Asymptotic theory of time varying networks with memory and heterogeneous activation pattern

In this thesis work we develop a new generative model of social networks belonging to the family of Time Varying Networks. The importance of correctly modelling the mechanisms shaping the growth of a network and the dynamics of the edges activation and inactivation are of central importance in network science. Indeed, by means of generative models that mimic the real-world dynamics of contacts in social networks it is possible to forecast the outcome of an epidemic process, optimize the immunization campaign or optimally spread an information among individuals. This task can now be tackled taking advantage of the recent availability of large-scale, high-quality and time-resolved datasets. This wealth of digital data has allowed to deepen our understanding of the structure and properties of many real-world networks. Moreover, the empirical evidence of a temporal dimension in networks prompted the switch of paradigm from a static representation of graphs to a time varying one. In this work we exploit the Activity-Driven paradigm (a modeling tool belonging to the family of Time-Varying-Networks) to develop a general dynamical model that encodes fundamental mechanism shaping the social networks' topology and its temporal structure: social capital allocation and burstiness. The former accounts for the fact that individuals does not randomly invest their time and social interactions but they rather allocate it toward already known nodes of the network. The latter accounts for the heavy-tailed distributions of the inter-event time in social networks. We then empirically measure the properties of these two mechanisms from seven real-world datasets and develop a data-driven model, analytically solving it. We then check the results against numerical simulations and test our predictions with real-world datasets, finding a good agreement between the two. Moreover, we find and characterize a non-trivial interplay between burstiness and social capital allocation in the parameters phase space. Finally, we present a novel approach to the development of a complete generative model of Time-Varying-Networks. This model is inspired by the Kaufman's adjacent possible theory and is based on a generalized version of the Polya's urn. Remarkably, most of the complex and heterogeneous feature of real-world social networks are naturally reproduced by this dynamical model, together with many high-order topological properties (clustering coefficient, community structure etc.).

Sensory and cortical activation of distinct glial cell subtypes in the somatosensory thalamus of young rats

The rodent ventrobasal (VB) thalamus receives sensory inputs from the whiskers and projects to the cortex, from which it receives reciprocal excitatory afferents. Much is known about the properties and functional roles of these glutamatergic inputs to thalamocortical neurons in the VB, but no data are available on how these afferents can affect thalamic glial cells. In this study, we used combined electrophysiological recordings and intracellular calcium ([Ca(2+)](i)) imaging to investigate glial cell responses to synaptic afferent stimulation. VB thalamus glial cells can be divided into two groups based on their [Ca(2+)](i) and electrophysiological responses to sensory and corticothalamic stimulation. One group consists of astrocytes, which stain positively for S100B and preferentially load with SR101, have linear current-voltage relations and low input resistance, show no voltage-dependent [Ca(2+)](i) responses, but express mGluR5-dependent [Ca(2+)](i) transients following stimulation of the sensory and/or corticothalamic excitatory afferent pathways. Cells of the other glial group, by contrast, stain positively for NG2, and are characterized by high input resistance, the presence of voltage-dependent [Ca(2+)](i) elevations and voltage-gated inward currents. There were no synaptically induced [Ca(2+)](i) elevations in these cells under control conditions. These results show that thalamic glial cell responses to synaptic input exhibit different properties to those of thalamocortical neurons. As VB astrocytes can respond to synaptic stimulation and signal to neighbouring neurons, this glial cell organization may have functional implications for the processing of somatosensory information and modulation of behavioural state-dependent thalamocortical network activities.

