The quality control of glycoprotein folding in the endoplasmic reticulum, a trip from trypanosomes to mammals

The present review deals with the stages of synthesis and processing of asparagine-linked oligosaccharides occurring in the lumen of the endoplasmic reticulum and their relationship to the acquisition by glycoproteins of their proper tertiary structures. Special emphasis is placed on reactions taking place in trypanosomatid protozoa since their study has allowed the detection of the transient glucosylation of glycoproteins catalyzed by UDP-Glc:glycoprotein glucosyltransferase and glucosidase II. The former enzyme has the unique property of covalently tagging improperly folded conformations by catalyzing the formation of protein-linked Glc1Man7GlcNAc2, Glc1Man8GlcNac2 and Glc1Man9GlcNAc2 from the unglucosylated proteins. Glucosyltransferase is a soluble protein of the endoplasmic reticulum that recognizes protein domains exposed in denatured but not in native conformations (probably hydrophobic amino acids) and the innermost N-acetylglucosamine unit that is hidden from macromolecular probes in most native glycoproteins. In vivo, the glucose units are removed by glucosidase II. The influence of oligosaccharides in glycoprotein folding is reviewed as well as the participation of endoplasmic reticulum chaperones (calnexin and calreticulin) that recognize monoglucosylated species in the same process. A model for the quality control of glycoprotein folding in the endoplasmic reticulum, i.e., the mechanism by which cells recognize the tertiary structure of glycoproteins and only allow transit to the Golgi apparatus of properly folded species, is discussed. The main elements of this control are calnexin and calreticulin as retaining components, the UDP-Glc:glycoprotein glucosyltransferase as a sensor of tertiary structures and glucosidase II as the releasing agent.

Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents)

This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI)6]+

Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI)6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI)6]+ since impurities such as99mTc-reduced-hydrolyzed (RH),99mTcO4- and [99mTc(cysteine)2]-complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

Physicochemical analyses indicated to the quality control of royal jelly with honey

Royal jelly (RJ) is used as a revitalizing tonic. In order to avoid rejection to its acid taste, it is added to honey. There are regulations for honey and for royal jelly separately but not for the mixture. The objective of this work is, therefore, to verify if the same methods used for pure honey quality control can be used for honey mixed with royal jelly and also the presence of RJ through 10-HDA determination. The methods used were: moisture, reducing sugars, apparent sucrose, ash, hydroxymethylfurfural, insoluble solids, diastase activity, acidity and 10-HDA. Samples were prepared by adding 0-100% of RJ in honey. The results showed that the ash method was the only suitable one to all the samples. The acidity analysis (direct titration) was suitable to 0-30%RJ samples; the reducing sugar analysis was suitable to 0-20% RJ samples. Concerning moisture analysis the refractometric method is suitable to 0-10% RJ and the Infra Red method is suggested to be used for samples with more than 10% RJ. The methods for diastase activity, HMF, apparent sucrose and insoluble solids were inadequate for all samples with RJ. The presence of RJ in the samples was confirmed by the 10-HDA analyses.

Empirical studies on software quality construction: Exploring human factors and organizational influences

Software quality has become an important research subject, not only in the Information and Communication Technology spheres, but also in other industries at large where software is applied. Software quality is not a happenstance; it is defined, planned and created into the software product throughout the Software Development Life Cycle. The research objective of this study is to investigate the roles of human and organizational factors that influence software quality construction. The study employs the Straussian grounded theory. The empirical data has been collected from 13 software companies, and the data includes 40 interviews. The results of the study suggest that tools, infrastructure and other resources have a positive impact on software quality, but human factors involved in the software development processes will determine the quality of the products developed. On the other hand, methods of development were found to bring little effect on software quality. The research suggests that software quality is an information-intensive process whereby organizational structures, mode of operation, and information flow within the company variably affect software quality. The results also suggest that software development managers influence the productivity of developers and the quality of the software products. Several challenges of software testing that affect software quality are also brought to light. The findings of this research are expected to benefit the academic community and software practitioners by providing an insight into the issues pertaining to software quality construction undertakings.

