1,729 research outputs found

    Robust cryogenic matched low-pass coaxial filters for quantum computing applications

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    Electromagnetic noise is one of the key external factors decreasing superconducting qubits coherence. Matched coaxial filters can prevent microwave and IR photons negative influence on superconducting quantum circuits. Here, we report on design and fabrication route of matched low-pass coaxial filters for noise-sensitive measurements at milliKelvin temperatures. A robust transmission coefficient with designed linear absorption (-1dB/GHz) and ultralow reflection losses less than -20 dB up to 20 GHz is achieved. We present a mathematical model for evaluating and predicting filters transmission parameters depending on their dimensions. It is experimentally approved on two filters prototypes different lengths with compound of Cu powder and Stycast commercial resin demonstrating excellent matching. The presented design and assembly route are universal for various compounds and provide high repeatability of geometrical and microwave characteristics. Finally, we demonstrate three filters with almost equal reflection and transmission characteristics in the range from 0 to 20 GHz, which is quite useful to control multiple channel superconducting quantum circuits.Comment: 5 pages, 4 figure

    Mutational re-modeling of di-aspartyl intramembrane proteases: uncoupling physiologically-relevant activities from those associated with Alzheimer\u27s disease

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    The intramembrane proteolytic activities of presenilins (PSEN1/PS1 and PSEN2/PS2) underlie production of beta-amyloid, the key process in Alzheimer\u27s disease (AD). Dysregulation of presenilin-mediated signaling is linked to cancers. Inhibition of the gamma-cleavage activities of PSENs that produce Abeta, but not the epsilon-like cleavage activity that release physiologically essential transcription activators, is a potential approach for the development of rational therapies for AD. In order to identify whether different activities of PSEN1 can be dissociated, we designed multiple mutations in the evolutionary conserved sites of PSEN1. We tested them in vitro and in vivo assays and compared their activities with mutant isoforms of presenilin-related intramembrane di-aspartyl protease (IMPAS1 (IMP1)/signal peptide peptidase (SPP)). PSEN1 auto-cleavage was more resistant to the mutation remodeling than the epsilon-like proteolysis. PSEN1 with a G382A or a P433A mutation in evolutionary invariant sites retains functionally important APP epsilon- and Notch S3- cleavage activities, but G382A inhibits APP gamma-cleavage and Abeta production and a P433A elevates Abeta. The G382A variant cannot restore the normal cellular ER Ca(2+) leak in PSEN1/PSEN2 double knockout cells, but efficiently rescues the loss-of-function (Egl) phenotype of presenilin in C. elegans. We found that, unlike in PSEN1 knockout cells, endoplasmic reticulum (ER) Ca(2+) leak is not changed in the absence of IMP1/SPP. IMP1/SPP with the analogous mutations retained efficiency in cleavage of transmembrane substrates and rescued the lethality of Ce-imp-2 knockouts. In summary, our data show that mutations near the active catalytic sites of intramembrane di-aspartyl proteases have different consequences on proteolytic and signaling functions

    Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells

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    B cell responses are critical for antiviral immunity. However, a comprehensive picture of antigen-specific B cell differentiation, clonal proliferation, and dynamics in different organs after infection is lacking. Here, by combining single-cell RNA and B cell receptor (BCR) sequencing of antigen-specific cells in lymph nodes, spleen, and lungs after influenza infection in mice, we identify several germinal center (GC) B cell subpopulations and organ-specific differences that persist over the course of the response. We discover transcriptional differences between memory cells in lungs and lymphoid organs and organ-restricted clonal expansion. Remarkably, we find significant clonal overlap between GC-derived memory and plasma cells. By combining BCR-mutational analyses with monoclonal antibody (mAb) expression and affinity measurements, we find that memory B cells are highly diverse and can be selected from both low- and high-affinity precursors. By linking antigen recognition with transcriptional programming, clonal proliferation, and differentiation, these finding provide important advances in our understanding of antiviral immunity

    In Vivo Fluorescence Lifetime Imaging Monitors Binding of Specific Probes to Cancer Biomarkers

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    One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the “image and treat” concept, especially for early evaluation of the efficacy of the therapy

    Transverse-momentum ptp_t correlations on (η,ϕ)(\eta,\phi) from mean-ptp_{t} fluctuations in Au-Au collisions at sNN=\sqrt{s_{NN}} = 200 GeV

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    We present first measurements of the pseudorapidity and azimuth (η,ϕ)(\eta,\phi) bin-size dependence of event-wise mean transverse momentum fluctuations for Au-Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV. We invert that dependence to obtain ptp_t autocorrelations on differences (ηΔ,ϕΔ)(\eta_\Delta,\phi_\Delta) interpreted to represent velocity/temperature distributions on (η,ϕ\eta,\phi). The general form of the autocorrelations suggests that the basic correlation mechanism is parton fragmentation. The autocorrelations vary strongly with collision centrality, which suggests that fragmentation is strongly modified by a dissipative medium in the more central Au-Au collisions relative to peripheral or p-p collisions. \\Comment: 7 pages, 3 figure

    Potential of Core-Collapse Supernova Neutrino Detection at JUNO

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    JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

    Detection of the Diffuse Supernova Neutrino Background with JUNO

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    As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO
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