Role of the mucins in pathogenesis of COPD: implications for therapy.

Introduction: Evidence accumulated in the last decade has started to reveal the enormous complexity in the expression, interactions and functions of the large number of different mucins present in the different compartments of the human lower airways. This occurs both in normal subjects and in COPD patients in different clinical phases and stages of severity.Areas covered: We review the known physiological mechanisms that regulate mucin production in human lower airways of normal subjects, the changes in mucin synthesis/secretion in COPD patients and the clinical efficacy of drugs that modulate mucin synthesis/secretion.Expert opinion: It is evident that the old simplistic concept that mucus hypersecretion in COPD patients is associated with negative clinical outcomes is not valid and that the therapeutic potential of 'mucolytic drugs' is under-appreciated due to the complexity of the associated molecular network(s). Likewise, our current knowledge of the effects of the drugs already available on the market that target mucin synthesis/secretion/structure in the lower airways is extremely limited and often indirect and more well-controlled clinical trials are needed in this area

Review of state-of-the-art wireless technologies and applications in smart cities

There are increasing preferences to employ wireless communication technologies for high mobility, high scalability and low-cost applications in smart city development. This paper gives a brief synopsis of typical wireless technologies in smart city applications and the comparison analysis between them. The trend for smart city wireless technology is also presented. Examples, for several key applications within smart city development (healthcare, smart grid, localization) are studied and current advanced solutions supporting these applications are summarized with futuristic trends and demands are presented

Inherently chiral, highly electroactive macrocyclic oligothiophenes: a new class with a "Portfolio" of outstanding potentialities

We have recently introduced1,2,3 an entirely new class of chiral oligothiophene macrocycles, easily accessible by either chemical or electrochemical oxidation of monomers, like the BT2-T4 one in Figure 1 (taken from ref. 3), endowed with "inherent chirality". Such property stems from a tailored torsion in the main conducting backbone,1,2 corresponding to a high rotational energy barrier. Thus the monomer can be separated into stable enantiopure antipodes, whose chirality is entirely transferred to the corresponding cyclic oligomers. The new molecules possess an uncommon pool of outstanding properties even as racemates. For example: \ub7 they idealize conducting polymers without end, that is, without defectivity connected with free terminals; \ub7 in CV and EIS experiments they exhibit very fast and reversible electron transfer and charge transport; \ub7 their HOMO and LUMO levels, which are modulable with the multiplicity and length of the monomer units in the cyclic oligomer, appear convenient for application in devices like bulk heterojunction solar cells; \ub7 they are electrochromic; \ub7 they exhibit (negative) photocurrent activity. Most impressive, however, are the properties as enantiopure antipodes, possibly as a consequence of the unique coincidence of the source of both chirality and electroactivity with the entire main conducting backbone, which affords inter alia to reversibly modulate chiroptical properties by electrochemical polarization. The enantiopure oligomers exhibit: \ub7 impressive optical rotatory power; \ub7 impressive circular dichroism signals, which can be finely and reversibly modulated by the electrical potential ("breathing chirality"); \ub7 remarkable circularly polarized luminescence (CPL); \ub7 outstanding enantiorecognition ability. In particular, we have recently highlighted3 their applicative potentialities as low-cost and easy-to-prepare artificial enantiopure electrode surfaces, which display an unprecedented ability to pronouncedly separate voltammetry peaks of enantiomers of quite different chiral probes, including the model ferrocenyl one in Figure 2 (adapted from ref. 2, and where 3 stays for the BT2-T4 cyclic trimer), or of applicative interest (e.g. pharmaceutical ones like DOPA, Figure 3 from ref. 3), concurrently with linear dynamic ranges for peak currents, affording enantiomer excess determination, particularly on disposable SPEs, testing small drops of enantiomer solutions. It is also remarkable that, while usual chiral recognition methods are based on selectors of natural origin and therefore available as a single enantiomer, this approach offers availability of both selector enantiomers. Thus inherently chiral enantiopure electrodes can indeed be regarded as a key to chiral voltammetry. With the contribution of Fondazione Cariplo, grant no.2011-0417 Patent deposited MI2014A000948-23/05/2014 References: [1] F. Sannicol\uf2, P.R. Mussini, T. Benincori, S. Arnaboldi, M. Panigati, E. Quartapelle Procopio et al., Chem. Eur. J. 2014, 20, 15298 \u2013 15302. [2] F. Sannicol\uf2, S. Arnaboldi, T. Benincori, P.R. Mussini, M. Panigati et al., Angew. Chem. Int. Ed. 2014, 53, 2623 \u20132627. [3] S. Arnaboldi, T. Benincori, R. Cirilli, W. Kutner, M. Magni, P.R. Mussini, K. Noworyta, F. Sannicol\uf2, Chemical Science, 2015, 6, 1706\u20131711

