Minor Changes Research Articles

Computational study of van der Waals interaction at the sub‐nanometer scale and its influence on the molecular behavior under confinement conditions in graphene‐2D h‐BN heterostructure

AbstractThe atomistic features of the van der Waals interaction between graphene and 2D h‐BN layer are investigated with and without doping using density functional theory. It is computationally shown, how different types of 2D materials can form heterojunctions with each other without the need for close lattice matching if the atomic species are neighbors in the periodic table. H2, N2, and O2 are introduced as the dopants separately to investigate the van der Waals interaction at the sub‐nanometer scale and its influence on the molecules and interlayer coupling. The geometrical forms and formation energies of differently bonded molecules and atoms immersed in van der Waals forces in the heterostructure are predicted accurately. The spatial dependence of the van der Waals energy between graphene and h‐BN and its effect on the confined molecule/atoms is well brought out in the present investigation. The weak van der Waals forces between graphene and h‐BN do introduce minor changes at the nanoscale but maintain the original band structure which is dominated by graphene. The present graphene and 2D h‐BN van der Waals heterostructure, with enhanced features, offers a unique opportunity to fabricate new materials with different properties. They will become the building blocks in engineering new functional materials.

Stability of temocillin in outpatient parenteral antimicrobial therapy: is it a real option?

Temocillin is an interesting alternative to carbapenems for susceptible Enterobacteriaceae. Although its use in outpatient parenteral antimicrobial therapy (OPAT) programmes has generated interest, this has been hampered by the lack of stability data. The purpose of the present study was to evaluate the physical and chemical stability of temocillin at the recommended dose for its use in OPAT programmes, contained in polypropylene infusion bags or polyisoprene elastomeric devices at different temperatures, and to describe a novel LC-MS/MS developed for the quantification of temocillin. Temocillin daily dose (6 g) was diluted in 500 mL of 0.9% sodium chloride to obtain a final concentration of 12 g/L. This solution was stored at 4°C, 25°C, 32°C and 37°C for 72 h, both in polypropylene infusion bags and in polyisoprene elastomeric pumps. Physical and chemical stability were evaluated during 72 h after manufacturing. Solutions were considered stable if colour, clearness and pH remained unchanged and if the percentage of intact drug was ≥90%. Temocillin attained the chemical stability criterion of ≥90% of the original concentration for the whole experiment in both devices at 4°C, 25°C and 32°C. At 37°C, temocillin was stable for 24 h but its concentration dropped below 90% from that timepoint. No precipitation occurred and minor colour changes were observed. Temocillin is stable under OPAT conditions and it would be an appropriate candidate for the treatment of patients who can be discharged to complete therapy in an OPAT programme. For this study, an LC-MS/MS method was developed.

Impact of wet-dry cycles on enhanced rock weathering of brucite, wollastonite, serpentinite and kimberlite: Implications for carbon verification

