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Abstract Infections caused by Gram-negative bacteria are leading causes of mortality worldwide. Due to the rise in antibiotic resistant strains, there is a desperate need for alternative strategies to control infections caused by these organisms. One such approach is the prevention of infection through vaccination. While live attenuated and heat-killed bacterial vaccines are effective, they can lead to adverse reactions. Newer vaccine technologies focus on utilizing polysaccharide or protein subunits for safer and more targeted vaccination approaches. One promising avenue in this regard is the use of proteins released by the Type 5 secretion system (T5SS). This system is the most prevalent secretion system in Gram-negative bacteria. These proteins are compelling vaccine candidates due to their demonstrated protective role in current licensed vaccines. Notably, Pertactin, FHA, and NadA are integral components of licensed vaccines designed to prevent infections caused by Bordetella pertussis or Neisseria meningitidis. In this review, we delve into the significance of incorporating T5SS proteins into licensed vaccines, their contributions to virulence, conserved structural motifs, and the protective immune responses elicited by these proteins.

Abstract α-Synuclein (α-syn) accumulates as insoluble amyloid but also forms soluble α-syn oligomers (αSOs), thought to be even more cytotoxic than fibrils. To detect and block the unwanted activities of these αSOs, we have raised 30 monoclonal antibodies (mAbs) against different forms of αSOs, ranging from unmodified αSOs to species stabilized by lipid peroxidation products and polyphenols, αSOs formed by C-terminally truncated α-syn, and multivalent display of α-syn on capsid virus-like particles (cVLPs). While the mAbs generally show a preference for αSOs, they also bind fibrils, but to variable extents. Overall, we observe great diversity in the mAbs’ relative affinities for monomers and αSOs, varied requirements for the C-terminal extension of α-syn, and only a modest effect on α-syn fibrillation. Several mAbs show several orders of magnitude preference for αSOs over monomers in in-solution studies, while the commercial antibody MJF14 only bound 10-fold more strongly to αSOs than monomeric α-syn. Gratifyingly, seven mAbs almost completely block αSO permeabilization of membrane vesicles. Five selected mAbs identified α-syn-related pathologies like Lewy bodies (LBs) and Lewy Neurites, as well as Glial Cytoplasmic Inclusions in postmortem brains from people diagnosed for PD, dementia with LBs or multiple system atrophy, although to different extents. Three mAbs were particularly useful for pathological evaluation of postmortem brain human tissue, including early stages of PD. Although there was no straightforward connection between the mAbs’ biophysical and immunohistochemical properties, it is encouraging that this comprehensive collection of mAbs able to recognize different aggregated α-syn species in vitro also holds diagnostic potential.

Abstract Background There is an increasing need to increase simulation-based learning opportunities for vascular surgery residents in endovascular skills training. This study aims to explore the effectiveness of remote expert instructional feedback of endovascular simulation-based education, as a means of increasing training opportunities in this area for vascular surgery residents. Methods A mixed-methods study design was adopted. Twelve vascular surgery residents from Ireland were tasked with completing two endovascular renal artery procedures: one with in-person expert feedback and the other with remote instruction. Participants ranged in experience levels from second year to final year of residency. Following the training activities, interviews and a questionnaire were employed to gather information on the usefulness of remote feedback. Results There was no significant difference reported by participants using a post-event validated questionnaire between remote and in-person feedback. During the interviews, participants expressed mixed feelings about the presence of the educator while practicing, but they eventually saw no limiting factors to their practice when the trainer provided remote feedback. When receiving performance feedback remotely, clear communication and a shared knowledge of the task development are critical to success. Conclusions We believe these findings can inform the design and development of remote learning and assessment of endovascular skills training and ultimately provide increased opportunities for more skills practice for vascular surgical residents.

Introduction/objective: As the coronavirus disease 2019 (COVID-19) pandemic progressed, the virus was found to cause long-term health complications known as long COVID (LC). This study aimed to investigate LC symptom severity and the factors associated with the likelihood of persistence beyond 1 year among COVID-19 survivors in Saudi Arabia. Methods: This descriptive, cross-sectional, questionnaire-based study was conducted via convenience sampling between December 1, 2023, and March 1, 2024. In-person interviews were performed, and 845 individuals with persistent symptoms after acute COVID-19 were included. Results: Hair loss and memory impairment were the most reported symptoms. In predicting LC persistence beyond 12 months, women were found to have higher odds of being symptomatic than men, and individuals from moderate-to-high-income households were more likely to report persistent symptoms than those from low-income households. Each additional acute COVID-19 symptom increased the likelihood of persistent symptoms by 1.14 times. Reporting more symptoms in the first 6 months post-infection significantly reduced the odds of long-term symptoms by approximately 30%. Conclusion: LC symptom severity varies among patients, and sociodemographic and clinical factors influence the likelihood of experiencing symptoms beyond 1 year. Understanding these factors can provide insights and help optimize management, leading to improved patient outcomes.

