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Showing papers by "Rutgers University published in 2010"


Journal ArticleDOI
TL;DR: This Review highlights the recent advances in optical properties of chemically derived GO, as well as new physical and biological applications that are attracting chemists for its own characteristics.
Abstract: Chemically derived graphene oxide (GO) is an atomically thin sheet of graphite that has traditionally served as a precursor for graphene, but is increasingly attracting chemists for its own characteristics. It is covalently decorated with oxygen-containing functional groups - either on the basal plane or at the edges - so that it contains a mixture of sp(2)- and sp(3)-hybridized carbon atoms. In particular, manipulation of the size, shape and relative fraction of the sp(2)-hybridized domains of GO by reduction chemistry provides opportunities for tailoring its optoelectronic properties. For example, as-synthesized GO is insulating but controlled deoxidation leads to an electrically and optically active material that is transparent and conducting. Furthermore, in contrast to pure graphene, GO is fluorescent over a broad range of wavelengths, owing to its heterogeneous electronic structure. In this Review, we highlight the recent advances in optical properties of chemically derived GO, as well as new physical and biological applications.

2,937 citations


Journal ArticleDOI
TL;DR: The 1000 Functional Connectomes Project (Fcon_1000) as discussed by the authors is a large-scale collection of functional connectome data from 1,414 volunteers collected independently at 35 international centers.
Abstract: Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

2,787 citations


Journal ArticleDOI
TL;DR: Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotids-artery stenting and the group undergoes carOTid endarterectomy.
Abstract: For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P = 0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P = 0.84) or sex (P = 0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P = 0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P = 0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P = 0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P = 0.18), for stroke (4.1% vs. 2.3%, P = 0.01), and for myocardial infarction (1.1% vs. 2.3%, P = 0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P = 0.85). CONCLUSIONS Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)

2,514 citations


Journal ArticleDOI
TL;DR: In this paper, a second version of the van der Waals density functional was proposed, employing a more accurate semilocal exchange functional and the use of a large N asymptote gradient correction in determining the vdW kernel.
Abstract: We propose a second version of the van der Waals density functional of Dion et al. [Phys. Rev. Lett. 92, 246401 (2004)], employing a more accurate semilocal exchange functional and the use of a large-N asymptote gradient correction in determining the vdW kernel. The predicted binding energy, equilibrium separation, and potential-energy curve shape are close to those of accurate quantum chemical calculations on 22 duplexes. We anticipate the enabling of chemically accurate calculations in sparse materials of importance for condensed matter, surface, chemical, and biological physics.

2,218 citations


Journal ArticleDOI
TL;DR: The MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2 hours with minimal hands-on time.
Abstract: Background Global control of tuberculosis is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms and in patients with human immunodeficiency virus infection. Early detection is essential to reduce the death rate and interrupt transmission, but the complexity and infrastructure needs of sensitive methods limit their accessibility and effect. Methods We assessed the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), with fully integrated sample processing in 1730 patients with suspected drug-sensitive or multidrug-resistant pulmonary tuberculosis. Eligible patients in Peru, Azerbaijan, South Africa, and India provided three sputum specimens each. Two specimens were processed with N-acetyl-l-cysteine and sodium hydroxide before microscopy, solid and liquid culture, and the MTB/RIF test, and one specimen was used for direct testing with microscopy and the MTB/RIF test. Results Among culture-positive patients, a single, direct MTB/RIF test identified 551 of 561 patients with smear-positive tuberculosis (98.2%) and 124 of 171 with smear-negative tuberculosis (72.5%). The test was specific in 604 of 609 patients without tuberculosis (99.2%). Among patients with smear-negative, culture-positive tuberculosis, the addition of a second MTB/RIF test increased sensitivity by 12.6 percentage points and a third by 5.1 percentage points, to a total of 90.2%. As compared with phenotypic drug-susceptibility testing, MTB/RIF testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant bacteria and 504 of 514 (98.1%) with rifampin-sensitive bacteria. Sequencing resolved all but two cases in favor of the MTB/RIF assay. Conclusions The MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2 hours with minimal hands-on time. (Funded by the Foundation for Innovative New Diagnostics.)

