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Newspapers, websites and other sources of information routinely describe the evolution of the total number of Covid-19 deaths using graphs that are either on a log scale or on a linear scale. We hypothesize that people will react differently to these graphs depending on the scale used, even if the data plotted is the same. The reason is twofold. First, linear scale looks "steeper" than the log scale. Second, even experts have a limited understanding of logarithmic scale (Menge et al 2018). We believe that this has a clear policy relevance. If the graph used affects people behavior and preferences, then the choice of the scale is not neutral. Newspapers and other sources of information must be aware that by choosing a given scale they are likely to generate a certain set of reactions among the general public. To test our main hypotheses, we show to one group the data on Covid-19 deaths in the United States using a log scale and to the other group we show the same data plotted on a linear scale. We ask people questions that capture their understanding of the graph. Moreover, we ask people questions on how worried they are about the crisis and on their policy preferences in relevant domains.

We plan to run an online experiment with a sample of 4000 American. Our main hypothesis is that colors are a more effective way to flag key clauses than the traditionally adopted solution of using capital letters.

La presente ricerca ha mirato ad individuare dei tratti morfo-fisiologici e biochimici adattativia condizioni di stress idrico e salino (NaCl) in un sistema diallelico di barbabietola da zucchero, e a caratterizzare i genotipi sulla base della tolleranza o sensibilità a tali stress. Lo studio ha preso in considerazione tratti morfo-fisiologici legati allo sviluppo dell'apparato radicale, con calcolo di parametri di allocazione, e tratti biochimici relativi all'attività di pompe protoniche in tessuti radicali e di enzimi con funzione antiossidante estratti dai tessuti fogliari. Tramitel'Analisi delle Componenti Principali (PCA) e l'Analisi Cluster è statopossibile descrivere la variabilità esistente tra i genotipi riducendo le variabili studiate in gruppi in grado di spiegare il diverso grado di tolleranza agli stress applicati. Analisi sui semi dei genotipi oggetto di studio, in condizioni di stress idrico e salino,sono state ugualmente eseguite.&nbsp

Understanding the complex communication between different cell populations and their interaction with the microenvironment in the central and peripheral nervous systems is fundamental in neuroscience research. The development of appropriate in vitro approaches and tools, able to selectively analyze and/or probe specific cells and cell portions (e.g., axons and cell bodies in neurons), driving their differentiation into specific cell phenotypes, has become therefore crucial in this direction. Here we report a multi-compartment microfluidic device where up to three different cell populations can be cultured in a fluidically independent circuit. The device allows cell migration across the compartments and their differentiation. We showed that an accurate choice of the device geometrical features and cell culture parameters allows to (1) maximize cell adhesion and proliferation of neuron-like human cells (SH-SY5Y cells), (2) control the inter-compartment cell migration of neuron and Schwann cells, (3) perform long-term cell culture studies in which both SH-SY5Y cells and primary rat Schwann cells can be differentiated towards specific phenotypes. These results can lead to a plethora of in vitro co-culture studies in the neuroscience research field, where tuning and investigating cell–cell and cell–microenvironment interactions are essential.

In this paper we present a new method for numerically modelling landslide-generated tsunamis in OpenFOAM® by using a new approach based on the Overset mesh technique. This technique, which is based on the use of two (or more) numerical domains, is new in the coastal engineering field and appears to be extremely powerful to model the interaction between a moving body and one or more fluids. Indeed, the accurate resolution around the moving body (i.e. body-fitted approach), guaranteed by this method, offers a great advantage to study the momentum exchange between the body and the water. Furthermore, in order to overcome a drawback of the Overset mesh implementation we modelled the solid boundaries, along which the landslide body moves, as a porous media with a very low permeability. The new approach has been preliminarily, and successfully, validated through the numerical reproduction of past experiments for landslide-generated tsunamis triggered by a solid and impermeable wedge at a sloping coast.

