54 research outputs found
Structural Determinants for Substrate and Inhibitor Recognition by the Dopamine Transporter
A long-standing postulate holds that cocaine inhibits DAT-mediated dopamine transport via competition with dopamine for formation of an ionic bond with the DAT transmembrane 1 aspartic acid residue 79. A recent study from our laboratory indicated that mutation of this aspartate to glutamate (D79E) had little or no effect on dopamine affinity or dopamine uptake inhibition potencies for WIN35,428 and cocaine, and decreased WIN35,428 affinity by only 3 fold (Wang et al., 2003). The study cast doubt on the requirement of a dopamine-D79 ion pair, but did not address whether the residue plays a role in recognizing the cocaine pharmacophore. In the present study, DAT inhibitors containing variations of three primary components of this pharmacophore- the positively charged tropane nitrogen atom, the seven-carbon tropane ring itself, and the aromatic substituent at the tropane C-3 position- were assessed for binding affinity and dopamine uptake inhibition at the same D79 DAT mutants. Only inhibitors with modifications of the phenyl ring substituent of cocaine, i.e. benztropine and its analogs, displayed considerably altered dopamine uptake inhibition potency as a function of the D79E mutation. These observations may suggest that the side chain of the D79 residue is important for the recognition of the aromatic components of DAT ligands.
Furthermore, we investigated the influence of cell passage number, the density of the cell monolayer and the effect of varying DAT expression levels by manipulation of transfection conditions on DAT function. It was observed that the DUIPs of cocaine, mazindol, methylphenidate, and benztropine fluctuated as a function of DAT-CHO cell passage number. The binding affinities of these DAT inhibitors, however, remained static. Also, the DUIP of cocaine fluctuated as a result of variations in DAT cell surface expression. It is therefore conceivable that an unidentified cellular mediator modulates DAT inhibitor DUIP but not binding affinity at the DAT protein
EFFECT OF COGNITIVE CRAFTING ON GRADUATION RATE OF STUDENTS IN FEDERAL UNIVERSITIES, SOUTH EAST, NIGERIA
The study investigated the effect of cognitive crafting on the graduation rate of students in Federal Universities, South East, Nigeria. The study is anchored on Elgar’s Performance Theory of organizations. The survey research method was adopted for the study, making use of structured questionnaire as instruments for data collection. Data were collected from both primary and secondary sources. Hypotheses were tested using the simple linear regression. The study found that cognitive crafting had significant positive effect on the graduation rate of students in Federal Universities, South East, Nigeria (r 0.803; P < 0.05). It was therefore, concluded that cognitive capabilities which promote students’ graduation rate enhances the overall performance of Universities in South East, Nigeria. The study recommended that Universities should be properly funded to encourage the employment and retention of professionals with cognitive capabilities that would enhance students’ graduation rate and overall performance of the Universities.
JEL: B10; A02; C06
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EFFECT OF SUCCESSION MANAGEMENT ON SUSTAINABILITY OF SMALL AND MEDIUM SCALE ENTERPRISES (SMEs) IN SOUTH EAST NIGERIA
Many prominent and even internationally acclaimed business organizations have gone into extinction due to succession management challenges, notwithstanding their richly endowed financial and material resources. Succession management ensures seamless transition of managerial decision making of a firm to the next generation when the owner is no longer part of the business. The study investigated the effect of succession management on sustainability of Small and Medium Scale Enterprises (SMEs) in South East, Nigeria. However, the specific objectives were to ascertain the effect of competitive intelligence on the growth of SMEs; and to determine the effect of technological advancements on competitive advantage of SMEs in South East Nigeria. The study is anchored on Elgar’s Performance Theory of organization and the Resource Based Firm theory which emphasizes that the physical, organizational strategies, financial and human resources have the potential to provide firms with sustainable competitive advantage. The study adopted the survey research method, making use of structured questionnaire as instruments for data collection. Data were collected from primary and secondary sources. Hypotheses were tested using Pearson Product Moment Correlation Coefficient and the simple linear regression. It was found that succession management through well-conceived competitive intelligence positively affected the growth of SMEs; technological advancements positively affected competitive advantage of SMEs. It was, therefore, concluded that succession management through competitive intelligence and technological advancement positively affected the sustainability of SMEs through firm growth and competitive advantage. The study recommended that for SMEs to be sustained and enhance its operational life span, effective succession management should be adopted growth and competitive advantage. The study recommended that for SMEs to be sustained and enhance its operational life span, effective succession management should be adopted.
