Bodenlos

Submission of five poems and two short texts for next Dossier on Brazilian Contemporary Literature

A diworsefication case study : rebuilding LEGO brick by brick

This paper examines how a company may successfully walk out of a diworsefication situation: stage in which a brand has excessively overdiversified over new extensions, to the point it got weaker and its performance started failing. The study explains why companies enter a failing stage, particularly, mature companies which desperately search for innovation. It also concludes that several internal and external factors may lead a company to extend its business and that the idea of leveraging brand awareness and reputation, and spreading business risk over products may be appealing for a company to enter new markets. Yet, hidden costs, the possibility of a bad reputation on the parent brand, and extreme deviation from the core business may lead a brand to become lost, distracted, failing and losing money due to overstretching. Thus, this study provides guidance on when to stop diversifying and how to do it. The presented recovery strategies are content-orientated and process-orientated. The first includes cost efficiencies, asset retrenchment, focus on the core activities and build for the future. The latter involves reinvigoration of firm leadership and culture change. To better understand these concepts, this paper uses LEGO’s case as a real-life example of a success story of a company which almost went bankrupt due to a blind chase after a brand extension strategy. Fortunately, the Danish company turned around mostly thanks to a fierce cut on unprofitable adjacencies and a rigid refocusing on the core business product, the bricks.Este estudo explora como uma empresa é capaz de sair com sucesso de uma situação de diworsification, termo derivado do inglês diverse + worse: estado que uma marca atinge após ter extendido excessivamente a sua oferta de productos e serviços, tendo por isso ficado mais fraca e com uma pior performance. Este estudo explica o que leva a performance das empresas a falhar, particularmente, empresas amadurecidas que procuram inovar-se. Esta tese conclui que são muitos os motivos externos e internos que levam uma empres a extender o seu negócio, e que a possibilidade de obter maior reconhecimento e de repartir o risco da marca por vários produtos alicia qualquer empresa a explorar novos mercados. Contudo, os custos escondidos destas extensões, e a possibilidade de deteriorização da marca e de que esta desvie o seu foco do negócio principal e se distraia, podem levar ao seu falhanço. Assim, este estudo apresenta várias estratégias de recuperação, nomeadamente estratégias de conteúdo e de processo. A primeira inclui eficiências de custos, foco nas atividades principais da empresa, e construção para o futuro. A segunda inclui uma liderança firme e cultura de mudança. Para melhor compreender estes conceitos, este estudo usa a LEGO como exemplo prático de uma empresa que saiu com sucesso de uma situação de quase falência, devido a uma estratégia desmedida de extensão de marca. Felizmente, a empresa Dinamarquesa, conseguiu dar a volta cortando extensões que apenas davam prejuízo, e adoptando uma estratégia de focalização no producto principal da marca, tijolos

