Kelly Conlon | Trinity College, Connecticut (original) (raw)
Papers by Kelly Conlon
Analytical Biochemistry, 1992
Quantitation of the conversion of nonradioactive supercoiled DNA to its open circular or linear f... more Quantitation of the conversion of nonradioactive supercoiled DNA to its open circular or linear forms on ethidium-stained electrophoretic gels has been difficult because of differential binding of ethidium to supercoiled DNA vs other forms under different conditions and the nonlinear response of photographic film. We have developed methods for adding a linear DNA as an internal fluorescence standard to "normalize" the quantity of DNA loaded into each lane of a gel. Inclusion of a linear normalizing DNA in samples before partitioning for individual supercoil cleavage reactions allows the quantitation of the resultant species, is technically easy, and does not require quantitative application of the sample to the gel. If the presence of a normalizing DNA during supercoil cleavage is undesirable, the addition of a normalizing plasmid to each sample after supercoil cleavage (but before electrophoresis) or the quantitative application of samples containing test DNA alone to the gel gives similar data, but with increased variability. We use the normalizing DNA method in cleavage by a physical agent (ionizing radiation) and in a more complex situation, by a protein-based, light-dependent synthetic endonuclease. We show how the fraction of intact supercoiled DNA can be calculated from measurement of the cleaved and normalizing species only. The method also can be used in reactions involving the depletion of one DNA species, whether supercoiled or not, such as protein-DNA interactions as detected by gel retardation assays.
Journal of The Autonomic Nervous System, 1999
Previous studies, using non-specific nitric oxide synthase (NOS) inhibitors, have shown that nitr... more Previous studies, using non-specific nitric oxide synthase (NOS) inhibitors, have shown that nitric oxide (NO) has a significant facilitatory effect on the actions of the vagus nerve on several aspects of cardiac function. The present study aims to identify a potential neuronal site for the action of NO by using the n-NOS inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM) in the ferret and other mammals. The effects of TRIM on vagally evoked alterations in heart rate and atrio-ventricular (a-v) conduction in the anaesthetised ferret, rabbit and guinea pig are described. In ferrets with both vagi sectioned and repeated infusions of propranolol, the vagally evoked, frequency-dependent bradycardia was significantly attenuated by infusion of TRIM (10-30 mg kg(-1)). This effect was reversed by subsequent infusion of L-arginine (20-6 mg kg(-1)). TRIM also attenuated to a similar extent the vagally evoked bradycardia in similarly prepared guinea pigs, but NOS inhibition and the use of the NO donor, molsidimine, failed to alter the heart rate effects of vagal stimulation in the rabbit. In studies on a-v conduction (dromotropy) in the ferret, electrical stimulation of the left cervical vagus increased the a-v conduction time in a frequency-dependent manner. Administration of TRIM (30 mg kg(-1)) significantly attenuated this response. Again, L-arginine (60 mg kg(-1)) reversed it. Since an alteration in heart rate may have a concomitant action on a-v conduction time, the effects of vagal stimulation on a-v conduction were also carried out in ferrets with the heart paced at a constant rate electrically. There was no significant difference between the effects of vagal stimulation obtained from hearts which were paced and those which were unpaced. This implies that vagal stimulation had a direct effect on a-v delay and the changes were not secondary to alterations in cardiac rate. Based on other evidence that TRIM is a powerful reversible n-NOS inhibitor in vivo, our studies support strongly the hypothesis that NO liberated from neuronal sources has an important facilitatory action on the vagal control of the heart. In relation to vagal heart rate control, it has now been shown that, in line with other studies in the dog and the rat, NO exerts a powerful facilitatory action in the ferret and the guinea pig but not in the rabbit. It is to be expected that these effects of NO will also be demonstrable on other vagal cardiac actions.
Metallurgical and Materials Transactions A-physical Metallurgy and Materials Science, 2006
A new technique is introduced to quantify microsegregation during rapid solidification. The quant... more A new technique is introduced to quantify microsegregation during rapid solidification. The quantification involves calculation of the average solute solubility in the primary phase during solidification of an Al-Cu binary alloy. The calculation is based on using volume percent eutectic and weight percent of second phase (in the eutectic), which were obtained experimentally. Neutron diffraction experiments and stereology calculation on scanning electron microscope images were done on impulse atomized Al-Cu alloys of three compositions (nominal), 5 wt pct Cu, 10 wt pct Cu, and 17 wt pct Cu, atomized under N2 and He gas. Neutron diffraction experiments yielded weight percent CuAl2 data and stereology yielded volume percent eutectic data. These two data were first used to determine the weight percent eutectic. Using the weight percent eutectic and weight percent CuAl2 in mass and volume balance equations, the average solute solubility in the primary phase could be calculated. The experimental results of the amount of eutectic, tomography results from previous work, and results from the calculations suggest that the atomized droplets are in metastable state during the nucleation undercooling of the primary phase, and the effect of metastability propagates through to the eutectic formation stage. The metastable effect is more pronounced in alloys with higher solute composition.
