Quantum Double Lock-in Amplifier

Quantum lock-in amplifier aims to extract an alternating signal within strong noise background by using quantum strategy. However, as the target signal usually has an unknown initial phase, we can't obtain the complete information of its amplitude, frequency and phase in a single lock-in measurement. Here, to overcome this challenge, we give a general protocol for achieving a quantum double lock-in amplifier and illustrate its realization. In analog to a classical double lock-in amplifier, our protocol is accomplished via two quantum mixers under orthogonal pulse sequences. The two orthogonal pulse sequences act the roles of two orthogonal reference signals in a classical double lock-in amplifier. Combining the output signals, the complete characteristics of the target signal can be obtained. As an example, we illustrate the realization of our quantum double lock-in amplifier via a five-level double-$\Lambda$ coherent population trapping system with $^{87}$Rb atoms, in which each $\Lambda$ structure acts as a quantum mixer and the two applied dynamical decoupling sequences take the roles of two orthogonal reference signals. Our numerical calculations show that the quantum double lock-in amplifier is robust against experimental imperfections, such as finite pulse length and stochastic noise. Our study opens an avenue for extracting complete characteristics of an alternating signal within strong noise background, which is beneficial for developing practical quantum sensing technologies

Error compensation and accuracy analysis of laser measurement system based on laser-beam calibration

Abstract(#br)In this paper, a novel measurement strategy, based on a 4D error-compensation model for the measurement of free-form surfaces in laser measurement systems, is presented. To improve the measurement accuracy, effects of the inclination angle and the azimuth angle (including the rotation angle and the deflection angle) on the measurement results are investigated experimentally. Considering the error compensation and the constructing iterative function, a calibration method for arbitrary positions and orientations of the laser-beam is presented, and a corresponding measurement strategy is presented. To verify the effectiveness and accuracy of the proposed measurement strategy, calibration schemes of a check bar geometry center are studied based on a 4-axis measuring platform. The obtained results demonstrate that the proposed strategy can greatly improve the measurement accuracy

Fine structures of radio bursts from flare star AD Leo with FAST observations

Radio bursts from nearby active M-dwarfs have been frequently reported and extensively studied in solar or planetary paradigms. Whereas, their sub-structures or fine structures remain rarely explored despite their potential significance in diagnosing the plasma and magnetic field properties of the star. Such studies in the past have been limited by the sensitivity of radio telescopes. Here we report the inspiring results from the high time-resolution observations of a known flare star AD Leo with the Five-hundred-meter Aperture Spherical radio Telescope (FAST). We detected many radio bursts in the two days of observations with fine structures in the form of numerous millisecond-scale sub-bursts. Sub-bursts on the first day display stripe-like shapes with nearly uniform frequency drift rates, which are possibly stellar analogs to Jovian S-bursts. Sub-bursts on the second day, however, reveal a different blob-like shape with random occurrence patterns and are akin to solar radio spikes. The new observational results suggest that the intense emission from AD Leo is driven by electron cyclotron maser instability which may be related to stellar flares or interactions with a planetary companion.Comment: 25 pages, 12 figures, accepted for publication in Ap

Xin-Li-Fang efficacy and safety for patients with chronic heart failure: A study protocol for a randomized, double-blind, and placebo-controlled trial

IntroductionXin-Li-Fang (XLF), a representative Chinese patent medicine, was derived from years of clinical experience by academician Chen Keji, and is widely used to treat chronic heart failure (CHF). However, there remains a lack of high-quality evidence to support clinical decision-making. Therefore, we designed a randomized controlled trial (RCT) to evaluate the efficacy and safety of XLF for CHF.Methods and designThis multicenter, double-blinded RCT will be conducted in China. 300 eligible participants will be randomly assigned to either an XLF group or a control group at a 1:1 ratio. Participants in the XLF group will receive XLF granules plus routine care, while those in the control group will receive placebo granules plus routine care. The study period is 26 weeks, including a 2-week run-in period, a 12-week treatment period, and a 12-week follow-up. The primary outcome is the proportion of patients whose serum NT-proBNP decreased by more than 30%. The secondary outcomes include quality of life, the NYHA classification evaluation, 6-min walking test, TCM symptom evaluations, echocardiography parameters, and clinical events (including hospitalization for worsening heart failure, all-cause death, and other major cardiovascular events).DiscussionThe results of the study are expected to provide evidence of high methodological and reporting quality on the efficacy and safety of XLF for CHF.Clinical trial registrationChinese Clinical Trial Registration Center (www.chictr.org.cn). The trial was registered on 13 April 2022 (ChiCTR2200058649)

Ecdysone Elicits Chronic Renal Impairment via Mineralocorticoid-Like Pathogenic Activities

