bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence and comparison of cylindrical engineered defects on detonation waveshape in a rubberized RDX explosive
Authors: Lawrence Joseph R. , Montoya Gabriel A. , Koeblitz Austin D. , Son Steven F. 
Published: May 2024

AbstractInhomogeneities within explosives affect the sensitivity and detonation waveshape of energetic materials. The influence of voids on explosive initiation has been well documented; however, the effects that voids between 0.1 mm and 10 mm have on a propagating detonation wave remains largely unexplored. The effect of single cylindrical voids on detonation waveshape and re‐initiation was examined here using manufactured voids in a rubberized 1,3,5‐trinitro‐1,3,5‐triazinane (RDX) explosive. Two streak imaging techniques were fielded to investigate void influence. For the first, back‐surface streak imaging, the location of the void on the samples was changed and the resulting change in detonation waveshape at the downstream breakout was captured using a streak camera in cut‐back experiments. The results from this experiment showed the effects of an initial jet form for short cut‐back distances and as shock propagation progressed, the jet formation was absorbed by the unaffected portions of the wave front. The second method, top‐surface streak imaging, was used to investigate the re‐initiation/downstream propagation of the detonation front and the detonation velocity of the rubberized explosive. These experiments were compared to similar experimental results from machined voids in PBX 9501, an 1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane (HMX)‐based explosive, to investigate the interaction of a detonation wave with a 0.5 mm void for different explosives. The experiments were also compared to simulations using a multi‐dimensional and multi‐material hydrodynamic code. These results showed the influence that small features can have on detonation waveshaping and how explosive properties play a key role in that interaction.
Electrostatics introduce a trade‐off between mesophilic stability and adaptation in halophilic proteins
Authors: Herrero‐Alfonso Pablo , Pejenaute Alba , Millet Oscar , Ortega‐Quintanilla Gabriel 
Published: May 2024

AbstractExtremophile organisms have adapted to extreme physicochemical conditions. Halophilic organisms, in particular, survive at very high salt concentrations. To achieve this, they have engineered the surface of their proteins to increase the number of short, polar and acidic amino acids, while decreasing large, hydrophobic and basic residues. While these adaptations initially decrease protein stability in the absence of salt, they grant halophilic proteins remarkable stability in environments with extremely high salt concentrations, where non‐adapted proteins unfold and aggregate. The molecular mechanisms by which halophilic proteins achieve this, however, are not yet clear. Here, we test the hypothesis that the halophilic amino acid composition destabilizes the surface of the protein, but in exchange improves the stability in the presence of salts. To do that, we have measured the folding thermodynamics of various protein variants with different degrees of halophilicity in the absence and presence of different salts, and at different pH values to tune the ionization state of the acidic amino acids. Our results show that halophilic amino acids decrease the stability of halophilic proteins under mesophilic conditions, but in exchange improve salt‐induced stabilization and solubility. We also find that, in contrast to traditional assumptions, contributions arising from hydrophobic effect and preferential ion exclusion are more relevant for haloadaptation than electrostatics. Overall, our findings suggest a trade‐off between folding thermodynamics and halophilic adaptation to optimize proteins for hypersaline environments.
ProkDBP: Toward more precise identification of prokaryoticDNAbinding proteins
Authors: Pradhan Upendra Kumar , Meher Prabina Kumar , Naha Sanchita , Das Ritwika , Gupta Ajit , Parsad Rajender 
Published: May 2024

AbstractProkaryotic DNA binding proteins (DBPs) play pivotal roles in governing gene regulation, DNA replication, and various cellular functions. Accurate computational models for predicting prokaryotic DBPs hold immense promise in accelerating the discovery of novel proteins, fostering a deeper understanding of prokaryotic biology, and facilitating the development of therapeutics targeting for potential disease interventions. However, existing generic prediction models often exhibit lower accuracy in predicting prokaryotic DBPs. To address this gap, we introduce ProkDBP, a novel machine learning‐driven computational model for prediction of prokaryotic DBPs. For prediction, a total of nine shallow learning algorithms and five deep learning models were utilized, with the shallow learning models demonstrating higher performance metrics compared to their deep learning counterparts. The light gradient boosting machine (LGBM), coupled with evolutionarily significant features selected via random forest variable importance measure (RF‐VIM) yielded the highest five‐fold cross‐validation accuracy. The model achieved the highest auROC (0.9534) and auPRC (0.9575) among the 14 machine learning models evaluated. Additionally, ProkDBP demonstrated substantial performance with an independent dataset, exhibiting higher values of auROC (0.9332) and auPRC (0.9371). Notably, when benchmarked against several cutting‐edge existing models, ProkDBP showcased superior predictive accuracy. Furthermore, to promote accessibility and usability, ProkDBP (https://iasri-sg.icar.gov.in/prokdbp/) is available as an online prediction tool, enabling free access to interested users. This tool stands as a significant contribution, enhancing the repertoire of resources for accurate and efficient prediction of prokaryotic DBPs.
Mutational and structural studies of (βα)8‐barrel fold methylene‐tetrahydropterin reductases utilizing a common catalytic mechanism
Authors: Gehl Manuel , Demmer Ulrike , Ermler Ulrich , Shima Seigo 
Published: May 2024

