Electroactive Ionic Polymer of Intrinsic Microporosity for High-Performance Capacitive Energy Storage.

Here, we report an ionic polymer of intrinsic microporosity (PIM) as a high-functioning supercapacitor electrode without the need for conductive additives or binders. The performance of this material is directly related to its large accessible surface area. By comparing electrochemical performance between a porous viologen PIM and a non-porous viologen polymer, we reveal that the high energy and power density are both due to the ability of ions to rapidly access the ionic PIM. In 0.1 M H2SO4 electrolyte, a pseudocapacitve energy of 315 F g-1 is observed, whereas in 0.1 M Na2SO4, a capacitive energy density of 250 F g-1 is obtained. In both cases, this capacity is retained over 10,000 charge-discharge cycles, without the need for stabilizing binders or conductive additives even at moderate loadings (5 mg cm-2). This desirable performance is maintained in a prototype symmetric two-electrode capacitor device, which had >99% Coloumbic efficiency and a <10 mF capacity drop over 2000 cycles. These results demonstrate that ionic PIMs function well as standalone supercapacitor electrodes and suggest ionic PIMs may perform well in other electrochemical devices such as sensors, ion-separation membranes, or displays. This article is protected by copyright. All rights reserved.

Darobactin Substrate Engineering and Computation Show Radical Stability Governs Ether versus C-C Bond Formation.

The Gram-negative selective antibiotic darobactin A has attracted interest owing to its intriguing fused bicyclic structure and unique targeting of the outer membrane protein BamA. Darobactin, a ribosomally synthesized and post-translationally modified peptide (RiPP), is produced by a radical S-adenosyl methionine (rSAM)-dependent enzyme (DarE) and contains one ether and one C-C cross-link. Herein, we analyze the substrate tolerance of DarE and describe an underlying catalytic principle of the enzyme. These efforts produced 51 enzymatically modified darobactin variants, revealing that DarE can install the ether and C-C cross-links independently and in different locations on the substrate. Notable variants with fused bicyclic structures were characterized, including darobactin W3Y, with a non-Trp residue at the twice-modified central position, and darobactin K5F, which displays a fused diether ring pattern. While lacking antibiotic activity, quantum mechanical modeling of darobactins W3Y and K5F aided in the elucidation of the requisite features for high-affinity BamA engagement. We also provide experimental evidence for ß-oxo modification, which adds support for a proposed DarE mechanism. Based on these results, ether and C-C cross-link formation was investigated computationally, and it was determined that more stable and longer-lived aromatic Cß radicals correlated with ether formation. Further, molecular docking and transition state structures based on high-level quantum mechanical calculations support the different indole connectivity observed for ether (Trp-C7) and C-C (Trp-C6) cross-links. Finally, mutational analysis and protein structural predictions identified substrate residues that govern engagement to DarE. Our work informs on darobactin scaffold engineering and further unveils the underlying principles of rSAM catalysis.

Electron beam response corrections for an ultra-high-dose-rate capable diode dosimeter.

BACKGROUND: Ultra-high-dose-rate (UHDR) electron beams have been commonly utilized in FLASH studies and the translation of FLASH Radiotherapy (RT) to the clinic. The EDGE diode detector has potential use for UHDR dosimetry albeit with a beam energy dependency observed. PURPOSE: The purpose is to present the electron beam response for an EDGE detector in dependence on beam energy, to characterize the EDGE detector's response under UHDR conditions, and to validate correction factors derived from the first detailed Monte Carlo model of the EDGE diode against measurements, particularly under UHDR conditions. METHODS: Percentage depth doses (PDDs) for the UHDR Mobetron were measured with both EDGE detectors and films. A detailed Monte Carlo (MC) model of the EDGE detector has been configured according to the blueprint provided by the manufacturer under an NDA agreement. Water/silicon dose ratios of EDGE detector for a series of mono-energetic electron beams have been calculated. The dependence of the water/silicon dose ratio on depth for a FLASH relevant electron beam was also studied. An analytical approach for the correction of PDD measured with EDGE detectors was established. RESULTS: Water/silicon dose ratio decreased with decreasing electron beam energy. For the Mobetron 9 MeV UHDR electron beam, the ratio decreased from 1.09 to 1.03 in the build-up region, maintained in range of 0.98-1.02 at the fall-off region and raised to a plateau in value of 1.08 at the tail. By applying the corrections, good agreement between the PDDs measured by the EDGE detector and those measured with film was achieved. CONCLUSIONS: Electron beam response of an UHDR capable EDGE detector was derived from first principles utilizing a sophisticated MC model. An analytical approach was validated for the PDDs of UHDR electron beams. The results demonstrated the capability of EDGE detector in measuring PDDs of UHDR electron beams.