Blockade of interleukin-6 effects on cytokine profiles and macrophage activation after spinal cord injury in mice

The objective of this study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL-6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on macrophage activation and the inflammatory response in the acute phase after spinal cord injury (SCI) in mice. MR16-1 antibodies versus isotype control antibodies or saline alone was administered immediately after thoracic SCI in mice. MR16-1-treated group samples showed increased neuronal regeneration and locomotor recovery compared with controls. Immunoblot analysis of the MR16-1-treated samples identified downregulation of Th1 and upregulation of Th2 cytokines. MR16-1 treatment promoted arginase-1-positive, CD206-positive M2 macrophages, with preferential localization of these cells at the injury site and enhanced positivity for Mac-2 and Mac-3, suggestive of increased phagocytic behavior. The results suggest that temporal blockade of IL-6 signaling after SCI abrogates damaging inflammatory activity and promotes functional recovery by promoting the formation of alternatively activated M2 macrophages.

Selective and specific activation of Rab5 during endocytosis of receptor tyrosine kinases

The Rab family of proteins are low molecular weight GTPases that have the ability to switch between GTP- (active) and GDP- (inactive) bound form, and in that sense act as molecular switches. Through distinct localization on various vesicles and organelles and by cycling through GTP/GDP bound forms, Rabs are able to recruit and activate numerous effector proteins, both spatially and temporally, and hence behave as key regulators of trafficking in both endocytic and biosynhtetic pathways. The Rab5 protein has been shown to regulate transport from plasma membrane to the early endosome as well as activate signaling pathways from the early endosome. This dissertation focused on understanding Rab5 activation via endocytosis of receptor tyrosine kinases (RTKs). First, tyrosine kinase activity of RTKs was linked to endosome fusion by demonstrating that tyrosine kinase inhibitors block endosome fusion and activation of Rab5, and a constitutively active form of Rab5 is able to rescue endosome fusion. However, depending on how much ligand is available at the cell surface, the receptor-ligand complexes can be internalized via a number of distinct pathways. Similarly, Rab5 was activated in a ligand-dependent concentration dependent manner via clathrin- and caveolin-mediated pathways, as well as a pathway independent of both. However, overexpression Rabex-5, a nucleotide exchange factor for Rab5, is able to rescue activation even when all of the pathways of EGF-receptor internalization were blocked. Next, the three naturally occurring splice variants of Rabex-5 selectively activated Rab5. Lastly, Rabex-5 inhibits differentiation of 3T3-L1 and PC12 cells through 1) degradation of signaling endosome via Rab5-dependent fusion with the early endosome, 2) and inhibition of signaling cascade via ubiquitination of Ras through the ZnF domain at the N-terminus of Rabex-5. In conclusion, these data shed light on complexity of the endosomal trafficking system where tyrosine kinase activity of the receptor is able to affect endosome fusion; how different endocytic pathways affect activation of one of the key regulators of early endocytic events; and how selective activation of Rab5 via Rabex-5 can control adipogenesis and neurogenesis.

A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2′,4′-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives

We thank European Commission (project “PET BRAIN: Mapping the brain with PET radiolabeled cannabinoid CB1 ligands”; FP7-People-2009-IAPP; Grant Agreement N.25142).

Carbon, nitrogen and lipid content and egg and pellet production of female C. hyperboreus in situ and during incubation experiments

The effects of temperature and food availability on feeding and egg production of the Arctic copepod Calanus hyperboreus were investigated in Disko Bay, western Greenland, from winter to spring 2009. The abundance of females in the near bottom layer and the egg production of C. hyperboreus prior to the spring bloom document that reproduction relies on lipid stores. The maximum in situ egg production (± SE) of 54 ± 8 eggs female/d was recorded in mid-February at chlorophyll a concentrations below 0.1 µg/l, whereas no egg production was observed in mid-April when the spring bloom developed. After reproduction, the females migrated to the surface layer to exploit the bloom and refill their lipid stores. In 2 laboratory experiments, initiated before and during the spring bloom, mature females were kept with and without food at 5 different temperatures ranging from 0 to 10°C and the fecal pellet and egg production were monitored. Food had a clear effect on fecal pellet production but no effect on egg production, while temperature did not have an effect on egg or fecal pellet production in any of the experiments. Analyses of carbon and lipid content of the females before and after the experiments did not reflect any effect of food or temperature in the pre-bloom experiment, whereas in the bloom experiment a clear positive effect of food was detected in female biochemical profiles. The lack of a temperature response suggests a future warmer ocean could be unfavorable for C. hyperboreus compared to smaller Calanus spp. which are reported to exploit minor temperature elevations for increased egg production.

