50 research outputs found
Genetic re-targeting and de-targeting of adenovirus type 5 in order to create vectors for gene therapy
No full textGene therapy has been considered to be a revolutionary development in medicine, whereby the cause and not the symptoms of the disease would be treated. These expectations have as yet not been realized, mainly due to lack of suitable vectors. Adenoviruses type 5 (Ad5) are the most commonly used vectors for gene therapy and have a great potential in this field.
The main aim of this thesis was to generate genetically re-targeted and de-targeted Ad5 in order to create suitable vectors for gene therapy. To re-target the Ad5 vector ligands have been incorporated into the C-terminus at the pIX protein and at different positions in the fiber protein. Ligands that have been used are affibody molecules, with specificity for Taq DNA polymerase and for the tumour antigen HER2/neu, and a hyperstable single chain antibody, scFv, directed against β-galactosidase. In order to generate a virus with double specificity and determine which position is best suited for ligand–target cell interaction a re-targeted Ad5 vector with two different affibody molecules in the same genome was constructed. The re-targeted vectors were evaluated for growth, infectivity and specificity. For de-targeting assessments the neutralizing antibody reactivity in blood donor sera have been tested against a recombinant Ad5 vector with a shortened knobless fiber and a new cell binding ligand and a re-targeted vector with three different de-targeting steps have been evaluated for vector characterizations, tissue distribution and interaction with blood cells.
Ligands that are to be used for re-targeting of Ad must be able to fold correctly and stably in the reducing milieu of the eukaryotic cytoplasm which is not conducive to the formation of disulphide bonds. Both the affibody molecules and the scFv did fulfill these criteria and could be rescued into functional Ad. Incorporation of ligands in the HI-loop of the fiber knob was shown to be superior to ligand insertions into truncated knobless fibers in terms of growth characteristics. It was possible to incorporate the scFv at the pIX protein with retained antigen binding when loaded on Ad5 virions, however transduction experiments could not be performed because a suitable cell line was not avalible. It was shown that generation of a vector with dual specificity was feasible, on the other hand it was important to evaluate which positions is best suited for efficient binding to target cell. The virus with a truncated knobless fiber and a new cellular ligand showed a much-reduced sensitivity to human pre-formed antibodies compared to wild type (WT) Ad5. The re- and de-targeted Ad vectors did not bind to normal tissues in mice as much as WT Ad5 and the association with human blood cells was much decreased for the recombinant vectors when compared to WT.
In conclusion, both the affibody molecules and the scFv evaluated in this thesis can be used for genetic re-targeting of Ad5. Re-targeted viruses with ligands in the fiber often suffer from low growth rate, high infectivity indexes (PP/pfu) and low fiber content. However virus with ligand incorporation in the HI-loop does largely overcome those obstacles and the virus with ligand specificity for the tumour antigen HER2/neu may have relevance as a clinical vector. The adenovirus minor capsid protein IX can function as an anchor protein for relatively large ligand insertions, which is promising for future de-targeting purposes. Generation of recombinant viruses with double specificity may exploit the possibility to target several tumour antigens. The reduced neutralizing activity against the short knobless fiber and the reduced binding to normal tissues and interaction with blood cells of the re-targeted viruses with additional de-targeting steps represents, to this author, an important step towards the construction of “stealth” adenoviruses for gene therapy
54/07/10 Find Few Real Clews In Bay Village Murder
No full textCleveland News Editorial writer, Paul Myhre, gives a small synopsis of the case up until this point. Dr. Sam\u27s t-shirt and the murder weapon are still missing. The author also mentions that during one of the many searches of Dr. Sam Sheppards home, a paperback novel was found, ironically entitled, My Dead Wife.https://engagedscholarship.csuohio.edu/newspaper_coverage/1248/thumbnail.jp
?Twist of Fate? by Michelle Schulz
No full textTerm paper based on the 1974 abduction of Doyle Schulz, a North Dakota Highway patrolman. Patrolman Schulz, abducted in Fargo, N.D., by Lewis J. Myhre, was later released near the South Dakota border. The paper relates the feelings and emotions Patricia Schulz, Doyle's wife, experienced until Doyle was safely found. The author, a NDSU student, wrote this paper for an English 110 class
Evaluating the impact of supplemental online math instruction and intervention
No full textThis study investigated the impact of the supplemental online math instruction and intervention program TenMarks.com on student achievement as measured by assessment scores in a school in California’s Central Valley. Sixty-three students from two different fifth grade classes participated in the study. Both classes were taught by the author. The scores on the standard curriculum chapter test and TenMarks.com post-test of students who supplemented their in-class instruction with TenMarks.com were compared to the scores of students who did not use TenMarks.com during the course of the study. The results found no statistically significant difference in chapter test scores from the standard curriculum. However, significantly higher achievement was found on TenMarks.com post-test scores for those who used the online program
The effects of online homework on achievement in college preparatory mathematics classes
No full textThis study investigated the effects the online homework system MathXLforschools.com (MXL) had on student achievement as measured by exam scores in a high school Algebra 1 course. One hundred eight high school students, ranging from ninth to eleventh grade, from three different Algebra 1 classes, participated in the study. All three classes were taught by the author. The scores on a benchmark and final exam of students who completed homework using the MXL online homework system were compared to the scores of students who completed their homework using their textbook. During the first semester of the 2013 – 2014 school year all participants of the study completed their homework using only their textbooks. The study then compared the first quarter benchmark scores of participants who completed their homework using the MXL online homework system with their third quarter benchmark scores. In addition, the study compared the semester one final exam scores of the same participants with their semester two final exam scores. The study found that there was no statistical difference in exam scores of students who completed homework using MXL compared to students who completed homework using their textbook
La banlieue souhaitée et non-souhaitée. Annexions et Identité urbaine. L'exemple de Christiana (Oslo) au XIXe siècle
No full text[eng] Abstract In this article, the author explains the suburban problems endured by a town in nothern Europe, Christiana, during the 19th Century. The town had a complicated suburban history during the Classic Era, as the suburbs were confined to a restricted perimeter. The size of the town grew phenonemally during the 19th Century, leading new suburbs to develop. Initially, everyone, both the town autorities and the people from the surrounding countryside alike, rejected these new suburbs. From 1850 onwards, however, the suburbs were only accepted, they were even wanted. The author explains the reasons fot this evolution. [fre] Résumé Dans cette communication, l'auteur explique le problème suburbain d'une ville du nord de l'Europe, Christiana, au XIXe siècle. Après avoir eu à l'époque classique une histoire de la banlieue très compliquée dans un périmètre limité, la ville a une croissance phénoménale au XIXe siècle qui entraîne le développement d'une nouvelle banlieue. En premier temps, celle-ci est rejetée par tous, aussi bien les autorités de la ville que celle de la campagne puis, en un second temps, à partir de 1850, elle est non seulement acceptée mais également souhaitée. L'auteur explique les raisons de cette évolution.
