Research papers

Model-based Analysis of ChIP-Seq (MACS)

Yong Zhang, Tao Liu, Clifford A. Meyer, Jérôme Eeckhoute, David S. Johnson, B Bernstein, Chad Nusbaum, R Myers, Myles Brown,…

We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size of ChIP-Seq tags, and uses it to improve the spatial resolution of predicted binding sites. MACS also uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions. MACS compares favorably to existing ChIP-Seq peak-finding algorithms, and is freely available.

Wolbachia: master manipulators of invertebrate biology

John H. Werren, Laura Baldo, Michael E. Clark

Review of Particle Physics

C. Amsler, M. Doser, M. Antonelli, D.M. Asner, K.S. Babu, Howie Baer, H.R. Band, R.M. Barnett, E. Bergren, J. Beringer, G. B…

Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models

Kristopher J. Preacher, Andrew F. Hayes

Digital Game-Based Learning in high school Computer Science education: Impact on educational effectiveness and student motivation

Μαρίνα Παπαστεργίου

Many-body physics with ultracold gases

Immanuel Bloch, Jean Dalibard, W. Zwerger

This paper reviews recent experimental and theoretical progress concerning many-body phenomena in dilute, ultracold gases. It focuses on effects beyond standard weak-coupling descriptions, such as the Mott-Hubbard transition in optical lattices, strongly interacting gases in one and two dimensions, or lowest-Landau-level physics in quasi-two-dimensional gases in fast rotation. Strong correlations in fermionic gases are discussed in optical lattices or near-Feshbach resonances in the BCS-BEC crossover.

Two topics in the physics of light nuclei

R. Schiavilla

Analyzing real-time PCR data by the comparative CT method

Thomas D. Schmittgen, Kenneth J. Livak

Simultaneous Inference in General Parametric Models

Torsten Hothorn, Frank Bretz, Peter H. Westfall

Simultaneous inference is a common problem in many areas of application. If multiple null hypotheses are tested simultaneously, the probability of rejecting erroneously at least one of them increases beyond the pre-specified significance level. Simultaneous inference procedures have to be used which adjust for multiplicity and thus control the overall type I error rate. In this paper we describe simultaneous inference procedures in general parametric models, where the experimental questions are specified through a linear combination of elemental model parameters. The framework described here is quite general and extends the canonical theory of multiple comparison procedures in ANOVA models to linear regression problems, generalized linear models, linear mixed effects models, the Cox model, robust linear models, etc. Several examples using a variety of different statistical models illustrate the breadth of the results. For the analyses we use the R add-on package multcomp, which provides a convenient interface to the general approach adopted here.

Technology Acceptance Model 3 and a Research Agenda on Interventions

Viswanath Venkatesh, Hillol Bala

ABSTRACT Prior research has provided valuable insights into how and why employees make a decision about the adoption and use of information technologies (ITs) in the workplace. From an organizational point of view, however, the more important issue is how managers make informed decisions about interventions that can lead to greater acceptance and effective utilization of IT. There is limited research in the IT implementation literature that deals with the role of interventions to aid such managerial decision making. Particularly, there is a need to understand how various interventions can influence the known determinants of IT adoption and use. To address this gap in the literature, we draw from the vast body of research on the technology acceptance model (TAM), particularly the work on the determinants of perceived usefulness and perceived ease of use, and: (i) develop a comprehensive nomological network (integrated model) of the determinants of individual level (IT) adoption and use; (ii) empirically test the proposed integrated model; and (iii) present a research agenda focused on potential pre‐ and postimplementation interventions that can enhance employees' adoption and use of IT. Our findings and research agenda have important implications for managerial decision making on IT implementation in organizations.

