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Showing papers by "University of Virginia published in 2009"


Journal ArticleDOI
TL;DR: An update on potentially effective antibacterial drugs in the late-stage development pipeline is provided, in the hope of encouraging collaboration between industry, academia, the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention work productively together.
Abstract: The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews,” and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.

4,256 citations


Journal ArticleDOI
TL;DR: Across 4 studies using multiple methods, liberals consistently showed greater endorsement and use of the Harm/care and Fairness/reciprocity foundations compared to the other 3 foundations, whereas conservatives endorsed and used the 5 foundations more equally.
Abstract: How and why do moral judgments vary across the political spectrum? To test moral foundations theory (J. Haidt & J. Graham, 2007; J. Haidt & C. Joseph, 2004), the authors developed several ways to measure people's use of 5 sets of moral intuitions: Harm/care, Fairness/reciprocity, Ingroup/loyalty, Authority/respect, and Purity/sanctity. Across 4 studies using multiple methods, liberals consistently showed greater endorsement and use of the Harm/care and Fairness/reciprocity foundations compared to the other 3 foundations, whereas conservatives endorsed and used the 5 foundations more equally. This difference was observed in abstract assessments of the moral relevance of foundation-related concerns such as violence or loyalty (Study 1), moral judgments of statements and scenarios (Study 2), "sacredness" reactions to taboo trade-offs (Study 3), and use of foundation-related words in the moral texts of religious sermons (Study 4). These findings help to illuminate the nature and intractability of moral disagreements in the American "culture war."

2,990 citations


Proceedings ArticleDOI
04 Oct 2009
TL;DR: This characterization shows that the Rodinia benchmarks cover a wide range of parallel communication patterns, synchronization techniques and power consumption, and has led to some important architectural insight, such as the growing importance of memory-bandwidth limitations and the consequent importance of data layout.
Abstract: This paper presents and characterizes Rodinia, a benchmark suite for heterogeneous computing. To help architects study emerging platforms such as GPUs (Graphics Processing Units), Rodinia includes applications and kernels which target multi-core CPU and GPU platforms. The choice of applications is inspired by Berkeley's dwarf taxonomy. Our characterization shows that the Rodinia benchmarks cover a wide range of parallel communication patterns, synchronization techniques and power consumption, and has led to some important architectural insight, such as the growing importance of memory-bandwidth limitations and the consequent importance of data layout.

2,697 citations


Journal ArticleDOI
TL;DR: This Review focuses on recent advances in the understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.
Abstract: One of the main engines that drives cellular transformation is the loss of proper control of the mammalian cell cycle. The cyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) promotes cell cycle arrest in response to many stimuli. It is well positioned to function as both a sensor and an effector of multiple anti-proliferative signals. This Review focuses on recent advances in our understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.

2,247 citations


Journal ArticleDOI
TL;DR: Non-muscle myosin II is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains.
Abstract: Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains. The three mammalian NM II isoforms have both overlapping and unique properties. Owing to its position downstream of convergent signalling pathways, NM II is central in the control of cell adhesion, cell migration and tissue architecture. Recent insight into the role of NM II in these processes has been gained from loss-of-function and mutant approaches, methods that quantitatively measure actin and adhesion dynamics and the discovery of NM II mutations that cause monogenic diseases.

1,745 citations


Journal ArticleDOI
TL;DR: The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.
Abstract: Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 × 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.

1,547 citations


Journal ArticleDOI
TL;DR: Results from three methods of estimating retest effects in this project converge on a conclusion that some aspects of age-related cognitive decline begin in healthy educated adults when they are in their 20s and 30s.

