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Efficient sampling of free energy landscapes with functions in Sobolev spaces

Molecular simulations of biological and physical phenomena generally involve sampling complicated, rough energy landscapes characterized by multiple local minima. In this work, we introduce a new family of methods for advanced sampling that draw inspiration from functional representations used in machine learning and approximation theory. As shown here, such representations are particularly well suited for learning free energies using artificial neural networks. As a system evolves through phase space, the proposed methods gradually build a model for the free energy as a function of one or more collective variables, from both the frequency of visits to distinct states and generalized force estimates corresponding to such states. Implementation of the methods is relatively simple and, more importantly, for the representative examples considered in this work, they provide computational efficiency gains of up to several orders of magnitude over other widely used simulation techniques.

Ethiopian antimicrobial consumption trends in human health sector: A surveillance report 2020–2022

Background Antimicrobial resistance (AMR) poses a severe global health threat, driven by the overuse and misuse of antimicrobials across the human, agricultural, and veterinary sectors. To combat this, global and national AMR prevention and containment strategies have been implemented, necessitating continuous monitoring of antimicrobial consumption (AMC) as an integral part of antimicrobial stewardship interventions. Objective This study aims to assess and analyze trends in AMC in Ethiopia from 2020 to 2022, with the goal of informing national and sub-national strategies to combat AMR. Methods A three-year AMC surveillance was conducted from 2020 to 2022. Data on locally manufactured and imported antimicrobials were collected from local manufacturers and Ethiopian Food and Drug Authority (EFDA)-regulated ports of entry. AMC was analyzed using the WHO GLASS AMC tool, with antimicrobials categorized using the WHO Anatomical Therapeutic Chemical (ATC) classification system. Consumption was measured in Defined Daily Doses (DDDs) and DDD per 1,000 inhabitants per day (DID), normalized using population estimates from the World Population Prospects for Ethiopia. Results The total AMC in Ethiopia increased from 432 million DDDs in 2020 to 485 million DDDs in 2022. The DID rose from 10.63 in 2020 to 11.34 in 2022. Antibacterials dominated consumption, comprising 98.87% in 2020, 95.96% in 2021, and 99.79% in 2022. Penicillins (J01C) and quinolones (J01M) were the most consumed antimicrobials. As per the Ethiopian AWaRe classification, the majority of antibacterial agents consumed were in the Access group, accounting for 71.14% in 2020, 70.65% in 2021, and 74.2% in 2022. Oral formulations consistently made up over 87% of the total consumption each year. Reliance on imported antimicrobials remained high, with imports comprising 64.76% in 2020 and 74.47% in 2022. Conclusion The increasing trend in AMC in Ethiopia from 2020 to 2022 underscores the urgent need to establish and strengthen national, sub-national, and facility-level surveillance and reporting systems to better monitor and ensure rational antimicrobial use.

FDEM numerical simulation of size effect on mechanical properties of basalts with hidden microcracks

Epitaxial thin films of pyrochlore iridates: A forward looking approach

Topological quantum materials that show strongly correlated electrons as well as topological order, for which spin–orbit coupling is a key ingredient, exhibit novel states of matter. One such example is the family of pyrochlore iridates, featuring strong spin–orbital coupling, strong electron interactions, as well as geometric frustration, making them an ideal platform to study novel topological phases. High-quality epitaxial pyrochlore iridate films, although challenging to produce, provide a pathway to explore unconventional behaviors and unravel the intrinsic properties of these largely unexplored materials. Additionally, designing interfaces with specific properties is crucial to creating multilayered devices that can achieve significant technological breakthroughs using topological states of these materials. This article reviews experimental research on epitaxial pyrochlore iridate thin films, discussing evidence of topological phases found in them. Future research directions are outlined, which include exploring the rich tunability offered by chemical doping, especially when combined with the design of epitaxial heterostructures.

