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Influenza infection remains constant threat to human health and results in huge financial loss every year. Rapid and accurate detection of influenza can help governments and health organizations monitor influenza activity and take measurements when necessary. In addition, influenza detection in a timingly manner can help doctors make diagnosis and provide effective treatment. On the other hand, novel inhibitors of influenza virus are in high demand because circulating strains have started to develop resistance to currently available anti-viral drugs. Influenza virus has two surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA), which play important roles in the influenza infection. The binding of HA to sialic acid-containing carbohydrates on cell surface initiates virus internalization, while cleavage of terminal sialic acid by NA facilitates viral particle release. In this dissertation, we focus on the development of glycan microarray that is comprised of a panel of NA resistant sialosides, and demonstrate the application of microarray to capture influenza virus at ambient temperature without the addition of NA inhibitors. We also describe a novel electrochemical biosensor for the detection of influenza virus. In addition, we have developed a new class of bivalent NA inhibitors that show promising inhibitory activities against influenza viruses.

No description available.

<p>The growth and proliferation of invasive bacteria in engineered systems is an ongoing problem. While there are a variety of physical and chemical processes to remove and inactivate bacterial pathogens, there are many situations in which these tools are no longer effective or appropriate for the treatment of a microbial target. For example, certain strains of bacteria are becoming resistant to commonly used disinfectants, such as chlorine and UV. Additionally, the overuse of antibiotics has contributed to the spread of antibiotic resistance, and there is concern that wastewater treatment processes are contributing to the spread of antibiotic resistant bacteria.</p><p>Due to the continually evolving nature of bacteria, it is difficult to develop methods for universal bacterial control in a wide range of engineered systems, as many of our treatment processes are static in nature. Still, invasive bacteria are present in many natural and engineered systems, where the application of broad acting disinfectants is impractical, because their use may inhibit the original desired bioprocesses. Therefore, to better control the growth of treatment resistant bacteria and to address limitations with the current disinfection processes, novel tools that are both specific and adaptable need to be developed and characterized.</p><p>In this dissertation, two possible biological disinfection processes were investigated for use in controlling invasive bacteria in engineered systems. First, antisense gene silencing, which is the specific use of oligonucleotides to silence gene expression, was investigated. This work was followed by the investigation of bacteriophages (phages), which are viruses that are specific to bacteria, in engineered systems.</p><p>&#8232;For the antisense gene silencing work, a computational approach was used to quantify the number of off-targets and to determine the effects of off-targets in prokaryotic organisms. For the organisms of <italic>Escherichia coli</italic> K-12 MG1655 and Mycobacterium tuberculosis H37Rv the mean number of off-targets was found to be 15.0 <underline>+</underline> 13.2 and 38.2 <underline>+</underline> 61.4, respectively, which results in a reduction of greater than 90% of the effective oligonucleotide concentration. It was also demonstrated that there was a high variability in the number of off-targets over the length of a gene, but that on average, there was no general gene location that could be targeted to reduce off-targets. Therefore, this analysis needs to be performed for each gene in question. It was also demonstrated that the thermodynamic binding energy between the oligonucleotide and the mRNA accounted for 83% of the variation in the silencing efficiency, compared to the number of off-targets, which explained 43% of the variance of the silencing efficiency. This suggests that optimizing thermodynamic parameters must be prioritized over minimizing the number of off-targets. In conclusion for the antisense work, these results suggest that off-target hybrids can account for a greater than 90% reduction in the concentration of the silencing oligonucleotides, and that the effective concentration can be increased through the rational design of silencing targets by minimizing off-target hybrids.