Добірка наукової літератури з теми "RBRV"

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Статті в журналах з теми "RBRV"

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Lotz, Henrike, Kai Sohn, Herwig Brunner, Fritz A. Mühlschlegel, and Steffen Rupp. "RBR1, a Novel pH-Regulated Cell Wall Gene of Candida albicans, Is Repressed by RIM101 and Activated by NRG1." Eukaryotic Cell 3, no. 3 (June 2004): 776–84. http://dx.doi.org/10.1128/ec.3.3.776-784.2004.

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ABSTRACT The transcription factor Rim101p of Candida albicans has been shown to play a major role in pH-dependent gene regulation. Rim101p is involved in cell wall biosynthesis, since it regulates PHR1 and PHR2, two almost functionally redundant cell wall glycosidases important for adaptation to either neutral or acidic habitats within the human host. To identify additional cell wall components regulated by Rim101p, we performed transcriptional profiling with a cell wall-specific DNA microarray. We showed that Rim101p contributes to the activation of known hypha-specific genes such as HWP1 and RBT1 but is also required for repression of the previously uncharacterized potential cell wall genes RBR1, RBR2, and RBR3. Further characterization of RBR1 revealed that it encodes a small glycosylphosphatidyl inositol protein that is expressed under acidic conditions predominantly at low temperature. Deletion of the gene resulted in a filamentation defect at low pH. Most interestingly, NRG1, a transcriptional repressor of hyphal growth in C. albicans, was required for RBR1 expression. The apparently activating effect of NRG1 observed in this study has not been described before. In addition, we showed that expression of NRG1 is not only temperature but also pH dependent.
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Sabelli, P. A., R. A. Dante, J. T. Leiva-Neto, R. Jung, W. J. Gordon-Kamm, and B. A. Larkins. "RBR3, a member of the retinoblastoma-related family from maize, is regulated by the RBR1/E2F pathway." Proceedings of the National Academy of Sciences 102, no. 37 (September 1, 2005): 13005–12. http://dx.doi.org/10.1073/pnas.0506160102.

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Lumppio, Heather L., Neeta V. Shenvi, Anne O. Summers, Gerrit Voordouw, and Donald M. Kurtz. "Rubrerythrin and Rubredoxin Oxidoreductase inDesulfovibrio vulgaris: a Novel Oxidative Stress Protection System." Journal of Bacteriology 183, no. 1 (January 1, 2001): 101–8. http://dx.doi.org/10.1128/jb.183.1.101-108.2001.

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ABSTRACT Evidence is presented for an alternative to the superoxide dismutase (SOD)-catalase oxidative stress defense system inDesulfovibrio vulgaris (strain Hildenborough). This alternative system consists of the nonheme iron proteins, rubrerythrin (Rbr) and rubredoxin oxidoreductase (Rbo), the product of therbo gene (also called desulfoferrodoxin). A Δrbo strain of D. vulgaris was found to be more sensitive to internal superoxide exposure than was the wild type. Unlike Rbo, expression of plasmid-borne Rbr failed to restore the aerobic growth of a SOD-deficient strain of Escherichia coli. Conversely, plasmid-borne expression of two different Rbrs from D. vulgaris increased the viability of a catalase-deficient strain of E. coli that had been exposed to hydrogen peroxide whereas Rbo actually decreased the viability. A previously undescribed D. vulgaris gene was found to encode a protein having 50% sequence identity to that of E. coliFe-SOD. This gene also encoded an extended N-terminal sequence with high homologies to export signal peptides of periplasmic redox proteins. The SOD activity of D. vulgaris is not affected by the absence of Rbo and is concentrated in the periplasmic fraction of cell extracts. These results are consistent with a superoxide reductase rather than SOD activity of Rbo and with a peroxidase activity of Rbr. A joint role for Rbo and Rbr as a novel cytoplasmic oxidative stress protection system in D. vulgaris and other anaerobic microorganisms is proposed.
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Spratt, Donald E., Helen Walden, and Gary S. Shaw. "RBR E3 ubiquitin ligases: new structures, new insights, new questions." Biochemical Journal 458, no. 3 (February 28, 2014): 421–37. http://dx.doi.org/10.1042/bj20140006.

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The RBR (RING-BetweenRING-RING) or TRIAD [two RING fingers and a DRIL (double RING finger linked)] E3 ubiquitin ligases comprise a group of 12 complex multidomain enzymes. This unique family of E3 ligases includes parkin, whose dysfunction is linked to the pathogenesis of early-onset Parkinson's disease, and HOIP (HOIL-1-interacting protein) and HOIL-1 (haem-oxidized IRP2 ubiquitin ligase 1), members of the LUBAC (linear ubiquitin chain assembly complex). The RBR E3 ligases share common features with both the larger RING and HECT (homologous with E6-associated protein C-terminus) E3 ligase families, directly catalysing ubiquitin transfer from an intrinsic catalytic cysteine housed in the C-terminal domain, as well as recruiting thioester-bound E2 enzymes via a RING domain. Recent three-dimensional structures and biochemical findings of the RBRs have revealed novel protein domain folds not previously envisioned and some surprising modes of regulation that have raised many questions. This has required renaming two of the domains in the RBR E3 ligases to more accurately reflect their structures and functions: the C-terminal Rcat (required-for-catalysis) domain, essential for catalytic activity, and a central BRcat (benign-catalytic) domain that adopts the same fold as the Rcat, but lacks a catalytic cysteine residue and ubiquitination activity. The present review discusses how three-dimensional structures of RBR (RING1-BRcat-Rcat) E3 ligases have provided new insights into our understanding of the biochemical mechanisms of these important enzymes in ubiquitin biology.
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Zouros, Theo J. M., Sofoklis Nikolaou, Ioannis Madesis, Angelos Laoutaris, Stefanos Nanos, Alain Dubois, and Emmanouil P. Benis. "Radiative Cascade Repopulation of 1s2s2p 4P States Formed by Single Electron Capture in 2–18 MeV Collisions of C4+ (1s2s 3S) with He." Atoms 8, no. 3 (September 21, 2020): 61. http://dx.doi.org/10.3390/atoms8030061.

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This study focuses on the details of cascade repopulation of doubly excited triply open-shell C3+(1s2s2p)4P and 2P± states produced in 2–18 MeV collisions of C4+(1s2s3S) with He. Such cascade calculations are necessary for the correct determination of the ratio R of their cross sections, used as a measure of spin statistics [Madesis et al. PRL 124 (2020) 113401]. Here, we present the details of our cascade calculations within a new matrix formulation based on the well-known diagrammatic cascade approach [Curtis, Am. J. Phys. 36 (1968) 1123], extended to also include Auger depopulation. The initial populations of the 1s2snℓ4L and 1s2snℓ2L levels included in our analysis are obtained from the direct nℓ single electron capture (SEC) cross sections, calculated using the novel three-electron close-coupling (3eAOCC) approach. All relevant radiative branching ratios (RBR) for n≤4 were computed using the COWAN code. While doublet RBRs are found to be very small, quartet RBRs are found to be large, indicating cascade feeding to be important only for quartets, consistent with previous findings. Calculations including up to third order cascades, extended to n→∞ using an n−3 SEC model, showed a ∼60% increase of the 1s2s2p4P populations due to cascades, resulting, for the first time, in R values in good overall agreement with experiment.
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Park, Eun Cheol. "Implementation of Korea RBRVS." Journal of the Korean Medical Association 40, no. 11 (1997): 1390. http://dx.doi.org/10.5124/jkma.1997.40.11.1390.

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Gott, Vincent L. "RBRVS and cardiothoracic surgery." Annals of Thoracic Surgery 55, no. 1 (January 1993): 5–7. http://dx.doi.org/10.1016/0003-4975(93)90465-t.

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SAKSENA, SANJEEV. "RBRVS: The Second Coming." Pacing and Clinical Electrophysiology 19, no. 2 (February 1996): 252–53. http://dx.doi.org/10.1111/j.1540-8159.1996.tb03317.x.

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Foreman, Julie. "RBRVS Rules Finally Completed!" Archives of Ophthalmology 109, no. 12 (December 1, 1991): 1656. http://dx.doi.org/10.1001/archopht.1991.01080120038017.

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Chamberlain, C. J., J. Kraus, P. D. Kohnen, C. E. Finn, and R. R. Martin. "First Report of Raspberry bushy dwarf virus in Rubus multibracteatus from China." Plant Disease 87, no. 5 (May 2003): 603. http://dx.doi.org/10.1094/pdis.2003.87.5.603a.

