Searching the hearts of graphene-like molecules for simplicity, sensitivity and logic

If quantum interference patterns in the hearts of polycyclic aromatic hydrocarbons (PAHs) could be isolated and manipulated, then a significant step towards realizing the potential of single-molecule electronics would be achieved. Here we demonstrate experimentally and theoretically that a simple, parameter-free, analytic theory of interference patterns evaluated at the mid-point of the HOMO-LUMO gap (referred to as M-functions) correctly predicts conductance ratios of molecules with pyrene, naphthalene, anthracene, anthanthrene or azulene hearts. M-functions provide new design strategies for identifying molecules with phase-coherent logic functions and enhancing the sensitivity of molecular-scale interferometers.

DAPK loss in colon cancer tumor buds: implications for migration capacity of disseminating tumor cells.

Defining new therapeutic strategies to overcome therapy resistance due to tumor heterogeneity in colon cancer is challenging. One option is to explore the molecular profile of aggressive disseminating tumor cells. The cytoskeleton-associated Death-associated protein kinase (DAPK) is involved in the cross talk between tumor and immune cells at the invasion front of colorectal cancer. Here dedifferentiated tumor cells histologically defined as tumor budding are associated with a high risk of metastasis and poor prognosis. Analyzing samples from 144 colorectal cancer patients we investigated immunhistochemical DAPK expression in different tumor regions such as center, invasion front, and buds. Functional consequences for tumor aggressiveness were studied in a panel of colon tumor cell lines using different migration, wound healing, and invasion assays. DAPK levels were experimentally modified by siRNA transfection and overexpression as well as inhibitor treatments. We found that DAPK expression was reduced towards the invasion front and was nearly absent in tumor buds. Applying the ECIS system with HCT116 and HCT116 stable lentiviral DAPK knock down cells (HCTshDAPK) we identified an important role for DAPK in decreasing the migratory capacity whereas proliferation was not affected. Furthermore, the migration pattern differed with HCTshDAPK cells showing a cluster-like migration of tumor cell groups. DAPK inhibitor treatment revealed that the migration rate was independent of DAPK's catalytic activity. Modulation of DAPK expression level in SW480 and DLD1 colorectal cancer cells significantly influenced wound closure rate. DAPK seems to be a major player that influences the migratory capability of disseminating tumor cells and possibly affects the dynamic interface between pro- and anti-survival factors at the invasion front of colorectal cancer. This interesting and new finding requires further evaluation.

Variable phenotypic expressivity in inbred retinal degeneration mouse lines: A comparative study of C3H/HeOu and FVB/N rd1 mice

PURPOSE Recent advances in optogenetics and gene therapy have led to promising new treatment strategies for blindness caused by retinal photoreceptor loss. Preclinical studies often rely on the retinal degeneration 1 (rd1 or Pde6b(rd1)) retinitis pigmentosa (RP) mouse model. The rd1 founder mutation is present in more than 100 actively used mouse lines. Since secondary genetic traits are well-known to modify the phenotypic progression of photoreceptor degeneration in animal models and human patients with RP, negligence of the genetic background in the rd1 mouse model is unwarranted. Moreover, the success of various potential therapies, including optogenetic gene therapy and prosthetic implants, depends on the progress of retinal degeneration, which might differ between rd1 mice. To examine the prospect of phenotypic expressivity in the rd1 mouse model, we compared the progress of retinal degeneration in two common rd1 lines, C3H/HeOu and FVB/N. METHODS We followed retinal degeneration over 24 weeks in FVB/N, C3H/HeOu, and congenic Pde6b(+) seeing mouse lines, using a range of experimental techniques including extracellular recordings from retinal ganglion cells, PCR quantification of cone opsin and Pde6b transcripts, in vivo flash electroretinogram (ERG), and behavioral optokinetic reflex (OKR) recordings. RESULTS We demonstrated a substantial difference in the speed of retinal degeneration and accompanying loss of visual function between the two rd1 lines. Photoreceptor degeneration and loss of vision were faster with an earlier onset in the FVB/N mice compared to C3H/HeOu mice, whereas the performance of the Pde6b(+) mice did not differ significantly in any of the tests. By postnatal week 4, the FVB/N mice expressed significantly less cone opsin and Pde6b mRNA and had neither ERG nor OKR responses. At 12 weeks of age, the retinal ganglion cells of the FVB/N mice had lost all light responses. In contrast, 4-week-old C3H/HeOu mice still had ERG and OKR responses, and we still recorded light responses from C3H/HeOu retinal ganglion cells until the age of 24 weeks. These results show that genetic background plays an important role in the rd1 mouse pathology. CONCLUSIONS Analogous to human RP, the mouse genetic background strongly influences the rd1 phenotype. Thus, different rd1 mouse lines may follow different timelines of retinal degeneration, making exact knowledge of genetic background imperative in all studies that use rd1 models.

