1,427 research outputs found

    A multi targeting conditionally replicating adenovirus displays enhanced oncolysis while maintaining expression of immunotherapeutic agents

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    Studies have demonstrated that oncolytic adenoviruses based on a 24 base pair deletion in the viral E1A gene (D24) may be promising therapeutics for treating a number of cancer types. In order to increase the therapeutic potential of these oncolytic viruses, a novel conditionally replicating adenovirus targeting multiple receptors upregulated on tumors was generated by incorporating an Ad5/3 fiber with a carboxyl terminus RGD ligand. The virus displayed full cytopathic effect in all tumor lines assayed at low titers with improved cytotoxicity over Ad5-RGD D24, Ad5/3 D24 and an HSV oncolytic virus. The virus was then engineered to deliver immunotherapeutic agents such as GM-CSF while maintaining enhanced heterogenic oncolysis

    Design and Vertical Tests of SPS-series Double-Quarter Wave (DQW) Cavity Prototypes for the HL-LHC Crab Cavity System

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    Crab crossing is essential for high-luminosity colliders. The High Luminosity Large Hadron Collider (HL-LHC) will equip one of its Interaction Points (IP1) with Double-Quarter Wave (DQW) crab cavities. A DQW cavity is a new generation of deflecting RF cavities that stands out for its compactness and broad frequency separation between fundamental and first high-order modes. The deflecting kick is provided by its fundamental mode. Each HL-LHC DQW cavity shall provide a nominal deflecting voltage of 3.4 MV, although up to 5.0 MV may be required. A Proof-of-Principle (PoP) DQW cavity was limited by quench at 4.6 MV. This paper describes a new, highly optimized cavity, designated DQW SPS-series, which satisfies dimensional, cryogenic, manufacturing and impedance requirements for beam tests at SPS and operation in LHC. Two prototypes of this DQW SPS-series were fabricated by US industry and cold tested after following conventional SRF surface treatment. Both units outperformed the PoP cavity, reaching a deflecting voltage of 5.3-5.9 MV. This voltage - the highest reached by a DQW cavity - is well beyond the nominal voltage of 3.4 MV and may even operate at the ultimate voltage of 5.0MVwith sufficient margin. This paper covers fabrication, surface preparation and cryogenic RF test results and implications

    “Take Off 4-Health�: Nutrition Education Curriculum for a Healthy Lifestyle Camp for Overweight Youth

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    There is evidence that residential summer weight loss camps can be effective to initiate or support the small change approach to address childhood obesity. This report describes the development and evaluation of nutrition education for overweight adolescents attending a three week healthy lifestyle camp. Campers were given a diet prescription based on MyPryamid and self-selected their meals and snacks that were served family style. The curriculum included eating strategies known to contribute to healthy weight in youth. Campers demonstrated improved ability to estimate portion sizes. Thirty-four campers completed the three week experience with a weight loss considered to be safe. Note: the deposited item is not the final published version, but rather is the last revised manuscript sent to the publisher

    Enzyme Sequence and Its Relationship to Hyperbaric Stability of Artificial and Natural Fish Lactate Dehydrogenases

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    The cDNAs of lactate dehydrogenase b (LDH-b) from both deep-sea and shallow living fish species, Corphaenoides armatus and Gadus morhua respectively, have been isolated, sequenced and their encoded products overproduced as recombinant enzymes in E. coli. The proteins were characterised in terms of their kinetic and physical properties and their ability to withstand high pressures. Although the two proteins are very similar in terms of their primary structure, only 21 differences at the amino acid level exist between them, the enzyme from the deep-sea species has a significantly increased tolerance to pressure and a higher thermostability. It was possible to investigate whether the changes in the N-terminal or C-terminal regions played a greater role in barophilic adaptation by the construction of two chimeric enzymes by use of a common restriction site within the cDNAs. One of these hybrids was found to have even greater pressure stability than the recombinant enzyme from the deep-living fish species. It was possible to conclude that the major adaptive changes to pressure tolerance must be located in the N-terminal region of the protein. The types of changes that are found and their spatial location within the protein structure are discussed. An analysis of the kinetic parameters of the enzymes suggests that there is clearly a trade off between Km and kcat values, which likely reflects the necessity of the deep-sea enzyme to operate at low temperatures
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