1,475 citations



Journal ArticleDOI
01 Sep 2009-Ecology
TL;DR: PanTHERIA as mentioned in this paper is a species-level data set compiled for analysis of life history, ecology, and geography of all known extant and recently extinct mammalian species, collected over a period of three years by 20 individuals.
Abstract: Analyses of life-history, ecological, and geographic trait differences among species, their causes, correlates, and likely consequences are increasingly important for understanding and conserving biodiversity in the face of rapid global change. Assembling multispecies trait data from diverse literature sources into a single comprehensive data set requires detailed consideration of methods to reliably compile data for particular species, and to derive single estimates from multiple sources based on different techniques and definitions. Here we describe PanTHERIA, a species-level data set compiled for analysis of life history, ecology, and geography of all known extant and recently extinct mammals. PanTHERIA is derived from a database capable of holding multiple geo-referenced values for variables within a species containing 100 740 lines of biological data for extant and recently extinct mammalian species, collected over a period of three years by 20 individuals. PanTHERIA also includes spatial databases o...

1,372 citations


Journal ArticleDOI
10 Sep 2009-Nature
TL;DR: Nucleotides are identified as a critical find-me cue released by apoptotic cells to promote P2Y2-dependent recruitment of phagocytes, and provide evidence for a clear relationship between a find- me signal and efficient corpse clearance in vivo.
Abstract: Phagocytic removal of apoptotic cells occurs efficiently in vivo such that even in tissues with significant apoptosis, very few apoptotic cells are detectable. This is thought to be due to the release of 'find-me' signals by apoptotic cells that recruit motile phagocytes such as monocytes, macrophages and dendritic cells, leading to the prompt clearance of the dying cells. However, the identity and in vivo relevance of such find-me signals are not well understood. Here, through several lines of evidence, we identify extracellular nucleotides as a critical apoptotic cell find-me signal. We demonstrate the caspase-dependent release of ATP and UTP (in equimolar quantities) during the early stages of apoptosis by primary thymocytes and cell lines. Purified nucleotides at these concentrations were sufficient to induce monocyte recruitment comparable to that of apoptotic cell supernatants. Enzymatic removal of ATP and UTP (by apyrase or the expression of ectopic CD39) abrogated the ability of apoptotic cell supernatants to recruit monocytes in vitro and in vivo. We then identified the ATP/UTP receptor P2Y(2) as a critical sensor of nucleotides released by apoptotic cells using RNA interference-mediated depletion studies in monocytes, and macrophages from P2Y(2)-null mice. The relevance of nucleotides in apoptotic cell clearance in vivo was revealed by two approaches. First, in a murine air-pouch model, apoptotic cell supernatants induced a threefold greater recruitment of monocytes and macrophages than supernatants from healthy cells did; this recruitment was abolished by depletion of nucleotides and was significantly decreased in P2Y(2)(-/-) (also known as P2ry2(-/-)) mice. Second, clearance of apoptotic thymocytes was significantly impaired by either depletion of nucleotides or interference with P2Y receptor function (by pharmacological inhibition or in P2Y(2)(-/-) mice). These results identify nucleotides as a critical find-me cue released by apoptotic cells to promote P2Y(2)-dependent recruitment of phagocytes, and provide evidence for a clear relationship between a find-me signal and efficient corpse clearance in vivo.

1,348 citations


Journal ArticleDOI
TL;DR: In this paper, the authors discuss the role of microRNAs in the etiology and progression of cancer and discuss the use of miRNAs as a tool for cancer therapy.
Abstract: Within the past few years, studies on microRNA (miRNA) and cancer have burst onto the scene Profiling of the miRNome (global miRNA expression levels) has become prevalent, and abundant miRNome data are currently available for various cancers The pattern of miRNA expression can be correlated with cancer type, stage, and other clinical variables, so miRNA profiling can be used as a tool for cancer diagnosis and prognosis miRNA expression analyses also suggest oncogenic (or tumor-suppressive) roles of miRNAs miRNAs play roles in almost all aspects of cancer biology, such as proliferation, apoptosis, invasion/metastasis, and angiogenesis Given that many miRNAs are deregulated in cancers but have not yet been further studied, it is expected that more miRNAs will emerge as players in the etiology and progression of cancer Here we also discuss miRNAs as a tool for cancer therapy