Enhanced rock weathering is a proposed CO2 removal strategy for mitigating climate change; its implementation can be facilitated by improving carbon verification methods. In this study, weathering experiments exposed brucite, wollastonite skarn, serpentinite, and kimberlite residues (Venetia Diamond Mine, South Africa), to wetting and drying cycles (4/day) for 1 yr to elucidate reaction pathways and rates while evaluating carbon verification tools, including mineral quantification, total inorganic carbon (TIC), and stable and radiogenic carbon isotopes. Two primary reaction pathways were identified: A) silicate and hydroxide dissolution leading to carbonate precipitation (desirable), and B) dissolution and reprecipitation of carbonates (undesirable). The kimberlite residues, containing serpentine (19–33 wt%) and calcite (4–5 wt%), experienced variable and minor changes in total inorganic carbon. The δ13C and δ18O values of the carbonate minerals approached those expected for atmospheric-derived CO2 and are best explained by the exchange of carbonate CO2 with atmospheric CO2 (pathway A) as opposed to net CO2 sequestration. In contrast, the reaction of brucite (1.22% to 5.98%) and wollastonite skarn (0.22% to 1.01%) with atmospheric CO2 was substantial, as indicated by the increases in TIC (pathway B) yet decreases in δ13C values were inconsistent with the incorporation of atmospheric CO2 as a result of kinetic isotope fractionation due to carbonation being CO2 supply limited. The pulverized serpentinite experience insufficient carbonation to be detected by TIC. Unweathered (blue ground) and naturally weathered (yellow ground) kimberlite from the Voorspoed Diamond Mine, South Africa were compared to kimberlite residues used in experiments. Yellow ground contained twice the TIC content compared to blue ground whereas quantitative scanning electron microscopy revealed calcite veinlets that are characteristic of secondary mineralization. While the blue and yellow ground samples were essentially radiocarbon dead (0.03 and 0.05 F14C, respectively), substantial modern carbon was incorporated into the kimberlite (up to +0.27 F14C; CO2 exchange), brucite (+0.55 F14C), and wollastonite skarn (+0.53 F14C; CO2 sequestration) powders during weathering experiments. Although stable and radiogenic carbon isotopes have been used to verify the mineralization of atmospheric CO2, these methods are affected by CO2 exchange and kinetic fractionation effects during weathering that can be misleading and, thus, should not be relied on as sole methods for carbon verification.

Phycocyanobilin is a new binding partner of human alpha-2-macroglobulin that protects the protein against oxidative stress

Under simulated physiological conditions, this study investigates the interaction between nutraceutical phycocyanobilin (PCB) and the universal anti-protease protein human alpha-2-macroglobulin (α2M). Extensive molecular docking analyses on multiple α2M conformations, spectroscopic techniques, and α2M activity assays were utilized to examine the complex formation. The results revealed that for every protein conformation, two high energy binding sites exist: the first, conformationally independent, at the interface region between two monomer chains and the second, conformationally dependent, in the pocket composed of amino acids from four distinct domains (TED, RBD, CUB, and MG2) of the single protein chain. Spectrofluorimetric measurements indicated a moderate affinity between α2M and PCB with a moderately high binding constant of 6.3 × 105 M−1 at 25 °C. The binding of PCB to α2M resulted in minor changes in the secondary structure content of α2M. Furthermore, PCB protected α2M from oxidation and preserved its anti-protease activity in the oxidative environment. These findings suggest that PCB binding could indirectly impact the body’s response to oxidative stress by influencing α2M's role in controlling enzyme activity during the inflammatory process. Communicated by Ramaswamy H. Sarma

Comprehensive assessment of chrononutrition behaviors among nationally representative adults: Insights from National Health and Nutrition Examination Survey (NHANES) data

Aligning the time of food intake, i.e., chrononutrition, with the body's circadian clock can have a significant impact on overall health, particularly cardiometabolic health. However, there is a lack of population-based information on various chrononutrition behaviors in the United States, where the prevalence of obesity is high. Our primary aim was to characterize chrononutrition behaviors and their 15-year trends among US adults. We also explored the temporal associations between trends in chrononutrition behaviors and trends in obesity. We utilized data from 8 cycles (2003-2018) of the National Health and Nutrition Examination Survey (NHANES) on 34,470 adults (age >19 years). The clock time of food/beverage consumption was extracted from two 24-h food recalls. The following chrononutrition behaviors were defined: 1) The clock time of the first, last, and midpoint (when 50% of total daily energy was consumed) of food/beverage intake; 2) Eating window (the time elapsed between the first and last intake); 3) Late-night eating (food intake between 21:00-23:59); and 4) Eating frequency. Survey-weighted % or mean±standard error (SE) was used to demonstrate chrononutrition behaviors and survey-weighted regression models were utilized to evaluate trends in chrononutrition behaviors, BMI, and obesity over a 15-year period. Thirty five percent of US adults had long eating windows lasting 13h or more, with 59% of individuals consuming calories after 9 PM. The patterns of food intake among American adults were skewed, with the highest proportion of their daily energy intake (36%) being consumed during dinner meals. Notable differences in chrononutrition behaviors observed among different population subgroups. Young adults and men had longer eating windows with a higher prevalence of late-night eating compared to their age- and sex-counterparts. Black individuals had shorter eating periods due to delayed breakfast, the highest proportion (68%) of late-night eating, and obtained a greater amount of energy intake from snacks compared to other racial/ethnic groups. Over the 15-year span, there were only minor changes in a few aspects of chrononutrition behaviors, including 2% reduction in the time of eating window, while most other meal timing behaviors remained unchanged. Trends in chrononutrition behaviors were disproportionately smaller than the trends in obesity rates. US adults persistently consume higher amounts of daily energy intake later in the day. Despite calls for Americans to shift intake to earlier parts of the day, this study shows that there is little change in the overall population over the 15-year period reviewed.