The effects of online homework on achievement in college preparatory mathematics classes
No full textThis study investigated the effects the online homework system\ud
MathXLforschools.com (MXL) had on student achievement as measured by exam\ud
scores in a high school Algebra 1 course. One hundred eight high school students,\ud
ranging from ninth to eleventh grade, from three different Algebra 1 classes,\ud
participated in the study. All three classes were taught by the author. The scores on a\ud
benchmark and final exam of students who completed homework using the MXL\ud
online homework system were compared to the scores of students who completed\ud
their homework using their textbook. During the first semester of the 2013 ??? 2014\ud
school year all participants of the study completed their homework using only their\ud
textbooks. The study then compared the first quarter benchmark scores of\ud
participants who completed their homework using the MXL online homework system\ud
with their third quarter benchmark scores. In addition, the study compared the\ud
semester one final exam scores of the same participants with their semester two final\ud
exam scores. The study found that there was no statistical difference in exam scores\ud
of students who completed homework using MXL compared to students who\ud
completed homework using their textbook
Trialectic archaeology : monuments and space in southwest Norway 1700-500 BC.
No full textThis book is based on the PhD thesis in archaeology at Jesus College, University of Cambridge, where the author was awarded the degree Doctor of Philosophy in 2004
Riserless Drilling Systems
No full textMaster's thesis in Petroleum engineeringAs the oil and gas recoverables are getting more inaccessible and harder to procure, the worlds demand for petroleum resources are constantly increasing. This entails the oil industry to expose themselves towards more challenging environments for oil and gas exploitation. To enable for this development to be beneficial, or even feasible, the industry is eagerly on the lookout for innovative solutions to counter for the given challenge.
This thesis will elucidate a new drilling technique that mitigates narrow pore-/fracture-pressure windows, wellbore instability, depleted formations, formation damage, excessive casing strings, fatigue life, large water depths and hostile environments. The mitigation of fatigue life on the Gullfaks Satellites (GFS) substructure is one of the main drivers for Statoil to implement this technology in the first instance. The technology, called Riserless Drilling Systems, enables for drilling of the entire well without the need of a large rigid riser. The research focus for this thesis will therefore be to evaluate the methods potential, and to see if it is a viable and adaptive solution for the oil and gas industry.
The research methods used for this thesis are an evaluation of the feasibility studies done by the Riserless Drilling System service providers, company visits, data retrieval from relevant sources and some experimental research through the use of the commercial spreadsheet Microsoft Excel. Through careful evaluation of the developing technology, the author is of the opinion that a Riserless Drilling System is a viable solution for the given purpose based on the performed research. The basis for this lies within the already filed proven RMR® technology, and the comprehensive underlying feasibility studies performed. Hence the author concludes, with reservation regarding pump technology, that the conceptual technology will be suitable for the presented water depths. As the water depth on GFS is not of any concern for this technology, it would be a highly potential candidate for the mitigation of further fatigue development on the wellhead systems.
Disregarded the cost involved in utilizing a Riserless Drilling System, the author is of the perception that further initiative is beneficial due to its many positive aspects. As a direct result of these, the technology will emerge and may with time become the best alternative to drill a well in the future
Om ritualer og sosiale relasjoner : Refleksjoner rundt et kraftfullt bytte
No full textThe article describes a bridewealth prestation amongthe Chagga-speaking people of Tanzania. Departingfrom approaches that rely on the notion of reciprocity,the author explores how the prestation per se constitutes,rather than represents, the relationship betweenwife-givers and wife-receivers. By investigating themateriality of the exchanged object, the relationships itforms part of are laid bare, and it is argued that theobject forms part of a reproductive network wherepersons, things and social relationships are mutuallyconstituted. Against this background, materiality andsociality, things and meanings, reality and representation,are interrelated and the problems raised by thenotion of reciprocity are transcended.</p
