Dissertations / Theses on the topic 'Environmental and medical sciences'
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1
Bell, Stephanie K. "Assessment of silicone polymer composites for the trace extraction of herbicides : a tool for environmental forensics." FIU Digital Commons, 2007. http://digitalcommons.fiu.edu/etd/1482.
Abstract:
Passive samplers are not only a versatile tool to integrate environmental concentrations of pollutants, but also to avoid the use of live sentinel organisms for environmental monitoring. This study introduced the use of magnetic silicone polymer composites (Fe-PDMS) as passive sampling media to pre-concentrate a wide range of analytes from environmental settings. The composite samplers were assessed for their accumulation properties by performing lab experiments with two model herbicides (Atrazine and Irgarol 1051) and evaluated for their uptake properties from environmental settings (waters and sediments). The Fe-PDMS composites showed good accumulation of herbicides and pesticides from both freshwater and saltwater settings and the accumulation mechanism was positively correlated with the log Kow value of individual analytes. Results from the studies show that these composites could be easily used for a wide number of applications such as monitoring, cleanup, and/or bioaccumulation modeling, and as a non-intrusive and nondestructive monitoring tool for environmental forensic purposes.
2
Meyers, Jacquelyn. "Elucidating Genetic and Environmental Influences on Alcohol-Related Phenotypes." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2830.
Abstract:
Decades of work has led researchers to believe that risk for complex behavioral phenotypes, such as alcohol use disorders, is likely influenced by multiple genes of small effect acting in conjunction with each other and the environment. Currently, the field of psychiatric genetics is developing methodologies for the identification of genetic risk variants that predispose individuals to the development of complex behavioral disorders. Several challenges related to the complex and polygenic nature of these phenotypes, must be considered. This dissertation study attempts to address these important challenges in the context of alcohol use disorders and related phenotypes. A rich twin and family study literature has indicated that 40-70% of the variance in alcohol use disorders (AUDs) is influenced by genetics. Recent attempts to identify specific x genetic risk variants associated with AUDs have been met with limited success. Meanwhile, evidence of the moderating effects of the environment on AUDs has been mounting, providing a strong rationale for examining gene-environment interaction. In the following chapters several studies will be described that integrate established twin methodologies into gene identification projects in an effort to reduce heterogeneity (both phenotypic and genotypic), elucidate environmental constructs that moderate genetic influences, and to enhance statistical power to detect the subtle genetic influences on alcohol related phenotypes.
3
Mahapatra, Indrani. "Modelling environmental risks and conceptualising 'responsible innovation' for nanotechnology enabled medical applications." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/7102/.
Abstract:
Medical products based on nanomaterials can revolutionise disease diagnosis and management modalities via faster, non-invasive diagnostic techniques and targeted therapeutic delivery and will be used extensively in coming years. The central goal of this thesis was to understand environmental risks that could potentially arise from mass production and wider use of nanotechnology enabled medical products and to gather insights from experts’ perceptions on “Responsible Innovation”. The research presented here uses a mixed methods approach to answer the research questions. By applying probabilistic mass flow modelling concept, prospective environmental concentrations of nanomedicine was estimated and a preliminary environmental risk assessment was done using gold nanoparticles in medical applications (potential of commercialisation and marketed) as a case study. This demonstrated that environmental risks from gold nanoparticles for the two major compartments (sludge applied soil and water) is likely to be minimal in the near future. The second component of the research involved 38 interviews with academics and 28 interviews with representatives from regulatory bodies, industry and funding bodies to understand their perceptions on environmental hazards and risks from nanomedicine and their views on the meaning of the concept of “Responsible Innovation”. This revealed that risks from nanomedicine can be compared with risks from existing chemicals and that “Responsible Innovation” is a phrase which can be discussed based on an individual’s experience and discipline.
4
Clauson, John. "Cryptococcus neoformans Serotype Groups Found in Clinical and Environmental Isolates." TopSCHOLAR®, 1993. http://digitalcommons.wku.edu/theses/1888.
Abstract:
Cryptococcus neoformans is an encapsulated yeast responsible for severe meningoencephalitis. The importance of epidemiological studies on cryptococcosis has increased since the beginning of the AIDS epidemic. C. neoformans exists in two varieties containing four serotypes, C. neoformans var. neoformans (serotypes A and D) and C. neoformans var. gattii (serotypes B and C). Locally C. neoformans var. neoformans has been associated with pigeon feces during those months having an average temperature of 64.2°F j(17.8°C) and above. Clinical and environmental isolates of C. neoformans obtained from regional hospitals and environmental samplings, respectively, have been grouped into their variety status utilizing canavanine-glycine-bromthymol blue agar. Polyclonal antisera against C. neoformans serotypes A, B, C and D were isolated from challenged rabbits. Serotyping C. neofromans isolates using the polyclonal antisera resulted in 57% (20 of 35) of the serotypes confirmed with a direct immunofluorescent assay utilizing a single monoclonal antibody (E1). Data from the immunofluorescence assay suggest all C. neoformans obtained from regional hospitals (26 of 26) and those isolated from the environment (9 of 9) belong to the A serotype group. These data have provided information leading to the origin of infection for cryptococcosis in our region, which may be beneficial to immunocompromised individuals.
5
Kirkland, Robert. "Actiononaias Ligamentina as a Biomonitor in the Green River: An Unique Approach for Analysis of Environmental Impacts." TopSCHOLAR®, 2002. http://digitalcommons.wku.edu/theses/605.
Abstract:
Biomonitoring has become an important component in bioassessment programs. It is used to maintain high water quality standards, and determine contaminant levels and biological affects in areas that have been heavily disturbed. The objectives of this research were 1) to improve and apply certain modern biomonitoring techniques and 2) to locate possible contaminant sources affecting the flora and fauna of the Green River and of Mammoth Cave. Actinonaias ligamentina (Lamarck, 1819), a freshwater mussel, was used for interpretation of these impacts as well as refinement of biomonitoring techniques. The mussels were collected in the Lawler Bend region of the Green River, an area upstream from the Mammoth Cave System, and from Haynes Shell Midden (dating 4000 - 6000 years before present) 45 miles downstream. Analyzing the shell nacre of these mussels, and the soft tissue of recently collected specimens, produced an abundance of information including high tissue concentrations of organochloride pesticides, significant concentrations of several metals including Cadmium, Copper, Mercury, Nickel, Silver and Zinc (with Mercury and Silver being found at the impact site), and numerous shell nacre stains. These results indicated possible impact from agriculture in the region and past and present contamination from local industries, and demonstrated the importance of the nacreous shell to biomonitoring programs.
6
Santos, Emmylou C. "Effects of patient and physician gender on the assessment of a medical complaint." Scholarly Commons, 2003. https://scholarlycommons.pacific.edu/uop_etds/2725.
Abstract:
This study investigated the effects of gender, both patient and physician, on how a medical complaint is perceived and acted upon by health professionals. A 2 x 2 factorial design was used, with gender of physician and patient as the two factors, respectively. The participants were physicians (M.D.s) who were recruited by approaching local hospitals/clinics and requesting their participation in the research. They were asked to respond to a patient vignette and a questionnaire assessing the physician's beliefs about and intentions toward the patient. Using a 2 x 2 ANOVA with a specified .05 significance level, no statistically significant differences were found in the assessment of the perceived seriousness of a medical complaint, in the aggressiveness of the work-up provided, and in the diagnoses given to patients. The findings from this study are of value in exploring the existence of gender bias in the medical setting. The absence of gender bias, as it occurred in this study, is an encouraging finding for members of the health care community.
7
Lindh, Joakim. "Development of an Identification System for Modules used in Medical Environments." Thesis, Linköpings universitet, Fysik och elektroteknik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-68065.
Abstract:
The objective of this thesis work is to find a suitable automatic identification solution for a medical system that utilizes several types of attachments. The solution should be cost efficient and sustainable enough to endure the medical environment. The thesis work was performed for Sectra Mamea AB in Linköping, Sweden. Five suitable solutions where evaluated on a theoretical basis and the feasibility of three of them were also experimentally verified on a more practical level. The experiments where performed on a Xilinx Virtex-5 FPGA platform with solution specific prototype boards, which were custom designed during the thesis work. The software development was made in several environments, where programming languages C, C# and VHDL were used. It was found that a solution based on 1-Wire technology was the most cost efficient and best-suited among the candidates. This was proven by validation of the technology and a thorough comparison to the other feasible solutions. This thesis presents the theory and practical results of the research. It is meant to serve as a comprehensive foundation supporting the decisions of future development.
8
Runeson, Roma. "Personality, Stress, and Indoor Environmental Symptomatology." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5899.
