No ordinary proteins: Adsorption and molecular orientation of monoclonal antibodies

The interaction of monoclonal antibodies (mAbs) with air/water interfaces plays a crucial role in their overall stability in solution. We aim to understand this behavior using pendant bubble measurements to track the dynamic tension reduction and x-ray reflectivity to obtain the electron density profiles (EDPs) at the surface. Native immunoglobulin G mAb is a rigid molecule with a flat, “Y” shape, and simulated EDPs are obtained by rotating a homology construct at the surface. Comparing simulations with experimental EDPs, we obtain surface orientation probability maps showing mAbs transition from flat-on Y-shape configurations to side-on or end-on configurations with increasing concentration. The modeling also shows the presence of β sheets at the surface. Overall, the experiments and the homology modeling elucidate the orientational phase space during different stages of adsorption of mAbs at the air/water interface. These finding will help define new strategies for the manufacture and storage of antibody-based therapeutics

Single-cell genetic models to evaluate orphan gene function: The case of QQS regulating carbon and nitrogen allocation

We demonstrate two synthetic single-cell systems that can be used to better understand how the acquisition of an orphan gene can affect complex phenotypes. The Arabidopsis orphan gene, Qua-Quine Starch (QQS) has been identified as a regulator of carbon (C) and nitrogen (N) partitioning across multiple plant species. QQS modulates this important biotechnological trait by replacing NF-YB (Nuclear Factor Y, subunit B) in its interaction with NF-YC. In this study, we expand on these prior findings by developing Chlamydomonas reinhardtii and Saccharomyces cerevisiae strains, to refactor the functional interactions between QQS and NF-Y subunits to affect modulations in C and N allocation. Expression of QQS in C. reinhardtii modulates C (i.e., starch) and N (i.e., protein) allocation by affecting interactions between NF-YC and NF-YB subunits. Studies in S. cerevisiae revealed similar functional interactions between QQS and the NF-YC homolog (HAP5), modulating C (i.e., glycogen) and N (i.e., protein) allocation. However, in S. cerevisiae both the NF-YA (HAP2) and NF-YB (HAP3) homologs appear to have redundant functions to enable QQS and HAP5 to affect C and N allocation. The genetically tractable systems that developed herein exhibit the plasticity to modulate highly complex phenotypes

Transportation and Batching Scheduling for Minimizing Total Weighted Completion Time

We consider the coordination of transportation and batching scheduling with one single vehicle for minimizing total weighted completion time. The computational complexity of the problem with batch capacity of at least 2 was posed as open in the literature. For this problem, we show the unary NP-hardness for every batch capacity at least 3 and present a polynomial-time 3-approximation algorithm when the batch capacity is at least 2

Selenium in Prostate Cancer: Prevention, Progression, and Treatment

Selenium, a trace mineral with various biological functions, has become a focal point in prostate cancer research. This review aims to present a comprehensive overview of selenium’s involvement in prostate cancer, covering its impact on prevention, development, treatment, and underlying mechanisms. Observational studies have revealed a link between selenium levels and selenoproteins with prostate cancer progression. However, randomized controlled studies have shown that selenium supplementation does not prevent prostate cancer (HR: 0.95; 95% CI 0.80–1.13). This discrepancy might be attributed to selenoprotein single nucleotide polymorphisms. In the context of combinatorial therapy, selenium has demonstrated promising synergistic potential in the treatment of prostate cancer. Emerging evidence highlights the significant role of selenium and selenoproteins in prostate cancer, encompassing AR signaling, antioxidative properties, cell death, cell cycle regulation, angiogenesis, epigenetic regulation, immunoregulation, epithelial–mesenchymal transformation, and redox signal. In conclusion, selenium’s diverse properties make it a promising trace mineral in prostate cancer prevention, development, and treatment and as a platform for exploring novel agents

Built-Up Area Change Detection Using Multi-Task Network with Object-Level Refinement

The detection and monitoring of changes in urban buildings, as a major place for human activities, have been considered profoundly in the field of remote sensing. In recent years, comparing with other traditional methods, the deep learning-based methods have become the mainstream methods for urban building change detection due to their strong learning ability and robustness. Unfortunately, often, it is difficult and costly to obtain sufficient samples for the change detection method development. As a result, the application of the deep learning-based building change detection methods is limited in practice. In our work, we proposed a novel multi-task network based on the idea of transfer learning, which is less dependent on change detection samples by appropriately selecting high-dimensional features for sharing and a unique decoding module. Different from other multi-task change detection networks, with the help of a high-accuracy building mask, our network can fully utilize the prior information from building detection branches and further improve the change detection result through the proposed object-level refinement algorithm. To evaluate the proposed method, experiments on the publicly available WHU Building Change Dataset were conducted. The experimental results show that the proposed method achieves F1 values of 0.8939, 0.9037, and 0.9212, respectively, when 10%, 25%, and 50% of change detection training samples are used for network training under the same conditions, thus, outperforming other methods

PCNet: Cloud Detection in FY-3D True-Color Imagery Using Multi-Scale Pyramid Contextual Information

