scispace - formally typeset
Search or ask a question

Showing papers by "New York University published in 2005"


Journal ArticleDOI
TL;DR: PicTar, a computational method for identifying common targets of micro RNAs, is presented and widespread coordinate control executed by microRNAs is suggested, thus providing evidence for coordinate microRNA control in mammals.
Abstract: MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript. Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375, miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals.

4,660 citations


Journal ArticleDOI
TL;DR: In this paper, a large-scale correlation function measured from a spectroscopic sample of 46,748 luminous red galaxies from the Sloan Digital Sky Survey is presented, which demonstrates the linear growth of structure by gravitational instability between z ≈ 1000 and the present and confirms a firm prediction of the standard cosmological theory.
Abstract: We present the large-scale correlation function measured from a spectroscopic sample of 46,748 luminous red galaxies from the Sloan Digital Sky Survey. The survey region covers 0.72h −3 Gpc 3 over 3816 square degrees and 0.16 < z < 0.47, making it the best sample yet for the study of large-scale structure. We find a well-detected peak in the correlation function at 100h −1 Mpc separation that is an excellent match to the predicted shape and location of the imprint of the recombination-epoch acoustic oscillations on the low-redshift clustering of matter. This detection demonstrates the linear growth of structure by gravitational instability between z ≈ 1000 and the present and confirms a firm prediction of the standard cosmological theory. The acoustic peak provides a standard ruler by which we can measure the ratio of the distances to z = 0.35 and z = 1089 to 4% fractional accuracy and the absolute distance to z = 0.35 to 5% accuracy. From the overall shape of the correlation function, we measure the matter density mh 2 to 8% and find agreement with the value from cosmic microwave background (CMB) anisotropies. Independent of the constraints provided by the CMB acoustic scale, we find m = 0.273 ±0.025+0.123(1+ w0)+0.137K. Including the CMB acoustic scale, we find that the spatial curvature is K = −0.010 ± 0.009 if the dark energy is a cosmological constant. More generally, our results provide a measurement of cosmological distance, and hence an argument for dark energy, based on a geometric method with the same simple physics as the microwave background anisotropies. The standard cosmological model convincingly passes these new and robust tests of its fundamental properties. Subject headings: cosmology: observations — large-scale structure of the universe — distance scale — cosmological parameters — cosmic microwave background — galaxies: elliptical and lenticular, cD

4,428 citations


Journal ArticleDOI
01 Dec 2005-Nature
TL;DR: It is shown that a novel class of chemically engineered oligonucleotides, termed ‘antagomirs’, are efficient and specific silencers of endogenous miRNA levels in mice and may represent a therapeutic strategy for silencing miRNAs in disease.
Abstract: MicroRNAs (miRNAs) are an abundant class of non-coding RNAs that are believed to be important in many biological processes through regulation of gene expression. The precise molecular function of miRNAs in mammals is largely unknown and a better understanding will require loss-of-function studies in vivo. Here we show that a novel class of chemically engineered oligonucleotides, termed 'antagomirs', are efficient and specific silencers of endogenous miRNAs in mice. Intravenous administration of antagomirs against miR-16, miR-122, miR-192 and miR-194 resulted in a marked reduction of corresponding miRNA levels in liver, lung, kidney, heart, intestine, fat, skin, bone marrow, muscle, ovaries and adrenals. The silencing of endogenous miRNAs by this novel method is specific, efficient and long-lasting. The biological significance of silencing miRNAs with the use of antagomirs was studied for miR-122, an abundant liver-specific miRNA. Gene expression and bioinformatic analysis of messenger RNA from antagomir-treated animals revealed that the 3' untranslated regions of upregulated genes are strongly enriched in miR-122 recognition motifs, whereas downregulated genes are depleted in these motifs. Analysis of the functional annotation of downregulated genes specifically predicted that cholesterol biosynthesis genes would be affected by miR-122, and plasma cholesterol measurements showed reduced levels in antagomir-122-treated mice. Our findings show that antagomirs are powerful tools to silence specific miRNAs in vivo and may represent a therapeutic strategy for silencing miRNAs in disease.

