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The RNA‐dependent RNA polymerase (RdRp) complex of SARS‐CoV‐2 lies at the core of its replication and transcription processes. The interfaces between holo‐RdRp subunits are highly conserved, facilitating the design of inhibitors with high affinity for the interaction interface hotspots. We, therefore, take this as a model protein complex for the application of a structural bioinformatics protocol to design peptides that inhibit RdRp complexation by preferential binding at the interface of its core subunit nonstructural protein, nsp12, with accessory factor nsp7. Here, the interaction hotspots of the nsp7‐nsp12 subunit of RdRp, determined from a long molecular dynamics trajectory, are used as a template. A large library of peptide sequences constructed from multiple hotspot motifs of nsp12 is screened in‐silico to determine sequences with high geometric complementarity and interaction specificity for the binding interface of nsp7 (target) in the complex. Two lead designed peptides are extensively characterized using orthogonal bioanalytical methods to determine their suitability for inhibition of RdRp complexation. Binding affinity of these peptides to accessory factor nsp7, determined using a surface plasmon resonance (SPR) assay, is slightly better than that of nsp12: dissociation constant of 133nM and 167nM, respectively, compared to 473nM for nsp12. A competitive ELISA is used to quantify inhibition of nsp7‐nsp12 complexation, with one of the lead peptides giving an IC50 of 25μM. Cell penetrability and cytotoxicity are characterized using a cargo delivery assay and MTT cytotoxicity assay, respectively. Overall, this work presents a proof‐of‐concept of an approach for rational discovery of peptide inhibitors of SARS‐CoV‐2 protein–protein interactions. [ABSTRACT FROM AUTHOR]

BACKGROUND: The implant template can effectively transfer the implant designed position to the patient’s jaw. It helps implant avoid important anatomical structures such as nerve and maxillary sinus, and effectively reduces the risk of surgery. Therefore, the accuracy of implant template surgery is particularly important. OBJECTIVE: To assess the design and manufacturing error of the tooth-supported surgical template and its implant accuracy in the fully positioned state. METHODS: A patient with missing teeth underwent a cone beam CT and a plaster model was established. According to the patien’s oral situation, implant plan with special positioning surface tooth-supported template was designed and implant template was made. Stereo Lithography Apparatus rapid prototyping technology was used to fabricate 10 templates and three-dimensional laser scanning was performed. After matching the scanning data with designed template model data, manufacturing error analysis was carried out. In addition, the 10 manufactured templates were worn on the patient’s plaster model to simulate implant position, and the simulated implant positions were matched with initial implant positions in the design plan for accuracy analysis. RESULTS AND CONCLUSION: (1) The mean positive deviation of the template was 0.093 mm; the mean negative deviation was 0.092 mm, and the mean standard deviation was 0.169 mm. (2) The simulated implant accuracy results showed that the neck center deviation of implant 12 was (1.172±0.283) mm; the top center deviation was (1.339±0.283) mm; the central axis angle deviation was (0.365±0.228)°; the neck center deviation of implant 21 was (1.274±0.379) mm; the top center deviation was (1.461±0.404) mm, and the center axis angle deviation was (0.643±0.276)°. (3) These results indicate that the design and manufacturing error of tooth-supported template with a specific positioning surface has a significant impact on implant accuracy. [ABSTRACT FROM AUTHOR]

The presented paper aims to design 3D templates of the sciatic muscle and thigh to simplify and speed up the process of modelling TF (transfemoral) sockets using the CAD/CAM method. A proposal for a general procedure for modelling the proximal part of the TF socket and a thorough description of the proximal part and the types of sockets that are used is presented. Ten individual scans of positives of TF amputated limbs were obtained from which ten mounting ring templates were designed via CAD modelling in the Autodesk Meshmixer software. In the last step a production simulation was generated in PrusaSlicer software for the overall price evaluation. [ABSTRACT FROM AUTHOR]

Template design on polymorph control, especially conformational polymorphs, is still in its infancy and the result of polymorph control is often accidental. A method of regulating the crystallization of conformational polymorphs based on the crystal structure similarity of templates and the target crystal form has been developed. Crystal structure similarity was considered to be able to introduce lattice matching (geometric term) with chemical interactions to regulate conformational polymorph nucleation. The method was successfully applied to induce the crystallization of DA7-II [HOOC–(CH2)n−2–COOH (diacids), named DAn, where n = 7, 9, 15, 17 and II represents the metastable polymorph] on the surface of DA15-II. An analogous two-dimensional plane – the (002) face of both DA15-II and DA7-II – was firstly predicted as the epitaxially attached face with similar lattice parameters and the strongest adsorption energy. The powder DA15-II template with the preferred orientation face in (002) presented much stronger inducing DA7-II ability than the template with other preferred orientation faces. The epitaxial growth of DA7-II on DA15-II through an identical (002) face was clearly observed and verified by the single-crystal inducing experiments. The molecular dynamics simulation results demonstrated that the strong interactions occurred between DA7 molecules and the (002) face of DA15-II. This method has been verified and further applied to the crystallization of DA7-II on the surface of DA17-II and DA9-II on the surface of DA15-II. This study developed a strategy based on structure similarity to regulate the conformational polymorph and verified the significant role of lattice matching and chemical effects on the design and preparation of templates.