9
Karssenberg, Derek. "Building dynamic spatial environmental models." Amsterdam : Utrecht : Koninklijk Nederlands Aardrijkskundig Genootschap ; Faculteit Ruimtelijke Wetenschappen, Universiteit Utrecht, 2002. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=010371322&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
10
Peterson, Roseann. "On the genetic and environmental associations between body composition, depression symptoms and smoking behavior." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2889.
Abstract:
Obesity is a serious public health crisis and recent estimates of its incidence are the highest in United States history, with 35% and 17% of American adults and children affected, respectively. The clinical definition of adult obesity is operationalized as a body mass index (BMI) greater than 30 kg/m2. Although the prevalence of common obesity has increased dramatically over the past 30 years–largely thought to be due to changes in the environment, such as high calorie diets and sedentary lifestyles—twin and family studies have shown consistently that relative body weight is under considerable genetic influence in both children and adults, with heritability estimates ranging from 40% to 90%. Elucidating the genetic and environmental liability to relative body weight is an important public health endeavor. To further our understanding of the genetics of BMI and common complex obesity, several studies are described that integrate clinical, twin, and genome-wide association (GWAS) methodology in the context of genetic risk scores, clinical risk prediction, development across adolescence into adulthood, and comorbidity with depression symptoms and smoking behavior. First, in two cross-sectional genetic association studies, the utility of genetic risk sum scores (GRSS) were assessed, which summarize the total number of risk alleles, as an alternative form of replication and for potential clinical utility for obesity risk prediction. Next, since there has been only limited research on when during development BMI-associated variants begin influencing BMI, a longitudinal twin study was utilized to assess the effects of adult-validated BMI-SNPs across adolescence into adulthood. In addition, obesity is comorbid with numerous medical conditions including cardiovascular disease, insulin-resistance and some forms of cancer, as well as, various psychiatric disorders including eating disorders, mood disorders, and substance use. The next series of studies aimed to understand phenotypic and genetic associations between BMI/obesity and binge eating disorder (BED), depression symptoms and smoking behavior. Using a clinical sample of overweight and obese women with and without BED, the relationship of BED, food intake and internalizing symptoms of depression and anxiety was examined. Next, twin study methodology was used to investigate if shared genetic and/or environmental liability was responsible for phenotypic associations found between BMI, depression symptoms, and impulsivity. Finally, a genetic association study aimed at investigating whether genetic variants were associated with multiple behaviors, body composition and smoking behavior, or were trait-specific is presented. By utilizing several samples and methodologies and by pursuing methods development, a comprehensive approach is presented that is hoped to represent a more powerful evidence-based strategy to understanding the genetic and environmental determinants of BMI and common complex obesity, along with associated depression symptoms and smoking behavior.
11
Nazir, Muhammad Shahid. "DNA persistence and preservation following environmental insult." Thesis, University of Central Lancashire, 2012. http://clok.uclan.ac.uk/6744/.
Abstract:
This research was conducted to provide empirical evidence to supplement advice available to the forensic community for the collection of muscle tissue for forensic analysis. This type of collection is normally carried out to determine the identity of individuals following mass disasters, such as plane crashes or natural disasters. DNA degradation was assessed in two model organisms, pig and rabbit (with human DNA as a control), over various time points. Rabbit recombination activating gene (RAG 1) was aligned to identify conserved regions in pig, rabbit and human. Primers were designed and optimised to create a 4-plex PCR multiplex that can amplify 70 bp, 194 bp, 305 bp and 384 bp in three species. The 4-plex multiplex was found to work efficiently in all three species down to 0.3 ng of DNA template. The multiplex was used to assess whether DNA degradation can be predicted by accumulated degree-days (ADD), which provides a measure of both time and temperature. A series of field studies were performed to assess DNA persistence in pig and rabbit soft muscle tissues using a combination of whole animals, suspended muscle tissues (insect activity free) and muscle fragments. Field studies were carried out in: August-September 2009; February-May 2010; May-June 2010; June-July 2010 and September-November 2010. Soft muscle tissue samples were collected at different ADD. 4-plex multiplex results showed that DNA was more persistent in pig tissues compared to rabbit tissues. In the September 2010 experiments, full multiplex amplification was obtained from rabbit until 137 ADD (whole carcases) and 210 ADD (body fragments and suspended tissues), while in the August 2009 experiments, full multiplex amplification was obtained until 112 ADD (whole carcases and body fragments) and until 141 ADD (suspended tissues). In the June 2010 experiments, full multiplex amplification was possible until 64 ADD. Pig whole carcases which were placed in the field in February 2010, showed multiplex amplification until day 90 (603 ADD), followed by September 2010 (until day 44 (490 ADD)) and May 2010 (until day 27 (338 ADD)). During the September 2010 project, body fragments produced full amplification until muscles were collected (342 ADD), while in case of whole carcases and suspended tissues; the amplification was possible until 490 ADD. There was complete failure of amplification of 305 bp and 384 bp in pig whole carcases after 342 ADD, while in suspended tissues, the amplification of 305 bp and 384 bp was possible until 420 ADD. The statistical analysis showed that amplification success of larger amplicons (194 bp, 305 bp and 384 bp) reduces with increase in ADD in pig and rabbit whole carcases, body fragments and suspended tissues while 70 bp was more persistence. The results showed that there was no significant difference in DNA persistence between whole carcases verses suspended tissues (Z=0.57, p>0.05) and whole carcases verses body fragments (Z=1.71, p>0.05), There was however a significant difference (Z=2.31, p<0.05) in DNA persistence in suspended tissues and body fragments with increase in ADD. The results from field experiments suggested that muscle tissues, if available, should be collected for DNA profiling, since even if degraded, a profile can be obtained. The results also suggested that the isolation of tissues from insect activity as quickly as possible (even if immediate storage is not possible) may be beneficial for DNA persistence. Seasonal variation in DNA persistence was observed due to maggot mass growth which increases carcase decomposition and ultimately effect on DNA persistence. Controlled incubation experiments were also performed at 27 °C, 37 °C and 47 °C until 21 days to assess DNA persistence, as these temperatures were not available under field conditions. The results showed that the amplification of 70 bp was more persistent compared to larger amplicons (194 bp, 305 bp and 384 bp). The drop-out in amplification of larger amplicons occurred more rapidly in samples incubated under laboratory conditions compared to the field samples. The statistical analysis showed species, ADD and temperature have strong effect (p<0.05) on DNA persistence under controlled conditions. The appearance of 70 bp amplicons in all samples collected from field and in most samples from controlled incubation experiments suggested that soft muscle tissues exposed to different environments can be used to perform SNP analysis. The full 4-plex multiplex amplification obtained from rabbit and pig preserved and dehydrated samples suggested that 96% ethanol, cell lysis solution (with and without 1% sodium azide) and dehydration can be used to preserve fresh and partially decomposed soft muscle tissues at room temperature for one year. The drop-out in amplification of larger amplicons in tissues preserved in 10% buffered formalin suggested that formalin was not suitable for long term storage. This system should therefore be considered as an additional method during Disaster victim identification (DVI) work to preserve fresh and partially decomposed samples. This study also suggested that the developed multiplex (4-plex) can be used to assess DNA persistence in human decomposing bodies and in experimental studies.
12
Ahsan, Rumana. "Association of self-reported different aspects of workplace environment and general wellbeing with maximum workload – A cross- sectional study." Thesis, Uppsala universitet, Internationell mödra- och barnhälsovård (IMCH), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-383592.
Abstract:
Introduction Cardiovascular disease (CVD) is the leading cause of death globally and similarly in United Kingdom (UK), accounting for 31% and 45% annual deaths respectively. Workplace environment consists of different elements (e.g.- physical and psychosocial environment, intra and extra organizational settings) and interrelationship of employer and employee, playing an important role on workers’ health. Current study aims to identify the association of different aspects of workplace environment and general wellbeing with maximum workload (MW) in a working population in UK. Method A cross-sectional study has been done including a total of 77,781 working people aged 39 to 72 years old who participated voluntarily in the UK Biobank baseline assessment cohort study. Exposures were selfreported that included information about both physical and psychosocial aspects of workplace environment and general well-being. The outcome variable was maximum workload calculated during electrocardiogram (ECG) stress test. Three different statistical models were tested through ordinal logistic regressions using the SPSS software. Results No/low health satisfaction was associated with reduction in maximum workload and this association was constant in all analytical model, both in crude (B -0.786, 95% CI -0.825, -0.748) and adjusted models (B -0.866, 95% CI -0.910, -0.823). Other variables regarding different aspects of workplace environment and well-being showed no statistically significant result on the adjusted models. Conclusion Health satisfaction may be considered as an important determinant of CVD among middle and old-aged working population. Future research required to establish the result and to formulate preventive measures in workplace for better health outcome of workers.