A multimodal transportation network between China and Europe

Organizations and the markets where they act upon are in constant change, therefore, companies have to innovate and adapt to what the market demands, otherwise they will become obsolete and lose their place. Constant innovation and improvement are a must in any business. The present investigation is based on multimodal network transportation, where document analysis is conducted and a research is made concerning transportation connections, modes of transportation, duration, costs, and potential departure and arrival cities. A multimodal network between Chongqing and London is constructed based on the information found within other freight forwarders. To design this network, the methodology used is based on a time-expanded model. The research and results show that based on a thorough research, it is possible to find information on multimodal networks in order to create one. Based on the time-expanded model methodology, the network will be created using information from some articles and also based on some assumptions. Furthermore, feasible solutions are represented within each given lead time, allowing the network to represent several possible connections to go from the origin to the destination during this time. From here, it is possible to determine the most efficient path. This thesis delivers a robust network, with a wide range of important information on costs, durations and weekly frequency on the different modes of transportation. The network methodology allows it to be adjusted to other case, it is flexible, and can be more complex.As empresas e os mercados nas quais estas se inserem estão em constante mudança, e, devido a isto, as empresas têm de inovar e de se adaptar às exigências do mercado, ou de outra forma irão tornar-se obsoletas. A inovação e melhoria constante são essenciais em qualquer negócio. A presente investigação baseia-se numa rede de transporte multimodal onde uma parte crucial passa pela procura de informação relativamente a rotas de transporte, modos de transporte, duração, custos e cidades potenciais como nodos de partida e chegada. Uma rede multimodal entre Chongqing e Londres será construída com base na informação recolhida. Para desenhar esta rede, a metodologia usada tem como base o "time-expanded models". Os resultados demonstram que com base numa pesquisa minuciosa, é possível encontrar informação relativa a redes multimodais de forma a ser possível criar uma. Com base no modelo "time-expanded" a rede será construída, usando informação não só de artigos, mas também de pressupostos necessários de criar. Além disto, a rede desenvolvida representará soluções admissíveis dado um certo "lead time", permitindo que a rede representada tenha várias possíveis conexões desde a origem até ao destino. A partir deste leque de conexões, será possível determinar o percurso mais eficiente. Esta tese apresenta uma rede bastante completa, com informação relevante relativa a custos, durações e frequências semanais dos diferentes modos de transporte. A metodologia utilizada para criar a rede permite que esta seja ajustada para ser utilizada noutros casos, pois esta é bastante flexível

Repurposing of terconazole as an anti Trypanosoma cruzi agent

Trypanosoma cruzi is the causative agent of Chagas disease, a parasitic infection endemic in Latin America. Currently there are no effective treatments for the chronic phase of the disease, when most patients are diagnosed, therefore the development of new drugs is a priority area. Several triazoles, used as fungicides, exhibit trypanocidal activity both in vitro and in vivo. The mechanism of action of such drugs, both in fungi and in T. cruzi, relies in the inhibition of ergosterol biosynthesis affecting the cell viability and growth. Among them, terconazole was the first triazole antifungal drug for human use. In this work, the trypanocidal activity of terconazole was evaluated using in vitro assays. In epimastigotes of two parasites strains from different discrete typing units (Y and Dm28c) the calculated IC50 were 25.7 μM and 21.9 μM, respectively. In trypomastigotes and amastigotes (the clinically relevant life-stages of T. cruzi) a higher drug susceptibility was observed with IC50 values of 4.6 μM and 5.9 μM, respectively. Finally, the molecular docking simulations suggest that terconazole inhibits the T. cruzi cytochrome P450 14-α-demethylase, interacting in a similar way that other triazole drugs. Drug repurposing to Chagas disease treatment is one of the recommended approach according to the criterion of international health organizations for their application in neglected diseases.Fil: Reigada, Chantal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Valera Vera, Edward Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Chagas disease treatment: From new therapeutic targets to drug discovery and repositioning