JEL: B10; A02; C06
Article visualizations
Functional assessments and histopathology of hepatorenal tissues of rats treated with raw and processed herbs
The present study ascertained the functional integrity of hepatic and renal tissues, concurrently with blood lipid patterns, of Wistar rats infused with CCl4 and treated with raw and hydrothermal processed herbs, namely, Monodora myristica, Chromolaena odorata, Buccholzia coriacea and Sphenostylis stenocarpa. Measurement of phytochemical contents of the herbs was according to standard methods. The rats were randomly designated on the bases of diets and treatments received for 28 consecutive days. Fibrosis was induced in the Wistar rats by single dose intra-peritoneal injection of CCl4 for 2 consecutive days. Liver and kidney function tests and serum lipid profile were measured using spectrophotometric methods. Renal and hepatic tissues were subjected to histopathological examinations. The concentrations of alkaloids in the four herbal extracts were within the range of 4.83±0.03 - 31.33±0.29 mg/100 g sample, whereas the concentrations of saponins varied within a relatively narrow range: 0.33±0.09 - 4.33±0.02 mg/100 g dry sample; p > 0.05. The activity ratios of AST to ALT of the rat groups were generally less than 1.0 unit. Atherogenic indices of fibrotic rats were within the following ranges: TAG/HDL-C ratio (3.59±0.03 - 6.76±0.06), TC/HDL-C ratio (3.72±0.02 - 6.94±0.05) and LDL-C/HDL-C ratio (2.00±0.01 - 4.59±0.02). Losses in phytochemical contents following hydrothermal processing of the herbs did not substantially affect their overall therapeutic scores against morpho-logical and functional impairments of hepatic and renal tissues following CCl4 intoxication of the rats.
DOI: http://dx.doi.org/10.5281/zenodo.82322
Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells
Pharmacological assays carried out in transfected cells have been very useful for describing the mechanism of action of cathinone new psychoactive substances (NPS). These in vitro characterizations provide fast and reliable information on psychoactive substances soon after they emerge for recreational use. Well-investigated comparator compounds, such as methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, and lysergic acid diethylamide, should always be included in the characterization to enhance the translation of the in vitro data into clinically useful information. We classified cathinone NPS according to their pharmacology at monoamine transporters and receptors. Cathinone NPS are monoamine uptake inhibitors and most induce transporter-mediated monoamine efflux with weak to no activity at pre- or postsynaptic receptors. Cathinones with a nitrogen-containing pyrrolidine ring emerged as NPS that are extremely potent transporter inhibitors but not monoamine releasers. Cathinones exhibit clinically relevant differences in relative potencies at serotonin vs. dopamine transporters. Additionally, cathinone NPS have more dopaminergic vs. serotonergic properties compared with their non-β-keto amphetamine analogs, suggesting more stimulant and reinforcing properties. In conclusion, in vitro pharmacological assays in heterologous expression systems help to predict the psychoactive and toxicological effects of NPS
Corporate Governance and Performance of Small And Medium-Sized Enterprises: A Catalyst for Entrepreneurship Growth and Sustainability in Nigeria
Advancing CFD fire modelling in mechanically ventilated nuclear facilities
The main goal of this PhD thesis is to advance knowledge on some physical phenomena
and improve existing numerical modelling capabilities for fire behaviour in mechanically
ventilated compartments. To achieve this goal, the following different studies were
undertaken in the project:
1. Implementation of a Mechanical Ventilation Model: This study improves the existing
numerical capabilities of the Computational Fluid Dynamics (CFD) code FireFOAM by
implementing a model based on a simplified Bernoulli Equation in order to predict the
pressure variations in the compartment and flow rates in the ventilation system.
2. Conjugate Heat Transfer (CHT) Study: Heat transferred between combustion gases
from the fire and the compartment’s walls, was studied using CHT. The work improves the
numerical modelling capability of the CFD solver by combining a combustion solver and a CHT
solver.
3. Modelling Liquid Fuel Evaporation: This study advances the modelling of the physical
phenomena involved in liquid fuel evaporation with the development of an evaporation
model and its numerical implementation in the CFD solver FireFOAM. The evaporation model
was validated by investigating its accuracy in predicting the fuel Mass Loss Rate (MLR). Spills
of flammable liquid leading to fires are typical scenarios encountered in nuclear power plants.
4. Vertical Smoke Propagation (VSP) Study: To further validate the predictive capability
of the evaporation model and provide more insights to physical phenomena, smoke
propagation through a horizontal opening between two superposed compartments was also
studied. The study of VSP was included in this thesis because of the nature of most nuclear
power plants compartments that have multiple rooms usually superposed that are connected
through a horizontal vent or opening.
5. In-depth Convective Heat Transfer Modelling: This study contributes to advancing the
modelling of physical phenomena, by modifying the developed evaporation model with
emphasis on heat transfer within the fuel. This was accomplished by implementing a novel
method of predicting convective currents within the fuel. It involved deriving the effective
thermal conductivity of the liquid fuel during combustion.
