Image-based high throughput (HT) screening provides a rich source of information on dynamic cellular response to external perturbations. The large quantity of data generated necessitates ...computer-aided quality control (QC) methodologies to flag imaging and staining artifacts. Existing image- or patch-level QC methods require separate thresholds to be simultaneously tuned for each image quality metric used, and also struggle to distinguish between artifacts and valid cellular phenotypes. As a result, extensive time and effort must be spent on per-assay QC feature thresholding, and valid images and phenotypes may be discarded while image- and cell-level artifacts go undetected. We present a novel cell-level QC workflow built on machine learning approaches for classifying artifacts from HT image data. First, a phenotype sampler based on unlabeled clustering collects a comprehensive subset of cellular phenotypes, requiring only the inspection of a handful of images per phenotype for validity. A set of one-class support vector machines are then trained on each biologically valid image phenotype, and used to classify individual objects in each image as valid cells or artifacts. We apply this workflow to two real-world large-scale HT image datasets and observe that the ratio of artifact to total object area (AR.sub.cell) provides a single robust assessment of image quality regardless of the underlying causes of quality issues. Gating on this single intuitive metric, partially contaminated images can be salvaged and highly contaminated images can be excluded before image-level phenotype summary, enabling a more reliable characterization of cellular response dynamics. Our cell-level QC workflow enables identification of artificial cells created not only by staining or imaging artifacts but also by the limitations of image segmentation algorithms. The single readout AR.sub.cell that summaries the ratio of artifacts contained in each image can be used to reliably rank images by quality and more accurately determine QC cutoff thresholds. Machine learning-based cellular phenotype clustering and sampling reduces the amount of manual work required for training example collection. Our QC workflow automatically handles assay-specific phenotypic variations and generalizes to different HT image assays.
Human performance while executing operating procedures is critically important for the safety of complex industrial systems. To predict and model human performance, several complexity measures have ...been developed. This study aims to compare the convergent validity and predictive validity of three existing complexity measures, step complexity (SC), task size, and task complexity (TC), using operator performance data collected from an emergency operating procedure (EOP) experiment. This comparative study shows that these measures have a high convergent validity with each other, most likely because all of them involve the size dimension of complexity. These measures and their sub-measures also have a high predictive validity for operation time and a moderate-to-high predictive validity for error rate, except the step logic complexity (SLC) measure, a component of the SC measure. SLC appears not to contribute to the predictive validity in the experimental EOPs. The use of visual, auditory, cognitive, and psychomotor (VACP) rating scales in the TC measure seems to be significantly beneficial for explaining the human error rate; however, these rating scales appear not to adequately reflect the complexity differences among the meta-operations in EOPs.
As the second most significant metal following steel, aluminum plays a vital role in the advancement of both strategic emerging industries and national economic development. The existing oil and gas ...drilling data indicate that the deep bauxite deposits is abundant around the Ordos Basin in China, at the depths ranging from several hundred meters to several kilometers. Based on the geological and hydrogeological characteristics analysis, it is found that deep bauxite deposits in the basin have distinct electrical characteristics, characterized by four highs and two lows. While there is scarcity of prior research on the exploration topic for the technique limitation. In this paper, a logging interpretation model has been developed, which allows the evaluation of bauxite deposits. An efficient technology was proposed for deep bauxite exploration, utilizing an in-situ leaching mining technique. This technology is well-suited to the geological conditions of the Ordos Basin, ensuring that the solution flows within the bauxite ore bed without any seepage loss. To prevent the leaching solution from seeping into and polluting the main aquifer around the basin, several measures have been proposed. These include filling with polymer resin, well pattern seepage control plugging, and establishing monitoring systems. The results of this study provide a theoretical basis for the adoption of environmentally sustainable mining techniques and the mitigation of water pollution in deep bauxite exploration.
By conducting a mixed-design experiment using simplified accident handling tasks performed by two-person teams, this study examined the effects of automation function and condition (before, during, ...and after malfunction) on human performance. Five different and non-overlapping functions related to human information processing model were considered and their malfunctions were set in a first-failure way. The results showed that while the automation malfunction impaired task performance, the performance degradation for information analysis was more severe than response planning. Contrary to other functions, the situation awareness for response planning and response implementation tended to increase during malfunctioning and decrease after. In addition, decreased task performance reduced trust in automation, and malfunctions in earlier stages of information processing resulted in lower trust. Suggestions provided for the design and training related to automation emphasise the importance of high-level cognitive support and the benefit of involving automation error handling in training.
