Novel Tests of Complex Recognition Memory in Animals and Humans

This thesis sought to address specific methodological issues relating to tasks of recognition memory in animals and humans. Such tasks are very widely used, so the need to reduce variability and improve the translation of animal work to humans is apparent. Study 1 sought to develop a reliable testing method based on the spontaneous recognition paradigm that would reduce the animal numbers required for such tasks. Rats displayed significant performance in multiple recognition tasks carried out in the continual trials apparatus, which allows for multiple trials within a session. Approximately 50% fewer animals were required for statistically meaningful results, compared to studies using the standard one trial a day paradigm. Study 2 sought to further develop the continual trials apparatus for an episodic-like memory task for rodents. This study focussed on the development of an object preference task to investigate the behavioural parameters that would affect recognition in the test phase of the E-maze task. Study 3 aimed to investigate whether the continual trials apparatus could be effectively applied with immediate-early gene imaging during a recognition memory task. Animals tested with novel stimuli showed greater fos expression than animals tested with familiar objects, though not significantly. Finally, Study 4 focussed on the translation of animal models of memory to humans. The analysis of receiver-operating characteristics was used to derive a quantifiable distinction between recollection- and familiarity-based processes of recognition, in a task based on paradigms typically used with rodents. The key findings of the work in this thesis include evidence of substantial animal reduction using a new behavioural apparatus for assessing recognition memory in rodents, and the successful development of an analogous human task of memory in which processes of recognition can be dissociated and quantified. These two key findings make a significant contribution to the field of recognition memory research as the new rodent behavioural tasks are a clear improvement on standard tasks with the potential to reduce variance and animal numbers, and reducing the reliance on human subjects’ introspective accounts of memory in Study 4 provides a shift away towards better controlled behavioural studies in humans, which more closely reflects the studies carried out with animals, and provides strong validation for particular animal models. Through further validation, the simplicity of the human memory task could make it a useful candidate for assessing different forms of recognition memory with neuropsychological subjects

STREAM WATER QUALITY MANAGEMENT: A STOCHASTIC MIXED-INTEGER PROGRAMMING MODEL

Water quality management under the watershed approach of Total Maximum Daily Load (TMDL) programs requires that water quality standards be maintained throughout the year. The main purpose of this research was to develop a methodology that incorporates inter-temporal variations in stream conditions through statistical distributions of pollution loading variables. This was demonstrated through a cost minimization mixed-integer linear programming (MIP) model that maintains the spatial integrity of the watershed problem. Traditional approaches for addressing variability in stream conditions are unlikely to satisfy the assumptions on which these methodologies are founded or are inadequate in addressing the problem correctly when distributions are not normal. The MIP model solves for the location and the maximum capacity of treatment plants to be built throughout the watershed which will provide the optimal level of treatment throughout the year. The proposed methodology involves estimation of parameters of the distribution of pollution loading variables from simulated data and use of those parameters to re-generate a suitable number of random observations in the optimization process such that the new data preserve the same distribution parameters. The objective of the empirical model was to minimize costs for implementing pH TMDLs for a watershed by determining the level of treatment required to attain water quality standards under stochastic stream conditions. The output of the model was total minimum costs for treatment and selection of the spatial pattern of the least-cost technologies for treatment. To minimize costs, the model utilized a spatial network of streams in the watershed, which provides opportunities for cost-reduction through trading of pollution among sources and/or least-cost treatment. The results were used to estimate the costs attributable to inter-temporal variations and the costs of different settings for the margin of safety. The methodology was tested with water quality data for the Paint Creek watershed in West Virginia. The stochastic model included nine streams in the optimal solution. An estimate of inter-temporal variations in stream conditions was calculated by comparing total costs under the stochastic model and a deterministic version of the stochastic model estimated with mean values of the loading variables. It was observed that the deterministic model underestimates total treatment cost by about 45 percent relative to the 97th percentile stochastic model. Estimates of different margin of safety were calculated by comparing total costs for the 99.9th percentile treatment (instead of an idealistic absolute treatment) with that of the 95th to 99th percentile treatment. The differential costs represent the savings due to the knowledge of the statistical distribution of pollution and an explicit margin of safety. Results indicate that treatment costs are about 7 percent lower when the level of assurance is reduced from 99.9 to 99 percent and 21 percent lower when 95 percent assurance is selected. The application of the methodology, however, is not limited to the estimation of TMDL implementation costs. For example, it could be utilized to estimate costs of anti-degradation policies for water quality management and other watershed management issues.Resource /Energy Economics and Policy,

International immigration and domestic out-migrants: Are domestic migrants moving to new jobs or away from immigrants?

