66 research outputs found

    Improved formulation of the latent variable model inversion¿based optimization problem for quality by design applications

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    [EN] Latent variable regression model (LVRM) inversion is a relevant tool for finding, if they exist, different combinations of manufacturing conditions that yield the desired process outputs. Finding the best manufacturing conditions can be done by optimizing an appropriately formulated objective function using nonlinear programming. To this end, different formulations of the optimization problem based on LVRM inversion have been proposed in the literatura that allow the use of happenstance data (eg, historical data) for this purpose, present lower computational costs than optimizing in the space of the original variables, and guarantee that the solution will conform to the correlation structure of available data from the past. However, these approaches, as presented, suffer from some limitations, such as having to actively modify the constraints imposed on the solution to achieve different sets of conditions to those available in the LVRM calibration dataset, or the lack of a standardized approach for optimizing a linear combination of variables. Furthermore, when minimizing or maximizing one or more outputs, a severe handicap is also present related to the definition of arbitrarily low or high "desired" values. This paper aims at tackling all of these issues. The resulting proposed formulation of the optimization problem is illustrated with three case studies.Agencia Estatal de Investigacion, Grant/Award Number: DPI2017-82896-C2-1-R; European Regional Development Fund; Ministerio de Economia, Industria y Competitividad, Gobierno de Espana; Universitat Politecnica de Valencia, Grant/Award Number: Erasmus 2014.93231Palací-López, D.; Villalba-Torán, PM.; Facco, P.; Barolo, M.; Ferrer, A. (2020). Improved formulation of the latent variable model inversion¿based optimization problem for quality by design applications. Journal of Chemometrics. 34(6):1-18. https://doi.org/10.1002/CEM.3230S118346FDA.Pharmaceutical CGMPs for the 21s Century—A Risk‐Based Approach; 2004.Liu, J. J., & MacGregor, J. F. (2005). Modeling and Optimization of Product Appearance:  Application to Injection-Molded Plastic Panels. Industrial & Engineering Chemistry Research, 44(13), 4687-4696. doi:10.1021/ie0492101Bonvin, D., Georgakis, C., Pantelides, C. C., Barolo, M., Grover, M. A., Rodrigues, D., … Dochain, D. (2016). Linking Models and Experiments. Industrial & Engineering Chemistry Research, 55(25), 6891-6903. doi:10.1021/acs.iecr.5b04801MontgomeryDC.Applied Statistics and Probability for Engineers Third Edition; 2003; Vol. 37.MacGregorJF.Empirical Models for Analyzing “Big” Data‐What´s the Difference. InSpring AIChE Conference; Orlando Florida USA 2018.Liu, Z., Bruwer, M.-J., MacGregor, J. F., Rathore, S. S. S., Reed, D. E., & Champagne, M. J. (2011). Modeling and Optimization of a Tablet Manufacturing Line. Journal of Pharmaceutical Innovation, 6(3), 170-180. doi:10.1007/s12247-011-9112-8MacGregor, J. F., Bruwer, M. J., Miletic, I., Cardin, M., & Liu, Z. (2015). Latent Variable Models and Big Data in the Process Industries. IFAC-PapersOnLine, 48(8), 520-524. doi:10.1016/j.ifacol.2015.09.020Jaeckle, C. M., & MacGregor, J. F. (2000). Industrial applications of product design through the inversion of latent variable models. Chemometrics and Intelligent Laboratory Systems, 50(2), 199-210. doi:10.1016/s0169-7439(99)00058-1García-Muñoz, S., Kourti, T., MacGregor, J. F., Apruzzese, F., & Champagne, M. (2006). Optimization of Batch Operating Policies. Part I. Handling Multiple Solutions#. Industrial & Engineering Chemistry Research, 45(23), 7856-7866. doi:10.1021/ie060314gTomba, E., Barolo, M., & García-Muñoz, S. (2012). General Framework for Latent Variable Model Inversion for the Design and Manufacturing of New Products. Industrial & Engineering Chemistry Research, 51(39), 12886-12900. doi:10.1021/ie301214cFacco, P., Dal Pastro, F., Meneghetti, N., Bezzo, F., & Barolo, M. (2015). Bracketing the Design Space within the Knowledge Space in Pharmaceutical Product Development. Industrial & Engineering Chemistry Research, 54(18), 5128-5138. doi:10.1021/acs.iecr.5b00863Bano, G., Facco, P., Bezzo, F., & Barolo, M. (2018). Probabilistic Design space determination in pharmaceutical product development: A Bayesian/latent variable approach. AIChE Journal, 64(7), 2438-2449. doi:10.1002/aic.16133Palací-López, D., Facco, P., Barolo, M., & Ferrer, A. (2019). New tools for the design and manufacturing of new products based on Latent Variable Model Inversion. Chemometrics and Intelligent Laboratory Systems, 194, 103848. doi:10.1016/j.chemolab.2019.103848MacGregor, J. F., & Bruwer, M.-J. (2008). A Framework for the Development of Design and Control Spaces. Journal of Pharmaceutical Innovation, 3(1), 15-22. doi:10.1007/s12247-008-9023-5Jaeckle, C., & Macgregor, J. (1996). Product design through multivariate statistical analysis of process data. Computers & Chemical Engineering, 20, S1047-S1052. doi:10.1016/0098-1354(96)00182-2Lakshminarayanan, S., Fujii, H., Grosman, B., Dassau, E., & Lewin, D. R. (2000). New product design via analysis of historical databases. Computers & Chemical Engineering, 24(2-7), 671-676. doi:10.1016/s0098-1354(00)00406-3García-Muñoz, S., MacGregor, J. F., Neogi, D., Latshaw, B. E., & Mehta, S. (2008). Optimization of Batch Operating Policies. Part II. Incorporating Process Constraints and Industrial Applications. Industrial & Engineering Chemistry Research, 47(12), 4202-4208. doi:10.1021/ie071437jWold, S., Sjöström, M., & Eriksson, L. (2001). PLS-regression: a basic tool of chemometrics. Chemometrics and Intelligent Laboratory Systems, 58(2), 109-130. doi:10.1016/s0169-7439(01)00155-1Ferrer, A. (2007). Multivariate Statistical Process Control Based on Principal Component Analysis (MSPC-PCA): Some Reflections and a Case Study in an Autobody Assembly Process. Quality Engineering, 19(4), 311-325. doi:10.1080/08982110701621304Feltens, J. (2008). Vector method to compute the Cartesian (X, Y, Z) to geodetic ( ϕ{\phi} , λ, h) transformation on a triaxial ellipsoid. Journal of Geodesy, 83(2), 129-137. doi:10.1007/s00190-008-0246-5Arteaga, F., & Ferrer, A. (2013). Building covariance matrices with the desired structure. Chemometrics and Intelligent Laboratory Systems, 127, 80-88. doi:10.1016/j.chemolab.2013.06.003Arteaga, F., & Ferrer, A. (2010). How to simulate normal data sets with the desired correlation structure. Chemometrics and Intelligent Laboratory Systems, 101(1), 38-42. doi:10.1016/j.chemolab.2009.12.00