Bioorganic & Medicinal Chemistry Letters, 2008
A novel series of central nervous system (CNS) penetrant indane 2-imidazoles have been identified... more A novel series of central nervous system (CNS) penetrant indane 2-imidazoles have been identified as potent, partial agonists of the alpha(1A) adrenergic receptor, having good selectivity over the alpha(1B), alpha(1D) and alpha(2) sub-types. A key structural motif to impart selectivity is a methylene spacer between the indane and a pendant substituent, which includes heterocycles, sulphones and ethers. Introduction of an ortho-halogen to this group led to a lowering of intrinsic efficacy (E(max)).
Cheminform, 2008
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Bioorganic & Medicinal Chemistry Letters, 2009
A range of heterocycle fused azepines were synthesized in order to find a CNS penetrant, selectiv... more A range of heterocycle fused azepines were synthesized in order to find a CNS penetrant, selective 5-HT 2C agonist for the treatment of incontinence. The pyridazo-azepines such as compound 11 were shown to be potent 5-HT 2C agonists and have potential for CNS penetration and good in vitro ADME properties but lacked selectivity against 5-HT 2B . Fusing a further heterocycle gave the selective triazolopyrimido-azepines. An example of this series, compound 36, was shown to be potent, selective, metabolically stable in vitro and efficacious in an in vivo model of stress urinary incontinence.
Cheminform, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Bioorganic & Medicinal Chemistry Letters, 2008
Novel 2-imidazoles have been identified as potent partial agonists of the a 1A adrenergic recepto... more Novel 2-imidazoles have been identified as potent partial agonists of the a 1A adrenergic receptor, with good selectivity over the a 1B , a 1D and a 2A receptor sub-types. Sulfonamide 23 possessed attractive drug-like properties with respect to physicochemical and ADME properties and wide ligand selectivity.
Analytical Biochemistry, 1992
Quantitation of the conversion of nonradioactive supercoiled DNA to its open circular or linear f... more Quantitation of the conversion of nonradioactive supercoiled DNA to its open circular or linear forms on ethidium-stained electrophoretic gels has been difficult because of differential binding of ethidium to supercoiled DNA vs other forms under different conditions and the nonlinear response of photographic film. We have developed methods for adding a linear DNA as an internal fluorescence standard to "normalize" the quantity of DNA loaded into each lane of a gel. Inclusion of a linear normalizing DNA in samples before partitioning for individual supercoil cleavage reactions allows the quantitation of the resultant species, is technically easy, and does not require quantitative application of the sample to the gel. If the presence of a normalizing DNA during supercoil cleavage is undesirable, the addition of a normalizing plasmid to each sample after supercoil cleavage (but before electrophoresis) or the quantitative application of samples containing test DNA alone to the gel gives similar data, but with increased variability. We use the normalizing DNA method in cleavage by a physical agent (ionizing radiation) and in a more complex situation, by a protein-based, light-dependent synthetic endonuclease. We show how the fraction of intact supercoiled DNA can be calculated from measurement of the cleaved and normalizing species only. The method also can be used in reactions involving the depletion of one DNA species, whether supercoiled or not, such as protein-DNA interactions as detected by gel retardation assays.
