155 research outputs found
Heterologous CD8 T Cell Immune Response to HSV Induced by Toll Like Receptor Ligands
No full textA memory response is established following primary antigen exposure that stays more or less constant. It appears to adopt a set-point in magnitude but upon re-exposure the response is quicker and better and there is an upward shift in memory frequency that varies with individuals based on the exposure pattern to other microbes or its components. Our investigations were designed to test such differences of non-specific stimulation by PAMPs in lowering the threshold of activation. Neonatal mice were pre-exposed to TLR-ligands intermittently and later analyzed for its resilience to challenge with virus during adult-life. Secondly, adult mice with pre-existing memory to virus were exposed to various TLR-ligands and analyzed for their quality of memory response. The TLR-ligands exposed animals were better responders to a new agent exposure compared to the animals kept in sterile surroundings. Moreover, immune memory recall and the viral specific CD8+ T cells response with TLR-ligands were comparable to the recall response with the cognate antigen. The results provide insights into the role of hyper-sanitized environment versus PAMPs mediated signaling in adaptive immunity and long-term immune memory
PLoS One
No full textMycobacterium bovis bacille Calmette-Gu\ue9rin (BCG) is the most widely used live attenuated vaccine. However, the correlates of protection and waning of its immunity against tuberculosis is poorly understood. In this study, we correlated the longitudinal changes in the magnitude and functional quality of CD4+ and CD8+ T-cell response over a period of two years after mucosal or parenteral BCG vaccination with the strength of protection against Mycobacterium tuberculosis in mice. The BCG vaccination-induced CD4+ and CD8+ T cells exhibited comparable response kinetics but distinct functional attributes in-terms of IFN-\u3b3, IL-2 and TNF-\u3b1 co-production and CD62L memory marker expression. Despite a near life-long BCG persistence and the induction of enduring CD4+ T-cell responses characterized by IFN-\u3b3 and/or TNF-\u3b1 production with comparable protection, the protective efficacy waned regardless of the route of vaccination. The progressive decline in the multifactorial functional abilities of CD4+ and CD8+ T cells in-terms of type-1 cytokine production, proliferation and cytolytic potential corresponded with the waning of protection against M. tuberculosis infection. In addition, simultaneous increase in the dysfunctional and terminally-differentiated T cells expressing CTLA-4, KLRG-1 and IL-10 during the contraction phase of BCG-induced response coincided with the loss of protection. Our results question the empirical development of BCG-booster vaccines and emphasize the pursuit of strategies that maintain superior T-cell functional capacity. Furthermore, our results underscore the importance of understanding the comprehensive functional dynamics of antigen-specific T-cell responses in addition to cytokine polyfunctionality in BCG-vaccinated hosts while optimizing novel vaccination strategies against tuberculosis.20141023
T regulatory cells: an overview and intervention techniques to modulate allergy outcome
No full textAbstract Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is growing evidence in support of T cells with regulatory potential that operates in non-allergic individuals. These regulatory T cells occur naturally are called natural T regulatory cells (nTregs) and express the transcription factor Foxp3. They are selected in the thymus and move to the periphery. The CD4 Th cells in the periphery can be induced to become regulatory T cells and hence called induced or adaptive T regulatory cells. These cells can make IL-10 or TGF-b or both, by which they attain most of their suppressive activity. This review gives an overview of the regulatory T cells, their role in allergic diseases and explores possible interventionist approaches to manipulate Tregs for achieving therapeutic goals.</p
Imaging the spread of reversible brain inactivations using fluorescent muscimol
No full textAuthor manuscript. Published in final edited form as:
J Neurosci Methods. 2008 June 15; 171(1): 30–38
Privacy-Aware State Estimation based on Obfuscated Transformation and Differential Privacy: With applications to smart grids and supply chain economics
No full textWith the emergence of many modern automated systems around us that rely heavily on the private data collected from individuals, the problem of privacy-preserving data analysis is now gaining a significant attention in the field of systems and control. In this thesis, we investigate the privacy concerns of these systems arising in the process of state estimation - a well known and a widely studied concept in systems and control. Our work draws motivation from smart grids and supply chain economics, and hence, we study two different privacy problems in the context of state estimation and rely on cryptography to solve these challenges.In the first problem, we study the privacy challenges of state estimation in smart grids. Smart grids promise a more reliable, efficient, economically viable, and an environment-friendly electricity infrastructure for the future. State estimation in smart grids plays a vital role in system monitoring, reliable operation, automation, and grid stabilization. However, the power consumption data collected from the users during estimation can be privacy-sensitive. Furthermore, the topology of the grid can be exploited by malicious entities during state estimation to launch attacks without getting detected. Motivated by the essence of a secure state estimation process, we propose a weighted-least-squares estimation carried out batch-wise at repeated