Franchisors' disclosure duty: market transparency and franchisee protection

The franchisee is usually the most vulnerable part of the franchise relationship, and should therefore receive greater protection from the legal framework. In this regard, the franchisor's pre-contractual disclosure duty has evolved in its legal status. Whereas its original purpose was to ensure transparency in the market, it now serves to protect the franchisee. In this paper, we compare the franchisor's obligations established by the legal framework in Spain with those set out in the Model Law drawn up by The International Institute for the Unification of Private Law.Lapiedra-Alcami, R.; Reig Fabado, I.; Rueda Armengot, C. (2014). Franchisors' disclosure duty: market transparency and franchisee protection. Service Industries Journal. 34(9-10):788-795. doi:10.1080/02642069.2014.905917S788795349-10Chaudey, M., & Fadairo, M. (2010). Contractual design and networks performance: empirical evidence from franchising. Applied Economics, 42(4), 529-533. doi:10.1080/00036840701704428Collins, H. (2008). Principles, Definitions and Model Rules of European Private Law: Draft Common Frame of Reference (DCFR) Interim Outline Edition, prepared by the Study Group on a European Civil Code and the Research group on EC Private Law (Acquis group) by Christian von Bar, Eric Clive, Hans Schulte-Nöcke (eds). Modern Law Review, 71(5), 840-844. doi:10.1111/j.1468-2230.2008.00718.xPeris-Ortiz, M., Peris Bonet, F. J., & Rueda-Armengot, C. (2011). Vertical integration in production and services: development in transaction cost economics. Service Business, 5(1), 87-97. doi:10.1007/s11628-011-0103-0Perryman, A. A., & Combs, J. G. (2011). Who should own it? An agency-based explanation for multi-outlet ownership and co-location in plural form franchising. Strategic Management Journal, 33(4), 368-386. doi:10.1002/smj.1947Rondan-Cataluña, F. J., Navarro-Garcia, A., Diez-De Castro, E. C., & Rodriguez-Rad, C. J. (2012). Reasons for the expansion in franchising: is it all said? The Service Industries Journal, 32(6), 861-882. doi:10.1080/02642069.2010.550041Shane, S. (2001). Organizational Incentives and Organizational Mortality. Organization Science, 12(2), 136-160. doi:10.1287/orsc.12.2.136.10108Vázquez, L. (2008). Complementarities between franchise contract duration and multi-unit propensity in franchise systems. The Service Industries Journal, 28(8), 1093-1105. doi:10.1080/0264206080218794

Protein-ligand complex for structure-based design: impact on the affinity and antitumor activity of new tubulin ligands

Resumen del trabajo presentado en el XVIII Congreso de la Sociedad Española de Química Terapéutica, celebrado en Salamanca (España), del 23 al 26 de enero de 2018Microtubules, made of ¿ß¿tubulin heterodimers, are the key components of the cytoskeleton and play a crucial role in many cellular processes, such as cell motility, morphogenesis and mitosis.[1] Interference with microtubule dynamics induces cell cycle arrest during mitosis and triggers cell death. Compounds that interact with tubulin, especially those binding at the colchicine domain, have been deeply investigated as anticancer drugs due to their dual mechanism of action as antimitotics and as vascular disrupting agents.[2,3] Our research group has recently described a new family of colchicine¿domain binders, based on a cyclohexanedione skeleton, with potent antiproliferative activity against tumor and endothelial cells.[4] Moreover, to gain insight into the binding mode of these cyclohexanediones, we have determined the crystal structure of ¿ß¿tubulin in complex with our hit compound (TUB075). Based on this detailed information and by applying the affinity maps program cGRILL, a structurebased synthesis of new cyclohexanedione derivatives has been accomplished with the objective of improving their affinity for tubulin and their antitumor activity. Following this approach, we have obtained new compounds with potent antiproliferative activity against tumor and endothelial cells (IC50=8¿31 nM) and with the highest Kb value reported for compounds binding at the colchicine site in tubulin. Additional studies have shown that they arrest cell cycle at G2/M and disrupt a network of endothelial cells. Moreover they keep antiproliferative activity against cell lines overexpressing P¿gp, further supporting the potential of these compounds.The financial support of the Spanish MINECO (SAF2012‐39760‐C02‐01 and SAF 2015‐64629‐C2‐1‐R), Comunidad de Madrid (BIPEDD2; ref P2010/BMD‐2457) and the COST action CM1407 (to M J. P.P., S.L., M.O.S. and J.F.D.) is sincerely acknowledge

