Optimal experimental design for cytogenetic dose-response calibration curves

Purpose: To introduce optimal experimental design techniques in the cytogenetic biological dosimetry practice. This includes the development of a new optimatility criterion for the calibration of radiation doses. Materials and Methods: The most typical optimal design criterion and the one developed in this research are introduced and applied in an example from the litera- ture. In another example from the literature, a simulation study has been performed to compare the standard error of the dose estimation using di erent experimental designs. An RStudio project and a GitHub project have been developed to repro- duce these results. Results: It is appreciated how the application of optimal experimental design tech- niques can reduce the standard error of biodosimetric dose estimations. Conclusions: Optimal experimental design techniques jointly with practitioners re- quirements may be applied. This practice would not involve an additional laboratory work

A generalized linear model for cardiovascular complications prediction in PD patients

[Abstract] This study was conducted using machine learning models to identify patient non-invasive information for cardiovascular complications prediction in peritoneal dialysis patients. Nowadays is well known that cardiovascular diseases are the key to mortality in patients undergoing peritoneal dialysis as the risk of cardiovascular disease increases with the progression of renal failure. Primary aim is to establish variables most associated with cardiovascular complications. To achieve this goal four different machine learning techniques were used. We found that the best classification algorithm was a Generalized Linear Model, which achieved AUC values above 96% using a small subset of the original variables following a feature selection approach. Our approach allows us to increase the interpretability of the combinations of traditional factors, advanced chronic kidney disease factors and peritoneal dialysis factors all related with cardiovascular risk profile. The final model is based primarily in the traditional factors.Instituto de Salud Carlos III; PI17/01826Xuinta de Galicia; ED431G/01Xunta de Galicia; ED431D 2017/1Xunta de Galicia; ED431D 2017/2Ministerio de Economía y Competitividad; UNLC08-1E-002Ministerio de Economía y Competitividad; UNLC13-13-350

High pressure effects on the activities of cathepsins B and D of mackerel and horse mackerel muscle

6 páginas, 4 figurasWe determined high pressure processing (HPP) effects on the activities of cathepsins B and D in the muscles of mackerel (Scomber scombrus) and horse mackerel (Trachurus trachurus). In mackerel, the cathepsin B activity decrease reached 40% at 450 MPa while in horse mackerel, low and intermediate pressures (150 and 300 MPa) caused an activity increase (30%) but at 450 MPa a decrease of up to 60%. In both species, cathepsin D activity increased after a 300 MPa treatment (up to 2-fold for mackerel and 60% for horse mackerel) and decreased on a 450 MPa treatment. The activity increase is probably due to HPP damage of lysosome releasing enzymes into the fish muscle. Based on the HPP effects on the activities of cathepsins B and D, 450 MPa may be used to reduce the proteolytic activity of cathepsin B prior to chilled or frozen storage of these fish speciesSupported by the Xunta de Galicia, Spain Project 10TAL402001PR, 2010-2012, and FCT (Portugal), European Union, QREN, FEDER and COMPETE thorough QOPNA research unit, Project PEst-C/QUI/UI0062/2013; FCOMP-01-0124-FEDER-037296. Also supported by he USDA National Institute of Food and Agriculture, Grants No. 2011-31200-06041 and 2012-31200-06041Peer reviewe

Effect of high-Pressure processing of atlantic mackerel (Scomber scombrus) on biochemical changes during commercial frozen storage

12 páginas, 4 tablas, 3 figurasThis research focuses on biochemical changes related to quality losses observed in Atlantic mackerel (Scomber scombrus) muscle stored under commercial frozen storage conditions (9 months, −18 °C) when subjected to high-hydrostatic pressure (HHP) treatments (125, 150, 175, and 200 MPa for 0 min) before freezing. After freezing, free fatty acid (FFA) formation (lipid hydrolysis assessment) showed a marked inhibition in HHP-treated fish and during frozen storage of samples treated at 175 MPa. Fluorescence ratio (FR) assessment of tertiary lipid oxidation showed a partial inhibitory effect during the 0–9-month period for samples treated at 175 and 200 MPa. After a 3-month storage of samples treated at these pressure levels, one-dimensional SDS-PAGE analysis of the sarcoplasmic protein fraction revealed the disappearance of a band; additionally, samples treated at 150 MPa showed the same effect at month 9. After gel excision, trypsin digestion, tandem mass spectrometry (MS/MS), and sequence database analysis, the band was identified as phosphoglycerate mutase 2 (28.7 kDa). On the other hand, HHP processing did not show a significant effect on trimethylamine (TMA) values, primary and secondary lipid oxidation, PUFA levels, 1-D myofibril protein pattern, and the activity of acid phosphatase and cathepsins B and D. Biochemical quality indices such as FFA, TMA, and FR and the activity of acid phosphatase and cathepsin B showed a progressive increase throughout the frozen storage of all samplesThe Xunta de Galicia and the European Social Fund are thankfully recognized for the financial support of the postdoctoral "Isidro Parga Pondal" contract to M. P. The Spanish Ministry of Science and Innovation is also gratefully acknowledged for the doctoral fellowship to L. M.Peer reviewe

