System theoretic approach for determining causal factors of quality loss in complex system design

Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 105-109).Identifying the factors that could lead to the loss of quality is difficult for large, complex systems. Traditional design methods such as Failure Modes and Effects Analysis (FMEA), Fault Tree Analysis (FTA), and Robust Design have been proven effective at the component level but are less effective for factors that involve interactions between components, software flaws and external noises. This thesis applies System Theoretic Process Analysis (STPA) to two case studies at Cummins, Inc. The first case study was a technology change to a subsystem in a new product development project. The intent of this case was to determine if STPA, applied broadly to safety and hazard analysis, would be effective in identifying causes of quality losses. The second case was a historical quality improvement project. The intent of this case was to determine if STPA would be effective for developing solutions to causes of quality losses. The results of the case studies were compared to the traditional design methods. Use of STPA allowed the design teams to identify more causal factors for quality losses than FMEA or FTA, including component interactions, software flaws, and omissions and external noises. STPA was also found to be complementary to Robust Design Methods. Finally, use of STPA was effective for analyzing the complete hierarchical structure of the system for solutions to potential causes of quality losses.by Stephanie L. Goerges.S.M

A multicenter survey of current practices of 99mTc-methoxy-isobutyl-isonitrile (MIBI) imaging for the diagnosis of thyroid nodules: more standardization is essential

Abstract Purpose Molecular imaging with 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI, MIBI) has been used in the assessment of thyroid nodules (TNs) for more than two decades. Many studies showed that MIBI imaging is a suitable tool to rule-out malignancy when negative. However, relatively low specificity and accuracy have been described, thus, limiting its acceptance in clinical practice. Additionally, different technologies, protocols, and interpretation criteria are adopted accounting for heterogeneous data reported in the literature. Therefore, the present study was undertaken to assess the clinical use and methodology of MIBI imaging in patients with nodular thyroid disease in Europe. Methods A questionnaire was sent to 12 European centers of Nuclear Medicine. The questionnaire encompassed ultrasound (US) and fine-needle aspiration cytology (FNAC) procedures and their evaluation as well scintigraphy imaging indications, technical procedures, and interpretation criteria of MIBI imaging. Results The survey showed a good agreement of different centers in approaching TNs by TSH measurement, US evaluation and 99mTc-pertechnetate thyroid scintigraphy. MIBI imaging is mainly used to assess TNs with inconclusive/indeterminate cytological findings and selection of target nodule(s) for FNAC in patients with multi-nodular goiter. Technical procedures adopted in different centers are globally comparable and the recorded differences are unlikely to impact clinical results. However, as the main result of the present study, substantial differences were found in interpretation criteria adopted in different centers. Conclusions Our survey supports the urgent need of standardized interpretation criteria of thyroid MIBI imaging in order to improve its diagnostic performance and make results comparable in clinical practice

Microenvironment Changes (in pH) Affect VEGF Alternative Splicing

Vascular endothelial growth factor-A (VEGF-A) has several isoforms, which differ in their capacity to bind extracellular matrix proteins and also in their affinity for VEGF receptors. Although the relative contribution of the VEGF isoforms has been studied in tumor angiogenesis, little is known about the mechanisms that regulate the alternative splicing process. Here, we tested microenvironment cues that might regulate VEGF alternative splicing. To test this, we used endometrial cancer cells that produce all VEGF isoforms as a model, and exposed them to varying pH levels, hormones, glucose and CoCl2 (to mimic hypoxia). Low pH had the most consistent effects in inducing variations in VEGF splicing pattern (VEGF121 increased significantly, p < 0.001, when compared to VEGF145, 165 or 189). This was accompanied by activation of the p38 stress pathway and SR proteins (splicing factors) expression and phosphorylation. SF2/ASF, SRp20 and SRp40 down-regulation by siRNA impaired the effects of pH stimulation, blocking the shift in VEGF isoforms production. Taken together, we show for the first time that acidosis (low pH) regulates VEGF-A alternative splicing, may be through p38 activation and suggest the possible SR proteins involved in this process

