302 research outputs found

    Epidermal Growth Factor Receptor Tyrosine Kinase Assays in Single Intact Cells Using Capillary Electrophoresis

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    Quantification of abnormal Epidermal Growth Factor Receptor (EGFR) tyrosine kinase activity is critical to the clinical success of targeted inhibitors used to treat EGFR-dependent cancers. Current selection criteria based on the presence or absence of activating mutations in the EGFR gene need to be supplemented with complementary assays which quantify EGFR biochemical activity in intact living cells. While in cellulo EGFR activity can be measured to great success in tissue cultured cells using genetically encoded reporters, such techniques are incompatible with small, highly heterogeneous tumor samples. A chemical cytometry approach to direct EGFR activity measurements is presented which consists of an in cellulo peptide reporter-based kinase assay coupled to ultrasensitive microelectrophoretic analysis. The major challenge to such a measurement is biological assay interference from off-target enzymes. A novel approach to minimizing selectivity-based assay interference and its application in single intact cells is presented.Doctor of Philosoph

    Attitudes and perceptions of Newfoundland and Labrador pharmacists toward participating in medical assistance in dying

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    Introduction: This thesis aimed to describe pharmacists’ willingness to participate in medical assistance in dying (MAiD) and potential barriers to their participation. Methods: A systematic review on the existing literature and a survey of Newfoundland and Labrador (NL) pharmacists were conducted. Results: The systematic review found the majority of studies were conducted before 2002 and before MAiD was legal or where MAiD is still not legal. Pharmacists’ willingness to participate varied, and there was a gap in the literature on barriers and facilitators to the pharmacist’s role in MAiD. The survey of NL pharmacists found the majority were willing to participate, however NL pharmacists felt they lacked knowledge regarding MAiD (e.g. MAiD process, MAiD medications, information to provide patients on MAiD) and had concerns about the consequences of participating in MAiD. Conclusion: The majority of NL pharmacists are willing to participate in MAiD however, more supports (i.e. educational, emotional) are needed to better prepare and assist pharmacists in this new practice area. Furthermore, research is needed to evaluate pharmacists’ experiences with actual participation in MAiD

    Cosmology between QUaD and the CMB

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    QUaD is a ground based bolometric polarimeter which observed the cosmic microwave background (CMB) at 100 and 150 GHz for three austral winters. Two different techniques field differencing and ground template subtraction, were used to analyze the data providing highly accurate maps and power spectra of both temperature and polarization. These measurements were then used to constrain cosmological parameters and in conjunction with the results of several other experiments further our knowledge and understanding of cosmology in the early universe. This thesis presents an investigation into the astrophysical phenomena in the fore ground of QUaD's observation region. Although an area with minimal foreground was selected for the experiment, nevertheless between QUaD and the CMB there are various sources of millimeter radiation that could potentially contaminate the measurements. Template temperature maps of the dust and synchrotron radiation in the region are extrapolated to CMB frequencies and correlated with QUaD's maps to quantify the extent of any structure similarity detected. These are compared with the correlation expected by chance in a single universe to confirm the cleanliness of the field and highlight the robustness of the published CMB results. The residual signal persistently observed in the difference spectrum between QUaD's 100 GHz and 150 GHz frequency data is fitted against template spectra for the far infrared background (FIRB) and the Sunyaev-Zel'dovich (SZ) effect. The fitting analysis serves to constrain the parameters, b (the galaxy clustering bias), and a8 (the rms mass fluctuations in a Sh l Mpc sphere) upon which the amplitudes of the template spectra are dependent. The contribution to the power from the predicted background of radio point sources is subtracted before a simultaneous fit to the two parameters is carried out. It is found that cr8 = l.lllo!o6 = 3-2T to 23. Whilst these values are shown to be consistent with other recent astronomical results, the amplitudes of the FIRB and SZ effect they imply are, once extrapolated to high-, incompatible with the QUaD data on these angular scales. This suggests that some other factors perhaps instrumental systematics, features in the analysis pipeline, or indeed other astrophysical phenomena could also be responsible for the signal seen in the frequency difference spectrum.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    How Should Context-Dependent Words Be Taught to Beginning Readers?

