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The quantum theory of optical coherence plays a ubiquitous role in identifying optical emitters. An unequivocal identification, however, presumes that the photon number statistics is resolved from timing uncertainties. We demonstrate from first principle that the observed nth-order temporal coherence is a n-fold convolution of the instrument responses and the expected coherence. The consequence is detrimental in which the photon number statistics is masked from the unresolved coherence signatures. The experimental investigations are thus far consistent with the theory developed. We envision the present theory will mitigate the false identification of optical emitters and enlarge the coherence deconvolution to an arbitrary order.

The collective spatial keyword query is a hot research topic in the database community in recent years, which considers both the positional relevance to the query location and textual relevance to the query keywords. However, in real life, the temporal information of object is not always valid. Based on this, we define a new query, namely time-aware collective spatial keyword query (TCoSKQ), which considers the positional relevance, textual relevance, and temporal relevance between objects and query at the same time. Two evaluation functions are defined to meet different needs of users, for each of which we propose an algorithm. Effective pruning strategies are proposed to improve query efficiency based on the two algorithms. Finally, the experimental results show that the proposed algorithms are efficient and scalable.

Nicotine withdrawal symptoms, mainly anxiety, cause high level of relapse rate after quitting smoking. Vitamin D supplementation has shown its potential for the prevention and treatment of anxiety disorders; however, neurobiological studies about the effect of vitamin D on nicotine withdrawal-induced anxiety are limited. To investigate the effect and molecular mechanism of vitamin D3 supplement by dietary on anxiety-like behavior during nicotine withdrawal, male C57/BL6 mice were divided into four groups: vehicle, nicotine only, vitamin D3 only, and nicotine plus vitamin D3. Mice were administrated with nicotine in drinking water (200 µg/mL), and vitamin D3 in feed for 6 weeks. During nicotine withdrawal, vitamin D3-treated mice showed significantly less anxiety-like behavior by an open-field test and marble buried test that performed an increase in the duration of the central zone and a decrease buried marble, respectively. Moreover, vitamin D3 supplementation attenuated the hippocampal NR2A expression on both protein and mRNA levels in nicotine and vitamin D3-treated mice. Our data showed that dietary supplementation with vitamin D3 ameliorated nicotine withdrawal-induced anxiety, which may be related to downregulation of NR2A expression in hippocampus. Vitamin D3 may provide a new dietary intervention with the easy access for smoking cessation.

Breast cancer is the most common cancer in women worldwide. Due to the heterogeneous nature of breast cancer, the optimal treatment and expected response for each patient may not necessarily be universal. Molecular imaging techniques could play an important role in the early detection and targeted therapy evaluation of breast cancer. This review focuses on the development of peptides labeled with SPECT and PET radionuclides for breast cancer imaging. We summarized the current status of radiolabeled peptides for different receptors in breast cancer. The characteristics of radionuclides and major techniques for peptide labeling are also briefly discussed.

A new brain circuit that contributes to aversive states, such as fear or anxiety, has been characterized in mice.

The rapid development of molecular targeted therapy brings hope to patients with advanced non-small-cell lung cancer (NSCLC). However, drug resistance inevitably occurs during treatment with EGFR-tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation EGFR-TKI, shows a favorable prognosis in T790M-positive NSCLC. Unfortunately, acquired resistance is still a challenge for both patients and clinicians. There is still no consensus on the optimal treatment. PD-1 and its ligand receptor 1 (PD-L1) inhibitors have yielded great progress, especially in patients with no actionable mutations. In this review, the authors take stock of the relationship betweenLung cancer is one of the most common malignant cancers worldwide. Specific genes are known to drive cancer growth in advanced non-small-cell lung cancer (NSCLC) and targeted therapies against these genes and their proteins have significantly improved survival. However, resistance to these therapies inevitably occurs and there is still no consensus on the best treatment strategy after resistance develops. Several related articles have discussed the relationship between treatment resistance and the production of PD-L1 proteins in cancer cells (which helps them avoid the body's immune system). EGFR-tyrosine kinase inhibitors (TKIs), a type of targeted therapy, were also reported to influence the production of PD-L1. Therefore, the authors hypothesize that immunotherapy (a type of targeted therapy that forces the body's immune system to attack cancers regardless of PD-L1 production) may be a new option for treatment-resistant patients. In this review, the feasibility of EGFR-TKIs in combination with immunotherapy is clarified.

