Jay Short - Academia.edu (original) (raw)
Papers by Jay Short
Cancer Research, 2021
The use of CD3/target bispecific molecules has great therapeutic potential in oncology. This pote... more The use of CD3/target bispecific molecules has great therapeutic potential in oncology. This potential, however, is diminished due to severe cytokine release effects as well as serious on-target off-tumor toxicities. Conditionally Active Biologic (CAB) technology is a proprietary platform that generates bispecific antibodies which have no or very little binding to CD3 and to the tumor target antigen (TAA) in healthy tissue (normal physiological conditions), but have strong binding in the context of diseased tissues (tumor microenvironment) based on the glycolytic tumor metabolism (including Warburg effect). Using our CAB technology, we have developed dual-CAB (CAB TAA x CAB CD3) bispecific antibodies targeting two well-established tumor associated antigens, B7H3 and Nectin4. These dual-CAB bispecific antibodies were developed so that they bind to recombinant CD3 and TAA as well as to CD3 and TAA expressing cells under in vitro tumor microenvironment conditions, but not in physiologi...
Escherichia coli strains. methylated DNA sequences in mcrA mcrB1 responsible for inhibiting propa... more Escherichia coli strains. methylated DNA sequences in mcrA mcrB1 responsible for inhibiting propagation of Identification and characterization of a gene
This research examines the role of community participation in urban design. It looks at developin... more This research examines the role of community participation in urban design. It looks at developing more efficient methods of facilitating participation so that it can become more feasible for developers and designers. A literature review and analysis of case studies found that community participation in urban design, in the developed world, is almost non-existent. In impoverished countries, however, it is more common - recognising that the commercial and political pressures of Western societies make participation in urban design difficult to justify. The research then moves to its major case study - Shelly Bay. This area is facing a large development which has been highly protested by members of the local and wider community. One of the more significant reasons for the protest was the lack of transparency in the development planning stages. So why does the public not have a say on the future of Shelly Bay? This thesis researches ways which developers, architects and urban designe...
There is an upward trend in demand for intellectual property protection in agriculture. While int... more There is an upward trend in demand for intellectual property protection in agriculture. While international agreements exist to protect agricultural biodiversity, the specific rights, benefits, and responsibilities of parties en tering into commercial agreements that involve the use of genetic resources still must be clarified. This chapter pro vides practical guidance for creating agreements around the use of biodiversity resources, as well as guidance that may provide valuable insights for creating similar agreements on the use of unique agricultural resources.
Journal of Biological Chemistry, 2004
There is a growing need in the textile industry for more economical and environmentally responsib... more There is a growing need in the textile industry for more economical and environmentally responsible approaches to improve the scouring process as part of the pretreatment of cotton fabric. Enzymatic methods using pectin-degrading enzymes are potentially valuable candidates in this effort because they could reduce the amount of toxic alkaline chemicals currently used. Using high throughput screening of complex environmental DNA libraries more than 40 novel microbial pectate lyases were discovered, and their enzymatic properties were characterized. Several candidate enzymes were found that possessed pH optima and specific activities on pectic material in cotton fibers compatible with their use in the scouring process. However, none exhibited the desired temperature characteristics. Therefore, a candidate enzyme was selected for evolution. Using Gene Site Saturation Mutagenesis TM technology, 36 single site mutants exhibiting improved thermotolerance were produced. A combinatorial library derived from the 12 best performing single site mutants was then generated by using Gene Reassembly TM technology. Nineteen variants with further improved thermotolerance were produced. These variants were tested for both improved thermotolerance and performance in the bioscouring application. The best performing variant (CO14) contained eight mutations and had a melting temperature 16°C higher than the wild type enzyme while retaining the same specific activity at 50°C. Optimal temperature of the evolved enzyme was 70°C, which is 20°C higher than the wild type. Scouring results obtained with the evolved enzyme were significantly better than the results obtained with chemical scouring, making it possible to replace the conventional and environmentally harmful chemical scouring process.
Applied and Environmental Microbiology, 2004
The inclusion of phytase in monogastric animal feed has the benefit of hydrolyzing indigestible p... more The inclusion of phytase in monogastric animal feed has the benefit of hydrolyzing indigestible plant phytate ( myo -inositol 1,2,3,4,5,6-hexakis dihydrogen phosphate) to provide poultry and swine with dietary phosphorus. An ideal phytase supplement should have a high temperature tolerance, allowing it to survive the feed pelleting process, a high specific activity at low pHs, and adequate gastric performance. For this study, the performance of a bacterial phytase was optimized by the use of gene site saturation mutagenesis technology. Beginning with the appA gene from Escherichia coli , a library of clones incorporating all 19 possible amino acid changes and 32 possible codon variations in 431 residues of the sequence was generated and screened for mutants exhibiting improved thermal tolerance. Fourteen single site variants were discovered that retained as much as 10 times the residual activity of the wild-type enzyme after a heated incubation regimen. The addition of eight individ...
