Showing papers by "New York University published in 2009"
Kevork N. Abazajian1, Jennifer K. Adelman-McCarthy2, Marcel A. Agüeros3, S. Allam4 +220 more•Institutions (77)
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
TL;DR: The authors showed that colonisation of mice with a segmented filamentous bacterium (SFB) is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria.
3,860 citations
TL;DR: It is reported that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age.
Abstract: Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
3,216 citations
TL;DR: In this article, the authors provide a model that links a security's market liquidity and traders' funding liquidity, i.e., their availability of funds, to explain the empirically documented features that market liquidity can suddenly dry up (i) is fragile), (ii) has commonality across securities, (iii) is related to volatility, and (iv) experiences “flight to liquidity” events.
Abstract: We provide a model that links a security’s market liquidity — i.e., the ease of trading it — and traders’ funding liquidity — i.e., their availability of funds. Traders provide market liquidity and their ability to do so depends on their funding, that is, their capital and the margins charged by their financiers. In times of crisis, reductions in market liquidity and funding liquidity are mutually reinforcing, leading to a liquidity spiral. The model explains the empirically documented features that market liquidity (i) can suddenly dry up (i.e. is fragile), (ii) has commonality across securities, (iii) is related to volatility, (iv) experiences “flight to liquidity” events, and (v) comoves with the market. Finally, the model shows how the Fed can improve current market liquidity by committing to improve funding in a potential future crisis.
3,166 citations
TL;DR: It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules to achieve sustained seizure freedom.
Abstract: To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.
3,017 citations
TL;DR: In this article, a field is emerging that leverages the capacity to collect and analyze data at a scale that may reveal patterns of individual and group behaviors at a large scale, such as behavior patterns.
Abstract: A field is emerging that leverages the capacity to collect and analyze data at a scale that may reveal patterns of individual and group behaviors.
2,619 citations
Posted Content•
TL;DR: This paper proposed Instructional manipulation check (IMC), a new tool for detecting participants who are not following instructions and demonstrated how the inclusion of an IMC can increase statistical power and reliability of a dataset.
Abstract: Participants are not always as diligent in reading and following instructions as experimenters would like them to be. When participants fail to follow instructions, this increases noise and decreases the validity of their data. This paper presents and validates a new tool for detecting participants who are not following instructions – the Instructional manipulation check (IMC). We demonstrate how the inclusion of an IMC can increase statistical power and reliability of a dataset.
2,220 citations
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, University of Gothenburg11, Boston Children's Hospital12, 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, Yale University25, Howard Hughes Medical Institute26, 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
Columbia University1, University of Oxford2, New York University3, Nathan Kline Institute for Psychiatric Research4, University College London5, University of Pennsylvania6, University of California, Los Angeles7, University of Iowa8, McGill University9, French Institute for Research in Computer Science and Automation10, French Institute of Health and Medical Research11, John Radcliffe Hospital12, Imperial College London13, Mauna Kea Technologies14
TL;DR: This study is the largest evaluation of nonlinear deformation algorithms applied to brain image registration ever conducted and suggests that the findings are generalizable to new subject populations that are labeled or evaluated using different labeling protocols.
2,214 citations
TL;DR: This paper proposed Instructional manipulation check (IMC), a new tool for detecting participants who are not following instructions and demonstrated how the inclusion of an IMC can increase statistical power and reliability of a dataset.
2,130 citations
TL;DR: DW-MRI should be tested as an imaging biomarker in the context of well-defined clinical trials, by adding DW-MRI to existing NCI-sponsored trials, particularly those with tissue sampling or survival indicators, and standards for measurement, analysis, and display are needed.
TL;DR: In this paper, the authors proposed a light boson invoked by XDM to mediate a large inelastic scattering cross section for the DAMA annual modulation signal at low velocities at redshift, which could produce observable effects on the ionization history of the universe.