This paper is a reflection through a disciplinary hybridization offered by the anthropo- logical perspective on the educational practices based on violence. In particular, the use of the socio-anthropological concept of “structural violence” is suggested, in order to claim that the use of punishment and violence in educational relationship, taking shape both in the family and in the school environment, is attributable not only to individual but also to social organization jointly responsible. In order to design effective education- al interventions, and to develop the person, and society, the need for careful analysis and reflection on the cultural reasons underlying the educational violence therefore emerges., Rivista Italiana di Educazione Familiare, Vol. 16 No. 1 (2020): n°1 gennaio-giugno 2020

Presented at: Coastal Structures Conference 2019, Hannover, Germany, September 30th – October 2nd, 2019

Presented at: Coastal Structures Conference 2019, Hannover, Germany, September 30th – October 2nd, 2019

Additional file 1: Table S1. List of the specific primers used for cloning and qPCR analysis. Sequence accession numbers, primer sequences and amplicon sizes are shown. Figure S1. Nucleotide and predicted amino acid sequence of zebrafish pept1a (slc15a1a) obtained using ORFfinder (https://www.ncbi.nlm.nih.gov/orffinder/). Numbers on the left refer to the nucleotide (upper row) and amino acid (lower row) positions. Nucleotides are numbered, starting from the first ATG initiation codon. * indicates the stop codon. The specific primers used for cloning and PCR analyses (Additional file 1: Table S1) are indicated in red and green, respectively. In the amino acid sequence, putative transmembrane domains, obtained using the TMHMM v. 2.0 program as implemented in SMART, are indicated and named I to XII. Potential extracellular N-glycosylation sites (white boxes), potential cAMP/cGMP-dependent protein kinase phosphorylation sites at the cytoplasmic surface (light gray boxes) and potential protein kinase C phosphorylation sites at the cytoplasmic surface (dark gray boxes) were obtained using the ScanProsite tool. Figure S2. Current-voltage relationships of transport-associated currents in zebrafish PepT1a, in the presence of 3 mmol/L Gly-Gln in sodium (NaCl) saline buffer (black square) and tetramethylammonium (TMACl) saline buffer (empty circle) at pH 7.6 (see Methods for details). Values are means ± SEM from 5 oocytes from one batch each group. The transport-associated current values reported were obtained by subtracting the current recorded in the absence of the substrate to that recorded in its presence. Figure S3. Expression analysis by RT-PCR on pept1a (slc15a1a) mRNA in different sections of adult zebrafish intestine. a RT-PCR assay on cDNA templates from total RNA extracted from whole gut (gut), intestinal bulb (I. bulb), mid intestine (mid) and posterior intestine (posterior); a PCR product of ~ 350 bp related to pept1a (slc15a1a) mRNA is present in all intestinal samples; L: 1 Kb Plus DNA ladder (Thermo Fisher Scientific). b A graphic representation of the adult zebrafish gut anatomy with its major adjacent tracts.

Figure S1. (A) Effects of missense mutations on the structure of GMPPB. The images show the close-up of the different mutation sites with the predicted consequences of the amino acid replacement. Wild-type protein is shown in gray and mutated proteins in magenta. The side chain of wild-type and mutated residues are shown as sticks. Mutated residues located in the N-terminal catalytic domain, inter-domains and C-terminal LbH domain are shown on orange, gray and green backgrounds, respectively. (B) Distribution of missense mutations between the domains and inter-domains of the GMPPB protein reported as number of mutations per amino acid. Orange bar, N-terminal catalytic domain; gray bar, inter-domains; green bar, C-terminal LbH domain. (PDF 8212 kb)

In this paper, we argue that the joint use of ex-ante regulation and ex-post liability rules is efficient when there are uncertainty surrounding causal investigations and regulatory myopia. As these conditions are generally met in environmental cases, we provide an explanation for the frequent coexistence of these two instruments to control activities that create a risk for the environment. Moreover, we suggest that a joint use of liability and regulation should more frequently be optimal at the European (Federal) level than at the Country (State) level.