Purpose: Tumor Necrosis Factor Receptor 1 (TNFR1) and integrin αvβ3 receptor are overexpressed in breast cancer. We hypothesized that a peptide ligand recognizing both receptors in a single receptor-binding probe would be advantageous. Here, we developed a novel 18F-labeled fusion peptide probe [18F]-NOTA-Gly3- E(2PEG4-RGD-WH701) targeting dual receptors (TNFR1 and αvβ3) and evaluated the diagnostic efficacy of this radioactive probe in both MDA-MB-231 and MCF-7 xenograft models in mice. Methods: The NOTA-conjugated RGD-WH701 analog was radiolabeled with 18F using NOTA-AlF chelation method. We used two PEG4 molecules and Glutamic acid (Glu) to covalently link c(RGDyK) with WH701. Gly3 was also added to further improve the water solubility and pharmacokinetic properties of the probe. The expression of TNFR1 and Integrin αvβ3 in MCF-7 and MDA-MB-231 cells was detected by western blot analysis and immunofluorescence staining. The tumor-targeting characteristics of [18F]-NOTA-Gly3-E(2PEG4-RGDWH701) were assessed in nude mice bearing MDA-MB-231 and MCF-7 xenografts. Results: HPLC analysis of the product NOTA-G3-E (2P4-RGD-WH701) revealed a purity >95%. The yield after attenuation correction was approximately 33.5%±2.8% (n=5), and the radiochemical purity was above 95%. The MDA-MB-231 tumor uptake of [18]-NOTA-Gly3-E(2PEG4-RGD-WH701) was 1.14±0.14%ID/g, as measured by PET at 40min postinjection (p.i.). In comparison, the tumor uptake of [18F]-NOTA-RGD and [18F]- NOTA-WH701 in MDA-MB-231 xenografts was 0.96±0.13%ID/g and 0.93±0.28%ID/g, respectively. The MCF-7 tumor uptake of [18F]-NOTA-Gly3-E(2PEG4-RGD-WH701) was 1.22±0.11%ID/g, as measured by PET at 40min postinjection (p.i.). In comparison, the tumor uptake of [18F]-NOTA-RGD and [18F]-NOTA-WH701 in MCF-7 xenografts was 0.99±0.18%ID/g and 0.57±0.08%ID/g, respectively. Conclusion: [18F]AlF-NOTA-Gly3-E(2PEG4-RGD-WH701) was successfully synthesized and labeled with 18F. The results from the microPET/CT and biodistribution studies of [18F]AlF-NOTA-Gly3-E(2PEG4-RGDWH701) showed that the tracer could specifically target TNFR1 and integrin αvβ3 receptors.

A dual-beam planar slow wave structure (SWS), named dielectric supported ring-bar SWS is proposed in this paper. The planar SWS is supported by two dielectric rods at the side edges, making it fit ...

The paper deals with a boundary feedback stabilization problem of a hybrid system with disturbances, which is clamped at one end and linked to a rigid body at the other end. The active disturbance rejection control approach is adopted in investigation. State observers are first designed to estimate disturbances, and then boundary feedback controllers are proposed to cancel the disturbances. Moreover, under different assumptions of time varying high gain functions, the asymptotical stability and the exponential stability of the closed-loop system are proved by the Lyapunov function approach. Finally, numerical simulations are presented to validate the theoretical conclusions.

Mach reflection in steady supersonic flow is an important phenomenon having received extensive studies, among which simplified theoretical models to predict the size of Mach stem and other flow structure are of particular interest. Past efforts for such models were based on inviscid assumption while in real cases the flow is viscous. Here in this paper we consider the influence of wedge boundary layer on the Mach stem height. This is done by including a simplified boundary layer model into a recently published inviscid model. In this viscous model, the wedge angle and the trailing edge height, which control the Mach stem height, are replaced by their equivalent ones accounting for the displacement effect of the wedge boundary layer, with the boundary layer assumed to be laminar or fully turbulent. This viscous model is shown to compare well with numerical results by computational fluid dynamics and gives a Mach stem height as function of the Reynolds number and Mach number. It is shown that due to the viscous effect, the Mach stem height is increased, through increasing the effective wedge angle. Keywords: Boundary-layer correction, Mach reflection, Shock waves, Supersonic flow, Viscous effect

The purpose of this investigation was to explore the prognostic value of phospholipase C delta (PLCD) genes in early stage pancreatic ductal adenocarcinoma (PDAC) and its potential molecular mechanisms. The prognostic value of PLCD genes in early stage PDAC was assessed using the Kaplan‐Meier method and multivariate Cox proportional hazards regression model. Genome‐wide correlation analysis was performed on PLCD3 to identify the highly correlated genes in the transcriptome. Then, PLCD3 and these correlated genes together underwent a bioinformatics analysis to elucidate the potential molecular biological functions of PLCD3 in PDAC. PLCD1 and PLCD3 are significantly overexpressed in PDAC. In PDAC patients, PLCD3 is overexpressed in certain groups of people with a history of alcoholism (P = .032). High expression of PLCD3 was found to be associated with lower overall survival (OS) of patients with early stage PDAC (P = .020; adjusted P = .016). A combination of PLCD3 and clinical variables was able to better predict the outcome of patients with early stage PDAC. These clinical variables are histological grade (P = .001; adjusted P = .001), targeted molecular therapy (P, In our investigation, PLCD1 and PLCD3 were found to be high expressed in PAAD tumor tissue compared with normal tissue. We also discovered that PDAC patients who drank alcohol had higher levels of PLCD3 than those without alcohol history. PLCD3 might be potential prognostic biomarkers for early stage PDAC according to the result of survival analysis. But in stratification analysis, PLCD3 was associated with OS only when early stage PDAC patients were in the age >60 group, female gender group, alcohol history group, low histologic grade group, with radiation therapy group, or R0 residual resection group.

