143 research outputs found

    DNA-protamine interactions

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    Three essays in demand analysis

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    In this study, flexible representation of consumer demand systems is investigated within the framework afforded by duality in consumer theory. The first essay examines the market situation where supplies are inelastic and prices must adjust to clear the market, a situation that arises for most agricultural commodities, particularly for perishable commodities. A price dependent or inverse demand system can reflect such a market situation. Two flexible inverse demand systems are proposed. The first of these is a linear inverse demand system (LIDS) derived from a flexible specification of a distance function, and presents a particularly convenient system of linear equations. A simulation exercise reveals that the LIDS performs as well and in fact slightly better than the older inverse Translog system. However, in order to specify market demands, aggregation conditions need to hold. A new system of inverse share dependent equations belonging to the class of quasi-homothetic preferences is also proposed;Between the two polar cases of direct and inverse demands lies the class of \u27mixed\u27 demands where the prices of some goods and the quantities (demanded) of others adjust to clear the market. However, the existing theoretical framework for mixed demands does not allow a convenient transition to an empirical model. The concept of \u27shadow\u27 price is used in developing a theoretical framework that does allow the specification of an empirical mixed demand system. The Slutsky equations are derived, the elasticity forms of which are implemented in a differential approximation of the mixed demand system. The empirical context is provided by the Canadian market for meats where free trade with the U.S. in beef and pork makes Canada a price taker for these commodities, while for poultry, domestic marketing boards restrict the supply, and prices must adjust to clear the markets;The notion of separability is frequently invoked in applied demand analysis. In general, separability is a strong maintained hypothesis and should ideally be tested before it is maintained. However, while the alternative of imposing local separability on a Flexible Functional Form (FFF) exists, imposing global separability parametrically on most of the commonly used FFFs renders them inflexible. In the third essay, the ability of a recently proposed globally separable FFF, as well as that of the locally separable model, in providing correct inferences about separability is examined in a Monte Carlo study

    Teaching Evolution: Blog as a Liminal Space

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    A threshold concept is a challenging concept that acts as a doorway leading to deeper understanding and a dramatic shift in perception. A learner that is in- volved in grasping a threshold concept is said to be undergoing a threshold expe- rience within a liminal space or learning environment. We used the blog as a lim- inal space for our students to engage with the theory of evolution, which is a threshold concept. In order to teach evolution effectively it is necessary to address both understanding and acceptance of evolutionary theory. To explore the latter in an introductory biology course, we used a series of reflection assignments, sub- mitted by students using a blog format, designed to inform, engage, and probe students’ views on evolution without dismissing their prior beliefs. Using the blog feature on our learning management system (LMS), students were asked to feel free to express their views on the nature of science (NOS), evidence for evolution and natural selection, and the application of the concept of non-overlapping mag- isteria (NOMA) to the evolution-versus-creationism debate without fear of being graded poorly for a wrong response. Grades were based solely on the level of en- gagement expressed via thoughtful responses to the specific prompts within each reflection assignment. A student reflection rubric was used to grade and assess student performance and allowed us to examine how students integrated evolution into their prior knowledge. We found the blog to be a highly effective online tool to closely analyze students’ written reflections on a topic that can be both intellec- tually and emotionally challenging

    Writing to Learn: Embedding a crucial study skill in a gateway science course

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    Handwriting is a multisensory process known to enhance memory, focus, engagement, and cognition in the learner, thereby making it a valuable study skill. In an attempt to embed handwriting as a study skill in a gateway science course, I used a combination of scaffolding and individual student consultations. Scaffolding emphasized the use of desirable difficulties and retrieval practice through the implementation of techniques such as the flipped learning approach and take home-in class hybrid essay exams. While the former helped to increase overall student success the latter technique was aimed at enhancing written fluency in the subject, curbing procrastination, and providing opportunities for high impact retrieval practice during the in-class essay exams. One-on-one student consultations that emphasized rewriting and maintaining good notes were used as interventions throughout the semester to promote positive study behavior and also as a crucial stage in preparing for each unit exam. Level of student engagement in using handwriting as a study skill was traced within the context of a typical threshold experience. Handwriting as a study skill was successfully embedded in this course and showed positive results in terms of student retention, engagement, and overall success

    An NGQD Based Diagnostic Tool for Pancreatic Cancer

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    Background: Pancreatic cancer remains difficult to detect at early stages which contributes to a poor five-yearsurvival rate. Therefore, early detection approaches based on novel technologies should be explored to address this critical health issue. Nanomaterials have recently emerged as frontrunners for diagnostic applications due to their small size in the 1-100 nm range, which facilitates one-on-one interactions with a variety of biomolecules like oligonucleotides and makes them suitable for a plethora of detection and delivery applications. In this work, the presence of specific pancreatic cancer miRNA (pre-miR-132) is detected utilizing the fluorescence properties of highly biocompatible nitrogen-doped graphene quantum dots (NGQDs). Methods: NGQDs were synthesized from Glucosamine HCl and deionized H2O. Cuvettes were filled with a mixture of bait ssDNA (13.7μM) and NGQDs (0.5 mg/ml) in deionized H2O that was vortexed for 5s before adding target strands. Samples were again vortexed for 5s and incubated at 4 ºC for 2hrs before excitation at 400 nm with an emission wavelength measured from 420 nm to 780 nm using a spectrofluorometer. Data analysis was performed using Origin software. Results: From the Zeta potential measurements, this platform is comprised of positively charged (1.14±0.36 mV) NGQDs binding with negatively charged (-22.4±6.00 mV) ssDNA electrostatically and/or via − stacking to form an NGQDs/ssDNA complex with an estimated size of 20 nm verified with TEM. Observing variations in fluorescence spectra of NGQDs/ssDNA complexes allows for the distinguishing of single-stranded and double-stranded DNA, as well as specific single-stranded DNA sequences due to bait-target complementarity. Furthermore, this enables detection of the loop of pre-miRNA of interest and can identify target miRNA from random controls with sensitivity in the nanomolar range. Conclusions: This approach allows for pancreatic cancer-specific miRNA sensing to facilitate pancreatic cancer detection at the early stages. Such early diagnosis is ultimately aimed to increase cancer patient survival rates

