1,676 research outputs found
A Relational Event Approach to Modeling Behavioral Dynamics
This chapter provides an introduction to the analysis of relational event
data (i.e., actions, interactions, or other events involving multiple actors
that occur over time) within the R/statnet platform. We begin by reviewing the
basics of relational event modeling, with an emphasis on models with piecewise
constant hazards. We then discuss estimation for dyadic and more general
relational event models using the relevent package, with an emphasis on
hands-on applications of the methods and interpretation of results. Statnet is
a collection of packages for the R statistical computing system that supports
the representation, manipulation, visualization, modeling, simulation, and
analysis of relational data. Statnet packages are contributed by a team of
volunteer developers, and are made freely available under the GNU Public
License. These packages are written for the R statistical computing
environment, and can be used with any computing platform that supports R
(including Windows, Linux, and Mac).
Genomic Expansion of Magnetotactic Bacteria Reveals an Early Common Origin of Magnetotaxis with Lineage-specific Evolution
The origin and evolution of magnetoreception, which in diverse prokaryotes and protozoa is known as magnetotaxis and enables these microorganisms to detect Earth’s magnetic field for orientation and navigation, is not well understood in evolutionary biology. The only known prokaryotes capable of sensing the geomagnetic field are magnetotactic bacteria (MTB), motile microorganisms that biomineralize intracellular, membrane-bounded magnetic single-domain crystals of either magnetite (Fe3O4) or greigite (Fe3S4) called magnetosomes. Magnetosomes are responsible for magnetotaxis in MTB. Here we report the first large-scale metagenomic survey of MTB from both northern and southern hemispheres combined with 28 genomes from uncultivated MTB. These genomes expand greatly the coverage of MTB in the Proteobacteria, Nitrospirae, and Omnitrophica phyla, and provide the first genomic evidence of MTB belonging to the Zetaproteobacteria and “Candidatus Lambdaproteobacteria” classes. The gene content and organization of magnetosome gene clusters, which are physically grouped genes that encode proteins for magnetosome biosynthesis and organization, are more conserved within phylogenetically similar groups than between different taxonomic lineages. Moreover, the phylogenies of core magnetosome proteins form monophyletic clades. Together, these results suggest a common ancient origin of iron-based (Fe3O4 and Fe3S4) magnetotaxis in the domain Bacteria that underwent lineage-specific evolution, shedding new light on the origin and evolution of biomineralization and magnetotaxis, and expanding significantly the phylogenomic representation of MTB
Who is the best player ever? A complex network analysis of the history of professional tennis
We consider all matches played by professional tennis players between 1968
and 2010, and, on the basis of this data set, construct a directed and weighted
network of contacts. The resulting graph shows complex features, typical of
many real networked systems studied in literature. We develop a diffusion
algorithm and apply it to the tennis contact network in order to rank
professional players. Jimmy Connors is identified as the best player of the
history of tennis according to our ranking procedure. We perform a complete
analysis by determining the best players on specific playing surfaces as well
as the best ones in each of the years covered by the data set. The results of
our technique are compared to those of two other well established methods. In
general, we observe that our ranking method performs better: it has a higher
predictive power and does not require the arbitrary introduction of external
criteria for the correct assessment of the quality of players. The present work
provides a novel evidence of the utility of tools and methods of network theory
in real applications.Comment: 10 pages, 4 figures, 4 table
A Novel Strategy to Screen Bacillus Calmette-Guérin Protein Antigen Recognized by γδ TCR
BACKGROUND: Phosphoantigen was originally identified as the main γδ TCR-recognized antigen that could activate γδ T cells to promote immune protection against mycobacterial infection. However, new evidence shows that the γδ T cells activated by phosphoantigen can only provide partial immune protection against mycobacterial infection. In contrast, whole lysates of Mycobacterium could activate immune protection more potently, implying that other γδ TCR-recognized antigens that elicit protective immune responses. To date, only a few distinct mycobacterial antigens recognized by the γδ TCR have been characterized. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we established a new approach to screen epitopes or protein antigens recognized by the γδ TCR using Bacillus Calmette-Guérin- (BCG-) specific γ TCR transfected cells as probes to pan a 12-mer random-peptide phage-displayed library. Through binding assays and functional analysis, we identified a peptide (BP3) that not only binds to the BCG-specific γδ TCR but also effectively activates γδ T cells isolated from human subjects inoculated with BCG. Importantly, the γδ T cells activated by peptide BP3 had a cytotoxic effect on THP-1 cells infected with BCG. Moreover, the oxidative stress response regulatory protein (OXYS), a BCG protein that matches perfectly with peptide BP3 according to bioinformatics analysis, was confirmed as a ligand for the γδ TCR and was found to activate γδ T cells from human subjects inoculated with BCG. CONCLUSIONS/SIGNIFICANCE: In conclusion, our study provides a novel strategy to identify epitopes or protein antigens for the γδ TCR, and provides a potential means to screen mycobacterial vaccines or candidates for adjuvant
The geography of recent genetic ancestry across Europe
The recent genealogical history of human populations is a complex mosaic
formed by individual migration, large-scale population movements, and other
demographic events. Population genomics datasets can provide a window into this
recent history, as rare traces of recent shared genetic ancestry are detectable
due to long segments of shared genomic material. We make use of genomic data
for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of
recent genealogical ancestry over the past three thousand years at a
continental scale. We detected 1.9 million shared genomic segments, and used
the lengths of these to infer the distribution of shared ancestors across time
and geography. We find that a pair of modern Europeans living in neighboring
populations share around 10-50 genetic common ancestors from the last 1500
years, and upwards of 500 genetic ancestors from the previous 1000 years. These
numbers drop off exponentially with geographic distance, but since genetic
ancestry is rare, individuals from opposite ends of Europe are still expected
to share millions of common genealogical ancestors over the last 1000 years.
