Smart Gate Driver Design for Silicon (Si) IGBTs and Silicon-Carbide (SiC) MOSFETs

The design of an efficient and smart gate driver for a Si IGBT and SiC MOSFET is addressed in thesis. First, the main IGBT parameters are evaluated thoroughly in order to understand their effects in the design of the gate driver. All known consequences of previously designed gate drivers are studied in order to achieve an optimum gate driver. As a result of this assessment, the designer is able to determine whether adding or removing components from the gate driver circuit are beneficial or not. Then, exhaustive research is done to identify suitable integrated circuits to use for the power supplies, isolation circuit, protection circuit, and gate driver circuitry. Next, the final design is laid out in PCB Editor in order to eventually manufacture it and test it out. During this process, important techniques in making an efficient and compact PCB are taken into consideration

Evaluating the middle school mathematics teacher preparation program at Riyadh Teachers\u27 College

Continuous evaluation and feedback are essential to improving the quality of teacher preparation programs. The purpose of this study was to evaluate the perceptions of various aspects of the preparation of preservice middle school mathematics teachers at Riyadh Teachers\u27 College, Saudi Arabia, from the perspective of both preservice middle school mathematics teachers and mathematics department faculty members. The focus of this study was on the mathematics department\u27s theoretical framework, its governance and resources, faculty qualifications and performance, courses and field experiences, approaches of teaching, and assessment forms. Two research questionnaires were developed for the purpose of collecting research data: one for the preservice middle mathematics teachers, and another for the teaching staff of the mathematics department who train these preservice teachers. The distribution and collection of questionnaires took an average of three weeks. The final number collected was one hundred sixty-nine, representing 63% of the total number of questionnaires distributed. The Statistical Package for the Social Sciences (SPSS) was used for various computational procedures employed. The result emphasized the need to explore reducing the number of mathematics specialization courses and/or connecting the content of these courses more to the school curricula. The findings in the current study indicate that the participants believe that the most critical aspects of the courses that need to be improved are knowledge of mathematics pedagogy and knowledge of technology. The results show that the program suffers from a lack of adequate teaching materials and equipment, such as computers and computer software, calculators, and electronic information resources. Further, the findings of the current study revealed that there might be a need to increase the number and type of early field experiences. The current study recommended the program to employ faculty members who have middle school level experience and expertise. The study suggested the faculty members in the mathematics department to explore alternative teaching styles. In addition to studying the needs and opinions of faculty members with regard to the program, the study encourages more research on the problems they face in such colleges

ANTIMICROBIAL AND ANTIOXIDANT EVALUATION OF DIFFERENT SOLVENT EXTRACTS OF MEDICINAL PLANT: FAGONIA MOLLIS DELILE

The present study was aimed to evaluation of the medicinal uses of Fagonia mollis by studying some active constituents, antioxidants and antimicrobial activities. Fagonia mollis Delile was collected from different sites from Tabuk, Saudi Arabia. The phytochemical analysis of the aerial parts of F. mollis indicated that the plant is rich in secondary compounds. F. mollis exhibited the highest content of tannins and saponins (19.9±1.68 and 16.8±1.32, mg/g D.W., respectively), followed by phenolics (11.6±0.72 mg/g D.W.), flavonoids (8.6±0.82 mg/g D.W.) and then alkaloids (5.6±0.64 mg/g D.W.). In the DPPH test system, the crud extract of F. mollis, with an IC50 value of 1.51 mg ml?1, but higher than that of the positive control catechol (0.37 mg ml?1). In the present study the petroleum ether and methylene chloride extracts of F. mollis inhibit all pathogenic bacteria with different rates. Ethyl acetate extract has no effect on both Escherichia coli and Klebsiella pneumonia, while the acetone inhibited all the bacteria except Escherichia coli and Staphylococcus aureus. Methyl alcohol extract of plant on tested bacteria proved a broad spectrum antimicrobial potential. On the other hand, petroleum ether extract inhibited the growth of Candidia albicans and Mucor spp (8 and 9.3 mm, respectively), but has no effect on the Aspergillus fumigatus and A. niger. The methylene chloride, Ethyl acetate and methyl alcohol extracts had no antifungal activities against all the pathogenic fungi. Acetone extract inhibited the growth of A. fumigatus (10.2mm) but has no effect on the others. The above results revealed that F. mollis have an excellent anti-bacterial activity and can be used for disease therapy

