Proving the performance of a new revenue management system

Revenue management (RM) is a complicated business process that can best be described ascontrol of sales (using prices, restrictions, or capacity), usually using software as a tool to aiddecisions. RM software can play a mere informative role, supplying analysts with formatted andsummarized data who use it to make control decisions (setting a price or allocating capacity fora price point), or, play a deeper role, automating the decisions process completely, at the otherextreme. The RM models and algorithms in the academic literature by and large concentrateon the latter, completely automated, level of functionality.A firm considering using a new RM model or RM system needs to evaluate its performance.Academic papers justify the performance of their models using simulations, where customerbooking requests are simulated according to some process and model, and the revenue perfor-mance of the algorithm compared to an alternate set of algorithms. Such simulations, whilean accepted part of the academic literature, and indeed providing research insight, often lackcredibility with management. Even methodologically, they are usually awed, as the simula-tions only test \within-model" performance, and say nothing as to the appropriateness of themodel in the first place. Even simulations that test against alternate models or competition arelimited by their inherent necessity on fixing some model as the universe for their testing. Theseproblems are exacerbated with RM models that attempt to model customer purchase behav-ior or competition, as the right models for competitive actions or customer purchases remainsomewhat of a mystery, or at least with no consensus on their validity.How then to validate a model? Putting it another way, we want to show that a particularmodel or algorithm is the cause of a certain improvement to the RM process compared to theexisting process. We take care to emphasize that we want to prove the said model as the causeof performance, and to compare against a (incumbent) process rather than against an alternatemodel.In this paper we describe a \live" testing experiment that we conducted at Iberia Airlineson a set of flights. A set of competing algorithms control a set of flights during adjacentweeks, and their behavior and results are observed over a relatively long period of time (9months). In parallel, a group of control flights were managed using the traditional mix of manualand algorithmic control (incumbent system). Such \sandbox" testing, while common at manylarge internet search and e-commerce companies is relatively rare in the revenue managementarea. Sandbox testing has an undisputable model of customer behavior but the experimentaldesign and analysis of results is less clear. In this paper we describe the philosophy behind theexperiment, the organizational challenges, the design and setup of the experiment, and outlinethe analysis of the results. This paper is a complement to a (more technical) related paper thatdescribes the econometrics and statistical analysis of the results.

Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T Lymphocytes during cell polarization

During activation, T lymphocytes become motile cells, switching from a spherical to a polarized shape. Chemokines and other chemotactic cytokines induce lymphocyte polarization with the formation of a uropod in the rear pole, where the adhesion receptors intercellular adhesion molecule-1 (ICAM-1), ICAM-3, and CD44 redistribute. We have investigated membrane-cytoskeleton interactions that play a key role in the redistribution of adhesion receptors to the uropod. Immunofluorescence analysis showed that the ERM proteins radixin and moesin localized to the uropod of human T lymphoblasts treated with the chemokine RANTES (regulated on activation, normal T cell expressed, and secreted), a polarization-inducing agent; radixin colocalized with arrays of myosin II at the neck of the uropods, whereas moesin decorated the most distal part of the uropod and colocalized with ICAM-1, ICAM-3, and CD44 molecules. Two other cytoskeletal proteins, ß-actin and ¿-tubulin, clustered at the cell leading edge and uropod, respectively, of polarized lymphocytes. Biochemical analysis showed that moesin coimmunoprecipitates with ICAM-3 in T lymphoblasts stimulated with either RANTES or the polarization- inducing anti-ICAM-3 HP2/19 mAb, as well as in the constitutively polarized T cell line HSB-2. In addition, moesin is associated with CD44, but not with ICAM-1, in polarized T lymphocytes. A correlation between the degree of moesin-ICAM-3 interaction and cell polarization was found as determined by immunofluorescence and immunoprecipitation analysis done in parallel. The moesin-ICAM-3 interaction was specifically mediated by the cytoplasmic domain of ICAM-3 as revealed by precipitation of moesin with a GST fusion protein containing the ICAM-3 cytoplasmic tail from metabolically labeled Jurkat T cell lysates. The interaction of moesin with ICAM-3 was greatly diminished when RANTES-stimulated T lymphoblasts were pretreated with the myosin-disrupting drug butanedione monoxime, which prevents lymphocyte polarization. Altogether, these data indicate that moesin interacts with ICAM-3 and CD44 adhesion molecules in uropods of polarized T cells; these data also suggest that these interactions participate in the formation of links between membrane receptors and the cytoskeleton, thereby regulating morphological changes during cell locomotion.

