1,442 research outputs found
Biomarkers and viral risk factors in multiple sclerosis
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
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
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
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
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
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Cascading Activation Across Levels of Representation in Children's Lexical Processing
Recent work in adult psycholinguistics has demonstrated that activation of semantic representations begins long before phonological processing is complete. This incremental propagation of information across multiple levels of analysis is a hallmark of adult language processing but how does this ability develop? In two experiments, we elicit measures of incremental activation of semantic representations during word recognition in children. Five-year-olds were instructed to select a target (logs) while their eye-movements were measured to a competitor (key) that was semantically related to an absent phonological associate (lock). We found that like adults, children made increased looks to competitors relative to unrelated control items. However unlike adults, children continued to look at the competitor even after the target word was uniquely identified and were more likely to incorrectly select this item. Altogether, these results suggest that early lexical processing involves cascading activation but less efficient resolution of competing entries.Psycholog
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Logic and Conversation Revisited: Evidence For a Division Between Semantic and Pragmatic Content in Real Time Language Comprehension
The distinction between semantics (linguistically encoded meaning) and pragmatics (inferences about communicative intentions) can often be unclear and counterintuitive. For example, linguistic theories argue that the meaning of some encompasses the meaning of all while the intuition that some implies not all results from an inference. We explored how online interpretation of some evolves using an eye-tracking while listening paradigm. Early eye-movements indicated that while some was initially interpreted as compatible with all, participants began excluding referents compatible with all approximately 800 ms later. These results contrast with recent evidence of immediate inferencing and highlight the presence of bottom-up semantic–pragmatic interactions which necessarily rely on initial access to lexical meanings to trigger inferences.Psycholog
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Semantic Meaning and Pragmatic Interpretation in 5-Year-Olds: Evidence from Real-Time Spoken Language Comprehension
Recent research on children's inferencing has found that although adults typically adopt the pragmatic interpretation of some (implying not all), 5- to 9-year-olds often prefer the semantic interpretation of the quantifier (meaning possibly all). Do these failures reflect a breakdown of pragmatic competence or the metalinguistic demands of prior tasks? In 3 experiments, the authors used the visual-world eye-tracking paradigm to elicit an implicit measure of adults' and children's abilities to generate scalar implicatures. Although adults' eye-movements indicated that adults had interpreted some with the pragmatic inference, children's looks suggested that children persistently interpreted some as compatible with all (Experiment 1). Nevertheless, both adults and children were able to quickly reject competitors that were inconsistent with the semantics of some; this confirmed the sensitivity of the paradigm (Experiment 2). Finally, adults, but not children, successfully distinguished between situations that violated the scalar implicature and those that did not (Experiment 3). These data demonstrate that children interpret quantifiers on the basis of their semantic content and fail to generate scalar implicatures during online language comprehension.Psycholog
Using Digital Maps to Find Shelter for Pedestrians and Cyclists During Inclement Weather
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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