Spectral properties of the Laplacian of multiplex networks.

One of the more challenging tasks in the understanding of dynamical properties of models on top of complex networks is to capture the precise role of multiplex topologies. In a recent paper, Gómez et al. [ Phys. Rev. Lett. 110 028701 (2013)], some of the authors proposed a framework for the study of diffusion processes in such networks. Here, we extend the previous framework to deal with general configurations in several layers of networks and analyze the behavior of the spectrum of the Laplacian of the full multiplex. We derive an interesting decoupling of the problem that allow us to unravel the role played by the interconnections of the multiplex in the dynamical processes on top of them. Capitalizing on this decoupling we perform an asymptotic analysis that allow us to derive analytical expressions for the full spectrum of eigenvalues. This spectrum is used to gain insight into physical phenomena on top of multiplex, specifically, diffusion processes and synchronizability.

Tumour biology, metastatic sites and taxanes sensitivity as determinants of eribulin mesylate efficacy in breast cancer: results from the ERIBEX retrospective, international, multicenter study.

BACKGROUND: Our retrospective, international study aimed at evaluating the activity and safety of eribulin mesylate (EM) in pretreated metastatic breast cancer (MBC) in a routine clinical setting. METHODS: Patients treated with EM for a locally advanced or MBC between March 2011 and January 2014 were included in the study. Clinical and biological assessment of toxicity was performed at each visit. Tumour response was assessed every 3 cycles of treatment. A database was created to collect clinical, pathological and treatment data. RESULTS: Two hundred and fifty-eight patients were included in the study. Median age was 59 years old. Tumours were Hormone Receptor (HR)-positive (73.3 %) HER2-positive (10.2 %), and triple negative (TN, 22.5 %). 86.4 % of the patients presented with visceral metastases, mainly in the liver (67.4 %). Median previous metastatic chemotherapies number was 4 [1-9]. Previous treatments included anthracyclines and/or taxanes (100 %) and capecitabine (90.7 %). Median number of EM cycles was 5 [1-19]. The relative dose intensity was 0.917. At the time of analysis (median follow-up of 13.9 months), 42.3 % of the patients were still alive. The objective response rate was 25.2 % (95 %CI: 20-31) with a 36.1 % clinical benefit rate (CBR). Median time to progression (TTP) and overall survival were 3.97 (95 %CI: 3.25-4.3) and 11.2 (95 %CI: 9.3-12.1) months, respectively. One- and 2-year survival rates were 45.5 and 8.5 %, respectively. In multivariate analysis, HER2 positivity (HR = 0.29), the presence of lung metastases (HR = 2.49) and primary taxanes resistance (HR = 2.36) were the only three independent CBR predictive factors, while HR positivity (HR = 0.67), the presence of lung metastases (HR = 1.52) and primary taxanes resistance (HR = 1.50) were the only three TTP independent prognostic factors. Treatment was globally well tolerated. Most common grade 3-4 toxicities were neutropenia (20.9 %), peripheral neuropathy (3.9 %), anaemia (1.6 %), liver dysfunction (0.8 %) and thrombocytopenia (0.4 %). Thirteen patients (5 %) developed febrile neutropenia. CONCLUSION: EM is an effective new option in heavily pretreated MBC, with a favourable efficacy/safety ratio in a clinical practice setting. Our results comfort the use of this new molecule and pledge for the evaluation of EM-trastuzumab combination in this setting. Tumour biology, primary taxanes sensitivity and metastatic sites could represent useful predictive and prognostic factors.

(MA)LDI MS Imaging at High Specificity and Sensitivity

(Matrix-assisted) laser desorption/ionization ((MA)LDI) mass spectrometry imaging (MSI) has been driven by remarkable technological developments in the last couple of years. Although molecular information of a wide range of molecules including peptides, lipids, metabolites, and xenobiotics can be mapped, (MA)LDI MSI only leads to the detection of the most abundant soluble molecules in the cells and, consequently, does not provide access to the least expressed species, which can be very informative in the scope of disease research. Within a short period of time, numerous protocols and concepts have been developed and introduced in order to increase MSI sensitivity, including in situ tissue chemistry and solvent-free matrix depositions. In this chapter, we will discuss some of the latest developments in the field of high-sensitivity MSI using solvent-free matrix depositions and will detail protocols of two methods with their capability of enriching molecular MSI signal as demonstrated within our laboratory.