6. Combustion Modelling: This study involved improving the prediction of the fuel MLR
by implementing a general combustion model. The combustion model was formulated by
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combining the already existing Eddy Dissipation Model (EDM) with the finite rate model. The
inclusion of the finite rate model would generate laminar flow that allows for fuel
vaporization without combustion at the initial stage.
7. Convective Heat Transfer modelling: Improvements were made in the predictive
capability of the evaporation model by making use of an average flame temperature value for
calculating the convective heat flux at the fuel surface.
The different studies summarized above include a mixture of phenomena that are well
understood and those that are still in early stages of development. The contribution from well
understood phenomena is the advancement of the predictive capability of the CFD code
FireFOAM which will allow the fire community to explore some new problems. The well
understood phenomena include the mechanical ventilation, CHT, combustion modelling and
convective heat transfer. The thesis makes some significant and novel contributions on
research areas that include modelling liquid fuel evaporation and in-depth convection heat
transfer. These research areas are in infancy and under-development particularly in the
context of mechanically ventilated fires. There have been previous works conducted on
evaporation modelling, but further knowledge continues to be developed due to the
increasing complexities surrounding fuel combustion i.e., open atmosphere, single and
multiple mechanically compartments. Phenomenon such as VSP are not well understood in
the nuclear fire safety, and in developing modelling capabilities in the CFD FireFOAM, the
thesis makes an important contribution.
Different experiments from the literature were used for verification and validation
purposes in the studies mentioned above. However, the main experiments used in this thesis
were conducted in the OECD PRISME Projects (PRISME 1 &2). The PRISME Projects consisted
of experiments conducted in open atmosphere and in a mechanically ventilated compartment
representative of a typical nuclear power plant. PRISM data were mostly used for the
validation of the models in a mechanically ventilated compartment. Additionally, the
experiments conducted by Vali, Nobes and Kostiuk (2014), and Kang, Lu and Chen (2010) were
used for further validation of some of the models in open atmosphere.
PRISME projects concerned nuclear power plants that constitute a major risk due to the
potential leak of radioactive materials during a fire incident. The use of well validated fire
models offers a better alternative to the use of traditional prescriptive fire safety regulations.
Nuclear power plants make use of mechanical ventilation which provides dynamic
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confinement for nuclear materials by maintaining the required pressure. The occurrence of
fires could potentially result in pressure variations within power plants. Although dynamic
confinement along with other safety measures are in place to prevent fires, there is a
continuous need to assess fire safety measures and reduce the risk of fire propagation with
the use of fire simulation codes. Nuclear power plants are usually superposed with a
horizontal vent or opening connecting both rooms. Therefore, VSP during fires poses another
major risk particularly if there are combustible or radioactive materials in the adjacent room.
The flow at the horizontal vent and inside a mechanically ventilated compartment can
undergo complex dynamics which would affect the behaviour of fire including liquid fuel
evaporation. This flow behaviour can be determined by several factors and from prior
experimental studies conducted, the major factors affecting the behaviour are the position of
the fuel, the ventilation configuration in both rooms and fuel MLR (Pretrel and Vaux, 2019;
Pretrel et al., 2014; Pretrel et al., 2017). These factors affecting the horizontal vent flow
coupled with the superposed nature of nuclear rooms provide justifications for some of the
studies undertaken above in this thesis.
As mentioned above, the presence of complex flows in mechanically ventilated
configurations could undoubtedly affect the validation study of the models developed in this
thesis. In order to address this, additional fuel evaporation is studied in open atmosphere
particularly to validate the evaporation model and in-depth convective heat transfer. The
results obtained in open atmosphere allows the assessment of the accuracy of the models
and provides the necessary confidence to perform the study in mechanically ventilated
nuclear compartments.
This thesis builds on existing research by making use of an emerging open-source
computational fluid dynamics (CFD) fire simulation code known as FireFOAM, to predict fire
behaviour in a mechanically ventilated nuclear compartment. An existing in-house modified
version of FireFOAM developed by the authors’ research group, is further modified in the
present work to implement the different models developed in this thesis. This includes the
Conjugate Heat Transfer (CHT) model to account for the heat transfer between combustion
gases and solid boundaries. The CHT is validated using the wall temperatures and heat fluxes
from PRISME experiments. Furthermore, a mechanical ventilation model has been developed
and implemented into FireFOAM. The mechanical ventilation model was coupled initially with
the experimental fuel MLR to predict the pressure variations in the nuclear compartment and
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predict the flow rates in the ventilation network. Further step was taken in modifying
FireFOAM by including an evaporation model used to predict the fuel MLR. The evaporation
model was initially validated by comparing it to the experimental fuel MLR. Further validation
of the evaporation model includes predictions of the flow behaviour at the horizontal vent
and the predictions of the flow rate at the mechanical ventilation. Modifications were made
to the evaporation model by the advancements of in-depth convective heat transfer,
combustion modelling and convective heat transfer mentioned above. The fuel MLR and
temperature values inside the liquid fuel were used to validate the In-depth convective heat
transfer model. Fuel MLR was used to validate the combustion model and convective heat
transfer.
