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While the benefits of pair housing have been well documented, less is known about increasing success in adult male macaque pair introductions. In this retrospective study, 95 unfamiliar adult male macaque (Macaca mulatta) pairs were examined to determine whether duration of visual contact, behavior, and age and weight were associated with success rate, with "success" defined as two weeks in full tactile contact without excessive behavioral indicators of incompatibility or injury requiring clinical treatment or care. Overall, the unfamiliar adult male pairs achieved a success rate of 72% and wounding requiring medical attention was rare (2%). A significant negative relationship between pair success and time in visual contact for pairs was found. Pairs who moved into tactile contact within 48-hours showed more positive social behaviors in protected and full contact and had a high rate of success (91%), while those who exhibited negative social behaviors were maintained in visual contact for longer. Nevertheless, rapid signs of compatibility were not necessary for the formation of successful pairs. While social introduction success rates steadily declined with increased periods of maintained visual contact, longer durations of 3 days to 1 week (70%), and 8+ days (58%), were still accompanied by high to moderate success, respectively. These results indicate that when negative social behavior is present early in visual contact success may be expected to decrease, but it is not necessarily indicative of incompatibility. Providing extra time in visual contact can reduce overall incidences of single housing.

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Various single-stranded and hairpin-forming DNA and 2´-O-methyl-RNA oligonucleotides bearing a single (2R,3S)-4-(methoxyamino)butane-1,2,3-triol residue esterified from either O1 and O2 or O1 and O3 were synthesized. Incubation of these oligonucleotides with equimolar mixtures of formylmethyl derivatives of the canonical nucleobases and 2-methylbenzimidazole under mildly acidic conditions revealed base-filling of the modified site to be strongly favored by base stacking of a double-helix, especially an A-type one. In 2´-O-methyl-RNA hairpin oligonucleotides, base-filling of the (2R,3S)-4-(methoxyamino)butane-1,2,3-triol residue with nucleobase aldehydes followed the rules of Watson-Crick base pairing, thymine being the only exception. In single-stranded oligonucleotides or the Hoogsteen strand of triple helices, both the yield and selectivity of base-filling were much more modest.

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During the development process of therapeutic monoclonal antibodies (mAbs), it is crucial to control (critical) quality attributes such as N-glycosylation influencing pharmacokinetics (PK) and Fc effector functions. Previous reports have shown that mAbs containing high-mannose N-glycans are cleared faster from blood circulation, leading to reduced half-lives. The high-mannose N-glycan content of mAbs can be influenced during the cell culture process by factors such as cell lines, process conditions, and media. Furthermore, mAbs have either one high mannose N-glycan (asymmetrical high-mannose glyco-pair) or two high mannose N-glycans (symmetrical high-mannose glyco-pair). The hypothesis that the mannose receptor (MR, CD206) accelerates clearance by facilitating their internalization and subsequent lysosomal degradation is widespread. However, the interaction between MR and mAbs has not been explicitly demonstrated. This study aimed to investigate this interaction, providing the first systematic demonstration of MR binding to the Fc region of mAbs with high-mannose N-glycans. Two novel analytical methods, MR surface plasmon resonance and MR affinity chromatography, were developed and applied to investigate the MR-mAb interaction. The interaction is found to be dependent on high-mannose content, but is independent of the mAb format or sequence. However, different glyco-pairs exhibited varying binding affinities to the MR, with the symmetrical high-mannose glyco-pair showing the strongest binding properties. These findings strengthen the hypothesis for the MR-mediated mAb interaction and contribute to a deeper understanding of the MR-mAb interaction, which could affect the criticality of high-mannose containing mAbs development strategies of IgG-based molecules and improve their PK profiles.

