Structural Analysis Research Articles

Ureidopenicillins Are Potent Inhibitors of Penicillin-Binding Protein 2 from Multidrug-Resistant Neisseria gonorrhoeae H041.

Effective treatment of gonorrhea is threatened by the increasing prevalence of Neisseria gonorrhoeae strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we demonstrated the promise of the third-generation cephalosporin cefoperazone as an antigonococcal agent due to its rapid second-order rate of acylation against penicillin-binding protein 2 (PBP2) from the ESC-resistant strain H041 and robust antimicrobial activity against H041. Noting the presence of a ureido moiety in cefoperazone, we evaluated a subset of structurally similar ureido β-lactams, including piperacillin, azlocillin, and mezlocillin, for activity against PBP2 from H041 using biochemical and structural analyses. We found that the ureidopenicillin piperacillin has a second-order rate of acylation against PBP2 that is 12-fold higher than cefoperazone and 85-fold higher than ceftriaxone and a lower MIC against H041 than ceftriaxone. Surprisingly, the affinity of ureidopenicillins for PBP2 is minimal, indicating that their inhibitory potency is due to a higher rate of the acylation step of the reaction compared to cephalosporins. Enhanced acylation results from the combination of a penam scaffold with a 2,3-dioxopiperazine-containing R1 group. Crystal structures show that the ureido β-lactams overcome the effects of resistance mutations present in PBP2 from H041 by eliciting conformational changes that are hindered when PBP2 interacts with the weaker inhibitor ceftriaxone. Overall, our results support the potential of piperacillin as a treatment for gonorrhea and provide a framework for the future design of β-lactams with improved activity against ESC-resistant N. gonorrhoeae.

Engineering Site 228 of Streptomyces coelicolor Laccase for Optimizing Catalytic Activity.

Malachite green (MG) poses a formidable threat to ecosystems and human health. Laccase emerges as a promising candidate for MG degradation, prompting an investigation into the catalytic activity modulation of a small laccase (SLAC) from Streptomyces coelicolor, with a focus on amino acid position 228. Through saturation mutagenesis, five mutants with a 50% increase in the specific activity were generated. Characterization revealed notable properties, Km of E228F was 8.8% of the wild type (WT), and E288T exhibited a 133% kcat compared to WT. Structural analyses indicated improved hydrophobicity and electrostatic potential on the mutants' surfaces, with the stable E228F-ABTS complex exhibiting reduced flexibility, possibly contributing to the observed decrease in turnover rate. Mutants demonstrated enhanced MG decolorization, particularly E228G. Site 228 acts as a crucial functional control switch, suggesting its potential role in SLAC engineering. This study provides insights into laccase modulation and offers promising avenues for enzymatic bioremediation applications.

Multi-strategy orthogonal enhancement and analysis of aldo-keto reductase thermal stability

Given their outstanding efficiency and selectivity, enzymes are integral in various domains such as drug synthesis, the food industry, and environmental management. However, the inherent instability of natural enzymes limits their widespread industrial application. In this study, we underscore the efficacy of enhancing protein thermal stability through comprehensive protein design strategies, encompassing elements such as the free energy of protein folding, internal forces within proteins, and the overall structural design. We also demonstrate the efficiency and precision of combinatorial screening in the thermal stability design of aldo-keto reductase (AKR7-2-1). In our research, three single-point mutations and five combinatorial mutations were strategically introduced into AKR7-2-1, using multiple computational techniques. Notably, the E12I/S235I mutant showed a significant increase of 25.4 °C in its melting temperature (Tm). Furthermore, the optimal mutant, E12V/S235I, maintained 80 % of its activity while realizing a 16.8 °C elevation in Tm. Remarkably, its half-life at 50 °C was increased to twenty times that of the wild type. Structural analysis indicates that this enhanced thermal stability primarily arises from reduced oscillation in the loop region and increased internal hydrogen bonding. The promising results achieved with AKR7-2-1 demonstrate that our strategy could serve as a valuable reference for enhancing the thermal stability of other industrial enzymes.

