Holonomy and parallel transport for Abelian gerbes

In this paper, we establish a one-to-one correspondence between U(1)-gerbes with connections, on the one hand, and their holonomies, for simply connected manifolds, or their parallel transports, in the general case, on the other hand. This result is a higher-order analogue of the familiar equivalence between bundles with connections and their holonomies for connected manifolds. The holonomy of a gerbe with group U(1) on a simply connected manifold M is a group morphism from the thin second homotopy group to U(1), satisfying a smoothness condition, where a homotopy between maps from [0,1](2) to M is thin when its derivative is of rank less than or equal to2. For the non-simply connected case, holonomy is replaced by a parallel transport functor between two special Lie groupoids, which we call Lie 2-groups. The reconstruction of the gerbe and connection from its holonomy is carried out in detail for the simply connected case. (C) 2002 Elsevier Science (USA).Programa Operacional ‘‘Ciencia # , Tecnologia, Inovacao* ’’ (POCTI) of the Fundacao para a Ci * encia e a Tecnologia # (FCT), cofinanced by the European Community fund FEDE

On the ordeal of quinolone preparation via cyclisation of aryl-enamines; synthesis and structure of ethyl 6-methyl-7-iodo-4-(3-iodo-4-methylphenoxy)-quinoline-3-carboxylate

Recent studies directed to the design of compounds targeting the bc(1) protein complex of Plasmodium falciparum, the parasite responsible for most lethal cases of malaria, identified quinolones (4-oxo-quinolines) with low nanomolar inhibitory activity against both the enzyme and infected erythrocytes. The 4-oxo-quinoline 3-ester chemotype emerged as a possible source of potent bc(1) inhibitors, prompting us to expand the library of available analogs for SAR studies and subsequent lead optimization. We now report the synthesis and structural characterization of unexpected ethyl 6-methyl-7-iodo-4-(3-iodo-4-methylphenoxy)quinoline-3-carboxylate, a 4-aryloxy-quinoline 3-ester formed during attempted preparation of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate (4-oxo-quinoline 3-ester). We propose that the 4-aryloxy-quinoline 3-ester derives from 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate (4-hydroxy-quinoline 3-ester), the enol form of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate. Formation of the 4-aryloxy-quinoline 3-ester confirms the impact of quinolone/hydroxyquinoline tautomerism, both on the efficiency of synthetic routes to quinolones and on pharmacologic profiles. Tautomers exhibit different cLogP values and interact differently with the enzyme active site. A structural investigation of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate and 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate, using matrix isolation coupled to FTIR spectroscopy and theoretical calculations, revealed that the lowest energy conformers of 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate, lower in energy than their most stable 4-oxo-quinoline tautomer by about 27 kJ mol(-1), are solely present in the matrix, while the most stable 4-oxo-quinoline tautomer is solely present in the crystalline phase.Fundacao para a Ciencia e Tecnologia (FCT - Portugal) [UID/Multi/04326/2013]; QREN-COMPETE-UE; CCMAR; FCT [SFRH/BD/81821/2011, RECI/BBB-BQB/0230/2012, UI0313/QUI/2013, UID/FIS/04564/2016]; FEDER/COMPETE-UE; [PTDC/QEQ-QFI/3284/2014 - POCI-01-0145-FEDER-016617]info:eu-repo/semantics/publishedVersio

Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohorts

We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.(SFRH/BPD/115169/2016) funded by Fundação para a Ciência e Tecnologia (FCT); ERDF (European Regional Development Fund) through the operations: POCI-01-0145-FEDER-029130 ('mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases—generalisation and evaluation of gamification, peer support and advanced image processing technologies') cofunded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).info:eu-repo/semantics/publishedVersio

Boundedness of the maximal operator and its commutators on vanishing generalized Orlicz-morrey spaces

We prove the boundedness of the Hardy-Littlewood maximal operator and their commutators with BMO-coefficients in vanishing generalized Orlicz-Morrey spaces VM Phi,phi(R-n) including weak versions of these spaces. The main advance in comparison with the existing results is that we manage to obtain conditions for the boundedness not in integral terms but in less restrictive terms of supremal operators involving the Young function Phi(u) and the function phi(x, r) defining the space. No kind of monotonicity condition on phi(x, r) in r is imposed.Ahi Evran University [PYO.FEN.4003.13.003, PYO.FEN.4001.14.017]; Science Development Foundation under Republic of Azerbaijan [EIF-2013-9(15)-46/10/1]; Russian Fund of Basic Research [15-01-02732

Potential role of immunotherapy in advanced non-small-cell lung cancer

Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD- 1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework.Pierre Fabr

Assessment of trace element pollution and its environmental risk to freshwater sediments influenced by anthropogenic contributions: The case study of Alqueva reservoir (Guadiana Basin)

The Guadiana Basin.(SW Iberian Peninsula) is affected by acid mine drainage (AMD), a consequence of ancient mining activities in the Iberian Pyrite Belt (IPB). Consequently, the sedimerits at the Alqueva reservoir (SE Portugal) in the Guadiana Basin are potentially contaminated by trace elements, which make important: (i) to characterize the status of trace element pollution of the sediments; (ii) to evaluate the mobility and the bioavailability of As, Cd, Cu, Cr, Pb and Zn; and (iii) to assess the environmental risk associated with the total and bioavailable concentrations of trace elements, using the sediment quality guidelines (SQGs) and the risk assessment code (RAC). Metal enrichment factors (EF) and geoaccumulation indexes (I-geo), determined taking into account the regional background levels, revealed that, among the metals analyzed, Cd contributed the highest to pollution levels followed by Pb and As. Despite the trace element contamination of the Alqueva sediments, the sequential extraction showed that Most of them are found in the oxidizable and residual fractions, which indicates that they are sparingly bioavailable, with exception of Cd (acid-labile fraction) and Pb (reducible fraction). Based on the RAC, Cd was the only metal that presented a high risk, while Pb, As and Zn showed a medium risk. Moreover, the SQGs revealed the existence of certain areas of extremely high risk, particularly related to high concentrations of total As and, in less extent, of Pb and Cd, associated with AMD, wastewater discharges and runoff of plant protection products from agricultural fields located near the reservoir. (C) 2015 Elsevier By. All rights reserved.FCT (Fundacao para a Ciencia e Tecnologia) [PTDC/AAC-AMB/103547/2008]; FEDER, through POFC (Eixo I - Programa Operacional Fatores de Competitividade) from QREN [COMPETE Re: FCOMP-01-0124-FEDER-008582]info:eu-repo/semantics/publishedVersio