The effects of automation function and malfunction on human performance are important for design and training. The experimental results in this study revealed the significance of high-level cognitive support. Also, introducing automation error handling in training can be helpful in improving situation awareness of the teams.
The transient build-up of DNA supercoiling during the translocation of replication forks threatens genome stability and is controlled by DNA topoisomerases (TOPs). This crucial process has been ...exploited with TOP poisons for cancer chemotherapy. However, pinpointing cellular determinants of the best clinical response to TOP poisons still remains enigmatic. Here, we present an integrated approach and demonstrate that endogenous and exogenous expression of the oncofetal high-mobility group AT-hook 2 (HMGA2) protein exhibited broad protection against the formation of hydroxyurea-induced DNA breaks in various cancer cells, thus corroborating our previously proposed model in which HMGA2 functions as a replication fork chaperone that forms a protective DNA scaffold at or close to stalled replication forks. We now further demonstrate that high levels of HMGA2 also protected cancer cells against DNA breaks triggered by the clinically important TOP1 poison irinotecan. This protection is most likely due to the recently identified DNA supercoil constraining function of HMGA2 in combination with exclusion of TOP1 from binding to supercoiled substrate DNA. In contrast, low to moderate HMGA2 protein levels surprisingly potentiated the formation of irinotecan-induced genotoxic covalent TOP1-DNA cleavage complexes. Our data from cell-based and several in vitro assays indicate that, mechanistically, this potentiating role involves enhanced drug-target interactions mediated by HMGA2 in ternary complexes with supercoiled DNA. Subtelomeric regions were found to be extraordinarily vulnerable to these genotoxic challenges induced by TOP1 poisoning, pointing at strong DNA topological barriers located at human telomeres. These findings were corroborated by an increased irinotecan sensitivity of patient-derived xenografts of colorectal cancers exhibiting low to moderate HMGA2 levels. Collectively, we uncovered a therapeutically important control mechanism of transient changes in chromosomal DNA topology that ultimately leads to enhanced human subtelomere stability.
The variable noise spectrum for many actual application scenarios requires a sound absorber to adapt to this variation. An adjustable sound absorber of multiple parallel-connection Helmholtz ...resonators with tunable apertures (TA-MPCHRs) is prepared by the low-force stereolithography of photopolymer resin, which aims to improve the applicability of the proposed sound absorber for noise with various frequency ranges. The proposed TA-MPCHR metamaterial contains five metamaterial cells. Each metamaterial cell contains nine single Helmholtz resonators. It is treated as a basic structural unit for an array arrangement. The tunable aperture is realized by utilizing four segments of extendable cylindrical chambers with length
, which indicates that the length of the aperture
is in the range of
, 4
, and that it is tunable. With a certain group of specific parameters for the proposed TA-MPCHR, the influence of the tunable aperture with a variable length is investigated by acoustic finite element simulation with a two-dimensional rotational symmetric model. For the given noise spectrum of certain actual equipment with four operating modes, the TA-MPCHR sample with a limited total thickness of 40 mm is optimized, which is made of photopolymer resin by the low-force stereolithography, and its actual average sound absorption coefficients for the frequency ranges of 500-800 Hz, 550-900 Hz, 600-1000 Hz and 700-1150 Hz reach 0.9203, 0.9202, 0.9436 and 0.9561, respectively. Relative to common non-adjustable metamaterials, the TA-MPCHR made of photopolymer resin can reduce occupied space and improve absorption efficiency, which is favorable in promoting its practical applications in the noise pollution prevention.
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•A stalagmite sub-decadally-resolved Asian monsoon record at MIS 5a/4 transition.•The termination of the CIS 21 is determined at 76.8 ± 0.2 kyr BP.•GIS 21 rebound event is revealed ...for the first time in the AM continental archive.