2,086 citations


Journal ArticleDOI
08 Oct 2010-Science
TL;DR: Humans must modify their behavior or risk causing irreversible changes to life on Earth, as the damage done by humans to the nitrogen economy of the planet will persist for decades, possibly centuries, if active intervention and careful management strategies are not initiated.
Abstract: Atmospheric reactions and slow geological processes controlled Earth's earliest nitrogen cycle, and by ~2.7 billion years ago, a linked suite of microbial processes evolved to form the modern nitrogen cycle with robust natural feedbacks and controls. Over the past century, however, the development of new agricultural practices to satisfy a growing global demand for food has drastically disrupted the nitrogen cycle. This has led to extensive eutrophication of fresh waters and coastal zones as well as increased inventories of the potent greenhouse gas nitrous oxide (N(2)O). Microbial processes will ultimately restore balance to the nitrogen cycle, but the damage done by humans to the nitrogen economy of the planet will persist for decades, possibly centuries, if active intervention and careful management strategies are not initiated.

1,882 citations


Journal ArticleDOI
03 Dec 2010-Science
TL;DR: A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases and does have a downside, however—cancer cells exploit it to survive in nutrient-poor tumors.
Abstract: Autophagy is a process of self-cannibalization Cells capture their own cytoplasm and organelles and consume them in lysosomes The resulting breakdown products are inputs to cellular metabolism, through which they are used to generate energy and to build new proteins and membranes Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones In starvation, it provides an internal source of nutrients for energy generation and, thus, survival A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases It does have a downside, however—cancer cells exploit it to survive in nutrient-poor tumors

1,669 citations


Journal ArticleDOI
TL;DR: In this paper, blue photoluminescence from chemically derived graphene oxide Goki Eda, Yun-Yue Lin, Cecilia Mattevi, Hisato Yamaguchi, Hsin-An Chen, I-Sheng Chen, Chun-Wei Chen, and Manish Chhowalla
Abstract: Blue photoluminescence from chemically derived graphene oxide Goki Eda, Yun-Yue Lin, Cecilia Mattevi, Hisato Yamaguchi, Hsin-An Chen, I-Sheng Chen, Chun-Wei Chen, and Manish Chhowalla 1 Department of Materials, Imperial College, Exhibition Road, London SW7 2AZ, UK. 2 Department of Materials Science and Engineering, Rutgers University 607 Taylor Road, Piscataway, NJ 08854, USA. 3 Department of Materials Science and Engineering, National Taiwan University No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.

1,655 citations


Journal ArticleDOI
TL;DR: The chemical changes of oxygen-containing functional groups on the annealing of graphene oxide are elucidated and the simulations reveal the formation of highly stable carbonyl and ether groups that hinder its complete reduction to graphene.
Abstract: The excellent electrical, optical and mechanical properties of graphene have driven the search to find methods for its large-scale production, but established procedures (such as mechanical exfoliation or chemical vapour deposition) are not ideal for the manufacture of processable graphene sheets. An alternative method is the reduction of graphene oxide, a material that shares the same atomically thin structural framework as graphene, but bears oxygen-containing functional groups. Here we use molecular dynamics simulations to study the atomistic structure of progressively reduced graphene oxide. The chemical changes of oxygen-containing functional groups on the annealing of graphene oxide are elucidated and the simulations reveal the formation of highly stable carbonyl and ether groups that hinder its complete reduction to graphene. The calculations are supported by infrared and X-ray photoelectron spectroscopy measurements. Finally, more effective reduction treatments to improve the reduction of graphene oxide are proposed.

1,624 citations


Journal ArticleDOI
TL;DR: Most of the evidence examined in this review supports the crucial role of public policy in encouraging bicycling, including infrastructure provision and pro-bicycle programs, supportive land use planning, and restrictions on car use.

1,266 citations


Journal ArticleDOI
TL;DR: A novel approach to generate transplantable liver grafts using decellularized liver matrix that preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture.
Abstract: Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease.

Journal ArticleDOI
TL;DR: The authors synthesize research on racial and ethnic patterns in school sanctions and considers how disproportionate discipline might contribute to lagging achievement among students of color, and offers promising directions for gap-reducing discipline policies and practices.
Abstract: The gap in achievement across racial and ethnic groups has been a focus of education research for decades, but the disproportionate suspension and expulsion of Black, Latino, and American Indian students has received less attention. This article synthesizes research on racial and ethnic patterns in school sanctions and considers how disproportionate discipline might contribute to lagging achievement among students of color. It further examines the evidence for student, school, and community contributors to the racial and ethnic patterns in school sanctions, and it offers promising directions for gap-reducing discipline policies and practices.

