Sensitive and selective liquid chromatography–mass spectrometry (LC–MS) analysis is a powerful and essential tool for metabolite identification in drug discovery and development. An MS2 (or tandem, ...MS/MS) mass spectrum is acquired from the fragmentation of a precursor ion by multiple methods including information-dependent acquisition (IDA), SWATH (sequential window acquisition of all theoretical fragment-ion spectra), and MSAll (also called MSE) techniques. We compared these three techniques in their capabilities to produce comprehensive MS2 data by assessing both metabolite MS2 acquisition hit rate and the quality of MS2 spectra. Rat liver microsomal incubations from eight test compounds were analyzed with four methods (IDA, MMDF (multiple mass defect filters)-IDA, SWATH, or MSAll) using an ultrahigh-performance liquid chromatography–qudrupole time-of-flight mass spectrometry (UHPLC–Q-TOF MS) platform. A combined total of 227 drug-related materials (DRM) were detected from all eight test article incubations, and among those, 5% and 4% of DRM were not triggered for MS2 acquisition with IDA and MMDF-IDA methods, respectively. When the same samples were spiked to an equal volume of blank rat urine (urine sample), the DRM without MS2 acquisition increased to 29% and 18%, correspondingly. In contrast, 100% of DRM in both matrixes were subjected to MS2 acquisition with either the SWATH or MSAll method. However, the quality of the acquired MS2 spectra decreased in the order of IDA, SWATH, and MSAll methods. An average of 10, 9, and 6 out of 10 most abundant ions in MS2 spectra were the real product ions of DRM detected in microsomal samples from IDA, SWATH, and MSAll methods, respectively. The corresponding numbers declined to 9, 6, and 3 in the urine samples. Overall, IDA-based methods acquired qualitatively better MS2 spectra but with a lower MS2 acquisition hit rate than the other two methods. SWATH outperformed the MSAll method given its better quality of MS2 spectra with an identical MS2 acquisition hit rate.
In this paper, we present a novel mechanism for recording at a head held significantly below the medium coercivity in a perpendicular recording geometry. By applying a localized ac field at adequate ...frequency to the perpendicular recording medium, saturation recording can be achieved with recording field amplitudes significantly below the medium coercivity, or the medium perpendicular anisotropy field. A scheme utilizing spin torque to generate a localized ac field at high frequency (tens of gigahertz) with kilo-oersted field amplitude in the medium is proposed along with a systematic modeling analysis. Recording simulations at high linear densities are presented.
Lakes play an important role in the water ecosystem on earth, and are vulnerable to climate change and human activities. Thus, the detection of water quality changes is of great significance for ...ecosystem assessment, disaster warning and water conservancy projects. In this paper, the dynamic changes of the Poyang Lake are monitored by Synthetic Aperture Radar (SAR). In order to extract water from SAR images to monitor water change, a water extraction algorithm composed of texture feature extraction, feature fusion and target segmentation was proposed. Firstly, the fractal dimension and lacunarity were calculated to construct the texture feature set of a water object. Then, an iterated function system (IFS) was constructed to fuse texture features into composite feature vectors. Finally, lake water was segmented by the multifractal spectrum method. Experimental results showed that the proposed algorithm accurately extracted water targets from SAR images of different regions and different imaging modes. Compared with common algorithms such as fuzzy C-means (FCM), the accuracy of the proposed algorithm is significantly improved, with an accuracy of over 98%. Moreover, the proposed algorithm can accurately segment complex coastlines with mountain shadow interference. In addition, the dynamic analysis of the changes of the water area of the Poyang Lake Basin was carried out with the local hydrological data. It showed that the extracted results of the algorithm in this paper are a good match with the hydrological data. This study provides an accurate monitoring method for lake water under complex backgrounds.
The TRIM37 (also known as MUL) gene is located in the 17q23 chromosomal region, which is amplified in up to ∼ 40% of breast cancers. TRIM37 contains a RING finger domain, a hallmark of E3 ubiquitin ...ligases, but its protein substrate(s) is unknown. Here we report that TRIM37 mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. We find that in human breast cancer cell lines containing amplified 17q23, TRIM37 is upregulated and, reciprocally, the major H2A ubiquitin ligase RNF2 (also known as RING1B) is downregulated. Genome-wide chromatin immunoprecipitation (ChIP)-chip experiments in 17q23-amplified breast cancer cells identified many genes, including multiple tumour suppressors, whose promoters were bound by TRIM37 and enriched for ubiquitinated H2A. However, unlike RNF2, which is a subunit of polycomb repressive complex 1 (PRC1), we find that TRIM37 associates with polycomb repressive complex 2 (PRC2). TRIM37, PRC2 and PRC1 are co-bound to specific target genes, resulting in their transcriptional silencing. RNA-interference-mediated knockdown of TRIM37 results in loss of ubiquitinated H2A, dissociation of PRC1 and PRC2 from target promoters, and transcriptional reactivation of silenced genes. Knockdown of TRIM37 in human breast cancer cells containing amplified 17q23 substantially decreases tumour growth in mouse xenografts. Conversely, ectopic expression of TRIM37 renders non-transformed cells tumorigenic. Collectively, our results reveal TRIM37 as an oncogenic H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and promotes transformation by facilitating silencing of tumour suppressors and other genes.