Backgrounds: Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide that is difficult to diagnose during the early stages and its tumors are recurrent. Long non-coding RNAs (lncRNAs) have increasingly been associated with tumor biomarkers for diagnosis and prognosis. This study attempts to explore the potential clinical significance of lncRNA DUXAP8 and its co-expression related protein coding genes (PCGs) for HCC. Method: Data from a total of 370 HCC patients from The Cancer Genome Atlas were utilized for the analysis. DUXAP8 and its top 10 PCGs were explored for their diagnostic and prognostic implications for HCC. A risk score model and nomogram were constructed for prognosis prediction using prognosis-related genes and DUXAP8. Molecular mechanisms of DUXAP8 and its PCGs involved in HCC initiation and progression were investigated. Then, potential target drugs were identified using genome-wide DUXAP8-related differentially expressed genes in a Connectivity Map database. Results: The top 10 PCGs were identified as: RNF2, MAGEA1, GABRA3, MKRN3, FAM133A, MAGEA3, CNTNAP4, MAGEA6, MALRD1, and DGKI. Diagnostic analysis indicated that DUXAP8, MEGEA1, MKRN3, and DGKI show diagnostic implications (all area under curves ≥0.7, p≤0.05). Prognostic analysis indicated that DUXAP8 and RNF2 had prognostic implications for HCC (adjusted p=0.014 and 0.008, respectively). The risk score model and nomogram showed an advantage for prognosis prediction. A total of 3 target drugs were determined: cinchonine, bumetanide and amiprilose and they may serve as potential therapeutic targets for HCC. Conclusion: Functioning as an oncogene, DUXAP8 is overexpressed in tumor tissue and may serve as both a diagnostic and prognosis biomarker for HCC. MEGEA1, MKRN3, and DGKI maybe potential diagnostic biomarkers and DGKI may also be potentially prognostic biomarkers for HCC.

Due to their unique properties, selenium-containing polymers have become one of the research focuses of polymer materials in recent years. First, selenium can transform among various states of selenoxide, selenone, and selenium free radicals, and then be restored under these conditions, which endows these polymers with multiresponsive behaviors, including responses to redox changes, light, radiation, etc. Second, these polymers show characteristic properties. Selenium-containing polymers exhibit unique multiple optical–electrical characteristics, including high photoconductivity, anisotropic thermoconductivity, high piezoelectric and thermoelectric responses, and a high refractive index. Based on these various properties, selenium-containing polymers are regarded as excellent functional polymer materials. Therefore, it is meaningful to synthesize selenium-containing polymers with various structures. This paper principally gives a summary of the organic reactions of organoselenium compounds and reviews the research on the synthesis of selenium-containing polymers via different methods, such as the use of selenium-containing monomers and their polymerization, selenium-containing initiators for polymerization, selenium-containing mediators for controlled polymerization and selenium-containing molecules for the postmodification of polymers. Moreover, applications of selenium-containing polymers are described, including their use as intrinsic high refractive index polymeric materials, oxidative- and reductive-responsive materials, dynamic exchanging polymers, selective metal adsorbents, and catalysts.

Human retinal microvascular endothelial cells (HRMECs) injury plays an essential role in the pathogenesis of diabetic retinopathy (DR). As one of the crucial pathogenetic factors, oxidative stress induces HRMECs apoptosis and microvascular lesions. Nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a molecular switch in oxidative stress-induced HRMECs injury. The present study was designed to investigate the protective effect and underlying mechanism of carnosol, a potential Nrf2 agonist, in tert-butyl hydroperoxide (t-BHP) induced HRMECs oxidative stress injury. In this study, carnosol was found to inhibit HRMECs injury induced by t-BHP. Transcriptomics and molecular biology illustrated that the mechanism was associated with oxidative stress, vascular system development, apoptosis, cell cycle, cell adhesion, cytoskeleton, and nitric oxide biosynthesis. Carnosol directly scavenged free radicals or activated the Nrf2 signaling pathway to alleviate HRMECs oxidative stress. ML385 pretreatment or Nrf2 small interference RNA (siRNA) inhibited the protective effect of carnosol on HRMECs injury. Moreover, the apoptosis and cell cycle arrest in HRMECs were suppressed by carnosol. Treatment with carnosol could also effectively regulate the adhesion and cytoskeleton. Overall, our data provide a systematic perspective for the mechanism of carnosol against HRMECs oxidative stress injury and reveal that carnosol may be a candidate drug for DR therapy.

Background. Early stage hepatocellular carcinoma (HCC) has a high recurrence rate after surgery and lacks reliable predictive tools. We explored the potential of combining enhanced CT with gut microbiome to develop a predictive model for recurrence after early HCC surgery. Methods. A total of 112 patients with early HCC who underwent hepatectomy from September 2018 to December 2020 were included in this study, and the machine learning method was divided into a training group ( N = 71 ) and a test group ( N = 41 ) with the observed endpoint of recurrence-free survival (RFS). Features were extracted from the arterial and portal phases of enhanced computed tomography (CT) images and gut microbiome, and features with minimum absolute contraction and selection operator regression were created, and the extracted features were scored to create a preoperative prediction model by using the multivariate Cox regression analysis with risk stratification analysis. Results. In the study cohort, the model constructed by combining radiological and gut flora features provided good predictive performance ( C index, 0.811 (0.650-0.972)). The combined radiology and gut flora-based model constructed risk strata with high, intermediate, or low risk of recurrence and different characteristics of recurrent tumor imaging and gut flora. Recurrence of early stage hepatocellular carcinoma may be associated with oxidative stress in the intestinal flora. Conclusions. This study successfully constructs a risk model integrating enhanced CT and gut microbiome characteristics that can be used for the risk of postoperative recurrence in patients with early HCC. In addition, intestinal flora associated with HCC recurrence may be involved in oxidative stress.