Benthic (C. wuellerstorfi) d18O, d13C and Cd/Ca in sediment core NEAP 4K across the last deglaciation

We present evidence that the characteristic chemical signature (based on coupled benthic foraminiferal Cd/Ca and d13C) of Antarctic Intermediate waters (AAIW) penetrated throughout the intermediate depths of the Atlantic basin to the high-latitude North Atlantic during the abrupt cooling events of the last deglaciation: Heinrich 1 and the Younger Dryas. AAIW may play the dynamic counterpart to the "bipolar seesaw" when near-freezing salty bottom waters from the Antarctic (AABW) sluggishly ventilate the deep ocean. Our data reinforce the concept that interglacial circulation is stabilized by salinity feedbacks between salty northern sourced deep waters (NADW) and fresh southern sourced waters (AABW and AAIW). Further, the glacial ocean may be susceptible to the more finely balanced relative densities of NADW and AAIW, due to either freshwater input or a reversal of the salinity gradient, such that the ocean is poised for NADW collapse via a negative salinity feedback. The unstable climate of the glacial period and its termination may arise from the closer competition for ubiquity at intermediate depths between northern and southern sourced intermediate waters.

(Table 1) Stable-isotopes for foraminifers at DSDP Holes 3-16 and 73-519

A stable-isotope stratigraphy was established for planktonic and benthic foraminifers from upper Miocene-lower Pliocene pelagic sediments from the Mid-Atlantic Ridge. A correlation of stable-isotope and biostratigraphic data with magnetostratigraphic age revealed the following: (1) the late Miocene carbon-isotope shift in the South Atlantic bottom waters was minute compared with the shift reported for other deep-sea locations (Haq et al., 1980), (2) a significant cooling or continental ice-volume increase occurred between 5.7 and 5.2 Ma, and (3) a period of warming or ice-volume decrease followed, with the rate of warming increasing beginning at 4.5 Ma and reaching a climax at 4.3 Ma. The timing of these paleoceanographic events is correlated with the onset and termination of the Messinian salinity crisis in the Mediterranean Sea.

Patterns of Play in the Fast attack of F. C. Barcelona, Manchester United and F. C. Internazionale Milano: a Mixed Method Approach

This study aimed to detect and analyse regular patterns of play in fast attack of football teams, through the combination of the sequential analysis technique and semi-structured interviews to experienced first League Portuguese coaches. The sample included 36 games (12 games of the respective national leagues per team) of the F.C. Barcelona, Inter Milan, and Manchester United teams that were coded with the observational instrument tool developed by Sarmento et al. (2010) and the data analysed through sequential analysis with the software SDIS-GSEQ 5.0. Based on the detected patterns, semi-structured interviews were carried out to 8 expert high-performance football coaches and data were analysed through the content analysis technique using the software NVivo 10. The detected patterns of play revealed specific characteristics of the teams under study. The combination of the results of sequential analysis with the qualitative interviews to the professional coaches proved to be very fruitful in this game the analysis of scope, allowing reconcile scientific knowledge with practical interpretation of coaches who develop their tasks in the field.

Association between ferritin, high sensitivity c-reactive protein (hsCRP) and relative abundance of Hepcidin mRNA with the risk of type 2 diabetes in obese subjects

