Glassy gels toughened by solvent.

Glassy polymers are generally stiff and strong yet have limited extensibility1. By swelling with solvent, glassy polymers can become gels that are soft and weak yet have enhanced extensibility1-3. The marked changes in properties arise from the solvent increasing free volume between chains while weakening polymer-polymer interactions. Here we show that solvating polar polymers with ionic liquids (that is, ionogels4,5) at appropriate concentrations can produce a unique class of materials called glassy gels with desirable properties of both glasses and gels. The ionic liquid increases free volume and therefore extensibility despite the absence of conventional solvent (for example, water). Yet, the ionic liquid forms strong and abundant non-covalent crosslinks between polymer chains to render a stiff, tough, glassy, and homogeneous network (that is, no phase separation)6, at room temperature. Despite being more than 54 wt% liquid, the glassy gels exhibit enormous fracture strength (42 MPa), toughness (110 MJ m-3), yield strength (73 MPa) and Young's modulus (1 GPa). These values are similar to those of thermoplastics such as polyethylene, yet unlike thermoplastics, the glassy gels can be deformed up to 670% strain with full and rapid recovery on heating. These transparent materials form by a one-step polymerization and have impressive adhesive, self-healing and shape-memory properties.

A lanthanide-rich kilonova in the aftermath of a long gamma-ray burst.

Observationally, kilonovae are astrophysical transients powered by the radioactive decay of nuclei heavier than iron, thought to be synthesized in the merger of two compact objects1-4. Over the first few days, the kilonova evolution is dominated by a large number of radioactive isotopes contributing to the heating rate2,5. On timescales of weeks to months, its behaviour is predicted to differ depending on the ejecta composition and the merger remnant6-8. Previous work has shown that the kilonova associated with gamma-ray burst 230307A is similar to kilonova AT2017gfo (ref. 9), and mid-infrared spectra revealed an emission line at 2.15 micrometres that was attributed to tellurium. Here we report a multi-wavelength analysis, including publicly available James Webb Space Telescope data9 and our own Hubble Space Telescope data, for the same gamma-ray burst. We model its evolution up to two months after the burst and show that, at these late times, the recession of the photospheric radius and the rapidly decaying bolometric luminosity (Lbol ∝ t-2.7±0.4, where t is time) support the recombination of lanthanide-rich ejecta as they cool.

Collaborative imagination synchronizes representations of the future and fosters social connection in the present.

From close friends to people on a first date, imagining a shared future appears fundamental to relationships. Yet, no previous research has conceptualized the act of imagination as a socially constructed process that affects how connected we feel to others. The present studies provide a framework for investigating imagination as a collaborative process in which individuals cocreate shared representations of hypothetical events-what we call collaborative imagination. Across two preregistered studies (N = 244), we provide evidence that collaborative imagination of a shared future fosters social connection in novel dyads-beyond imagining a shared future individually or shared experience in general. Subjective ratings and natural language processing of participants' imagined narratives illuminate the representational features of imagined events shaped by collaborative imagination. Together, the present findings have the potential to shift how we view the structure and function of imagination with implications for better understanding interpersonal relationships and collective cognition.

How Imagination and Memory Shape the Moral Mind.

Interdisciplinary research has proposed a multifaceted view of human cognition and morality, establishing that inputs from multiple cognitive and affective processes guide moral decisions. However, extant work on moral cognition has largely overlooked the contributions of episodic representation. The ability to remember or imagine a specific moment in time plays a broadly influential role in cognition and behavior. Yet, existing research has only begun exploring the influence of episodic representation on moral cognition. Here, we evaluate the theoretical connections between episodic representation and moral cognition, review emerging empirical work revealing how episodic representation affects moral decision-making, and conclude by highlighting gaps in the literature and open questions. We argue that a comprehensive model of moral cognition will require including the episodic memory system, further delineating its direct influence on moral thought, and better understanding its interactions with other mental processes to fundamentally shape our sense of right and wrong.

Education Innovations in the Department of Psychiatry at Washington University.