Intrinsically thermally conductive polymers.

Here, we describe the design features that lead to intrinsically thermally conductive polymers. Though polymers are conventionally assumed to be thermal insulators (<0.3 W m-1 K-1), significant efforts by the thermal transport community have shown that polymers can be intrinsically thermally conductive (>1.0 W m-1 K-1). However, these findings have not yet driven comprehensive synthetic efforts to expose how different macromolecular features impact thermal conductivity. Preliminary theoretical and experimental investigations have revealed that high k polymers can be realized by enhancing the alignment, crystallinity, and intermolecular interactions. While a holistic mechanistic framework does not yet exist for thermal transport in polymeric materials, contemporary literature suggests that phonon-like heat carriers may be operative in macromolecules that meet the abovementioned criteria. In this review, we offer a perspective on how high thermal conductivity polymers can be systematically engineered from this understanding. Reports for several classes of macromolecules, including linear polymers, network polymers, liquid-crystalline polymers, and two-dimensional polymers substantiate the design principles we propose. Throughout this work, we offer opportunities for continued fundamental and technological development of polymers with high thermal conductivity.

Anesthetic Oxygen Use and Sex Are Critical Factors in the FLASH Sparing Effect.

Purpose: Ultra High Dose-Rate (UHDR) radiation has been reported to spare normal tissue, compared with Conventional Dose-Rate (CDR) radiation. However, important work remains to be done to improve the reproducibility of the FLASH effect. A better understanding of the biologic factors that modulate the FLASH effect may shed light on the mechanism of FLASH sparing. Here, we evaluated whether sex and/or the use of 100% oxygen as a carrier gas during irradiation contribute to the variability of the FLASH effect. Methods and Materials: C57BL/6 mice (24 male, 24 female) were anesthetized using isoflurane mixed with either room air or 100% oxygen. Subsequently, the mice received 27 Gy of either 9 MeV electron UHDR or CDR to a 1.6 cm2 diameter area of the right leg skin using the Mobetron linear accelerator. The primary postradiation endpoint was time to full thickness skin ulceration. In a separate cohort of mice (4 male, 4 female), skin oxygenation was measured using PdG4 Oxyphor under identical anesthesia conditions. Results: Neither supplemental oxygen nor sex affected time to ulceration in CDR irradiated mice. In the UHDR group, skin damage occured earlier in male and female mice that received 100% oxygen compared room air and female mice ulcerated sooner than male mice. However, there was no significant difference in time to ulceration between male and female UHDR mice that received room air. Oxygen measurements showed that tissue oxygenation was significantly higher when using 100% oxygen as the anesthesia carrier gas than when using room air, and female mice showed higher levels of tissue oxygenation than male mice under 100% oxygen. Conclusions: The skin FLASH sparing effect is significantly reduced when using oxygen during anesthesia rather than room air. FLASH sparing was also reduced in female mice compared to male mice. Both tissue oxygenation and sex are likely sources of variability in UHDR studies. These results suggest an oxygen-based mechanism for FLASH, as well as a key role for sex in the FLASH skin sparing effect.

Electronic health record reveals community-level cardiometabolic health benefits associated with 10 years of community-based participatory research.

