Large Changes Research Articles

Private Medicare plans' responses to benchmark changes and competition before and after the Affordable Care Act's payment cuts.

To examine how private Medicare Advantage (MA) plans responded to slower growth in federal payments after the Affordable Care Act (ACA). We used publicly available data from the Centers for Medicare and Medicaid Services on MA plan subsidies ("benchmarks"), asking prices ("bids"), plan premiums, cost-sharing, and covered benefits. Data covered all counties with MA plans between 2006 through 2019. We examined plan responses to changes in benchmark subsidies by comparing changes in bids, rebates, and other outcomes between counties experiencing larger changes in benchmarks and counties with smaller changes, pre- and post-ACA. We used longitudinal fixed effects regression models to assess heterogeneity in how plans adjusted premiums and benefits across more and less competitive markets. Analyses included all counties with at least one MA plan available to individual beneficiaries. Plans targeting special populations were excluded. Average plan benchmarks fell by $89 per month post-ACA, adjusted for inflation. Plans responded similarly to benchmark subsidy decreases and increases, increasing bids by 62 cents for every dollar increase in subsidies pre-ACA (95% confidence interval [CI]: 0.56 to 0.67) and decreasing them by 57 cents for every dollar reduction in subsidies post-ACA (95% CI: 0.49-0.65). However, post-ACA, plans altered less salient benefits, such as cost-sharing, by about twice as much as they had pre-ACA. Premiums changed by similar amounts before and after the ACA (-$0.07, 95% CI: from -$0.09 to -$0.06). Plans in more competitive markets responded less to payment changes than plans did in less competitive markets, suggesting the former are operating closer to marginal costs. Finally, payments to plans declined far less than projected due in part to other changes in MA policy. Plans used partial pass-through of benchmark subsidy decreases to shield beneficiaries from cuts and allocated benchmark decreases to benefits that were less salient to the average enrollee. These findings, combined with higher-than-projected payments post-ACA, may explain the continued growth in MA enrollment.

The Impact of Hydrostatic Pressure on the Structural, Mechanical, Thermal, and Optoelectronic Characteristics of the RbV3Sb5 Kagome Compound: Ab initio Approach.

We studied the RbV3Sb5 kagome compound's structural, mechanical, thermal, and optoelectronic properties. Mulliken and Hirshfeld population analysis found ionic and covalent connections in RbV3Sb5. The Born stability criterion shows that pure RbV3Sb5 is mechanically stable. The precise measurement of 3.96 indicates that our sample has higher machinability at 20 GPa. Low anticipated hardness of RbV3Sb5 suggests it can be used as a soft solid lubricant. Hardness ratings rise with pressure, however there are exceptions. Pressure causes large nonmonotonic changes in RbV3Sb5's anisotropic characteristics. A comparable 20 GPa Zener anisotropic value, RbV3Sb5 has the highest. The structure's projected Debye temperature at 0 GPa is 284.39 K, indicating softness. Dispersion curves with negative frequencies suggest ground state structural dynamical instability. The structure has no negative-energy phonon branches under 10 GPa stress. From band structure and density of state analysis, the structure behaves metallically under hydrostatic pressure. Also, the structure has maximal ultra-violet conductivity and absorption. The absorption coefficient, conductivity, and loss function plots show uniform patterns at all pressures. As pressure rises, these graphs' peaks blue shift.

Impact of lake expansion on the underwater topography: a case study of Lexiewudan and Yanhu Lakes on the Tibetan Plateau

ABSTRACT With increased precipitation and meltwater, most lakes on the Tibetan Plateau have expanded rapidly. However, the impact of erosion and sedimentation following lake expansion remains unclear. Using Lexiewudan and Yanhu Lakes as examples, we created a water depth inversion model using random forest method and combined it with lake bathymetric data and Landsat images and analyzed changes in underwater topography using SRTM and ICESat-2 data. The average water depths of two lakes were 5.92 and 9.82 m, and the root mean square error of inversion values were 0.85 and 0.93 m, respectively. Results showed that the underwater topography underwent considerable changes, in which at least half of the study areas experienced large topographic changes with 2–5 m. Lexiewudan Lake had a topographic change of more than 2 m in 61.28% of the total, while Yanhu Lake made up 69.78% of the total. The erosion and sedimentation volume of Lexiewudan Lake were 0.19 and 0.03 km3 and those of Yanhu Lake were 0.38 and 0.03 km3, respectively. Extensive underwater erosion and sedimentation are closely related to the original topography. Lake water movement, sediment transport, and permafrost degradation in flooded areas may also affect changes in underwater topography.