Abstract: � > 1GeV 1 . The long range allows a Sommerfeld enhancement to boost the annihilation cross section as required, without altering the weak-scale annihilation cross section during dark matter freeze-out in the early universe. If the dark matter annihilates into the new force carrier φ, its low mass can make hadronic modes kinematically inaccessible, forcing decays dominantly into leptons. If the force carrier is a non-Abelian gauge boson, the dark matter is part of a multiplet of states, and splittings between these states are naturally generated with size αm� � MeV, leading to the eXciting dark matter (XDM) scenario previously proposed to explain the positron annihilation in the galactic center observed by the INTEGRAL satellite; the light boson invoked by XDM to mediate a large inelastic scattering cross section is identified with the φ here. Somewhat smaller splittings would also be expected, providing a natural source for the parameters of the inelastic dark matter (iDM) explanation for the DAMA annual modulation signal. Since the Sommerfeld enhancement is most significant at low velocities, early dark matter halos at redshift � 10 potentially produce observable effects on the ionization history of the universe. Because of the enhanced cross section, detection of substructure is more probable than with a conventional WIMP. Moreover, the low velocity dispersion of dwarf galaxies and Milky Way subhalos can increase the substructure annihilation signal by an additional order of magnitude or more.
TL;DR: Traditional applications of recombinant FGFs and small-molecule FGF receptor kinase inhibitors in the treatment of cancer and cardiovascular disease and their emerging potential in thetreatment of metabolic syndrome and hypophosphataemic diseases are discussed.
Abstract: The family of fibroblast growth factors (FGFs) regulates a plethora of developmental processes, including brain patterning, branching morphogenesis and limb development. Several mitogenic, cytoprotective and angiogenic therapeutic applications of FGFs are already being explored, and the recent discovery of the crucial roles of the endocrine-acting FGF19 subfamily in bile acid, glucose and phosphate homeostasis has sparked renewed interest in the pharmacological potential of this family. This Review discusses traditional applications of recombinant FGFs and small-molecule FGF receptor kinase inhibitors in the treatment of cancer and cardiovascular disease and their emerging potential in the treatment of metabolic syndrome and hypophosphataemic diseases.
TL;DR: Recent findings that demonstrate the plasticity of CD4(+) T cell differentiation and the biological implications of this flexibility are discussed.
TL;DR: This review examines recent theory and research concerning the structure, contents, and functions of ideological belief systems and considers the consequences of ideology, especially with respect to attitudes, evaluations, and processes of system justification.
Abstract: Ideology has re-emerged as an important topic of inquiry among social, personality, and political psychologists. In this review, we examine recent theory and research concerning the structure, contents, and functions of ideological belief systems. We begin by defining the construct and placing it in historical and philosophical context. We then examine different perspectives on how many (and what types of) dimensions individuals use to organize their political opinions. We investigate (a) how and to what extent individuals acquire the discursive contents associated with various ideologies, and (b) the social-psychological functions that these ideologies serve for those who adopt them. Our review highlights “elective affinities” between situational and dispositional needs of individuals and groups and the structure and contents of specific ideologies. Finally, we consider the consequences of ideology, especially with respect to attitudes, evaluations, and processes of system justification.
TL;DR: Fractionated but not single-dose radiotherapy induces an abscopal effect when in combination with anti–CTLA-4 antibody in two preclinical carcinoma models.
Abstract: Purpose This study tested the hypothesis that the type of dose fractionation regimen determines the ability of radiotherapy to synergize with anti-CTLA-4 antibody. Experimental design TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice at two separate sites, defined as a "primary" site that was irradiated and a "secondary" site outside the radiotherapy field. When both tumors were palpable, mice were randomly assigned to eight groups receiving no radiotherapy or three distinct regimens of radiotherapy (20 Gy x 1, 8 Gy x 3, or 6 Gy x 5 fractions in consecutive days) in combination or not with 9H10 monoclonal antibody against CTLA-4. Mice were followed for tumor growth/regression. Similar experiments were conducted in the MCA38 mouse colon carcinoma model. Results In either of the two models tested, treatment with 9H10 alone had no detectable effect. Each of the radiotherapy regimens caused comparable growth delay of the primary tumors but had no effect on the secondary tumors outside the radiation field. Conversely, the combination of 9H10 and either fractionated radiotherapy regimens achieved enhanced tumor response at the primary site (P Conclusions Fractionated but not single-dose radiotherapy induces an abscopal effect when in combination with anti-CTLA-4 antibody in two preclinical carcinoma models.