Cognitive Reappraisal Moderates the Longitudinal Relationship between Adolescents' Peer Victimization and Self-Esteem. A Latent Interaction Model.

Poor self-esteem relates closely to youth maladjustment and appears to be predicted by peer victimization experiences. However, not all peer victimized adolescents face the same risk for self-esteem erosion over time. Drawing upon the Bi-Dimensional Framework for resilience and extant research, the present study examined the potential moderating role of cognitive reappraisal in the prospective relationship from peer victimization to self-esteem. To increase precision of findings the long-term impact of self-esteem on peer victimization was also tested. Self-reported data were collected from 285 early adolescents (Mage = 10.53 years, SD = 0.16; 54.0% girls) at two waves, spaced 1-year. Latent moderated structural equation analysis showed that peer victimization was negatively related to later self-esteem, but only for youth displaying low levels of cognitive reappraisal. For adolescents with high levels of cognitive reappraising, peer victimization was not found to predict any changes in self-esteem over time. The long-term impact of self-esteem on peer victimization was not supported. Overall the present study suggests that enhancing cognitive reappraisal could be a promising avenue for lowering risk for poor self-esteem in young individuals experiencing peer victimization.

Factors affecting small and medium enterprises access to capital: Evidence from Vietnam

Purpose: The capacity of a business to operate and grow depends on its capital, particularly for small and medium-sized businesses (SMEs). However, access to capital sources depends on many factors such as collateral assets, business plans requiring loans, the social relations of business owners, etc. This study identifies factors affecting SMEs' access to capital in Vietnam.
 Design/Methodology/Approach: A typical survey was conducted on 450 SMEs in Vietnam, and structural model analysis methods were employed through PLS-SEM software to analyze the data.
 Findings: Research results show that there are nine groups of factors affecting the ability of SMEs in Vietnam to access capital ranked from high to low level of influence, including (i) operational characteristics of the business, (ii) financial reporting, (iii) financial behaviour of enterprises, (iv) social relations of enterprises, (v) capability of the enterprise, (vi) production and business plan of the enterprise, (vii) ability to adapt to the risks of the enterprise, (viii) characteristics of the business owner and the lowest is institutional environment.
 Conclusion: Regression analysis proved to be useful in identifying nine groups of elements that impact SMEs' access to capital in Vietnam. The study has proposed management implications to improve access to capital for SMEs in Vietnam.
 Research Limitations and Implications: The study selected samples based on the principle of random convenience, so the study's sample does not represent all SMEs in Vietnam according to the distribution of regions and territories where the businesses are located.
 Practical Implications: This research has practical significance in supporting managers at SMEs to make decisions to improve access to capital for businesses contributing to sustainable business development.
 Contribution to the Literature: This research makes a significant contribution to the field of practical research on capital and capital access for SMEs in Vietnam.

A 12-Vertex Metallacarborane of Silver(I).

The discovery of ferrocene in 1951 was a significant landmark in the field of organometallic chemistry, and since then, numerous sandwich- or half-sandwich metallic complexes have been reported. However, silver stands as an intriguing exception in this regard, and knowledge of its bonding situation has remained undisclosed. Herein, unprecedented 12-vertex metallacarboranes of Ag(I) (2a and 2b) were synthesized through the reaction of sodium hexamethyldisilazide (NaHMDS) with the mixture of nido-C2B9 carborane anion-supported N-heterocyclic carbene precursors (1a and 1b) and [Ag(PPh3)Cl]4. The X-ray structural analysis of the resulting metallacarboranes revealed a unique "slipped" half-sandwich structure, which is a rarity among cyclopentadienyl analogues. DFT calculations provided insights into the asymmetric π-interactions between the pentagonal C2B3 face and the silver ion.

Structures, Mechanisms, and Physiological Functions of Zinc Transporters in Different Biological Kingdoms.