An important measure of the development of quantum computing platforms has been the simulation of increasingly complex physical systems. Prior to fault-tolerant quantum computing, robust error mitigation strategies are necessary to continue this growth. Here, we study physical simulation within the seniority-zero electron pairing subspace, which affords both a computational stepping stone to a fully correlated model, and an opportunity to validate recently introduced ``purification-based'' error-mitigation strategies. We compare the performance of error mitigation based on doubling quantum resources in time (echo verification) or in space (virtual distillation), on up to $20$ qubits of a superconducting qubit quantum processor. We observe a reduction of error by one to two orders of magnitude below less sophisticated techniques (e.g. post-selection); the gain from error mitigation is seen to increase with the system size. Employing these error mitigation strategies enables the implementation of the largest variational algorithm for a correlated chemistry system to-date. Extrapolating performance from these results allows us to estimate minimum requirements for a beyond-classical simulation of electronic structure. We find that, despite the impressive gains from purification-based error mitigation, significant hardware improvements will be required for classically intractable variational chemistry simulations., Comment: 10 pages, 13 page supplementary material, 12 figures. Experimental data available at https://doi.org/10.5281/zenodo.7225821

Integrated third-harmonic generators enable on-chip wavelength conversion translating telecom signals to the visible spectrum. Despite the desirable functionality, the device performance is susceptible to phase distortions. Here, we present a design method of compensating the Kerr-induced distortions in third-harmonic generation. The design method yields a chirped Bragg grating theoretically improving the conversion efficiency by ∼30 dB. We envision the design method will pave the way for demonstrating efficient infrared-to-visible upconversion in silicon nitride chips.

Interactions in quantum systems can spread initially localized quantum information into the exponentially many degrees of freedom of the entire system. Understanding this process, known as quantum scrambling, is key to resolving several open questions in physics. Here, by measuring the time-dependent evolution and fluctuation of out-of-time-order correlators, we experimentally investigate the dynamics of quantum scrambling on a 53-qubit quantum processor. We engineer quantum circuits that distinguish operator spreading and operator entanglement and experimentally observe their respective signatures. We show that whereas operator spreading is captured by an efficient classical model, operator entanglement in idealized circuits requires exponentially scaled computational resources to simulate. These results open the path to studying complex and practically relevant physical observables with near-term quantum processors.

PurposeRadiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inhibitors for diagnostic and radionuclide therapeutic applications. Here, we performed a systematic evaluation by varying the molar activity of [18F]olaparib and the injected mass of [TotalF]olaparib to investigate the effects on tumour and normal tissue uptake in two subcutaneous human glioblastoma xenograft models.Methods[18F]Olaparib uptake was evaluated in the human glioblastoma models: in vitro on U251MG and U87MG cell lines, and in vivo on tumour xenograft-bearing mice, after administration of [TotalF]olaparib (varying injected mass: 0.04-8.0 µg, and molar activity: 1-320 GBq/μmol).ResultsSelective uptake of [18F]olaparib was demonstrated in both models. Tumour uptake was found to be dependent on the injected mass of [TotalF]olaparib (µg), but not the molar activity per sé. An injected mass of 1 μg resulted in the highest tumour uptake (up to 6.9 ± 1.3%ID/g), independent of the molar activity. In comparison, both the lower and higher injected masses of [TotalF]olaparib resulted in lower relative tumour uptake (%ID/g; PEx vivo analysis of U87MG xenograft sections showed that the heterogeneity in [18F]olaparib intratumoural uptake correlated with PARP1 expression. Substantial upregulation of PARP1-3 expression was observed after administration of [TotalF]olaparib (>0.5 µg).Conclusion Our findings show that the injected mass of [TotalF]olaparib has significant effects on tumour uptake. Moderate injected masses of PARP inhibitor-derived radiopharmaceuticals may lead to improved relative tumour uptake and tumour-to-background ratio for cancer diagnosis and radionuclide therapy.

Background Compared with singleton pregnancy, twin gestation is featured by a greater increase in cardiac output. Therefore, norepinephrine might be more suitable than phenylephrine for maintaining blood pressure during cesarean section for twins, as phenylephrine causes reflex bradycardia and a resultant decrease in cardiac output. This study was to determine whether norepinephrine was superior to phenylephrine in maintaining maternal hemodynamics during cesarean section for twins. Methods Informed consent was obtained from all the patients before enrollment. In this double-blinded, randomized clinical trial, 100 parturients with twin gestation undergoing cesarean section with spinal anesthesia were randomized to receive prophylactic norepinephrine (3.2 μg/min) or phenylephrine infusion (40 μg/min). The primary outcome was the change of heart rate and blood pressure during the study period. The secondary outcomes were to compare maternal complications, neonatal outcomes, Apgar scores and umbilical blood acid-base status between the two vasopressors. Results There was no significant difference observed for the change of heart rate between two vasopressors. The mean standardized area under the curve of heart rate was 78 ± 12 with norepinephrine vs. 74 ± 11 beats/min with phenylephrine (mean difference 4.4, 95%CI − 0.1 to 9.0; P = .0567). The mean standardized area under the curve of systolic blood pressure (SBP) was significantly lower in parturients with norepinephrine, as the mean of differences in standardized AUC of SBP was 6 mmHg, with a 95% CI from 2 to 9 mmHg (P = .0013). However, requirements of physician interventions for correcting maternal hemodynamical abnormalities (temporary cessation of vasopressor infusion for reactive hypertension, rescuing vasopressor bolus for hypotension and atropine for heart rate less Conclusion Infusion of norepinephrine was not associated with less overall decrease in heart rate during cesarean section for twins, compared with phenylephrine. Trial registration Chinese Clinical Trial Registry (ChiCTR1900021281).