The Department of Psychiatry at Washington University has been innovating psychiatric education during the second millennium at all levels of training - undergraduate medical, general residency, and child and adolescent psychiatry (CAP) fellowship training. Undergraduate medical education now occurs in three phases. The 18-month pre-clerkship phase is divided into seven multidisciplinary modules that span basic, social, and clinical sciences. Psychiatry is part of the seven-week long Brain and Behavior module. The yearlong second phase includes a six-week traditional psychiatry clerkship-like experience bracketed by an introductory foundational week and a one-week consolidation period. The third phase is 18 months in length and provides in-depth exploration of both clinical and non-clinical areas. The residency training program has enlarged the number of residents undergoing training and simultaneously greatly expanded the clinical exposure to include rotations in eating disorders and perinatal psychiatry. In addition, our residents can choose to enhance their training in either our research or leadership focused options, both of which are also available to trainees in our child and adolescent program. Additionally, our CAP trainees are exposed to several unique areas including eating disorders and substance use disorders. We believe that these innovations across the educational spectrum allow us to prepare our learners for the practice of psychiatry in the 21st century.

A molecular interaction-diffusion framework for predicting organic solar cell stability.

Rapid increase in the power conversion efficiency of organic solar cells (OSCs) has been achieved with the development of non-fullerene small-molecule acceptors (NF-SMAs). Although the morphological stability of these NF-SMA devices critically affects their intrinsic lifetime, their fundamental intermolecular interactions and how they govern property-function relations and morphological stability of OSCs remain elusive. Here, we discover that the diffusion of an NF-SMA into the donor polymer exhibits Arrhenius behaviour and that the activation energy Ea scales linearly with the enthalpic interaction parameters χH between the polymer and the NF-SMA. Consequently, the thermodynamically most unstable, hypo-miscible systems (high χ) are the most kinetically stabilized. We relate the differences in Ea to measured and selectively simulated molecular self-interaction properties of the constituent materials and develop quantitative property-function relations that link thermal and mechanical characteristics of the NF-SMA and polymer to predict relative diffusion properties and thus morphological stability.

Organic-based photodetectors for multiband spectral imaging.

Using organic photodetectors for multispectral sensing is attractive due to their unique capabilities to tune spectral response, transmittance, and polarization sensitivity. Existing methods lack tandem multicolor detection and exhibit high spectral cross talk. We exploit the polarization sensitivity of organic photodetectors, together with birefringent optical filters to design single-pixel multispectral detectors that achieve high spectral selectivity and good radiometric performance. Two different architectures are explored and optimized, including the Solc-based and multitwist-retarder-based organic photodetectors. Although the former demonstrated a higher spectral resolution, the latter enables a more compact sensor as well as greater flexibility in device fabrication.

Optical crosstalk and off-axis modeling of an intrinsic coincident polarimeter.

Polarimeters have broad applications in remote sensing, astronomy, and biomedical imaging to measure the emitted, reflected, or transmitted state of polarization. An intrinsic coincident (IC) full-Stokes polarimeter was previously demonstrated by our group, in a free space configuration, by using stain-aligned polymer-based organic photovoltaics. To minimize the model's complexity, these were tilted to avoid crosstalk from back-reflections. We present a theoretical model of a monolithic IC polarimeter that considers the back-reflection's influence for on-axis light. The model was validated using a monolithic four-detector polarimeter, which achieved an error of less than 3%. Additionally, an off-axis model was produced and validated for a simpler two detector polarimeter, demonstrating an error between the TM and TE polarized components of less than 3% for angles spanning an 18° incidence cone.

Competition between exceptionally long-range alkyl sidechain ordering and backbone ordering in semiconducting polymers and its impact on electronic and optoelectronic properties.

Intra- and intermolecular ordering greatly impact the electronic and optoelectronic properties of semiconducting polymers. Despite much prior efforts regarding molecular packing, the interrelationship between ordering of alkyl sidechains and conjugated backbones has not been fully detailed. We report here the discovery of a highly ordered alkyl sidechain phase in six representative semiconducting polymers, determined from distinct spectroscopic and diffraction signatures. The sidechain ordering exhibits unusually large coherence lengths of at least 70 nm, induces torsional/twisting backbone disorder, and results in a vertically layered multilayer nanostructure with ordered sidechain layers alternating with disordered backbone layers. Calorimetry and in-situ variable temperature scattering measurements in a model system PBnDT-FTAZ clearly delineate this competition of ordering that prevents the simultaneous long-range order of both moieties. The long-range sidechain ordering can be exploited as a transient state to fabricate PBnDT-FTAZ films with an atypical edge-on texture and 2.5x improved OFET mobility. The observed influence of ordering between the moieties implies that improved molecular design could produce synergistic rather than destructive ordering effects. Given the large sidechain coherence lengths observed, such synergistic ordering should greatly improve the coherence length of backbone ordering and thereby improve electronic and optoelectronic properties such as charge transport and exciton diffusion lengths.

