Functional equations and the Cauchy mean value theorem

The aim of this note is to characterize all pairs of sufficiently smooth functions for which the mean value in the Cauchy mean value theorem is taken at a point which has a well-determined position in the interval. As an application of this result, a partial answer is given to a question posed by Sahoo and Riedel.

Genetic and functional analyses of cell division proteins FtsZ and FtsA in Escherichia coli

In the current model for bacterial cell division, the FtsZ protein forms a ring that marks the division plane, creating a cytoskeletal framework for the subsequent action of other essential division proteins such as FtsA and ZipA. The putative protein complex ultimately generates the division septum. The essential cell division protein FtsZ is a functional and structural homolog of eukaryotic tubulin, and like tubulin, FtsZ hydrolyzes GTP and self-assembles into protein filaments in a strictly GTP-dependent manner. FtsA shares sequence similarity with members of the ATPase superfamily that include actin, but its actual function remains unknown. To test the division model and elucidate functions of the division proteins, this dissertation primarily focuses on the analysis of FtsZ and FtsA in Escherichia coli. ^ By tagging with green fluorescent protein, we first demonstrated that FtsA also exhibits a ring-like structure at the potential division site. The localization of FtsA was dependent on functional FtsZ, suggesting that FtsA is recruited to the septum by the FtsZ ring. In support of this idea, we showed that FtsA and FtsZ directly interact. Using a novel E. coli in situ assay, we found that the FtsA-FtsZ interaction appears to be species-specific, although an interspecies interaction could occur between FtsA and FtsZ proteins from two closely related organisms. In addition, mutagenesis of FtsA revealed that no single domain is solely responsible for its septal localization or interaction with FtsZ. To explore the function of FtsA, we purified FtsA protein and demonstrated that it has ATPase activity. Furthermore, purified FtsA stimulates disassembly of FtsZ polymers in a sedimentation assay but does not affect GTP hydrolysis of FtsZ. This result suggests that in the cell, FtsA may function similarly in regulating dynamic instability of the FtsZ ring during the cell division process. ^ To elucidate the structure-function relationship of FtsZ, we carried out thorough genetic and functional analyses of the mutagenized FtsZ derivatives. Our results indicate that the conserved N-terminal domain of FtsZ is necessary and sufficient for FtsZ self-assembly and localization. Moreover, we discovered a critical role for an extreme C-terminal domain of FtsZ that consists of only 12 residues. Truncated FtsZ derivatives lacking this domain, though able to polymerize and localize, are defective in ring formation in vivo as well as interaction with FtsA and ZipA. Alanine scanning mutagenesis of this region pinpointed at least five residues necessary for the function of FtsZ. Studies of protein levels and protein-protein interactions suggested that these residues may be involved in regulating protein stability and/or FtsZ-FtsA interactions. Interestingly, two of the point mutants exhibited dominant-negative phenotypes. ^ In summary, results from this thesis work have provided additional support for the division machinery model and will contribute to a better understanding of the coordinate functions of FtsA and FtsZ in the cell division process. ^

