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Research paper thumbnail of Methodology for software development estimation optimization based on neural networks

IEEE Latin America Transactions, 2011

One of the most important tasks of a software development project manager is to produce accurate ... more One of the most important tasks of a software development project manager is to produce accurate time and effort estimations. Improving the estimation accuracy is a widely recognized benefit for several software development processes. In order to achieve these objectives, there are proposals based on Artificial Intelligence techniques and specifically artificial neural networks. This paper proposes an optimization methodology for searching the best neural model applicable to the effort estimation of software projects. This will draw on a set of known factors in the early stages of development, outside the complex calculation of function points, which would entail a high level of maturity and definition of the project. This methodology has allowed, on the one hand, ensure the adequacy of the proposed neural network model and, on the other hand, optimize the performance, both in time and accuracy.

Research paper thumbnail of Sensitivity of Philippines' Forest Tree Species to Climate Change: Policy Implications and Future Directions

Research paper thumbnail of Networking Beyond Rio+20: Climate Adaptation Partnerships for Sustainable Development — A Policy Brief

Research paper thumbnail of The Political Development of Valencia City, Bukidnon: A Historical Survey

Research paper thumbnail of Target-Site" Drug Metabolism and Transport

Drug metabolism and disposition: the biological fate of chemicals, 2015

The recent symposium on "Target-Site" Drug Metabolism and Transport that was sponsored ... more The recent symposium on "Target-Site" Drug Metabolism and Transport that was sponsored by the American Society for Pharmacology and Experimental Therapeutics at the 2014 Experimental Biology meeting in San Diego is summarized in this report. Emerging evidence has demonstrated that drug-metabolizing enzyme and transporter activity at the site of therapeutic action can affect the efficacy, safety, and metabolic properties of a given drug, with potential outcomes including altered dosing regimens, stricter exclusion criteria, or even the failure of a new chemical entity in clinical trials. Drug metabolism within the brain, for example, can contribute to metabolic activation of therapeutic drugs such as codeine as well as the elimination of potential neurotoxins in the brain. Similarly, the activity of oxidative and conjugative drug-metabolizing enzymes in the lung can have an effect on the efficacy of compounds such as resveratrol. In addition to metabolism, the active transp...

Research paper thumbnail of The Hippo pathway effector Yki downregulates Wg signaling to promote retinal differentiation in the Drosophila eye

Journal of Cell Science, 2015

The evolutionarily conserved Hippo signaling pathway is known to regulate cell proliferation and ... more The evolutionarily conserved Hippo signaling pathway is known to regulate cell proliferation and maintain tissue homeostasis during development. We found that activation of Yorkie (Yki), the effector of the Hippo signaling pathway, causes separable effects on growth and differentiation of the Drosophila eye. We present evidence supporting a role for Yki in suppressing eye fate by downregulation of the core retinal determination genes. Other upstream regulators of the Hippo pathway mediate this effect of Yki on retinal differentiation. Here, we show that, in the developing eye, Yki can prevent retinal differentiation by blocking morphogenetic furrow (MF) progression and R8 specification. The inhibition of MF progression is due to ectopic induction of Wingless (Wg) signaling and Homothorax (Hth), the negative regulators of eye development. Modulating Wg signaling can modify Yki-mediated suppression of eye fate. Furthermore, ectopic Hth induction due to Yki activation in the eye is dependent on Wg. Last, using Cut (Ct), a marker for the antennal fate, we show that suppression of eye fate by hyperactivation of yki does not change the cell fate (from eye to antenna-specific fate). In summary, we provide the genetic mechanism by which yki plays a role in cell fate specification and differentiationa novel aspect of Yki function that is emerging from multiple model organisms.