Journal ArticleDOI
TL;DR: This work has highlighted the potential endothelial mechanotransducers that might mediate responses to blood flow, the effects of atheroprotective rather than atherogenic flow,The mechanisms that contribute to the progression of the disease and how systemic factors interact with flow patterns to cause atherosclerosis.
Abstract: Forces that are associated with blood flow are major determinants of vascular morphogenesis and physiology. Blood flow is crucial for blood vessel development during embryogenesis and for regulation of vessel diameter in adult life. It is also a key factor in atherosclerosis, which, despite the systemic nature of major risk factors, occurs mainly in regions of arteries that experience disturbances in fluid flow. Recent data have highlighted the potential endothelial mechanotransducers that might mediate responses to blood flow, the effects of atheroprotective rather than atherogenic flow, the mechanisms that contribute to the progression of the disease and how systemic factors interact with flow patterns to cause atherosclerosis.

Journal ArticleDOI
TL;DR: The authors argued that exposure to such supports is predictive of greater student learning gains and that teachers' behavioral interactions with students can be assessed observationally using standardized protocols, analyzed systematically with regard to sources of error, validated for predicting student learning, and changed (improved) as a function of specific and aligned supports provided to teachers.
Abstract: The authors advance an argument that placing observation of actual teaching as a central feature of accountability frameworks, teacher preparation, and basic science could result in substantial improvements in instruction and related social processes and a science of the production of teaching and teachers. Teachers’ behavioral interactions with students can be (a) assessed observationally using standardized protocols, (b) analyzed systematically with regard to sources of error, (c) validated for predicting student learning, and (d) changed (improved) as a function of specific and aligned supports provided to teachers; exposure to such supports is predictive of greater student learning gains. These methods have considerable promise; along with measurement challenges, some of which pertain to psychometrics, efficiency, and costs, they merit attention, rigorous study, and substantial research investments.

Journal ArticleDOI
TL;DR: This paper provided a statistical analysis of core contentions of the "varieties of capitalism" perspective on comparative capitalism and constructed indices to assess whether patterns of co-ordination in the OECD economies conform to the predictions of the theory and compared the correspondence of institutions across subspheres of the political economy.
Abstract: This article provides a statistical analysis of core contentions of the ‘varieties of capitalism’ perspective on comparative capitalism. The authors construct indices to assess whether patterns of co-ordination in the OECD economies conform to the predictions of the theory and compare the correspondence of institutions across subspheres of the political economy. They test whether institutional complementarities occur across these subspheres by estimating the impact of complementarities in labour relations and corporate governance on growth rates. To assess the durability of varieties of capitalism, they report on the extent of institutional change in the 1980s and 1990s. Powerful interaction effects across institutions in the subspheres of the political economy must be considered if assessments of the economic impact of institutional reform in any one sphere are to be accurate.

Journal ArticleDOI
24 Dec 2009-Nature
TL;DR: The results strongly support the need for systematic ‘phylogenomic’ efforts to compile a phylogeny-driven ‘Genomic Encyclopedia of Bacteria and Archaea’ in order to derive maximum knowledge from existing microbial genome data as well as from genome sequences to come.
Abstract: Sequencing of bacterial and archaeal genomes has revolutionized our understanding of the many roles played by microorganisms. There are now nearly 1,000 completed bacterial and archaeal genomes available, most of which were chosen for sequencing on the basis of their physiology. As a result, the perspective provided by the currently available genomes is limited by a highly biased phylogenetic distribution. To explore the value added by choosing microbial genomes for sequencing on the basis of their evolutionary relationships, we have sequenced and analysed the genomes of 56 culturable species of Bacteria and Archaea selected to maximize phylogenetic coverage. Analysis of these genomes demonstrated pronounced benefits (compared to an equivalent set of genomes randomly selected from the existing database) in diverse areas including the reconstruction of phylogenetic history, the discovery of new protein families and biological properties, and the prediction of functions for known genes from other organisms. Our results strongly support the need for systematic phylogenomic efforts to compile a phylogeny-driven Genomic Encyclopedia of Bacteria and Archaea in order to derive maximum knowledge from existing microbial genome data as well as from genome sequences to come. © 2009 Macmillan Publishers Limited. All rights reserved.