4,045 citations


Proceedings ArticleDOI
20 Jun 2005
TL;DR: The idea is to learn a function that maps input patterns into a target space such that the L/sub 1/ norm in the target space approximates the "semantic" distance in the input space.
Abstract: We present a method for training a similarity metric from data. The method can be used for recognition or verification applications where the number of categories is very large and not known during training, and where the number of training samples for a single category is very small. The idea is to learn a function that maps input patterns into a target space such that the L/sub 1/ norm in the target space approximates the "semantic" distance in the input space. The method is applied to a face verification task. The learning process minimizes a discriminative loss function that drives the similarity metric to be small for pairs of faces from the same person, and large for pairs from different persons. The mapping from raw to the target space is a convolutional network whose architecture is designed for robustness to geometric distortions. The system is tested on the Purdue/AR face database which has a very high degree of variability in the pose, lighting, expression, position, and artificial occlusions such as dark glasses and obscuring scarves.

3,870 citations


Journal ArticleDOI
TL;DR: In this paper, a meta-analysis reviewed the literature on socioeconomic status and academic achievement in journal articles published between 1990 and 2000 and showed a medium to strong SES-achievement relation.
Abstract: This meta-analysis reviewed the literature on socioeconomic status (SES) and academic achievement in journal articles published between 1990 and 2000. The sample included 101,157 students, 6,871 schools, and 128 school districts gathered from 74 independent samples. The results showed a medium to strong SES–achievement relation. This relation, however, is moderated by the unit, the source, the range of SES variable, and the type of SES–achievement measure. The relation is also contingent upon school level, minority status, and school location. The author conducted a replica of White’s (1982) meta-analysis to see whether the SES–achievement correlation had changed since White’s initial review was published. The results showed a slight decrease in the average correlation. Practical implications for future research and policy are discussed.

3,656 citations


Journal ArticleDOI
TL;DR: Extracellular ATP regulates microglial branch dynamics in the intact brain, and its release from the damaged tissue and surrounding astrocytes mediates a rapid microglia response towards injury.
Abstract: Parenchymal microglia are the principal immune cells of the brain. Time-lapse two-photon imaging of GFP-labeled microglia demonstrates that the fine termini of microglial processes are highly dynamic in the intact mouse cortex. Upon traumatic brain injury, microglial processes rapidly and autonomously converge on the site of injury without cell body movement, establishing a potential barrier between the healthy and injured tissue. This rapid chemotactic response can be mimicked by local injection of ATP and can be inhibited by the ATP-hydrolyzing enzyme apyrase or by blockers of G protein-coupled purinergic receptors and connexin channels, which are highly expressed in astrocytes. The baseline motility of microglial processes is also reduced significantly in the presence of apyrase and connexin channel inhibitors. Thus, extracellular ATP regulates microglial branch dynamics in the intact brain, and its release from the damaged tissue and surrounding astrocytes mediates a rapid microglial response towards injury.

3,251 citations


Book
29 Aug 2005
TL;DR: The mixed logit model is introduced, a model for applied choice analysis that combines logit terms and commands with MNL, the workhorse of choice models.
Abstract: Almost without exception, everything human beings undertake involves a choice. In recent years there has been a growing interest in the development and application of quantitative statistical methods to study choices made by individuals with the purpose of gaining a better understanding both of how choices are made and of forecasting future choice responses. In this primer the authors provide an unintimidating introduction to the main techniques of choice analysis and include detail on themes such as data collection and preparation, model estimation and interpretation and the design of choice experiments. A companion website to the book provides practice data sets and software to estimate the main discrete choice models such as multinomial logit, nested logit and mixed logit. This primer will be an invaluable resource to students as well as of immense value to consultants and professionals, researchers and anyone else interested in choice analysis and modelling.

2,974 citations


Journal ArticleDOI
20 Oct 2005-Neuron
TL;DR: Five major research topics are highlighted that illustrate parallel roles for the amygdala in humans and other animals, including implicit emotional learning and memory, emotional modulation of memory,otional influences on attention and perception, emotion and social behavior, and emotion inhibition and regulation.

2,799 citations


Journal ArticleDOI
TL;DR: This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France, where topics brought to consensus included approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns.
Abstract: Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.