Journal ArticleDOI
TL;DR: In this article, satellite-based estimates of forest loss suggest that urban population growth and urban and international demand for agricultural products are key drivers of tropical deforestation in the tropics and that efforts need to focus on reducing deforestation for industrial-scale, export-oriented agricultural production, concomitant with efforts to increase yields in non-forested lands to satisfy demands for agricultural product.
Abstract: Reducing tropical deforestation is at present considered a cost-effective option for mitigating climate change. Satellite-based estimates of forest loss suggest that urban population growth and urban and international demand for agricultural products are key drivers of deforestation in the tropics. Reducing atmospheric carbon emissions from tropical deforestation is at present considered a cost-effective option for mitigating climate change. However, the forces associated with tropical forest loss are uncertain1. Here we use satellite-based estimates of forest loss for 2000 to 2005 (ref. 2) to assess economic, agricultural and demographic correlates across 41 countries in the humid tropics. Two methods of analysis—linear regression and regression tree—show that forest loss is positively correlated with urban population growth and exports of agricultural products for this time period. Rural population growth is not associated with forest loss, indicating the importance of urban-based and international demands for agricultural products as drivers of deforestation. The strong trend in movement of people to cities in the tropics is, counter-intuitively, likely to be associated with greater pressures for clearing tropical forests. We therefore suggest that policies to reduce deforestation among local, rural populations will not address the main cause of deforestation in the future. Rather, efforts need to focus on reducing deforestation for industrial-scale, export-oriented agricultural production, concomitant with efforts to increase yields in non-forested lands to satisfy demands for agricultural products.

Journal ArticleDOI
04 Nov 2010-Neuron
TL;DR: It is hypothesized that cell assemblies are best understood in light of their output product, as detected by "reader-actuator" mechanisms, and it is suggested that the hierarchical organization of cell assemblies may be regarded as a neural syntax.

Journal ArticleDOI
Sushmita Roy1, Jason Ernst1, Peter V. Kharchenko2, Pouya Kheradpour1, Nicolas Nègre3, Matthew L. Eaton4, Jane M. Landolin5, Christopher A. Bristow1, Lijia Ma3, Michael F. Lin1, Stefan Washietl6, Bradley I. Arshinoff7, Ferhat Ay8, Patrick E. Meyer9, Nicolas Robine10, Nicole L. Washington5, Luisa Di Stefano2, Eugene Berezikov11, Christopher D. Brown3, Rogerio Candeias6, Joseph W. Carlson5, Adrian Carr12, Irwin Jungreis1, Daniel Marbach1, Rachel Sealfon1, Michael Y. Tolstorukov2, Sebastian Will6, Artyom A. Alekseyenko2, Carlo G. Artieri13, Benjamin W. Booth5, Angela N. Brooks14, Qi Dai10, Carrie A. Davis15, Michael O. Duff16, X. Feng, Andrey A. Gorchakov2, Tingting Gu17, Jorja G. Henikoff10, Philipp Kapranov18, Renhua Li13, Heather K. MacAlpine4, John H. Malone13, Aki Minoda5, Jared T. Nordman6, Katsutomo Okamura10, Marc D. Perry7, Sara K. Powell4, Nicole C. Riddle17, Akiko Sakai2, Anastasia Samsonova2, Jeremy E. Sandler5, Yuri B. Schwartz2, Noa Sher6, Rebecca Spokony3, David Sturgill13, Marijke J. van Baren17, Kenneth H. Wan5, Li Yang16, Charles Yu5, Elise A. Feingold13, Peter J. Good13, Mark S. Guyer13, Rebecca F. Lowdon13, Kami Ahmad2, Justen Andrews19, Bonnie Berger1, Steven E. Brenner14, Michael R. Brent17, Lucy Cherbas19, Sarah C. R. Elgin17, Thomas R. Gingeras18, Robert L. Grossman3, Roger A. Hoskins5, Thomas C. Kaufman19, W. J. Kent20, Mitzi I. Kuroda2, Terry L. Orr-Weaver6, Norbert Perrimon2, Vincenzo Pirrotta21, James W. Posakony22, Bing Ren22, Steven Russell12, Peter Cherbas19, Brenton R. Graveley16, Suzanna E. Lewis5, Gos Micklem12, Brian Oliver13, Peter J. Park2, Susan E. Celniker5, Steven Henikoff23, Gary H. Karpen14, Eric C. Lai10, David M. MacAlpine4, Lincoln Stein7, Kevin P. White3, Manolis Kellis1 
24 Dec 2010-Science
TL;DR: The Drosophila Encyclopedia of DNA Elements (modENCODE) project as mentioned in this paper has been used to map transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines.
Abstract: To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

