Current Search:  inhibition (x)

View All Items

  • CSV Spreadsheet
(1 - 6 of 6)
Two-Component Covalent Inhibitors (TCCI) of the Human Immunodeficiency Virus Reverse Transcriptase (HIV-RT)
Title
Two-Component Covalent Inhibitors (TCCI) of the Human Immunodeficiency Virus Reverse Transcriptase (HIV-RT).
Creator
Ledezma, Carlos, Kolpashchikov, Dmitry, Yestrebsky, Cherie, Hernandez, Florencio, Zhai, Lei, Tatulian, Suren, University of Central Florida
Abstract / Description
The traditional design of nucleoside reverse transcriptase inhibitors (NRTI's) involves the synthesis of chain-terminated nucleoside analogs. HIV-RT has relatively low fidelity which facilitates mutations that confer resistance towards NRTI's, also, drug promiscuity from NRTI's result in various side-effects that lead to poor patient adherence to treatment. We designed and tested two-component covalent inhibitors against HIV-RT. Our inhibitor design results in higher specificity due to its...
Show moreThe traditional design of nucleoside reverse transcriptase inhibitors (NRTI's) involves the synthesis of chain-terminated nucleoside analogs. HIV-RT has relatively low fidelity which facilitates mutations that confer resistance towards NRTI's, also, drug promiscuity from NRTI's result in various side-effects that lead to poor patient adherence to treatment. We designed and tested two-component covalent inhibitors against HIV-RT. Our inhibitor design results in higher specificity due to its binary approach, which has previously been used in biosensing applications, where both components are necessary for therapeutic effect, and lower chances for mutagenesis because of its inhibitory action. The TCCI approach results in up to 93% inhibition of HIV-RT Furthermore, our inhibitor design is highly modular and can be adjusted towards the therapeutic targeting of other biopolymers.
Show less
Date Issued
2017
Identifier
CFE0006893, ucf:51712
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0006893
Cerium oxide Nanoparticles: Their Phosphatase Activity and its Control
Title
Cerium oxide Nanoparticles: Their Phosphatase Activity and its Control.
Creator
Dhall, Atul, Self, William, Seal, Sudipta, Zervos, Antonis, University of Central Florida
Abstract / Description
Cerium oxide nanoparticles are established scavengers of reactive oxygen and nitrogen species. They have many potential biomedical applications that depend on their physicochemical properties and mode of preparation. Recent studies have found these nanoparticles possess phosphatase mimetic activity. Studying such catalytic activities will qualify their biomedical applications and render information on their bioavailability and potential toxicity.Two oxidation states of cerium exist in these...
Show moreCerium oxide nanoparticles are established scavengers of reactive oxygen and nitrogen species. They have many potential biomedical applications that depend on their physicochemical properties and mode of preparation. Recent studies have found these nanoparticles possess phosphatase mimetic activity. Studying such catalytic activities will qualify their biomedical applications and render information on their bioavailability and potential toxicity.Two oxidation states of cerium exist in these nanoparticles (3+ or 4+). It is hypothesized that the oxidation state of cerium in the nanoparticles determines the amount of adsorbed water on the crystal lattices. This in turn governs their activity as phosphatases. Nanoparticles with higher levels of cerium in the 4+ state exhibit phosphatase activity while those with higher levels of cerium in the 3+ state do not. This phosphatase activity may be controlled with the addition of inhibitory anions. It is hypothesized that anions with structures similar to phosphate can inhibit phosphatase activity by leading to the production of complexes on the surface of cerium oxide nanoparticles.Substrates that were used to test this activity include para-nitrophenyl phosphate (pNPP), 4-methylumbelliferyl phosphate (MUP) and adenosine triphosphate (ATP). To highlight the role of adsorbed water, we also performed experiments on pNPP with methanol as a solvent. The activity was measured by absorbance (pNPP and ATP) or fluorescence (MUP) and reported as nmol of phosphate/min. In some cases this rate was calculated through coupled reactions or by measuring the rate of formation of other colored products formed along with the release of phosphate such as pNP (para-nitrophenol).The phosphatase activity increased as the amount of adsorbed water increased implying that the abundance of adsorbed water makes the surface of 4+ ceria nanoparticles more active. Phosphatase activity for all the substrates exhibited Michaelis-Menten kinetics. Although the phosphatase activity of these nanoparticles is slow (turnover rate) as compared to real biological phosphatases, it can be used as a model catalytic activity to follow other catalytic activities that are associated with nanoparticles that have an abundance of cerium in the 4+ state, such as catalase activity. These results also provide information on the nature of the active sites involved in the catalytic activities associated with these nanoparticles.We identified three inhibitors, tungstate, molybdate and arsenate, which decreased the phosphatase activity of these nanoparticles in a dose dependent manner. Vmax, Km and Ki values were determined by varying substrate concentrations in the presence and absence of inhibitors. A partial mixed inhibition model was fit for each of these inhibitors.Summary: Phosphatase activity of cerium oxide nanoparticles with higher levels of cerium in the 4+ oxidation state was used as a model catalytic activity to study the nature of the active sites involved in catalysis. The study of inhibitors can reveal more information as to the surface binding of substrates in catalysis.
