1,442 research outputs found

    Biomarkers and viral risk factors in multiple sclerosis

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    Multiple sclerosis (MS) is a chronic inflammatory disease resulting in axonal injury and demyelination of nerve fibers in the central nervous system. The causal factor and pathological mechanisms governing disease progression have remained elusive, limiting the available clinical tools for MS diagnosis and treatment monitoring, particularly in the periphery. In the following studies, we investigated potential [1] protein biomarkers capable of differentiating MS and characterizing disease activity and [2] serological biomarkers that may predict MS risk or adverse events associated with immunomodulatory treatment. Studies I-III measured proteins in cerebrospinal fluid (CSF) and plasma using a highsensitivity proximity extension immunoassay to characterize the differential protein profile associated with MS. Although many require further validation, several proteins in CSF (e.g., IL12B and CD79B) and plasma (e.g., OSM) show promise in differentiating early stages of MS and assessing progressive disease, relapse activity, and severity of disability progression. Many also complement current diagnostic tools for MS, including oligoclonal bands, IgG index, and MRI T2 lesions. Measures were responsive to common disease-modifying drugs, including natalizumab and fingolimod, indicating the potential for monitoring treatment efficacy. Lastly, in Study IV, we characterized the susceptibility of several of these inflammation-related proteins to sample processing conditions, a necessary consideration for reliable usage in clinical practice. In Study V, we showed high anti-EBNA1 IgG levels (Epstein-Barr virus, EBV), particularly against the aa385-420 peptide fragment, were associated with an increased risk for MS, independent of any history of infectious mononucleosis. Genome-wide association analysis showed HLA as the primary genetic risk factor for high EBNA-1/VCAp18 antibody response, particularly the MS risk haplotype with DRB1*15:01. A bi-directional relationship between EBV and MS genetic susceptibility was observed, with genetic susceptibility to high EBNA- 1 IgG resulting in an increased risk for MS and vice versa. Overlapping HLA associations with MS and previous auto-antigen studies may indicate the role of molecular mimicry. Study VI identified genetic risk factors affecting JC polyomavirus (JCV) seropositivity, a risk assessment measure for progressive multifocal leukoencephalopathy (PML). In addition to HLA, genetic polymorphisms in the FUT2 and ABO genes, corresponding with secretor status and blood group phenotypes, were associated with anti-JCV(VP1) IgG levels. These findings indicate a potential neutralization effect of ABH antigens against JCV. However, further investigation is needed to assess the implications of HLA and blood phenotypes in the risk assessment of PML, particularly for MS treatment

    Homotopy Path Algebras

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    We define a basic class of algebras which we call homotopy path algebras. We find that such algebras always admit a cellular resolution and detail the intimate relationship between these algebras, stratifications of topological spaces, and entrance/exit paths. As examples, we prove versions of homological mirror symmetry due to Bondal-Ruan for toric varieties and due to Berglund-H\"ubsch-Krawitz for hypersurfaces with maximal symmetry. We also demonstrate that a form of shellability implies Koszulity and the existence of a minimal cellular resolution. In particular, when the algebra determined by the image of the toric Frobenius morphism is directable, then it is Koszul and admits a minimal cellular resolution.Comment: 40 pages. Mistakes in Ch. 6 of previous version corrected. Submitte

    Rouquier dimension is Krull dimension for normal toric varieties

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    We prove that for any normal toric variety, the Rouquier dimension of its bounded derived category of coherent sheaves is equal to its Krull dimension. Our proof uses the coherent-constructible correspondence to translate the problem into the study of Rouquier dimension for certain categories of constructible sheaves.Comment: 9 pages. Added acknowledgements and additional citations. Small errors and typos fixe

    A Survey on the Role of Individual Differences on Visual Analytics Interactions: Masters Project Report

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    There is ample evidence in the visualization commu- nity that individual differences matter. These prior works high- light various traits and cognitive abilities that can modulate the use of the visualization systems and demonstrate a measurable influence on speed, accuracy, process, and attention. Perhaps the most important implication of this body of work is that we can use individual differences as a mechanism for estimating people’s potential to effectively leverage visual interfaces or to identify those people who may struggle. As visual literacy and data fluency continue to become essential skills for our everyday lives, we must embrace the growing need to understand the factors that divide our society, and identify concrete steps for bridging this gap. This paper presents the current understanding of how individual differences interact with visualization use and draws from recent research in the Visualization, Human-Computer Interaction, and Psychology communities. We focus on the specific designs and tasks for which there is concrete evidence of performance divergence due to individual characteristics. The purpose of this paper is to underscore the need to consider individual differences when designing and evaluating visualization systems and to call attention to this critical future research direction

    The Use of Lexical and Referential Cues in Children’s Online Interpretation of Adjectives

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    Recent research on moment-to-moment language comprehension has revealed striking differences between adults and preschool children. Adults rapidly use the referential principle to resolve syntactic ambiguity, assuming that modification is more likely when there are 2 possible referents for a definite noun phrase. Young children do not. We examine the scope of this phenomenon by exploring whether children use the referential principle to resolve another form of ambiguity. Scalar adjectives (big, small) are typically used to refer to an object when contrasting members of the same category are present in the scene (big and small coins). In the present experiment, 5-year-olds and adults heard instructions like “Point to the big (small) coin” while their eye-movements were measured to displays containing 1 or 2 coins. Both groups rapidly recruited the meaning of the adjective to distinguish between referents of different sizes. Critically, like adults, children were quicker to look to the correct item in trials containing 2 possible referents compared with 1. Nevertheless, children's sensitivity to the referential principle was substantially delayed compared to adults', suggesting possible differences in the recruitment of this top- down cue. The implications of current and previous findings are discussed with respect to the development of the architecture of language comprehension.LinguisticsPsycholog

    Using Digital Maps to Find Shelter for Pedestrians and Cyclists During Inclement Weather

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    Walkers, runners, hikers, and bicyclists or other travelers that use non-motorized vehicles are at risk of being caught in bad weather. Currently, such users of a road or hiking/bicycling pathway need to find shelters on their own or ask locals or fellow travelers for advice. This disclosure describes techniques that enable road or trail users to find nearby shelters to stay in during periods of bad weather or in other situations where they may need to take shelter. With user permission, data from observed points where stops are made during bad weather events, geographic data, reviews and other textual materials, etc. are used to train a prediction model to generate route recommendations that include shelters. The identified route is provided in a digital map provided to the user. The map includes markings for shelters that are determined based on the form of transport
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