Showing papers by "University of Cagliari published in 2016"

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis

Abstract: Objective To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). Methods GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. Results Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema. Conclusion We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.

Is the Gravitational-Wave Ringdown a Probe of the Event Horizon?

Abstract: It is commonly believed that the ringdown signal from a binary coalescence provides a conclusive proof for the formation of an event horizon after the merger. This expectation is based on the assumption that the ringdown waveform at intermediate times is dominated by the quasinormal modes of the final object. We point out that this assumption should be taken with great care, and that very compact objects with a light ring will display a similar ringdown stage, even when their quasinormal-mode spectrum is completely different from that of a black hole. In other words, universal ringdown waveforms indicate the presence of light rings, rather than of horizons. Only precision observations of the late-time ringdown signal, where the differences in the quasinormal-mode spectrum eventually show up, can be used to rule out exotic alternatives to black holes and to test quantum effects at the horizon scale.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group

Abstract: The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Angular analysis of the B 0 → K *0 μ + μ − decay using 3 fb −1 of integrated luminosity

Abstract: An angular analysis of the B0 → K*0(→ K+π−)μ+μ− decay is presented. The dataset corresponds to an integrated luminosity of 3.0 fb−1 of pp collision data collected at the LHCb experiment. The complete angular information from the decay is used to determine CP-averaged observables and CP asymmetries, taking account of possible contamination from decays with the K+π− system in an S-wave configuration. The angular observables and their correlations are reported in bins of q2, the invariant mass squared of the dimuon system. The observables are determined both from an unbinned maximum likelihood fit and by using the principal moments of the angular distribution. In addition, by fitting for q2-dependent decay amplitudes in the region 1.1 < q2 < 6.0 GeV2/c4, the zero-crossing points of several angular observables are computed. A global fit is performed to the complete set of CP-averaged observables obtained from the maximum likelihood fit. This fit indicates differences with predictions based on the Standard Model at the level of 3.4 standard deviations. These differences could be explained by contributions from physics beyond the Standard Model, or by an unexpectedly large hadronic effect that is not accounted for in the Standard Model predictions.[Figure not available: see fulltext.]

Modeling Radicalization Phenomena in Heterogeneous Populations.

Abstract: The phenomenon of radicalization is investigated within a mixed population composed of core and sensitive subpopulations. The latest includes first to third generation immigrants. Respective ways of life may be partially incompatible. In case of a conflict core agents behave as inflexible about the issue. In contrast, sensitive agents can decide either to live peacefully adjusting their way of life to the core one, or to oppose it with eventually joining violent activities. The interplay dynamics between peaceful and opponent sensitive agents is driven by pairwise interactions. These interactions occur both within the sensitive population and by mixing with core agents. The update process is monitored using a Lotka-Volterra-like Ordinary Differential Equation. Given an initial tiny minority of opponents that coexist with both inflexible and peaceful agents, we investigate implications on the emergence of radicalization. Opponents try to turn peaceful agents to opponents driving radicalization. However, inflexible core agents may step in to bring back opponents to a peaceful choice thus weakening the phenomenon. The required minimum individual core involvement to actually curb radicalization is calculated. It is found to be a function of both the majority or minority status of the sensitive subpopulation with respect to the core subpopulation and the degree of activeness of opponents. The results highlight the instrumental role core agents can have to hinder radicalization within the sensitive subpopulation. Some hints are outlined to favor novel public policies towards social integration.

Novel Feature Extraction, Selection and Fusion for Effective Malware Family Classification

Abstract: Modern malware is designed with mutation characteristics, namely polymorphism and metamorphism, which causes an enormous growth in the number of variants of malware samples. Categorization of malware samples on the basis of their behaviors is essential for the computer security community, because they receive huge number of malware everyday, and the signature extraction process is usually based on malicious parts characterizing malware families. Microsoft released a malware classification challenge in 2015 with a huge dataset of near 0.5 terabytes of data, containing more than 20K malware samples. The analysis of this dataset inspired the development of a novel paradigm that is effective in categorizing malware variants into their actual family groups. This paradigm is presented and discussed in the present paper, where emphasis has been given to the phases related to the extraction, and selection of a set of novel features for the effective representation of malware samples. Features can be grouped according to different characteristics of malware behavior, and their fusion is performed according to a per-class weighting paradigm. The proposed method achieved a very high accuracy ($\approx$ 0.998) on the Microsoft Malware Challenge dataset.

