5,401 research outputs found

    State estimation for aggressive flight in GPS-denied environments using onboard sensing

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    In this paper we present a state estimation method based on an inertial measurement unit (IMU) and a planar laser range finder suitable for use in real-time on a fixed-wing micro air vehicle (MAV). The algorithm is capable of maintaing accurate state estimates during aggressive flight in unstructured 3D environments without the use of an external positioning system. Our localization algorithm is based on an extension of the Gaussian Particle Filter. We partition the state according to measurement independence relationships and then calculate a pseudo-linear update which allows us to use 20x fewer particles than a naive implementation to achieve similar accuracy in the state estimate. We also propose a multi-step forward fitting method to identify the noise parameters of the IMU and compare results with and without accurate position measurements. Our process and measurement models integrate naturally with an exponential coordinates representation of the attitude uncertainty. We demonstrate our algorithms experimentally on a fixed-wing vehicle flying in a challenging indoor environment

    Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.

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    One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting human GUCY2C-expressing metastases. Human GUCY2C-targeted murine CAR-T cells promoted antigen-dependent T-cell activation quantified by activation marker upregulation, cytokine production, and killing of GUCY2C-expressing, but not GUCY2C-deficient, cancer cells in vitro. GUCY2C CAR-T cells provided long-term protection against lung metastases of murine colorectal cancer cells engineered to express human GUCY2C in a syngeneic mouse model. GUCY2C murine CAR-T cells recognized and killed human colorectal cancer cells endogenously expressing GUCY2C, providing durable survival in a human xenograft model in immunodeficient mice. Thus, we have identified a human GUCY2C-specific CAR-T cell therapy approach that may be developed for the treatment of GUCY2C-expressing metastatic colorectal cancer

    Prediction of breast cancer prognosis using gene set statistics provides signature stability and biological context

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    <p>Abstract</p> <p>Background</p> <p>Different microarray studies have compiled gene lists for predicting outcomes of a range of treatments and diseases. These have produced gene lists that have little overlap, indicating that the results from any one study are unstable. It has been suggested that the underlying pathways are essentially identical, and that the expression of gene sets, rather than that of individual genes, may be more informative with respect to prognosis and understanding of the underlying biological process.</p> <p>Results</p> <p>We sought to examine the stability of prognostic signatures based on gene sets rather than individual genes. We classified breast cancer cases from five microarray studies according to the risk of metastasis, using features derived from predefined gene sets. The expression levels of genes in the sets are aggregated, using what we call a set statistic. The resulting prognostic gene sets were as predictive as the lists of individual genes, but displayed more consistent rankings via bootstrap replications within datasets, produced more stable classifiers across different datasets, and are potentially more interpretable in the biological context since they examine gene expression in the context of their neighbouring genes in the pathway. In addition, we performed this analysis in each breast cancer molecular subtype, based on ER/HER2 status. The prognostic gene sets found in each subtype were consistent with the biology based on previous analysis of individual genes.</p> <p>Conclusions</p> <p>To date, most analyses of gene expression data have focused at the level of the individual genes. We show that a complementary approach of examining the data using predefined gene sets can reduce the noise and could provide increased insight into the underlying biological pathways.</p

    Central charges, S-duality and massive vacua of N=1* super Yang-Mills

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    We provide a simple derivation of the extremal values of the superpotential in massive vacua of N=1* SYM, making use of the required modular weight for the central charge of BPS walls interpolating between these vacua. This modular weight descends from the action of S-duality on the N=4 superalgebra which in turn is inherited from its classical action on the dyon spectrum. We show that this kinematic information, combined with minimal knowledge of the weak coupling asymptotics, is sufficient to determine the exact vacuum superpotentials in terms of Eisenstein series.Comment: 8 pages; v2: reference added, to appear in Phys. Lett.

    Topical CpG Oligodeoxynucleotide Adjuvant Enhances the Adaptive Immune Response against Influenza A Infections

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    Current influenza vaccines generate humoral immunity, targeting highly variable epitopes and thus fail to achieve long-term protection. T cells recognize and respond to several highly conserved epitopes across influenza serotypes. A strategy of raising strong cytotoxic T cell memory responses to epitopes conserved across serotypes would provide cross serotype protection, eliminating the need for annual vaccination. We explored the adjuvant potential of epicutaneous (ec) and subcutaneous (sc) delivery of CpG oligodeoxynucleotide in conjunction with subcutaneous protein immunization to improve protection against influenza A virus infections using a mouse model. We found enhanced long-term protection with ecCpG compared to scCpG as demonstrated by reduced viral titers in the lungs. This correlated with increased antigen-specific CD8 T cells in the airways and the lungs. The memory T cell response after immunization with ecCpG adjuvant was comparable to memory response by priming with influenza A virus infection in the lungs. In addition, ecCpG was more efficient than scCpG in inducing the generation of IFN-γ producing CD4 T cells. The adjuvant effect of ecCpG was accompanied with its ability to modulate tissue-homing molecules on T cells that may direct them to the site of infection. Together, this work provides evidence for using ecCpG to induce strong antibody and memory T cell responses to confer protection against influenza A virus infection

    Further investigations of the deep double donor magnesium in silicon

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    The deep double donor levels of substitutional chalcogen impurities in silicon have unique optical properties which may enable a spin/photonic quantum technology. The interstitial magnesium impurity (Mgi_i) in silicon is also a deep double donor but has not yet been studied in the same detail as have the chalcogens. In this study we look at the neutral and singly ionized Mgi_i absorption spectra in natural silicon and isotopically enriched 28-silicon in more detail. The 1s(A1_1) to 1s(T2_2) transitions, which are very strong for the chalcogens and are central to the proposed spin/photonic quantum technology, could not be detected. We observe the presence of another double donor (Mgi_{i*}) that may result from Mgi_i in a reduced symmetry configuration, most likely due to complexing with another impurity. The neutral species of Mgi_{i*} reveal unusual low lying ground state levels detected through temperature dependence studies. We also observe a shallow donor which we identify as a magnesium-boron pair

    Decoupling Information and Connectivity in Information-Centric Networking

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    This paper introduces and demonstrates the concept of Information-Centric Transport as a mechanism for cleanly decoupling the information plane from the connectivity plane in Information-Centric Networking (ICN) architectures, such as NDN and CICN. These are coupled in today\u27s incarnations of NDN and CICN through the use of forwarding strategy, which is the architectural component for deciding how to forward packets in the presence of either multiple next-hop options or dynamic feedback. As presently designed, forwarding strategy is not sustainable: application developers can only confidently specify strategy if they understand connectivity details, while network node operators can only confidently assign strategies if they understand application expectations. We show how Information-Centric Transport allows applications to operate on the information plane, concerned only with the namespace and identities relevant to the application, leaving network node operators free to implement ICT services in whatever way makes sense for the connectivity that they manage. To illustrate ICT, we introduce sync*, a synchronization service, and show how a) its use enables applications to operate well regardless of connectivity details and b) its implementation can be completely managed by network operators with no knowledge of application details

    First-order framework and generalized global defect solutions

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    This work deals with defect structures in models described by scalar fields. The investigations focus on generalized models, with the kinetic term modified to allow for a diversity of possibilities. We develop a new framework, in which we search for first-order differential equations which solve the equations of motion. The main issue concerns the introduction of a new function, which works like the superpotential usually considered in the standard situation. We investigate the problem in the general case, with an arbitrary number of fields, and we present several explicit examples in the case of a single real scalar field.Comment: 8 pages, 6 figures; version to appear in PL
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