Noble Metals on the Nanoscale: Optical and Photothermal Properties and Some Applications in Imaging, Sensing, Biology, and Medicine

Prashant K. Jain, Xiaohua Huang, Ivan H. El‐Sayed, Mostafa A. El‐Sayed

Noble metal nanostructures attract much interest because of their unique properties, including large optical field enhancements resulting in the strong scattering and absorption of light. The enhancement in the optical and photothermal properties of noble metal nanoparticles arises from resonant oscillation of their free electrons in the presence of light, also known as localized surface plasmon resonance (LSPR). The plasmon resonance can either radiate light (Mie scattering), a process that finds great utility in optical and imaging fields, or be rapidly converted to heat (absorption); the latter mechanism of dissipation has opened up applications in several new areas. The ability to integrate metal nanoparticles into biological systems has had greatest impact in biology and biomedicine. In this Account, we discuss the plasmonic properties of gold and silver nanostructures and present examples of how they are being utilized for biodiagnostics, biophysical studies, and medical therapy. For instance, taking advantage of the strong LSPR scattering of gold nanoparticles conjugated with specific targeting molecules allows the molecule-specific imaging and diagnosis of diseases such as cancer. We emphasize in particular how the unique tunability of the plasmon resonance properties of metal nanoparticles through variation of their size, shape, composition, and medium allows chemists to design nanostructures geared for specific bio-applications. We discuss some interesting nanostructure geometries, including nanorods, nanoshells, and nanoparticle pairs, that exhibit dramatically enhanced and tunable plasmon resonances, making them highly suitable for bio-applications. Tuning the nanostructure shape (e.g., nanoprisms, nanorods, or nanoshells) is another means of enhancing the sensitivity of the LSPR to the nanoparticle environment and, thereby, designing effective biosensing agents. Metal nanoparticle pairs or assemblies display distance-dependent plasmon resonances as a result of field coupling. A universal scaling model, relating the plasmon resonance frequency to the interparticle distance in terms of the particle size, becomes potentially useful for measuring nanoscale distances (and their changes) in biological systems. The strong plasmon absorption and photothermal conversion of gold nanoparticles has been exploited in cancer therapy through the selective localized photothermal heating of cancer cells. For nanorods or nanoshells, the LSPR can be tuned to the near-infrared region, making it possible to perform in vivo imaging and therapy. The examples of the applications of noble metal nanostructures provided herein can be readily generalized to other areas of biology and medicine because plasmonic nanomaterials exhibit great range, versatility, and systematic tunability of their optical attributes.

A methodology for performing global uncertainty and sensitivity analysis in systems biology

Simeone Marino, Ian B. Hogue, Christian J. Ray, Denise E. Kirschner

Modeling of species distributions with Maxent: new extensions and a comprehensive evaluation

Steven J. Phillips, Miroslav Dudı́k

Accurate modeling of geographic distributions of species is crucial to various applications in ecology and conservation. The best performing techniques often require some parameter tuning, which may be prohibitively time‐consuming to do separately for each species, or unreliable for small or biased datasets. Additionally, even with the abundance of good quality data, users interested in the application of species models need not have the statistical knowledge required for detailed tuning. In such cases, it is desirable to use “default settings”, tuned and validated on diverse datasets. Maxent is a recently introduced modeling technique, achieving high predictive accuracy and enjoying several additional attractive properties. The performance of Maxent is influenced by a moderate number of parameters. The first contribution of this paper is the empirical tuning of these parameters. Since many datasets lack information about species absence, we present a tuning method that uses presence‐only data. We evaluate our method on independently collected high‐quality presence‐absence data. In addition to tuning, we introduce several concepts that improve the predictive accuracy and running time of Maxent. We introduce “hinge features” that model more complex relationships in the training data; we describe a new logistic output format that gives an estimate of probability of presence; finally we explore “background sampling” strategies that cope with sample selection bias and decrease model‐building time. Our evaluation, based on a diverse dataset of 226 species from 6 regions, shows: 1) default settings tuned on presence‐only data achieve performance which is almost as good as if they had been tuned on the evaluation data itself; 2) hinge features substantially improve model performance; 3) logistic output improves model calibration, so that large differences in output values correspond better to large differences in suitability; 4) “target‐group” background sampling can give much better predictive performance than random background sampling; 5) random background sampling results in a dramatic decrease in running time, with no decrease in model performance.

