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High entropy oxides are emerging as an exciting new avenue to design highly tailored functional behaviors that have no traditional counterparts. Study and application of these materials are bringing together scientists and engineers from physics, chemistry, and materials science. The diversity of each of these disciplines comes with perspectives and jargon that may be confusing to those outside of the individual fields, which can result in miscommunication of important aspects of research. In this Perspective, we provide examples of research and characterization taken from these different fields to provide a framework for classifying the differences between compositionally complex oxides, high entropy oxides, and entropy stabilized oxides, which is intended to bring a common language to this emerging area. We highlight the critical importance of understanding a material’s crystallinity, composition, and mixing length scales in determining its true definition.

The potential of artificial metalloenzymes has led to an increase in interest for the design of novel metal-binding sites in proteins. Metal-chelating unnatural amino acids offer an auspicious solution to engineer active metal sites in a defined way. Herein, we describe the introduction of four metal-chelating unnatural amino acids into HaloTag, an attractive scaffold for the assembly of functional artificial metalloenzymes. HaloTag, engineered with 2-amino-3-(8-hydroxyquinolin-5-yl)propanoic acid (HQ-Ala-1) was used to assemble an artificial metalloenzyme for improved allylic deamination upon complementation with [(η5-C5H5)Ru(MeCN)3]+.

In this work, the high entropy oxide A2CuO4 Ruddlesden-Popper (La0.2Pr0.2Nd0.2Sm0.2Eu0.2)2CuO4 is explored by charge doping with Ce+4 and Sr+2 at concentrations known to induce superconductivity in the simple parent compounds, Nd2CuO4 and La2CuO4. Electron doped (La0.185Pr0.185Nd0.185Sm0.185Eu0.185Ce0.075)2CuO4 and hole doped (La0.18Pr0.18Nd0.18Sm0.18Eu0.18Sr0.1)2CuO4 are synthesized and shown to be single crystal, epitaxially strained, and highly uniform. Transport measurements demonstrate that all as-grown films are insulating regardless of doping. Annealing studies show that resistivity can be tuned by modifying oxygen stoichiometry and inducing metallicity but without superconductivity. These results in turn are connected to extended x-ray absorption fine structure (EXAFS) results indicating that the lack of superconductivity in the high entropy cuprates likely originates from a large distortion within the Cu-O plane ({\sigma}2>0.015 {\AA}2) due to A-site cation size variance, which drives localization of charge carriers. These findings describe new opportunities for controlling charge- and orbital-mediated functional responses in Ruddlesden-Popper crystal structures, driven by balancing of cation size and charge variances that may be exploited for functionally important behaviors such as superconductivity, antiferromagnetism, and metal-insulator transitions, while opening less understood phase spaces hosting doped Mott insulators, strange metals, quantum criticality, pseudogaps, and ordered charge density waves.

Background The role of CT angiography-derived fractional flow reserve (CT-FFR) in pre-transcatheter aortic valve replacement (TAVR) assessment is uncertain. Purpose To evaluate the predictive value of on-site machine learning-based CT-FFR for adverse clinical outcomes in candidates for TAVR. Materials and Methods This observational retrospective study included patients with severe aortic stenosis referred to TAVR after coronary CT angiography (CCTA) between September 2014 and December 2019. Clinical end points comprised major adverse cardiac events (MACE) (nonfatal myocardial infarction, unstable angina, cardiac death, or heart failure admission) and all-cause mortality. CT-FFR was obtained semiautomatically using an on-site machine learning algorithm. The ability of CT-FFR (abnormal if ≤0.75) to predict outcomes and improve the predictive value of the current noninvasive work-up was assessed. Survival analysis was performed, and the C-index was used to assess the performance of each predictive model. To compare nested models, the likelihood ratio χ2 test was performed. Results A total of 196 patients (mean age ± standard deviation, 75 years ± 11; 110 women [56%]) were included; the median time of follow-up was 18 months. MACE occurred in 16% (31 of 196 patients) and all-cause mortality in 19% (38 of 196 patients). Univariable analysis revealed CT-FFR was predictive of MACE (hazard ratio [HR], 4.1; 95% CI: 1.6, 10.8; P = .01) but not all-cause mortality (HR, 1.2; 95% CI: 0.6, 2.2; P = .63). CT-FFR was independently associated with MACE (HR, 4.0; 95% CI: 1.5, 10.5; P = .01) when adjusting for potential confounders. Adding CT-FFR as a predictor to models that include CCTA and clinical data improved their predictive value for MACE (P = .002) but not all-cause mortality (P = .67), and it showed good discriminative ability for MACE (C-index, 0.71). Conclusion CT angiography-derived fractional flow reserve was associated with major adverse cardiac events in candidates for transcatheter aortic valve replacement and improved the predictive value of coronary CT angiography assessment. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Choe in this issue.