High pressure effects on the activities of cathepsins B and D of mackerel and horse mackerel muscle

We determined high pressure processing (HPP) effects on the activities of cathepsins B and D in the muscles of mackerel (Scomber scombrus) and horse mackerel (Trachurus trachurus). In mackerel, the cathepsin B activity decrease reached 40% at 450 MPa while in horse mackerel, low and intermediate pressures (150 and 300 MPa) caused an activity increase (30%) but at 450 MPa a decrease of up to 60%. In both species, cathepsin D activity increased after a 300 MPa treatment (up to 2-fold for mackerel and 60% for horse mackerel) and decreased on a 450 MPa treatment. The activity increase is probably due to HPP damage of lysosome releasing enzymes into the fish muscle. Based on the HPP effects on the activities of cathepsins B and D, 450 MPa may be used to reduce the proteolytic activity of cathepsin B prior to chilled or frozen storage of these fish speciesSupported by the Xunta de Galicia, Spain Project 10TAL402001PR, 2010-2012, and FCT (Portugal), European Union, QREN, FEDER and COMPETE thorough QOPNA research unit, Project PEst-C/QUI/UI0062/2013; FCOMP-01-0124-FEDER-037296. Also supported by he USDA National Institute of Food and Agriculture, Grants No. 2011-31200-06041 and 2012-31200-06041S

Upregulation of tRNA-Ser-AGA-2-1 promotes malignant behavior in normal bronchial cells

Serine tRNAs (tRNASer) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at testing whether increasing tRNASer abundance could foster tumor establishment through activation of the UPR. In order to do so, firstly we confirmed that the expression of tRNA-Ser-AGA-2-1 [hereafter tRNASer(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNASer(AGA) in early stage tumorigenesis, we induced its upregulation in a non-tumoral bronchial cell line, BEAS-2B. Upregulation of this tRNA increased cellular proliferation and protein synthesis rate, driven by eIF2α dephosphorylation and ATF4 activation downstream of PERK signaling. Futhermore, tRNASer(AGA) enhanced transformation potential in vitro, and promoted the establishment of slow growing tumors with aggressive features in nude mice. Our work highlights the importance of studying tRNA deregulation on early stage tumorigenesis, as they may be potential malignancy and aggressiveness biomarkers.publishe

High Pressure Effects on the Activities of Cathepsins B and D of Mackerel and Horse Mackerel Muscle

This work sought to determine high pressure processing (HPP) effects on the activity of cathepsins B and D in the muscle of mackerel (Scomber scombrus) and horse mackerel (Trachurus trachurus). In mackerel, the cathepsin B activity decrease reached 40% at 450 MPa while in horse mackerel, low and intermediate pressures (150 and 300 MPa) caused an activity increase (30%) but a decrease of up to 60% at 450 MPa. In both species, cathepsin D activity increased after a 300 MPa treatment (up to 2-fold for mackerel and 60% for horse mackerel) while decreasing after a 450 MPa treatment. The activity increase is probably due to HPP damage of lysosome releasing enzymes into the fish muscle. Based on the HPP effects on the activity of cathepsins B and D, 450 MPa may be used to reduce the proteolytic activity of cathepsin B prior to chilled or frozen storage of these fish species.Keywords: High pressure processing, Cathepsins B and D, Scomber scombrus, Freshwater fishes, Trachurus trachurus, Proteolytic enzyme

Effect of high pressure processing of Atlantic mackerel (Scomber scombrus) on biochemical changes during commercial frozen storage

This research focuses on biochemical changes related to quality losses observed in Atlantic mackerel (Scomber scombrus) muscle stored under commercial frozen storage conditions (9 months, -18 ºC) when subjected to high-hydrostatic pressure (HHP) treatments (125, 150, 175 and 200 MPa for 0 min) before freezing. After freezing, free fatty acid (FFA) formation (lipid hydrolysis assessment) showed a marked inhibition in HHP-treated fish and during frozen storage of samples treated at 175 MPa. Fluorescence ratio (FR) assessment of tertiary lipid oxidation showed a partial inhibitory effect during the 0-9-month period for samples treated at 175 and 200 MPa. After 3 months storage of samples treated at these pressure levels, one-dimensional SDS-PAGE analysis of the sarcoplasmic protein fraction revealed the disappearance of a band; while samples treated at 150 MPa showed the same effect at month 9. After gel excision, trypsin digestion, tandem mass spectrometry (MS/MS) and sequence database analysis, the band was identified as phosphoglycerate mutase 2 (28.7 kDa). On the other hand, HHP processing did not show a significant effect on trimethylamine (TMA) values, primary and secondary lipid oxidation, PUFA levels, 1-D myofibril protein pattern and the activity of acid phosphatase and cathepsins B and D. Biochemical quality indices such as FFA, TMA, and FR, and the activity of acid phosphatase and cathepsin B showed a progressive increase throughout the frozen storage of all samples.Keywords: Lipids, Enzymes, Frozen storage, Proteins, Scomber scombrus, High pressure processingKeywords: Lipids, Enzymes, Frozen storage, Proteins, Scomber scombrus, High pressure processin

