Extreme Response Research Articles

When local and foreign investors meet the Chinese government's risk perception about COVID-19

This paper explores the nuanced extreme market responses exhibited by segmented domestic and foreign investors in reaction to state media coverage of the COVID-19 pandemic in China’s A-share and H-share markets. Our findings indicate that an extreme increase (or decrease) in this unexpected attention is likely to lead to an extreme increase (or decrease) in stock prices. Domestic investors show increased sensitivity to an abnormal decrease in state media attention, whereas foreign investors are more responsive to an increase in this attention. An extreme unexpected decline in state media coverage of the pandemic significantly influences extreme fluctuations in the A-share market’s trading volume. In contrast, an abnormal increase in state media coverage of the pandemic tends to extremely decrease the H-share market’s trading volume. In the early panic phase, domestic (foreign) investors tend to reach a consensus more on abnormal declines (increases) in state media reports on the pandemic.

Vibration control of a monopile offshore wind turbines under recorded seismic waves

The dynamics and vibration control of offshore wind turbines (OWTs) under wind, wave, and earthquake loads is an important but understudied topic, especially for fully coupled seismic analysis considering pile foundation flexibility of OWTs. In this work, we study the effect of multiple passive tuned mass dampers (MTMD) on a monopile OWT by using the fully coupled seismic analysis method. A combined shutdown procedures and MTMD vibration control strategy is proposed for the OWT. First, a state-of-the-art aeroelastic tool, FAST, is extended with a seismic load calculation module, and the numerically modeled monopile OWT addresses the effect of pile-soil interaction (PSI) by establishing ElasPile module in the updated FAST. Then, the focus is placed on the normal operation and emergency shutdown status of OWTs under the combined earthquakes, wind and wave conditions, and structural and motion responses are analyzed under various combination conditions through time-domain simulations, the dynamic characteristics of the OWT during realistic seismic events are shown. Sequentially, based on the proposed MTMD, the vibration migitation effects are evident for the operation OWT and the OWT with shutdown strategies during the combined loading conditions. The reduction in the extreme responses can be as high as 10.53% and 55.02% for the bending moment at the mudline in different OWT conditions, respectively. Therefore, the combined shutdown procedures and MTMD vibration control strategy of OWT is an effective vibration reduction method. Additionally, it is found that PSI has a significant impact on the dynamic characteristics and vibration control effects of OWT structures under wind, wave, and earthquake loads, and the coupled spring boundary condition on the basis of developed ElasPile module is recommended for seismic control analysis of OWT using the combined shutdown procedures and MTMD vibration control strategy.

Wind-resistant reliability assessment of a super-high tower crane considering the randomness and correlation of turbulent spectral parameters

The need for wind-sensitive super-high tower cranes during the construction of high-rise structures has been growing, which makes it critical to assess the wind-resistant reliability of cranes. The accuracy of assessment is dominated by the refined simulation of real stochastic wind fields, which is usually based on the deterministic turbulent spectra including fixed spectral parameters. However, it might cause significant errors to estimate extreme responses of structures. Therefore, a simulation method for stochastic wind fields considering the randomness and correlation of turbulent spectral parameters is proposed in this study. The random functions of correlated spectral parameters are constructed based on several independent elementary random variables. A novel simulation method for stochastic wind fields involving the established random turbulent spectral functions is utilized to generate fluctuating wind samples at the Ma'anshan Yangtze River (MYR) Bridge site. In combination with the probability density evolution method, the stochastic response analysis and reliability assessment of wind-induced vibration of the crane are addressed. Results prove the effectiveness of the proposed approach in depicting probabilistic properties of real wind fields. Meanwhile, the wind-resistant comfort reliability of the tower crane is higher when considering the randomness and correlation of turbulent spectral parameters.

Error modelled gene expression analysis (EMOGEA) provides a superior overview of time course RNA-seq measurements and low count gene expression.