Optimized dark matter searches in deep observations of Segue 1 with MAGIC

We present the results of stereoscopic observations of the satellite galaxy Segue 1 with the MAGIC Telescopes, carried out between 2011 and 2013. With almost 160 hours of good-quality data, this is the deepest observational campaign on any dwarf galaxy performed so far in the very high energy range of the electromagnetic spectrum. We search this large data sample for signals of dark matter particles in the mass range between 100 GeV and 20 TeV. For this we use the full likelihood analysis method, which provides optimal sensitivity to characteristic gamma-ray spectral features, like those expected from dark matter annihilation or decay. In particular, we focus our search on gamma-rays produced from different final state Standard Model particles, annihilation with internal bremsstrahlung, monochromatic lines and box-shaped signals. Our results represent the most stringent constraints to the annihilation cross-section or decay lifetime obtained from observations of satellite galaxies, for masses above few hundred GeV. In particular, our strongest limit (95% confidence level) corresponds to a ~ 500 GeV dark matter particle annihilating into τ+τ−, and is of order langleσannvrangle simeq 1.2 × 10−24 cm3 s−1 a factor ~ 40 above the langleσannvrangle simeq thermal value.

Sensitive photonic system to measure oxidative potential of airborne nanoparticles and ROS levels in exhaled air

A photonic system has been developed that enables sensitive quantitative determination of reactive oxygen species (ROS) - mainly hydrogen peroxide (H2O2) - in aerosol samples such as airborne nanoparticles and exhaled air from patients. The detection principle relies on the amplification of the absorbance under multiple scattering conditions due to optical path lengthening [1] and [2]. In this study, the presence of cellulose membrane that acts as random medium into the glass optical cell considerably improved the sensitivity of the detection based on colorimetric FOX assay (FeII/orange xylenol). Despite the loss of assay volume (cellulose occupies 75% of cell volume) the limit of detection is enhanced by one order of magnitude reaching the value of 9 nM (H2O2 equivalents). Spectral analysis is performed automatically with a periodicity of 5 to 15 s, giving rise to real-time ROS measurements. Moreover, the elution of air sample into the collection chamber via a micro-diffuser (impinger) enables quantitative determination of ROS contained in or generated from airborne samples. As proof-of-concept the photonic ROS detection system was used in the determination of both ROS generated from traffic pollution and ROS contained in the exhaled breath as lung inflammation biomarkers.

Maladaptive emotion regulation strategies and stress sensitivity mediate the relation between adverse life events and attenuated positive psychotic symptoms.

INTRODUCTION: There is now solid evidence for a relation between adverse life events (ALE) and psychotic symptoms in patients with psychosis and in the general population. A recent study has shown that this relation may be partially mediated by stress sensitivity, suggesting the influence of other factors. The aim of this study was to assess the mediation effect of emotion regulation strategies and stress sensitivity in the relation between ALE and attenuated positive psychotic symptoms (APPS) in the general population. METHODS: Hundred and twelve healthy volunteers were evaluated with measures of APPS, emotion regulation strategies, ALE and stress sensitivity. RESULTS: Results demonstrated that the relation between ALE, hallucination and delusion proneness was completely mediated by maladaptive emotion regulation strategies, but not by stress sensitivity. However, in addition to maladaptive emotion regulation strategies, stress sensitivity demonstrated a mediation effect between ALE and attenuated positive psychotic positive symptoms when positive psychotic symptoms were grouped together. CONCLUSIONS: There are probably several possible trajectories leading to the formation of positive psychotic symptoms and the results of the present study reveal that one such trajectory may involve the maladaptive regulation of negative emotions alongside a certain general vulnerability after experiencing ALE.

The relationship between virtual body ownership and temperature sensitivity.