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Raspberry bushy dwarf virus (RBDV), genus Idaeovirus, has been reported in commercial Rubus spp. from North and South America, Europe, Australia, New Zealand, and South Africa. Infection can cause reduced vigor and drupelet abortion leading to crumbly fruit and reduced yields (3,4). In recent years, Rubus germplasm in the form of seed, was obtained on several collection trips to The People's Republic of China to increase the diversity of Rubus spp. in the USDA-ARS National Clonal Germplasm Repository, (Corvallis, OR). Before planting in the field, seedlings were tested for the presence of RBDV, Tomato ringspot virus, and Tobacco streak virus using triple-antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA) (antiserum produced by R. R. Martin). One symptomless plant of R. multibracteatus H. Lev. & Vaniot (PI 618457 in USDA-ARS GRIN database), from Guizhou province in China, tested positive for RBDV (RBDV-China). After mechanical transmission on Chenopodium quinoa Willd., this isolate produced typical symptoms of RBDV (3). To determine if RBDV-China was a contaminant during the handling of the plants, or if the source was a seedborne virus, the coat protein gene was sequenced and compared to published sequences of RBDV. RNA was extracted from leaves of R. multibracteatus and subjected to reverse transcription-polymerase chain reaction (RT-PCR) using primers that flank the coat protein gene. Products from four separate PCR reactions were sequenced directly or were cloned into the plasmid vector pCR 2.1 (Invitrogen, Carlsbad, CA) and then sequenced. The coding sequence of the coat protein gene of RBDV-China was 87.5% (722/825) identical to that isolated from black raspberry (Genbank Accession No. s55890). The predicted amino acid sequences were 91.6% (251/274) identical. Previously, a maximum of five amino acid differences had been observed in the coat proteins of different RBDV strains (1). The 23 differences observed between RBDV-China and the isolate from black raspberry (s55890) confirm that the RBDV in R. multibracteatus is not a greenhouse contaminant but is indeed a unique strain of RBDV. In addition, monoclonal antibodies (MAbs) to RBDV (2) were tested against RBDV-China. In these tests, MAb D1 did not detect RBDV-China, whereas MAb R2 and R5 were able to detect the strain. This is the first strain of RBDV that has been clearly differentiated by MAbs using standard TAS-ELISA tests. Although RBDV is common in commercial Rubus spp. worldwide, to our knowledge, this is the first report of RBDV in R. multibracteatus, and the first report of RBDV from China. The effects of this new strain of RBDV could be more or less severe, or have a different host range than previously studied strains. It is more divergent from the type isolate than any other strain that has been studied to date. Phylogenetic analysis of coat protein genes of RBDV may be useful in understanding the evolution and spread of this virus. References: (1) A. T. Jones et al. Eur. J. Plant Pathol. 106:623, 2000. (2) R. R. Martin. Can. J. Plant. Pathol. 6:264, 1984. (3) A. F. Murant. Raspberry Bushy Dwarf. Page 229 in: Virus Diseases of Small Fruits. R. H. Converse, ed. U.S. Dep. Agric. Agric. Handb. 631, 1987. (4) B. Strik and R. R. Martin. Plant Dis. 87:294, 2003.
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Дисертації з теми "RBRV"

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Lindgren, Simon. "Shaft stability analysis of the RBR S5 : Stabilitetsanalys av axel tillhörande RBR S5." Thesis, Umeå universitet, Institutionen för tillämpad fysik och elektronik, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-160472.

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This bachelor’s thesis work completed for Spinchem intend to calculate and simulate the deflectionof a rotating shaft belonging to the rotating bed reactor S5, RBR S5. The shaft is the part thattransfers the torsion to the RBR S5 and is the part that will behave as a spring due to the rotationalvelocity. This elasticity needs to be evaluated so that Spinchem can, if needed, re-dimension theshaft thickness and profile. The work is needed for Spinchem to make a name for itself in the globalmarket where processing large quantities of liquid is essential.Primarily theoretical calculations and finite element analysis have been utilized, but also a practicalmeasurement with a camera equipped with a macro lens, capable of filming in 50 FPS. The finiteelement analysis has been done with Ansys mechanical modal analysis tool to calculate andsimulate the frequencies and deformation that occurs.The main results show that the currently used 30 mm solid shaft is in fact the optimal choice forthe product. The used shaft and the critical speed of the systems does not coincide too much andwill not cause unnecessarily large vibration amplitudes which in turn will compromise the expectedlife span of the product. There is a possibility that other shaft profiles and dimensions are suitablechoices for the shaft. These are determined by equ (5) and depends on whether the stiffness orthe mass is changed. Another criterion for the selection of the new shaft will be whether thesystem runs under- or -overcritically.The system is working well at the chosen speed, which means that there are no advantages inswitching the system to running over critically. Therefore, the recommendation of this thesis iskeeping the solid 30 mm shaft.
Detta examensarbete avser att beräkna och simulerautböjningen aven axel tillhörande Spinchems roterande bäddreaktor S5, RBR S5.Axeln är den del som överför motorns vridmoment till själva RBRen och är den delen som kommer att fjädra vid rotation. Denna fjädring måste ses över så att Spinchem vid behov kan dimensionera om axeln.Arbetet grundar sig i en önskan attskala upp produkterna för att slå sig in på marknaden där större volymer vätska behandlas. Primärt har arbetet behandlats i Ansys mechanical där en modalanalys har använts för att beräkna utböjning och frekvenser av axeln. En praktisk mätning harockså gjorts för att se hur det stämmer överens med verkligheten.Den praktiska mätningen har gjortsmed en kameramed makroobjektivsom kan filma upp till 50 FPS. De huvudsakliga resultaten visar på att den nuvarande 30mm solida axeln är den bäst dimensioneradeföratt motstå utböjning och självsvängning. De frekvenser som uppstår ger inte upphov till förstora svängningsamplituder och har ett acceptabelt frekvensförhållande mellan drifthastigheten och axelns egenfrekvens. Det finns sannolikt flera olika profiler som kan användas vilket bestäms av axelns egenfrekvens. Förändras styvheten eller massan kan olika axlar passa in olika bra beroende på om driften sker över-eller underkritiskt. Eftersom RBRenfungerar väl vid det varvtal som används finns det inga fördelar med att ändra till att köra överkritiskt. Därför rekommenderas inte en förändring av axelprofilen eller dimensioneringen av denna
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Ininns, Graham D. "Applying Resource Based Relative Value Scales (RBRVS) to the CHAMPUS program." Thesis, Monterey, California : Naval Postgraduate School, 1990. http://handle.dtic.mil/100.2/ADA246396.

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Thesis (M.S. in Management)--Naval Postgraduate School, December 1990.
Thesis Advisor(s): Doyle, Richard. Second Reader: Gates, William R. "December 1990." Description based on title screen as viewed on March 30, 2010. DTIC Identifier(s): Cost Analysis, Medical Services, RBRVS(Resource Based Relative Value Scales Theses), CHAMPUS, Physicians, Medicare. Author(s) subject terms: RBVS, CHAMPUS, RBVS and CHAMPUS. Includes bibliographical references (p. 64). Also available in print.
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Aquino, Rita de Cássia Mascarenhas de. "Venda baseada em valor : integrando RBV com marketing." Universidade Presbiteriana Mackenzie, 2017. http://tede.mackenzie.br/jspui/handle/tede/3582.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
The sales process has been changing over the years (BORG; YOUNG, 2004) and from this evolution the value-based selling (VBS) has arisen. VBS is the successor of consultative selling. The value-based selling is defined here as the identification, quantification and communication of value through the understanding of the customer's business, value proposition creation and communication to the customer. Understanding how value is created in the process of value-based selling is essential to respond the research question, which aims to identify the resources and capabilities that support the value-based selling on creating value to the customer from the marketing perspective. Raised literature identifies the need to study the association of value-based selling with the Resource-Based View (RBV) to analyze how the resources and capabilities, as part of the sales activities, can be combined and explored to generate value to the customer. This research was conducted in the information technology sector, more specifically, software companies. Customers and suppliers (sales team) were interviewed and the perception of value on both sides were analyzed, thus it was identified that resources and capabilities generate value in the value-based selling process. The research demonstrates that there is a synergy between the value perceived by the customers and the value generated by suppliers. As a result of interviews, it was identified two capabilities: understanding customer needs and sales team effectiveness; and one resource: sales tools that generate value in the value-based selling process. Therefore, the characterization of such resources and capabilities revealed that they are valuable, rare and they are also organized in a processes underpinning the creation of value in value-based selling.
O processo de vendas vem se modificando ao longo dos anos (BORG; YOUNG, 2004) e desta evolução surgiu a venda baseada em valor, sucessora da venda consultiva. A venda baseada em valor foi, aqui, definida como a identificação, quantificação e comunicação de valor por meio da compreensão do negócio do cliente, elaboração e comunicação da proposta de valor. Entender como o valor é criado no processo de venda baseada em valor é fundamental para responder à questão de pesquisa desse trabalho, que tem como objetivo identificar os recursos e capacidades que sustentam a venda baseada em valor na criação de valor para o cliente sob o ponto de vista de marketing. A literatura levantada identificou a necessidade de estudar a associação da venda baseada em valor com a Visão Baseada em Recursos (RBV) para analisar de que maneira os recursos e capacidades presentes na atividade de vendas podem ser combinados e explorados para gerar valor para o cliente. A presente pesquisa foi realizada no segmento de tecnologia da informação, mais especificamente, empresas de software. Foram entrevistados clientes e fornecedores, confrontadas a percepção de valor de ambos os lados e identificados os recursos e capacidades que geram valor no processo de venda baseada em valor. A pesquisa revelou que há sinergia entre o valor percebido pelos clientes e o valor gerado pelos fornecedores. Por meio das entrevistas, foram identificadas duas capacidades: entendimento das necessidades do cliente e eficácia da equipe de vendas; e um recurso: instrumentos de vendas, que geram valor no processo de venda baseada em valor. A caracterização de tais recursos e capacidades revelou que os mesmos são valiosos, raros e estão organizados em processos que sustentam a criação de valor na venda baseada em valor.
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Pellissari, Felipe Rolim. "RBRP Protocolo de reputação baseado em papéis para redes Peer-to-Peer." Florianópolis, SC, 2005. http://repositorio.ufsc.br/handle/123456789/102654.