Functional Characterization of AtxA, the Bacillus anthracis Virulence Regulator

Coordinated expression of virulence genes in Bacillus anthracis occurs via a multi-faceted signal transduction pathway that is dependent upon the AtxA protein. Intricate control of atxA gene transcription and AtxA protein function have become apparent from studies of AtxA-induced synthesis of the anthrax toxin proteins and the poly-D-glutamic acid capsule, two factors with important roles in B. anthracis pathogenesis. The amino-terminal region of the AtxA protein contains winged-helix (WH) and helix-turn-helix (HTH) motifs, structural features associated with DNA-binding. Using filter binding assays, I determined that AtxA interacted non-specifically at a low nanomolar affinity with a target promoter (Plef) and AtxA-independent promoters. AtxA also contains motifs associated with phosphoenolpyruvate: sugar phosphotransferase system (PTS) regulation. These PTS-regulated domains, PRD1 and PRD2, are within the central amino acid sequence. Specific histidines in the PRDs serve as sites of phosphorylation (H199 and H379). Phosphorylation of H199 increases AtxA activity; whereas, H379 phosphorylation decreases AtxA function. For my dissertation, I hypothesized that AtxA binds target promoters to activate transcription and that DNA-binding activity is regulated via structural changes within the PRDs and a carboxy-terminal EIIB-like motif that are induced by phosphorylation and ligand binding. I determined that AtxA has one large protease-inaccessible domain containing the PRDs and the carboxy-terminal end of the protein. These results suggest that AtxA has a domain that is distinct from the putative DNA-binding region of the protein. My data indicate that AtxA activity is associated with AtxA multimerization. Oligomeric AtxA was detected when co-affinity purification, non-denaturing gel electrophoresis, and bis(maleimido)hexane (BMH) cross-linking techniques were employed. I exploited the specificity of BMH for cysteine residues to show that AtxA was cross-linked at C402, implicating the carboxy-terminal EIIB-like region in protein-protein interactions. In addition, higher amounts of the cross-linked dimeric form of AtxA were observed when cells were cultured in conditions that promote toxin gene expression. Based on the results, I propose that AtxA multimerization requires the EIIB-like motif and multimerization of AtxA positively impacts function. I investigated the role of the PTS in the function of AtxA and the impact of phosphomimetic residues on AtxA multimerization. B. anthracis Enzyme I (EI) and HPr did not facilitate phosphorylation of AtxA in vitro. Moreover, markerless deletion of ptsHI in B. anthracis did not perturb AtxA function. Taken together, these results suggest that proteins other than the PTS phosphorylate AtxA. Point mutations mimicking phosphohistidine (H to D) and non-phosphorylated histidine (H to A) were tested for an impact on AtxA activity and multimerization. AtxA H199D, AtxA H199A, and AtxA H379A displayed multimerization phenotypes similar to that of the native protein, whereas AtxA H379D was not susceptible to BMH cross-linking or co-affinity purification with AtxA-His. These data suggest that phosphorylation of H379 may decrease AtxA activity by preventing AtxA multimerization. Overall, my data support the following model of AtxA function. AtxA binds to target gene promoters in an oligomeric state. AtxA activity is increased in response to the host-related signal bicarbonate/CO2 because this signal enhances AtxA multimerization. In contrast, AtxA activity is decreased by phosphorylation at H379 because multimerization is inhibited. Future studies will address the interplay between bicarbonate/CO2 signaling and phosphorylation on AtxA function.

CONFORMATIONAL DYNAMICS OF K-RAS AND H-RAS PROTEINS: IS THERE FUNCTIONAL SPECIFICITY AT THE CATALYTIC DOMAIN?

Ras proteins serve as crucial signaling modulators in cell proliferation through their ability to hydrolyze GTP and exist in a GTP “on” state and GTP “off” state. There are three different human Ras isoforms: H-ras, N-ras and K-ras (4A and 4B). Although their sequence identity is very high at the catalytic domain, these isoforms differ in their ability to activate different effectors and hence different signaling pathways. Much of the previous work on this topic has attributed this difference to the hyper variable region of Ras proteins, which contains most of the sequence variance among the isoforms and encodes specificity for differential distribution in the membrane. However, we hypothesize that sequence variation on lobe II of Ras catalytic domain alters dynamics and leads to differential preference for different effectors or modulators. In this work, we used all atom molecular dynamics to analyze the dynamics in the catalytic domain of H-ras and K-ras. We have also analyzed the dynamics of a transforming mutant of H-ras and K-ras and further studied the dynamics of an effectorselective mutant of H-ras. Collectively we have determined that wild type K-ras is more dynamic than H-ras and that the structure of the effector binding loop more closely resembles that of the T35S Raf-selective mutant, possibly giving us a new view and insight into the v mode of effector specificity. Furthermore we have determined that specific mutations at the same location perturb the conformational equilibrium differently in H-ras and K-ras and that an enhanced oncogenic potential may arise from different structural perturbations for each point mutation of a specific isoform.

Functional activation of p53 induces apoptosis in the absence of MDM2

The p53 tumor suppressor gene product is negatively regulated by the product of its downstream target, mdm2. The mdm2 oncogene abrogates p53 transactivation function. Amplification of mdm2 occurs in 36% of human sarcomas, which often retain p53 in wild type form, suggesting that overexpression of mdm2 in tumors results in p53 inactivation. Thus, the relationship of p53 to mdm2 is important in tumorigenesis. The deletion of mdm2 in the mouse results in embryonic lethality by 5.5 days post coitum. Embryonic lethality of the mdm2 null embryos was overcome by simultaneous loss of the p53 tumor suppressor, which substantiates the importance of the negative regulatory function of MDM2 on p53 function in vivo. These data suggest that the loss of MDM2 function allowed the constitutively active p53 protein to induce either a complete G1 arrest or the p53-dependent apoptotic pathway, resulting in the death of the mdm2−/− embryos.^ The present study examines the hypothesis that the absence of mdm2 induces apoptosis due to p53 activation. Viability of the p53−/−mdm2−/− mice has allowed establishment of mouse embryo fibroblasts (MEFs) and a detailed examination of the properties of these cells. To introduce p53 into this system, and essentially recreate a mdm2 null cell, a temperature sensitive p53 (tsp53) point mutant (A135V) was used, which exhibits a nonfunctional, mutant conformation at 39°C and wild type, functional conformation at 32°C. Infected pools of p53−/− and p53−/−mdm2−/− MEFs with the tsp53 gene were established and single-cell clonal populations expressing tsp53 were selected. Shifting the cells from 39°C to 32°C caused p53−/−mdm2 −/− lines expressing tsp53 to undergo up to 80% apoptosis, which did not occur in the p53−/− lines expressing tsp53 nor the parental lines lacking p53 expression. Furthermore, the amount of p53 present in the clonal population determined the extent of apoptosis. Tsp53 is transcriptionally active in this system, however, it discriminates among different target promoters and does not induce the apoptosis effector targets bax or Fas/Apo1. ^ In summary, this study indicates that the presence or absence of mdm2 is the determining factor for the ability of p53 to trigger apoptosis in this system. The loss of mdm2 promotes p53-dependent apoptosis in MEFs in a cell cycle and dose-dependent manner. p53 is differentially phosphorylated in the presence and absence of mdm2, but does not induce the apoptosis effectors, bax or Fas/ Apo1. ^

