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Showing papers by "University of Colorado Boulder published in 2008"


Journal ArticleDOI
TL;DR: The Compact Muon Solenoid (CMS) detector at the Large Hadron Collider (LHC) at CERN as mentioned in this paper was designed to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 10(34)cm(-2)s(-1)
Abstract: The Compact Muon Solenoid (CMS) detector is described. The detector operates at the Large Hadron Collider (LHC) at CERN. It was conceived to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 10(34)cm(-2)s(-1) (10(27)cm(-2)s(-1)). At the core of the CMS detector sits a high-magnetic-field and large-bore superconducting solenoid surrounding an all-silicon pixel and strip tracker, a lead-tungstate scintillating-crystals electromagnetic calorimeter, and a brass-scintillator sampling hadron calorimeter. The iron yoke of the flux-return is instrumented with four stations of muon detectors covering most of the 4 pi solid angle. Forward sampling calorimeters extend the pseudo-rapidity coverage to high values (vertical bar eta vertical bar <= 5) assuring very good hermeticity. The overall dimensions of the CMS detector are a length of 21.6 m, a diameter of 14.6 m and a total weight of 12500 t.

5,193 citations


Journal ArticleDOI
20 Jun 2008-Science
TL;DR: It is indicated that host diet and phylogeny both influence bacterial diversity, which increases from carnivory to omnivory to herbivory; that bacterial communities codiversified with their hosts; and that the gut microbiota of humans living a modern life-style is typical of omnivorous primates.
Abstract: Mammals are metagenomic in that they are composed of not only their own gene complements but also those of all of their associated microbes. To understand the coevolution of the mammals and their indigenous microbial communities, we conducted a network-based analysis of bacterial 16S ribosomal RNA gene sequences from the fecal microbiota of humans and 59 other mammalian species living in two zoos and in the wild. The results indicate that host diet and phylogeny both influence bacterial diversity, which increases from carnivory to omnivory to herbivory; that bacterial communities codiversified with their hosts; and that the gut microbiota of humans living a modern life-style is typical of omnivorous primates.

3,072 citations


Journal ArticleDOI
TL;DR: Soil pH was the best predictor of bacterial community composition across this landscape while fungal community composition was most closely associated with changes in soil nutrient status, suggesting specific changes in edaphic properties, not necessarily land-use type itself, may best predict shifts in microbialcommunity composition across a given landscape.
Abstract: Land-use change can have significant impacts on soil conditions and microbial communities are likely to respond to these changes. However, such responses are poorly characterized as few studies have examined how specific changes in edaphic characteristics do, or do not, influence the composition of soil bacterial and fungal communities across land-use types. Soil samples were collected from four replicated ( n = 3) land-use types (hardwood and pine forests, cultivated and livestock pasture lands) in the southeastern US to assess the effects of land-use change on microbial community structure and distribution. We used quantitative PCR to estimate bacterial–fungal ratios and clone libraries targeting small-subunit rRNA genes to independently characterize the bacterial and fungal communities. Although some soil properties (soil texture and nutrient status) did significantly differ across land-use types, other edaphic factors (e.g., pH) did not vary consistently with land-use. Bacterial–fungal ratios were not significantly different across the land-uses and distinct land-use types did not necessarily harbor distinct soil fungal or bacterial communities. Rather, the composition of bacterial and fungal communities was most strongly correlated with specific soil properties. Soil pH was the best predictor of bacterial community composition across this landscape while fungal community composition was most closely associated with changes in soil nutrient status. Together these results suggest that specific changes in edaphic properties, not necessarily land-use type itself, may best predict shifts in microbial community composition across a given landscape. In addition, our results demonstrate the utility of using sequence-based approaches to concurrently analyze bacterial and fungal communities as such analyses provide detailed phylogenetic information on individual communities and permit the robust assessment of the biogeographical patterns exhibited by soil microbial communities.