ABSTRACT Salmonella enterica is a globally disseminated pathogen that is the cause of over 100 million infections per year. The resulting diseases are dependent upon host susceptibility and the infecting serovar. As S. enterica serovar Typhimurium induces a typhoid-like disease in mice, this model has been used extensively to illuminate various aspects of Salmonella infection and host responses. Due to the severity of infection in this model, researchers often use strains of mice resistant to infection or attenuated Salmonella. Despite decades of research, many aspects of Salmonella infection and fundamental biology remain poorly understood. Here, we use a transposon insertion sequencing technique to interrogate the essential genomes of widely used isogenic wild-type and attenuated S. Typhimurium strains. We reveal differential essential pathways between strains in vitro and provide a direct link between iron starvation, DNA synthesis, and bacterial membrane integrity.IMPORTANCESalmonella enterica is an important clinical pathogen that causes a high number of deaths and is increasingly resistant to antibiotics. Importantly, S. enterica is used widely as a model to understand host responses to infection. Understanding how Salmonella survives in vivo is important for the design of new vaccines to combat this pathogen. Live attenuated vaccines have been used clinically for decades. A widely used mutation, aroA, is thought to attenuate Salmonella by restricting the ability of the bacterium to access particular amino acids. Here we show that this mutation limits the ability of Salmonella to acquire iron. These observations have implications for the interpretation of many previous studies and for the use of aroA in vaccine development.

BackgroundThe COVID-19 pandemic has significantly raised public health concerns and efforts to limit its spread, impacting societies and health systems worldwide. As challenges persist, the emergence of Long COVID (LC) marks a turning point in understanding the pandemic’s long-term effects.AimThis study aimed to determine the prevalence of LC in the Eastern Province of the Kingdom of Saudi Arabia (KSA) and explore factors contributing to its persistence.MethodsThis descriptive, cross-sectional, questionnaire-based study was carried out between December 1, 2023, and March 1, 2024, involving 1,355 patients who recovered from COVID-19. Participants were conveniently chosen and information was gathered through in-person interviews in public settings after obtaining consent.ResultsA majority of the patients (N = 1,355; 47.5% female; 93.8% Saudis; mean Age ± SD 33.13 ± 12.60 years) had received three COVID-19 vaccine doses (89.5%). Women experienced 17.4% more LC symptoms than men (p 0.05).ConclusionSociodemographic and clinical factors contribute differently to the chances of having LC and the count of symptoms. Awareness of such factors could provide insight into improving management, leading to better health outcomes.

Wildlife in the Anthropocene is increasingly spatially and temporally constrained by lethal and non-lethal human disturbance. For large carnivores with extensive space requirements, like wolves and Eurasian lynx, avoiding human disturbance in European landscapes is challenging when sufficient space with low disturbance is rarely available. Consequently, investigating behavioural adjustments to human presence is critical to understanding the capacity to adapt to human disturbance. We hypothesised that under low human disturbance conditions, large carnivores would adjust their temporal behaviours to make use of daytime, and when daytime human disturbance is high, they would opt for nocturnality. Using camera trap data from nine European study sites along a gradient in human disturbance, we analysed wolf and Eurasian lynx activity patterns. Our data spanned multiple years, 2014 – 2022, and we focused our analysis on September until April, when most large carnivore monitoring takes place. For wolves, our analysis revealed i) increased nocturnal behaviour, ii) decreased diurnal overlap with increasing human activity, and iii) a significant association between a higher probability of nocturnal activity and increasing human disturbance. For Eurasian lynx, we found iv) consistently nocturnal behaviours across all study sites, regardless of human disturbance, and v) no association between human disturbance and increased probability of being active during the night. Our results show that wolves can adjust to diurnal or cathemeral behaviours under low human disturbance, but shift to nocturnality when human disturbance increases. Eurasian lynx, however, consistently maintain their nocturnal behaviour, which we attribute to their principal hunting strategy of stalk and ambush. If human disturbance constrains large carnivore activity to nighttime, it could influence their interactions with prey, leading to cascading effects in the ecosystem. On the other hand, maintaining nocturnal behaviours in human-dominated landscapes may benefit large carnivore conservation, by decreasing negative interactions with humans thereby contributing to a landscape of coexistence.

Abstract Zoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are becoming more prevalent, but require novel thinking, tools and cross-disciplinary collaboration. Bovine tuberculosis (bTB) is one example of a costly One Health challenge with a complex epidemiology involving humans, domestic animals, wildlife and environmental factors, which require sophisticated collaborative approaches. We undertook a scoping review of multi-host bTB epidemiology to identify trends in species publication focus, methodologies, and One Health approaches. We aimed to identify knowledge gaps where novel research could provide insights to inform control policy, for bTB and other zoonoses. The review included 532 articles. We found different levels of research attention across episystems, with a significant proportion of the literature focusing on the badger-cattle-TB episystem, with far less attention given to tropical multi-host episystems. We found a limited number of studies focusing on management solutions and their efficacy, with very few studies looking at modelling exit strategies. Only a small number of studies looked at the effect of human disturbances on the spread of bTB involving wildlife hosts. Most of the studies we reviewed focused on the effect of badger vaccination and culling on bTB dynamics with few looking at how roads, human perturbations and habitat change may affect wildlife movement and disease spread. Finally, we observed a lack of studies considering the effect of weather variables on bTB spread, which is particularly relevant when studying zoonoses under climate change scenarios. Significant technological and methodological advances have been applied to bTB episystems, providing explicit insights into its spread and maintenance across populations. We identified a prominent bias towards certain species and locations. Generating more high-quality empirical data on wildlife host distribution and abundance, high-resolution individual behaviours and greater use of mathematical models and simulations are key areas for future research. Integrating data sources across disciplines, and a “virtuous cycle” of well-designed empirical data collection linked with mathematical and simulation modelling could provide additional gains for policy-makers and managers, enabling optimised bTB management with broader insights for other zoonoses.

