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Multimodel and Multidiagnostic Ensemble-Based Deep Convective Area Forecast for Aviation Operations Using the Global Unified Model and Korean Integrated Model
No full textTo provide safe and efficient guidance for aircraft operation to avoid deep convective areas (DCAs) in Korea and broader East Asia, we developed a multimodel and multidiagnostic ensemble (MMDE)-based forecast system. This system utilizes two global numerical weather prediction (NWP) models based on the Unified Model (UM) and the Korean Integrated Model (KIM) operated by the Korea Meteorological Administration. To predict hazardous weather conditions, we defined DCAs using ground-based radar mosaic data where the 15-dBZ echo-top height exceeds flight level (FL) 250 (about z = 6.5 km) and FL350 (about z = 9 km). For predictors, we employed a total of 22 diagnostics, which were derived either directly from physical parameterization schemes within the NWP models or indirectly from various mesoscale forcings responsible for deep convection. Performance skills of the individual DCA diagnostics from both the UM and KIM models were evaluated against radar-based DCA observations from June to September 2022. Finally, the normalized individual DCA diagnostics from the two NWP models were used as ensemble members for deterministic and probabilistic forecast systems. As a result, the newly developed MMDE-based deterministic and probabilistic DCA forecasts outperformed both individual diagnostics and single-model-based forecasts. Eventually, this newly developed DCA forecasting system is expected to be highly valuable for strategic planning of aviation operations in Korea and East Asia
Dynamic Mutational Profiling of Binding Interactions and Allosteric Networks in Conformational Ensembles of the SARS-CoV-2 Spike Protein Complexes with Classes of Antibodies Targeting Cryptic Binding Sites: Confluence of Binding and Allostery Determines Molecular Mechanisms and Hotspots of Immune Escape
No full textThe ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could underlie complexity of broad and escape-resistant neutralization. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how Class 4 antibodies (represented by S2X35, 25F9, and SA55) and Class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the antibody complexes with the spike protein and ensemble-based mutational scanning of binding interactions we showed that these antibodies through targeting conserved cryptic sites can exert allosteric effects that influence global conformational dynamics in the RBD functional regions. The ensemble-based mutational scanning of binding interactions revealed an excellent agreement with experimentally derived deep mutational scanning (DMS) data accurately recapitulating the known binding hotspots and escape mutations across all studied antibodies. The predicted destabilization values in functional sites are consistent with experimentally observed reductions in antibody binding affinity and immune escape profiles demonstrating that computational models can robustly reproduce and forecast mutation-induced immune escape trends. Using dynamic network modeling we characterized the antibody-induced changes in residue interaction networks and long-range interactions. The results revealed that class 4 antibodies can exhibit distinct patterns of allosteric influence despite targeting overlapping regions, while class 5 antibodies celicit consistently dense and broadly distributed allosteric networks and long-range stabilization of the RBD conformations. Dynamic network analysis identifies a conserved allosteric network core that mediates long-range interactions and incudes antibody specific allosteric extensions that connect the binding interface hotspots with allosteric hubs. This study suggests that mechanisms of binding and immune escape for classes of antibodies targeting cryptic binding sites may be determined by confluence of multiple factors including high-affinity binding, long-range allosteric effects that modulate RBD adaptability and propagation of dynamic constraints that can reshape the conformational equilibrium and ultimately determine efficacy and neutralization patterns
Naming Practice Effects and Inconsistencies Relate to Treatment Outcome in People with Aphasia
No full textBackground and aims Intra-individual variability in language performance has been proposed as a factor associated with treatment outcomes in chronic aphasia. However, the nature of linguistic variability and the degree to which it informs therapeutic success remains poorly understood. In this study, we sought to (1) assess person- and item-level factors associated with naming variability, practice effects, and item-based inconsistencies, (2) determine the relation between intra-individual naming variability, practice effects, and item-based inconsistencies at baseline and treatment outcome in aphasia, and (3) determine the treatment impact on the change in variability and consistency of naming responses. Method Seventy-eight participants with chronic (\u3e6 months post-stroke) aphasia after a unilateral left-hemisphere stroke completed the Philadelphia Naming Test (PNT) twice over two consecutive days prior (at baseline) to receiving six weeks of lexical processing treatment. For each participant, we calculated the absolute difference in correctly named items between the two PNTs at baseline (which we termed “naming variability”) and the change from the first to second PNT at baseline (which we termed “naming practice effect”). Further, we classified participants’ naming responses for each item on the two PNTs as correct-correct, one-correct, and incorrect-incorrect. One-correct responses reflected intra-individual naming inconsistencies for the same item across the two baseline PNTs (which we termed “naming inconsistencies”). We assessed the relationship between naming variability, practice effects, inconsistencies, and person-level factors (aphasia severity, aphasia type, apraxia of speech, stroke severity, age, education), item-level factors (word frequency, length, phonological neighborhood density), treatment response (the change in the rate of correct responses from before to after treatment). Results The rate of correct naming responses on the two baseline PNTs did not statistically differ across the 78 participants; thus, there was no significant practice effect. However, variability and inconsistencies were common, with a difference of up to 17 % in correctly named items and up to 45 % of the same items named once correctly and once incorrectly between the two baseline PNTs. Naming variability was significantly related to aphasia type and severity, and inconsistencies were related to aphasia type, severity, the presence of apraxia of speech, and target word frequency. While naming variability was not associated with treatment outcome, practice effects and inconsistencies at baseline were significantly associated with treatment outcome and explained 36 % and 6 % of the variance in the change in the rate of correct responses from before to after treatment, respectively. Using 5-fold cross-validation, practice effects and inconsistencies had a coefficient of determination (R2) of 0.32 and 0, respectively, for predicted vs actual responses. After treatment, naming variability and inconsistencies significantly decreased, counterbalanced by an increase in consistently correctly named items. Discussion We observed greater treated naming improvement in participants with stronger practice effects or more inconsistencies at baseline than in participants with smaller practice effects or more consistent naming at baseline, independent of aphasia severity. However, the generalizability to new data to predict treatment outcomes was weak for practice effects and poor for inconsistencies. After treatment, participants produced less variable and more consistent responses, indicating that treatment led to an overall strengthening of lexical-semantic retrieval processes
Additive Effects of N-Acetylcysteine and [R\u3csub\u3e4\u3c/sub\u3eW\u3csub\u3e4\u3c/sub\u3e] Combination Treatment on \u3cem\u3eMycobacterium avium\u3c/em\u3e
No full textMycobacterium avium is an opportunistic pathogen and a leading contributor to nontuberculous mycobacterial infections in immunocompromised individuals. However, treatment duration, antibiotic toxicity, and resistance present challenges in the management of mycobacterium infections, prompting the need for novel treatment. N-acetylcysteine (NAC) has demonstrated potent antimycobacterial activity, while antimicrobial peptides such as the cyclic [R4W4] have shown additive effects when combined with first-line antibiotics. This study aimed to investigate the mechanism and efficacy of NAC and [R4W4] combination therapy against M. avium. A membrane depolarization assay was used to evaluate the effects of NAC and [R4W4] on M. avium cell membrane integrity. Antimycobacterial activity was assessed by treating cultures with varying concentrations of NAC, [R4W4], a combination, or a sham treatment. The same regimens were applied to M. avium-infected THP-1-derived macrophages to assess intracellular efficacy. NAC and [R4W4] each disrupted the M. avium membrane potential, with enhanced effects in combination. The combination treatment significantly reduced M. avium survival in both the culture and infected macrophages compared with NAC alone and untreated controls. [R4W4] and NAC also demonstrated potent antibacterial activity, while the lowest MIC and the combination of [R4W4] and NAC displayed additive effects, indicating an improved bacterial inhibition compared to individual treatments. These findings demonstrate the additive activity of NAC and [R4W4] against M. avium in vitro and suggest that combining antioxidant compounds with antimicrobial peptides may represent a promising strategy for treating mycobacterial infections
Phi Beta Kappa, Psi of California Chapter, Induction Ceremony 2025
No full texthttps://digitalcommons.chapman.edu/pbk_induction_ceremony_2025/1005/thumbnail.jp
Phi Beta Kappa, Psi of California Chapter, Induction Ceremony 2025
No full texthttps://digitalcommons.chapman.edu/pbk_induction_ceremony_2025/1008/thumbnail.jp
Phi Beta Kappa, Psi of California Chapter, Induction Ceremony 2025
No full texthttps://digitalcommons.chapman.edu/pbk_induction_ceremony_2025/1010/thumbnail.jp
Phi Beta Kappa, Psi of California Chapter, Induction Ceremony 2025
No full texthttps://digitalcommons.chapman.edu/pbk_induction_ceremony_2025/1011/thumbnail.jp
Phi Beta Kappa, Psi of California Chapter, Induction Ceremony 2025
No full texthttps://digitalcommons.chapman.edu/pbk_induction_ceremony_2025/1018/thumbnail.jp
Phi Beta Kappa, Psi of California Chapter, Induction Ceremony 2025
No full texthttps://digitalcommons.chapman.edu/pbk_induction_ceremony_2025/1023/thumbnail.jp