An ultra-robust fingerprinting method for quality assessment of traditional Chinese medicine using multiple reaction monitoring mass spectrometry / 药物分析学报

Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale finger-printing method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM tech-nique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.

Advances in stress tolerance mechanisms and synthetic biology for the industrial robustness of Corynebacterium glutamicum / 生物工程学报

As a model industrial host and microorganism with the generally regarded as safe (GRAS) status, Corynebacterium glutamicum not only produces amino acids on a large scale in the fermentation industry, but also has the potential to produce various new products. C. glutamicum usually encounters various stresses in the process of producing compounds, which severely affect cell viability and production performance. The development of synthetic biology provides new technical means for improving the robustness of C. glutamicum. In this review, we discuss the tolerance mechanisms of C. glutamicum to various stresses in the fermentation process. At the same time, we highlight new synthetic biology strategies for boosting C. glutamicum robustness, including discovering new stress-resistant elements, modifying transcription factors, and using adaptive evolution strategies to mine stress-resistant functional modules. Finally, prospects of improving the robustness of engineered C. glutamicum strains ware provided, with an emphasis on biosensor, screening and design of transcription factors, and utilizing the multiple regulatory elements.

UV Spectrophotometric Determination Of Rupatadine Fumarate In Bulk And Tablet Dosage Form By Using Single Point Standardization Method

Objective: To develop and validate a simple, selective, precise and accurate method for the estimation of rupatadine fumarate in bulk and tablet dosage form by using the single point standardization method as per international conference on harmonization (ICH) guidelines. Methods: In this proposed method, the absorbance of a standard solution of known concentration and a sample solution was measured. From this, the concentration of the unknown can be calculated. Results: Rupatadine fumarate showed maximum absorbance at 246 nm with methanol. Linearity was checked in different concentrations. The calibration curve was obtained in the range of 2-10 µg/ml. The slope, intercept and correlation coefficient (R2) values of Rupatadine fumarate were found to be 0.047, 0.0034 and 0.9995 respectively. Intra-day and inter-day precision studies were carried out and there % RSD values were found within limits i.e. less than 2%. The recovery studies were carried out by adding a known amount of standard drug to preanalysed formulation and % Recovery was found to be within 99.7-101.6%. LOD and LOQ of Rupatadine fumarate were found to be 0.1 µg/ml and 0.3 µg/ml respectively. Robustness studies were performed at different wavelengths and the % RSD was found within the limits i.e. less than 2 %. Conclusion: The developed single point standardization method for the estimation of Rupatadine fumarate was found to be simple, precise, accurate, reproducible and cost-effective. Statistical analysis of the developed method confirms that the proposed method is an appropriate and it can be useful for the routine analysis. The proposed method gives the basic idea to the researcher who is working in the area like product development.

Plan robustness of craniospinal irradiation with VMAT / 国际生物医学工程杂志

Objective To compare the dosimetric characteristics of the methods of volumetric modulated arc therapy ( VMAT ) for craniospinal irradiation , and to compare their robustness to the field placement error . Methods Six patients receiving craniospinal irradiation were included. VMAT plans of each patient were optimized with overlap method and gradient-optimization method respectively using Pinnacle 9.8 VMAT treatment planning system. The length of the overlap region was set as 3 and 9 cm, respectively. Then the dose distributions under different VMAT programs were measured. Moreover, a 3 mm placement error was introduced, and the dose cold spot in the field junction region obtained by each plan was compared for robustness analysis. Results Under different overlapping lengths, the overlap method and the gradient optimization method both can optimize the VMAT plan that meeting the clinical requirements. In the field junction region, the dose distribution obtained by the overlap method was more uniform, and the difference in the uniformity index was statistically significant. When introducing a 3 mm placement error, the gradient optimization method obtained the most robust VMAT plan at 9 cm overlap length, and the overlap method could not obtained stabilized robust plan. Conclusions For the optimization of craniospinal irradiation VMAT plan, the commonly used overlap method can obtain a better dose distribution, but it can't improve robustness by increasing overlap length. However, using the gradient optimization method, the dose homogeneity in the field junction region is not good as the overlap method, but the plan robustness can be improved by increasing the overlap length.

