ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo

Background: ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair. Aim: The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble form of ICOS, on skin wound healing. Methods: The effect of human ICOS-Fc on wound healing was assessed, in vitro, and, in vivo, by skin wound healing assay using ICOS^−/− and ICOSL^−/− knockout (KO) mice and NOD-SCID-IL2R null (NSG) mice. Results: We show that, in wild type mice, treatment with ICOS-Fc improves wound healing, promotes angiogenesis, preceded by upregulation of IL-6 and VEGF expression; increases the number of fibroblasts and T cells, whereas it reduces that of neutrophils; and increases the number of M2 vs. M1 macrophages. Fittingly, ICOS-Fc enhanced M2 macrophage migration, while it hampered that of M1 macrophages. ICOS^−/− and ICOSL^−/− KO, and NSG mice showed delayed wound healing, and treatment with ICOS-Fc improved wound closure in ICOS^−/− and NSG mice. Conclusion: These data show that the ICOS/ICOSL network cooperates in tissue repair, and that triggering of ICOSL by ICOS-Fc improves cutaneous wound healing by increasing angiogenesis and recruitment of reparative macrophages.     

Data-driven generation of spatio-temporal routines in human mobility

The generation of realistic spatio-temporal trajectories of human mobility is of fundamental importance in a wide range of applications, such as the developing of protocols for mobile ad-hoc networks or what-if analysis in urban ecosystems. Current generative algorithms fail in accurately reproducing the individuals’ recurrent schedules and at the same time in accounting for the possibility that individuals may break the routine during periods of variable duration. In this article we present Ditras (DIary-based TRAjectory Simulator), a framework to simulate the spatio-temporal patterns of human mobility. Ditras operates in two steps: the generation of a mobility diary and the translation of the mobility diary into a mobility trajectory. We propose a data-driven algorithm which constructs a diary generator from real data, capturing the tendency of individuals to follow or break their routine. We also propose a trajectory generator based on the concept of preferential exploration and preferential return. We instantiate Ditras with the proposed diary and trajectory generators and compare the resulting algorithm with real data and synthetic data produced by other generative algorithms, built by instantiating Ditras with several combinations of diary and trajectory generators. We show that the proposed algorithm reproduces the statistical properties of real trajectories in the most accurate way, making a step forward the understanding of the origin of the spatio-temporal patterns of human mobility.     

Exploring networks with traceroute-like probes: Theory and simulations

Mapping the Internet generally consists in sampling the network from a limited set of sources by using traceroute-like probes. This methodology, akin to the merging of different spanning trees to a set of destination, has been argued to introduce uncontrolled sampling biases that might produce statistical properties of the sampled graph which sharply differ from the original ones. In this paper, we explore these biases and provide a statistical analysis of their origin. We derive an analytical approximation for the probability of edge and vertex detection that exploits the role of the number of sources and targets and allows us to relate the global topological properties of the underlying network with the statistical accuracy of the sampled graph. In particular, we find that the edge and vertex detection probability depends on the betweenness centrality of each element. This allows us to show that shortest path routed sampling provides a better characterization of underlying graphs with broad distributions of connectivity. We complement the analytical discussion with a throughout numerical investigation of simulated mapping strategies in network models with different topologies. We show that sampled graphs provide a fair qualitative characterization of the statistical properties of the original networks in a fair range of different strategies and exploration parameters. Moreover, we characterize the level of redundancy and completeness of the exploration process as a function of the topological properties of the network. Finally, we study numerically how the fraction of vertices and edges discovered in the sampled graph depends on the particular deployements of probing sources. The results might hint the steps toward more efficient mapping strategies.     

Gate‐Controlled Energy Barrier at a Graphene/Molecular Semiconductor Junction

The formation of an energy‐barrier at a metal/molecular semiconductor junction is a universal phenomenon which limits the performance of many molecular semiconductor‐based electronic devices, from field‐effect transistors to light‐emitting diodes. In general, a specific metal/molecular semiconductor combination of materials leads to a fixed energy‐barrier. However, in this work, a graphene/C₆₀ vertical field‐effect transistor is presented in which control of the interfacial energy‐barrier is demonstrated, such that the junction switches from a highly rectifying diode at negative gate voltages to a highly conductive nonrectifying behavior at positive gate voltages and at room temperature. From the experimental data, an energy‐barrier modulation of up to 660 meV, a transconductance of up to five orders of magnitude, and a gate‐modulated photocurrent are extracted. The ability to tune the graphene/molecular semiconductor energy‐barrier provides a promising route toward novel, high performance molecular devices.     

Chronic Hyperkaliemia in Chronic Kidney Disease: An Old Concern with New Answers

Increasing potassium intake ameliorates blood pressure (BP) and cardiovascular (CV) prognoses in the general population; therefore the World Health Organization recommends a high-potassium diet (90–120 mEq/day). Hyperkalaemia is a rare condition in healthy individuals due to the ability of the kidneys to effectively excrete dietary potassium load in urine, while an increase in serum K⁺ is prevalent in patients with chronic kidney disease (CKD). Hyperkalaemia prevalence increases in more advanced CKD stages, and is associated with a poor prognosis. This scenario generates controversy on the correct nutritional approach to hyperkalaemia in CKD patients, considering the unproven link between potassium intake and serum K⁺ levels. Another concern is that drug-induced hyperkalaemia leads to the down-titration or withdrawal of renin-angiotensin system inhibitors (RASI) and mineralocorticoids receptors antagonists (MRA) in patients with CKD, depriving these patients of central therapeutic interventions aimed at delaying CKD progression and decreasing CV mortality. The new K⁺-binder drugs (Patiromer and Sodium-Zirconium Cyclosilicate) have proven to be adequate and safe therapeutic options to control serum K⁺ in CKD patients, enabling RASI and MRA therapy, and possibly, a more liberal intake of fruit and vegetables.     