BACKGROUND: Cognitive decline affects the quality of life, and dementia affects independence in daily life activities. Multimorbidity in older adults is associated with a higher risk of cognitive impairment. This research aims to study the relationship between cognitive decline and multimorbidity in the elderly population in the Eastern Province, Saudi Arabia. MATERIALS AND METHODS: This cross-sectional research was conducted from July to October 2022 among adults over 60 years. All patients with two or more comorbidities were contacted for a face-to-face interview and cognitive testing to estimate cognitive function by trained family physicians using St. Louis University Mental State Examination. ANOVA and Chi-square test were used to test for statistical significance. Binary logistic regression was used to show the odds of having cognitive impairment and multimorbidity. All tests were performed at 5% level of significance. RESULTS: The study involved 343 individuals; majority (74.1%) aged 60-75 years and were males (67.9%). Hypertension, diabetes, and chronic pain were reported by 56%, 48%, and 44% participants, respectively. Thirty percent participants had 3 or more comorbidities. About 36% had mild neurocognitive disorder and 31.2% had dementia. The results showed that age, gender (female), diabetes, stroke, chronic pain, and multimorbidity were significantly associated with cognitive impairment. In our study, hypertension, coronary artery diseases, depression, and anxiety were not significantly associated with risk of cognitive decline. CONCLUSION: Our study found that multimorbidity is significantly associated with cognitive decline. Controlling comorbidities and preventing risk factors in midlife could help in delaying the progression of the disease.

Abstract Magnetic storms on stars manifest as remarkable, randomly occurring changes of the luminosity over durations that are tiny in comparison to the normal evolution of stars. These stellar flares are bursts of electromagnetic radiation from X-ray to radio wavelengths, and they occur on most stars with outer convection zones. They are analogous to the events on the Sun known as solar flares, which impact our everyday life and modern technological society. Stellar flares, however, can attain much greater energies than those on the Sun. Despite this, we think that these phenomena are rather similar in origin to solar flares, which result from a catastrophic conversion of latent magnetic field energy into atmospheric heating within a region that is relatively small in comparison to normal stellar sizes. We review the last several decades of stellar flare research. We summarize multi-wavelength observational results and the associated thermal and nonthermal processes in flaring stellar atmospheres. Static and hydrodynamic models are reviewed with an emphasis on recent progress in radiation-hydrodynamics and the physical diagnostics in flare spectra. Thanks to their effects on the space weather of exoplanetary systems (and thus in our search for life elsewhere in the universe) and their preponderance in Kepler mission data, white-light stellar flares have re-emerged in the last decade as a widely-impactful area of study within astrophysics. Yet, there is still much we do not understand, both empirically and theoretically, about the spectrum of flare radiation, its origin, and its time evolution. We conclude with several big-picture questions that are fundamental in our pursuit toward a greater understanding of these enigmatic stellar phenomena and, by extension, those on the Sun.

Abstract Background The mechanisms by which cigarette smoking increases the risk of respiratory disease have been studied. However, less is known about risks of respiratory symptoms and outcomes associated with smoking cigars, and risks by cigar types have not been previously explored. The aim of this study was to examine associations between cigar use, including traditional cigars, cigarillos, filtered cigars, and dual cigar and cigarette use, and functionally important respiratory symptoms (FIRS), lifetime asthma diagnosis, uncontrolled asthma, and new cases of FIRS. Methods Data from Waves 2–5 (2014–19) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal study, were analyzed in two ways. For cross-sectional analysis, the analytic sample included adults 18 and older at each wave, resulting in 44,040 observations. Separately, longitudinal analyses were assessed among adults 18 and older at Wave 2, resulting in 7,930 individuals. Both analyses excluded adults with chronic obstructive pulmonary disease (COPD) or non-asthma respiratory disease. Results Current established cigarillo smokers had higher odds of having FIRS (Adjusted odds ratio (AOR): 1.72; 95% CI: 1.08, 2.74) compared to never smokers of cigarillos and cigarettes, after adjusting for covariates. Current established filtered cigar smokers had higher odds of asthma diagnosis (AOR: 1.35; 95% CI: 1.10, 1.66) while current established dual smokers of filtered cigars and cigarettes had higher odds of uncontrolled asthma (AOR: 5.13; 95% CI: 1.75, 15.02) compared to never smokers of filtered cigars or cigarettes. Both current established cigar smokers and current established dual smokers of cigarettes and cigars had higher odds of new FIRS compared to never cigar or cigarette smokers (AORs: 1.62; 95% CI: 1.02, 2.60 for exclusive cigars and 2.55; 95% CI 1.57, 4.14 for dual smokers). Conclusions This study provides evidence that cigar smokers or dual smokers of cigars and cigarettes have greater odds of FIRS, asthma, and uncontrolled asthma and that new incidence of FIRS is higher among any cigar smokers compared to never cigar or cigarette smokers. Understanding health impacts associated with cigar use provides information for supporting policy development, as well as for designing clinical interventions focused on smoking cessation for cigars.