There is substantial regional variation in the number of shared genetic
ancestors: especially high numbers of common ancestors between many eastern
populations likely date to the Slavic and/or Hunnic expansions, while much
lower levels of common ancestry in the Italian and Iberian peninsulas may
indicate weaker demographic effects of Germanic expansions into these areas
and/or more stably structured populations. Recent shared ancestry in modern
Europeans is ubiquitous, and clearly shows the impact of both small-scale
migration and large historical events. Population genomic datasets have
considerable power to uncover recent demographic history, and will allow a much
fuller picture of the close genealogical kinship of individuals across the
world.Comment: Full size figures available from
http://www.eve.ucdavis.edu/~plralph/research.html; or html version at
http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm
Methods for adjusting population structure and familial relatedness in association test for collective effect of multiple rare variants on quantitative traits
Because of the low frequency of rare genetic variants in observed data, the statistical power of detecting their associations with target traits is usually low. The collapsing test of collective effect of multiple rare variants is an important and useful strategy to increase the power; in addition, family data may be enriched with causal rare variants and therefore provide extra power. However, when family data are used, both population structure and familial relatedness need to be adjusted for the possible inflation of false positives. Using a unified mixed linear model and family data, we compared six methods to detect the association between multiple rare variants and quantitative traits. Through the analysis of 200 replications of the quantitative trait Q2 from the Genetic Analysis Workshop 17 data set simulated for 697 subjects from 8 extended families, and based on quantile-quantile plots under the null and receiver operating characteristic curves, we compared the false-positive rate and power of these methods. We observed that adjusting for pedigree-based kinship gives the best control for false-positive rate, whereas adjusting for marker-based identity by state slightly outperforms in terms of power. An adjustment based on a principal components analysis slightly improves the false-positive rate and power. Taking into account type-1 error, power, and computational efficiency, we find that adjusting for pedigree-based kinship seems to be a good choice for the collective test of association between multiple rare variants and quantitative traits using family data
Modeling the scaling properties of human mobility
While the fat tailed jump size and the waiting time distributions
characterizing individual human trajectories strongly suggest the relevance of
the continuous time random walk (CTRW) models of human mobility, no one
seriously believes that human traces are truly random. Given the importance of
human mobility, from epidemic modeling to traffic prediction and urban
planning, we need quantitative models that can account for the statistical
characteristics of individual human trajectories. Here we use empirical data on
human mobility, captured by mobile phone traces, to show that the predictions
of the CTRW models are in systematic conflict with the empirical results. We
introduce two principles that govern human trajectories, allowing us to build a
statistically self-consistent microscopic model for individual human mobility.
The model not only accounts for the empirically observed scaling laws but also
allows us to analytically predict most of the pertinent scaling exponents
Quasi-Normal Modes of Stars and Black Holes
Perturbations of stars and black holes have been one of the main topics of
relativistic astrophysics for the last few decades. They are of particular
importance today, because of their relevance to gravitational wave astronomy.
In this review we present the theory of quasi-normal modes of compact objects
from both the mathematical and astrophysical points of view. The discussion
includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om,
Kerr and Kerr-Newman) and relativistic stars (non-rotating and
slowly-rotating). The properties of the various families of quasi-normal modes
are described, and numerical techniques for calculating quasi-normal modes
reviewed. The successes, as well as the limits, of perturbation theory are
presented, and its role in the emerging era of numerical relativity and
supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in
Relativity
Host-Pathogen O-Methyltransferase Similarity and Its Specific Presence in Highly Virulent Strains of Francisella tularensis Suggests Molecular Mimicry
Whole genome comparative studies of many bacterial pathogens have shown an overall high similarity of gene content (>95%) between phylogenetically distinct subspecies. In highly clonal species that share the bulk of their genomes subtle changes in gene content and small-scale polymorphisms, especially those that may alter gene expression and protein-protein interactions, are more likely to have a significant effect on the pathogen's biology. In order to better understand molecular attributes that may mediate the adaptation of virulence in infectious bacteria, a comparative study was done to further analyze the evolution of a gene encoding an o-methyltransferase that was previously identified as a candidate virulence factor due to its conservation specifically in highly pathogenic Francisella tularensis subsp. tularensis strains. The o-methyltransferase gene is located in the genomic neighborhood of a known pathogenicity island and predicted site of rearrangement. Distinct o-methyltransferase subtypes are present in different Francisella tularensis subspecies. Related protein families were identified in several host species as well as species of pathogenic bacteria that are otherwise very distant phylogenetically from Francisella, including species of Mycobacterium. A conserved sequence motif profile is present in the mammalian host and pathogen protein sequences, and sites of non-synonymous variation conserved in Francisella subspecies specific o-methyltransferases map proximally to the predicted active site of the orthologous human protein structure. Altogether, evidence suggests a role of the F. t. subsp. tularensis protein in a mechanism of molecular mimicry, similar perhaps to Legionella and Coxiella. These findings therefore provide insights into the evolution of niche-restriction and virulence in Francisella, and have broader implications regarding the molecular mechanisms that mediate host-pathogen relationships
Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children
Background: Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there
is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation
of therapy in African children.
Methods: The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum
malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996
and 2008.
Results: 1,237 of 2,752 children (45%) had delay in parasite clearance. Overall 211 children (17%) with delay in
clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291
children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or
equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of
fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75,
P < 0.0001), and enrolment before year 2000 (AOR= 1.55, 95% CI = 1.22-1.96, P < 0.0001). Following treatment,
a body temperature ≥ 38°C and parasitaemia > 20000/μl a day after treatment began, were independent risk
factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and
treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in
clearance significantly increased gametocyte carriage (P < 0.0001).
Conclusion: Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in
uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa
- …