Optimization of data packet encryption algorithm in network link transport layer

ABSTRACT With the rapid development of information technology, huge data information is exchanged every moment in various types of networks, which contain information such as commercial secrets and personal privacy, and data security has a great impact on people’s lives. To address the issues of low efficiency and poor security in network link transmission layer database security encryption systems, a new system is studied and designed to strengthen the protection of data information from both hardware and software aspects. Then, a discrete chaotic system is introduced to ensure the stability of the dynamic grouping encryption algorithm. Finally, trajectory loop rotation is used to obtain address clusters using the discrete chaotic system, and dual address loop rotation is used to achieve the variability of the dynamic grouping algorithm. The experiment shows that for different file sizes, the encryption speed of the Dynamic Packet Encryption Optimization (DPEO) algorithm is stable between 5.84 and 5.98 mb/s. And after minor changes in the key, the NPCR of the ciphertext obtained by the DPEO algorithm exceeds 99.5%. In addition, its operation efficiency is excellent, reaching the stable entropy value in only 0. 52 s. In summary, the DPEO algorithm in the network link transport layer database security encryption system can combine high efficiency and excellent security performance.

Correlation between Targeted qPCR Assays and Untargeted DNA Shotgun Metagenomic Sequencing for Assessing the Fecal Microbiota in Dogs.

DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs (n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI < 0 with any targeted taxa outside the reference interval, RI), mild-moderate changes (R = 0.24, 0 < DI < 2), and significant dysbiosis (R = 0.54, 0.73, and 0.91 for DI > 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing in dogs.

A self-management psychoeducational eHealth program to support and empower people with advanced cancer and their family caregivers: Development using the scrum methodology

BackgroundeHealth programs could be a flexible and scalable resource to support and empower people with advanced cancer and their family caregivers. A face-to-face intervention that has demonstrated effectiveness is the “FOCUS” program, developed and tested in the USA. Recently the FOCUS program was translated and adapted to the European context as part of an international study in six European countries, resulting in the “FOCUS+” program. FOCUS+ served as the basis for development of the web-based iFOCUS program. ObjectiveWe aim to (1) describe the development process of the iFOCUS program, (2) outline the challenges we encountered and how they were overcome, and (3) present findings regarding the acceptability and usability of iFOCUS. MethodsWe used the four phased agile Scrum methodology to develop iFOCUS and applied set timeframes of rapid program development and evaluation (sprints). Five teams were involved in the development i.e. a core development group, a web development team, an international consortium, audio-visual experts, and potential end-users. ResultsDevelopment followed seven steps, integrated across the four phases of Scrum: (1) concept design, (2) development of mock-ups, (3) Feedback from the international consortium, (4) technical development of iFOCUS, (5) creating versions for the six participating countries, (6) preliminary testing of iFOCUS and (7) implementing the final version in a randomized controlled trial. User testing included 42 participants (twenty patient-family caregiver dyads and two bereaved family caregivers) who reviewed the iFOCUS program. Users found the iFOCUS program to be acceptable and usable. Feedback mainly focused on text size and fonts. Minor changes to the content, tailoring, and program flow were required. During development we encountered program specific and general challenges. Using the Scrum methodology facilitated iterative development to address these issues. For some challenges, such as tailoring, we had to make pragmatic choices due to time and resource limitations. Conclusions/discussionThe development of a tailored, self-managed psychoeducational eHealth program for people with advanced cancer and their family caregivers is an intense process and requires pragmatic choices. By keeping the emphasis on the target population during development, no specific remarks pertaining to advanced cancer were identified. Some challenges we encountered are common to eHealth development, others were related to program specific requirements. Using the Scrum methodology allows teams to efficiently collaborate during program development and increases the flexibility of the development process. Interpersonal contact between research staff and potential end-users is recommended during and after the development of eHealth programs.