Temporal RNA-sequencing (RNA-seq) studies of bulk samples provide an opportunity for improved understanding of gene regulation during dynamic phenomena such as development, tumor progression or response to an incremental dose of a pharmacotherapeutic. Moreover, single-cell RNA-seq (scRNA-seq) data implicitly exhibit temporal characteristics because gene expression values recapitulate dynamic processes such as cellular transitions. Unfortunately, temporal RNA-seq data continue to be analyzed by methods that ignore this ordinal structure and yield results that are often difficult to interpret. Here, we present Error Modelled Gene Expression Analysis (EMOGEA), a framework for analyzing RNA-seq data that incorporates measurement uncertainty, while introducing a special formulation for those acquired to monitor dynamic phenomena. This method is specifically suited for RNA-seq studies in which low-count transcripts with small-fold changes lead to significant biological effects. Such transcripts include genes involved in signaling and non-coding RNAs that inherently exhibit low levels of expression. Using simulation studies, we show that this framework down-weights samples that exhibit extreme responses such as batch effects allowing them to be modeled with the rest of the samples and maintain the degrees of freedom originally envisioned for a study. Using temporal experimental data, we demonstrate the framework by extracting a cascade of gene expression waves from a well-designed RNA-seq study of zebrafish embryogenesis and an scRNA-seq study of mouse pre-implantation and provide unique biological insights into the regulation of genes in each wave. For non-ordinal measurements, we show that EMOGEA has a much higher rate of true positive calls and a vanishingly small rate of false negative discoveries compared to common approaches. Finally, we provide two packages in Python and R that are self-contained and easy to use, including test data.

Probabilistic Design Methods for Gust-Based Loads on Wind Turbines

The IEC 61400-1 standard specifies design load cases (DLCs) to be considered in the design of wind turbine structures. Specifically, DLC 2.3 considers the occurrence of a gust while the turbine shuts down due to an electrical fault. Originally, this load case used a deterministic wind event called the extreme operating gust (EOG), but the standard now also includes an approach for calculating the extreme response based on stochastic simulations with turbulent wind. This study presents and compares existing approaches with novel probabilistic design approaches for DLC 2.3 based on simulations with turbulent wind. First, a semiprobabilistic approach is proposed, where the inverse first-order reliability method (iFORM) is used for the extrapolation of the response for electrical faults occurring at a given rate. Next, three probabilistic approaches are formulated for the calculation of the reliability index, which differs in how the aggregation is performed over wind conditions and whether faults are modeled using a Poisson distribution or just by the rate. An example illustrates the methods considering the tower fore-aft bending moment at the tower base and shows that the approach based on iFORM can lead to reductions in material usage compared to the existing methods. For reliability assessment, the probabilistic approach using the Poisson process is needed for high failure rates, and the reliabilities obtained for designs using all semiprobabilistic methods are above the target level, indicating that further reductions may be obtained via the use of probabilistic design methods.

Abstract 7471: Cancer-associated fibroblasts drive T cell infiltration and resistance to immunotherapy in non-small cell lung cancer with mature tertiary lymphoid structures