Background/Aims: Ecdysteroids are steroidal insect molting hormones that also exist in herbs. Ecdysteroid-containing adaptogens have been popularly used to improve well-being and by bodybuilders for muscle growth. However, the use of ecdysone in mammals is also associated with kidney growth and enlargement, indications of disturbed kidney homeostasis. The underlying pathogenic mechanism remains to be clarified. Methods: Virtual screening tools were employed to identify compounds that are homologous to ecdysone and to predict putative ecdysone-interacting proteins. The kidney effect of ecdysone was examined in vitro and in vivo and compared with that of aldosterone. Cellular apoptosis was estimated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Cell motility was assessed by scratch-wound cell migration assay. Blood urea nitrogen was measured to evaluate renal function. Western immunblot analysis was employed to determine the expression profile of interested proteins. Results: Computational molecular structure analysis revealed that ecdysone is highly homologous to aldosterone. Moreover, virtual screening based on compound-protein interaction profiles identified the Mineralocorticoid Receptor (MR) to potentially interact with ecdysone. Accordingly, to assess potential biological functions of ecdysone in mammals, ecdysone was applied to mineralocorticoid-sensitive inner medullar collecting duct cells. Ecdysone induced mesenchymal accumulation of extracellular matrix and epithelial dedifferentiation characterized by de novo expression of α-smooth muscle actin. In addition, ecdysone elicited cellular apoptosis and retarded cell motility, akin to the effect of aldosterone. In vivo, daily treatment of mice with ecdysone increased cell apoptosis in the kidney, impaired renal function and elicited early signs of renal fibrogenesis, marked by deposition of collagen and fibronectin in tubulointerstitium, reminiscent of the action of aldosterone. The MR signaling pathway is likely responsible for the cellular and pathobiological effects of ecdysone, as evidenced by strong ecdysone-induced MR nuclear translocation in renal tubular cells both in vitro and in vivo, while blockade of MR by concomitant spironolactone treatment largely abolished the detrimental effects of ecdysone. Conclusion: Our findings suggest that ecdysone induces mineralocorticoid-dependent activities that impair renal function and elicit renal injury

Optimizing the face paradigm of BCI system by modified mismatch negative paradigm

Many recent studies have focused on improving the performance of event-related potential (ERP) based brain computer interfaces (BCIs). The use of a face pattern has been shown to obtain high classification accuracies and information transfer rates (ITRs) by evoking discriminative ERPs (N200 and N400) in addition to P300 potentials. Recently, it has been proved that the performance of traditional P300-based BCIs could be improved through a modification of the mismatch pattern. In this paper, a mismatch inverted face pattern (MIF-pattern) was presented to improve the performance of the inverted face pattern (IF-pattern), one of the state of the art patterns used in visual-based BCI systems. Ten subjects attended in this experiment. The result showed that the mismatch inverted face pattern could evoke significantly larger vertex positive potentials (p < 0.05) and N400s (p < 0.05) compared to the inverted face pattern. The classification accuracy (mean accuracy is 99.58%) and ITRs (mean bit rate is 27.88 bit/min) of the mismatch inverted face pattern was significantly higher than that of the inverted face pattern (p < 0.05)

Common Minor Histocompatibility Antigen Discovery Based upon Patient Clinical Outcomes and Genomic Data

BackgroundMinor histocompatibility antigens (mHA) mediate much of the graft vs. leukemia (GvL) effect and graft vs. host disease (GvHD) in patients who undergo allogeneic stem cell transplantation (SCT) [1], [2], [3], [4]. Therapeutic decision making and treatments [5] based upon mHAs will require the evaluation of multiple candidate mHAs and the selection of those with the potential to have the greatest impact on clinical outcomes. We hypothesized that common, immunodominant mHAs, which are presented by HLA-A, B, and C molecules, can mediate clinically significant GvL and/or GvHD, and that these mHAs can be identified through association of genomic data with clinical outcomes.Methodology/Principal FindingsBecause most mHAs result from donor/recipient cSNP disparities, we genotyped 57 myeloid leukemia patients and their donors at 13,917 cSNPs [6]. We correlated the frequency of genetically predicted mHA disparities with clinical evidence of an immune response and then computationally screened all peptides mapping to the highly associated cSNPs for their ability to bind to HLA molecules. As proof-of-concept, we analyzed one predicted antigen, T4A, whose mHA mismatch trended towards improved overall and disease free survival in our cohort. T4A mHA mismatches occurred at the maximum theoretical frequency for any given SCT. T4A-specific CD8+ T lymphocytes (CTLs) were detected in 3 of 4 evaluable post-transplant patients predicted to have a T4A mismatch.Conclusions/SignificanceOur method is the first to combine clinical outcomes data with genomics and bioinformatics methods to predict and confirm a mHA. Refinement of this method should enable the discovery of clinically relevant mHAs in the majority of transplant patients and possibly lead to novel immunotherapeutics [5]

A Novel T-Cell Engaging Bi-specific Antibody Targeting the Leukemia Antigen PR1/HLA-A2

Despite substantial advances in the treatment of acute myeloid leukemia (AML), only 30% of patients survive more than 5 years. Therefore, new therapeutics are much needed. Here, we present a novel therapeutic strategy targeting PR1, an HLA-A2 restricted myeloid leukemia antigen. Previously, we have developed and characterized a novel T-cell receptor-like monoclonal antibody (8F4) that targets PR1/HLA-A2 and eliminates AML xenografts by antibody-dependent cellular cytotoxicity (ADCC). To improve the potency of 8F4, we adopted a strategy to link T-cell cytotoxicity with a bi-specific T-cell-engaging antibody that binds PR1/HLA-A2 on leukemia and CD3 on neighboring T-cells. The 8F4 bi-specific antibody maintained high affinity and specific binding to PR1/HLA-A2 comparable to parent 8F4 antibody, shown by flow cytometry and Bio-Layer Interferometry. In addition, 8F4 bi-specific antibody activated donor T-cells in the presence of HLA-A2+ primary AML blasts and cell lines in a dose dependent manner. Importantly, activated T-cells lysed HLA-A2+ primary AML blasts and cell lines after addition of 8F4 bi-specific antibody. In conclusion, our studies demonstrate the therapeutic potential of a novel bi-specific antibody targeting the PR1/HLA-A2 leukemia-associated antigen, justifying further clinical development of this strategy

Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78–83%), high retention of cell viability (71–74%), high tumour cell enrichment against leukocytes (1.7–2 × 10^3), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4–0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research