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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Ciência da Computação.
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Grande parte do tráfego de dados existente na Internet atualmente pertence a aplicações peer-to-peer para troca de arquivos. Uma das maiores preocupações dos usuários dessas aplicações é encontrar a fonte mais segura de um determinado recurso. Os protocolos de reputação se propõem a resolver esse problema usando experiências anteriores pelos nós para encontrar a melhor fonte de um determinado recurso. Esta dissertação define o Role-Based Reputation Protocol (RBRP), um protocolo de reputação para redes peer-to-peer baseado em papéis para definição de valores de reputação de um sistema peer-topeer, fazendo assim uma classificação dos nós de uma rede de acordo com o comportamento exercido pelos nós. O RBRP, assim como outros protcolos de reputação, auxilia no provimento de segurança em uma rede peer-to-peer elegendo os nós do sistema com maior chance de possuir um recurso válido, ou seja, um recurso sem a presença de vírus ou de conteúdo impróprio, como pornografia infantil. Entretanto, como o RBRP usa uma classificação baseada em papéis para valores de reputação, o protocolo usa uma abordagem diferente para enfrentar o mesmo problema. Essa abordagem está mais próxima dos usuários das redes, portanto deve possuir uma melhor aceitação com relação ao seu uso. O trabalho mostra que, com o pleno uso do RBRP, uma rede pode ter o consumo de largura de banda reduzido. Isto se deve ao fato do protocolo prevenir trocas inválidas, ou seja, o RBRP evita desperdício de largura de banda, já que, além dos danos potenciais que vírus podem trazer a um sistema, a transferência de tal conteúdo gera tráfego na rede. Por fim, o trabalho mostra a implementação do RBRP em uma rede peer-to-peer para verificar a validade da implantação de um protocolo de reputação em um sistema real. A implementação desenvolvida mostra que um protocolo de reputação baseado em papéis possui uma interface mais amigável, auxiliando na aceitação e no pleno uso do protocolo pelos usuários da rede.
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Bugin, Elisabetta. "Warfarin e PEG-IFN/RBV: sviluppo di test farmacogenetici per la personalizzazione della terapia farmacologica." Doctoral thesis, Università degli studi di Padova, 2014. http://hdl.handle.net/11577/3423583.

