Comparative analysis of evolutionarily conserved motifs of epidermal growth factor receptor 2 (HER2) predicts novel potential therapeutic epitopes

Overexpression of human epidermal growth factor receptor 2 (HER2) is associated with tumor aggressiveness and poor prognosis in breast cancer. With the availability of therapeutic antibodies against HER2, great strides have been made in the clinical management of HER2 overexpressing breast cancer. However, de novo and acquired resistance to these antibodies presents a serious limitation to successful HER2 targeting treatment. The identification of novel epitopes of HER2 that can be used for functional/region-specific blockade could represent a central step in the development of new clinically relevant anti-HER2 antibodies. In the present study, we present a novel computational approach as an auxiliary tool for identification of novel HER2 epitopes. We hypothesized that the structurally and linearly evolutionarily conserved motifs of the extracellular domain of HER2 (ECD HER2) contain potential druggable epitopes/targets. We employed the PROSITE Scan to detect structurally conserved motifs and PRINTS to search for linearly conserved motifs of ECD HER2. We found that the epitopes recognized by trastuzumab and pertuzumab are located in the predicted conserved motifs of ECD HER2, supporting our initial hypothesis. Considering that structurally and linearly conserved motifs can provide functional specific configurations, we propose that by comparing the two types of conserved motifs, additional druggable epitopes/targets in the ECD HER2 protein can be identified, which can be further modified for potential therapeutic application. Thus, this novel computational process for predicting or searching for potential epitopes or key target sites may contribute to epitope-based vaccine and function-selected drug design, especially when x-ray crystal structure protein data is not available

Tunable topological phase transition in soft Rayleigh beam system with imperfect interfaces

Acoustic metamaterials, particularly the topological insulators, exhibit exceptional wave characteristics that have sparked considerable research interest. The study of imperfect interfaces affect is of significant importance for the modeling of wave propagation behavior in topological insulators. This paper models a soft Rayleigh beam system with imperfect interfaces, and investigates its topological phase transition process tuned by mechanical loadings. The model reveals that the topological phase transition process can be observed by modifying the distance between imperfect interfaces in the system. When a uniaxial stretch is applied, the topological phase transition points for longitudinal waves decrease within a limited frequency range, while they increase within a larger frequency scope for transverse waves. Enhancing the rigidity of the imperfect interfaces also enables shifting of the topological phase transition point within a broader frequency range for longitudinal waves and a confined range for transverse waves. The transition of topologically protected interface modes in the transmission performance of a twenty-cell system is verified, which include altering frequencies, switching from interface mode to edge mode. Overall, this study provides a new approach and guideline for controlling topological phase transition in composite and soft phononic crystal systems.Comment: 39 pages,8 figure

Median Filter Based Compressed Sensing Model with Application to MR Image Reconstruction

Magnetic resonance imaging (MRI) has become a helpful technique and developed rapidly in clinical medicine and diagnosis. Magnetic resonance (MR) images can display more clearly soft tissue structures and are important for doctors to diagnose diseases. However, the long acquisition and transformation time of MR images may limit their application in clinical diagnosis. Compressed sensing methods have been widely used in faithfully reconstructing MR images and greatly shorten the scanning and transforming time. In this paper we present a compressed sensing model based on median filter for MR image reconstruction. By combining a total variation term, a median filter term, and a data fitting term together, we first propose a minimization problem for image reconstruction. The median filter term makes our method eliminate additional noise from the reconstruction process and obtain much clearer reconstruction results. One key point of the proposed method lies in the fact that both the total variation term and the median filter term are presented in the L1 norm formulation. We then apply the split Bregman technique for fast minimization and give an efficient algorithm. Finally, we apply our method to numbers of MR images and compare it with a related method. Reconstruction results and comparisons demonstrate the accuracy and efficiency of the proposed model

Springtime spatial distributions of biogenic sulfur compounds in the Yangtze River Estuary and their responses to seawater acidification and dust

The spatial distributions of dimethylsulfide (DMS), dimethylsulfoniopropionate (DMSP), and dimethylsulfoxide (DMSO) were investigated in the Yangtze River Estuary from 9 to 23 March, 2018. Besides, we analyzed the vertical distributions of DMS, DMSP, and DMSO in early spring. An onboard incubation experiment was also carried out to study how the production and release of biogenic sulfur compounds responded to simulated seawater acidification and dust deposition

Molecular identification and phylogenetic analysis of the mitogenome of Solenaia oleivora MG

Solenaia oleivora, belongs to Bivalvia, Unionidae, and Gonideinae, is a burrowing bivalve uniquely distributed in China. In this study, the complete mitochondrial genome of S. oleivora MG was sequenced and determined. The complete mitogenome of S. oleivora MG is 16,392 bp in total length, consist of 22 tRNA genes, 13 protein-coding genes (PCGs), and 2 rRNA genes. The overall base composition of the S. oleivora MG mitogenome is 36.90% A, 23.85% T, 27.09% C, and 12.16% G, respectively, exhibits a similar AT bias (60.75%) feature to other invertebrate bivalve mitogenomes. The phylogenetic analysis that S. oleivora MG clustered in genus Solenaia. This result provides useful data to the conservation and sustainable utilization of S. oleivora MG and other invertebrate mussels