HaloTag is a small self-labeling protein that is frequently used for creating fluorescent reporters in living cells. The small-molecule dyes used with HaloTag are almost exclusively based on rhodamine scaffolds, which are often expensive and challenging to synthesize. Herein, we report the engineering of HaloTag for use with a chemically accessible, inexpensive fluorophore based on the dimethylamino-styrylpyridium dye. Through directed evolution, the maximum fluorogenicity and the apparent second-order bioconjugation rate constants could be improved up to 4-fold and 42-fold, respectively. One of the top variants, HT-SP5, enabled reliable imaging in mammalian cells, with a 113-fold fluorescence enhancement over the parent protein. Additionally, crystallographic characterization of selected mutants suggests the chemical origin of the fluorescent enhancement. The improved dye system offers a valuable tool for imaging and illustrates the viability of engineering self-labeling proteins for alternative fluorophores.

Although liver biopsies (LBs) are being increasingly performed under endoscopic ultrasound (EUS) guidance, there are limited data comparing outcomes with current standard-of-care, transabdominal ultrasound (US)-guided percutaneous (PC) methods. In a randomised trial, we observed that the PC, US-guided method yielded significantly more optimal specimens, defined as specimen length of 25 mm or greater and presence of at least 11 complete portal tracts, compared with the EUS-guided method (57.9% vs 23.8%, p=0.028). Also, the PC method resulted in worse initial postprocedural pain but was less costly (US$1824 vs US$3240, p

The Wechsler Intelligence Scale for Children (WISC) is the most widely used intelligence test in the world. Now in its fifth edition, the WISC-V has been translated and adapted for use in nearly a dozen countries. Despite its popularity, numerous concerns have been raised about some of the procedures used to develop and validate translated and adapted versions of the test around the world. The purpose of this article is to survey the most salient of those methodological and statistical limitations. In particular, empirical data are presented that call into question the equating procedures used to validate the WISC-V Spanish, suggesting cautious use of that instrument. It is believed that the issues raised in the present article will be instructive for school psychologists engaged in the clinical assessment of intelligence with the WISC-V Spanish and with other translated and adapted versions around the world.

