Publications by authors named "Shang Gao"

193 Publications

A new species of Dactylolabis subgenus Dactylolabis Osten Sacken, 1860 from China (Diptera, Limoniidae).

Zookeys 2021 28;1047:91-100. Epub 2021 Jun 28.

Department of Entomology, College of Plant Protection, China Agricultural University, Beijing 100193, China China Agricultural University Beijing China.

Only two species of Dactylolabis subgenus Dactylolabis Osten Sacken, 1860 were previously known from China. Here, a new species, Dactylolabis (Dactylolabis) wudangensis, is reported from China. Dactylolabis (D.) gracilistylus Alexander, 1926 is re-described and illustrated. A key to males of species of the subgenus Dactylolabis from China is presented.
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http://dx.doi.org/10.3897/zookeys.1047.62033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257563PMC
June 2021

A Bayesian inference transcription factor activity model for the analysis of single-cell transcriptomes.

Genome Res 2021 Jun 30. Epub 2021 Jun 30.

Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 60612, USA.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful experimental approach to study cellular heterogeneity. One of the challenges in scRNA-seq data analysis is integrating different types of biological data to consistently recognize discrete biological functions and regulatory mechanisms of cells, such as transcription factor activities and gene regulatory networks in distinct cell populations. We have developed an approach to infer transcription factor activities from scRNA-seq data that leverages existing biological data on transcription factor binding sites. The Bayesian inference transcription factor activity model (BITFAM) integrates ChIP-seq transcription factor binding information into scRNA-seq data analysis. We show that the inferred transcription factor activities for key cell types identify regulatory transcription factors that are known to mechanistically control cell function and cell fate. The BITFAM approach not only identifies biologically meaningful transcription factor activities, but also provides valuable insights into underlying transcription factor regulatory mechanisms.
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http://dx.doi.org/10.1101/gr.265595.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256867PMC
June 2021

Luteolin inhibits HO-induced cellular senescence modulation of SIRT1 and p53.

Korean J Physiol Pharmacol 2021 Jul;25(4):297-305

Department of Biochemistry, Wonkwang University School of Medicine, Iksan 54538, Korea.

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (HO)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated -galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against HO-induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.
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http://dx.doi.org/10.4196/kjpp.2021.25.4.297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255127PMC
July 2021

Two new species of genus Spilolonchoptera Yang, 1998 from China (Diptera, Lonchopteridae).

Zootaxa 2021 Jun 1;4980(2):389394. Epub 2021 Jun 1.

Department of Entomology, China Agricultural University, Beijing 100193, China..

Only five species of the genus Spilolonchoptera Yang, 1998 were previously known from China. Here two new species, Spilolonchoptera hainanensis sp. nov. and Spilolonchoptera zhejiangensis sp. nov. are reported from China. A key to species of the genus Spilolonchoptera from China is presented.
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http://dx.doi.org/10.11646/zootaxa.4980.2.10DOI Listing
June 2021

Foam film stratification studies probe intermicellar interactions.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Department of Chemical Engineering, University of Illinois at Chicago, Chicago, IL 60608;

Ultrathin foam films containing supramolecular structures like micelles in bulk and adsorbed surfactant at the liquid-air interface undergo drainage via stratification. At a fixed surfactant concentration, the stepwise decrease in the average film thickness of a stratifying micellar film yields a characteristic step size that also describes the quantized thickness difference between coexisting thick-thin flat regions. Even though many published studies claim that step size equals intermicellar distance obtained using scattering from bulk solutions, we found no reports of a direct comparison between the two length scales. It is well established that step size is inversely proportional to the cubic root of surfactant concentration but cannot be estimated by adding micelle size to Debye length, as the latter is inversely proportional to the square root of surfactant concentration. In this contribution, we contrast the step size obtained from analysis of nanoscopic thickness variations and transitions in stratifying foam films using Interferometry Digital Imaging Optical Microscopy (IDIOM) protocols, that we developed, with the intermicellar distance obtained using small-angle X-ray scattering. We find that stratification driven by the confinement-induced layering of micelles within the liquid-air interfaces of a foam film provides a sensitive probe of non-DLVO (Derjaguin-Landau-Verwey-Overbeek) supramolecular oscillatory structural forces and micellar interactions.
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http://dx.doi.org/10.1073/pnas.2024805118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237596PMC
June 2021

Extraction of the Structural Properties of Skin Tissue via Diffuse Reflectance Spectroscopy: An Inverse Methodology.

Sensors (Basel) 2021 May 28;21(11). Epub 2021 May 28.