AbstractMethylene‐tetrahydropterin reductases catalyze the reduction of a methylene to a methyl group bound to a reduced pterin as C1 carrier in various one‐carbon (C1) metabolisms. F420‐dependent methylene‐tetrahydromethanopterin (methylene‐H4MPT) reductase (Mer) and the flavin‐independent methylene‐tetrahydrofolate (methylene‐H4F) reductase (Mfr) use a ternary complex mechanism for the direct transfer of a hydride from F420H2 and NAD(P)H to the respective methylene group, whereas FAD‐dependent methylene‐H4F reductase (MTHFR) uses FAD as prosthetic group and a ping–pong mechanism to catalyze the reduction of methylene‐H4F. A ternary complex structure and a thereof derived catalytic mechanism of MTHFR is available, while no ternary complex structures of Mfr or Mer are reported. Here, Mer from Methanocaldococcus jannaschii (jMer) was heterologously produced and the crystal structures of the enzyme with and without F420 were determined. A ternary complex of jMer was modeled on the basis of the jMer‐F420 structure and the ternary complex structure of MTHFR by superimposing the polypeptide after fixing hydride‐transferring atoms of the flavins on each other, and by the subsequent transfer of the methyl‐tetrahydropterin from MTHFR to jMer. Mutational analysis of four functional amino acids, which are similarly positioned in the three reductase structures, indicated despite the insignificant sequence identity, a common catalytic mechanism with a 5‐iminium cation of methylene‐tetrahydropterin as intermediate protonated by a shared glutamate. According to structural, mutational and phylogenetic analysis, the evolution of the three reductases most likely proceeds via a convergent development although a divergent scenario requiring drastic structural changes of the common ancestor cannot be completely ruled out.
Decoding the mechanism governing the structural stability of wheat germ agglutinin and its isolated domains: A combined calorimetric, NMR, and MD simulation study
Authors: Medrano‐Cerano Jorge Luis , Cofas‐Vargas Luis Fernando , Leyva Eduardo , Rauda‐Ceja Jesús Antonio , Calderón‐Vargas Mateo , Cano‐Sánchez Patricia , Titaux‐Delgado Gustavo , Melchor‐Meneses Carolina Monserrath , Hernández‐Arana Andrés , del Río‐Portilla Federico , García‐Hernández Enrique 
Published: May 2024

AbstractWheat germ agglutinin (WGA) demonstrates potential as an oral delivery agent owing to its selective binding to carbohydrates and its capacity to traverse biological membranes. In this study, we employed differential scanning calorimetry and molecular dynamics simulations to comprehensively characterize the thermal unfolding process of both the complete lectin and its four isolated domains. Furthermore, we present the nuclear magnetic resonance structures of three domains that were previously lacking experimental structures in their isolated forms. Our results provide a collective understanding of the energetic and structural factors governing the intricate unfolding mechanism of the complete agglutinin, shedding light on the specific role played by each domain in this process. The analysis revealed negligible interdomain cooperativity, highlighting instead significant coupling between dimer dissociation and the unfolding of the more labile domains. By comparing the dominant interactions, we rationalized the stability differences among the domains. Understanding the structural stability of WGA opens avenues for enhanced drug delivery strategies, underscoring its potential as a promising carrier throughout the gastrointestinal environment.
Effects of natural Ionones and derived novel analogues with simplified structures on behavioral responses of whiteflies
Authors: Qi Wensong , Lu Yiming , Shao Xusheng , Maienfisch Peter 
Published: May 2024