Anti-Angiogenic Therapy Induces Integrin-Linked Kinase 1 Up-Regulation in a Mouse Model of Glioblastoma

BACKGROUND: In order to improve our understanding of the molecular pathways that mediate tumor proliferation and angiogenesis, and to evaluate the biological response to anti-angiogenic therapy, we analyzed the changes in the protein profile of glioblastoma in response to treatment with recombinant human Platelet Factor 4-DLR mutated protein (PF4-DLR), an inhibitor of angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: U87-derived experimental glioblastomas were grown in the brain of xenografted nude mice, treated with PF4-DLR, and processed for proteomic analysis. More than fifty proteins were differentially expressed in response to PF4-DLR treatment. Among them, integrin-linked kinase 1 (ILK1) signaling pathway was first down-regulated but then up-regulated after treatment for prolonged period. The activity of PF4-DLR can be increased by simultaneously treating mice orthotopically implanted with glioblastomas, with ILK1-specific siRNA. As ILK1 is related to malignant progression and a poor prognosis in various types of tumors, we measured ILK1 expression in human glioblastomas, astrocytomas and oligodendrogliomas, and found that it varied widely; however, a high level of ILK1 expression was correlated to a poor prognosis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that identifying the molecular pathways induced by anti-angiogenic therapies may help the development of combinatorial treatment strategies that increase the therapeutic efficacy of angiogenesis inhibitors by association with specific agents that disrupt signaling in tumor cells

The thiophene-based inherently chiral monomer family grows: molecular design and electrochemical properties

Our group has recently presented electroactive thiophenebased polyconjugated films of unprecedented chirality manifestations and enantiorecognition ability,[1] based on the "inherent chirality" concept, implying that the whole electroactive backbone coincides with the stereogenic element, consisting in a tailored torsion induced by an atropisomeric bi-benzothiophene scaffold. Such films are easily prepared as enantiopure electrode surfaces by electrooligomerization of (R) and (S) enantiopure monomer 1. Now, concurrently with the exploration of the applicative potentialities of this "parent" molecular material, both racemic and enantiopure, we are widening the class of available monomers designed according the same strategy, but with different atropisomeric heteroaromatic scaffolds, different side chains, and/or with the addition of a further stereogenic element. The electrochemical properties of a selection of the new inherently chiral monomers now available will be presented in detail and rationalized as a function of their molecular structure, also in the perspective of potential applications. With the contribution of Fondazione Cariplo, grant no. 2011-0417. [1] F. Sannicol\uf2, S. Arnaboldi, T. Benincori, V. Bonometti, R. Cirilli, L. Dunsch, W. Kutner, G. Longhi, P.R. Mussini, M. Panigati, M. Pierini, S. Rizzo, Angew. Chemie 2014, 53, 2623-2627

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Bacterial laccases: some recent advances and applications

Laccases belong to the large family of multi-copper oxidases (MCOs) that couple the one-electron oxidation of substrates with the four-electron reduction of molecular oxygen to water. Because of their high relative non-specific oxidation capacity particularly on phenols and aromatic amines as well as the lack of requirement for expensive organic cofactors, they have found application in a large number of biotechnological fields. The vast majority of studies and applications were performed using fungal laccases, but bacterial laccases show interesting properties such as optimal temperature above 50 °C, optimal pH at the neutral to alkaline range, thermal and chemical stability and increased salt tolerance. Additionally, bacterial systems benefit from a wide range of molecular biology tools that facilitates their engineering and achievement of high yields of protein production and set-up of cost-effective bioprocesses. In this review we will provide up-to-date information on the distribution and putative physiological role of bacterial laccases and highlight their distinctive structural and biochemical properties, discuss the key role of copper in the biochemical properties, discuss thermostability determinants and, finally, review biotechnological applications with a focus on catalytic mechanisms on phenolics and aromatic amines.info:eu-repo/semantics/publishedVersio