State Key Laboratory of Multiphase Flow in Power Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

For the laser treatment of vascular dermatosis, the blood vessel morphology and depth in skin tissue is essential to achieve personalized intelligent therapy. The morphology can be obtained from the laser speckle imaging, and vessel depth was extracted by an inverse methodology based on diffuse reflectance spectrum. With optimized spot size of 0.5 mm and known optical properties, the proposed method was experimentally validated via the spectral measurement of microcapillary with known size and depth embedded in an epoxy resin-based skin phantom. Results prove that vessel depth can be extracted with an average relative error of 5%, thereby providing the foundation for a personalized, precise, and intelligent laser treatment of vascular dermatosis.
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http://dx.doi.org/10.3390/s21113745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199232PMC
May 2021

Functional specificity, diversity, and redundancy of Arabidopsis JAZ family repressors in jasmonate and COI1-regulated growth, development, and defense.

New Phytol 2021 08 19;231(4):1525-1545. Epub 2021 Jun 19.

Beijing Key Laboratory of Plant Gene Resources and Biotechnology for Carbon Reduction and Environmental Improvement, RNA Center, College of Life Sciences, Capital Normal University, Beijing, 100048, China.

In response to jasmonates (JAs), the JA receptor Coronatine Insensitive 1 (COI1) recruits JA-zinc-finger inflorescence meristem (ZIM)-domain (JAZ) family repressors for destruction to regulate plant growth, development, and defense. As Arabidopsis encodes 13 JAZ repressors, their functional specificity, diversity, and redundancy in JA/COI1-mediated responses remain unclear. We generated a broad range of jaz mutants based on their phylogenetic relationship to investigate their roles in JA responses. The group I JAZ6 may play an inhibitory role in resistance to Botrytis cinerea, group II (JAZ10)/III (JAZ11/12) in JA-regulated root growth inhibition and susceptibility to Pseudomonas syringae pv tomato DC3000, and group IV JAZ3/4/9 in flowering time delay and defense against insects. JAZs exhibit high redundancy in apical hook curvature. The undecuple jaz1/2/3/4/5/6/7/9/10/11/12 (jaz1-7,9-12) mutations enhance JA responses and suppress the phenotypes of coi1-1 in flowering time, rosette growth, and defense. The JA hypersensitivity of jaz1-7,9-12 in root growth, hook curvature, and leaf yellowing is blocked by coi1-1. jaz1-7,9-12 does not influence the stamen phenotypes of wild-type and coi1-1. jaz1-7,9-12 affects JA-regulated transcriptional profile and recovers a fraction of that in coi1-1. This study contributes to elucidating the specificity, diversity, and redundancy of JAZ members in JA/COI1-regulated growth, development, and defense responses.
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http://dx.doi.org/10.1111/nph.17477DOI Listing
August 2021

The mitochondrial genome of () (Diptera: Limoniidae).

Mitochondrial DNA B Resour 2021 Mar 31;6(4):1321-1323. Epub 2021 Mar 31.

Department of Entomology, College of Plant Protection, China Agricultural University, Beijing, China.

The crane fly () Mao and Yang, belongs to subfamily Limnophilinae of family Limoniidae. This mitogenome of () was sequenced used next-generation sequencing (NGS), the new representative of the mitogenome of the subfamily. The nearly complete mitogenome is 14,858 bp totally, consisting of 13 protein-coding genes, 2 rRNAs and 22 transfer RNAs. All genes have the similar locations and strands with that of other published species of Limoniidae. The nucleotide composition biases toward A and T, which together made up 75.2% of the entirety. Bayesian inference analysis strongly supported the monophyly of Tipuloidea. It suggested that Pediciidae is the basal clade of Tipuloidea and the monophyletic Tipulidae was assigned as the sister to the monophyletic Cylindrotomidae. The phylogenetic relationship within Tipuloidea was as follows: Pediciidae + (Limoniidae + (Tipulidae + Cylindrotomidae)).
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http://dx.doi.org/10.1080/23802359.2021.1907808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018454PMC
March 2021

Deep active learning for classifying cancer pathology reports.

BMC Bioinformatics 2021 Mar 9;22(1):113. Epub 2021 Mar 9.

Oak Ridge National Lab, Oak Ridge, TN, USA.

Background: Automated text classification has many important applications in the clinical setting; however, obtaining labelled data for training machine learning and deep learning models is often difficult and expensive. Active learning techniques may mitigate this challenge by reducing the amount of labelled data required to effectively train a model. In this study, we analyze the effectiveness of 11 active learning algorithms on classifying subsite and histology from cancer pathology reports using a Convolutional Neural Network as the text classification model.

Results: We compare the performance of each active learning strategy using two differently sized datasets and two different classification tasks. Our results show that on all tasks and dataset sizes, all active learning strategies except diversity-sampling strategies outperformed random sampling, i.e., no active learning. On our large dataset (15K initial labelled samples, adding 15K additional labelled samples each iteration of active learning), there was no clear winner between the different active learning strategies. On our small dataset (1K initial labelled samples, adding 1K additional labelled samples each iteration of active learning), marginal and ratio uncertainty sampling performed better than all other active learning techniques. We found that compared to random sampling, active learning strongly helps performance on rare classes by focusing on underrepresented classes.

