A bottom-up design framework for CAD tools to support design for additive manufacturing

Additive manufacturing (AM) technology is enabling a platform to produce parts with enhanced shape complexity. Design engineers are exploiting this capability to produce high performance functional parts. The current top-down approach to design for AM requires the designer to develop a design model in CAD software and then use optimization tools to adapt the design for the AM technology, however this approach neglects a number of desired criteria. This paper proposes an alternative bottom-up design framework for a new type of CAD tool which combines the knowledge required to design a part with evolutionary programming in order to design parts specifically for the AM platform.</p

Effects of chronic inflammatory bowel diseases on left ventricular structure and function: a study protocol

BACKGROUND: Experimental evidences suggest an increased collagen deposition in inflammatory bowel diseases (IBD). In particular, large amounts of collagen type I, III and V have been described and correlated to the development of intestinal fibrotic lesions. No information has been available until now about the possible increased collagen deposition far from the main target organ. In the hypothesis that chronic inflammation and increased collagen metabolism are reflected also in the systemic circulation, we aimed this study to evaluate the effects on left ventricular wall structure by assessing splancnic and systemic collagen metabolism (procollagen III assay), deposition (ultrasonic tissue characterization), and cardiac function (echocardiography) in patients with different long standing history of IBD, before and after surgery. METHODS: Thirty patients affected by active IBD, 15 with Crohn and 15 with Ulcerative Colitis, submitted to surgery will be enrolled in the study in a double blind fashion. They will be studied before the surgical operation and 6, 12 months after surgery. A control group of 15 healthy age and gender-matched subjects will also be studied. At each interval blood samples will be collected in order to assess the collagen metabolism; a transthoracic echocardiogram will be recorded for the subsequent determination of cardiac function and collagen deposition. DISCUSSION: From this study protocol we expect additional information about the association between IBD and cardiovascular disorders; in particular to address the question if chronic inflammation, through the altered collagen metabolism, could affect left ventricular structure and function in a manner directly related to the estimated duration of the disease

Real-Time Monitoring of Tumorigenesis, Dissemination, & Drug Response in a Preclinical Model of Lymphangioleiomyomatosis/Tuberous Sclerosis Complex

Background: TSC2-deficient cells can proliferate in the lungs, kidneys, and other organs causing devastating progressive multisystem disorders such as lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC). Preclinical models utilizing LAM patient-derived cells have been difficult to establish. We developed a novel animal model system to study the molecular mechanisms of TSC/LAM pathogenesis and tumorigenesis and provide a platform for drug testing. Methods and Findings: TSC2-deficient human cells, derived from the angiomyolipoma of a LAM patient, were engineered to co-express both sodium-iodide symporter (NIS) and green fluorescent protein (GFP). Cells were inoculated intraparenchymally, intravenously, or intratracheally into athymic NCr nu/nu mice and cells were tracked and quantified using single photon emission computed tomography (SPECT) and computed tomography (CT). Surprisingly, TSC2-deficient cells administered intratracheally resulted in rapid dissemination to lymph node basins throughout the body, and histopathological changes in the lung consistent with LAM. Estrogen was found to be permissive for tumor growth and dissemination. Rapamycin inhibited tumor growth, but tumors regrew after the drug treatment was withdrawn. Conclusions: We generated homogeneous NIS/GFP co-expressing TSC2-deficient, patient-derived cells that can proliferate and migrate in vivo after intratracheal instillation. Although the animal model we describe has some limitations, we demonstrate that systemic tumors formed from TSC2-deficient cells can be monitored and quantified noninvasively over time using SPECT/CT, thus providing a much needed model system for in vivo drug testing and mechanistic studies of TSC2-deficient cells and their related clinical syndromes

Action de la methyl-4-ombelliferone * sur l'hydrodynamique de la voie biliaire principale chez l'homme : ETUDE RADIOMANODEBITMETRIQUE PER-OPERATOIRE

Poursuivant nos recherches de physiopathologie des voies biliaires extra-hépatiques, notre attention a été attirée par l'action pharmacodynamique de la méthyl-4-ombelliférone. Les travaux expérimentaux de Fontaine (1 et 2) chez l'animal de laboratoire ont montré que cette drogue est un cholérétique non cholagogue et un spasmolytique type papavérinique avec une action élective sur le sphincter d'Oddi. L'intérêt clinique d'un tel rôle est évident pour la thérapeutique médicale des dyskinésies biliaires. Notre but a été de vérifier l'efficacité de ce produit réputé « myo-relaxant » sur le sphincter d'Oddi et d'apprécier ses effets hydrodynamiques immédiats sur la voie biliaire principale chez l'homme. Pendant un an (avril 1973 à avril 1974) nous avons systématiquement étudié pour 105 opérés biliaires consécutifs, l'action immédiate de la méthyl-4-ombelliférone sous contrôle radiomanodébitmétrique per-opératoire. Au terme de ce travail nous pouvons définir les limites d'action de la méthyl-4-ombelliférone sur le tonus et le jeu fonctionnel du sphincter d'Oddi normal et pathologique