Fat and Beyond: The Diverse Biology of PPARγ

Peter Tontonoz, Bruce M. Spiegelman

The nuclear receptor PPARgamma is a ligand-activated transcription factor that plays an important role in the control of gene expression linked to a variety of physiological processes. PPARgamma was initially characterized as the master regulator for the development of adipose cells. Ligands for PPARgamma include naturally occurring fatty acids and the thiazolidinedione (TZD) class of antidiabetic drugs. Activation of PPARgamma improves insulin sensitivity in rodents and humans through a combination of metabolic actions, including partitioning of lipid stores and the regulation of metabolic and inflammatory mediators termed adipokines. PPARgamma signaling has also been implicated in the control of cell proliferation, atherosclerosis, macrophage function, and immunity. Here, we review recent advances in our understanding of the diverse biological actions of PPARgamma with an eye toward the expanding therapeutic potential of PPARgamma agonist drugs.

Mixed-effects modeling with crossed random effects for subjects and items

R. Harald Baayen, Douglas Davidson, Douglas M. Bates

Systems biology towards life in silico: mathematics of the control of living cells

Hans V. Westerhoff

Hematopoiesis: An Evolving Paradigm for Stem Cell Biology

Stuart H. Orkin, Leonard I. Zon

Diet, size and reproductive biology of the silver catfish, Chrysichthys nigrodigitatus (Siluformes: Bagridae) in the Cross River, Nigeria

Benedict Obeten Offem, Yemi Akegbejo Samsons, I. T. Omoniyi

The silver catfish, Chrysichthys nigrodigitatus (Lacépède: 1803) is a highly valued food-fish included among the dominant commercial catches exploited in major rivers of Africa. To provide useful biological data for management, samples were collected monthly between January (2005) and December (2007) in three zones: I: Upper Cross River (grassland), II: Middle Cross River (mixed forest and grassland), and III: Lower Cross River (rainforest)] along 200 km length of the Cross River, Nigeria. Data from 1 248 specimens were processed using: allometric coefficient (b), gonado-somatic index, Fulton's condition factor and diversity indices. Male dominance was observed in all populations; C. nigrodigitatus reached maturity at 11.5 cm (male) and 16.7cm (female) total length. Gonado-somatic index was higher for females with a peak in the early rains. The breeding period was between April and August with mean fecundity ranging between 4522 +/- 1924 eggs and 20321 +/- 5543 eggs. This was directly related to total length and weight by the regression models: F = 2365.88 + 560.22 log L and F = 5025.81 +56.34 log W respectively. Exponential equations for length-weight relationships were Wt = -1.997 Lt(2.206) (Zone I), W = -2.831 Lt(3.040) (Zone II) and Wt = -2.245 Lt(2.995) (Zone III). The mean allometric coefficient (b) showed significant departure from cubic value (negative allometry) for Zone I while Zones II and III showed no difference, indicating isometry. Dominant items in the diet were fish and fish parts constituting 21.6% with Food Richness and Gut Repletion Index of 18 and 100% respectively, in all zones. Diet Breadth of 0.802 (Zone 1), 0.922 (Zone II) and 0.910 (Zone III) indicate a high trophic flexibility that enables switching from one diet to another according to availability. Mean condition factor for males varied from 0.718 +/- 0.117 minimum in Zone I to 0.996 +/- 0.062 maximum in Zone III. Forest inland wetlands (Zone II and III) of Cross River provided better condition for C. nigrodigitatus.