1,420 citations


Journal ArticleDOI
TL;DR: A unified view of principles that underlie the stability of particles protected by thiolate or phosphine and halide ligands is provided and is best described by a “noble-gas superatom” analogy.
Abstract: Synthesis, characterization, and functionalization of self-assembled, ligand-stabilized gold nanoparticles are long-standing issues in the chemistry of nanomaterials. Factors driving the thermodynamic stability of well documented discrete sizes are largely unknown. Herein, we provide a unified view of principles that underlie the stability of particles protected by thiolate (SR) or phosphine and halide (PR3, X) ligands. The picture has emerged from analysis of large-scale density functional theory calculations of structurally characterized compounds, namely Au102(SR)44, Au39(PR3)14X6−, Au11(PR3)7X3, and Au13(PR3)10X23+, where X is either a halogen or a thiolate. Attributable to a compact, symmetric core and complete steric protection, each compound has a filled spherical electronic shell and a major energy gap to unoccupied states. Consequently, the exceptional stability is best described by a “noble-gas superatom” analogy. The explanatory power of this concept is shown by its application to many monomeric and oligomeric compounds of precisely known composition and structure, and its predictive power is indicated through suggestions offered for a series of anomalously stable cluster compositions which are still awaiting a precise structure determination.

1,398 citations


Journal ArticleDOI
TL;DR: It is proposed that the recently initiated international Human Microbiome Project should strive to include a broad representation of humans, as well as other mammalian and environmental samples, as comparative analyses of microbiotas and their microbiomes are a powerful way to explore the evolutionary history of the biosphere.
Abstract: In this Analysis we use published 16S ribosomal RNA gene sequences to compare the bacterial assemblages that are associated with humans and other mammals, metazoa and free-living microbial communities that span a range of environments. The composition of the vertebrate gut microbiota is influenced by diet, host morphology and phylogeny, and in this respect the human gut bacterial community is typical of an omnivorous primate. However, the vertebrate gut microbiota is different from free-living communities that are not associated with animal body habitats. We propose that the recently initiated international Human Microbiome Project should strive to include a broad representation of humans, as well as other mammalian and environmental samples, as comparative analyses of microbiotas and their microbiomes are a powerful way to explore the evolutionary history of the biosphere.

1,395 citations


Journal ArticleDOI
TL;DR: A recently developed method to rapidly quantify the elemental composition of bulk organic aerosols (OA) using a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) is improved and applied to ambient measurements.
Abstract: A recently developed method to rapidly quantify the elemental composition of bulk organic aerosols (OA) using a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) is improved and applied to ambient measurements. Atomic oxygen-to-carbon (O/C) ratios characterize the oxidation state of OA, and O/C from ambient urban OA ranges from 0.2 to 0.8 with a diurnal cycle that decreases with primary emissions and increases because of photochemical processing and secondary OA (SOA) production. Regional O/C approaches ∼0.9. The hydrogen-to-carbon (H/C, 1.4–1.9) urban diurnal profile increases with primary OA (POA) as does the nitrogen-to-carbon (N/C, ∼0.02). Ambient organic-mass-to-organic-carbon ratios (OM/OC) are directly quantified and correlate well with O/C (R2 = 0.997) for ambient OA because of low N/C. Ambient O/C and OM/OC have values consistent with those recently reported from other techniques. Positive matrix factorization applied to ambient OA identifies factors with distinct O/C and OM/O...

1,364 citations


Journal ArticleDOI
TL;DR: A multivariate twin study of 3 executive functions (inhibiting dominant responses, updating working memory representations, and shifting between task sets), measured as latent variables, examined why people vary in these executive control abilities and why they are correlated but separable from a behavioral genetic perspective.
Abstract: Recent psychological and neuropsychological research suggests that executive functions--the cognitive control processes that regulate thought and action--are multifaceted and that different types of executive functions are correlated but separable. The present multivariate twin study of 3 executive functions (inhibiting dominant responses, updating working memory representations, and shifting between task sets), measured as latent variables, examined why people vary in these executive control abilities and why these abilities are correlated but separable from a behavioral genetic perspective. Results indicated that executive functions are correlated because they are influenced by a highly heritable (99%) common factor that goes beyond general intelligence or perceptual speed, and they are separable because of additional genetic influences unique to particular executive functions. This combination of general and specific genetic influences places executive functions among the most heritable psychological traits. These results highlight the potential of genetic approaches for uncovering the biological underpinnings of executive functions and suggest a need for examining multiple types of executive functions to distinguish different levels of genetic influences.