There is a widespread consensus that Credit Rating Agencies have systematically inflated their ratings. In this paper, we analyze how the European regulator has addressed this issue. Specific attention is paid to the legislative framework introduced by the Reg. (Ec) no. 1060/2009, the Reg. (Eu) no. 513/2011, and the Reg. (Eu) no. 462/2013. We argue that these regulations are inadequate to provide Cras with the correct incentives. In this vein, we suggest the introduction of a mitigated version of strict liability rule. We develop specific mechanisms to protect Cras from systemic risk, to limit their liability, and to allow them to choose how much to «bet» on their own predictions.

This study aimed to evaluate the effect of TGF-β1 on RSC96 Schwann cell migration and to study its intracellular transduction pathways. We found that TGF-β1 induced the activation of key signaling molecules involved in non-Smad (Akt and MAPK) and focal adhesion signaling pathways (FAK and Src) that cooperatively regulated the process of RSC96 cells migration together with MMP-2 and MMP-9 upregulation. These findings indicate a regulatory pathway of TGF-β1 in MMP-9/-2 expression which may be significant in regulating Schwann cell migration and physiology in peripheral nervous sytem injury.

Nanotechnology has been utilized recently in medicine for the development of Drug Delivery Systems able to alter the kinetic profile of drug release that is very important in the administration of therapies for long periods as chemotherapy treatments, preventing damages to the normal surrounding tissue. This work aims to test new types of engineered green nanocarriers produced by an environmentalfriendly procedure for epithelial tumors treatment. Epithelial cancer is the largest single cause of death in both men and women, claiming over 6 million lives each year worldwide. For this reason, recently nanotechnology is attracting great interest in the search for new cancer therapies.

In this article, we deal with a variant of the classical course timetabling problem that has a practical application in many areas of education. In particular, in this paper we are interested in high schools remedial courses. The purpose of such courses is to provide under-prepared students with the skills necessary to succeed in their studies. In particular, a student might be under prepared in an entire course, or only in a part of it. The limited availability of funds, as well as the limited amount of time and teachers at disposal, often requires schools to choose which courses and/or which teaching units to activate. Thus, schools need to model the training offer and the related timetabling, with the goal of ensuring the highest possible teaching quality, by meeting the above-mentioned financial, time and resources constraints. Moreover, there are some prerequisites between the teaching units that must be satisfied. We first present a Mixed-Integer Programming (MIP) model to solve this problem to optimality. However, the presence of many peculiar constraints contributes inevitably in increasing the complexity of the mathematical model. Thus, solving it through a general-purpose solver may be performed for small instances only, while solving real-life-sized instances of such model requires specific techniques or heuristic approaches. For this purpose, we also propose a heuristic approach, in which we make use of a fast constructive procedure to obtain a feasible solution. To assess our exact and heuristic approaches we perform extensive computational results on both real-life instances (obtained from a high school in Lecce, Italy) and randomly generated instances. Our tests show that the MIP model is never solved to optimality, with an average optimality gap of 57%. On the other hand, the heuristic algorithm is much faster (in about the 50% of the considered instances it converges in approximately half of the time limit) and in many cases allows achieving an improvement on the objective function value obtained by the MIP model. Such an improvement ranges between 18% and 66%., {"references":["C. Gotlieb, The construction of class-teacher timetables, in: IFIP congress,\nVol. 62, 1963, pp. 73–77.","N. L. Lawrie, An integer linear programming model of a school\ntimetabling problem, The Computer Journal 12 (4) (1969) 307–316.","M. Sørensen, F. H. Dahms, A two-stage decomposition of high school\ntimetabling applied to cases in denmark, Computers & Operations\nResearch 43 (2014) 36–49.","S. M. Al-Yakoob, H. D. Sherali, Mathematical models and algorithms for\na high school timetabling problem, Computers & Operations Research 61\n(2015) 56–68.","R. Alvarez-Valdes, E. Crespo, J. M. Tamarit, Design and implementation\nof a course scheduling system using tabu search, European Journal of\nOperational Research 137 (3) (2002) 512–523.","Z. L¨u, J.-K. Hao, Adaptive tabu search for course timetabling, European\nJournal of Operational Research 200 (1) (2010) 235–244.","S. Abdullah, H. Turabieh, On the use of multi neighbourhood structures\nwithin a tabu-based memetic approach to university timetabling problems,\ninformation sciences 191 (2012) 146–168.","A. Gunawan, K. M. Ng, K. L. Poh, A hybridized lagrangian relaxation\nand simulated annealing method for the course timetabling problem,\nComputers & Operations Research 39 (12) (2012) 3074–3088.","S. S. Brito, G. H. Fonseca, T. A. Toffolo, H. G. Santos, M. J. Souza,\nA sa-vns approach for the high school timetabling problem, Electronic\nNotes in Discrete Mathematics 39 (2012) 169–176.\n[10] P. Guo, J.-x. Chen, L. Zhu, The design and implementation of timetable\nsystem based on genetic algorithm, in: Mechatronic Science, Electric\nEngineering and Computer (MEC), 2011 International Conference on,\nIEEE, 2011, pp. 1497–1500.\n[11] S. Yang, S. N. Jat, Genetic algorithms with guided and local\nsearch strategies for university course timetabling, Systems, Man, and\nCybernetics, Part C: Applications and Reviews, IEEE Transactions on\n41 (1) (2011) 93–106.\n[12] C. Nothegger, A. Mayer, A. Chwatal, G. R. Raidl, Solving the post\nenrolment course timetabling problem by ant colony optimization, Annals\nof Operations Research 194 (1) (2012) 325–339.\n[13] C. Valouxis, E. Housos, Constraint programming approach for\nschool timetabling, Computers & Operations Research 30 (10) (2003)\n1555–1572."]}