Zinc transporters take up/release zinc ions (Zn2+) across biological membranes and maintain intracellular and intra-organellar Zn2+ homeostasis. Since this process requires a series of conformational changes in the transporters, detailed information about the structures of different reaction intermediates is required for a comprehensive understanding of their Zn2+ transport mechanisms. Recently, various Zn2+ transport systems have been identified in bacteria, yeasts, plants, and humans. Based on structural analyses of human ZnT7, human ZnT8, and bacterial YiiP, we propose updated models explaining their mechanisms of action to ensure efficient Zn2+ transport. We place particular focus on the mechanistic roles of the histidine-rich loop shared by several zinc transporters, which facilitates Zn2+ recruitment to the transmembrane Zn2+-binding site. This review provides an extensive overview of the structures, mechanisms, and physiological functions of zinc transporters in different biological kingdoms.

Tracking Coordination Environment and Reaction Intermediates in Homogeneous and Heterogeneous Epoxidation Catalysts via Ti L2,3-Edge Near-Edge X-ray Absorption Fine Structures.

Ti-based molecules and materials are ubiquitous and play a major role in both homogeneous and heterogeneous catalytic processes. Understanding the electronic structures of their active sites (oxidation state, local symmetry, and ligand environment) is key to developing molecular-level structure-property relationships. In that context, X-ray absorption spectroscopy (XAS) offers a unique combination of elemental selectivity and sensitivity to local symmetry. Commonly, for early transition metals such as Ti, K-edge XAS is applied for in situ characterization and subsequent structural analysis with high sensitivity toward tetrahedral species. Ti L2,3-edge spectroscopy is in principle complementary and offers specific opportunities to interrogate the electronic structure of five-and six-coordinated species. It is, however, much more rarely implemented because the use of soft X-rays implies ultrahigh vacuum conditions. Furthermore, the interpretation of the data can be challenging. Here, we show how Ti L2,3-edge spectroscopy can help to obtain unique information about both homogeneous and heterogeneous epoxidation catalysts and develop a molecular-level relationship between spectroscopic signatures and electronic structures. Toward this goal, we first establish a spectral library of molecular Ti reference compounds, comprising various coordination environments with mono- and dimeric Ti species having O, N, and Cl ligands. We next implemented a computational methodology based on multiplet ligand field theory and maximally localized Wannier orbitals benchmarked on our library to understand Ti L2,3-edge spectroscopic signatures. We finally used this approach to track and predict the spectra of catalytically relevant intermediates, focusing on Ti-based olefin epoxidation catalysts.

Shaping the climate transition: Multistakeholder networks, elites, and sustainable finance policy in Europe

Abstract As sustainable finance has entered the mainstream, it has become an area of contestation among civil society, political and business. In response, policy makers seek to resolve stalemates and enhance legitimacy by utilising multistakeholder, consensus-driven approaches to policymaking. In this paper, we examine these emergent ‘cooperative’ structures from a network analytic perspective. Our structural analysis is based on six national and three EU policy spaces. We conduct compositional analyses to explore the makeup of the network(s) and use a range of centrality measures to capture emerging elites. We find an increase in civil society participation in these policy spaces over time; however, financial firms and pro-business voices remain dominant players. We also find a small cluster of elite actors from a range of stakeholder groups. We conclude that the increasing structural balance of stakeholder interests, however, does not translate into power for civil society to alter the direction of policymaking, but appears to serve enhancing the legitimacy of a policy process that departs from the priority and aspirations of civil society organisations.

Influence of Variation in Tie Reinforcement Diameter on the Ductility of Reinforced Concrete Columns