1,320 citations


Journal ArticleDOI
TL;DR: Using error-correcting DNA barcodes, one run of a massively parallel pyrosequencer is constructed that characterized nearly as many 16S rRNA genes as have been sequenced to date by Sanger sequencing.
Abstract: We constructed error-correcting DNA barcodes that allow one run of a massively parallel pyrosequencer to process up to 1,544 samples simultaneously. Using these barcodes we processed bacterial 16S rRNA gene sequences representing microbial communities in 286 environmental samples, corrected 92% of sample assignment errors, and thus characterized nearly as many 16S rRNA genes as have been sequenced to date by Sanger sequencing.

1,301 citations


Journal ArticleDOI
TL;DR: Age differences in sensation seeking and impulsivity in a socioeconomically and ethnically diverse sample of 935 individuals between the ages of 10 and 30 are examined, showing a curvilinear pattern and suggesting Heightened vulnerability to risk taking in middle adolescence may be due to the combination of relatively higher inclinations to seek excitement and relatively immature capacities for self-control.
Abstract: It has been hypothesized that sensation seeking and impulsivity, which are often conflated, in fact develop along different timetables and have different neural underpinnings, and that the difference in their timetables helps account for heightened risk taking during adolescence. In order to test these propositions, the authors examined age differences in sensation seeking and impulsivity in a socioeconomically and ethnically diverse sample of 935 individuals between the ages of 10 and 30, using self-report and behavioral measures of each construct. Consistent with the authors' predictions, age differences in sensation seeking, which are linked to pubertal maturation, follow a curvilinear pattern, with sensation seeking increasing between 10 and 15 and declining or remaining stable thereafter. In contrast, age differences in impulsivity, which are unrelated to puberty, follow a linear pattern, with impulsivity declining steadily from age 10 on. Heightened vulnerability to risk taking in middle adolescence may be due to the combination of relatively higher inclinations to seek excitement and relatively immature capacities for self-control that are typical of this period of development.

1,275 citations


Journal ArticleDOI
TL;DR: Important considerations for designing biodegradable hydrogels for cell encapsulation are described and recent advances in material design and their applications in tissue engineering are highlighted.
Abstract: Encapsulating cells in biodegradable hydrogels offers numerous attractive features for tissue engineering, including ease of handling, a highly hydrated tissue-like environment for cell and tissue growth, and the ability to form in vivo. Many properties important to the design of a hydrogel scaffold, such as swelling, mechanical properties, degradation, and diffusion, are closely linked to the crosslinked structure of the hydrogel, which is controlled through a variety of different processing conditions. Degradation may be tuned by incorporating hydrolytically or enzymatically labile segments into the hydrogel or by using natural biopolymers that are susceptible to enzymatic degradation. Because cells are present during the gelation process, the number of suitable chemistries and formulations are limited. In this review, we describe important considerations for designing biodegradable hydrogels for cell encapsulation and highlight recent advances in material design and their applications in tissue engineering.

1,179 citations


Journal ArticleDOI
TL;DR: This paper found that the majority of variation in leverage ratios is driven by an unobserved time-invariant effect that generates surprisingly stable capital structures: high (low) levered firms tend to remain as such for over two decades.
Abstract: We find that the majority of variation in leverage ratios is driven by an unobserved time-invariant effect that generates surprisingly stable capital structures: High (low) levered firms tend to remain as such for over two decades. This feature of leverage is largely unexplained by previously identified determinants, is robust to firm exit, and is present prior to the IPO, suggesting that variation in capital structures is primarily determined by factors that remain stable for long periods of time. We then show that these results have important implications for empirical analysis attempting to understand capital structure heterogeneity.

Journal ArticleDOI
TL;DR: Here, the minimum information about a genome sequence (MIGS) specification is introduced with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange.
Abstract: With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.

Journal ArticleDOI
TL;DR: The SzGene project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia and could serve as a model for field synopses of genetic associations in other common and genetically complex disorders.
Abstract: In an effort to pinpoint potential genetic risk factors for schizophrenia, research groups worldwide have published over 1,000 genetic association studies with largely inconsistent results. To facilitate the interpretation of these findings, we have created a regularly updated online database of all published genetic association studies for schizophrenia ('SzGene'). For all polymorphisms having genotype data available in at least four independent case-control samples, we systematically carried out random-effects meta-analyses using allelic contrasts. Across 118 meta-analyses, a total of 24 genetic variants in 16 different genes (APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53 and TPH1) showed nominally significant effects with average summary odds ratios of approximately 1.23. Seven of these variants had not been previously meta-analyzed. According to recently proposed criteria for the assessment of cumulative evidence in genetic association studies, four of the significant results can be characterized as showing 'strong' epidemiological credibility. Our project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia. As such, it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders.