Cell uptake of small peptides is mediated by membrane transport proteins of the Peptide TRansporter (PTR) family. Members of this family have been described in bacteria, fungi, plants, fruitfly, nematodes, birds and mammals, but not in lower vertebrates. We hereby report the first molecular and functional characterization of a piscine peptide transporter, orthologue to mammalian and avian PEPT1, from the zebrafish Danio rerio. An EST cDNA clone was obtained from IMAGE and the nucleotide sequence of its 2746 pb insert determined. The open reading frame was 2157 bp and encoded for a protein of 718 amino acids with 12 potential transmembrane domains and highest identity (60-62%) to PEPT1 transporters within the PTR family. Electrophysiological analysis after cRNA injection in Xenopus laevis oocytes suggested that zebrafish PEPT1 is a low-affinity/high-capacity system, kinetically similar to the mammalian counterparts. However, in contrast to mammalian transporters which maximal transport activity is independent on extracellular pH, zebrafish PEPT1 maximal transport rates unexpectedly increased at alkaline extracellular pH. Zebrafish pept1 was highly expressed in the proximal intestine since day 4 post-fertilisation, thus preceding functional maturation of the gut, first feeding and complete yolk resorption. Zebrafish PEPT1 will help to understand the evolutionary/functional relations among vertebrate peptide transporters. Moreover, zebrafish pept1 can be a useful marker to screen mutations affecting gut regionalization, differentiation and morphogenesis.

