Reverse engineering, modeling, and redesign of a vibratory conveyor

Some successful products are still developed and produced without the benefit of modern design techniques. One such product is a vibratory conveyor that has been developed largely through prototype iteration. The manufacturer has collaborated with Oregon State University to introduce model-based design into the development process. This research details a proposed framework for the reverse engineering of a mature product line. The framework is applied to a vibratory conveyor that is used in processing plants for corn and other raw foods. First, the project's origin and goals are described, followed by an explanation of the reverse engineering based framework used for guiding model selection. Next the selected dynamics model, built from the dynamic properties measured during reverse engineering, is applied and refined to accurately reflect the system's measured performance. Further modeling with finite element analysis, for improving performance and durability of specific components, is also described. This work concludes with the final research outcomes - redesign of fiberglass composite elements within the dynamic system and a set of guiding principles for designing a vibratory system, specifically this manufacturer's line of vibratory equipment

Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers

PURPOSE: Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. EXPERIMENTAL DESIGN: Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ). RESULTS: Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation. CONCLUSIONS: The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual

Research Progress Reports: Fruit and Vegetable Processing and Technology Division, Department of Horticulture [1969]

Blueberry cultivars for frozen pies / J. F. Gallander, W. A. Gould, and H. Stammer -- Grape cultivars for jelly making / J. F. Gallander, W. A. Gould and G. A. Cahoon -- Evaluation of various grape cultivars for processing. III. Table wines / J. F. Gallander -- Evaluation of snap bean cultivars for processing / William Hildebolt and W. A. Gould -- Kraut snacks / J. R. Geisman -- Mechanical harvesting and bulk handling evaluation of tomato cultivars for processing / W. A. Gould, Jonnie Budke, Carol Foglesong and Louise Howiler --The effects of lye peeling variables upon tomato cultivars / Loren Lucas and W. A. Gould -- Amino acids in canned tomato juice / Jenia D. Dormitorio and W. A. Gould -- Factors affecting the viscosity of tomato juice / David E. Crean and W. A. Goul

The Layer 0 Inner Silicon Detector of the D0 Experiment

This paper describes the design, fabrication, installation and performance of the new inner layer called Layer 0 (L0) that was inserted in the existing Run IIa Silicon Micro-Strip Tracker (SMT) of the D0 experiment at the Fermilab Tevatron collider. L0 provides tracking information from two layers of sensors, which are mounted with center lines at a radial distance of 16.1 mm and 17.6 mm respectively from the beam axis. The sensors and readout electronics are mounted on a specially designed and fabricated carbon fiber structure that includes cooling for sensor and readout electronics. The structure has a thin polyimide circuit bonded to it so that the circuit couples electrically to the carbon fiber allowing the support structure to be used both for detector grounding and a low impedance connection between the remotely mounted hybrids and the sensors.Comment: 28 pages, 9 figure

Defects in the Fanconi Anemia Pathway in Head and Neck Cancer Cells Stimulate Tumor Cell Invasion through DNA-PK and Rac1 Signaling

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) remains a devastating disease, and Fanconi anemia (FA) gene mutations and transcriptional repression are common. Invasive tumor behavior is associated with poor outcome, but relevant pathways triggering invasion are poorly understood. There is a significant need to improve our understanding of genetic pathways and molecular mechanisms driving advanced tumor phenotypes, to develop tailored therapies. Here we sought to investigate the phenotypic and molecular consequences of FA pathway loss in HNSCC cells. EXPERIMENTAL DESIGN: Using sporadic HNSCC cell lines with and without FA gene knockdown, we sought to characterize the phenotypic and molecular consequences of FA deficiency. FA pathway inactivation was confirmed by the detection of classic hallmarks of FA following exposure to DNA cross-linkers. Cells were subjected to RNA sequencing with qRT-PCR validation, followed by cellular adhesion and invasion assays in the presence and absence of DNA-dependent protein kinase (DNA-PK) and Rac1 inhibitors. RESULTS: We demonstrate that FA loss in HNSCC cells leads to cytoskeletal reorganization and invasive tumor cell behavior in the absence of proliferative gains. We further demonstrate that cellular invasion following FA loss is mediated, at least in part, through NHEJ-associated DNA-PK and downstream Rac1 GTPase activity. CONCLUSIONS: These findings demonstrate that FA loss stimulates HNSCC cell motility and invasion, and implicate a targetable DNA-PK/Rac1 signaling axis in advanced tumor phenotypes

Design and Implementation of the New D0 Level-1 Calorimeter Trigger

Increasing luminosity at the Fermilab Tevatron collider has led the D0 collaboration to make improvements to its detector beyond those already in place for Run IIa, which began in March 2001. One of the cornerstones of this Run IIb upgrade is a completely redesigned level-1 calorimeter trigger system. The new system employs novel architecture and algorithms to retain high efficiency for interesting events while substantially increasing rejection of background. We describe the design and implementation of the new level-1 calorimeter trigger hardware and discuss its performance during Run IIb data taking. In addition to strengthening the physics capabilities of D0, this trigger system will provide valuable insight into the operation of analogous devices to be used at LHC experiments.Comment: 43 pages, 20 figures, version published in Nucl. Instrum. and Methods

Design and Expression of a Dimeric Form of the Human Immunodeficiency Virus Type 1 Antibody 2G12 with Increased Neutralization Potency

The antigen-binding fragment of the broadly neutralizing Human Immunodeficiency Virus Type 1 (HIV-1) antibody 2G12 has an unusual 3D domain-swapped structure with two aligned combining sites that facilitates recognition of its carbohydrate epitope on gp120. When expressed as an intact IgG, 2G12 formed typical IgG monomers containing two combining sites and a small fraction of a higher molecular weight species, which showed a significant increase in neutralization potency (50- to 80-fold compared to 2G12 monomer) across a range of clade A and B strains of HIV-1. Here we show that the higher molecular weight species corresponds to a 2G12 dimer containing four combining sites, and present a model for how intermolecular 3D domain swapping could create a 2G12 dimer. Based on the structural model for a 3D domain-swapped 2G12 dimer, we designed and tested a series of 2G12 mutants predicted to increase the ratio of 2G12 dimer to monomer. We report a mutation that effectively increases the 2G12 dimer/monomer ratio without decreasing the expression yield. Increasing the proportion of 2G12 dimer compared with monomer could lead to a more potent reagent for gene therapy or passive immunization

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well as in the adult