Treatment Emergent Suicidal Ideation in depressed older adults.

BACKGROUND: Treatment-Emergent Suicidal Ideation (TESI) in older adults is poorly understood. We characterized TESI in older depressed adults during treatment with venlafaxine and explored whether TESI is related to antidepressant exposure versus dimensions of the psychiatric illness. We examined the relationship among medication exposure, onset of TESI, and clinical characteristics. METHODS: We analyzed data on 233 clinical trial participants with major depression and no baseline suicidal ideation who were treated for up to 12 weeks with venlafaxine XR (target dose: 150-300 mg/day). Suicidal ideation was assessed weekly with the Scale for Suicide Ideation. A Kaplan-Meier curve displayed the time course of TESI. Differences in baseline demographic and clinical variables between the TESI and Non-TESI groups were assessed with analyses of covariance or logistic regression. A final multivariate logistic regression model indicated baseline predictors of TESI. Depression treatment outcomes in subjects developing TESI versus those who did not were examined with a mixed effects model. RESULTS: TESI occurred in 10% of participants, typically with onset within 4 weeks of the start of treatment. Anxiety, and depression severity at baseline were predictors of TESI. Most TESI was mild and transient, with 6/233 participants having TESI considered clinically meaningful. TESI was not associated with venlafaxine blood levels or side effects. CONCLUSIONS: In older depressed adults, TESI is relatively uncommon and it is likely related to the underlying illness rather than to a medication adverse effect. This suggests that TESI requires continuing rather than discontinuing antidepressant treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Structural behaviour and gene delivery in complexes formed between DNA and arginine-containing peptide amphiphiles.

We describe in depth the structure of complexes formed between DNA and two classes of arginine-containing peptide amphiphiles, namely, the lipopeptide PRW-C16 (P = proline, R = arginine, W = tryptophan, C16 = C16 : 0 alkyl chain) and the bolaamphiphile RFL4FR (R = arginine, F = phenylalanine, L = leucine). A combination of X-ray and neutron scattering provided unprecedented insights into the local structure of these complexes. Lipopeptide-based complexes self-assembled into layered structures with large-scale fractal features, hosting DNA in the interstices. Bola-amphiphile scaffolds were characterized by planar structures with DNA strands presumably sandwiched in-between peptide nanotapes. Importantly, complexation did not affect the structural integrity of DNA in either of the two complexes. The bolaamphiphile conjugates displayed high levels of molecular ordering in contrast to the liquid-crystalline features observed in lipopeptide assemblies. Peptide-DNA complexes were assessed for their potential as a means to deliver the reporter vector pEGFP-N1 into SW480 human colon carcinoma cells. Successfully transfected cells expressed green fluorescent protein. The potentiating effect of PRW-C16 on the cellular uptake of ectopic DNA was found to be much greater than that observed with RFL4FR. In contrast to the bolaamphiphile-based conjugate, the liquid-crystalline nature of the lipopeptide complex is likely to play a key role in DNA release and transfection efficiency since these weakly bound structures require lower energy expenditure during disassembly and load release.

Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa.

BACKGROUND: Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. METHOD: Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. The resulting expression clones were then functionally screened to identify clones expressing rPA-IL proteins with altered carbohydrate binding properties. RESULTS: This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for ß-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. Key amino acid substitutions were identified and linked with specific carbohydrate binding activities. Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. CONCLUSIONS: The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. GENERAL SIGNIFICANCE: The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. The ability to readily produce these RPLs in gram quantities could enable them to find larger scale applications for glycoprotein or biotherapeutic purification.

Ethical reasoning versus empathic bias: a false dichotomy?