In the rubber hand illusion tactile stimulation seen on a rubber hand, that is synchronous with tactile stimulation felt on the hidden real hand, can lead to an illusion of ownership over the rubber hand. This illusion has been shown to produce a temperature decrease in the hidden hand, suggesting that such illusory ownership produces disownership of the real hand. Here we apply immersive virtual reality (VR) to experimentally investigate this with respect to sensitivity to temperature change. Forty participants experienced immersion in a VR with a virtual body (VB) seen from a first person perspective. For half the participants the VB was consistent in posture and movement with their own body, and in the other half there was inconsistency. Temperature sensitivity on the palm of the hand was measured before and during the virtual experience. The results show that temperature sensitivity decreased in the consistent compared to the inconsistent condition. Moreover, the change in sensitivity was significantly correlated with the subjective illusion of virtual arm ownership but modulated by the illusion of ownership over the full virtual body. This suggests that a full body ownership illusion results in a unification of the virtual and real bodies into one overall entity - with proprioception and tactile sensations on the real body integrated with the visual presence of the virtual body. The results are interpreted in the framework of a"body matrix" recently introduced into the literature.

Combining T2-preparation with spectral and spatial selectivity for improved coronary MRA

Cardiovascular disease is the leading cause of death worldwide. Within this subset, coronary artery disease (CAD) is the most prevalent. Magnetic resonance angiography (MRA) is an emerging technique that provides a safe, non-invasive way of assessing CAD progression. To generate contrast between tissues, MR images are weighted according to the magnetic properties of those tissues. In cardiac MRI, T2 contrast, which is governed by the rate of transverse signal loss, is often created through the use of a T2-Preparation module. T2-Preparation, or T2-Prep, is a magnetization preparation scheme used to improve blood/myocardium contrast in cardiac MRI. T2-Prep methods generally use a non-selective +90°, 180°, 180°, -90° train of radiofrequency (RF) pulses (or variant thereof), to tip magnetization into the transverse plane, allow it to evolve, and then to restore it to the longitudinal plane. A key feature in this process is the combination of a +90° and -90° RF pulse. By changing either one of these, a mismatch occurs between signal excitation and restoration. This feature can be exploited to provide additional spectral or spatial selectivity. In this work, both of these possibilities are explored. The first - spectral selectivity - has been examined as a method of improving fat saturation in coronary MRA. The second - spatial selectivity - has been examined as a means of reducing imaging time by decreasing the field of view, and as a method of reducing artefacts originating from the tissues surrounding the heart. Two additional applications, parallel imaging and self-navigation, are also presented. This thesis is thus composed of four sections. The first, "A Fat Signal Suppression for Coronary MRA at 3T using a Water-Selective Adiabatic T2-Preparation Technique", was originally published in the journal Magnetic Resonance in Medicine (MRM) with co-authors Ruud B. van Heeswijk and Matthias Stuber. The second, "Combined T2-Preparation and 2D Pencil Beam Inner Volume Selection", again with co-authors Ruud van Heeswijk and Matthias Stuber, was also published in the journal MRM. The third, "A cylindrical, inner volume selecting 2D-T2-Prep improves GRAPPA-accelerated image quality in MRA of the right coronary artery", written with co-authors Jerome Yerly and Matthias Stuber, has been submitted to the "Journal of Cardiovascular Magnetic Resonance", and the fourth, "Combined respiratory self-navigation and 'pencil-beam' 2D-T2 -Prep for free-breathing, whole-heart coronary MRA", with co¬authors Jerome Chaptinel, Giulia Ginami, Gabriele Bonanno, Simone Coppo, Ruud van Heeswijk, Davide Piccini, and Matthias Stuber, is undergoing internal review prior to submission to the journal MRM. -- Les maladies cardiovasculaires sont la cause principale de décès dans le monde : parmi celles-ci, les maladies coronariennes sont les plus répandues. L'angiographie par résonance magnétique (ARM) est une technique émergente qui fournit une manière sûre, non invasive d'évaluer la progression de la coronaropathie. Pour obtenir un contraste entre les tissus, les images d'IRM sont pondérées en fonction des propriétés magnétiques de ces tissus. En IRM cardiaque, le contraste en T2, qui est lié à la décroissance du signal transversal, est souvent créé grâce à l'utilisàtion d'un module de préparation T2. La préparation T2, ou T2-Prep, est un système de préparation de l'aimantation qui est utilisé pour améliorer le contraste entre le sang et le myocarde lors d'une IRM cardiaque. Les méthodes de T2-Prep utilisent généralement une série non-sélective d'impulsions de radiofréquence (RF), typiquement [+ 90°, 180°, 180°, -90°] ou une variante, qui bascule l'aimantation dans le plan transversal, lui permet d'évoluer, puis la restaure dans le plan longitudinal. Un élément clé de ce processus est la combinaison des impulsions RF de +90° et -90°. En changeant l'une ou l'autre des impulsions, un décalage se produit entre l'excitation du signal et de la restauration. Cette fonction peut être exploitée pour fournir une sélectivité spectrale ou spatiale. Dans cette thèse, les deux possibilités sont explorées. La première - la sélectivité spectrale - a été examinée comme une méthode d'améliorer la saturation de la graisse dans l'IRM coronarienne. La deuxième - la sélectivité spatiale - a été étudiée comme un moyen de réduire le temps d'imagerie en diminuant le champ de vue, et comme une méthode de réduction des artefacts provenant des tissus entourant le coeur. Deux applications supplémentaires, l'imagerie parallèle et la self-navigation, sont également présentées. Cette thèse est ainsi composée de quatre sections. La première, "A Fat Signal Suppression for Coronary MRA at 3T using a Water-Selective Adiabatic T2-Preparation Technique", a été publiée dans la revue médicale Magnetic Resonance .in Medicine (MRM) avec les co-auteurs Ruud B. van Heeswijk et Matthias Stuber. La deuxième, Combined T2-Preparation and 2D Pencil Beam Inner Volume Selection", encore une fois avec les co-auteurs Ruud van Heeswijk et Matthias Stuber, a également été publiée dans le journal MRM. La troisième, "A cylindrical, inner volume selecting 2D-T2-Prep improves GRAPPA- accelerated image quality in MRA of the right coronary artery", écrite avec les co-auteurs Jérôme Yerly et Matthias Stuber, a été présentée au "Journal of Cardiovascular Magnetic Resonance", et la quatrième, "Combined respiratory self-navigation and 'pencil-beam' 2D-T2 -Prep for free-breathing, whole-heart coronary MRA", avec les co-auteurs Jérôme Chaptinel, Giulia Ginami, Gabriele Bonanno , Simone Coppo, Ruud van Heeswijk, Davide Piccini, et Matthias Stuber, subit un examen interne avant la soumission à la revue MRM.