</p><p>Regarding the work with phages, the disinfection rates of bacteria in the presence of phages was determined. The disinfection rates of <italic>E. coli</italic> K12 MG1655 in the presence of coliphage Ec2 ranged up to 2 h<super>-1</super>, and were dependent on both the initial phage and bacterial concentrations. Increasing initial phage concentrations resulted in increasing disinfection rates, and generally, increasing initial bacterial concentrations resulted in increasing disinfection rates. However, disinfection rates were found to plateau at higher bacterial and phage concentrations. A multiple linear regression model was used to predict the disinfection rates as a function of the initial phage and bacterial concentrations, and this model was able to explain 93% of the variance in the disinfection rates. The disinfection rates were also modeled with a particle aggregation model. The results from these model simulations suggested that at lower phage and bacterial concentrations there are not enough collisions to support active disinfection rates, which therefore, limits the conditions and systems where phage based bacterial disinfection is possible. Additionally, the particle aggregation model over predicted the disinfection rates at higher phage and bacterial concentrations of 10<super>8</super> PFU/mL and 10<super>8</super> CFU/mL, suggesting other interactions were occurring at these higher concentrations. Overall, this work highlights the need for the development of alternative models to more accurately describe the dynamics of this system at a variety of phage and bacterial concentrations. Finally, the minimum required hydraulic residence time was calculated for a continuous stirred-tank reactor and a plug flow reactor (PFR) as a function of both the initial phage and bacterial concentrations, which suggested that phage treatment in a PFR is theoretically possible.</p><p>In addition to determining disinfection rates, the long-term bacterial growth inhibition potential was determined for a variety of phages with both Gram-negative and Gram-positive bacteria. It was determined, that on average, phages can be used to inhibit bacterial growth for up to 24 h, and that this effect was concentration dependent for various phages at specific time points. Additionally, it was found that a phage cocktail was no more effective at inhibiting bacterial growth over the long-term than the best performing phage in isolation.</p><p>Finally, for an industrial application, the use of phages to inhibit invasive <italic>Lactobacilli</italic> in ethanol fermentations was investigated. It was demonstrated that phage 8014-B2 can achieve a greater than 3-log inactivation of <italic>Lactobacillus plantarum</italic> during a 48 h fermentation. Additionally, it was shown that phages can be used to protect final product yields and maintain yeast viability. Through modeling the fermentation system with differential equations it was determined that there was a 10 h window in the beginning of the fermentation run, where the addition of phages can be used to protect final product yields, and after 20 h no additional benefit of the phage addition was observed.</p><p>In conclusion, this dissertation improved the current methods for designing antisense gene silencing targets for prokaryotic organisms, and characterized phages from an engineering perspective. First, the current design strategy for antisense targets in prokaryotic organisms was improved through the development of an algorithm that minimized the number of off-targets. For the phage work, a framework was developed to predict the disinfection rates in terms of the initial phage and bacterial concentrations. In addition, the long-term bacterial growth inhibition potential of multiple phages was determined for several bacteria. In regard to the phage application, phages were shown to protect both final product yields and yeast concentrations during fermentation. Taken together, this work suggests that the rational design of phage treatment is possible and further work is needed to expand on this foundation.</p> / Dissertation