Does empathy necessarily impede equity in altruism? Emerging findings from cognitive and affective science suggest that rationality and empathy are mutually compatible, contradicting some earlier, prominent arguments that empathy impedes equitable giving. We propose alternative conceptualizations of relationships among empathy, rationality, and equity, drawing on interdisciplinary advances in altruism research.

From memory to motivation: Probing the relationship between episodic simulation, empathy, and helping intentions.

Research has documented a strong link between constructing episodic simulations-vivid imaginations of specific events-and empathy. To date, most studies have used episodic simulations of helping someone to facilitate affective empathy and promote helping intentions, but have not studied how episodic simulations of another's distressing situation affect empathy. Moreover, affective empathy encompasses both personal distress (i.e., an egocentric experience of distress in response to another's circumstances) and empathic concern (i.e., compassion for another), but we do not know how episodic simulations affect each component. To address these questions, we ran three experiments testing how different episodic simulations influenced personal distress and empathic concern, and thereby willingness to help. In Experiment 1 (N = 216), we found that participants who constructed episodic simulations of another's situation reported increased personal distress (but not empathic concern) and increased helping intentions compared to a control group; additional analyses revealed that personal distress mediated the simulation effect on helping. Furthermore, in Experiment 2 (N = 213), we contrasted episodic simulation of helping versus the distressing scenario; we found no differences in personal distress or helping intentions, but simulating helping led to higher empathic concern. Experiment 3 (N = 571) included both simulation conditions and a control condition; we fully replicated our findings, additionally showing that simulating a helping interaction increased personal distress, empathic concern, and helping intentions relative to the control condition, which consisted of prior work. Taken together, our work illustrates how distinct forms of episodic simulation differentially guide empathic responding and highlights the importance of personal distress in motivating helping. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Functional consequence of positive selection revealed through rational mutagenesis of human myeloperoxidase.

Myeloperoxidase (MPO) is a member of the mammalian heme peroxidase (MHP) multigene family. Whereas all MHPs oxidize specific halides to generate the corresponding hypohalous acid, MPO is unique in its capacity to oxidize chloride at physiologic pH to produce hypochlorous acid (HOCl), a potent microbicide that contributes to neutrophil-mediated host defense against infection. We have previously resolved the evolutionary relationships in this functionally diverse multigene family and predicted in silico that positive Darwinian selection played a major role in the observed functional diversities (Loughran NB, O'Connor B, O'Fagain C, O'Connell MJ. 2008. The phylogeny of the mammalian heme peroxidases and the evolution of their diverse functions. BMC Evol Biol. 8:101). In this work, we have replaced positively selected residues asparagine 496 (N496), tyrosine 500 (Y500), and leucine 504 (L504) with the amino acids present in the ancestral MHP and have examined the effects on the structure, biosynthesis, and activity of MPO. Analysis in silico predicted that N496F, Y500F, or L504T would perturb hydrogen bonding in the heme pocket of MPO and thus disrupt the structural integrity of the enzyme. Biosynthesis of the mutants stably expressed in human embryonic kidney 293 cells yielded apoproMPO, the heme-free, enzymatically inactive precursor of MPO, that failed to undergo normal maturation or proteolytic processing. As a consequence of the maturational arrest at the apoproMPO stage of development, cells expressing MPO with mutations N496F, Y500F, L504T, individually or in combination, lacked normal peroxidase or chlorinating activity. Taken together, our data provide further support for the in silico predictions of positive selection and highlight the correlation between positive selection and functional divergence. Our data demonstrate that directly probing the functional importance of positive selection can provide important insights into understanding protein evolution.

FROM ISOLATION TO COMMUNITY: EXPLORATORY STUDY OF A SENSE-OF-COMMUNITY INTERVENTION.

This exploratory pilot study analyzes the role a facilitated neighborhood intervention, geared towards meeting one's neighbors and discussing local needs and civic action, can play in moving individuals from isolation to community. It focuses on whether NeighborCircles, a neighborhood intervention run by a non-profit in Massachusetts, is associated with increases in social capital (SC); the main constructs used are Perkins and Long's (2002) four dimensions of SC (sense of community (SOC), collective efficacy, neighboring and participation), with a primary focus on SOC. Surveys and interviews with a majority Latino sample group reveal NeighborCircles is associated with increases in all four dimensions of SC. The author concludes by considering what may have led to these reported increases, as well as implications for both future research about and experimentation with similar interventions.