Adversarial Feature Selection Against Evasion Attacks

Abstract: Pattern recognition and machine learning techniques have been increasingly adopted in adversarial settings such as spam, intrusion, and malware detection, although their security against well-crafted attacks that aim to evade detection by manipulating data at test time has not yet been thoroughly assessed. While previous work has been mainly focused on devising adversary-aware classification algorithms to counter evasion attempts, only few authors have considered the impact of using reduced feature sets on classifier security against the same attacks. An interesting, preliminary result is that classifier security to evasion may be even worsened by the application of feature selection. In this paper, we provide a more detailed investigation of this aspect, shedding some light on the security properties of feature selection against evasion attacks. Inspired by previous work on adversary-aware classifiers, we propose a novel adversary-aware feature selection model that can improve classifier security against evasion attacks, by incorporating specific assumptions on the adversary’s data manipulation strategy. We focus on an efficient, wrapper-based implementation of our approach, and experimentally validate its soundness on different application examples, including spam and malware detection.

Hencky-type discrete model for pantographic structures: numerical comparison with second gradient continuum models

Abstract: Hencky (Uber die angenaherte Losung von Stabilitatsproblemen im Raum mittels der elastischen Gelenkkette. Ph.D. thesis, Engelmann, 1921) proposed a discrete model for elasticae by introducing rigid bars and rotational springs. Hencky (Proc R Soc Lond A Math Phys Eng Sci 472(2185), 2016) approach has been introduced to heuristically motivate the need of second gradient continua. Here, we present a novel numerical code implementing directly the discrete Hencky-type model which is robust enough to solve the problem of the determination of equilibrium configurations in the large deformation and displacement regimes. We apply this model to study some potentially applicable problems, and we compare its performances with those of the second gradient continuum model. The numerical evidence presented supports the conjecture that Hencky-type converges to second gradient model.

Isogeometric analysis of plane-curved beams:

Abstract: A curved beam element based on the Timoshenko model and non-uniform rational B-splines (NURBS) interpolation both for geometry and displacements is presented. Such an element can be used to suitably analyse plane-curved beams and arches. Some numerical results will explore the effectiveness and accuracy of this novel method by comparing its performance with those of some accurate finite elements proposed in the technical literature, and also with analytical solutions: for the cases where such closed-form solutions were not available in the literature, they have been computed by exact integration of the governing differential equations. It is shown that the presented element is almost insensitive to both membrane- and shear-locking, and that such phenomena can be easily controlled by properly choosing the number of elements or the NURBS degree.

Agarose and Its Derivatives as Supports for Enzyme Immobilization

Abstract: Agarose is a polysaccharide obtained from some seaweeds, with a quite particular structure that allows spontaneous gelation. Agarose-based beads are highly porous, mechanically resistant, chemically and physically inert, and sharply hydrophilic. These features—that could be further improved by means of covalent cross-linking—render them particularly suitable for enzyme immobilization with a wide range of derivatization methods taking advantage of chemical modification of a fraction of the polymer hydroxyls. The main properties of the polymer are described here, followed by a review of cross-linking and derivatization methods. Some recent, innovative procedures to optimize the catalytic activity and operational stability of the obtained preparations are also described, together with multi-enzyme immobilized systems and the main guidelines to exploit their performances.