Design and analytical validation of a duplex PCR for Ehrlichia and Rickettsia detection in ticks / Diseño y validación analítica de una PCR dúplex para la detección de Ehrlichia y Rickettsia en garrapatas / Projeto e validação analítica de uma PCR duplex para detecção de Ehrlichia e Rickettsia em carrapatos

Abstract Background: Ehrlichia and Rickettsia are two major rickettsial genera transmitted by ticks that affect a number of wild and domestic animal species and human populations around the world. Objective: To design and validate a duplex PCR for Ehrlichia and Rickettsia in ticks. Methods: Assay validation included testing for sensitivity, specificity, reproducibility, and robustness of the PCR. The groEL and 23sr RNA genes were used for Ehrlichia and Rickettsia, respectively. Results: The limit of detection was one hundred gene copies per 50 μL of reaction for Ehrlichia spp, and one gene copy of Rickettsia per 50 μL of reaction. In general, the primers of the test only amplified in silico those bacterial agents for which they were originally designed, with the exception of the primers for Rickettsia that also amplified Methylocystis sp. The test was reproducible (intermediate precision) 96.7% of the times for both agents. The test was robust enough to tolerate concentration changes of all reagents with the exception of Taq DNA polymerase. Conclusions: The validation results indicated that this PCR is useful for detection in both bacterial genera and it is a good candidate for diagnostic validation.

Resumen Antecedentes: Ehrlichia spp. y Rickettsia spp. son dos de los principales géneros rickettsiales transmitidos por garrapatas que afectan a animales silvestres, domésticos y humanos alrededor del mundo. Objetivo: Diseñar y validar una prueba PCR dúplex para Ehrlichia y Rickettsia en garrapatas. Métodos: La validación de la prueba incluyó ensayos de sensibilidad, especificidad, reproducibilidad y robustez. En la PCR se usó groEL y ARNr 23S como genes blanco para Ehrlichia y Rickettsia, respectivamente. Resultados: El límite de detección fue de 100 copias del gen por 50 μL de reacción para Ehrlichia spp y una copia del gen de Rickettsia por 50 μL de reacción. En general, los cebadores de la prueba solo amplificaron in silico los agentes bacterianos para los cuales fueron originalmente diseñados, con la excepción de los cebadores de Rickettsia que también amplificaron Methylocystis sp. La prueba fue reproducible (precisión intermedia) en un 96.7% de las veces para ambos agentes. La prueba fue suficientemente robusta como para tolerar cambios de concentración de los diferentes reactivos, con excepción de la Taq DNA polimerasa. Conclusión: Los resultados de validación indican que la PCR es útil para detectar ambos géneros bacterianos y podria usarse para validación diagnostica.

Resumo Antecedentes: Ehrlichia e Rickettsia são dois dos principais gêneros de rickettsias transmitidos por carrapatos que infectam tanto animais selvagens quanto animais domésticos e até homens em todo o mundo. Objetivo: O objetivo principal foi elaborar e validar uma PCR duplex para Ehrlichia e Rickettsia em carrapatos. Métodos: A validação incluiu testes de sensibilidade, especificidade, reprodução e robustez. Para o PCR, utilizamos os genes groEl e 23Sr-RNA para Ehrlichia e Rickettsia, respectivamente. Resultados: O limite de detecção foi de 100 cópias de genes por 50 ml de reação para Erliquia spp e uma cópia de gene de Rickettsia por 50 ml de reação. Em geral, os iniciadores dos testes amplificaram em modelos computacionais os agentes bacterianos para os quais eles foram projetados, exceto os primers de Rickettsia que também amplificou Methylocystis sp. Os testes foram reproduzíveis (precisão intermediária) 96,7% para ambos os agentes e foram também robustos para tolerar mudanças de concentração em todos os reagentes, exceto o reagente Taq DNA polymerase. Conclusões: Os resultados da validação indicaram que o PCR é útil para detecção em ambos os gêneros bacterianos, portanto, um bom exame para validação diagnóstica.