BACKGROUND: While a major goal of community-based participatory research (CBPR) is to improve community health; it is unclear how to measure longstanding success of CBPR. OBJECTIVE: We sought to determine the impact of ongoing CBPR on cardiometabolic health of participating communities, including in people not directly participating in research. METHODS: We used linear mixed-effects modelling with electronic medical records from 2002 to 2012 from the Yukon-Kuskokwim Health Corporation, which provides health care to all Alaska Native people in southwestern Alaska, to compare rates of change in cardiometabolic risk factors between communities that did and did not participate in ongoing CBPR beginning in 2003. RESULTS: We analysed 1,262,035 medical records from 12,402 individuals from 10 study and 38 control communities. Blood pressure declined faster in study than in control communities: systolic blood pressure (0.04 mmHg/year; 95% confidence interval [CI]: 0.01, 0.08); diastolic blood pressure (DBP) (0.07 mmHg/year; 95% CI: 0.04, 0.09). Body mass index increased 0.04 units/year faster in study communities than in control communities (95% CI: 0.03, 0.05). More study visits were associated with faster reduction of DBP and triglyceride levels in study communities. CONCLUSIONS: Ongoing CBPR may improve overall cardiometabolic health in communities, perhaps by increasing engagement in health and advocacy.

The Relationship of Anxious Arousal With Treatment of Dysphoria Using Virtual Reality Mindfulness and 2 Accelerated Transcranial Magnetic Stimulation Protocols.

Objective: This secondary analysis investigated the relationship of anxious arousal, as measured by the Tension Anxiety subscale of the Profile of Mood States (TA-POMS), to treatment outcome across diagnoses for each phase of the study. Sequential treatment phases of virtual reality (VR) mindfulness followed by left dorsolateral prefrontal cortex (dlPFC) accelerated transcranial magnetic stimulation (accel-TMS) and then dorsomedial prefrontal cortex (dmPFC) accel-TMS were used to treat dysphoria across diagnoses in an open trial from September 2021 to August 2023.Methods: The change in the TA-POMS subscale was compared to the percent change in primary clinician scale scores using a bivariate analysis. Baseline TA-POMS subscales were compared to treatment response using linear regression models to assess anxious arousal's impact on treatment outcome for the 3 phases. Significance was defined as P < .05, 2-tailed.Results: Twenty-three participants were enrolled in VR mindfulness, 19 in left dlPFC accel-TMS, and 12 in dmPFC accel TMS. Although the change in TA-POMS scores did not significantly correlate with the percent change in primary clinician scale ratings for the VR phase, they did for both the dlPFC (P = .041) and the dmPFC (P = .003) accel-TMS treatment phases. Importantly, baseline anxious arousal levels as measured by TA-POMS were not predictive of treatment outcome in any treatment phase.Conclusion: The outcome of accel-TMS treatment was not adversely affected by anxious arousal and similarly improved along with primary rating scales.Trial Registration: ClinicalTrials.gov identifier: NCT05061745.

Evidence for a role of the basolateral amygdala in regulating regional metabolism in the stressed brain.

The brain regulates every physiological process in the body, including metabolism. Studies investigating brain metabolism have shown that stress can alter major metabolic processes, and that these processes can vary between regions. However, no study has investigated how metabolic pathways may be altered by stressor perception, or whether stress-responsive brain regions can also regulate metabolism. The basolateral amygdala (BLA), a region important for stress and fear, has reciprocal connections to regions responsible for metabolic regulation. In this study, we investigated how BLA influences regional metabolic profiles within the hippocampus (HPC) and medial prefrontal cortex (mPFC), regions involved in regulating the stress response and stress perception, using optogenetics in male C57BL/6 mice during footshock presentation in a yoked shuttlebox paradigm based on controllable (ES) and uncontrollable (IS) stress. RNA extracted from HPC and mPFC were loaded into NanoString® Mouse Neuroinflammation Panels, which also provides a broad view of metabolic processes, for compilation of gene expression profiles. Results showed differential regulation of carbohydrate and lipid metabolism, and insulin signaling gene expression pathways in HPC and mPFC following ES and IS, and that these differences were altered in response to optogenetic excitation or inhibition of the BLA. These findings demonstrate for the first time that individual brain regions can utilize metabolites in a way that are unique to their needs and function in response to a stressor, and that vary based on stressor controllability and influence by BLA.