Impairment of the Bacterial Biofilm Stability by Triclosan

The accumulation of the widely-used antibacterial and antifungal compound triclosan (TCS) in freshwaters raises concerns about the impact of this harmful chemical on the biofilms that are the dominant life style of microorganisms in aquatic systems. However, investigations to-date rarely go beyond effects at the cellular, physiological or morphological level. The present paper focuses on bacterial biofilms addressing the possible chemical impairment of their functionality, while also examining their substratum stabilization potential as one example of an important ecosystem service. The development of a bacterial assemblage of natural composition – isolated from sediments of the Eden Estuary (Scotland, UK) – on non-cohesive glass beads (,63 mm) and exposed to a range of triclosan concentrations (control, 2 – 100 mg L21) was monitored over time by Magnetic Particle Induction (MagPI). In parallel, bacterial cell numbers, division rate, community composition (DGGE) and EPS (extracellular polymeric substances: carbohydrates and proteins) secretion were determined. While the triclosan exposure did not prevent bacterial settlement, biofilm development was increasingly inhibited by increasing TCS levels. The surface binding capacity (MagPI) of the assemblages was positively correlated to the microbial secreted EPS matrix. The EPS concentrations and composition (quantity and quality) were closely linked to bacterial growth, which was affected by enhanced TCS exposure. Furthermore, TCS induced significant changes in bacterial community composition as well as a significant decrease in bacterial diversity. The impairment of the stabilization potential of bacterial biofilm under even low, environmentally relevant TCS levels is of concern since the resistance of sediments to erosive forces has large implications for the dynamics of sediments and associated pollutant dispersal. In addition, the surface adhesive capacity of the biofilm acts as a sensitive measure of ecosystem effects

Emerging functions of myelin associated proteins during development neuronal plasticity and and neurpdegeneration.

Adult mammalian central nervous system (CNS) axons have a limited regrowth capacity following injury. Myelin-associated inhibitors (MAIs) limit axonal outgrowth and their blockage improves the regeneration of damaged fiber tracts. Three of these proteins, Nogo-A, MAG and OMgp, share two common neuronal receptors: NgR1, together with its co-receptors (p75(NTR), TROY and Lingo-1), and the recently described paired immunoglobulin-like receptor B (PirB). These proteins impair neuronal regeneration by limiting axonal sprouting. Some of the elements involved in the myelin inhibitory pathways may still be unknown, but the discovery that blocking both PirB and NgR1 activities leads to near-complete release from myelin inhibition, sheds light on one of the most competitive and intense fields of neuroregeneration study during in recent decades. In parallel with the identification and characterization of the roles and functions of these inhibitory molecules in axonal regeneration, data gathered in the field strongly suggest that most of these proteins have roles other than axonal growth inhibition. The discovery of a new group of interacting partners for myelin-associated receptors and ligands, as well as functional studies within or outside the CNS environment, highlights the potential new physiological roles for these proteins in processes such as development, neuronal homeostasis, plasticity and neurodegeneration.