Lectin Affinity Chromatography.

Glycosylation is a non-template-driven posttranslational modification during which linked-sugars and glycans are added to the nascent polypeptide. Over 70% of the eukaryotic proteome is thought to be glycosylated. It is now known that correct glycosylation is essential for the correct folding, solubility, stability, and immunogenicity of proteins. In this chapter, we describe the technique of lectin affinity chromatography (LAC), a procedure that has the ability to distinguish different glycans, which are attached to proteins or lipids, termed glycoproteins or glycolipids, respectively. This method utilizes different immobilized lectins that have affinity for specific sugar substrates, to separate a wide range of glycan-attached complexes (Ambrosi et al., Org Biomol Chem 3:1593-1608, 2005). To further enhance the specificity of LAC, a corresponding free sugar may be used to produce a specific elution. In general, the conditions under which lectin affinity chromatography operates are relatively mild resulting in good biological recoveries of the glycoproteins.

Social value at a distance: Higher identification with all of humanity is associated with reduced social discounting.

How much we value the welfare of others has critical implications for the collective good. Yet, it is unclear what leads people to make more or less equal decisions about the welfare of those from whom they are socially distant. The current research sought to explore the psychological mechanisms that might underlie welfare judgements across social distance. Here, a social discounting paradigm was used to measure the tendency for the value of a reward to be discounted as the social distance of its recipient increased. Across two cohorts (one discovery, one replication), we found that a more expansive identity with all of humanity was associated with reduced social discounting. Additionally, we investigated the specificity of this association by examining whether this relationship extended to delay discounting, the tendency for the value of a reward to be discounted as the temporal distance to its receipt increases. Our findings suggest that the observed association with identity was unique to social discounting, thus underscoring a distinction in value-based decision-making processes across distances in time and across social networks. As data were collected during the COVID-19 pandemic, we also considered how stress associated with this global threat might influence welfare judgements across social distances. We found that, even after controlling for COVID-19 related stress, correlations between identity and social discounting held. Together, these findings elucidate the psychological processes that are associated with a more equal distribution of generosity.

Appendicitis-related acute referrals to Children's Health Ireland from Non-Specialist Paediatric Surgical Centres.

BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Eighty percent of paediatric appendicectomies are performed by adult general surgeons on an annual basis. The remaining 20% are performed at Children's Health Ireland (CHI) centres. Occasionally patients are transferred from Non-Specialist Paediatric Surgical Centres (NSPSC) for specialised pre-operative or post-operative care. AIM: To assess the rates of and characterise appendicitis-related referrals to CHI at Crumlin from NSPSC. METHODS: A retrospective review of all appendicitis-related transfers to CHI at Crumlin between January 2020 and December 2021 was performed. Data relating to indications for transfer, referring hospital level, patient demographics, management, type of surgery, length of stay (LOS), and radiological studies were collected and analysed. RESULTS: Seventy-two patients were transferred to CHI at Crumlin over the 2-year period. A total of 60.9% were male, mean age 9 ± 4.3 years, mean LOS 6.0 ± 2.2 days (range 1-30 days). Nineteen percent were under 5 years of age. Seventy-three percent were transferred from level 4 centres. Ninety-seven percent were transferred pre-operatively, 25% of those transferred pre-operatively had imaging in CHI confirming appendicitis. Fifty-five percent (40/72) of patients had pre-operative imaging performed. A total of 37.5% (15/40) confirmed complicated appendicitis. Twenty percent (8/40) underwent both ultrasound and computerised tomography (CT) at the referring centre. A total of 2.7% (2/72) were transferred with known co-morbidities. Ninety-two percent (66/72) underwent appendicectomy. Eight percent (6/72) were managed non-operatively (NOM) - 2 failed NOM, 2 underwent interval appendicectomy. Of those managed operatively, 76% (50/66) underwent laparoscopic appendicectomy, and 24% (16/66) were performed open. CONCLUSION: The majority of paediatric appendicectomies are performed at Non-Specialist Paediatric Surgical Centres. It is vital to maintain this working relationship so that specialist paediatric centres are available to provide care to complex paediatric patients.