A robust classification method for five types of leukocytes in peripheral blood based on mean-shift clustering / 生物医学工程学杂志

A new leukocyte classification method for recognition of five types of human peripheral blood smear based on mean-shift clustering is proposed. The key idea of the proposed method is to extract the texture features of leukocytes in a visual manner which can benefit from human eyes. Firstly, some feature points are extracted in a gray leukocyte image by mean-shift. Secondly, these feature points are used as seeds of the region growing to expand feature regions which can express texture in visual mode to a certain extent. Finally, a parameter vector of these regions is extracted as the texture feature. Combing the vector with the geometric features of the leukocyte, the five typical classes of leukocytes can be recognized successfully using artificial neural network (ANN). A total number of 1 310 leukocyte images have been tested and the accurate rate of recognition for neutrophil, eosinophil, basophil, lymphocyte and monocyte are 95.4%, 93.8%, 100%, 93.1% and 92.4%, respectively, which shows the feasibility and high robustness of the proposed method.

Desarrollo y estandarización de métodos de calibración para equipos utilizados en salud visual (queratómetros, lensómetros y tonómetros), implementados en el hospital universitario de san vicente fundación / Development and standardization of calibration methods for equipment used in visual health (keratometers, lensometers and tonometers), implemented in the hospital universitario de san vicente fundación / Desenvolvimento e estandardização de métodos de calibração para equipamentos utilizados em saúde visual (keratometômetros, lensômetros e tonômetros), implementados no hospital universitario san vicente fundación

Resumen En el campo de la salud visual se utilizan una serie de equipos que ayudan al diagnóstico de la patología del paciente, pero actualmente no existe un método de calibración estandarizado para asegurar las mediciones que se realizan con estos dispositivos. El objetivo era estandarizar métodos de calibración para algunos de los equipos utilizados en el campo de la salud visual como son: queratómetros, lensómetros y tonómetros. Para la calibración de los tres tipos de equipos incluidos en este desarrollo, se utilizaron métodos de comparación directa de la indicación con la magnitud de los patrones utilizados que tenían trazabilidad con laboratorios nacionales e internacionales acreditados bajo la Norma NTC-ISO/IEC 17025:2005. Las mediciones realizadas por cada uno de los técnicos a los diferentes tipos de equipos en condiciones de repetibilidad y utilizando el método adoptado, se hicieron estadísticamente con la herramienta Anova Simple de Statgraphics, arrojando resultados satisfactorios con un valor-P por encima de 0,05, igualmente se realizaron pruebas de exactitud, linealidad y robustez con resultados positivos. Los métodos adoptados fueron exitosamente validados y posteriormente estandarizados bajo la acreditación en la Norma NTC-ISO/IEC 17025:2005.

Abstract In the field of visual health a series of equipment are used to aid in the diagnosis and treatment of the patient's pathology. Urrently there is no standardized calibration method to ensure the measurements performed with these devices. The objective was to standardize calibration methods for some of the equipment used in the field of visual health such as keratometers, lensometers and tonometers. For the calibration of the three types of equipment included in this development, methods of direct comparison were used of the indication with the magnitude of the standards that had traceability with national and international laboratories accredited under the NTC-ISO / IEC 17025: 2005 standard. The measurements made by each of the technicians to the different types of equipment were done under repeatable conditions and using the adopted methods. Results were analyzed statistically with the simple Anova tool of Statgraphics, yielding satisfactory outcomes with a P-value above 0.05. Tests of accuracy, linearity and robustness were also performed with positive results. The adopted methods were successfully validated and later standardized under the accreditation in NTC-ISO / IEC 17025: 2005 standard.

Resumo No campo da saúde visual utilizam-se uma série de equipas que ajudam ao diagnóstico da patologia do paciente, mas, atualmente não existe um método de calibração padronizado para assegurar as medidas que se realizam com estes dispositivos. O objetivo foi estandardizar métodos de calibração para alguns das equipas utilizadas no campo da saúde visual como são: ceratômetro, lenteômetros e tonometros. Para a calibração dos três tipos de equipamentos incluídos neste desenvolvimento, utilizaram-se métodos de comparação direta da indicação com a magnitude dos padrões utilizados que tinham rastreabilidade com laboratórios nacionais e internacionais acreditados baixo a Norma NTC-ISO/IEC 17025:2005. As medidas realizadas por cada um dos técnicos aos diferentes tipos de equipamentos em condições de repetir-se e utilizando o método adoptado, se analisaram estatisticamente com a ferramenta anova simples de statgraphics, produzindo resultados satisfatórios com um valor-P acima de 0,05, igualmente se realizaram provas de exatidão linearidade e robustez com resultados positivos. Os métodos adoptados foram validados de maneira exitosa e posteriormente padronizados baixo a acreditação na Norma NTC-ISO/ IEC 17025:2005.