Journal ArticleDOI
TL;DR: The data suggest that tRFs are not random by-products of tRNA degradation or biogenesis, but an abundant and novel class of short RNAs with precise sequence structure that have specific expression patterns and specific biological roles.
Abstract: New types of small RNAs distinct from microRNAs (miRNAs) are progressively being discovered in various organisms. In order to discover such novel small RNAs, a library of 17- to 26-base-long RNAs was created from prostate cancer cell lines and sequenced by ultra-high-throughput sequencing. A significant number of the sequences are derived from precise processing at the 5' or 3' end of mature or precursor tRNAs to form three series of tRFs (tRNA-derived RNA fragments): the tRF-5, tRF-3, and tRF-1 series. These sequences constitute a class of short RNAs that are second most abundant to miRNAs. Northern hybridization, quantitative RT-PCR, and splinted ligation assays independently measured the levels of at least 17 tRFs. To demonstrate the biological importance of tRFs, we further investigated tRF-1001, derived from the 3' end of a Ser-TGA tRNA precursor transcript that is not retained in the mature tRNA. tRF-1001 is expressed highly in a wide range of cancer cell lines but much less in tissues, and its expression in cell lines was tightly correlated with cell proliferation. siRNA-mediated knockdown of tRF-1001 impaired cell proliferation with the specific accumulation of cells in G2, phenotypes that were reversed specifically by cointroducing a synthetic 2'-O-methyl tRF-1001 oligoribonucleotide resistant to the siRNA. tRF-1001 is generated in the cytoplasm by tRNA 3'-endonuclease ELAC2, a prostate cancer susceptibility gene. Our data suggest that tRFs are not random by-products of tRNA degradation or biogenesis, but an abundant and novel class of short RNAs with precise sequence structure that have specific expression patterns and specific biological roles.

Journal ArticleDOI
TL;DR: Percutaneous repair with the MitraClip system can be accomplished with low rates of morbidity and mortality and with acute MR reduction to < 2+ in the majority of patients, and with sustained freedom from death, surgery, or recurrent MR in a substantial proportion.

Journal ArticleDOI
TL;DR: The results of studies using recall, video induction, event-contingent diary, and letter-writing methods to induce other-praising emotions suggest that elevation motivates prosocial and affiliative behavior, gratitude motivates improved relationships with benefactors, and admiration motivates self-improvement.
Abstract: People are often profoundly moved by the virtue or skill of others, yet psychology has little to say about the ‘other-praising’ family of emotions. Here we demonstrate that emotions such as elevation, gratitude, and admiration differ from more commonly studied forms of positive affect (joy and amusement) in many ways, and from each other in a few ways. The results of studies using recall, video induction, event-contingent diary, and letter-writing methods to induce other-praising emotions suggest that: elevation (a response to moral excellence) motivates prosocial and affiliative behavior, gratitude motivates improved relationships with benefactors, and admiration motivates self-improvement. Mediation analyses highlight the role of conscious emotion between appraisals and motivations. Discussion focuses on implications for emotion research, interpersonal relationships, and morality.

Journal ArticleDOI
TL;DR: Brachial artery flow-mediated dilation is a predictor of incident cardiovascular events in population-based adults and improved the classification of subjects as low, intermediate, and high CVD risk compared with the FRS.
Abstract: Background— Although brachial artery flow-mediated dilation (FMD) predicts recurrent cardiovascular events, its predictive value for incident cardiovascular disease (CVD) events in adults free of CVD is not well established. We assessed the predictive value of FMD for incident CVD events in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods and Results— Brachial artery FMD was measured in a nested case-cohort sample of 3026 of 6814 subjects (mean±SD age, 61.2±9.9 years) in MESA, a population-based cohort study of adults free of clinical CVD at baseline recruited at 6 clinic sites in the United States. The sample included 50.2% female, 34.3% white, 19.7% Chinese, 20.8% black, and 25.1% Hispanic subjects. Probability-weighted Cox proportional hazards analysis was used to examine the association between FMD and 5 years of adjudicated incident CVD events, including incident myocardial infarction, definite angina, coronary revascularization (coronary artery bypass grafting, percutaneous transluminal cor...

