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Stroke is one of the main causes of long-term disability and death around the world. For its significant impact, stroke is also defined as a medical emergency, where immediate treatment is vital to save patients’ lives. For these reasons, an efficient prediction plays an important role in stroke prevention and cure. In this paper, attempting to implement a model predicting stroke efficiently, logistic regression and random forest algorithms are adopted, as well as a stroke dataset. They are trained and make predictions with the preprocessed dataset independently. Multiple evaluation indicators are employed to evaluate the two models’ results. Comparisons between their performances and the reasons for their discrepancies are both introduced, based on which the more suitable one is chosen as the final model. Models’ bias and variance and how they influence the results are discussed as well. In addition, some helpful propositions and approaches to improve the model’s performance will also be introduced.

MXene materials have shown numerous useful mechanical and electronic properties, and have been found to possess nice potential in the field of optical modulation. Here, we fabricated a MXene Cr2C saturable absorber by the liquid-phase exfoliation method, and systemically analyzed the surface morphology and nonlinear properties of the Cr2C sample. Applying the Cr2C saturable absorber as a Q-switch in a thulium-doped yttrium aluminum perovskite (Tm: YAP) laser, the shortest single pulse was obtained with a width of 602 ns under an absorbed pump power of 3.3 W at a repetition rate of 55 kHz with a T = 1% output coupler. The maximum output power was obtained with a T = 5% output coupler at a repetition rate of 58 kHz. The obtained maximum pulse energy and peak power were 3.96 μJ and 4.36 W, separately, which reveal that the MXene Cr2C can be applied as a promising modulation material in the near-infrared pulsed lasers.

Background: Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) could directly increase cancellous bone formation and was playing an essential role in bone modeling and remodeling. However, whether an increase of HIF-1α in ADSCs promoted osteogenic differentiation and bone formation was not known. Results: In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression cDNA were established to investigate the proliferation, migration, adhesion, and osteogenic capacity in ADSCs, and angiogenic ability in HUVEC. Overexpression of HIF-1α could promote cell proliferation, migration, adhesive and osteogenic capacity of ADSCs and angiogenic ability of HUVEC. Western blotting showed that the protein levels of osteogenesis-related factors were upregulated when overexpression of HIF-1α. Furthermore, the influence of up-regulating HIF-1α in ADSCs sheets on osseointegration had evaluated using the SD rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The over-expression of HIF-1α in ADSCs enhanced osteogenic differentiation and osseointegration around implants. Whereas transfecting HIF-1α-silenced ADSCs attenuated the osteogenic and angiogenic capacity. Finally, to explore the mechanism underlying HIF-1α promoted osteogenesis and angiogenesis, Western blotting was measured to analyze the VEGF/AKT/mTOR signaling pathway. Conclusions: These data first demonstrated that up-regulation of HIF-1α in ADSCs significantly improved the osteogenic capacity and peri-implant bone formation via VEGF/AKT/mTOR signaling pathway. Our findings revealed that HIF-1α exerts a critical effect on promoting osseointegration by improving osteogenesis and angiogenesis via VEGF/AKT/mTOR signaling pathway, and hence offered the considerable therapeutic potential for modifying stem cells to enhance osseointegration.