Klebsiella pneumoniae is a global public health concern due to the rising myriad of hypervirulent and multidrug-resistant clones both alarmingly associated with high mortality. The molecular mechanisms underpinning these recalcitrant K. pneumoniae infection, and how virulence is coupled with the emergence of lineages resistant to nearly all present-day clinically important antimicrobials, are unclear. In this study, we performed a genome-wide screen in K. pneumoniae ECL8, a member of the endemic K2-ST375 pathotype most often reported in Asia, to define genes essential for growth in a nutrient-rich laboratory medium (Luria-Bertani [LB] medium), human urine, and serum. Through transposon directed insertion-site sequencing (TraDIS), a total of 427 genes were identified as essential for growth on LB agar, whereas transposon insertions in 11 and 144 genes decreased fitness for growth in either urine or serum, respectively. These studies not only provide further knowledge on the genetics of this pathogen but also provide a strong impetus for discovering new antimicrobial targets to improve current therapeutic options for K. pneumoniae infections.

Abstract The tectonic configuration of the Caribbean plate is defined by inward‐dipping double subduction at its boundaries with the North American and Cocos plates. This geometry resulted from a Paleogene plate reorganization, which involved the abandonment of an older subduction system, the Great Arc of the Caribbean (GAC), and conversion into a transform margin during Lesser Antilles (LA) arc formation. Previous models suggest that a collision between the GAC and the Bahamas platform along the North American passive margin caused this event. However, geological and geophysical constraints from the Greater Antilles do not show a large‐scale compressional episode that should correspond to such a collision. We propose an alternative model for the evolution of the region where lower mantle penetration of the Farallon slab promotes the onset of subduction at the LA. We integrate tectonic constraints with seismic tomography to analyze the timing and dynamics of the reorganization, showing that the onset of LA subduction corresponds to the timing of Farallon/Cocos slab penetration. With numerical subduction models, we explore whether slab penetration constitutes a dynamically feasible set of mechanisms to initiate subduction in the overriding plate. In our models, when the first slab (Farallon/Cocos) enters the lower mantle, compressive stresses increase at the eastern margin of the upper plate, and a second subduction zone (LA) is initiated. The resulting first‐order slab geometries, timings, and kinematics compare well with plate reconstructions. More generally, similar slab dynamics may provide a mechanism not only for the Caribbean reorganization but also for other tectonic episodes throughout the Americas.

Neurodegenerative and neuroinflammatory diseases, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, affect millions of people globally. As aging is a major risk factor for neurodegenerative diseases, the continuous increase in the elderly population across Western societies is also associated with a rising prevalence of these debilitating conditions. The complement system, a crucial component of the innate immune response, has gained increasing attention for its multifaceted involvement in the normal development of the central nervous system (CNS) and the brain but also as a pathogenic driver in several neuroinflammatory disease states. Although complement is generally understood as a liver-derived and blood or interstitial fluid operative system protecting against bloodborne pathogens or threats, recent research, particularly on the role of complement in the healthy and diseased CNS, has demonstrated the importance of locally produced and activated complement components. Here, we provide a succinct overview over the known beneficial and pathological roles of complement in the CNS with focus on local sources of complement, including a discussion on the potential importance of the recently discovered intracellularly active complement system for CNS biology and on infection-triggered neurodegeneration.

Summary: Supplementing influenza vaccines with additional protective antigens such as neuraminidase (NA) is a promising strategy for increasing the breadth of the immune response. Here, we improved the immunogenicity and stability of secreted recombinant NA (rNA) tetramers by covalently conjugating them onto the surface of AP205 capsid virus-like particles (cVLPs) using a Tag/Catcher ligation system. cVLP display increased the induction of IgG2a subclass anti-NA antibodies, which exhibited cross-reactivity with an antigenically distant homologous NA. It also reduced the single dose rNA amounts needed for protection against viral challenge in mice, demonstrating a dose-sparing effect. Moreover, effective cVLP-display was achieved across different NA subtypes, even when the conjugation was performed shortly before administration. Notably, the rNA-cVLP immunogenicity was retained upon mixing or co-administering with commercial vaccines. These results highlight the potential of this approach for bolstering the protective immune responses elicited by influenza vaccines.

This study aimed to report the extraction of micro-fibrillated cellulose (MFC) from rice husk (RH) through a series of processes including alkalization, bleaching, chemical hydrolysis, and mechanical treatment. The chemical structure, morphology, and crystallinity were assessed using Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscope (SEM), and X-ray diffraction (XRD). The results showed that alkalization was more effective in removing unwanted substances such as silica, hemicellulose, and lignin compared to bleaching. Chemical or mechanical treatment was more targeted towards removing the amorphous phase while fibrillating MFC. Further mechanical treatment significantly enhanced the crystallinity index (CI) of MFC, reaching 87.47%, while chemical treatment remained at 78.54%. The mechanical treatment led to a larger void size due to rigorous fibrillation, resulting in increased water retention during extraction compared to chemically treated MFC with a negatively charged surface. Crystal extraction through mechanical treatment disrupted the hydrogen bond, transforming cellulose crystal from triclinic I? to monoclinic The comprehensive evaluation of MFC extracted from RH showed its potential for biomedical application.

