Summary The contribution of thymic antigen presenting cell (APC) subsets in selecting a selftolerant T cell population remains unclear. We show that bone marrow (BM) APCs and medullary thymic epithelial cells (mTECs) played non-overlapping roles in shaping the T cell receptor (TCR) repertoire by deletion and regulatory T (Treg) cell selection of distinct TCRs. Aire, which induces tissue-specific-antigen expression in mTECs, affected the TCR repertoire in a manner distinct from mTEC presentation. Approximately half of Aire-dependent deletion or Treg cell selection utilized a pathway dependent on antigen presentation by BM APCs. Batf3-dependent CD8α+ dendritic cells (DCs) were the crucial BM APC for Treg cell selection via this pathway, showing enhanced ability to present antigens from stromal cells. These results demonstrate the division of function between thymic APCs in shaping the self-tolerant TCR repertoire, and reveal an unappreciated cooperation between mTECs and CD8α+ DCs for presentation of Aire-induced self-antigens to developing thymocytes.
The proliferation of wireless localization technologies provides a promising future for serving human beings in indoor scenarios. Their applications include real-time tracking, activity recognition, health care, navigation, emergence detection, and target-of-interest monitoring, among others. Additionally, indoor localization technologies address the inefficiency of GPS (Global Positioning System) inside buildings. Since people spend most of their time in indoor environments, indoor tracking service is in great public demand. Based on this observation, this paper aims to provide a better understanding of state-of-the-art technologies and stimulate new research efforts in this field. For these purposes, existing localization technologies that can be used for tracking individuals in indoor environments are reviewed, along with some further discussions.
Proper subcellular localization of focal adhesion kinase (FAK) is crucial for many cellular processes. It remains, however, unclear how FAK activity is regulated at subcellular compartments. To visualize the FAK activity at different membrane microdomains, we develop a fluorescence resonance energy transfer (FRET)-based FAK biosensor, and target it into or outside of detergent-resistant membrane (DRM) regions at the plasma membrane. Here we show that, on cell adhesion to extracellular matrix proteins or stimulation by platelet-derived growth factor (PDGF), the FRET responses of DRM-targeting FAK biosensor are stronger than that at non-DRM regions, suggesting that FAK activation can occur at DRM microdomains. Further experiments reveal that the PDGF-induced FAK activation is mediated and maintained by Src activity, whereas FAK activation on cell adhesion is independent of, and in fact essential for the Src activation. Therefore, FAK is activated at membrane microdomains with distinct activation mechanisms in response to different physiological stimuli.
Globally, the recommendation services have become important due to the fact that they support e-commerce applications and different research communities. Recommender systems have a large number of applications in many fields, including economic, education, and scientific research. Different empirical studies have shown that the recommender systems are more effective and reliable than the keyword-based search engines for extracting useful knowledge from massive amounts of data. The problem of recommending similar scientific articles in scientific community is called scientific paper recommendation. Scientific paper recommendation aims to recommend new articles or classical articles that match researchers' interests. It has become an attractive area of study since the number of scholarly papers increases exponentially. In this paper, we first introduce the importance and advantages of the paper recommender systems. Second, we review the recommendation algorithms and methods, such as Content-based, collaborative filtering, graph-based, and hybrid methods. Then, we introduce the evaluation methods of different recommender systems. Finally, we summarize the open issues in the paper recommender systems, including cold start, sparsity, scalability, privacy, serendipity, and unified scholarly data standards. The purpose of this survey is to provide comprehensive reviews on the scholarly paper recommendation.
We demonstrate a label-free biosensor imaging approach that utilizes a photonic crystal (PC) surface to detect surface attachment of individual dielectric and metal nanoparticles through measurement of localized shifts in the resonant wavelength and resonant reflection magnitude from the PC. Using a microscopy-based approach to scan the PC resonant reflection properties with 0.6 μm spatial resolution, we show that metal nanoparticles attached to the biosensor surface with strong absorption at the resonant wavelength induce a highly localized reduction in reflection efficiency and are able to be detected by modulation of the resonant wavelength. Experimental demonstrations of single-nanoparticle imaging are supported by finite-difference time-domain computer simulations. The ability to image surface-adsorption of individual nanoparticles offers a route to single molecule biosensing, in which the particles can be functionalized with specific recognition molecules and utilized as tags.
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