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The aim of this study was the development and the validation of two pharmacogenetic tests for determination of the personalized dosage of drugs used in clinical settings (Warfarin and PEG-Interferone/Ribavirin) in which genetic testing is necessary and recommended. Warfarin (Coumadin®) is a widely prescribed anticoagulant used for treatment and prevention of thrombotic disorders. Although highly efficacious, Warfarin’s narrow therapeutic index and wide inter-individual variability in dose response make its dosing difficult. The standard procedure to define the personalized dose is an iterative process that can take weeks or months and exposes the patients to an increased risk of over- or underanticoagulation and thus to serious side effects like thromboembolism or bleeding. The anticoagulation effect of the Coumadin® drug therapy is influenced by combination of genetic and non-genetic factors , which account for more than half of the inter-individual variation in Warfarin doses required to achieve a therapeutic level of anticoagulation or therapeutic INR (Prothrombin International Normalized Ratio). Since 2011, the FDA requires the product label to include a recommended daily Warfarin dose (mg/day) for therapeutic INR, which is to be based on the genotypes of CYP2C9 and VKORC1. In addition, Genome-Wide Association Studies (GWAS) have confirmed that CYP2C9, VKORC1 and CYP4F2 are the main genetic factors determining the effective Warfarin dose in Caucasians. Therefore, knowledge of the genetic profile provides a means to assess the differential risk of adverse reactions and allows the personalization of the therapy, e.g. lowering the dosage for patients with the alleles CYP2C9 *2 and *3 or that are homozygous for the A-allele (A/A) of the rs9923231 polymorphism in the VKORC1 gene. The goal of this study was to develop an innovative genotyping system assessing the gene polymorphisms that mainly determine the clinical response to Warfarin. Four polymorphisms were investigated: rs9923231 in the VKORC1 gene, rs1799853 and rs1057910 in the CYP2C9 gene and rs2108622 in the CYP4F2 gene. To evaluate already available systems and decide on the method to be used for the test we performed a benchmarking of the tests present in the market. The genotyping is performed using a multiplex PCR in combination with a Reverse Line Blot hybridization assay (mPCR/RLB). To ensure specific amplification the test uses the SSP-PCR (Sequence Specific Primer PCR) approach. The high specificity of this PCR method was confirmed by direct sequencing. The test identifies and differentiates SNPs using ASO probes (Allele Specific Oligonucleotide) that recognize the different alleles. The hybrid formed between the amplified target DNA sequence and the complementary probes is detected by a colorimetric reaction using biotin-streptavidin and alkaline phosphatase. In the first part of the study several parameters like assay temperature, typology of hybridization and washing solutions, incubation time and probe design were analyzed in order to assess their influence on the assay’s performance. Next, the amplification protocol was defined and the conditions of the RLB assay were set up. The kit prototype was then validated on 125 samples, which had been previously genotyped with a standard method (TaqMan® Drug Metabolism Genotyping Assay, Life Technologies), and the analytical sensitivity of the assay was determined. All tested samples were accurately genotyped (100% diagnostic specificity and sensitivity) and the method efficiently worked in a broad range of DNA concentrations. Sensitivity tests demonstrated that the method developed in this study, provided reliable results within a DNA concentration range of 1 ng/reaction to 500 ng/reaction. The shelf life of the reagents was determined to be at least twelve months. In addition, the assay was shown to work on/with the following combinations of probe support materials (a nylon membrane and a nitrocellulose blotting membrane) and PCR master mixes (three commercial available master mixes). A software was developed that automates and facilitates interpretation of the RLB (strip) patterns. After completion, the system, GENEQUALITY AB WARFARIN TYPE cod. 04-74A-20 (AB ANALITICA), was notified to the Ministero della Salute and was CE IVD marked for commercialization in the European Community. As this system is the only assay on the market that analyzes the CYP4F2 gene in combination with the CYP2C9 and the VKORC1 gene, it represents the most complete approach for determining the genetic factors influencing Warfarin dosage in Caucasians. The Hepatitis C virus (HCV) infection is a major health problem with more than 170 million infected individuals worldwide (2-2.5% of the world’s population). Approximately 30% of the infections are cleared spontaneously, whereas 40% of the patients develop a chronic infection that can lead to cirrhosis, hepatocellular carcinoma and end-stage liver disease. The current standard of care is a combination treatment with pegylated interferon (PEG-INF) and Ribavirin (RBV), but its efficacy and tolerability are limited. Many efforts have been made to identify the factors that influence host resistance to HCV infection and treatment outcome. Several Genome-Wide Association Studies (GWAS) have demonstrated independently that variations in the IL28B (Interleukin 28B) gene are strongly associated with spontaneous clearance of the virus, early viral kinetics and with the varying PEG-INF/RBV therapy response in different populations. Particularly, polymorphism IL28B rs12979860 influences the prospect of recovery from an HCV infection. Patients homozygous for allele rs12979860-C show a two- to threefold higher SVR (Sustained Virological Response) rate compared to persons with a non-CC genotype when undergoing Peg-INF/RBV treatment, have a higher probability of spontaneous clearance of the virus and, during therapy, display a stronger reduction of virus RNA levels, which is reflected in higher RVR (Rapid Virological Response) and EVR (Early Virological Response) rates. Other studies reported an association of certain functional variants of the ITPA (Inosine Triphosphatase) protein with the reduction of hemoglobin during Peg-INF/RBV therapy. These allelic variants of the ITPA gene decrease the enzymatic activity of ITPA, thus protecting from RBV-induced anemia. The aim was to develop an innovative system to genotype the most significant genetic polymorphisms important for the prediction of treatment response and risk of adverse reactions in patients infected with HCV. Four polymorphisms were investigated in this study: rs12979860 and rs8099917 in the IL28B gene and rs7270101 and rs1127354 in the ITPA gene. Human genomic DNA was extracted from peripheral blood using an automated system (EZ1, Qiagen). Genotyping of the genetic variants was performed combining multiplex PCR with a Reverse Line Blot hybridization assay (mPCR/RLB). For amplification (PCR) of the target sequences, biotinylated primers were used. The primers were designed and analyzed in silico using bioinformatics alignment tools like “blat” (UCSC) and ClustalW, excluding genomic sequences that contain SNPs, SINEs/LINEs or other repetitive elements and all primer binding sites that show a sequence similarity of more than 95% with other genomic sequences. Due to the fact that a sequence that is highly homologous to the target region in IL28B gene is located on the same chromosome 15.000 bp upstream, the SSP-PCR approach was adopted in order to ensure a high specificity of the amplification. To evaluate the efficacy of the SPP-PCR, the amplification products were analyzed by direct sequencing. Subsequently, the protocol for the multiplex amplification was set up. Probes recognizing the different alleles of each investigated SNP (two ASO, Allele Specific Oligonucleotide, per SNP) were designed and their specificity analyzed under varying experimental conditions. This allowed estimation of the effect of parameters like temperature and time of incubation on the assay performance. The analytical sensitivity of the assay was determined using a range of DNA concentrations between 0.5 ng/µl and 200 ng/µl. The diagnostic specificity of the test was assessed analyzing 160 samples of a known genotype. The test provided a result within a DNA concentration of 1 ng/reaction to 400 ng/reaction and all tested samples were accurately genotyped. This underlines the reliability and specificity of the assay. The shelf life of the reagents was determined to be at least eight months and the compatibility of the assay with other amplification master mixes or probe supports (membranes) was tested. The system, GENEQUALITY IL28B-ITPA TYPE cod. 04-47A-20 (AB ANALITICA), was notified to the Ministero della Salute and CE IVD marked for commercialization in the European Community. RLB is a convenient way to identify up to 8 targets in 20 individual specimens simultaneously. It is more flexible and less costly than DNA microarrays while providing the same specificity and sensitivity. The system developed in this study, GENEQUALITY IL28B-ITPA TYPE, code 04-47A-20 (AB ANALITICA), allows analysis of the most important host genetic factors influencing the efficacy of the Peg-INF/RBV therapy and determining the risk of RBV-induced anemia. It is the only assay on the market that analyzes ITPA and IL28B polymorphisms together and therefore represents the most complete approach for determining the genetic constitution in regard to the IL28B and the ITPA gene for personalized management of patients with Hepatitis C. A genotype-phenotype correlation analysis was performed to evaluate the association between IL28B and ITPA polymorphisms and the therapy outcome in a sub-group of patients (N=52). Genetic analysis of the IL28B polymorphism rs12979860 revealed that 27% of the patients carried the C/C genotype, whereas 56% and 17% carried the C/T and the T/T genotype, respectively. The T/T genotype of the IL28B polymorphism rs8099917 was in 40% of patients, whereas 48% carried T/G and 12% the G/G. No association was found between variants of the IL28B polymorphisms and SVR rates: 57% of patients with IL28B rs12979860-CC and 52% with IL28B rs8099917-TT achieved SVR and 43% and 48%, respectively, failed to clear the HCV virus. For analysis of the influence of ITPA, the patients were subdivided into the following three groups: normal ITPase activity (100% ITPA), mild ITPase deficiency (60% ITPA- 60% ITPase activity) and moderate to severe ITPase deficiency (≤30% ITPA, ≤30% ITPase activity). These groups reflected the individual Composite ITPase Deficiency Variable based on the genotypes of the ITPA polymorphisms rs7270101 and rs1127354. Patients with normal ITPase activity were compared to the groups of patients with mild ITPase deficiency and moderate to severe ITPase deficiency by statistical analysis. The results showed that the predicted ITPase deficiency correlated to a reduction of median Hb levels at 4, 12 and 24 weeks of treatment. A statistically significant difference was observed between the groups with normal ITPase activity and moderate to severe ITPase deficiency (≤30% ITPA) at 4 and 24 weeks (Dunnett’s Multiple Comparison Test: T4, p < 0.0001; T24, p < 0.0451). This clearly shows that patients with an at least by 70% decreased ITPase activity are protected from anemia throughout the treatment.
L’attività di ricerca ha avuto come obiettivo quello di sviluppare due test diagnostici di interesse commerciale, utili a predire il dosaggio di farmaci utilizzati in ambito clinico (Warfarin e PEG-IFN/Ribavirina), per i quali si rende necessaria la personalizzazione della terapia ed è raccomandato eseguire il test genetico. Il Warfarin (Coumadin®) è uno degli anticoagulanti più largamente utilizzati in clinica per la prevenzione e il trattamento di eventi trombotici, il cui utilizzo si associa però a dei rischi molto gravi per la salute del paziente a causa sia dell’indice terapeutico molto ristretto sia dell’ampia variabilità individuale nella risposta al farmaco. Questi aspetti rendono necessaria la personalizzazione della terapia, attualmente ottenuta a posteriori, con aggiustamenti posologici in base a misurazioni seriali dell’INR. Durante le fasi iniziali della terapia, tuttavia, è particolarmente elevato il rischio di eventi trombotici o emorragici dovuti rispettivamente a sotto- e sovra-dosaggio farmacologico. Recentemente numerosi studi di associazione genome-wide hanno messo in luce il ruolo chiave di alcuni polimorfismi nei geni CYP2C9 (rs1799853 e rs1057910), CYP4F2 (rs2108622) e VKORC1 (rs9923231) nell’influenzare l’efficacia anticoagulante del farmaco modificandone sia la farmacocinetica che la farmacodinamica. La conoscenza del profilo genetico permette di prevedere un rischio differenziale di manifestare reazioni avverse e quindi di personalizzare il dosaggio del farmaco, orientandosi verso dosaggi minori nel caso di pazienti che presentino le varianti alleliche *2 e *3 del gene CYP2C9 o siano omozigoti A/A per il polimorfismo rs9923231 nel gene VKORC1. L’utilità di associare alla prescrizione del farmaco un test genetico è stata sottolineata anche dall’FDA che nel 2010 ha revisionato il foglietto illustrativo del farmaco inserendo una tabella con i dosaggi (mg/die) raccomandati di farmaco per raggiungere un INR terapeutico sulla base del dato genetico. L’obiettivo di questo studio è stato quindi quello di sviluppare un test per l’identificazione dei più significativi polimorfismi associati alla risposta clinica al Warfarin e di preparare la documentazione necessaria per poter marcare il kit come dispositivo diagnostico in vitro commercializzabile nella Comunità Europea. A tal scopo si è proceduto effettuando un’attività di benchmarking per valutare i sistemi già presenti nel mercato e successivamente definendo la metodica del test. Considerando l’utilità che deriverebbe dall’analisi simultanea di tutte le varianti alleliche di interesse, si è deciso di sviluppare un test farmacogenetico basato sulla metodica Reverse Line Blot che combina una multiplex PCR ad un saggio di ibridazione su strip mediante oligonucleotidi sequenza-specifici adesi ad un supporto di membrana. Per garantire l’amplificazione univoca delle sequenze target, è stato utilizzato un approccio SSP-PCR (Sequence Specific Primer – PCR), la cui efficienza e specificità sono state valutate mediante sequenziamento diretto. Per la detection su strip di ciascun polimorfismo sono state poi progettate due sonde ASO (Allele-Specific Oligonucleotide), la cui funzionalità è stata valutata su campioni informativi per i polimorfismi indagati e precedentemente genotipizzati con un metodo di riferimento. Questa prima fase di definizione del prototipo si è conclusa con la messa a punto delle condizioni sperimentali del saggio, relative ai protocolli di amplificazione in multiplex e di rivelazione su strip. Tale fase ha richiesto un notevole impegno tecnico per superare alcuni dei limiti tecnici sulla costruzione degli oligonucleotidi, imposti dalle sequenze altamente omologhe dei citocromi e per la difficoltà di riuscire a individuare le giuste condizioni sperimentali che consentono di discriminare in modo univoco, specifico e sensibile, sequenze che differiscono tra loro di una singola base (sequenza wild-type Vs. sequenza polimorfica). La fase successiva è stata quella di definire la sensibilità analitica del metodo e le performance del test, analizzando 125 campioni precedentemente genotipizzati da un laboratorio di riferimento (Laboratorio di Biochimica Clinica e Biologia Molecolare Clinica dell’Azienda Ospedaliera di Padova), mediante sistema in Real-Time (TaqMan® Drug Metabolism Genotyping Assay, Life Technologies). Le prove effettuate con concentrazioni scalari di DNA di partenza hanno permesso di definire una sensibilità analitica di 0,5 ng di DNA/µl e un range di quantità ottimale di DNA di partenza che va da 10 ng/µl a 100 ng/µl, sebbene il test garantisca un risultato corretto anche per quantità di DNA pari a 500 ng/reazione. Inoltre, tutti i 125 campioni analizzati in fase di validazione sono stati correttamente genotipizzati; per ciascuno dei polimorfismi indagati: rs1799853 (c.430 C>T, Cys144Arg, CYP2C9*2), rs1057910 (c.1075 A>C, Ile359Leu, CYP2C9*3), rs2108622 (c.1297 C>T, Val433Met, CYP4F2*3) e rs9923231 (c.-1639 G>A, VKORC1) il dispositivo ha fornito un risultato concorde al 100% al dato ottenuto con il metodo di riferimento ed è stato possibile calcolare un valore di sensibilità e specificità diagnostica del 100%, esprimibile anche come accuratezza del 100%, ossia numero di genotipizzazioni corrette sul totale delle genotipizzazioni effettuate (osservato/atteso). Ai fini della marcatura CE IVD, è stata valutata la stabilità dei reagenti a intervalli di tempo regolari di 1 mese per 14 mesi e le prove condotte hanno permesso di definire una shelf life di 12 mesi; da studi di compatibilità effettuati variando le mix di amplificazione e i supporti su cui vengono fatte aderire le sonde è emerso, inoltre, che il dispositivo risulta compatibile con tre tipi di master mix di amplificazione disponibili in commercio e due tipologie di materiali usati per il blotting delle probes (una membrana in nylon e membrana in nitrocellulosa). Per facilitare l’interpretazione dei risultati, il kit è stato implementato con un software interpretativo conforme ai requisiti della norma IEC 62304 – “Medical Device Software – Software Life Cycle Processes” e rispondente alle esigenze di rendere automatico e ripetibile il processo di lettura e interpretazione del risultato della strip e di archiviare i risultati in un format stampabile. Il test sviluppato in questo lavoro di dottorato, GENEQUALITY AB WARFARIN TYPE cod. 04-74A-20 (AB ANALITICA), è stato notificato al Ministero della Salute, è stato marcato come dispositivo diagnostico in vitro CE IVD e può pertanto essere commercializzato. Il dispositivo rappresenta uno dei sistemi più completi per la personalizzazione della terapia in pazienti con disordini tromboembolici e in cura con Warfarin. Nessuno dei sistemi presenti nel mercato, infatti, analizza il polimorfismo rs2108622 C>T nel gene CYP4F2 che, però, soprattutto per la popolazione caucasica è associato in modo statisticamente significativo ad un incremento del dosaggio di anticoagulante, necessario per raggiungere un INR terapeutico; lo SNP rs2108622 spiega in media circa il 10% delle differenze di dosaggio osservate tra i portatori della variante CYP4F2 c.1297 T e i soggetti CYP4F2 c.1297 C/C e si conferma il terzo locus genico in ordine di importanza come predittore di risposta terapeutica al Warfarin e ai suoi derivati. L’epatite C cronica (CHC) è una delle maggiori cause di cirrosi epatica ed epatocarcinoma. Nel corso degli anni la terapia dell’epatite C ha subito una notevole evoluzione che ha portato a definire come Standard of Care (SOC) la combinazione di Interferone Peghilato e Ribavirina (PEG-IFN/RBV, duplice terapia). L’efficacia di tale associazione, tuttavia, è elevata (80%) nei casi di infezione da HCV di genotipo 2-3, ma non supera il 50% nei casi di infezione da HCV di genotipo 1. Grazie anche alla migliore comprensione dei meccanismi molecolari di replicazione virale e dei meccanismi patogenetici dell’infezione, negli ultimi decenni sono stati sviluppati agenti antivirali di nuova generazione da utilizzarsi in pazienti intolleranti alla terapia standard oppure da usarsi in combinazione con PEG-IFN e Ribavirina (triplice terapia) per aumentare l’efficacia della SOC, ridurne la durata e la tossicità e facilitare la compliance del paziente. Sia nel caso della duplice che della triplice terapia, però, il numero e la gravità delle reazioni avverse non sono trascurabili (anemia e neutropenia gravi, disturbi a carico del sistema nervoso centrale, reazioni di ipersensibilità) e hanno determinato un notevole interesse nell’identificazione di fattori prognostici in grado di predire l’efficacia della terapia. La probabilità di risposta alla terapia antivirale dipende in primis dal genotipo virale, ma sono emersi significativi anche fattori dell’ospite, sia clinici che genetici. In particolare, numerosi studi hanno evidenziato un’associazione statisticamente significativa tra i polimorfismi rs12979860 e rs8099917 nel gene IL28B e il tasso di SVR (Sustained Virological Response) identificando nel gene IL28B uno dei più importanti predittori pretrattamento di risposta alla terapia. E’ stato riportato che pazienti con genotipo rs12979860-CC e rs8099917-TT rispondono più efficacemente alla terapia antivirale rispetto agli eterozigoti o agli omozigoti rs12979860-TT e rs8099917-GG (tassi di SVR da due a tre volte maggiori). Il polimorfismo rs12979860 è correlato anche alla probabilità di clearance spontanea del virus, che è tre volte maggiore nei portatori della variante protettiva rs12979860-C e alla cinetica di declino virale durante la terapia; indipendentemente dall’etnia, i pazienti CC mostrano un’elevata riduzione dei livelli di RNA virale nel siero che si riflette in più alti tassi di RVR (Rapid Virological Response) ed EVR (Early Virological Response) rispetto a quelli osservabili in pazienti con genotipo rs12979860-CT o –TT. Da diverse evidenze scientifiche, inoltre, è emersa una correlazione tra il rischio di manifestare anemia emolitica cronica indotta da Ribavirina e due polimorfismi (rs1127354 e rs7270101) nel gene ITPA che codifica per l’inosina trifosfatasi, un enzima coinvolto nell’idrolisi di nucleotidi tri- e difosfato. Sia nel caso del gene IL28B che del gene ITPA, la conoscenza del dato genotipico può indirizzare quindi il clinico nella scelta del regime più adatto e fornisce un’ informazione aggiuntiva per valutare meglio il rapporto rischio/beneficio del trattamento rispetto al non trattamento. Con questo studio ci si è quindi proposti di sviluppare un test farmacogenetico per la discriminazione allelica delle varianti genetiche associate alla resistenza al trattamento antivirale (duplice o triplice terapia) e al rischio di manifestare anemia emolitica indotta da Ribavirina. Scopo di questo lavoro è stato anche quello di confermare tali correlazioni nel campione di pazienti analizzati in questo studio. Il test si basa sulla metodica del Reverse Line Blot e prevede una prima fase di amplificazione in multiplex delle regioni a cavallo dei polimorfismi di interesse, una seconda fase di rivelazione colorimetrica su strip e infine una fase di interpretazione dei dati. Per assicurare un appaiamento univoco dei primers al genoma, ciascun oligo è stato progettato ed analizzato in silico utilizzando tools bioinformatici di allineamento con il genoma, come “blat” (UCSC) e ClustalW, escludendo così dalle regioni candidate quelle contenenti SNPs, SINE, LINE o altri elementi ripetuti e tutte le regioni per le quali esistano sequenze con percentuali di identità superiori al 95%. Per quanto riguarda il gene IL28B, in particolare, la presenza di un blocco ripetuto, localizzato sullo stesso cromosoma circa 15000 nucleotidi più a monte, con omologia di sequenza estremamente elevata alla regione di interesse, ha portato a scegliere un approccio SSP-PCR (Sequence-Specific Primer PCR) come metodo di elezione per aumentare la specificità della reazione di amplificazione. Una volta messo a punto il protocollo di amplificazione, si sono settate le condizioni sperimentali del saggio RLB andando a valutare l’influenza di diversi parametri sperimentali (quantità e tipologia delle probes, temperatura, tipologia delle soluzioni di ibridazione e di lavaggio, tempi di incubazione) sulle performance del saggio, in termini di sensibilità analitica e specificità diagnostica. Il prototipo è stato quindi validato e a tal scopo sono stati analizzati 160 campioni precedentemente genotipizzati con sistemi di riferimento in Real Time (TaqMan Allelic Discrimination Assay, Life Technologies, LightMix in vitro diagnostics kit IL28B, LigthMix rs7270101 ITPA e LigthMix rs1127354 ITPA, Roche). Dai dati raccolti è stato possibile definire una sensibilità analitica di 0,5 ng/µl e un’accuratezza del test del 100%; per ciascuno dei campioni analizzati, infatti, i polimorfismi rs12979860 e rs8099917 nel gene IL28B e rs7270101 e rs1127354 nel gene ITPA sono stati correttamente identificati e genotipizzati dal dispositivo in esame, in accordo al dato ottenuto con il metodo di riferimento. In prospettiva di marcare il kit CE IVD, è stata poi valutata la stabilità dei reagenti e dalle prove effettuate finora è stato possibile definire una shelf life di 8 mesi, da implementare con i dati derivanti dal completamento delle prove di stabilità a 14 mesi, come indicato nel relativo piano di stabilità. Le prestazioni del dispositivo sono state analizzate anche variando i reagenti di amplificazione oppure il supporto su cui sono adese le sonde sequenza-specifica, mantenendo inalterati tutti gli altri parametri sperimentali; anche in tal caso, i risultati ottenuti in ciascuna prova sono stati del tutto equiparabili a quelli ottenuti con i reagenti usati in fase di validazione. Visti e considerati gli ottimi risultati ottenuti, il test sviluppato in questo lavoro di dottorato, GENEQUALITY IL28B-ITPA TYPE cod. 04-47A-20 (AB ANALITICA), è stato notificato al Ministero della Salute ricevendo la marcatura come dispositivo diagnostico in vitro CE IVD e può pertanto essere commercializzato. L’utilizzo di un saggio mPCR/RLB per l’identificazione dei polimorfismi nei geni IL28B e ITPA risulta essere un metodo rapido e altamente specifico che trova spazio in ambito diagnostico per la genotipizzazione dei pazienti in corso di terapia con agenti antivirali standard e di nuova generazione (PEG-IFN/RBV, Boceprevir, Telaprevir). Attualmente, inoltre, il dispositivo GENEQUALITY IL28B-ITPA TYPE cod. 04-47A-20 è l’unico kit sul mercato ad analizzare insieme tutti i polimorfismi più significativi per predire la risposta alla terapia antivirale dell’epatite C cronica e il rischio di reazioni avverse, pertanto rappresenta l’approccio più completo per la personalizzazione della terapia in pazienti con epatite C cronica. Per 52 dei campioni analizzati è stato possibile ottenere i dati clinici relativi ai parametri biochimici ed ematologici e all’outcome terapeutico. Il 63% dei soggetti presentava un’infezione a carico dei genotipi virali 1-4 più difficili da trattare e la terapia si è dimostrata efficace (raggiungimento della SVR, negativizzazione dell’RNA virale nel siero a 24 settimana dalla fine del trattamento) nel 27% dei pazienti con infezione da HCV GT 1-4 e nel 74% dei soggetti con infezione da HCV GT 2-3, riflettendo quanto riportato in letteratura. Nel campione analizzato la maggior parte dei pazienti, indipendentemente dal genotipo virale, era portatore in eterozigosi di almeno uno dei due polimorfismi del gene IL28B, rs12979860 e rs8099917 (27% dei pazienti era rs12979860-CC, mentre il 56% e il 17% era C/T o T/T; il 40% dei pazienti era rs8099917-TT, il 48% T/G e il 12% G/G). La valutazione dei polimorfismi in relazione alla risposta alla terapia non ha mostrato alcuna correlazione significativa. Su 14 soggetti rs12979860-CC, il 57 % ha raggiunto l’SVR, mentre il 43% non è riuscito a eradicare il virus e tale situazione di sostanziale equilibrio si è riscontrata anche nel gruppo di soggetti rs8099917-TT; nel 52% dei casi, infatti, la terapia ha determinato il raggiungimento della risposta virologica sostenuta, mentre nel 48% dei casi si è registrato un fallimento terapeutico. L’analisi di correlazione genotipo-fenotipo nel sottogruppo di pazienti indagati (N=52) ha messo in luce, invece, un’associazione tra la riduzione media dei livelli di emoglobina e l’aplotipo definito dalle varianti polimorfiche rs7270101-C e rs1127354-A del gene ITPA. Nei pazienti che presentavano un’attività ITPasica inferiore al 30% rispetto al basale, predetta su base genetica, la riduzione media di Hb è stata inferiore al 5% nelle prime 4 settimane di trattamento e non ha superato il 15% nell’arco delle 24 settimane, mentre nei soggetti con il 100% di attività enzimatica (rs7270101-AA e rs1127354-CC), il declino di Hb ha raggiunto quasi il 20% fin dal primo mese di trattamento. Il calo di emoglobina nei pazienti con attività enzimatica ridotta al 60% rispetto al wild-type (gruppo 60% ITPA) ha assunto nel tempo un andamento intermedio. I pazienti con deficit enzimatico severo (gruppo ≤30% ITPA) risultano quindi protetti dalla riduzione di Hb indotta da Ribavirina e tale associazione è stata confermata anche dall’analisi statistica, condotta effettuando un confronto multiplo a gruppi tra le tre classi di rischio (100% ITPA, 60% ITPA e ≤30% ITPA), in relazione ai livelli di emoglobina dopo 4, 12 e 24 settimane di trattamento (Dunnett’s Multiple Comparison Test, 100% ITPA Vs. 30% ITPA a 4 settimane: p < 0.001 con α= 0.05, a 24 settimane: p < 0.05 con α = 0.05).
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Schelini, André Luiz Spinelli. "Gestão de projetos e a internacionalização de empresas brasileiras: um estudo sob a perspectiva da RBV." Universidade Nove de Julho, 2015. http://bibliotecadigital.uninove.br/handle/tede/1182.