Novel Strategy for Optimizing the Antibacterial Activity of Psidium guajava Against Clinical Isolates of Escherichia coli, Staphylococcus aureus, Salmonella spp., and Streptococcus spp.

The development of a new antibiotic is a challenging task, with an estimated failure rate of 95%. Minor changes in the chemical structure of a drug, such as stereochemistry, geometry, or functional group modifications, can significantly impact its medicinal activity. In this study, we aim to devise novel strategies for optimizing the antimicrobial properties of guava leaf extract through simple reactions, either by self-reaction or combination reactions with a reagent, drug, or different plant extract. Fourier transform infrared spectroscopy analysis revealed conjugation and formation of new functional groups in the prepared sample of Guava Guava (GG) and Guava Aspirin Guava (GAG), which were further confirmed by weight analysis. The results demonstrated that the antimicrobial activity of medicinal plants can be improved or optimized through simple reactions, such as combining the plant extract with a non-antimicrobial drug like aspirins or adding a small volume of concentrated sulfuric acid to the plant extract by heating at a temperature range of 100 &amp;ndash; 110&amp;deg;C. Among the two combinatory methods used, GG exhibited better performance in inhibiting the growth of all tested bacterial strains at a concentration of 0.1 mg/mL compared to GAG at the same concentration, which inhibited the growth of only two bacterial strains: Escherichia coli and Streptococcus spp. These methods can be further explored and applied in various studies, including antifungal, anti-inflammatory, antiviral, and anticancer research, leveraging the availability and diverse range of natural products found in medicinal plants.

Fruit ripening under heat stress: The intriguing role of ethylene-mediated signaling

Crop production is significantly influenced by climate, and even minor climate changes can have a substantial impact on crop yields. Rising temperature due to climate change can lead to heat stress (HS) in plants, which not only hinders plant growth and development but also result in significant losses in crop yields. To cope with the different stresses including HS, plants have evolved a variety of adaptive mechanisms. In response to these stresses, phytohormones play a crucial role by generating endogenous signals that regulate the plant’s defensive response. Among these, Ethylene (ET), a key phytohormone, stands out as a major regulator of stress responses in plants and regulates many plant traits, which are critical for crop productivity and nutritional quality. ET is also known as a ripening hormone for decades in climacteric fruit and many studies are available deciphering the function of different ET biosynthesis and signaling components in the ripening process. Recent studies suggest that HS significantly affects fruit quality traits and perturbs fruit ripening by altering the regulation of many ethylene biosynthesis and signaling genes resulting in substantial loss of fruit yield, quality, and postharvest stability. Despite the significant progress in this field in recent years the interplay between ET, ripening, and HS is elusive. In this review, we summarized the recent advances and current understanding of ET in regulating the ripening process under HS and explored their crosstalk at physiological and molecular levels to shed light on intricate relationships

Best practices in assessing cardiac protein O-GlcNAcylation by immunoblot.