Journal ArticleDOI
TL;DR: It is suggested that implicit stereotypes and sex differences in science participation and performance are mutually reinforcing, contributing to the persistent gender gap in science engagement.
Abstract: About 70% of more than half a million Implicit Association Tests completed by citizens of 34 countries revealed expected implicit stereotypes associating science with males more than with females. We discovered that nation-level implicit stereotypes predicted nation-level sex differences in 8th-grade science and mathematics achievement. Self-reported stereotypes did not provide additional predictive validity of the achievement gap. We suggest that implicit stereotypes and sex differences in science participation and performance are mutually reinforcing, contributing to the persistent gender gap in science engagement.

Journal ArticleDOI
TL;DR: The UUO model is likely to reveal useful biomarkers of progression of renal disease, as well as new therapies, which are desperately needed to allow intervention before the establishment of irreversible renal injury.

Journal ArticleDOI
TL;DR: A strategy for modulating fluorescence/phosphorescence for a single-component, dual-emissive, iodide-substituted difluoroboron dibenzoylmethane-poly(lactic acid) (BF(2)dbm(I)PLA) solid-state sensor material is reported.
Abstract: Luminescent materials are widely used for imaging and sensing owing to their high sensitivity, rapid response and facile detection by many optical technologies. Typically materials must be chemically tailored to achieve intense, photostable fluorescence, oxygen-sensitive phosphorescence or dual emission for ratiometric sensing, often by blending two dyes in a matrix. Dual-emissive materials combining all of these features in one easily tunable molecular platform are desirable, but when fluorescence and phosphorescence originate from the same dye, it can be challenging to vary relative fluorescence/phosphorescence intensities for practical sensing applications. Heavy-atom substitution alone increases phosphorescence by a given, not variable amount. Here, we report a strategy for modulating fluorescence/phosphorescence for a single-component, dual-emissive, iodide-substituted difluoroboron dibenzoylmethane-poly(lactic acid) (BF(2)dbm(I)PLA) solid-state sensor material. This is accomplished through systematic variation of the PLA chain length in controlled solvent-free lactide polymerization combined with heavy-atom substitution. We demonstrate the versatility of this approach by showing that films made from low-molecular-weight BF(2)dbm(I)PLA with weak fluorescence and strong phosphorescence are promising as 'turn on' sensors for aerodynamics applications, and that nanoparticles fabricated from a higher-molecular-weight polymer with balanced fluorescence and phosphorescence intensities serve as ratiometric tumour hypoxia imaging agents.

Journal ArticleDOI
TL;DR: Modification to the Olfati-Saber algorithm is proposed and it is shown that the resulting algorithm enables the asymptotic tracking of the virtual leader.
Abstract: All agents being informed and the virtual leader traveling at a constant velocity are the two critical assumptions seen in the recent literature on flocking in multi-agent systems. Under these assumptions, Olfati-Saber in a recent IEEE Transactions on Automatic Control paper proposed a flocking algorithm which by incorporating a navigational feedback enables a group of agents to track a virtual leader. This paper revisits the problem of multi-agent flocking in the absence of the above two assumptions. We first show that, even when only a fraction of agents are informed, the Olfati-Saber flocking algorithm still enables all the informed agents to move with the desired constant velocity, and an uninformed agent to also move with the same desired velocity if it can be influenced by the informed agents from time to time during the evolution. Numerical simulation demonstrates that a very small group of the informed agents can cause most of the agents to move with the desired velocity and the larger the informed group is the bigger portion of agents will move with the desired velocity. In the situation where the virtual leader travels with a varying velocity, we propose modification to the Olfati-Saber algorithm and show that the resulting algorithm enables the asymptotic tracking of the virtual leader. That is, the position and velocity of the center of mass of all agents will converge exponentially to those of the virtual leader. The convergent rate is also given.