Journal ArticleDOI
29 Jan 2010-Science
TL;DR: It is shown theoretically that recurrent neural networks can generate an asynchronous state characterized by arbitrarily low mean spiking correlations despite substantial amounts of shared input, which generates negative correlations in synaptic currents which cancel the effect of sharedinput.
Abstract: Correlated spiking is often observed in cortical circuits, but its functional role is controversial. It is believed that correlations are a consequence of shared inputs between nearby neurons and could severely constrain information decoding. Here we show theoretically that recurrent neural networks can generate an asynchronous state characterized by arbitrarily low mean spiking correlations despite substantial amounts of shared input. In this state, spontaneous fluctuations in the activity of excitatory and inhibitory populations accurately track each other, generating negative correlations in synaptic currents which cancel the effect of shared input. Near-zero mean correlations were seen experimentally in recordings from rodent neocortex in vivo. Our results suggest a reexamination of the sources underlying observed correlations and their functional consequences for information processing.

Journal ArticleDOI
26 Aug 2010-Nature
TL;DR: Two major patterns emerged: coastal species showed maximum diversity in the Western Pacific, whereas oceanic groups consistently peaked across broad mid-latitudinal bands in all oceans, and changes in ocean temperature, in conjunction with other human impacts, may ultimately rearrange the global distribution of life in the ocean.
Abstract: Using large-scale data sets, these authors present a new assessment of global marine species diversity and its correlation with environmental and spatial parameters.

Journal ArticleDOI
TL;DR: Fault zones and fault systems have a key role in the development of the Earth's crust and control the mechanics and fluid flow properties of the crust, and the architecture of sedimentary deposits in basins as discussed by the authors.

Journal ArticleDOI
TL;DR: In this paper, it was shown that when graphite's graphene sheets are rotated out of their usual alignment, it can generate low-energy Van Hove singularities for which the position is controlled by the angle of rotation.
Abstract: When a Van Hove singularity exists near the Fermi energy of a solid’s density of states, it can cause a variety of exotic phenomena to emerge. Scanning tunnelling microscope measurements indicate that when graphite’s graphene sheets are rotated out of their usual alignment, it can generate low-energy Van Hove singularities for which the position is controlled by the angle of rotation.

Journal ArticleDOI
TL;DR: In this article, a variety of interacting, mutually reinforcing mechanistic pathways, including species' resource acquisition traits; population densities; ability to engineer changes to physical environmental conditions; effects on disturbance, especially fire; regimes; the ability to structure habitat for other species; and their impact on food webs, are discussed.
Abstract: Exotic species affect the biogeochemical pools and fluxes of materials and energy, thereby altering the fundamental structure and function of their ecosystems. Rapidly accumulating evidence from many species of both animal and plant invaders suggests that invasive species often increase pool sizes, particularly of biomass, and promote accelerated flux rates, but many exceptions can be found. Ecosystem dynamics are altered through a variety of interacting, mutually reinforcing mechanistic pathways, including species’ resource acquisition traits; population densities; ability to engineer changes to physical environmental conditions; effects on disturbance, especially fire; regimes; the ability to structure habitat for other species; and their impact on food webs. Local factors of landscape setting, history, and other sources of disturbance constrain ecosystem responses to invasions. New research directions are suggested, including the need for whole-system budgets, the quantification of abundance-impact relationships for particular ecosystem processes, and a better exploration of food web impacts on ecosystem processes.