The modification of serine and threonine amino acids of proteins by O-linked N-acetylglucosamine (O-GlcNAc) regulates the activity, stability, function, and subcellular localization of proteins. Dysregulation of O-GlcNAc homeostasis is well established as a hallmark of various cardiac diseases, including cardiac hypertrophy, heart failure, complications associated with diabetes, and responses to acute injuries such as oxidative stress and ischemia-reperfusion. Given the limited availability of site-specific O-GlcNAc antibodies, studies of changes in O-GlcNAcylation in the heart frequently use pan-O-GlcNAc antibodies for semiquantitative evaluation of overall O-GlcNAc levels. However, there is a high degree of variability in many published cardiac O-GlcNAc blots. For example, many blots often have regions that lack O-GlcNAc positive staining of proteins either below 50 or above 100 kDa. In some O-GlcNAc blots, only a few protein bands are detected, while in others, intense bands around 75 kDa dominate the gel due to nonspecific IgM band staining, making it difficult to visualize less intense bands. Therefore, the goal of this study was to develop a modifiable protocol that optimizes O-GlcNAc positive banding of proteins in cardiac tissue extracts. We showed that O-GlcNAc blots using CTD110.6 antibody of proteins ranging from <30 to ∼450 kDa could be obtained while also limiting nonspecific staining. We also show that some myofilament proteins are recognized by the CTD110.6 antibody. Therefore, by protocol optimization using the widely available CTD110.6 antibody, we found that it is possible to obtain pan-O-GlcNAc blots of cardiac tissue, which minimizes common limitations associated with this technique.NEW & NOTEWORTHY The post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) is recognized as mediating cardiac pathophysiology. However, there is considerable variability in the quality of O-GlcNAc immunoblots used to evaluate changes in cardiac O-GlcNAc levels. Here we show that with relatively minor changes to a commonly used protocol it is possible to minimize the intensity of nonspecific bands while also reproducibly generating O-GlcNAc immunoblots covering a range of molecular weights from <30 to ∼450 kDa.

Non-surgical rhinoplasty using polydioxanone threads.

To demonstrate the effects of PDO threads non-surgical rhinoplasty on patients' quality of life (using FACE-Q Scale) and first impression assessments. This is a prospective cohort study of 10 adult patients who sought non surgical rhinoplasty to improve tip rotation or reduce the appearance of a dorsal hump. All patients fulfilled the study's enrollment criteria. Prior to treatment, patients completed pre-treatment FACE-Q surveys and pre-treatment photos were obtained. Each patient was treated with the appropriate size and number of PDO threads necessary to achieve optimal correction result (OCR). Two weeks after treatment, the patient completed posttreatment FACE-Q surveys and posttreatment photos were obtained and analyzed. First impression surveys were created using pre- and posttreatment photos, and the survey was completed by 146 blinded evaluators. There was statistically significant improvement in the FACE-Q scores for social function (p = 0.02), psychological function (p = 0.0009) and satisfaction with nose (p = 0.0001). There was significant reduction in scores for appearance related psychosocial distress (p = 0.03). For the first impression surveys, there was a statistically significant improvement (p = 0.029) in the attractiveness scale posttreatment. Although not statistically significant, there was reduction of the dorsal hump (p = 0.15) and increase in the nasolabial angle (p = 0.48) and Goode's ratio (p = 0.16). There were no major adverse events or complications. This study shows that the PDO threads alone can be used safely to achieve minor nasal changes especially in tip rotation and appearance of dorsal hump, to improve patients' quality of life, and perceived attractiveness of treated patients.

Integrating Media Literacy Across the Content Areas

AbstractTeachers must first acquire the necessary media literacy skills, strategies, dispositions, and pedagogy to impactfully integrate media literacy into their instruction. Furthermore, previous studies have suggested designing curricular resources as an effective form of media literacy professional learning. This case study examined how high school teachers of different content areas integrate media literacy into their instruction while participating in an online professional development course and how high school teachers applied the content from a media literacy online professional development course to design media literacy instruction. Findings indicated teachers made minor changes to their previous instructional practice, which indicated that participating in the online course led them to think about media literacy integration in new ways. Additionally, teachers applied the online professional development content by using media to build background knowledge, offering explicit media literacy strategy instruction and support, promoting independent practice at the intersection of content curricula and media literacy, and assigning media production to demonstrate content knowledge. Recommendations include equipping teachers with media literacy background knowledge, examining instruction stemming from media literacy professional development, and empowering teachers to design media literacy instruction through critical lenses.