Immigration is one of the most emotional topics in the political arena, which is an issue that has not gone unnoticed by economists. Recent studies usually examine sub-national areas to take advantage of the widely varying local concentrations of immigrants. Yet, there is no consensus on the overall local effects of immigration on migration behavior of domestic residents, although there is consensus that immigration has little influence on local area wages (but there is debate about immigration's influence on national wages). One reason why the regional influence of immigrants is so hard to pin down is the many offsetting economic responses. For example, in response to an influx of recent immigrants, natives and previous immigrants may out-migrate to produce no net effect on total labor supply and, hence, no net effect on local employment or wages. In addition, very little is known about the destinations of native out-migrants. Do they avoid states with greater shares of immigrants, or do they respond to more standard economic measures such as relative growth rates. Using U.S. state-level data, this study examines the effects of recent and past immigration on state-to-state net-migration patterns and on the behavior of domestic state-to-state out-migrants. A key advantage of our migration measures is that we measures of state-to-state migration flows. Thus, we can examine differences across all 1,128 state-to-state migration flows for the lower 48 states. This sample provides considerably more information than the standard approach, which would be analogous to only estimating the 48 state net-migration rates on immigration rates and other control variables. Moreover, state-to-state data allows us to consider whether the domestic out-migrants are moving to states with relatively greater shares of immigrant levels than the origin state, which is an issue that has not been considered in past research. For example, we can answer whether domestic out-migrants are primarily driven by labor market effects or by possible aversion to states with greater shares of immigrants (not just new immigrants)

Analysis of the fatty acid composition of Caulerpa lentillifera using Gas Chromatography Mass Spectrometry

Caulerpa lentillifera, also known as Sea Grape or Green Caviar is a type of green seaweed from the class of Caurlepacea and species of Lentillifera. They are common seaweed communities in tropical and subtropical waters. They have different biochemical compounds from various seaweedspecies. However, the study onphytochemical components andthe biological activity of C. lentillifera are not fully understood yet. This study was carried out to determine the best extraction solvents and to evaluate the phytocomponent in the n- hexane, Dichloromethane (DCM) and methanol extract of C. lentillifera using Gas Chromatography-Mass Spectrometry (GC-MS) analysis. C. lentillifera was collected from the coastal area of Sabah, Malaysia. Then, it was subjected for purification, drying and soxhlet extraction process using n- hexane, DCM and methanol. Only fatty acid compound was analysed using a Perkin Elmer Turbo Mass Spectrophotometer. It showed that, methanol is the most efficient solvent as it recorded the highest extraction yield in C. lentillifera. Twenty phytocomponents have been identified from all extracts of C. lentillifera by GC-MS analysis. This analysis discovered the presence of major constituents like palmitic acid, oleic acid, pentadecanoic acid, behenic acid, myristic acid, etc. Many studies have shown that, most of the identified major compounds were proven to exhibit antibacterial, antifungal, anti- inflammatory, antiviral, etc. Thus, it is apparent that C. lentillifera has the potential to be used as seaweed of phytopharmaceutical importance as it contains numerous bioactive compounds

The impacts of the COVID-19 pandemic crisis on rural entrepreneurs

Rural entrepreneurs are significant business groups, being the contributors to the nation’s economy. They are the creators of job opportunities, but they are facing great challenges during the COVID-19 pandemic crisis. The objective of this research is to explore the impact of the pandemic on rural entrepreneurs. The current research was carried out at the Rural Community Centre (RCC) of Kg. Jelintoh, Gopeng, Perak, Malaysia. Being the most active RCC in conducting entrepreneurship programmes in 2019, that centre was chosen for this study. This exploration research utilised qualitative approach which involved an in-depth interview by using a semi-structured interview format with seven rural entrepreneurs. They were selected through a purposive sampling from the list of rural entrepreneurs. The data were analysed using a thematic analysis method. The results revealed two main themes of the impacts. The first theme was business operation which includes operation disruption, decrease in demand, shortage of logistic supply, and operation closure. The second theme involves business finance that consists of cash flow problems, unexpected increase in production cost, and access to economic stimulus package. The findings from this research provide good inputs to relevant agencies in assisting the rural entrepreneurs to resume their businesses. It is recommended that all types of rural businesses to be allowed to run their normal operations, ensure the smoothness of logistics supply, being offered with financial aids, reduce the production cost, and create an easy-access entry to economic stimulus package

Strength of Binary and Ternary Blended Cement Pastes Containing Palm Oil Fuel Ash and Metakaolin Exposed To Sodium Sulphate

The compressive strength of binary (BBCP) and ternary blended cement pastes (TBCP) containing Palm Oil Fuel Ash (POFA) and Metakaolin (MK) exposed to 3 % sodium sulphate solution has been studied. The ordinary Portland cement (OPC) was partially replaced with POFA and MK on mass-for-mass basis. All specimens were first cured for 28 days in normal water and subsequently subjected to full immersion in sodium sulphate solution for 150 days for the compressive strength evaluation. The results show that partial replacement of cement with POFA and MK improved the durability of the cement pastes by reducing the damage caused by sulphate attack