Background A large number of type 2 diabetic patients were needed for oral implants, but bone complications create uncertainty in implant success rates. Type 2 diabetes with insulin deficiency would be combined with insulin injections, but analysis of the effects of bone metabolism is lacking. We targeted Wnt signaling, which is closely related to diabetic bone metabolism, to compare the osteogenic differences between insulin and exenatide in vivo and in vitro, and to explore the role of Wnt signaling in implant osseointegration as well as in regulating osteogenic and lipogenic induction in T2DM rats. Methods A T2DM model was induced in four-week-old SD rats and implants were placed in the femur. The optimal concentration and duration of action of insulin and exenatide were explored based on BMSCs of T2DM rat origin. The rats were euthanized after four weeks of intraperitoneal injection with PBS, insulin and exenatide, respectively. Micro-CT to detect differences in bone microarchitecture of peri-implant osseointegration. Histology, double fluorescence labeling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. T2DM-derived BMSCs were extracted from successfully modeled SD rats, and their cellular characteristics were identified by flow cytometry and induced osteogenic differentiation as well as lipogenic differentiation. Osteogenic and lipogenic differentiation were induced by PBS, 500 µM insulin and 80 µM exenatide medium, respectively, and differentiation ability was identified by ALP, alizarin red staining and oil red O staining. RT-PCR and Western blotting were performed to detect the differences in expression of proteins of osteogenic-related genes and Lrp5/6/Gsk3β/β-catenin. Afterwards, BMSCs were cultured with no intervention, 80 µM exenatide and 80 µM exenatide combined with 200 ng/ml DKK1, respectively. Differences in osteogenic differentiation ability were detected by ALP and alizarin red staining, and differences in mRNA of Tgf and Bmp cascade reactions were detected by RT-PCR. Results Micro-CT and section staining showed that exenatide extensively promoted peri-implant osseointegration and insulin promoted localized implant osseointegration. Immunostaining showed that exenatide significantly promoted the rate of osteogenesis, with high expression of RUNX2, BMP2, ALP and LRP5/6, GSK3β, and β-catenin proteins. Alizarin red and ALP staining together with semi-quantitative analysis showed that exenatide cultured T2DM-derived BMSCs had the strongest osteogenic differentiation ability. Oil red staining and lipogenesis-related RT-PCR showed no difference in lipogenic differentiation ability of hypoglycemic treatment, but significantly reduced mRNA levels of Perilipin and C/ebpα. RT-PCR and Western blotting showed that exenatide significantly promoted the expression of osteogenic-related gene proteins and Lrp5/6/Gsk3β/β-catenin. In an in vivo experiment in which DKK1 inhibition of Lrp5/6 induced inactivation of Wnt signaling, alizarin red and ALP staining together with semi-quantitative analysis showed that DKK1 reduced osteogenic capacity, but combined with exenatide was still significantly stronger than the blank control. RT-PCR showed that exenatide activated Pi3k and repressed Bmpr1a transcription regardless of whether Wnt signaling was inactivated. Moreover, activation of Bmp6 and inhibition of Tgfβr3 by Wnt-inactivated exenatide were significantly greater than both exenatide alone and the blank control. Conclusions Hypoglycemic agents significantly improved peri-implant osseointegration in T2DM rats and significantly promoted osteogenic induction in T2DM-derived BMSCs. The osteogenic induction of insulin was weaker in vivo and in vitro than exenatide, which promoted the expression of Wnt/β-catenin signaling with significant activation of Lrp5/6. The inactivation of Wnt signaling caused by inhibition of Lrp5/6 significantly affected the osteogenic induction ability of exenatide. However, exenatide still promoted osteogenesis directly by activating Pi3k signaling to bypass Lrp5/6 and activating downstream β-catenin signaling, while promoting osteogenesis indirectly by inhibiting Bmpr1a signaling, which favors lipogenesis induction. Moreover, inactivation of Wnt signaling also stimulated exenatide to significantly activate osteogenic Bmp6 and significantly inhibit transcription of osteogenically compromised Tgfβr3, achieving improved poor bone formation under severe diabetic conditions.

Measurement has a special role in quantum theory1: by collapsing the wavefunction it can enable phenomena such as teleportation2 and thereby alter the "arrow of time" that constrains unitary evolution. When integrated in many-body dynamics, measurements can lead to emergent patterns of quantum information in space-time3-10 that go beyond established paradigms for characterizing phases, either in or out of equilibrium11-13. On present-day NISQ processors14, the experimental realization of this physics is challenging due to noise, hardware limitations, and the stochastic nature of quantum measurement. Here we address each of these experimental challenges and investigate measurement-induced quantum information phases on up to 70 superconducting qubits. By leveraging the interchangeability of space and time, we use a duality mapping9,15-17 to avoid mid-circuit measurement and access different manifestations of the underlying phases—from entanglement scaling3,4 to measurement-induced teleportation18—in a unified way. We obtain finite-size signatures of a phase transition with a decoding protocol that correlates the experimental measurement record with classical simulation data. The phases display sharply different sensitivity to noise, which we exploit to turn an inherent hardware limitation into a useful diagnostic. Our work demonstrates an approach to realize measurement-induced physics at scales that are at the limits of current NISQ processors.