13
Giulio, Disanto. "Genetic and environmental factors influencing susceptibility to the complex disease multiple sclerosis." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:e44ea559-b48f-4e03-944c-7703f31a3aa6.
Abstract:
Multiple sclerosis is a complex immune mediated condition of the central nervous system characterized by myelin loss and progressive neurodegeneration. The risk of developing MS is influenced by both genetic and environmental agents and, among them, several lines of evidence support a role for vitamin D deficiency, Epstein-Barr virus (EBV) infection and smoking in the aetiology of this disease. The aim of this work was to further elucidate how nature and nurture act in the causal cascade leading to MS. In chapter 1, I show that the main genetic factor in adult MS (the HLA-DRB1*1501 allele) plays an equally important role in paediatric cases of MS (PMS) and that EBV negative PMS patients represent a separate entity characterized by lower age at disease onset, lower female to male ratio and a trend towards a lower frequency of the HLA-DRB1*1501 allele. In chapter 2, I provide evidence in support of month of birth having a role on MS risk and T cell production and that vitamin D may underlie this effect. In chapter 3 I demonstrate the presence of a link between vitamin D deficiency and the immune response against EBV, whereby the proportion of EBV seropositive MS patients and controls increases with increasing latitude and high dose vitamin D supplementation appears to reduce the level of antibodies against this virus. In chapter 4, I show that MS associated genetic variants are located in genomic regions that exert a regulatory function and are active in immune cell types. In chapter 5, I illustrate how vitamin D receptor binding is also located within active regulatory regions in immune cells and that this is particularly evident near MS associated genes. Finally, in chapter 6, I use chromatin data on more than 100 different cell types and conclude that MS associated genetic variants are particularly active in T helper, T cytotoxic and B cells. Further work is needed to elucidate how genetic and environmental agents play a role in the cause of MS and to develop effective strategies for disease treatment and prevention.
14
Richards, Karen A. "Development of an Instructional Design Model for Problem-Based Online Learning Environments in Continuing Medical Education." NSUWorks, 2004. http://nsuworks.nova.edu/gscis_etd/802.
Abstract:
Traditional methods that emphasize didactics and rote learning seem deficient to some medical educators. These approaches typically emphasize knowledge acquisition and retention of little relevance to practice. To improve problem solving, knowledge retention, and transfer, the educational strategy and philosophy of problem-based learning (PBL) is being used in medical education on-ground, face-to-face settings. The information age and advances in information technology now provide exciting new online education alternatives for physicians wanting to use this method to meet lifelong learning needs. The challenge for the instructional designer is how to migrate established face-to-face instructional methods to the online environment.
The goal of this dissertation was to provide a unique instructional design model that details criteria to guide the development of online PBL environments in continuing medical education (CME). The work addresses the following research questions: What influence should learning theory have on the instructional architecture of online PBL used to educate professionals in medical practice? How can computer technologies used in online instruction delivery incorporate relevant learning theories and cognitive principles to deliver effective online learning environments (OLEs) using the PBL method? What are the necessary elements in the development and implementation of a validated instructional design model for delivering online PBL in CME? This developmental research project also described how an OLE could be developed for physician continuing education in pain management along framework guidelines in order to illustrate concepts in the model and how it could be adapted to accommodate the course content of a particular medical specialty. Lessons learned in the process and implications for instructional design practice were discussed.
15
Meyers, Ronald B. "A Heuristic for Environmental Values and Ethics, and a Psychometric Instrument to Measure Adult Environmental Ethics and Willingness to Protect the Environment." The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1039113836.
16
Zhang, Rui. "Sex differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: The role of endothelium-derived relaxing factors." Scholarly Commons, 2013. https://scholarlycommons.pacific.edu/uop_etds/161.
Abstract:
Several studies suggest that diabetes affects male and female vascular beds differently. However, the mechanisms underlying the interaction of sex and diabetes remain to be investigated. This study investigates whether there are 1) sex differences in the development of abnormal vascular responses and 2) changes in the relative contributions of endothelium-derived relaxing factors (EDRFs) in modulating vascular reactivity of mesenteric arteries taken from streptozotocin (STZ)-induced diabetic rats at early and intermediate stages of the disease (one and eight weeks, respectively). We also investigated the mesenteric expression of the mRNAs for endothelial nitric oxide synthase (eNOS) and NADPH oxidase (Nox) in STZ-induced diabetes in both sexes. Vascular responses to acetylcholine (ACh) in mesenteric arterial rings pre-contracted with phenylephrine were measured before and after pretreatment with indomethacin (cyclooxygenase inhibitor), L -NAME (NOS inhibitor), or barium chloride (K IR blocker) plus ouabain (Na + -K + ATPase inhibitor). We demonstrated that ACh-induced relaxations were significantly impaired in mesenteric arteries from both male and female diabetic rats at one and eight weeks. However, at eight weeks the extent of impairment was significantly greater in diabetic females than diabetic males. Our data also showed that in females, the levels of eNOS and Nox2- and Nox4-dependent NADPH oxidase mRNA expression and the relative importance of NO to the regulation of vascular reactivity were substantially enhanced, while the importance of endothelium-derived hyperpolarizing factor (EDHF) was significantly reduced at both one and eight weeks after the induction of diabetes. This study reveals the predisposition of female rat mesenteric arteries to vascular injury after the induction of diabetes, may be due to a shift away from a putative EDHF, initially the major vasodilatory factor, towards a greater reliance on NO, and the interaction of oxidative stress with elevated NO.
17
Nichols, Alexander J. "Optical Molecular Sensing in Complex Biological Environments." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:14226087.
Abstract:
Although techniques in molecular imaging have advanced considerably over the past several decades, there remain numerous categories of biological molecular targets that are refractory to straightforward imaging. Among these is molecular oxygen, which is vital to a host of physiological as well as pathological processes, as well as the amorphous pigment pheomelanin, which may play a formerly unappreciated role in melanoma carcinogenesis.
This thesis describes two related bodies of work that advance techniques in oxygen and pheomelanin imaging, respectively. First, inspired by a desire to understand how hypoxia affects cancer chemotherapy on a cellular level, we designed and synthesized a novel oxygen-sensitive, dendritic nanoconstruct that is capable of spontaneously penetrating through hundreds of microns of multiple cellular layers. After demonstrating our nanoconjugate's oxygen sensitivity using time-domain phosphorescence lifetime measurements, we demonstrate that it retains its oxygen sensitivity in a 3D spheroid in vitro model of ovarian cancer through the use of a custom-made, near infrared-optimized confocal phosphorescence imaging system. Drawing from this approach, we then describe the fabrication and calibration of a separate oxygen-sensing bandage platform for use in wound-healing applications, and demonstrate its use in ex vivo and in vivo animal systems.
The second body of work describes the use of non-linear four-wave mixing techniques to facilitate straightforward imaging of the molecular pigment pheomelanin. Recent findings suggest that pheomelanin may play a previously unappreciated role in melanoma carcinogenesis, even in the complete absence of an ultraviolet light insult. However, due to its pale color, pheomelanin is difficult to visualize against a skin background, making its study challenging. After constructing a femtosecond-pulsed coherent anti-Stokes Raman scatter (CARS) microscopy imaging system, we use imaging and spectroscopy to provide proof-of-concept that pheomelanin can be imaged through a combination of CARS microscopy and electronically-enhanced four-wave mixing. We then use our non-linear imaging system to specifically observe pheomelanin in isolated "redhead" mouse melanocytes, and show through an siRNA gene knock-down strategy that our system can be used to observe changes in pheomelanin signal upon modification of biological pathways known to affect pheomelanin synthesis.
18
Wamono, Aye Aye. "Exploring students' conceptions of the racial and socio-cultural differences in the learning environment of a medical specialty." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29230.
Abstract:
Study problem
In the education of South African postgraduate medical specialities, various challenges that could have negative impacts on learning are evident. Racial and socio-cultural diversity in South Africa has roots in a previous societal structure that systematically discriminated against particular social groups resulting in significant political, economic and social inequalities between the groupings. With the current processes of transformation underway, the sphere of training postgraduate students in medical specialities reveals visible differences in racial backgrounds between students and consultants at the training centres across the nation, with the majority of consultants being Whites and Indians, whilst the majority of students are Black Africans and a few Indians. The recent high failure rate of the summative exit examination in certain specialities has stimulated a high level of interest into how racial and socio-cultural diversity may have influenced the training and learning of postgraduate students or registrars.