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The template design problem (TDP) is a combinatorial problem that is difficult to attack and that presents a high number of symmetries that adds complexity to solution. Several techniques have been proposed in the literature to optimize your solution, ranging from complete methods to stochastic methods. In this article we are proposing the use of hybrid techniques. We intend to use a hybrid integrative approach that combines neighborhood-based and population-based local search techniques set up a technique called Memetic algorithm. We will use local neighborhood-based searches as local improvement operators, which allow us to exploit search areas that are potential. The use of a genetic algorithm will contribute as a mechanism to perform the search space exploration. An empirical analysis that compares the performance of all methods (that is, basic or hybrid algorithms) in the optimization of the problem, allows us to compare the proposal described with the results obtained in the existing scientific literature

Aroma is one of the most important factors affecting the quality of citrus fruit and its processed products. We use electronic nose (E-nose) to detect and analyze volatile components in citrus. An E-nose is an artificial intelligence system with strong independence and fast detection speed. It combines an array of gas sensors and intelligent algorithms designed to analyze gas. Moreover, it has the ability to detect and analyze volatile components. Feature extraction is the first step of sensor signal processing and plays an important role in subsequent pattern recognition. Cellular neural network (CNN) is a real-time high-speed parallel array processor and a locally connected network, which has mature applications in the field of image processing. Previous researches have shown that CNN has an outstanding impact on image feature extractio. In this paper, the traditional CNN is improved and a template for dynamic feature extraction of the E-nose response curve is proposed. In addition, we provide users with single-template and multi-template solutions which can be applied in different environments. To free up the computational power of occupancy, the effect of the single-template version of CNN is not as effective as the multi-template version, but it still has good feature extraction ability. These two solutions prove that CNN is sensitive to dynamic features. In order to make the results more representative, we choose several traditional feature extraction methods for comparison. [ABSTRACT FROM AUTHOR]

Production planning under uncertain demands leads to optimization problems that are hard both to model and to solve. We describe an integer linear model for a template design problem under uncertainty, and investigate its solution by a general-purpose local search algorithm for integer linear programs. Several such algorithms have previously been proposed as tools for solving large combinatorial optimization problems, and ours is based on a recent Boolean Satisfiability algorithm. In experiments it was slower than other methods on small instances, but rapidly outstripped them as the problem size and number of templates increased. It also found near-optimal solutions to all instances much more quickly. A general-purpose local search algorithm provides a rapid and convenient way of finding high-quality solutions to complex production problems. [ABSTRACT FROM AUTHOR]

Nanopatterning complex uneven surface of numerous functional devices to improve their performance is significantly appealing; however, it is extremely challenging. This study proposes a discretely-supported transfer nanoimprint technique to fabricate nanostructures on complex device surfaces containing multi-spatial frequencies. First, a discretely-supported nanoimprint template was designed based on the built energy criterion. A contact fidelity of over 99% was achieved between the designed template and the targeted complex uneven substrate surface. Next, the prefilled nanostructures on the template were transferred to the target surface after contact. By precisely controlling the amount of micro-droplet jetting on the template on-demand, the accumulation of the polymer in the micro-valley sites on the complex substrate was avoided, thus maintaining the morphology and generating function of the devices. Finally, high-quality Fresnel lenses with broadband wide-directional antireflection and excellent imaging performance were developed by imprinting subwavelength-tapered nanostructures on the relief surface., (© 2023 IOP Publishing Ltd.)

Introduction: Currently, there are few evidence-based guidelines to inform optimal clinical data-entry template design that maximizes usability while reducing unintended consequences. This study explored the impact of data-entry template design and anesthesia provider workload on documentation accuracy, documentation efficiency, and user-satisfaction to identify the most beneficial data-entry methods for use in future documentation interface design.Methodology: A study using observational data collection and psychometric instruments (for perceived workload and user-satisfaction) was conducted at three hospitals using different methods of data-entry for perioperative documentation (auto-filling with unstructured data, computer-assisted data selection with semi-structured documentation, and paper-based documentation). Nurse anesthetists at each hospital (N = 30) were observed completing documentation on routine abdominal surgical cases.Results: Auto-filling (61.2%) had the lowest documentation accuracy scores compared to computer-assisted (81.3%) and paper-based documentation (76.2%). Computer-assisted data-entry had the best documentation efficiency scores and required the least percentage of the nurse anesthetists' time (9.65%) compared to auto-filling (11.43%) and paper-based documentation (15.23%). Paper-based documentation had the highest perceived workload scores (M = 288, SD = 88) compared to auto-filling (M = 160, SD = 93, U = 16.5, p < 0.01) and computer assisted data-entry (M = 93, SD = 50, U = 4.0, P < 0.001).Conclusions: Auto-filling with unstructured data needs to be used sparingly because of its low documentation accuracy. Computer-assisted data entry with semi-structured data needs to be further study because of its better documentation accuracy, documentation efficiency, and perceived workload. [ABSTRACT FROM AUTHOR]