Effects of sleeve gastrectomy and Roux-en-Y gastric bypass on pharmacokinetics of lamotrigine and valproate: A cohort study

BackgroundBariatric surgeries may affect the pharmacokinetics of medications through alterations of the gastrointestinal physiology. Pharmacokinetic changes of first-line antiseizure medications such as lamotrigine and valproate following bariatric treatment have received little research attention so far. MethodsIn our prospective case study we included lamotrigine- or valproate-treated patients undergoing bariatric surgery at hospitals in Central Norway. Lamotrigine and valproate concentrations were assessed using serial blood samples over a dose interval, before and one, six and twelve months following surgery. Primary outcomes included changes in area under the time-concentration curve (AUC) with secondary outcomes comprising full pharmacokinetic profiling. ResultsSix lamotrigine-treated obese patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 3) and sleeve gastrectomy (SG) (n = 3), as well as two valproate-treated patients (one undergoing RYGB and one SG) were included. Largest changes for dose-adjusted AUC values after surgery were seen in RYGB-treated patients on lamotrigine (average increases of 38 % one month and 32 % 12 months postoperatively). In the patients on valproate, AUC values were decreased by 22 % after 6 months and by 30 % after 12 months. The interindividual variation was high. Formal statistical testing was not done due to few cases. ConclusionPostoperative pharmacokinetic changes for lamotrigine and valproate were modest, but for lamotrigine changes may be larger in patients undergoing RYGB than in those undergoing SG. Given the substantial interindividual variation, therapeutic drug monitoring should be used to capture pharmacokinetic changes and guide dose adjustments after bariatric surgery.

Single-pot extractive double divided wall column for Acetonitrile, Ethanol, and water Separation: Design and control

An integrated single-pot double divided wall column (DDWC) process is designed for separating acetonitrile, ethanol and water into its constituent pure components using dimethyl sulfoxide (DMSO) as the homogenous extractive entrainer. Comparison with the recently reported side-stream extractive distillation (SSED) design with three columns shows the single-pot process to be more cost-effective and energy-efficient. The SSED process has a Total Annualized Cost (TAC) that is higher by 9.91% and an energy consumption that is higher by 7.27%. Also, a decentralized temperature inferential control system is shown to effectively reject large throughput and moderate feed composition changes to establish the controllability of the proposed design. The developed single-pot process is thus a promising alternative, particularly for space-constrained production facilities.

Variability of Dry Days and Sequences of Dry Days in the Polish Carpathians in the Period 1986–2020

This study provides a climatological analysis of annual and long-term variability of dry days and sequences of dry days in the Polish Carpathians between 1986 and 2020. The input data for the research was compiled from the daily precipitation totals from 17 meteorological stations and the T. Niedźwiedź catalogue of circulation types over southern Poland. The frequency of sequences of dry days of different duration has been presented. The incidence of long-term periods has been related to the atmospheric circulation. The number of dry days and the averages of both the number and of the duration of sequences of dry days were analysed for the study period. This yielded an average annual number of dry days ranging from 142 to 195 (39–53% of days in a year), depending on the altitude above sea level and longitude. A general pattern emerged in which the number of dry days increased from west to east. At most stations, there were no statistically significant trends with respect to the dry day characteristics analysed. This is an obvious result of high year-to-year variability, which means that only large changes can achieve statistical significance. Dry days have been evidenced to relate to circulation types. The vast majority of dry days are related to anticyclonic systems, particularly the anticyclonic wedge (Ka) and western anticyclonic (Wa) situations. On the other hand, no clear-cut relationship was established between an increase in air temperature and the occurrence of dry days.