    A Systematic Review of Extended Reality (XR) for Understanding and Augmenting Vision Loss

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    Over the past decade, extended reality (XR) has emerged as an assistive technology not only to augment residual vision of people losing their sight but also to study the rudimentary vision restored to blind people by a visual neuroprosthesis. To make the best use of these emerging technologies, it is valuable and timely to understand the state of this research and identify any shortcomings that are present. Here we present a systematic literature review of 227 publications from 106 different venues assessing the potential of XR technology to further visual accessibility. In contrast to other reviews, we sample studies from multiple scientific disciplines, focus on augmentation of a person's residual vision, and require studies to feature a quantitative evaluation with appropriate end users. We summarize prominent findings from different XR research areas, show how the landscape has changed over the last decade, and identify scientific gaps in the literature. Specifically, we highlight the need for real-world validation, the broadening of end-user participation, and a more nuanced understanding of the suitability and usability of different XR-based accessibility aids. By broadening end-user participation to early stages of the design process and shifting the focus from behavioral performance to qualitative assessments of usability, future research has the potential to develop XR technologies that may not only allow for studying vision loss, but also enable novel visual accessibility aids with the potential to impact the lives of millions of people living with vision loss

    Failure to Censor Forbidden Clones of CD4 T Cells in Autoimmune Diabetes

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    Type 1 diabetes and other organ-specific autoimmune diseases often cluster together in human families and in congenic strains of NOD (nonobese diabetic) mice, but the inherited immunoregulatory defects responsible for these diseases are unknown. Here we track the fate of high avidity CD4 T cells recognizing a self-antigen expressed in pancreatic islet β cells using a transgenic mouse model. T cells of identical specificity, recognizing a dominant peptide from the same islet antigen and major histocompatibility complex (MHC)-presenting molecule, were followed on autoimmune susceptible and resistant genetic backgrounds. We show that non-MHC genes from the NOD strain cause a failure to delete these high avidity autoreactive T cells during their development in the thymus, with subsequent spontaneous breakdown of CD4 cell tolerance to the islet antigen, formation of intra-islet germinal centers, and high titre immunoglobulin G1 autoantibody production. In mixed bone marrow chimeric animals, defective thymic deletion was intrinsic to T cells carrying diabetes susceptibility genes. These results demonstrate a primary failure to censor forbidden clones of self-reactive T cells in inherited susceptibility to organ-specific autoimmune disease, and highlight the importance of thymic mechanisms of tolerance in organ-specific tolerance

    Detection of Pancreatic Cancer miRNA with Biocompatible Nitrogen-Doped Graphene Quantum Dots

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    Early-stage pancreatic cancer remains challenging to detect, leading to a poor five-year patient survival rate. This obstacle necessitates the development of early detection approaches based on novel technologies and materials. In this work, the presence of a specific pancreatic cancer-derived miRNA (pre-miR-132) is detected using the fluorescence properties of biocompatible nitrogen-doped graphene quantum dots (NGQDs) synthesized using a bottom-up approach from a single glucosamine precursor. The sensor platform is comprised of slightly positively charged (1.14 ± 0.36 mV) NGQDs bound via π-π stacking and/or electrostatic interactions to the negatively charged (-22.4 ± 6.00 mV) bait ssDNA; together, they form a complex with a 20 nm average size. The NGQDs\u27 fluorescence distinguishes specific single-stranded DNA sequences due to bait-target complementarity, discriminating them from random control sequences with sensitivity in the micromolar range. Furthermore, this targetability can also detect the stem and loop portions of pre-miR-132, adding to the practicality of the biosensor. This non-invasive approach allows cancer-specific miRNA detection to facilitate early diagnosis of various forms of cancer

    Breakpoints in immunoregulation required for Th1 cells to induce diabetes

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    We describe a novel TCR-transgenic mouse line, TCR7, where MHC class II-restricted, CD4+ T cells are specific for the subdominant H-2b epitope (HEL74-88) of hen egg lysozyme (HEL), and displayed an increased frequency in the thymus and in peripheral lymphoid compartments over that seen in non-transgenic littermate controls. CD4+ T cells responded vigorously to HEL or HEL74-88 epitope presented on APC and could develop into Th1 or Th2 cells under appropriate conditions. Adoptive transfer of TCR7 Ly5.1 T cells into Ly5.2 rat insulin promoter (RIP)-HEL transgenic recipient hosts did not lead to expansion of these cells or result in islet infiltration, although these TCR7 cells could expand upon transfer into mice expressing high levels of HEL in the serum. Islet cell infiltration only occurred when the TCR7 cells had been polarized to either a Th1 or Th2 phenotype prior to transfer, which led to insulitis. Progression from insulitis to autoimmune diabetes only occurred in these recipients when Th1 but not Th2 TCR7 cells were transferred and CTLA-4 signaling was simultaneously blocked. These findings show that regulatory pathways such as CTLA-4 can hold in check already differentiated autoreactive effector Th1 cells, to inhibit the transition from tolerance to autoimmune diabetes.Schering Plough Research Institute, NJ, and then continued by the Medical Research Council, U
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