Along party Lines: Examining the gubernatorial party difference in COVID-19 mortality rates in U.S. Counties

Drawing upon the literatures on risk factors for COVID-19 and the roles of political party and political partisanship in COVID-19 policies and outcomes, this study quantifies the extent to which differences in Republican- and Democrat-governed counties\u27 observable characteristics explain the Republican - Democrat gap in COVID-19 mortality rate in the United States. We analyze the county COVID-19 mortality rate between February 1 and December 31, 2020 and employ the Blinder-Oaxaca decomposition method. We estimate the extent to which differences in county characteristics - demographic, socioeconomic, employment, health status, healthcare access, area geography, and Republican vote share, explain the difference in COVID-19 mortality rates in counties governed by Republican vs Democrat governors. Among 3,114 counties, Republican-governed counties had significantly higher COVID-19 mortality than did Democrat-governed counties (127 ± 86 vs 97 ± 80 per 100,000 population, p \u3c 0.001). Results are sensitive to which weights are used: of the total gap of 30.3 deaths per 100,000 population, 12.8 to 20.5 deaths, or 42.2-67.7 %, are explained by differences in observable characteristics of Republican- and Democratic-governed counties. Difference in support for President Trump between Republican- and Democrat-governed counties explains 25 % of the additional deaths in Republican counties. Policies aimed at improving population health and lowering racial disparity in COVID-19 outcomes may also be correlated with reducing the partisan gap in COVID-19 mortality

Application of population pharmacokinetic-pharmacodynamic modelling evaluate and optimise aminoglycoside therapy in patients with cystic fibrosis