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Firms face challenges of various natures in different competitive environments, depending on the target market, the business model and corporate strategies. Operate in international markets is a constant challenge on the schedule of firms in the global environment to start their internationalization process. Are challenges since the capitalization of resources, new markets and customers, development of competencies and capabilities, directed to the strategic formation of the company's internationalization, among others. This study focuses on three theoretical areas: project management, internationalization of companies and the resource-based view (RBV). Thus defined the following research question: "How the project management maturity contributes to internationalization of Brazilian companies from the perspective of resource-based view?” Particularly analyzed the contributions of mature project management for internationalization features in international Brazilian companies from the RBV-VRIO analysis, ie, examined whether the mature nature of the management of projects adopted by the selected companies are considered strategic resources, with implications competitive, sustainable competitive advantage for the company. The research strategy adopted was a multiple case study of descriptive exploratory approach within-case analysis and cross-case method, in internationalized Brazilian companies from different business segments. As a result, the study found that the project management features: sustainability of the project, involvement of stakeholders, defining objectives and strategies, change management and risk management, have the greatest contribution to the internationalization of selected companies, with implication of competitive advantage sustainable, considering the RBV-VRIO analysis. Thus, the research presents contributions for companies that are or intend to initiate a process of internationalization, so the process is clearer and driven to a better use of market opportunities.
As empresas enfrentam desafios de diversas naturezas em diferentes ambientes competitivos, dependendo do mercado-alvo, do modelo do negócio e das estratégias corporativas. Atuar em mercados internacionais é um desafio constante na pauta das empresas no ambiente globalizado ao iniciar seu processo de internacionalização. São desafios desde a capitalização de recursos, conquista de novos mercados e clientes, desenvolvimento de competências e capacidades, instruídas para a formação estratégica de internacionalização da empresa, entre outros. Este estudo concentra-se em três eixos teóricos: a gestão de projetos, a internacionalização de empresas e a visão baseada em recursos (RBV). Assim, definiu-se a seguinte questão de pesquisa: “Como a maturidade em gestão de projetos contribui para internacionalização de empresas brasileiras sob a ótica da visão baseada em recursos?”. Particularmente foram analisadas as contribuições das características da gestão madura de projetos para internacionalização em empresas brasileiras internacionais a partir da análise RBV-VRIO, ou seja, analisou se as características maduras da gestão de projetos adotados pelas empresas selecionadas são consideradas como recursos estratégicos, com implicação competitiva, de uma vantagem competitiva sustentável para empresa. A estratégia de pesquisa adotada foi de estudo de múltiplos casos, de abordagem exploratória descritiva com método de análise inter-caso e intra-caso, em empresas brasileiras internacionalizadas de diferentes segmentos empresariais. Como resultado, o estudo identificou que as características da gestão de projetos: sustentabilidade do projeto, envolvimento dos stakeholders, definição de objetivos e estratégias, gerenciamento da mudança e gerenciamento de riscos, possuem alta contribuição para internacionalização das empresas selecionadas, com implicação de vantagem competitiva sustentável, considerando a análise RBV-VRIO. Com isso, a pesquisa apresenta contribuições para as empresas que estão ou pretendem iniciar um processo de internacionalização, de forma que o processa seja mais claro e orientado para um melhor aproveitamento das oportunidades de mercado.
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Amjad, Muhammad. "Towards competitive theorizing of strategy implementation process : empirical evidence from applying the RBV lens on implementation process." Thesis, University of Central Lancashire, 2013. http://clok.uclan.ac.uk/8565/.