Information-centric communication in mobile and wireless networks

Information-centric networking (ICN) is a new communication paradigm that has been proposed to cope with drawbacks of host-based communication protocols, namely scalability and security. In this thesis, we base our work on Named Data Networking (NDN), which is a popular ICN architecture, and investigate NDN in the context of wireless and mobile ad hoc networks. In a first part, we focus on NDN efficiency (and potential improvements) in wireless environments by investigating NDN in wireless one-hop communication, i.e., without any routing protocols. A basic requirement to initiate informationcentric communication is the knowledge of existing and available content names. Therefore, we develop three opportunistic content discovery algorithms and evaluate them in diverse scenarios for different node densities and content distributions. After content names are known, requesters can retrieve content opportunistically from any neighbor node that provides the content. However, in case of short contact times to content sources, content retrieval may be disrupted. Therefore, we develop a requester application that keeps meta information of disrupted content retrievals and enables resume operations when a new content source has been found. Besides message efficiency, we also evaluate power consumption of information-centric broadcast and unicast communication. Based on our findings, we develop two mechanisms to increase efficiency of information-centric wireless one-hop communication. The first approach called Dynamic Unicast (DU) avoids broadcast communication whenever possible since broadcast transmissions result in more duplicate Data transmissions, lower data rates and higher energy consumption on mobile nodes, which are not interested in overheard Data, compared to unicast communication. Hence, DU uses broadcast communication only until a content source has been found and then retrieves content directly via unicast from the same source. The second approach called RC-NDN targets efficiency of wireless broadcast communication by reducing the number of duplicate Data transmissions. In particular, RC-NDN is a Data encoding scheme for content sources that increases diversity in wireless broadcast transmissions such that multiple concurrent requesters can profit from each others’ (overheard) message transmissions. If requesters and content sources are not in one-hop distance to each other, requests need to be forwarded via multi-hop routing. Therefore, in a second part of this thesis, we investigate information-centric wireless multi-hop communication. First, we consider multi-hop broadcast communication in the context of rather static community networks. We introduce the concept of preferred forwarders, which relay Interest messages slightly faster than non-preferred forwarders to reduce redundant duplicate message transmissions. While this approach works well in static networks, the performance may degrade in mobile networks if preferred forwarders may regularly move away. Thus, to enable routing in mobile ad hoc networks, we extend DU for multi-hop communication. Compared to one-hop communication, multi-hop DU requires efficient path update mechanisms (since multi-hop paths may expire quickly) and new forwarding strategies to maintain NDN benefits (request aggregation and caching) such that only a few messages need to be transmitted over the entire end-to-end path even in case of multiple concurrent requesters. To perform quick retransmission in case of collisions or other transmission errors, we implement and evaluate retransmission timers from related work and compare them to CCNTimer, which is a new algorithm that enables shorter content retrieval times in information-centric wireless multi-hop communication. Yet, in case of intermittent connectivity between requesters and content sources, multi-hop routing protocols may not work because they require continuous end-to-end paths. Therefore, we present agent-based content retrieval (ACR) for delay-tolerant networks. In ACR, requester nodes can delegate content retrieval to mobile agent nodes, which move closer to content sources, can retrieve content and return it to requesters. Thus, ACR exploits the mobility of agent nodes to retrieve content from remote locations. To enable delay-tolerant communication via agents, retrieved content needs to be stored persistently such that requesters can verify its authenticity via original publisher signatures. To achieve this, we develop a persistent caching concept that maintains received popular content in repositories and deletes unpopular content if free space is required. Since our persistent caching concept can complement regular short-term caching in the content store, it can also be used for network caching to store popular delay-tolerant content at edge routers (to reduce network traffic and improve network performance) while real-time traffic can still be maintained and served from the content store.

The Process of Starting a Business

Many students are inspired to start their own business venture after taking some courses in school or simply just taking an idea and turning it into a business. The beginning process is usually most difficult in terms of establishing a functioning business, getting the right connections, and avoiding discouragement to follow through with the business. That is why many businesses fall into the categories of starting, failing along the process, or failing to get started. There is a lot to be learned from the process of starting a business venture. In addressing this issue, some of the questions this research study aims to explore and study are how people go about their new venture efforts? Second, what steps they undertake? Third, from whom do they get information? And fourth, how do they use that information? This study will seek a variety of insights that can help answer these questions and improve our understanding of why some businesses fail, succeed, or never get started.

¿Qué son las llamadas economías alternativas?

Dada la compleja situación de vulnerabilidad del tejido social debido al actual modelo de acumulación, las características que asume el trabajo, la desaparición del Estado Protector, comienzan a plantearse, para y desde los sectores más perjudicados, la necesidad de elaborar nuevas estrategias de supervivencia. En este trabajo se intentará analizar aquellas estrategias que conviven con el sistema capitalista, pero que no corresponden completamente a su lógica, que no son generadas ni por el Estado, ni por el sector privado y que intentan elaborar alternativas de desarrollo- comunitario, local, regional- frente a la situación esbozada anteriormente.

Effects of Galleria mellonella cadavers infected with Heterorhabditis bacteriophora and Steinernema rarum, their macerates and dead infective juveniles on Meloidogyne javanica suppression

Nematodes of the Meloidogyne genus affect to most of crops of an economic importance in Argentina. Researches related to new control strategies are needed to reduce the damage produced by these organisms. The objective of this work was to compare the effects of Galleria mellonella cadavers infected with the Argentine isolates Heterorhabditis bacteriophora Rama Caída and Steinernema rarum NOE, cadaver macerates and dead infective juveniles (IJs) on M. javanica suppression. Experiments were performed using 24-well plates and pepper plants grown in a growth chamber. The entomopathogenic nematodes-infected G. mellonella cadavers, their cadaver macerates and dead IJs were effective in suppressing M. javanica second-stage juveniles under laboratory conditions. The use of H. bacteriophora-infected cadavers caused a significant decrease in the number of galls and egg masses on pepper plants parasitized by M. javanica, in a growth-chamber.