Este estudo buscou descrever o uso da vigilância de primatas não humanos na vigilância da Febre Amarela Silvestre e avaliar a utilidade na prevenção de casos humanos no Brasil. A vigilância de epizootias iniciou seus registros em 1999 e ampliou a atividade assim como o número de notificações depois de 2006, quando a morte ou adoecimentos de primatas não humanos passou a ser considerado um evento de relevância epidemiológica e, portanto, de notificação compulsória, conforme atualmente define a portaria 104/GM/MS/2011. Foram registradas 2.748 epizootias de primatas não humanos no Brasil. A confirmação para a febre amarela ocorreu em 8,8% das notificações. Foi característica da febre amarela no período do estudo, dois períodos epizoóticos epidêmicos, com dispersão das áreas de ocorrência a partir do norte e centro oeste com disseminação posterior para as regiões sudeste e sul. No período do estudo a febre amarela atingiu áreas de populações não vacinadas, na qual a atividade de vigilância de epizootias contribuiu para identificar áreas afetadas evitando que casos humanos fossem registrados. A vigilância de primatas não humanos revelou a participação de outros agentes etiológicos possivelmente envolvidos nas epizootias notificadas e destaca o potencial de contribuição dessa ferramenta de vigilância para outras causas infecciosas de importância em saúde pública assim como quando foi identificada sorologia reagente para outros arbovírus em populações de primatas em vida livre, demonstrando que essa estratégia de vigilância animal pode ser útil para outras arboviroses com importância em saúde pública. A estratégia de vigilância animal permitiu detectar áreas de circulação do vírus da FA e orientar as campanhas de vacinação, principalmente, em situações de surto, prevenindo casos humanos da doença e demonstrando sua utilidade e contribuição para a vigilância da FA. Essa estratégia de vigilância pode ser aprimorada ampliando as suas finalidades já que possivelmente pode contribuir para a vigilância de outras doenças como importante interface da saúde humana e animal. This study sought to describe the use of surveillance of non-human primates in surveillance of Sylvatic Yellow Fever and evaluate the usefulness in the prevention of human cases in Brazil. The epizootic surveillance began its records in 1999 and expanded the activity and the number of notifications after 2006, when the deaths or illnesses of nonhuman primates came to be considered an event of epidemiological relevance and therefore compulsory notification, as currently defines the ordinance 104/GM/MS/2011. 2748 epidemics were recorded in non-human primates in Brazil. The confirmation of yellow fever occurred in 8.8% of notifications. It was characteristic of yellow fever during the study period, two epizootic epidemic periods, with dispersal occurring from areas of Northern and central west with subsequent spread to the South and Southeast regions. During the study period yellow fever hit areas unvaccinated populations where the activity of epizootic surveillance helped to identify affected areas preventing human cases were recorded. The surveillance of NHP revealed the involvement of other infectious agents possibly involved in epizootics reported and highlights the potential contribution of this surveillance strategy for other infectious causes of public health importance and has been identified as seropositive for other arboviruses in primate populations in free life, demonstrating that this surveillance strategy animal may be useful to other map areas of occurrence of other arboviruses. The surveillance strategy allowed animals to detect areas of circulation of YF virus and direct vaccination campaigns, especially in outbreak situations, preventing human cases of the disease and demonstrating its utility and contribution to the monitoring of YF. This monitoring strategy can be enhanced by broadening their purposes as may possibly contribute to the surveillance of other diseases as an important interface of human and animal health.

Although inflammation appears to play a role in neurolymphomatosis (NL), the mechanisms leading to degeneration in the peripheral nervous system are poorly understood. The purpose of this exploratory study was to identify molecular pathways underlying NL pathogenesis, combining clinical and neuropathological investigation with gene expression (GE) studies. We characterized the clinical and pathological features of eight patients with NL. We further analysed GE changes in sural nerve biopsies obtained from a subgroup of NL patients (n=3) and thirteen patients with inflammatory neuropathies as neuropathic controls. Based on the neuropathic symptoms and signs, NL patients were classified into three forms of neuropathy: chronic symmetrical sensorimotor polyneuropathy (SMPN, n=3), multiple mononeuropathy (MN, n=4) and acute motor-sensory axonal neuropathy (AMSAN, n=1). Predominantly diffuse malignant cells infiltration of epineurium was present in chronic SMPN, whereas endoneurial perivascular cells invasion was observed in MN. In contrast, diffuse endoneurium malignant cells localization occurred in AMSAN. We identified alterations in the expression of 1266 genes, with 115 up-regulated and 1151 down-regulated genes, which were mainly associated with ribosomal proteins (RP) and olfactory receptors (OR) signaling pathways, respectively. Among the top up-regulated genes were actin alpha 1 skeletal muscle (ACTA1) and desmin (DES). Similarly, in NL nerves ACTA1, DES and several RPs were highly expressed, associated with endothelial cells and pericytes abnormalities. Peripheral nerve involvement may be due to conversion towards a more aggressive phenotype, potentially explaining the poor prognosis. The candidate genes reported in this study may be a source of clinical biomarkers for NL.