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This study identified the core knowledge gap of a lack of competitive theorizing of strategy implementation (SIMP) in the processual and resource-based views of strategy. This gap exists due to tactical perception and relative inattention to variety in strategy implementation process and related competitive implications. It is argued that strategy process and the RBV perspectives can provide complementary insights necessary to move towards competitive theorizing of strategy implementation. A grounded research is conducted to compare how strategy implementation patterns explain implementation success and how those patterns explain heterogeneity in resources management in different firm types – foreign and indigenous. Content analysis of the interview data revealed significant heterogeneity in the strategy implementation process patterns and achieved implementation success. These SIMP process patterns are categorised based on the approach towards strategy implementation as a strategic phenomenon, firm’s type, and thrust of implementation process. Important sources of variations in implementation success emerged in the Competitive and Tactical implementing patterns. Three resources management activities emerged from the data and revealed important distinctions for the heterogeneous implementing patterns. The Tactical implementing patterns showed preference of strategic actors for use of internally available resources and acquisition of ready-made resources. The Competitive implementing patterns showed a balanced approach towards resources management by pursuing optimization of resources. These resources management heterogeneities are shaped by the SIMP process pattern and revealed implementation process performance, action timing and resources optimization as the key sources of competitiveness from strategy implementation. The empirical findings refute the notion that the role of strategy implementation is only to complement as an operational process without much competitive gains. This empirically challenges the conventional conceptions of implementation to adopt and institutionalize strategy and extends to the contribution of SIMP for strategy refinements to gain competitive gains. These findings strongly support that competitive theorizing of strategy implementation is a worthwhile scholarly pursuit via using the complementary views of strategy. Future research should build on this agenda of competitive theorizing of strategy implementation using other firm types, research settings and more micro level analysis.
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Mårtensson, Åsa, and Karin Rantala. "Effektivisering av kommunala välfärdstjänster med hjälp av interna resurser." Thesis, Högskolan i Skövde, Institutionen för handel och företagande, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-12418.