Vascular network remodeling via vessel cooption, regression and growth in tumors

The transformation of the regular vasculature in normal tissue into a highly inhomogeneous tumor specific capillary network is described by a theoretical model incorporating tumor growth, vessel cooption, neo-vascularization, vessel collapse and cell death. Compartmentalization of the tumor into several regions differing in vessel density, diameter and in necrosis is observed for a wide range of parameters in agreement with the vessel morphology found in human melanoma. In accord with data for human melanoma the model predicts, that microvascular density (MVD, regarded as an important diagnostic tool in cancer treatment, does not necessarily determine the tempo of tumor progression. Instead it is suggested, that the MVD of the original tissue as well as the metabolic demand of the individual tumor cell plays the major role in the initial stages of tumor growth.Comment: 30 pages, 11 figures (higher resolution at http://www.uni-saarland.de/fak7/rieger/HOMEPAGE/BJ0.pdf

Soluble perlecan domain i enhances vascular endothelial growth factor-165 activity and receptor phosphorylation in human bone marrow endothelial cells

<p>Abstract</p> <p>Background</p> <p>Immobilized recombinant perlecan domain I (PlnDI) binds and modulates the activity of heparin-binding growth factors, <it>in vitro</it>. However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ability of soluble forms to modulate vascular endothelial growth factor-165 (VEGF₁₆₅) enhanced capillary tube-like formation, and VEGF receptor-2 phosphorylation of human bone marrow endothelial cells, <it>in vitro</it>.</p> <p>Results</p> <p>In solution, PlnDI binds VEGF₁₆₅in a heparan sulfate and pH dependent manner. Capillary tube-like formation is enhanced by exogenous PlnDI; however, PlnDI/VEGF₁₆₅mixtures combine to enhance formation beyond that stimulated by either PlnDI or VEGF₁₆₅alone. PlnDI also stimulates VEGF receptor-2 phosphorylation, and mixtures of PlnDI/VEGF₁₆₅reduce the time required for peak VEGF receptor-2 phosphorylation (Tyr-951), and increase Akt phosphorylation. PlnDI binds both immobilized neuropilin-1 and VEGF receptor-2, but has a greater affinity for neuropilin-1. PlnDI binding to neuropilin-1, but not to VEGF receptor-2 is dependent upon the heparan sulfate chains adorning PlnDI. Interestingly, the presence of VEGF₁₆₅but not VEGF₁₂₁significantly enhances PlnDI binding to Neuropilin-1 and VEGF receptor-2.</p> <p>Conclusions</p> <p>Our observations suggest soluble forms of PlnDI are biologically active. Moreover, PlnDI heparan sulfate chains alone or together with VEGF₁₆₅can enhance VEGFR-2 signaling and angiogenic events, <it>in vitro</it>. We propose PlnDI liberated during basement membrane or extracellular matrix turnover may have similar activities, <it>in vivo</it>.</p

Edible films and coatings as carriers of living microorganisms: a new strategy towards biopreservation and healthier foods

Edible films and coatings have been extensively studied in recent years due to their unique properties and advantages over more traditional conservation techniques. Edible films and coatings improve shelf life and food quality, by providing a protective barrier against physical and mechanical damage, and by creating a controlled atmosphere and acting as a semipermeable barrier for gases, vapor, and water. Edible films and coatings are produced using naturally derived materials, such as polysaccharides, proteins, and lipids, or a mixture of these materials. These films and coatings also offer the possibility of incorporating different functional ingredients such as nutraceuticals, antioxidants, antimicrobials, flavoring, and coloring agents. Films and coatings are also able to incorporate living microorganisms. In the last decade, several works reported the incorporation of bacteria to confer probiotic or antimicrobial properties to these films and coatings. The incorporation of probiotic bacteria in films and coatings allows them to reach the consumers gut in adequate amounts to confer health benefits to the host, thus creating an added value to the food product. Also, other microorganisms, either bacteria or yeast, can be incorporated into edible films in a biocontrol approach to extend the shelf life of food products. The incorporation of yeasts in films and coatings has been suggested primarily for the control of the postharvest disease. This work provides a comprehensive review of the use of edible films and coatings for the incorporation of living microorganisms, aiming at the biopreservation and probiotic ability of food products.Ana Guimaraes received support through grant SFRH/BD/ 103245/2014 from the Portuguese Foundation for Science and Technology (FCT). Luís Abrunhosa was supported by grant UMINHO/BPD/51/2015 from project UID/BIO/04469/2013 financed by FCT/MEC (OE). This study was supported by FCT under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), and of BioTecNorte operation (NORTE-01-0145-FEDER000004) funded by European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Vectors used in Figure were designed by Freepik.info:eu-repo/semantics/publishedVersio