The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treatBRCA-mutated cancers. Herein, we report two strategies to access the18F-isotopologue of rucaparib by applying a copper-mediated nucleophilic18F-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-18F-labeling and affords [18F]rucaparib with an activity yield of 11% ± 3% (n= 3) and a molar activity (Am) up to 30 GBq/μmol. Preliminaryin vitrostudies are presented.

The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat

BACKGROUND Coronavirus disease 2019 (COVID-19) has emerged as a global threat. This study was performed to gain an understanding of COVID-19-related knowledge, attitudes, and practices among susceptible individuals. MATERIAL AND METHODS Patients who had been diagnosed with old myocardial infarction were followed up via telephone survey based on an established follow-up system at the beginning of the COVID-19 outbreak (January 2020) in Chongqing, Southwest China. RESULTS A total of 631 eligible patients participated in this survey, and 40.6% of the rural respondents did not know the transmission routes of SARS-CoV-2, which was higher than the proportion of urban respondents (40.6% vs 31.0). Rural residents had a lower rate of adopting preventive measures than urban residents, such as wearing masks (76.7% vs 90.1%), avoiding meetings and gatherings (58.6% vs 68.5%), and hand washing (56.0% vs 63.8%). A higher percentage of women than men did not take any preventive measures (11.3% vs 7.6%), while a lower percentage of women than men wore masks (77.7% vs 84.5%). Multiple logistic regression revealed that rural patients were more likely to lack knowledge about transmission (odds ratio (OR): 1.51). Rural patients had an increased risk of failing to implement protective measures. CONCLUSIONS Female and rural populations lacked knowledge and failed to adopt protective measures during the beginning of the COVID-19 epidemic. Therefore, these populations may benefit from health education campaigns and policies.

Realizing the potential of quantum computing requires sufficiently low logical error rates1. Many applications call for error rates as low as 10−15 (refs. 2–9), but state-of-the-art quantum platforms typically have physical error rates near 10−3 (refs. 10–14). Quantum error correction15–17 promises to bridge this divide by distributing quantum logical information across many physical qubits in such a way that errors can be detected and corrected. Errors on the encoded logical qubit state can be exponentially suppressed as the number of physical qubits grows, provided that the physical error rates are below a certain threshold and stable over the course of a computation. Here we implement one-dimensional repetition codes embedded in a two-dimensional grid of superconducting qubits that demonstrate exponential suppression of bit-flip or phase-flip errors, reducing logical error per round more than 100-fold when increasing the number of qubits from 5 to 21. Crucially, this error suppression is stable over 50 rounds of error correction. We also introduce a method for analysing error correlations with high precision, allowing us to characterize error locality while performing quantum error correction. Finally, we perform error detection with a small logical qubit using the 2D surface code on the same device18,19 and show that the results from both one- and two-dimensional codes agree with numerical simulations that use a simple depolarizing error model. These experimental demonstrations provide a foundation for building a scalable fault-tolerant quantum computer with superconducting qubits., Repetition codes running many cycles of quantum error correction achieve exponential suppression of errors with increasing numbers of qubits.

Implementation of an error-corrected quantum computer is believed to require a quantum processor with a million or more physical qubits, and, in order to run such a processor, a quantum control system of similar scale will be required. Such a controller will need to be integrated within the cryogenic system and in close proximity with the quantum processor in order to make such a system practical. Here, we present a prototype cryogenic CMOS quantum controller designed in a 28-nm bulk CMOS process and optimized to implement a 16-word (4-bit) XY gate instruction set for controlling transmon qubits. After introducing the transmon qubit, including a discussion of how it is controlled, design considerations are discussed, with an emphasis on error rates and scalability. The circuit design is then discussed. Cryogenic performance of the underlying technology is presented, and the results of several quantum control experiments carried out using the integrated controller are described. This article ends with a comparison to the state of the art and a discussion of further research to be carried out. It has been shown that the quantum control IC achieves promising performance while dissipating less than 2 mW of total ac and dc power and requiring a digital data stream of less than 500 Mb/s.

As a novel two-stage greedy approximation algorithm, Forward-Backward Pursuit (FBP) algorithm attracts wide attention because of its high reconstruction accuracy and no need for sparsity as a priori information. However, the FBP algorithm has to spend much more time to get a higher accuracy. In view of this, an Improved Adaptive Forward-Backward Matching Pursuit (IAFBP) algorithm is proposed in this paper. In the forward stage, the IAFBP algorithm uses an adaptive threshold to select the appropriate number of atoms into support set, so that the number of selected atoms is more random. In the backward stage, the projection coefficient of the atoms is taken as the basis of rejection, and the deletion threshold is introduced to reject the atoms adaptively, so that more right atoms are retained in each iteration and the reconstruction speed can be accelerated. At the same time, it overcomes the excessive backtracking phenomenon existing in the adaptive process and improves the accuracy of the algorithm. The simulation results of one-dimensional sparse signals and two-dimensional images show that the IAFBP algorithm has more advantages than the FBP algorithm in reconstruction performance and computational time.