BACKGROUND: The coverage of the seasonal influenza vaccine has always been sub-par. Understanding the motivators of receiving vaccines, especially during pandemics, could enhance and increase the coverage rates. The Saudi Ministry of Health launched its annual influenza vaccination campaign during the 2021 influenza season and provided vaccinations in primary healthcare settings. This study aims to explore public motivators to receive influenza vaccination, particularly during the coronavirus disease 2019 global pandemic. MATERIALS AND METHODS: This cross-sectional study enrolled 783 participants who attended the influenza vaccination campaign. All persons who received the influenza vaccine in the influenza vaccination campaign held in Dammam, Saudi Arabia, from October to November 2021, were interviewed and completed a self-administered questionnaire. Odds ratio with a 95% confidence interval were estimated using the full model fit. The significance level was set as α = 0.05. RESULTS: The majority of the participants had more than high school education (81%), were males (66.2%), and married (59.6%), and 50.6% were below 35 years of age. Participants with higher education, health-care workers, and those who had been previously counseled on influenza vaccination were less likely to have started taking the influenza vaccination, whereas smokers and persons who do not have routine checkups were more likely to start influenza vaccination. The main motivator to take the influenza vaccine was the establishment of a vaccination campaign near the participant’s workplace (62.2%), followed by advice from their physician (30.3%), and fear of having influenza disease (29.6%). CONCLUSION: Accessibility to the vaccination campaigns was the main motivator for receiving the vaccine followed by the advice from physician. Advice from physician and increasing mobile vaccination campaigns and mobile clinics would substantially increase influenza vaccine uptake.

Human activities can induce significant behavioural changes in wildlife. Often explored through extractive interactions (e.g. hunting) that can favour certain behavioural traits, the implications of non-extractive ones, such as wildlife feeding, remain understudied. Research shows that people tend to favour bolder individuals within populations despite their dynamics and consequences being unclear. Using fallow deer in a peri-urban environment, we studied whether mothers that show reduced fear of humans and consistently approach them for food adopt weaker anti-predator strategies by selecting less concealed fawning bedsites closer to human hotspots. This would provide the advantage of additional feeding opportunities in comparison with shyer mothers while keeping their fawns close. Our dataset encompassed 281 capture events of 172 fawns from 110 mothers across 4 years. Surprisingly, mothers that regularly accepted food from humans selected more concealed bedsites farther from human hotspots, giving their offspring better protection while also benefitting from additional food during lactation. Our results show behavioural adaptations by a subset of females and, for the first time, link the tendency to approach humans and strategies to protect offspring. Given previous findings that these begging females also deliver heavier fawns at birth, our research further investigates human–wildlife feeding interactions and their behavioural implications.

Abstract We report the small-signal characterization of a PCSEL device, extracting damping factors and modulation efficiencies, and demonstrating -3 dB modulation bandwidths of up to 4.26 GHz. Based on modelling we show that, by reducing the device width and improving the active region design for high-speed modulation, direct modulation frequencies in excess of 50 GHz are achievable.

Abstract Resistance mechanisms to immune checkpoint blockade therapy (ICBT) limit its response duration and magnitude. Paradoxically, Interferon γ (IFNγ), a key cytokine for cellular immunity, can promote ICBT resistance. Using syngeneic mouse tumour models, we confirm that chronic IFNγ exposure confers resistance to immunotherapy targeting PD-1 (α-PD-1) in immunocompetent female mice. We observe upregulation of poly-ADP ribosyl polymerase 14 (PARP14) in chronic IFNγ-treated cancer cell models, in patient melanoma with elevated IFNG expression, and in melanoma cell cultures from ICBT-progressing lesions characterised by elevated IFNγ signalling. Effector T cell infiltration is enhanced in tumours derived from cells pre-treated with IFNγ in immunocompetent female mice when PARP14 is pharmacologically inhibited or knocked down, while the presence of regulatory T cells is decreased, leading to restoration of α-PD-1 sensitivity. Finally, we determine that tumours which spontaneously relapse in immunocompetent female mice following α-PD-1 therapy upregulate IFNγ signalling and can also be re-sensitised upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance.

A vaccine protecting against malaria caused by Plasmodium falciparum is urgently needed. The blood-stage invasion complex PCRCR consists of the five malarial proteins PfPTRAMP, PfCSS, PfRipr, PfCyRPA, and PfRH5. As each subcomponent represents an essential and highly conserved antigen, PCRCR is considered a promising vaccine target. Furthermore, antibodies targeting the complex can block red blood cell invasion by the malaria parasite. However, extremely high titers of neutralizing antibodies are needed for this invasion-blocking effect, and a vaccine based on soluble PfRH5 protein has proven insufficient in inducing a protective response in a clinical trial. Here, we present the results of two approaches to increase the neutralizing antibody titers: (A) immunofocusing and (B) increasing the immunogenicity of the antigen via multivalent display on capsid virus-like particles (cVLPs). The immunofocusing strategies included vaccinating with peptides capable of binding the invasion-blocking anti-PfCyRPA monoclonal antibody CyP1.9, as well as removing non-neutralizing epitopes of PfCyRPA through truncation. Vaccination with PfCyRPA coupled to the AP205 cVLP induced nearly two-fold higher IgG responses compared to vaccinating with soluble PfCyRPA protein. Immunofocusing using a linear peptide greatly increased the neutralizing capacity of the anti-PfCyRPA antibodies. However, significantly lower total anti-PfCyRPA titers were achieved using this strategy. Our results underline the potential of a cVLP-based malaria vaccine including full-length PfCyRPA, which could be combined with other leading malaria vaccine antigens presented on cVLPs.