University of California, Davis1, Columbia University2, Spectrum Health3, George Washington University4, University of Utah5, University of Pennsylvania6, Johns Hopkins University7, University of Michigan8, University of Rochester9, Washington University in St. Louis10, Wayne State University11, University of Maryland, Baltimore12, University at Buffalo13, New York University14, Holy Cross Hospital15, State University of New York Upstate Medical University16, Medical College of Wisconsin17, University of Cincinnati18, Harvard University19, Saint Barnabas Medical Center20, Northwestern University21, Memorial Hospital of South Bend22, Calvert Memorial Hospital23
TL;DR: These validated prediction rules identified children at very low risk of clinically-important traumatic brain injuries (ciTBI) for whom CT might be unnecessary and missed neurosurgery in validation populations.
TL;DR: A dynamic matched sample estimation framework is developed to distinguish influence and homophily effects in dynamic networks, and this framework is applied to a global instant messaging network of 27.4 million users, finding that previous methods overestimate peer influence in product adoption decisions in this network by 300–700%, and thathomophily explains >50% of the perceived behavioral contagion.
Abstract: Node characteristics and behaviors are often correlated with the structure of social networks over time. While evidence of this type of assortative mixing and temporal clustering of behaviors among linked nodes is used to support claims of peer influence and social contagion in networks, homophily may also explain such evidence. Here we develop a dynamic matched sample estimation framework to distinguish influence and homophily effects in dynamic networks, and we apply this framework to a global instant messaging network of 27.4 million users, using data on the day-by-day adoption of a mobile service application and users' longitudinal behavioral, demographic, and geographic data. We find that previous methods overestimate peer influence in product adoption decisions in this network by 300–700%, and that homophily explains >50% of the perceived behavioral contagion. These findings and methods are essential to both our understanding of the mechanisms that drive contagions in networks and our knowledge of how to propagate or combat them in domains as diverse as epidemiology, marketing, development economics, and public health.
TL;DR: In this paper, the authors propose a method for quantifying the variance risk premium on financial assets using the market prices of options written on this asset, which is an over-the-counter contract that pays the difference between a standard estimate of the realized variance and the fixed variance swap rate.
Abstract: We propose a direct and robust method for quantifying the variance risk premium on financial assets. We show that the risk-neutral expected value of return variance, also known as the variance swap rate, is well approximated by the value of a particular portfolio of options. We propose to use the difference between the realized variance and this synthetic variance swap rate to quantify the variance risk premium. Using a large options data set, we synthesize variance swap rates and investigate the historical behavior of variance risk premiums on five stock indexes and 35 individual stocks. (JEL G10, G12, G13) It has been well documented that return variance is stochastic. When investing in a security, an investor faces at least two sources of uncertainty, namely the uncertainty about the return as captured by the return variance, and the uncertainty about the return variance itself. It is important to know how investors deal with the uncertainty in return variance to effectively manage risk and allocate assets, to accurately price and hedge derivative securities, and to understand the behavior of financial asset prices in general. We develop a direct and robust method for quantifying the return variance risk premium on an asset using the market prices of options written on this asset. Our method uses the notion of a variance swap, which is an over-thecounter contract that pays the difference between a standard estimate of the realized variance and the fixed variance swap rate. Since variance swaps cost zero to enter, the variance swap rate represents the risk-neutral expected value of the realized variance. We show that the variance swap rate can be synthesized accurately by a particular linear combination of option prices. We propose to
TL;DR: For example, this paper found that sin stocks are less held by norm-constrained institutions such as pension plans as compared to mutual or hedge funds that are natural arbitrageurs, and they receive less coverage from analysts than do stocks of otherwise comparable characteristics.
Proceedings Article•
07 Dec 2009TL;DR: This paper describes a deconvolution approach that is several orders of magnitude faster than existing techniques that use hyper-Laplacian priors and is able to deconvolve a 1 megapixel image in less than ~3 seconds, achieving comparable quality to existing methods that take ~20 minutes.