Understanding how different sources of concern interact in people's mind is a question that has entertained generations of scholars. The finite-pool-of-worry (FPW) hypothesis states that humans have limited resources to worry, thus when they are worried about one issue they become less worried about other issues. Instead, the affect-generalization theory (AGT) posits that an increased level of worry about one threat increases concerns about related threats. Understanding how concerns for the environment interact with concerns for other sources of worry is extremely useful in the fight against global warming. To this end, we adopt a Lotka-Volterra model to detect instances of AGT and FPW among worries for the environment, economy, safety, social issues and immigration in 31 European countries between 2012--2019 (Eurobarometer data). Our findings suggest that, consistently with AGT, an increase in the concerns for the environment often favors the growth of concerns for the economy. Meanwhile, consistently with FPW, an increase in the concerns for the economy, but also for the other sources of concern, often pushes down concerns for the environment. Moreover, we find that an increase in concerns for immigration and social issues generally pushes down concerns for the environment. Furthermore, we find that AGT and FPW can coexist not only over time and across countries, but also as a result of an asymmetric interaction. Building on our results, we hypothesize the existence of a pyramid of worries. At the bottom of the pyramid lie worries like concerns for the economy, which generally predate other worries. Concerns for the environment lie at the very top of the pyramid as they are generally predated by other worries.Building on our results, we hypothesize the existence of a pyramid of worries. At the bottom of the pyramid lie worries like concerns for the economy, which generally predate other worries.

The neurovascular system (NVS) is a complex anatomic-functional unit that synergically works to maintain organs/tissues homeostasis of the entire body. NVS alterations have recently emerged as a common distinct feature in the pathogenesis of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Despite their undeniable involvement, neurovascular signalling pathways remain still far unknown in ALS. This review underlines the importance of endothelial, mural, and fibroblast cells as novel targets for ALS investigation and identifies in the interplay between neuronal and vascular systems the way to disclose novel molecular mechanisms behind the pathogenesis of ALS.

Motor neuron diseases are neurodegenerative diseases that predominantly affect the neuromuscular system. To date, there are no valid therapeutic treatments for such diseases, and the classical experimental models fail in faithfully reproducing the pathological mechanisms behind them. In this regard, the use of three-dimensional (3D) culture systems, which more closely reproduce the native in vivo environment, can be a promising approach. Hydrogel-based systems are among the most used materials to reproduce the extracellular matrix, featuring an intrinsic similarity with its physiological characteristics. In this study, we developed a thermosensitive chitosan-based hydrogel combined with beta-glycerophosphate (beta GP) and sodium hydrogen carbonate (SHC), which give the system optimal mechanical properties and injectability, inducing the hydrogel sol-gel transition at 37 degrees C. An ad hoc protocol for the preparation of the hydrogel was established in order to obtain a highly homogeneous system, leading to reproducible physicochemical characteristics and easy cell encapsulation. All formulations supported the viability of a neuroblastoma/spinal cord hybrid cell line (NSC-34) beyond two weeks of culture and enabled cell differentiation towards a motor neuron-like morphology, characterized by the presence of extended neurites. Based on our results, these hydrogels represent excellent candidates for establishing 3D in vitro models of motor neuron diseases.

Máster en Ingeniería costera y portuaria

We propose an integrable nonautonomous Lotka-Volterra model to carry out a quantitative study of the interaction among container ports located in the Le Havre-Hamburg range. We find that mutualism is emerging among the ports located in the Benelux area, but not among German ports. Moreover, we develop three alternative scenarios and find that (i) for mutualism to emerge no port must be too strong vis-a-vis the others; (ii) the kind of interaction among ports depends on their geographic location, the services they provide, and demand-side factors; and (iii) upgrading intermodal connections can produce externalities that are not internalized by the investing port/country.

Remedial education aims to assist students that need to achieve particular competencies in several skills at different levels. In this article, we model and solve the problem of selecting the training offer and the related timetabling for high-school remedial courses subject to a number of common budget and operational constraints. We propose an Integer Programming formulation as well as a heuristic to quickly find feasible solutions of good quality for large scale instances. Our algorithms are then tested on randomly-generated instances resembling real-world situations. Computational results show that the exact approach becomes not viable as the size of the instances grows, while the heuristic achieves a good trade-off between solution quality and running time.

