Biblos-e Archivo

    Automating the transformation-based analysis of visual languages

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    The final publication is available at Springer via present a novel approach for the automatic generation of model-to-model transformations given a description of the operational semantics of the source language in the form of graph transformation rules. The approach is geared to the generation of transformations from Domain-Specific Visual Languages (DSVLs) into semantic domains with an explicit notion of transition, like for example Petri nets. The generated transformation is expressed in the form of operational triple graph grammar rules that transform the static information (initial model) and the dynamics (source rules and their execution control structure). We illustrate these techniques with a DSVL in the domain of production systems, for which we generate a transformation into Petri nets. We also tackle the description of timing aspects in graph transformation rules, and its analysis through their automatic translation into Time Petri netsWork sponsored by the Spanish Ministry of Science and Innovation, project METEORIC (TIN2008-02081/TIN) and by the Canadian Natural Sciences and Engineering Research Council (NSERC)

    Bilateral and unilateral load-velocity profiling in a machine-based, single-joint, lower body exercise

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    To analyze the goodness of fit of the load-velocity relationship in a machine-based, single-joint exercise performed both in a bilateral and unilateral manner, as well as to study its accuracy to estimate one repetition maximum (1-RM). Methods Fifteen resistance trained males performed an incremental test in the bilateral and unilateral leg extension exercise up to the 1-RM in two separate occasions. Mean vertical velocity of the weight plates in the leg extension machine was measured for every repetition using a smartphone application (My Lift). Results Linear regression analyses showed a high goodness of fit (R2 > 0.93) and small standard errors of estimate (SEE 1.0, p 0.05). Conclusions This proof of concept highlights that computing load-velocity relationships in a machine-based, single-joint, angular exercise can be appropriately performed by measuring the mean vertical velocity of the weight plates. These results could help strength and conditioning researchers and coaches who wish to analyze load-velocity relationship in other common machine-based exercise

    Massive spin 2 excitations in AdS6 × S2 warped spacetimes

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    We study (massive) spin-2 fluctuations around warped AdS6 solutions with 16 supersymmetries in type IIB supergravity. We identify two classes of fluctuations which are universally present for all solutions of this form. The holographically dual operators have scaling dimensions ∆ = 5 + 3` and ∆ = 6 + 3`, where the integer ` encodes the R-symmetry charge. They are identified as descendant states in respective BPS multiplets (the current multiplet for ∆ = 5). We also compute the normalization of the energy-momentum tensor two-point function and show that it is related to the S 5 partition function of the dual 5d SCFTsThe work of MG and CFU is supported in part by the National Science Foundation under grant PHY- 16-19926. OV is supported by NSF grant PHY-1720364 and, partially, by grant FPA2015-65480-P (MINECO/FEDER UE) from the Spanish Government. MG is grateful to the International Solvay Institutes, ULB, Brussels for hospitality while this paper was finalize

    Towards extensible structural analysis of Petri Net product lines

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    In order to represent the behaviour of a (potentially large) set of concurrent systems, we propose a notion of product line of Petri nets, where presence conditions can be flexibly attached to places, transitions and arcs. To enable an efficient analysis of the whole set of nets, we have lifted several structural analysis methods for Petri nets, to the product line level. This avoids analysing each particular net in isolation. Finally, we propose an extensible tool infrastructure, based on Eclipse and on top of FeatureIDE, which supports the approach and permits adding new analysis methods in a non-intrusive wayWork funded by the Spanish Ministry of Science (project MASSIVE, RTI2018-095255- B-I00) and the R&D programme of Madrid (project FORTE, P2018/TCS-4314

    Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy

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    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality. Objective The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT. Material and methods Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated. Results The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94–159.8) Conclusion Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapyThis project received support from the Instituto de Salud Carlos III and Fondos Feder Europeos, MINECO (FIS PI15/00974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

    Distinguishing features of cetuximab and panitumumab in colorectal cancer and other solid tumors

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    Cetuximab and panitumumab are two distinct monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR), and both are widely used in combination with chemotherapy or as monotherapy to treat patients with RAS wild-type metastatic colorectal cancer. Although often considered interchangeable, the two antibodies have different molecular structures and can behave differently in clinically relevant ways. More specifically, as an immunoglobulin (Ig) G1 isotype mAb, cetuximab can elicit immune functions such as antibody-dependent cell-mediated cytotoxicity involving natural killer cells, T-cell recruitment to the tumor, and T-cell priming via dendritic cell maturation. Panitumumab, an IgG2 isotype mAb, does not possess these immune functions. Furthermore, the two antibodies have different binding sites on the EGFR, as evidenced by mutations on the extracellular domain that can confer resistance to one of the two therapeutics or to both. We consider a comparison of the properties of these two antibodies to represent a gap in the literature. We therefore compiled a detailed, evidence-based educational review of the known molecular, clinical, and functional differences between the two antibodies and concluded that they are distinct therapeutic agents that should be considered individually during treatment planning. Available data for one agent can only partly be extrapolated to the other. Looking to the future, the known immune activity of cetuximab may provide a rationale for this antibody as a combination partner with investigational chemotherapy plus immunotherapy regimens for colorectal cance

    Towards a model of normative diagnosis in the organizational context: The evaluative model of normative appeals