Journal of The Autonomic Nervous System, 1999
Previous studies, using non-specific nitric oxide synthase (NOS) inhibitors, have shown that nitr... more Previous studies, using non-specific nitric oxide synthase (NOS) inhibitors, have shown that nitric oxide (NO) has a significant facilitatory effect on the actions of the vagus nerve on several aspects of cardiac function. The present study aims to identify a potential neuronal site for the action of NO by using the n-NOS inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM) in the ferret and other mammals. The effects of TRIM on vagally evoked alterations in heart rate and atrio-ventricular (a-v) conduction in the anaesthetised ferret, rabbit and guinea pig are described. In ferrets with both vagi sectioned and repeated infusions of propranolol, the vagally evoked, frequency-dependent bradycardia was significantly attenuated by infusion of TRIM (10-30 mg kg(-1)). This effect was reversed by subsequent infusion of L-arginine (20-6 mg kg(-1)). TRIM also attenuated to a similar extent the vagally evoked bradycardia in similarly prepared guinea pigs, but NOS inhibition and the use of the NO donor, molsidimine, failed to alter the heart rate effects of vagal stimulation in the rabbit. In studies on a-v conduction (dromotropy) in the ferret, electrical stimulation of the left cervical vagus increased the a-v conduction time in a frequency-dependent manner. Administration of TRIM (30 mg kg(-1)) significantly attenuated this response. Again, L-arginine (60 mg kg(-1)) reversed it. Since an alteration in heart rate may have a concomitant action on a-v conduction time, the effects of vagal stimulation on a-v conduction were also carried out in ferrets with the heart paced at a constant rate electrically. There was no significant difference between the effects of vagal stimulation obtained from hearts which were paced and those which were unpaced. This implies that vagal stimulation had a direct effect on a-v delay and the changes were not secondary to alterations in cardiac rate. Based on other evidence that TRIM is a powerful reversible n-NOS inhibitor in vivo, our studies support strongly the hypothesis that NO liberated from neuronal sources has an important facilitatory action on the vagal control of the heart. In relation to vagal heart rate control, it has now been shown that, in line with other studies in the dog and the rat, NO exerts a powerful facilitatory action in the ferret and the guinea pig but not in the rabbit. It is to be expected that these effects of NO will also be demonstrable on other vagal cardiac actions.
Metallurgical and Materials Transactions A-physical Metallurgy and Materials Science, 2006
A new technique is introduced to quantify microsegregation during rapid solidification. The quant... more A new technique is introduced to quantify microsegregation during rapid solidification. The quantification involves calculation of the average solute solubility in the primary phase during solidification of an Al-Cu binary alloy. The calculation is based on using volume percent eutectic and weight percent of second phase (in the eutectic), which were obtained experimentally. Neutron diffraction experiments and stereology calculation on scanning electron microscope images were done on impulse atomized Al-Cu alloys of three compositions (nominal), 5 wt pct Cu, 10 wt pct Cu, and 17 wt pct Cu, atomized under N2 and He gas. Neutron diffraction experiments yielded weight percent CuAl2 data and stereology yielded volume percent eutectic data. These two data were first used to determine the weight percent eutectic. Using the weight percent eutectic and weight percent CuAl2 in mass and volume balance equations, the average solute solubility in the primary phase could be calculated. The experimental results of the amount of eutectic, tomography results from previous work, and results from the calculations suggest that the atomized droplets are in metastable state during the nucleation undercooling of the primary phase, and the effect of metastability propagates through to the eutectic formation stage. The metastable effect is more pronounced in alloys with higher solute composition.
Bioorganic & Medicinal Chemistry Letters, 2008
A novel series of central nervous system (CNS) penetrant indane 2-imidazoles have been identified... more A novel series of central nervous system (CNS) penetrant indane 2-imidazoles have been identified as potent, partial agonists of the alpha(1A) adrenergic receptor, having good selectivity over the alpha(1B), alpha(1D) and alpha(2) sub-types. A key structural motif to impart selectivity is a methylene spacer between the indane and a pendant substituent, which includes heterocycles, sulphones and ethers. Introduction of an ortho-halogen to this group led to a lowering of intrinsic efficacy (E(max)).
Cheminform, 2008
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Bioorganic & Medicinal Chemistry Letters, 2009
A range of heterocycle fused azepines were synthesized in order to find a CNS penetrant, selectiv... more A range of heterocycle fused azepines were synthesized in order to find a CNS penetrant, selective 5-HT 2C agonist for the treatment of incontinence. The pyridazo-azepines such as compound 11 were shown to be potent 5-HT 2C agonists and have potential for CNS penetration and good in vitro ADME properties but lacked selectivity against 5-HT 2B . Fusing a further heterocycle gave the selective triazolopyrimido-azepines. An example of this series, compound 36, was shown to be potent, selective, metabolically stable in vitro and efficacious in an in vivo model of stress urinary incontinence.
Cheminform, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Bioorganic & Medicinal Chemistry Letters, 2008
Novel 2-imidazoles have been identified as potent partial agonists of the a 1A adrenergic recepto... more Novel 2-imidazoles have been identified as potent partial agonists of the a 1A adrenergic receptor, with good selectivity over the a 1B , a 1D and a 2A receptor sub-types. Sulfonamide 23 possessed attractive drug-like properties with respect to physicochemical and ADME properties and wide ligand selectivity.