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Droplet microfluidics has become a very powerful tool in high-throughput screening, including antibody discovery. Screens are usually carried out by physically sorting droplets hosting cells of the desired phenotype, breaking them, recovering the encapsulated cells, and sequencing the paired antibody light and heavy chain genes at the single-cell level. This series of multiple consecutive manipulation steps of rare screening hits is complex and challenging, resulting in a significant loss of clones with the desired phenotype or large fractions of cells with incomplete antibody information. Here, we present fluorescence-activated droplet sequencing, in which droplets showing the desired phenotype are selectively picoinjected with reagents for RT-PCR. Subsequently, light and heavy chain genes are natively paired, fused into a single-chain fragment variant format, and amplified before off-chip transfer and downstream nanopore sequencing. This workflow is sufficiently sensitive for obtaining different paired full-length antibody sequences from as little as five droplets, fulfilling the desired phenotype. Replacing physical sorting by specific sequencing overcomes a general bottleneck in droplet microfluidic screening and should be compatible with many more applications.

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Food processing, cooking, and consumption introduce various factors that affect food flavor, distinguishing it from its objective composition. This study focuses on liquor-accompanying food pairing, investigating the interaction between baijiu aroma compounds and peanut proteins, and the effect of ethanol on it. Peanut globulins significantly inhibited the release of baijiu aroma compounds through hydrogen bonding (2.63-3.23 Å), hydrophobic interactions, and covalent reactions (-2.85 to -5.64 kcal/mol), resulting in flavor modification. In the presence of ethanol, peanut globulins adopt a more compact and aggregated structure, reducing their affinity for binding aroma compounds. Surprisingly, this structural change promotes a salting-out effect, significantly promoting the release of aldehydes, phenols, and aromatic compounds, enhancing the grassy, floral, and sweet aroma of baijiu. This finding improves the understanding of alcohol pairing and proposes a novel strategy for enhancing the overall flavor profile of baijiu by modifying accompanying food choices.

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The inclusion of hollow channels in tissue-engineered hydrogels is crucial for mimicking the natural physiological conditions and facilitating the delivery of nutrients and oxygen to cells. Although bio-fabrication techniques provide diverse strategies to create these channels, many require sophisticated equipment and time-consuming protocols. Herein, collagenase, a degrading agent for methacrylated gelatin hydrogels, and magnetic nanoparticles (MNPs) are combined and processed into enzymatically active spherical structures using a straightforward oil bath emulsion methodology. The generated microgels are then used to microfabricate channels within biomimetic hydrogels via a novel sculpturing approach that relied on the precise coupling of protein-enzyme pairs (for controlled local degradation) and magnetic actuation (for directional control). Results show that the sculpting velocity can be tailored by adjusting the magnetic field intensity or concentration of MNPs within the microgels. Additionally, varying the magnetic field position or microgel size generated diverse trajectories and channels of different widths. This innovative technology improves the viability of encapsulated cells through enhanced medium transport, outperforming non-sculpted hydrogels and offering new perspectives for hydrogel vascularization and drug/biomolecule administration. Ultimately, this novel concept can help design fully controlled channels in hydrogels or soft materials, even those with complex tortuosity, in a single wireless top-down biocompatible step.

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Polyploids are essential in plant evolution and species formation, providing a rich genetic reservoir and increasing species diversity. Complex polyploids with higher ploidy levels often have a dosage effect on the phenotype, which can be highly detrimental to gametes, making them rare. In this study, offspring plants resulting from an autoallotetraploid (RRRC) derived from the interspecific hybridization between allotetraploid Raphanobrassica (RRCC, 2n = 36) and diploid radish (RR, 2n = 18) were obtained. Fluorescence in situ hybridization (FISH) using C-genome-specific repeats as probes revealed two main genome configurations in these offspring plants: RRRCC (2n = 43, 44, 45) and RRRRCC (2n = 54, 55), showing more complex genome configurations and higher ploidy levels compared to the parental plants. These offspring plants exhibited extensive variation in phenotypic characteristics, including leaf type and flower type and color, as well as seed and pollen fertility. Analysis of chromosome behavior showed that homoeologous chromosome pairing events are widely observed at the diakinesis stage in the pollen mother cells (PMCs) of these allopolyploids, with a range of 58.73% to 78.33%. Moreover, the unreduced C subgenome at meiosis anaphase II in PMCs was observed, which provides compelling evidence for the formation of complex allopolyploid offspring. These complex allopolyploids serve as valuable genetic resources for further analysis and contribute to our understanding of the mechanisms underlying the formation of complex allopolyploids.