Conclusions: Active learning can save annotation cost by helping human annotators efficiently and intelligently select which samples to label. Our results show that a dataset constructed using effective active learning techniques requires less than half the amount of labelled data to achieve the same performance as a dataset constructed using random sampling.
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http://dx.doi.org/10.1186/s12859-021-04047-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941989PMC
March 2021

Differences between diploid donors are the main contributing factor for subgenome asymmetry measured in either gene ratio or relative diversity in allopolyploids.

Genome 2021 Mar 4:1-10. Epub 2021 Mar 4.

CSIRO Agriculture and Food, St Lucia, QLD 4067, Australia.

Subgenome asymmetry (SA) has routinely been attributed to different responses between the subgenomes of a polyploid to various stimuli during evolution. Here, we compared subgenome differences in gene ratio and relative diversity between artificial and natural genotypes of several allopolyploid species. Surprisingly, consistent differences were not detected between these two types of polyploid genotypes, although they differ in times exposed to evolutionary selection. The estimated ratio of shared genes between a subgenome and its diploid donor was invariably higher for the artificial allopolyploid genotypes than those for the natural genotypes, which is expected as it is now well-known that many genes in a species are not shared among all individuals. As the exact diploid parent for a given subgenome is unknown, the estimated ratios of shared genes for the natural genotypes would also include difference among individual genotypes of the diploid donor species. Further, we detected the presence of SA in genotypes before the completion of the polyploidization events as well as in those which were not formed via polyploidization. These results indicate that SA may, to a large degree, reflect differences between its diploid donors or that changes occurred during polyploid evolution are defined by their donor genomes.
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http://dx.doi.org/10.1139/gen-2020-0024DOI Listing
March 2021

Limitations of Transformers on Clinical Text Classification.

IEEE J Biomed Health Inform 2021 Feb 26;PP. Epub 2021 Feb 26.

Bidirectional Encoder Representations from Transformers (BERT) and BERT-based approaches are the current state-of-the-art in many natural language processing (NLP) tasks; however, their application to document classification on long clinical texts is limited. In this work, we introduce four methods to scale BERT, which by default can only handle input sequences up to approximately 400 words long, to perform document classification on clinical texts several thousand words long. We compare these methods against two much simpler architectures -- a word-level convolutional neural network and a hierarchical self-attention network -- and show that BERT often cannot beat these simpler baselines when classifying MIMIC-III discharge summaries and SEER cancer pathology reports. In our analysis, we show that two key components of BERT -- pretraining and WordPiece tokenization -- may actually be inhibiting BERT's performance on clinical text classification tasks where the input document is several thousand words long and where correctly identifying labels may depend more on identifying a few key words or phrases rather than understanding the contextual meaning of sequences of text.
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http://dx.doi.org/10.1109/JBHI.2021.3062322DOI Listing
February 2021

A pre-training and self-training approach for biomedical named entity recognition.

PLoS One 2021 9;16(2):e0246310. Epub 2021 Feb 9.

Computational Sciences and Engineering Division, Oak Ridge National Laboratory, Oak Ridge, TN, United States of America.

Named entity recognition (NER) is a key component of many scientific literature mining tasks, such as information retrieval, information extraction, and question answering; however, many modern approaches require large amounts of labeled training data in order to be effective. This severely limits the effectiveness of NER models in applications where expert annotations are difficult and expensive to obtain. In this work, we explore the effectiveness of transfer learning and semi-supervised self-training to improve the performance of NER models in biomedical settings with very limited labeled data (250-2000 labeled samples). We first pre-train a BiLSTM-CRF and a BERT model on a very large general biomedical NER corpus such as MedMentions or Semantic Medline, and then we fine-tune the model on a more specific target NER task that has very limited training data; finally, we apply semi-supervised self-training using unlabeled data to further boost model performance. We show that in NER tasks that focus on common biomedical entity types such as those in the Unified Medical Language System (UMLS), combining transfer learning with self-training enables a NER model such as a BiLSTM-CRF or BERT to obtain similar performance with the same model trained on 3x-8x the amount of labeled data. We further show that our approach can also boost performance in a low-resource application where entities types are more rare and not specifically covered in UMLS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246310PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872256PMC
July 2021

The Influence of Sliding Speed on the Friction Behavior of Silica Surface.

ACS Omega 2021 Feb 22;6(4):3384-3389. Epub 2021 Jan 22.

School of Mechanical Engineering, University of Shanghai for Science and Technology, No. 516, Jungong Road, Yangpu District, Shanghai 200082, China.