Journal ArticleDOI
TL;DR: Experimental approaches that focus on identifying the mechanisms that limit task failure rather than those that cause muscle fatigue are reviewed, providing insight into the rate‐limiting adjustments that constrain muscle function during fatiguing contractions.
Abstract: Much is known about the physiological impairments that can cause muscle fatigue. It is known that fatigue can be caused by many different mechanisms, ranging from the accumulation of metabolites within muscle fibres to the generation of an inadequate motor command in the motor cortex, and that there is no global mechanism responsible for muscle fatigue. Rather, the mechanisms that cause fatigue are specific to the task being performed. The development of muscle fatigue is typically quantified as a decline in the maximal force or power capacity of muscle, which means that submaximal contractions can be sustained after the onset of muscle fatigue. There is even evidence that the duration of some sustained tasks is not limited by fatigue of the principal muscles. Here we review experimental approaches that focus on identifying the mechanisms that limit task failure rather than those that cause muscle fatigue. Selected comparisons of tasks, groups of individuals and interventions with the task-failure approach can provide insight into the rate-limiting adjustments that constrain muscle function during fatiguing contractions.

Journal ArticleDOI
24 Oct 2008-Science
TL;DR: “Warmth” is the most powerful personality trait in social judgment, and it is hypothesized that experiences of physical warmth would increase feelings of interpersonal warmth, without the person's awareness of this influence.
Abstract: "Warmth" is the most powerful personality trait in social judgment, and attachment theorists have stressed the importance of warm physical contact with caregivers during infancy for healthy relationships in adulthood. Intriguingly, recent research in humans points to the involvement of the insula in the processing of both physical temperature and interpersonal warmth (trust) information. Accordingly, we hypothesized that experiences of physical warmth (or coldness) would increase feelings of interpersonal warmth (or coldness), without the person's awareness of this influence. In study 1, participants who briefly held a cup of hot (versus iced) coffee judged a target person as having a "warmer" personality (generous, caring); in study 2, participants holding a hot (versus cold) therapeutic pad were more likely to choose a gift for a friend instead of for themselves.

Journal ArticleDOI
TL;DR: The variation within and between individuals in microbial ecology illustrated by this study emphasizes the challenges inherent in defining what constitutes a “healthy” bacterial community; addressing these challenges will be critical for the International Human Microbiome Project.
Abstract: Bacteria thrive on and within the human body. One of the largest human-associated microbial habitats is the skin surface, which harbors large numbers of bacteria that can have important effects on health. We examined the palmar surfaces of the dominant and nondominant hands of 51 healthy young adult volunteers to characterize bacterial diversity on hands and to assess its variability within and between individuals. We used a novel pyrosequencing-based method that allowed us to survey hand surface bacterial communities at an unprecedented level of detail. The diversity of skin-associated bacterial communities was surprisingly high; a typical hand surface harbored >150 unique species-level bacterial phylotypes, and we identified a total of 4,742 unique phylotypes across all of the hands examined. Although there was a core set of bacterial taxa commonly found on the palm surface, we observed pronounced intra- and interpersonal variation in bacterial community composition: hands from the same individual shared only 17% of their phylotypes, with different individuals sharing only 13%. Women had significantly higher diversity than men, and community composition was significantly affected by handedness, time since last hand washing, and an individual's sex. The variation within and between individuals in microbial ecology illustrated by this study emphasizes the challenges inherent in defining what constitutes a “healthy” bacterial community; addressing these challenges will be critical for the International Human Microbiome Project.

Journal ArticleDOI
TL;DR: This review summarizes the rationale, preclinical evidence, retrospective clinical analyses, and the interim clinical data pertaining HER2 therapies in gastric cancer.