Effect of high-pressure pre-treatments on enzymatic activities of Atlantic mackerel (Scomber scombrus) during frozen storage

The effect of high pressure processing (HPP) pre-treatments at three pressure levels (150, 300 and 450 MPa) and holding times (0, 2.5 and 5 min) on the activity of key enzymes in Atlantic mackerel (Scomber scombrus) muscle was studied after HPP treatments and during frozen storage. Acid phosphatase, cathepsins (B and D) and lipase activity was determined during 3 months of accelerated storage at -10 °C. An empirical model was applied to determine the effect of pressure level, holding time, and frozen storage time on enzyme activity. Except for a minor decrease at 450 MPa, no substantial effect on acid phosphatase activity was observed. On the other hand, lipase and cathepsins were affected by HPP and by frozen storage time. Increasing the pressure level decreased cathepsin B and lipase activity. Increasing the holding time at 150 MPa increased cathepsin B and lipase activity, while at 300 MPa lipase activity decreased and no effect was observed at 450 MPa. Cathepsin D activity increased at 150 and 300 MPa and decreased at 450 MPa, while increasing with frozen storage time. This work provides novel information on the application of HPP pre treatments lowering enzyme activity during frozen storage of Atlantic mackerel.Keywords: Frozen storage, Acid phosphatase, Enzymatic activity, High-pressure processing, Lipase, Scomber scombrus, Cathepsins B and DKeywords: Frozen storage, Acid phosphatase, Enzymatic activity, High-pressure processing, Lipase, Scomber scombrus, Cathepsins B and

Estimación de la distribución vertical de combustibles finos del dosel de copas en masas de Pinus sylvestris empleando datos LiDAR de baja densidad

[ES] La altura de la base de la copa, la carga de combustible disponible y la densidad aparente son características estructurales del dosel de copas utilizadas para predecir la actividad de fuego de copas. La medición directa en campo de estas variables es impráctica y por tanto sus valores se estiman habitualmente mediante el empleo de modelos predictivos. Avances en la modelización del comportamiento del fuego hacen que sea de gran interés explorar la posibilidad de estimar de forma precisa y a escala de paisaje la distribución vertical de los combustibles en el dosel de copas. En este sentido, este estudio pretende analizar el potencial de los datos obtenidos de sensores LiDAR (Light Detection and Ranging) aerotransportados para modelizar dicha distribución vertical en masas de pino silvestre en Galicia. Para ello se usaron datos del vuelo LiDAR del PNOA (Plan Nacional de Ortofotografía Aérea) con una densidad de 0,5 primeros retornos m–2 y datos de campo procedentes del Cuarto Inventario Forestal Nacional (IFN4). En un primer paso, la distribución vertical fue caracterizada empleando la función de densidad de probabilidad de Weibull para, en un segundo paso, ajustar un sistema de ecuaciones que relacionan las variables del dosel con métricas derivadas de los datos LiDAR. Las ecuaciones se ajustaron simultáneamente para corregir los posibles problemas de correlación entre errores. Las distribuciones verticales finalmente estimadas explicaron el 41% de la variabilidad observada en las parcelas de estudio. El sistema de ecuaciones propuesto puede ser usado también para evaluar la efectividad de diferentes alternativas de gestión del combustible para reducir el riesgo de fuego de copa en rodales de pino silvestre[EN] Canopy fuel load, canopy bulk density and canopy base height are structural variables used to predict crown fire initiation and spread. Direct measurement of these variables is not functional, and they are usually estimated indirectly by modelling. Advances in fire behaviour modelling require accurate and landscape scale estimates of the complete vertical distribution of canopy fuels. The goal of the present study is to model the vertical profile of available canopy fuels in Scots pine stands by using data from the Spanish national forest inventory and low-density LiDAR data (0.5 first returns m–2) provided by Spanish PNOA project (Plan Nacional de Ortofotografía Aérea). In a first step, the vertical distribution of the canopy fuel load was modelled using the Weibull probability density function. In a second step, a system of models was fitted to relate the canopy variables to Lidar-derived metrics. Models were fitted simultaneously to compensate the effects of the inherent cross-model correlation between errors. Heteroscedasticity was also analyzed, but correction in the fitting process was not necessary. The estimated canopy fuel load profiles from LiDAR-derived metrics explained 41% of the variation in canopy fuel load in the analysed plots. The proposed models can be used to assess the effectiveness of different forest management alternatives for reducing crown fire hazardS