Actinomycin is a family of chromogenic lactone peptides that differ in their peptide portions of the molecule. An antimicrobial peptide, actinomycin X2 (Ac.X2), was produced through the fermentation of a Streptomyces cyaneofuscatus strain. Immobilization of Ac.X2 onto a prepared silk fibroin (SF) film was done through a carbodiimide reaction. The physical properties of immobilized Ac.X2 (antimicrobial films, AMFs) were analyzed by ATR-FTIR, SEM, AFM, and WCA. The findings from an in vitro study showed that AMFs had a more broad-spectrum antibacterial activity against both S. aureus and E. coli compared with free Ac.X2, which showed no apparent strong effect against E. coli. These AMFs showed a suitable degradation rate, good hemocompatibility, and reduced cytotoxicity in the biocompatibility assay. The results of in vivo bacterially infected wound healing experiments indicated that wound inflammation was prevented by AMFs, which promoted wound repair and improved the wound microenvironment. This study revealed that Ac.X2 transformation is a potential candidate for skin wound healing.

Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and in cell differentiation, and alteration of PRC2 activity has been associated with cancer. On a molecular level, PRC2 catalyzes methylation of histone H3 lysine 27 (H3K27), resulting in mono-, di-, or trimethylated forms of H3K27, of which the trimethylated form H3K27me3 leads to transcriptional repression of polycomb target genes. Previously, we have shown that binding of the low-molecular-weight compound EED226 to the H3K27me3 binding pocket of the regulatory subunit EED can effectively inhibit PRC2 activity in cells and reduce tumor growth in mouse xenograft models. Here, we report the stepwise optimization of the tool compound EED226 toward the potent and selective EED inhibitor MAK683 (compound

The Eu3+ doped monoclinic phase of Gd2(MoO4)3 (M-Gd2(MoO4)3) and the Eu3+ doped orthorhombic phase of Gd2(MoO4)3 (O-Gd2(MoO4)3) red phosphors were synthesized by adjusting the synthesis temperatures. The XRD (X-ray diffraction) patterns, the EDS (energy-dispersive spectra), and the FE-SEM (field emission scanning electron microscope) images were used to comparatively study crystalline structures, compositions, and morphologies of the two materials. The DRS (diffuse reflection spectra), the room and high temperature PL (photoluminescence) spectra, and the fluorescence decay curves were recorded to compare the PL properties of the two phosphors. The characterization results suggest that the M-Gd2(MoO4)3 phosphor has lower synthesis temperature, while the O-Gd2(MoO4)3 phosphor has bigger particles, larger energy band gap value, stronger PL intensities, longer lifetimes, and better thermal stabilities. For Eu3+, the research results prove that the O-Gd2(MoO4)3 is a better host material choice than that of the M-Gd2(MoO4)3.

Nearest close friend query (k?NCF) in geo-social networks, aims to find the k nearest user objects from among the ?-hop friends of the query user. Existing efforts on k?-NCF find the user objects in the Euclidean space. In this paper, we study the problem of nearest close friend query in road-social networks.We propose two methods. One is based on Dijkstra algorithm, and the other is based on ISLabel. For the Dijkstra-based method, Dijkstra algorithm is used to traverse the user objects needed. For the label-based method, we make use of IS-Label to calculate the distance between two vertices to avoid traversing the edges that do not contain the desired user object. For each method, we propose effective termination conditon to terminate the query process early. Finally, we conduct a variety of experiments on real and synthetic datasets to verify the efficiency of the proposed methods.