The capability of nanolasers to generate coherent light in small volume resonators has made them attractive to be implemented in future ultra-compact photonic integrated circuits. However, compared to conventional lasers, nanolasers are also known for their broader spectral linewidths, that are usually on the order of 1 nm. While it is well known that the broad linewidths in light emitters originate from various noise sources, there has been no rigorous study on evaluating the origins of the linewidth broadening for nanolasers to date to the best of our knowledge. In this manuscript, we investigate the impact of fundamental thermal fluctuations on the nanolaser linewidth. We show that such thermal fluctuations are one of the intrinsic noise sources in a sub-wavelength metal-clad nanolaser inducing significant linewidth broadening. We further show that with the reduction of the nanolaser’s dimensions, i.e., mode volume, and the increase of the ambient temperature, such linewidth broadening is enhanced, due to the effect of more pronounced fundamental thermal fluctuation. Specifically, we show that the finite linewidths induced by the thermal fluctuations at room temperature are 1.14nm and 0.16nm, for nanolasers with core radii of 250nm and 750nm, respectively. Although our study was performed on a metallo-dielectric nanolaser, it is reasonable to assume that, in general, other nanolaser architectures are also more prone to thermal fluctuations, and hence exhibit larger finite linewidths than conventional large mode volume lasers.

The prevalence rates of heart failure (HF) are greater than 10% in individuals aged >75 years, indicating an intrinsic link between aging and HF. It has been recognized that mitochondrial dysfunction contributes to the pathology of HF. Mitokines are a type of cytokines, peptides, or signaling pathways produced or activated by the nucleus or the mitochondria through cell non-autonomous responses during cellular stress. In addition to promoting the communication between the mitochondria and the nucleus, mitokines also exert a systemic regulatory effect by circulating to distant tissues. It is noteworthy that increasing evidence has demonstrated that mitokines are capable of reducing the metabolic-related HF risk factors and are associated with HF severity. Consequently, mitokines might represent a potential therapy target for HF.

To identify the key residues of Thermus thermophilus (T. thermophilus) RTCB in RNA ligation and DNA activation. The biochemical activities of RTCB from T. thermophilus were purified, characterized, and compared. Structure and sequence alignment between T. thermophilus RTCB and Pyrococcus horikoshii (P. horikoshii) RTCB identified six conserved residues (D64, D95, N203, H204, E207, H399) that were essential for RNA ligation. Mutation analysis showed that the expression levels of mutants D95A, N203A, H204A, E207A and H399A were relatively low. Compared to wide-type RTCB, variant D64A protein had no RNA ligation and DNA activation activity. In addition, T. thermophilus RTCB showed acceptable catalytic activity of 3′-phosphate DNA activation at 37 °C. D64 was proved to be essential for RTCB-catalyzed RNA ligation and DNA activation (from 37 to 70 °C) in T. thermophilus.

The existing spatial keyword cover query only considers the relevance of the text and the position, and ignores the temporal information of the geospatial objects. In this paper, we define a new query, time-aware spatial keyword cover query (TSKCQ), which takes into account the textual relevance, positional relevance, and temporal information of the objects. A new cost function is proposed in TSKCQ, which is used to evaluate the user’s satisfaction in time and space under the premise of satisfying textual constraints proposed by the user. With this function, an object set with the best cost function value would be returned by TSKCQ. We propose a TR-tree for indexing the temporal and spatial information of objects. Based on this, we propose an exact algorithm to tackle TSKCQ, in which effective pruning strategies are used. Finally, experiments demonstrate the efficiency of the proposed algorithm.

The incidence of depressive symptoms in patients with stable coronary artery disease (SCAD) has significantly increased. However, its pathogenesis and treatment mechanisms are still incompletely understood. In this study, 144 patients with SCAD were recruited. Depressive symptoms of patients with SCAD were evaluated using Zung Self-Rating Depression Scale during hospitalization, and the patients were categorized into two subgroups: the non-depressive and depressive groups (further divided into mild and moderate/severe depressive groups). The rate of moderate/severe depressive symptoms in patients with SCAD was 18.8%. The mean age of patients in the depressive and mild depressive groups was older than that of those in the non-depressive group, and patients in the moderate/severe depressive group had higher high-density lipoprotein (HDL) and lower creatinine (Cr) levels. Binary logistic regression analysis showed that lower low-density lipoprotein (LDL) levels were significantly associated with increased risks of mild depressive symptoms, whereas higher HDL and lower Cr levels were significantly associated with moderate/severe depressive symptoms, suggesting that patients with SCAD were prone to experience depressive symptoms, especially in the elderly. Abnormality in LDL, HDL, and Cr levels might contribute to the depressive symptoms.

The neural substrates for predatory hunting, an evolutionarily conserved appetitive behavior, remain largely undefined. Photoactivation of zona incerta (ZI) GABAergic neurons strongly promotes hunting of both live and artificial prey. Conversely, photoinhibition of these neurons or deletion of their GABA function severely impairs hunting. Here electrophysiological recordings reveal that ZI neurons integrate prey-related multisensory signals and discriminate prey from non-prey targets. Visual or whisker sensory deprivation reduces calcium responses induced by prey introduction and attack and impair hunting. ZI photoactivation largely corrects the hunting impairment caused by sensory deprivations. Motivational and reinforcing assays reveal that ZI photoactivation is associated with a strong appetitive drive, causing repetitive self-stimulatory behaviors. These ZI neurons project to the periaqueductal gray matter to induce hunting and motivation. Thus, we have delineated the function of ZI GABAergic neurons in hunting, which integrates prey-related sensory signals into prey detection and attack and induces a strong appetitive motivational drive.