Journal ArticleDOI
TL;DR: Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo, and also significantly reduced the risk of hospitalization involving hepaticEncephalopathy.
Abstract: Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. Results Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P = 0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events. Conclusions Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.)

Journal ArticleDOI
TL;DR: Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses are focused on.
Abstract: The last 10 years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate in the development and/or maintenance of human anxiety disorders. The simplicity and robustness of this learning paradigm, coupled with the fact that the underlying circuitry is evolutionarily well conserved, make it an ideal model to study the basic biology of memory and identify genetic factors and neuronal systems that regulate the normal and pathological expressions of learned fear. Critical advances have been made in determining how modified neuronal functions upon fear acquisition become stabilized during fear memory consolidation and how these processes are controlled in the course of fear memory extinction. With these advances came the realization that activity in remote neuronal networks must be coordinated for these events to take place. In this paper, we review these mechanisms of coordinated network activity and the molecular cascades leading to enduring fear memory, and allowing for their extinction. We will focus on Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses.

Journal ArticleDOI
TL;DR: The first analysis of the Cepheid Gene Xpert System's MTB/RIF assay is developed and performed, an integrated hands-free sputum-processing and real-time PCR system with rapid on-demand, near-patient technology, to simultaneously detect M. tuberculosis and rifampin resistance.
Abstract: Current nucleic acid amplification methods to detect Mycobacterium tuberculosis are complex, labor-intensive, and technically challenging. We developed and performed the first analysis of the Cepheid Gene Xpert System's MTB/RIF assay, an integrated hands-free sputum-processing and real-time PCR system with rapid on-demand, near-patient technology, to simultaneously detect M. tuberculosis and rifampin resistance. Analytic tests of M. tuberculosis DNA demonstrated a limit of detection (LOD) of 4.5 genomes per reaction. Studies using sputum spiked with known numbers of M. tuberculosis CFU predicted a clinical LOD of 131 CFU/ml. Killing studies showed that the assay's buffer decreased M. tuberculosis viability by at least 8 logs, substantially reducing biohazards. Tests of 23 different commonly occurring rifampin resistance mutations demonstrated that all 23 (100%) would be identified as rifampin resistant. An analysis of 20 nontuberculosis mycobacteria species confirmed high assay specificity. A small clinical validation study of 107 clinical sputum samples from suspected tuberculosis cases in Vietnam detected 29/29 (100%) smear-positive culture-positive cases and 33/39 (84.6%) or 38/53 (71.7%) smear-negative culture-positive cases, as determined by growth on solid medium or on both solid and liquid media, respectively. M. tuberculosis was not detected in 25/25 (100%) of the culture-negative samples. A study of 64 smear-positive culture-positive sputa from retreatment tuberculosis cases in Uganda detected 63/64 (98.4%) culture-positive cases and 9/9 (100%) cases of rifampin resistance. Rifampin resistance was excluded in 54/55 (98.2%) susceptible cases. Specificity rose to 100% after correcting for a conventional susceptibility test error. In conclusion, this highly sensitive and simple-to-use system can detect M. tuberculosis directly from sputum in less than 2 h.

Journal ArticleDOI
TL;DR: The past decade has witnessed renewed interest and numerous unexpected discoveries in the area of main group organometallic chemistry, and unusual bonding modes have been uncovered and new materials have been developed and new applications are being pursued.
Abstract: The past decade has witnessed renewed interest and numerous unexpected discoveries in the area of main group organometallic chemistry. Unusual bonding modes have been uncovered,1-4 new materials have been developed,5,6 and new applications are being pursued.7-12 With respect to new materials with unusual properties, an exciting field is the development of hybrid polymers that combine main group elements with typical organic structures in one framework.13,14 Among main group organic-inorganic hybrid polymers, those involving Group 14 and Group 15 elements have received tremendous attention over the past several decades, with silicones, polysilanes, and polyphosphazenes among the most thoroughly studied materials.15-17 A variety of other classes of new polymers containing not only silicon and phosphorus,18-22 but also the heavier homologues, such as germanium, tin, arsenic, and antimony have been introduced more recently.23-26

Proceedings ArticleDOI
06 Feb 2010
TL;DR: A content-based categorization of the type of messages posted by Twitter users is developed, based on which the analysis shows two common types of user behavior in terms of the content of the posted messages, and exposes differences between users in respect to these activities.
Abstract: In this work we examine the characteristics of social activity and patterns of communication on Twitter, a prominent example of the emerging class of communication systems we call "social awareness streams." We use system data and message content from over 350 Twitter users, applying human coding and quantitative analysis to provide a deeper understanding of the activity of individuals on the Twitter network. In particular, we develop a content-based categorization of the type of messages posted by Twitter users, based on which we examine users' activity. Our analysis shows two common types of user behavior in terms of the content of the posted messages, and exposes differences between users in respect to these activities.