Functional studies of a LIM -homeodomain transcription factor lmx1b in murine mid -hindbrain and limb development

This thesis is centered on applying molecular genetics to study pattern formation during animal development. More specifically, this thesis describes the functional studies of a LIM-homeodomain gene called lmx1b during murine embryogenesis. Lmx1b expression is restricted to the mid-hindbrain junction as well as to the dorsal mesenchyme of the limb, suggesting important functions during mid-hindbrain and limb development. To test these possibilities, lmx1b homozygous mutant mice were generated and their limb and CNS phenotypes examined. Lmx1b homozygous mutant mice exhibit a large reduction of mid-hindbrain structures, and that their limbs are symmetrical along the dorsal-ventral axis as the result of a dorsal to ventral transformation. Taken together, these studies define essential functions for lmx1b in mid-hindbrain patteming and in dorsal limb cell fate determination. However, the molecular mechanisms which accounts for these phenotypes are unknown, and whether lmx1b has same or distinctive functions during the mid-hindbrain and limb development is also unclear. ^ Recently, insight into molecular mechanisms of mid-hindbrain patterning and limb development has resulted from the identification of several factors with restricted expression patterns within these regions. These include the secreted factors wnt-1, fgf-8, wnt-7a and the transcription factors pax-2, and en-1. Targeted disruption of any of these genes in mice suggests that these genes might be involved in similar regulatory pathways. Analysis of the expression of these genes in lmx1b mutants demonstrates that lmxlb is not required for the initiation, but is required to maintain their expression at the mid-hindbrain junction. Thus, lmxlb is not required for specifying mid-hindbrain cell fates, rather, it functions to ensure the establishment or maintenance of a proper organizing center at the mid-hindbrain junction. Interestingly, lmxlb functions cell non-autonomously in chimera analysis, which indicates that lmx1b might regulate the expression of secreted factors such as wnt-1 and/or fgf-8 in the organizing center. In contrast, lmx1b functions cell autonomously in the dorsal limb to govern dorsal ventral limb development and its expression is regulated by with wnt-7a and en-1. However, single and double mutant analysis suggest that all three genes have partially overlapping functions as well as independent functions. The results point toward a complicated network of cross-talks among all three limb axes. ^

Structural and functional analysis of p84N5

Normal development and tissue homeostasis requires the carefully orchestrated balance between cell proliferation and cell death. Cell cycle checkpoints control the extent of cell proliferation. Cell death is coordinated through the activation of a cell suicide pathway that results in the morphologically recognizable form of death, apoptosis. Tumorigenesis requires that the balance between these two pathways be disrupted. The tumor suppressor protein Rb has not only been shown to be involved in the enforcement of cell cycle checkpoints, but has also been implicated in playing a role in the regulation of apoptosis. The manner in which Rb enforces cell cycle checkpoints has been well studied; however, its involvement in the regulation of apoptosis is still very unclear. p84N5 is a novel nuclear death domain containing protein that has been shown to interact with the N-terminus of Rb. The fact that it contains a death domain and the fact that it is nuclear localized possibly provides the first known mechanism for apoptotic signaling from the nucleus. The following study tested the hypothesis that the novel exclusively nuclear death domain containing protein p84N5 is an important mediator of programmed cell death and that its apoptotic function is reliant upon its nuclear localization and is regulated by unique functional domains within the p84N5 protein. We identified the p84N5 nuclear localization signal (NLS), eliminated it, and tested the functional significance of nuclear localization by using wild type and mutant sequences fused to EGFP-C1 (Clontech) to create wild type GFPN5 and subsequent mutants. The results of these assays demonstrated exclusive nuclear localization of GFPN5 is required for normal p84N5 induced apoptosis. We further conducted large-scale mutagenesis of the GFPN5 construct to identify a minimal region within p84N5 capable of interacting with Rb. We were able to identify a minimal sequence containing p84N5 amino acids 318 to 464 that was capable of interacting with Rb in co-immunoprecipitation assays. We continued by conducting a structural and functional analysis to identify the region or regions within p84N5 responsible for inducing apoptosis. Point mutations and small-scale deletions within the death domain of p84N5 lessened the effect but did not eliminate p84N5-induced cytotoxicity. Further analysis revealed that the minimal sequence of 318 to 464 of p84N5 was capable of inducing apoptosis to a similar degree as wild-type GFPN5 protein. Since amino acids 318 to 464 of p84N5 are capable of inducing apoptosis and interacting with Rb, we propose possible mechanisms whereby p84N5 may function in a Rb regulated manner. These results demonstrate that p84N5 induced apoptosis is reliant upon its nuclear localization and is regulated by unique functional domains within the p84N5 protein. ^