2,636 citations


BookDOI
01 Jan 2005
TL;DR: The purpose of this text is to offer a comprehensive and self-contained presentation of some of the most successful and popular domain decomposition preconditioners for finite and spectral element approximations of partial differential equations.
Abstract: The purpose of this text is to offer a comprehensive and self-contained presentation of some of the most successful and popular domain decomposition preconditioners for finite and spectral element approximations of partial differential equations. Strong emphasis is placed on both algorithmic and mathematical aspects. Some important methods such FETI and balancing Neumann-Neumann methods and algorithms for spectral element methods, not treated previously in any monograph, are covered in detail. Winner of the 2005 Award for Excellence in Professional and Scholarly Publishing - Mathematics/Statistics - of the Association of American Publishers

2,313 citations


Journal ArticleDOI
TL;DR: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults and significantly reduced the burden of illness due to herpesZoster.
Abstract: background The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella– zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. methods We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine (“zoster vaccine”). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. results More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. conclusions The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Journal ArticleDOI
TL;DR: From the study of six healthy adult subjects, the excess diffusional kurtosis is found to be significantly higher in white matter than in gray matter, reflecting the structural differences between these two types of cerebral tissues.
Abstract: A magnetic resonance imaging method is presented for quantifying the degree to which water diffusion in biologic tissues is non-Gaussian. Since tissue structure is responsible for the deviation of water diffusion from the Gaussian behavior typically observed in homogeneous solutions, this method provides a specific measure of tissue structure, such as cellular compartments and membranes. The method is an extension of conventional diffusion-weighted imaging that requires the use of somewhat higher b values and a modified image postprocessing procedure. In addition to the diffusion coefficient, the method provides an estimate for the excess kurtosis of the diffusion displacement probability distribution, which is a dimensionless metric of the departure from a Gaussian form. From the study of six healthy adult subjects, the excess diffusional kurtosis is found to be significantly higher in white matter than in gray matter, reflecting the structural differences between these two types of cerebral tissues. Diffusional kurtosis imaging is related to q-space imaging methods, but is less demanding in terms of imaging time, hardware requirements, and postprocessing effort. It may be useful for assessing tissue structure abnormalities associated with a variety of neuropathologies. Magn Reson Med 53:1432–1440, 2005. © 2005 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: In this paper, a simple equilibrium model with liquidity risk is proposed, where a security's required return depends on its expected liquidity as well as on the covariances of its own return and liquidity with the market return.

Journal ArticleDOI
01 Apr 2005-Sleep
TL;DR: These practice parameters are an update of the previously-published recommendations regarding the indications for polysomnography and related procedures in the diagnosis of sleep disorders.
Abstract: These practice parameters are an update of the previously-published recommendations regarding the indications for polysomnography and related procedures in the diagnosis of sleep disorders. Diagnostic categories include the following: sleep related breathing disorders, other respiratory disorders, narcolepsy, parasomnias, sleep related seizure disorders, restless legs syndrome, periodic limb movement sleep disorder, depression with insomnia, and circadian rhythm sleep disorders. Polysomnography is routinely indicated for the diagnosis of sleep related breathing disorders; for continuous positive airway pressure (CPAP) titration in patients with sleep related breathing disorders; for the assessment of treatment results in some cases; with a multiple sleep latency test in the evaluation of suspected narcolepsy; in evaluating sleep related behaviors that are violent or otherwise potentially injurious to the patient or others; and in certain atypical or unusual parasomnias. Polysomnography may be indicated in patients with neuromuscular disorders and sleep related symptoms; to assist in the diagnosis of paroxysmal arousals or other sleep disruptions thought to be seizure related; in a presumed parasomnia or sleep related seizure disorder that does not respond to conventional therapy; or when there is a strong clinical suspicion of periodic limb movement sleep disorder. Polysomnography is not routinely indicated to diagnose chronic lung disease; in cases of typical, uncomplicated, and noninjurious parasomnias when the diagnosis is clearly delineated; for patients with seizures who have no specific complaints consistent with a sleep disorder; to diagnose or treat restless legs syndrome; for the diagnosis of circadian rhythm sleep disorders; or to establish a diagnosis of depression.

Journal ArticleDOI
TL;DR: In this article, the main results obtained by the BRAHMS Collaboration on the properties of hot and dense hadronic and partonic matter produced in ultrarelativistic heavy ion collisions at RHIC are reviewed.

Posted Content
TL;DR: This article found evidence that the use of discretionary accruals to manipulate reported earnings is more pronounced at firms where the CEO's potential total compensation is more closely tied to the value of stock and option holdings.
Abstract: We provide evidence that the use of discretionary accruals to manipulate reported earnings is more pronounced at firms where the CEO's potential total compensation is more closely tied to the value of stock and option holdings. In addition, during years of high accruals, CEOs exercise unusually large amounts of options and CEOs and other insiders sell large quantities of shares.