Predatory hunting plays a fundamental role in animal survival. Little is known about the neural circuits that convert sensory cues into neural signals to drive this behavior. Here we identified an excitatory subcortical neural circuit from the superior colliculus to the zona incerta that triggers predatory hunting. The superior colliculus neurons that form this pathway integrate motion-related visual and vibrissal somatosensory cues of prey. During hunting, these neurons send out neural signals that are temporally correlated with predatory attacks, but not with feeding after prey capture. Synaptic inactivation of this pathway selectively blocks hunting for prey without impairing other sensory-triggered behaviors. These data reveal a subcortical neural circuit that is specifically engaged in translating sensory cues into neural signals to provoke predatory hunting.

We discuss the stabilisation problem of a constrained one-link flexible arm with boundary disturbance flowing to the control end. By the active disturbance rejection control (ADRC) approach, we fir...

Given a set of spatial objects O, the search radius r and the submodular function f are specified by the user. The best region search (BRS) is to find an optimal area with fixed range size, in which the object set has the maximum submodular function value. The BRS problem has long been studied because of its wide application in spatial data mining, facility locating and so on. However, most of the existing work focus on either Euclidean space or motionless objects, which is not applicable in many real-life cases. In this paper, we propose the best region monitoring problem in the spatial data streams in road networks (MBRS). Many real life applications can obtain benefit from MBRS problem, such as monitoring traffic and tracking in ecology. We first propose an efficient algorithm to the static BRS problem in road networks, and extend the solution to a naive method to solve the MBRS problem. Then, we put forward effective pruning strategies and branch-and-bound algorithm GER on the basis of the preprocessing to monitor best region at different times. Finally, a large number of experiments verify the efficiency of the proposed method.

Bile leakage (BL) is a common complication of partial hepatectomy for hepatocellular carcinoma (HCC). However, various intraoperative approaches to detect BL have not been widely accepted owing to uncertainty in their treatment effectiveness and complexity of use.A novel BL-detection approach (Peng's test) was developed in a swine model to determine the pressures generated in the gallbladder and common bile duct (CBD) during the test. A comparative study was then conducted on a prospective cohort of patients using Peng's test versus a retrospective historical cohort patient group using the White Gauze test in partial hepatectomy for HCC. Propensity score matching (PSM) was performed in a 1:1 ratio to balance confounding factors.The maximum pressures with methylene blue injection in the gallbladder and CBD without Pringle's maneuver in the four swines were 103.8 ± 11.8 and 42.3 ± 6.1, respectively. After Pringle's maneuver, 32.0 ± 6.8 mL methylene blue injection led to a maximum pressure in the CBD of 85.3 ± 9.5 cmHPeng's test for intraoperative BL detection is safe and effective in reducing BL after hepatectomy.

The global prevalence of inflammatory bowel disease (IBD) is increasing, and mucosal healing is the preferred treatment target of IBD. Sodium (aS,9 R)- 3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.1We characterized its therapeutic properties in vitro and in vivo using Caco-2 cell monolayer and dextran sodium sulfate (DSS)- or 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced colitis models. We conducted nonclinical toxicology and safety pharmacology research, including general toxicity, toxicokinetics, pharmacokinetics, metabolism and plasma protein binding, cardiovascular safety pharmacology, central nervous system safety pharmacology, respiratory safety pharmacology, fertility and early embryonic development toxicity, reverse mutation assay, chromosomal aberration assay and micronucleus test.The results showed that SDH promoted expression of tight junction proteins, and protected the integrity and permeability of the epithelial barrier in both cell and animal models. Moreover, lower doses of SDH showed the similar or better efficacy than cyclosporine A (CsA) and mesalazine in DSS- or TNBS-induced colitis animals. Furthermore, our results identified that SDH has satisfactory safety in these studies we tested. In summary, SDH restored the epithelial barrier through tight junction proteins and was expected to be a novel therapeutic agent for the treatment of IBD.

The de Winter electrocardiogram pattern is an acute ST-segment elevation myocardial infarction equivalent, however this specific electrocardiogram change is easily ignored by clinicians. The de Winter electrocardiogram pattern in patients with acute chest pain mostly indicates sub-complete or complete occlusion of the left anterior descending or the diagonal branch. Patients with acute chest pain and such electrocardiographic finding should undergo emergency coronary angiography immediately to determine the coronary condition, and reperfusion therapy should be performed as soon as possible to reduce the incidence of adverse cardiovascular events.de Winter心电图改变是急性ST段抬高型心肌梗死的一种等危症，但该心电图改变容易被临床医师忽视。急性胸痛患者出现de Winter 心电图表现，多数提示前降支或对角支次全或者完全闭塞。一旦发现这类心电图表现的急性胸痛患者，应立即行急诊冠状动脉造影以明确冠状动脉状况，尽早行再灌注治疗，以降低不良心血管事件的发生。.

Background The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients. Methods A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed. Results A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival. Conclusions We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.