Language choice and code-mixing in a longitudinal study of an Estonian-English bilingual child

The input that bilingual children receive influences their language proportions, language development, and code-mixing. Most studies on these topics have included early bilinguals whose input proportions undergo large changes in early childhood and whose parents use the one-parent-one-language family language policy. This paper examines the input-output proportions of an Estonian-English bilingual child over a period of 2.5 years (2;3-5;01) using recorded spontaneous speech from a situation where the input language proportions did not change and where the family language policy was different from the one-parent-one-language policy that is presented in most studies: the family rotated the language they all spoke by the day of the week. Additionally, the child’s code-mixing rate and her MLU scores are investigated to provide an overview of these factors in an unstudied input situation. Lastly, it is analyzed whether code-mixing by older siblings influences the code-mixing rate of the younger sibling. The results indicate that in the early phases of language development the child uses all the linguistic resources available to her, and as her language develops, she responds more in the language of the conversation and code-mixes less. However, there is also a period where the child unexpectedly almost stops speaking in Estonian regardless of the unchanged input. The data shows that code-mixed utterances are the longest, hence supporting previous research findings and indicating that code-mixing is a tool that helps the child communicate better. Code-mixing by siblings does not show any signs of affecting the younger sibling’s code-mixing rate, though a more thorough analysis is necessary. Hence, the results indicate the importance of input and shed light on input effects in bilingual language acquisition in an understudied input situation.

Use Of Digital Technologies In Prosthodontic Clinical Practice Among Prosthodontists In Tamilnadu And Pondicherry

Background: Digital dentistry includes treatments performed by means of digital or computer-controlled components rather than using mechanical or electrical equipment. The advancement of digital technology and the commencement of Computer-Aided Design (CAD) and Computer-Aided Manufacturing (CAM) and 3D printing has brought large changes to the traditional manufacturing method, where manual work is carried out after oral impression taking. Aim: To conduct a questionnaire survey on use of digital technology in prosthodontic clinical practice among Prosthodontists in Tamilnadu and Pondicherry. Materials and methods: A cross-sectional questionnaire based online survey was undertaken amongst 183 Prosthodontists in Tamilnadu and Pondicherry (Group 1 – Both private practitioners and teaching faculty, Group 2 – Private practitioners, Group 3 – Teaching faculty). The questionnaire consisted of 21 questions which evaluated their awareness, knowledge and practices towards digital dentistry. Statistical analysis was done using Chi-square test in each group, using Statistical Package for the Social Sciences (SPSS) version 23.0. The p-value 0.05 was considered significant. Results: Majority of the study participants were private practitioners in the age group of 25 – 45 years(93%).Among the three groups private practitioners had good knowledge, practice and awareness about the application of digital technologies. Conclusion: Most of the participants were aware about digital technology in dentistry. The private practitioners showed better understanding about the digital technology. However, to make them familiar with CAD/CAM, dental education programs, workshops and hands on program should be conducted which will enable an emerging dentists who will be well versed with digital dentistry.

Release of selected nutrients from polymer-coated fertilisers in the soil environment

The aim of the study was to evaluate the release of NH4-N and PO4-P from polymer-coated fertilisers in the soil environment, and to analyse their impact on pH and conductivity of the soil leachates. In this investigation mineral NPK(S) 6-20-30(7) fertiliser (as a starting material), commercial, controlled-release OsmocoteTM fertiliser (as a reference material) and four polymer-coated fertilisers have been used. Biodegradable polybutylene(succinate-co- dilinoleate), polyethylene(succinate-co-terepftalate) and chitosan have been used as coating materials. The experiments were conducted in the laboratory conditions, in PVC columns filled with air-dry soil. The nutrients release from the investigated materials was explained based on the diffusion mechanism and it was interpreted with the use of the Korsmeyer–Peppas kinetic model. Two mechanisms dominate in the release process of nutrients: the mechanism based on quasi-Fickian diffusion and non-Fickian (anomalous case) mechanism. The largest changes of pH and electrical conductivity (EC) of soil leachates occurred in the initial period of research for all tested fertilisers (pH: 9.5–20.3% – loamy sand (S1) 7.9–20.6% – sandy loam (S2); EC: 438–1667% – S1, 771–1509% – S2). The polymer coating significantly reduces the nutrient release from the fertiliser core. The size of these changes depends on the type and thickness of the polymer layer and the physicochemical properties of the soils.