Theoretical framework
In this thesis, a conceptual framework is used that combines dimensions from the theories of Collins (1987), Collins, Brown and Holum (1991) on cognitive apprenticeship, Vygotsky (1978), Lave and Wenger (1991) on socio-cognitive and socio-cultural learning, and Bronfenbrenner’s (1977) theory on Human Ecology. Collectively they posit that relationships are central to the quality of learning and training. The education of postgraduate students, so called registrars or intermediary novices, is structured as personal mentoring in the form of cognitive apprenticeship and their legitimate participation in the departmental Community of Practice. Learning in this context occurs through daily service provision under supervision or mentorship, as well as unscheduled informal discussions (engagement) that reflect socio-cultural learning in which novices and consultant specialists interact socially and academically. This form of learning is dependent on effective mediation and participation, which depends upon understanding, trust and mutual respect in a relationship between the two parties. This relationship could be influenced by factors such as inter-personal differences. Whether the factors translate into socio-cultural differences such as language, culture and social identities, need to be determined.
Aim and objectives
The aim of the study was to explore the conceptions of two student groups, one who had left the specialist programme, and the other who had recently qualified, regarding the nature of racial and socio-cultural diversity in their learning environment, the influences on their learning, and how they responded to them.
Methodology
Using one of the medical speciality disciplines as a focus area, a qualitative enquiry using faceto-face in-depth interviews followed by a thematic analysis of descriptive data was employed. Participants were former students who had either left the formal training programme after being unsuccessful in the summative examination and reached the end of their employment contracts, or those who had recently passed the examination and qualified as junior specialists. The interviews were semi-structured to explore participant’s learning background through schooling, undergraduate and postgraduate studies, with focus on experiences in formative learning through these stages. The participant’s family socio-cultural background was also explored. Data analysis and interpretation were done using a social constructionist epistemology where meanings were co-constructed based on multiple perspectives
Findings and analysis
The following themes were identified from the data analysis: Theme
1: Racial and socio-cultural differences as barriers in learning, with the sub-themes: constructing ‘race’, ‘language’, ‘culture’, and ‘feeling excluded by social status’ as barriers to learning;
Theme 2: Relationships in the learning environment shaping learning, with sub-themes: ‘relationships in the early learning stage’, ‘relationships in undergraduate medicine’, and ‘relationships in postgraduate learning stage of speciality training’;
Theme 3: Challenges in the learning process, with sub-themes as: ‘lack of curricular clarity’, and ‘lack of formative learning structure’;
Theme 4: Resilience, with sub-themes: ‘capacity for adaption’, and ‘the ways in which resilience has been shaped by the micro- and macro-environments’.
The further analysis found the socio-cultural diversity and relationships affecting engagement during formative learning themes to be inter-related, whilst sub-themes race, language, culture and social identities were also inter-connected. The curriculum, formative training, relationships, people’s perspectives and culture of the community were found to be intricate and complex, yet difficulties could still be overcome using certain attributes and skills.
Conclusion
Participants perceived the racial and socio-cultural diversity such as language, culture, personality and socio-economic status in the postgraduate learning environment as barriers to learning. Participants in the group who had qualified were however able to negotiate the diversity by being resilient, adaptable and emotionally mature. These attributes enabled them to navigate difficulties and remain focussed on their goal. An ability to initiate and form relationships with new peers and consultants emerged as an important feature in this group. These findings could hopefully benefit both current and future students and highlight the need to create opportunities for cross-cultural engagement activities in medical speciality training programmes.
19
Dong, T. T. Trang. "Chemical composition and toxicity of emissions from burning five vegetation types of Western Australia under experimental combustion conditions." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2019. https://ro.ecu.edu.au/theses/2180.
Abstract:
This study investigated the emission factors (EFs) for inorganic gases (CO2, CO, SO2, NO and NO2), carbonyls (formaldehyde, acetaldehyde, acetone, propionaldehyde, butyraldehyde and benzaldehyde), volatile organic compounds (VOCs) and particulate matter (PM2.5 and PM10) from laboratory-based fires of vegetation from five typical vegetation types of Western Australia. Species burnt were three grasslands (Spinifex represented by Triodia basedowii, Kimberley grass represented by Sehima nervosum and Heteropogon contortus, and an invasive grass represented by Ehrharta calycina (Veldt grass)), Banksia woodland and Jarrah forest under different combustion conditions. Chemical composition (water-soluble metals and polycyclic aromatic hydrocarbons – PAHs) and in vitro toxicity of PM2.5 were also measured. Vegetation samples were burnt in a ceramic chamber in varying combustion conditions altered by controlling the vegetation moisture content (<10%, 12–16% and 20–25%) and the air flow rate (0, 1.25 and 2.94 m.s-1). Burns of woodland (Banksia) and forest (Jarrah) had significantly higher EFs for CO, SO2 and PM2.5 compared with those from grassland (Spinifex). Emissions of temperate grass (Veldt) fires were significantly different from those of the tropical grass (Spinifex and Kimberley grasses), with lower EFCO2 and higher EFs for CO, carbonyls and PM2.5. EFs for SO2, NO and NO2 were variable between different vegetation types, indicating variation in the nitrogen and sulphur content of the fuels. The EFs for most carbonyls were similar between most vegetation types, with the exception of Veldt grass. Functions which may be useful to predict emissions of infrequently measured carbonyls (acetaldehyde, acetone and propionaldehyde) from the EF for formaldehyde, a commonly measured and reported substance, were also proposed. Fifteen VOCs were identified in the smoke, but concentrations were too low to be quantified. Benzene, toluene, styrene and indene were the most frequently detected VOCs.
Moisture content did not strongly influence the modified combustion efficiency (MCE) and EFs for gaseous pollutants, but significantly affected the EF for PM2.5 with higher emissions from burns of moister vegetation. Increasing the air flow rate significantly increased the emissions of most pollutants. However, combustion conditions did not strongly affect the PM2.5 chemical composition.
The MCE, EFs for CO and CO2 results in this study were similar to values reported from field measurements for similar vegetation types in Australia, indicating the applicability of these laboratory-based results. Emission factors were different to the profiles generated from vegetation fires in other parts of the world.
Toxicity of PM2.5 on human lung epithelial (A549) cells was assessed using cell viability and cytokine production measurements. Responses on cell viability were associated with K and Na concentrations in PM2.5, whilst the cytokine production of cells was more affected by the PM2.5-bound PAH, Al, Cu and Mn concentrations. Toxicity between vegetation types was different, which might be due to the differences in chemical composition of PM2.5. PM2.5 emitted from Jarrah burns appeared to have the highest toxicity on epithelial cells, followed by those from Banksia, Veldt grass and Spinifex. The findings of this study on toxicity of PM2.5 demonstrate the adverse impact on human health of particulate from bushfires and emphasise the importance of vegetation type on toxicological outcomes of bushfire-derived PM2.5.
The EFs obtained in this study can be used in models to estimate the emissions from bushfires in Australia, particularly Western Australia. Results on toxicity of PM2.5 provide information for relevant government agencies to preliminarily evaluate the risk to human health, especially for firefighters and communities in close proximity to bushfire events.
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Triglia, Concetta. "Interpretive Phenomenological Analysis: Exploring the Experiences of Eye Bank Coordinators When Approaching Families of Decedents for Eye Donation." Diss., NSUWorks, 2018. https://nsuworks.nova.edu/hpd_hs_stuetd/9.
Abstract:
This dissertation was used to addresses a group of individuals who work as eye bank coordinators. These individuals call families and approach them for eye donations from a loved one who has just passed away. An interpretative phenomenological analysis (IPA) was used to explain the lived experience of eye bank coordinators who call families for consent of eye tissue. The focus was to understand the dedication of the coordinators to giving the gift of sight and exploring the positive and negative experiences of eye bank coordinators. IPA is used for a keen understanding of eye bank coordinators, and the investigator gained insight as to why their role and well-being is important to eye banks by conducting and analyzing the interviews through the lived experiences of eye bank coordinators. The theoretical underpinnings of this research were based on the theory of planned behavior and self-perception theory. Four participants were interviewed as to their positive and negative experiences in their daily work. The research questions were What are the positive and negative experiences of eye bank coordinators when requesting permission for eye donations from bereaved families (RQ1)? and How do the positive and negative lived experience of eye bank coordinators influence their adjustment of strategies when requesting permission for eye donations from bereaved families (RQ2)? Encountering positive and enthusiastic family donors, needing to understand the situation or grief of family members, encountering closed-minded family members, and limited negative encounters experienced were the main themes that addressed RQ1. The main themes that addressed RQ2 were having the energy and motivation to seek for more donors, ensuring the right information was conveyed to the families, feeling more relaxed and comfortable, continuing to explain and ensure the correct information was conveyed, coaching and collecting oneself back, knowing how to read the actions and reactions of families, and learning from experiences and becoming more cautious.
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Hernandez, Denise Marie. "Immunotoxicological Evaluation Of Critical Windows Of Development Following Exposure to 1,2:5,6 Dibenzanthracene in B6C3F1 Mice." VCU Scholars Compass, 2006. http://hdl.handle.net/10156/1605.