Research paper thumbnail of Role of orbitofrontal cortex in incubation of oxycodone craving in male rats

Research paper thumbnail of Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

Neuropsychopharmacology, 2015

The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The ... more The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotinemediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 μg), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 μg/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC 0-45min were both twofold higher (po0.05) with C8-xanthate vs vehicle pretreatment; there was no difference in peripheral nicotine levels. Rats were then given ICV pretreatment with C8-xanthate/ASCF and underwent intravenous nicotine self-administration with 3.75-30 μg/kg per infusion dose. C8-xanthate pretreatment increased responding in progressive ratio (15 μg/kg per infusion dose, po0.05). In a separate cohort, C8-xanthate increased the percentage of rats that acquired self-administration (7.5 μg/kg per infusion dose, po0.05) from 40% after vehicle pretreatment to 100%, with no difference in peripheral nicotine levels measured at the end of behavior. In a third cohort, C8-xanthate increased the number of sessions required to meet extinction criteria (po0.05). Together these data demonstrate that the brain CYP2B activity can influence nicotine brain levels and subsequent behaviors independent of hepatic metabolism. This suggests that human smokers with variable CYP2B brain levels could have different nicotine levels and reinforcement, which might have a role in smoking behaviors and dependence.

Research paper thumbnail of Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

Neuropsychopharmacology, 2015

The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The ... more The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotinemediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 μg), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 μg/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC 0-45min were both twofold higher (po0.05) with C8-xanthate vs vehicle pretreatment; there was no difference in peripheral nicotine levels. Rats were then given ICV pretreatment with C8-xanthate/ASCF and underwent intravenous nicotine self-administration with 3.75-30 μg/kg per infusion dose. C8-xanthate pretreatment increased responding in progressive ratio (15 μg/kg per infusion dose, po0.05). In a separate cohort, C8-xanthate increased the percentage of rats that acquired self-administration (7.5 μg/kg per infusion dose, po0.05) from 40% after vehicle pretreatment to 100%, with no difference in peripheral nicotine levels measured at the end of behavior. In a third cohort, C8-xanthate increased the number of sessions required to meet extinction criteria (po0.05). Together these data demonstrate that the brain CYP2B activity can influence nicotine brain levels and subsequent behaviors independent of hepatic metabolism. This suggests that human smokers with variable CYP2B brain levels could have different nicotine levels and reinforcement, which might have a role in smoking behaviors and dependence.

Research paper thumbnail of Methodology for software development estimation optimization based on neural networks

IEEE Latin America Transactions, 2011

One of the most important tasks of a software development project manager is to produce accurate ... more One of the most important tasks of a software development project manager is to produce accurate time and effort estimations. Improving the estimation accuracy is a widely recognized benefit for several software development processes. In order to achieve these objectives, there are proposals based on Artificial Intelligence techniques and specifically artificial neural networks. This paper proposes an optimization methodology for searching the best neural model applicable to the effort estimation of software projects. This will draw on a set of known factors in the early stages of development, outside the complex calculation of function points, which would entail a high level of maturity and definition of the project. This methodology has allowed, on the one hand, ensure the adequacy of the proposed neural network model and, on the other hand, optimize the performance, both in time and accuracy.

Research paper thumbnail of Sensitivity of Philippines' Forest Tree Species to Climate Change: Policy Implications and Future Directions

Research paper thumbnail of Networking Beyond Rio+20: Climate Adaptation Partnerships for Sustainable Development — A Policy Brief

Research paper thumbnail of The Political Development of Valencia City, Bukidnon: A Historical Survey

Research paper thumbnail of Target-Site" Drug Metabolism and Transport

Drug metabolism and disposition: the biological fate of chemicals, 2015

The recent symposium on "Target-Site" Drug Metabolism and Transport that was sponsored ... more The recent symposium on "Target-Site" Drug Metabolism and Transport that was sponsored by the American Society for Pharmacology and Experimental Therapeutics at the 2014 Experimental Biology meeting in San Diego is summarized in this report. Emerging evidence has demonstrated that drug-metabolizing enzyme and transporter activity at the site of therapeutic action can affect the efficacy, safety, and metabolic properties of a given drug, with potential outcomes including altered dosing regimens, stricter exclusion criteria, or even the failure of a new chemical entity in clinical trials. Drug metabolism within the brain, for example, can contribute to metabolic activation of therapeutic drugs such as codeine as well as the elimination of potential neurotoxins in the brain. Similarly, the activity of oxidative and conjugative drug-metabolizing enzymes in the lung can have an effect on the efficacy of compounds such as resveratrol. In addition to metabolism, the active transp...

