Timing interactions in social simulations: The voter model

The recent availability of huge high resolution datasets on human activities has revealed the heavy-tailed nature of the interevent time distributions. In social simulations of interacting agents the standard approach has been to use Poisson processes to update the state of the agents, which gives rise to very homogeneous activity patterns with a well defined characteristic interevent time. As a paradigmatic opinion model we investigate the voter model and review the standard update rules and propose two new update rules which are able to account for heterogeneous activity patterns. For the new update rules each node gets updated with a probability that depends on the time since the last event of the node, where an event can be an update attempt (exogenous update) or a change of state (endogenous update). We find that both update rules can give rise to power law interevent time distributions, although the endogenous one more robustly. Apart from that for the exogenous update rule and the standard update rules the voter model does not reach consensus in the infinite size limit, while for the endogenous update there exist a coarsening process that drives the system toward consensus configurations.Comment: Book Chapter, 23 pages, 9 figures, 5 table

Anomalous lifetime distributions and topological traps in ordering dynamics

We address the role of community structure of an interaction network in ordering dynamics, as well as associated forms of metastability. We consider the voter and AB model dynamics in a network model which mimics social interactions. The AB model includes an intermediate state between the two excluding options of the voter model. For the voter model we find dynamical metastable disordered states with a characteristic mean lifetime. However, for the AB dynamics we find a power law distribution of the lifetime of metastable states, so that the mean lifetime is not representative of the dynamics. These trapped metastable states, which can order at all time scales, originate in the mesoscopic network structure.Comment: 7 pages; 6 figure

Chemotherapeutic agent 5-fluorouracil increases survival of SOD1 mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease with no cure. Currently there are only two ALS drugs approved by the FDA, both with a limited therapeutic effect. In the search for drug candidates for ALS, we studied the effect of known stem cell mobilizing agents (treatment) and antimetabolite 5-fluorouracil (5-FU) (anti-treatment) in SOD1G93A model of ALS. Surprisingly, we found that anti-cancer drug 5-FU increases lifespan, delays the disease onset and improves motor performance in ALS mice. Although we were not able to demonstrate the mechanistic basis of the beneficial 5-FU action in ALS mice, our findings suggest that 5-FU or similar drugs are possible drug candidates for the treatment of motor neuron diseases through drug repurposing.This work was funded by Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) from the European Union (Grants PI14/00947 and PI17/00949), Asociación Adelante de La Roda, Plataforma Afectados por la ELA, Asociación Juntos Venceremos ELA, AVPA Zaragoza (RO), TERCEL (RD12/0019/0011 and RD16/0011/0035) and CIBERNED (CB06/05/1105) funds from the Instituto de Salud Carlos III of Spain (XN), and Fondazione Roma and Agenzia Spaziale Italiana (AM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Critical parameters and performance tests for the evaluation of digital data acquisition hardware

Recent developments of digital data acquisition systems allow real-time pre-processing of detector signals at a high count rate. These so-called pulse processing digitizers are powerful and versatile instruments offering techniques which are important for nuclear security, critical infrastructure protection, nuclear physics and radiation metrology. Certain aspects of digital data acquisition affect the performance of the total system in a critical way and therefore require special attention. This report presents a short introduction to digital data acquisition, followed by a discussion of the critical parameters which affect the performance in the lab and in the field. For some of the parameters, tests are proposed to assess the performance of digital data acquisition systems. Good practices are offered to guide the selection and evaluation of digital data acquisition systems. More general performance criteria which are not specifically related to digital data acquisition systems are discussed separately.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Determinants of Polylepis (Rosaceae) Forest Distribution and Treeline Formation in the High Andes