22
Vargas, Leah E. "The Ideology of the Federal Policy and Institutional Review Boards and its Effects on Research." Scholarly Commons, 2013. https://scholarlycommons.pacific.edu/uop_etds/208.
Abstract:
The Federal Policy for the protection of human subjects in research is built on a positivist ideology which effects Institutional Review Boards (IRB) and the research it reviews. An ideological criticism of the regulations through a positivist and postmodernist perspective reveals its initial purpose for biomedical research and its negative effects on research not discussed during its development. Such effects are a shift in focus on regulation over ethics in IRBs, extended oversight of regulations, revisions in research design and objectives, and self-regulation through the punishment of noncompliance.
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Juneby, Hans Bertil. "Sunlight - Essential for Health." Thesis, Umeå universitet, Yrkes- och miljömedicin, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-54040.
Abstract:
Sunlight is recognized as one of the most important environmental factors that influence human health. There is strong evidence in the scientific literature that adequate exposure to sunlight is associated with many physical and mental health benefits, including reduced overall mortality, prevention of many deadly forms of cancer, as well as a number of metabolic, cardiovascular, autoimmune, infectious and neuropsychatric diseases. Vitamin D deficiency, which is mainly due to insufficient exposure to sunlight, is now one of the most common medical conditions, estimated to affect more than a billion people worldwide. Health professionals, patients and the general public should receive more evidence-based information about the many health benefits of sunlight, and how to use it in prevention and treatment of disease.
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Alexander, Andrew William. "MMCTP : a radiotherapy research environment for Monte Carlo and patient-specific treatment planning." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101699.
Abstract:
Accurate dose calculations and analysis tools are essential to radiotherapy treatment planning. Radiotherapy deliveries utilize the information provided by the treatment planning system and it is generally accepted that clinical outcome can be improved if accuracy in the dose delivery is further improved. Proven Monte Carlo calculations increase the planning accuracy however, most radiotherapy departments do not use Monte Carlo. The McGill Monte Carlo treatment planning system, MMCTP, provides a flexible software environment to integrate Monte Carlo planning with current and new treatment modalities and deliveries. The MMCTP design consists of a graphical user interface, which runs on a simple workstation connected through standard secure-shell protocol to a cluster for lengthy Monte Carlo calculations. The impact of this tool lies in the fact that it allows for systematic, platform independent, large-scale Monte Carlo planning calculations for different treatment sites. Various measurements and patient recalculations were preformed to validate the software and ensure proper functionality.
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Krueger, Janice Maria. "Peer learning among family practice residents: Implications for instructional strategies and curriculum enhancement in medical education." Scholarly Commons, 2005. https://scholarlycommons.pacific.edu/uop_etds/2454.
Abstract:
Over the years, graduate medical education has changed in order to create learning environments to best prepare physicians. The present system of residency and hospital affiliation was the model adopted to give students opportunities for active learning along with lecture and observation. This study investigated the varied ways residents learn the knowledge, skills, and dispositions necessary for family practice. A within-site case study approach was used since this was a study of peer learning among family practice residents at a single community based hospital in a university affiliated network having an opposed program. A purposeful and typical case sampling strategy was used so that key participants provided information about their experiences with how the peer interactions among residents contributed to learning. The study had a sample of 11 residents progressing through this program and each participant was interviewed twice. Additional data were collected through observations of the morning and teaching rounds, an observation of the orientation session for new residents, and from program requirement documents. Each interview, observation, and document underwent content analysis for the identification of any emerging central themes or patterns and patterns were grouped according to recurring categories. Of particular interest were the themes that flowed from the interview and observation analysis for each resident class and the application of these themes to major learning theories. Matrix displays of themes that emerged between resident classes, of themes within the same resident class, and of the themes demonstrating relevant learning theories were developed and presented. Data analysis revealed themes categorized by learning process, achievement, identity as a physician, competence, and program improvement. The learning process consisted of various strategies, peer interactions, and use of resources. The within class analysis found varying degrees of strategies and peer interactions for each of the classes and the between class analysis found a progression of strategies, skills, achievement, identity, and changing peer interactions. Themes analyzed according to major learning theories demonstrated similarities to activity theory, social learning theory, and communities of practice. This study revealed that peer mentoring, coaching, and learning occurred within the context of a community of practice.
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Russell-Babin, Kathleen. "Comparison of educational interventions to impact behavioral intent toward pressure ulcer prevention among nurses on medical surgical units." Thesis, NSUWorks, 2013. https://nsuworks.nova.edu/hpd_con_stuetd/5.
Abstract:
Background: Implementation of evidence-based knowledge in healthcare is challenging with success rates less than optimal at times. This is particularly true in the area of pressure ulcer prevention. Attention to use of the affective domain in educational interventions to implement best practices may be part of the solution. Purpose: The ultimate purpose of this study was to compare the use of two different educational interventions on medical-surgical nurses' behavioral intent to use evidence-based practice in preventing pressure ulcers. Theoretical Framework: The theoretical framework for this study was the theory of planned behavior. Methods: This study proceeded in three phases and collected both qualitative and quantitative data for instrument development and instrument testing. The resultant instrument was used to collect data for hypothesis testing in a cluster randomized experiment. Results: The theory of planned behavior was not fully supported in this study. Attitudes toward pressure ulcers were predictive of behavioral intent. Nurses who experienced the affective domain educational intervention showed significant improvements over the control group on attitude and perceived behavioral control. Behavioral intent and subjective norm were not impacted. Conclusions: A reliable and valid theory of planned behavior derived instrument was created. The theory of planned behavior was partially supported. An affective domain intervention has the potential to favorably impact nurses in valuing pressure ulcer prevention, despite any barriers.
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Tejomurthula, Sravanthi. "Overexpression of Human Aryl Hydrocarbon Receptor in E.coli Using Two Different Solubility Enhancing Tags." Scholarly Commons, 2017. https://scholarlycommons.pacific.edu/uop_etds/261.
Abstract:
Dioxins such as TCDD are environment pollutants whose toxic effects are mediated via aryl hydrocarbon receptor (AhR) signaling pathway. AhR is a ligand sensitive transcription factor. The unbound AhR resides in cytoplasm as a complex containing p23, Hsp90 and XAP2. Upon ligand binding, AhR undergoes conformational change and translocates into the nucleus. Once the AhR dimerizes with AhR nuclear translocator (Arnt), the chaperone proteins in the complex get dissociated followed by the activation of transcription of various genes such as CYP1A1 and CYP1A2 by AhR-ARNT heterodimer. Various cancers have altered levels of AhR in the absence of ligand. Our current knowledge is only limited in the regulation of AhR protein levels in its ligand bound state. However, the mechanism involved in the regulation of AhR protein levels in the absence of ligand is still unknown. To make the study of AhR signaling pathway possible, our lab has been working on the expression of various AhR constructs in E.coli using recombinant DNA technology. As AhR forms inclusion bodies due to its poor solubility in the cytoplasm of the host bacteria, it is tagged as a “difficult to express” protein. Therefore, it is challenging to generate functional recombinant AhR protein. My thesis documents the expression of human AhR construct amino acid 108-400 using two different solubility enhancing tags (thioredoxin and maltose binding protein). Western blot data revealed that the soluble expression of the human AhR construct by thioredoxin solubility enhancing tag has outperformed the other.
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Patlolla, Karthik Reddy. "Predicting aqueous solubility of pharmaceutical agents by solid dispersion prepared by solvent evaporation method." Scholarly Commons, 2015. https://scholarlycommons.pacific.edu/uop_etds/268.
Abstract:
Solubility of active pharmaceutical agents is a crucial process that determines drug absorption and ultimately its bioavailability. Many of the new therapeutically beneficial compounds discovered are lipophilic requiring various solubility enhancement strategies to improve their solubility. Among these strategies, solubility enhancement using solid dispersions is a leading method. To obtain a desirable increase in the solubility of a poorly-soluble compound, a good understanding of the molecular descriptors influencing the enhancement of solubility is essential. Therefore, the major research objective was to determine the descriptors which significantly influence the solubility enhancement by solid dispersions. After enhancing the solubility of selected poorly-soluble model compounds, a regression analysis was performed to determine the correlation of molecular descriptors of the active agent, polymer, and solvent with solubility enhancement. The partition co-efficient, hydrogen bonding and solubility parameters of polymer and water were found to influence the aqueous solubility of the poorly-soluble compounds. Aqueous solubility of a compound had an inverse relation with difference in solubility parameters of polymer and water. Similarly partition coefficient was found to be inversely related to aqueous solubility. However for an increase in hydrogen bond acceptors present in pharmaceutical agents increased their solubility, while the higher number hydrogen bond donors resulted in lower solubility. This complexity can be attributed to the contribution of hydrogen bonding in a crystal lattice and in aqueous environment. In conclusion, the contribution of partition co-efficient, solubility parameter and hydrogen bonding were found to be significant for a given set of poorly-soluble model compounds selected with a wide range of descriptors. Several models estimating aqueous solubility of compounds have been employed as screening tool in drug development process. However, all such models were developed to estimate aqueous solubility of pure active agents. Hence, the second research objective was to develop a model that could estimate aqueous solubility of Active Pharmaceutical Ingredient (API) in solubility-enhanced solid dispersions. Using multiple linear regression, a computational model was developed using the molecular descriptors of poorly-soluble compound, polymer and water. S=(2.02*HBA)-(3.37*??)-(11.56*log?P )-(0.9*HBD)+119.66 The model showed a regression (R2) value of 0.858. Upon validation, the model estimated the aqueous solubility of 79% of the compositions evaluated with within 20% variability.