    Linear relations among pigeon pea traits

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    The objective of this research was to evaluate the linear relations among pigeon pea (Cajanus cajan (L.) Millsp.), cultivar BRS Mandarim, traits and identify the ones applied for indirect selection. Two uniformity experiments were carried out, in an experimental area located 29º42’S, 53º49’W and with 95m of altitude, selecting 360 plants per experiment, totaling 720 plants. For each plant, the number of nodes was counted and the height and stem diameter were measured, for ten evaluation times (62, 69, 76, 83, 90, 98, 104, 111, 119 and 125 days after sowing - DAS) in the first experiment and 18 times (44, 51, 58, 65, 72, 79, 86, 93, 100, 107, 114, 120, 128, 135, 141, 148, 156 and 162 DAS) in the second experiment. During plant flowering, i.e. the 125 DAS in the first experiment and 162 DAS in the second experiment, the fresh and dry mass for each plant was obtained. The sigmoidal model was adjusted and it was studied the relations among the traits through correlation and path analysis. In the pigeon pea crop, the stem diameter has a positive and linear relation with the fresh and dry mass and it can be used for indirect selection.The objective of this research was to evaluate the linear relations among pigeon pea (Cajanus cajan (L.) Millsp.), cultivar BRS Mandarim, traits and identify the ones applied for indirect selection. Two uniformity experiments were carried out, in an experimental area located 29º42’S, 53º49’W and with 95m of altitude, selecting 360 plants per experiment, totaling 720 plants. For each plant, the number of nodes was counted and the height and stem diameter were measured, for ten evaluation times (62, 69, 76, 83, 90, 98, 104, 111, 119 and 125 days after sowing - DAS) in the first experiment and 18 times (44, 51, 58, 65, 72, 79, 86, 93, 100, 107, 114, 120, 128, 135, 141, 148, 156 and 162 DAS) in the second experiment. During plant flowering, i.e. the 125 DAS in the first experiment and 162 DAS in the second experiment, the fresh and dry mass for each plant was obtained. The sigmoidal model was adjusted and it was studied the relations among the traits through correlation and path analysis. In the pigeon pea crop, the stem diameter has a positive and linear relation with the fresh and dry mass and it can be used for indirect selection