Greenland Interstadial 21 (GIS 21), one of the longest warm episodes during the last glacial period, occurred at the transition from Marine Isotope Stage (MIS) 5a to 4. Precise determination of the timing and duration of this interstadial can improve our understanding of the hydroclimatic connection between low and high latitudes across this MIS boundary. δ18O records of two stalagmites from Sanxing Cave, Southwest China, provide a sub-decadally resolved record of Asian Summer Monsoon (ASM) evolution from 79.0 ± 0.2 to 75.7 ± 0.2 thousand years before present (kyr BP, before 1950 CE) revealing the detailed structure of the Chinese Interstadial 21 (CIS 21). The replicate Sanxing record, for the first time, captures three centennial-scale intervals of strong monsoon and a 700-yr-long weak monsoon period within the CIS 21 “rebound-type” event, concurrent with its counterpart GIS 21. This synchronicity between SW China and Greenland suggests a rapid atmospheric teleconnection between the North Atlantic and the ASM region. Marked by ∼400 yr-long decrease in ASM, CIS 21 ended at 76.8 ± 0.2 kyr BP, which is 0.5–1.0 kyr younger than the corresponding termination of GIS 21 on AICC2012 and GICC05modelext timescales. Given its high accuracy and precision, the Sanxing stalagmite chronology can serve as a benchmark for chronological refinements for ice-core records.
The increased use of silica and silicon-containing nanoparticles (Si-NP) in agricultural applications has stimulated interest in determining their potential migration in the environment and their ...uptake by living organisms. Understanding the fate and behavior of Si-NPs will require their accurate analysis and characterization in very complex environmental matrices. In this study, we investigated Si-NP analysis in soil using single-particle ICP-MS. A magnetic sector instrument was operated at medium resolution to overcome the impact of polyatomic interferences (e.g.,
N
N and
C
O) on
Si determinations. Consequently, a size detection limit of 29 ± 3 nm (diameter of spherical SiO
NP) was achieved in Milli-Q water. Si-NP were extracted from agricultural soil using several extractants, including Ca(NO
)
, Mg(NO
)
, BaCl
, NaNO
, Na
P
O
, fulvic acid (FA) and Na
H
EDTA. The best extraction efficiency was found for Na
P
O
for which the size distribution of Si-NP in the leachates was well preserved for at least one month. On the other hand, Ca(NO
)
, Mg(NO
)
and BaCl
were relatively less effective and generally led to particle agglomeration. A time-of-flight ICP-MS was also used to examine the nature of the extracted Si-NP on a single-particle basis. Aluminosilicates accounted for the greatest number of extracted NP (~46%), followed by NP where Si was the only detected metal (presumably SiO
, ~30%).
Polycomb group proteins Bmi-1 and Ring1B are core subunits of the PRC1 complex, which plays important roles in the regulation of Hox gene expression, X-chromosome inactivation, tumorigenesis, and ...stem cell self-renewal. The RING finger protein Ring1B is an E3 ligase that participates in the ubiquitination of lysine 119 of histone H2A, and the binding of Bmi-1 stimulates the E3 ligase activity. We have mapped the regions of Bmi-1 and Ring1B required for efficient ubiquitin transfer and determined a 2.5-Å structure of the Bmi-1-Ring1B core domain complex. The structure reveals that Ring1B “hugs” Bmi-1 through extensive RING domain contacts and its N-terminal tail wraps around Bmi-1. The two regions of interaction have a synergistic effect on the E3 ligase activity. Our analyses suggest a model where the Bmi-1-Ring1B complex stabilizes the interaction between the E2 enzyme and the nucleosomal substrate to allow efficient ubiquitin transfer.
In order to understand the origin of high-temperature superconductivity in copper oxides, we must understand the normal state from which it emerges. Here, we examine the evolution of the normal state ...electronic excitations with temperature and carrier concentration in BiâSrâCaCuâOââδ using angle-resolved photoemission. In contrast to conventional superconductors, where there is a single temperature scale Tc separating the normal from the superconducting state, the high-temperature superconductors exhibit two additional temperature scales. One is the pseudogap scale T*, below which electronic excitations exhibit an energy gap. The second is the coherence scale Tcoh, below which sharp spectral features appear due to increased lifetime of the excitations. We find that T* and Tcoh are strongly doping dependent and cross each other near optimal doping. Thus the highest superconducting Tc emerges from an unusual normal state that is characterized by coherent excitations with an energy gap.
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