Journal ArticleDOI
TL;DR: Parasitism is the most common consumer strategy among organisms, yet only recently has there been a call for the inclusion of infectious disease agents in food webs, and the value of this effort hinges on whether parasites affect food-web properties.
Abstract: Parasitism is the most common consumer strategy among organisms, yet only recently has there been a call for the inclusion of infectious disease agents in food webs. The value of this effort hinges on whether parasites affect food-web properties. Increasing evidence suggests that parasites have the potential to uniquely alter food-web topology in terms of chain length, connectance and robustness. In addition, parasites might affect food-web stability, interaction strength and energy flow. Food-web structure also affects infectious disease dynamics because parasites depend on the ecological networks in which they live. Empirically, incorporating parasites into food webs is straightforward. We may start with existing food webs and add parasites as nodes, or we may try to build food webs around systems for which we already have a good understanding of infectious processes. In the future, perhaps researchers will add parasites while they construct food webs. Less clear is how food-web theory can accommodate parasites. This is a deep and central problem in theoretical biology and applied mathematics. For instance, is representing parasites with complex life cycles as a single node equivalent to representing other species with ontogenetic niche shifts as a single node? Can parasitism fit into fundamental frameworks such as the niche model? Can we integrate infectious disease models into the emerging field of dynamic food-web modelling? Future progress will benefit from interdisciplinary collaborations between ecologists and infectious disease biologists.

Journal ArticleDOI
TL;DR: This work demonstrates that encapsulated human mesenchymal stem cells can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups tethered to the hydrogel material.
Abstract: Cell-matrix interactions have critical roles in regeneration, development and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in three dimensions prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small-molecule chemical functional groups tethered to the hydrogel material. Strategies using simple chemistry to control complex biological processes would be particularly powerful as they could make production of therapeutic materials simpler, cheaper and more easily controlled.

Journal ArticleDOI
TL;DR: Genty et al. as mentioned in this paper explored the possibility of assessing the allocation of photons absorbed by photosystem II (PSII) antennae to thermal energy dissipation and photosynthetic electron transport in leaves of several plant species under field conditions.
Abstract: In the present study we explored the possibility of assessing the allocation of photons absorbed by photosystem II (PSII) antennae to thermal energy dissipation and photosynthetic electron transport in leaves of several plant species under field conditions. Changes in chlorophyll fluorescence parameters were determined in situ over the course of an entire day in the field in sun-exposed leaves of two species with different maximal rates of photosynthesis, Helianthus annuus (sunflower) and Vinca major. Leaves of Vinca minor (periwinkle) growing in a deeply shaded location were also monitored. We propose using diurnal changes in the efficiency of open PSII centers (F′v/F′m) in these sun and shade leaves to (a) assess diurnal changes in the allocation of absorbed light to photochemistry and thermal energy dissipation and, furthermore, (b) make an estimate of changes in the rate of thermal energy dissipation, an analogous expression to the rate of photochemistry. The fraction of light absorbed in PSII antennae that is dissipated thermally (D) is proposed to be estimated from D = 1-F′v/F′m, in analogy to the widely used estimation of the fraction of light absorbed in PSII antennae (P) that is utilized in PSII photochemistry from P = F′v/F′m× qP (where qP is the coefficient for photochemical quenching; Genty, B., Briantais, J.-M. & Baker, N. R. 1989. Biochim. Biophys. Acta 990: 87-92). The rate of thermal dissipation is consequently given by D × PFD (photon flux density), again in analogy to the rate of photochemistry P × PFD, both assuming a matching behavior of photosystems I and II. Characterization of energy dissipation from the efficiency of open PSII centers allows an assessment from a single set of measurements at any time of day; this is particularly useful under field conditions where the fully relaxed reference values of variable or maximal fluorescence needed for the computation of nonphotochemical quenching may not be available. The usefulness of the assessment described above is compared with other currently used parameters to quantify nonphotochemical and photochemical chlorophyll fluorescence quenching.

Journal ArticleDOI
TL;DR: The authors explored the use of classroom video as a tool for fostering productive discussions about teaching and learning in a 2-year mathematics professional development program based on the Problem-Solving Cycle model, which relies on video from the teachers own classrooms and emphasizes creating a community in which members feel comfortable learning from video.