Process of Purification of Dihydromyricetin by Cooling Crystallization / 医药导报

Objective To development a cooling crystallization process that is suitable for industrial preparation of purified dihydromyricetin.Methods Screen design was used to investigate effects of process parameters such as,temperature,concentration ethanol aqueous,quantity of activated charcoal and adsorption time on yield and purity of dihydromyricetin.Purity was verified by high performance liquid chromatography and thin layer chromatography.The solubility of dihydromyricetin in water at viable temperature and ethanol proportion was also determined by UV spectrophotometry.The solid form was characterized by thermal analysis and powder X-ray diffractometry.Results When temperature was ＞ 85 ℃,ethanol concentration ＜ 10％,dosage of activated charcoal 0.1％-0.3％,and adsorption time 1-3 min,yield of dihydromyricetin was more than 70％,and the purity greater than 98％.The crystals,prepared by cooling crystallization from water and ethanol aqueous,had the same physical form and crystal habit.Conclusion Cooling crystallization from low concentration of ethanol aqueous gets higher yield and the process is more robust than crystallization from water.

Simulation of sparse views CT image iterative reconstruction based on defective projection data / 医疗卫生装备

Objective To reconstruct sparse views CT image based on defective projection data.Methods The position of bad bins in detector determined whether the linear interpolation was applied to the defective projection data.Moreover,reconstruction of air pixels in CT image was achieved rapidly and accurately.Results he experimental results showed that the proposed method could solve the problem from classical ART-TV method that the robustness was unstable due to the different positions of bad bin in CT detector.Conclusion Compared to analytical reconstruction methods,iterative methods can solve the reconstruction problems in this modality so that the radiologist is facilitated to perform image processing and quantitative analysis.

Aplicación del procedimiento FePIA en la medición de la robustez en cadenas de suministro

Introducción. La incertidumbre en las cadenas de suministro es un factor importante que puede influenciar la efectividad de su configuración y coordinación. Una manera de abordarla en el proceso de diseño de una cadena de suministros es tomando en consideración el concepto de robustez, entendido como la preservación de ciertas características deseadas del sistema, a pesar de que se presenten fluctuaciones en el comportamiento de sus partes componentes o del ambiente. Objetivo. Evaluar el Procedimiento FePIA (Features, Perturbation, Impact, Analysis) en la determinación de la robustez en el problema de planeación de la capacidad y localización de almacenes en cadenas de suministro. Materiales y métodos. El procedimiento FePIA fue evaluado mediante un modelo de programación lineal entera-mixta multiperíodo y de único producto de una cadena de suministros compuesta por tres eslabones. Resultados. La aplicación de este procedimiento permitió definir requerimientos de robustez, características de desempeño y parámetros de perturbación; sin embargo, no se pudo encontrar una relación general entre los parámetros de perturbación y las características de desempeño para el 62 % de las instancias utilizadas. Por tanto, no fue posible obtener con la metodología original una región de robustez para el problema tratado. Un análisis posterior permitió observar que la estructura de la cadena está asociada a dicha problemática. Conclusiones. El procedimiento FePIA debe ser modificado para su completa aplicación al problema de planeación de la capacidad y localización de almacenes en cadenas de suministro.

Introduction. Uncertainty on supply chains is an important factor that can influence the effectiveness of their configuration and coordination. A way to approach it in the design process of supply chains is taking into account the concept of robustness, understanding it as the preservation of certain desired characteristics in the system, in spite of the fluctuations in their components or in the environment. Objective. Evaluate the FePIA (Features, Perturbation, Impact, Analysis) procedure in the determination of the robustness in capacity planning and warehouse location problem in supply chains. Materials and methods. The FePIA procedure was evaluated by means of a multi-period mixed integer programming and of only one product model, applied on a supply chain composed of three links. Results. The application of such procedure allowed the definition of robustness requirements, performance features and perturbation parameters. It was not possible, however, to find a general relationship between the perturbation parameters and the performance features for 62% of the instances used. Therefore, it was not possible to obtain a robustness region with the original methodology. Further analysis could demonstrate that the structure of the chain is associated to that problem. Conclusions. The FePIA procedure must suffer modifications for being fully applied to the capacity planning and warehouse location problem in supply chains.