Cross-Cultural Adaptation, Reliability, and Validity Tests of the Thai Version of the Manchester-Oxford Foot Questionnaire in Individuals with Chronic Foot Pain

Objective: To adapt cross-culturally and examine the reliability and validity of the Thai version of MOXFQ (Thai-MOXFQ) among individuals with chronic foot pain. Material and Methods: The Thai-MOXFQ was successfully adapted cross-culturally from the original version with minor changes according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. Its reliability and construct validity were then investigated in individuals with chronic foot pain. The test-retest reliability was evaluated among 30 participants by calculating the intraclass correlation coefficient (ICC 3,1). Meanwhile, the internal consistency of the Thai-MOXFQ was studied in 100 participants by computing Cronbach’s alpha. Additionally, the construct validity was analyzed via Spearman’s rank correlation analysis to determine the relationship between the Thai-MOXFQ, Foot and Ankle Ability Measure (FAAM), 36-item Short-Form Health Survey (SF-36), and Visual Analogue Scale (VAS). Results: The Thai-MOXFQ demonstrated a good level of test-retest reliability (ICC of 0.763 to 0.885) and an acceptable level of internal consistency (Cronbach’s alpha of 0.738 to 0.871) when used in individuals with chronic foot pain. Moreover, the Thai-MOXFQ was shown to have moderate to strong relationships with FAAM, SF-36, and VAS (p-value&lt;0.05, Spearman rank correlation coefficients of 0.543 to 0.711). Furthermore, the results of the construct validity of the Thai version were in line with the original English and other translated versions. Conclusion: The Thai-MOXFQ is a reliable and valid, foot-specific, patient-reported outcome measurement (PROM) for assessing outcomes in individuals with chronic foot pain.

In silico prediction of siRNA to silence the SARS-CoV-2 omicron variant targeting BA.4, BA.5, BQ.1, BQ1.1. and XBB: an alternative to traditional therapeutics

BackgroundAfter the first infection in December 2019, the mutating strains of SARS-CoV2 have already affected a lot of healthy people around the world. But situations have not been as devastating as before the first pandemic of the omicron strains of SARS-CoV2. As of January 2023, five more Omicron offshoots, BA.4, BA.5, B.Q.1, B.Q.1.1 and XBB are now proliferating worldwide. Perhaps there are more variants already dormant that require only minor changes to resurrect. So, this study was conducted with a view to halting the infection afterwards. The spike protein found on the virus outer membrane is essential for viral attachment to host cells, thus making it an attractive target for vaccine, drug, or any other therapeutic development. Small interfering RNAs (siRNAs) are now being used as a potential treatment for various genetic conditions or as antiviral or antibacterial therapeutics. Thus, in this study, we looked at spike protein to see if any potential siRNAs could be discovered from it.ResultsIn this study, by approaching several computational assays (e.g., GC content, free energy of binding, free energy of folding, RNA–RNA binding, heat capacity, concentration plot, validation, and finally molecular docking analysis), we concluded that two siRNAs could be effective to silence the spike protein of the omicron variant. So, these siRNAs could be a potential target for therapeutic development against the SARS-CoV2 virus by silencing the spike protein of this virus.ConclusionWe believe our research lays the groundwork for the development of effective therapies at the genome level and might be used to develop chemically produced siRNA molecules as an antiviral drug against SARS-CoV2 virus infection.Graphical abstract

Optimization of dissolved hydrogen concentration for mitigating corrosive conditions of pressurized water reactor primary coolant under irradiation (1) evaluation of water radiolysis