The SARS-CoV-2 pandemic and the emergence of novel virus variants have had a dramatic impact on public health and the world economy, underscoring the need for detailed studies that explore the high efficacy of additional vaccines in animal models. In this study, we confirm the pathogenicity of the SARS-CoV-2/Leiden_008 isolate (GenBank accession number MT705206.1) in K18-hACE2 transgenic mice. Using this isolate, we show that a vaccine consisting of capsid virus-like particles (cVLPs) displaying the receptor-binding domain (RBD) of SARS-CoV-2 (Wuhan strain) induces strong neutralizing antibody responses and sterilizing immunity in K18-hACE2 mice. Furthermore, we demonstrate that vaccination with the RBD-cVLP vaccine protects mice from both a lethal infection and symptomatic disease. Our data also indicate that immunization significantly reduces inflammation and lung pathology associated with severe disease in mice. Additionally, we show that the survival of naïve animals significantly increases when sera from animals vaccinated with RBD-cVLP are passively transferred, prior to a lethal virus dose. Finally, the RBD-cVLP vaccine has a similar antigen composition to the clinical ABNCOV2 vaccine, which has shown non-inferiority to the Comirnaty mRNA vaccine in phase I-III trials. Therefore, our study provides evidence that this vaccine design is highly immunogenic and confers full protection against severe disease in mice.

Background: The identification of clinical factors affecting the gray-scale median (GSM) and determination of GSM diagnostic utility for differentiating between symptomatic and asymptomatic internal carotid artery (ICA) stenosis. Methods: This study included 45 patients with asymptomatic and 40 patients with symptomatic ICA stenosis undergoing carotid endarterectomy (CEA). Echolucency of carotid plaque was determined using computerized techniques for the GSM analysis. Study groups were compared in terms of clinical risk factors, coexisting comorbidities, and used pharmacotherapy. Results: Mean GSM values in the symptomatic group were significantly lower than in the asymptomatic group (p < 0.001). Both in the univariate as well as in the multiple regression analysis, GSM was significantly correlated with D-dimers and fasting plasma glucose levels and tended to correlate with β-adrenoceptor antagonist use in the symptomatic group. In asymptomatic patients, GSM was associated with the presence of grade 2 and grade 3 hypertension, and tended to correlate with the use of metformin, sulfonylureas, and statin. Independent factors for GSM in this group remained as grade 3 hypertension and statin’s therapy. The receiver operating characteristic (ROC) analysis revealed that GSM differentiated symptomatic from asymptomatic ICA stenosis with sensitivity and specificity of 73% and 80%, respectively. Conclusion: The completely diverse clinical parameters may affect GSM in symptomatic and asymptomatic patients undergoing CEA, whose clinical characteristics were similar in terms of most of the compared parameters. GSM may be a clinically useful parameter for differentiating between symptomatic and asymptomatic ICA stenosis.

We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War veterans (42 with GWI and 69 controls). GWI was diagnosed in 47.1% of vaccinated veterans but only in 17.2% of non-vaccinated veterans (Pearson χ2 = 7.08, p = 0.008; odds ratio = 3.947; relative risk = 2.617), with 1.6x higher GWI symptom severity in vaccinated veterans (p = 0.007, F-test in analysis of covariance). Next, we tested the hypothesis that the susceptibility to GWI following anthrax vaccination could be due to inability to make antibodies against the anthrax protective antigen (PA), the key protein contained in the vaccine. Since the first step in initiating antibody production would be the binding of PA peptide fragments (typically 15-amino acid long [15-mer]) to peptide-binding motifs of human leukocyte antigen (HLA) Class II molecules, we assessed the binding-motif affinities of such HLA specific molecules to all linear 15-mer peptide fragments of the anthrax PA. We identified a total of 58 HLA Class II alleles carried by the veterans in our sample and found that, of those, 18 (31%) were present in the vaccinated group that did not develop GWI but were absent from the vaccinated group who developed GWI. Remarkably, in silico analyses revealed very high binding affinities of peptide-binding motifs of those 18 HLA alleles with fragments of anthrax vaccine PA, leading to the successful production of anti-PA antibodies. Conversely, the absence of these protective HLA alleles points to a reduced ability to develop antibodies against PA, thus resulting in harmful PA persistence and development of GWI.

Refined palm oil products may contain a harmful substance called as 3-monochloropropane-1,2-diol (3-MCPD), which can potentially be carcinogenic if consumed in excess. The determination of 3-MCPD depends on the sophisticated machine and highly skilled technicians but it is time-consuming. A simple method that proposes rapid detection remains a challenge. Hence, this research aims to develop a colorimetric-based rapid detection sensor using gold nanoparticles functionalized with a ligand, glutathione (GSH) to be bound to 3-MCPD. Varied concentrations of GSH were evaluated to obtain stable GSH-AuNPs. The characterization results showed that the composition of the stable GSH-AuNPs has been achieved by 250 µL of 0.02 M GSH addition. A stable GSH-AuNPs was ruby red with surface plasmon resonance (SPR) band at 520 nm and an average nanoparticle size of 30 nm. The indication for detection of 3-MCPD was marked by the decrease in the absorbance intensity. Thus, GSH-AuNPs have potential to be developed for the 3-MCPD sensor application.