Introdução. A incerteza nas cadeias de suprimentos é um fator importante que pode influenciar a efetividade de sua configuração e coordenação. Uma maneira de abordar isso no processo de desenho de uma cadeia de suprimentos é tomando em consideração o conceito de robustez, entendido como a preservação de certas características desejadas do sistema, apesar de que se apresentem flutuações no comportamento de suas partes componentes ou do ambiente. Objetivo. Avaliar o Procedimento FePIA (Features, Perturbation, Impact, Analysis) na determinação da robustez no problema de planejamento da capacidade e localização de armazéns em cadeias de suprimentos. Materiais e métodos. O procedimento FePIA foi avaliado mediante um modelo de programação lineal inteiramista multi-período e de único produto numa cadeia de suprimentos composta por três elos. Resultados. A aplicação deste procedimento permitiu definir requerimentos da robustez, características de desempenho e parâmetros de perturbação; porém, não se pôde encontrar uma relação geral entre os parâmetros de perturbação e as características de desempenho para 62 % das instâncias utilizadas. Por tanto, não foi possível obter com a metodologia original uma região da robustez para o problema tratado. Uma análise posterior permitiu observar que a estrutura da cadeia está associada com a referida problemática. Conclusões. O procedimento FePIA deve ser modificado para sua completa aplicação no problema de planejamento da capacidade e localização de armazéns em cadeias de suprimentos.

Effects of positioning robustness on dosimetry for intensity-modulated radiation therapy and volumetric modulated arc therapy / 中华放射肿瘤学杂志

Objective To compare the effects of positioning robustness on dose distribution between intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for head and neck tumor,and to evaluate their needs for image-based guidance.Methods Thirty patients with nasopharyngeal carcinoma undergoing IMRT were enrolled as subjects.The VMAT plans were designed according to the clinical dosimetric requirements and the dose calculation was made by the AAA method.For the two plans in each patient,the isocenters were shifted by ±1.0,±3.0,and ±5.0 mm along the original x,y,and z axes to simulate the impacts of positioning errors in left-right (LR),superior-inferior (SI),and anterior-posterior (AP) directions,respectively,on dose distribution.The dose-volume histogram parameters were analyzed in 60 references and 1080 re-calculated plans.Comparison was made by paired t-test.Results When the error was 1 mm,the average deviations of gross tumor volume (GTV) D98,clinical target volume (CTV) D95 and heterogeneity index,and planning gross tumor volume (PGTV) V95 were＜0.5％.When the error was 3 mm,the average dose deviations of GTV and CTV were＜1.0％ and significantly larger in VMAT than in IMRT;the average dose deviation of PGTV was large (GTV D98,P=0.00;CTV D95,P=0.00);the average deviations of PGTVnxV95 and PGTVndV95 were significantly smaller in IMRT than in VMAT (1.64％vs.1.95％,P=0.01;1.73％ vs.2.63％,P=0.00).The deviations of parameters became larger with the increasing positioning error and were significantly larger in VMAT than in IMRT (GTV D98,P=0.00;CTV D95,P=0.00;CTV HI;P=0.00;PGTV V95;P=0.01).Compared with the target volume,Dmax to the spinal cord and brain stem had larger deviations.However,there were no significant differences in Dmax to the spinal cord and brain stem between IMRT and VMAT.Conclusions The IMRT and VMAT plans are both robust when the positioning error is small (＜3 mm).Compared with IMRT,VAMT is more sensitive to the positioning error,mainly in the target volume.The difference between the two plans becomes larger with the increasing positioning error.An increase in the frequency of image-based guidance is recommended for patients undergoing VMAT.