Comportamiento del paciente de la clínica dental. Modelo basado en la percepción de la calidad del servicio y fidelización del paciente

Esta tesis doctoral propone un modelo de comportamiento del paciente de la clínica dental, basado en la percepción de la calidad del servicio (SERVQUAL), la fidelización del paciente, acciones de Marketing Relacional y aspectos socioeconómicos relevantes, de los pacientes de clínicas dentales. En particular, el estudio de campo se lleva a cabo en el ámbito geográfico de la Comunidad de Madrid, España, durante los años 2012 y 2013. La primera parte del proceso de elaboración del modelo está basada en la recolección de datos. Para ello, se realizaron cinco entrevistas a expertos dentistas y se aplicaron dos tipos encuestas diferentes: una para el universo formado por el conjunto de los pacientes de las clínicas dentales y la otra para el universo formado el conjunto de los dentistas de las clínicas dentales de la Comunidad de Madrid. Se obtuvo muestras de: 200 encuestas de pacientes y 220 encuestas de dentistas activos colegiados en el Ilustre Colegio Oficial de Odontólogos y Estomatólogos de la I Región Madrid. En la segunda parte de la elaboración del modelo, se realizó el análisis de los datos, la inducción y síntesis del modelo propuesto. Se utilizó la metodología de modelos gráficos probabilísticos, específicamente, una Red Bayesiana, donde se integraron variables (nodos) y sus dependencias estadísticas causales (arcos dirigidos), que representan el conocimiento obtenido de los datos recopilados en las encuestas y el conocimiento derivado de investigaciones precedentes en el área. Se obtuvo una Red Bayesiana compuesta por 6 nodos principales, de los cuales dos de ellos son nodos de observación directa: “Revisit Intention” y “SERVQUAL”, y los otros cuatro nodos restantes son submodelos (agrupaciones de variables), estos son respectivamente: “Attitudinal”, “Disease Information”, “Socioeconomical” y “Services”. Entre las conclusiones principales derivadas del uso del modelo, como herramientas de inferencia y los análisis de las entrevistas realizadas se obtiene que: (i) las variables del nodo “Attitudinal” (submodelo), son las más sensibles y significativas. Al realizarse imputaciones particulares en las variables que conforman el nodo “Attitudinal” (“RelationalMk”, “Satisfaction”, “Recommendation” y “Friendship”) se obtienen altas probabilidades a posteriori en la fidelidad del paciente de la clínica dental, medida por su intención de revisita. (ii) En el nodo “Disease Information” (submodelo) se destaca la relación de dependencia causal cuando se imputa la variable “Perception of disease” en “SERVQUAL”, demostrando que la percepción de la gravedad del paciente condiciona significativamente la percepción de la calidad del servicio del paciente. Como ejemplo destacado, si se realiza una imputación en la variable “Clinic_Type” se obtienen altas probabilidades a posteriori de las variables “SERVQUAL” y “Revisit Intention”, lo que evidencia, que el tipo de clínica dental influye significativamente en la percepción de la calidad del servicio y en la fidelidad del paciente (intención de revisita). (iii) En el nodo “Socioeconomical” (submodelo) la variable “Sex” resultó no ser significativa cuando se le imputaban diferentes valores, por el contrario, la variable “Age” e “Income” mostraban altas variabilidades en las probabilidades a posteriori cuando se imputaba alguna variable del submodelo “Services”, lo que evidencia, que estas variables condicionan la intención de contratar servicios (“Services”), sobretodo en las franjas de edad de 30 a 51 años en pacientes con ingresos entre 3000€ y 4000€. (iv) En el nodo “Services” (submodelo) los pacientes de las clínicas dentales mostraron altas probabilidades a priori para contratar servicios de fisiotrapia oral y gingival: “Dental Health Education” y “Parking”. (v) Las variables de fidelidad del paciente medidas desde su perspectiva comportamental que fueron utilizadas en el modelo: “Visit/year” “Time_clinic”, no aportaron información significativa. Tampoco, la variable de fidelidad del cliente (actitudinal): “Churn Efford”. (vi) De las entrevistas realizadas a expertos dentistas se obtiene que, los propietarios de la clínica tradicional tienen poca disposición a implementar nuevas estrategias comerciales, debido a la falta de formación en la gestión comercial y por falta de recursos y herramientas. Existe un rechazo generalizado hacia los nuevos modelos de negocios de clínicas dentales, especialmente en las franquicias y en lo que a políticas comerciales se refiere. Esto evidencia una carencia de gerencia empresarial en el sector. Como líneas futuras de investigación, se propone profundizar en algunas relaciones de dependencia (causales) como SERVQUALServices; SatisfactionServices; RelationalMKServices, Perception of diseaseSatisfaction, entre otras. Así como, otras variables de medición de la fidelidad comportamental que contribuyan a la mejora del modelo, como por ej. Gasto del paciente y rentabilidad de la visita. ABSTRACT This doctoral dissertation proposes a model of the behavior of the dental-clinic customer, based on the service-quality perception (SERVQUAL), loyalty, Relational Marketing and some relevant socio-economical characteristics, of the dental-clinic customers. In particular, the field study has been developed in the geographical region of Madrid, Spain during the years 2012 and 2013. The first stage of the preparation of the model consist in the data gathering process. For this purpose, five interviews where realized to expert dentists and also two different types of surveys: one for the universe defined by the set of dental-clinic patients and the second for the universe defined by the set of the dentists of the dental clinics of the Madrid Community. A sample of 200 surveys where collected for patients and a sample of 220 surveys where collected from active dentists belonging to the Ilustre Colegio Oficial de Odontólogos y Estomatólogos de la I Región Madrid. In the second stage of the model preparation, the processes of data-analysis, induction and synthesis of the final model where performed. The Graphic Probabilistic Models methodology was used to elaborate the final model, specifically, a Bayesian Network, where the variables (nodes) and their statistical and causal dependencies where integrated and modeled, representing thus, the obtained knowledge from the data obtained by the surveys and the scientific knowledge derived from previous research in the field. A Bayesian Net consisting on six principal nodes was obtained, of which two of them are directly observable: “Revisit Intention” y “SERVQUAL”, and the remaining four are submodels (a grouping of variables). These are: “Attitudinal”, “Disease Information”, “Socioeconomical” and “Services”. The main conclusions derived from the model, as an inference tool, and the analysis of the interviews are: (i) the variables inside the “Attitudinal” node are the most sensitive and significant. By making some particular imputations on the variables that conform the “Attitudinal” node (“RelationalMk”, “Satisfaction”, “Recommendation” y “Friendship”), high posterior probabilities (measured in revisit intention) are obtained for the loyalty of the dental-clinic patient. (ii) In the “Disease Information” node, the causal relation between the “Perception of disease” and “SERVQUAL” when “Perception of disease” is imputed is highlighted, showing that the perception of the severity of the patient’s disease conditions significantly the perception of service quality. As an example, by imputing some particular values to the “Clinic_Type” node high posterior probabilities are obtained for the “SERVQUAL” variables and for “Revisit Intention” showing that the clinic type influences significantly in the service quality perception and loyalty (revisit intention). (iii) In the “Socioeconomical” variable, the variable “Sex” showed to be non-significant, however, the “Age” variable and “Income” show high variability in its posterior probabilities when some variable from the “Services” node where imputed, showing thus, that these variables condition the intention to buy new services (“Services”), especially in the age range from 30 to 50 years in patients with incomes between 3000€ and 4000€. (iv) In the “Services” submodel the dental-clinic patients show high priors to buy services such as oral and gingival therapy, Dental Health Education and “Parking” service. (v) The obtained loyalty measures, from the behavioral perspective, “Visit/year” and “Time_clinic”, do not add significant information to the model. Neither the attitudinal loyalty component “Churn Efford”. (vi) From the interviews realized to the expert dentists it is observed that the owners of the traditional clinics have a low propensity to apply new commercial strategies due to a lack of resources and tools. In general, there exists an opposition to new business models in the sector, especially to the franchise dental model. All of this evidences a lack in business management in the sector. As future lines of research, a deep look into some statistical and causal relations is proposed, such as: SERVQUALServices; SatisfactionServices; RelationalMKServices, Perception of diseaseSatisfaction, as well as new measurement variables related to attitudinal loyalty that contribute to improve the model, for example, profit per patient and per visit.