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Sammanfattning Bakgrund: Det finns ett stort behov av effektivisering inom kommunal äldreomsorg för att motverka en eventuell framtida skatteökning. Detta behov har uppkommit dels på grund av en förändrad demografi, med ökat antal äldre, men också de svårigheter som finns i att effektivisera tjänster som utgörs av personlig arbetskraft. En effektivisering av kommunala välfärdstjänster får inte medföra någon negativ inverkan på tjänsternas utförande i form av kvalitet. Kraven på tjänsternas utförande och kvalitet tenderar dock att öka i samband med en högre välfärd och bättre levnadsstandard. Genom uppmärksammande av kommunala intressenters olika behov och önskemål är det viktigt att en effektivisering sker både produktivt och ändamålsenligt för att förhindra en skatteökning eller försämrad kvalitet. Det resursbaserade perspektivet, resource-based view (RBV), kan ses som ett effektivitetsorienterat analysverktyg, vilket framförallt nyttjats inom kommersiella företag. RBV fokuserar på organisationens interna resurser och hur dessa kan stärkas, vilket således kan medföra en positiv inverkan på både produktiviteten och kvaliteten. Det finns dock en viss mätningsproblematik inom RBV eftersom de interna resurser som synsättet belyser framförallt är av immateriell karaktär.   Syfte: Syftet med denna uppsats är att undersöka huruvida RBV kan utgöra ett lämpligt verktyg vid effektivisering av kommunala välfärdstjänster och på så vis skapa en ökad förståelse om interna resurser och hur dessa kan stärkas. Då RBV fundamentalt utgår från kommersiella företag är uppsatsens syfte dessutom att belysa de faktorer som gör synsättet applicerbart även på offentlig sektor. Metod: Materialet till den empiriska studien samlades in genom triangulering. En förstudie genomfördes för att få underlag till det urval som sedan resulterade i att två äldreboenden valdes ut för att studeras mer ingående. På de två utvalda äldreboendena genomfördes sedan totalt sex stycken kvalitativa intervjuer, varav två med enhetschefer och fyra med medarbetare. Intervjuerna genomfördes med stöd av en temamall vilket medförde en diskussion kring uppsatsens ämnesområden. Med hjälp av intervjuerna identifierades interna resurser som var relaterade till verksamhetens mål och förväntningar från organisationens intressenter. Som komplement till uppsatsens studie har boendenas balanserade styrkort nyttjats. Slutsats: Uppsatsen har belyst de mest betydande skillnaderna vid applicering av RBV på offentlig sektor gentemot kommersiella företag. Interna resurser som arbetssätt, ekonomisk kompetens, tyst kunskap, förmågan att interagera med andra organisationer, förmågan att tillvarata personalens kompetens samt förmågan att skapa en bra dialog mellan personal, brukare och dennes anhöriga har identifierats. Utöver dessa immateriella resurser har den materiella resurs som utgörs av fastigheternas utformning lyfts fram då det är en resurs som visat sig ha stor betydelse för enheternas dagliga verksamhet. Uppsatsen har även synliggjort hur resurser och förmågor kan skapas och stärkas genom interaktion med andra organisationer. Genom att belysa RBVs applicerbarhet på offentlig sektor, olika resurser och hur dessa kan stärkas har uppsatsen uppnått sitt syfte.
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Nandialath, Anup Menon. "ESSAYS ON THE ROLE OF UNOBSERVABLES IN CORPORATE STRATEGY." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1250270664.

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Rodrigues, de Azevedo Jamana. "Análise do processo de desenvolvimento de recursos competitivos em empresas exportadoras de uva do Vale do São Francisco." Universidade Federal de Pernambuco, 2007. https://repositorio.ufpe.br/handle/123456789/834.

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A presente pesquisa tem como objetivo analisar o processo de desenvolvimento de recursos competitivos de empresas que são consideradas mais competitivas, dentre as exportadoras de uva da região do Submédio do São Francisco. Para a construção do referencial teórico, tomou-se como base a perspectiva da Resource-Based View of the Firm (RBV), que procura explicar o desempenho superior das organizações e as estratégias que permitiram alcançá-lo mediante a análise dos recursos de uma organização, sejam eles recursos tangíveis ou intangíveis. O processo de internacionalização foi analisado com base nos modelos de Uppsala (JOHANSON; WIEDERSHEIM-PAUL, 1975; JOHANSON; VAHLNE, 1977) e baseado em recursos (SHARMA; ERRAMILLI, 2004) que explica a internacionalização de empresas como um processo evolutivo, na qual a entrada no mercado internacional passa por estágios a medida que a empresa acumula experiências e conhecimentos a respeito do mercado global. Como procedimento metodológico, foi realizada uma pesquisa exploratória e descritiva, fundamentada na perspectiva qualitativa. O foco metodológico foi lastreado no método do estudo de caso. A pesquisa passou por três etapas, para a seleção da amostra. Inicialmente, selecionou-se um grupo de empresas a serem estudadas, com base no volume entre US$ 1 e 10 milhões de dólares exportados, dado disponibilizado pelo Ministério do Desenvolvimento, Indústria e Comércio. Em seguida, aplicaram-se questionários compostos por questões fechadas na lista de empresas exportadoras de uva da região do Submédio do São Francisco, com o intuito de se obter aquela que fosse vista pelos concorrentes como a mais competitiva. Com base em estatística descritiva, emergiu a Cooperativa A, composta por cinco fazendas: A, B, C, D e E. As técnicas de coleta de dados utilizadas nesta segunda etapa da pesquisa foram entrevistas semi-estruturadas, observação e análise documental. Na análise dos dados emergiram três recursos estratégicos competitivos como sendo responsáveis pelo sucesso da empresa. Assim, por meio deste estudo, identificou-se que recursos idiossincráticos, como o Relacionamento baseado na confiança , Cultura orientada para a qualidade e Know how , apresentam significativa influência no desempenho superior da empresa. Os recursos estratégicos Relacionamento baseado na confiança e Cultura orientada para a qualidade aparentemente possuem sustentabilidade maior devido a deseconomia resultante da compressão temporal, conforme advogam Dierickx e Cool (1989), quanto pela ambigüidade causal decorrente de caminho histórico único e pela subjetividade associada a fatores humanos envolvidos
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Книги з теми "RBRV"

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Nilsson, Ylva. Modelling for fuel optimal control of a variable compression engine. Linko ping: Department of Electrical Engineering, Linko pings universitet, 2007.

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United States. General Accounting Office. Human Resources Division. RBRVS and administrative costs. Washington, D.C: The Office, 1992.

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Inc, Relative Value Studies, ed. The McGraw-Hill complete RBRVS. New York: McGraw-Hill, 1996.

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C, Hsiao William, and Cambridge Health Economics Group, eds. Physician's reference to RBRVS, resource-based relative value scale. Chestnut Hill, Mass. (850 Boylston St., Suite 406, Chestnut Hill 02167): Cambridge Health Economics Group, 1988.

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Services, United States Department of Health and Human. Impact analysis of a resource-based relative value scale (RBRVS). [Washington, D.C.?: Department of Health and Human Services], 1989.

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American Medical Association. Dept. of Health Care Financing., ed. Use of the resource based relative value scale (RBRVS) beyond Medicare. Chicago: American Medical Association, 1994.

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Gosfield, Alice G. Med-Index RBRVS special report: A legal look at physician payment reform. [United States]: Med-Index, 1991.

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1951-, Burstein Philip L., ed. The RBRVS as a model for workers' compensation medical fee schedules: Pros and cons. Cambridge, Mass: Workers Compensation Research Institute, 1996.

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Lyle, James R. Physician's guide to RBRVS: Implications and strategies to position your practice for the 1990s. Augusta, Ga: HealthCare Consultants, 1992.

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L, Gilham Joan, and University of Sheffield Library, eds. Rowlandson caricatures: Contents lists and title index to two volumes presented by Sir Charles Harding Firth in 1932 (RBR F 741.5(R) & LF100). [Sheffield]: Sheffield University Library, 1987.

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Частини книг з теми "RBRV"

1

Friedrich, Stephan A., Kurt Matzler, and Heinz K. Stahl. "Quo vadis RBV?" In Aktionsfelder des Kompetenz-Managements, 29–58. Wiesbaden: Deutscher Universitätsverlag, 2002. http://dx.doi.org/10.1007/978-3-322-81415-9_2.

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Beasley, Steven A., Yaya Wang, and Donald E. Spratt. "RBR E3 Ubiquitin Ligases." In Encyclopedia of Signaling Molecules, 4529–37. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_101592.

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Beasley, Steven A., Yaya Wang, and Donald E. Spratt. "RBR E3 Ubiquitin Ligases." In Encyclopedia of Signaling Molecules, 1–9. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_101592-1.

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Mabry, Charles D., and Jan Nagle. "A Resource-Based Relative Value Scale (RBRVS) System." In Principles of Coding and Reimbursement for Surgeons, 45–56. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-43595-4_4.

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Giuliani, Saverio, and Carlo Meloni. "Connections Among Optimization Models with Uncertainties, ABC and RBV." In Uncertainty Management in Simulation-Optimization of Complex Systems, 123–49. Boston, MA: Springer US, 2015. http://dx.doi.org/10.1007/978-1-4899-7547-8_6.

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Bertram, Matthias. "Theoretical foundation: The resource-based view (RBV) of the firm." In The Strategic Role of Software Customization, 67–102. Wiesbaden: Springer Fachmedien Wiesbaden, 2016. http://dx.doi.org/10.1007/978-3-658-14858-4_3.

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Liu, Jain Shing, and Chun-Hung Richard Lin. "RBR: Refinement-Based Route Maintenance Protocol in Wireless Ad Hoc Networks." In IFIP International Federation for Information Processing, 359–70. Boston, MA: Springer US, 2005. http://dx.doi.org/10.1007/0-387-23150-1_31.

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Xu, Bing, and Liqun Liu. "Research of Litchi Diseases Diagnosis Expertsystem Based on Rbr and Cbr." In IFIP Advances in Information and Communication Technology, 681–88. Boston, MA: Springer US, 2009. http://dx.doi.org/10.1007/978-1-4419-0209-2_70.

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Shi, Wenqi, and John A. Barnden. "How to Combine CBR and RBR for Diagnosing Multiple Medical Disorder Cases." In Case-Based Reasoning Research and Development, 477–91. Berlin, Heidelberg: Springer Berlin Heidelberg, 2005. http://dx.doi.org/10.1007/11536406_37.