Obesity and Type 2 diabetes mellitus share a strong pro-inflammatory profile. It has been observed that iron is a risk factor in the development of type 2 diabetes. The aim of this study was to evaluate the relationship between iron nutritional status and inflammation with the risk of type 2 diabetes development in obese subjects. We studied 30 obese men with type 2 diabetes (OBDM); 30 obese subjects without diabetes (OB) and 30 healthy subjects (Cn). We isolated peripheral mononuclear cells (PMCs) and challenged them with high Fe concentrations. Total mRNA was isolated and relative abundance of TNF-αIL-6 and hepcidin were determined by qPCR. Iron status, biochemical, inflammatory and oxidative stress parameters were also characterized. OBDM and OB patients showed increased hsCRP levels compared to the Cn group. OBDM subjects showed higher levels of ferritin than the Cn group. TNF-α and IL-6 mRNA relative abundances were increased in OBDM PMCs treated with high/Fe. Hepcidin mRNA was increased with basal and high iron concentration. We found that the highest quartile of ferritin was associated with an increased risk of type 2 diabetes when it was adjusted to BMI and HOMA-IR; this association was independent of the inflammatory status. The highest level of hepcidin gene expression also showed a trend of increased risk of diabetes, however it was not significant. Levels of hsCRP over 2 mg/L showed a significant trend of increasing the risk of diabetes. In conclusion, iron may stimulate the expression of pro-inflammatory genes (TNF-α and IL-6), and both hepcidin and ferritin gene expression levels could be a risk factor for the development of type 2 diabetes. Subjects that have an increased cardiovascular risk also have a major risk to develop type 2 diabetes, which is independent of the BMI and insulin resistance state.

DnaG interacts with a linker region that joins the N- and C-domains of DnaB and induces the formation of 3-fold symmetric rings

Loading of the replicative ring helicase onto the origin of replication (oriC) is the final outcome of a well coordinated series of events that collectively constitute a primosomal cascade. Once the ring helicase is loaded, it recruits the primase and signals the switch to the polymerization mode. The transient nature of the helicase-primase (DnaB-DnaG) interaction in the Escherichia coli system has hindered our efforts to elucidate its structure and function. Taking advantage of the stable DnaB-DnaG complex in Bacillus stearothermophilus, we have reviewed conflicting mutagenic data from other bacterial systems and shown that DnaG interacts with the flexible linker that connects the N- and C-terminal domains of DnaB. Furthermore, atomic force microscopy (AFM) imaging experiments show that binding of the primase to the helicase induces predominantly a 3-fold symmetric morphology to the hexameric ring. Overall, three DnaG molecules appear to interact with the hexameric ring helicase but a small number of complexes with two and even one DnaG molecule bound to DnaB were also detected. The structural/functional significance of these data is discussed and a speculative structural model for this complex is suggested.

Analysis of the Solarus C-PVT solar collector and design of the new prototype

Tesi hau Solarus AB enpresaren konzentratzailedun eguzki kolektore fotovoltaiko termikoei (C-PVT) buruz doa eta bi helburu nagusi ditu. Lehena Solarus-eko oraingo diseinuaren alderaketak diseinatzea da, MaReCo (Maximum Reflector Collector) diseinuaren eta parabola puruaren alderaketa batzuekin batera. Diseinu hauetan eguzki zelulen ebaketa berriak daude barruan eta 4 busbar-eko eguzki zeluletan oinarritua dago. Honi esker analisi sakon bat egin ahalko da hargailu eta estruktura diseinuak konparatuz. Bigarren helburua Solarus AB-k Gävleko unibertsitatean (HiG) kokaturik dituen kolektoreen errendimendu elektriko eta termikoa aztertzean datza. Datuak simulazio eta software espezifikoen bidez lortu dira eta ondoren Microsoft Excel®-en aztertu. Bi proiektu txikiagoak egin dira ere enpresan, bata eguzki kolektore fotovoltaiko termikoen merkatuaren ikerketan datza eta bestea eguzki kolektoreen produkzio prozesuaren gida batean. Hargailuen eta estrukturaren diseinu berriak preparatuta utzi dira prototipoen hurreneko eraikuntzarako eta proiektuarekin jarraitzeko etorkizuneko lan bat planeatu da. Unibertsitateko instalakuntzaren analisiari dagokionez, errendimendu elektriko eta termikoa estimatuena baino nabarmenki txikiagoak izan dira.