Role of π-Radical Localization on Thermally Stable Cross-Links Between Polycyclic Aromatic Hydrocarbons.

The thermal stability of cross-links between polycyclic aromatic hydrocarbons (PAHs) is critical for understanding the formation of soot pollutants, graphite, and carbon blacks. Recently, a variety of different π-radicals have been directly imaged and suggested to enable thermally stable bonding; however, a systematic study of reactivity has been lacking. In this work, we use density functional theory to study the reactivity of PAH π-radicals. The Mulliken spin densities are initially used to categorize the different classes of localization, and the bond energy is computed to determine the degree of localization required for thermal stability. The results showed that the bond energies of PAHs are strongly correlated with the calculated spin densities, but bond energies do not exist with the bond lengths due to significant rearrangement and steric effects during bond formation. A threshold for π-radical localization is suggested that will be stable in combustion and pyrolysis environments of ρMα ≥ 0.5. Finally, the formation of multicenter bonds between localized and delocalized π-radicals was investigated using the nudge elastic band (NEB) scan, and it was found that only delocalized π-radicals provided local energy minima. These results show that the localization of π-radicals is critical for the formation of thermally stable single-center bonds between aromatic radicals.

Portraits of Soot Molecules Reveal Pathways to Large Aromatics, Five-/Seven-Membered Rings, and Inception through π-Radical Localization.

Incipient soot early in the flame was studied by high-resolution atomic force microscopy and scanning tunneling microscopy to resolve the atomic structure and orbital densities of single soot molecules prepared on bilayer NaCl on Cu(111). We resolved extended catacondensed and pentagonal-ring linked (pentalinked) species indicating how small aromatics cross-link and cyclodehydrogenate to form moderately sized aromatics. In addition, we resolved embedded pentagonal and heptagonal rings in flame aromatics. These nonhexagonal rings suggest simultaneous growth through aromatic cross-linking/cyclodehydrogenation and hydrogen abstraction acetylene addition. Moreover, we observed three classes of open-shell π-radical species. First, radicals with an unpaired π-electron delocalized along the molecule's perimeter. Second, molecules with partially localized π-electrons at zigzag edges of a π-radical. Third, molecules with strong localization of a π-electron at pentagonal- and methylene-type sites. The third class consists of π-radicals localized enough to enable thermally stable bonds, as well as multiradical species such as diradicals in the open-shell triplet state. These π-diradicals can rapidly cluster through barrierless chain reactions enhanced by van der Waals interactions. These results improve our understanding of soot formation and the products formed by combustion and could provide insights for cleaner combustion and the production of hydrogen without CO2 emissions.

Investigating gender-based differential item functioning on the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD): An item response theory analysis.

The McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) is a popular screening tool for identifying people who may have borderline personality disorder (BPD). However, because women are more frequently diagnosed with the disorder than men, it is possible that the MSI-BPD differs in its ability to identify BPD as a function of gender identity. Using item response theory (IRT), we sought to determine if components of the MSI-BPD would demonstrate differential item functioning (DIF), such that one gender identity would be more likely to endorse certain items. Twenty-two thousand thirty-five college undergraduates (14,305 women) aged 18-55 years (M = 18.77, SD = 1.75) were assessed using the MSI-BPD as part of a subject pool screening between 2008 and 2019. The MSI-BPD contains 10 items that are measured dichotomously, and the authors recommend a cut-off of 7 of 10 items endorsed to maximize sensitivity and specificity to BPD. Results suggested that a two-parameter model was the best fit to the data and that unidimensionality and local independence assumptions were met. The following items demonstrated DIF: self-harm/suicidality, affective lability, abandonment, impulsivity, and anger. At equal levels of the latent construct of BPD, women were more likely to endorse self-harm/suicidality, affective lability, and abandonment. Women were more likely to endorse impulsivity at higher levels of BPD, and men were more likely to endorse anger at lower levels of BPD. Ultimately, the effect sizes of these differences were small, however, and likely do not impact the individual's overall outcome on the measure. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A dynamic kinetic model captures cell-free metabolism for improved butanol production.