Pulsed discharge jet laser spectroscopy of the stibino (SbH2) free radical: Hyperfine and isotopic structure in the high-resolution electronic spectrum

The Ã2A1–X̃2B1 0-0 bands of the overlapping LIF spectra of 121SbH2 and 123SbH2 have been recorded at high resolution under supersonic expansion conditions. The radicals were made by a pulsed electric discharge through a dilute mixture of SbH3 in high pressure argon at the exit of a pulsed molecular beam valve. The Sb isotopic lines, magnetic hyperfine structure, and large spin-rotation splittings have been assigned in the spectra. The transitions of the two isotopologues were fitted independently, and the rotational constants were used to obtain the following zero-point effective molecular structures: r″ = 1.7203(1) Å, θ″ = 90.370(4)°; r′ = 1.6915(4) Å and θ′ = 120.80(2)°. The fitted molecular constants have been validated using isotope relations and by comparison with theoretical formulas. The T0 antimony isotope splitting of SbH2 is only 0.0098 cm−1.

Molecular screening and dynamics simulation reveal potential phytocompounds in Swertia chirayita targeting the UspA1 protein of Moraxella catarrhalis for COPD therapy

Chronic obstructive pulmonary disease (COPD) is a global health burden, with Moraxella catarrhalis significantly contributing to acute exacerbations and increased healthcare challenges. This study aimed to identify potential drug candidates in Swertia chirayita, a traditional Himalayan medicinal plant, demonstrating efficacy against the ubiquitous surface protein A1 (UspA1) of M. catarrhalis through an in-silico computational approach. The three-dimensional structures of 46 phytocompounds of S. chirayita were retrieved from the IMPPAT 2.0 database. The structures underwent thorough analysis and screening, emphasizing key factors such as binding energy, molecular docking performance, drug-likeness, and toxicity prediction to assess their therapeutic potential. Considering the spectrometry, pharmacokinetic properties, docking results, drug likeliness, and toxicological effects, five phytocompounds such as beta-amyrin, calendol, episwertenol, kairatenol and swertanone were identified as the inhibitors of the UspA1 in M. catarrhalis. UspA1 demonstrated binding affinities of –9.1 kcal/mol for beta-amyrin, –8.9 kcal/mol for calendol, –9.4 kcal/mol for episwertenol, –9.6 kcal/mol for kairatenol, and –9.0 kcal/mol for swertanone. All of these affinities were stronger than that of the control drug ceftobiprole, which had a binding score of –6.6 kcal/mol. The toxicity analysis confirmed that all five compounds are safe potential therapeutic options, showing no toxicity or carcinogenicity. We also performed a 100 ns molecular dynamics simulation of the phytocompounds to analyze their stability and interactions as protein-ligand complexes. Among the five screened phytocompounds, beta-amyrin and episwertenol exhibited favorable characteristics, including stable root mean square deviation values, minimal root mean square fluctuations, and consistent radius of gyration values. Throughout the simulations, intermolecular interactions such as hydrogen bonds and hydrophobic contacts were maintained. Additionally, the compounds demonstrated strong affinity, as indicated by negative binding free energy values. Taken together, findings of this study strongly suggest that beta-amyrin and episwertenol have the potential to act as inhibitors against the UspA1 protein of M. catarrhalis, offering promising prospects for the treatment and management of COPD.

Publisher Correction: Identification of potential biomarkers and pathways involved in high-altitude pulmonary edema using GC-MS and LC-MS metabolomic methods

Contribution of holes to the thermoelectric properties of gated bilayer graphene junctions

The study of 2D materials in renewable energies has been of great interest due to the growing demand for energy generation without affecting the environment. This includes 2D materials such as bilayer graphene in the context of thermoelectricity. Here, we study the thermoelectric properties of bilayer graphene junctions, in particular, the Seebeck coefficient, power factor, and figure of merit in single and double junctions as well as superlattices. We employ the hybrid matrix method and the Landauer–Bütikker formalism. We pay special attention to the contribution of holes to the mentioned thermoelectric properties. We find that the accessibility of the holes as well as the thermal activation of the charge carriers have a considerable impact on the Seebeck coefficient, power factor, and figure of merit around the bilayer graphene charge neutrality point. In particular, the thermoelectric properties at low temperatures improve when the hole contribution is taken into account. The thermal activation of the charge carriers in conjunction with the accessibility of the holes give rise to a reduction of the thermoelectric properties. In short, our findings indicate that the contribution of holes is fundamental in shaping the thermoelectric properties of bilayer graphene junctions around the charge neutrality point.

