Radiofármacos são compostos radioativos que podem ser usados tanto para diagnóstico como para terapia. O radiofármaco 99m-Tc-MIBI é a formação de um complexo contendo o radionúclideo Tecnécium-99m e seis moléculas de Sestamibi, usado principalmente para cintilografias do miocárdio, sendo o procedimento mais realizado dentro da medicina nuclear, por consequência, o radiofármaco mais comercializado. Já o radiofármaco 99m-Tc-DTPA é composto também pelo mesmo radioisótopo e por uma molécula de ácido pentético, a qual tem característica de um quelante com afinidade pelos rins, por isso, é possível fazer avaliação do sistema renal. Como os radiofármacos são considerados medicamentos, estão sujeitos às mesmas normativas, logo o objetivo deste trabalho foi desenvolver metodologia de doseamento destes insumos ativos antes da complexação com o radionuclídeo através da metodologia de Cromatografia Líquida de Alta Eficiência (CLAE). Dois métodos simples e eficientes foram desenvolvidos e validados para o MIBI em produto acabado e para a matéria-prima ácido pentético (DTPA), utilizando-se misturas de solvente orgânico e tampão. Os parâmetros de validação foram avaliados, obtendo resultados satisfatórios. Um teste de estabilidade para o radiofármaco MIBI em solução foi realizado e o resultado indicou uma preservação das características de aproximadamente 60 dias, e quando liofilizado de mais de 12 meses. Sendo assim, os métodos propostos foram considerados adequados para utilização na rotina da indústria farmacêutica. Como perspectivas, novas condições serão testadas para obter método de quantificação para o radiofármaco 99m-Tc-DTPA em produto acabado. / Radiopharmaceuticals are radioactive compounds that can be used for diagnostic and therapeutic purposes. Technetium (99mTc) sestamibi is a radiopharmaceutical including a coordination complex consisting of the radioisotope technetium-99m bound to six Sestamibi ligands, which is mainly used to image the myocardium via scintigraphy. This is the most common nuclear medicine procedure, making Technetium (99mTc) sestamibi the most commercialized radiopharmaceutical. Technetium (99mTC)-DTPA in turn is composed by the same radioisotope plus a molecule of Pentetic Acid, which, by its chelating properties, is used to scan renal system. As radiopharmaceuticals are regarded as drugs, they are subject to the same regulations; therefore, the objective of this study is to develop quantification methodology for these both active pharmaceutical ingredients before their complexation with the radioisotope by employing high-performance liquid chromatography (HPLC) methodology. Two simple, efficient methods were developed and validated for Sestamibi at its final form as well as for DTPA's raw material by using buffer and organic solvent mixtures. The validation parameters were evaluated with satisfactory results. A stability test was carried out for Sestamibi, indicating the preservation of characteristics for nearly 60 days, and for over 12 months when at its freezedryed form. The proposed methods were thus considered adequate for pharmaceutical industries. As perspectives, new conditions shall be tested to obtain a quantification method for Technetium (99mTC)-DTPA at its final form.