Abstract Background: The presence of mature tertiary lymphoid structures (mTLS) within the tumor microenvironment (TME) has been linked to the effectiveness of PD-L1 blockade in non-small cell lung cancer (NSCLC). However, only a subset of patients experiencing clinical benefit. Our study aims to delve into the determinants of immunotherapy response in mTLS-positive NSCLC. Methods: We included 77 TLS-positive NSCLC from the BIP study (NCT02534649). First, we employed the GeoMx whole-transcriptome atlas (WTA) assay to spatially profiled the expression of >18,000 protein-coding in patients exhibiting extreme responses (3 responders [R] and 3 non-responders [NR]). To target regions of interest (ROIs), we selected areas that encompassed TLS (CD3+/CD20+) as entire areas of illumination (AOIs). Additionally, we segmented areas outside TLS into ‘tumor’ (PanCK+/CD45−) vs ‘stroma’ (PanCK−/CD45+) AOIs. To validate our findings, we conducted multiplex immunofluorescence (mIF) and complemented our results with bulk gene expression analysis using the HTG whole human transcriptome panel. Results: Spatial transcriptomic analysis pinpointed significant differences in gene expression within the stromal compartment between R and NR. Notably, a subset of cancer-associated fibroblasts (CAFs) expressing both FAP and αSMA markers emerged as the most differentially expressed genes. Subsequently, we used FFPE tissue mIF to delineate the histological profile CAF subsets and the spatial distribution of T cells. Notably, the stromal density of FAP+αSMA+ CAFs and MYH11+αSMA+ CAFs were significantly higher in NR compared to R. Correspondingly, tumors enriched in FAP+αSMA+ CAFs and MYH11+αSMA+ CAFs exhibited significantly lower overall response rates (ORR) and progression-free survival (PFS) than those with a low abundance of CAFs. Interestingly, tumors with elevated FAP+αSMA+ CAFs and MYH11+αSMA+ CAFs were associated with a higher infiltration of CD8+ T cells. To delve deeper into the CD8+ T cell infiltrate, we conducted a comparative bulk transcriptomic analysis. Both FAP+αSMA+ CAFs High and MYH11+αSMA+ CAFs High demonstrated significant associations with regulatory T cells (Treg), exhaustion signatures, and inflammatory processes. To validate the CD8+ T cell phenotype, we performed complementary mIF. Consistently, the CD8+ T cell infiltrate in tumors featuring FAP+αSMA+ CAFs High and MYH11+αSMA+ CAFs High exhibited higher levels of exhaustion markers (PD1, LAG3, TIM3, TIGIT) and Treg infiltration, underscoring an immunosuppressive TME. Conclusions: FAP+αSMA+ CAFs and MYH11+αSMA+ CAFs play a pivotal role in driving T cell exhaustion and Treg cell infiltration, contributing to the resistance to immune checkpoint inhibition. Targeting these specific CAF subsets may hold significant promise in overcoming resistance in mature TLS-positive NSCLC. Citation Format: Florent Peyraud, Jean-Philippe Guegan, Lucile Vanhersecke, Christophe Rey, Oren Lara, Ophélie Odin, Emma Clot, Maxime Brunet, Thomas Grellety, Marie Del Castillo, Sylvestre Le Moulec, François Le Loarer, Alban Bessede, Antoine Italiano. Cancer-associated fibroblasts drive T cell infiltration and resistance to immunotherapy in non-small cell lung cancer with mature tertiary lymphoid structures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7471.

The response of atmospheric blocking and East Asian cold extremes to future Arctic Sea ice loss

The effect of Arctic warming on cold extremes over middle latitude remains a controversial and unresolved issue, particularly considering potential enhanced Arctic amplification in future scenarios. Here we examine the possible responses of winter cold extremes to the projected sea ice loss under 2 °C global warming scenario in four models, based on the atmosphere-only experiments of the Polar Amplification Model Inter-comparison Project (PAMIP). We find agreement with the increased responses of extreme cold days over East Asia (EA), characterized by longer duration or stronger intensity of temperature drop during cold events. Accordingly, most models exhibit a weak response of the Ural blocking in the corresponding composite circulation fields, whereas the westward movement of an anomalous anticyclonic system from eastern Siberia before the maturing of the Ural blocking is notable in four models. We suggest that this westward shifting pattern may prolong the duration of Ural blocking or modulate the strength of the Northeast Asian cold vortex, resulting in longer or stronger cold anomalies in EA. Accordingly, increased blocking frequency with a more pronounced westward response of shipment signals is also found over eastern Siberia, where a reduced meridional potential vorticity gradient (PVy) exists. The background of weak PVy can enhance the atmospheric nonlinearity, resulting in the anticyclonic anomalies less prone to dispersion and presenting a westward characteristic. Our results highlight the impact of the nonlinear response of circulation to Arctic sea ice loss. In contrast to more concerned Ural blocking influence, it is suggested that the downstream impact of eastern Siberia blocking on cold extremes in EA may be more pronounced in an enhanced Arctic amplification climate.