Risk assessment method for civil aircraft approach and landing at high plateau based on QAR data

Civil aircraft approach and landing at high altitude is a high-risk stage of plateau flight. In order to effectively implement the risk identification and grade judgment of approach and landing at high altitude, an LSTM-DNN deep learning risk assessment method based on variable fuzzy recognition with weights removed is proposed. This method is first based on the high-altitude flight data recorded by the quick access recorder (QAR), and draws on the civil aircraft flight quality monitoring project specification (FOQA) consultation notice and industry QAR monitoring standards. Combined with the indicator importance analysis and Delphi expert survey, five key monitoring items are extracted as the risk assessment indicators of civil aircraft approach and landing at high altitude, including large heading change during landing, low track, large descent rate during 2000-1000 ft approach, vertical acceleration at touchdown, and large descent rate during 500-50ft approach. Then, in order to overcome the subjective bias of the evaluation indicator weight, the weight of the evaluation indicator is determined by the weight removal method, and the risk grade membership function is constructed based on the variable fuzzy recognition method. Finally, a risk assessment model for civil aircraft approach and landing at high altitude based on LSTM-DNN is established. Taking the Chengdu-Lhasa approach and landing segment as an example, the QAR data was extracted to train and test the risk assessment model, and the results were compared with those of Logistic multivariate regression, support vector machine (SVM) and other evaluation methods. The results show that the average recognition rate of the LSTM-DNN deep learning model based on variable fuzzy recognition with weights removed reaches 94.18%, and the highest can reach 94.79%, which verifies the objective effectiveness of the risk assessment method.

Determining Bandgaps in the Layered Group‐10 2D Transition Metal Dichalcogenide PtSe2

AbstractUnlike traditional group‐6 transition metal dichalcogenides (TMDs), group‐10 TMDs such as PtSe2 and PdTe2 possess highly tuneable indirect bandgaps, transitioning from semiconducting in the near‐infrared to semimetal behavior with a number of monolayers (MLs). This opens up the possibility of TMD‐based mid‐infrared and terahertz optoelectronics. Despite this large potential, the optical properties of such materials have shown an extremely large disparity between that predicted and measured. For example, simulations show that a few MLs is required for the semiconductor–semimetal transition, whilst tens of MLs is found experimentally. This is a result of widely used optical extrapolation methods to determine bandgaps, such as the Tauc plot approach, that are not adapted here owing to i) nearby direct transitions, ii) the material dimensionality and iii) large changes in the non‐parabolic bandstructure with MLs. Here, uniquely combining optical ellipsometry to determine the complex permittivity, terahertz time resolved spectroscopy for the complex conductivity and in‐depth density functional theory (DFT) simulations, it is shown that the optical properties and bandstructure can be determined reliably and demonstrate clearly that the semiconductor‐semimetal transition occurs for PtSe2 layers ≈5 MLs. The microscopic origins of the observed transitions and the crucial role of the Coulomb interaction for thin semiconducting layers, and that of interlayer van der Waals forces for multilayer semimetallic samples are also demonstrated. This work of combining complimentary experimental techniques and extensive simulations avoids the application of constrained extrapolation methods to determine the optical properties of group‐10 TMDs, and will be of importance for future mid‐infrared and terahertz applications.

Platinum Stabilises a Molten-Globule Conformation of a Small Globular Cytosolic Protein SUMO1.

Proteins are generally resistant to large conformational changes under physiological conditions. Here, we show that platinum (Pt(II)), which is widely-used metal centre in cancer therapeutic drugs, binds to a cytosolic protein, small ubiquitin-like modifier 1 (SUMO1), under physiological conditions and changes its conformation to a molten globule (MG). Mass spectrometry (ICP-MS) studies confirmed stoichiometric Pt(II) binding to SUMO1. Fluorescence spectroscopy showed Tyr fluorescence quenching and increased ANS binding. Fluorescence assays on Trp-mutants indicated conformational changes and circular dichroism (CD) suggested MG formation upon Pt(II) binding. In contrast, structural homologues of SUMO1 (ubiquitin (Ubq) and SUMO2) showed no conformational changes on Pt(II) titration. Further studies compared the impact of distinct His residues in SUMO1 on Pt(II) binding and protein structure to SUMO2 and Ubq. Experiments at low pH (5.0) implicated His residues interacting with Pt(II), corroborated by the absence of conformational change in the H75L mutant of SUMO1. Pt(II)-His binding in SUMO1 unravels key molecular determinants of Pt(II)-protein interactions and their conformational consequences. SUMO1 with other SUMOylation components are shown to have enhanced expression in several cancers, hence, our study suggests a possible fate of the non-targetability of Pt(II)-based drugs on SUMOylation in cancer cells, upon interaction with SUMO1.