Journal ArticleDOI
TL;DR: In this article, the authors explored how affect relates to creativity at work using both quantitative and qualitative longitudinal data from the daily diaries of 222 employees in seven companies, and examined the nature, form, and temporal dynamics of the affect-creativity relationship.
Abstract: This study explored how affect relates to creativity at work. Using both quantitative and qualitative longitudinal data from the daily diaries of 222 employees in seven companies, we examined the nature, form, and temporal dynamics of the affect-creativity relationship. The results indicate that positive affect relates positively to creativity in organizations and that the relationship is a simple linear one. Time-lagged analyses identify positive affect as an antecedent of creative thought, with incubation periods of up to two days. Qualitative analyses identify positive affect as a consequence of creative thought events, as well as a concomitant of the creative process. A preliminary theory of the affect-creativity cycle in organizations includes each of these links and proposes mechanisms by which they may operate.

Journal ArticleDOI
TL;DR: Vitamin E had no benefit in patients with mild cognitive impairment and donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, a finding supported by the secondary outcome measures.
Abstract: background Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer’s disease. methods In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer’s disease; secondary outcomes were cognition and function. results A total of 769 subjects were enrolled, and possible or probable Alzheimer’s disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer’s disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer’s disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer’s disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E e 4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer’s disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E e 4 carriers. conclusions Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer’s disease during the first 12 months of treatment, the rate of progression to Alzheimer’s disease after three years was not lower among patients treated with donepezil than among those given placebo.

Journal ArticleDOI
TL;DR: These data definitively implicate perturbation of TGFβ signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.
Abstract: We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor β receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFβ signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetics of the acute phase response to administered ligand. Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFβ signaling. These data definitively implicate perturbation of TGFβ signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.

Journal ArticleDOI
29 Aug 2005-Oncogene
TL;DR: The distinct physiological contexts of EMT and the underlying molecular signaling networks controlled by TGF-β are reviewed.
Abstract: Remarkable phenotype plasticity of epithelial cells underlies morphogenesis, epithelial repair and tumor invasiveness. Detailed understanding of the contextual cues and molecular mediators that control epithelial plasticity will be required in order to develop viable therapeutic approaches targeting epithelial-to-mesenchymal transition (EMT), an advanced manifestation of epithelial plasticity. Members of the transforming growth factor (TGF-β) family of growth factors can initiate and maintain EMT in a variety of biological systems and pathophysiological context by activating major signaling pathways and transcriptional regulators integrated in extensive signaling networks. Here we will review the distinct physiological contexts of EMT and the underlying molecular signaling networks controlled by TGF-β.

Journal ArticleDOI
TL;DR: This paper examines several extensions of the stochastic frontier that account for unmeasured heterogeneity as well as firm inefficiency, and considers a special case of the random parameters model that produces a random effects model that preserves the central feature of the Stochastic frontier model and accommodates heterogeneity.

Journal ArticleDOI
TL;DR: The authors believe that the time-honored requirement to follow every small indeterminate nodule with serial CT should be revised and new guidelines are proposed for follow-up and management of small pulmonary nodules detected on CT scans.
Abstract: Lung nodules are detected very commonly on computed tomographic (CT) scans of the chest, and the ability to detect very small nodules improves with each new generation of CT scanner. In reported studies, up to 51% of smokers aged 50 years or older have pulmonary nodules on CT scans. However, the existing guidelines for follow-up and management of noncalcified nodules detected on nonscreening CT scans were developed before widespread use of multi–detector row CT and still indicate that every indeterminate nodule should be followed with serial CT for a minimum of 2 years. This policy, which requires large numbers of studies to be performed at considerable expense and with substantial radiation exposure for the affected population, has not proved to be beneficial or cost-effective. During the past 5 years, new information regarding prevalence, biologic characteristics, and growth rates of small lung cancers has become available; thus, the authors believe that the time-honored requirement to follow every smal...