Physicochemical sea ice and water characteristics near Point Barrow 2005-2006

Photosynthetic parameters of phytoplankton and sea ice algae from landfast sea ice of the Chukchi Sea off Point Barrow, Alaska, were assessed in spring 2005 and winter through spring 2006 using Pulse Amplitude Modulated (PAM) fluorometry including estimates of maximum quantum efficiency (Fv/Fm), maximum relative electron transport rate (rETRmax), photosynthetic efficiency (alpha), and the photoadaptive index (Ek). The use of centrifuged brine samples allowed to document vertical gradients in ice algal acclimation with 5 cm vertical resolution for the first time. Bottom ice algae (0-5 cm from ice-water interface) expressed low Fv/Fm (0.331-0.426) and low alpha (0.098-0.130 /(µmol photons/m**2/s)) in December. Fv/Fm and alpha increased in March and May (0.468-0.588 and 0.141-0.438 /(µmol photons/m**2/s), respectively) indicating increased photosynthetic activity. In addition, increases in rETRmax (3.3-16.4 a.u.) and Ek (20-88 µmol photons/m**2/s) from December to May illustrates a higher potential for primary productivity as communities become better acclimated to under-ice light conditions. In conclusion, photosynthetic performance by ice algae (as assessed by PAM fluorometry) was tightly linked to sea ice salinity, temperature, and inorganic nutrient concentrations (mainly nitrogen).

Estimation of the normal boiling point of organic compounds via group contributions

The normal boiling point is a fundamental thermo-physical property, which is important in describing the transition between the vapor and liquid phases. Reliable method which can predict it is of great importance, especially for compounds where there are no experimental data available. In this work, an improved group contribution method, which is second order method, for determination of the normal boiling point of organic compounds based on the Joback functional first order groups with some changes and added some other functional groups was developed by using experimental data for 632 organic components. It could distinguish most of structural isomerism and stereoisomerism, which including the structural, cis- and trans- isomers of organic compounds. First and second order contributions for hydrocarbons and hydrocarbon derivatives containing carbon, hydrogen, oxygen, nitrogen, sulfur, fluorine, chlorine and bromine atoms, are given. The fminsearch mathematical approach from MATLAB software is used in this study to select an optimal collection of functional groups (65 functional groups) and subsequently to develop the model. This is a direct search method that uses the simplex search method of Lagarias et al. The results of the new method are compared to the several currently used methods and are shown to be far more accurate and reliable. The average absolute deviation of normal boiling point predictions for 632 organic compounds is 4.4350 K; and the average absolute relative deviation is 1.1047 %, which is of adequate accuracy for many practical applications.

Code and readme of a MATLAB-based graphical user interface program for computing functionals of the geopotential

We present a novel graphical user interface program GrafLab (GRAvity Field LABoratory) for spherical harmonic synthesis (SHS) created in MATLAB®. This program allows to comfortably compute 38 various functionals of the geopotential up to ultra-high degrees and orders of spherical harmonic expansion. For the most difficult part of the SHS, namely the evaluation of the fully normalized associated Legendre functions (fnALFs), we used three different approaches according to required maximum degree: (i) the standard forward column method (up to maximum degree 1800, in some cases up to degree 2190); (ii) the modified forward column method combined with Horner's scheme (up to maximum degree 2700); (iii) the extended-range arithmetic (up to an arbitrary maximum degree). For the maximum degree 2190, the SHS with fnALFs evaluated using the extended-range arithmetic approach takes only approximately 2-3 times longer than its standard arithmetic counterpart, i.e. the standard forward column method. In the GrafLab, the functionals of the geopotential can be evaluated on a regular grid or point-wise, while the input coordinates can either be read from a data file or entered manually. For the computation on a regular grid we decided to apply the lumped coefficients approach due to significant time-efficiency of this method. Furthermore, if a full variance-covariance matrix of spherical harmonic coefficients is available, it is possible to compute the commission errors of the functionals. When computing on a regular grid, the output functionals or their commission errors may be depicted on a map using automatically selected cartographic projection.