Journal ArticleDOI
TL;DR: Risk matrices-tables mapping "frequency" and "severity" ratings to corresponding risk priority levels-are popular in applications as diverse as terrorismrisk analysis, highway construction project management, office building risk analysis, climate change risk management, and enterprise risk management-are examined.
Abstract: Risk matrices-tables mapping "frequency" and "severity" ratings to corresponding risk priority levels-are popular in applications as diverse as terrorism risk analysis, highway construction project management, office building risk analysis, climate change risk management, and enterprise risk management (ERM). National and international standards (e.g., Military Standard 882C and AS/NZS 4360:1999) have stimulated adoption of risk matrices by many organizations and risk consultants. However, little research rigorously validates their performance in actually improving risk management decisions. This article examines some mathematical properties of risk matrices and shows that they have the following limitations. (a) Poor Resolution. Typical risk matrices can correctly and unambiguously compare only a small fraction (e.g., less than 10%) of randomly selected pairs of hazards. They can assign identical ratings to quantitatively very different risks ("range compression"). (b) Errors. Risk matrices can mistakenly assign higher qualitative ratings to quantitatively smaller risks. For risks with negatively correlated frequencies and severities, they can be "worse than useless," leading to worse-than-random decisions. (c) Suboptimal Resource Allocation. Effective allocation of resources to risk-reducing countermeasures cannot be based on the categories provided by risk matrices. (d) Ambiguous Inputs and Outputs. Categorizations of severity cannot be made objectively for uncertain consequences. Inputs to risk matrices (e.g., frequency and severity categorizations) and resulting outputs (i.e., risk ratings) require subjective interpretation, and different users may obtain opposite ratings of the same quantitative risks. These limitations suggest that risk matrices should be used with caution, and only with careful explanations of embedded judgments.

Journal ArticleDOI
TL;DR: A comparison of the strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case–Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene.
Abstract: We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case-control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.

Journal ArticleDOI
TL;DR: In this paper, the authors argue that institutional arrangements operating at other governance scales, such as national government agencies, international organizations, NGOs at multiple scales, and private associations, also often have critical roles to play in natural resource governance regimes, including self-organized regimes.
Abstract: This article seeks to shed new light on the study of decentralized natural resource governance by applying institutional theories of polycentricity—the relationships among multiple authorities with overlapping jurisdictions. The emphasis on multi-level dynamics has not penetrated empirical studies of environmental policy reforms in non-industrial countries. On the contrary, many of today’s decentralization proponents seem to be infatuated with the local sphere, expecting that local actors are always able and willing to govern their natural resources effectively. Existing studies in this area often focus exclusively on characteristics and performance of local institutions. While we certainly do not deny the importance of local institutions, we argue that institutional arrangements operating at other governance scales—such as national government agencies, international organizations, NGOs at multiple scales, and private associations—also often have critical roles to play in natural resource governance regimes, including self-organized regimes.

Journal ArticleDOI
TL;DR: In this article, the results of Rayleigh wave and Love wave phase velocity tomography in the western United States using ambient seismic noise observed at over 250 broad-band stations from the EarthScope/USArray Transportable Array and regional networks were presented.
Abstract: SUMMARY We present the results of Rayleigh wave and Love wave phase velocity tomography in the western United States using ambient seismic noise observed at over 250 broad-band stations from the EarthScope/USArray Transportable Array and regional networks. All available threecomponent time-series for the 12-month span between 2005 November 1 and 2006 October 31 have been cross-correlated to yield estimated empirical Rayleigh and Love wave Green’s functions. The Love wave signals were observed with higher average signal-to-noise ratio (SNR) than Rayleigh wave signals and hence cannot be fully explained by the scattering of Rayleigh waves. Phase velocity dispersion curves for both Rayleigh and Love waves between 5 and 40 speriod were measured for each interstation path by applying frequency‐time analysis. The average uncertainty and systematic bias of the measurements are estimated using a method based on analysing thousands of nearly linearly aligned station-triplets. We find that empirical Green’s functions can be estimated accurately from the negative time derivative of the symmetric component ambient noise cross-correlation without explicit knowledge of the source distribution. The average traveltime uncertainty is less than 1 s at periods shorter than 24 s. We present Rayleigh and Love wave phase speed maps at periods of 8, 12, 16,and 20 s. The maps show clear correlations with major geological structures and qualitative agreement with previous results based on Rayleigh wave group speeds.