Non-destructive soluble solids content determination for ‘Rocha’ Pear Based on VIS-SWNIR spectroscopy under ‘Real World’ sorting facility conditions

In this paper we report a method to determine the soluble solids content (SSC) of 'Rocha' pear (Pyrus communis L. cv. Rocha) based on their short-wave NIR reflectance spectra (500-1100 nm) measured in conditions similar to those found in packinghouse fruit sorting facilities. We obtained 3300 reflectance spectra from pears acquired from different lots, producers and with diverse storage times and ripening stages. The macroscopic properties of the pears, such as size, temperature and SSC were measured under controlled laboratory conditions. For the spectral analysis, we implemented a computational pipeline that incorporates multiple pre-processing techniques including a feature selection procedure, various multivariate regression models and three different validation strategies. This benchmark allowed us to find the best model/preproccesing procedure for SSC prediction from our data. From the several calibration models tested, we have found that Support Vector Machines provides the best predictions metrics with an RMSEP of around 0.82 ∘ Brix and 1.09 ∘ Brix for internal and external validation strategies respectively. The latter validation was implemented to assess the prediction accuracy of this calibration method under more 'real world-like' conditions. We also show that incorporating information about the fruit temperature and size to the calibration models improves SSC predictability. Our results indicate that the methodology presented here could be implemented in existing packinghouse facilities for single fruit SSC characterization.Funding Agency CEOT strategic project UID/Multi/00631/2019 project OtiCalFrut ALG-01-0247-FEDER-033652 Ideias em Caixa 2010, CAIXA GERAL DE DEPOSITOS Fundacao para a Ciencia e a Tecnologia (Ciencia)info:eu-repo/semantics/publishedVersio

Drosophila protein kinase N (Pkn) is a negative regulator of actin-myosin activity during oogenesis

Nurse cell dumping is an actin-myosin based process, where 15 nurse cells of a given egg chamber contract and transfer their cytoplasmic content through the ring canals into the growing oocyte. We isolated two mutant alleles of protein kinase N (pkn) and showed that Pkn negatively-regulates activation of the actin-myosin cytoskeleton during the onset of dumping. Using live-cell imaging analysis we observed that nurse cell dumping rates sharply increase during the onset of fast dumping. Such rate increase was severely impaired in pkn mutant nurse cells due to excessive nurse cell actin-myosin activity and/or loss of tissue integrity. Our work demonstrates that the transition between slow and fast dumping is a discrete event, with at least a five to six-fold dumping rate increase. We show that Pkn negatively regulates nurse cell actin-myosin activity. This is likely to be important for directional cytoplasmic flow. We propose Pim provides a negative feedback loop to help avoid excessive contractility after local activation of Rho GTPase. (C) 2014 Elsevier Inc. All rights reserved.National Portuguese Funding through Grants FCT-Fundacao para Ciencia e Tecnologia [PTDC/SAU-BID/111796/2009, PTDC/BIA-BCM/111822/2009, PTDC/BBB-BQB/0712/2012, PEst-OE/EQB/LA0023/2013]; Fundacao para Ciencia e Tecnologia [SFRH/BD/37587/2007]info:eu-repo/semantics/publishedVersio

Weighted Sobolev theorem with variable exponent for spatial and spherical potential operators

We prove Sobolev-type p((.)) -> q ((.))-theorems for the Riesz potential operator I-alpha in the weighted Lebesgue generalized spaces L-p(.)(R-n, p) with the variable exponent p (x) and a two-parametrical power weight fixed to an arbitrary finite point and to infinity, as well as similar theorems for a spherical analogue of the Riesz potential operator in the corresponding weighted spaces L-p(.)(S-n, p) on the unit sphere S-n in Rn+1. (c) 2005 Elsevier Inc. All rights reserved.info:eu-repo/semantics/publishedVersio

COPD and cardiovascular disease

COPD is one of the major public health problems in people aged 40 years or above. It is currently the 4th leading cause of death in the world and projected to be the 3rd leading cause of death by 2020. COPD and cardiac comorbidities are frequently associated. They share common risk factors, pathophysiological processes, signs and symptoms, and act synergistically as negative prognostic factors. Cardiac disease includes a broad spectrum of entities with distinct pathophysiology, treatment and prognosis. From an epidemiological point of view, patients with COPD are particularly vulnerable to cardiac disease. Indeed, mortality due to cardiac disease in patients with moderate COPD is higher than mortality related to respiratory failure. Guidelines reinforce that the control of comorbidities in COPD has a clear benefit over the potential risk associated with the majority of the drugs utilized. On the other hand, the true survival benefits of aggressive treatment of cardiac disease and COPD in patients with both conditions have still not been clarified. Given their relevance in terms of prevalence and prognosis, we will focus in this paper on the management of COPD patients with ischemic coronary disease, heart failure and dysrhythmia.Novartis Portugal Novartisinfo:eu-repo/semantics/publishedVersio