Studies have shown that the relative sliding speed of the silicon-based material surface has an effect on its friction behavior. In this study, the molecular dynamics method was used to simulate the sliding of the SiO surface at different speeds. This is to explore the internal mechanism between SiO surface friction behavior and the relative sliding speed. First of all, this study constructed a 3D model of the SiO friction surface and simulated the sliding process under two different environments of absolute dryness and full wetness. Then, the sliding of the SiO surface at different speeds in dry and wet environments is simulated and verified the rationality of the simulation through experiments. The final results show that the lattice distortion and tribochemical reactions that occur on the SiO surface of the material have varying degrees of influence on the friction behavior of the material surface. In the dry environment, the coefficient of friction of the SiO surface increases with the speed. On the contrary, in the humid environment, the SiO surface decreases as the speed increases. The analysis results found that the speed has varying degrees of influence on the lattice distortion and tribochemical reaction of the SiO surface. Eventually, this study quantifies the effect of speed on SiO surface tribochemical reactions and lattice distortion in two different environments.
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http://dx.doi.org/10.1021/acsomega.0c05897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860513PMC
February 2021

The mitochondrial genome of sp. (Diptera: Empididae).

Mitochondrial DNA B Resour 2020 Jun 12;5(3):2438-2439. Epub 2020 Jun 12.

College of Plant Protection, China Agricultural University, Beijing, China.

The dance fly sp. belongs to the subfamily Ocydromiinae of Empididae. The mitogenome (GenBank accession number: MT483943) of sp. was sequenced, the new representative of the mitogenome of the subfamily. The nearly complete mitogenome is 15,142 bp totally, consisting of 13 protein-coding genes, 2 rRNAs, and 22 transfer RNAs. All genes have the similar locations and strands with that of other published species of Empididae. The nucleotide composition biases toward A and T, which together made up 78.6% of the entirety. Bayesian inference analysis strongly supported the monophyly of Empidoidea, Empididae, and Dolichopodidae. It is clear that the phylogenetic relationship within Empidoidea: (Dolichopodinae + Neurigoninae) + ((Empidinae + (Trichopezinae + Oreogetoninae)) + Ocydromiinae) in this study.
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http://dx.doi.org/10.1080/23802359.2020.1775523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782628PMC
June 2020

Effect of Strain Rate on the Deformation Characteristic of AlN Ceramics under Scratching.

Micromachines (Basel) 2021 Jan 12;12(1). Epub 2021 Jan 12.

Key Laboratory for Precision and Non-Traditional Machining Technology of Ministry of Education, Dalian University of Technology, Dalian 116024, China.

To clarify the influence mechanism of strain rate effect on deformation characteristics of aluminum nitride (AlN) ceramics, some varied-velocity nanoscratching tests were carried out using a Berkovich indenter in this paper. The deformation characteristics of the scratched grooves were observed using the scanning electron microscope. The experimental results showed higher scratch speed would lead to shallower penetration depth, fewer cracks, and indenter fewer slipping, which was more conducive to the plastic deformation of AlN ceramics. Considering the strain rate effect and the elastic recovery of material, a model for predicting the Berkovich indenter penetration depth under edge-forward mode was established. The prediction results were consistent with the experimental data, and the error was less than 5%, indicating that the model is effective. Based on the Boussinesq field, the Cerruti field, and the Sliding bubble field, a strain rate dependent scratch stress field model was established. The stress field revealed higher scratch speed may significantly reduce the maximum principal stress in the stress field under the indenter, which is the fundamental reason for reducing the crack damage and promoting the plastic deformation. The above study can provide theoretical guidance for reducing the processing damage of AlN ceramics.
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http://dx.doi.org/10.3390/mi12010077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828136PMC
January 2021

The mitochondrial genome of sp. (Diptera: Empididae).

Mitochondrial DNA B Resour 2020 27;5(3):2178-2179. Epub 2020 May 27.

College of Plant Protection, China Agricultural University, Beijing, China.

The dance fly sp. belongs to the subfamily Hemerodromiinae of Empididae. The mitogenome (GenBank accession number: MT396991) of sp. was sequenced, the first representative of the mitogenome of the subfamily. The nearly complete mitogenome is 14,976 bp totally, consisting of 13 protein-coding genes, 2 rRNAs, and 22 transfer RNAs. All genes have the similar locations and strands compared with that of other published species of Empididae. The nucleotide composition biases toward A and T, which together made up 77.2%of the entirety. Bayesian inference analysis strongly supported the monophyly of Empidoidea, Empididae and Dolichopodidae. The phylogenetic relationship within Empidoidea is as follows: (Dolichopodinae + Neurigoninae) + (((Empidinae + Hemerodromiinae) + (Trichopezinae + Oreogetoninae)) + Ocydromiinae) in this study.
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http://dx.doi.org/10.1080/23802359.2020.1768945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510568PMC
May 2020

Responses of human gingival fibroblasts to superhydrophilic hydrogenated titanium dioxide nanotubes.

Colloids Surf B Biointerfaces 2021 Feb 24;198:111489. Epub 2020 Nov 24.

