3,742 research outputs found
If Not Now: An Account of the Challenges and Experiences of Writing, Directing, and Editing a Graduate Thesis Film
In this paper, I will catalog and describe my process involved in the creation of my thesis film If Not Now. In the main body of the paper I will cover the topics of Writing, Casting, Directing, Production Design, Cinematography, Editing, and Sound, as well as Technology and Workflow. Special emphasis will be placed on Writing, Directing, Editing, and Sound. The Analysis section will discuss the overall effectiveness of my goals to communicate a story about self-identity and community, as well as the film\u27s artistic merit and quality
If Not Now: An Account of the Challenges and Experiences of Writing, Directing, and Editing a Graduate Thesis Film
In this paper, I will catalog and describe my process involved in the creation of my thesis film If Not Now. In the main body of the paper I will cover the topics of Writing, Casting, Directing, Production Design, Cinematography, Editing, and Sound, as well as Technology and Workflow. Special emphasis will be placed on Writing, Directing, Editing, and Sound. The Analysis section will discuss the overall effectiveness of my goals to communicate a story about self-identity and community, as well as the film\u27s artistic merit and quality
The use of retroviral vectors for gene therapy-what are the risks? A review of retroviral pathogenesis and its relevance to retroviral vector-mediated gene delivery
Retroviral vector-mediated gene transfer has been central to the development of gene therapy. Retroviruses have several distinct advantages over other vectors, especially when permanent gene transfer is the preferred outcome. The most important advantage that retroviral vectors offer is their ability to transform their single stranded RNA genome into a double stranded DNA molecule that stably integrates into the target cell genome. This means that retroviral vectors can be used to permanently modify the host cell nuclear genome. Recently, retroviral vector-mediated gene transfer, as well as the broader gene therapy field, has been re-invigorated with the development of a new class of retroviral vectors which are derived from lentiviruses. These have the unique ability amongst retroviruses of being able to infect non-cycling cells. Vectors derived from lentiviruses have provided a quantum leap in technology and seemingly offer the means to achieve significant levels of gene transfer in vivo. The ability of retroviruses to integrate into the host cell chromosome also raises the possibility of insertional mutagenesis and oncogene activation. Both these phenomena are well known in the interactions of certain types of wild-type retroviruses with their hosts. However, until recently they had not been observed in replication defective retroviral vector-mediated gene transfer, either in animal models or in clinical trials. This has meant the potential disadvantages of retroviral mediated gene therapy have, until recently, been seen as largely, if not entirely, hypothetical. The recent clinical trial of γc mediated gene therapy for X-linked severe combined immunodeficiency (X-SCID) has proven the potential of retroviral mediated gene transfer for the treatment of inherited metabolic disease. However, it has also illustrated the potential dangers involved, with 2 out of 10 patients developing T cell leukemia as a consequence of the treatment. A considered review of retroviral induced pathogenesis suggests these events were qualitatively, if not quantitatively, predictable. In addition, it is clear that the probability of such events can be greatly reduced by relatively simple vector modifications, such as the use of self-inactivating vectors and vectors derived from non-oncogenic retroviruses. However, these approaches remain to be fully developed and validated. This review also suggests that, in all likelihood, there are no other major retroviral pathogenetic mechanisms that are of general relevance to replication defective retroviral vectors. These are important conclusions as they suggest that, by careful design and engineering of retroviral vectors, we can continue to use this gene transfer technology with confidence
High Multiplicity Searches at the LHC Using Jet Masses
This article introduces a new class of searches for physics beyond the
Standard Model that improves the sensitivity to signals with high jet
multiplicity. The proposed searches gain access to high multiplicity signals by
reclustering events into large-radius, or "fat," jets and by requiring that
each event has multiple massive jets. This technique is applied to
supersymmetric scenarios in which gluinos are pair-produced and then
subsequently decay to final states with either moderate quantities of missing
energy or final states without missing energy. In each of these scenarios, the
use of jet mass improves the estimated reach in gluino mass by 20 % to 50 %
over current LHC searches.Comment: 9 pages, 6 figures; v3 corrects a few small typo
Refinement of lentiviral vector for improved RNA processing and reduced rates of self inactivation repair
Background Lentiviral gene therapy vectors are now finding clinical application. In order to fully exploit their potential it is important that vectors are made as efficient and as safe as possible. Accordingly, we have modified a previously reported vector to improve RNA processing, minimise Human Immunodeficiency Virus Type-1 (HIV-1) sequence content and reduce repair of the self inactivating (SIN) deletion. Results HIV-1 sequence in the vector was reduced by substituting the polyadenylation signal with a heterologous signal. Mutation of splice donor sites was undertaken to prevent the majority of splicing within the vector genomic RNA. In addition, a number of other sequences within the vector were deleted. The combination of these modifications was able to significantly reduce the rates of both vector mobilisation and repair of the self inactivating deletion after two rounds of marker rescue. Conclusion RNA processing can be improved by mutation of the major and minor HIV-1 splice donor sites in the vector. In addition the rate of vector mobilisation and repair of SIN vectors can be successfully reduced by careful vector design that reduces homology between the 5' and 3' long terminal repeats (LTRs) to a minimum.Rachel M Koldej and Donald S Anso