Non-clinical studies required for new drug development - Part I: early in silico and in vitro studies, new target discovery and validation, proof of principles and robustness of animal studies

This review presents a historical overview of drug discovery and the non-clinical stages of the drug development process, from initial target identification and validation, through in silico assays and high throughput screening (HTS), identification of leader molecules and their optimization, the selection of a candidate substance for clinical development, and the use of animal models during the early studies of proof-of-concept (or principle). This report also discusses the relevance of validated and predictive animal models selection, as well as the correct use of animal tests concerning the experimental design, execution and interpretation, which affect the reproducibility, quality and reliability of non-clinical studies necessary to translate to and support clinical studies. Collectively, improving these aspects will certainly contribute to the robustness of both scientific publications and the translation of new substances to clinical development.

Towards Routine Clinical Use of Radial Stack-of-Stars 3D Gradient-Echo Sequences for Reducing Motion Sensitivity

PURPOSE: To describe how a robust implementation of a radial 3D gradient-echo sequence with stack-of-stars sampling can be achieved, to review the imaging properties of radial acquisitions, and to share the experience from more than 5000 clinical patient scans. MATERIALS AND METHODS: A radial stack-of-stars sequence was implemented and installed on 9 clinical MR systems operating at 1.5 and 3 Tesla. Protocols were designed for various applications in which motion artifacts frequently pose a problem with conventional Cartesian techniques. Radial scans were added to routine examinations without selection of specific patient cohorts. RESULTS: Radial acquisitions show significantly lower sensitivity to motion and allow examinations during free breathing. Elimination of breath-holding reduces failure rates for non-compliant patients and enables imaging at higher resolution. Residual artifacts appear as streaks, which are easy to identify and rarely obscure diagnostic information. The improved robustness comes at the expense of longer scan durations, the requirement for fat suppression, and the nonexistence of a time-to-center value. Care needs to be taken during the configuration of receive coils. CONCLUSION: Routine clinical use of radial stack-of-stars sequences is feasible with current MR systems and may serve as substitute for conventional fat-suppressed T1-weighted protocols in applications where motion is likely to degrade the image quality.

Validación e implementación de una metodología para el análisis microbiológico de un producto líquido preservado, elaborado en una industria farmacéutica / Validation and implementation of a methodology for the microbiological analysis of a preserved liquid product produced in a pharmaceutical industry

Objetivo: validar e implementar una metodología para el análisis microbiológico de un producto líquido preservado con parabenos, elaborado en una industria farmacéutica, según las técnicas de análisis propuestas por la United States Pharmacopeia (USP), versión XXXIV, 2011. Métodos: para los ensayos cuantitativos se trabajó con Staphylococcus aureus y Candida albicans, y para los ensayos cualitativos con Escherichia coli, Staphylococcus aureus y Pseudomonas aeruginosa. Resultados: se obtuvieron resultados acordes con lo establecido por la USP. La metodología descrita se consideró reproducible y robusta al tener la capacidad de no ser afectada por variaciones al desarrollar la técnica, lo cual genera resultados confiables y precisos. Conclusiones: todos los parámetros de validación cumplen la especificación según la USP, lo que muestra conformidad en la totalidad de los parámetros evaluados.

Objective: to validate and to implement a methodology for microbiological analysis of a liquid product preserved with parabens produced by a pharmaceutical company, based on the United States Pharmacopeia analytical methods, XXXIV version, 2011. Methods: the quantitative tests were carrying out for Staphylococcus aureus and Candida albicans, and qualitative tests for Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Results: the results were consistent with those established by the USP. The described methodology was considered reproducible and robust because of its capacity of being unaffected by variations when implementing the technique, thus generating reliable and accurate results. Conclusions: all validation parameters met the USP specification, showing compliance with all the evaluated parameters.

Robustez de cinco estadísticos univariados para analizar diseños Split-Plot en condiciones adversas / Robustness of five univariate statistics in analyzing Split-Plot desings under adverse conditions

En esta investigación examinamos el comportamiento de cinco estadísticos univariados para analizar datos en un diseño Split-Plot. Cuatro de ellos asumen que la matriz de desviación subyacente es no esférica. Sin embargo, existe una clara distinción entre dos alternativas, dos procedimientos presuponen que la correlación entre los datos no sigue un patrón determinado y otros dos asumen que existe autocorrelación serial de primer orden. Todos ellos fueron comparados con respecto a su robustez para poner a prueba las fuentes de variación intra-sujeto (tratamiento e interacción) bajo distribución no normal en ausencia de esfericidad y en ambas situaciones, bajo correlación serial de primer orden y bajo correlación arbitraria. Los resultados muestran que cuando la distribución es no normal simétrica todos los procedimientos muestran una tasa de error de Tipo I similar a la obtenida bajo distribución normal. Conforme el grado de sesgo y curtosis incrementa, todos los procedimientos experimentan una alteración en su estimación de la tasa de error de Tipo I y que depende de la estructura de la matriz de covarianza que subyace a los datos. En el conjunto de condiciones sometidas a estudio los procedimientos más robustos fueron HCH, JN y LEC.