A framework proposal for new multiaxial fatigue damage and extreme response spectra in random vibrations frequency analysis

Fatigue Damage Spectra (FDS) and Extreme Response Spectra (ERS) are well-established tools for characterizing and evaluating the impact of vibration loads on mechanical structures. While this is particularly valuable in producing test-tailored specifications, their current application is limited to uniaxial analysis despite evidence indicating their inadequacy in representing real-world loads, which are often multiaxial.The proposed method offers a system-oriented approach to characterize and compare multiaxial environments in terms of their severity, independently or not of any physical structure. In addition, it introduces a generalization of the FDS and ERS, referred to as Fatigue Damage multi-Spectrum (FDmS) and Extreme Response multi-Spectrum (ERmS) respectively. These extensions allows for the consideration of multiaxial phenomena, such as correlation and modal proximity. Finally, this paper demonstrates through several case studies the method’s capability to capture phenomena not addressed by established uniaxial approaches.

A new metamodel for predicting the nonlinear time-domain response of offshore structures subjected to stochastic wave current and wind loads

Offshore structures are subjected to stochastic loads from wave, current, and wind. A long-term response analysis is important for evaluating the structural safety; however, it is computationally demanding to perform the large number of nonlinear time-domain simulations. Metamodeling is an attractive prospect, but there are two existing obstacles to overcome. First, existing metamodels are mostly confined to a single sea state and are unable to predict the response for different wave directions. Second, for floating systems, the inputs are usually vessel loads/motions, which are a priori unknown. This paper develops a new metamodel framework for accurately predicting the time series response under short-term uncertainties from the stochastic process, and seven long-term variables, namely the significant wave height, spectral period, wave direction, and speeds and directions of current and wind. The exogenous input is based only on the environmental variables, which can be predefined. The proposed metamodel is implemented on a floating system and used to predict the time series of riser stress, the extreme stress response and fatigue damage. Four cases with increasing number of long-term variables are tested. Excellent agreement is found between the metamodel prediction and numerical simulation even for the most critical case with all variables included.

The function of timbre in the perception of affective intentions: Effect of enculturation in different musical traditions

Timbre has been identified as a potential component in the communication of affect in music. Although its function as a carrier of perceptually useful information about sound source mechanics has been established, less is understood about whether and how it functions as a carrier of information for communicating affect in music. To investigate these issues, listeners trained in Chinese and Western musical traditions were presented with Phrases, Measures, and Notes of recorded excerpts interpreted with a variety of affective intentions by performers on instruments from the two cultures. Results showed greater accuracy and more extreme responses in Chinese musician listeners and lowest accuracy in nonmusicians suggesting that musical training plays a role in listeners’ decoding of affective intention. Responses were more differentiated and more accurate with more musical information. Excerpts were also analyzed to determine acoustic features that are correlated with timbre characteristics. Temporal, spectral, and spectrotemporal attributes were consistently used in judging affective intent in music, suggesting purposeful use of these properties by listeners. Comparison between listeners’ use of acoustic features reveals a greater number of shared features between Western musicians and nonmusicians compared to Chinese musicians for valence, although the three groups shared more features for arousal. How timbre is utilized in musical communication appears to be different across musical traditions, and valence responses seem to be more culture-specific and arousal responses more similar across cultures.

Cognitive Functioning and the Quality of Survey Responses: An Individual Participant Data Meta-Analysis of 10 Epidemiological Studies of Aging.

