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Geometric information such as distance information is essential for dose calculations in radiotherapy. However, state-of-the-art dose prediction methods use only binary masks without distance information. This study aims to develop a dose prediction deep learning method for nasopharyngeal carcinoma radiotherapy by taking advantage of the distance information as well as the mask information.A novel transformation method based on boundary distance was proposed to facilitate the prediction of dose distributions. Radiotherapy datasets of 161 nasopharyngeal carcinoma patients were retrospectively collected, including binary masks of organs-at-risk (OARs) and targets, planning CT, and clinical plans. The patients were randomly divided into 130, 11 and 20 cases for training, validating, and testing the models, respectively. Furthermore, 40 patients from an external cohort were used to test the generalizability of the models.The proposed method shows superior performance. The predicted dose error and dose-volume histogram (DVH) error of our method were 7.51% and 11.6% lower than the mask-based method, respectively. For the inverse planning, compared with mask-based methods, our method provided similar performances on the GTVnx and OARs and outperformed on the GTVnd and the CTV, the pass rates of which increased from 89.490% and 90.016% to 96.694% and 91.189%, respectively.The preliminary results on nasopharyngeal carcinoma radiotherapy cases showed that our proposed distance-guided method for dose prediction achieved better performance than mask-based methods. Further studies with more patients and on other cancer sites are warranted to fully validate the proposed method.

This study aimed to develop an automated delineation method of nasopharynx gross tumor volume (GTVnx) for nasopharyngeal carcinoma (NPC) in computed tomography (CT) image for radiotherapy applicati...

With the addition of the compstatin-based complement C3 inhibitor pegcetacoplan, another class of complement targeted therapeutics have recently been approved. Moreover, compstatin derivatives with enhanced pharmacodynamic and pharmacokinetic profiles are in clinical development (e.g., Cp40/AMY-101). Despite this progress, the target binding and inhibitory modes of the compstatin family remain incompletely described. Here, we present the crystal structure of Cp40 complexed with its target C3b at 2.0-Å resolution. Structure-activity-relationship studies rationalize the picomolar affinity and long target residence achieved by lead optimization, and reveal a role for structural water in inhibitor binding. We provide explanations for the narrow species specificity of this drug class and demonstrate distinct target selection modes between clinical compstatin derivatives. Functional studies provide further insight into physiological complement activation and corroborate the mechanism of its compstatin-mediated inhibition. Our study may thereby guide the application of existing and development of next-generation compstatin analogs.

This article mainly briefly introduces the related content of computer-aided innovation technology. This article discusses the effective application of computer-aided innovation product design technology by analyzing the necessity of knowledge utilization in the process of product innovation design. This article takes full advantage of computer technology, constantly innovates product design, develops products that meet people’s actual needs based on market demand, and optimizes product design. This can guarantee the quality of product design and enhance the company’s market competitiveness. The effective use of key knowledge can not only solve the technical difficulties in product design innovation, but also improve the technical level of computer-aided innovation product design.

PELE projectile is a new type of armor-piercing warhead and has a more obvious fragmentation effect, which solves the problem of insufficient after-effects of conventional armor-piercing projectiles. Reactive material is a new type of energetic material, which has some characteristics similar to the traditional explosives but has better mechanical properties. Reactive material is insensitive under normal conditions, and it can release huge energy under external impact loading. This paper hopes to study the application of reactive materials to the inner core of PELE projectiles to further improve the fragmentation effect of PELE projectiles. The fragmentation effect of PELE projectile is mainly reflected in the radial scattering velocity of fragments after it perforates the target plate. In this paper, three energy sources for the radial scattering of fragments were obtained by analyzing the penetration process of PELE projectile, that is, the axial kinetic energy of outer casing, the radial compression potential energy generated by the inner core to the outer casing, and the chemical energy released by the reactive core material. Based on the simplification and assumptions, the theoretical model of radial scattering velocity of fragments of the reactive core PELE projectile was established. In addition, numerical simulations were carried out to verify the theoretical model. The results show that the numerical simulation results are in good agreement with the theoretical calculation results, which indicates that the model established in this paper is scientific and reasonable. The reactive core PELE projectile has a more significant fragmentation effect, which further enhances the comprehensive damage power of traditional PELE projectile. The theoretical model established in this paper can quickly assess the power of reactive core PELE projectile’s fragmentation effect, which can be used to provide guidance and reference for engineering application.