Cell-free systems are useful tools for prototyping metabolic pathways and optimizing the production of various bioproducts. Mechanistically-based kinetic models are uniquely suited to analyze dynamic experimental data collected from cell-free systems and provide vital qualitative insight. However, to date, dynamic kinetic models have not been applied with rigorous biological constraints or trained on adequate experimental data to the degree that they would give high confidence in predictions and broadly demonstrate the potential for widespread use of such kinetic models. In this work, we construct a large-scale dynamic model of cell-free metabolism with the goal of understanding and optimizing butanol production in a cell-free system. Using a combination of parameterization methods, the resultant model captures experimental metabolite measurements across two experimental conditions for nine metabolites at timepoints between 0 and 24 h. We present analysis of the model predictions, provide recommendations for butanol optimization, and identify the aldehyde/alcohol dehydrogenase as the primary bottleneck in butanol production. Sensitivity analysis further reveals the extent to which various parameters are constrained, and our approach for probing valid parameter ranges can be applied to other modeling efforts.

Phosphoinositide acyl chain saturation drives CD8+ effector T cell signaling and function.

How lipidome changes support CD8+ effector T (Teff) cell differentiation is not well understood. Here we show that, although naive T cells are rich in polyunsaturated phosphoinositides (PIPn with 3-4 double bonds), Teff cells have unique PIPn marked by saturated fatty acyl chains (0-2 double bonds). PIPn are precursors for second messengers. Polyunsaturated phosphatidylinositol bisphosphate (PIP2) exclusively supported signaling immediately upon T cell antigen receptor activation. In late Teff cells, activity of phospholipase C-γ1, the enzyme that cleaves PIP2 into downstream mediators, waned, and saturated PIPn became essential for sustained signaling. Saturated PIP was more rapidly converted to PIP2 with subsequent recruitment of phospholipase C-γ1, and loss of saturated PIPn impaired Teff cell fitness and function, even in cells with abundant polyunsaturated PIPn. Glucose was the substrate for de novo PIPn synthesis, and was rapidly utilized for saturated PIP2 generation. Thus, separate PIPn pools with distinct acyl chain compositions and metabolic dependencies drive important signaling events to initiate and then sustain effector function during CD8+ T cell differentiation.

UAV rapidly-deployable stage sensor with electro-permanent magnet docking mechanism for flood monitoring in undersampled watersheds.

The availability of historical flood data is vital in recognizing weather-related trends and outlining necessary precautions for at-risk communities. Flood frequency, magnitude, endurance, and volume are traditionally recorded using established streamgages; however, the material and installation costs allow only a few streamgages in a region, which yield a narrow data selection. In particular, stage, the vertical water height in a water body, is an important parameter in determining flood trends. This work investigates a low-cost, compact, rapidly-deployable alternative to traditional stage sensors that will allow for denser sampling within a watershed and a more detailed record of flood events. The package uses a HC-SR04 ultrasonic sensor to measure stage, onboard memory for recording flood events, and an electropermanet magnet (EPM) to enable Unmanned Aerial Vehicle (UAV) deployments. Optional modules for solar panels and wireless communication can also be added to extend package longevity or allow wireless control of the EPM. The stage sensor package was found to have a range of 0.02 to 4 m with a 6.9 mm accuracy and capable of a 6.4 day long deployment. With the total cost of production at 271.37 USD, it is a cheaper and more flexible alternative to traditional stage sensors that will enable dense sensor networks and rapid response to flooding events.

Cost-effectiveness analysis of a resource-intensive approach versus minimally invasive strategy for high-risk transcatheter aortic valve replacement patients.

Aortic stenosis has a high mortality rate in patients who do not receive aortic valve replacement. Previously, transcatheter aortic valve replacement (TAVR) was an intervention reserved for individuals deemed high-risk for surgery. Since that time, TAVR has increasingly been offered to lower risk patients, yet it is unclear whether TAVR will meet an acceptable cost-effectiveness threshold in this group. In this cost-effectiveness study, we employed a decision tree model with Monte Carlo probability sensitivity analysis to determine the incremental cost (in US$) per quality-adjusted life year (QALY) and life year (LY) of performing the TAVR procedure using the resource-intensive approach versus the minimally invasive strategy in high-risk surgical patients.

Chronic feelings of emptiness in a large undergraduate sample: Starting to fill the void.