High elevation treelines are formed under common temperature conditions worldwide, but the functional mechanisms that ultimately constrain tree growth are poorly known. In addition to environmental constraints, the distribution of high elevation forests is largely affected by human influence. Andean Polylepis (Rosaceae) forests are an example of such a case, forests commonly growing in isolated stands disconnected from the lower elevation montane forests. There has been ample discussion as to the role of environmental versus anthropogenic causes of this fragmented distribution of Polylepis forests, but the importance of different factors is still unclear. In this thesis, I studied functional, environmental and anthropogenic aspects determining Polylepis forest distribution. Specifically, I assessed the degree of genetic determinism in the functional traits that enable Polylepis species to grow in cold and dry conditions. I also studied the role of environment and human influence constraining Polylepis forest distribution. I found evidence of genetically determined climatic adaptations in the functional traits of Polylepis. High elevation species had reduced leaf size and increased root tip abundance compared to low elevation species. Thus these traits have potentially played an important role in species evolution and adaptation to high elevation habitats, especially to low temperatures. I also found reduced photosynthesis rate among high elevation tree species compared to low elevation species, supporting carbon source limitation at treelines. At low elevations, Polylepis forest distribution appeared to be largely defined by human influence. This suggests that the absence of Polylepis forests in large areas in the Andes is the result of several environmental and anthropogenic constraints, the role of environment becoming stronger towards high elevations. I also show that Polylepis trees grow at remarkably low air and soil temperatures near treelines, and present new evidence of the role of air temperatures in constraining tree growth at high elevations. I further show that easily measurable indices of accessibility are related to the degree of degradation of Polylepis forest, and can therefore be used in the rapid identification of potentially degraded Polylepis forests. This is of great importance for the conservation and restoration planning of Polylepis forests in the Andes. In a global context, the results of this thesis add to our scientific knowledge concerning high elevation adaptations in trees, and increase our understanding of the factors constraining tree growth and forest distribution at high-­elevation treelines worldwide.El límite altitudinal arbóreo está formado bajo condiciones similares de temperatura a nivel mundial, pero los mecanismos funcionales que finalmente constriñen el crecimiento de los árboles son poco conocidos. Además de los factores ambientales, la distribución de los bosques de alturas está afectada por las acciones humanas. Los bosques andinos de Polylepis (Rosaceae) son un ejemplo de este caso: estos bosques crecen en rodales aislados y desconectados de los bosques montanos a menor altitud. Ha habido una amplia discusión sobre el rol de los factores ambientales y antropogénicos que causan esta distribución fragmentada de los bosques de Polylepis, pero la importancia de diferentes factores no está todavía clara. En esta tesis estudié los aspectos ecofisiológicos, ambientales y antropogénicos que pueden determinar la distribución de los bosques de Polylepis. Específicamente, evalué el grado del determinismo genético sobre las características ecofisiológicas que permiten a las especies de Polylepis crecer en condiciones frías y secas. Además, estudié el rol de los factores medio ambientales y antropogénicos que restringen la distribución de los bosques de Polylepis. Mis resultados dan evidencias de adaptaciones climáticos genéticamente determinadas en las características ecofisiológicas de las especies de Polylepis. Las especies de las zonas altas presentan hojas de tamaño reducido e incremento en la abundancia de ápices radiculares en comparación con las especies de las zonas más bajas. Estas características parecen haber desempeñado un rol importante en la evolución de las especies y en la adaptación a los hábitats de mayor altitud, especialmente a temperaturas bajas. Asimismo, encontré una tasa reducida de fotosíntesis en las especies de las zonas altas en comparación con las especies de las zonas más bajas. Esto apoya la hipótesis de limitación de adquisición de carbono en el límite altitudinal arbóreo. A menor altitud, la distribución de los bosques de Polylepis parece estar fuertemente afectada por las acciones antropogénicas. Esto sugiere que la ausencia de los bosques de Polylepis en la mayor parte de los Andes es el resultado de una serie de limitaciones ambientales y antropogénicas, donde el rol de los factores ambientales se incrementa hacia las zonas altas. También encontré que los árboles de Polylepis cerca del límite altitudinal arbóreo crecen a considerablemente bajas temperaturas del aire y del suelo. Además presento nuevas evidencias del rol de la temperatura del aire en la limitación del crecimiento de los árboles en las zonas altas. Adicionalmente, demuestro que los índices de accesibilidad que son fácilmente medibles están relacionados con el grado de degradación de los bosques de Polylepis y pueden ser aplicados para una identificación rápida de los bosques degradados. Esto es de gran importancia para la conservación y planificación de restauración de los bosques de Polylepis en los Andes. En el contexto mundial, los resultados de esta tesis contribuyen a incrementar el conocimiento científico relacionado a las adaptaciones de especies arbóreas en hábitats montañosos y el entendimiento de los factores que limitan el crecimiento de los árboles y la distribución de los bosques en el límite a altitudinal arbóreo a nivel mundial.Vuoristopuurajat esiintyvät maailmanlaajuisesti samanlaisissa lämpötilaolosuhteissa, mutta puiden kasvua rajoittavat ekofysiologiset mekanismit tunnetaan kuitenkin huonosti. Ympäristöolosuhteiden lisäksi ihmisvaikutuksella on myös suuri merkitys vuoristometsien levinneisyyteen. Andien Polylepis-metsät ovat yksi esimerkki tällaisesta tapauksesta. Metsät kasvavat eristyneinä laikkuina alemman yhtenäisen vuoristometsävyöhykkeen yläpuolella. Ympäristöolosuhteiden ja ihmisvaikutuksen merkitystä Polylepis-metsien levinneisyydelle on tutkittu paljon, mutta eri tekijöiden merkitys metsien levinneisyydelle on edelleen epäselvä. Tutkin väitöskirjassani puiden ekofysiologiaan, ympäristöolosuhteisiin ja ihmisvaikutukseen liittyviä tekijöitä, jotka voivat selittää Polylepis­metsien levinneisyyttä. Tulokseni osoittivat, että osa tutkimistani Polylepis-­puiden ekofysiologisista piirteistä ilmensi geneettisesti määräytyneitä ilmastollisia sopeumia: korkean paikan lajeilla oli pienemmät lehdet ja enemmän juurenkärkiä kuin matalampien paikkojen lajeilla. Näillä piirteillä on todennäköisesti ollut tärkeä merkitys lajien evoluutiossa ja sopeutumisessa ylävuoriston elinympäristöihin, erityisesti mataliin lämpötiloihin. Tuloksieni mukaan korkean paikan lajeilla oli myös alentunut fotosynteesikapasiteetti matalampien paikkojen lajeihin verrattuna. Tämä tukee hypoteesia hiilen sitomiseen liittyvistä rajoitteista vuoristopuurajalla. Alemmilla korkeuksilla ihmistoiminnalla näytti olevan erityisen suuri merkitys Polylepis-metsien levinneisyyteen. Tuloksieni perusteella voidaan todeta, että Polylepis-metsien nykylevinneisyys on seurausta useasta eri ympäristöön ja ihmistoimintaan liittyvästä tekijästä, joista ympäristön merkitys levinneisyyden selittäjänä kasvaa siirryttäessä kohti ylävuoristoa. Tutkimustulokseni myös osoittivat, että Polylepis-­puut kasvavat huomattavan alhaisissa lämpötilaolosuhteissa lähellä puurajaa, sekä ilman että maaperän lämpötilan suhteen. Lisäksi tulokseni osoittivat, että erityisesti ilman lämpötilalla on merkitystä puiden kasvulle vuoristossa. Havaitsin myös, että helposti mitattavat, metsien saavutettavuuteen perustuvat indeksit selittävät Polylepis-­metsien rakennetta, ja näin ollen myös metsien kunnon heikkenemistä. Näitä indeksejä voidaan käyttää tunnistamaan nopeasti ja helposti alueita, joilla Polylepis-­metsät ovat huonokuntoisimpia. Tällä tiedolla on merkitystä Polylepis-­metsien suojelu-­ ja kunnostussuunnitelmille Andeilla. Väitöskirjatyöni tulokset lisäävät myös tietoa puiden sopeutumisesta vuoristo-­olosuhteisiin ja auttavat ymmärtämään eri tekijöiden merkitystä puiden kasvulle ja metsien levinneisyydelle vuoristopuurajoilla maailmanlaajuisesti.Siirretty Doriast