IDT-3D: Identification and tracking in controlled environments using a 3D unified user interface

Identification and tracking of objects in specific environments such as harbors or security areas is a matter of great importance nowadays. With this purpose, numerous systems based on different technologies have been developed, resulting in a great amount of gathered data displayed through a variety of interfaces. Such amount of information has to be evaluated by human operators in order to take the correct decisions, sometimes under highly critical situations demanding both speed and accuracy. In order to face this problem we describe IDT-3D, a platform for identification and tracking of vessels in a harbour environment able to represent fused information in real time using a Virtual Reality application. The effectiveness of using IDT-3D as an integrated surveillance system is currently under evaluation. Preliminary results point to a significant decrease in the times of reaction and decision making of operators facing up a critical situation. Although the current application focus of IDT-3D is quite specific, the results of this research could be extended to the identification and tracking of targets in other controlled environments of interest as coastlines, borders or even urban areas.

Neighborhood-corrected interface discontinuity factors for multi-group pin-by-pin diffusion calculations for LWR

Performing three-dimensional pin-by-pin full core calculations based on an improved solution of the multi-group diffusion equation is an affordable option nowadays to compute accurate local safety parameters for light water reactors. Since a transport approximation is solved, appropriate correction factors, such as interface discontinuity factors, are required to nearly reproduce the fully heterogeneous transport solution. Calculating exact pin-by-pin discontinuity factors requires the knowledge of the heterogeneous neutron flux distribution, which depends on the boundary conditions of the pin-cell as well as the local variables along the nuclear reactor operation. As a consequence, it is impractical to compute them for each possible configuration; however, inaccurate correction factors are one major source of error in core analysis when using multi-group diffusion theory. An alternative to generate accurate pin-by-pin interface discontinuity factors is to build a functional-fitting that allows incorporating the environment dependence in the computed values. This paper suggests a methodology to consider the neighborhood effect based on the Analytic Coarse-Mesh Finite Difference method for the multi-group diffusion equation. It has been applied to both definitions of interface discontinuity factors, the one based on the Generalized Equivalence Theory and the one based on Black-Box Homogenization, and for different few energy groups structures. Conclusions are drawn over the optimal functional-fitting and demonstrative results are obtained with the multi-group pin-by-pin diffusion code COBAYA3 for representative PWR configurations.

A comparison of the two most popular word processors from the point of view of their conviviality

In this paper, we aim to prove, firstly, that the argument of the excess of complexity is not a whim. We will focous our attention on a particular and widespread case within the Tool Box, word processors, and on the most widely sold products inside this category respectively, the one a few years ago, the other at the present moment: WordStar y WordPerfect. The aspect of their complexity we are interested in is their user interface, because in the first place it is the aspect that most influences the human job.

Large-scale identification of gibberellin-related transcription factor defines group VII ERFs as functional of DELLA partners

DELLA proteins are the master negative regulators in gibberellin (GA) signaling acting in the nucleus as transcriptional regulators. The current view of DELLA action indicates that their activity relies on the physical interaction with transcription factors (TFs). Therefore, the identification of TFs through which DELLAs regulate GA responses is key to understanding these responses from a mechanistic point of view. Here, we have determined the TF interactome of the Arabidopsis (Arabidopsis thaliana) DELLA protein GIBBERELLIN INSENSITIVE and screened a collection of conditional TF overexpressors in search of those that alter GA sensitivity. As a result, we have found RELATED TO APETALA2.3, an ethylene-induced TF belonging to the group VII ETHYLENE RESPONSE FACTOR of the APETALA2/ethylene responsive element binding protein superfamily, as a DELLA interactor with physiological relevance in the context of apical hook development. The combination of transactivation assays and chromatin immunoprecipitation indicates that the interaction with GIBBERELLIN INSENSITIVE impairs the activity of RELATED TO APETALA2.3 on the target promoters. This mechanism represents a unique node in the cross regulation between the GA and ethylene signaling pathways controlling differential growth during apical hook development.