Show less
Date Issued
2014
Identifier
CFE0005603, ucf:50261
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0005603
Impulsivity and Attention-Deficit/Hyperactivity Disorder (ADHD): Testing competing predictions from the working memory and behavioral inhibition models of ADHD
Title
Impulsivity and Attention-Deficit/Hyperactivity Disorder (ADHD): Testing competing predictions from the working memory and behavioral inhibition models of ADHD.
Creator
Raiker, Joseph, Rapport, Mark, Beidel, Deborah, Mouloua, Mustapha, University of Central Florida
Abstract / Description
Impulsivity is a hallmark of two of the three DSM-IV ADHD subtypes and is associated with myriad adverse outcomes. Limited research, however, is available concerning the mechanisms and processes that contribute to impulsive responding by children with ADHD. The current study tested predictions from two competing models of ADHD (-) working memory (WM) and behavioral inhibition (BI) (-) to examine the extent to which ADHD-related impulsive responding was attributable to model-specific...
Show moreImpulsivity is a hallmark of two of the three DSM-IV ADHD subtypes and is associated with myriad adverse outcomes. Limited research, however, is available concerning the mechanisms and processes that contribute to impulsive responding by children with ADHD. The current study tested predictions from two competing models of ADHD (-) working memory (WM) and behavioral inhibition (BI) (-) to examine the extent to which ADHD-related impulsive responding was attributable to model-specific mechanisms and processes. Children with ADHD (n = 21) and typically developing children (n = 20) completed laboratory tasks that provided WM (domain-general central executive [CE], phonological/visuospatial storage/rehearsal) and BI indices (stop-signal reaction time [SSRT], stop-signal delay, mean reaction time). These indices were examined as potential mediators of ADHD-related impulsive responding on two diverse laboratory tasks used commonly to assess impulsive responding (CPT: continuous performance test; VMTS: visual match-to-sample). Bias-corrected, bootstrapped mediation analyses revealed that CE processes significantly attenuated between-group impulsivity differences, such that the initial large-magnitude impulsivity differences were no longer significant on either task after accounting for ADHD-related CE deficits. In contrast, SSRT partially mediated ADHD-related impulsive responding on the CPT but not VMTS. This partial attenuation was no longer significant after accounting for shared variance between CE and SSRT; CE continued to attenuate the ADHD-impulsivity relationship after accounting for SSRT. These findings add to the growing literature implicating CE deficits in core ADHD behavioral and functional impairments, and suggest that cognitive interventions targeting CE rather than storage/rehearsal or BI processes may hold greater promise for alleviating ADHD-related impairments.
Show less
Date Issued
2011
Identifier
CFE0004155, ucf:49070
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0004155
IDENTIFICATION OF SMALL MOLECULES THAT INHIBIT PROSTATE CANCER CELL PROLIFERATION
Title
IDENTIFICATION OF SMALL MOLECULES THAT INHIBIT PROSTATE CANCER CELL PROLIFERATION.
Creator
Zelaya, Rainel, Chakrabarti, Ratna, University of Central Florida
Abstract / Description
Prostate cancer is the second most often diagnosed cancer and internationally the sixth foremost cause of cancer death in males, as of 2011. Within the United States it is the most common form of cancer in men with 186,000 new cases and with an overall 28,600 deaths in 2008, and it is the second leading kind of cancer-related death in men. The widespread threat that prostate cancer poses against men across the globe cannot be understated, and its initiation and progression must be understood...
Show moreProstate cancer is the second most often diagnosed cancer and internationally the sixth foremost cause of cancer death in males, as of 2011. Within the United States it is the most common form of cancer in men with 186,000 new cases and with an overall 28,600 deaths in 2008, and it is the second leading kind of cancer-related death in men. The widespread threat that prostate cancer poses against men across the globe cannot be understated, and its initiation and progression must be understood in order to truly comprehend its implicated risks and possible forms of treatment. As its name implies, prostate cancer is a form of cancer that develops in the prostate gland located in the male reproductive system. Its progress starts when standard semen-secreting prostate gland cells mutate into cancer cells. Although its developments may start at the prostate gland, cancer cells may metastasize to other parts of the body through circulation systems such as the lymph nodes. The main sites of metastasis for prostate cancer include the adrenal gland,the bones, the liver and the lungs. Although there are treatments available for prostate cancer, there is no definitive cure. The primary goal of this project was to find an alternative form of treatment, which is what will be necessary to combat this cancer.