Significance Turner syndrome (TS) is caused by having only one X chromosome (X0), and Klinefelter syndrome (KS) by having two X chromosomes and one Y chromosome (XXY). In this study we carried out a direct comparison analysis of the effect these chromosome copy number aberrations have on gene expression networks, analyzing genes located on the X chromosome or anywhere else in the genome, in primary samples from KS and TS patients. In both KS and TS, we found gene expression level changes not only in genes on the X chromosome, but also in many genes on all the other chromosomes, revealing a genomewide ripple effect of the chromosome X copy number aberrations., In both Turner syndrome (TS) and Klinefelter syndrome (KS) copy number aberrations of the X chromosome lead to various developmental symptoms. We report a comparative analysis of TS vs. KS regarding differences at the genomic network level measured in primary samples by analyzing gene expression, DNA methylation, and chromatin conformation. X-chromosome inactivation (XCI) silences transcription from one X chromosome in female mammals, on which most genes are inactive, and some genes escape from XCI. In TS, almost all differentially expressed escape genes are down-regulated but most differentially expressed inactive genes are up-regulated. In KS, differentially expressed escape genes are up-regulated while the majority of inactive genes appear unchanged. Interestingly, 94 differentially expressed genes (DEGs) overlapped between TS and female and KS and male comparisons; and these almost uniformly display expression changes into opposite directions. DEGs on the X chromosome and the autosomes are coexpressed in both syndromes, indicating that there are molecular ripple effects of the changes in X chromosome dosage. Six potential candidate genes (RPS4X, SEPT6, NKRF, CX0rf57, NAA10, and FLNA) for KS are identified on Xq, as well as candidate central genes on Xp for TS. Only promoters of inactive genes are differentially methylated in both syndromes while escape gene promoters remain unchanged. The intrachromosomal contact map of the X chromosome in TS exhibits the structure of an active X chromosome. The discovery of shared DEGs indicates the existence of common molecular mechanisms for gene regulation in TS and KS that transmit the gene dosage changes to the transcriptome.

Engineered enzyme cascades offer powerful tools to convert renewable resources into value-added products. Man-made catalysts give access to new-to-nature reactivities that may complement the enzyme’s repertoire. Their mutual incompatibility, however, challenges their integration into concurrent chemo-enzymatic cascades. Herein we show that compartmentalization of complex enzyme cascades within E. coli whole cells enables the simultaneous use of a metathesis catalyst, thus allowing the sustainable one-pot production of cycloalkenes from oleic acid. Cycloheptene is produced from oleic acid via a concurrent enzymatic oxidative decarboxylation and ring-closing metathesis. Cyclohexene and cyclopentene are produced from oleic acid via either a six- or eight-step enzyme cascade involving hydration, oxidation, hydrolysis and decarboxylation, followed by ring-closing metathesis. Integration of an upstream hydrolase enables the usage of olive oil as the substrate for the production of cycloalkenes. This work highlights the potential of integrating organometallic catalysis with whole-cell enzyme cascades of high complexity to enable sustainable chemistry., Cycloalkenes are bulk petrochemicals that are currently obtained from fossil fuels. Here, the authors developed multi enzyme pathways in combination with a Ru-catalyzed metathesis reaction for the one-pot production of cyclopentene, cyclohexene, and cycloheptene from olive oil-derived intermediates.

As the relationship between CT scout landmarks and chest CT boundaries is not known, the selected scan length is often greater than necessary for the CT scan, resulting in increased radiation dose to the neck and upper abdomen. The purpose of this study is to establish the relationship between CT scout landmarks with the superior and inferior boundaries of the lungs on chest CT. Retrospective comparison of the location of the top of the first rib on frontal scout and the most inferior costophrenic angle on lateral scout to the chest CT slice just above and below the lungs. The percent of scans that would exclude part of the lung based on CT initiated at several distances above or below these landmarks was calculated. There was 2.7 times greater variability between scout landmarks and lung boundaries inferiorly than superiorly on chest CT (p

Photochemistry usually functions on a one-photon-one-electron basis, leading to unstable radical intermediates that must be intercepted rapidly to allow efficient product formation. This can render multi-electron reductions and enantioselective reactions particularly challenging. In this minireview, we discuss recent advances in the area of photo-driven multi-electron transfer with a particular focus on our own work on reductive amination and the enantioselective synthesis of amines by combined photoredox and enzyme catalysis. Polarity-matched hydrogen atom transfer (HAT) between photochemically-generated alpha-amino alkyl radicals and thiols is a key step in these reactions. A cyclic reaction network comprised of light-driven imine reduction by an Ir-photocatalyst and enantioselective amine oxidation by the enzyme monoamine oxidase (MAO-N-9) was used to obtain enantioenriched amines from imines.