    Cross-talk between chronic lymphocytic leukemia (CLL) tumor B cells and mesenchymal stromal cells (MSCs): implications for neoplastic cell survival

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    Leukemic cells from Chronic Lymphocytic Leukemia (CLL) patients interact with stromal cells of the surrounding microenvironment. Mesenchymal Stromal Cells (MSCs) represent the main population in CLL marrow stroma, which may play a key role for disease support and progression. In this study we evaluated whether MSCs influence in vitro CLL cell survival. MSCs were isolated from the bone marrow of 46 CLL patients and were characterized by flow cytometry analysis. Following co-culture of MSCs and leukemic B cells, we demonstrated that MSCs were able to improve leukemic B cell viability, this latter being differently dependent from the signals coming from MSCs. In addition, we found that the co-culture of MSCs with leukemic B cells induced an increased production of IL-8, CCL4, CCL11, and CXCL10 chemokines.As far as drug resistance is concerned, MSCs counteract the cytotoxic effect of Fludarabine/Cyclophosphamide administration in vivo, whereas they do not protect CLL cells from the apoptosis induced by the kinase inhibitors Bafetinib and Ibrutinib. The evidence that leukemic clones are conditioned by environmental stimuli suggest new putative targets for therapy in CLL patients

    IFMIF, the European–Japanese efforts under the Broader Approach agreement towards a Li(d,xn) neutron source: Current status and future options

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    The necessity of a neutron source for fusion materials research was identified already in the 70s. Though neutrons induced degradation present similarities on a mechanistic approach, thresholds energies for crucial transmutations are typically above fission neutrons spectrum. The generation of He via 56Fe (n,α) 53Cr in future fusion reactors with around 12 appm/dpa will lead to swelling and structural materials embrittlement. Existing neutron sources, namely fission reactors or spallation sources lead to different degradation, attempts for extrapolation are unsuccessful given the absence of experimental observations in the operational ranges of a fusion reactor. Neutrons with a broad peak at 14 MeV can be generated with Li(d,xn) reactions; the technological efforts that started with FMIT in the early 80s have finally matured with the success of IFMIF/EVEDA under the Broader Approach Agreement. The status today of five technological challenges, perceived in the past as most critical, are addressed. These are: 1. the feasibility of IFMIF accelerators, 2. the long term stability of lithium flow at IFMIF nominal conditions, 3. the potential instabilities in the lithium screen induced by the 2 × 5 MW impacting deuteron beam, 4. the uniformity of temperature in the specimens during irradiation, and 5. the validity of data provided with small specimens. Other ideas for fusion material testing have been considered, but they possibly are either not technologically feasible if fixed targets are considered or would require the results of a Li(d,xn) facility to be reliably designed. In addition, today we know beyond reasonable doubt that the cost of IFMIF, consistently estimated throughout decades, is marginal compared with the cost of a fusion reactor. The less ambitious DEMO reactor performance being considered correlates with a lower need of fusion neutrons flux; thus IFMIF with its two accelerators is possibly not needed since with only one accelerator as the European DONES or the Japanese A-FNS propose, the present needs > 10 dpa/fpy would be fulfilled. World fusion roadmaps stipulate a fusion relevant neutron source by the middle of next decade, the success of IFMIF/EVEDA phase is materializing this four decades old dream

    Rhizophagus Clarus and Phosphorus in Crotalaria juncea: growth, glomalin content and acid phosphatase activity in a copper-contaminated soil