The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity. One cleavage in C3b does not affect its overall structure, whereas two cleavages unfold CUB and dislodge the thioester-containing domain (TED), affecting binding of regulators and thereby determining the number of cleavages. These data explain how FI generates late-stage opsonins iC3b or C3dg in a context-dependent manner, to react to foreign, danger or healthy self signals.

Background: The diagnosis of neonatal sepsis remains a challenge as the condition lacks early clinical signs and reliable biomarkers. Objectives: The aim of our study was to determine whether serum mannose binding lectin (MBL) levels and genotypes of MBL2 gene could be used as markers for predicting neonatal sepsis in the Chinese Han population. Methods: This prospective study was hospital-based in design. 48 neonates with clinical signs and symptoms of septicemia (study group), and 96 infants with no infection (control) were included. All the neonates are Chinese Han descent. MBL2 promoter polymorphisms at positions -550, -221 and +4 were analyzed by direct sequencing, and serum MBL levels were estimated by enzyme-linked immunesorbent assay. Results: Frequencies of genotype -221 YX were significantly higher in the study group (45.8%) compared with the control group (15.60%; P = 0.00009). The median serum MBL level was found to be significantly lower in infants who had the -221YX genotype (214.54 ng/mL) compared with those who had the -221YY genotype (597.85 ng/mL; P < 0.0001). Additionally, the median of serum MBL was significantly lower in infants with septicemia (289.65 ng/mL) than in controls (597.75 ng/mL; P = 0.041). According to ROC analysis, the cutoff value of MBL concentration ≤ 384.60 (ng/mL) had a sensitivity of 0.806 and a specificity of 0.777 for predicting sepsis. Conclusions: This study suggested that serum MBL and the -221 YX genotype of the MBL2 gene might be predisposed factors for sepsis in the Chinese Han population.

Regulators of complement activation (RCA) inhibit complement‐induced immune responses on healthy host tissues. We present crystal structures of human RCA (MCP, DAF, and CR1) and a smallpox virus homolog (SPICE) bound to complement component C3b. Our structural data reveal that up to four consecutive homologous CCP domains (i–iv), responsible for inhibition, bind in the same orientation and extended arrangement at a shared binding platform on C3b. Large sequence variations in CCP domains explain the diverse C3b‐binding patterns, with limited or no contribution of some individual domains, while all regulators show extensive contacts with C3b for the domains at the third site. A variation of ~100° rotation around the longitudinal axis is observed for domains binding at the fourth site on C3b, without affecting the overall binding mode. The data suggest a common evolutionary origin for both inhibitory mechanisms, called decay acceleration and cofactor activity, with variable C3b binding through domains at sites ii, iii, and iv, and provide a framework for understanding RCA disease‐related mutations and immune evasion.

Stiffened composite panels are used within many applications, from aerospace to marine applications. Stiffened panels are utilized for their high strength to weight ratio and flexibility of layups while counteracting the low stiffness exhibited by composites. Complications arise when attempting to utilize the full variability of layups in conjunction with reliability constraints creating a complex design problem when constrained by both buckling and material strength. To aid the process of optimizing the design of composite structures and layups, while ensuring a low mass, this paper presents a bi-level optimization scheme for minimization of the weight of tophat stiffened composite panels with probabilistic deflection constraints. To improve the computational efficiency, an energy based grillage method is formulated and applied for the investigation of buckling problems under bi-directional in-plane loads. The method is validated by comparing the results obtained from FE model calculations. The variables that have a large impact on the structural safety have been identified by both safety index and COV based reliability analysis. A parametric study of plate dimensions and loading ratios is conducted to investigate the coupling effects on critical buckling load. The method presented in this paper, makes it possible for engineers to improve their designs, at an early stage, with an integrated consideration between product performance and design parameters.

The traditional economic model create wealth and bring the problems of resources, energy and environment. So we need to change the traditional economic model, realize coupling optimization on industrial system, natural systems and social system by using ecological development model, promote the natural, social and economic coordinated development.

This paper conduct a comprehensive analysis of the scale, structure, development characteristics of cultural industries in Hebei Province and the industry's status in the country, put forward the following countermeasures: To promote cultural industries with the system reform of cultural industry, to build a solid support with the effective development of cultural resources, to provide the impetus with technological and cultural innovation, to provide intellectual guarantee with the cultivation of human resources, etc.