El rol del paciente experto en el tratamiento de las adicciones: una propuesta para paliar las altas tasas de abandono prematuro en comunidades terapéuticas

El objetivo de este estudio recae en cómo y de qué forma el ex adicto a sustancias alteradoras del ánimo (E-ASAA), cursando por el estadio de mantenimiento, puede ejercer el rol de asesor y promotor de salud, como “Paciente Experto”, conjuntamente con los profesionales especializados en drogodependencias. Paralelamente este “cómo y de qué forma” viene a dar respuesta a una necesidad existente en las Comunidades Terapéuticas, a saber, reducir las Altas Voluntarias (AV) de los residentes recién incorporados y tras su Alta Terapéutica (AT). Sin embargo, se requiere de una investigación de tipo cualitativo para determinar los factores desencadenantes que inducen a esta prevalencia de AV y recaídas post-AT. Los resultados extraídos de la investigación a informantes clave muestran como existe un deficitario asesoramiento pre-entrada y acompañamiento post-AT. El E-ASAA, debidamente formado, podría dar respuesta a estas demandas asistenciales, mejorando así la completa reinserción de los usuarios de CCTT. La Propuesta del Proyecto “Mi amigo de Comunidad” integra este conocimiento aportando soluciones.

Estudi del procés de neurodegeneració

Les anomenades malalties neurodegeneratives tenen una simptomatologia i unes manifestacions clíniques molt diferents entre elles. No obstant, totes elles convergeixen en el mateix procés final, la neurodegeneració, que es manifestarà en diferents localitzacions o tipus cel·lulars del sistema nerviós. Nosaltres, plantegem la hipòtesi de que els processos moleculars i cel·lulars subjacents a la neurodegeneració són comuns per totes elles. Després de dur a terme un procés de selecció, es decideix treballar amb la malaltia de Parkinson, la d’Alzheimer, l’Esclerosi lateral amiotròfica i l’esclerosi múltiple. Hem pogut determinar que hi ha set processos moleculars o cel·lulars que estan associats al procés de neurodegeneració i que són comuns a totes elles. Havent-les estudiat per separat s’observa que el procés de neurodegeneració consisteix en una fallada en cadena de diferents sistemes moleculars i cel·lulars que tenen com a punt d’origen l’estrès oxidatiu. A aquest estrès s’hi pot arribar de diferents maneres. Una d’elles és l’exposició excessiva a certs metalls, que provoca la pèrdua dels sistemes antioxidants cel·lulars. Degut a això, els mitocondris reben un impacte oxidatiu massa gran i comencen a fallar. El fet que aquest orgànul actuï com a tampó del calci intracel·lular en provoca la seva desregulació, alterant d’aquesta manera el senyal nerviós. En resposta a l’estrès oxidatiu i tèrmic que genera la disfunció mitocondrial, s’activen les Proteïnes de Xoc Tèrmic (HSP) que actuant de citocines i presentadores d’antígens, inicien la resposta immunològica contra les cèl·lules danyades. Paral·lelament, s’observa un increment de la permeabilitat de la barrera hematoencefàlica degut a la pèrdua de les adhesions cel·lulars estretes per l’alta presència d’espècies reactives. Com a conseqüència de l’afebliment o el trencament de la barrera hematoencefàlica, es pot produir una entrada al SNC de diferents substàncies neurotòxiques i de cèl·lules del sistema immunitàri que, en condicions normals tenen l’accés restringit. Juntament amb aquestes cèl·lules immunològiques, també s’activen les cèl·lules del sistema immunitari innat residents al cervell, la micròglia, i totes elles secreten citocines proinflamatòries que contribueixen al procés de neurodegeneració. Nosaltres presentem els mecanismes pels quals aquesta inflamació, lluny d’atenuar-se, es cronifica per l’acció de certs bucles de retroalimentació positiva. Les diferents peculiaritats de cada malaltia contribueixen en aquest procés de diferents maneres, com és el cas dels pèptids β-amilides en la malaltia d’Alzheimer, l’α-sinucleina en el Parkinson, la superòxid dismutasa (SOD) en l’esclerosi lateral amiotròfica, o l’infiltració de leucòcits al cervell degut a la resposta autoimmune de l’esclerosi múltiple.Deixant de banda aquestes diferències, si el procés és comú entre totes elles, l’estudi a fons d’aquest procés hauria de poder permetre identificar dianes tarapèutiques que siguin comunes per les quatre malalties.