Accelerating food safety and quality control: The use of antibody engineering techniques in the detec-tion of low-molecular weight food contaminants

The increased awareness and evolved consumer habits have set more demanding standards for the quality and safety control of food products. The production of foodstuffs which fulfill these standards can be hampered by different low-molecular weight contaminants. Such compounds can consist of, for example residues of antibiotics in animal use or mycotoxins. The extremely small size of the compounds has hindered the development of analytical methods suitable for routine use, and the methods currently in use require expensive instrumentation and qualified personnel to operate them. There is a need for new, cost-efficient and simple assay concepts which can be used for field testing and are capable of processing large sample quantities rapidly. Immunoassays have been considered as the golden standard for such rapid on-site screening methods. The introduction of directed antibody engineering and in vitro display technologies has facilitated the development of novel antibody based methods for the detection of low-molecular weight food contaminants. The primary aim of this study was to generate and engineer antibodies against low-molecular weight compounds found in various foodstuffs. The three antigen groups selected as targets of antibody development cause food safety and quality defects in wide range of products: 1) fluoroquinolones: a family of synthetic broad-spectrum antibacterial drugs used to treat wide range of human and animal infections, 2) deoxynivalenol: type B trichothecene mycotoxin, a widely recognized problem for crops and animal feeds globally, and 3) skatole, or 3-methyindole is one of the two compounds responsible for boar taint, found in the meat of monogastric animals. This study describes the generation and engineering of antibodies with versatile binding properties against low-molecular weight food contaminants, and the consecutive development of immunoassays for the detection of the respective compounds.

Cohesion Metrics for Improving Software Quality

Abstract Software product metrics aim at measuring the quality of software. Modu- larity is an essential factor in software quality. In this work, metrics related to modularity and especially cohesion of the modules, are considered. The existing metrics are evaluated, and several new alternatives are proposed. The idea of cohesion of modules is that a module or a class should consist of related parts. The closely related principle of coupling says that the relationships between modules should be minimized. First, internal cohesion metrics are considered. The relations that are internal to classes are shown to be useless for quality measurement. Second, we consider external relationships for cohesion. A detailed analysis using design patterns and refactorings confirms that external cohesion is a better quality indicator than internal. Third, motivated by the successes (and problems) of external cohesion metrics, another kind of metric is proposed that represents the quality of modularity of software. This metric can be applied to refactorings related to classes, resulting in a refactoring suggestion system. To describe the metrics formally, a notation for programs is developed. Because of the recursive nature of programming languages, the properties of programs are most compactly represented using grammars and formal lan- guages. Also the tools that were used for metrics calculation are described.

Development of a New Welding Product Quality Control and Management System Model for China

The Chinese welding industry is growing every year due to rapid development of the Chinese economy. Increasingly, companies around the world are looking to use Chinese enterprises as their cooperation partners. However, the Chinese welding industry also has its weaknesses, such as relatively low quality and weak management. A modern, advanced welding management system appropriate for local socio-economic conditions is required to enable Chinese enterprises to enhance further their business development. The thesis researches the design and implementation of a new welding quality management system for China. This new system is called ‗welding production quality control management model in China‘ (WQMC). Constructed on the basis of analysis of a survey and in-company interviews, the welding management system comprises the following different elements and perspectives: a ‗Localized congenital existing problem resolution strategies‘ (LCEPRS) database, a ‗human factor designed training system‘ (HFDT) training strategy, the theory of modular design, ISO 3834 requirements, total welding management (TWM), and lean manufacturing (LEAN) theory. The methods used in the research are literature review, questionnaires, interviews, and the author‘s model design experiences and observations, i.e. the approach is primarily qualitative and phenomenological. The thesis describes the design and implementation of a HFDT strategy in Chinese welding companies. Such training is an effective way to increase employees‘ awareness of quality and issues associated with quality assurance. The study identified widely existing problems in the Chinese welding industry and constructed a LCEPRS database that can be used in efforts to mitigate and avoid common problems. The work uses the theory of modular design, TWM and LEAN as tools for the implementation of the WQMC system.

Role of E3-ligase parkin in mitochondrial quality control in a cardiotoxicity model to anthracyclines

Dues à leur importance croissante dans la dégénérescence musculaire, les mitochondries sont de plus en plus étudiées en relation à diverses myopathies. Leurs mécanismes de contrôle de qualité sont reconnus pour leur rôle important dans la santé mitochondrial. Dans cette étude, nous tentons de déterminer si le déficit de mitophagie chez les souris déficiente du gène Parkin causera une exacerbation des dysfonctions mitochondriales normalement induite par la doxorubicine. Nous avons analysé l’impact de l’ablation de Parkin en réponse à un traitement à la doxorubicine au niveau du fonctionnement cardiaque, des fonctions mitochondriales et de l’enzymologie mitochondriale. Nos résultats démontrent qu’à l’état basal, l’absence de Parkin n’induit pas de pathologie cardiaque mais est associé à des dysfonctions mitochondriales multiples. La doxorubicine induit des dysfonctions respiratoires, du stress oxydant mitochondrial et une susceptibilité à l’ouverture du pore de transition de perméabilité (PTP). Finalement, contrairement à notre hypothèse, l’absence de Parkin n’accentue pas les dysfonctions mitochondriales induites par la doxorubicine et semble même exercer un effet protecteur.