Background: Policies, procedures, and guidelines standardize care, meet regulatory requirements, and can promote safety in clinical practice. The existing protocols, policies, guidelines, and directives (PPGDs) at a level 1 trauma academic medical center were underused by the intensive care unit clinicians and did not always clearly represent the supporting evidence. Aims: The goals of this project were to update the Critical Care Practice Manual (CCPM) and to ensure that clinical practice was aligned with best evidence. The aim was to design a new PPGD template that used technology to enhance the presentation and functionality of these documents. Methods: Nurse project consultants reviewed every PPGD and solicited feedback from critical care nurses who consistently identified 2 barriers to utilization of CCPM: difficulty finding PPGDs and the cumbersomeness of lengthy policies. This improvement project used the principles of the Plan-Do-Study-Act cycle to test changes in real time. When 95% of the PPGDs were in the new format, a 22-question survey was created to elicit feedback from the direct care nurses who used the PPGD in the new electronic format. Results: On the basis of the survey results, nurses at the medical center accessed a PPGD at least once a month. The overall results indicated that the respondents agreed or strongly agreed that the PPGDs provided guidance (85%), reflected current practice (76%), were clear and concise (75%), and were evidence based (73%). Only 24% of those surveyed were still having difficulty finding PPGDs. Discussion/Conclusion: To facilitate timely modification and early adoption of the new PPGD format, the Plan-Do-Study-Act cycle was effectively used. The CCPM adopted a new electronic format that met the aims of the project. When making a commitment to develop evidence-based practice policies and guidelines, it is important to revisit the process, consider ongoing support, and educate frontline staff as applicable. The new template restored and enhanced the standardization of PPGDs. Technology can enhance usability and improve functionality, but it can also prove to be frustrating when implementing changes that use it, especially if users are not comfortable with it. [ABSTRACT FROM AUTHOR]

We focused on developing a management system that provides a design process in which the important attributes of the product can be easily incorporated. We developed a knowledge template to express the product information using five types of knowledge, namely, knowledge about product structure, product entity, product function, product constraint, and product design process. To determine a suitable design process, we first compared the knowledge template of existing products with the product being designed. We calculated the consistency between the two models. From the results of the consistency calculation, we selected and extracted the available knowledge. We created a new design process by using the knowledge extracted from the design template. Finally, we evaluated the process from three perspectives: the ease with which the customer requirements could be reflected, the level of difficulty of the design conflict problem, and the level of difficulty of the design loop problem. Based on the results of this evaluation, designers can select a process to design a new product. We developed a prototype system and used it to design an ocean thermal energy conversion (OTEC) system. The design knowledge for an actual OTEC design was adequately represented by the proposed knowledge template. The most important attribute has a higher value in the design process obtained using the proposed management system process than in the existing system. The proposed management system yields a design process that can easily reflect customer requirements.

The ability to catalyze diverse reactions with relevance for chemical and pharmaceutical research and industry has led to an increasing interest in fungal enzymes. There is still an enormous potential considering the sheer amount of new enzymes from the huge diversity of fungi. Most of these fungal enzymes have not been characterized yet due to the lack of high throughput synthesis and analysis methods. This bottleneck could be overcome by means of cell-free protein synthesis. In this study, cell-free protein synthesis based on eukaryotic cell lysates was utilized to produce a functional glycoside hydrolase (GH78) from the soft-rot fungus Xylaria polymorpha (Ascomycota). The enzyme was successfully synthesized under different reaction conditions. We characterized its enzymatic activities and immobilized the protein via FLAG-Tag interaction. Alteration of several conditions including reaction temperature, template design and lysate supplementation had an influence on the activity of cell-free synthesized GH78. Consequently this led to a production of purified GH78 with a specific activity of 15.4 U mg− 1. The results of this study may be foundational for future high throughput fungal enzyme screenings, including substrate spectra analysis and mutant screenings. • Cell-free protein synthesis of active rhamnosidase GH78 from Xylaria polymorpha with straightforward kinetic evaluation. • Parameters such as synthesis temperature and template modifications influence activity of a cell-free produced GH78. • Substrate specificity of GH78 depends on the synthesis process. A different rhamnosidase activity was detected. [ABSTRACT FROM AUTHOR]