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Yang, Dazhou. "Synthesis and biophysical evaluation of thiazole orange derivatives as DNA binding ligands." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/141.
Abstract:
Guanine-rich telomeric DNA at the end of chromosomes can form a unique DNA tertiary structure - G-quadruplex, which is known to inhibit the binding of telomerase to telomeric regions in cancer cells and thus regulate unrestricted cancer cell growth. Hence, G-quadruplex DNA has recently become a promising target in oncology. The formation of G-quadruplex structures is greatly facilitated by G-quadruplex binding ligands such as Thiazole orange (TO). Compared with other G-quadruplex binding ligands, TO has an intriguing tunable fluorescence property. Upon binding to DNA, the fluorescence of TO can increase up to 1000-fold, making it an attractive probe for studying ligand-DNA interactions. However, the poor binding affinity and minimal binding selectivity towards different DNA conformations greatly limit its applications. My research focuses on developing G-quadruplex binding ligands using TO as a scaffold. In the first part of this work, we investigated the feasibility of increasing the TO binding affinity and selectivity toward G-quadruplex DNA by introducing side chains to the molecule. TO derivatives containing various side chains were successfully synthesized and characterized. Biophysical and biochemical studies with duplex and G-quadruplex DNA showed that tethering side chains to TO is an effective approach to tune its ability of binding to duplex or G-quadruplex DNA. Possible binding modes of the effective derivatives were studied using AutoDock. Their inhibition of telomerase activities was studied using the TRAP assay. The cytotoxicity of these derivatives toward three cancer cell lines was also investigated using the MTS assay. The second part of this work focuses on development of TO-based G-quadruplex DNA binding ligands that can bind to DNA via the dual recognition mode. TO was tethered with pyrene, naphthalene diimide, and anthraquinone respectively to yield three novel conjugates. Further investigation suggested that the conjugate of TO with naphthalene diimide (TO-NF) gave the best G-quadruplex binding affinity. It binds to G-quadruplex DNA via the end stack mode and strongly inhibits the telomerase activity. The cytotoxicity results will also be discussed in this presentation.
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Naidu, Prathyusha. "Catalase-loaded liposomal magnesium phosphate nanoparticles for intracellular protein delivery." Scholarly Commons, 2016. https://scholarlycommons.pacific.edu/uop_etds/266.
Abstract:
Proteins are large biomolecules that have great therapeutic potential in treating many human diseases. Proteins exert higher specificity and more complicated functions; they are well endured and less inclined to evoke immune responses when compared to small molecule drugs. However, exogenous proteins when administered intravenously are prone to immune reactions. Chemical and enzymatic denaturation, and poor penetration into cells are some other challenges for clinical use of intracellular proteins. Proteins that enter cells through endocytosis will be eventually degraded in lysosomes if they do not escape the endosomal pathway before reaching lysosomes. Therefore, the development of protein delivery systems, including liposomal and/or polymeric nanoparticles would substantially facilitate the clinical use of proteins. This approach can protect the proteins from denaturation and immune reactions. Previously, our group has developed cationic lipid-coated magnesium phosphate nanoparticle (CAT-LP MgP NP) formulations to enhance the intracellular delivery of the protein, catalase. The objective of the current research is to improve the physicochemical properties of CAT-LP MgP NP. The magnesium phosphate (MgP) nanoparticles were prepared by water-in-oil micro emulsion precipitation. The cargo protein catalase was complexed with cationic liposome prepared by lipid hydration and extrusion. Then magnesium phosphate (MgP) nanoparticles were mixed with the catalase-complexed cationic liposome to form the final complexed CAT-LP MgP NP formulation. By sonication, extrusion and modification of the lipid composition, we have successfully prepared complexed CAT-LP MgP NP formulations of reduced size. The pH-sensitivity of the improved delivery system was observed at pH 6.0. Furthermore, the improved delivery system reduced the Reactive Oxygen Species (ROS) level inside EA.hy.926 cells (human umbilical vein endothelial cells) to 35% of the control, whereas the previously reported catalase formulation of our group reduced the ROS levels to 50%, indicating that the complexed formulation delivers functional catalase more efficiently into the EA.hy.926 cells. Complexed CAT-LP MgP NP with reduced size has delivered cargo protein more efficiently than encapsulated CAT-LP MgP NP.
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Kondepudi, Karthik Chalam. "Computational prediction of enhanced solubility of poorly aqueous soluble drugs prepared by hot melt method." Scholarly Commons, 2015. https://scholarlycommons.pacific.edu/uop_etds/267.
Abstract:
Solubility is the concentration of a solute in a saturated solution at a given temperature and pressure. Solubility of a drug in aqueous media is a pre-requisite to achieve desired concentration of a drug in the systemic circulation. Low aqueous solubility is a major problem encountered with formulation development of recently designed new chemical entities. Solubility of poorly soluble drugs is enhanced by physical and chemical modifications of drug. Shake flask method is the most commonly used experimental method to determine solubility. However, this method has several limitations. A single solubility experiment can go on for several days and even weeks. Besides this, a large amount of drug is required to carry out the experiment. In order to overcome this and make initial screening easier, computational method can be used to predict solubility. In this study, the solubility of 12 small molecules of BCS class II having a wide range of physicochemical properties were studied to enhance their solubility by hot melt method. Three different grades of PEG (1450, 4000, 8000), PVP K17 and Urea as the hydrophilic carriers was employed for the solubility enhancement. The overall objective of this investigation is to develop a model that could estimate enhanced solubility using physicochemical descriptors. Multiple linear regression (MLR), a statistical tool, was used to generate a equation for the solubility by correlating physicochemical properties of the drug like- molecular size, logP, pKa, HBA, HBD, melting point, polar surface area, and number of rotatable bonds. Solubility enhancement is also influenced by the carrier used, we included the physicochemical properties of the carriers like molecular weight and solubility parameter in the development of the model. MLR analysis model, resulted in an equation, where, Log solubility = 5.982-0.010 MW (drug)-0.452 LogP-0.320 HBA-0.095 ?solubility parameter+0.015 MV. A regression analysis yielded a good fit with a regression value (adjusted R2) of 0.74. The model has been validated by leave one out method. This model has the potential to estimate the solubility of a physically modified drug in screening stages of drug development.
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Vutukuru, Naresh Kumar Reddy. "Apparent dissolution rate enhancement of poorly-water soluble drugs by adsorption technique." Scholarly Commons, 2015. https://scholarlycommons.pacific.edu/uop_etds/269.
Abstract:
Nearly 70% of the new chemical entities (NCE’s) discovered are poorly-water soluble drugs and the number of poorly-water soluble drugs are increasing rapidly in the drug discovery. Most of the NCE’s are lipophilic and have dissolution rate issues. Low dissolution rate of the drugs result in poor bioavailability. To overcome poor bioavailability, an adsorption technique is developed to enhance the apparent dissolution rate of poorly-water soluble drugs. In this study, two poor-water soluble model drugs, ibuprofen and carvedilol were used. Methanol, DMF, DMSO and PEG400 were used as solvents and microcrystalline cellulose was used as an adsorbent. Pure model drugs, physical mixtures and prepared composites were characterized by using FTIR, DSC, XRD and dissolution testing. Results showed that the composites prepared with solvents DMF, DMSO and PEG400 showed enhancement in dissolution rates of two model drugs. Characterization of the composites prepared by using non-volatile solvents showed successful conversion of crystalline model drugs into solution state. Whereas, composites prepared by using volatile solvent showed similar results like physical mixtures and pure drug. Ibuprofen composites containing DMF, DMSO and PEG400 showed 9.4, 7.4 and 1.8 folds of increase in apparent dissolution rate, respectively. Whereas carvedilol composites containing DMF and DMSO showed 11.52 and 3.4 folds of increase in apparent dissolution rate. Four months of stability study were conducted on prepared composites at both 40°C and room temperature. It was observed that prepared composites were stable after 4 months and exhibited similar dissolution rate. In conclusion, the use of non-volatile solvents disrupted the crystal structure but also retained the drug in solution state which in turn enhanced the apparent dissolution rate of model drugs used. From the observed results we conclude that this method has a potential to replace existing techniques to enhance the apparent dissolution rate of the drug and stability of the composites.
