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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.

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.

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)

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.

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.

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.

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.

Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is a neurological disease with mutations in SACS, encoding sacsin, a multidomain protein of 4,579 amino acids. The large size of SACS and its translated protein has hindered biochemical analysis of ARSACS, and how mutant sacsins lead to disease remains largely unknown. Three repeated sequences, called sacsin repeating region (SRR) supradomains, have been recognized, which contribute to sacsin chaperone-like activity. We found that the three SRRs are much larger (≥1,100 residues) than previously described, and organized in discrete subrepeats. We named the large repeated regions Sacsin Internal RePeaTs (SIRPT1, SIRPT2, and SIRPT3) and the subrepeats sr1, sr2, sr3, and srX. Comparative analysis of vertebrate sacsins in combination with fine positional mapping of a set of human mutations revealed that sr1, sr2, sr3, and srX are functional. Notably, the position of the pathogenic mutations in sr1, sr2, sr3, and srX appeared to be related to the severity of the clinical phenotype, as assessed by defining a severity scoring system. Our results suggest that the relative position of mutations in subrepeats will variably influence sacsin dysfunction. The characterization of the specific role of each repeated region will help in developing a comprehensive and integrated pathophysiological model of function for sacsin.

In this work, we assessed the capacity of RNA polymerases to use platinated ribonucleotides as substrates for RNA synthesis by testing the incorporation of the model compound [Pt(dien)(N7-5'-GTP)] (dien=diethylenetriamine; GTP=5'-guanosine triphosphate) into a natural RNA sequence. The yield of in vitro transcription operated by T7 RNA polymerase, on the LacZ (Escherichia coli gene encoding for β-galactosidase) sequence, decreases progressively with decreasing the concentration of natural GTP, in favor of the platinated nucleotide, [Pt(dien)(N7-5'-GTP)]. Comparison of the T7 RNA polymerase transcription activities for [Pt(dien)(N7-5'-GTP)] compound incorporation reaction test, with respect to the effect of a decreasing concentration of natural GTP, showed no major differences. A specific inhibitory effect of compound [Pt(dien)(N7-5'-GTP)] (which may pair the complementary base on the DNA strand, without being incorporated in the RNA by the T7 RNA polymerase) was evidenced. Our findings therefore suggest that RNA polymerases, unlike DNA polymerases, are unable to incorporate N7-platinated nucleotides into newly synthesized nucleic acids. In this respect, specifically designed N7-platinated nucleotides based compounds could be used in alternative to the classical platinum based drugs. This approach may offer a possible strategy to target specifically DNA, without affecting RNA, and is potentially able to better modulate pharmacological activity.

On 19 October 2014 Matteo Miceli, a known italian oceanic sailor, left the Port of Riva di Traiano (Rome, IT) with the italian sailing boat ECO 40, for the Roma Ocean World Project. This ambitious challenge consists of a non-stop sailing alone around the World in energy and food self-sufficiency. ECO 40 is a Class 40 oceanic vessel (LOA of 12,0 m) that has been equipped with a data acquisition system for measuring both the met-ocean parameters recorded (apparent and real wind speed and wind direction, atmospheric pressure, current velocity, air temperature, sea temperature, etc.) and the kinematic characteristics of the boat itself (i.e., speed and course over ground). Furthermore, the boat has been equipped with three high precision GPS receivers, provided by Leica Geosystem, for measuring the motion of the boat and an inertial platform. Due to these high-precision instruments it is possible to fully measure and characterize the six degrees of freedom of the boat, and accordingly to use her as a sailing wave buoy. Within this paper we present the analysis of the met-ocean data measured by the boat during the storm occurred in the Gulf of Lion on the 21–22 October 2014 that ECO 40 has faced just few days after her departure. Furthermore, by analyzing the GPS signals by means of an innovative application of differential kinematic positioning technique, a detailed analysis of the boat heeling during the Gulf of Lion event has been carried out. The boat heeling measurements have been used to correct the measured wind data that have been compared with the hindcast time series.

The relevant adsorption of cis -[Pt(NH 3 ) 2 (P 2 O 7 )] 2 − ( phosphaplatin ) on hydroxyapatite nanocrystals (nHAP) was observed and studied in water suspension. Phosphaplatin cytotoxicity, which is very low for HeLa, MCF-7 and HS-5 cell lines could be enhanced, reaching that of cisplatin , by interaction with solid nHAP. This effect stems from nHAP ability to catalyze the phosphaplatin hydrolysis, producing the same hydrolytic species responsible for cisplatin antitumor activity.

Carnosine is an endogenous dipeptide abundant in the central nervous system, where by acting as intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anti-crosslinking agent, it exerts a well-recognized multi-protective homeostatic function for neuronal and non-neuronal cells. Carnosine seems to counteract proteotoxicity and protein accumulation in neurodegenerative conditions, such as Alzheimer's Disease (AD). However, its direct impact on the dynamics of AD-related fibril formation remains uninvestigated. We considered the effects of carnosine on the formation of fibrils/aggregates of the amyloidogenic peptide fragment A beta 1-42, a major hallmark of AD injury. Atomic force microscopy and thioflavin T assays showed inhibition of A beta 1-42 fibrillogenesis in vitro and differences in the aggregation state of A beta 1-42 small pre-fibrillar structures (monomers and small oligomers) in the presence of carnosine. in silico molecular docking supported the experimental data, calculating possible conformational carnosine/A beta 1-42 interactions. Overall, our results suggest an effective role of carnosine against A beta 1-42 aggregation