The present work investigated the neural mechanisms underlying cognitive inhibition/thought suppression in Anderson’s and Green’s Think/No-Think paradigm (TNT), as well as different variables influencing these mechanisms at the cognitive, the neurophysiological, the electrophysiological and the molecular level. Neurophysiological data collected with fNIRS and fMRI have added up to the existing evidence of a fronto-hippocampal network interacting during the inhibition of unwanted thoughts. Some evidence has been presented suggesting that by means of external stimulation of the right dlPFC through iTBS thought suppression might be improved, providing further evidence for an implication of this region in the TNT. A combination of fNIRS with ERP has delivered evidence of a dissociation of early condition-independent attentional and later suppression-specific processes within the dlPFC, both contributing to suppression performance. Due to inconsistencies in the previous literature it was considered how stimulus valence would influence thought suppression by manipulating the emotional content of the to-be-suppressed stimuli. Findings of the current work regarding the ability to suppress negative word or picture stimuli have, however, been inconclusive as well. It has been hypothesized that performance in the TNT might depend on the combination of valence conditions included in the paradigm. Alternatively, it has been suggested that inconsistent findings regarding the suppression of negative stimuli or suppression at all might be due to certain personality traits and/or genetic variables, found in the present work to contribute to thought inhibition in the TNT. Rumination has been shown to be a valid predictor of thought suppression performance. Increased ruminative tendencies led to worse suppression performance which, in the present work, has been linked to less effective recruitment of the dlPFC and in turn less effective down-regulation of hippocampal activity during suppression trials. Trait anxiety has also been shown to interrupt thought suppression despite higher, however, inefficient recruitment of the dlPFC. Complementing the findings regarding ruminative tendencies and decreased thought inhibition a functional polymorphism in the KCNJ6 gene, encompassing a G-to-A transition, has been shown to disrupt thought suppression despite increased activation of the dlPFC. Through the investigation of thought suppression at different levels, the current work adds further evidence to the idea that the TNT reflects an executive control mechanism, which is sensitive to alterations in stimulus valence to some extent, neurophysiological functioning as indicated by its sensitivity to iTBS, functional modulations at the molecular level and personality traits, such as rumination and trait anxiety. / Diese Arbeit befasste sich mit der Untersuchung der neuronalen Grundlagen kognitiver Inhibition /Gedankenunterdrückung in Anderson’s und Green’s ‘Think/No-Think‘ Paradigma (TNT), sowie der Erfassung verschiedener Einflussgrößen auf der kognitiven, der neurophysiologischen, der elektrophysiologischen und der molekularen Ebene. Mit fNIRS und fMRT durchgeführte neurophysiologische Studien haben die Annahme der Beteiligung eines Fronto-Hippocampalen Netzwerkes an der Unterdrückung unerwünschter Gedanken bekräftigt. Hinweise auf eine Verbesserung der Unterdrückungsleistung mittels externer Manipulation der neuronalen Aktivität durch iTBS unterstützen die Annahme einer Beteiligung des dlPFC an den Mechanismen innerhalb des TNT weiter. Durch die Kombination von fNIRS und ERP wurde eine Dissoziation zwischen frühen bedingungsunabhängigen Aufmerksamkeits- und späteren unterdrückungsspezifischen Prozessen innerhalb des dlPFC aufgezeigt. Vor dem Hintergrund widersprüchlicher Resultate bezüglich des Einflusses der Stimulus-Valenz auf die kognitive Inhibition in der vorhandenen Literatur wurde dieser Aspekt auch in der vorliegenden Arbeit berücksichtigt. Auch in dieser Arbeit aufgetretene widersprüchliche Ergebnisse bezüglich der Unterdrückung negativer Stimuli führten zu der Hypothese, dass die Unterdrückungsleistung in dem TNT in Abhängigkeit der Valenz der weiteren eingeschlossenen Stimuli erfolgt. Alternativ wurde eine Abhängigkeit von Persönlichkeitsmerkmalen und/oder genetischen Variablen vorgeschlagen, welche in der vorliegenden Arbeit als Einflussgrößen nachgewiesen wurden. So konnte gezeigt werden, dass die Erhebung ruminativer Tendenzen eine zuverlässige Vorhersage der Unterdrückungsleistung zulässt. Höhere ruminative Tendenzen führten zu signifikant verschlechterter Unterdrückungsleistung. Dies konnte auf eine ineffektive Rekrutierung des dlPFC gefolgt von ungenügender Aktivierungsabnahme im Hippocampus während der Gedankeninhibition zurückgeführt werden. Darüber hinaus konnte gezeigt werden, dass mit der Zunahme ängstlicher Persönlichkeitsmerkmale die Unterdrückungsleistung trotz erhöhter Aktivität im dlPFC abnimmt. In Ergänzung zu den Ergebnissen bezüglich ruminativer Tendenzen und gestörter kognitiver Inhibition konnte ein störender Einfluss eines funktionellen genetischen Polymorphismus im KCNJ6 Gen unter Einbeziehung einer Punktmutation (G-A Transition) nachgewiesen werden. Durch die Untersuchung der Gedankenunterdrückung auf unterschiedlichen Ebenen, konnte die vorliegende Arbeit weitere Hinweise dafür liefern, dass mit dem TNT exekutive Kontrollfunktionen abgegriffen werden, welche durch Stimulusvalenz, neurophysiologische Prozesse (durch eine die iTBS betreffende Sensitivität angezeigt), funktionelle Modulationen auf der molekularen Ebene, sowie Persönlichkeitsmerkmale wie ruminative Tendenzen und Ängstlichkeit beeinflussbar sind.