Most physical model tests carried out to quantify wave overtopping are conducted using a wave energy spectrum, which is then used to generate a free surface wave time series at the wave paddle. This method means that an infinite number of time series can be generated, but, due to the expense of running physical models, often only a single time series is considered. The aim of this work is to investigate the variation in the main overtopping measures when multiple wave times series generated from the same spectrum are used. Physical model tests in a flume measuring 15 m (length) by 0.23 m (width) with an operating depth up to 0.22 m were carried out using a stochastic approach on two types of structures (a smooth slope and a vertical wall), and a variety of wave conditions. Results show variation of overtopping discharge, computed by normalising the range of the discharges at a certain wave condition with the maximum value of the discharge in the range up to 10 % , when the same wave time series is used, but this range increases to 75 % when different time series are used. This variation is found to be of a similar magnitude to both the one found with similar experiments looking at the phenomena in numerical models, and that specified by the confidence bounds in empirical methods.

Human bocavirus (HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool samples, from patients with gastroenteritis. Since then, other viruses related to the first HBoV isolate (HBoV1), namely HBoV2, HBoV3 and HBoV4, have been detected principally in human faeces. HBoVs are small non-enveloped single-stranded DNA viruses of about 5300 nucleotides, consisting of three open reading frames encoding the first two the non-structural protein 1 (NS1) and nuclear phosphoprotein (NP1) and the third the viral capsid proteins 1 and 2 (VP1 and VP2). HBoV pathogenicity remains to be fully clarified mainly due to the lack of animal models for the difficulties in replicating the virus in in vitro cell cultures, and the fact that HBoV infection is frequently accompanied by at least another viral and/or bacterial respiratory and/or gastroenteric pathogen infection. Current diagnostic methods to support HBoV detection include polymerase chain reaction, real-time PCR, enzyme-linked immunosorbent assay and enzyme immunoassay using recombinant VP2 or virus-like particle capsid proteins, although sequence-independent amplification techniques combined with next-generation sequencing platforms promise rapid and simultaneous detection of the pathogens in the future. This review presents the current knowledge on HBoV genotypes with emphasis on taxonomy, phylogenetic relationship and genomic analysis, biology, epidemiology, pathogenesis and diagnostic methods. The emerging discussion on HBoVs as true pathogen or innocent bystander is also emphasized.

In this paper, we test a method for forecasting in real-time the properties of offshore propagating tsunami waves generated by landslides, with the aim of supporting tsunami early warning systems. The method uses an inversion procedure, that takes input data measurements of water surface elevation at a point close to the tsunamigenic source. The measurements are used to correct the results of pre-computed numerical simulations, reproducing the wave field induced by different landslide scenarios. The accuracy of the method is evaluated using the results of laboratory experiments, aimed at studying tsunamis generated by landslides sliding along the flank of a circular shoreline island. The paper investigates what the optimal position is of where to measure the tsunamis, what the effects are, the accuracy of the results, and of uncertainties on the landslide scenarios. Finally, the method is successfully tested using partial input time series, simulating the behaviour of the system in real-time during the tsunami event when forecasts are updated, as the measurements become available.

Interest in extracellular vesicles and in particular microvesicles and exosomes, which are constitutively produced by cells, is on the rise for their huge potential as biomarkers in a high number of disorders and pathologies as they are considered as carriers of information among cells, as well as being responsible for the spreading of diseases. Current methods of analysis of microvesicles and exosomes do not fulfill the requirements for their in-depth investigation and the complete exploitation of their diagnostic and prognostic value. Lab-on-chip methods have the potential and capabilities to bridge this gap and the technology is mature enough to provide all the necessary steps for a completely automated analysis of extracellular vesicles in body fluids. In this paper we provide an overview of the biological role of extracellular vesicles, standard biochemical methods of analysis and their limits, and a survey of lab-on-chip methods that are able to meet the needs of a deeper exploitation of these biological entities to drive their use in common clinical practice.