European Integration: Partisan Motives or Economic Benefits?

In this paper we examine the influence of economic factors to explain partisan support for European integration over the last three decades. We find that partisan support is larger in `poorer' countries with direct economic bene fits from EU membership. On the contrary, parties in countries aff ected by the Maastricht criteria are more Euro-sceptical. Moreover, we find weak evidence for larger partisan support in countries with more developed welfare states, and that the support for European integration fluctuates in parallel with the business cycle. Finally, our results indicate that the importance of economic factors in determining partisan support for European integration has grown in recent periods. JEL classi fication: F15, F42, F53, F55, H60. Key words: European Integration; Partisan Ideology; Maastricht Criteria; European Budget; Benefi ts from Trade.

Systematic review protocol to define classical IgE-associated diseases from birth to adolescence: the MeDALL study

BACKGROUND: Classical disease phenotypes are mainly based on descriptions of symptoms and the hypothesis that a given pattern of symptoms provides a diagnosis. With refined technologies there is growing evidence that disease expression in patients is much more diverse and subtypes need to be defined to allow a better targeted treatment. One of the aims of the Mechanisms of the Development of Allergy Project (MeDALL,FP7) is to re-define the classical phenotypes of IgE-associated allergic diseases from birth to adolescence, by consensus among experts using a systematic review of the literature and identify possible gaps in research for new disease markers. This paper describes the methods to be used for the systematic review of the classical IgE-associated phenotypes applicable in general to other systematic reviews also addressing phenotype definitions based on evidence. METHODS/DESIGN: Eligible papers were identified by PubMed search (complete database through April 2011). This search yielded 12,043 citations. The review includes intervention studies (randomized and clinical controlled trials) and observational studies (cohort studies including birth cohorts, case-control studies) as well as case series. Systematic and non-systematic reviews, guidelines, position papers and editorials are not excluded but dealt with separately. Two independent reviewers in parallel conducted consecutive title and abstract filtering scans. For publications where title and abstract fulfilled the inclusion criteria the full text was assessed. In the final step, two independent reviewers abstracted data using a pre-designed data extraction form with disagreements resolved by discussion among investigators. DISCUSSION: The systematic review protocol described here allows to generate broad,multi-phenotype reviews and consensus phenotype definitions. The in-depth analysis of the existing literature on the classification of IgE-associated allergic diseases through such a systematic review will 1) provide relevant information on the current epidemiologic definitions of allergic diseases, 2) address heterogeneity and interrelationships and 3) identify gaps in knowledge.

Evolución de la mortalidad por cáncer de mama y diseminación de la mamografía de cribado en Cataluña: un análisis por regiones sanitarias

Fundamento: El descenso de las tasas de mortalidad por cáncer de mama (CM) se ha atribuido a la implantación de programas de cribado y a avances terapéuticos. El objetivo de este trabajo es comparar la evolución de su mortalidad en las regiones sanitarias de Cataluña en el periodo 1993-2007. Paralelamente, se ha analizado la diseminación de la mamografía periódica en las regiones sanitarias. Métodos: Se analizaron los datos del registro de mortalidad y encuestas de salud. Se utilizaron regresiones de Poisson y «joinpoint» para comparar las tasas de mortalidad por CM y analizar su evolución temporal. Se utilizaron modelos de efectos mixtos para comparar el nivel y la evolución de la mortalidad por regiones. Resultados. La tasa de mortalidad por CM descendió un 3% anual en Cataluña. Entre 1993 y 2007, la tasa estandarizada varió de 34,8 a 23,3 por 100.000 mujeres. Barcelona ciutat presentó unas tasas de mortalidad más elevadas que las regiones Centre (ratio de tasas (RT)=0,87), Costa de Ponent (RT=0,89), Tarragona (RT=0,9) y Lleida (RT=0,915), pero estas diferencias tendieron a desaparecer. No se observaron cambios de tendencia en la evolución de la mortalidad de las regiones, excepto en la región Centre. Durante los años 1990 Barcelona ciutat presentó unos porcentajes de utilización de mamografía periódica del 36,1% de las mujeres de 40-74 años, en la encuesta de 1994, la región Centre (23,7%) y Costa de Ponent (25,2%). Conclusiones: La progresiva utilización de mamografía periódica y la disminución de la mortalidad por CM fueron similares en las regiones sanitarias de Cataluña.