Reinforced concrete columns are crucial structural elements in ensuring the strength and stability of buildings. Column ductility, which is the ability to absorb energy and undergo deformation before failure, is a primary concern in structural engineering, especially in extreme external loading situations such as earthquakes. This study aims to evaluate the influence of variation in Tie reinforcement diameter on the ductility of reinforced concrete columns using Xtract software. The research method involves creating column structure models with specified dimensions and specifications, followed by the gradual application of axial loads to each model. Three models were created with varying Tie reinforcement diameters, namely 10 mm, 12 mm, and 14 mm. Structural analysis was conducted to examine the structure's response to the applied axial and moment loads, including evaluation of stresses, deformations, and column capacities. The analysis results show differences in ductility levels among the models. The model with a 10 mm Tie reinforcement diameter achieves higher ductility levels at low axial loads but fails to meet the requirements at higher axial loads according to the SNI 1726:2019 standard. However, models with Tie reinforcement diameters of 12 mm and 14 mm also exhibit a similar pattern, with good ductility at low axial loads but failing to meet the requirements at higher axial loads. In conclusion, variations in Tie reinforcement diameter affect the ductility of reinforced concrete columns. To ensure full ductility under various axial load conditions, adjustments to the design or specifications of the reinforced concrete column structure are necessary. This research contributes to understanding the factors influencing the ductility of reinforced concrete columns and can serve as a basis for the development of more effective design methods in the future.

Isolation of a Cyclic Trinuclear Gold(I) Complex with Metalated Phosphorus Ylides: Synthesis and Structural Properties.

The first chiral and luminescent cyclic trinuclear gold(I) complex, [{AuCH(PPh2Me)(Ph2P)}3]3+, has been isolated with metalated phosphorus ylides (PY). This complex was initially obtained through the reaction of either mononuclear [C6F5SAuCH(PPh2Me)(Ph2P)]OTf or dinuclear [C6F5S{AuCH(PPh2Me)(Ph2P)}2](OTf)2 thiolate-gold-phosphane complexes in the presence of NaH, followed by the abstraction of the thiopyridine moiety employing either AgOTf or [Cu(CH3CN)4]PF6. Our quest for a more efficient synthesis route led to the development of a streamlined one-pot synthesis method, employing Ag(acac) as both a halogen abstractor and a base, offering a quicker and more direct path to this intriguing trimer. Comprehensive computational studies have unveiled the luminescent characteristics of this complex, which can be attributed to phosphorescence. These emissions originate from ligand-to-metal (LMCT) and metal-centered (MC) charge transfer excited states. Furthermore, the structural analysis via X-ray crystallography corroborated the formation of a trimeric species, featuring three monomers with the [AuCH(PPh2Me)(Ph2P)] motif. Each monomer exhibits a single chiral center, leading to four possible absolute configurations (RRR, RRS, RSR, and SRR). NMR and X-ray spectroscopy have provided valuable insights, establishing that the former configuration (RRR) is disfavored due to steric hindrance, while the three remaining configurations can interconvert, arising from the structural arrangement of the metallacycle and inherent symmetry operations.

A hierarchic isogeometric hyperelastic solid-shell

AbstractThe present study aims to develop an original solid-like shell element for large deformation analysis of hyperelastic shell structures in the context of isogeometric analysis (IGA). The presented model includes a new variable to describe the thickness change of the shell and allows for the application of unmodified three-dimensional constitutive laws defined in curvilinear coordinate systems and the analysis of variable thickness shells. In this way, the thickness locking affecting standard solid-shell-like models is cured by enhancing the thickness strain by exploiting a hierarchical approach, allowing linear transversal strains. Furthermore, a patch-wise reduced integration scheme is adopted for computational efficiency reasons and to annihilate shear and membrane locking. In addition, the Mixed-Integration Point (MIP) format is extended to hyperelastic materials to improve the convergence behaviour, hence the efficiency, in Newton iterations. Using benchmark problems, it is shown that the proposed model is reliable and resolves locking issues that were present in the previously published isogeometric solid-shell formulations.

The effects of corporate social responsibility on innovation and performance of firms in China: a structural equation model analysis

Purpose This study aims to analyze and discuss the impact of corporate social responsibility (CSR) on firms’ performance, as well as to examine the interplay between CSR and the economy, society and innovation. Design/methodology/approach This paper collects data from 420 manufacturing firms across various geographical regions in China. By using a structural equation model, the paper investigates the impact of CSR on enterprise innovation, customer management capability, market competitiveness (MC) and firm financial performance. Findings The findings demonstrate that CSR performance positively contributes to enhancing the level of enterprise innovation, as well as customer management capability and market competitiveness. Furthermore, it assists enterprises in improving market competitiveness and elevating customer management capabilities. Thus, CSR can have a positive effect on the firm financial performance. Originality/value The outcomes presented in this paper offer valuable evidence regarding the influence of implementing CSR on different aspects of enterprise performance and innovation. Moreover, it provides practical recommendations for enterprises seeking to transition towards low-carbon practices and upgrade their manufacturing industry.