Show less
Date Issued
2014
Identifier
CFH0004595, ucf:45228
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFH0004595
ADHD AND STOP-SIGNAL BEHAVIORAL INHIBITION: IS MEAN REACTION TIME CONTAMINATED BY EXPOSURE TO INTERMITTENT STOP-SIGNALS?
Title
ADHD AND STOP-SIGNAL BEHAVIORAL INHIBITION: IS MEAN REACTION TIME CONTAMINATED BY EXPOSURE TO INTERMITTENT STOP-SIGNALS?.
Creator
Alderson, Robert, Rapport, Mark, University of Central Florida
Abstract / Description
The current study investigates two recently identified threats to the construct validity of behavioral inhibition as a core deficit of attention-deficit/hyperactivity disorder (ADHD) based on the Stop-signal task: calculation of mean reaction time from go-trials presented adjacent to intermittent stop-trials, and non-reporting of the stop-signal delay metric. Children with ADHD (n=12) and typically developing children (TD) (n=11) were administered the standard stop-signal task and three...
Show moreThe current study investigates two recently identified threats to the construct validity of behavioral inhibition as a core deficit of attention-deficit/hyperactivity disorder (ADHD) based on the Stop-signal task: calculation of mean reaction time from go-trials presented adjacent to intermittent stop-trials, and non-reporting of the stop-signal delay metric. Children with ADHD (n=12) and typically developing children (TD) (n=11) were administered the standard stop-signal task and three variant stop-signal conditions. These included a No-Tone condition administered without the presentation of an auditory tone; an Ignore-Tone condition that presented a neutral (i.e., not associated with stopping) auditory tone; and a second Ignore-Tone condition that presented a neutral auditory tone after the tone had been previously paired with stopping. Children with ADHD exhibited significantly slower and more variable reaction times to go-stimuli, and slower stop-signal reaction times (SSRT) relative to TD controls. Stop-signal delay (SSD) was not significantly different between groups, and both groups' go-trial reaction times slowed following meaningful tones. Collectively, these findings corroborate recent meta-analyses and indicate that previous findings of stop-signal performance deficits in ADHD reflect slower and more variable responding to visually presented stimuli and concurrent processing of a second stimulus, rather than deficits of motor behavioral inhibition.
Show less
Date Issued
2008
Identifier
CFE0002218, ucf:47881
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0002218
Do programs designed to train working memory, other executive functions, and attention benefit children with ADHD? A meta-analytic review of cognitive, academic, and behavioral outcomes
Title
Do programs designed to train working memory, other executive functions, and attention benefit children with ADHD? A meta-analytic review of cognitive, academic, and behavioral outcomes.
Creator
Orban, Sarah, Rapport, Mark, Beidel, Deborah, Cassisi, Jeffrey, University of Central Florida
Abstract / Description
Children with ADHD are characterized frequently as possessing underdeveloped executive functions and sustained attentional abilities, and recent commercial claims suggest that computer-based cognitive training can remediate these impairments and provide significant and lasting improvement in their attention, impulse control, social functioning, academic performance, and complex reasoning skills. The present review critically evaluates these claims through meta-analysis of 25 studies of...
Show moreChildren with ADHD are characterized frequently as possessing underdeveloped executive functions and sustained attentional abilities, and recent commercial claims suggest that computer-based cognitive training can remediate these impairments and provide significant and lasting improvement in their attention, impulse control, social functioning, academic performance, and complex reasoning skills. The present review critically evaluates these claims through meta-analysis of 25 studies of facilitative intervention training (i.e., cognitive training) for children with ADHD. Random effects models corrected for publication bias and sampling error revealed that studies training short-term memory alone resulted in moderate magnitude improvements in short-term memory (d= 0.63), whereas training attention did not significantly improve attention and training mixed executive functions did not significantly improve the targeted executive functions (both nonsignificant: 95% confidence intervals include 0.0). Far transfer effects of cognitive training on academic functioning, blinded ratings of behavior (both nonsignificant), and cognitive tests (d= 0.14) were nonsignificant or negligible. Unblinded raters (d= 0.48) reported significantly larger benefits relative to blinded raters and objective tests (both p (<) .05), indicating the likelihood of Hawthorne effects. Critical examination of training targets revealed incongruence with empirical evidence regarding the specific executive functions that are (a) most impaired in ADHD, and (b) functionally related to the behavioral and academic outcomes these training programs are intended to ameliorate. Collectively, meta-analytic results indicate that claims regarding the academic, behavioral, and cognitive benefits associated with extant cognitive training programs are unsupported in ADHD. The methodological limitations of the current evidence base, however, leaves open the possibility that cognitive training techniques designed to improve empirically documented executive function deficits may benefit children with ADHD.
Show less
Date Issued
2013
Identifier
CFE0005040, ucf:49962
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0005040