Antivascular and antitumor properties of the tubulin-binding chalcone TUB091

We investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series of chalcones, whose prototype compound is (E)-3-(3’’-amino-4’’-methoxyphenyl)-1-(5’-methoxy-3’,4’-methylendioxyphenyl)- 2-methylprop-2-en-1-one (TUB091). X-ray crystallography showed that these chalcones bind to the colchicine site of tubulin and therefore prevent the curved-tostraight structural transition of tubulin, which is required for microtubule formation. Accordingly, TUB091 inhibited cancer and endothelial cell growth, induced G2/M phase arrest and apoptosis at 1-10 nM. In addition, TUB091 displayed vascular disrupting effects in vitro and in the chicken chorioallantoic membrane (CAM) assay at low nanomolar concentrations. A water-soluble L-Lys-L-Pro derivative of TUB091 (i.e. TUB099) showed potent antitumor activity in melanoma and breast cancer xenograft models by causing rapid intratumoral vascular shutdown and massive tumor necrosis. TUB099 also displayed anti-metastatic activity similar to that of combretastatin A4-phosphate. Our data indicate that this novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs). Moreover, we provide evidence that our prodrug approach may be valuable for the development of anti-cancer drugs.M-DC thanks the Fondo Social Europeo (FSE) and the JAE Predoc Programme for a predoctoral fellowship. This work has received the Ramón Madroñero award for young researchers (to M-DC and OB) in the XVII call www.impactjournals.com/oncotarget 17 Oncotarget sponsored by the Spanish Society of Medicinal Chemistry (SEQT). This project has been supported by the Spanish Ministerio de Economia y Competitividad (SAF2012- 39760-C02-01 to M-JC, M-JP-P, SV and E-MP; and BIO2013-42984-R to JFD), Comunidad de Madrid (BIPEDD2; ref. P2010/BMD-2457 to M-JC and J-FD), the Swiss National Science Foundation (310030B_138659 and 31003A_166608; to MOS). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery” and COST action CM1470.Peer reviewe

Physics of Solar Prominences: II - Magnetic Structure and Dynamics

Observations and models of solar prominences are reviewed. We focus on non-eruptive prominences, and describe recent progress in four areas of prominence research: (1) magnetic structure deduced from observations and models, (2) the dynamics of prominence plasmas (formation and flows), (3) Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and large-scale patterns of the filament channels in which prominences are located. Finally, several outstanding issues in prominence research are discussed, along with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape

A search for point sources of EeV photons

Measurements of air showers made using the hybrid technique developed with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for point sources of EeV photons anywhere in the exposed sky. A multivariate analysis reduces the background of hadronic cosmic rays. The search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been detected. An upper limit on the photon flux has been derived for every direction. The mean value of the energy flux limit that results from this, assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in which EeV cosmic ray protons are emitted by non-transient sources in the Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical Journa

Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory

On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within $\pm 500$ s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory

The azimuthal asymmetry in the risetime of signals in Auger surface detector stations is a source of information on shower development. The azimuthal asymmetry is due to a combination of the longitudinal evolution of the shower and geometrical effects related to the angles of incidence of the particles into the detectors. The magnitude of the effect depends upon the zenith angle and state of development of the shower and thus provides a novel observable, $(\sec \theta)_\mathrm{max}$, sensitive to the mass composition of cosmic rays above $3 \times 10^{18}$ eV. By comparing measurements with predictions from shower simulations, we find for both of our adopted models of hadronic physics (QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass increases slowly with energy, as has been inferred from other studies. However, the mass estimates are dependent on the shower model and on the range of distance from the shower core selected. Thus the method has uncovered further deficiencies in our understanding of shower modelling that must be resolved before the mass composition can be inferred from $(\sec \theta)_\mathrm{max}$.Comment: Replaced with published version. Added journal reference and DO

Reconstruction of inclined air showers detected with the Pierre Auger Observatory

We describe the method devised to reconstruct inclined cosmic-ray air showers with zenith angles greater than $60^\circ$ detected with the surface array of the Pierre Auger Observatory. The measured signals at the ground level are fitted to muon density distributions predicted with atmospheric cascade models to obtain the relative shower size as an overall normalization parameter. The method is evaluated using simulated showers to test its performance. The energy of the cosmic rays is calibrated using a sub-sample of events reconstructed with both the fluorescence and surface array techniques. The reconstruction method described here provides the basis of complementary analyses including an independent measurement of the energy spectrum of ultra-high energy cosmic rays using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of Cosmology and Astroparticle Physics (JCAP

The Pierre Auger Observatory: Contributions to the 34th International Cosmic Ray Conference (ICRC 2015)

Contributions of the Pierre Auger Collaboration to the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The NetherlandsComment: 24 proceedings, the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The Netherlands; will appear in PoS(ICRC2015

Calibration of the Logarithmic-Periodic Dipole Antenna (LPDA) Radio Stations at the Pierre Auger Observatory using an Octocopter

An in-situ calibration of a logarithmic periodic dipole antenna with a frequency coverage of 30 MHz to 80 MHz is performed. Such antennas are part of a radio station system used for detection of cosmic ray induced air showers at the Engineering Radio Array of the Pierre Auger Observatory, the so-called Auger Engineering Radio Array (AERA). The directional and frequency characteristics of the broadband antenna are investigated using a remotely piloted aircraft (RPA) carrying a small transmitting antenna. The antenna sensitivity is described by the vector effective length relating the measured voltage with the electric-field components perpendicular to the incoming signal direction. The horizontal and meridional components are determined with an overall uncertainty of 7.4^{+0.9}_{-0.3} % and 10.3^{+2.8}_{-1.7} % respectively. The measurement is used to correct a simulated response of the frequency and directional response of the antenna. In addition, the influence of the ground conductivity and permittivity on the antenna response is simulated. Both have a negligible influence given the ground conditions measured at the detector site. The overall uncertainties of the vector effective length components result in an uncertainty of 8.8^{+2.1}_{-1.3} % in the square root of the energy fluence for incoming signal directions with zenith angles smaller than 60{\deg}.Comment: Published version. Updated online abstract only. Manuscript is unchanged with respect to v2. 39 pages, 15 figures, 2 table