ABSTRACT A major subject for evaluating the corrosive conditions in the pressurized water reactor (PWR) primary coolant is to determine the optimal hydrogen concentration for mitigating primary water stress corrosion cracking (PWSCC) without adverse effects on major structural materials. An analytical method combining water radiolysis and electrochemical corrosion potential (ECP) analyses was proposed for evaluating the corrosive conditions in PWR primary coolant. These procedures originally developed for boiling water reactors (BWRs) were successfully extended to PWRs with different water chemistry parameters, including pH, temperature, and radiation qualities, after minor changes in the original procedures and major input parameters, such as the inclusion of the effects of alpha radiolysis and Li+ (Na+) and H+ effects for the anodic polarization curve. This study discusses the results of water radiolysis analysis for PWR primary coolant, and the characteristic behavior of hydrogen peroxide (H2O2) as a function of hydrogen inlet concentrations in PWR primary coolant conditions (higher pH and α-ray irradiation). A possible reaction scheme involving eaq – was proposed for H2O2 suppression under alkaline conditions. The corrosive conditions were discussed in the following publication, using ECP as the major index for PWR corrosive conditions.

Can Free Energy Perturbation Simulations Coupled with Replica-Exchange Molecular Dynamics Study Ligands with Distributed Binding Sites?

Free energy perturbation coupled with replica exchange with solute tempering (FEP/REST) offers a rigorous approach to compute relative free energy changes for ligands. To determine the applicability of FEP/REST for the ligands with distributed binding poses, we considered two alchemical transformations involving three putative inhibitors I0, I1, and I2 of the Venezuelan equine encephalitis virus nuclear localization signal sequence binding to the importin-α (impα) transporter protein. I0 → I1 and I0 → I2 transformations, respectively, increase or decrease the polarity of the parent molecule. Our objective was three-fold─(i) to verify FEP/REST technical performance and convergence, (ii) to estimate changes in binding free energy ΔΔG, and (iii) to determine the utility of FEP/REST simulations for conformational binding analysis. Our results are as follows. First, our FEP/REST implementation properly follows FEP/REST formalism and produces converged ΔΔG estimates. Due to ligand inherent unbinding, the better FEP/REST strategy lies in performing multiple independent trajectories rather than extending their length. Second, I0 → I1 and I0 → I2 transformations result in overall minor changes in inhibitor binding free energy, slightly strengthening the affinity of I1 and weakening that of I2. Electrostatic interactions dominate binding interactions, determining the enthalpic changes. The two transformations cause opposite entropic changes, which ultimately govern binding affinities. Importantly, we confirm the validity of FEP/REST free energy estimates by comparing them with our previous REST simulations, directly probing binding of three ligands to impα. Third, we established that FEP/REST simulations can sample binding ensembles of ligands. Thus, FEP/REST can be applied (i) to study the energetics of the ligand binding without defined poses and showing minor differences in affinities |ΔΔG| ≲ 0.5 kcal/mol and (ii) to collect ligand binding conformational ensembles.

Structural tailoring of p-terphenyl scaffold: Towards advanced plastic scintillator

A comprehensive series of fifteen p-terphenyl derivatives has been designed and prepared using facile synthetic approaches (Suzuki-Miyaura and Friedel-Crafts reactions). Various alkyl, alkoxy or trifluoromethyl groups have been attached to p-terphenyl to gain both symmetrical and unsymmetrical derivatives. Symmetry breaking accounts for improved solubility of mono-substituted derivatives. Thermal analysis revealed a reversible formation of several crystalline phases and very high thermal robustness. Reduction and oxidation of the parent p-terphenyl π-system affected by the electronic and steric effects of the substituents were recorded by cyclic voltammetry. When compared to parent p-terphenyl, a narrowed HOMO–LUMO gap has been measured/calculated for most of the prepared derivatives. The absorption and emission maxima ranged from 286 to 293 and 341–360 nm, respectively. The latter is affected by the substitution more significantly, the fluorescence quantum yields are within the range of 0.52–0.75. Stokes shifts up to 6400 cm−1 were measured pointing to a large structural rearrangement (planarization) upon excitation. PTP derivatives were further used as primary and secondary luminophores for scintillation. 4-Methyl-p-terphenyl proved to be a superior luminophore with a straightforward synthesis, easy isolation, large solubility and excellent luminescence characteristic. Based on this derivative, a plastic scintillator has been manufactured that showed superior performance as compared to standard and widely used unsubstituted p-terphenyl. Thus, a relatively minor structural change (appending single methyl group) altered scintillation properties significantly.