Cystic fibrosis (CF) is an inherited autosomal recessive disorder that is characterised by frequent lung infections commonly caused by P.aeruginosa. The standard treatment for this infection is an aminoglycoside combined with a β-lactam and patients often receive multiple courses of these antibiotics over many years. Aminoglycosides are narrow therapeutic index drugs where the margin between safety and toxicity is small. Therefore, it is important to monitor patients who are on aminoglycosides to ensure safety and efficacy of therapy and advise on current and future dosage regimens. The focus of this thesis was to use population pharmacokinetic methodologies to examine how aminoglycoside pharmacokinetic parameters change over time in this group of patients and to develop and evaluate dosing regimens and data interpretation methods. A population pharmacokinetic analysis was first conducted using the package NONMEM with the FOCE (parametric) algorithm. Aminoglycoside concentration-time profiles were available from 166 patients treated within the Glasgow Cystic Fibrosis Unit and comprised 1075 courses of therapy and 2238 concentration measurements collected over 15 years. The final, two compartment, population model identified an influence of height and creatinine clearance on clearance and height on volume of distribution of the central compartment. Inclusion of these descriptors reduced between subject variability from 23% to 18% for clearance and 14% to 12% for volume of distribution of the central compartment. Within-subject variability was low at 11%, and there were no changes in aminoglycoside clearance over time. Internal valuation of the population model using bootstrap, prediction corrected visual predictive check and normalised prediction distribution errors indicated that this model was stable and with good predictive ability. In addition, an external model evaluation was conducted using data from The Hague that comprised tobramycin concentration measurements from 165 patients who received 415 courses of therapy. The results of this analysis indicated good performance of the model in predicting pharmacokinetic parameters and concentrations in another group of patients with cystic fibrosis. The combined Glasgow and The Hague datasets were subsequently analysed using a non-parametric approach with the software Pmetrics (Neely MN et al., 2012). In total, data from 331 patients with 1490 courses of therapy and 3690 aminoglycoside concentration measurements were analysed. Despite the different assumptions of the two methods, the final models were the same and the final parameter estimates were very similar. The standard dose of aminoglycoside used in patients with cystic fibrosis is 10 mg/kg administered once daily. The typical daily area under the concentration-time curve (AUC) arising from this dose was determined using pharmacokinetic parameter estimates reported in the TOPIC study (Smyth A et al., 2005) and by examining the raw data from patients within The Hague dataset who received this dosage regimen. The results of this analysis led to a target daily AUC of 106 mg.h/L (range 80-120 mg.h/L). A simulated dataset of 5000 patients was created with clinical characteristics based on patients with cystic fibrosis from Glasgow and The Hague. The final population model was then used to estimate pharmacokinetic parameters and to predict concentrations at defined time points according to the standard dose of 10 mg/kg/day and three alternative regimens (13 mg/kg/day lean body weight, 3 mg/cm/day and 326 mg/m2/day). It was found that the dose based on height (3mg/cm/day) had the highest probability of achieving the combined targets of daily AUC range, peak concentrations of 20-30 mg/L and trough concentrations < 1 mg/L. For standard "once daily" aminoglycoside therapy, dosage adjustment nomograms are available that help clinicians to interpret aminoglycoside concentrations and advise on dose adjustments (Nicolau DP et al., 1995). For adult patients with cystic fibrosis there is no dosage adjustment nomogram available for the 10 mg/kg aminoglycoside dose. Therefore, one of the aims of the thesis was to develop an aminoglycoside (tobramycin) dosage adjustment nomogram that could be used with doses of 10 mg/kg/day and 3 mg/kg/day. The nomogram was derived from the concentration-time profiles that were generated from the simulation approach described above and consisted of three areas representing below, within and above the target ranges. Preliminary validation work indicated that the nomogram could identify patients with low, within and above target daily area under the concentration-time curve range from one sample point. Importantly, the nomogram was able to identify patients with poor renal function. The goal for any antibacterial therapy is to ensure efficacy against treated organism and to achieve high probability of treatment success. In this thesis, the likelihood of treatment success for the 10 mg/kg and 3 mg/cm dosage regimens were determined against P.aeruginosa. This was achieved by determining the susceptibility breakpoint and cumulative fraction of response for these dosage regimens and comparing them with the breakpoints obtained from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the British Society for Antimicrobial Chemotherapy (BSAC). Breakpoints and cumulative fraction of response were also examined for doses of 12 mg/kg/day and 4 mg/cm/day. The results showed that these regimens had similar MIC breakpoints of ≤ 2 mg/L to achieve a Peak/MIC ratio ≥ 10, and MIC breakpoint of ≤ 0.5 mg/L for a daily AUC/ MIC ratio ≥ 100 mg.h/L against P.aeruginosa. However, they were lower than the EUCAST and BSAC susceptibility breakpoints against gram-negative pathogens (≤ 4 mg/L). Analysis of the cumulative fraction of response identified an overall treatment success of more than 90 % with all regimens for a Peak/MIC ratio ≥ 10 against P.aeruginosa using the EUCAST MIC distribution. At a daily AUC/MIC ratio greater than 100, the cumulative fraction of response for tobramycin indicated a success rate between 70 - 80 % for all dosage regimens, with the higher values being observed with the doses of 12 mg/kg/day and 4 mg/cm/day. However, the 12 mg/kg/day dosage regimen was associated with high peak and daily exposure and might result in more toxicity compared with the high 4 mg/cm/day dosage regimen. The population model developed in this thesis was able to describe and predict the handling of aminoglycoside in patients with cystic fibrosis. The model was used to evaluate the current 10 mg/kg/day dosage regimen, develop a new dosage regimen and develop a dosage adjustment nomogram for clinical application. Furthermore, the model was used to predict the efficacy of the standard and new dosage regimens through determining the susceptibility breakpoints and cumulative fraction of response against gram-negative organisms. In the future, the models could be used to help estimate individual pharmacokinetic parameters and design individualised dosage regimens using both parametric and non-parametric clinical pharmacokinetic software.Cystic