European Pulsar Timing Array Limits on Continuous Gravitational Waves from Individual Supermassive Black Hole Binaries

Abstract: We have searched for continuous gravitational wave (CGW) signals produced by individually resolvable, circular supermassive black hole binaries (SMBHBs) in the latest European Pulsar Timing Array (EPTA) data set, which consists of ultraprecise timing data on 41-ms pulsars. We develop frequentist and Bayesian detection algorithms to search both for monochromatic and frequency-evolving systems. None of the adopted algorithms show evidence for the presence of such a CGW signal, indicating that the data are best described by pulsar and radiometer noise only. Depending on the adopted detection algorithm, the 95 per cent upper limit on the sky-averaged strain amplitude lies in the range 6 × 10−15 10^9M⊙ out to a distance of about 25 Mpc, and with Mc > 10^10M⊙ out to a distance of about 1Gpc (z ≈ 0.2). We show that state-of-the-art SMBHB population models predict <1 per cent probability of detecting a CGW with the current EPTA data set, consistent with the reported non-detection. We stress, however, that PTA limits on individual CGW have improved by almost an order of magnitude in the last five years. The continuing advances in pulsar timing data acquisition and analysis techniques will allow for strong astrophysical constraints on the population of nearby SMBHBs in the corning years.

The Virtual Object as a Major Element of the Internet of Things: A Survey

Abstract: The Internet of Things (IoT) paradigm has been evolving toward the creation of a cyber-physical world where everything can be found, activated, probed, interconnected, and updated, so that any possible interaction, both virtual and/or physical, can take place. A Crucial concept of this paradigm is that of the virtual object, which is the digital counterpart of any real (human or lifeless, static or mobile, solid or intangible) entity in the IoT. It has now become a major component of the current IoT platforms, supporting the discovery and mash up of services, fostering the creation of complex applications, improving the objects energy management efficiency, as well as addressing heterogeneity and scalability issues. This paper aims at providing the reader with a survey of the virtual object in the IoT world. Virtualness is addressed from several perspectives: historical evolution of its definitions, current functionalities assigned to the virtual object and how they tackle the main IoT challenges, and major IoT platforms, which implement these functionalities. Finally, we illustrate the lessons learned after having acquired a comprehensive view of the topic.

ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study

Abstract: To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. Aim: To examine the association between these variants and sprint time in elite athletes. We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants. On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively. Despite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final.

XIPE: the x-ray imaging polarimetry explorer

Abstract: XIPE, the X-ray Imaging Polarimetry Explorer, is a mission dedicated to X-ray Astronomy. At the time of writing XIPE is in a competitive phase A as fourth medium size mission of ESA (M4). It promises to reopen the polarimetry window in high energy Astrophysics after more than 4 decades thanks to a detector that efficiently exploits the photoelectric effect and to X-ray optics with large effective area. XIPE uniqueness is time-spectrally-spatially- resolved X-ray polarimetry as a breakthrough in high energy astrophysics and fundamental physics. Indeed the payload consists of three Gas Pixel Detectors at the focus of three X-ray optics with a total effective area larger than one XMM mirror but with a low weight. The payload is compatible with the fairing of the Vega launcher. XIPE is designed as an observatory for X-ray astronomers with 75 % of the time dedicated to a Guest Observer competitive program and it is organized as a consortium across Europe with main contributions from Italy, Germany, Spain, United Kingdom, Poland, Sweden.

Classification and characterization of human endogenous retroviruses; mosaic forms are common