Kinetics and Mechanism of Azole n-π*-Catalyzed Amine Acylation.

Azole anions are highly competent in the activation of weak acyl donors, but, unlike neutral (aprotic) Lewis bases, are not yet widely applied as acylation catalysts. Using a combination of in situ and stopped-flow 1H/19F NMR spectroscopy, kinetics, isotopic labeling, 1H DOSY, and electronic structure calculations, we have investigated azole-catalyzed aminolysis of p-fluorophenyl acetate. The global kinetics have been elucidated under four sets of conditions, and the key elementary steps underpinning catalysis deconvoluted using a range of intermediates and transition state probes. While all evidence points to an overarching mechanism involving n-π* catalysis via N-acylated azole intermediates, a diverse array of kinetic regimes emerges from this framework. Even seemingly minor changes to the solvent, auxiliary base, or azole catalyst can elicit profound changes in the temporal evolution, thermal sensitivity, and progressive inhibition of catalysis. These observations can only be rationalized by taking a holistic view of the mechanism and a set of limiting regimes for the kinetics. Overall, the analysis of 18 azole catalysts spanning nearly 10 orders of magnitude in acidity highlights the pitfall of pursuing ever more nucleophilic catalysts without regard for catalyst speciation.

Silicon Incorporation Reduces the Reactivity of Short-range Ordered Aluminosilicates Toward Organic Acids

The structure and composition of short-range ordered aluminosilicates (SROAS) may control their affinity for organic acids with potential effects on soil organic matter stabilization. Adsorption mechanisms of model organic acids were studied to resolve the effect of Si incorporation. Adsorption of oxalic, salicylic, and octanoic acid on Al-rich (Al:Si = 3.7) and Si-rich (Al:Si = 1.4) SROAS was quantified by analyses of dissolved organic carbon using catalytic high-temperature combustion. The initial pH of 5 and 6.5 increased to 6.3–8.2 during adsorption of oxalic and salicylic acid, demonstrating hydroxyl release by ligand exchange. Minor changes in pH indicated weak interactions of octanoic acid with both SROAS. Adsorbates were characterized by Fourier-transform infrared spectroscopy. Asymmetric stretching of carboxylate groups at 1720 and 1700 cm–1, and symmetric stretching at 1430 cm–1 evinced the formation of chelate complexes for oxalic acid. An absorption band centered at 1545 cm–1 indicated partial inner-sphere binding of salicylic acid on both SROAS. Silicon-rich SROAS adsorbed 80–90% less than Al-rich SROAS, suggesting that adsorption of oxalic and salicylic acid was controlled by surface aluminol groups. Fast kinetics of oxalate adsorption on Al sites was studied by a conductivity-based stopped-flow technique. Ligand exchange proceeded at a rate constant of 3.5 s–1 (25°C), similar to solute Al complexation, with an activation energy of up to 34.1 kJ mol–1. A slow process with a rate constant of 0.13 s–1 (25°C) was attributed to diffusion of oxalate at the surface or into SROAS particles. As supported by structural characterization of Si-rich SROAS, the much lower susceptibility of Si-rich SROAS to ligand exchange relates to Al speciation. The formation of tetrahedral Al precludes its complexation by carboxyl groups.