Scalable quantum computing can become a reality with error correction, provided coherent qubits can be constructed in large arrays. The key premise is that physical errors can remain both small and sufficiently uncorrelated as devices scale, so that logical error rates can be exponentially suppressed. However, energetic impacts from cosmic rays and latent radioactivity violate both of these assumptions. An impinging particle ionizes the substrate, radiating high energy phonons that induce a burst of quasiparticles, destroying qubit coherence throughout the device. High-energy radiation has been identified as a source of error in pilot superconducting quantum devices, but lacking a measurement technique able to resolve a single event in detail, the effect on large scale algorithms and error correction in particular remains an open question. Elucidating the physics involved requires operating large numbers of qubits at the same rapid timescales as in error correction, exposing the event's evolution in time and spread in space. Here, we directly observe high-energy rays impacting a large-scale quantum processor. We introduce a rapid space and time-multiplexed measurement method and identify large bursts of quasiparticles that simultaneously and severely limit the energy coherence of all qubits, causing chip-wide failure. We track the events from their initial localised impact to high error rates across the chip. Our results provide direct insights into the scale and dynamics of these damaging error bursts in large-scale devices, and highlight the necessity of mitigation to enable quantum computing to scale.

BACKGROUND The aim of this study was to emphasize the impact of the aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) on the prognosis of patients with stable coronary artery disease (SCAD) undergoing percutaneous coronary intervention (PCI). MATERIAL AND METHODS Patients with SCAD who underwent elective PCI at Shinonoi General Hospital were included. SCAD was defined as epicardial coronary artery diameter stenosis ≥90% or epicardial coronary artery diameter stenosis ≥75% accompanied by symptoms or stress-induced myocardial ischemia. Clinical data were collected, and cardiovascular events were followed after discharge. One-way Cox proportional risk analysis was performed to assess the risk stratification value of the De Ritis ratio, using major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality as the primary and secondary endpoints, respectively. The independent risk stratification value was evaluated by multivariate Cox proportional risk analysis. RESULTS Among 204 patients with SCAD undergoing PCI, during a median follow-up period of 706 days (24 months), 13.7% (28/204) patients experienced MACCE, and 8.8% (18/204) experienced all-cause mortality. Multifactorial Cox regression analysis revealed that a high De Ritis ratio was an independent risk factor for MACCE (HR=2.96, 95% CI: 1.29-6.78, P=0.01) and all-cause mortality (HR=3.61, 95% Cl: 1.31-9.86, P=0.012). The sensitivity analysis further confirmed the incremental value of the De Ritis ratio for adverse cardiovascular events. CONCLUSIONS A high De Ritis ratio was an independent and valuable risk stratification factor for MACCE and all-cause mortality in patients with SCAD after PCI.

Actinomycins as clinical medicine have been extensively studied, while few investigations were conducted to discover the feasibility of actinomycins as antimicrobial natural dye contributing to the medical value of the functional fabrics. This study was focused on the application of actinomycin X2 (Ac.X2), a peptide pigment cultured from marine-derived Streptomyces cyaneofuscatus, in the dyeing and finishing of silk fabric. The dyeing potential of Ac.X2 with silk vs. cotton fabrics was assessed. As a result, the silk fabric exhibited greater uptake and color fastness with Ac.X2. Through Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analyses, some changes of chemical property for the dyed fabric and Ac.X2 were studied. The silk fabric dyed with Ac.X2 exhibited good UV protection ability. The antibacterial properties of dyed and finished silk were also evaluated, which exhibited over 90% antibacterial activity even after 20 washing cycles. In addition, the brine shrimp assay was conducted to evaluate the general toxicity of the tested fabric, and the results indicated that the dyed silk fabrics had a good biological safety property.

Quantum many-body systems display rich phase structure in their low-temperature equilibrium states1. However, much of nature is not in thermal equilibrium. Remarkably, it was recently predicted that out-of-equilibrium systems can exhibit novel dynamical phases2–8 that may otherwise be forbidden by equilibrium thermodynamics, a paradigmatic example being the discrete time crystal (DTC)7,9–15. Concretely, dynamical phases can be defined in periodically driven many-body-localized (MBL) systems via the concept of eigenstate order7,16,17. In eigenstate-ordered MBL phases, the entire many-body spectrum exhibits quantum correlations and long-range order, with characteristic signatures in late-time dynamics from all initial states. It is, however, challenging to experimentally distinguish such stable phases from transient phenomena, or from regimes in which the dynamics of a few select states can mask typical behaviour. Here we implement tunable controlled-phase (CPHASE) gates on an array of superconducting qubits to experimentally observe an MBL-DTC and demonstrate its characteristic spatiotemporal response for generic initial states7,9,10. Our work employs a time-reversal protocol to quantify the impact of external decoherence, and leverages quantum typicality to circumvent the exponential cost of densely sampling the eigenspectrum. Furthermore, we locate the phase transition out of the DTC with an experimental finite-size analysis. These results establish a scalable approach to studying non-equilibrium phases of matter on quantum processors., A study establishes a scalable approach to engineer and characterize a many-body-localized discrete time crystal phase on a superconducting quantum processor.