The Rehabilitation of the Historical Bridge of Konitsa, Epirus, Greece: A Documentation-Based Methodology of Structural Analysis and Rehabilitation Strategy

The bridge of Konitsa over the Aoos river, in Epirus, Greece, was built in 1869. It is one of the most important stone arched bridges in the Balkans, listed by the Hellenic Ministry of Culture (1982). The bridge, damaged by the Ottoman Army in 1913, was restored the same year by French engineers using reinforced concrete. Structural deterioration, located mainly in the area damaged by the explosion and subsequently repaired, led to the study of the bridge by the National Technical University of Athens (NTUA), in the framework of a Contract among the Prefecture of Epirus, the Municipality of Konitsa (owner of the bridge), the Ministry of Culture and NTUA. The entire study includes the exhaustive documentation of the bridge, its numerical modelling and assessment at its current state, the selection of adequate interventions and the numerical investigation of the efficiency of the proposed interventions. During this process, one of the main issues was the treatment of the concrete intervention of 1913. For the choice and for the design of the restoration measures, a calculation methodology was adopted, based on the findings of the documentation of the bridge, while taking into account the critical phases (construction, damage and repair) over its lifetime. This work has proven the available safety of the bridge under its self-weight, as well as the need for reconstruction of the RC jacket at the intrados of the arch, which was applied as a repair measure to the bridge in 1913.

Bacterial hypothetical proteins may be of functional interest

Genomic analysis is part of the daily routine for many microbiology researchers. These analyses frequently unveil genes that encode proteins with uncertain functions, and for many bacterial species, these unknown genes constitute a significant proportion of their genomic coding sequences. Because these genes do not have defined functions, they are often overlooked in analyses. Experimentally determining the function of a gene can be challenging; however, ongoing advancements in bioinformatics tools, especially in protein structural analysis, are making it progressively easier to assign functions to hypothetical sequences. Leveraging various complementary tools and automated pipelines for annotating hypothetical sequences could ultimately enhance our comprehension of microbial functions and provide direction for new laboratory experiments.

Comments on the book of Tereza Matějčková Gibt es eine Welt in Hegels Phänomenologie des Geistes? / “Is there a world in Hegelʼs Phenomenology of Spirit?”, Tübingen: Mohr Siebeck 2018

Tereza Matějčková’s book presents a highly interesting phenomenological reading of Hegel’s early masterpiece. The result is a proposal to take the title seriously – such that we can see the book as the earliest introduction into the methods and topics of philosophical phenomenology, despite the fact that Husserl himself, in contrast to Heidegger, did not seem to see the narrow relation. I especially value Tereza Matějčkováʼs very deep understanding of the dialectical humour and irony of Hegel’s writings. However, I understand the Phenomenology of Spirit in a somehow more radical way as a most general ‘logicֹ’ of self-consciousness. It shows how referring to myself is referring to the world and vice versa, despite the fact that the word ‘world’ does not play a prominent role in Hegelʼs text. Some disagreements result over Hegelʼs wide use of metaphors and analogies in his structural analysis of personal self-relations, for example in his reconstruction and critique of the age-old (in fact Platonic) image of a fight between a thinking soul as master and a system of immediate bodily desires as slave. We cannot get rid of inclinations and appetites, and we cannot retreat, as the Stoics had thought, into pure thinking. In other words, there is no fight ‘for recognition’ between different individuals in Hegelʼs book, but in the end an answer to a classical theodicy saying that the world, as it is, is the best one we have because there is only one world.