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    Purpose: The aim of the present work is to advance in a topic that has received little attention in the literature: normative diagnosis; contributing new empirical evidence to a recently proposed model: The Evaluative Model of Normative Appeals (EMNA). Design/methodology: Two field studies were carried out. In Study 1 we tested the EMNA premises by appraising a normative appeal in a university organizational context (N = 304). In Study 2, we contributed to the predictive validity of the model by analyzing the perception and adherence with two normative appeals in the context of labor organizations (N = 296). Findings: The results of both studies supported the premises of the EMNA and its potential as a normative diagnostic tool for the organizational context. Research limitations/implications: The EMNA should be analyzed in relation to other models in order to complement its explanatory and diagnostic value. The results obtained and the validity of the scales should be tested in new samples from different countries. Practical implications: From an applied point of view, the EMNA represents a tool to support the diagnosis and management of organizational normative appeals in at least two situations: in establishing predictions regarding levels of adherence or willingness to comply, and in monitoring the effectiveness of the measures that have been adopted to modify the perception of certain regulations. Social implications: The transgression of the rules generates large direct (e.g., money laundering, corruption) and indirect losses (e.g., loss of prestige, dysfunctional behavior), so achieving more efficient regulatory management is a constant challenge, both socially and organizationally. The present work represents an advance in the challenge of reducing the levels of transgression and its associated costs. Originality/value: The present work provides complementary evidence that supports the utility of a recently proposed model, as a tool for normative diagnosis in the organizational field.This work has been supported mainly by the “Programa CONICYT, FONDECYT Iniciación 11130710 (Chile)”; and to a lesser extent, by the “Universidad de La Frontera, Proyecto DIUFRO DI15-0056”; and by the “Convenio de Desempeño Regional, FRO 1301”

    Segmentally homologous neurons acquire two different terminal neuropeptidergic fates in the Drosophila nervous system

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    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In this study, we identify the means by which segmentally homologous neurons acquire different neuropeptide fates in Drosophila. Ventral abdominal (Va)-neurons in the A1 segment of the ventral nerve cord express DH31 and AstA neuropeptides (neuropeptidergic fate I) by virtue of Ubx activity, whereas the A2-A4 Va-neurons express the Capa neuropeptide (neuropeptidergic fate II) under the influence of abdA. These different fates are attained through segment-specific programs of neural subtype specification undergone by segmentally homologous neurons. This is an attractive alternative by which Hox genes can shape Drosophila segmental neural architecture (more sophisticated than the previously identified binary “to live” or “not to live” mechanism). These data refine our knowledge of the mechanisms involved in diversifying neuronal identity within the central nervous systemThis study was supported by grant number: BFU2013-43858-

    A new family of nitrate/nitrite transporters involved in denitrification

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    Denitrifying bacteria carry out nitrate and nitrite respiration inside and outside the cell, respectively. In Thermus thermophilus, nitrate and nitrite transport processes are carried out by major facilitator superfamily (MFS) transporters. The sequence of the nar operon of nitrate-only respiring strains of T. thermophilus includes two tandemly organized MFS transporter genes (narK and narT) of the NarK1 and NarK2 families. Both can function as nitrate/nitrite antiporters, but NarK has been proposed as more specific for nitrate whereas NarT more specific for nitrite. In some nitrate- and nitrite-respiring strains of the same species, a single MFS transporter (NarO) belonging to a different MFS subfamily appears. To analyze the role of this single MFS in the same genetic context, we transferred the two types of nar operon to the aerobic strain HB27, and further included in both of them the ability to respire nitrite. The new denitrifying strains HB27dn, with two MFS, and HB27dp, with a single one, were used to isolate mutants devoid of transporters. Through in trans complementation experiments, we demonstrate that the NarO single MFS works efficiently in the transport of both nitrate and nitrite.This work was supported by grant BIO2016-77031-R from the Spanish Ministry of Economy and Competitiveness. An institutional grant from Fundación Ramón Areces to the CBMSO is also acknowledge

    Andreev spectrum and supercurrents in nanowire-based SNS junctions containing Majorana bound states

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    Hybrid superconductor-semiconductor nanowires with Rashba spin-orbit coupling are arguably becoming the leading platform for the search of Majorana bound states (MBSs) in engineered topological superconductors. We perform a systematic numerical study of the low-energy Andreev spectrum and supercurrents in short and long superconductor-normal-superconductor junctions made of nanowires with strong Rashba spin-orbit coupling, where an external Zeeman field is applied perpendicular to the spin-orbit axis. In particular, we investigate the detailed evolution of the Andreev bound states from the trivial into the topological phase and their relation with the emergence of MBSs. Due to the finite length, the system hosts four MBSs, two at the inner part of the junction and two at the outer one. They hybridize and give rise to a finite energy splitting at a superconducting phase difference of p, a wellvisible effect that can be traced back to the evolution of the energy spectrum with the Zeeman field: from the trivial phase with Andreev bound states into the topological phase with MBSs. Similarly, we carry out a detailed study of supercurrents for short and long junctions from the trivial to the topological phases. The supercurrent, calculated from the Andreev spectrum, is 2p-periodic in the trivial and topological phases. In the latter it exhibits a clear sawtooth profile at a phase difference of p when the energy splitting is negligible, signalling a strong dependence of current-phase curves on the length of the superconducting regions. Effects of temperature, scalar disorder and reduction of normal transmission on supercurrents are also discussed. Further, we identify the individual contribution of MBSs. In short junctions the MBSs determine the current-phase curves, while in long junctions the spectrum above the gap (quasi-continuum) introduces an important contributionJ.C. thanks O. A. Awoga, K. Björnson, M. Benito and S. Pradhan for motivating and helpful discussions. J.C. and A.B.S. acknowledge financial support from the Swedish Research Council (Vetenskapsrådet), the Göran Gustafsson Foundation, the Swedish Foundation for Strategic Research (SSF), and the Knut and Alice Wallenberg Foundation through the Wallenberg Academy Fellows program. We also acknowledge financial support from the Spanish Ministry of Economy and Competitiveness through Grant No. FIS2015-64654-P (R. A.), FIS2016-80434-P (AEI/FEDER, EU) (E. P.) and the Ramón y Cajal programme through grant No. RYC-2011-09345 (E. P
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