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    Crotalaria juncea is used as plant cover in grape vineyards in Brazil, which usually present soils with high copper (Cu) levels due to the application of Cu-based phyto-sanitary products. Under this condition an increase growth and cover of C. juncea is needed to improve the phytoremediation processes in those soils. Some alternatives to achieve this condition is the inoculation with arbuscular mycorrhizal fungi (AMF), which has demonstrated an important increase of plant growth in Cu-contaminated soils at different soil P levels. The aims of this study were to evaluate the effect of AMF inoculation in soils with high Cu contents on the growth of C. juncea, the acid phosphatase (APase) enzyme activity in plants and soil, and the presence of glomalin under different P supply conditions, as a basis to identify if there is a synergistic interaction between AMF inoculation and P supply on soils with high Cu levels. The experiment was carried under greenhouse conditions in a factorial 3 × 2 design (natural P content, addition of 40 and 100 mg kg-1 P, with and without the inoculation of the AMF Rhizophagus clarus with three replicates) in a soil with high Cu content (60 mg kg-1). The addition of 40 and 100 mg kg-1 P favored plant growth both in the presence and in the absence of AMF. However, when plants were grown in soil with a natural P level, the inoculation with AMF increased by 116 % the shoot biomass, compared to the non-inoculated treatment. Our results showed that the combination of P supply and R. clarus inoculation could be an adequate strategy to reduce Cu phytotoxicity in C. juncea, as it increases plant biomass and modify the APase enzyme activity in the soil and plant. Additionally, glomalin produced by the AMF and accumulated in the soil can decrease the availability of Cu to the plants by means of sequestration beyond the root surface, with a consequent plant protective effect

    Evaluation of Rhizobia strains UFLA 02 100 and CIAT 899 in line LEP 02 11 of Phaseolus vulgaris L.

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    The growing quest for sustainability in agricultural production systems has been pushing researchers to develop new technologies under different soil and climatic conditions. Based on this, and knowing the socioeconomic importance of the bean, the use of biological nitrogen fixation (BNF) is explored. Thus, the quest for quantitative knowledge of BNF at the phenological stages in a new bean line using promising and commercial strains becomes necessary. The objective of this study was to evaluate the strains UFLA 02 100 and CIAT 899 in the different phenological stages of the LEP 02 11 common bean strain using the biological nitrogen fixation. The experiment was conducted in a greenhouse on the Maringá-PR campus of the State University of Maringá. The design was a randomized complete block design in a 6x4 factorial scheme with four replications. The factor A comprised six nitrogen sources: Control, strain UFLA 02 100, strain CIAT 899, Nitrogen 60 kg ha-1, strain UFLA 02 100 + Nitrogen 30 kg ha-1, strain CIAT 899 + Nitrogen 30 kg ha-1 and the B factor is the phenological stages V4, R5, R6 and R8. The analyzed variables were: dry mass of nodules (DMN, grams/plant), dry mass of shoot (DMS, grams/plant), nitrogen content in shoot (NCS, %) and accumulation of nitrogen in shoot (ANS, grams/plant). For the statistical analysis of the data, the means test was used for the variables in the stages. The CIAT 899 strain statistically outperformed UFLA 02 100 for most variables and it was found that nitrogen fertilization negatively affected nodulation

    Tamanho de amostra para avaliar caracteres produtivos de linho

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    O objetivo deste trabalho foi determinar o tamanho de amostra (número de cápsulas) necessário para a estimação da média de caracteres produtivos de linho (Linum usitatissimum L.), cultivar CDC Normandy, em níveis de precisão. Em área experimental de 15m×15m (225 m2) aos 137 dias após a semeadura, foram selecionadas, aleatoriamente, 300 plantas e coletada uma cápsula por planta. Em cada cápsula foram avaliados os caracteres massa de cápsula, massa de grãos por cápsula, número de grãos por cápsula e massa de mil grãos. Para cada caractere, foram calculadas medidas de tendência central, variabilidade, assimetria e curtose. Foi determinado o tamanho de amostra por meio de reamostragem, com reposição, de 10.000 reamostras. Para a estimação da média desses caracteres de linho, cultivar CDC Normandy, com amplitude do intervalo de confiança de 95% igual a 10% da estimativa da média são necessárias 78 cápsulas
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