Modelo multidimensional de los factores que afectan la interacción entre marketing y ventas en el lanzamiento de nuevos productos en Latino América

Esta tesis se centra en la identificación y análisis de los factores que pueden favorecer o actuar como barreras del éxito de la implementación de la innovación y las relaciones entre sí, desde el enfoque de la interface marketing-ventas. El trabajo empírico se enmarca en el vacío de investigación existente en el campo del proceso de lanzamiento de nuevos productos en los mercados donde operan subsidiarias de empresas multinacionales de consumo masivo (FMCG). Las empresas FMCG son altamente dependientes de la innovación como proceso clave determinante del crecimiento competitivo de mediano y largo plazo. En un contexto de acortamiento del ciclo de vida de los productos, como resultado del desarrollo tecnológico y científico que impactan en el comportamiento de los consumidores, las empresas invierten un mayor nivel de recursos en el desarrollo de nuevos productos, reingeniería y programas de innovación (Mundra, Gulati y Gupta, 2013). Sin embargo, a pesar del aumento en la inversión, las tasas de éxito de la innovación reportadas son inferiores al 25% (Evanschitzky, Eisend, Calantone y Jiang, 2012). Aumentar las tasas de éxito de los proyectos de innovación es reconocida en la literatura como un elemento clave para la supervivencia y competitividad de las empresas, para ser superiores a su competencia y desarrollar nuevos modelos de negocios. A pesar de la existencia de estudios que intentan comprender el proceso de lanzamiento de nuevos productos, no se ha identificado un claro prototipo de gestión de la innovación (Gupta et al, 2007). Profundizando en los factores de éxito, los autores Keupp, Palmié y Gassman (2012) reconocen que la innovación exitosa no depende solamente de la estrategia de selección de los proyectos de innovación, sino también la forma en que los mismos son implementados (Klein and Sorra, 1996; Repenning, 2002; Keupp, Palmié y Gassmann, 2012). Al analizar la implementación de los proyectos de lanzamiento de nuevos productos al mercado, en empresas FMCG, dicho proceso es responsabilidad principalmente de las funciones de marketing y ventas a través de la comunicación con los consumidores y los clientes respectivamente (Ernst, Hoyer y Rubsaamen, 2010). Es decir que el éxito en la implementación de la innovación requiere la gestión efectiva de la relación inter-funcional entre marketing y ventas (Ernst, Hoyer y Rubsaamen, 2010; Hughes, Le Bon y Malshe, 2012). A pesar de la importancia de la integración entre marketing y ventas en la conceptualización e implementación de la innovación, este tema no ha sido estudiado en profundidad (Hughes, Le Bon y Malshe, 2012; Keupp, Palmié y Gassmann, 2012). En las empresas multinacionales, está demostrado que el desempeño de las subsidiarias determinan el éxito competitivo de la empresa a nivel global. El desafío de dichas subsidiarias es conjugar el desarrollo global de innovación y comunicación con las características locales de comportamiento del consumidor y el mercado. Por lo tanto, esta investigación empírica responde a la pregunta académica y de gestión acerca de cómo mejorar las tasas de éxito de lanzamiento de nuevos productos al mercado en subsidiarias de empresas de consumo masivo, desde la perspectiva de la relación entre marketing y ventas. En particular analiza cómo afectan la formalización de los procesos y los mecanismos de comunicación a la confianza interpersonal y a la efectividad de la interface marketing-ventas y dichos factores a su vez sobre la planificación integrada de la implementación de la innovación. La determinación de los factores o ítems que conforman cada uno de los constructos del proceso de ejecución de la innovación, se llevó a cabo a partir de una revisión exhaustiva del estado del arte de la literatura sobre las interfaces funcionales y el proceso de innovación. Posteriormente, los ítems seleccionados (más de 50 en total) fueron validados por referentes de marketing y ventas de Argentina y Uruguay a través de entrevistas en profundidad. A partir de los factores identificados se construyeron dos modelos teóricos: • (1) relativo a la influencia de las dimensiones de confianza interpersonal sobre la efectividad de las uniones inter-funcionales y como los mecanismos organizacionales, tales como la frecuencia y la calidad de la comunicación entre las áreas, afectan la confianza y la relación entre ellas; • (2) relativo a la dimensión planificación integrada de la implementación de la innovación, ya que durante el lanzamiento de nuevos productos al mercado, marketing y ventas utilizan procesos formales que facilitan la comunicación frecuente y efectiva, desarrollando confianza inter-personal que no solamente afecta la efectividad de su relación sino también el desarrollo de planes integrados entre ambas áreas. El estudio fue llevado a cabo en una empresa multinacional de consumo masivo que integra la lista Global 500 (Fortune, 2015), presente en todo el mundo con más de 25 marcas participantes en más de 15 categorías, implementando 150 proyectos de innovación en el último año. El grupo de subsidiarias en estudio fue reconocido a nivel mundial por su desempeño en crecimiento competitivo y su alta contribución al crecimiento total. El modelo analizado en esta tesis fue expandido al resto de América Latina, tratándose entonces de un caso ejemplar que representa una práctica de excelencia en la implementación de la innovación en subsidiarias de una empresa multinacional. La recolección de los datos fue llevado a cabo a través de un cuestionario estructurado y confidencial, enviado a la base de datos de todo el