fibrosis (CF) is an inherited autosomal recessive disorder that is characterised by frequent lung infections commonly caused by P.aeruginosa. The standard treatment for this infection is an aminoglycoside combined with a β-lactam and patients often receive multiple courses of these antibiotics over many years. Aminoglycosides are narrow therapeutic index drugs where the margin between safety and toxicity is small. Therefore, it is important to monitor patients who are on aminoglycosides to ensure safety and efficacy of therapy and advise on current and future dosage regimens. The focus of this thesis was to use population pharmacokinetic methodologies to examine how aminoglycoside pharmacokinetic parameters change over time in this group of patients and to develop and evaluate dosing regimens and data interpretation methods. A population pharmacokinetic analysis was first conducted using the package NONMEM with the FOCE (parametric) algorithm. Aminoglycoside concentration-time profiles were available from 166 patients treated within the Glasgow Cystic Fibrosis Unit and comprised 1075 courses of therapy and 2238 concentration measurements collected over 15 years. The final, two compartment, population model identified an influence of height and creatinine clearance on clearance and height on volume of distribution of the central compartment. Inclusion of these descriptors reduced between subject variability from 23% to 18% for clearance and 14% to 12% for volume of distribution of the central compartment. Within-subject variability was low at 11%, and there were no changes in aminoglycoside clearance over time. Internal valuation of the population model using bootstrap, prediction corrected visual predictive check and normalised prediction distribution errors indicated that this model was stable and with good predictive ability. In addition, an external model evaluation was conducted using data from The Hague that comprised tobramycin concentration measurements from 165 patients who received 415 courses of therapy. The results of this analysis indicated good performance of the model in predicting pharmacokinetic parameters and concentrations in another group of patients with cystic fibrosis. The combined Glasgow and The Hague datasets were subsequently analysed using a non-parametric approach with the software Pmetrics (Neely MN et al., 2012). In total, data from 331 patients with 1490 courses of therapy and 3690 aminoglycoside concentration measurements were analysed. Despite the different assumptions of the two methods, the final models were the same and the final parameter estimates were very similar. The standard dose of aminoglycoside used in patients with cystic fibrosis is 10 mg/kg administered once daily. The typical daily area under the concentration-time curve (AUC) arising from this dose was determined using pharmacokinetic parameter estimates reported in the TOPIC study (Smyth A et al., 2005) and by examining the raw data from patients within The Hague dataset who received this dosage regimen. The results of this analysis led to a target daily AUC of 106 mg.h/L (range 80-120 mg.h/L). A simulated dataset of 5000 patients was created with clinical characteristics based on patients with cystic fibrosis from Glasgow and The Hague. The final population model was then used to estimate pharmacokinetic parameters and to predict concentrations at defined time points according to the standard dose of 10 mg/kg/day and three alternative regimens (13 mg/kg/day lean body weight, 3 mg/cm/day and 326 mg/m2/day). It was found that the dose based on height (3mg/cm/day) had the highest probability of achieving the combined targets of daily AUC range, peak concentrations of 20-30 mg/L and trough concentrations < 1 mg/L. For standard "once daily" aminoglycoside therapy, dosage adjustment nomograms are available that help clinicians to interpret aminoglycoside concentrations and advise on dose adjustments (Nicolau DP et al., 1995). For adult patients with cystic fibrosis there is no dosage adjustment nomogram available for the 10 mg/kg aminoglycoside dose. Therefore, one of the aims of the thesis was to develop an aminoglycoside (tobramycin) dosage adjustment nomogram that could be used with doses of 10 mg/kg/day and 3 mg/kg/day. The nomogram was derived from the concentration-time profiles that were generated from the simulation approach described above and consisted of three areas representing below, within and above the target ranges. Preliminary validation work indicated that the nomogram could identify patients with low, within and above target daily area under the concentration-time curve range from one sample point. Importantly, the nomogram was able to identify patients with poor renal function. The goal for any antibacterial therapy is to ensure efficacy against treated organism and to achieve high probability of treatment success. In this thesis, the likelihood of treatment success for the 10 mg/kg and 3 mg/cm dosage regimens were determined against P.aeruginosa. This was achieved by determining the susceptibility breakpoint and cumulative fraction of response for these dosage regimens and comparing them with the breakpoints obtained from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the British Society for Antimicrobial Chemotherapy (BSAC). Breakpoints and cumulative fraction of response were also examined for doses of 12 mg/kg/day and 4 mg/cm/day. The results showed that these regimens had similar MIC breakpoints of ≤ 2 mg/L to achieve a Peak/MIC ratio ≥ 10, and MIC breakpoint of ≤ 0.5 mg/L for a daily AUC/ MIC ratio ≥ 100 mg.h/L against P.aeruginosa. However, they were lower than the EUCAST and BSAC susceptibility breakpoints against gram-negative pathogens (≤ 4 mg/L). Analysis of the cumulative fraction of response identified an overall treatment success of more than 90 % with all regimens for a Peak/MIC ratio ≥ 10 against P.aeruginosa using the EUCAST MIC distribution. At a daily AUC/MIC ratio greater than 100, the cumulative fraction of response for tobramycin indicated a success rate between 70 - 80 % for all dosage regimens, with the higher values being observed with the doses of 12 mg/kg/day and 4 mg/cm/day. However, the 12 mg/kg/day dosage regimen was associated with high peak and daily exposure and might result in more toxicity compared with the high 4 mg/cm/day dosage regimen. The population model developed in this thesis was able to describe and predict the handling of aminoglycoside in patients with cystic fibrosis. The model was used to evaluate the current 10 mg/kg/day dosage regimen, develop a new dosage regimen and develop a dosage adjustment nomogram for clinical application. Furthermore, the model was used to predict the efficacy of the standard and new dosage regimens through determining the susceptibility breakpoints and cumulative fraction of response against gram-negative organisms. In the future, the models could be used to help estimate individual pharmacokinetic parameters and design individualised dosage regimens using both parametric and non-parametric clinical pharmacokinetic software