Review. Characterization and selection of hexaploid wheats containing resistance to Heterodera avenae or Mayetiola destructor introgressed from Aegilops

Cereal cyst nematode (CCN, Heterodera avenae) and Hessian fly (HF, Mayetiola destructor) are two major pests affecting wheat crops worldwide including important cereal areas of Spain. Aegilops ventricosa and Ae. triuncialis were used as donors in a strategy to introduce resistance genes (RG) for these pests in hexaploid wheat (Triticum aestivum L.). Two 42 chromosomes introgression lines have been derived from Ae. ventricosa: H-93-8 and H-93-33 carrying genes Cre2 and H27 conferring resistance to CCN and HF, respectively. Line TR-3531 with 42 chromosomes has been derived from Ae. triuncialis and carries RGs conferring resistance for CCN (Cre7) and for HF (H30). Alien material has been incorporated in lines H-93 by chromosomal substitution and recombination, while in line TR-3531 homoeologous recombination affecting small DNA fragments has played a major role. It has been demonstrated that Cre2, Cre7, H27 and H30 are major single dominant genes and not allelic of other previously described RGs. Biochemical and molecular-biology studies of the defense mechanism triggered by Cre2 and Cre7 have revealed specific induction of peroxidase and other antioxidant enzymes. In parallel to these basic studies advanced lines carrying resistance genes for CNN and/or HF have been developed. Selection was done using molecular markers for eventually «pyramiding» resistance genes. Several isozyme and RAPD markers have been described and, currently, new markers based on transposable elements and NBS-LRR sequences are being developed. At present, two advanced lines have already been included at the Spanish Catalogue of Commercial Plant Varieties.

Reexposure and advection of C-14-depleted organic carbon from old deposits at the upper continental slope

Outcrops of old strata at the shelf edge resulting from erosive gravity-driven flows have been globally described on continental margins. The reexposure of old strata allows for the reintroduction of aged organic carbon (OC), sequestered in marine sediments for thousands of years, into the modern carbon cycle. This pool of reworked material represents an additional source of C-14-depleted organic carbon supplied to the ocean, in parallel with the weathering of fossil organic carbon delivered by rivers from land. To understand the dynamics and implications of this reexposure at the shelf edge, a biogeochemical study was carried out in the Gulf of Lions (Mediterranean Sea) where erosive processes, driven by shelf dense water cascading, are currently shaping the seafloor at the canyon heads. Mooring lines equipped with sediment traps and current meters were deployed during the cascading season in the southwestern canyon heads, whereas sediment cores were collected along the sediment dispersal system from the prodelta regions down to the canyon heads. Evidence from grain-size, X-radiographs and Pb-210 activity indicate the presence in the upper slope of a shelly-coarse surface stratum overlying a consolidated deposit. This erosive discontinuity was interpreted as being a result of dense water cascading that is able to generate sufficient shear stress at the canyon heads to mobilize the coarse surface layer, eroding the basal strata. As a result, a pool of aged organic carbon (Delta C-14 = -944.5 +/- 24.7%; mean age 23,650 +/- 3,321 ybp) outcrops at the modern seafloor and is reexposed to the contemporary carbon cycle. This basal deposit was found to have relatively high terrigenous organic carbon (lignin = 1.48 +/- 0.14 mg/100 mg OC), suggesting that this material was deposited during the last low sea-level stand. A few sediment trap samples showed anomalously depleted radiocarbon concentrations (Delta C-14 = -704.4 +/- 62.5%) relative to inner shelf (Delta C-14 = -293.4 +/- 134.0%), mid-shelf (Delta C-14 = -366.6 +/- 51.1%), and outer shelf (Delta C-14 = -384 +/- 47.8%) surface sediments. Therefore, although the major source of particulate material during the cascading season is resuspended shelf deposits, there is evidence that this aged pool of organic carbon can be eroded and laterally advected downslope.