The accurate estimation of Li/Ni mixing degree of lithium nickel oxide cathode materials

Abstract Li/Ni mixing negatively influences the discharge capacity of lithium nickel oxide and high-nickel ternary cathode materials. However, accurately measuring the Li/Ni mixing degree is difficult due to the preferred orientation of lab-based XRD measurements using Bragg-Brentano geometry. Here, we find that employing spherical harmonics in Rietveld refinement to eliminate the preferred orientation can significantly decrease the measurement error of the Li/Ni mixing ratio. The Li/Ni mixing ratio obtained from Rietveld refinement with spherical harmonics shows a strong correlation with discharge capacity, which means the electrochemical capacity of lithium nickel oxide and high-nickel ternary cathode can be estimated by the Li/Ni mixing degree. Our findings provide a simple and accurate method to estimate the Li/Ni mixing degree, which is valuable to the structural analysis and screening of the synthesis conditions of lithium nickel oxide and high-nickel ternary cathode materials.

Structural and practical identifiability analysis in bioengineering: a beginner’s guide

Advancements in digital technology have brought modelling to the forefront in many disciplines from healthcare to architecture. Mathematical models, often represented using parametrised sets of ordinary differential equations, can be used to characterise different processes. To infer possible estimates for the unknown parameters, these models are usually calibrated using associated experimental data. Structural and practical identifiability analyses are a key component that should be assessed prior to parameter estimation. This is because identifiability analyses can provide insights as to whether or not a parameter can take on single, multiple, or even infinitely or countably many values which will ultimately have an impact on the reliability of the parameter estimates. Also, identifiability analyses can help to determine whether the data collected are sufficient or of good enough quality to truly estimate the parameters or if more data or even reparameterization of the model is necessary to proceed with the parameter estimation process. Thus, such analyses also provide an important role in terms of model design (structural identifiability analysis) and the collection of experimental data (practical identifiability analysis). Despite the popularity of using data to estimate the values of unknown parameters, structural and practical identifiability analyses of these models are often overlooked. Possible reasons for non-consideration of application of such analyses may be lack of awareness, accessibility, and usability issues, especially for more complicated models and methods of analysis. The aim of this study is to introduce and perform both structural and practical identifiability analyses in an accessible and informative manner via application to well established and commonly accepted bioengineering models. This will help to improve awareness of the importance of this stage of the modelling process and provide bioengineering researchers with an understanding of how to utilise the insights gained from such analyses in future model development.

Synthesis, Structural Analysis, Theoretical Calculations, In Silico Prediction of Antibacterial Efficacy, Toxicity Assessment, In Vitro Antioxidant Evaluation and Polymerization Activity of Cobalt(II) Coordination Complexes of Para-biphenylol

Synthesis, Structural Analysis, Theoretical Calculations, In Silico Prediction of Antibacterial Efficacy, Toxicity Assessment, In Vitro Antioxidant Evaluation and Polymerization Activity of Cobalt(II) Coordination Complexes of Para-biphenylol

Bayesian active learning line sampling with log-normal process for rare-event probability estimation

Line sampling (LS) stands as a powerful stochastic simulation method for structural reliability analysis, especially for assessing small failure probabilities. To further improve the performance of traditional LS, a Bayesian active learning idea has recently been pursued. This work presents another Bayesian active learning alternative, called ‘Bayesian active learning line sampling with log-normal process’ (BAL-LS-LP), to traditional LS. In this method, we assign an LP prior instead of a Gaussian process prior over the distance function so as to account for its non-negativity constraint. Besides, the approximation error between the logarithmic approximate distance function and the logarithmic true distance function is assumed to follow a zero-mean normal distribution. The approximate posterior mean and variance of the failure probability are derived accordingly. Based on the posterior statistics of the failure probability, a learning function and a stopping criterion are developed to enable Bayesian active learning. In the numerical implementation of the proposed BAL-LS-LP method, the important direction can be updated on the fly without re-evaluating the distance function. Four numerical examples are studied to demonstrate the proposed method. Numerical results show that the proposed method can estimate extremely small failure probabilities with desired efficiency and accuracy.