Biomarkers in prostate cancer : defining 'pussycat versus tiger' phenotype by proteomic modeling

Prostate cancer is the one of the major causes of morbidity and mortality in the western world. It affects the prostate gland of males with a significant increase in the disease incidence every year. Current diagnostic and prognostic markers, such as prostate specific antigen (PSA), rectal examination and Gleason grades have their own limitations in a wider context of disease treatment and prediction. There is therefore a pressing need for novel and powerful biomarkers at protein or metabolite level. This study attempts to profile and identify candidate prostate cancer stage specific markers, within a defined population of samples. The samples were classified, based on the pathological information as “aggressive” (Gleason grade > 7) and “nonaggressive “(Gleason grade < 7). The proteomic protocols standardised at the John van Geest Cancer Research Centre, were used for the initial characterisation of the samples. The MS spectra obtained from the samples were used applied to an artificial neural network (ANN) based algorithm to generate predictive ions able to classify the samples. Three ions (m/z 1268.8, 998.6, 910.4) were able to predict and classify with high specificity and sensitivity. 24 samples were immunodepleted and subjected to nano-LC fractionation and MALDI-TOF analysis, generating 80-120 protein identities per sample. The three ions predicted previously by the ANN identified as Haemopexin, Gelsolin and Apolipoprotein B 100. Using ProfileAnalysis software, this study identified Apolipoprotein isoforms, including Apolipoprotein B 100, and Afamin as the proteins which showed differential expression in between the groups. This study identifies Apolipoprotein B 100 as a potential marker using two different modeling approaches suggesting this protein as the potential biomarker candidate. The utility of high throughput proteomic platforms such as Robotic liquid handling, MALDI-TOF and LC-MALDI for serum biomarker identification in PCa has been shown during this investigation

Plural Leadership During Organisational Transformation Initiatives (Vertical & Horizontal)

Organizational transformation and change scholars and researchers published many articles linking and studying the effect of vertical (transactional) leadership and horizontal (transformational) leadership on organizations during transformation. As much attention has been given in the last two decades to transformational leadership as being one of the trendiest leadership styles that focuses on the relation between followers and leaders to achieve better performance during organizational transformation, transactional leadership is still of benefit. This paper bridges organizational transformation and leadership literature and show the importance of transformational (horizontal) leadership alongside transactional (vertical) leadership in achieving efficient performance and optimal results during organizational transformation. Methodology: A literature review will be conducted based on literature related to certain key word and through a systematic literature review protocol. Keywords: organizational transformation, leadership, transactional leadership, transformational leadershi