It is of great importance to be able to unambiguously interpret deoxyribonucleic acid (DNA) profiles, especially with Low Template (LT) DNA and mixture DNA that may contain major and minor contributors. Reducing stochastic effects, such as heterozygote peak imbalance, dropouts, and stutter artifacts have been studied by scientists in order to improve the evaluation of low quality DNA profile. There has been much research on a compatible solute, trehalose, in its effectiveness in enhancing the polymerase chain reaction (PCR), especially with GC-rich templates of DNA, and thermal stabilizing Thermus Aquaticus (Taq) DNA polymerases. Based on previous research, the effect of trehalose on peak heights, peak height ratios, and stutter ratios (n-1) from 15 short tandem repeats (STR) loci of the AmpFℓSTR® Identifiler® Plus PCR Amplification Kit was evaluated with 0.025ng, 0.05ng, 0.1ng, and 1ng of DNA, through the addition of 0M (control), 0.2M, and 0.4M of trehalose for each quantity of DNA. Although there was an observation regarding changes in average peak heights at 1ng of DNA with the addition of 0.2M, and 0.4M of trehalose, no conclusions could be made with the average peak heights for 0.025ng, 0.05ng, 0.1ng, and 1ng of DNA. The reason is that the propagation of pipetting error during the preparation of each batch could have contributed to the difference in the amount of DNA between each conditions which can be directly reflected in peak heights. Furthermore, unexpected discrepancy between the average peak heights for 0.1ng of DNA from the first and the second experiments rendered 0.1ng of DNA incompatible for comparison. With regards to average peak height ratios for 0.025ng, 0.05ng, 0.1ng, and 1ng of DNA, and average reverse stutter ratios for 0.1ng, and 1ng of DNA, there were no evidence to suggest that 0.2M or 0.4M of trehalose had any effects. Consistent trends for 0.1ng (Exp. 1 and 2) and 1ng of DNA from a statistical analysis through one-way ANOVA of individual loci, suggested that trehalose may have varying effects on certain loci. However, this observation must be approached with caution as it is uncertain whether unique trends across each data sets for certain loci were observed by chance due to small sample sizes or due to mechanisms of stutters and trehalose that are currently unknown. Future studies regarding the effect of trehalose on peak heights should be done with more precision through minimizing pipetting error, which can be accomplished by preparing one batch from which aliquots are taken. The result of the research does not show enough evidence to prove the usefulness of trehalose since the addition of trehalose does not yield consistently higher average peak heights and peak height ratios, and lower average reverse stutter ratios across 15 STR loci. Therefore, our results do not support that 0.2M and 0.4M of trehalose are useful within the parameter of forensic DNA analysis as they do not enhance the polymerase chain reaction (PCR) and improve stochastic effects for DNA profiles.

The interactive nature of web applications or “web apps” makes it an excellent medium for conveying complex scientific concepts to lay audiences and creating decision support tools that harness cutting edge modeling techniques. However, the technical expertise required to develop them represents a barrier for would-be developers. The barrier can be characterized by the following hurdles that developers must overcome: (1) identify, select, and install software that meet the spatial and computational capabilities commonly required for water resources modeling; (2) orchestrate the use of multiple FOSS and FOSS4G projects and navigate their differing application programming interfaces (APIs); (3) learn the multi-language programming skills required for modern web development; and (4) develop a web-safe and fully featured web site to host the app. This research has resulted in two primary products that effectively lower the barrier to water resources web app development: (1) a literature review of free and open source software (i.e. software review) and (2) Tethys Platform. The software review included earth science web apps that were published in the peer-reviewed literature in the last decade and it was performed to determine which FOSS4G and FOSS web software has been used to develop such web apps. The review highlights 11 FOSS4G software projects and 9 FOSS projects for web development that were used to develop 45 earth sciences web apps, which constitutes a significantly reduced list of possible software projects that could be used to meet the needs of water resources web app development—greatly lowering the barrier for entry to water resources web development. While the software review addresses the hurdle of identifying FOSS software to provide a web framework and spatial data capabilities for water resources web apps, there are still other hurdles that needed to be overcome to make development more viable. Tethys Platform was developed to address these other hurdles and streamline the development of water resources web apps. It includes (1) a suite of free and open source software that address the unique data and computational needs common to water resources web app development, (2) a Python software development kit for incorporating the functionality of each software element into web apps and streamlining their development, and (3) a customizable web portal that is used to deploy the completed web apps. Tethys Platform has been used to develop a broad array of web apps for water resources modeling and decision support.