Compatibilidad de Eretmocerus mundus Mercet (Hymenoptera: Aphelinidae) y Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae), importantes enemigos naturales de la mosca blanca Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) en cultivos hortícolas, con nuevas barreras físicas selectivas y modernos plaguicidas

Los programas de Gestión Integrada de Plagas (GIP) promueven el uso de estrategias de control que sean respetuosas con el medio ambiente, sin embargo el uso de insecticidas en los cultivos hortícolas sigue siendo necesario para el control de determinadas plagas, como es el caso de la mosca blanca Bemisia tabaci (Gennadius). Por ello, el objetivo de esta tesis es el estudio de la integración de las tres estrategias de control más empleadas hoy en día para el control de plagas: el control biológico, el físico y el químico. Una primera parte de este trabajo ha consistido en el estudio de los efectos letales y subletales de once insecticidas, aplicados a la dosis máxima de campo, sobre los enemigos naturales Eretmocerus mundus Mercet y Amblyseius swirskii Athias-Henriot, mediante ensayos de laboratorio y persistencia (laboratorio extendido). Para la evaluación de la toxicidad de los insecticidas sobre los estados de vida más protegidos de estos enemigos naturales, se trataron bajo la Torre de Potter las pupas de E. mundus y los huevos de A. swirskii. Además, se llevaron a cabo ensayos de contacto residual para determinar los efectos letales y subletales de estos insecticidas sobre el estado adulto de ambas especies de enemigos naturales. Para ello, los pesticidas se aplicaron sobre placas de cristal (laboratorio) o sobre plantas (laboratorio extendido: persistencia). Los resultados mostraron que los insecticidas flonicamida, flubendiamida, metaflumizona, metoxifenocida, spiromesifen y spirotetramat eran compatibles con el estado de pupa de E. mundus (OILB 1: Inocuos). Sin embargo, abamectina, deltametrina y emamectina fueron categorizadas como ligeramente tóxicas (OILB 2) al causar efectos deletéreos. Los dos pesticidas más tóxicos fueron spinosad y sulfoxaflor, los cuales redujeron significativamente la emergencia de las pupas tratadas (OILB 4: Tóxicos). Flonicamida, flubendiamida, metoxifenocida y spiromesifen fueron compatibles con el estado adulto de E. mundus (OILB 1: Inocuos). Abamectina, deltametrina, emamectina, metaflumizona y spiromesifen pueden ser recomendados para su uso en programas de GIP, si se usan los plazos de seguridad apropiados, de acuerdo con la persistencia de cada uno de estos insecticidas, antes de la liberación del enemigo natural. Al contrario, spinosad y sulfoxaflor no resultaron ser compatibles (OILB D: Persistentes), aunque la realización de ensayos adicionales es necesaria para ver los efectos de los mismos en campo. Todos los insecticidas estudiados, excepto el spirotetramat (OILB 2: Ligeramente tóxico), fueron selectivos para el estado de huevo de A. swirskii (OILB 1: Inocuos). Flonicamida, flubendiamida, metaflumizona, metoxifenocida, spiromesifen, spirotetramat y sulfoxaflor, fueron compatibles con el estado adulto de A. swirskii (OILB 1: Inocuos). Abamectina, deltametrina, emamectina y spinosad pueden ser recomendados para su uso en programas de GIP, si se usan los plazos de seguridad apropiados, de acuerdo con la persistencia de cada uno de estos insecticidas, antes de la liberación del enemigo natural. Entre las nuevas estrategias de la GIP, los plásticos y mallas fotoselectivas han demostrado ser una herramienta importante para el control de plagas y enfermedades en cultivos hortícolas protegidos. Por ello, en una segunda parte de este trabajo, se estudiaron tanto los efectos directos, como la combinación de efectos directos y mediados por planta y plaga de ambientes pobres en luz UV, en presencia o ausencia del Virus del rizado amarillo del tomate (TYLCV), sobre E. mundus. En primer lugar, se realizó un ensayo al aire libre para la evaluación de la capacidad de vuelo de E. mundus en cajas tipo túnel (1 x 0,6 x 0,6 m) cubiertas con distintas barreras absorbentes de luz UV. Se detectó un efecto directo en la capacidad de orientación de E. mundus, debido a que este parasitoide utiliza estímulos visuales para localizar a sus huéspedes, únicamente en las barreras que bloqueaban más del 65% de la luz UV (malla G). En segundo lugar, bajo condiciones de invernadero, se evaluó la combinación de efectos directos y mediados por planta y plaga sobre E. mundus, usando plantas de tomate sanas o infectadas con el TYLCV y cajas (30 x 30 x 60 cm) cubiertas con los distintos plásticos fotoselectivos. En este caso, no se observó ningún efecto en la capacidad benéfica del parasitoide cuando este estaba en contacto con plantas de tomate infestadas con ninfas de B. tabaci, lo que demuestra que este insecto usa estímulos táctiles para encontrar a sus huéspedes a cortas distancias. Además, las diferentes condiciones de radiación UV estudiadas tuvieron cierto impacto en la morfología, fisiología y bioquímica de las plantas de tomate, infestadas o no con el virus de la cuchara, detectándose pequeñas alteraciones en alguno de los parámetros estudiados, como el peso fresco