Application of Near-Infrared Spectroscopy for Screening of Chlorothiazide Sodium Vials.

Chlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide. Chlorothiazide sodium has a molecular weight of 317.71 amu. Since 2020 there have been multiple national shortages of chlorothiazide. Recent studies target chlorothiazide's low bioavailability, aiming to enhance it through nanoparticle production via a supercritical method. The drug's solubility in supercritical carbon dioxide (scCO2) is vital, with measurements ranging from 0.417×10-5 to 1.012×10-5 mole fraction under specific conditions. Adding co-solvents, like ethanol, DMSO, and acetone, to scCO2 boosts solubility, with ethanol proving most effective, enhancing solubility by 2.02-11.75 times. Intra-lot variability was discovered in a sample of a lot of chlorothiazide sodium by the University of Kentucky Drug Quality Task Force. Two vials of six screened in one lot were displaced from the center of the lot by 4.0 and 4.2 SDs, respectively. Inter-lot variability was confirmed in the near-IR spectra of 204 vials obtained from 28 different lots of chlorothiazide sodium. Using full spectrum BEST analysis 13 vials (6.4%) were outliers.

Alterations in Blood-Brain Barrier Integrity and Lateral Ventricle Differ in Rats Exposed to Space Radiation and Social Isolation.

The proposed Mars missions will expose astronauts to long durations of social isolation (SI) and space radiation (SR). These stressors have been shown to alter the brain's macrostructure and microenvironment, including the blood-brain barrier (BBB). Breakdown of the BBB is linked to impaired executive functions and physical deficits, including sensorimotor and neurocognitive impairments. However, the precise mechanisms mediating these effects remain unknown. Additionally, the synergistic effects of combined exposure to SI and SR on the structural integrity of the BBB and brain remain unknown. We assessed the BBB integrity and morphology in the brains of male rats exposed to ground-based analogs of SI and SR. The rats exposed to SR had enlarged lateral ventricles and increased BBB damage associated with a loss of astrocytes and an increased number of leaky vessels. Many deficits observed in SR-treated animals were attenuated by dual exposure to SI (DFS). SI alone did not show BBB damage but did show differences in astrocyte morphology compared to the Controls. Thus, determining how single and combined inflight stressors modulate CNS structural integrity is crucial to fully understand the multiple pathways that could impact astronaut performance and health, including the alterations to the CNS structures and cell viability observed in this study.

Supramolecular design as a route to high-performing organic electrodes.

Organic electrodes may someday replace transition metals oxides, the current standard in electrochemical energy storage, including those with severe issues of availability, cost, and recyclability. To realize this more sustainable future, a thorough understanding of structure-property relationships and design rules for organic electrodes must be developed. Further, it is imperative that supramolecular interactions between organic species, which are often overlooked, be included in organic electrode design. In this review, we showcase how molecular and polymeric electrodes that host non-covalent interactions outperform materials without these features. Using select examples from the literature, we emphasize how dispersion forces, hydrogen-bonding, and radical pairing can be leveraged to improve the stability, capacity, and energy density of organic electrodes. Throughout this review, we identify potential next-generation designs and opportunities for continued investigation. We hope that this review will serve as a catalyst for collaboration between synthetic chemists and the energy storage community, which we view as a prerequisite to achieving high-performing supramolecular electrode materials.

Lysophosphatidic Acid Receptor 1 (LPA1) Antagonists as Potential Migrastatics for Triple Negative Breast Cancer.

Metastasis is responsible for about 90 % of cancer deaths. Anti-metastatic drugs, termed as migrastatics, offer a distinctive therapeutic approach to address cancer migration and invasion. However, therapeutic exploitation of metastasis-specific targets remains limited, and the effective prevention and suppression of metastatic cancer continue to be elusive. Lysophosphatidic acid receptor 1 (LPA1) is activated by an endogenous lipid molecule LPA, leading to a diverse array of cellular activities. Previous studies have shown that the LPA/LPA1 axis supports the progression of metastasis for many types of cancer. In this study, we report the synthesis and biological evaluation of fluorine-containing triazole derivatives as potent LPA1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compound 12 f, the most potent and highly selective in this series with an IC50 value of 16.0 nM in the cAMP assay and 18.4 nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBC cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA1 as a migrastatic target. Consequently, the LPA1 antagonists developed in this study hold promise as potential migrastatic candidates for TNBC.

