A General Optimization Technique for High Quality Community Detection in Complex Networks

Recent years have witnessed the development of a large body of algorithms for community detection in complex networks. Most of them are based upon the optimization of objective functions, among which modularity is the most common, though a number of alternatives have been suggested in the scientific literature. We present here an effective general search strategy for the optimization of various objective functions for community detection purposes. When applied to modularity, on both real-world and synthetic networks, our search strategy substantially outperforms the best existing algorithms in terms of final scores of the objective function; for description length, its performance is on par with the original Infomap algorithm. The execution time of our algorithm is on par with non-greedy alternatives present in literature, and networks of up to 10,000 nodes can be analyzed in time spans ranging from minutes to a few hours on average workstations, making our approach readily applicable to tasks which require the quality of partitioning to be as high as possible, and are not limited by strict time constraints. Finally, based on the most effective of the available optimization techniques, we compare the performance of modularity and code length as objective functions, in terms of the quality of the partitions one can achieve by optimizing them. To this end, we evaluated the ability of each objective function to reconstruct the underlying structure of a large set of synthetic and real-world networks.Comment: MAIN text: 14 pages, 4 figures, 1 table Supplementary information: 19 pages, 8 figures, 5 table

Delineating Geographical Regions with Networks of Human Interactions in an Extensive Set of Countries

Large-scale networks of human interaction, in particular country-wide telephone call networks, can be used to redraw geographical maps by applying algorithms of topological community detection. The geographic projections of the emerging areas in a few recent studies on single regions have been suggested to share two distinct properties: first, they are cohesive, and second, they tend to closely follow socio-economic boundaries and are similar to existing political regions in size and number. Here we use an extended set of countries and clustering indices to quantify overlaps, providing ample additional evidence for these observations using phone data from countries of various scales across Europe, Asia, and Africa: France, the UK, Italy, Belgium, Portugal, Saudi Arabia, and Ivory Coast. In our analysis we use the known approach of partitioning country-wide networks, and an additional iterative partitioning of each of the first level communities into sub-communities, revealing that cohesiveness and matching of official regions can also be observed on a second level if spatial resolution of the data is high enough. The method has possible policy implications on the definition of the borderlines and sizes of administrative regions.National Science Foundation (U.S.)Singapore-MIT Alliance for Research and Technolog

Analytical expressions for stopping-power ratios relevant for accurate dosimetry in particle therapy

In particle therapy, knowledge of the stopping-power ratios (STPRs) of the ion beam for air and water is necessary for accurate ionization chamber dosimetry. Earlier work has investigated the STPRs for pristine carbon ion beams, but here we expand the calculations to a range of ions (1 <= z <= 18) as well as spread out Bragg peaks (SOBPs) and provide a theoretical in-depth study with a special focus on the parameter regime relevant for particle therapy. The Monte Carlo transport code SHIELD-HIT is used to calculate complete particle-fluence spectra which are required for determining STPRs according to the recommendations of the International Atomic Energy Agency (IAEA). We confirm that the STPR depends primarily on the current energy of the ions rather than on their charge z or absolute position in the medium. However, STPRs for different sets of stopping-power data for water and air recommended by the International Commission on Radiation Units & Measurements (ICRU) are compared, including also the recently revised data for water, yielding deviations up to 2% in the plateau region. In comparison, the influence of the secondary particle spectra on the STPR is about two orders of magnitude smaller in the whole region up till the practical range. The gained insights enable us to propose an analytic approximation for the STPR for both pristine and SOBPs as a function of penetration depth, which parametrically depend only on the initial energy and the residual range of the ion, respectively.Comment: 21 pages, 5 figures, fixed bug with figures in v

Amino Terminal Domains of the NMDA Receptor Are Organized as Local Heterodimers

The N-methyl-D-aspartate (NMDA) receptor, an obligate heterotetrameric assembly organized as a dimer of dimers, is typically composed of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits. Despite the crucial role that the NMDA receptor plays in the nervous system, the specific arrangement of subunits within the dimer-of-dimer assemblage is not conclusively known. Here we studied the organization of the amino terminal domain (ATD) of the rat GluN1/GluN2A and GluN1/GluN2B NMDA receptors by cysteine-directed, disulfide bond-mediated cross-linking. We found that GluN1 ATDs and GluN2 ATDs spontaneously formed disulfide bond-mediated dimers after introducing cysteines into the L1 interface of GluN2A or GluN2B ATD. The formation of dimer could be prevented by knocking out endogenous cysteines located near the L1 interface of GluN1. These results indicate that GluN1 and GluN2 ATDs form local heterodimers through the interactions in the L1-L1 interface and further demonstrate a dimer-of-heterodimer arrangement in GluN1/GluN2A and GluN1/GluN2B NMDA receptors

