630 research outputs found
The role of part structure in the perceptual localization of a shape
No full textThe process of object localization may be accomplished with respect to a particularreference location, such as the center of gravity, COG (eg Vishwanath and Kowler, 2003 VisionResearch 43 1637-1653). Here, we investigated how part structure affects an object's referencelocation. The reference location was evaluated with a measure of the illusory displacement of an internal target element embedded within a larger object (Morgan et al, 1990 Vision Research 30 1793-1810). To examine whether the reference location is different for shapes with part structure, two shapes were tested: circle (small and large; no part structure) and bell (shape with two parts, one larger than the other). Results were examined with respect to two predictions: either the location of an object is based on its shape as a whole, disregarding part structure (ie a single, overall COG), or the parts are processed separately (different COGs).With the circles, the results showed a systematic illusory displacement of the internal target toward the COG. With the bell, the illusion was significantly weaker than with both circles--even though the main part of the bell had the same size as the small circle, and its horizontal axis had the same extent as the large circle. Moreover, the distance judgments for the bell were consistent with a (weaker) reference point being located at the COG of the larger part, rather than at the COG of the entire bell. These results show that the part structure of a shape plays a role in the representation of its location, and that for complex shapes the perceived location of an embedded element depends more on the parts within which it is embedded, rather than on the whole shape.Supported by the Air Force Office of Scientific Research, Grant AF 49620- 02-1-0112, Life Sciences Directorate to Eileen Kowler, and by NSF, Grant BCS-0216944 to Manish Singh.AF 29620-02-1-0112; to Eileen KowlerNSF BCS-0216944; to Manish SinghDenisova, Kristina, Manish Singh, Eileen Kowler, 2006. The definitive, peer-reviewed and edited version of this article is published in Perception, 35, 1073-1087, DOI:10.1068/p5518
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Empirical Reverse Engineering of Vaccine Neoantigens
No full textSince the advent of immunization, vaccines have been composed of natural antigens pulled from the proteome of the infectious agent. To pick potentially protective antigens, pathogens must be deeply studied to elucidate their life cycles, patterns of protein expression, and interactions with their hosts. This reliance on understanding pathogen biology requires the etiology of disease to be known, hampers the speed of vaccine development, and generates vaccines with curtailed efficacy. Infectious pandemics and the cancer epidemic provide unambiguous motivation for the creation of an agnostic platform to develop potent vaccines.Here, we outline our vaccine development approach to (1) characterize T-cell receptors (TCRs) responding to an insult, (2) perform antigen discovery for discovered TCRs, and (3) vaccinate with found, novel neoantigens. We hypothesize that novel, synthetic peptide ligands can effectively prime the same repertoire of na�ve T cells that clonally respond to infection. To find the optimal synthetic antigens, we designed a NFκB-driven, cell-based antigen discovery platform to interrogate TCRs with a diverse and streamlined pool of peptide antigens. Using our functional, unbiased method to screen for peptide ligands, we performed antigen discovery for known TCRs and novel TCRs from an in vivo cancer model. Our platform was specific, sensitive, and tunable in finding TCR-activating antigens. The system was able to successfully find cognate antigens for known TCRs. When performing antigen discovery for T cells resulting from an in vivo tumor model, our platform found antigens corresponding to known, expressed tumor antigens. Furthermore, we found that a streamlined peptide library can reduce peptide library complexity while still providing useful information on TCR-binding motifs. Our future directions include in vitro and in vivo testing with discovered neoantigens for known and novel TCRs.Overall, identifying TCRs and screening TCR-binding ligands can aid in the development of vaccines in the fields of infection, cancer, allergy, autoimmunity, and transplantation. Our long-term goal is to bring about a new method for developing effective antigens for vaccines by identifying peptides that stimulate discovered, insult-specific protective T cells. If successful, our approach will have a major impact on vaccinology: we enable the possibility of developing effective vaccines without having to identify the insult as an initial step, a major boon for emerging infections or epidemics of known or unknown etiology
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Enhancing Tumor-Infiltrating T cells with an Exclusive Fuel Source