The different studies conducted in this thesis are highly important for fire risk safety
assessment in nuclear facilities and any findings would help in future assessment. In nuclear
power plants, pool fires may result from ignition of spilled lubricating oil from turbines and
pumps, or from liquid fuel spilled from standby generators. The thesis work could also go
beyond nuclear facility and into other industry like the petrochemical industry and building
services industry that continuously face fire hazards. The overall work performed in this thesis
is believed to have advanced CFD fire modelling in mechanically ventilated compartments.
The summary of the individual work accomplished in this thesis are highlighted below:
• Mechanical Ventilation: The mechanical ventilation model predicted the pressure
variations and flow rates at the ventilation branch with a relatively good level of
accuracy. The results from the validations show that the burning rate is controlled
by both the mechanical ventilation and the flow from the vent.
• Conjugate Heat Transfer (CHT): It was concluded that there is no significant
difference between the use of CHT and wall laws in simulating the interaction
between the wall and combustion gases. However, suggestions were made
regarding complex configurations where the use of CHT would be much more
beneficial than wall laws.
• Evaporation Model: The evaporation model was able to predict the fuel MLR in
open atmosphere and in a compartment, particularly the steady state stage of fuel
MLR. The lack of a gas phase extinction model that would capture the effects of
lack of oxygen, led to discrepancies in the predictions of fuel MLR particularly in
the compartment.
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• Vertical Smoke Propagation: The direction of flow at the horizontal vent was
captured for some of the tests. The absence of a gas phase extinction model led
to discrepancies in predictions of flow at the vent.
• In-depth Convective Heat Transfer: Heat transfer within the fuel was improved
with the use of an effective thermal conductivity. It was shown that without the
convective currents inside the fuel, the fuel MLR is over-predicted in open
atmosphere, including temperatures inside the fuel.
• Combustion Modelling: Improvement was made at the initial start of fuel
combustion. The initial spikes of fuel MLR observed in previous studies was
reduced with the general combustion model.
• Convective Heat Transfer: The convective heat flux derived with grid cell
temperature was found to be dependent on grid size, while the use of an average
flame temperature was discovered not to be dependent on grid size
Geophysical and Hydro-Chemical Investigations of Oke Asunle Dumpsite in Ile-Ife, Southwestern Nigeria for Subsoil and Surface Water Pollution
Background. Waste deposited in dumpsites immediately becomes part of the hydrological system. Over time, waste components bio-accumulate and/or decompose into contaminant liquid, leading to pollution of soil and water and posing a risk to human health.
Objectives. The present study employed integrated hydro-chemical and geophysical methods to assess surface water and soil/subsoil within the premises of the Obafemi Awolowo University waste dumpsite in Ile-Ife, southwest Nigeria, for possible leachate pollution.
Methods. The electrical resistivity method involving 1D vertical electrical sounding (VES) and 2D dipole-dipole profiling techniques and hydro-chemical analysis were used. Two-dimensional profiling data were gathered along two orthogonal traverses and inverted into 2D resistivity images. Schlumberger VES data were gathered and quantitatively interpreted using partial curve matching and computer assisted 1D forward modeling. Hydro-chemical analysis was carried out on three water samples collected from the Asunle River for water quality testing. Anthropogenic pollution determinant parameters such as pH, conductivity, total dissolved solid, cations (calcium, magnesium, sodium, and potassium), anions (chloride, sulphate, biocarbonate, and nitrate) and the less abundant heavy metals in granitic gneiss-derived soil such as cadmium, copper, iron, manganese and lead were analyzed.
Results. Three geologic layers: topsoil, weathered basement and fresh basement were identified. Within the topsoil and weathered layer, two zones with contrasting geoelectrical characteristics were observed. The first zone, outside the dumpsite boundary, was characterized by relatively high resistivities (78–178 Ωm), typical of unimpacted soil. The second zone, within the dumpsite boundary, was characterized by relatively low resistivity values (15–47 Ωm) up to depth levels between 2.5 and > 15 m. The analyzed physico-chemical parameters, except for turbidity, fell within set limits for potable water quality. However, the concentration levels of heavy metals such as cadmium (0.017 - 0.018 mg/l); iron (0.544 - 0.739 mg/l) and lead (0.501 -0.551 mg/l) significantly exceeded standard limits.
Conclusions. The results of the present study indicate that subsoil and surface water within and around the dumpsite can be considered to be polluted.
Competing Interests. The authors declare no competing financial interests
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