Cloud, one of the poor atmospheric conditions, significantly reduces the usability of optical remote-sensing data and hampers follow-up applications. Thus, the identification of cloud remains a priority for various remote-sensing activities, such as product retrieval, land-use/cover classification, object detection, and especially for change detection. However, the complexity of clouds themselves make it difficult to detect thin clouds and small isolated clouds. To accurately detect clouds in satellite imagery, we propose a novel neural network named the Pyramid Contextual Network (PCNet). Considering the limited applicability of a regular convolution kernel, we employed a Dilated Residual Block (DRB) to extend the receptive field of the network, which contains a dilated convolution and residual connection. To improve the detection ability for thin clouds, the proposed new model, pyramid contextual block (PCB), was used to generate global information at different scales. FengYun-3D MERSI-II remote-sensing images covering China with 14,165 × 24,659 pixels, acquired on 17 July 2019, are processed to conduct cloud-detection experiments. Experimental results show that the overall precision rates of the trained network reach 97.1% and the overall recall rates reach 93.2%, which performs better both in quantity and quality than U-Net, UNet++, UNet3+, PSPNet and DeepLabV3+

Research on Urban Spatial Connection and Network Structure of Urban Agglomeration in Yangtze River Delta—Based on the Perspective of Information Flow

Exploration of urban spatial connections and network structures of urban agglomeration in the Yangtze River Delta, as well as its influencing factors, is of great significance regarding optimization of the development pattern of the Yangtze River Delta urban agglomeration and promotion of regional high-quality development. Therefore, based on Baidu index data in 2015 and 2019, this paper first analyzes the spatiotemporal variation characteristics of information-flow connections in the Yangtze River Delta urban agglomeration. Then it uses social network analysis to explore the information-flow network structure in the Yangtze River Delta urban agglomeration, and finally explores the influencing factors of information-flow intensity in the Yangtze River Delta urban agglomeration. The main conclusions are as follows: (1) The total amount of information flow in the Yangtze River Delta urban agglomeration has had no obvious change, and the coverage of information flow in the central urban circle has expanded. (2) The network hierarchy presents a relatively stable “pyramid” distribution pattern, which tends to develop into a “spindle” pattern. (3) The overall network density of the Yangtze River Delta urban agglomeration is high and is increasing. The backbone network is a “triangle” structure. The central cities in the region are stable, and the subgroups are adjacent to each other geographically. (4) Gross Domestic Product, resident population of the region and the number of Internet broadband subscribers all have important effects on the total information flow, among which the number of Internet broadband subscribers has the greatest effect on the total information flow. In addition, urban functions and their positioning, urban events, history and culture, and other factors that are difficult to quantify also have a certain impact on the information-flow network among cities

Isolation and identification of EST‐SSR markers in Ixonanthes chinensis (Ixonanthaceae)

Premise Ixonanthes (Ixonanthaceae) consists of between three and 19 species, among which I. chinensis and I. khasiana are considered vulnerable. Here, 58 microsatellite markers were developed for further conservation of these two Ixonanthes species. Methods and Results RNA transcripts of I. chinensis were sequenced and assembled into 19,545 unigenes, and 994 simple sequence repeat (SSR) loci were identified from 920 contigs. Based on these, 106 primer pairs were designed, 58 were successfully amplified, and 12 demonstrated polymorphism among five populations. The number of alleles per locus varied from three to 10, and the levels of observed and expected heterozygosity ranged from 0.000 to 1.000 and 0.000 to 0.844, respectively. Further assessment of the transferability of the 58 amplifiable primers reported 30 being successfully cross‐amplified in I. icosandra and three in Erythroxylum sinense. Conclusions These novel SSR markers will be useful for future genetic conservation studies on these Ixonanthes species

Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat

Abnormal growth of cardiac fibroblasts is critically involved in the pathophysiology of cardiac hypertrophy/remodeling. Hexarelin is a synthetic growth hormone secretagogue (GHS), which possesses a variety of cardiovascular protective activities mediated via the GHS receptor (GHSR), including improving cardiac dysfunction and remodeling. The cellular and molecular mechanisms underlying the effect of GHS on cardiac fibrosis are, however, not clear. In this report, cultured cardiac fibroblasts from 8-day-old rats were stimulated with ANG II or FCS to induce proliferation. The fibroblast proliferation and DNA and collagen synthesis were evaluated utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 3H-thymidine incorporation, and 3H-proline incorporation. The level of mRNA of transforming growth factor (TGF)-beta was evaluated by RT-PCR, and the active TGF-beta1 release from cardiac fibroblasts was evaluated by ELISA. The level of cellular cAMP was measured by radioimmunoassay. In addition, the effects of 3,7-dimethyl-l-propargylxanthine (DMPX; a specific adenosine receptor A2R antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; a specific A1R antagonist) were tested. It was found that incubation with 10–7 mol/l hexarelin for 24 h 1) inhibited the ANG II-induced proliferation and collagen synthesis and the 5% FCS- and TGF-beta-induced increase of DNA synthesis in cardiac fibroblast and 2) reduced ANG II-induced upregulation of TGF-beta mRNA expression and active TGF-beta1 release from fibroblasts. Hexarelin increased the cellular level of cAMP in cardiac fibroblasts. DMPX (10–8 mol/l) but not DPCPX abolished the effect of hexarelin on cardiac fibroblast DNA synthesis. It is concluded that hexarelin inhibits DNA and collagen synthesis and proliferation of cardiac fibroblasts through activation of both GHSR and A2R and diminishment of ANG II-induced increase in TGF-beta expression and release