y seco, el contenido en H y el espesor de las cutículas y de las paredes celulares de la epidermis foliar. Por último, no se observaron efectos de la radiación UV mediados por planta, ni en B. tabaci ni en su parasitoide, E. mundus. En una tercera parte, se evaluaron los efectos de una malla tratada con bifentrin sobre ambos enemigos naturales, en ensayos de laboratorio, semicampo y campo. Las mallas tratadas fueron diseñadas originariamente para el control de mosquitos vectores de la malaria, y actualmente se está trabajando para su uso en agricultura, como una nueva estrategia de control de plagas. En ensayos de laboratorio, cuando adultos de E. mundus y A. swirskii se expusieron por contacto durante 72 horas con la malla tratada (cajas de 6 cm diámetro), se registró una alta mortalidad. Sin embargo, en el ensayo de preferencia, estos enemigos naturales no fueron capaces de detectar la presencia de bifentrin y, en aquellos individuos forzados a atravesar la malla tratada, no se observó mortalidad a corto plazo (72 horas). En estudios de semicampo, llevados a cabo bajo condiciones de invernadero en cajas de 25 x 25 x 60 cm de altura, la capacidad benéfica de E. mundus no se vio afectada. Finalmente, en ensayos de campo llevados a cabo en invernaderos comerciales (4000m2) en Almería, A. swirskii no se vio afectado por la presencia en el cultivo de la malla tratada con bifentrin y los niveles de infestación de B. tabaci y F. occidentalis detectados bajo dicha malla, fueron inferiores a los del control. Por último, se ha evaluado la composición de la microflora bacteriana de tres especies de parasitoides, E. mundus, Eretmocerus eremicus Rose & Zolnerowich y Encarsia formosa Gahan, y la influencia de la misma en su susceptibilidad a insecticidas. Se llevó a cabo una extracción total de ADN de los insectos y la región variable V4 del ARNr se amplificó usando cebadores universales bacterianos. Para identificar las secuencias de los géneros bacterianos presentes en los parasitoides, se realizó una Next Generation sequencing (Illumina sequencing). Una vez identificados los géneros bacterianos, el gen ADNr 16S de las Actinobacterias se amplificó del ADN extraído de los insectos, usando cebadores universales bacterianos y específicos de Actinobacterias, y los productos de la Nested PCR fueron clonados para identificar todas las especies del género Arthrobacter. Tres bacterias (A. aurescens Phillips, A. nicotinovarans Kodama, Yamamoto, Amano and Amichi y A. uratoxydans Stackebrandt, Fowler, Fiedler and Seiler), próximas a las especies de Arthrobacter presentes en los parasitoides, se obtuvieron de la colección bacteriana del BCCMTM/LMG y se midió su actividad esterasa. Finalmente, se realizaron ensayos con antibióticos (tetraciclina) y de contacto residual con insecticidas (abamectina) para determinar la influencia de las especies de Arthrobacter en la susceptibilidad de E. mundus a insecticidas. Los resultados muestran que este género bacteriano puede afectar a la toxicidad de E. mundus a abamectina, mostrando la importancia de la comunidad microbiana en enemigos naturales, factor que debe ser considerado en los estudios de evaluación de los riesgos de los insecticidas. ABSTRACT Integrated Pest Management (IPM) programs promote the use of control strategies more respectful with the environment; however the use of insecticides in vegetable crops is still needed to control certain pests, such as the whitefly Bemisia tabaci (Gennadius). Therefore, the objective of this work is to study the integration of the three most commonly used pest control strategies nowadays: biological, physical and chemical control. Firstly, the lethal and sublethal effects of eleven insecticides, applied at their maximum field recommended concentration, on the parasitic wasp Eretmocerus mundus Mercet and the predator Amblyseius swirskii Athias-Henriot has been assessed in the laboratory and in persistence tests (extended laboratory). To test the effects of pesticides on the most protected life stage of these natural enemies, E. mundus pupae and A. swirskii eggs were sprayed under a Potter precision spray tower. Laboratory contact tests were therefore conducted to determine the lethal and sublethal effects of these pesticides on the adult stage of these natural enemies. In the residual contact tests the pesticides were applied on glass plates (laboratory) or plants (extended laboratory: persistence). The study showed that the insecticides flonicamid, flubendiamide, metaflumizone, methoxyfenozide, spiromesifen and spirotetramat were selective for E. mundus pupae (IOBC 1: Harmless). Nevertheless, abamectin, deltamethrin and emamectin were categorized as slightly harmful (IOBC 2) due to the deleterious effects caused. The two most harmful pesticides were spinosad and sulfoxaflor, which significantly reduced the adult emergence from treated pupae (IOBC 4: Harmful). Flonicamid, flubendiamide, methoxyfenozide and spiromesifen were compatible with E. mundus adults (IOBC 1: Harmless). Base on the duration of the harmful activity, abamectin, deltamethrin, emamectin, metaflumizone and spirotetramat could be recommended for use in IPM programs