2,470 research outputs found
Cell-Based Assays in High-Throughput Screening for Drug Discovery
Drug screening is a long and costly process confronted with low productivity and challenges in using animals, which limit the discovery of new drugs. To improve drug screening efficacy and minimize animal testing, recent efforts have been dedicated to developing cell-based high throughput screening (HTS) platforms that can provide more relevant in vivo biological information than biochemical assays and thus reduce the number of animal tests and accelerate the drug discovery process. Today, cell-based assays are used in more than half of all high-throughput drug screenings for target validation and ADMET (absorption, distribution, metabolism, elimination and toxicity) in the early stage of drug discovery. In this review, we discuss the uses of different types of cells and cell culture systems, including 2D, 3D and perfusion cell cultures, in cell-based HTS for drug discovery. Optical and electrochemical methods for online, non-invasive detection and quantification of cells or cellular activities are discussed. Recent progresses and applications of 3D cultures and microfluidic systems for cell-based HTS are also discussed, followed with several successful examples of using cell-based HTS in commercial development of new drugs. Finally, a brief discussion on potential applications of cell-based HTS for screening phytochemicals and herbal medicines is provided in this review
Rapid identification of time-frequency domain gravitational wave signals from binary black holes using deep learning
Recent developments in deep learning techniques have offered an alternative
and complementary approach to traditional matched filtering methods for the
identification of gravitational wave (GW) signals. The rapid and accurate
identification of GW signals is crucial for the progress of GW physics and
multi-messenger astronomy, particularly in light of the upcoming fourth and
fifth observing runs of LIGO-Virgo-KAGRA. In this work, we use the 2D U-Net
algorithm to identify the time-frequency domain GW signals from stellar-mass
binary black hole (BBH) mergers. We simulate BBH mergers with component masses
from 5 to 80 and account for the LIGO detector noise. We find that
the GW events in the first and second observation runs could all be clearly and
rapidly identified. For the third observation run, about GW events could
be identified and GW190814 is inferred to be a BBH merger event. Moreover,
since the U-Net algorithm has advantages in image processing, the
time-frequency domain signals obtained through U-Net can preliminarily
determine the masses of GW sources, which could help provide the mass priors
for future parameter inferences. We conclude that the U-Net algorithm could
rapidly identify the time-frequency domain GW signals from BBH mergers and
provide great help for future parameter inferences.Comment: 11 pages, 9 figure
Efficient parameter inference for gravitational wave signals in the presence of transient noises using temporal and time-spectral fusion normalizing flow
Glitches represent a category of non-Gaussian and transient noise that
frequently intersects with gravitational wave (GW) signals, exerting a notable
impact on the processing of GW data. The inference of GW parameters, crucial
for GW astronomy research, is particularly susceptible to such interference. In
this study, we pioneer the utilization of temporal and time-spectral fusion
normalizing flow for likelihood-free inference of GW parameters, seamlessly
integrating the high temporal resolution of the time domain with the frequency
separation characteristics of both time and frequency domains. Remarkably, our
findings indicate that the accuracy of this inference method is comparable to
traditional non-glitch sampling techniques. Furthermore, our approach exhibits
greater efficiency, boasting processing times on the order of milliseconds. In
conclusion, the application of normalizing flow emerges as pivotal in handling
GW signals affected by transient noises, offering a promising avenue for
enhancing the field of GW astronomy research.Comment: 13 pages, 10 figure
Analysis of the clinicopathological characteristics and prognosis of triple-positive breast cancer and HER2-positive breast cancer—A retrospective study
BackgroundAdjuvant chemotherapy and targeted therapy have become standard postoperative therapeutic modalities for human epidermal growth factor receptor 2 (HER2)-positive breast cancer(HER2-positive,HR-negative), including triple-positive breast cancer(HER2-positive,HR-positive). However, these two types of breast cancer differ in terms of pathogenesis. This article analyzes these two types of breast cancer by comparing their prognoses.MethodsThe clinicopathological characteristics of 135 patients, including 60 patients with triple-positive breast cancer and 75 patients with HER2-positive breast cancer, were analyzed to compare the disease-free survival (DFS) and overall survival (OS) of the two groups over a 5-year period. A multifactorial Cox risk model was constructed by grouping age, menstrual status, maximum tumor diameter, number of lymph node metastases, pathological staging, and Ki-67 staining results. All statistical data were analyzed in detail using SPSS25.0 statistical software.ResultsThe 5-year OS rates of patients with breast cancer in the triple-positive and HER2-positive groups were 96.7% and 82.7%, respectively, and the 5-year DFS rates were 90% and 73.3%, respectively. The Cox results revealed that molecular staging was an independent factor affecting recurrent metastasis and survival of breast cancer patients (hazard ratio [HR] =2.199, 95% confidence interval [CI], 1.296-8.266; HR = 9.994, 95% CI, 2.019-49.465).ConclusionThe 5-year DFS and OS rates were significantly better in the triple-positive group than in the HER2-positive group. Subgroups received different prognosis for different chemotherapy regimens. Breast cancer patients should be treated according to the risk of recurrence with symptomatic treatment and precise regulation
The Photometric System of Tsinghua-NAOC 80-cm Telescope at NAOC Xinglong Observatory
Tsinghua-NAOC (National Astronomical Observatories of China) Telescope
(hereafter, TNT) is an 80-cm Cassegrain reflecting telescope located at
Xinglong bservatory of NAOC, with main scientific goals of monitoring various
transients in the universe such as supernovae, gamma-ray bursts, novae,
variable stars, and active galactic nuclei. We present in this paper a
systematic test and analysis of the photometric performance of this telescope.