Chronic emptiness in borderline personality disorder (BPD) has received little empirical attention. We sought to examine basic properties of a single chronic emptiness item, including prevalence, reliability, validity, the relation of the emptiness item to other BPD criteria, and measures of personality. Undergraduates enrolled in psychology courses over 12 years' time completed the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) (N = 22,217). Subsets of participants completed the International Personality Disorder Examination-Screening Questionnaire (IPDE-SQ) (N = 2732), The Revised NEO Personality Inventory (Anxiety, Angry Hostility, Depression, Positive Emotions [reversed], and Impulsivity facets) (N = 10,506), and the Depression Anxiety Stress Scales (DASS) (N = 1110) as validity indicators; 10.0% of respondents endorsed emptiness. Reliability indices suggested moderate levels of reliability between two emptiness items (r(2730) = 0.61, p < 0.001). Among BPD criteria, emptiness and identity disturbance correlated most strongly (r(22,215) = 0.81, p < 0.001). MSI emptiness was more correlated with depression on the NEO (r(10,504) = 0.43, p < 0.001) and DASS (r(1108) = 0.51, p < 0.001) than other facets of negative affect. Emptiness was more correlated with greater borderline pathology than any other MSI-BPD item (Sample 1, rtet = 0.87; Sample 2, rtet = 0.86). This criterion warrants further study and attention, especially related to assessment of BPD.

Development and validation of a prediction model for actionable aspects of frailty in the text of clinicians' encounter notes.

OBJECTIVE: Frailty is a prevalent risk factor for adverse outcomes among patients with chronic lung disease. However, identifying frail patients who may benefit from interventions is challenging using standard data sources. We therefore sought to identify phrases in clinical notes in the electronic health record (EHR) that describe actionable frailty syndromes. MATERIALS AND METHODS: We used an active learning strategy to select notes from the EHR and annotated each sentence for 4 actionable aspects of frailty: respiratory impairment, musculoskeletal problems, fall risk, and nutritional deficiencies. We compared the performance of regression, tree-based, and neural network models to predict the labels for each sentence. We evaluated performance with the scaled Brier score (SBS), where 1 is perfect and 0 is uninformative, and the positive predictive value (PPV). RESULTS: We manually annotated 155 952 sentences from 326 patients. Elastic net regression had the best performance across all 4 frailty aspects (SBS 0.52, 95% confidence interval [CI] 0.49-0.54) followed by random forests (SBS 0.49, 95% CI 0.47-0.51), and multi-task neural networks (SBS 0.39, 95% CI 0.37-0.42). For the elastic net model, the PPV for identifying the presence of respiratory impairment was 54.8% (95% CI 53.3%-56.6%) at a sensitivity of 80%. DISCUSSION: Classification models using EHR notes can effectively identify actionable aspects of frailty among patients living with chronic lung disease. Regression performed better than random forest and neural network models. CONCLUSIONS: NLP-based models offer promising support to population health management programs that seek to identify and refer community-dwelling patients with frailty for evidence-based interventions.

Comparison of V̇o2peak and V̇o2max at Different Sampling Intervals in Collegiate Wrestlers.

ABSTRACT: Sell, KM, Ghigiarelli, JJ, Prendergast, JM, Ciani, GJ, Martin, J, and Gonzalez, AM. Comparison of V̇o2peak and V̇o2max at different sampling intervals in collegiate wrestlers. J Strength Cond Res 35(10): 2915-2917, 2021-The purpose of this study was to determine the difference in the highest oxygen uptake (V̇o2peak) achieved during a maximal effort graded exercise test (GXT) in 20 NCAA Division I male wrestlers using breath-by-breath (BbB) values to the maximal uptake averaged across different time- and breath-based oxygen consumption sampling intervals (V̇o2max). Given the need for aerobic fitness and anaerobic power in wrestling, the accurate determination of V̇o2max is imperative if it is to be used to identify current aerobic fitness and consequently guide sport-specific training programs to address weaknesses in this area. Each subject completed a cycle ergometer GXT during which BbB data were collected via indirect calorimetry and V̇o2peak determined as the highest value. V̇o2max was considered as the average value of 3-s, 5-s, 10-s, 20-s, and 30-s sampling, and 3-b, 7-b, and 11-b sampling during the GXT. Results show that the BbB V̇o2peak was significantly higher than the 5-s, 10-s, 20-s, 30-s, and 11-b (p < 0.05). The 3-b V̇o2max was significantly higher than the 20-s and 30-s V̇o2max values (p < 0.05). The underestimation of V̇o2peak for each time-based interval sampling approach compared with BbB V̇o2peak is consistent with previous research, but the comparison of BbB data to breath-based interval sampling has not been widely addressed in prior research. The use of a 7-b sampling interval for the determination of V̇o2max may be a promising approach to minimize the systematic errors associated with BbB or less frequent sampling intervals, but future research is needed to further support its application with elite athletic populations such as those in the current study.