AbstractBACKGROUNDWhiteflies are major pests in agriculture, causing damage to crops and transmitting plant viruses. Using Volatile Organic Compounds (VOCs) as semiochemicals offers a sustainable approach for combating whiteflies. One such group of compounds, represented by β‐ionone, has been found to possess repellent/attractant properties. To further explore the behavioral effects of these compounds on whiteflies, we selected five natural ionone compounds and synthesized six novel analogues to examine the impact of structural variations on whitefly behavior.RESULTSOur results demonstrated that β‐ionone and its analogues have a significant impact on the behavior of whiteflies. Among them, 0.01% pseudo ionone solution exhibited an attractant effect on whiteflies. Notably, the application of 1% β‐ionone and 0.1% β‐ionol solution demonstrated a notable repellent effect and oviposition deterrent effect on whitefly. We also found that the novel ionone analogue (±)1A exhibited a strong repellent effect. Both β‐ionol and compound (±)1A possess high logP values and low saturation vapor pressures, which contribute to enhanced lipophilicity, making them more likely to penetrate insect antennae and prolong their presence in the air.CONCLUSIONThe newly discovered ionone analogue (±)1A and β‐ionol exhibit improved repellent effects, while pseudo ionone shows an attractant effect. These three compounds hold promising potential for development as novel biological control agents. Our work highlights the efficacy of VOCs as a protection method against whiteflies. These findings indicate that our new technology for a ‘push–pull’ control method of B. tabaci can offer a novel tool for integrated pest management (IPM). © 2024 Society of Chemical Industry.
Elucidating nonlinear pharmacokinetics of telmisartan: Integration of target‐mediated drug disposition and OATP1B3‐mediated hepatic uptake in a physiologically based model
Authors: Tsuchitani Toshiaki , Tomaru Atsuko , Aoki Yasunori , Ishiguro Naoki , Tsuda Yasuhiro , Sugiyama Yuichi 
Published: May 2024

AbstractTelmisartan, a selective inhibitor of angiotensin II receptor type 1 (AT1), demonstrates nonlinear pharmacokinetics (PK) when orally administered in ascending doses to healthy volunteers, but the underlying mechanisms remain unclear. This study presents a physiologically based pharmacokinetic model integrated with target‐mediated drug disposition (TMDD‐PBPK model) to explore the mechanism of its nonlinear PK. We employed the Cluster‐Gauss Newton method for top‐down analysis, estimating the in vivo Km,OATP1B3 (Michaelis–Menten constant for telmisartan hepatic uptake via Organic Anion Transporting Polypeptide 1B3) to be 2.0–5.7 nM. This range is significantly lower than the reported in vitro value of 810 nM, obtained in 0.3% human serum albumin (HSA) conditions. Further validation was achieved through in vitro assessment in plated human hepatocytes with 4.5% HSA, showing a Km of 4.5 nM. These results underscore the importance of albumin‐mediated uptake effect for the hepatic uptake of telmisartan. Our TMDD‐PBPK model, developed through a “middle‐out” approach, underwent sensitivity analysis to identify key factors in the nonlinear PK of telmisartan. We found that the nonlinearity in the area under the concentration–time curve (AUC) and/or maximum concentration (Cmax) of telmisartan is sensitive to Km,OATP1B3 across all dosages. Additionally, the dissociation constant (Kd) for telmisartan binding to the AT1 receptor, along with its receptor abundance, notably influences PK at lower doses (below 20 mg). In conclusion, the nonlinear PK of telmisartan appears primarily driven by hepatic uptake saturation across all dose ranges and by AT1‐receptor binding saturation, notably at lower doses.
Global seroprevalence and prevalence of infection of influenza in dogs (Canis familiaris): A systematic review and meta‐analysis
Authors: Leung Char , King Amy Nishio , Barker Phoebe Rosemary Alice , Alshallal Abdulwahab Dhari , Lee Jia Yi , Su Li 
Published: May 2024