Analysis and implementation of volume reflection gratings in photorefractive lithium niobate for edge enhancement.

Diffraction from volume reflection gratings written in bulk photorefractive lithium niobate is modeled for the case of longitudinally varying index modulation depths. Numerical solutions to the Helmholtz equation are found in the spatial frequency domain, leading to transfer functions for the volume reflection grating. These transfer functions are then used to show the spatial frequency filtering effect of the volume reflection grating on input light fields containing 2D spatial information. It is shown, first through simulations and then by experiment, that the 0th order transmitted beam undergoes a 2D edge enhancement.

Transport of intensity and phase: applications to digital holography [Invited].

We first review transport of intensity and phase and show their use as a convenient tool to directly determine the unwrapped phase of an imaged object, either through conventional imaging or using digital holography. For both cases, either the traditional transport of intensity and phase, or with a modification, viz., electrically controllable transport of intensity and phase, can be used. The use of digital holography with transport of intensity for 3D topographic mapping of fingermarks coated with columnar thin films is shown as an illustrative application of this versatile technique.

Comprehensive Assessment of the Intrinsic Pancreatic Microbiome.

OBJECTIVE: We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome. SUMMARY BACKGROUND DATA: Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intra-pancreatic microbial dysbiosis may drive malignant transformation. METHODS: Pancreatic samples were collected at the time of resection from 109 patients. Samples included tumor tissue (control, n=20; IPMN, n=20; PDAC, n=19) and pancreatic cyst fluid (IPMN, n=30; SCA, n=10; MCN, n=10). Assessment of bacterial DNA by quantitative PCR and 16S ribosomal RNA gene sequencing was performed. Downstream analyses determined the relative abundances of individual taxa between groups and compared intergroup diversity. Whole-genome sequencing data from 140 patients with PDAC in the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were analyzed to validate findings. RESULTS: Sequencing of pancreatic tissue yielded few microbial reads regardless of diagnosis, and analysis of pancreatic tissue showed no difference in the abundance and composition of bacterial taxa between normal pancreas, IPMN, or PDAC groups. Low-grade dysplasia (LGD) and high-grade dysplasia (HGD) IPMN were characterized by low bacterial abundances with no difference in tissue composition and a slight increase in Pseudomonas and Sediminibacterium in HGD cyst fluid. Decontamination analysis using the CPTAC database confirmed a low-biomass, low-diversity intrinsic pancreatic microbiome that did not differ by pathology. CONCLUSIONS: Our analysis of the pancreatic microbiome demonstrated very low intrinsic biomass that is relatively conserved across diverse neoplastic conditions and thus unlikely to drive malignant transformation.

Effects of social isolation and galactic cosmic radiation on fine motor skills and behavioral performance.

Future NASA missions will require astronauts to travel farther and spend longer durations in space than ever before. This will also expose astronauts to longer periods of several physical and psychological challenges, including exposure to space radiation (SR) and periods of social isolation (SI), which could have unknown negative effects on physical and mental health. Each also has the potential to negatively impact sleep which can reduce the ability to cope with stressful experiences and lead to sensorimotor, neurocognitive, and physical deficits. The effects of SI and SR on gross motor performance has been shown to vary, and depend on, individual differences in stress resilience and vulnerability based on our established animal model in which stress produces different effects on sleep. In this study, the impact that SI and SR, either alone or together, had on fine motor skill performance (bilateral tactile adhesive removal task (BTAR)) was assessed in male rats. We also examined emotional, exploratory, and other off-task behavioral responses during testing and assessed whether sensorimotor performance and emotion varied with individual differences in resilience and vulnerability. BTAR task performance was differentially impacted by SI and SR, and were further influenced by the stress resilience/vulnerability phenotype of the rats. These findings further demonstrate that identifying individual responses to stressors that can impact sensorimotor ability and behavior necessary to perform mission-related tasks will be of particular importance for astronauts and future missions. Should similar effects occur in humans, there may be considerable inter-individual variability in the impact that inflight stressors have on astronauts and their ability to perform mission-related tasks.