if appropriate safety deadlines are used before the natural enemy release. On the contrary, spinosad and sulfoxaflor were not compatible (IOBC D: persistent), although additional studies are required to determine their effects under field conditions. All the pesticides tested, except spirotetramat (IOBC 2: Slightly harmful), were selective for A. swirskii eggs (IOBC 1: Harmless). Flonicamid, flubendiamide, metaflumizone, methoxyfenozide, spiromesifen, spirotetramat and sulfoxaflor were compatible with A. swirskii adults (IOBC 1: Harmless). However, abamectin, deltamethrin, emamectin and spinosad could be recommended for use in IPM programs if appropriate safety deadlines are used before the natural enemy release. Among new IPM strategies, UV-absorbing photoselective plastic films and nets have been shown to be an important tool for the control of pests and diseases in horticultural protected crops. Because of that, we secondly studied the plant and pest insect-mediated and/or the direct effects on E. mundus under different UV radiation conditions, in presence or absence of the Tomato Yellow Leaf Curl Virus (TYLCV). In the first experiment, performed outdoors, the flight activity of E. mundus was studied in one-chamber tunnels (1 x 0.6 x 0.6 m) covered with different photoselective barriers. Because E. mundus uses visual cues for host location at a long distance, a direct effect on its host location ability was detected, but only in the UV-absorbing barriers blocking more than 65% of the UV light (G net). In a second experiment, the direct and plant and pest insect-mediated effects of different UV radiation conditions on E. mundus were studied, inside cages (30 x 30 x 60 cm) covered with the different UVplastic films and under greenhouse conditions, using healthy or TYLCV-virus infected tomato plants. In this case, not any effect on the beneficial capacity of this parasitoid was detected, proving that he uses tactile cues at a short distance of the host. Moreover, the different UV radiation conditions studied had a certain direct impact in the morphology, physiology and biochemistry of tomato plants infested or not with the TYLCV, and small alterations in some parameters such as fresh and dry weight, H percentage and cuticle and cell wall thickness of epidermal cells of the leaves, were detected. Finally, none plant-mediated UV effects neither in the whitefly B. tabaci nor in their parasitic wasp were found. Thirdly, the effects of a bifenthrin treated net were evaluated in different laboratory, semi-field and field experiments on the natural enemies studied. Treated nets were developed long time ago aiming at the control of the mosquitoes vectors of malaria, and nowadays, there is a great interest on assessing the possibility of their use in agriculture. In laboratory assays, a high mortality was recorded when E. mundus and A. swirskii adults were exposed by contact to the bifenthrin treated net for 72 hours in small cages (12 cm diameter). However, these natural enemies were not able to detect the presence of bifenthrin in a dual-choice test and no short-term mortality (72 hours) was recorded in those individuals that went through the treated net. In semi-field assays, performed under greenhouse conditions with cages of 25 x 25 x 60 cm high, the beneficial capacity of E. mundus was not affected. Finally, in field assays carried out in commercial multispan greenhouses (4000 m2) in Almería, A. swirskii was not affected by the presence of the bifenthrin treated net in the crop and the B. tabaci and F. occidentalis infestation levels were significantly lower than in the control. Finally, the composition of the microflora present in three species of parasitoids, E. mundus, Eretmocerus eremicus Rose & Zolnerowich and Encarsia formosa Gahan, and its influence in their susceptibility to insecticides, have been assessed. A total DNA extraction was performed on insects and universal bacterial primers were used to amplify the variable V4 region of the rRNA. A Next Generation sequencing (Illumina sequencing) was performed to identify the sequences of the bacterial genera present in the parasitic wasps. Once, the bacterial genera were identified, 16S rDNA gene of Actinobacteria were amplified from insects DNA extracts using the universal bacterial and actinobacterial primers, and the nested PCR products, were cloned to identify the Arthrobacter species. Three bacteria (A. aurescens Phillips, A. nicotinovarans Kodama, Yamamoto, Amano and Amichi and A. uratoxydans Stackebrandt, Fowler, Fiedler and Seiler), having the closest match with the Arthrobacter species present in the parasitic wasps, were obtained from the BCCMTM/LMG bacteria collection and its esterase activity was measured. Finally, antibiotic and residual contact tests were done to determine the influence of Arthrobacter species in the susceptibility of E. mundus to pesticides (abamectin). The results suggest that this bacterial genus can affect the toxicity of E. mundus to abamectin, which in turn supports the importance of the microbial community in natural enemies that it should be considered as a factor in risk assessment tests of pesticides.