Perirhinal cortex and the recognition of relative familiarity

Spontaneous object recognition (SOR) is a widely used task of recognition memory in rodents which relies on their propensity to explore novel (or relatively novel) objects. Network models typically define perirhinal cortex as a region required for recognition of previously seen objects largely based on findings that lesions or inactivations of this area produce SOR deficits. However, relatively little is understood about the relationship between the activity of cells in the perirhinal cortex that signal novelty and familiarity and the behavioural responses of animals in the SOR task. Previous studies have used objects that are either highly familiar or absolutely novel, but everyday memory is for objects that sit on a spectrum of familiarity which includes objects that have been seen only a few times, or objects that are similar to objects which have been previously experienced. We present two studies that explore cellular activity (through c-fos imaging) within perirhinal cortex of rats performing SOR where the familiarity of objects has been manipulated. Despite robust recognition memory performance, we show no significant changes in perirhinal activity related to the level of familiarity of the objects. Reasons for this lack of familiarity-related modulation in perirhinal cortex activity are discussed. The current findings support emerging evidence that perirhinal responses to novelty are complex and that task demands are critical to the involvement of perirhinal cortex in the control of object recognition memory

Biocontrol of Bacillus cereus by Lactobacillus plantarum in Kareish cheese and yogurt

This study aims to biocontrol of Bacillus cereus by Lactobacillus plantarum in Kareish cheese and yogurts. The minimum inhibitory concentrations (MICs), antioxidant potentials, total flavonoids content (TFC) and total phenolic content (TPC) of L. plantarum were also estimated. Results showed that incidence of B. cereus in Kareish cheese and yogurt was 16 and 4%, respectively. Four virulence genes were investigated by PCR in B. cereus isolates (n = 10). Two toxin producing genes, cytotoxin K (cytK), and phosphatidylcholine-hydrolyzing phospholipase C (Pc-plc), were detected in all B. cereus, whereas enterotoxigenic (nhe) and hemolysin BL (hbl) genes were detected in 90 and 50%, respectively. All isolates were vulnerable to erythromycin and gentamicin (100%) with intermediate sensitivity to ciprofloxacin and complete resistance to tetracycline (100%). L. plantarum showed antibacterial power against B. cereus EMCC1006 reference strain with MIC at 3.1 mg/mL. From the different concentrations (1.5, 3.1, 6.25, 12.5, 25.0, 50.0, 100.0 mg/mL) of L. plantarum which mixed with Kareish cheese and yogurt samples, the minimum concentrations displayed the excellent sensory parameters. TPC and TFC of L. plantarum CFS were 18.5 (μg GAE/g) and 2.67 (μg QE/g), respectively. Regarding antioxidant activity, IC50 of L. plantarum was 53.84 μg/mL, while IC50 of ascorbic acid was 26.36 μg/mL. In sum, L. plantarum could be used as a promising antibacterial and antioxidant agent for biocontrol of B. cereus to ensure dairy safe without negative impact on sensorial attributes.Universidade de Vigo/CISU

Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes

Background: In pre-clinical research, systematic reviews have the potential to mitigate translational challenges by facilitating understanding of how pre-clinical studies can inform future clinical research. Yet their conduct is encumbered by heterogeneity in the outcomes measured and reported, and those outcomes may not always relate to the most clinically important outcomes. We aimed to systematically review outcomes measured and reported in pre-clinical in vivo studies of pharmacological interventions to treat high blood glucose in mouse models of type 2 diabetes. Methods: A systematic review of pre-clinical in vivo studies of pharmacological interventions aimed at addressing elevated blood glucose in mouse models of type 2 diabetes was completed. Studies were screened for eligibility and outcomes extracted from the included studies. The outcomes were recorded verbatim and classified into outcome domains using an existing outcome taxonomy. Outcomes were also compared to those identified in a systematic review of registered phase 3/4 clinical trials for glucose lowering interventions in people with type 2 diabetes. Results: Review of 280 included studies identified 532 unique outcomes across 19 domains. No single outcome, or domain, was measured in all studies and only 132 (21%) had also been measured in registered phase 3/4 clinical trials. A core outcome set, representing the minimum that should be measured and reported, developed for type 2 diabetes effectiveness clinical trials includes 18 core outcomes, of these 12 (71%) outcomes were measured and reported in one or more of the included pre-clinical studies. Conclusions: There is heterogeneity of outcomes reported in pre-clinical research. Harmonisation of outcomes across the research pathway using a core outcome set may facilitate interpretation, evidence synthesis and translational success, and may contribute to the refinement of the use of animals in research. Systematic review registration: The study was prospectively registered on the PROSPERO Database, registration number CRD4201810683