Calibração multivariada para sistemas com bandas sobrepostas através da análise da fatores do tipo Q

A multivariate calibration method to determine chemical compositions of systems with severely overlapped bands is proposed. Q mode factors are determined from the spectral data and subsequently rotated using the varimax and oblique transformation of Imbrie. The method is applied to two sets of simulated data to test the sensitivity of analytical results to random experimental error. The chemical concentrations of alanine and threonine mixture are determined from spectral data of the 302,5 - 548,5 nm region.

A correlation sensitivity analysis of non-life underwriting risk in solvency capital requirement estimation

This paper analyses the impact of using different correlation assumptions between lines of business when estimating the risk-based capital reserve, the Solvency Capital Requirement -SCR-, under Solvency II regulations. A case study is presented and the SCR is calculated according to the Standard Model approach. Alternatively, the requirement is then calculated using an Internal Model based on a Monte Carlo simulation of the net underwriting result at a one-year horizon, with copulas being used to model the dependence between lines of business. To address the impact of these model assumptions on the SCR we conduct a sensitivity analysis. We examine changes in the correlation matrix between lines of business and address the choice of copulas. Drawing on aggregate historical data from the Spanish non-life insurance market between 2000 and 2009, we conclude that modifications of the correlation and dependence assumptions have a significant impact on SCR estimation.