Research paper thumbnail of The Hippo pathway effector Yki downregulates Wg signaling to promote retinal differentiation in the Drosophila eye

Journal of Cell Science, 2015

The evolutionarily conserved Hippo signaling pathway is known to regulate cell proliferation and ... more The evolutionarily conserved Hippo signaling pathway is known to regulate cell proliferation and maintain tissue homeostasis during development. We found that activation of Yorkie (Yki), the effector of the Hippo signaling pathway, causes separable effects on growth and differentiation of the Drosophila eye. We present evidence supporting a role for Yki in suppressing eye fate by downregulation of the core retinal determination genes. Other upstream regulators of the Hippo pathway mediate this effect of Yki on retinal differentiation. Here, we show that, in the developing eye, Yki can prevent retinal differentiation by blocking morphogenetic furrow (MF) progression and R8 specification. The inhibition of MF progression is due to ectopic induction of Wingless (Wg) signaling and Homothorax (Hth), the negative regulators of eye development. Modulating Wg signaling can modify Yki-mediated suppression of eye fate. Furthermore, ectopic Hth induction due to Yki activation in the eye is dependent on Wg. Last, using Cut (Ct), a marker for the antennal fate, we show that suppression of eye fate by hyperactivation of yki does not change the cell fate (from eye to antenna-specific fate). In summary, we provide the genetic mechanism by which yki plays a role in cell fate specification and differentiationa novel aspect of Yki function that is emerging from multiple model organisms.

Research paper thumbnail of Role of orbitofrontal cortex in incubation of oxycodone craving in male rats

Research paper thumbnail of Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

Neuropsychopharmacology, 2015

The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The ... more The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotinemediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 μg), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 μg/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC 0-45min were both twofold higher (po0.05) with C8-xanthate vs vehicle pretreatment; there was no difference in peripheral nicotine levels. Rats were then given ICV pretreatment with C8-xanthate/ASCF and underwent intravenous nicotine self-administration with 3.75-30 μg/kg per infusion dose. C8-xanthate pretreatment increased responding in progressive ratio (15 μg/kg per infusion dose, po0.05). In a separate cohort, C8-xanthate increased the percentage of rats that acquired self-administration (7.5 μg/kg per infusion dose, po0.05) from 40% after vehicle pretreatment to 100%, with no difference in peripheral nicotine levels measured at the end of behavior. In a third cohort, C8-xanthate increased the number of sessions required to meet extinction criteria (po0.05). Together these data demonstrate that the brain CYP2B activity can influence nicotine brain levels and subsequent behaviors independent of hepatic metabolism. This suggests that human smokers with variable CYP2B brain levels could have different nicotine levels and reinforcement, which might have a role in smoking behaviors and dependence.

Research paper thumbnail of Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

Neuropsychopharmacology, 2015

The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The ... more The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotinemediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 μg), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 μg/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC 0-45min were both twofold higher (po0.05) with C8-xanthate vs vehicle pretreatment; there was no difference in peripheral nicotine levels. Rats were then given ICV pretreatment with C8-xanthate/ASCF and underwent intravenous nicotine self-administration with 3.75-30 μg/kg per infusion dose. C8-xanthate pretreatment increased responding in progressive ratio (15 μg/kg per infusion dose, po0.05). In a separate cohort, C8-xanthate increased the percentage of rats that acquired self-administration (7.5 μg/kg per infusion dose, po0.05) from 40% after vehicle pretreatment to 100%, with no difference in peripheral nicotine levels measured at the end of behavior. In a third cohort, C8-xanthate increased the number of sessions required to meet extinction criteria (po0.05). Together these data demonstrate that the brain CYP2B activity can influence nicotine brain levels and subsequent behaviors independent of hepatic metabolism. This suggests that human smokers with variable CYP2B brain levels could have different nicotine levels and reinforcement, which might have a role in smoking behaviors and dependence.