Self-reported survey data are essential for monitoring the health and well-being of the population as it ages. For studies of aging to provide precise and unbiased results, it is necessary that the self-reported information meets high psychometric standards. In this study, we examined whether the quality of survey responses in panel studies of aging depends on respondents' cognitive abilities. Over 17 million survey responses from 157,844 participants aged 50 years and older in 10 epidemiological studies of aging were analyzed. We derived 6 common statistical indicators of response quality from each participant's data and estimated the correlations with participants' cognitive test scores at each study wave. Effect sizes (correlations) were synthesized across studies, cognitive tests, and waves using individual participant data meta-analysis methods. Respondents with lower cognitive scores showed significantly more missing item responses (overall effect size ρ^ = -0.144), random measurement error (ρ^ = -0.192), Guttman errors (ρ^ = -0.233), multivariate outliers (ρ^ = -0.254), and acquiescent responses (ρ^ = -0.078); the overall effect for extreme responses (ρ^ = -0.045) was not significant. Effect sizes were consistent across studies, modes of survey administsration, and different cognitive functioning domains, although some cognitive domain specificity was also observed. Lower-quality responses among respondents with lower cognitive abilities add random and systematic errors to survey measures, reducing the reliability, validity, and reproducibility of survey study results in aging research.

Studying the correlation of inflammatory cytokines to COVID-19 disease

Extreme response of the immune system develops cytokine storm which might be crucial in the pathology of COVID-19. The research aims to evaluate the serum level of IL-6, TNF-α, and IP-10 in severe, mild, and pre-vaccinated one-dose COVID-19 patients and investigate their clinical value and effect in the disease development among different groups of patients. A total of 72 samples were collected 18 as healthy control and 54 from confirmed COVID-19 patients including 18 mild, 18 severe, and 18 pre-vaccinated (one dose). It was confirmed that the severe group of COVID-19 patients had the highest circulating IL-6, TNF- α, and IP-10. IL-6 level in mild and pre-vaccinated (one dose) was significantly lower than in severe. In conclusion, IL-6, TNF-α, and IP-10 are associated with the pathogenicity of COVID-19, furthermore, vaccination could help to control severity of the disease.

Protective roles of highly conserved motif 1 in tardigrade cytosolic-abundant heat soluble protein in extreme environments.

Tardigrades are remarkable microscopic animals that survive harsh conditions such as desiccation and extreme temperatures. Tardigrade-specific intrinsically disordered proteins (TDPs) play an essential role in the survival of tardigrades in extreme environments. Cytosolic-abundant heat soluble (CAHS) protein, a key TDP, is known to increase desiccation tolerance and to protect the activity of several enzymes under dehydrated conditions. However, the function and properties of each CAHS domain have not yet been elucidated in detail. Here, we aimed to elucidate the protective role of highly conserved motif 1 of CAHS in extreme environmental conditions. To examine CAHS domains, three protein constructs, CAHS Full (1-229), CAHS ∆Core (1-120_184-229), and CAHS Core (121-183), were engineered. The highly conserved CAHS motif 1 (124-142) in the CAHS Core formed an amphiphilic α helix, reducing the aggregate formation and protecting lactate dehydrogenase activity during dehydration-rehydration and freeze-thaw treatments, indicating that CAHS motif 1 in the CAHS Core was essential for maintaining protein solubility and stability. Aggregation assays and confocal microscopy revealed that the intrinsically disordered N- and C-terminal domains were more prone to aggregation under our experimental conditions. By explicating the functions of each domain in CAHS, our study proposes the possibility of using engineered proteins or peptides derived from CAHS as a potential candidate for biological applications in extreme environmental stress responses.

Multitier regulation of the E. coli extreme acid stress response by CsrA.