The discovery of topological order has revolutionized the understanding of quantum matter in modern physics and provided the theoretical foundation for many quantum error correcting codes. Realizing topologically ordered states has proven to be extremely challenging in both condensed matter and synthetic quantum systems. Here, we prepare the ground state of the toric code Hamiltonian using an efficient quantum circuit on a superconducting quantum processor. We measure a topological entanglement entropy near the expected value of $\ln2$, and simulate anyon interferometry to extract the braiding statistics of the emergent excitations. Furthermore, we investigate key aspects of the surface code, including logical state injection and the decay of the non-local order parameter. Our results demonstrate the potential for quantum processors to provide key insights into topological quantum matter and quantum error correction., Comment: 6 pages 4 figures, plus supplementary materials

Background: Neuropilin-1 (NRP-1) and integrin αvβ3 receptors are both overexpressed in breast cancer. Methods: We developed and synthesized a heterodimeric tracer consisting of Arg−Gly−Asp (RGD) and Ala-Thr-Trp-Leu-Pro-Pro-Arg (ATWLPPR) peptides that simultaneously targets integrin αvβ3 and NRP-1. We then investigated the diagnostic efficacy of RGD-ATWLPPR heterodimeric peptides in MCF-7 xenograft models in mice. DOTA-conjugated RGD-ATWLPPR peptides were then radiolabeled with 68Ga, and the receptor-binding characteristics and tumor-targeting efficacy of 68Ga-DOTA-RGD-ATWLPPR were investigated in vitro and in vivo. We also detected integrin αvβ3 and NRP-1 expression in MCF-7 cells and tumor tissues. Results: The peptide showed high stability in vitro. Static PET/CT imaging studies showed that MCF-7 tumors were clearly visible 30 min and 60 min after 68Ga-DOTA-RGD-ATWLPPR injection. Further, the heterodimer showed higher tumor uptake than 68Ga-DOTA-RGD or 68Ga-DOTA-ATWLPPR alone. High specificity was shown in blocking studies using RGD and ATWLPPR peptides. MicroPET/CT and biodistribution studies using 68Ga-DOTA-RGD-ATWLPPR showed that the tracer specifically targets NRP-1 and integrin ανβ3 receptors. Conclusions: Compared with 68Ga-DOTA-RGD and 68Ga-DOTA-ATWLPPR, 68Ga-DOTA-RGD-ATWLPPR has higher binding affinity, better targeting efficiency, and longer tumor retention time. It therefore has potential as an imaging probe for breast cancer detection.

Quantum computing can become scalable through error correction, but logical error rates only decrease with system size when physical errors are sufficiently uncorrelated. During computation, unused high energy levels of the qubits can become excited, creating leakage states that are long-lived and mobile. Particularly for superconducting transmon qubits, this leakage opens a path to errors that are correlated in space and time. Here, we report a reset protocol that returns a qubit to the ground state from all relevant higher level states. We test its performance with the bit-flip stabilizer code, a simplified version of the surface code for quantum error correction. We investigate the accumulation and dynamics of leakage during error correction. Using this protocol, we find lower rates of logical errors and an improved scaling and stability of error suppression with increasing qubit number. This demonstration provides a key step on the path towards scalable quantum computing., Correlated errors coming from leakage out of the computational subspace are an obstacle to fault-tolerant superconducting circuits. Here, the authors use a multi-level reset protocol to improve the performances of a bit-flip error correcting code by reducing the magnitude of correlations.

Gasdermin-D (GSDMD), the executioner of pyroptotic cell death when it is cleaved by inflammatory caspases, plays a crucial role in host defense and the response to danger signals. So far, there are no known mechanisms, other than cleavage, for regulating GSDMD. Here, we show that tripartite motif protein TRIM21 acts as a positive regulator of GSDMD-dependent pyroptosis. TRIM21 interacted with GSDMD via its PRY-SPRY domain, maintaining GSDMD stable expression in resting cells yet inducing the N-terminus of GSDMD (GSDMD-N) aggregation during pyroptosis. TRIM21-deficient cells displayed a reduced cell death in response to NLRP3 or NLRC4 inflammasome activation. Genetic ablation of TRIM21 in mice conferred protection from LPS-induced inflammation and dextran sulfate sodium-induced colitis. Therefore, TRIM21 plays an essential role in GSDMD-mediated pyroptosis and may be a viable target for controlling and treating inflammation-associated diseases.

To explore the electrocardiogram manifestations and clinical characteristics of patients with the de Winter electrocardiogram pattern.This retrospective study was performed on acute coronary syndrome (ACS), patients with culprit lesion in left anterior descending branch (LAD), who admitted to Yongchuan Hospital of Chongqing Medical University from August 2017 to October 2018. Patients were categorized into those with or without the de Winter electrocardiogram pattern. The characteristics of de Winter electrocardiogram were analyzed by the clinical data of the patients.Among 230 patients with left anterior descending branch lesion, 14 (6%) had the de Winter electrocardiogram pattern. Compared with the control group, patients with de Winter electrocardiogram pattern were younger [(53.86±10.26) years old vs (67.20± 11.60) years oldThe de Winter electrocardiogram pattern syndrome in patients with acute chest pain mostly indicates that the left anterior descending or the diagonal branch is subtotal or completely occluded, which is a special ST-segment elevation myocardial infarction equivalent and should attract the clinicians' extensive attention.