Development of an Educational Program to Obtain and Maintain Healthy Weights Among 4th and 5th Grade Students By Stephanie D. Black MSN, University of Phoenix, 2008 BSN, Southwest Baptist University, 2006 ASN, Southwest Baptist University, 2003 Capstone Project Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Nursing Practice Walden University October 2017 Obesity is prevalent in schoolchildren and increases risk of chronic diseases throughout the lifespan. Strategies are needed to address this growing health problem. Education in elementary schools targeting the topics of nutritional choices and prevention of obesity, particularly in 4th-5th grade population, is one strategy researchers have identified as effective. This quality improvement project designed an educational toolkit to provide students educational knowledge and assist them to develop and explore how to incorporate healthy habits and choices into their daily lives. The purpose of this project was to develop an educational program for use in a southwestern elementary school to improve and/or maintain the weights of 4th and 5th grade students. The educational tool kit was developed for the school to implement to fill a gap their curriculum identified by school board members and educators. Orem's self-care deficit theory informed the development of this program, the educational toolkit, and all associated supplementary materials. An interdisciplinary project team of community and institutional stakeholders led by the Doctor of Nursing Practice student worked together to review peer-reviewed evidence, consider contextual challenges, and develop a curriculum suitable for the population. Plans for program implementation and evaluation were also developed to provide the school with a turnkey solution to the problem of child obesity. This initiative has great potential to promote positive social change through improving the health of local elementary school students and other elementary schools in the area may use it as a model for their own curriculum to improve knowledge, habits, and practices of elementary students relevant to positive nutritional choices.

<p>Communication and digital signal processing applications of today are often developed as fully integrated systems on one single chip and are implemented as application specific integrated circuits using e.g. VLSI technology. As the systems are getting more and more complex in terms of speed and performance the chip size and the design time tend to increase rapidly. This will result in search for cheaper and less time consuming alternatives. One alternative is field programmable gate arrays, so called FPGAs. The FPGAs are getting faster, cheaper and the number of gates increases all the time. A long list of ready to use functional blocks so called intellectual property (IP) blocks can be used in FPGAs. The latest FPGAs can also be bought with one or more embedded processors, in form of hard processor cores or as licenses for soft processor cores. This will speed up the design phase and of course also decrease the crucial time to market even more. </p><p>The purpose of this master’s thesis was to develop a waveform generator to generate a sine signal and a cosine signal, I and Q, used for radio/radar applications. The digital signals should have an output data rate of at least 100 MHz. The digital part of the system should be implemented in hardware using e.g. an FPGA. To convert the digital signals to analog signals two D/A converters are used. The analog signals, I and Q, should have a bandwidth of 1 MHz - 11 MHz. </p><p>The waveform generator was developed and implemented using a Virtex II FPGA from Xilinx. An embedded microprocessor within the FPGA, MicroBlaze, in form of a soft processor core was used to control the system. A user interface program running on the microprocessor was also developed. Testing of the whole system, both hardware and software, was done. The system is able to generate digital sine and cosine curves of an output data rate of 100 MHz.</p>

<p> </p><p>Genotyping can be used to link genetic variation among individuals to certain diseases or conditions. Some known disorders and states that are dependent on single nucleotide polymorphism (SNPs) are lactose intolerance, venous thrombosis, hereditary hemochromatosis and the difference in sensibility among people to metabolise drugs.</p><p>In this project a new kit, TaqManÒ Sample-to-SNP KitÔ <strong>for extraction of DNA and preparation of the extract for genotyping with real-time PCR and allelic discrimination, was evaluated. QIAamp® DNA Blood Biorobot® MDx Kit was used as the reference method.</strong></p><p>The purpose of the comparison was to find a method that makes DNA extraction from blood samples cheaper and faster, but with the same reliability as the reference procedure.</p><p>The results of the evaluation showed a complete agreement of the genotype results between the methods tested, which means that the new method was as reliable as the reference method. The costs of reagents and material would be reduced with 52% if the new method is adopted, that alone would result in a cost reduction of 144 000SEK a year with a sample volume of 650 samples/month. The time for DNA extraction would also be reduced with the new procedure.</p><p> </p>

Genotyping can be used to link genetic variation among individuals to certain diseases or conditions. Some known disorders and states that are dependent on single nucleotide polymorphism (SNPs) are lactose intolerance, venous thrombosis, hereditary hemochromatosis and the difference in sensibility among people to metabolise drugs. In this project a new kit, TaqManÒ Sample-to-SNP KitÔ for extraction of DNA and preparation of the extract for genotyping with real-time PCR and allelic discrimination, was evaluated. QIAamp® DNA Blood Biorobot® MDx Kit was used as the reference method. The purpose of the comparison was to find a method that makes DNA extraction from blood samples cheaper and faster, but with the same reliability as the reference procedure. The results of the evaluation showed a complete agreement of the genotype results between the methods tested, which means that the new method was as reliable as the reference method. The costs of reagents and material would be reduced with 52% if the new method is adopted, that alone would result in a cost reduction of 144 000SEK a year with a sample volume of 650 samples/month. The time for DNA extraction would also be reduced with the new procedure.