In the recent decades, the design and development of biomimetic micro air vehicles have gained increased interest by the global scientific and engineering communities. This has given greater motivation to study and understand the aerodynamics involved with winged insects. Dragonflies demonstrate unique and superior flight performance than most of the other insect species and birds. They are capable of sustained gliding flight as well as hovering and able to change direction very rapidly. Pairs of independently controlled forewings and hindwings give them an agile flying ability. This article presents a review of all published journal articles, listed in the Thomson-Reuters Web-of-Science database (1985–2018), that are related to the flight aerodynamics of dragonflies or micro air vehicles that biomimic them. The effects of dragonfly wing motions and interactions (between forewing and hindwing) that are necessary to generate the appropriate aerodynamic forces in different flight modes are described. The associated power requirements of these modes are also addressed. This article aims to provide a valuable reference to the aerodynamic design and control of dragonfly-inspired biomimetic micro air vehicles.

Cyclic oligochalcogenides (COCs) are emerging as promising systems to penetrate cells. Clearly better than and different to the reported diselenolanes and epidithiodiketopiperazines, we introduce the benzopolysulfanes (BPS), which show efficient delivery, insensitivity to inhibitors of endocytosis, and compatibility with substrates as large as proteins. This high activity coincides with high reactivity, selectively toward thiols, exceeding exchange rates of disulfides under tension. The result is a dynamic‐covalent network of extreme sulfur species, including cyclic oligomers, from dimers to heptamers, with up to nineteen sulfurs in the ring. Selection from this unfolding adaptive network then yields the reactivities and selectivities needed to access new uptake pathways. Contrary to other COCs, BPS show high retention on thiol affinity columns. The identification of new modes of cell penetration is important because they promise new solutions to challenges in delivery and beyond.

The influence of hole doping on magnetic properties is mapped for the compositionally complex high-entropy oxide ${AB\mathrm{O}}_{3}$ perovskite ${\mathrm{La}}_{1\text{\ensuremath{-}}x}{\mathrm{Sr}}_{x}({\mathrm{Cr}}_{0.2}{\mathrm{Mn}}_{0.2}{\mathrm{Fe}}_{0.2}{\mathrm{Co}}_{0.2}{\mathrm{Ni}}_{0.2}){\mathrm{O}}_{3}$ $(0\ensuremath{\le}x\ensuremath{\le}0.5)$. It is found that aliovalent A-site substitution is a viable means to manipulate the magnetically active B-site sublattice. A series of single-crystal films are synthesized and show a general trend toward stronger ferromagnetic response and a shift in magnetic anisotropy as the Sr concentration increases. Magnetometry demonstrates complex and nonuniform responses similar to rigid and uncoupled composites at intermediate dopings. This behavior points to the presence of locally inhomogeneous magnetic phase competition, where ferromagnetic and antiferromagnetic magnetic contributions create a frustrated matrix containing uncompensated spins at the boundaries between these regions. The observations are discussed in the context of known responses to hole doping in the less complex ternary $\mathrm{La}{T}_{M}{\mathrm{O}}_{3}$ $({T}_{M}=\mathrm{Cr},\mathrm{Mn},\mathrm{Fe},\mathrm{Co},\mathrm{Ni})$ oxides, and they are found to be different from a simple sum of the doped parents. The results are summarized in a preliminary magnetic phase diagram.