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Integrating anodic biomass valorization with carbon dioxide electroreduction (CO2RR) can produce value-added chemicals on both the cathode and anode; however, anodic oxidation still suffers from high overpotential. Herein, a photothermal-assisted method was developed to reduce the potential of 5-hydroxymethyl furfural (HMF) electrooxidation. Capitalizing on the copious oxygen vacancies, defective Co3O4 (D-Co3O4) exhibited a stronger photothermal effect, delivering a local temperature of 175.47 oC under near infrared light illumination. The photothermal assistance decreased the oxidation potential of HMF from 1.7 V over pristine Co3O4 to 1.37 V over D-Co3O4 to achieve a target current density of 30 mA cm-2, with 2,5-furandicarboxylic acid as the primary product. Mechanistic analysis disclosed that the photothermal effect did not change the HMF oxidation route but greatly enhanced the adsorption capacity of HMF. Meanwhile, faster electron transfer for direct HMF oxidation and the surface conversion to cobalt (oxy)hydroxide, which contributed to indirect HMF oxidation, was observed. Thus, rapid HMF conversion was realized, as evidenced by in situ surface-enhanced infrared spectroscopy. Upon coupling cathodic CO2RR with an atomically dispersed Ni-N/C catalyst, the Faradaic efficiencies of CO (cathode) and 2,5-furandicarboxylic acid (FDCA, anode) exceeded 90.0% under a low cell potential of 1.77 V.

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The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs are formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing interactions between boundaries are typically orientation-dependent. Pairing can be head-to-tail or head-to-head. The former generates a stem-loop TAD, while the latter gives a circle-loop TAD. The TAD that encompasses the Drosophila even skipped (eve) gene is formed by the head-to-tail pairing of the nhomie and homie boundaries. To explore the relationship between loop topology and the physical and regulatory landscape, we flanked the nhomie boundary region with two attP sites. The attP sites were then used to generate four boundary replacements: λ DNA, nhomie forward (WT orientation), nhomie reverse (opposite of WT orientation), and homie forward (same orientation as WT homie). The nhomie forward replacement restores the WT physical and regulatory landscape: in MicroC experiments, the eve TAD is a 'volcano' triangle topped by a plume, and the eve gene and its regulatory elements are sequestered from interactions with neighbors. The λ DNA replacement lacks boundary function: the endpoint of the 'new' eve TAD on the nhomie side is ill-defined, and eve stripe enhancers activate a nearby gene, eIF3j. While nhomie reverse and homie forward restore the eve TAD, the topology is a circle-loop, and this changes the local physical and regulatory landscape. In MicroC experiments, the eve TAD interacts with its neighbors, and the plume at the top of the eve triangle peak is converted to a pair of 'clouds' of contacts with the next-door TADs. Consistent with the loss of isolation afforded by the stem-loop topology, the eve enhancers weakly activate genes in the neighboring TADs. Conversely, eve function is partially disrupted.

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Two different models have been proposed to explain how the endpoints of chromatin looped domains ('TADs') in eukaryotic chromosomes are determined. In the first, a cohesin complex extrudes a loop until it encounters a boundary element roadblock, generating a stem-loop. In this model, boundaries are functionally autonomous: they have an intrinsic ability to halt the movement of incoming cohesin complexes that is independent of the properties of neighboring boundaries. In the second, loops are generated by boundary:boundary pairing. In this model, boundaries are functionally non-autonomous, and their ability to form a loop depends upon how well they match with their neighbors. Moreover, unlike the loop-extrusion model, pairing interactions can generate both stem-loops and circle-loops. We have used a combination of MicroC to analyze how TADs are organized, and experimental manipulations of the even skipped TAD boundary, homie, to test the predictions of the 'loop-extrusion' and the 'boundary-pairing' models. Our findings are incompatible with the loop-extrusion model, and instead suggest that the endpoints of TADs in flies are determined by a mechanism in which boundary elements physically pair with their partners, either head-to-head or head-to-tail, with varying degrees of specificity. Although our experiments do not address how partners find each other, the mechanism is unlikely to require loop extrusion.