First heterometallic GaIII-DyIII single-molecule magnets: Implication of GaIII in extracting Fe-Dy interaction
The compounds of the system [M4M′2(μ3-OH)2(nbdea)4(C6H5CO2)8]·MeCN, where M = GaIII, M′ = DyIII (2), M = FeIII, M′ = YIII (3) are isostructural to the known [Fe4Dy2] compound (1). Those of the system [M4M′4(μ3-OH)4(nbdea)4(m-CH3C6H4CO2)12]·nMeCN, where M = GaIII, M′ = DyIII, n = 4 (5), M = FeIII, M′ = YIII, n = 1 (6) are isostructural to the [Fe4Dy4] compound (4). This allows for comparisons between single ion effects of the paramagnetic ions. The structures were determined using single crystal analysis. Magnetic susceptibility measurements reveal that the GaIII–DyIII compounds 2 and 5 are SMMs. The energy barrier for 2 is close to that for the known isostructural Fe4Dy2 compound (1), but with a significantly increased relaxation time
Efficacy of cognitive behaviour therapy versus anxiety management for body dysmorphic disorder: a randomised controlled trial
Background: The evidence base for the effectiveness of cognitive behaviour therapy (CBT) for treating Body Dysmorphic Disorder (BDD) is weak. Aims: To determine if CBT is more effective than anxiety management (AM) in an out-patient setting. Method: A single blind, stratified parallel-group randomized controlled trial. The primary endpoint was at 12 weeks, and the Yale Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS) was the primary outcome measure. Secondary measures for BDD included the Brown Assessment of Beliefs (BABS), the Appearance Anxiety Inventory (AAI) and the Body Image Quality of Life Inventory (BIQLI). The outcome measures were collected at baseline and week 12. The CBT group, unlike the AM group, had 4 further weekly sessions that were analysed for their added value. Both groups then completed measures at their 1-month follow-up. Forty-six participants, with DSM-IV diagnosis of BDD including those with a delusional BDD were randomly allocated to either CBT or AM. Results: At 12 weeks, CBT was found to be significantly superior to AM on the BDD-YBOCS ( = -7.19, S.E. () = 2.61, p < .01, C.I. = -12.31, -2.07, d 0.99) as well as the secondary outcome measures of the BABS, AAI and BIQL. Further benefits occurred by Week 16 within the CBT group. There were no differences in outcome for those with delusional BDD or depression. Conclusions: CBT is an effective intervention for people with BDD even with delusional beliefs or depression and is more effective than anxiety management over 12 weeks
Development of a liquid chromatography tandem mass spectrometry method for the simultaneous measurement of voriconazole, posaconazole and itraconazole
Background Azole-based antifungals are the first-line therapy for some of the most common mycoses and are now also being used prophylactically to protect immunocompromised patients. However, due to variability in both their metabolism and bioavailability, therapeutic drug monitoring is essential to avoid toxicity but still gain maximum efficacy. Methods Following protein precipitation of serum with acetonitrile, 20  µL of extract was injected onto a 2.1 × 50 mm Waters Atlantis dC18 3  µm column. Detection was via a Waters Quattro Premier XE tandem mass spectrometer operating in ESI-positive mode. Multiple reaction monitoring (MRM) detected two product ions for each compound and one for each isotopically labelled internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of measuring interval and detection were all assessed. Results Optimal chromatographic separation was achieved using gradient elution over 8 minutes. Voriconazole, posaconazole and itraconazole eluted at 1.71, 2.73 and 3.41 min, respectively. The lower limits of measuring interval for all three compounds was 0.1 mg/L. The assay was linear to 10 mg/L for voriconazole (R2 = 0.995) and 5 mg/L for posaconazole (R2 = 0.990) and itraconazole (R2 = 0.991). The assay was both highly accurate and precise with % bias of voriconazole, posaconazole and itraconazole, respectively, when compared with previous NEQAS samples. The intra-assay precision (CV%) was 1.6%, 2.5% and 1.9% for voriconazole, posaconazole and itraconazole, respectively, across the linear range. Conclusion A simple and robust method has been validated for azole antifungal therapeutic drug monitoring. This new assay will result in a greatly improved sample turnaround time and will therefore vastly increase the clinical utility of azole antifungal drug monitoring. </jats:sec
A Critical Analysis of the Theoretical Basis of Ultrasonic Scattering Measurements
There are three elements involved in the backscattering from inhomogeneous media; the scattering properties of a single particle or scattering element, the scattering associated with a group of such particles and the relationship of the scattered wave to the measured signal. Ideally it should be possible to obtain information about the material microstructure from ultrasonic backscattering measurements. However, a number of assumptions and approximations must be made before the problem becomes tractable, and it is the purpose of the present investigation to compare the various approaches available in the literature in an attempt to quantify the errors involved with some of these approximations
The Effect of Luteolin on Human Glioblastoma
Glioblastoma multiforme (GBM) is widely recognized as the most common and lethal of the malignant gliomas. Few effective therapeutic treatments are available as five-year survival rates of diagnosed individuals are less than five percent. Luteolin, a common flavonoid found in a variety of fruits and vegetables, has demonstrated significant promise in combating cancers of the breast, colon, liver, lung, and bone. In this study, we investigated the effects of luteolin on glioblastoma multiforme cell lines U-251, U-87, and U-1242. Cell viability was assessed using cell count with trypan blue exclusion and MTT assays. Results revealed that luteolin reduces GBM cell viability and cell proliferation in a time and concentration-dependent manner. Western Blot analysis indicated that luteolin decreased AKT, ERK, and MAPK phosphorylation following treatment with EGF. Additionally, luteolin promoted apoptosis in GBM cells by inducing PARP and caspase-3 cleavage, and decreasing levels of the anti-apoptotic protein BCL-XL. Our results indicate that luteolin exhibits a biological effect and may be used as a therapeutic agent for glioblastoma multiforme
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