Abstract Plate reconstruction models are constructed to fit constraints such as magnetic anomalies, fracture zones, paleomagnetic poles, geological observations and seismic tomography. However, these models do not consider the physical equations of plate driving forces when reconstructing plate motion. This can potentially result in geodynamically-implausible plate motions, which has implications for a range of work based on plate reconstruction models. We present a new algorithm that calculates time-dependent slab pull, ridge push (GPE force) and mantle drag resistance for any topologically closed reconstruction, and evaluates the residuals—or missing components—required for torques to balance given our assumed plate driving force relationships. In all analyzed models, residual torques for the present-day are three orders of magnitude smaller than the typical driving torques for oceanic plates, but can be of the same order of magnitude back in time—particularly from 90 to 50 Ma. Using the Pacific plate as an example, we show how our algorithm can be used to identify areas and times with high residual torques, where either plate reconstructions have a high degree of geodynamic implausibility or our understanding of the underlying geodynamic forces is incomplete. We suggest strategies for plate model improvements and also identify times when other forces such as active mantle flow were likely important contributors. Our algorithm is intended as a tool to help assess and improve plate reconstruction models based on a transparent and expandable set of a priori dynamic constraints.

Abstract Subduction zones are fundamental features of Earth's mantle convection and plate tectonics, but mantle flow and pressure around slabs are poorly understood because of the lack of direct observational constraints on subsurface flow. To characterize the linkages between slabs and mantle flow, we integrate high‐resolution representations of Earth's lithosphere and slabs into a suite of global mantle convection models to produce physically plausible present‐day flow fields for Earth's mantle. We find that subduction zones containing wide, thick, and long slabs dominate regional mantle flow in the neighboring regions and this flow conforms to patterns predicted by simpler regional subduction models. These subduction zones, such as Kuril‐Japan‐Izu‐Bonin‐Mariana, feature prismatic poloidal flow coupled to the downgoing slab that rotates toward toroidal slab‐parallel flow near the slab edge. However, other subduction zones, such as Sumatra, deviate from this pattern because of the competing influence of other slabs or longer‐wavelength mantle flow, showing that upper mantle flow can link separate subduction zones and how flow at subduction zones is influenced by broader scale mantle flow. We find that the non‐linear dislocation creep reduces the coupling between slab motion and asthenospheric flow and increases the occurrence of non‐ideal flow, in line with inferences derived from seismological constraints on mantle anisotropy.

The sequestration of Plasmodium falciparum-infected erythrocytes to the host endothelium is central to the pathogenesis of malaria. The sequestration is mediated by the parasite´s diverse Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants, which bind select human receptors on the endothelium. Severe malaria is associated with PfEMP1 binding human endothelial protein C receptor (EPCR) via their CIDRα1 domains. Antibodies binding and inhibiting across the sequence diverse CIDRα1 domains are likely important in acquired immunity against severe malaria. In this study, we explored if immunization with AP205 bacteriophage capsid-virus-like particles (cVLPs) presenting a mosaic of diverse CIDRα1 protein variants would stimulate broadly reactive and inhibitory antibody responses in mice. Three different mosaic cVLP vaccines each composed of five CIDRα1 protein variants with varying degrees of sequence conservation of residues at and near the EPCR binding site, were tested. All mosaic cVLP vaccines induced functional antibodies comparable to those induced by matched cocktails of cVLPs decorated with the single CIDRα1 variant. No broadly reactive responses were observed. However, the vaccines did induce some cross-reactivity and inhibition within the CIDRα1 subclasses included in the vaccines, demonstrating potential use of the cVLP vaccine platform for the design of multivalent vaccines.

Brain tumor detection and segmentation are the main issues in biomedical engineering research fields, and it is always challenging due to its heterogeneous shape and location in MRI. The quality of the MR images also plays an important role in providing a clear sight of the shape and boundary of the tumor. The clear shape and boundary of the tumor will increase the probability of safe medical surgery. Analysis of this different scope of image types requires refined computerized quantification and visualization tools. This paper employed deep learning to detect and segment brain tumor MRI images by combining the convolutional neural network (CNN) and fully convolutional network (FCN) methodology in serial. The fundamental finding is to detect and localize the tumor area with YOLO-CNN and segment it with the FCN-UNet architecture. This analysis provided automatic detection and segmentation as well as the location of the tumor. The segmentation using the UNet is run under four scenarios, and the best one is chosen by the minimum loss and maximum accuracy value. In this research, we used 277 images for training, 69 images for validation, and 14 images for testing. The validation is carried out by comparing the segmentation results with the medical ground truth to provide the correct classification ratio (CCR). This study succeeded in the detection of brain tumors and provided a clear area of the brain tumor with a high CCR of about 97%.

Abstract Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.5%) hypermethylation events. We find that 80% of these events are allele-specific and predicted to cause loss of regulatory element activity. We demonstrate heritability of extreme hypermethylation including rare cis variants associated with short (~200 bp) and large hypermethylation events (>1 kb), respectively. We identify repeat expansions in proximal promoters predicting allelic gene silencing via hypermethylation and demonstrate allelic transcriptional events downstream. On average 30–40 rare hypermethylation tiles overlap rare disease genes per patient, providing indications for variation prioritization including a previously undiagnosed pathogenic allele in DIP2B causing global developmental delay. We propose that use of HiFi genome sequencing in unsolved rare disease cases will allow detection of unconventional diseases alleles due to loss of regulatory element activity.