Laboratory of Biomaterials and Biomechanics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China. Electronic address:

Soft tissue integration is critical for the long-term retention of dental implants. The surface properties including topography and wettability can impact soft tissue sealing. In our work, a thermal hydrogenation technique was applied to modify anodized titanium dioxide nanotubes (TNTs). However, the effects of the hydrogenated surface on soft-tissue cells remain unclear. The aim of the present study was to investigate the bioactivities of human gingival fibroblasts (HGFs) on structured surfaces, which determine the early formation of soft tissue sealing. Three groups were examined: commercially pure titanium (Ti), anodized TNTs (air-TNTs) and hydrogenated TNTs (H-TNTs). Scanning electron microscopy showed the nanotubular topography on the titanium surfaces after anodization. Then, hydrogenation ensured that the H-TNTs were superhydrophilic with a contact angle of 3.5 ± 0.8°. In vitro studies such as cell adhesion assays, cell morphology, immunocytochemistry, wound healing assays, real-time PCR and enzyme-linked immunosorbent assays displayed enhanced adhesion, migration, relative gene expression levels, and extracellular matrix synthesis of the HGFs on H-TNTs. Interestingly, focal adhesion kinase activation and integrin-mediated adhesion seemed to be induced by the H-TNT surface. Our results revealed that a superhydrophilic nanostructure modified by anodization and hydrogenation can improve the bioactivity of HGFs and connective tissue regeneration, which will further promote and expand the application of titanium dioxide nanotubes in dental implants.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111489DOI Listing
February 2021

Microstructure of the hyoid bone based on micro-computed tomography findings.

Medicine (Baltimore) 2020 Oct;99(44):e22246

Human Anatomy Teaching and Research Section (Digital Medical Center), Inner Mongolia Medical University Basic Medical College.

In this study, micro-CT was used to observe the microscopic anatomy of the hyoid bone, examine the variation of the trabecular bone inside the hyoid bone, and investigate the internal structure of the hyoid bone.A total of 22 hyoid bones were scanned using micro-CT. The changes in the internal bone trabeculae were assessed with 3D reconstructions, and the fine anatomical structure of the hyoid bone was further analyzed.Micro-CT images showed the microstructure of various parts of the hyoid bone. There were significant differences in total volume, bone volume, bone area, bone density, and volume fraction between the body and greater horns of the hyoid bone (P < .05), but no significant differences in the ratio of bone area/volume and bone surface density were found between the body and greater horns of the hyoid bone (P > .05). In addition, significant differences in the trabecular bone measurements, bone trabecular connectivity, and Euler number were found between the body and greater horns of the hyoid bone (P < .05). Other parameters, including bone trabecular thickness, number of trabecular bones, bone trabecular structure model index, and anisotropy of bone trabeculae, did not differ between the body and greater horns of the hyoid bone (P > .05). There was noticeably ossified healing at the joint between the body and greater horns of the hyoid bone.Micro-CT can adequately display the internal structure of the hyoid bone. The identified bone structure may help clarify the physiological function of the hyoid bone. The present findings provide a theoretical basis for further studies aimed at pathological changes due to hyoid injury in clinical and forensic medicine.
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http://dx.doi.org/10.1097/MD.0000000000022246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598853PMC
October 2020

A SMOC2 variant inhibits BMP signaling by competitively binding to BMPR1B and causes growth plate defects.

Bone 2021 01 12;142:115686. Epub 2020 Oct 12.

Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address:

Endochondral ossification is the major process of long bone formation, and chondrogenesis is the final step of this process. Several studies have indicated that bone morphogenetic proteins (BMPs) are required for chondrogenesis and regulate multiple growth plate features. Abnormal BMP pathways lead to growth plate defects, resulting in osteochondrodysplasia. The SPARC-related modular calcium binding 2 (SMOC2) gene encodes an extracellular protein that is considered to be an antagonist of BMP signaling. In this study, we generated a mouse model by knocking-in the SMOC2 mutation (c.1076 T > G), which showed short-limbed dwarfism, reduced, disorganized, and hypocellular proliferative zones and expanded hypertrophic zones in tibial growth plates. To determine the underlying pathophysiological mechanism of SMOC2 mutation, we used knock-in mice to investigate the interaction between SMOC2 and the BMP-SMAD1/5/9 signaling pathway in vivo and in vitro. Eventually, we found that mutant SMOC2 could not bind to COL9A1 and HSPG. Furthermore, mutant SMOC2 inhibited BMP signaling by competitively binding to BMPR1B, which lead to defects in growth plates and short-limbed dwarfism in knock-in mice.
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http://dx.doi.org/10.1016/j.bone.2020.115686DOI Listing
January 2021

Development of α,α-Disubstituted Crotylboronate Reagents and Stereoselective Crotylation via Brønsted or Lewis Acid Catalysis.

J Am Chem Soc 2020 10 14;142(43):18355-18368. Epub 2020 Oct 14.

Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849, United States.