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The nurse scheduling problem (NSP) has been a crucial and challenging research issue for hospitals, especially considering the serious deterioration in nursing shortages in recent years owing to long working hours, considerable work pressure, and irregular lifestyle, which are important in the service industry. This study investigates the NSP that aims to maximize nurse satisfaction with the generated schedule subject to government laws, internal regulations of hospitals, doctor-nurse pairing rules, shift and day off preferences of nurses, etc. The computational experiment results show that our proposed hybrid metaheuristic outperforms other metaheuristics and manual scheduling in terms of both computation time and solution quality. The presented solution procedure is implemented in a real-world clinic, which is used as a case study. The developed scheduling technique reduced the time spent on scheduling by 93% and increased the satisfaction of the schedule by 21%, which further enhanced the operating efficiency and service quality.

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Fludarabine (FA) is still considered as a first-line chemotherapy drug for hematological tumors related to B lymphocytes. However, it is worth noting that the non-specific distribution and non-different cytotoxicity of FA may lead to irreversible consequences such as central nervous system damage such as blindness, coma, and even death. Therefore, it is very important to develop a system to targeting delivery FA. In preliminary studies, it was found that B lymphoma cells would specific highly expressing the sialic acid-binding immunoglobulin-like lectin 2 (known as CD22). Inspired by the specific recognition of sialic acid residues and CD22, we have developed a supramolecular prodrug based on polysialic acid, an endogenous biomacromolecule, achieving targeted-therapy of B-cell non-Hodgkin's lymphoma (B-NHL). Specifically, the prepared hydrophobic reactive oxygen species-responsive FA dimeric prodrug (F2A) interacts with the TPSA, which polysialic acid were modified by the thymidine derivatives, through non-covalent intermolecular interactions similar to "Watson-Crick" base pairing, resulting in the formation of nanoscale supramolecular prodrug (F@TPSA). Cell experiments have confirmed that F@TPSA can be endocytosed by CD22+ B lymphoma cells including Raji and Ramos cells, and there is a significant difference of endocytosis in other leukocytes. Furthermore, in B-NHL mouse model, compared with FA, F@TPSA is determined to have a stronger tumor targeting and inhibitory effect. More importantly, the distribution of F@TPSA in vivo tends to be enriched in lymphoma tissue rather than nonspecific, thus reducing the leukopenia of FA. The targeted delivery system based on PSA provides a new prodrug modification strategy for targeted treatment of B-NHL.

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BACKGROUND AND AIMS: Durum wheat, Triticum turgidum, and bread wheat, Triticum aestivum, are two allopolyploid species of very recent origin that have been subjected to intense selection programs during the thousands of years they have been cultivated. In this paper, we study the durum wheat satellitome and establish a comparative analysis with the previously published bread wheat satellitome. METHODS: We revealed the durum wheat satellitome using the satMiner protocol which is based on consecutive rounds of clustering of Illumina reads by RepeatExplorer2, and estimated abundance and variation for each identified satDNA with RepeatMasker v4.0.5. We have also performed a deep satDNA families characterization including chromosomal location by Fluorescence In Situ Hybridization (FISH) in durum wheat and its comparison with FISH patterns in bread wheat. Basic Local Alignment Search Tool (BLAST®) was used for trailing each satDNA in the assembly of durum wheat genome through NCBI's Genome Data Viewer (GDW) and the genome assemblies of both species were compared. Sequence divergence and consensus turnover rate (CTR) between homologous satDNA families of durum and bread wheat were estimated using MEGA11. KEY RESULTS: This study reveals that in an exceedingly short period, significant qualitative and quantitative changes have occurred in the set of satellite DNAs (satDNAs) of both species, with expansions/contractions of the number of repeats and the loci per satellite, different in each species, and a high rate of sequence change for most of these satellites, in addition to the emergence/loss of satDNAs not shared between the two species analysed. These evolutionary changes in satDNA are common between species but what is truly remarkable and novel about this study is that these processes have taken place in less than the last ~8000 years separating the two species, indicating an accelerated evolution of their satDNAs. CONCLUSIONS: These results, together with the relationship of many of these satellites with transposable elements and the polymorphisms they generate at the level of centromeres and subtelomeric regions of their chromosomes, are analysed and discussed in the context of the evolutionary origin of these species and the selection pressure exerted by man throughout the history of their cultivation.