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Vangala, Swathi. "Human Cytochrome P450 3A4 Over-Expressing IEC-18 and MDCK Cell Lines as an In-Vitro Model to Assess Gut Permeability and the Enzyme Metabolism." Scholarly Commons, 2013. https://scholarlycommons.pacific.edu/uop_etds/273.
Abstract:
Purpose. The fate of an orally administered drug is dependent on many parameters before it can reach the systemic circulation, including drug absorption and first-pass metabolism in the gut and the liver. Mammalian cells lines such as MDCK and Caco-2 are commonly employed to assess drug permeability but they lack or have low expression level of drug metabolism enzyme expression such as CYP3A4, which contributes to significant first-pass gut and liver metabolism for many drugs. Consequently, these cell lines are not sufficient to integrate metabolism when assessing drug absorption. Here, we tested MDCK and IEC-18 cells transiently over-expressing CYP3A4 as models that can simultaneously assay a compound's permeability and metabolism potential in a single experiment. Method. A recombinant adenovirus carrying the hCYP3A4 cDNA was constructed according to Stratagene's AdEasy XL Adenoviral system. This adenovirus was used to transiently transfect hCYP3A4 into MDCK and IEC-18 cells. Western blot was performed to assess the level of hCYP3A4 expression in the wild type and CYP3A4 over-expressing IEC-18 and MDCK cells. In situ metabolism and transport studies were performed with wild-types and IEC-18-3A4 or MDCK-3A4 cells. Results. The amount of CYP3A4 present in MDCK-3A4 cells was 250 times to that of wild type cells which 1/4th the amount present in human liver microsomes. The amount of CYP3A4 present in IEC-18-3A4 cells was 150 times to that of wild type cells which 1/6th the amount present in human liver microsomes. In metabolism studies, there was higher formation of metabolites in cells transfected with hCYP3A4 compared to controls. In addition, apical to basal transport studies of several drugs in IEC-18-3A4 and MDCK-3A4 showed increased appearance of metabolites compared to the wild-type cells. Conclusions. This model may be a useful to assess the extent of drug absorption into systemic circulation after oral administration.
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Nannapaneni, Vijaysri. "Preparation of amorphous forms to increase the solubility of poorly soluble drugs using spray drying." Scholarly Commons, 2011. https://scholarlycommons.pacific.edu/uop_etds/274.
Abstract:
Spray drying is widely used in enhancing the aqueous solubility of poorly soluble compounds. In this study, the mechanism of solubility enhancement was characterized using three model drugs-naproxen, ketoprofen and furosemide. Physical mixtures of the model drug with polyvinylpyrrolidine and spray dried composites were subjected to Fourier Transform Infrared Sprectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (XRPD). The data showed that the crystalline model drugs were converted to amorphous form upon spray drying, whereas the physical mixtures did not change their crystallinity. The effect of the amorphous forms produced by Spray drying on apparent solubility and intrinsic dissolution rate was determined. All the spray dried composites exhibited higher apparent solubility and intrinsic dissolution rate when compared to the pure drugs and their physical mixtures. The stability of the spray dried composites upon storage was also determined. The amorphous nature of the compounds in the spray dried composites were retained during 3 months storage as shown by FTIR, DSC and XRPD characterization and their apparent solubility and intrinsic dissolution rates also did not change.
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Higashi, Carol Judie. "A Correlational Study Of The Characteristic Values And Needs With Work Related Factors Among Registered Nurses (Aspiration, Job Satisfaction)." Scholarly Commons, 1986. https://scholarlycommons.pacific.edu/uop_etds/3231.
Abstract:
Purpose. The purpose of this study was to determine whether there were distinctive interpersonal characteristic values and personality needs which related to registered nurses as a group and, whether these characteristics differed within the categories of various work related factors. Procedures. A multistage cluster sampling procedure was used within a four county area in northern California. A random sample of staff-level nurses from five acute care hospitals provided data for this study. Dependent variables were derived from Gordon's Survey of Interpersonal Values, Edwards Personal Preference Schedule, and a questionnaire devised and pre-tested by the researcher measuring the nurses' level of job satisfaction and aspiration in nursing. Independent variables included demographic data which included work related factors. The t-test, Pearson product-moment correlation, one-way analysis of variance, Fisher's L.S.D. multiple comparisons approach, and multiple regression analysis procedures were used to answer the research questions in this study. Findings. The sample group demonstrated significant correlations between job satisfaction scores and the interpersonal characteristic values of Conformity and Independence with Independence being negatively correlated. Significant positive correlations were noted between the nurses' aspiration level in nursing and Leadership, Affiliation, Dominance, and Heterosexuality, whereas, negative correlations were noted with Independence, Deference, and Order. Diploma nurses scored higher than associate and baccalaureate degree nurses on Conformity and Order. Nurses employed within the categories of twelve years or more scored higher on Deference. Nurses who were employed less than twelve years scored higher on Heterosexuality. Results also indicated a significant relationship between the intensity level of the nurses' work assignment and Heterosexuality. Recommendations. Development of a research instrument which is more specific to the assessment of critical elements associated with the nurses' values and needs and employment factors is recommended. Although the variables measured by the instruments employed in this study were appropriate, it was a very time consuming process for the participants. Further research questions were generated from this study.
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Ponnakanti, Himaja. "Soluble and Functional Overexpression of the Ligand Binding Domain of Mouse Aryl Hydrocarbon Receptor in E.Coli." Scholarly Commons, 2017. https://scholarlycommons.pacific.edu/uop_etds/260.
Abstract:
The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor whose toxicity and carcinogenesis is mediated through various polyaromatic hydrocarbons and other environmental pollutants. The role of AhR in carcinogenesis is an area of concern due its altered levels in various tumors. AhR binds structurally diverse ligands and may elicit different responses upon ligand binding. The crystal structure of mouse AhR PAS-A domain was already obtained due to the robustness of mouse AhR in comparison to human. There is a possibility of overexpressing mouse AhR ligand binding domain in its soluble and functional form, which could be used to perform ligand binding studies. This forms the aim of this thesis. Mouse AhR ligand binding domain was constructed as mAhR aa211-384, which was purified under native conditions with the use of 6 histidine tag but soluble overexpression was not possible. Thus a solubility enhancing tag called maltose binding protein (MBP) was used for purification of mAhR aa211-384 under native conditions, which still did not yield soluble overexpression. The strategy was modified to solubilize the protein by denaturation with the use of 8M Urea, which solubilized the protein but included an issue of protein binding to column. Subsequent use of an even stronger denaturant, 6M guanidine hydrochloride, solubilized most of the protein and purified mAhR aa211-384 in huge amount. Successful refolding of mAhR aa211-384 with the help of MBP was made possible by gradual reduction of denaturant in the presence of arginine, but 6 histidine tag failed to refold the protein. The refolded protein was tested for its secondary structure by circular dichroism. Thus, mAhR aa211-384 was solubilized and purified under denaturing conditions with the help of both 6 histidine and MBP, however efficient refolding of mAhR aa211-384 was only possible with the help of MBP but not 6 histidine. The MBP-refolded mAhR aa211-384 stayed in solution even after the removal of 0.1 M arginine, thus confirming the effectiveness of MBP in protein refolding in comparison to 6 histidine tag.
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Kim, Jeong-Lim. "Environmental Factors in Relation to Asthma and Respiratory Symptoms among Schoolchildren in Sweden and Korea." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7418.
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Ivy, Devon. "DEFINING THE RADIORESPONSE OF MOSSY CELLS." CSUSB ScholarWorks, 2018. https://scholarworks.lib.csusb.edu/etd/633.
Abstract:
Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in detail. I hypothesize that mossy cells are critical targets for ionizing radiation, whereby damage to these targets contributes to the mechanisms associated with radiation-induced hippocampal dysfunction.
To test this idea, wild-type mice were exposed to clinically relevant doses of cranial x-ray irradiation and their hippocampi were examined 1 month and 3 months post treatment. A significant decline in both the number of mossy cells and their activity were observed. In addition, dentate granular cells demonstrated reduced levels of activity, as well as reduced proliferation within the subgranular zone. A second cohort of mice was introduced to a novel environment in order to induce the expression of immediate early genes. Analysis of c-Fos mRNA yielded a significant increase in control but not irradiated animals, suggesting that radiotherapy impaired immediate early gene expression and resultant functional behavioral outcomes. These findings support the proposition that radiation-induced damage to mossy cells contributes to hippocampal deficiencies which result in cognitive dysfunction.