Bridge connectivity effects on photoinduced ground-state electron spin polarization

Transient electron paramagnetic resonance (TREPR) spectroscopy has been used to probe photoinduced electron spin polarization in the recovered ground states of four radical-elaborated (CAT)Pt(bpy) donor-acceptor complexes (CAT = catechol; bpy = 4,4′-di-tert-butyl-2,2′-bipyridine). These complexes are comprised of one or two S = 1/2 nitronyl nitroxide radicals attached through different phenylethynyl bridges to the 3- or 3,6 positions of the CAT donor. In this study, we demonstrate the effects of substitution patterns on the magnitude of the TREPR signal, thereby guiding future design principles for generating and understanding the origin of photoinduced electron spin polarization in these and related chromophores.

Factors influencing disaster preparedness behaviors of older adults

This study examines the heterogeneity in disaster preparedness behaviors among older adults and the factors that influence them, with the aim of offering policy recommendations to mitigate casualties among older adults during natural disasters. This is a secondary data analysis of cross-sectional data involving 394 participants aged 65 and above, with data sourced from the seventh wave of the Basic Social Change Survey conducted by Academia Sinica. These cross-sectional data were collected through face-to-face interviews, where interviewers conducted one-on-one questioning to gather general information and assess disaster preparedness. Hierarchical regression analysis was employed to explore the relationship between various factors and disaster preparedness behaviors. Descriptive statistics show that among the six disaster preparedness behaviors, 32.5% of the elderly moved vehicles or household items to a safe location, and 27.2% secured cabinets or large appliances. The remaining four disaster preparedness behaviors—including purchasing disaster insurance, preparing a disaster emergency kit, identifying and planning evacuation locations and routes, and participating in disaster response drills—were exhibited by less than 11.9% of the participants. Hierarchical regression showed that younger age, higher education, lower income, better health, community involvement, disaster experience, and higher perceived risk were associated with increased preparedness among older adults. The study found that most older adults do not invest time or money in disaster preparedness. Government agencies should encourage older adults to participate and account for their heterogeneity, such as through targeted interventions in health promotion, disaster response education, and social support. Initiatives like health check-ups, exercise classes to improve physical fitness, and simple, understandable disaster response courses can enhance risk perception. For high-income groups, emphasizing the importance of disaster preparedness through data and real-life examples is crucial. Older adults should also be encouraged to join community organizations and disaster drills, and a platform for sharing disaster experiences should be established to improve overall disaster resilience.

Author Correction: Slowing down single-molecule trafficking through a protein nanopore reveals intermediates for peptide translocation

Spatial description of dislocation nucleation in the shock response of single-crystal aluminum

Nonequilibrium molecular dynamics simulations of shock loaded single-crystal Al in the ⟨100⟩, ⟨110⟩, ⟨111⟩, and ⟨123⟩ orientations are conducted to study elastic and plastic shockwave formation and details associated with dislocation activity. A computer vision-based approach is implemented to capture the presence of dislocations and describe their spatial characteristics in the zone of nucleation behind the propagating shockwave. The methodology developed relies on the sequences of images extracted during shock loading that show dislocation activity within a cross section of the sample. Results reveal that the spacing between activated slip systems is orientation dependent and exhibits a modest reduction for the ⟨100⟩ and ⟨111⟩ orientations as shock pressure increases. Comparisons are made to existing theoretical models. Such relationships between shock pressure and dislocation activity, extracted from molecular dynamics simulations, can be used to inform higher length scale simulations or modeling of dislocation-based plasticity during shock.

<i>Ab initio</i> spin-mapping non-adiabatic dynamics simulations of photochemistry

We perform on-the-fly non-adiabatic molecular dynamics simulations using the recently developed spin-mapping formalism. Two quantum dynamics approaches based on this mapping formalism, (i) the fully linearized Spin-LSC and (ii) the partially linearized Spin-PLDM, are explored using the quasi-diabatic propagation scheme. We have performed dynamics simulations in four ab initio molecular models for which benchmark ab initio multiple spawning (AIMS) data have been published. We find that the spin-LSC and the previously reported symmetric quasi-classical (SQC) approaches provide nearly equivalent population dynamics. While we expected the more involved spin-PLDM method to provide superior accuracy compared to the other mapping-based approaches, SQC and spin-LSC, we found that it performed with equivalent accuracy compared to the AIMS benchmark results. We further explore the underpinnings of the spin-PLDM correlation function by decomposing its N2 density matrix-focused initial conditions, where N is the number of states in the quantum subsystem. Finally, we found an approximate form of the spin-PLDM correlation function, which simplifies the simulation and reduces the computational costs from N2 to N.