The p38/MK2/Hsp25 pathway is required for BMP-2-induced cell migration.

Background: Bone morphogenetic proteins (BMPs) have been shown to participate in the patterning and specification of several tissues and organs during development and to regulate cell growth, differentiation and migration in different cell types. BMP-mediated cell migration requires activation of the small GTPase Cdc42 and LIMK1 activities. In our earlier report we showed that activation of LIMK1 also requires the activation of PAKs through Cdc42 and PI3K. However, the requirement of additional signaling is not clearly known. Methodology/Principal Findings: Activation of p38 MAPK has been shown to be relevant for a number of BMP-2¿s physiological effects. We report here that BMP-2 regulation of cell migration and actin cytoskeleton remodelling are dependent on p38 activity. BMP-2 treatment of mesenchymal cells results in activation of the p38/MK2/Hsp25 signaling pathway downstream from the BMP receptors. Moreover, chemical inhibition of p38 signaling or genetic ablation of either p38¿ or MK2 blocks the ability to activate the downstream effectors of the pathway and abolishes BMP-2-induction of cell migration. These signaling effects on p38/MK2/Hsp25 do not require the activity of either Cdc42 or PAK, whereas p38/MK2 activities do not significantly modify the BMP-2-dependent activation of LIMK1, measured by either kinase activity or with an antibody raised against phospho-threonine 508 at its activation loop. Finally, phosphorylated Hsp25 colocalizes with the BMP receptor complexes in lamellipodia and overexpression of a phosphorylation mutant form of Hsp25 is able to abolish the migration of cells in response to BMP-2. Conclusions: These results indicate that Cdc42/PAK/LIMK1 and p38/MK2/Hsp25 pathways, acting in parallel and modulating specific actin regulatory proteins, play a critical role in integrating responses during BMP-induced actin reorganization and cell migration.

Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4.

Background: Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle tocause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective: This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods: We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP14 were assayed on the activated mast cells. Betahexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results: Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogenactivated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by betahexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase,and p38 phosphorylation were diminished when compared with mannitol activation alone. Conclusions: Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition.

La gestió del regadiu a Catalunya: plans, actors i reptes de futur

Irrigation has traditionally constituted one of the most characteristic and emblematic agricultural mosaics of the Mediterranean as a key factor of socio-economic dynamism of the territorial matrix. In recent years there has been an important scientific, intellectual and social environment mobilization around water uses and, in particular, around the main socio-economic use of resource: irrigation, which is undergoing an intense and accelerated transformation process. Thus, in parallel with the decline of traditional irrigation systems, located in areas with natural availability of water, fertile soil and appropriate topographic conditions, the socio-economic changes in the last decade have stimulated the appearance of new irrigated areas with environmental, social and economic disparate characteristics. As a result, the irrigation management model has been conditioned to respond to the new parameters of water scarcity and resource efficiency. In addition, policies and actors have evolved over time as a consequence of disparate priorities –and often conflicting– in terms of irrigation, making necessary the gear of different discourses. In this context, the Model of social commitment of irrigation proposed by the Institutional and Social Innovations in Irrigation Mediterranean Management (ISIIMM) can become a starting example