39
Fang, Yunzhou. "A novel intracellular protein delivery system - Magnesium phosphate nanoparticles with cationic lipid coating for catalase intracellular delivery." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/270.
Abstract:
Protein therapeutics have great potential in treating human disease, especially for those caused by alternations in the functions of intracellular proteins. However, clinical use of protein by intracellular delivery has been hampered by the instability due to proteins' physicochemical properties, and some barriers in the delivery pathway. This study was to prepare and test a novel intracellular protein delivery system - magnesium phosphate nanoparticles with cationic lipid coating for catalase intracellular delivery (LP MgP NP-CAT), and investigate whether it can release the encapsulated catalase to cytosol. LP MgP NP-CAT was designed, prepared and characterized, showing that it had an average diameter around 300 nm and zeta potential around +40mV. The pH - triggered catalase release from LP MgP NP-CAT was determined by a hydrogen peroxide degradation assay, where the concentration of remaining hydrogen peroxide was measured by UV-Vis spectroscopy, indicating catalase was released in response to the drop of pH, which was confirmed by the morphology change of LP MgP NP-CAT observed by transmission electron microscopy. The in vitro catalase release behavior was conducted on MCF-7 cells and EA.hy926 cells. LP MgP NP-CAT was delivered into MCF-7 cells and the release behavior was determined by the resultant resistance of the cells against hydrogen peroxide using MTS cell viability assay. The delivery of LP MgP NP-CAT into EA.hy926 cells was determined by the decrease of the reactive oxygen species level. Both of the studies showed that catalase was successfully delivered and released which is supported by the reduction of hydrogen peroxide.
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Sachdeva, Sameer. "Design and applications of antibody mimics against epidermal growth factor receptor." Scholarly Commons, 2015. https://scholarlycommons.pacific.edu/uop_etds/132.
Abstract:
Antibodies have been widely used as reagents, homing devices, diagnostics and as therapeutic agents against different targets in clinic and research. Recently a number of monoclonal antibodies and their drug conjugates have been approved as therapeutic agents. While these molecules have great potential in various applications and therapeutics, extensive use of full length antibodies has been hampered by the high cost of production, large molecular weight and limited ability to penetrate tumor tissues. These limitations have led to the research for antibody alternatives with lower molecular weight, similar binding and affinity properties but without the lengthy and complicate process of generating antibodies. Some examples of these efforts include minibodies, fragment antigen binding (FAB), ScFv, and synthetic antibody mimics. Although these antibody alternatives have low molecular weight, as compared to the antibody, they are either derived from full size antibodies or by a long and tedious in vitro screening process. Therefore, a rational design of molecules that mimic antibody binding is a logical first step for the development of antibody alternatives. In this study, a novel approach to design antibody mimics without involving massive experimental screening was developed. The design was developed by mapping and identifying EGFR epitope region where Cetuximab CDR binds and modifying sequences using knob-socket computational model. The binding of antibody mimics were first analyzed by using MOE to obtain the binding energy, total and preserved interactions as compared to the interactions between EGFR and Cetuximab. Further, the designed antibody mimics were used to form a peptide drug conjugate (PDC). Antibody mimics were found to specifically bind and internalized by EGFR overexpressing cell lines with three to four folds higher than control cells. Antibody mimics showed binding in nanomolar range with Pep11 with binding affinity (K D ) of 252nM as shown by SPR studies. EGFR phosphorylation studies also showed that antibody mimics were able to inhibit the binding of EGF to the EGFR in a similar fashion as Cetuximab. Specific binding, affinity and functional activity of the antibody mimics demonstrated that these peptides were able to mimic all the three important characteristics of antibodies. Peptide drug conjugate (PDC) was found to be around 10 fold more potent as compared to the drug itself towards EGFR overexpressed cancer cells. PDC also showed more than 100 fold low potency against control cells. These studies demonstrated that a rational design of molecules to mimic the antibody characteristics is feasible. The antibody mimics were also successfully applied and used as targeting moiety to design peptide drug conjugates for efficient targeted drug delivery system than antibody drug conjugates.
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Sun, Jingjing. "Exploring the effect of alpha2 receptor on brain 5-HT via a mechanism-based pharmacodynamic model." Scholarly Commons, 2012. https://scholarlycommons.pacific.edu/uop_etds/154.
Abstract:
Purpose: 5-hydroxytryptamine (5-HT) is an important neurotransmitter in depression. It is believed that α 1 and α 2 adrenoceptors mediate the 5-HT level in the brain. The mechanism is complex and not well explored. Especially in different combination treatments, the receptor systems may show varied modulation capability. Additionally, some research has suggested that α 2 heteroceptors may contribute to the time delay problem in dual depression treatment which is thought as the time needed for certain inhibition receptor to get desensitized. We hypothesized that the α 2 adrenoceptors had inhibition effect on 5-HT level in dorsal raphé nucleus (DRN), Prefrontal cortex (PFC) and Hippocampus (HP) with the dual reuptake inhibition. The present study was undertaken to explore the effect of BRL44408 (α 2 receptor antagonist) on 5-HT level in rat PFC, DRN and HP under dual antidepressant with blocking the α 1 receptor. Method: Serotonin reuptake inhibitor and norepinephrine reuptake inhibitor were used to mimic the dual reuptake inhibition antidepressant. To differentiate the α 2 adrenoceptors effect from al adrenoceptors effect, prazosin, an antagonist of α 1 adrenoceptors, was added to block α 1 adrenoceptors. Using the microdialysis method, the drug combination was examined in HP area and then DRN area to explore the drug effect on time course of 5-HT release in DRN and PFC. Based on the experiment results from DRN and PFC, a mechanism-based pharmacodynamic model was developed. Result: BRL44408 increased the serotonin (5-HT) level in rat PFC, DRN and HP to different degrees with the dual reuptake inhibition (p < 0.05). The overall model reasonably captured the time course of 5-HT in both DRN and PFC with different dose schemes of BRL44408. The model predicted EC50 of BRL44408 (0.0075 µM) for the α 2 heteroreceptor which control PFC 5-HT is close to the reported value of BRL44408 for α 2 adrenorceptor (0.008 µM). However, the model predicted EC50 of BRL44408 on the α 2 heteroreceptor which control DRN 5-HT need to be explained. Simulation result from this model suggested varied modulation capability of α 2 adrenoceptors on the 5-HT in DRN and the 5-HT in PFC. Conclusion: α 2 heteroceptor play a role in regulation 5-HT level under dual reuptake inhibition. Further exploration may bring a potential target for depression treatment. The mechanism model was developed to characterize and better understand the neurotransmitter mechanisms, providing estimations of various parameters of the disease related receptor system.
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Schneidereit, Dominik [Verfasser], Oliver [Akademischer Betreuer] Friedrich, Oliver [Gutachter] Friedrich, and Boris [Gutachter] Martinac. "Novel Opto-Biomechatronics System Technologies in the Cardio- and Musculoskeletal Environment of Medical and Life Sciences / Dominik Schneidereit ; Gutachter: Oliver Friedrich, Boris Martinac ; Betreuer: Oliver Friedrich." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2021. http://d-nb.info/1226428142/34.
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Barbosa, Melanie Audrey Gomes. "Obesity and environmental pollutants: a reason for concern?" Master's thesis, 2017. https://repositorio-aberto.up.pt/handle/10216/109123.
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Barbosa, Melanie Audrey Gomes. "Obesity and environmental pollutants: a reason for concern?" Dissertação, 2017. https://repositorio-aberto.up.pt/handle/10216/109123.
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Baptista, Vânia Catarina Vieira. "Impacts of environmental changes on bivalves harvesting in Portuguese coast." Master's thesis, 2012. https://repositorio-aberto.up.pt/handle/10216/107755.
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Baptista, Vânia Catarina Vieira. "Impacts of environmental changes on bivalves harvesting in Portuguese coast." Dissertação, 2012. https://repositorio-aberto.up.pt/handle/10216/107755.
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Magalhães, Mariana Leite Silva de. "Review of Environmental Factors in Antisocial Behavior." Dissertação, 2015. https://repositorio-aberto.up.pt/handle/10216/88436.
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Lima, Daniela da Silva. "Environmental origins of obesity: are phthalates to blame?" Dissertação, 2019. https://hdl.handle.net/10216/120543.
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Silva, Cátia Sofia Rodrigues. "HPLC enantioseparation of tramadol and its metabolites: method validation and application to environmental samples." Master's thesis, 2016. https://repositorio-aberto.up.pt/handle/10216/86860.
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Silva, Cátia Sofia Rodrigues. "HPLC enantioseparation of tramadol and its metabolites: method validation and application to environmental samples." Dissertação, 2016. https://repositorio-aberto.up.pt/handle/10216/86860.