Cancer Research, 2021
The use of CD3/target bispecific molecules has great therapeutic potential in oncology. This pote... more The use of CD3/target bispecific molecules has great therapeutic potential in oncology. This potential, however, is diminished due to severe cytokine release effects as well as serious on-target off-tumor toxicities. Conditionally Active Biologic (CAB) technology is a proprietary platform that generates bispecific antibodies which have no or very little binding to CD3 and to the tumor target antigen (TAA) in healthy tissue (normal physiological conditions), but have strong binding in the context of diseased tissues (tumor microenvironment) based on the glycolytic tumor metabolism (including Warburg effect). Using our CAB technology, we have developed dual-CAB (CAB TAA x CAB CD3) bispecific antibodies targeting two well-established tumor associated antigens, B7H3 and Nectin4. These dual-CAB bispecific antibodies were developed so that they bind to recombinant CD3 and TAA as well as to CD3 and TAA expressing cells under in vitro tumor microenvironment conditions, but not in physiologi...
Escherichia coli strains. methylated DNA sequences in mcrA mcrB1 responsible for inhibiting propa... more Escherichia coli strains. methylated DNA sequences in mcrA mcrB1 responsible for inhibiting propagation of Identification and characterization of a gene
This research examines the role of community participation in urban design. It looks at developin... more This research examines the role of community participation in urban design. It looks at developing more efficient methods of facilitating participation so that it can become more feasible for developers and designers. A literature review and analysis of case studies found that community participation in urban design, in the developed world, is almost non-existent. In impoverished countries, however, it is more common - recognising that the commercial and political pressures of Western societies make participation in urban design difficult to justify. The research then moves to its major case study - Shelly Bay. This area is facing a large development which has been highly protested by members of the local and wider community. One of the more significant reasons for the protest was the lack of transparency in the development planning stages. So why does the public not have a say on the future of Shelly Bay? This thesis researches ways which developers, architects and urban designe...
There is an upward trend in demand for intellectual property protection in agriculture. While int... more There is an upward trend in demand for intellectual property protection in agriculture. While international agreements exist to protect agricultural biodiversity, the specific rights, benefits, and responsibilities of parties en tering into commercial agreements that involve the use of genetic resources still must be clarified. This chapter pro vides practical guidance for creating agreements around the use of biodiversity resources, as well as guidance that may provide valuable insights for creating similar agreements on the use of unique agricultural resources.
Journal of Biological Chemistry, 2004
There is a growing need in the textile industry for more economical and environmentally responsib... more There is a growing need in the textile industry for more economical and environmentally responsible approaches to improve the scouring process as part of the pretreatment of cotton fabric. Enzymatic methods using pectin-degrading enzymes are potentially valuable candidates in this effort because they could reduce the amount of toxic alkaline chemicals currently used. Using high throughput screening of complex environmental DNA libraries more than 40 novel microbial pectate lyases were discovered, and their enzymatic properties were characterized. Several candidate enzymes were found that possessed pH optima and specific activities on pectic material in cotton fibers compatible with their use in the scouring process. However, none exhibited the desired temperature characteristics. Therefore, a candidate enzyme was selected for evolution. Using Gene Site Saturation Mutagenesis TM technology, 36 single site mutants exhibiting improved thermotolerance were produced. A combinatorial library derived from the 12 best performing single site mutants was then generated by using Gene Reassembly TM technology. Nineteen variants with further improved thermotolerance were produced. These variants were tested for both improved thermotolerance and performance in the bioscouring application. The best performing variant (CO14) contained eight mutations and had a melting temperature 16°C higher than the wild type enzyme while retaining the same specific activity at 50°C. Optimal temperature of the evolved enzyme was 70°C, which is 20°C higher than the wild type. Scouring results obtained with the evolved enzyme were significantly better than the results obtained with chemical scouring, making it possible to replace the conventional and environmentally harmful chemical scouring process.
Applied and Environmental Microbiology, 2004
The inclusion of phytase in monogastric animal feed has the benefit of hydrolyzing indigestible p... more The inclusion of phytase in monogastric animal feed has the benefit of hydrolyzing indigestible plant phytate ( myo -inositol 1,2,3,4,5,6-hexakis dihydrogen phosphate) to provide poultry and swine with dietary phosphorus. An ideal phytase supplement should have a high temperature tolerance, allowing it to survive the feed pelleting process, a high specific activity at low pHs, and adequate gastric performance. For this study, the performance of a bacterial phytase was optimized by the use of gene site saturation mutagenesis technology. Beginning with the appA gene from Escherichia coli , a library of clones incorporating all 19 possible amino acid changes and 32 possible codon variations in 431 residues of the sequence was generated and screened for mutants exhibiting improved thermal tolerance. Fourteen single site variants were discovered that retained as much as 10 times the residual activity of the wild-type enzyme after a heated incubation regimen. The addition of eight individ...