CsrA is an RNA-binding protein that regulates processes critical for growth and survival, including central carbon metabolism, motility, biofilm formation, stress responses, and expression of virulence factors in pathogens. Transcriptomics studies in Escherichia coli suggested that CsrA repressed genes involved in surviving extremely acidic conditions. Here, we examine the effects of disrupting CsrA-dependent regulation on the expression of genes and circuitry for acid stress survival and demonstrate CsrA-mediated repression at multiple levels. We show that this repression is critical for managing the trade-off between growth and survival; overexpression of acid stress genes caused by csrA disruption enhances survival under extreme acidity but is detrimental for growth under mildly acidic conditions. In vitro studies confirmed that CsrA binds specifically to mRNAs of structural and regulatory genes for acid stress survival, causing translational repression. We also found that translation of the top-tier acid stress regulator, evgA, is coupled to that of a small leader peptide, evgL, which is repressed by CsrA. Unlike dedicated acid stress response genes, csrA and its sRNA antagonists, csrB and csrC, did not exhibit a substantial response to acid shock. Furthermore, disruption of CsrA regulation of acid stress genes impacted host-microbe interactions in Caenorhabditis elegans, alleviating GABA deficiencies. This study expands the known regulon of CsrA to genes of the extreme acid stress response of E. coli and highlights a new facet of the global role played by CsrA in balancing the opposing physiological demands of stress resistance with the capacity for growth and modulating host interactions.IMPORTANCETo colonize/infect the mammalian intestinal tract, bacteria must survive exposure to the extreme acidity of the stomach. E. coli does this by expressing proteins that neutralize cytoplasmic acidity and cope with molecular damage caused by low pH. Because of the metabolic cost of these processes, genes for surviving acid stress are tightly regulated. Here, we show that CsrA negatively regulates the cascade of expression responsible for the acid stress response. Increased expression of acid response genes due to csrA disruption improved survival at extremely low pH but inhibited growth under mildly acidic conditions. Our findings define a new layer of regulation in the acid stress response of E. coli and a novel physiological function for CsrA.

Simplified Strength Assessment for Preliminary Structural Design of Floating Offshore Wind Turbine Semi-Submersible Platform

The study aims to develop a simplified strength assessment method for the preliminary structural design of a semi-submersible floating offshore wind turbine platform. The method includes load cases with extreme wave load effects and a load case dominated by wind load. The extreme load effects due to waves are achieved using the design waves. Seven characteristic responses of the semi-submersible platform due to waves are chosen. The design waves for the extreme characteristic responses are all from extreme wave conditions where the significant wave heights are close to the one for a return period of 100 years. The extreme load effects dominated by wind loads are approximated using the modified environmental contour method. The load effects are the tower base shear force and bending moment. The two load effects are correlated, and a linear equation can approximate the relationship between their extreme values. The finite element analysis results show that the frame design of the bottom of the outer column is essential for structural strength. The wave load can also result in significant stress in the area close to the tower base.

Augmenting Neutrophil Extracellular Traps with Carbonized Polymer Dots: A Potential Treatment for Bacterial Sepsis.

Sepsis is a life-threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin-resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as-formed CCM-CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM-CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA-induced septic mouse model, it is observed that CCM-CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti-inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM-CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM-CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA-infected mice treated with CCM-CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life-threatening infectious diseases.

On the response of daily precipitation extremes to local mean temperature in the Yangtze River basin

This study explores the response of daily extreme precipitation (PEX) to local mean temperatures (T) of the previous 0-day (T0), 1-day (T1), and 1 to 9-days (T1–9) in the Yangtze River basin (YRB) using the non-stationarity test, binning method and copula theory. Results show that the annual scaling rate of PEX with T during 1961–2020 exhibits positive, negative and positive changing trends from southwest to northeast with the maximum magnitudes in the west, and experiences significant abrupt change only at 14.1% grids. The PEX-T scaling relation in the entire study period is predominantly characterized by a peak pattern over the YRB, with precipitation peaking at about 8 °C in the western highlands and at 25 °C in the east-central lowlands. However, the use of T1–9 yields a positive PEX-T pattern at more grids compared to T1 and T0, which highlights the important role of atmospheric moisture residence time in minimizing cooling artefacts in the scaling estimation. Generally, the full scaling rate of PEX with T in the study period is larger in the west-central part but smaller in the eastern YRB, and more sensitive to antecedent temperatures, with the ranges of −8–20%/°C, −8–30%/°C and −10–30%/°C against T0, T1 and T1–9, respectively. As precipitation intensifies, the full scaling decreases in plateau-mountain areas but increases in low-lying regions, gradually approaching the Clausius-Clapeyron (CC) scaling and exhibiting a “super-CC, CC-like and sub-CC scaling” pattern from west to east. Additionally, heavier precipitation events are most likely to occur at higher local temperatures in most areas even with peak structure. These findings provide new insights into the PEX-T relationships, which is conducive to understanding future changes in precipitation extremes and assessing precipitation-related risks under climate change.