Abstract: Human endogenous retroviruses (HERVs) represent the inheritance of ancient germ-line cell infections by exogenous retroviruses and the subsequent transmission of the integrated proviruses to the descendants. ERVs have the same internal structure as exogenous retroviruses. While no replication-competent HERVs have been recognized, some retain up to three of four intact ORFs. HERVs have been classified before, with varying scope and depth, notably in the RepBase/RepeatMasker system. However, existing classifications are bewildering. There is a need for a systematic, unifying and simple classification. We strived for a classification which is traceable to previous classifications and which encompasses HERV variation within a limited number of clades. The human genome assembly GRCh 37/hg19 was analyzed with RetroTector, which primarily detects relatively complete Class I and II proviruses. A total of 3173 HERV sequences were identified. The structure of and relations between these proviruses was resolved through a multi-step classification procedure that involved a novel type of similarity image analysis (“Simage”) which allowed discrimination of heterogeneous (noncanonical) from homogeneous (canonical) HERVs. Of the 3173 HERVs, 1214 were canonical and segregated into 39 canonical clades (groups), belonging to class I (Gamma- and Epsilon-like), II (Beta-like) and III (Spuma-like). The groups were chosen based on (1) sequence (nucleotide and Pol amino acid), similarity, (2) degree of fit to previously published clades, often from RepBase, and (3) taxonomic markers. The groups fell into 11 supergroups. The 1959 noncanonical HERVs contained 31 additional, less well-defined groups. Simage analysis revealed several types of mosaicism, notably recombination and secondary integration. By comparing flanking sequences, LTRs and completeness of gene structure, we deduced that some noncanonical HERVs proliferated after the recombination event. Groups were further divided into envelope subgroups (altogether 94) based on sequence similarity and characteristic “immunosuppressive domain” motifs. Intra and inter(super)group, as well as intraclass, recombination involving envelope genes (“env snatching”) was a common event. LTR divergence indicated that HERV-K(HML2) and HERVFC had the most recent integrations, HERVL and HUERSP3 the oldest. A comprehensive HERV classification and characterization approach was undertaken. It should be applicable for classification of all ERVs. Recombination was common among HERV ancestors.

The effect of epoch length on estimated EEG functional connectivity and brain network organisation.

Abstract: OBJECTIVE: Graph theory and network science tools have revealed fundamental mechanisms of functional brain organization in resting-state M/EEG analysis. Nevertheless, it is still not clearly understood how several methodological aspects may bias the topology of the reconstructed functional networks. In this context, the literature shows inconsistency in the chosen length of the selected epochs, impeding a meaningful comparison between results from different studies. APPROACH: The aim of this study was to provide a network approach insensitive to the effects that epoch length has on functional connectivity and network reconstruction. Two different measures, the phase lag index (PLI) and the amplitude envelope correlation (AEC) were applied to EEG resting-state recordings for a group of 18 healthy volunteers using non-overlapping epochs with variable length (1, 2, 4, 6, 8, 10, 12, 14 and 16 s). Weighted clustering coefficient (CCw), weighted characteristic path length (L w) and minimum spanning tree (MST) parameters were computed to evaluate the network topology. The analysis was performed on both scalp and source-space data. MAIN RESULTS: Results from scalp analysis show a decrease in both mean PLI and AEC values with an increase in epoch length, with a tendency to stabilize at a length of 12 s for PLI and 6 s for AEC. Moreover, CCw and L w show very similar behaviour, with metrics based on AEC more reliable in terms of stability. In general, MST parameters stabilize at short epoch lengths, particularly for MSTs based on PLI (1-6 s versus 4-8 s for AEC). At the source-level the results were even more reliable, with stability already at 1 s duration for PLI-based MSTs. SIGNIFICANCE: The present work suggests that both PLI and AEC depend on epoch length and that this has an impact on the reconstructed network topology, particularly at the scalp-level. Source-level MST topology is less sensitive to differences in epoch length, therefore enabling the comparison of brain network topology between different studies.

Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.

Abstract: Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 × 10 - 9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 × 10 - 9; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.

Perinatal Parenting Stress, Anxiety, and Depression Outcomes in First-Time Mothers and Fathers: A 3- to 6-Months Postpartum Follow-Up Study.

