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.     

Chemical composition,sensory and cooking quality evaluation of durum wheat spaghetti enriched with pea flour

The goal of the study was to obtain spaghetti enriched with pea flour with sensory properties close to conventional pasta. To this aim, the study has been organised in two subsequent trials. In the first, the pea flour amount added to the spaghetti was continuously increased until the overall sensory quality reached its threshold value (pea flour concentration = 15%). In fact, the spaghetti samples supplemented with 15% pea flour (15%S‐P) showed less elasticity, unpleasant colour and higher firmness compared to the control sample (CTRL). The second step was aimed to improve the overall sensory quality of the 15%S‐P spaghetti by means of guar gum (GUAR). The sample with GUAR (15%S‐P/GUAR) showed a pleasant colour, odour and taste. Furthermore, the 15%S‐P/GUAR sample recorded a low starch digestibility value (i.e. 54) and a higher soluble fibre content with respect to the 15%S‐P sample.     

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.