Exploring the narrative landscape: The discursive construction of identity for Chinese enterprises in Africa

This study investigates the construction of corporate identities by Chinese enterprises in Africa, employing the Three-dimensional Model of Fairchough in conjunction with the corporate communication strategies outlined by Kim and Rader. Through an extensive analysis of official website content from 200 Chinese companies, this study explores how these corporations utilize communication strategies to project their identities. The findings reveal a strategic use of discourse to align corporate practices with local cultures and business norms, facilitating their expansion and acceptance in African markets. This study contributes to understanding the dynamic and constructed nature of corporate identities in cross-cultural settings and provides insights into the strategic communication practices of Chinese firms in Africa.

Acute and chronic gene expression activation following medial forebrain bundle DBS and selective dopamine pathway stimulation

Abstract Deep brain stimulation (DBS) of the medial forebrain bundle (mfb) demonstrated anti-depressant effects both clinically and experimentally. Modulation of mesocorticolimbic dopaminergic (DA) activity could contribute—in part—to the therapeutic effects. By comparing selective and pathway specific midbrain DA optogenetic stimulation with the global, non-pathway specific mfb-DBS, the study explored changes in gene-expression of key biomarkers associated with neurocircuitry of depression. Rats received either optogenetic DAergic or mfb-DBS, delivered as acute/single or chronic/repeated stimulation. Micro-dissected regions were prepared for in situ hybridization targeting biomarkers of GABAergic, glutamatergic, and dopaminergic systems. Mfb-DBS mediated DA independent pathway increased GABAergic biomarkers (GABAA, GAD1) in frontal and accumbal regions, not in midbrain. The combinations of low frequency/high pulse width and high frequency/low pulse width stimulation generally increased biomarker expression similarly, but chronic/repetitive stimulation had no accumulative effect. Interestingly, unilateral stimulation had bilateral effects, but stimulation modalities had little impact on DAT and Vglut2 expression. In conclusion, both low and high frequency, acute/single and chronic/repetitive mfb-DBS—but not selective optogenetic stimulation -activated gene expression of biomarkers associated with GABAergic transmission. The increased expression was transitory and less chronic than predicted. Importantly, the study provides evidence that the anti-depressant therapeutic effects of clinical medial forebrain bundle DBS occurs—in part—be via modulation of GABAergic signalling which in turn could regulate the release of dopamine in frontal and accumbal regions. In addition, clinical implication of the data is that unilateral stimulation had bilateral consequences on the gene expression, although the physiological and functional sequelae of this are yet unknown.

Strain-induced flatbands in large-angle twisted bilayer graphene

Twisted bilayer graphene (TBG) has attracted widespread attention due to its unique and tunable properties. In this study, we systematically investigate the effects of in-plane biaxial tensile strain on the electronic properties of TBG with a twist angle greater than the magic angle by the tight-binding approach. Our results reveal that the energy bands near the Fermi level gradually narrow as the strain increases, resulting in a continuous decrease in Fermi velocity and the formation of flatbands. Especially, TBG with a larger twist angle requires a greater critical strain to achieve flatbands. The strain-induced flatbands exhibit a narrow bandwidth and vanishing Fermi velocity, similar to the band structures observed at the magic angle. Furthermore, the formation of these flatbands can be understood by the enhancement of charge localization and the competition between kinetic energy and interlayer hybridization energy during the strain process. Our findings present a potential avenue to produce flatbands in large-angle TBG, paving the way for further exploration and application in advanced materials science.