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The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD. We developed sustained release nor-LAAM-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (MP) using a hydrophobic ion pairing (HIP) approach. The nor-LAAM-MP prepared using HIP with pamoic acid had high drug loading and exhibited minimal initial burst release and sustained release. The nor-LAAM-MP was further optimized for desirable particle size, drug loading, and release kinetics. The lead nor-LAAM-MP (F4) had a relatively high drug loading (11 wt%) and an average diameter (19 µm) and maintained a sustained drug release for 4 weeks. A single subcutaneous injection of nor-LAAM-MP (F4) provided detectable nor-LAAM levels in rabbit plasma for at least 15 days. We further evaluated the therapeutic efficacy of nor-LAAM-MP (F4) in a well-established fentanyl-addiction rat model, and revealed a marked reduction in fentanyl choice and withdrawal symptoms in fentanyl-dependent rats. These findings provide insights into further developing long-acting nor-LAAM-MP for treating OUD. It has the potential to offer a new effective medication to the existing sparse armamentarium of products available to treat OUD.

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The detection of the highly toxic per- and polyfluoroalkyl substances, PFAS, constitutes a challenging task in terms of developing a generic method that could be rapid and applicable simultaneously to both long and short-chain PFAS at ppt concentration level. In the present study, the method introduced by the USA Environmental Protection Agency, EPA, to detect surfactants, using methylene blue, MB, which is identified an ideal candidate for PFAS-MB ion pairing, is extended at the lowest concentration range by a simple additional step that involves the dissociation of the ion pairs in water. In this work, Surface Enhanced Raman Scattering, SERS, is applied via Ag nanocolloidal suspensions to probe MB and indirectly either/or both short-chain (perfluorobutyric acid, PFBA) and long-chain (perfluoloctanoic acid, PFOA) PFAS downt to 5 ppt. This method, which can be further optimized to sub-ppt level via a custom-made SERS-PFAS dedicated Raman system, offers the possibility to be applied to either specific PFAS (both short and long-chain) in a targeted analysis or to total PFAS in a non-targeted analysis at very low detection limits, following any type of MB detection method in aqueous solutions and obviously with any type of SERS substrate.

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Redox-active organic molecules have potential as electrode materials, but their cycling stability is often limited by the irreversible formation of σ-bonds from the radical intermediates. Herein, we present an effective approach to achieve high reversibility by using lone pair electrons to mediate intramolecular radical-radical coupling. Azatriangulenetrione (1) was examined as the anode in sodium-ion batteries, which displayed a reversible four-step, one-electron redox chemistry. In situ electron spin resonance, ex situ Fourier transform infrared/X-ray photoelectron spectroscopy, and density functional theory calculation revealed that the unstable radical anions can couple with each other through the lone pair electrons of the central nitrogen atom, leading to stabilized radical species. Furthermore, scan-rate-dependent cyclic voltammetry measurements and galvanostatic intermittent titration techniques demonstrated that the redox reaction kinetics for radical formation were much faster than the radical paring process. This study offers deep insights into the design of highly reversible organic electrodes.

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The cheese wine pairing is a beloved combination subject to a certain subjectivity due to sensorial, psychological, chemical, and cultural factors. This work represents a first attempt to explore the in vitro interactions between cheese, wine, and saliva to objectively measure the pairing. Two experimental red wines obtained from the same grape cultivar and four different cheeses were studied for their composition. Binding reactions between wine and cheese were carried out in three simulated tasting trials and, after precipitation, the wine phenolic content, Saliva Precipitation Index (SPI), and total proteins were evaluated. The optimal pairing (OP) was calculated considering the decrease in salivary and cheese proteins by wine, defined as the cleansing effect; the decrease in astringency due to the cheese, measured by the SPI, and the coating fat which would remain in mouth after eating a piece of cheese. Based on obtained results, the semi-hard cheese was identified as the best pairing option for the two experimental red wines. The differences in the phenolic content between the two wines were instead not enough to show a significant influence on the OP. The in vitro cheese wine pairing can contribute to understanding of wine tasting but it is only a part of the puzzle. However, this first contribution paves the way for additional studies on the molecular and chemical interactions involved in aroma and textural perception in simulated trials.