Reverse top-k keyword-based location query (RTkKL), aims to find the maximum spatial region such that the query object is contained in the result of any top-k spatial keyword query with users’ queried keywords and any location in the region as arguments. Existing efforts on RTkKL find the objects in the Euclidean space. In this paper, we study the problem of reverse top-k keyword-based location query on road networks. We propose two methods. One is based on mark vertex, and the other is based on bisector. For the mark vertex based method, we identify the mark vertex according to the definition of RTkKL on road networks. Based on the mark vertex, we will get the mark segments in the result. For the bisector-based method, we find the border points for the query q and some objects. With Dijkstra algorithm, we start from the query point q. For each closed edge, whose two adjacent vertices have been extracted from the min heap, we would search the border points on the edge, and count the border points for the adjacent vertex. For each method, we propose effective pruning strategy to reduce the search range and computation cost. Finally, experiments demonstrate the efficiency of the proposed algorithm.

Disrupting memories that associate environmental cues with drug experiences holds promise for treating addiction, yet accessing the distributed neural network that stores such memories is challenging. Here, we show that the paraventricular nucleus of the thalamus (PVT) orchestrates the acquisition and maintenance of opiate-associated memories via projections to the central nucleus of the amygdala (CeA) and nucleus accumbens (NAc). PVT→CeA activity associates morphine reward to the environment, whereas transient inhibition of the PVT→NAc pathway during retrieval causes enduring protection against opiate-primed relapse. Using brain-wide activity mapping, we revealed distributed network activities that are altered in non-relapsing mice, which enabled us to find that activating the downstream NAc→lateral hypothalamus (LH) pathway also prevents relapse. These findings establish the PVT as a key node in the opiate-associated memory network and demonstrate the potential of targeting the PVT→NAc→LH pathway for treating opioid addiction.

Purpose Radiopharmaceuticals 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). Results Selective 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. 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; P 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.

We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in which the active nonlinear element is implemented using an array of rf-SQUIDs. The device is matched to the 50 $\Omega$ environment with a Klopfenstein-taper impedance transformer and achieves a bandwidth of 250-300 MHz, with input saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor was used to benchmark these devices, providing a calibration for readout power, an estimate of amplifier added noise, and a platform for comparison against standard impedance matched parametric amplifiers with a single dc-SQUID. We find that the high power rf-SQUID array design has no adverse effect on system noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with this design show no degradation in readout fidelity due to gain compression, which can occur in multi-tone multiplexed readout with traditional JPAs., Comment: 10 pages, 10 figures

Purpose Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted. With this aim, we developed [18F]rucaparib, an 18F-labelled isotopologue of rucaparib, and employed it as a PARP-targeting agent for cancer imaging with PET. Here, we report the in vitro and in vivo evaluation of [18F]rucaparib in human pancreatic cancer models. Method We incorporated the positron-emitting 18F isotope into rucaparib, enabling its use as a PET imaging agent. [18F]rucaparib binds to the DNA damage repair enzyme, PARP, allowing direct visualisation and measurement of PARP in cancerous models before and after PARP inhibition or other genotoxic cancer therapies, providing critical information for cancer diagnosis and therapy. Proof-of-concept evaluations were determined in pancreatic cancer models. Results Uptake of [18F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [18F]rucaparib. In vivo studies revealed relatively fast blood clearance of [18F]rucaparib in PSN1 tumour-bearing mice, with a tumour uptake of 5.5 ± 0.5%ID/g (1 h after i.v. administration). In vitro and in vivo studies showed significant reduction of [18F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding. Conclusion Taken together, we demonstrate the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers.