaques but is singularly absent in SIV-infected natural hosts. To investigate whether natural killer T (NKT) lymphocytes contribute to the differential modulation of immune activation in AIDS-susceptible and AIDS-resistant hosts, we compared NKT function in macaques and sooty mangabeys in the absence and presence of SIV infection. Cynomolgus macaques had significantly higher frequencies of circulating invariant NKT lymphocytes compared to both rhesus macaques and AIDS-resistant sooty mangabeys. Despite this difference, mangabey NKT lymphocytes were functionally distinct from both macaque species in their ability to secrete significantly more IFN-γ, IL-13, and IL-17 in response to CD1d/α-galactosylceramide stimulation. While NKT number and function remained intact in SIV-infected mangabeys, there was a profound reduction in NKT activation-induced, but not mitogen-induced, secretion of IFN-γ, IL-2, IL-10, and TGF-β in SIV-infected macaques. SIV-infected macaques also showed a selective decline in CD4+ NKT lymphocytes which correlated significantly with an increase in circulating activated memory CD4+ T lymphocytes. Macaques with lower pre-infection NKT frequencies showed a significantly greater CD4+ T lymphocyte decline post SIV infection. The disparate effect of SIV infection on NKT function in mangabeys and macaques could be a manifestation of their differential susceptibility to AIDS. Alternately...

‣ The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals

Dickerson, Bradford Clark; Bakkour, Akram; Salat, David H.; Feczko, Eric; Pacheco, Jenni; Greve, Douglas N.; Grodstein, Francine; Wright, Christopher Ian; Blacker, Deborah Lynne; Rosas, Herminia Diana; Sperling, Reisa Anne; Atri, Alireza; Growdon, John He
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This “disease signature” approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses...

‣ Automated MRI Measures Identify Individuals with Mild Cognitive Impairment and Alzheimer's Disease

Desikan, Rahul S.; Cabral, Howard J.; Hess, Christopher P.; Dillon, William P.; Glastonbury, Christine M.; Weiner, Michael W.; Schmansky, Nicholas J.; Salat, David H.; Greve, Douglas N.; Buckner, Randy Lee; Fischl, Bruce R.; Alzheimer’s Disease Neuroima
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
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Mild cognitive impairment can represent a transitional state between normal ageing and Alzheimer's disease. Non-invasive diagnostic methods are needed to identify mild cognitive impairment individuals for early therapeutic interventions. Our objective was to determine whether automated magnetic resonance imaging-based measures could identify mild cognitive impairment individuals with a high degree of accuracy. Baseline volumetric T1-weighted magnetic resonance imaging scans of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with mild cognitive impairment, while the second cohort included 94 older controls and 57 mild cognitive impairment individuals. Sixty-five patients with probable Alzheimer's disease were also included for comparison. For the discrimination of mild cognitive impairment, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94%, sensitivity 74%, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91%...

‣ Social Ecology of Children’s Vulnerability to Environmental Pollutants

Weiss, Bernard; Bellinger, David C.
Fonte: National Institute of Environmental Health Sciences Publicador: National Institute of Environmental Health Sciences
Tipo: Artigo de Revista Científica
Português
Background: The outcomes of exposure to neurotoxic chemicals early in life depend on the properties of both the chemical and the host’s environment. When our questions focus on the toxicant, the environmental properties tend to be regarded as marginal and designated as covariates or confounders. Such approaches blur the reality of how the early environment establishes enduring biologic substrates. Objectives: In this commentary, we describe another perspective, based on decades of biopsychological research on animals, that shows how the early, even prenatal, environment creates permanent changes in brain structure and chemistry and behavior. Aspects of the early environment—encompassing enrichment, deprivation, and maternal and neonatal stress—all help determine the functional responses later in life that derive from the biologic substrate imparted by that environment. Their effects then become biologically embedded. Human data, particularly those connected to economically disadvantaged populations, yield equivalent conclusions. Discussion: In this commentary, we argue that treating such environmental conditions as confounders is equivalent to defining genetic differences as confounders, a tactic that laboratory research, such as that based on transgenic manipulations...

‣ Luminal B Breast Tumors Are Not HER2 Positive – Authors' Response

Tamimi, Rulla May; Schnitt, Stuart Jay; Colditz, Graham A.; Collins, Laura Christine
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
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‣ Effect Modification of Air Pollution on Urinary 8-Hydroxy-2'-Deoxyguanosine by Genotypes: An Application of the Multiple Testing Procedure to Identify Significant SNP Interactions

Ren, Cizao; Vokonas, Pantel S; Suh MacIntosh, Helen H.; Fang, Shona C.; Christiani, David C.; Schwartz, Joel David
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Português
Background: Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related genotypes may modify the oxidative response defenses to pollution exposure. Methods: We explored the potential pathway by examining whether an array of oxidative stress-related genes (twenty single nucleotide polymorphisms, SNPs in nine genes) modified associations of pollutants (organic carbon (OC), ozone and sulfate) with urinary 8-hydroxy-2-deoxygunosine (8-OHdG), a biomarker of oxidative stress among the 320 aging men. We used a Multiple Testing Procedure in R modified by our team to identify the significance of the candidate genes adjusting for a priori covariates. Results: We found that glutathione S-tranferase P1 (GSTP1, rs1799811), M1 and catalase (rs2284367) and group-specific component (GC, rs2282679, rs1155563) significantly or marginally significantly modified effects of OC and/or sulfate with larger effects among those carrying the wild type of GSTP1, catalase, non-wild type of GC and the non-null of GSTM1. Conclusions: Polymorphisms of oxidative stress-related genes modified effects of OC and/or sulfate on 8-OHdG...

‣ On the Analysis of Genome-Wide Association Studies in Family-Based Designs: A Universal, Robust Analysis Approach and an Application to Four Genome-Wide Association Studies

Won, Sungho; Mathias, Rasika A.; Barnes, Kathleen; O'Connor, George T.; Wilk, Jemma B; O'Donnell, Christopher Joseph; Silverman, Edwin Kepner; Weiss, Scott Tillman; Lange, Christoph
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
For genome-wide association studies in family-based designs, we propose a new, universally applicable approach. The new test statistic exploits all available information about the association, while, by virtue of its design, it maintains the same robustness against population admixture as traditional family-based approaches that are based exclusively on the within-family information. The approach is suitable for the analysis of almost any trait type, e.g. binary, continuous, time-to-onset, multivariate, etc., and combinations of those. We use simulation studies to verify all theoretically derived properties of the approach, estimate its power, and compare it with other standard approaches. We illustrate the practical implications of the new analysis method by an application to a lung-function phenotype, forced expiratory volume in one second (FEV1) in 4 genome-wide association studies.

‣ Protocol for Investigating Genetic Determinants of Posttraumatic Stress Disorder in Women from the Nurses' Health Study II

DeVivo, Immaculata; Koenen, Karestan; Rich-Edwards, Janet Wilson; Smoller, Jordan W; Wright, Rosalind Jo; Purcell, Shaun
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
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Background: One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder. Methods and design: We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD. The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis...

‣ P16-12. Relative Dominance of Gag-Specific Cytotoxic T Lymphocytes Is Associated with Viral Load Inversely in HIV-1 Clade B' Infected Chinese

Jia, M; Altfeld, Marcus; Walker, Bruce David; Yu, Xu; Chen, J; Hong, K; Liu, S; Zhang, X; Zhao, H; Shao, Y
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
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