The receptor tyrosine kinase (RTK) c-Kit is expressed in hematopoietic stem and progenitor cells, mast cells and in several non-hematopoietic tissues. In the hematopoietic system c-Kit and its ligand Steel Factor (SF, aka Stem Cell Factor) are critical for proliferation, survival and differentiation. Mutations in either receptor or ligand lead to lethal anaemia, hematopoietic stem cell defects, mast cell deficiency and a series of non-hematological defects. The aims of the studies included in this thesis are to describe the signalling pathways downstream c-Kit in hematopoietic stem/progenitor cells and to further analyse the role of c-Kit signalling in fundamental biological functions. To study c-Kit signalling in the hematopoietic system we have employed hematopoietic stem cell-like cell lines which share many properties with primary hematopoietic stem cells in vitro and in vivo, including surface markers, multipotentiality, capacity for self-renewal and long term repopulation. In paper I we demonstrate that upon SF activation the RTK c-Kit is autophosphorylated and downstream signalling mediators are transiently activated. Surprisingly we find that the c-Kit mediated activation of the MAPK pathway is dependent on the activation of phosphoinositide 3-kinase (PI3K) in hematopoietic progenitor cells and that differentiation of these progenitors to mast cells results in a signalling switch where Raf activation changes from PI3K dependent to PI3K independent. We here establish that PI3K activity is required for viability and proliferation of hematopoietic progenitor cells. In paper II we studied the conventional protein kinase C (cPKC) involvement in c-Kit signalling. We observe that the cPKCs can phosphorylate c-Kit on serine 746 and that this phosphorylation negatively regulates the activation of the receptor. We demonstrate that inhibition of this negative phosphorylation results in dramatically increased protein kinase B (PKB) activation and as a consequence inhibition of cPKCs rescues cells from starvation induced apoptosis. Moreover we exhibit that the cPKCs are necessary for full activation of extracellular signal-regulated kinase (Erk) and that impaired PKC activity leads to hampered proliferation. In paper III we demonstrate that in addition to the cPKCs also the novel PKC is required for Erk activation and proliferation. Furthermore we present results indicating that PKC negatively regulates differentiation of bone marrow. In conclusion, with the studies in this thesis we display details in the signalling pathways induced upon RTK c-Kit activation and we demonstrate that c-Kit has significant effects on hematopoietic cell-physiology.

No description available.

Communication and digital signal processing applications of today are often developed as fully integrated systems on one single chip and are implemented as application specific integrated circuits using e.g. VLSI technology. As the systems are getting more and more complex in terms of speed and performance the chip size and the design time tend to increase rapidly. This will result in search for cheaper and less time consuming alternatives. One alternative is field programmable gate arrays, so called FPGAs. The FPGAs are getting faster, cheaper and the number of gates increases all the time. A long list of ready to use functional blocks so called intellectual property (IP) blocks can be used in FPGAs. The latest FPGAs can also be bought with one or more embedded processors, in form of hard processor cores or as licenses for soft processor cores. This will speed up the design phase and of course also decrease the crucial time to market even more. The purpose of this master’s thesis was to develop a waveform generator to generate a sine signal and a cosine signal, I and Q, used for radio/radar applications. The digital signals should have an output data rate of at least 100 MHz. The digital part of the system should be implemented in hardware using e.g. an FPGA. To convert the digital signals to analog signals two D/A converters are used. The analog signals, I and Q, should have a bandwidth of 1 MHz - 11 MHz. The waveform generator was developed and implemented using a Virtex II FPGA from Xilinx. An embedded microprocessor within the FPGA, MicroBlaze, in form of a soft processor core was used to control the system. A user interface program running on the microprocessor was also developed. Testing of the whole system, both hardware and software, was done. The system is able to generate digital sine and cosine curves of an output data rate of 100 MHz.