Redrawing the Map of Great Britain from a Network of Human Interactions

Do regional boundaries defined by governments respect the more natural ways that people interact across space? This paper proposes a novel, fine-grained approach to regional delineation, based on analyzing networks of billions of individual human transactions. Given a geographical area and some measure of the strength of links between its inhabitants, we show how to partition the area into smaller, non-overlapping regions while minimizing the disruption to each person's links. We tested our method on the largest non-Internet human network, inferred from a large telecommunications database in Great Britain. Our partitioning algorithm yields geographically cohesive regions that correspond remarkably well with administrative regions, while unveiling unexpected spatial structures that had previously only been hypothesized in the literature. We also quantify the effects of partitioning, showing for instance that the effects of a possible secession of Wales from Great Britain would be twice as disruptive for the human network than that of Scotland.National Science Foundation (U.S.)AT & TAudi AGUnited States. Dept. of Defense (National Defense Science and Engineering Fellowship Program

Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors

Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; IP) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol. © 2013 den Hartog et al

Synapse Pathology in Psychiatric and Neurologic Disease

Inhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical signals. In recent years, it has become evident that spine morphology is intimately linked to synapse function—smaller spines have smaller synapses and support reduced synaptic transmission. The relationship between synaptic signaling, spine shape, and brain function is never more apparent than when the brain becomes dysfunctional. Many psychiatric and neurologic disorders, ranging from mental retardation and autism to Alzheimer’s disease and addiction, are accompanied by alterations in spine morphology and synapse number. In this review, we highlight the structure and molecular organization of synapses and discuss functional effects of synapse pathology in brain disease

Exploring the potential of phone call data to characterize the relationship between social network and travel behavior

[EN] Social network contacts have significant influence on individual travel behavior. However, transport models rarely consider social interaction. One of the reasons is the difficulty to properly model social influence based on the limited data available. Non-conventional, passively collected data sources, such as Twitter, Facebook or mobile phones, provide large amounts of data containing both social interaction and spatiotemporal information. The analysis of such data opens an opportunity to better understand the influence of social networks on travel behavior. The main objective of this paper is to examine the relationship between travel behavior and social networks using mobile phone data. A huge dataset containing billions of registers has been used for this study. The paper analyzes the nature of co-location events and frequent locations shared by social network contacts, aiming not only to provide understanding on why users share certain locations, but also to quantify the degree in which the different types of locations are shared. Locations have been classified as frequent (home, work and other) and non-frequent. A novel approach to identify co-location events based on the intersection of users' mobility models has been proposed. Results show that other locations different from home and work are frequently associated to social interaction. Additionally, the importance of non-frequent locations in co-location events is shown. Finally, the potential application of the data analysis results to improve activity-based transport models and assess transport policies is discussed.The authors would like to thank the anonymous reviewers for their valuable comments and suggestions to improve the quality of the paper. The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no 318367 (EUNOIA project) and no 611307 (INSIGHT project). The work of ML has been funded under the PD/004/2013 project, from the Conselleria de Educacion, Cultura y Universidades of the Government of the Balearic Islands and from the European Social Fund through the Balearic Islands ESF operational program for 2013-2017.Picornell Tronch, M.; Ruiz Sánchez, T.; Lenormand, M.; Ramasco, JJ.; Dubernet, T.; Frías-Martínez, E. (2015). Exploring the potential of phone call data to characterize the relationship between social network and travel behavior. Transportation. 42(4):647-668. https://doi.org/10.1007/s11116-015-9594-1S647668424Ahas, R., Aasa, A., Silm, S., Tiru, M.: Daily rhythms of suburban commuters’ movements in the tallinn metropolitan area: case study with mobile positioning data. Transp. Res. 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Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity

K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9)-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R).JWH-018, five potential monohydroxylated metabolites (M1-M5), and one carboxy metabolite (M6) were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3)H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35)S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i) values that were lower than or equivalent to Δ(9)-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9)-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9)-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251.Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations, combined with higher CB1R affinity and activity relative to Δ(9)-THC, may contribute to the greater prevalence of adverse effects observed with JWH-018-containing products relative to cannabis