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.     

Pressure‐Tunable Ambipolar Conduction and Hysteresis in Thin Palladium Diselenide Field Effect Transistors

Few‐layer palladium diselenide (PdSe₂) field effect transistors are studied under external stimuli such as electrical and optical fields, electron irradiation, and gas pressure. The ambipolar conduction and hysteresis are observed in the transfer curves of the as‐exfoliated and unprotected PdSe₂ material. The ambipolar conduction and its hysteretic behavior in the air and pure nitrogen environments are tuned. The prevailing p‐type transport observed at atmospheric pressure is reversibly turned into a dominant n‐type conduction by reducing the pressure, which can simultaneously suppress the hysteresis. The pressure control can be exploited to symmetrize and stabilize the transfer characteristics of the device as required in high‐performance logic circuits. The transistors are affected by trap states with characteristic times in the order of minutes. The channel conductance, dramatically reduced by the electron irradiation during scanning electron microscope imaging, is restored after an annealing of several minutes at room temperature. The work paves the way toward the exploitation of PdSe₂ in electronic devices by providing an experiment‐based and deep understanding of charge transport in PdSe₂ transistors subjected to electrical stress and other external agents.     

BETaaS: A Platform for Development and Execution of Machine-to-Machine Applications in the Internet of Things

Wireless Personal Communications - The integration of everyday objects into the Internet represents the foundation of the forthcoming Internet of Things (IoT). Smart objects will be the building...     

NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease

Standard treatment for advanced non-small cell lung cancer (NSCLC) historically consisted of systemic cytotoxic chemotherapy until the early 2000s, when precision medicine led to a revolutionary change in the therapeutic scenario. The identification of oncogenic driver mutations in EGFR, ALK and ROS1 rearrangements identified a subset of patients who largely benefit from targeted agents. However, since the proportion of patients with druggable alterations represents a minority, the discovery of new potential driver mutations is still an urgent clinical need. We provide a comprehensive review of the emerging molecular targets in NSCLC and their applications in the advanced setting.     

Tissue Engineering and Regenerative Medicine in Pediatric Urology: Urethral and Urinary Bladder Reconstruction

In the case of pediatric urology there are several congenital conditions, such as hypospadias and neurogenic bladder, which affect, respectively, the urethra and the urinary bladder. In fact, the gold standard consists of a urethroplasty procedure in the case of urethral malformations and enterocystoplasty in the case of urinary bladder disorders. However, both surgical procedures are associated with severe complications, such as fistulas, urethral strictures, and dehiscence of the repair or recurrence of chordee in the case of urethroplasty, and metabolic disturbances, stone formation, urine leakage, and chronic infections in the case of enterocystoplasty. With the aim of overcoming the issue related to the lack of sufficient and appropriate autologous tissue, increasing attention has been focused on tissue engineering. In this review, both the urethral and the urinary bladder reconstruction strategies were summarized, focusing on pediatric applications and evaluating all the biomaterials tested in both animal models and patients. Particular attention was paid to the capability for tissue regeneration in dependence on the eventual presence of seeded cell and growth factor combinations in several types of scaffolds. Moreover, the main critical features needed for urinary tissue engineering have been highlighted and specifically focused on for pediatric application.     

达涅利薄板坯连铸连轧设备最新技术成果

给出达涅利薄板坯连铸连轧技术的最新应用成果.这些成果表明,达涅利技术不仅用于生产普通钢种,还可用于生产质量要求严格的优质钢种和高附加值产品.由达涅利在尼兹尼.诺夫戈罗德区Vyksa建设1套CRC(连铸连轧)设备.这是在俄罗斯建设的第1套薄板坯连铸连轧设备,也是世界上第1套利用薄板坯连铸连轧工艺路线生产北极高寒地区用API管线钢的生产设备.另外2套设备已在中国唐山钢铁集团有限公司和本溪钢铁集团有限公司进入满负荷生产阶段,前者一直保持着设备生产能力世界纪录,后者则成为中国第一家利用薄板坯连铸连轧工艺生产硅钢的厂家.     

A highly efficient receiver for satellite‐based automatic identification system signal detection

An innovative receiver architecture for the satellite‐based automatic identification system has been recently proposed. In this paper, we describe a few modifications that can be introduced on the algorithms for synchronization and detection, which provide an impressive performance improvement. The receiver architecture has been designed for an on‐board implementation, and a prototype has been implemented by the University of Parma and CGS S.p.A. Compagnia Generale per lo Spazio under the European Space Agency project FENICE (Flexible innovative AIS receiver prototype). A few modifications are also here described that could allow a further performance improvement in case of processing moved to ground‐based stations, based on a priori information there available. Copyright © 2014 John Wiley & Sons, Ltd.     

A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation

The M1 zinc metalloproteases ERAP1, ERAP2, and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have also been entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes, one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents, wherein the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independent of the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic micro-environment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt us to reconsider the role of ERAP2, which might have been maintained in humans due to fulfilling a relevant function in its “short” form.     

Challenges in Metabolomics-Based Tests,Biomarkers Revealed by Metabolomic Analysis,and the Promise of the Application of Metabolomics in Precision Medicine

Metabolomics helps identify metabolites to characterize/refine perturbations of biological pathways in living organisms. Pre-analytical, analytical, and post-analytical limitations that have hampered a wide implementation of metabolomics have been addressed. Several potential biomarkers originating from current targeted metabolomics-based approaches have been discovered. Precision medicine argues for algorithms to classify individuals based on susceptibility to disease, and/or by response to specific treatments. It also argues for a prevention-based health system. Because of its ability to explore gene–environment interactions, metabolomics is expected to be critical to personalize diagnosis and treatment. Stringent guidelines have been applied from the very beginning to design studies to acquire the information currently employed in precision medicine and precision prevention approaches. Large, prospective, expensive and time-consuming studies are now mandatory to validate old, and discover new, metabolomics-based biomarkers with high chances of translation into precision medicine. Metabolites from studies on saliva, sweat, breath, semen, feces, amniotic, cerebrospinal, and broncho-alveolar fluid are predicted to be needed to refine information from plasma and serum metabolome. In addition, a multi-omics data analysis system is predicted to be needed for omics-based precision medicine approaches. Omics-based approaches for the progress of precision medicine and prevention are expected to raise ethical issues.     

Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.