Quantum Information Patterns Between Atoms in a Molecule.

Quantum information theory provides a powerful toolbox of descriptors that characterize many-electron systems based on quantum information patterns between open quantum systems. Despite the wealth of insights gained in the condensed matter community, the use of these descriptors to study interactions between atoms in a molecule remains limited. In this study, we develop a quantum information framework for molecules that characterizes the quantum information patterns between quantum atoms as defined in the Quantum Theory of Atoms in Molecules. We show that quantum information analyses capture key properties of quantum atoms and how they interact with their molecular environment. Additionally, we show that the presence of bond critical points can remain invariant despite large changes in the quantum information patterns between the quantum atoms. Our findings indicate that quantum information theory can shed a new light on molecular electronic structure.

Umami-enhancing effect of Agaricus bisporus-pork bone stocks based on the EUC value and sensory evaluation

In this study, Agaricus bisporus and pork bone stocks (PBS) were enzymatically digested, and the equivalent umami concentration (EUC) value, sensory evaluation and hydrolysis degree (DH) were used as indexes to find the optimal enzyme digestion conditions. Finally, the optimal enzymatic solution was mixed and analyzed for flavor compounds in the optimal enzymatic solution before and after Maillard reaction (MR) by GC × GC-O-MS. The results showed that the enzymatic digestion of mushroom stocks (MS) with a combination of Cellulase-Protamex™ (C-P) yielded high levels of flavor amino acids (40.733 ± 0.340 g/L), and 5′-nucleotides (12.807 ± 0.239 mg/g), and EUC values up to 1755.786 ± 40.759 g/100 g. Meanwhile, the simultaneous enzymatic hydrolysis of PBS with a combination of Flavourzyme™-Protamex™ (F-P) yielded high levels of flavor amino acids (51.265 ± 0.550 g/L) and 5′-nucleotides (17.477 ± 0.260 mg/g) with EUC values up to 3420.619 ± 114.193 g/100 g. Using the DH and sensory evaluation as indicators, the results showed that the greatest DH and the highest sensory scores were obtained with the addition of C-P-MS and F-P-MS at 7:3 (m/m). Finally, the compounds with large changes in concentration were mainly mushroom flavored 1-octen-3-ol (2208.614 ± 12.879 μg/kg), sweet-flavored 3-octanone (269.871 ± 11.691 μg/kg), floral-flavored benzyl alcohol (156.704 ± 14.859 μg/kg), green flavored 2-pentylfuran (190.470 ± 12.934 μg/kg), and almond-flavored furfural (523.555 ± 5.674 μg/kg).

Changes in suicide literacy and intentions to ask about suicide: “Community Linker” training for those supporting Aboriginal people

ObjectiveGatekeeper training programs are widely used with promising results for suicide prevention. However, studies have found that when delivered to Indigenous communities, outcomes can be variable or ineffective. This study is a feasibility trial of a gatekeeper program based on the standardised ‘Question, Persuade and Refer’ (QPR) approach, which was adapted to the cultural needs of local Aboriginal communities in the Shoalhaven region of New South Wales, Australia. The study aims to identify whether 1) knowledge of suicide and intentions to help increase over the course of completing the gatekeeper program; 2) participants of different educational backgrounds have similar outcomes in suicide literacy and intentions to help; and 3) Aboriginal people and non-Aboriginal people have similar outcomes. MethodsOne hundred individuals participated in the research, of which 50% identified as an Aboriginal person. Pre- and post-training questionnaires assessed whether participants experienced an increase in suicide literacy and intentions to support others at risk of suicide. ResultsAlthough pre-test scores for suicide literacy and intentions to help were high, these increased significantly from pre- to post-test. Those with no prior gatekeeper training showed larger changes in both suicide literacy and intentions to ask about suicide compared to those with prior training. ConclusionOverall, this study highlights that delivery of culturally adapted gatekeeper training is associated with improved suicide literacy and intentions to ask about suicide amongst trainees.