Journal ArticleDOI
TL;DR: These data provide the first clear evidence that functionally distinct subpopulations of macrophages exist in the same tissue and that these macrophage play critical roles in both the injury and recovery phases of inflammatory scarring.
Abstract: Macrophages perform both injury-inducing and repair-promoting tasks in different models of inflammation, leading to a model of macrophage function in which distinct patterns of activation have been proposed. We investigated macrophage function mechanistically in a reversible model of liver injury in which the injury and recovery phases are distinct. Carbon tetrachloride--–induced liver fibrosis revealed scar-associated macrophages that persisted throughout recovery. A transgenic mouse (CD11b-DTR) was generated in which macrophages could be selectively depleted. Macrophage depletion when liver fibrosis was advanced resulted in reduced scarring and fewer myofibroblasts. Macrophage depletion during recovery, by contrast, led to a failure of matrix degradation. These data provide the first clear evidence that functionally distinct subpopulations of macrophages exist in the same tissue and that these macrophages play critical roles in both the injury and recovery phases of inflammatory scarring.

01 Jan 2005
TL;DR: This review explores insights into the relations between emotion and cognition that have resulted from studies of the human amygdala, suggesting that the classic division between the study of emotion and Cognition may be unrealistic and that an understanding of human cognition requires the consideration of emotion.
Abstract: Traditional approaches to the study of cognition emphasize an information-processing view that has generally excluded emotion. In contrast, the recent emergence of cognitive neuroscience as an inspiration for understanding human cognition has highlighted its interaction with emotion. This review explores insights into the relations between emotion and cognition that have resulted from studies of the human amygdala. Five topics are explored: emotional learning, emotion and memory, emotion's influence on attention and perception, processing emotion in social stimuli, and changing emotional responses. Investigations into the neural systems underlying human behavior demonstrate that the mechanisms of emotion and cognition are intertwined from early perception to reasoning. These findings suggest that the classic division between the study of emotion and cognition may be unrealistic and that an understanding of human cognition requires the consideration of emotion.

Journal ArticleDOI
TL;DR: This work unequivocally identified autophagosomes and other prelysosomal autophagic vacuoles (AVs), which were morphologically and biochemically similar to AVs highly purified from mouse liver, and provides the first evidence that macroautophagy is extensively involved in the neurodegenerative/regenerative process in AD.
Abstract: The accumulation of lysosomes and their hydrolases within neurons is a well-established neuropathologic feature of Alzheimer disease (AD). Here we show that lysosomal pathology in AD brain involves extensive alterations of macroautophagy, an inducible pathway for the turnover of intracellular constituents, including organelles. Using immunogold labeling with compartmental markers and electron microscopy on neocortical biopsies from AD brain, we unequivocally identified autophagosomes and other prelysosomal autophagic vacuoles (AVs), which were morphologically and biochemically similar to AVs highly purified from mouse liver. AVs were uncommon in brains devoid of AD pathology but were abundant in AD brains particularly, within neuritic processes, including synaptic terminals. In dystrophic neurites, autophagosomes, multivesicular bodies, multilamellar bodies, and cathepsin-containing autophagolysosomes were the predominant organelles and accumulated in large numbers. These compartments were distinguishable from lysosomes and lysosomal dense bodies, previously shown also to be abundant in dystrophic neurites. Autophagy was evident in the perikarya of affected neurons, particularly in those with neurofibrillary pathology where it was associated with a relative depletion of mitochondria and other organelles. These observations provide the first evidence that macroautophagy is extensively involved in the neurodegenerative/regenerative process in AD. The striking accumulations of immature AV forms in dystrophic neurites suggest that the transport of AVs and their maturation to lysosomes may be impaired, thereby impeding the suspected neuroprotective functions of autophagy.