FUSÕES E AQUISIÇÕES: UMA EXPERIÊNCIA DE INTEGRAÇÃO COM SUCESSO

Esta dissertação apresenta um estudo exploratório que tem como objetivo analisar o caso de uma experiência de integração com sucesso de uma fusão de duas empresas com estruturas organizacionais diferentes, tomando como referência a experiência internacional diante da escassez de estudos sistemáticos sobre a integração de fusões e aquisições no Brasil. O estudo se propõe a investigar como foi processada a integração entre as duas empresas buscando analisar os fatores que ocasionaram o sucesso dessa fusão. A metodologia adotada consiste na pesquisa bibliográfica e documental com observação participativa. Os dados foram obtidos por meio de documentos públicos sobre a empresa, que serviram de apoio à pesquisa realizada. Para objeto de pesquisa foi selecionada a empresa SmithKline Beecham, por ser uma empresa global com fabricas no Brasil. Os resultados obtidos apontaram que a integração da empresa foi feita com sucesso, significando que os objetivos estratégicos e de sinergias da fusão, representados por resultados financeiros, de mercado, pesquisa, desenvolvimento e lançamento de novos produtos foram alcançados. A empresa combinada, depois de terminado o processo de integração, apresentava resultados superiores do que quando as duas atuavam separadamente, comprovando que os mecanismos utilizados na integração das duas empresas funcionaram com eficácia. Entretanto, recomendamos que outros estudos como este sejam organizados na busca de novos aspectos que possam servir de suporte às decisões dos empresários quanto à adoção da abordagem estratégica das fusões e aquisições.(AU)

FUSÕES E AQUISIÇÕES: UMA EXPERIÊNCIA DE INTEGRAÇÃO COM SUCESSO

Esta dissertação apresenta um estudo exploratório que tem como objetivo analisar o caso de uma experiência de integração com sucesso de uma fusão de duas empresas com estruturas organizacionais diferentes, tomando como referência a experiência internacional diante da escassez de estudos sistemáticos sobre a integração de fusões e aquisições no Brasil. O estudo se propõe a investigar como foi processada a integração entre as duas empresas buscando analisar os fatores que ocasionaram o sucesso dessa fusão. A metodologia adotada consiste na pesquisa bibliográfica e documental com observação participativa. Os dados foram obtidos por meio de documentos públicos sobre a empresa, que serviram de apoio à pesquisa realizada. Para objeto de pesquisa foi selecionada a empresa SmithKline Beecham, por ser uma empresa global com fabricas no Brasil. Os resultados obtidos apontaram que a integração da empresa foi feita com sucesso, significando que os objetivos estratégicos e de sinergias da fusão, representados por resultados financeiros, de mercado, pesquisa, desenvolvimento e lançamento de novos produtos foram alcançados. A empresa combinada, depois de terminado o processo de integração, apresentava resultados superiores do que quando as duas atuavam separadamente, comprovando que os mecanismos utilizados na integração das duas empresas funcionaram com eficácia. Entretanto, recomendamos que outros estudos como este sejam organizados na busca de novos aspectos que possam servir de suporte às decisões dos empresários quanto à adoção da abordagem estratégica das fusões e aquisições.(AU)

T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function

T helper (Th) cells can be categorized according to their cytokine expression. The differential induction of Th cells expressing Th1 and/or Th2 cytokines is key to the regulation of both protective and pathological immune responses. Cytokines are expressed transiently and there is a lack of stably expressed surface molecules, significant for functionally different types of Th cells. Such molecules are of utmost importance for the analysis and selective functional modulation of Th subsets and will provide new therapeutic strategies for the treatment of allergic or autoimmune diseases. To this end, we have identified potential target genes preferentially expressed in Th2 cells, expressing interleukin (IL)-4, IL-5, and/or IL-10, but not interferon-γ. One such gene, T1/ST2, is expressed stably on both Th2 clones and Th2-polarized cells activated in vivo or in vitro. T1/ST2 expression is independent of induction by IL-4, IL-5, or IL-10. T1/ST2 plays a critical role in Th2 effector function. Administration of either a mAb against T1/ST2 or recombinant T1/ST2 fusion protein attenuates eosinophilic inflammation of the airways and suppresses IL-4 and IL-5 production in vivo following adoptive transfer of Th2 cells.