intervals where the resource-constrained clients utilize a malicious cloud for computation services. We exploit a highly efficient and verifiable obfuscation-based cryptographic solution to perform the computations of the estimation process securely in the presence of a malicious adversary. Simulation results demonstrate a high level of obscurity both in time and frequency domain making it difficult for the malicious adversary to interpret information about the original power consumption data of the consumers and the grid topology from the obfuscated datasets. Our second problem deals with the challenge of protecting a dynamical supply chain model while releasing the state sequences generated by the model for data aggregation to an external possible adversary. Releasing state samples generated by a dynamical system model with high accuracy for data aggregation and other statistical purposes can also be used for reverse engineering and estimating sensitive model parameters. Upon identification of the system model, the adversary may even use it for predicting sensitive data in the future. Hence, preserving a confidential dynamical process model is crucial for the survival of many industries. Motivated by the need to protect the system model as a trade secret, we propose a mechanism based on differential privacy to render such model identification techniques ineffective while preserving the utility of the state samples for data aggregation purposes. We deploy differential privacy by generating noise according to the sensitivity of the query and adding it to the state vectors at each time instant. We derive analytical expressions to quantify the bound on the sensitivity function and estimate the minimum noise level required to guarantee differential privacy. Furthermore, we present numerical analysis and characterize the privacy-utility trade-off that arises when deploying differential privacy. Simulation results demonstrate that through differential privacy, we achieve acceptable privacy level sufficient to mislead the adversary while still managing to retain high utility level of the state samples for data aggregation. Mechanical Engineering | Systems and Contro
The Role of High-Tech Capital Formation for Swedish Productivity Growth
No full textWhile using new data and standard growth-accounting techniques, this paper takes a closer look at the Swedish productivity revival in the second half of the 1990s. In particular, I find large total factor productivity growth in high-tech producing sectors and capital deepening associated with high-tech equipment elsewhere. In addition, for high-tech producers, high-tech capital deepening has as a rule contributed negatively to labor productivity growth - a result above all driven by large increases in hours worked in this sector. I also find that in the business sector, the contribution from high-tech capital deepening to labor productivity growth increased from about 1 percent 1994 to 9 percent 1999.
PLoS One
No full textBackgroundThe identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis.Methods and Principal FindingsIn this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study.Conclusion and SignificanceOverall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis
Evaluating Macroscopic DTA Models – For Who, When and How?
No full textOver the past few decades, transport authorities globally have resorted to transport models for testing policy interventions and simulating the results as part of the ex-ante analysis. Within the domains of traffic assignment, there is a greater focus on the dynamic representation of traffic, which has proved to be more accurate when compared to their static counterparts. This has put Dynamic Traffic Assignment (DTA) Models at the forefront of development. Departing from the classical traffic flow theories Macroscopic DTA’s simulates aggregated traffic analogous to the flow of fluids or gases. This aggregation enables high-speed computation with the ability to achieve a stable equilibrium state within feasible model run times. Due to the large number of Macroscopic DTA models developed worldwide, the model user is posed with the problem of using the correct model for the correct application. The current research aims to provide an answer to this problem through the design, development, and validation of an evaluation framework for Macroscopic DTA’s. The objective evaluation of the DTA’s is performed through certain Measures of Performances (MoPs). The subjective side of evaluation showcases the differences in importance associated with model features which vary from model users to application domains. Three macroscopic DTA models popular in the Netherlands are used for the application of the framework: the MARPLE (Model for Assignment and Regional Policy Evaluation), StreamLine: MaDAM (Macroscopic Dynamic Assignment Model), and StreamLine: eGLTM (event-based Generalized Link Transmission Model). From the results, it is observed that For a Strategic Planning application, both MARPLE and StreamLine: eGLTM proved to be better alternatives, as they performed exceedingly better in achieving a stable state of convergence. However, as the time horizons of application became smaller as is the case with Tactical and Operational planning, the final score for StreamLine: MaDAM improved substantially due to its accuracy involved in link-level propagation and queuing. The evaluation scores also showcase the fundamental trade-off between model complexity and computational speed was visible from the results. We can observe variations across model users, which validates our original hypothesis that the right choice of a model primary depends on the person using it and the application it is deployed for.Civil Engineering | Transport and Plannin
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