Journal ArticleDOI
TL;DR: Questions remain about which groups of patients benefit from therapy and at which point in the course of disease this therapy should be initiated, and limited rigorous evidence exists demonstrating the effect of these therapies on important long-term clinical outcomes.
Abstract: National Institutes of Health (NIH) consensus and stateof-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ); 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; 3) questions and statements from conference attendees during open discussion periods that are part of the public session; and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The statement reflects the panel’s assessment of medical knowledge available at the time the statement was written. Thus, it provides a “snapshot in time” of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research. Hepatitis B is a major cause of liver disease worldwide, ranking as a substantial cause of cirrhosis and hepatocellular carcinoma. The development and use of a vaccine for hepatitis B virus (HBV) has resulted in a substantial decline in the number of new cases of acute hepatitis B among children, adolescents, and adults in the United States. However, this success has not yet been duplicated worldwide, and both acute and chronic HBV infection continue to represent important global health problems. Seven treatments are currently approved for adult patients with chronic HBV infection in the United States: interferon-, pegylated interferon-, lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate. Interferon- and lamivudine have been approved for children with HBV infection. Although available randomized, controlled trials (RCTs) show encouraging short-term results— demonstrating the favorable effect of these agents on such intermediate markers of disease as HBV DNA level, liver enzyme tests, and liver histology— limited rigorous evidence exists demonstrating the effect of these therapies on important long-term clinical outcomes, such as the development of hepatocellular carcinoma or a reduction in deaths. Questions therefore remain about which groups of patients benefit from therapy and at which point in the course of disease this therapy should be initiated.

Journal ArticleDOI
TL;DR: Evidence for domain specificity emerged, in which gains in behavioral regulation predicted gains in mathematics but not in language and literacy over the kindergarten year (p < .01) after site, child gender, and other background variables were controlled.
Abstract: The authors examined a new assessment of behavioral regulation and contributions to achievement and teacher-rated classroom functioning in a sample (N = 343) of kindergarteners from 2 geographical sites in the United States. Behavioral regulation was measured with the Head-Toes-Knees-Shoulders (HTKS) task, a structured observation requiring children to perform the opposite of a dominant response to 4 different oral commands. Results revealed considerable variability in HTKS scores. Evidence for construct validity was found in positive correlations with parent ratings of attentional focusing and inhibitory control and teacher ratings of classroom behavioral regulation. Hierarchical linear modeling indicated that higher levels of behavioral regulation in the fall predicted stronger levels of achievement in the spring and better teacher-rated classroom self-regulation (all ps < .01) but not interpersonal skills. Evidence for domain specificity emerged, in which gains in behavioral regulation predicted gains in mathematics but not in language and literacy over the kindergarten year (p < .01) after site, child gender, and other background variables were controlled. Discussion focuses on the importance of behavioral regulation for successful adjustment to the demands of kindergarten.

Journal ArticleDOI
TL;DR: In this paper, the authors investigate the association between aggressive tax and financial reporting and find a strong, positive relation, concluding that insufficient costs exist to offset financial and tax reporting incentives, such that nonconformity between financial accounting standards and tax law allows firms to manage book income upward and taxable income downward in the same reporting period.
Abstract: We investigate the association between aggressive tax and financial reporting and find a strong, positive relation. Our results suggest that insufficient costs exist to offset financial and tax reporting incentives, such that nonconformity between financial accounting standards and tax law allows firms to manage book income upward and taxable income downward in the same reporting period. To examine the relation between these aggressive reporting behaviors, we develop a measure of tax reporting aggressiveness that statistically detects tax shelter activity at least as well as, and often better than, other measures. In supplemental stock returns analyses, we confirm that the market overprices financial reporting aggressiveness. We also find that the market overprices tax reporting aggressiveness, but only for firms with the most aggressive financial reporting.

Journal ArticleDOI
TL;DR: This article found that expert entrepreneurs framed problems in a dramatically different way than novices, focusing more on building the venture as a whole, paying less attention to predictive information, and worrying more about making do with resources on hand to invest only what they could afford to lose.