universo de directores y gerentes de marketing y ventas. El nivel de respuesta fue muy elevado (70%), logrando 152 casos válidos. El análisis de datos comprendió el análisis descriptivo de los mismos, estimación de fiabilidad y análisis factorial exploratorio a través del software SPSS v.20. El análisis factorial confirmatorio y el análisis de senderos para examinar las relaciones entre los factores se estudiaron mediante el software R (Package 2.15.1., R Core Team, 2012) (Fox, 2006). Finalmente se llevaron a cabo entrevistas en profundidad a gerentes de marketing y ventas de cada uno de los seis países con el fin de profundizar en los constructos y sus relaciones. Los resultados de los modelos demuestran que la frecuencia de comunicación impacta positivamente en la calidad de la misma, que a su vez afecta directamente la relación entre marketing y ventas. Adicionalmente, la calidad de la comunicación impacta sobre la confianza cognitiva, que a su vez se relaciona no solamente con la confianza afectiva sino también con la relación entre ambas áreas. Esto significa que para mejorar la implementación de la innovación, los gerentes deberían orientarse a reforzar la relación entre marketing y ventas facilitando la construcción de confianza interpersonal primero cognitiva y luego afectiva, incrementando la frecuencia de la comunicación que alimenta la calidad de la comunicación entre ambas áreas. A través del segundo modelo se demuestra que durante el lanzamiento de nuevos productos al mercado, marketing y ventas necesitan emplear procesos formales que faciliten la comunicación frecuente y efectiva. De esta forma se contrarresta el efecto negativo de la formalización sobre la planificación integrada entre ambas áreas. Adicionalmente, los gerentes de ambos departamentos deberían promover la construcción de confianza interpersonal, no solamente para mejorar la efectividad de la relación, sino también para desarrollar planes integrados de implementación de nuevos productos. Finalmente, se valida que la frecuencia de la comunicación, la confianza afectiva y la relación marketing-ventas, se relacionan positivamente con la planificación integrada en la implementación de la innovación. El estudio contribuye a la comprensión de los factores que las empresas pueden emplear para mejorar la relación inter-funcional entre marketing y ventas y la implementación de la innovación en empresas de consumo masivo. El aporte de esta investigación puede ser valorado de dos maneras, los aportes a la gestión y a la academia. Desde el punto de vista empresarial, provee a los líderes al frente de empresas de consumo masivo, del conocimiento sobre los factores que afectan la implementación de la innovación y en definitiva el éxito del negocio a mediano y largo plazo. Desde el punto de vista académico aporta al conocimiento del proceso de implementación de la innovación y en la efectividad de la interface marketing y ventas en un caso de buenas prácticas en el mercado de consumo masivo. A su vez incorpora por primera vez un estudio empírico en geografías emergentes capaces de recuperar el camino de crecimiento posterior a una profunda crisis económica a través de la exitosa implementación de la innovación en sus mercados. ABSTRACT This thesis is focused on the identification, analysis and relationship study of factors which may benefit or hinder the successful deployment of innovation, from a marketing-sales interface perspective. Considering the non-existent investigation dedicated to the study of new products launches into markets in which Fast Moving Consumer Goods (FMCG) companies’ subsidiaries operate, it is that this investigation has been carried out. FMCG companies rely on innovation as their key process for a competitive growth on a medium and long term basis. Nowadays, the life-cycle of products is getting shorter as a result of new technological and scientific development, having impact on consumer behavior, and therefore companies are forced to dedicating more resources to the development of new products, reengineering and innovation programs (Mundra, Gulati and Gupta, 2013). However, in spite of the investment increase, the innovation success rates have been reported to be lower than 25% (Evanschitzky, Eisend, Calantone y Jiang, 2012). Increasing success rates on innovation processes has been considered as a key element on the survival and competitiveness of companies, outperforming competitors and developing new business models. Despite new studies which try to comprehend the process of new products launch, a prototype of innovation management has not yet been identified (Gupta et al, 2007). Emphasizing on success factors, authors Keupp, Palmié and Gassman (2012) recognize that successful innovation does not solely depend on innovation processes’ selection strategy, but it is also based on the way in which these are implemented (Klein and Sorra, 1996; Repenning, 2002; Keupp, Palmié y Gassmann, 2012). While analyzing the implementation of projects for new products releases on massive consumption companies, the two departments in charge of taking this forward are marketing and sales, by focusing on communication strategies with consumers and clients respectively (Ernst, Hoyer y Rubsaamen, 2010). This means that having success on innovation implementation requires an effective management of inter-functional relationship among marketing and sales (Ernst, Hoyer y Rubsaamen, 2010; Hughes, Le Bon y Malshe, 2012). In spite of the importance on the integration between marketing and sales on the conceptualization and implementation of innovation, this subject has not been studied in depth (Hughes, Le Bon y Malshe, 2012; Keupp, Palmié y Gassmann, 2012). In