High-Performance Sodium-Ion Batteries with Graphene: An Overview of Recent Developments and Design.

Due to their low production cost, sodium-ion batteries (SIBs) are considered attractive alternatives to lithium-ion batteries (LIBs) for next generation sustainable and large-scale energy storage systems. However, during the charge/discharge cycle, a large volume strain is resulted due to the presence of a large radius of sodium ions and high molar compared to lithium ions, which further leads to poor cyclic stability and lower reversible capacity. In the past, researchers have devoted significant efforts to explore various anode materials to achieve SIBs with high energy density. Hence, as a promising anode material for SIBs, the two-dimensional (2D) materials including graphene and its derivatives and metal oxides have attracted remarkable attention due to their layered structure and superior physical and chemical properties. The inclusion of graphene and metal oxides with other nanomaterials in electrodes have led to the significant enhancements in electrical conductivity, reaction kinetics, capacity, rate performance and accommodating the large volume change respectively. Moreover, these 2D materials facilitated large surface areas and shorter paths for sodium ion adsorption and transportation respectively. In this review article, the fabrication techniques, structural configuration, sodium ion storage mechanism and its electrochemical performances will be introduced. Subsequently, an insight into the recent advancements in SIBs associated with 2D anode materials (graphene, graphene oxide (GO), transition metal oxides etc.) and other graphene-like elementary analogues (germanene, stanine etc.) as anode materials respectively will be discussed. Finally, the key challenges and future perspectives of SIBs towards enhancing the sodium storage performance of graphene-based electrode materials are discussed. In summary, we believe that this review will shed light on the path towards achieving long-cycling life, low operation cost and safe SIBs with high energy density using 2D anode materials and to be suitably commercialized for large-scale energy storage applications in the future.

HaloTag-Modified, Ferrocene Labeled Self-Assembled Monolayers for Protein Sensing.

Ferrocene (Fc)-based disulfide molecules of various lengths with amino acid scaffolds and alkane or oligo(phenylene-ethynylene) (OPE) bridges are used in a mixed SAM with a di-(ethylene oxide) terminal mercaptoundecanol diluent (PEG2). The relative height of the Fc redox reporter in the SAM is compared to determine if there are protective effects like antifouling and specific detection. The HaloTag-binding motif is used as a proof-of-concept to investigate the electrochemical response to the HaloTag protein due to its known covalent and fast linkage. When the Fc-SAMs are exposed to the HaloTag protein, there are an antifouling nature and more specific detection for the engulfed Fc-based molecules (C6tBu/Halo). The further out the Fc is from the SAM layer, the more nonspecific adsorption is detected. The double layer capacitance (CDL) has the smallest change for the C6tBu control (ΔCDL = -0.1 μF cm-2) showing antifouling properties and produces a large change (ΔCDL = 0.9 μF cm-2) as well as a shift in oxidation potential when the active C6Halo is exposed to the HaloTag protein (ΔE1/2 = 50 ± 10 mV). The remaining Fc molecules are partially in or outside the PEG2 layer, allowing more ion penetration/mobility even when the HaloTag protein is bound. Generally, a more disordered environment was observed for the Fc-based molecules when adding the HaloTag ligand, which is evident from a larger Efwhm and higher CDL. Desorption of the SAMs with sodium iodide (NaI) showed retention of the HaloTag protein bound with the corresponding ligand, whereas negative controls did not. Self-assembled monolayers for MALDI mass spectrometry (SAMDI-MS) were used as an orthogonal detection technique to show the qualitative binding of the HaloTag protein to the electrode. Together, these results provide insight into the antifouling and detection methods of engulfing the redox molecules in the SAM diluent.