It is difficult to obtain a large number of high‐quality labelled Synthetic Aperture Radar (SAR) image data. In order to solve the classification task of an SAR image with limited data, this paper ...proposes a dual‐network classification model of pre‐training and fine‐tuning based on contrastive learning and pseudo‐label training strategy. The algorithm firstly obtains the initial weight of the network through unsupervised pre‐training and then takes advantage of the pseudo‐label information to realise the fine tuning of the dual network. It effectively reduces the number of samples required during classification. Compared with the classification network without optimisation strategy, the proposed algorithm achieves higher classification accuracy in the ablation study.
In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥70 years with hematologic malignancies across the United States. Adults ≥70 years ...with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥70 years underwent HCT across 103 transplant centers. The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% 95% confidence interval (CI), 21% to 33% in 2000-2007 to 39% 95% CI, 35% to 42% in 2008-2013, P < .001; PFS: 22% 16% to 28% in 2000-2007 to 32% 95% CI, 29% to 36% in 2008-2013, P = .003). Two-year TRM ranged from 33% to 35% and was unchanged over time (P = .54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ≥3 (hazard ratio HR, 1.27; P = .006), umbilical cord blood graft (HR, 1.97; P = .0002), and myeloablative conditioning (HR, 1.61; P = .0002) as adverse factors. Over the past decade, utilization and survival after allogeneic transplant have increased in patients ≥70 years. Select adults ≥70 years with hematologic malignancies should be considered for transplant.
•Over the last decade, allogeneic HCT has been increasingly administered in the United States to adults aged 70 and older with hematologic malignancies.•Allogeneic transplant outcomes were reasonable; high comorbidity and ablative conditioning regimens were associated with inferior outcomes.
In this paper, we present a micromagnetic analysis of two novel magnetoresistive memory designs, both of which utilize the material-intrinsic perpendicular uniaxial magnetic anisotropy for retaining ...memory states. The analysis shows that such perpendicular memory element design allows the utilization of thick magnetic film, thereby enabling downsize scalability of each memory element while maintaining sufficient thermal stability. One of the designs is to utilize direct current injection for switching the memory states via the effect of spin momentum transfer. The other design utilizes current-generated field for switching. The performance characteristics of both designs are reported
The fatigue strength and fatigue life of high-strength steels are greatly affected by their surface roughness. This study investigates the underlying mechanisms responsible for fatigue failure of the ...high-strength steel 42CrMo. Bending fatigue tests of stepped shafts with different levels of surface roughness were conducted to observe the fatigue live reduction affected by surface topography. Besides, the mechanical properties of 42CrMo and its strain–life relationship were established. Moreover, the analytical formulas to describe the stress concentration factor (SCF) and fatigue notch factor (FNF) induced by surface topography were introduced. To estimate the fatigue life of machined specimens with the consideration of surface roughness, the elastic portion of the total strain–life curve of the material was revised with the proposed analytical FNF imposed by surface topography. Comparisons between the estimated fatigue lives and experimentally obtained fatigue lives show that the effect of surface roughness on fatigue lives could be estimated effectively and conveniently by the proposed procedure.
This paper introduces a novel method for road target segmentation in the context of autonomous driving based on stereo disparity maps. The proposed method utilizes topological persistence threshold ...analysis to address the challenges of selecting appropriate thresholds. The approach involves converting stereo road images into uv-disparity maps, extracting road planes using v-disparity maps, and calculating occupancy grid maps using u-disparity maps. Persistence diagrams are then constructed by generating segmentation results under various threshold parameters. By establishing persistence boundaries in these diagrams, the most significant regions are identified, enabling the determination of robust segmentation thresholds. Experimental validation using KITTI stereo image datasets demonstrates the effectiveness of the proposed method, with low error rates and superior performance compared to other segmentation methods. The research holds potential for application in autonomous driving systems.
A production status monitoring method based on edge computing is proposed for traditional machining offline equipment to address the deficiencies that traditional machining offline equipment have, ...which cannot automatically count the number of parts produced, obtain part processing time information, and discern anomalous operation status. Firstly, the total current signal of the collected equipment was filtered to extract the processing segment data. The processing segment data were then used to manually calibrate the feature vector of the equipment for specific parts and processes, and the feature vector was used as a reference to match with the real-time electric current data on the edge device to identify and obtain the processing start time, processing end time, and anomalous marks for each part. Finally, the information was uploaded to further obtain the part processing time, loading and unloading standby time, and the cause of the anomaly. To verify the reliability of the method, a prototype system was built, and extensive experiments were conducted on many different types of equipment in an auto parts manufacturer. The experimental results show that the proposed monitoring algorithm based on the calibration vector can stably and effectively identify the production information of each part on an independently developed edge device.
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