Journal ArticleDOI
TL;DR: MIPSGAL as discussed by the authors is a 278 deg^2 survey of the inner Galactic plane using the Multiband Infrared Photometer for Spitzer aboard the Spitzer Space Telescope.
Abstract: MIPSGAL is a 278 deg^2 survey of the inner Galactic plane using the Multiband Infrared Photometer for Spitzer aboard the Spitzer Space Telescope. The survey field was imaged in two passbands, 24 and 70 μm with resolutions of 6″ and 18″, respectively. The survey was designed to provide a uniform, well-calibrated and well-characterized data set for general inquiry of the inner Galactic plane and as a longer-wavelength complement to the shorter-wavelength Spitzer survey of the Galactic plane: Galactic Plane Infrared Mapping Survey Extraordinaire. The primary science drivers of the current survey are to identify all high-mass (M > 5 M⊙) protostars in the inner Galactic disk and to probe the distribution, energetics, and properties of interstellar dust in the Galactic disk. The observations were planned to minimize data artifacts due to image latents at 24 μm and to provide full coverage at 70 μm. Observations at ecliptic latitudes within 15° of the ecliptic plane were taken at multiple epochs to help reject asteroids. The data for the survey were collected in three epochs, 2005 September–October, 2006 April, and 2006 October with all of the data available to the public. The estimated point-source sensitivities of the survey are 2 and 75 mJy (3 σ) at 24 and 70 μm, respectively. Additional data processing was needed to mitigate image artifacts due to bright sources at 24 μm and detector responsivity variations at 70 μm due to the large dynamic range of the Galactic plane. Enhanced data products including artifact-mitigated mosaics and point-source catalogs are being produced with the 24 μm mosaics already publicly available from the NASA/IPAC Infrared Science Archive. Some preliminary results using the enhanced data products are described.

Proceedings ArticleDOI
16 May 2009
TL;DR: A fully automated method for locating and repairing bugs in software that works on off-the-shelf legacy applications and does not require formal specifications, program annotations or special coding practices is introduced.
Abstract: Automatic program repair has been a longstanding goal in software engineering, yet debugging remains a largely manual process. We introduce a fully automated method for locating and repairing bugs in software. The approach works on off-the-shelf legacy applications and does not require formal specifications, program annotations or special coding practices. Once a program fault is discovered, an extended form of genetic programming is used to evolve program variants until one is found that both retains required functionality and also avoids the defect in question. Standard test cases are used to exercise the fault and to encode program requirements. After a successful repair has been discovered, it is minimized using structural differencing algorithms and delta debugging. We describe the proposed method and report experimental results demonstrating that it can successfully repair ten different C programs totaling 63,000 lines in under 200 seconds, on average.

Journal ArticleDOI
TL;DR: Fibrillar Aβ burden in cognitively normal older people is associated with APOE ε4 gene dose, the major genetic risk factor for AD, and was highest in an additional homozygote who had recently developed mild cognitive impairment.
Abstract: Fibrillar amyloid-beta (Abeta) is found in the brains of many cognitively normal older people. Whether or not this reflects a predisposition to Alzheimer's disease (AD) is unknown. We used Pittsburgh Compound B (PiB) PET to characterize the relationship between fibrillar Abeta burden and this predisposition in cognitively normal older people at 3 mean levels of genetic risk for AD. Dynamic PiB PET scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest (ROIs) were used to characterize and compare cerebral-to-cerebellar PIB distribution volume ratios, reflecting fibrillar Abeta burden, in 28 cognitively normal persons (mean age, 64 years) with a reported family history of AD and 2 copies, 1 copy, and no copies of the apolipoprotein E (APOE) epsilon4 allele. The 8 epsilon4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar Abeta was significantly associated with APOE epsilon4 carrier status and epsilon4 gene dose in AD-affected mean cortical, frontal, temporal, posterior cingulate-precuneus, parietal, and basal ganglia ROIs, and was highest in an additional homozygote who had recently developed mild cognitive impairment. These findings suggest that fibrillar Abeta burden in cognitively normal older people is associated with APOE epsilon4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar Abeta accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar Abeta, alone or in combination with other biomarkers and risk factors, predicts rates of cognitive decline and conversion to clinical AD; and to establish the role of fibrillar Abeta imaging in primary prevention trials.