Legal regime of quality control in goods

It has long been said that market itself is the ideal regulator of all evils that may come up among traders. Free and fair competition among manufacturers in the market will adequately ensure a fair dealing to the consumers. However, these are pious hopes. that markets anywhere in the world could not accomplish so far. Consumers are being sought to be lured by advertisements issued by manufacturers and sellers that are found often false and misleading. Untrue statements and claims about quality and performance of the products virtually deceive them. The plight of the consumers remains as an unheard cry in the wildemess. In this sorry state of affairs, it is quite natural that the consumers look to the governments for a helping hand. It is seen that the governmental endeavours to ensure quality in goods are diversified. Different tools are formulated and put to use, depending upon the requirements necessitated by the facts and circumstances. This thesis is an enquiry into these measures

Interacting software-agents to support a kind of expert supervision systems

Expert supervision systems are software applications specially designed to automate process monitoring. The goal is to reduce the dependency on human operators to assure the correct operation of a process including faulty situations. Construction of this kind of application involves an important task of design and development in order to represent and to manipulate process data and behaviour at different degrees of abstraction for interfacing with data acquisition systems connected to the process. This is an open problem that becomes more complex with the number of variables, parameters and relations to account for the complexity of the process. Multiple specialised modules tuned to solve simpler tasks that operate under a co-ordination provide a solution. A modular architecture based on concepts of software agents, taking advantage of the integration of diverse knowledge-based techniques, is proposed for this purpose. The components (software agents, communication mechanisms and perception/action mechanisms) are based on ICa (Intelligent Control architecture), software middleware supporting the build-up of applications with software agent features

Identification and Semiactive Control of Smart Structures Equipped with Magnetorheological Actuators

This paper deals with the problem of identification and semiactive control of smart structures subject to unknown external disturbances such as earthquake, wind, etc. The experimental setup used is a 6-story test structure equipped with shear-mode semiactive magnetorheological actuators being installed in WUSCEEL. The experimental results obtained have verified the effectiveness of the proposed control algorithms

Diseño de un prototipo de software para control en línea de tráfico telefónico en CDRs registrados por un softswitch, para Ecuador

El presente trabajo de Tesis, se enfoca en las nuevas tecnologías utilizadas por las empresas de telecomunicaciones para proveer el servicio de tráfico internacional, haciendo énfasis en los switches de nueva generación (Softswitch), sus potencialidades y la forma de registrar la información detallada de las llamadas telefónicas internacionales CDRs, que son el insumo más importante para el análisis del comportamiento del tráfico telefónico internacional a nivel de Operadores internacionales, rutas de interconexión física e IPs utilizadas para la conexión lógica; entre otras. Se hace también un análisis de la información contenida en un CDR, información que permite determinar el comportamiento del tráfico, y es utilizada a demás para la facturación a los clientes finales y para realizar el proceso de compensación con los operadores internacionales, y para el control de Fraude. Finalmente se hace un estudio de la metodología para desarrollo de software basada en prototipos, la cual es empleada para realizar la implementación de un prototipo informático que permite realizar el análisis de tráfico, y la determinación de posibles indicios de fraude que pueda estar presente en la Red de Telefonía Fija. Para el desarrollo del prototipo se definen las características de un sistema informático que permita mantener un control detallado del tráfico que cursa por la red NGN y es registrado en el Softswitch. El producto final del presente trabajo de tesis es un prototipo de software que consta de dos partes, un módulo de Pseudo-Mediación y otro módulo de Análisis de iiiinformación y configuración. El software desarrollado es funcional y de hecho esta en depuración para ser puesto en producción en una empresa de Telecomunicaciones. La experiencia de la realización del prototipo finalmente permite emitir algunas políticas que deben ser tomadas en cuentas por las empresas de telecomunicaciones al momento de tomar la decisión de desarrollar o comprar una herramienta para control de tráfico.