multinational companies, previous research has confirmed that the performance of their subsidiaries determine the competitive success of the company on a global scale. The challenge of said subsidiaries is to conjugate the global innovation development and communication with the local consumer and market behavior. Therefore, this empirical study aims to respond to the academic and management question of how to improve the success rates of new product launches into MNE subsidiary’ markets, from a marketing-sales relationship perspective. Particularly, this investigation analyses how the formalization of products and communication mechanisms affect interpersonal trust and marketing-sales interface effectiveness and also on how these factors affect the overall planning of the implementation of innovation. The determination of which factors build the hypothesis of the innovation execution process was taken forward through an extensive research on the extant literature on functional interfaces and innovation processes. More than 50 items were selected which were in turn validated by marketing and sales referents on Uruguay and Argentina through in depth interviews. Based on the identified factors, two theoretical models were proposed: (1) Relative to the influence that interpersonal trust dimensions have on inter functional linkages effectiveness and how organizational mechanisms such as frequency and quality of communication between departments affect trust and their relationship. (2) Relative to the integrated planning and innovation implementation dimensions. Marketing and sales department use formal process thus allowing inter-personal trust, which affects positively their relationship and also enables the development of integrated planning between them. The study was performed within a massive consumption company which is part of the “Global 500” (Fortune, 2015), with subsidiaries all over the world and more than 25 participant brands in 15 categories, having implemented over 150 innovation projects in the year under study. The analyzed subsidiary group has been awarded worldwide for their performance in competitive growth and their high contribution to the total growth. The model being analyzed in this thesis was implemented throughout Latin America, representing a remarkable case of innovation implementation excellence for subsidiaries of multinational companies. Data recollection was carried out through a structured and confidential questionnaire, sent to the universe of marketing-sales directors and managers’ database available with a high level of responsiveness of 70%, resulting in 152 valid cases. Data exploration involved a descriptive analysis, followed by a reliability estimation and an exploratory factorial analysis carried out through SPSS v.20. Confirmatory factorial analysis and path analysis (to examine relations between the different study factors) were studied using “R” software (Package 2.15.1., R Core Team, 2012) (Fox, 2006). Finally, in depth interviews were carried out to several marketing and sales managers in each of the six countries so as to further confirm the hypothesis and their relations. The models results prove that communication frequency has a positive impact on the quality of the same, which in turn has direct effects on the marketing-sales relations. Additionally, communication quality has an impact on the cognitive trust, which also relates not only to affective trust, but also to the relation between both areas. This means that in order to improve the implementation of innovation, managers should strive to enforce marketing-sales relations, facilitating the interpersonal trust construction (firstly cognitive, followed by affective trust), increasing the communication frequency, and therefore nurturing the communication quality among both areas. Through the second model, the results confirm the importance of creating effective relationships between sales and marketing to facilitate planning integrated new product implementations. While formalized new product development processes provide opportunities for sales and marketing to communicate, this does not directly influence the planning of integrated new product implementations. By using these formal opportunities to communicate to create information quality, it is possible to improve sales and marketing’s ability to integrate information during the planning process. Further, communication quality creates inter-personal trust in the other party’s competences (cognitive-based trust), leading to affect-based trust. Affect-based inter-personal trust, not only to improve the overall effectiveness of the sales and marketing relationship, but also helps in planning integrated new product implementations. This study contributes to the understanding of factors which enterprises can use to improve the inter-functional relations between marketing and sales, and the implementation of innovation in FMCG companies. The contribution of this investigation can be measured in two ways: enrichment of management and contribution to the academic area. From a business perspective, it provides massive consumption businesses leaders with knowledge on which factors affect innovation implementation, which results on mid and long-term success for the company. From an academic point of view, it provides knowledge on a prototype of successful innovation implementation management based on the marketing-sales interface effectiveness through a case study in the FMCG consumption market. Last but not least, it incorporates for the first time an empiric study on emerging geographies capable of recovery post a deep economic crisis through successful innovation implementation on their markets.