Proceedings ArticleDOI
13 Dec 2010
TL;DR: A detailed study of 11 widely used internal clustering validation measures for crisp clustering and shows that S\_Dbw is the only internal validation measure which performs well in all five aspects, while other measures have certain limitations in different application scenarios.
Abstract: Clustering validation has long been recognized as one of the vital issues essential to the success of clustering applications. In general, clustering validation can be categorized into two classes, external clustering validation and internal clustering validation. In this paper, we focus on internal clustering validation and present a detailed study of 11 widely used internal clustering validation measures for crisp clustering. From five conventional aspects of clustering, we investigate their validation properties. Experiment results show that S\_Dbw is the only internal validation measure which performs well in all five aspects, while other measures have certain limitations in different application scenarios.

Journal ArticleDOI
Jody Hey1
TL;DR: A method for studying the divergence of multiple closely related populations is described and assessed and analysis of simulated data sets reveals the kinds of history that are accessible with a multipopulation analysis.
Abstract: A method for studying the divergence of multiple closely related populations is described and assessed. The approach of Hey and Nielsen (2007, Integration within the Felsenstein equation for improved Markov chain Monte Carlo methods in population genetics. Proc Natl Acad Sci USA. 104:2785-2790) for fitting an isolation-with-migration model was extended to the case of multiple populations with a known phylogeny. Analysis of simulated data sets reveals the kinds of history that are accessible with a multipopulation analysis. Necessarily, processes associated with older time periods in a phylogeny are more difficult to estimate; and histories with high levels of gene flow are particularly difficult with more than two populations. However, for histories with modest levels of gene flow, or for very large data sets, it is possible to study large complex divergence problems that involve multiple closely related populations or species.

Journal ArticleDOI
TL;DR: In this paper, the authors show that the mantle was warming in deep Archean-Hadean time because internal heating exceeded surface heat loss, and it has been cooling from 2.5 to 3.0 Ga to the present.

Journal ArticleDOI
TL;DR: In this article, the authors examine the co-evolution of MNE activities and institutions external and internal to the firm, and highlight the scope for firm-level creativity and institutional entrepreneurship that may lead to coevolution with the environment.
Abstract: This paper examines the co-evolution of MNE activities and institutions external and internal to the firm. We develop a theoretical framework for this analysis that draws on the more recent writings of Douglass North on institutions as a response to complex forms of uncertainty associated with the rise in global economic interconnectedness, and of Richard Nelson on the co-evolution of technology and institutions. We link historical changes in the character of MNE activities to changes in the institutional environment, and highlight the scope for firm-level creativity and institutional entrepreneurship that may lead to co-evolution with the environment. We argue that the main drivers for institutional entrepreneurship are now found in the increasing autonomy of MNE subsidiaries. Thus MNE agency derives from more decentralized forms of experimentation in international corporate networks, which competence-creating nodes of new initiatives can co-evolve with local institutions. Unlike most other streams of related literature, our approach connects patterns of institutional change in wider business systems with more micro processes of variety generation and experimentation within and across individual firms. This form of co-evolutionary analysis is increasingly important to understanding the interrelationships between MNE activities and public policy.

Journal ArticleDOI
TL;DR: A mathematical model is provided that model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion, providing understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians.
Abstract: Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the current study, we provide a mathematical model that begins to address this challenge. We model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion. Using the model, we observe tremendous variation in the rate of tumor development—providing an understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians. Furthermore, the model provides a simple formula for the number of driver mutations as a function of the total number of mutations in the tumor. Finally, when applied to recent experimental data, the model allows us to calculate the actual selective advantage provided by typical somatic mutations in human tumors in situ. This selective advantage is surprisingly small—0.004 ± 0.0004—and has major implications for experimental cancer research.