Reverse turns are common structural motifs and recognition sites in protein/protein interactions. The design of peptidomimetics is often based on replacing the amide backbone of peptides by a non-peptidic scaffold while retaining the biologic mode of action. This study evaluates the potential of metal complexes of chiral pentaazacrowns conceptually derived by reduction of cyclic pentapeptides as reverse-turn mimetics. The possible conformations of metal complexes of chiral pentaazacrown scaffolds have been probed by analysis of 28 crystal structures complexed with six different metals (Mn, Fe, Co, Ni, Cu, and Zn). The solvated structures as well as the impact of complexation with different metals/oxidation states have been examined with density functional theory (DFT) calculation as explicitly represented by interactions with a single water molecule. The results suggest that most reverse-turn motifs seen in proteins could be mimicked effectively with a subset of metal complexes of chiral pentaazacrown scaffolds with an RMSD of approximately 0.3 Å. Due to the relatively fixed orientation of the pendant chiral side groups in these metal complexes, one can potentially elicit information about the receptor-bound conformation of the parent peptide from their binding affinities. The presence of 20 H-atoms on the pentaazacrown ring that could be functionalized as well as the conformational perturbations available from complexation with different metals offer a desirable diversity to probe receptors for reverse-turn recognition. [ABSTRACT FROM AUTHOR]

Protein–protein interactions are ubiquitous, essential to almost all known biological processes, and offer attractive opportunities for therapeutic intervention. Developing small molecules that modulate protein–protein interactions is challenging, owing to the large size of protein-complex interface, the lack of well-defined binding pockets, etc. We describe a general approach based on the “privileged-structure hypothesis” [Che, Ph.D. Thesis, Washington University, 2003] – that any organic templates capable of mimicking surfaces of protein-recognition motifs are potential privileged scaffolds as protein-complex antagonists – to address the challenges inherent in the discovery of small-molecule inhibitors of protein–protein interactions. [ABSTRACT FROM AUTHOR]

We present an approach to automatic image segmentation, in which user selected sets of examples and counter-examples supply information about the specific segmentation problem. In our approach, image segmentation is guided by a genetic algorithm which learns the appropriate subset and spatial combination of a collection of discriminating functions, associated with image features. The genetic algorithm encodes discriminating functions into a functional template representation, which can be applied to the input image to produce a candidate segmentation. The performance of each candidate segmentation is evaluated within the genetic algorithm, by a comparison to two physics-based techniques for region growing and edge detection. Through the process of segmentation, evaluation, and recombination, the genetic algorithm optimizes functional template design efficiently. Results are presented on real synthetic aperture radar (SAR) imagery of varying complexity. [Copyright &y& Elsevier]

The stability and dynamics of a class of Cellular Neural Networks (CNNs) in the central linear part is investigated using the decoupling technique based on discrete spatial transforms, Nyquist and root locus techniques. The influence of the cell order and template neighborhood is discussed and computer simulations are presented. It is shown that, as in the case of Turing patterns, for 1D CNNs, the patterns predicted by the linear theory of the decoupling technique are often valid even when the nonlinearity has been reached. [ABSTRACT FROM AUTHOR]

Template design on polymorph control, especially conformational polymorphs, is still in its infancy and the result of polymorph control is often accidental. A method of regulating the crystallization of conformational polymorphs based on the crystal structure similarity of templates and the target crystal form has been developed. Crystal structure similarity was considered to be able to introduce lattice matching (geometric term) with chemical interactions to regulate conformational polymorph nucleation. The method was successfully applied to induce the crystallization of DA7-II [HOOC-(CH 2 ) n -2 -COOH (diacids), named DA n , where n = 7, 9, 15, 17 and II represents the metastable polymorph] on the surface of DA15-II. An analogous two-dimensional plane - the (002) face of both DA15-II and DA7-II - was firstly predicted as the epitaxially attached face with similar lattice parameters and the strongest adsorption energy. The powder DA15-II template with the preferred orientation face in (002) presented much stronger inducing DA7-II ability than the template with other preferred orientation faces. The epitaxial growth of DA7-II on DA15-II through an identical (002) face was clearly observed and verified by the single-crystal inducing experiments. The molecular dynamics simulation results demonstrated that the strong interactions occurred between DA7 molecules and the (002) face of DA15-II. This method has been verified and further applied to the crystallization of DA7-II on the surface of DA17-II and DA9-II on the surface of DA15-II. This study developed a strategy based on structure similarity to regulate the conformational polymorph and verified the significant role of lattice matching and chemical effects on the design and preparation of templates., (© Jiawei Lin et al. 2021.)