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Yang, Bo, Guodong Wang, and Wentao Yao. "A Flight-Test Information Reasoning System Combining Textual CBR and RBR Approaches." In Advances in Intelligent Systems and Computing, 651–58. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-37832-4_59.

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Тези доповідей конференцій з теми "RBRV"

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Hanchak, Michael S., and Andrew P. Murray. "Kinematic Synthesis of Binary Actuated Mechanisms for Rigid Body Guidance." In ASME 2000 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2000. http://dx.doi.org/10.1115/detc2000/mech-14072.

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Abstract This paper presents a method for designing mechanisms composed of Revolute-Binary state prismatic-Revolute (RBR) chains for rigid body guidance. Where a prismatic joint allows for any distance between two revolute joints, a binary state prismatic joint reaches two distances precisely. A single RBR chain can be designed to reach six positions. A parallel arrangement of three RBR chains can be assembled at the six positions but, in general, is not a viable kinematic solution. By requiring the arrangement of three RBR chains to share specific fixed and moving pivots, called an N-type arrangement, four positions are reachable. Further, the design space is quickly searchable for singularity-free solutions. Examples illustrate a solution to a four position synthesis problem and a ten position problem using a serial assembly of these mechanisms.
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Afonso, Alan Wellington Pantoja, Marcelo da Costa Souza, maria veronica leite pereira moura, Nina Claudia Barboza Da Silva, and SHARON SANTOS DE LIMA. "COLEÇÃO ETNOBOTÂNICA DO HERBÁRIO RBR – UFRRJ." In Anais do Simpósio Brasileiro de Farmacognosia - XIII SBFgnosia. Recife, Brasil: Even3, 2021. http://dx.doi.org/10.29327/146976.1-2.

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Chuang, Po-Yao, Ming-Tsun Lu, and Chi-Ying Wu. "Novel Application and Advantage of Reverse Blind Microvia (RBMV) on PCB." In Circuits Technology Conference (IMPACT). IEEE, 2008. http://dx.doi.org/10.1109/impact.2008.4783816.

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Pellissari, Felipe Rolim, Rafael da Rosa Righi, and Carla Merkle Westphall. "RBRP: Protocolo de Reputação Baseado em Papéis para Redes Peer-to-Peer." In Simpósio Brasileiro de Segurança da Informação e de Sistemas Computacionais. Sociedade Brasileira de Computação - SBC, 2005. http://dx.doi.org/10.5753/sbseg.2005.21536.

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Grande parte do tráfego de dados existente na Internet pertence a aplicações peer-to-peer para troca de arquivos. Uma das maiores preocupações dos usuários dessas aplicações é encontrar a fonte mais segura de um recurso desejado. Os protocolos de reputação se propõem a resolver esse problema usando experiências passadas pelos nós para encontrar a melhor fonte de um determinado recurso. Este artigo define e desenvolve um protótipo do Role-Based Reputation Protocol (RBRP), um protocolo de reputação para redes peer-to-peer baseado em papéis para definição de valores de reputação de um sistema peer-to-peer, classificando os nós de uma rede de acordo com o comportamento exercido por cada um.
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Donà, Marco, Alan H. Muhr, Giovanni Tecchio, Simone Salvia, and Claudio Modena. "EFFECTIVENESS OF THE RBRL ISOLATION SYSTEM: EVIDENCES FROM SEISMIC TESTS AND NUMERICAL SIMULATION." In 6th International Conference on Computational Methods in Structural Dynamics and Earthquake Engineering Methods in Structural Dynamics and Earthquake Engineering. Athens: Institute of Structural Analysis and Antiseismic Research School of Civil Engineering National Technical University of Athens (NTUA) Greece, 2017. http://dx.doi.org/10.7712/120117.5428.18432.

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Hastuti, Dwi, Juhriyansyah Dalle, and Husnul Khatimi. "An empirical evaluation of ERP values using RBV approach in Indonesia." In 2016 2nd International Conference on Science in Information Technology (ICSITech). IEEE, 2016. http://dx.doi.org/10.1109/icsitech.2016.7852602.

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Onyeka, Emebo, Daramola Olawande, and Ayo Charles. "CAES: A model of an RBR-CBR course advisory expert system." In 2010 International Conference on Information Society (i-Society 2010). IEEE, 2010. http://dx.doi.org/10.1109/i-society16502.2010.6018791.

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Abohtyra, Rammah M., C. V. Hollot, J. Horowitz, M. G. Germain, and Y. Chait. "Designing Robust Ultrafiltration Rate Profiles Based on Identifying Fluid Volume Model Parameters During Hemodialysis." In ASME 2017 Dynamic Systems and Control Conference. American Society of Mechanical Engineers, 2017. http://dx.doi.org/10.1115/dscc2017-5341.

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Chronic dialysis is a necessary treatment for end-stage kidney disease (ESKD) patients in order to increase life span, with hemodialysis (HD) being the dominant modality. Despite significant advances in HD technology, only half of ESKD patients treated with this modality survive more than 3 years. Fluid management remains one of the most challenging aspects of HD care, with serious implications for morbidity and mortality. Ultrafiltration has been associated with intradialytic hypotension, also associated with adverse outcomes. Therefore, removing a specified fluid volume to achieve an adequate balance without negative outcomes remains a critical challenge to improving patient outcomes. Therefore, it has been suggested that in addition to blood pressure information, routine HD treatments should include blood volume monitoring. Sensors integrated in dialysis machines are able to track the concentration of various blood components, such as hematocrit, with high accuracy and resolution and to derive a relative blood volume (RBV) changes. In this paper, we propose a novel algorithm to design an optimal, robust ultrafiltration rate profile based on identifying the parameters of a fluid volume model of an individual patient during HD and RBV sensor. Our design achieves, if exists, an optimal ultrafiltration profile for the identified nominal model under maximum ultrafiltration and hematocrit constraints, and guarantees that these constraints are satisfied over a pre-defined set of parameter uncertainty. We demonstrate the performance of our algorithm through a combination of clinical data and simulations.
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Somsuk, N., T. Laosirihongthong, and M. W. McLean. "Strategic management of university business incubators (UBIs): Resource-based view (RBV) theory." In 2012 IEEE 6th International Conference on Management of Innovation & Technology (ICMIT 2012). IEEE, 2012. http://dx.doi.org/10.1109/icmit.2012.6225876.

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Xie, Feng, Ming Xu, and Zhen Chen. "RBRA: A Simple and Efficient Rating-Based Recommender Algorithm to Cope with Sparsity in Recommender Systems." In 2012 IEEE Workshops of International Conference on Advanced Information Networking and Applications (WAINA). IEEE, 2012. http://dx.doi.org/10.1109/waina.2012.11.

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Звіти організацій з теми "RBRV"

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Reeves, Edmond. RBR-ACES Validation Activities. Office of Scientific and Technical Information (OSTI), January 2021. http://dx.doi.org/10.2172/1760549.

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Samios N. P. RBRC Scientific Review Committee Meeting, Volume 101. Office of Scientific and Technical Information (OSTI), January 2011. http://dx.doi.org/10.2172/1093764.

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Samios, N. P. RBRC Scientific Review Committee Meeting, Volume 97. Office of Scientific and Technical Information (OSTI), November 2009. http://dx.doi.org/10.2172/972031.

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ORGANIZERS: OZAKI, S., and N. P. SAMIOS. PROCEEDINGS OF RIKEN BNL RESEARCH CENTER WORKSHOP: RBRC QCDOC COMPUTER DEDICATION AND SYMPOSIUM ON RBRC QCDOC (VOLUME 74). Office of Scientific and Technical Information (OSTI), July 2005. http://dx.doi.org/10.2172/15020005.

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En'yo, Hideto, and Taku Izubuchi. RIKEN/RBRC Scientific Review Committee Meeting (Vol. 132). Office of Scientific and Technical Information (OSTI), May 2019. http://dx.doi.org/10.2172/1524567.

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Reeves, Geoffrey D. 2012 DREAM-HANE-RBR Summary Report. Office of Scientific and Technical Information (OSTI), April 2019. http://dx.doi.org/10.2172/1506012.

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Baltz A. RIKEN/RBRC Workshop: future Directions in High Energy QCD. Office of Scientific and Technical Information (OSTI), October 2011. http://dx.doi.org/10.2172/1044786.

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LEE, T. D. PROCEEDING OF RIKEN BNL RESEARCH CENTER: VOLUME 38: RBRC SCIENTIFIC REVIEW COMM. MTG. Office of Scientific and Technical Information (OSTI), January 2002. http://dx.doi.org/10.2172/792261.

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Ludlam, Thomas W., Larry McLerran, Edward Shuryak, Berndt Muller, Xin-Nian Wang, Horst Stocker, J. P. Blaizot, and F. Gelis. NEW DISCOVERIES AT RHIC--THE STRONGLY INTERACTIVE QGP (RBRC SCIENTIFIC ARTICLES) VOLUME 9. Office of Scientific and Technical Information (OSTI), April 2004. http://dx.doi.org/10.2172/15007913.

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SAMIOS, N. P. LEE,T D. PROCEEDINGS OF RIKEN BNL RESEARCH CENTER WORKSHOP: VOLUME 56 RBRC SCIENTIFIC REVIEW COMMITTEE MEETING. Office of Scientific and Technical Information (OSTI), January 2004. http://dx.doi.org/10.2172/15006731.

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