Modeling Lung Carcinoids with Zebrafish Tumor Xenograft

Lung carcinoids are neuroendocrine tumors that comprise well-differentiated typical (TCs) and atypical carcinoids (ACs). Preclinical models are indispensable for cancer drug screening since current therapies for advanced carcinoids are not curative. We aimed to develop a novel in vivo model of lung carcinoids based on the xenograft of lung TC (NCI-H835, UMC-11, and NCI-H727) and AC (NCI-H720) cell lines and patient-derived cell cultures in Tg(fli1a:EGFP)^y1 zebrafish embryos. We exploited this platform to test the anti-tumor activity of sulfatinib. The tumorigenic potential of TC and AC implanted cells was evaluated by the quantification of tumor-induced angiogenesis and tumor cell migration as early as 24 h post-injection (hpi). The characterization of tumor-induced angiogenesis was performed in vivo and in real time, coupling the tumor xenograft with selective plane illumination microscopy on implanted zebrafish embryos. TC-implanted cells displayed a higher pro-angiogenic potential compared to AC cells, which inversely showed a relevant migratory behavior within 48 hpi. Sulfatinib inhibited tumor-induced angiogenesis, without affecting tumor cell spread in both TC and AC implanted embryos. In conclusion, zebrafish embryos implanted with TC and AC cells faithfully recapitulate the tumor behavior of human lung carcinoids and appear to be a promising platform for drug screening.     

The Role of NLRP3 Inflammasome Activation and Oxidative Stress in Varicocele-Mediated Male Hypofertility

Varicocele (VC) is the most common abnormality identified in men evaluated for hypofertility. Increased levels of reactive oxygen species (ROS) and reduced antioxidants concentrations are key contributors in varicocele-mediated hypofertility. Moreover, inflammation and alterations in testicular immunity negatively impact male fertility. In particular, NLRP3 inflammasome activation was hypothesized to lead to seminal inflammation, in which the levels of specific cytokines, such as IL-1β and IL-18, are overexpressed. In this review, we described the role played by oxidative stress (OS), inflammation, and NLRP3 inflammasome activation in VC disease. The consequences of ROS overproduction in testis, including inflammation, lipid peroxidation, mitochondrial dysfunction, chromatin damage, and sperm DNA fragmentation, leading to abnormal testicular function and failed spermatogenesis, were highlighted. Finally, we described some therapeutic antioxidant strategies, with recognized beneficial effects in counteracting OS and inflammation in testes, as possible therapeutic drugs against varicocele-mediated hypofertility.     

On the Modeling of the Diffraction Pattern from Metal Nanocrystals

The powder diffraction patterns of spherical nanocrystals made of five different fcc metals were generated using atomistic models within a Molecular Dynamics simulation. Static and dynamic effects are interpreted and discussed within the framework of two different approaches, respectively, based on (1) a Reciprocal Space and (2) a Direct Space representation of diffraction. Chosen elements display a wide range of properties, especially related to material stiffness and elastic anisotropy, so to deeply challenge interpretation paradigms. The effect of the shape on static and dynamic features is also addressed.     

Designing a personal informatics system for users without experience in self-tracking: a case study

Thanks to the advancements in ubiquitous and wearable technologies, Personal Informatics (PI) systems can now reach a larger audience of users. However, it is not still clear whether this kind of tool can fit the needs of their daily lives. Our research aims at identifying specific barriers that may prevent the widespread adoption of PI and finding solutions to overcome them. We requested users without competence in self-tracking to use different PI instruments during their daily practices, identifying five user requirements by which to design novel PI tools. On such requirements, we developed a new system that can stimulate the use of these technologies, by enhancing the perceived benefits of collecting personal data. Then, we explored how naïve and experienced users differently explore their personal data in our system through a user trial. Results showed that the system was successful at helping individuals manage and interpret their own data, validated the usefulness of the requirements found and inspired three further design opportunities that could orient the design of future PI systems.     

The value of quality clues in the wine market: evidences from Lazio,Italy

The purpose of the paper is to contribute to understanding the role and effectiveness of different quality clues in the creation of value for the main wines of the Lazio region. The study presents a hedonic price model. An ordinary least squares and a quantile regression models were estimated. The latter is able to detect additional patterns related to the effects of the covariates. Prices are regressed on wine color, sub-regional area of origin, the type of certification of origin, and on experts' evaluation. The analysis is based on data released by three major Italian wine guides: Gambero Rosso, l'Espresso, and AIS (Italian Sommelier Association). Results show that: (i) white and red wines follow two different price patterns; (ii) prices are correlated with experts' evaluation; (iii) the impact of the latter is higher when other quality clues, such as geographical indications, are less effective; (iv) the role of different quality clues varies at different price levels and it is different for red and white wines; overall, wines from the Lazio region are associated with poor to mediocre quality levels. This may explain the decline in reputation and in market share that these wines are experiencing after centuries of popularity.