BookDOI
13 Mar 2008
TL;DR: The work in this paper provides a state-of-the-art, integrative, and comprehensive approach to understanding variation in working memory by presenting explicit, detailed comparisons of the leading theories.
Abstract: Working memory - the ability to keep important information in mind while comprehending, thinking, and acting - varies considerably from person to person and changes dramatically during each person's life. Understanding such individual and developmental differences is crucial because working memory is a major contributor to general intellectual functioning. This volume offers a state-of-the-art, integrative, and comprehensive approach to understanding variation in working memory by presenting explicit, detailed comparisons of the leading theories. It incorporates views from the different research groups that operate on each side of the Atlantic, and covers working-memory research on a wide variety of populations, including healthy adults, children with and without learning difficulties, older adults, and adults and children with neurological disorders. A particular strength of this volume is that each research group explicitly addresses the same set of theoretical questions, from the perspective of both their own theoretical and experimental work and from the perspective of relevant alternative approaches. Through these questions, each research group considers their overarching theory of working memory, specifies the critical sources of working memory variation according to their theory, reflects on the compatibility of their approach with other approaches, and assesses their contribution to general working memory theory. This shared focus across chapters unifies the volume and highlights the similarities and differences among the various theories. Each chapter includes both a summary of research positions and a detailed discussion of each position. Variation in Working Memory achieves coherence across its chapters, while presenting the entire range of current theoretical and experimental approaches to variation in working memory.

Journal ArticleDOI
11 Jul 2008-Cell
TL;DR: In a mouse mutant where the long 3' UTR is truncated, dendritic targeting of BDNF mRNAs is impaired and a mechanism for differential regulation of subcellular functions of proteins is revealed.

Journal ArticleDOI
04 Jul 2008-Science
TL;DR: In this paper, a new data set of fossil occurrences representing 3.5 million specimens was presented, and it was shown that global and local diversity was less than twice as high in the Neogene as in the mid-Paleozoic.
Abstract: It has previously been thought that there was a steep Cretaceous and Cenozoic radiation of marine invertebrates. This pattern can be replicated with a new data set of fossil occurrences representing 3.5 million specimens, but only when older analytical protocols are used. Moreover, analyses that employ sampling standardization and more robust counting methods show a modest rise in diversity with no clear trend after the mid-Cretaceous. Globally, locally, and at both high and low latitudes, diversity was less than twice as high in the Neogene as in the mid-Paleozoic. The ratio of global to local richness has changed little, and a latitudinal diversity gradient was present in the early Paleozoic.

Journal ArticleDOI
TL;DR: In this paper, the authors present a tomographic model of 3D variations in mantle P wave velocity, parameterized by means of rectangular cells in latitude, longitude, and radius, the size of which adapts to sampling density by short-period (1 Hz) data.
Abstract: [1] We document our tomographic method and present a new global model of three-dimensional (3-D) variations in mantle P wave velocity. The model is parameterized by means of rectangular cells in latitude, longitude, and radius, the size of which adapts to sampling density by short-period (1 Hz) data. The largest single data source is ISC/NEIC data reprocessed by Engdahl and coworkers, from which we use routinely picked, short-period P, Pg, Pn, pP, and pwP data (for earthquakes during the period 1964∼2007). To improve the resolution in the lowermost and uppermost mantle, we use differential times of core phases (PKPAB − PKPDF, PKPAB − PKPBC, Pdiff − PKPDF) and surface-reflected waves (PP-P). The low-frequency differential times (Pdiff, PP) are measured by waveform cross correlation. Approximate 3-D finite frequency kernels are used to integrate the long-period data (Pdiff, PP) and short-period (P, pP, PKP) data. This global data set is augmented with data from regional catalogs and temporary seismic arrays. A crust correction is implemented to mitigate crustal smearing into the upper mantle. We invert the data for 3-D variations in P wave speed and effects of hypocenter mislocation subject to norm and gradient regularization. Spatial resolution is ∼100 km in the best sampled upper mantle regions. Our model, which is available online and which will be updated periodically, reveals in unprecedented detail the rich variation in style of subduction of lithospheric slabs into the mantle. The images confirm the structural complexity of downwellings in the transition zone discussed in previous papers and show with more clarity the structure of slab fragments stagnant in the transition zone beneath east Asia. They also reveal low wave speed beneath major hot spots, such as Iceland, Afar, and Hawaii, but details of these structures are not well resolved by the data used.

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TL;DR: In this paper, the authors present a review of recent work on the origin of the concept of enhanced multiple electron-hole pair (i.e. exciton) production in semiconductor quantum dots (QDs).