The coastal zone hosts many human activities and interests, which have significantly increased in the last few decades [...]

Background Dystroglycanopathy (α-DG) is a relatively common, clinically and genetically heterogeneous category of congenital forms of muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) associated with hypoglycosylated α-dystroglycan. To date, mutations in at least 19 genes have been associated with α-DG. One of them, GMPPB, encoding the guanosine-diphosphate-mannose (GDP-mannose) pyrophosphorylase B protein, has recently been associated with a wide clinical spectrum ranging from severe Walker-Warburg syndrome to pseudo-metabolic myopathy and even congenital myasthenic syndromes. We re-sequenced the full set of known disease genes in 73 Italian patients with evidence of either reduced or nearly absent α-dystroglycan to assess genotype-phenotype correlations in this cohort. We used innovative bioinformatic tools to calculate the effects of all described GMPPB mutations on protein function and attempted to correlate them with phenotypic expressions. Results We identified 13 additional cases from 12 families and defined seven novel mutations. Patients displayed variable phenotypes including less typical pictures, ranging from asymptomatic hyperCKemia, to arthrogryposis and congenital clubfoot at birth, and also showed neurodevelopmental comorbidities, such as seizures and ataxic gait, as well as autism-spectrum disorder, which is seldom described in clinical reports of dystroglycanopathies. We also demonstrated that few mutations recur in the Italian GMPPB-mutated population and that alterations of protein stability are the main effects of GMPPB missense variants. Conclusion This work adds to the data on genotype-phenotype correlations in α-DG and offers new bionformatic tools to provide the conceptual framework needed to understand the complexity of these disorders. Electronic supplementary material The online version of this article (10.1186/s13023-018-0863-x) contains supplementary material, which is available to authorized users.

Kabuki syndrome is a rare autosomal dominant condition characterized by facial features, various organs malformations, postnatal growth deficiency and intellectual disability. The discovery of frequent germline mutations in the histone methyltransferase KMT2D and the demethylase KDM6A revealed a causative role for histone modifiers in this disease. However, the role of missense mutations has remained unexplored. Here, we expanded the mutation spectrum of KMT2D and KDM6A in KS by identifying 37 new KMT2D sequence variants. Moreover, we functionally dissected 14 KMT2D missense variants, by investigating their impact on the protein enzymatic activity and the binding to members of the WRAD complex. We demonstrate impaired H3K4 methyltransferase activity in 9 of the 14 mutant alleles and show that this reduced activity is due in part to disruption of protein complex formation. These findings have relevant implications for diagnostic and counseling purposes in this disease.

Real-time vehicle routing problems arise in a number of applications spanning from couriers to emergency services. In this article, we present a new dispatching policy for the dynamic and stochastic pickup and delivery problem, in which a fleet of vehicles must service a set of dynamically occurring customers requests that are partitioned in several classes (according to their priority). The basic idea of our policy is to reserve a fraction of the fleet capacity to the top prior classes that deserve to be serviced as soon as possible. Moreover, our dispatching policy is parameterized and the optimal parameter setting is determined by solving an off-line training problem on a sample of the instance population. To asses the quality of our approach, we compare it with two policies already proposed in the literature, namely a reactive and an anticipatory procedure. Computational results on randomly-generated instances indicate that our procedure can often match the quality of an anticipatory algorithm with a computational effort comparable to that of a reactive approach.

During the earthquake that occurred on February 6, 2012, between the Negros and Cebu islands (Philippines), a scuba diver who was about 12 km from the epicenter zone, in about 10 m water depth, was taking audio and video recordings using a GoPro camera. The recorded audio reveals a specific spectral signature few seconds after the earthquake occurrence that appears to be related to hydroacoustic waves. Numerical reproduction of the phenomenon produced waves exhibit a frequency spectrum similar to that recorded. Several previous researches, based on theoretical and/or numerical approaches, indicate that hydroacoustic waves are tsunami precursors and can significantly improve the Tsunami Early Warning System. Currently, such pressure waves generated by submarine earthquakes are seldom measured. Therefore, the records presented in this paper can enhance the research on the in situ data analysis.