Le Traçage : un outil pour l'établissement des zones de surveillance des captages en terrain karstique. Le cas de Hastière (Province de Namur, Belgique)

A la demande du Service des Eaux souterraines de la Région wallonne et pour le compte de celle-ci, la Commission wallonne d'Etude et de Protection des Sites souterrains (CWEPSS) a organisé un traçage d'eaux souterraines en région karstique à Hastière (Province de Namur). La CWEPSS a effectué l'étude et le travail avec la collaboration de la Société Geologica de Gembloux pour le traçage et celle de l'Université de Liège pour divers paramètres connexes (analyses des eaux, mesures de débit, spectrofluorimétrie, etc.). Il y a à Hastière plusieurs résurgences d'eaux karstiques provenant d'un vaste synclinal calcaire complexe; deux captages y prélèvent des eaux pour les besoins de la population. Des traceurs fluorescents ont été injectés dans trois points d'engouffrement naturel des eaux. Trois traceurs différents ont été utilisés simultanément (un dans chaque point de perte) et recherchés dans 9 lieux de résurgence potentielle. En une seule campagne d'un mois, l'alimentation de 9 points a ainsi pu être contrôlée. En dépit d'un régime de basses eaux lors de l'expérience, certains écoulements souterrains ont parcouru plus de 3,5 km en 8 jours. Ceci montre l'importance de la surveillance de l'alimentation des captages en zone karstique. Le captage communal d' Anthée s'est révélé propre, non contaminé. La zone de surveillance y afférente a été définie et on a distingué et délimité une sous-zone de surveillance prioritaire dans la formation qui alimente directement le captage. Le captage du camping privé s'est avéré alimenté à la fois par une perte qui reçoit les rejets d'une station d'épuration et par un cours d'eau recevant des eaux d'égout. Ceci explique la pollution observée à ce captage et montre l'urgence d'un traitement des eaux. D'autres constatations faites à la même occasion montrent l'utilité de cette technique de traçage pour la détection des sources de pollution et la définition des zones de surveillance.In response to the request of the Groundwater Service of the Walloon Region, the Commission Wallonne d'Etude et de Protection des Sites Souterrains (CWEPSS) has carried out underground water tracing in the karstic area of Hastière (Province of Namur, Belgium).The CWEPSS has carried on the task with the cooperation of Geologica SA, Gembloux, for the tracing tests and the collaboration of the Université de Liège for several related parameters (stream gauging, water analyzes, spectrofluorimetry, etc.). At Hastière, several karstic Springs resurge from a large and complex limestone syncline; two water supply stations pump water from this syncline for local use. Fluorescent tracers have been injected into three swallowholes. Three different tracers have been used simultaneously - one in each injection site. They have been traced downstream in 9 potential points of reappearance. In a single one-month field-campaign, the origin of 9 streams has been questioned. Despite the low-water levels during this period, some underground streams have covered more than 3,5 km in 8 days. This shows how important is to permanently watch water supplies in karstic areas. The water intake of the Municipality at Anthée proved to be clean, unpolluted. The authors could define the watch-zone and delineate a prioritary watch sub-zone in the geological formation supplying directly the intake. A private camping intake appeared to be supplied by a sinkhole collecting water from a water purifying station and by another sinking stream swallowing sewage water, hence a high pollution and an important sanitary problem. These findings, among others, show how us « the water tracing technique is in detecting sources and in defining watch and protection zones

Das Kind im ersten Lebensjahr

on Th[eodor] Goerge