Artificial metalloenzymes (ArMs) combine characteristics of both homogeneous catalysts and enzymes. Merging abiotic and biotic features allows for the implementation of new-to-nature reactions in living organisms. Here, we present the directed evolution of an artificial metalloenzyme based on Escherichia coli surfacedisplayed streptavidin (SavSD hereafter). Through the binding of a ruthenium-pianostool cofactor to SavSD, an artificial allylic deallylase (ADAse hereafter) is assembled, which displays catalytic activity toward the deprotection of alloc-protected 3-hydroxyaniline. The uncaged aminophenol acts as a gene switch and triggers the overexpression of a fluorescent green fluorescent protein (GFP) reporter protein. This straightforward readout of ADAse activity allowed the simultaneous saturation mutagenesis of two amino acid residues in Sav near the ruthenium cofactor, expediting the screening of 2762 individual clones. A 1.7-fold increase of in vivo activity was observed for SavSD S112T-K121G compared to the wild-type SavSD (wt-SavSD). Finally, the best performing Sav isoforms were purified and tested in vitro (SavPP hereafter). For SavPP S112M-K121A, a total turnover number of 372 was achieved, corresponding to a 5.9-fold increase vs wt-SavPP. To analyze the marked difference in activity observed between the surface-displayed and purified ArMs, the oligomeric state of SavSD was determined. For this purpose, crosslinking experiments of E. coli cells overexpressing SavSD were carried out, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDSPAGE) and Western blot. The data suggest that SavSD is most likely displayed as a monomer on the surface of E. coli. We hypothesize that the difference between the in vivo and in vitro screening results may reflect the difference in the oligomeric state of SavSD vs soluble SavPP (monomeric vs tetrameric). Accordingly, care should be applied when evolving oligomeric proteins using E. coli surface display., ACS Catalysis, 11 (17), ISSN:2155-5435

Operative courses of laparoscopic cholecystectomies vary widely due to differing pathologies. Efforts to assess intra-operative difficulty include the Parkland grading scale (PGS), which scores inflammation from the initial view of the gallbladder on a 1-5 scale. We investigated the impact of PGS on intra-operative outcomes, including laparoscopic duration, attainment of the critical view of safety (CVS), and gallbladder injury. We additionally trained an artificial intelligence (AI) model to identify PGS.One surgeon labeled surgical phases, PGS, CVS attainment, and gallbladder injury in 200 cholecystectomy videos. We used multilevel Bayesian regression models to analyze the PGS's effect on intra-operative outcomes. We trained AI models to identify PGS from an initial view of the gallbladder and compared model performance to annotations by a second surgeon.Slightly inflamed gallbladders (PGS-2) minimally increased duration, adding 2.7 [95% compatibility interval (CI) 0.3-7.0] minutes to an operation. This contrasted with maximally inflamed gallbladders (PGS-5), where on average 16.9 (95% CI 4.4-33.9) minutes were added, with 31.3 (95% CI 8.0-67.5) minutes added for the most affected surgeon. Inadvertent gallbladder injury occurred in 25% of cases, with a minimal increase in gallbladder injury observed with added inflammation. However, up to a 28% (95% CI - 2, 63) increase in probability of a gallbladder hole during PGS-5 cases was observed for some surgeons. Inflammation had no substantial effect on whether or not a surgeon attained the CVS. An AI model could reliably (Krippendorff's α = 0.71, 95% CI 0.65-0.77) quantify inflammation when compared to a second surgeon (α = 0.82, 95% CI 0.75-0.87).An AI model can identify the degree of gallbladder inflammation, which is predictive of cholecystectomy intra-operative course. This automated assessment could be useful for operating room workflow optimization and for targeted per-surgeon and per-resident feedback to accelerate acquisition of operative skills.

BackgroundThe growing interest in analysis of surgical video through machine learning has led to increased research efforts; however, common methods of annotating video data are lacking. There is a need to establish recommendations on the annotation of surgical video data to enable assessment of algorithms and multi-institutional collaboration.MethodsFour working groups were formed from a pool of participants that included clinicians, engineers, and data scientists. The working groups were focused on four themes: (1) temporal models, (2) actions and tasks, (3) tissue characteristics and general anatomy, and (4) software and data structure. A modified Delphi process was utilized to create a consensus survey based on suggested recommendations from each of the working groups.ResultsAfter three Delphi rounds, consensus was reached on recommendations for annotation within each of these domains. A hierarchy for annotation of temporal events in surgery was established.ConclusionsWhile additional work remains to achieve accepted standards for video annotation in surgery, the consensus recommendations on a general framework for annotation presented here lay the foundation for standardization. This type of framework is critical to enabling diverse datasets, performance benchmarks, and collaboration.