AbstractInfluenza in dogs holds considerable public health significance due to their close companionship with humans, yet several facets of this phenomenon remain largely unexplored. This study undertook a systematic review and meta‐analysis of observational studies to gauge the global seroprevalence of influenza in dogs. We also assessed whether pet dogs exhibited a higher seroprevalence of influenza compared to non‐pet dogs, explored seasonal variations in seroprevalence, scrutinised the design and reporting standards of existing studies, and elucidated the geographical distribution of canine influenza virus (cIV). A comprehensive analysis of 97 studies spanning 27 countries revealed that seroprevalence of various influenza strains in dogs consistently registered below 10% and exhibited relative stability over the past decade. Significantly, we noted that seroprevalence of human influenza virus was notably higher in pet dogs compared to their non‐pet counterparts, whereas seroprevalence of other influenza strains remained relatively uniform among both categories of dogs. Seasonal variations in seroprevalence of cIV were not observed. In summary, our findings indicated the global circulation of cIV strains H3N2 and H3N8, with other strains primarily confined to China. Given the lack of reported cases of the transmission of cIV from dogs to humans, our findings suggest a higher risk of reverse zoonosis than zoonosis. Finally, we strongly advocate for standardised reporting guidelines to underpin future canine influenza research endeavours.
Soil moisture and probe characteristics affect core integrity and soil test results
Authors: Drescher Gerson L. , Slaton Nathan A. , Ahmad Uzair , Smartt Alden D. , Roberts Trenton L. , Gbur Edward E. 
Published: May 2024

AbstractProper soil sampling is critical for accurate fertilizer recommendations. Samples collected in extremely wet or dry conditions may compromise the integrity of the sample and influence analytical results. We evaluated the effects of six soil moistures, two sampling depths (0–10 and 0–15 cm), and two soil probes on soil core uniformity and soil test results. Moisture treatments encompassed a range from dry (11.2%–18.5% moisture) to saturated conditions in Captina, Dewitt, Calhoun, and Calloway silt loam soils. Core depth and dry core weight were measured in all soils, and pH and Mehlich‐3 extractable P, K, S, and Zn were assessed for Calhoun and Calloway soils. Soil moisture, probe, or their interaction influenced core depth and weight, while chemical properties were significantly affected only by soil moisture. Sampling very dry or saturated soils compromised the collection of uniform cores mainly for the 0‐ to 15‐cm depth. Soil pH tended to increase with increasing moisture, but the mean values fluctuated only ±0.3 units. Across soils and depths, extractable S consistently decreased by 16%–48% as soil moisture at sampling time increased. Phosphorus was affected by soil moisture for 0–15 cm samples in both soils but showed no clear pattern. Soil moisture at the time of sampling affected soil test K for both soils and sample depths with individual cores varying up to 47 mg kg−1 (i.e., 59–106 mg kg−1). Greater soil test P and K variability occurred for very dry and wet conditions, which often prohibit collecting samples to the proper depth and could impact fertilizer rate recommendations.
Design and sample size determination for multiple‐dose randomized phase II trials for dose optimization
Authors: Yang Peng , Li Daniel , Lin Ruitao , Huang Bo , Yuan Ying 
Published: May 2024

AbstractThe U.S. Food and Drug Administration (FDA) has launched Project Optimus to shift dose selection from the maximum tolerated dose (MTD) to the dose that produces the optimal risk‐benefit tradeoff. One approach highlighted in the FDA's guidance involves conducting a randomized phase II trial following the completion of a phase I trial, where multiple doses (typically including the MTD and one or two doses lower than the MTD) are compared to identify the optimal dose that maximizes the benefit‐risk tradeoff. This article focuses on the design of such a multiple‐dose randomized trial, specifically the determination of the sample size. We generalized the standard definitions of type I error and power to accommodate the unique characteristics of dose optimization and derived a decision rule along with an algorithm to determine the optimal sample size. The resulting design is referred to as MERIT (Multiple‐dosE RandomIzed Trial design for dose optimization based on toxicity and efficacy). Simulation studies demonstrate that MERIT has desirable operating characteristics, and a sample size between 20 and 40 per dosage arm often offers reasonable power and type I errors to ensure patient safety and benefit. To facilitate the implementation of the MERIT design, we provide software, available at https://www.trialdesign.org.
Incorporating Fluorescent Organosilica and Zeolitic Imidazolate Frameworks into Periodic Mesoporous Organosilica for the Enhanced Cargo Delivery of 5‐Fluorouracil
Authors: Huynh Linh Ty , Nguyen Thao Vy Thi , Mai Ngoc Xuan Dat , Doan Tan Le Hoang , Do Han Hoang , Pham Quyen Toan , Minh Tri Le , Ung Thuy Dieu Thi , Thuy Nguyen Linh Ho 
Published: May 2024

AbstractNanosized zeolitic imidazolate frameworks (nZIFs) are being researched as 5‐fluorouracil (5‐FU) carriers for the treatment of cancer. The surface functionalization of ZIFs with periodic mesoporous organosilicas (PMOs) is expected to enhance stability and prevent the flocculation of nZIFs. In this study, ZIF‐7 nanomaterials and fluorescent organosilicas (FITC−APTES) were effectively introduced into PMO nanoparticles, and the resulting product was named ZIF‐7@PMO. The surface functionalization with the PMO nanoparticles enhanced the chemical stability of ZIF‐7 nanoparticles in ethanol. The study examined the impact of temperature on the synthesis of ZIF‐7@PMO and found that low temperatures were more conducive to the encapsulation of ZIF‐7 nanoparticles and fluorescent organosilica, as well as pore size retention. Moreover, the drug storage capacity of the ZIF‐7@PMO nanoparticles was evaluated via their loading and release of 5‐FU. The results revealed that the ZIF‐7@PMO nanoparticles could adsorb 5‐FU with a loading capacity of 100–140 mg g−1 for 24 h. ZIF‐7@PMO released half of 5‐FU amount within 8 h before releasing a maximum of 75 % within 3 days. Therefore, the fluorescent ZIF‐7@PMO nanoparticles could be a potential drug carrier in the field of controlled drug delivery.
Phosphate Esters: New Coating Materials for a Sustainable Release Paper.
Authors: Abenghal Lahbib , Brouillette François 
Published: May 2024

AbstractPaper manufacturers have long used silicone as the coating agent for release liners. However, silicone‐based release paper is very difficult to recycle due to covalent bonds between silicone and fibers. The most suitable solution to overcome this problem is to use alternative coating materials with adequate release properties, provided that they can be easily repulped in typical paper recycling facilities. We proposed a coating agent composed of phosphate esters and dimethylacetamide in order to manufacture a recyclable and efficient release paper. Analyses carried out on coated sheets showed that phosphate esters allowed the formation of a surface with adequate release properties (low peeling force and surface free energy). In addition, the residual adhesion values obtained with phosphate esters confirmed that they are well anchored on the backing paper surface, thus limiting the mass transfer to the adhesive tape.
One‐Step Synthesis of Phase‐Controlled Co2P Nanoparticles as an Electrocatalyst for Hydrogen Evolution Reaction
Authors: Kumaravel Sabarish , Joseph Sahaya Anand T. , Saravanan P. , Haldorai Yuvaraj , Kumar Ramasamy Thangavel Rajendra 
Published: May 2024

AbstractCobalt phosphides have been investigated as potentially useful electrocatalysts for accelerating hydrogen evolution. Cobalt phosphide electrocatalysts are synthesized in a single step at varied phosphating temperatures (350, 400, 450 °C) via the gas phase approach. Synthesized at a phosphating temperature of 350 °C, Co2P (CP‐350) transforms into a mixed phase that contains both Co2P and CoP (CP‐400 and CP‐450) as the phosphating temperature goes up which is confirmed by XRD. CP‐350, CP‐400, and CP‐450 exhibited overpotentials of 181, 270, and 293 mV respectively with Tafel slopes of 112, 146, and 175 mV/dec. In contrast to CP‐400 and CP‐450, CP‐350 revealed superior hydrogen evolution reaction (HER) performance and stability for up to 12 h due to its pure phase (Co2P), high surface area (151 m2/g), and high electrochemical surface area (7.02 cm2) with low charge transfer resistance. According to our work, changing the phase and active surface area of transition metal phosphide catalysts can greatly increase their HER catalytic efficiency.
Transition‐Metal Free Arylation of Therapeutically Important Heterocycles
Authors: Priyadarshan Ambarish , Tripathi Garima , Venneti Naresh Murty , Kishor Kaushal , Singh Anil Kumar , Kumar Abhijeet 
Published: May 2024

AbstractThe transition‐metal‐free synthesis of organic compounds especially heterocycles is in resonance with one of the twelve principles proposed by Prof. Paul Anastas in his renowned work towards the sustainable development of green chemistry. Traditional‐metal‐catalyzed reactions often involve expensive or toxic metal catalysts, and there is a growing interest in developing more sustainable and environmentally friendly methods. The arylation of heterocycles is an important area of research in organic chemistry, particularly in the synthesis of biologically active compounds and pharmaceuticals. Arylation of heterocycles at different positions enhances the potency and stability of biologically and pharmaceutically important scaffolds. In this review, an overview of the synthetic protocols developed for the arylation of a variety of heterocyclic compounds including, pyrroles, pyridines, thiophene, indole, oxindoles, purines, xanthene, etc. has been described.