Response of winter climate and extreme weather to projected Arctic sea-ice loss in very large-ensemble climate model simulations

Very large (~2000 members) initial-condition ensemble simulations have been performed to advance understanding of mean climate and extreme weather responses to projected Arctic sea-ice loss under 2 °C global warming above preindustrial levels. These simulations better sample internal atmospheric variability and extremes for each model compared to those from the Polar Amplification Model Intercomparison Project (PAMIP). The mean climate response is mostly consistent with that from the PAMIP multi-model ensemble, including tropospheric warming, reduced midlatitude westerlies and storm track activity, an equatorward shift of the eddy-driven jet and increased mid-to-high latitude blocking. Two resolutions of the same model exhibit significant differences in the stratospheric circulation response; however, these differences only weakly modulate the tropospheric response. The response of temperature and precipitation extremes largely follows the seasonal-mean response. Sub-sampling confirms that large ensembles (e.g. ≥400) are needed to robustly estimate the seasonal-mean large-scale circulation response, and very large ensembles (e.g. ≥1000) for regional climate and extremes.

Assessing some statistical and physical modelling uncertainties of extreme responses for monopile-based offshore wind turbines, using metocean contours

This study examines the influence of probabilistic models for wave parameters in the joint environmental model and hydrodynamic/soil models on extreme mudline bending moments for monopile-based wind turbines at representative wind speeds, using the environmental contour method. For significant wave height, the 3-parameter Weibull model using the method of moments (MoM) provides the best fit to hindcast data across different wind classes, for the statistical models and data considered in the study. The hybrid Log-normal-Weibull (LonoWe) model also provides a reasonable fit but is sensitive to the transition point between distributions. Both models yield the largest extreme responses, with differences of approximately 0.5–3.5%. The 3-parameter Weibull model with maximum likelihood estimation (MLE) and the 2-parameter Weibull model result in less conservative contours, leading to up to 13% lower extreme responses, compared to LonoWe and Weibull (MoM). Regarding peak period, both the Log-normal and 3-parameter Weibull models provide reasonable fits, with the latter being more accurate near the steepness (breaking) limit. The stochastic variation among maxima due to seed variability and the uncertainty in quantile estimates as a function of number of samples was found to be crucial, particularly for severe sea states at the cut-out speed. Soil modelling is particularly important when the turbine is parked and encounters peak wave periods close to the turbine’s natural periods, while the effect of soil modelling on the extremes during turbine operation is negligible. Additionally, the impact of diffraction becomes relatively important for short wave periods. However, it is worth noting that the choice of load models has less impact on extreme responses compared to variations in the contours caused by different statistical models or seed variability.

Genetic diversity drives extreme responses to traumatic brain injury and post-traumatic epilepsy

Traumatic brain injury (TBI) is a complex and heterogeneous condition that can cause wide-spectral neurological sequelae such as behavioral deficits, sleep abnormalities, and post-traumatic epilepsy (PTE). However, understanding the interaction of TBI phenome is challenging because few animal models can recapitulate the heterogeneity of TBI outcomes. We leveraged the genetically diverse recombinant inbred Collaborative Cross (CC) mice panel and systematically characterized TBI-related outcomes in males from 12 strains of CC and the reference C57BL/6J mice. We identified unprecedented extreme responses in multiple clinically relevant traits across CC strains, including weight change, mortality, locomotor activity, cognition, and sleep. Notably, we identified CC031 mouse strain as the first rodent model of PTE that exhibit frequent and progressive post-traumatic seizures after moderate TBI induced by lateral fluid percussion. Multivariate analysis pinpointed novel biological interactions and three principal components across TBI-related modalities. Estimate of the proportion of TBI phenotypic variability attributable to strain revealed large range of heritability, including >70% heritability of open arm entry time of elevated plus maze. Our work provides novel resources and models that can facilitate genetic mapping and the understanding of the pathobiology of TBI and PTE.