In this research we examine the behaviour of five univariate statistics for analyzing the data of a Split-Plot design. Four of them assume that the dispersion matrix underlying is not spherical. However, they do so with a clear distinction between two alternatives, insofar as two of them presuppose that the correlation between the data does not have a certain structure and other two assume that there exists first-order serial autocorrelation. All of them were compared with regard to their robustness to test the sources of variation within-subject (treatment and interaction) under non-normality in the absence of sphericity, both when there was first-order serial autocorrelation and when the underlying correlation was arbitrary. The results show that when the distribution is non-normal symmetric all the procedures show a Type I error rate similar to the obtained one under normal distribution. As the degree of skewness and kurtosis increases, all the procedures experience an alteration in their estimation of the Type I error rate and that it depends on the structure of covariance matrix underlying in the data. In the set of conditions submitted to study the most robust procedures were HCH, JN and LEC.

Genotype by environment interaction for 450-day weight of Nelore cattle analyzed by reaction norm models

Genotype by environment interactions (GEI) have attracted increasing attention in tropical breeding programs because of the variety of production systems involved. In this work, we assessed GEI in 450-day adjusted weight (W450) Nelore cattle from 366 Brazilian herds by comparing traditional univariate single-environment model analysis (UM) and random regression first order reaction norm models for six environmental variables: standard deviations of herd-year (RRMw) and herd-year-season-management (RRMw-m) groups for mean W450, standard deviations of herd-year (RRMg) and herd-year-season-management (RRMg-m) groups adjusted for 365-450 days weight gain (G450) averages, and two iterative algorithms using herd-year-season-management group solution estimates from a first RRMw-m and RRMg-m analysis (RRMITw-m and RRMITg-m, respectively). The RRM results showed similar tendencies in the variance components and heritability estimates along environmental gradient. Some of the variation among RRM estimates may have been related to the precision of the predictor and to correlations between environmental variables and the likely components of the weight trait. GEI, which was assessed by estimating the genetic correlation surfaces, had values < 0.5 between extreme environments in all models. Regression analyses showed that the correlation between the expected progeny differences for UM and the corresponding differences estimated by RRM was higher in intermediate and favorable environments than in unfavorable environments (p < 0.0001).

Conservation of glycolytic oscillations in Saccharomyces cerevisiae and human pancreatic b-cells: a study of metabolic robustness

The present study compares two computer models of the first part of glucose catabolism in different organisms in search of evolutionarily conserved characteristics of the glycolysis cycle and proposes the main parameters that define the stable steady-state or oscillatory behavior of the glycolytic system. It is suggested that in both human pancreatic b-cells and Saccharomyces cerevisiae there are oscillations that, despite differences in wave form and period of oscillation, share the same robustness strategy: the oscillation is not controlled by only one but by at least two parameters that will have more or less control over the pathway flux depending on the initial state of the system as well as on extra-cellular conditions. This observation leads to two important interpretations: the first is that in both S. cerevisiae and human b-cells, despite differences in enzyme kinetics and mechanism of feedback control, evolution seems to have kept an oscillatory behavior coupled to the glucose concentration outside the cytoplasm, and the second is that the development of drugs to regulate metabolic dysfunctions in more complex systems may require further study, not only determining which enzyme is controlling the flux of the system but also under which conditions and how its control is maintained by the enzyme or transferred to other enzymes in the pathway as the drug starts acting.

Design of medical diagnosis and treatment system based on component technology / 医疗卫生装备

This paper designs the component-based workflow architecture of a medical diagnosis and treatment system. The introduction of component technology enhances the expansibility and robustness of the system. At the end of this paper, a component -based technique for designing medical diagnosis and treatment system, named "Building Block", is brought forward and validated.