Based on the calibration observations on twelve photometric nights, spanning
the period from year 2004 to year 2012, we derived an accurate transformation
relationship between the instrumental magnitudes and standard Johnson
and Cousins magnitudes. In particular, the color terms and the
extinction coefficients of different passbands are well determined. With these
data, we also obtained the limiting magnitudes and the photometric precision of
TNT. It is worthwhile to point out that the sky background at Xinglong
Observatory may become gradually worse over the period from year 2005 to year
2012 (e.g., 21.4 mag vs. 20.1 mag in the V band).Comment: 12 pages,9 figures, accepted by RA
Effect of carbon-coated Al2O3 powder on structure and properties of low-carbon MgO-C refractory composites
In this study, low-carbon MgO-C refractory composites with addition of uncoated (UA) and carbon-coated Al2O3 (CCA) powders were prepared. The effect of heat-treatment temperature on apparent porosity, cold modulus of rupture and thermal expansion was investigated. The results indicated that the CCA was present in the form of porous agglomerates of 400–800 µm in diameter in MgO-C matrix. The formation of spinel started at 1100 °C and 1250 °C in UA-MgO-C and CCA-MgO-C specimens, respectively. In the specimen CCA-MgOC, cyclic spinel was formed on the outer layer of CCA agglomerates, and the dense spinel layer hindered the diffusion of Mg(g) to the interior of the agglomerates, resulting in alumina residues at 1550 °C. The specimen CCA-MgO-C showed better mechanical properties and reduced porosity. Additionally, the average coefficient of thermal expansion of CCA-MgO-C was significantly lower than that of UA-MgO-C. Thus, CCA powder could improve the volume stability of the low-carbon MgO-C refractory composites
Absence of topological Hall effect in FeRh epitaxial films: revisiting their phase diagram
A series of FeRh () films were epitaxially
grown using magnetron sputtering, and were systematically studied by
magnetization-, electrical resistivity-, and Hall resistivity measurements.
After optimizing the growth conditions, phase-pure FeRh films
were obtained, and their magnetic phase diagram was revisited. The
ferromagnetic (FM) to antiferromagnetic (AFM) transition is limited at narrow
Fe-contents with in the bulk FeRh alloys. By
contrast, the FM-AFM transition in the FeRh films is extended to
cover a much wider range between 33 % and 53 %, whose critical temperature
slightly decreases as increasing the Fe-content. The resistivity jump and
magnetization drop at the FM-AFM transition are much more significant in the
FeRh films with 50 % Fe-content than in the Fe-deficient
films, the latter have a large amount of paramagnetic phase. The
magnetoresistivity (MR) is rather weak and positive in the AFM state, while it
becomes negative when the FM phase shows up, and a giant MR appears in the
mixed FM- and AFM states. The Hall resistivity is dominated by the ordinary
Hall effect in the AFM state, while in the mixed state or high-temperature FM
state, the anomalous Hall effect takes over. The absence of topological Hall
resistivity in FeRh films with various Fe-contents implies that
the previously observed topological Hall effect is most likely extrinsic. We
propose that the anomalous Hall effect caused by the FM iron moments at the
interfaces nicely explains the hump-like anomaly in the Hall resistivity. Our
systematic investigations may offer valuable insights into the spintronics
based on iron-rhodium alloys.Comment: 9 pages, 10 figures; accepted by Phys. Rev.
Gate-tunable negative differential conductance in hybrid semiconductor-superconductor devices
Negative differential conductance (NDC) manifests as a significant
characteristic of various underlying physics and transport processes in hybrid
superconducting devices. In this work, we report the observation of
gate-tunable NDC outside the superconducting energy gap on two types of hybrid
semiconductor-superconductor devices, i.e., normal metal-superconducting
nanowire-normal metal and normal metal-superconducting nanowire-superconductor
devices. Specifically, we study the dependence of the NDCs on back-gate voltage
and magnetic field. When the back-gate voltage decreases, these NDCs weaken and
evolve into positive differential conductance dips; and meanwhile they move
away from the superconducting gap towards high bias voltage, and disappear
eventually. In addition, with the increase of magnetic field, the NDCs/dips
follow the evolution of the superconducting gap, and disappear when the gap
closes. We interpret these observations and reach a good agreement by combining
the Blonder-Tinkham-Klapwijk (BTK) model and the critical supercurrent effect
in the nanowire, which we call the BTK-supercurrent model. Our results provide
an in-depth understanding of the tunneling transport in hybrid
semiconductor-superconductor devices.Comment: 15+6 pages, 4+6 figure
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