Biomarkers in prostate cancer : defining 'pussycat versus tiger' phenotype by proteomic modeling

Prostate cancer is the one of the major causes of morbidity and mortality in the western world. It affects the prostate gland of males with a significant increase in the disease incidence every year. Current diagnostic and prognostic markers, such as prostate specific antigen (PSA), rectal examination and Gleason grades have their own limitations in a wider context of disease treatment and prediction. There is therefore a pressing need for novel and powerful biomarkers at protein or metabolite level. This study attempts to profile and identify candidate prostate cancer stage specific markers, within a defined population of samples. The samples were classified, based on the pathological information as “aggressive” (Gleason grade > 7) and “nonaggressive “(Gleason grade < 7). The proteomic protocols standardised at the John van Geest Cancer Research Centre, were used for the initial characterisation of the samples. The MS spectra obtained from the samples were used applied to an artificial neural network (ANN) based algorithm to generate predictive ions able to classify the samples. Three ions (m/z 1268.8, 998.6, 910.4) were able to predict and classify with high specificity and sensitivity. 24 samples were immunodepleted and subjected to nano-LC fractionation and MALDI-TOF analysis, generating 80-120 protein identities per sample. The three ions predicted previously by the ANN identified as Haemopexin, Gelsolin and Apolipoprotein B 100. Using ProfileAnalysis software, this study identified Apolipoprotein isoforms, including Apolipoprotein B 100, and Afamin as the proteins which showed differential expression in between the groups. This study identifies Apolipoprotein B 100 as a potential marker using two different modeling approaches suggesting this protein as the potential biomarker candidate. The utility of high throughput proteomic platforms such as Robotic liquid handling, MALDI-TOF and LC-MALDI for serum biomarker identification in PCa has been shown during this investigation

Understanding Michael Pisaro’s Solo Piano Music through Alain Badiou’s theory of the Event

This thesis focuses on the works of the composer Michael Pisaro and their connection with the concept of truth as outlined by the philosopher Alain Badiou (Being and Event, 1988). The main concern of this research is with the relation between silence, Pisaro’s piano music, and Badiou’s theory of the event. The thesis argues that Badiou’s faithful subject can be mapped onto the performer’s faithful interpretation of Pisaro’s composition, and involves the performance of many of Piasro’s piano works: fields have ears (1), Les Jours, Mon Aubépine, floating, drifting, C. Wolff, half-sleep beings, time, presence, movement, pi (1-2594), Fade, distance (1) and Akasa. The thesis argues, taking Badiou’s and Pisaro’s arguments through to their logical (if sometimes seemingly extreme) conclusions, that it is in the performance (and recording) of these pieces that the research ‘proper’ of the thesis rests. I begin with a discussion of Pisaro’s encounter with the music of John Cage – one of the most famous and leading experimental composers – and the influence it had on Pisaro in terms of using silence as a contingent part of his music. Pisaro’s compositions reveal a kind of respect for silence; silent moments reflect an openness to the world of truth, which is expressed in the form of incalculable events. As such, Pisaro’s encounter with Cage is conceived as a sort of truth process, in the terms Alain Badiou describes. It is not a coincidence that Badiou is, alongside Cage, one of the seminal influences on Pisaro, and the relationship of Pisaro’s compositional work to Badiou’s thought is a central aspect of the written portion of the thesis. Through employing Badiou’s philosophy, this research argues that, though representation and its entire pursuit of beauty in art may be regarded as being at the outset of artistic truth procedures, representation in and of itself is not and cannot be integral to a truth procedure. The thesis concludes that to accept that Badiou’s philosophy represents a profound and significant influence on Pisaro’s music means that the performer must take, almost dogmatically, a faithful attitude to Pisaro’s scores. Furthermore, it demonstrates that by understanding Pisaro’s music through Badiou’s theory of the event, new events (in the form of silences) intervene in performance situations, keeping in mind that the performer can only act faithfully on the basis of the demands of Pisaro’s scores, and thus cannot ‘force’ silence to produce truth, but can only act in the faith that that will have happened