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    This study examined three different instructional methods for teaching beginners to read context-dependent words. Two types of context-dependent words were taught: irregular past tense verbs and function words. The words were embedded either in scrambled contexts or in meaningful sentence contexts. Three different instructional conditions to teach the words were compared. In the Meaningful Context condition, students studied the target words embedded in meaningful sentences. In the Scrambled condition, students studied target words placed in scrambled word sequences. In the Combination condition, students studied target words in both types of contexts that were alternated across learning trials. Participants were 53 pre-kindergarten and kindergarten students, ages 5 to 6 years, who qualified as beginning readers based on pretests. The two word types were read on separate training days, with two sets of posttests administered a day after each training session. Posttests included measures of sight word reading, spelling, sentence production, irregular past tense verb transformations, and syntactic awareness. It was hypothesized that instructional condition would affect the word identities that were learned. Results showed that instructional condition did not affect word reading measures during training or on any of the posttests. It was also hypothesized that function words would be easier to learn across measures. Results showed that function words were easier to read and spell, while past tense verbs were easier to embed in sentence contexts. Findings carry instructional implications for how to teach context-dependent words to beginning readers

    HIV and STI among women in Uganda, Zimbabwe and Thailand: associations with male circumcision and changes in condom use

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    The results of most HIV-prevention programs over the 25-year history of the AIDS epidemic have been disappointing. Two interventions have been notable exceptions in the string of prevention failures: in 1983, researchers reported that consistent use of male condoms reduced risk of HIV transmission, and much more recently, in February 2007, large-scale randomized trials determined that circumcision reduced men's risk of HIV acquisition by 40-65%. These separate interventions - male circumcision and condom use - are the focus of these dissertation analyses. We examined whether the circumcision status of women's primary sexual partner was associated with her risk of HIV and three sexually transmitted infections (STIs): Chlamydia trachomatis (Ct), Neisseria gonorrhoeae (GC), and Trichomonas vaginalis (Tv). We used data from a prospective cohort study on hormonal contraception and incident HIV and STI (HC-HIV study) among women from Uganda, Zimbabwe and Thailand (HIV analyses included 4,417 Ugandan and Zimbabwean women; STI analyses included 5,925 women from Uganda, Zimbabwe and Thailand). After adjustment, women with circumcised partners had similar risk to women with uncircumcised partners for HIV (hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.69-1.53), Ct (HR: 1.22, 95% CI: 0.94-1.59), GC (HR: 0.93, 95% CI: 0.70-1.24), and Tv (HR: 1.05, 95% CI: 0.81-1.37). Among women who became HIV-infected during HC-HIV, we also examined whether HIV diagnosis, together with counseling and free condoms, was sufficient to induce changes in women's condom use over both short (2-6 months) and longer time periods (12-16 months). After diagnosis, the number of HIV-infected women reporting any unprotected acts in a typical month declined significantly (short-term: from 72% to 56%; long-term: from 74% to 56%). After adjustment, among women reporting any unprotected acts, HIV-infected women also reduced the number of unprotected acts by 29% (short term) and 38% (long term). When assessing the proportion of acts where male condoms were used, however, women had no reduction over time. Circumcision was not associated with women's risk of HIV, Ct, Tv or GC among most participants. HIV-infected women reduced their overall number of unprotected sex acts, but the proportion of unprotected acts was unchanged from pre-infection behavior

    Cosmology between QUaD and the CMB

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    QUaD is a ground based bolometric polarimeter which observed the cosmic microwave background (CMB) at 100 and 150 GHz for three austral winters. Two different techniques field differencing and ground template subtraction, were used to analyze the data providing highly accurate maps and power spectra of both temperature and polarization. These measurements were then used to constrain cosmological parameters and in conjunction with the results of several other experiments further our knowledge and understanding of cosmology in the early universe. This thesis presents an investigation into the astrophysical phenomena in the fore ground of QUaD's observation region. Although an area with minimal foreground was selected for the experiment, nevertheless between QUaD and the CMB there are various sources of millimeter radiation that could potentially contaminate the measurements. Template temperature maps of the dust and synchrotron radiation in the region are extrapolated to CMB frequencies and correlated with QUaD's maps to quantify the extent of any structure similarity detected. These are compared with the correlation expected by chance in a single universe to confirm the cleanliness of the field and highlight the robustness of the published CMB results. The residual signal persistently observed in the difference spectrum between QUaD's 100 GHz and 150 GHz frequency data is fitted against template spectra for the far infrared background (FIRB) and the Sunyaev-Zel'dovich (SZ) effect. The fitting analysis serves to constrain the parameters, b (the galaxy clustering bias), and a8 (the rms mass fluctuations in a Sh l Mpc sphere) upon which the amplitudes of the template spectra are dependent. The contribution to the power from the predicted background of radio point sources is subtracted before a simultaneous fit to the two parameters is carried out. It is found that cr8 = l.lllo!o6 = 3-2T to 23. Whilst these values are shown to be consistent with other recent astronomical results, the amplitudes of the FIRB and SZ effect they imply are, once extrapolated to high-, incompatible with the QUaD data on these angular scales. This suggests that some other factors perhaps instrumental systematics, features in the analysis pipeline, or indeed other astrophysical phenomena could also be responsible for the signal seen in the frequency difference spectrum
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