Accelerated linear algebra for large scale DFT calculations of materials on CPU/GPU architectures with CRYSTAL

We discuss the implementation strategy, numerical accuracy, and computational performance of the acceleration of linear algebra operations through graphics processing units (GPUs) for the self-consistent field driver of the Crystal electronic structure package for solid state density functional theory simulations. Accelerated tasks include matrix multiplication, diagonalization, and inversion, as well as Cholesky decomposition. The scaling of the implemented strategy over multiple accelerating devices is assessed in the range of 1–8 GPUs per node and found to be remarkably regular. Tests are performed on three systems: α-quartz, a microporous zeolitic imidazolate framework (ZIF-8), and a giant mesoporous metal–organic framework (bio-MOF). Scaling with system size is investigated via supercells of increasing size of both α-quartz and ZIF-8 (up to 648 and 2208 atoms per cell, respectively). The bio-MOF model structure has 2808 atoms per cell, with 33 672 basis functions. We test the performance of the accelerated code with both generalized gradient approximation (GGA) and hybrid GGA exchange–correlation functionals. The efficiency of the new accelerated code is compared to the previous central processing unit (CPU)-only parallelization strategies based on MPI or MPI/OpenMP within either replicated or distributed memory (i.e., massively parallel) approaches. Such a comparison highlights how the new GPU-accelerated code enables calculations on large systems at a significantly reduced computational cost relative to CPU-only strategies. For instance, we find that for the bio-MOF system, the computing time of the linear algebra tasks from a single GPU is comparable to that from the reference approach in the range of 512–1024 CPU cores and 4–8 nodes.

Why are critical event checklists not always used in the perioperative setting?: A retrospective survey

Introduction During surgery and anesthesia, life-threatening critical events, including cardiac arrest, may occur. By facilitating recall of key management steps, suggesting diagnostic possibilities, and providing dose and drug information, cognitive aids may improve clinician performance during such events. In actual clinical practice, however, cognitive aids may be available but inconsistently used. One possibility explaining aid non-use during critical events is a lack of familiarity with how cognitive aids may be helpful. We hypothesized that introduction of critical event cognitive aids along with implementation of cognitive aid resources would change the quantitative incidence of cognitive aid use and qualitative reasons for aid non-use. We surveyed members of an academic anesthesia department before and after implementation of critical event cognitive aid resources. Methods All anesthesia clinicians at a single academic medical center were surveyed. Participants were surveyed both pre- and post-training with a focused program to introduce critical event cognitive aid resources. Incidences of and reasons for cognitive aid use and non-use were collected and analyzed. Survey responses were compared pre- and post-implementation. Results The response rate was 64.5%. One-hundred eighty-five reasons for non-use were collected before the focused program and 149 after. Overall, 80% of clinicians had encountered at least one critical event during the study period and use of cognitive aids during all reported events was 7%. Six categories of reasons for non-use were identified: ‘Not Available’, ‘Not Needed’, ‘No Time’, ‘Another Person In Charge’, ‘Used In Another Way’, ‘No Reason Given’. After implementation, a decrease in the number of respondents who cited availability and who cited ‘another person running crisis,’ as reasons for non-use was observed (p &lt; 0.001). Conclusions Implementation of cognitive aids for critical events in an academic anesthesia environment improved the perception of cognitive aid availability and decreased the number of subjects who chose to not use the aid due to another person running the crisis response. Looking at the multiple reasons for cognitive aid non-use may guide implementation, training, and design.

Carbonate mineral precipitation induced by microorganisms enriched from the cave water and biofilm in a lime-decorated lava tube

Al0.8Sc0.2N film-based BAW filters using transfer process for Wi-Fi6 applications

With the emergence of fifth-generation communication systems, filters with bandwidth (BW) &amp;gt;5% and center frequency &amp;gt;4 GHz are in urgent need. This work presents film bulk acoustic resonators (FBARs) and bulk acoustic wave (BAW) filters based on Al0.8Sc0.2N films. To obtain a better quality AlScN film, we deposited AlScN by physical vaper deposition method on metal-organic chemical vapor deposition developed AlN seed, which was deposited directly on a Si (111) substrate. Using film transfer technology combined with adopting different FBAR structures, filter topology circuits, and external circuits, a BAW filter with a minimum insertion loss of 1.819 dB, a center frequency of 5.56 GHz, a −3 dB BW of 599 MHz, and an out-of-band suppression of at least 35 dB is fabricated and presented in this work.