Abstract: Objective: Although the proven link between parenting stress, postnatal depression and anxiety, no study has investigated such relationship among fathers and mothers. The specific aims of this study were: 1) to investigate whether there were any differences between first-time fathers’ and mothers’ postnatal parenting stress, anxiety and depression symptoms and to see their evolution between 3 and 6 months after the child’s birth; 2) to explore how one’s own parenting stress and anxiety levels and the anxiety-depressive symptoms of the partner contribute to parental postnatal depression. Method: The sample was composed by 362 parents – 181 couples - (mothers’ MAge = 35.03, SD = 4.7; fathers’ MAge = 37.9, SD = 5.6) of a healthy baby. At three (T1) and six months (T2) postpartum, both parents filled out, in a counterbalanced order, the Parenting Stress Index-Short Form, the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory. Results: Analyses showed that, compared to fathers, mothers reported higher scores on postpartum anxiety, depression and parenting stress. Scores on all measures for both mothers and fathers decreased from T1 to T2. However, path analyses suggested that the persistence of both maternal and paternal postnatal depression were influenced directly by one’s own levels of anxiety and parenting stress as well as by the presence of partner’s depression. Discussion: The study pointed out the relevant impact and effects of both maternal and paternal stress, anxiety and depression symptoms during the transition to parenthood. Therefore, in order to provide efficacious, targeted, early interventions, perinatal screening should always be directed to both parents.

Studying the effect of Zn-substitution on the magnetic and hyperthermic properties of cobalt ferrite nanoparticles

Abstract: The possibility to finely control nanostructured cubic ferrites (M(II)Fe2O4) paves the way to design materials with the desired magnetic properties for specific applications. However, the strict and complex interrelation among the chemical composition, size, polydispersity, shape and surface coating renders their correlation with the magnetic properties not trivial to predict. In this context, this work aims to discuss the magnetic properties and the heating abilities of Zn-substituted cobalt ferrite nanoparticles with different zinc contents (ZnxCo1-xFe2O4 with 0 100 emu g(-1)). The increase in the zinc content up to x = 0.46 in the structure has resulted in an increase of the saturation magnetisation (Ms) at 5 K. High Ms values have also been revealed at room temperature (∼90 emu g(-1)) for both CoFe2O4 and Zn0.30Co0.70Fe2O4 samples and their heating ability has been tested. Despite a similar saturation magnetisation, the specific absorption rate value for the cobalt ferrite is three times higher than the Zn-substituted one. DC magnetometry results were not sufficient to justify these data, the experimental conditions of SAR and static measurements being quite different. The synergic combination of DC with AC magnetometry and (57)Fe Mossbauer spectroscopy represents a powerful tool to get new insights into the design of suitable heat mediators for magnetic fluid hyperthermia.

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA).

Abstract: The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substance's potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen . The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ‘glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential’. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected. EFSA concluded ‘that there is very limited evidence for an association between glyphosate-based formulations …

DroidScribe: Classifying Android Malware Based on Runtime Behavior

Abstract: The Android ecosystem has witnessed a surge in malware, which not only puts mobile devices at risk but also increases the burden on malware analysts assessing and categorizing threats. In this paper, we show how to use machine learning to automatically classify Android malware samples into families with high accuracy, while observing only their runtime behavior. We focus exclusively on dynamic analysis of runtime behavior to provide a clean point of comparison that is dual to static approaches. Specific challenges in the use of dynamic analysis on Android are the limited information gained from tracking low-level events and the imperfect coverage when testing apps, e.g., due to inactive command and control servers. We observe that on Android, pure system calls do not carry enough semantic content for classification and instead rely on lightweight virtual machine introspection to also reconstruct Android-level inter-process communication. To address the sparsity of data resulting from low coverage, we introduce a novel classification method that fuses Support Vector Machines with Conformal Prediction to generate high-accuracy prediction sets where the information is insufficient to pinpoint a single family.