Cross-national prevalence and risk factors for suicidal ideation, plans and attempts

Matthew K. Nock, Guilherme Borges, Evelyn J. Bromet, Jordi Alonso, Matthias C. Angermeyer, Annette L. Beautrais, Ronny Bruff…

BACKGROUND: Suicide is a leading cause of death worldwide; however, the prevalence and risk factors for the immediate precursors to suicide - suicidal ideation, plans and attempts - are not wellknown, especially in low- and middle-income countries. AIMS: To report on the prevalence and risk factors for suicidal behaviours across 17 countries. METHOD: A total of 84 850 adults were interviewed regarding suicidal behaviours and socio-demographic and psychiatric risk factors. RESULTS: The cross-national lifetime prevalence of suicidal ideation, plans, and attempts is 9.2% (s.e.=0.1), 3.1% (s.e.=0.1), and 2.7% (s.e.=0.1). Across all countries, 60% of transitions from ideation to plan and attempt occur within the first year after ideation onset. Consistent cross-national risk factors included being female, younger, less educated, unmarried and having a mental disorder. Interestingly, the strongest diagnostic risk factors were mood disorders in high-income countries but impulse control disorders in low- and middle-income countries. CONCLUSION: There is cross-national variability in the prevalence of suicidal behaviours, but strong consistency in the characteristics and risk factors for these behaviours. These findings have significant implications for the prediction and prevention of suicidal behaviours.

Structural Equation Modelling: Guidelines for Determining Model Fit

Daire Hooper, Joseph Coughlan, Michael R. Mullen

The following paper presents current thinking and research on fit indices for structural equation modelling. The paper presents a selection of fit indices that are widely regarded as the most informative indices available to researchers. As well as outlining each of these indices, guidelines are presented on their use. The paper also provides reporting strategies of these indices and concludes with a discussion on the future of fit indices.

The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation

Ralph J. DeBerardinis, Julian J. Lum, Georgia Hatzivassiliou, Craig B. Thompson

Microcavity Plasmas: Physics and Applications

K.H. Schoenbach, Kurt Becker

Molecular Biology of the Cell

Bruce Alberts, Alexander D. Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter

For nearly a quarter century Molecular Biology of the Cell has been the leading cell biology textbook. This tradition continues with the new Fifth Edition, which has been completely revised and updated to describe our current, rapidly advancing understanding of cell biology. To list but a few examples, a large amount of new material is presented on epigenetics; stem cells; RNAi; comparative genomics; the latest cancer therapies; apoptosis (now its own separate chapter); and cell cycle control and the mechanics of M phase (now integrated into one chapter). The hallmark features of Molecular Biology of the Cell have been retained, such as its consistent and comprehensive art program, clear concept headings, and succinct section summaries. Additionally, in response to extensive feedback from readers, the Fifth Edition now includes several new features. It is now more portable. Chapters 1-20 are printed and Chapters 21-25, covering multicellular systems, are provided as PDF files on the free Media DVD-ROM which accompanies the book.* And for the first time, Molecular Biology of the Cell now contains end-of-chapter questions. These problems, written by John Wilson and Tim Hunt, emphasize a quantitative approach and the art of reasoning from experiments, and they will help students review and extend their knowledge derived from reading the textbook. The Media DVD-ROM, which is packaged with every copy of the book, contains PowerPoint® presentations with all of the figures, tables and micrographs from the text (available as JPEGs too). Also included is the Media Player, which plays over 125 movies—animations, videos, and molecular models—all with voice-over narration. A new reader-friendly feature is the integration of media codes throughout the text that link directly to relevant videos and animations. The Media DVD-ROM holds the multicellular systems chapters (21-25) of the text as well. By skillfully extracting the fundamental concepts from this enormous and ever-growing field, the authors tell the story of cell biology, and thereby create a coherent framework through which readers may approach and enjoy this subject that is so central to all of biology. * There is also a reference edition of Molecular Biology of the Cell, Fifth Edition (ISBN 978-0-8153-4111-6) that contains Chapters 1-25 entirely in printed format.

Fluorine in medicinal chemistry

Sophie Purser, Peter R. Moore, Steve Swallow, Véronique Gouverneur

It has become evident that fluorinated compounds have a remarkable record in medicinal chemistry and will play a continuing role in providing lead compounds for therapeutic applications. This tutorial review provides a sampling of renowned fluorinated drugs and their mode of action with a discussion clarifying the role and impact of fluorine substitution on drug potency.