The development of α,α-disubstituted crotylboronate reagents is reported. Chiral Brønsted acid-catalyzed asymmetric aldehyde addition with the developed -crotylboron reagent gave ()--1,2-oxaborinan-3-enes with excellent enantioselectivities and -selectivities. With BF·OEt catalysis, the stereoselectivity is reversed, and ()-δ-boryl--homoallylic alcohols are obtained with excellent -selectivities from the same -crotylboron reagent. The -crotylboron reagent also participates in BF·OEt-catalyzed crotylation to furnish ()-δ-boryl--homoallylic alcohols with good -selectivities. DFT computations establish the origins of observed enantio- and stereoselectivities of chiral Brønsted acid-catalyzed asymmetric allylation. Stereochemical models for BF·OEt-catalyzed reactions are proposed to rationalize the -selective allyl additions. These reactions generate highly valuable homoallylic alcohol products with a stereodefined trisubstituted alkene unit. The synthetic utility is further demonstrated by the total syntheses of salinipyrones A and B.
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http://dx.doi.org/10.1021/jacs.0c04107DOI Listing
October 2020

Fractional antiferromagnetic skyrmion lattice induced by anisotropic couplings.

Nature 2020 10 23;586(7827):37-41. Epub 2020 Sep 23.

Laboratory for Neutron Scattering and Imaging, Paul Scherrer Institut, Villigen, Switzerland.

Magnetic skyrmions are topological solitons with a nanoscale winding spin texture that hold promise for spintronics applications. Skyrmions have so far been observed in a variety of magnets that exhibit nearly parallel alignment for neighbouring spins, but theoretically skyrmions with anti-parallel neighbouring spins are also possible. Such antiferromagnetic skyrmions may allow more flexible control than conventional ferromagnetic skyrmions. Here, by combining neutron scattering measurements and Monte Carlo simulations, we show that a fractional antiferromagnetic skyrmion lattice is stabilized in MnScS through anisotropic couplings. The observed lattice is composed of three antiferromagnetically coupled sublattices, and each sublattice is a triangular skyrmion lattice that is fractionalized into two parts with an incipient meron (half-skyrmion) character. Our work demonstrates that the theoretically proposed antiferromagnetic skyrmions can be stabilized in real materials and represents an important step towards their implementation in spintronic devices.
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http://dx.doi.org/10.1038/s41586-020-2716-8DOI Listing
October 2020

Accelerated training of bootstrap aggregation-based deep information extraction systems from cancer pathology reports.

J Biomed Inform 2020 10 9;110:103564. Epub 2020 Sep 9.

National Center for Computational Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37830, United States of America. Electronic address:

Objective: In machine learning, it is evident that the classification of the task performance increases if bootstrap aggregation (bagging) is applied. However, the bagging of deep neural networks takes tremendous amounts of computational resources and training time. The research question that we aimed to answer in this research is whether we could achieve higher task performance scores and accelerate the training by dividing a problem into sub-problems.

Materials And Methods: The data used in this study consist of free text from electronic cancer pathology reports. We applied bagging and partitioned data training using Multi-Task Convolutional Neural Network (MT-CNN) and Multi-Task Hierarchical Convolutional Attention Network (MT-HCAN) classifiers. We split a big problem into 20 sub-problems, resampled the training cases 2,000 times, and trained the deep learning model for each bootstrap sample and each sub-problem-thus, generating up to 40,000 models. We performed the training of many models concurrently in a high-performance computing environment at Oak Ridge National Laboratory (ORNL).

Results: We demonstrated that aggregation of the models improves task performance compared with the single-model approach, which is consistent with other research studies; and we demonstrated that the two proposed partitioned bagging methods achieved higher classification accuracy scores on four tasks. Notably, the improvements were significant for the extraction of cancer histology data, which had more than 500 class labels in the task; these results show that data partition may alleviate the complexity of the task. On the contrary, the methods did not achieve superior scores for the tasks of site and subsite classification. Intrinsically, since data partitioning was based on the primary cancer site, the accuracy depended on the determination of the partitions, which needs further investigation and improvement.

Conclusion: Results in this research demonstrate that 1. The data partitioning and bagging strategy achieved higher performance scores. 2. We achieved faster training leveraged by the high-performance Summit supercomputer at ORNL.
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http://dx.doi.org/10.1016/j.jbi.2020.103564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276580PMC
October 2020

Exponential Stability of Fractional-Order Complex Multi-Links Networks With Aperiodically Intermittent Control.

IEEE Trans Neural Netw Learn Syst 2020 Sep 7;PP. Epub 2020 Sep 7.

In this article, the exponential stability problem for fractional-order complex multi-links networks with aperiodically intermittent control is considered. Using the graph theory and Lyapunov method, two theorems, including a Lyapunov-type theorem and a coefficient-type theorem, are given to ensure the exponential stability of the underlying networks. The theoretical results show that the exponential convergence rate is dependent on the control gain and the order of fractional derivative. To be specific, the larger control gain, the higher the exponential convergence rate. Meanwhile, when aperiodically intermittent control degenerates into periodically intermittent control, a corollary is also provided to ensure the exponential stability of the underlying networks. Furthermore, to show the practicality of theoretical results, as an application, the exponential stability of fractional-order multi-links competitive neural networks with aperiodically intermittent control is investigated and a stability criterion is established. Finally, the effectiveness and feasibility of the theoretical results are demonstrated through a numerical example.
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http://dx.doi.org/10.1109/TNNLS.2020.3016672DOI Listing
September 2020

Leaf to panicle ratio (LPR): a new physiological trait indicative of source and sink relation in japonica rice based on deep learning.

Plant Methods 2020 26;16:117. Epub 2020 Aug 26.

College of Agriculture, Nanjing Agricultural University, Nanjing, 210095 China.

Background: Identification and characterization of new traits with sound physiological foundation is essential for crop breeding and production management. Deep learning has been widely used in image data analysis to explore spatial and temporal information on crop growth and development, thus strengthening the power of identification of physiological traits. Taking the advantage of deep learning, this study aims to develop a novel trait of canopy structure that integrate source and sink in japonica rice.

Results: We applied a deep learning approach to accurately segment leaf and panicle, and subsequently developed the procedure of GvCrop to calculate the leaf to panicle ratio (LPR) of rice canopy during grain filling stage. Images of training dataset were captured in the field experiments, with large variations in camera shooting angle, the elevation and the azimuth angles of the sun, rice genotype, and plant phenological stages. Accurately labeled by manually annotating the panicle and leaf regions, the resulting dataset were used to train FPN-Mask (Feature Pyramid Network Mask) models, consisting of a backbone network and a task-specific sub-network. The model with the highest accuracy was then selected to check the variations in LPR among 192 rice germplasms and among agronomical practices. Despite the challenging field conditions, FPN-Mask models achieved a high detection accuracy, with Pixel Accuracy being 0.99 for panicles and 0.98 for leaves. The calculated LPR displayed large spatial and temporal variations as well as genotypic differences. In addition, it was responsive to agronomical practices such as nitrogen fertilization and spraying of plant growth regulators.

Conclusion: Deep learning technique can achieve high accuracy in simultaneous detection of panicle and leaf data from complex rice field images. The proposed FPN-Mask model is applicable to detect and quantify crop performance under field conditions. The newly identified trait of LPR should provide a high throughput protocol for breeders to select superior rice cultivars as well as for agronomists to precisely manage field crops that have a good balance of source and sink.
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http://dx.doi.org/10.1186/s13007-020-00660-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449046PMC
August 2020

Topological Nernst Effect of the Two-Dimensional Skyrmion Lattice.

Phys Rev Lett 2020 Aug;125(7):076602

RIKEN Center for Emergent Matter Science (CEMS), Wako, Saitama 351-0198, Japan.

The topological Hall effect (THE) and its thermoelectric counterpart, the topological Nernst effect (TNE), are hallmarks of the skyrmion lattice phase (SkL). We observed the giant TNE of the SkL in centrosymmetric Gd_{2}PdSi_{3}, comparable in magnitude to the largest anomalous Nernst signals in ferromagnets. Significant enhancement (suppression) of the THE occurs when doping electrons (holes) to Gd_{2}PdSi_{3}. On the electron-doped side, the topological Hall conductivity approaches the characteristic threshold ∼1000  (Ω cm)^{-1} for the intrinsic regime. We use the filling-controlled samples to confirm Mott's relation between TNE and THE and discuss the importance of Gd-5d orbitals for transport in this compound.
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http://dx.doi.org/10.1103/PhysRevLett.125.076602DOI Listing
August 2020

Correction to: A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus.

J Clin Immunol 2020 Oct;40(7):1062-1063

Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Basic Medical Sciences, No. 44 West Wenhua Road, Jinan, 250012, Shandong, China.

Figure 4a in Manuscript ID#JOCI-D-19-00318 has been revised due to the replacement of immunoblot lane of β-catenin by Zo-1 in NHA group.
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http://dx.doi.org/10.1007/s10875-020-00838-yDOI Listing
October 2020

Identifying barley pan-genome sequence anchors using genetic mapping and machine learning.

Theor Appl Genet 2020 Sep 24;133(9):2535-2544. Epub 2020 May 24.

Agriculture and Food, CSIRO, St Lucia, QLD, 4067, Australia.