Fully Textile, PEDOT:PSS Based Electrodes for Wearable ECG Monitoring Systems

Abstract: Goal: To evaluate a novel kind of textile electrodes based on woven fabrics treated with PEDOT:PSS, through an easy fabrication process, testing these electrodes for biopotential recordings. Methods: Fabrication is based on raw fabric soaking in PEDOT:PSS using a second dopant, squeezing and annealing. The electrodes have been tested on human volunteers, in terms of both skin contact impedance and quality of the ECG signals recorded at rest and during physical activity (power spectral density, baseline wandering, QRS detectability, and broadband noise). Results: The electrodes are able to operate in both wet and dry conditions. Dry electrodes are more prone to noise artifacts, especially during physical exercise and mainly due to the unstable contact between the electrode and the skin. Wet (saline) electrodes present a stable and reproducible behavior, which is comparable or better than that of traditional disposable gelled Ag/AgCl electrodes. Conclusion: The achieved results reveal the capability of this kind of electrodes to work without the electrolyte, providing a valuable interface with the skin, due to mixed electronic and ionic conductivity of PEDOT:PSS. These electrodes can be effectively used for acquiring ECG signals. Significance: Textile electrodes based on PEDOT:PSS represent an important milestone in wearable monitoring, as they present an easy and reproducible fabrication process, very good performance in wet and dry (at rest) conditions and a superior level of comfort with respect to textile electrodes proposed so far. This paves the way to their integration into smart garments.

Molecular basis for inhibition of AcrB multidrug efflux pump by novel and powerful pyranopyridine derivatives.

Abstract: The Escherichia coli AcrAB-TolC efflux pump is the archetype of the resistance nodulation cell division (RND) exporters from Gram-negative bacteria. Overexpression of RND-type efflux pumps is a major factor in multidrug resistance (MDR), which makes these pumps important antibacterial drug discovery targets. We have recently developed novel pyranopyridine-based inhibitors of AcrB, which are orders of magnitude more powerful than the previously known inhibitors. However, further development of such inhibitors has been hindered by the lack of structural information for rational drug design. Although only the soluble, periplasmic part of AcrB binds and exports the ligands, the presence of the membrane-embedded domain in AcrB and its polyspecific binding behavior have made cocrystallization with drugs challenging. To overcome this obstacle, we have engineered and produced a soluble version of AcrB [AcrB periplasmic domain (AcrBper)], which is highly congruent in structure with the periplasmic part of the full-length protein, and is capable of binding substrates and potent inhibitors. Here, we describe the molecular basis for pyranopyridine-based inhibition of AcrB using a combination of cellular, X-ray crystallographic, and molecular dynamics (MD) simulations studies. The pyranopyridines bind within a phenylalanine-rich cage that branches from the deep binding pocket of AcrB, where they form extensive hydrophobic interactions. Moreover, the increasing potency of improved inhibitors correlates with the formation of a delicate protein- and water-mediated hydrogen bond network. These detailed insights provide a molecular platform for the development of novel combinational therapies using efflux pump inhibitors for combating multidrug resistant Gram-negative pathogens.

Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants.

Abstract: New psychoactive substances (NPS) are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, “dark net”) as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society (UNODC, World Drug Report, 2014; EMCDDA, European Drug Report 2014: Trends and developments). The chemical structure (phenethylamines, piperazine, cathinones, tryptamines, synthetic cannabinoids) of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant) help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%)(WDR, 2014). Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone and MDMA analogues). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc) shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of dependence associated with “Spice” use, will be described (De Luca et al., 2015a). Considering the growing evidence of a widespread use of NPS, this review will be useful to understand the new trends in the field of drug reward and drug addiction by revealing the rewarding properties of NPS, and will be helpful to gather reliable data regarding the abuse potential of these compounds.

Covalent docking using autodock: Two‐point attractor and flexible side chain methods

Abstract: We describe two methods of automated covalent docking using Autodock4: the two-point attractor method and the flexible side chain method. Both methods were applied to a training set of 20 diverse protein-ligand covalent complexes, evaluating their reliability in predicting the crystallographic pose of the ligands. The flexible side chain method performed best, recovering the pose in 75% of cases, with failures for the largest inhibitors tested. Both methods are freely available at the AutoDock website (http://autodock.scripps.edu).