Deciding what information we attend to has implications on our ability to remain valuable and productive in our respective academic and economic domains. This study investigated if attentional switching due to information technology interruptions would deplete resources in a unique way and impair performance on a response inhibition task. Three groups were compared on the Simon task after participants either did or did not receive interruptions during a self-regulation task. Unexpectedly, a larger Simon effect was found for participants who did not receive interruptions. These results conform to previous evidence showing sustained directed attention may result in depletion and effect subsequent inhibitory control. Although not supporting predictions, these results may provide a basis for further research, particularly because younger generations are developing in a more connected world than preceding generations. By understanding these differences, younger generations may better adapt to technological advances and leverage them to their advantage. / Includes bibliography. / Thesis (M.A.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

Neurons are constantly integrating information from external and internal sources, causing them to spike at particular times. The exact timing of spikes is determined by a neuron's intrinsic properties, as well as the interplay between local excitatory and inhibitory inputs. Although inhibitory interneurons have been extensively studied, their contribution to neuronal integration and spike timing remains poorly understood. To elucidate the functional role of GABAergic interneurons during cortical activity, we combined molecular identification of interneurons, two photon imaging and electrophysiological recordings in mouse thalamocortical slices. In this preparation, cortical UP states, a network state characterized by prolonged periods of depolarization and synchronized spiking, can be evoked by thalamic stimulation and can also occur spontaneously. To assay the role of inhibition, we first characterized the firing properties of Parvalbumin (PV) and Somatostatin (SOM) interneurons during UP states activity, and found a higher probability and rate of spiking in these two subtypes compared to excitatory cells. These subtypes did not display differential timing of activation during the evoked response. Furthermore, calcium imaging showed low correlations among PV and SOM interneurons, indicating that neurons sharing these neurochemical markers do not coordinate their firing. Intracellular recordings confirmed that nearby interneurons, known to be electrically coupled, do not display more synchronous spiking than excitatory cells, suggesting that this coupling may not function to synchronize the activity of interneurons on fast time scales¬¬¬. After characterizing inhibitory interneuron outputs, we next studied the timing and correlation of inhibitory inputs, which we isolated from excitatory inputs by voltage clamping at the reversal for excitation (0mV) or inhibition (-70mV). In both thalamically triggered and spontaneous activations, IPSCs between cell pairs were remarkably well correlated, with correlation coefficients reaching over .9 in some cases. This high degree of correlation has previously been assumed to be due to interneuron synchrony, but our population imaging and paired recordings did not support this view. In addition, we found that the connection rate between interneurons is very high (~80%), and quantal analysis revealed that each IPSC recorded in neighboring cells during an UP state could be due to a single presynaptic interneuron. Therefore, we explain the high IPSCs correlations in nearby pyramidal cells are emerging from the common input from individual interneurons, rather than from synchronization of interneuron activity across the population. In a final set of experiments, we found that a partial pharmacological block of inhibitory signaling increased EPSC correlations. Our data support a model in which inhibitory neurons do not fire in a correlated fashion but have strong, dense connections to pyramidal neurons that serve to prevent local excitatory synchrony during UP states. This would mean that inhibition may not, as previously thought, serve to synchronize the firing of excitatory cells, but have precisely the opposite effect, decorrelating their activity by breaking down their coordinated firing. This is consistent with the hypothesis that pyramidal cells are carrying out an essentially integrative function in the circuit and that interneurons expand the temporal dynamic range of this integration.

The purpose of this study was to examine the contribution of temperament to childrenâ??s behaviors in the classroom and their school readiness. Data was collected on 60 preschool children enrolled in Head Start. Teachers rated temperament using the Preschool Temperament Classification System. Trained coders observed childrenâ??s engagement and play during circle time and free play, respectively. School readiness was directly assessed using the Learning Express. Three main findings emerged: (1) Temperamentally-extreme children performed lower than resilient children on the school readiness assessment, suggesting that temperamentally-extreme children begin to lag behind their resilient peers as early as the preschool years. (2) Off-task behavior in the classroom affects undercontrolled childrenâ??s school readiness; however, the degree of influence appears to depend on the complexity of learning specific domains. That is, off-task behavior in the classroom may have a larger influence on more complex subject matter than simpler ones. Classroom behaviors were not related to overcontrolled childrenâ??s school readiness scores. (3) Behavioral differences were found between temperament groups during circle time, however no differences were found during free play. This suggests that classroom context may play a role in temperamentally-extreme childrenâ??s classroom behaviors.

Although the integrated relationship that exists between the lumbar spine and hip joints is frequently acknowledged in scientific journals and by medical professionals, specific functional and injury relationships, are speculative and have not been substantiated. Lumbar spine and hip dysfunctions are suspected to be associated with inhibition of the surrounding extensor musculature, particularly the gluteal muscles, and facilitation of the flexor musculature. This phenomenon has been observed in other joints following effusion and is often termed ‘arthrogenic inhibition’. Its apparent occurrence about the hip has never been validated. The primary objective of this thesis was to investigate whether arthrogenic inhibition occurred about the hip. If inhibition was found to exist, its relationship with volume vs pressure was investigated to determine if either of these factors were a more appropriate predictor of inhibition. Finally, compensatory motor patterns in response to apparent inhibition were of interest. Participants were allocated to the following groups: 1) Control 2) Intervention I (magnetic resonance arthrogram) or 3) Intervention II (therapeutic arthrogram). Electromyography was collected on the rectus abdominis, erector spinae, gluteus maximus and semimenbranosis bilaterally during hip rehabilitation exercises prior to and following the intervention. Intra-capsular pressure was measured during the intervention. The findings provided support for the presence of extensor-inhibition in the hip following infusion of intra-articular fluid with intra-capsular pressure being the most appropriate predictor of the magnitude of inhibition. Hip extensor inhibition appeared to be compensated for by lumbar spine extensors during the selected tasks. Arthrogenic inhibition should be considered in the clinical evaluation and management of patients with hip joint effusions and/or elevated intra-capsular pressure.

Diss.--Universität Regensburg, 2004. / Bibliogr. p. 149-166.