Dopamine-dependent responses to morphine depend on glucocorticoid receptors

Previous work has shown that glucocorticoid hormones facilitate the behavioral and dopaminergic effects of morphine. In this study we examined the possible role in these effects of the two central corticosteroid receptor types: mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish this, specific antagonists of these receptors were infused intracerebroventricularly and 2 hr later we measured: (i) locomotor activity induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity induced by an infusion of morphine (1 μg per side) into the ventral tegmental area, which is a dopamine-dependent behavioral response to morphine; (iii) morphine-induced dopamine release in the nucleus accumbens, a dopaminergic projection site mediating the locomotor and reinforcing effects of drugs of abuse. Blockade of MRs by spironolactone had no significant effects on locomotion induced by systemic morphine. In contrast, blockade of GRs by either RU38486 or RU39305, which is devoid of antiprogesterone effects, reduced the locomotor response to morphine, and this effect was dose dependent. GR antagonists also reduced the locomotor response to intraventral tegmental area morphine as well as the basal and morphine-induced increase in accumbens dopamine, as measured by microdialysis in freely moving rats. In contrast, spironolactone did not modify dopamine release. In conclusion, glucocorticoids, via GRs, facilitate the dopamine-dependent behavioral effects of morphine, probably by facilitating dopamine release. The possibility of decreasing the behavioral and dopaminergic effects of opioids by an acute administration of GR antagonists may open new therapeutic strategies for treatment of drug addiction.

Suppression of glucocorticoid secretion and antipsychotic drugs have similar effects on the mesolimbic dopaminergic transmission

Specific antagonists of central dopaminergic receptors constitute the major class of antipsychotic drugs (APD). Two principal effects of APD are used as criteria for the pre-clinical screening of their antipsychotic action: (i) inhibition of basal and depolarization-induced activity of mesolimbic dopaminergic neurons; (ii) antagonism of the locomotor effects of dopaminergic agonists. Given that glucocorticoid hormones in animals increase dopamine release and dopamine-mediated behaviors and that high levels of glucocorticoids can induce psychotic symptoms in humans, these experiments examined whether inhibition of endogenous glucocorticoids might have APD-like effects on mesolimbic dopaminergic transmission in rats. It is shown that suppression of glucocorticoid secretion by adrenalectomy profoundly decreased (by greater than 50%): (i) basal dopaminergic release and the release of dopamine induced by a depolarizing stimulus such as morphine (2 mg/kg, s.c.), as measured in the nucleus accumbens of freely moving animals by microdialysis; (ii) the locomotor activity induced by the direct dopaminergic agonist apomorphine. The effects of adrenalectomy were glucocorticoid specific given that they were reversed by the administration of glucocorticoids at doses within the physiological range. Despite its profound diminution of dopaminergic neurotransmission, adrenalectomy neither modified the number of mesencephalic dopaminergic neurons nor induced gliosis in the mesencephalon or in the nucleus accumbens, as shown by tyrosine hydroxylase and glial fibrillary acidic protein immunostaining. In conclusion, these findings suggest that blockade of central effects of glucocorticoids might open new therapeutic strategies of behavioral disturbances.

Identification of eIF2Bγ and eIF2γ as cofactors of hepatitis C virus internal ribosome entry site-mediated translation using a functional genomics approach

The 5′-untranslated region of hepatitis C virus (HCV) is highly conserved, folds into a complex secondary structure, and functions as an internal ribosome entry site (IRES) to initiate translation of HCV proteins. We have developed a selection system based on a randomized hairpin ribozyme gene library to identify cellular factors involved in HCV IRES function. A retroviral vector ribozyme library with randomized target recognition sequences was introduced into HeLa cells, stably expressing a bicistronic construct encoding the hygromycin B phosphotransferase gene and the herpes simplex virus thymidine kinase gene (HSV-tk). Translation of the HSV-tk gene was mediated by the HCV IRES. Cells expressing ribozymes that inhibit HCV IRES-mediated translation of HSV-tk were selected via their resistance to both ganciclovir and hygromycin B. Two ribozymes reproducibly conferred the ganciclovir-resistant phenotype and were shown to inhibit IRES-mediated translation of HCV core protein but did not inhibit cap-dependent protein translation or cell growth. The functional targets of these ribozymes were identified as the gamma subunits of human eukaryotic initiation factors 2B (eIF2Bγ) and 2 (eIF2γ), respectively. The involvement of eIF2Bγ and eIF2γ in HCV IRES-mediated translation was further validated by ribozymes directed against additional sites within the mRNAs of these genes. In addition to leading to the identification of cellular IRES cofactors, ribozymes obtained from this cellular selection system could be directly used to specifically inhibit HCV viral translation, thereby facilitating the development of new antiviral strategies for HCV infection.