Abstract: The heavy-tailed distribution of gradients in natural scenes have proven effective priors for a range of problems such as denoising, deblurring and super-resolution. These distributions are well modeled by a hyper-Laplacian (p(x) ∝ e-k|x|α ), typically with 0.5 ≤ α ≤ 0.8. However, the use of sparse distributions makes the problem non-convex and impractically slow to solve for multi-megapixel images. In this paper we describe a deconvolution approach that is several orders of magnitude faster than existing techniques that use hyper-Laplacian priors. We adopt an alternating minimization scheme where one of the two phases is a non-convex problem that is separable over pixels. This per-pixel sub-problem may be solved with a lookup table (LUT). Alternatively, for two specific values of α, 1/2 and 2/3 an analytic solution can be found, by finding the roots of a cubic and quartic polynomial, respectively. Our approach (using either LUTs or analytic formulae) is able to deconvolve a 1 megapixel image in less than ~3 seconds, achieving comparable quality to existing methods such as iteratively reweighted least squares (IRLS) that take ~20 minutes. Furthermore, our method is quite general and can easily be extended to related image processing problems, beyond the deconvolution application demonstrated.
TL;DR: In this paper, a cohort of 221 children with high-risk B-cell-progenitor ALL with the use of single-nucleotide-polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis were studied.
Abstract: Background Despite best current therapy, up to 20% of pediatric patients with acute lymphoblastic leukemia (ALL) have a relapse. Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined. Methods We studied a cohort of 221 children with high-risk B-cell–progenitor ALL with the use of single-nucleotide–polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis. Children with known very-high-risk ALL subtypes (i.e., BCR-ABL1–positive ALL, hypodiploid ALL, and ALL in infants) were excluded from this cohort. A copy-number abnormality was identified as a predictor of poor outcome, and it was then tested in an independent validation cohort of 258 patients with B-cell–progenitor ALL. Results More than 50 recurring copy-number abnormalities were identified, most commonly involving genes that encode regulators of B-cell development (in 66.8% of patients...
TL;DR: In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Abstract: Background: Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older. Methods and Findings: We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: ,5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: $30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80– 1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleepdisordered breathing showed a pattern of association similar to all-cause mortality. Conclusions: Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing. Please see later in the article for the Editors’ Summary.
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.
TL;DR: The authors argue that fluency is a ubiquitous metacognitive cue in reasoning and social judgment and offers the first comprehensive review of such mechanisms and their implications for judgment and decision making.
Abstract: Processing fluency, or the subjective experience of ease with which people process information, reliably influences people’s judgments across a broad range of social dimensions. Experimenters have manipulated processing fluency using a vast array of techniques, which, despite their diversity, produce remarkably similar judgmental consequences. For example, people similarly judge stimuli that are semantically primed (conceptual fluency), visually clear (perceptual fluency), and phonologically simple (linguistic fluency) as more true than their less fluent counterparts. The authors offer the first comprehensive review of such mechanisms and their implications for judgment and decision making. Because every cognition falls along a continuum from effortless to demanding and generates a corresponding fluency experience, the authors argue that fluency is a ubiquitous metacognitive cue in reasoning and social judgment.
TL;DR: It is shown that the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and that this leads to the allosteric activation of the methyltransferase activity of PRC2.
Abstract: Polycomb group proteins have an essential role in the epigenetic maintenance of repressive chromatin states. The gene-silencing activity of the Polycomb repressive complex 2 (PRC2) depends on its ability to trimethylate lysine 27 of histone H3 (H3K27) by the catalytic SET domain of the EZH2 subunit, and at least two other subunits of the complex: SUZ12 and EED. Here we show that the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and that this leads to the allosteric activation of the methyltransferase activity of PRC2. Mutations in EED that prevent it from recognizing repressive trimethyl-lysine marks abolish the activation of PRC2 in vitro and, in Drosophila, reduce global methylation and disrupt development. These findings suggest a model for the propagation of the H3K27me3 mark that accounts for the maintenance of repressive chromatin domains and for the transmission of a histone modification from mother to daughter cells.
TL;DR: It is speculated that iTreg cell development is driven by the need to maintain a noninflammatory environment in the gut, to suppress immune responses to environmental and food allergens, and to decrease chronic inflammation, whereas nTreg cells prevent autoimmunity and raise the activation threshold for all immune responses.
TL;DR: It is shown that learning and daily sensory experience leave minute but permanent marks on cortical connections and suggest that lifelong memories are stored in largely stably connected synaptic networks.