Nanoparticle Labels in Bioaffinity Assays

Nanoparticles offer adjustable and expandable reactive surface area compared to the more traditional solid phase forms utilized in bioaffinity assays due to the high surface to-volume ratio. The versatility of nanoparticles is further improved by the ability to incorporate various molecular complexes such as luminophores into the core. Nanoparticle labels composed of polystyrene, silica, inorganic crystals doped with high number of luminophores, preferably lanthanide(III) complexes, are employed in bioaffinity assays. Other label species such as semiconductor crystals (quantum dots) or colloidal gold clusters are also utilized. The surface derivatization of such particles with biomolecules is crucial for the applicability to bioaffinity assays. The effectiveness of a coating is reliant on the biomolecule and particle surface characteristics and the selected coupling technique. The most critical aspects of the particle labels in bioaffinity assays are their size-dependent features. For polystyrene, silica and inorganic phosphor particles, these include the kinetics, specific activity and colloidal stability. For quantum dots and gold colloids, the spectral properties are also dependent on particle size. This study reports the utilization of europium(III)-chelate-embedded nanoparticle labels in the development of bioaffinity assays. The experimental covers both the heterogeneous and homogeneous assay formats elucidating the wide applicability of the nanoparticles. It was revealed that the employment of europium(III) nanoparticles in heterogeneous assays for viral antigens, adenovirus hexon and hepatitis B surface antigen (HBsAg), resulted in sensitivity improvement of 10-1000 fold compared to the reference methods. This improvement was attributed to the extreme specific activity and enhanced monovalent affinity of the nanoparticles conjugates. The applicability of europium(III)-chelate-doped nanoparticles to homogeneous assay formats were proved in two completely different experimental settings; assays based on immunological recognition or proteolytic activity. It was shown that in addition to small molecule acceptors, particulate acceptors may also be employed due to the high specific activity of the particles promoting proximity-induced reabsorptive energy transfer in addition to non-radiative energy transfer. The principle of proteolytic activity assay relied on a novel dual-step FRET concept, wherein the streptavidin-derivatized europium(III)-chelate-doped nanoparticles were used as donors for peptide substrates modified with biotin and terminal europium emission compliant primary acceptor and a secondary quencher acceptor. The recorded sensitized emission was proportional to the enzyme activity, and the assay response to various inhibitor doses was in agreement with those found in literature showing the feasibility of the technique. Experiments regarding the impact of donor particle size on the extent of direct donor fluorescence and reabsorptive excitation interference in a FRET-based application was conducted with differently sized europium(III)-chelate-doped nanoparticles. It was shown that the size effect was minimal

Has concentration evolved similarly in manufacturing and services? A sensitivity analysis

Our first objective is to compare the degree of concentration in manufacturing and services, with special emphasis on its evolution in these two sectors, using a sensitivity analysis for different concentration indices and different geographic units of analysis: municipalities and local labour systems of Catalonia in 1991 and 2001. Most concentration measures fail to consider the space in which a particular municipality is located. Our second objective is to overcome this problem by applying two different techniques: by using a clustering measure, and by analysing whether the location quotients computed for each municipality and sector present some kind of spatial autocorrelation process. We take special account of the differences in patterns of concentration according to the technological level of the sectors.

Role of Selected Spectral Attributes in the Perception of Synthetic Vowels

This thesis is an experimental study regarding the identification and discrimination of vowels, studied using synthetic stimuli. The acoustic attributes of synthetic stimuli vary, which raises the question of how different spectral attributes are linked to the behaviour of the subjects. The spectral attributes used are formants and spectral moments (centre of gravity, standard deviation, skewness and kurtosis). Two types of experiments are used, related to the identification and discrimination of the stimuli, respectively. The discrimination is studied by using both the attentive procedures that require a response from the subject, and the preattentive procedures that require no response. Together, the studies offer information about the identification and discrimination of synthetic vowels in 15 different languages. Furthermore, this thesis discusses the role of various spectral attributes in the speech perception processes. The thesis is divided into three studies. The first is based only on attentive methods, whereas the other two concentrate on the relationship between identification and discrimination experiments. The neurophysiological methods (EEG recordings) reveal the role of attention in processing, and are used in discrimination experiments, while the results reveal differences in perceptual processes based on the language, attention and experimental procedure.