Chagas disease, caused by the protozoan Trypanosoma cruzi, currently affects millions of people worldwide although it is only endemic in America. Chagas is considered a neglected tropical disease because it afflicts the low-income and poorest populations in developing regions of the Americas, particularly in remote, rural areas where infrastructure such as adequate housing, sanitation and clinical resources are limited. In addition, governments pay scarce or no attention to this health problem.Benznidazole and nifurtimox, both discovered more than 50 years ago, are the only two drugs available to treat Chagas disease and not only present severe side effects but also are ineffective in the chronic phase of the disease when most of the patients are diagnosed. Recent efforts to develop new treatments for Chagas disease, including posaconazole repositioning and the prodrug of ravuconazole (E1224) trial, have been unsuccessful and remark the urgent need to develop new therapeutic alternatives. The scientific effort must be focused in finding simple, safe and effective drugs that directly target the parasite without harming the patients.It is known that the identification of reliable molecular targets for drug development is challenging, with high rates of failure at the stage of validating potential candidates. Thus, we propose in this Special Issue to revise different potential drug targets of the parasite T. cruzi and to explore the latest advances in drug design and drug repositioning.The first review introduces the challenges of Chagas disease and evidenced the requirement of new therapies to treat it. Egui et al. [1] focus on the immunologic profile associated with the clinical status and evolution of Chagas disease patients as wells as the effectiveness of the current treatment including different biomarkers to monitor the T. cruzi infection. In the next revisions, different metabolic pathways and proteins are explored as therapeutic targets against the parasite T. cruzi, and the final two reviews include the latest strategies to identify new potential targets.Alonso et al. [2] explore the bromodomain-containing proteins as potential targets in protozoa since some of these proteins are essential for viability and diverge from the mammalian ones, which are also approach in their review. Cordeiro [3] describes the importance of the NADPH producing enzymes in biosynthetic processes as well as in the neutralization of reactive oxygen and nitrogen species. He propose them as potential targets, highlighting the role of glucose-6-phosphate dehydrogenase and the cytosolic malic enzyme.Schoijet et al. [4] propose the signal transduction pathway in trypanosomatids as a novel therapeutic target, particularly the cAMP signaling pathway. The authors shed light in phosphodiesterases (PDEs) as druggable target, because of the prominent roles they play in the life cycle and the essentiality for parasite survival. Despite they are highly conserved enzymes, authors highlight the potentiality of differential inhibition from their human orthologs and suggest the drug repositioning approach as a promising strategy to find inhibitors among the numerous drugs against human PDEs that are available in the market.Sangenito et al. [5] introduce the aspartyl peptidase inhibitors used to treat the infection with the human immunodeficiency virus (HIV) as a drug repositioning strategy. Co-infection of patients with HIV with other microorganisms, such as protozoan parasites, is common and the use of HIV peptidase inhibitors evidenced a decrease both in prevalence and incidence of these co-infections. Indeed, several of these inhibitors have been tested in T. cruzi showing multiple pathophysiological effects on the parasite.Talevi et al. [6] present the thiol-polyamine metabolism, a well-known and validated T. cruzi target because many of its components are absent or significantly differ from the host homologs offering interesting candidates for a rational design of selective drugs. In this review, the authors critically revise the state of the art of the thiol-polyamine metabolism deepening in the pharmacological potential of its components and, properly introducing to the different computer-aided approximations to assist systematic drug repositioning strategies. Sayé et al. [7], propose the most represented family of amino acid and derivative transporters in T. cruzi as drug targets, focalizing in proline and polyamine permeases. This family is absent in the human host and their members are responsible of the acquisition of relevant nutrients for the survival of the parasite. The review also discusses the latest advances in drug repositioning strategy applied to these transporters. Saavedra et al. [8] explore new fields in drug target development and open new interrogations about target prioritization. The authors analyse the fundamentals of Metabolic Control Analysis and kinetic modelling of metabolic pathways and apply them to the trypanothion metabolism of T. cruzi. They conclude that the enzymes with the highest pathway control are the most convenient targets for therapeutic intervention, leaving under discussion if the agreed criterion of gene essentiality is enough to guarantee a valid target. Last, Salas-Sarduy et al. [9] introduce the initiative made by public-private programs for drug discovery against Chagas disease. This strategy consists in taking advantage of the resources invested by the pharmaceutical industry in other commercial areas allowing the evaluation of libraries of millions of low-molecular weight synthetic compounds. These strategies require high-throughput screenings and setting up of robust enzymatic assays to identify and validate small molecule inhibitors, a matter as well addressed by the authors.Recognizing that Chagas disease requires urgent attention is the first step to develop new alternative treatments with less toxic effects, and this Special Issue is responding directly to this need.Fil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