Abstract: Connections between neurons are thought to be remodelled when we learn new tasks or acquire new information. However, this plasticity must also occur against a backdrop of stable memory maintenance. In mice, a paradigm of either enhanced sensory experience or specific motor learning produced new putative neuronal connections that remained stable alongside developmentally preserved connections much later in life. This suggests that learning can produce changes in the neuronal connectivity that can be stable for the lifetime of the network. Connections between neurons are thought to be remodelled when we learn new tasks or acquire new information; however, it is unclear how neural circuits undergo continuous synaptic changes during learning while maintaining lifelong memories. Here, by following post-synaptic dendritic spines in the mouse cortex, it is shown that a small fraction of new spines induced by novel experience are preserved and provide a structural basis for lifelong memory retention. Changes in synaptic connections are considered essential for learning and memory formation1,2,3,4,5,6. However, it is unknown how neural circuits undergo continuous synaptic changes during learning while maintaining lifelong memories. Here we show, by following postsynaptic dendritic spines over time in the mouse cortex7,8, that learning and novel sensory experience lead to spine formation and elimination by a protracted process. The extent of spine remodelling correlates with behavioural improvement after learning, suggesting a crucial role of synaptic structural plasticity in memory formation. Importantly, a small fraction of new spines induced by novel experience, together with most spines formed early during development and surviving experience-dependent elimination, are preserved and provide a structural basis for memory retention throughout the entire life of an animal. These studies indicate that learning and daily sensory experience leave minute but permanent marks on cortical connections and suggest that lifelong memories are stored in largely stably connected synaptic networks.
TL;DR: The two major nodes comprising the DMN are differentiated with respect to the specific brain systems with which they interact, suggesting greater heterogeneity within this network than is commonly appreciated.
Abstract: The default mode network (DMN), based in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), exhibits higher metabolic activity at rest than during performance of externally-oriented cognitive tasks. Recent studies have suggested that competitive relationships between the DMN and various task-positive networks involved in task performance are intrinsically represented in the brain in the form of strong negative correlations (anticorrelations) between spontaneous fluctuations in these networks. Most neuroimaging studies characterize the DMN as a homogenous network, thus few have examined the differential contributions of DMN components to such competitive relationships. Here we examined functional differentiation within the default mode network, with an emphasis on understanding competitive relationships between this and other networks. We used a seed correlation approach on resting-state data to assess differences in functional connectivity between these two regions and their anticorrelated networks. While the positively correlated networks for the vmPFC and PCC seeds largely overlapped, the anticorrelated networks for each showed striking differences. Activity in vmPFC negatively predicted activity in parietal visual spatial and temporal attention networks, whereas activity in PCC negatively predicted activity in prefrontal-based motor control circuits. Granger causality analyses suggest that vmPFC and PCC exert greater influence on their anticorrelated networks than the other way around, suggesting that these two default mode nodes may directly modulate activity in task-positive networks. Thus, the two major nodes comprising the default mode network are differentiated with respect to the specific brain systems with which they interact, suggesting greater heterogeneity within this network than is commonly appreciated.
TL;DR: This article investigated the relationship between forecastable variation in excess bond returns and macroeconomic fundamentals and found that "real" and "inflation" factors have important forecasting power for future excess returns on U.S. government bonds, above and beyond the predictive power contained in forward rates and yield spreads.
Abstract: Are there important cyclical fluctuations in bond market premiums and, if so, with what macroeconomic aggregates do these premiums vary? We use the methodology of dynamic factor analysis for large datasets to investigate possible empirical linkages between forecastable variation in excess bond returns and macroeconomic fundamentals. We find that “real” and “inflation” factors have important forecasting power for future excess returns on U.S. government bonds, above and beyond the predictive power contained in forward rates and yield spreads. This behavior is ruled out by commonly employed affine term structure models where theforecastability ofbondreturns andbondyields is completely summarized by the cross-section of yields or forward rates. An important implication of these findings is that the cyclical behavior of estimated risk premia in both returns and long-term yields depends importantly on whether the information in macroeconomic factors is included in forecasts of excess bond returns. Without the macro factors, risk premia appear virtually acyclical, whereas with the estimated factors risk premia have a marked countercyclical component, consistent with theories that imply investors must be compensated for risks associated with macroeconomic activity. (JEL E0, E4, G10, G12)