π-Diradical Aromatic Soot Precursors in Flames.

Soot emitted from incomplete combustion of hydrocarbon fuels contributes to global warming and causes human disease. The mechanism by which soot nanoparticles form within hydrocarbon flames is still an unsolved problem in combustion science. Mechanisms proposed to date involving purely chemical growth are limited by slow reaction rates, whereas mechanisms relying on solely physical interactions between molecules are limited by weak intermolecular interactions that are unstable at flame temperatures. Here, we show evidence for a reactive π-diradical aromatic soot precursor imaged using non-contact atomic force microscopy. Localization of π-electrons on non-hexagonal rings was found to allow for Kekulé aromatic soot precursors to possess a triplet diradical ground state. Barrierless chain reactions are shown between these reactive sites, which provide thermally stable aromatic rim-linked hydrocarbons under flame conditions. Quantum molecular dynamics simulations demonstrate physical condensation of aromatics that survive for tens of picoseconds. Bound internal rotors then enable the reactive sites to find each other and become chemically cross-linked before dissociation. These species provide a rapid, thermally stable chain reaction toward soot nanoparticle formation and could provide molecular targets for limiting the emission of these toxic combustion products.

Syphilitic interstitial keratitis treated with topical tacrolimus.

PURPOSE: To report a case of syphilitic interstitial keratitis successfully managed with topical tacrolimus after the development of steroid-induced intraocular pressure elevation in a pediatric patient. OBSERVATIONS: A 4-year-old female with a history of congenital syphilis that was reportedly treated after birth presented with bilateral conjunctival redness, tearing, and photosensitivity. Initial ophthalmic examination revealed corneal vascularization with diffuse haze of the right eye and circumferential vascularization with stromal infiltrates of the left eye. She was diagnosed with bilateral syphilitic interstitial keratitis and initially managed with topical steroids but developed steroid-induced elevation of her intraocular pressure. She experienced several recurrences of keratitis as steroids were tapered. After a recurrence in her right eye, she was treated with topical tacrolimus. Since then, she has remained recurrence-free for almost three years with normal intraocular pressure. CONCLUSION AND IMPORTANCE: Tacrolimus represents a novel alternative for the treatment of syphilitic interstitial keratitis, which is particularly useful in patients that develop elevated intraocular pressures in response to long-term treatment with steroid eye drops.

Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates.

Antigen accumulation in lymph nodes (LNs) is critical for vaccine efficacy, but understanding of vaccine biodistribution in humans or large animals remains limited. Using the rhesus macaque model, we employed a combination of positron emission tomography (PET) and fluorescence imaging to characterize the whole-animal to tissue-level biodistribution of a subunit vaccine comprised of an HIV envelope trimer protein nanoparticle (trimer-NP) and lipid-conjugated CpG adjuvant (amph-CpG). Following immunization in the thigh, PET imaging revealed vaccine uptake primarily in inguinal and iliac LNs, reaching distances up to 17 cm away from the injection site. Within LNs, trimer-NPs exhibited striking accumulation on the periphery of follicular dendritic cell (FDC) networks in B cell follicles. Comparative imaging of soluble Env trimers (not presented on nanoparticles) in naïve or previously-immunized animals revealed diffuse deposition of trimer antigens in LNs following primary immunization, but concentration on FDCs in pre-immunized animals with high levels of trimer-specific IgG. These data demonstrate the capacity of nanoparticle or "albumin hitchhiking" technologies to concentrate vaccines in genitourinary tract-draining LNs, which may be valuable for promoting mucosal immunity.

Stepping on the Gas to a Circular Economy: Accelerating Development of Carbon-Negative Chemical Production from Gas Fermentation.

Owing to rising levels of greenhouse gases in our atmosphere and oceans, climate change poses significant environmental, economic, and social challenges globally. Technologies that enable carbon capture and conversion of greenhouse gases into useful products will help mitigate climate change by enabling a new circular carbon economy. Gas fermentation usingcarbon-fixing microorganisms offers an economically viable and scalable solution with unique feedstock and product flexibility that has been commercialized recently. We review the state of the art of gas fermentation and discuss opportunities to accelerate future development and rollout. We discuss the current commercial process for conversion of waste gases to ethanol, including the underlying biology, challenges in process scale-up, and progress on genetic tool development and metabolic engineering to expand the product spectrum. We emphasize key enabling technologies to accelerate strain development for acetogens and other nonmodel organisms.