Isolated during adolescence: long-term impact on social behavior, pain sensitivity, and the oxytocin system in male and female rats

BackgroundAdolescent social isolation (ASI) has profound long-term effects on behavioral and neural development. Despite this, the specific long-term impact of ASI during different adolescent stages and across sexes remain underexplored.MethodsOur study addresses this gap by examining the effects of early- and late- adolescent social isolation on both male and female rats. Rats were either isolated (or group-housed) starting from PD 21 (early) or PD 42 (late) for three weeks and then rehoused into groups. In adulthood (PD 90), rats underwent a battery of tests: elevated plus-maze, open field, novel object recognition, social interaction and social recognition memory and hotplate tests. Finally, we analyzed oxytocin receptor binding in several regions in the brains of a second cohort of rats.ResultsBoth, male and female rats from the late adolescent social isolation (LASI) groups spent significantly less time interacting in the social interaction test. Additionally, we observed a general decrease in social recognition memory regardless of sex. Both male ASI groups demonstrated heightened thermal pain sensitivity, while the opposite was observed in early adolescent social isolation (EASI) female rats. In the brain, we observed changes in oxytocin receptor (OTR) binding in the paraventricular nucleus of the hypothalamus (PVN) and paraventricular nucleus of the thalamus (PVT) and central amygdala (CeA) with the largest changes in EASI and LASI female rats.ConclusionOur model demonstrates long-lasting alterations on behavior and oxytocin receptor binding levels following ASI providing insights into the long-term effects of ASI in a time- and sex-specific manner.

A fitness distribution law for amino-acid replacements.

The effect of replacing the amino acid at a given site in a protein is difficult to predict. Yet, evolutionary comparisons have revealed highly regular patterns of interchangeability between pairs of amino acids, and such patterns have proved enormously useful in a range of applications in bioinformatics, evolutionary inference, and protein design. Here we reconcile these apparently contradictory observations using fitness data from over 350,000 experimental amino acid replacements. Almost one-quarter of the 20 × 19 = 380 types of replacements have broad distributions of fitness effects (DFEs) that closely resemble the background DFE for random changes, indicating an overwhelming influence of protein context in determining mutational effects. However, we also observe that the 380 pair-specific DFEs closely follow a maximum entropy distribution, specifically a truncated exponential distribution. The shape of this distribution is determined entirely by its mean, which is equivalent to the chance that a replacement of the given type is fitter than a random replacement. In this type of distribution, modest deviations in the mean correspond to much larger changes in the probability of falling in the far right tail, so that modest differences in mean exchangeability may result in much larger differences in the chance of a highly fit mutation. Indeed, we show that under the assumption that purifying selection filters out the vast majority of mutations, the maximum entropy distributions of fitness effects inferred from deep mutational scanning experiments predict the characteristic patterns of amino acid change observed in molecular evolution. These maximum entropy distributions of mutational effects not only provide a tuneable model for molecular evolution, but also have implications for mutational effect prediction and protein engineering.

Structural Rigidification Strategy Based on Self-Assembly Enabled Reversible Excited-State Conversion of Iridium(III) Complexes for Multiple-Stimulus-Responsive Data Encryption.

Stimulus-responsive chromic materials exhibit color-switching properties under specific external stimuli and have been widely used in various fields. Transition-metal complexes show great potential applications as promising candidates for stimulus-responsive chromic materials, as their excited states not only depend on the chemical composition but are also affected by the intermolecular stacking modes. Owing to the intrinsic difficulty in the ordered stacking of the octahedral configuration, changing the stacking modes of iridium(III) complexes for multiple-stimulus responsiveness remains a significant challenge. In this work, we propose a structural rigidification strategy based on self-assembly to reversibly regulate the excited states of iridium(III) complexes, therefore achieving color switch under different stimulus conditions. We prepare cationic iridium(III) complexes by using tetrakis(perfluorophenyl)-borate ([B(PhF5)4]-) as the counterion, whose matching tetrahedral configuration and electron-deficient aromaticity enables polar-π interaction with the octahedral iridium(III) cations, inducing self-assembly to form structural rigidification. The structural rigidity restricts the large conformational changes of the metal-to-ligand charge transfer (3MLCT) excited state, and facilitates the conversion from the 3MLCT to the ligand-center (3LC) excited state in aggregated states. The excited-state conversion results in a 54 nm blue shift (from yellow to sky blue) in the photoluminescence spectra. As a result, we report a series of cationic iridium(III) complexes with different responses to low temperature, vapor fuming, and mechanical force, therefore achieving multiple-stimulus-responsive data encryption. Our work provides a novel strategy to achieve ordered stacking of octahedral complexes, shows a deeper understanding of the photophysical processes of transition-metal complexes, and offers a new perspective to develop multiple-stimulus-responsive chromic materials.