New approaches to model and study social networks

We describe and develop three recent novelties in network research which are particularly useful for studying social systems. The first one concerns the discovery of some basic dynamical laws that enable the emergence of the fundamental features observed in social networks, namely the nontrivial clustering properties, the existence of positive degree correlations and the subdivision into communities. To reproduce all these features we describe a simple model of mobile colliding agents, whose collisions define the connections between the agents which are the nodes in the underlying network, and develop some analytical considerations. The second point addresses the particular feature of clustering and its relationship with global network measures, namely with the distribution of the size of cycles in the network. Since in social bipartite networks it is not possible to measure the clustering from standard procedures, we propose an alternative clustering coefficient that can be used to extract an improved normalized cycle distribution in any network. Finally, the third point addresses dynamical processes occurring on networks, namely when studying the propagation of information in them. In particular, we focus on the particular features of gossip propagation which impose some restrictions in the propagation rules. To this end we introduce a quantity, the spread factor, which measures the average maximal fraction of nearest neighbors which get in contact with the gossip, and find the striking result that there is an optimal non-trivial number of friends for which the spread factor is minimized, decreasing the danger of being gossiped.Comment: 16 Pages, 9 figure

Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia

In a double-blind, controlled study, we examined the therapeutic effects of high-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) on schizophrenia symptoms. A total of 22 chronic hospitalized schizophrenia patients were randomly assigned to 2 weeks (10 sessions) of real or sham rTMS. rTMS was given with the following parameters: 20 trains of 5-second 10-Hz stimulation at 100 percent motor threshold, 30 seconds apart. Effects on positive and negative symptoms, self-reported symptoms, rough neuropsychological functioning, and hormones were assessed. Although there was a significant improvement in both groups in most of the symptom measures, no real differences were found between the groups. A decrease of more than 20 percent in the total PANSS score was found in 7 control subjects but only 1 subject from the real rTMS group. There was no change in hormone levels or neuropsychological functioning, measured by the MMSE, in either group. Left prefrontal rTMS (with the used parameters) seems to produce a significant nonspecific effect of the treatment procedure but no therapeutic effect in the most chronic and severely ill schizophrenia patients.Peer reviewe

Adaptive correlations between seed size and germination time

We present a model for the coevolution of seed size and germination time within a season when both affect the ability of the seedlings to compete for space. We show that even in the absence of a morphological or physiological constraint between the two traits, a correlation between seed size and germination time is nevertheless likely to evolve. This raises the more general question to what extent a correlation between any two traits should be considered as an a priori constraint or as an evolved means (or instrument) to actually implement a beneficial combination of traits. We derive sufficient conditions for the existence of a positive or a negative correlation. We develop a toy model for seed and seedling survival and seedling growth and use this to illustrate in practice how to determine correlations between seed size and germination time.Peer reviewe