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The amount of free ions, ion pairs, and higher aggregate of the possible species present in a solution during the gold(I)-catalyzed alkoxylation of unsaturated hydrocarbon, i.e., ISIP (inner sphere ion pair) [(NHC)AuX] and OSIP (outer sphere ion pairs) [(NHC)Au(TME)X] [NHC 1,3-bis(2,6-di-isopropylphenyl)-imidazol-2-ylidene; TME = tetramethylethylene (2,3-bis methyl-butene); X- = Cl-, BF4-, OTf-; and OTs- BArF4- (ArF = 3,5-(CF3)2C6H3)], has been determined. The 1H and 19F DOSY NMR measurements conducted in catalytic conditions indicate that the dissociation degree (α) of the equilibrium ion pair/free ions {[(NHC)Au(TME)X] [(NHC)Au(TME)]+ + X-} depends on the nature of the counterion (X-) when chloroform is the catalytic solvent: while the compounds containing OTs- and OTf- as the counterion gave a low α (which means a high number of ion pairs) of 0.13 and 0.24, respectively, the compounds containing BF4- and BArF4- showed higher α values of 0.36 and 0.32, respectively. These results experimentally confirm previous deductions based on catalytic and theoretical data: the lower the α value, the greater the catalytic activity because the anion that can activate methanol during a nucleophilic attack, although the lower propensity to activate methanol of BF4- and BArF4-, as suggested by the DFT calculations, cannot be completely overlooked. As for the effect of the solvent, α increases as the dielectric constant increases, as expected, and in particular, green solvents with high dielectric constants show a very high α (0.90, 0.84, 0.80, and 0.70 for propylene carbonate, γ-valerolactone, acetone, and methanol, respectively), thus confirming that the moderately high activity of NHC-Au-OTf in these solvents is due to the specific effect of polar functionalities (O-H, C=O, O-R) in activating methanol. Finally, the DOSY measurements conducted in p-Cymene show the formation of quadrupole species: under these conditions, the anion can better exercise its 'template' and 'activating' roles, giving the highest TOF.

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Pairing is a commonly recommended practice used to build rapport and create positive therapeutic environments. However, there are limited evaluations of training procedures to teach pairing skills to direct-care staff. The purpose of the present study was to formalize and improve the efficiency of the training process for the initial stages of pairing using video modeling with embedded voice-over instructions plus performance feedback. Participants included three dyads of behavior technicians and children with autism. The results indicated that the training package increased the consistency of pairing implementation. These outcomes were maintained in a novel setting and for up to 4 weeks following training. We also measured relevant child behaviors such as joint attention, engagement, indices of happiness, and calm. Specific areas for future research are described.

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Ferromagnetic Josephson junctions play a key role in understanding the interplay between superconductivity and ferromagnetism in condensed matter physics. The magnetic domain structures of the ferromagnet in such junctions can significantly affect the tunneling of the superconducting Cooper pairs due to the strong interactions between Cooper pairs and local magnetic moments in the ferromagnetic tunnel barrier. However, the underlying microscopic mechanism of relevant quasiparticle tunneling processes with magnetic domain structures remains largely unexplored. Here, the manipulation of Cooper-pair tunneling in the NbSe2/Cr2Ge2Te6/NbSe2 ferromagnetic Josephson junction is demonstrated by using a multidomain ferromagnetic barrier with anisotropic magnetic moments. The evolution of up-, down-magnetized domain and Bloch domain structures in Cr2Ge2Te6 barrier under external magnetic fields leads to the enhancement of the critical tunneling supercurrent and an unconventional dual-peak feature with two local maxima in the field-dependent critical current curve. The phenomenon of magnetic-field-modulated critical tunneling supercurrent can be well explained by the competition between the coherence length of tunneling Cooper pairs and the size of magnetic domain walls in Cr2Ge2Te6 barrier. This kind of ferromagnetic Josephson junction provides an intriguing material system for manipulating Cooper-pair tunneling by tuning the local magnetic moments within magnetic Josephson junction devices.