Journal ArticleDOI
TL;DR: The New York University Value-Added Galaxy Catalog (NYU-VAGC) as mentioned in this paper is a catalog of local galaxies (mostly below z ≈ 0.3) based on a set of publicly released surveys matched to the SDSS Data Release 2.
Abstract: Here we present the New York University Value-Added Galaxy Catalog (NYU-VAGC), a catalog of local galaxies (mostly below z ≈ 0.3) based on a set of publicly released surveys matched to the Sloan Digital Sky Survey (SDSS) Data Release 2. The photometric catalog consists of 693,319 galaxies, QSOs, and stars; 343,568 of these have redshift determinations, mostly from the SDSS. Excluding areas masked by bright stars, the photometric sample covers 3514 deg2, and the spectroscopic sample covers 2627 deg2 (with about 85% completeness). Earlier, proprietary versions of this catalog have formed the basis of many SDSS investigations of the power spectrum, correlation function, and luminosity function of galaxies. Future releases will follow future public releases of the SDSS. The catalog includes matches to the Two Micron All Sky Survey Point Source Catalog and Extended Source Catalog, the IRAS Point Source Catalog Redshift Survey, the Two-Degree Field Galaxy Redshift Survey, the Third Reference Catalogue of Bright Galaxies, and the Faint Images of the Radio Sky at Twenty cm survey. We calculate and compile derived quantities from the images and spectra of the galaxies in the catalogs (for example, K-corrections and structural parameters for the galaxies). The SDSS catalog presented here is photometrically calibrated in a more consistent way than that distributed by the SDSS Data Release 2 Archive Servers and is thus more appropriate for large-scale structure statistics, reducing systematic calibration errors across the sky from ~2% to ~1%. We include an explicit description of the geometry of the catalog, including all imaging and targeting information as a function of sky position. Finally, we have performed eyeball quality checks on a large number of objects in the catalog in order to flag errors (such as errors in deblending). This catalog is complementary to the SDSS Archive Servers in that NYU-VAGC's calibration, geometric description, and conveniently small size are specifically designed for studying galaxy properties and large-scale structure statistics using the SDSS spectroscopic catalog.

Journal ArticleDOI
11 Feb 2005-Science
TL;DR: Salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events and suggests that selective chemical inhibitors of eIF2α deph phosphorylation may be useful in diseases involving ER stress or viral infection.
Abstract: Most protein phosphatases have little intrinsic substrate specificity, making selective pharmacological inhibition of specific dephosphorylation reactions a challenging problem. In a screen for small molecules that protect cells from endoplasmic reticulum (ER) stress, we identified salubrinal, a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha). Salubrinal also blocks eIF2alpha dephosphorylation mediated by a herpes simplex virus protein and inhibits viral replication. These results suggest that selective chemical inhibitors of eIF2alpha dephosphorylation may be useful in diseases involving ER stress or viral infection. More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events.

Journal ArticleDOI
06 May 2005-Science
TL;DR: Injection of miR-430 miRNAs rescues the brain defects in MZdicer mutants, revealing essential roles for miRNas during morphogenesis.
Abstract: MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally. To block all miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZdicer) mutants that disrupt the Dicer ribonuclease III and double-stranded RNA-binding domains. Mutant embryos do not process precursor miRNAs into mature miRNAs, but injection of preprocessed miRNAs restores gene silencing, indicating that the disrupted domains are dispensable for later steps in silencing. MZdicer mutants undergo axis formation and differentiate multiple cell types but display abnormal morphogenesis during gastrulation, brain formation, somitogenesis, and heart development. Injection of miR-430 miRNAs rescues the brain defects in MZdicer mutants, revealing essential roles for miRNAs during morphogenesis.

Journal ArticleDOI
TL;DR: For a VAR with drifting coefficients and stochastic volatilities, the authors present posterior densities for several objects that are pertinent for designing and evaluating monetary policy, including measures of inflation persistence, the natural rate of unemployment, a core rate of inflation, and ‘activism coefficients' for monetary policy rules.

Journal ArticleDOI
TL;DR: A multidimensional (MD) approach to recommender systems that can provide recommendations based on additional contextual information besides the typical information on users and items used in most of the currentRecommender systems is presented.
Abstract: The article presents a multidimensional (MD) approach to recommender systems that can provide recommendations based on additional contextual information besides the typical information on users and items used in most of the current recommender systems. This approach supports multiple dimensions, profiling information, and hierarchical aggregation of recommendations. The article also presents a multidimensional rating estimation method capable of selecting two-dimensional segments of ratings pertinent to the recommendation context and applying standard collaborative filtering or other traditional two-dimensional rating estimation techniques to these segments. A comparison of the multidimensional and two-dimensional rating estimation approaches is made, and the tradeoffs between the two are studied. Moreover, the article introduces a combined rating estimation method, which identifies the situations where the MD approach outperforms the standard two-dimensional approach and uses the MD approach in those situations and the standard two-dimensional approach elsewhere. Finally, the article presents a pilot empirical study of the combined approach, using a multidimensional movie recommender system that was developed for implementing this approach and testing its performance.