Gentrification drives patterns of alpha and beta diversity in cities.

While there is increasing recognition that social processes in cities like gentrification have ecological consequences, we lack nuanced understanding of the ways gentrification affects urban biodiversity. We analyzed a large camera trap dataset of mammals (>500 g) to evaluate how gentrification impacts species richness and community composition across 23 US cities. After controlling for the negative effect of impervious cover, gentrified parts of cities had the highest mammal species richness. Change in community composition was associated with gentrification in a few cities, which were mostly located along the West Coast. At the species level, roughly half (11 of 21 mammals) had higher occupancy in gentrified parts of a city, especially when impervious cover was low. Our results indicate that the impacts of gentrification extend to nonhuman animals, which provides further evidence that some aspects of nature in cities, such as wildlife, are chronically inaccessible to marginalized human populations.

5-Factor Modified Frailty Index as a Predictor of Outcomes After Hemiarthroplasty or Total Hip Arthroplasty for Femoral Neck Fracture.

INTRODUCTION: Although the 5-factor modified frailty index (mFI-5) has been shown to be an independent predictor of complications after primary total hip arthroplasty (THA), its predictive value has not been evaluated in the setting of hip fracture. We therefore assessed the utility of mFI-5 score as an independent predictor of morbidity and mortality in patients who underwent THA or hemiarthroplasty for femoral neck fracture. METHODS: The American College of Surgeons National Surgical Quality Improvement database was queried for all patients with femoral neck fractures treated with THA or hemiarthroplasty between 2006 and 2020. A multivariate logistic regression analysis was done using mFI-5 as a predictor while controlling for baseline demographic and clinical variables. RESULTS: In total, 45,185 patients (hemiarthroplasty: 37,645; THA: 7,540) were identified. For hemiarthroplasty patients, the mFI-5 strongly predicted risk of any complication (OR, 1.1; 95% CI, 1.1 to 1.2; P < 0.001), bleeding (OR, 1.2; 95% CI, 1.1 to 1.3; P < 0.001), and readmission (OR, 1.2; 95% CI, 1.1 to 1.3; P < 0.001). For THA patients, the mFI-5 was a strong predictor of any complication (OR, 1.2; 95% CI, 1.0 to 1.3; P = 0.023), pneumonia (OR, 1.4; 95% CI, 1.0 to 2.0; P = 0.047), and readmission (OR, 1.3; 95% CI, 1.1 to 1.6; P = 0.004). DISCUSSION: The mFI-5 is an independent predictor of morbidity and complications after hemiarthroplasty and THA for femoral neck fracture. Importantly, readmission risk was predicted by the mFI-5. The mFI-5 may present a valuable clinical tool for assessment of high-risk patients who might require additional resources and specialized care after femoral neck fracture.

Retrieving autobiographical memories in autobiographical contexts: are age-related differences in narrated episodic specificity present outside of the laboratory?

The Autobiographical Interview, a method for evaluating detailed memory of real-world events, reliably detects differences in episodic specificity at retrieval between young and older adults in the laboratory. Whether this age-associated reduction in episodic specificity for autobiographical event retrieval is present outside of the laboratory remains poorly understood. We used a videoconference format to administer the Autobiographical Interview to cognitively unimpaired older adults (N = 49, M = 69.5, SD = 5.94) and young adults (N = 54, M = 22.5, SD = 4.19) who were in their homes at the time of retrieval. Relative to young adults, older adults showed reduced episodic specificity in their home environment, as reflected by fewer episodic or "internal" details (t (101) = 3.23, p = 0.009) and more "external" details (i.e., semantic, language-based details) (t (101) = 3.60, p = 0.003). These findings, along with detail subtype profiles in the narratives, bolster the ecological validity of the Autobiographical Interview and add promise to the use of virtual cognitive testing to improve the accessibility, participant diversity, scalability, and ecological validity of memory research.