No full textSolid tumors harbor immunosuppressive microenvironments that inhibit tumor-infiltrating lymphocytes (TILs) through the voracious consumption of glucose. We sought to restore TIL function by providing them with an exclusive fuel source. The glucose disaccharide cellobiose, which is a building block of cellulose, contains a β-1,4-glycosidic bond that cannot be hydrolyzed by animals (or their tumors), but fungal and bacterial organisms have evolved enzymes to catabolize cellobiose and use the resulting glucose. By equipping T cells with two proteins that enable import and hydrolysis of cellobiose, we demonstrate that supplementation of cellobiose during glucose withdrawal restores T cell cytokine production and cellular proliferation. Murine tumor growth is suppressed, and survival is prolonged. Offering exclusive access to a natural disaccharide is a new tool that augments cancer immunotherapies. Beyond cancer, this approach could be used to answer questions about the regulation of glucose metabolism across many cell types, biological processes, and diseases
Dynamic modeling and forecasting algorithms for financial data systems
No full textIt is a valid question that why a Control Systems Engineer would be interested in dealing with financial instruments. Financial instruments involving option theory are very elegant, math oriented and practical. These mathematical tools have created a new industry known as 'Derivative Industry' or 'Hedge-Fund Industry' or so called 'Risk-Management Industry'. This thesis is aimed at developing investment strategies involving the decision making needs via control system techniques. The problem, in general, is computationally challenging particularly when investment of many securities is involved resulting in a high dimensional computational framework. Furthermore, complications may arise due to realistic restrictions and non-linearities. The various areas of financial engineering are very fertile for the application of the system methodology and control theory techniques. Modeling, optimization, identification and computational methods used in the Systems Engineering can be successfully applied to the financial instruments. The ideas developed in this thesis are more about the scientific reasoning involving financial instruments rather than specific situations alone. Major contribution of this thesis is the time series optimal prediction filter and the development of the Dynamic Modeling and Forecasting Algorithm (DMFA). The proposed algorithm predicts the next data point of the financial time series while dynamically computing the parameters from existing data. The computation of the parameters is optimized by use of the recursive matrix inversion algorithm. The system is solved via an innovative technique of inversion such that it avoids explicit inversion of more than a 2 X 2 matrix and computation of higher dimensional determinants and co-factors. This results in new contributions to computation finance and numerical methodology along with arbitrage decision and hedging strategies under market uncertainties as well as robust control applications. The minimum mean-square algorithm used assures system stability via poles within the unit circle. The DMFA method is a superior auto regression (AR) model as a general system of time-series realizations in-order to calculate the coefficients that fit the model for a better prediction. Theoretical modeling and market specific volatility models, updated volatility computation are derived from the observation data.Ph.D.Includes bibliographical referencesIncludes vitaby Manish Mahaja
Engineered, localized depletion of regulatory T cells produces global anti-tumor immunity
No full textData used to make the figures for Majedi et al, Engineered, localized depletion of regulatory T cells produces global anti-tumor immunity</p
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Macromolecular structures of receptor-ligand complexes from developmental neurobiology and cancer biology
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The relationship between spatial pooling and attention in saccadic and perceptual tasks
No full textAbstractSaccades aimed at spatially extended targets land reliably at central locations determined by pooling information across the target shape [Melcher, D., & Kowler, E. (1999). Shape, surfaces and saccades. Vision Research, 39, 2929–2946; Vishwanath, D., & Kowler, E. (2003). Localization of shapes: Eye movements and perception compared. Vision Research, 43, 1637–1653]. Previous findings of saccadic errors when attempting to look at a target in the midst of distractors encouraged suggestions that pooling occurs indiscriminately, with little or no influence of a selective filter to eliminate the influence of nearby distractors. To determine the effectiveness of filtering, saccadic localization was studied for saccades made to a set of target elements (discs) interleaved with an equivalent set of distractors of a different color. With such interleaved elements, selection and spatial pooling are constrained to occur over the same spatial region. The results showed that filtering was effective and saccadic landing position was determined mainly by the target elements. Concurrent perceptual judgments made about the same stimuli (estimating the mean size of either target or distractor discs) showed better performance for the target discs than distractors, confirming that perceptual attention was allocated to the set of target elements. These results: (1) support the role of attention in setting the input to the spatial pooling process that guides saccades to spatially extended targets, and (2) show that perceptual judgments of mean value, often thought to impose modest attentional demands, are not immune to the constraints of this pre-saccadic filter
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