El Marketing : Los Paradigmas de Marketing

La presente investigación de carácter bibliográfico tiene como tema el marketing como parte de los ejes de investigación del departamento de administración de empresas de la facultad de ciencias económicas de UNAN Managua y su sub tema los paradigmas del marketing. Se tiene como objetivo general el describir los paradigmas del marketing y su impacto hacia el consumidor por medio de los estilos de vida, su relación de consumo y consecuencias del consumo simbólico. La base teórica que sustenta este informe se hace énfasis en cuatro capítulos tales como nuevos paradigmas del marketing , paradigmas del consumidor, estilos de vida paradigmas del mercado, y por último antecedentes y consecuencias del consumo simbólico. Las técnicas utilizadas para el desarrollo de este informe fueron la lectura y recolección de documentación bibliográfica basado en el marketing, así mismo la tabulación del informe se hará aplicando las normas APAs 6 de Javeriano. Los resultados o presentación del informe están basados en la normativa de presentación de seminario de graduación plan 1999 de la UNAN Managua. Los principales términos descriptores del informe, son la introducción, justificación, objetivo

Compositional analysis of soybean event IND-ØØ41Ø-5

Soybean (Glycine max L.) is the world’s largest source of protein feed and the second largest source of vegetable oil. Water restriction is the main limiting factor to achieve maximum soybean yields. Therefore, development of varieties that maintain yield under environmental stresses is a major objective of soybean breeding programs. The HaHB4 (Helianthus annuus homeobox 4) gene from sunflower encodes for a transcription factor involved in the plant´s tolerance to environmental stress. The introduction of HaHB4 in soybean led to the development of event IND-ØØ41Ø-5 (HB4® soybean), which displayed higher yield in environments having low productivity potential, compared with the parental control variety. Compositional analyses of soybean event IND-ØØ41Ø-5 were conducted both in Argentina and the United Sates. A total of 44 components were analyzed in grain and 9 components in forage. Based on the results of these studies it was concluded that soybean event IND-ØØ41Ø-5 was compositionally equivalent to its non-transgenic parental control.Fil: Chiozza, Mariana V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Agrobiotecnología de Rosario; Argentina. University of Iowa; Estados UnidosFil: Burachik, Moises. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Agrobiotecnología de Rosario; ArgentinaFil: Miranda, Patricia Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Agrobiotecnología de Rosario; Argentin

Identification of Trypanosoma cruzi Polyamine Transport Inhibitors by Computational Drug Repurposing

Trypanosoma cruzi is the causative agent of Chagas disease, a parasitic infection endemic in Latin America. In T. cruzi the transport of polyamines is essential because this organism is unable to synthesize these compounds de novo. Therefore, the uptake of polyamines from the extracellular medium is critical for survival of the parasite. The anthracene-putrescine conjugate Ant4 was first designed as a polyamine transport probe in cancer cells. Ant4 was also found to inhibit the polyamine transport system and produced a strong trypanocidal effect in T. cruzi. Considering that Ant4 is not currently approved by the FDA, in this work we performed computer simulations to find trypanocidal drugs approved for use in humans that have structures and activities similar to Ant4. Through a similarity ligand-based virtual screening using Ant4 as reference molecule, four possible inhibitors of polyamine transport were found. Three of them, promazine, chlorpromazine and clomipramine, showed to be effective inhibitors of putrescine uptake, and also revealed a trypanocidal activity in epimastigotes (IC50 values of 69.0, 50.8 and 49.4 μM, respectively) and trypomastigotes (IC50 values of 3.5, 2.8 and 1.4 μM, respectively). Finally, molecular docking simulations suggest that the interactions between the T. cruzi polyamine transporter TcPAT12 and all the identified inhibitors occur in the same region of the protein. However, this location is different from the site occupied by the natural substrates. The value of this effort is that repurposing known drugs in the treatment of other pathologies, especially neglected diseases such as Chagas disease, significantly decreases the time and economic cost of implementation.Fil: Reigada, Chantal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Phanstiel, Otto. University Of Central Florida; Estados UnidosFil: Valera Vera, Edward Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin