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Due to the nonlinearity of the imaging of sonar equipment and the complexity of the underwater sound field environment, the gray level of the target area of the acquired underwater sonar image is relatively small. These characteristics are the target of the subsequent sonar image. Work such as detection and location tracking has brought great challenges. It has brought great challenges to solving the work of positioning and tracking, which makes the research of sonar image target detection based on deep learning very important. This article aims at studying the use of sonar to detect image targets based on deep learning technology. This article proposes a variety of sound image denoising methods based on multiresolution tools. The purpose of this article is to divide the natural image into blocks at an appropriate rate according to the change of the sampling matrix and measure the underwater natural image. The sound image defines an information model. These methods have greatly changed the image and period of using remote and temporary information. The translation results of these methods are all valid. The sharpening separation method based on filtered image and bidirectional detection should be published through a solution algorithm and different frames, and the expected algorithm can be reused and extracted as an action to improve the similarity of the image and should be saved and separated in detail. The result is correct. This article studies the application of deep learning methods in sonar image target detection and designs corresponding algorithms for improvement and functional realization in view of the current deficiencies and needs in this field. The experimental results show that the improved scheme and applied algorithm proposed in this article can achieve good results, the verification sample set includes 184 remote-sensing aircraft targets, and the resolution of remote-sensing images is unified to 1644 × 971 size. The accuracy of the target detection algorithm has been significantly improved, reaching 74.6%, and the detection speed has also been greatly improved. Compared with the RNN algorithm, the speed has been increased by 7 times. The detection results confirmed that the improved algorithm has higher positioning accuracy and faster detection speed.

Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4-/- bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4-/- BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity.

The wingless pathway has a powerful influence on bone metabolism and is a therapeutic target in skeletal disorders. Wingless signaling is mediated in part through the Frizzled (FZD) receptor family. FZD transcriptional regulation is poorly understood. Herein we tested the hypothesis that Sp1 plays an important role in the transcriptional regulation of FZD1 expression in osteoblasts and osteoblast mineralization. To test this hypothesis, we conducted FZD1 promoter assays in Saos2 cells with and without Sp1 overexpression. We found that Sp1 significantly up-regulates FZD1 promoter activity in Saos2 cells. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift (EMSA) assays identified a novel and functional Sp1 binding site at -44 to -40 from the translation start site in the FZD1 promoter. The Sp1-dependent activation of the FZD1 promoter was abolished by mithramycin A (MMA), an antibiotic affecting both Sp1 binding and Sp1 protein levels in Saos2 cells. Similarly, down-regulation of Sp1 in hFOB cells resulted in less FZD1 expression and lower alkaline phosphatase activity. Moreover, over-expression of Sp1 increased FZD1 expression and Saos2 cell mineralization while MMA decreased Sp1 and FZD1 expression and Saos2 cell mineralization. Knockdown of FZD1 prior to Sp1 overexpression partially abolished Sp1 stimulation of osteoblast differentiation markers. Taken together, our results suggest that Sp1 plays a role in human osteoblast differentiation and mineralization, which is at least partially mediated by Sp1-dependent transactivation of FZD1.

Parathyroid hormone (PTH) is a potent anabolic agent for the treatment of osteoporosis. However, its mechanism of action in osteoblast and bone is not well understood. In this study, we show that the anabolic actions of PTH in bone are severely impaired in both growing and adult ovariectomized mice lacking bone-related activating transcription factor 4 (ATF4). Our study demonstrates that ATF4 deficiency suppresses PTH-stimulated osteoblast proliferation and survival and abolishes PTH-induced osteoblast differentiation, which, together, compromise the anabolic response. We further demonstrate that the PTH-dependent increase in osteoblast differentiation is correlated with ATF4-dependent up-regulation of Osterix. This regulation involves interactions of ATF4 with a specific enhancer sequence in the Osterix promoter. Furthermore, actions of PTH on Osterix require this same element and are associated with increased binding of ATF4 to chromatin. Taken together these experiments establish a fundamental role for ATF4 in the anabolic actions of PTH on the skeleton.

Background Osteosarcoma (OS) is the most common primary bone tumor, with a propensity to metastasize to the lungs. Five-year survival for metastatic OS is below 30%, and has not improved for several decades despite the introduction of multi-agent chemotherapy. Understanding OS cell migration to the lungs requires an evaluation of the lung microenvironment. Here we utilized an in vitro lung cell and OS cell co-culture model to explore the interactions between OS and lung cells, hypothesizing that lung cells would promote OS cell migration and survival. The impact of a novel anti-OS chemotherapy on OS migration and survival in the lung microenvironment was also examined. Methods Three human OS cell lines (SJSA-1, Saos-2, U-2) and two human lung cell lines (HULEC-5a, MRC-5) were cultured according to American Type Culture Collection recommendations. Human lung cell lines were cultured in growth medium for 72 h to create conditioned media. OS proliferation was evaluated in lung co-culture and conditioned media microenvironment, with a murine fibroblast cell line (NIH-3 T3) in fresh growth medium as controls. Migration and invasion were measured using a real-time cell analysis system. Real-time PCR was utilized to probe for Aldehyde Dehydrogenase (ALDH1) expression. Osteosarcoma cells were also transduced with a lentivirus encoding for GFP to permit morphologic analysis with fluorescence microscopy. The anti-OS efficacy of Disulfiram, an ALDH-inhibitor previously shown to inhibit OS cell proliferation and metastasis in vitro, was evaluated in each microenvironment. Results Lung-cell conditioned medium promoted osteosarcoma cell migration, with a significantly higher attractive effect on all three osteosarcoma cell lines compared to basic growth medium, 10% serum containing medium, and NIH-3 T3 conditioned medium ( p <0.05). Lung cell conditioned medium induced cell morphologic changes, as demonstrated with GFP-labeled cells. OS cells cultured in lung cell conditioned medium had increased alkaline phosphatase staining. Conclusions Lung endothelial HULEC-5a cells are attractants for OS cell migration, proliferation, and survival. The SJSA-1 osteosarcoma cell line demonstrated greater metastatic potential than Saos-2 and U-2 cells. ALDH appears to be involved in the interaction between lung and OS cells, and ALP may be a valuable biomarker for monitoring functional OS changes during metastasis.

Genetic association studies in chronic obstructive pulmonary disease have primarily tested for association with common variants, the results of which explain only a portion of disease heritability. Because rare variation is also likely to contribute to susceptibility, we used whole-genome sequencing of subjects with clinically extreme phenotypes to identify genomic regions enriched for rare variation contributing to chronic obstructive pulmonary disease susceptibility. To identify regions of rare genetic variation contributing to emphysema with severe airflow obstruction. We identified heavy smokers that were resistant (n = 65) or susceptible (n = 64) to emphysema with severe airflow obstruction in the Pittsburgh Specialized Center of Clinically Oriented Research cohort. We filtered whole-genome sequencing results to include only rare variants and conducted single variant tests, region-based tests across the genome, gene-based tests, and exome-wide tests. We identified several suggestive associations with emphysema with severe airflow obstruction, including a suggestive association of all rare variation in a region within the gene ZNF816 (19q13.41; P = 4.5 × 10 ), and a suggestive association of nonsynonymous coding rare variation in the gene PTPRO (P = 4.0 × 10 ). Association of rs61754411, a rare nonsynonymous variant in PTPRO, with emphysema and obstruction was demonstrated in all non-Hispanic white individuals in the Pittsburgh Specialized Center of Clinically Oriented Research cohort. We found that cells containing this variant have decreased signaling in cellular pathways necessary for survival and proliferation. PTPRO is a novel candidate gene in emphysema with severe airflow obstruction, and rs61754411 is a previously unreported rare variant contributing to emphysema susceptibility. Other suggestive candidate genes, such as ZNF816, are of interest for future studies.

Summary We determined factors associated with serum sclerostin in 446 Afro-Caribbean family members. Age, weight, sex, diabetes and kidney function were associated with sclerostin. Sclerostin was heritable, and nine SNPs in the SOST gene region were associated with sclerostin. Variation in serum sclerostin is a heritable factor that is determined by both genetic and environmental factors. Introduction Sclerostin, encoded by the SOST gene, is a Wnt inhibitor that regulates bone mineralization and is a candidate gene locus for osteoporosis. However, little is known about the genetic and non-genetic sources of inter-individual variation in serum sclerostin levels. Methods Serum sclerostin was measured in 446 Afro-Caribbean men and women aged 18+ from seven large, multigenerational families (mean family size, 64; 3,840 relative pairs). Thirty-six common single nucleotide polymorphisms (SNP) were genotyped within a 100 kb region encompassing the gene encoding sclerostin ( SOST ). Genetic and non-genetic factors were tested for association with serum sclerostin. Results Mean serum sclerostin was 41.3 pmol/l and was greater in men than in women ( P  < 0.05). Factors associated with higher serum sclerostin were increased age and body weight, male sex, diabetes and decreased glomerular filtration rate, which collectively accounted for 25.4 % of its variation. Residual genetic heritability of serum sclerostin was 0.393 ( P  < 0.0001). Nine SNPs reached nominal significance with sclerostin. Three of those nine SNPs represented independent association signals (rs851056, rs41455049 and rs9909172), which accounted for 7.8 % of the phenotypic variation in sclerostin, although none of these SNPs surpassed a Bonferroni correction for multiple comparisons. Conclusions Serum sclerostin is a heritable trait that is also determined by environmental factors including age, sex, adiposity, diabetes and kidney function. Three independent common SNPs within the SOST region may collectively account for a significant proportion of the variation in serum sclerostin.

The aim of the study was to determine the heritability of serum dickkopf-1 (DKK1) and its association with DKK1 polymorphisms in African ancestry subjects. Serum DKK1 was measured in 422 Afro–Caribbean men and women aged 18+ from 7 large, multi-generational families (mean family size: 60; 3,215 relative pairs). Twenty-four common single nucleotide polymorphisms (SNPs) were genotyped within an 80 kilobase-pair region encompassing the DKK1 gene. Heritability was estimated and SNPs were tested for association with serum DKK1 using variance components analysis. DKK1 mRNA expression was tested in peripheral blood of 16 individuals from each of the rs7069912 genotypes. Mean serum DKK1 was 1724.1 pg/mL and was significantly lower in women than men ( P  = 0.043). Residual genetic heritability of serum DKK1 was 0.4460 ( P  < 0.0001). Six SNPs reached nominal significance with DKK1, with rs7069912 being significant after adjustment for multiple comparisons. Two of these six SNPs represented independent association signals (rs7069912 and rs16928725), which accounted for 4.6 % of the phenotypic variation in DKK1. Additionally, carriers of the rs7069912 variant had significantly greater DKK1 expression than non-carriers ( P  = 0.036). Serum DKK1 levels are highly heritable in the African ancestry families. Two SNPs within the DKK1 region accounted for nearly 5 % of the variation in serum DKK1.

The resistive switching effect in memristors typically stems from the formation and rupture of localized conductive filament paths, and HfO 2 has been accepted as one of the most promising resistive switching materials. However, the dynamic changes in the resistive switching process, including the composition and structure of conductive filaments, and especially the evolution of conductive filament surroundings, remain controversial in HfO 2 -based memristors. Here, the conductive filament system in the amorphous HfO 2 -based memristors with various top electrodes is revealed to be with a quasi-core-shell structure consisting of metallic hexagonal-Hf 6 O and its crystalline surroundings (monoclinic or tetragonal HfO x ). The phase of the HfO x shell varies with the oxygen reservation capability of the top electrode. According to extensive high-resolution transmission electron microscopy observations and ab initio calculations, the phase transition of the conductive filament shell between monoclinic and tetragonal HfO 2 is proposed to depend on the comprehensive effects of Joule heat from the conductive filament current and the concentration of oxygen vacancies. The quasi-core-shell conductive filament system with an intrinsic barrier, which prohibits conductive filament oxidation, ensures the extreme scalability of resistive switching memristors. This study renovates the understanding of the conductive filament evolution in HfO 2 -based memristors and provides potential inspirations to improve oxide memristors for nonvolatile storage-class memory applications. Understanding the mechanism of the formation and rupture of conductive filaments in HfO 2 -based memristors is essential to solve the problem of scalability of the devices. Here, Zhang et al. visualize this process by tracking atomic-scale evolution of conductive filaments during resistive switching cycles.

Sandstones are widespread on the earth and are often damaged by water. Although there is a consensus that the strength of sandstones will decrease when they are in contact with water, the intrinsic properties controlling the water-weakening mechanism of sandstones are not completely clear. In this study, the uniaxial compression strength (UCS), point load index (PLI), and Brazilian tensile strength (BTS) of four clay-bearing sandstones with water saturation from 0 to 100% were measured by experiments. The results showed that a remarkable strength loss occurred when the water saturation increased from 0 to 60% ~ 80%, and then, the reduction rate slowed dramatically. Therefore, the critical water saturation level at which considerable strength loss due to the water-weakening effect is produced is 60 ~ 80%. In addition, the strength loss law caused by increasing water saturation satisfied both the exponential decay function and logarithmic decay function. The multiple linear regression method was used to model the relationship between the intrinsic properties and UCS loss caused by water-weakening effects considering the effect of water saturation. The porosity, elastic modulus and clay mineral content were automatically selected by the best subset regression as the main intrinsic properties controlling the water-weakening degree of sandstones. In addition, the critical water saturation level and the role that clay minerals play in the water-weakening effects of sandstones were comprehensively discussed. This study contributes to a better understanding of the water-weakening mechanism and provides a better strength estimation model for sandstones with different water saturation levels.