Key Message: We identified 1.844 million barley pan-genome sequence anchors from 12,306 genotypes using genetic mapping and machine learning. There is increasing evidence that genes from a given crop genotype are far to cover all genes in that species; thus, building more comprehensive pan-genomes is of great importance in genetic research and breeding. Obtaining a thousand-genotype scale pan-genome using deep-sequencing data is currently impractical for species like barley which has a huge and highly repetitive genome. To this end, we attempted to identify barley pan-genome sequence anchors from a large quantity of genotype-by-sequencing (GBS) datasets by combining genetic mapping and machine learning algorithms. Based on the GBS sequences from 11,166 domesticated and 1140 wild barley genotypes, we identified 1.844 million pan-genome sequence anchors. Of them, 532,253 were identified as presence/absence variation (PAV) tags. Through aligning these PAV tags to the genome of hulless barley genotype Zangqing320, our analysis resulted in a validation of 83.6% of them from the domesticated genotypes and 88.6% from the wild barley genotypes. Association analyses against flowering time, plant height and kernel size showed that the relative importance of the PAV and non-PAV tags varied for different traits. The pan-genome sequence anchors based on GBS tags can facilitate the construction of a comprehensive pan-genome and greatly assist various genetic studies including identification of structural variation, genetic mapping and breeding in barley.
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http://dx.doi.org/10.1007/s00122-020-03615-yDOI Listing
September 2020

Nanometric square skyrmion lattice in a centrosymmetric tetragonal magnet.

Nat Nanotechnol 2020 Jun 18;15(6):444-449. Epub 2020 May 18.

RIKEN Center for Emergent Matter Science (CEMS), Wako, Japan.

Magnetic skyrmions are topologically stable spin swirls with a particle-like character and are potentially suitable for the design of high-density information bits. Although most known skyrmion systems arise in non-centrosymmetric systems with a Dzyaloshinskii-Moriya interaction, centrosymmetric magnets with a triangular lattice can also give rise to skyrmion formation, with a geometrically frustrated lattice being considered essential in this case. Until now, it remains an open question if skyrmions can also exist in the absence of both geometrically frustrated lattice and inversion symmetry breaking. Here we discover a square skyrmion lattice state with 1.9 nm diameter skyrmions in the centrosymmetric tetragonal magnet GdRuSi without a geometrically frustrated lattice by means of resonant X-ray scattering and Lorentz transmission electron microscopy experiments. A plausible origin of the observed skyrmion formation is four-spin interactions mediated by itinerant electrons in the presence of easy-axis anisotropy. Our results suggest that rare-earth intermetallics with highly symmetric crystal lattices may ubiquitously host nanometric skyrmions of exotic origins.
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http://dx.doi.org/10.1038/s41565-020-0684-7DOI Listing
June 2020

Phase reduction for FitzHugh-Nagumo neuron with large timescale separation.

Phys Rev E 2020 Apr;101(4-1):042203

State Key Laboratory of Mechanics and Control of Mechanical Structures, College of Aerospace Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

Phase reduction approach is a useful tool to reduce the dimension of limit-cycle oscillators. In this paper, it is applied to the FitzHugh-Nagumo neuron model with large timescale separation. To quantitate the response of the oscillator to the external perturbations, the asymptotic behaviors of the phase sensitivity functions for fast and slow variables are obtained. It is shown that in the relaxation limit, apart from the jump points which are the vertices of the cubic nullcline, the phase is insensitive to the perturbations on the fast variable. By using the phase sensitivity functions, two cases, namely, periodic pulse train perturbation and common noise perturbation, are investigated. Theoretical and numerical results suggest better performance for the synchronization behaviors of the perturbations on the slow variable for large timescale separation.
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http://dx.doi.org/10.1103/PhysRevE.101.042203DOI Listing
April 2020

HS induces NO in the regulation of AsA-GSH cycle in wheat seedlings by water stress.

Protoplasma 2020 Sep 12;257(5):1487-1493. Epub 2020 May 12.

School of Life Sciences, Henan University, Kaifeng, 475004, China.

In current study, we investigated the relationship between hydrogen sulfide (HS) and nitric oxide (NO) in the regulation of ascorbate-glutathione (AsA-GSH) cycle in wheat seedlings by water stress. Findings showed that water stress significantly stimulated the production of HS and NO, the transcript levels and activities of enzymes in AsA-GSH cycle, as well as malondialdehyde (MDA) production and electrolyte leakage, but significantly decreased AsA/DHA and GSH/GSSG. Meanwhile, water stress significantly decreased plant height and dry biomass. Except MDA and electrolyte leakage, above changes induced by water stress were reversed by HS synthesis inhibitor aminooxyacetic acid (AOA) and NO synthesis inhibitor N-nitro-L-arginine methyl ester (L-NAME). However, AOA and L-NAME significantly enhanced MDA production and electrolyte leakage, which further decreased plant height and dry biomass of wheat seedlings under water stress. Application of exogenous HS donor sodium hydrosulfide (NaHS) to AOA-treated plants and application of exogenous NO donor sodium nitroprusside (SNP) to L-NAME-treated plants reversed above effects of AOA and L-NAME, respectively. Application of L-NAME plus water stress significantly decreased NO production induced by water stress. However, application of L-NAME plus water stress had no obvious influence on HS production induced by water stress, while application of AOA plus water stress significantly reduced the production of HS and NO induced by water stress. Current findings suggested that HS acted upstream of NO in the regulation of AsA-GSH cycle in wheat seedlings by water stress.
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http://dx.doi.org/10.1007/s00709-020-01510-3DOI Listing
September 2020
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