Abstract Intentionally disordered metal–organic frameworks (MOFs) display rich functional behaviour. However, the characterisation of their atomic structures remains incredibly challenging. X-ray pair distribution function techniques have been pivotal in determining their average local structure but are largely insensitive to spatial variations in the structure. Fe-BTC (BTC = 1,3,5-benzenetricarboxylate) is a nanocomposite MOF, known for its catalytic properties, comprising crystalline nanoparticles and an amorphous matrix. Here, we use scanning electron diffraction to first map the crystalline and amorphous components to evaluate domain size and then to carry out electron pair distribution function analysis to probe the spatially separated atomic structure of the amorphous matrix. Further Bragg scattering analysis reveals systematic orientational disorder within Fe-BTC’s nanocrystallites, showing over 10° of continuous lattice rotation across single particles. Finally, we identify candidate unit cells for the crystalline component. These independent structural analyses quantify disorder in Fe-BTC at the critical length scale for engineering composite MOF materials.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

Abstract The Eurasian lynx is a large carnivore widely distributed across Eurasia. However, our understanding of population status is heterogeneous across their range, with some populations isolated that are at risk of reduced genetic variation and a complete lack of information about others. In many European countries, Eurasian lynx are monitored through demographic studies crucial for their conservation and management. Even so, there are only rough and fragmented population assessments from Ukraine and Belarus, despite strict protection in both countries and their importance for lynx connectivity across Europe. We monitored lynx from October 2020 to March 2021 and used camera trapping in combination with spatial capture–recapture (SCR) methods in a Bayesian framework to provide the first SCR density estimation of three lynx populations across Ukraine and Belarus, including the Ukrainian Chornobyl Exclusion Zone, southern Belarus and the Ukrainian Carpathians. Our density estimates varied within our study areas ranging from 0.45 to 1.54 individuals/100 km2. This work provides a substantial scientific component to the overall understanding of lynx conservation for a region where only broad information is available and opens the doors for further large‐scale monitoring and trend assessments. The crucial information we provide can greatly enhance the range‐wide assessments of the status of this protected species. We also discuss the implications for Eurasian lynx conservation, despite the geopolitical realities impacting species monitoring in the region. Our work serves as a baseline, not only for future conservation interventions but also to evaluate the effects of disturbance and threats to these protected populations.

Competent T-cells with sufficient levels of fitness combat cancer formation and progression. In multiple myeloma (MM), T-cell exhaustion is caused by several factors including tumor burden, constant immune activation due to chronic disease, age, nutritional status, and certain MM treatments such as alkylating agents and proteasome inhibitors. Many currently used therapies, including bispecific T-cell engagers, anti-CD38 antibodies, proteasome inhibitors, and CART-cells, directly or indirectly depend on the anti-cancer activity of T-cells. Reduced T-cell fitness not only diminishes immune defenses, increasing patient susceptibility to opportunistic infections, but can impact effectiveness MM therapy effectiveness, bringing into focus sequencing strategies that could modulate T-cell fitness and potentially optimize overall benefit and clinical outcomes. Certain targeted agents used to treat MM, such as selective inhibitors of nuclear export (SINE) compounds, have the potential to mitigate T-cell exhaustion. Herein referred to as XPO1 inhibitors, SINE compounds inhibit the nuclear export protein exportin 1 (XPO1), which leads to nuclear retention and activation of tumor suppressor proteins and downregulation of oncoprotein expression. The XPO1 inhibitors selinexor and eltanexor reduced T-cell exhaustion in cell lines and animal models, suggesting their potential role in revitalizating these key effector cells. Additional clinical studies are needed to understand how T-cell fitness is impacted by diseases and therapeutic factors in MM, to potentially facilitate the optimal use of available treatments that depend on, and impact, T-cell function. This review summarizes the importance of T-cell fitness and the potential to optimize treatment using T-cell engaging therapies with a focus on XPO1 inhibitors.

Abstract Low muscle quality and a sedentary lifestyle are indicators for a slow recovery after a total knee arthroplasty (TKA). Mitochondrial function is an important part of muscle quality and a key driver of sarcopenia. However, it is not known whether it relates to recovery. In this pilot study, we monitored activity after TKA using a wrist mounted activity tracker and assessed the relation of mitochondrial function on the rate of recovery after TKA. Additionally, we compared the increase in activity as a way to measure recovery to traditional outcome measures. Patients were studied 2 weeks before TKA and up to 6 months after. Activity was monitored continuously. Baseline mitochondrial function (citrate synthase and complex [CP] 1–5 abundance of the electron transport chain) was determined on muscle tissue taken during TKA. Traditional outcome measures (Knee Injury and Osteoarthritis Outcome Score [KOOS], timed up‐and‐go [TUG] completion time, grip, and quadriceps strength) were performed 2 weeks before, 6 weeks after, and 6 months after TKA. Using a multivariate regression model with various clinical baseline parameters, the following were significantly related to recovery: CP5 abundance, grip strength, and activity (regression weights 0.13, 0.02, and 2.89, respectively). During recovery, activity correlated to the KOOS‐activities of daily living (ADL) score (r = 0.55, p = 0.009) and TUG completion time (r = −0.61, p = 0.001). Mitochondrial function seems to be related to recovery, but so are activity and grip strength, all indicators of sarcopenia. Using activity trackers before and after TKA might give the surgeon valuable information on the expected recovery and the opportunity to intervene if recovery is low.

Abstract Development of B-cell-based hepatitis C virus (HCV) vaccines that induce broadly neutralizing antibodies (bNAbs) is hindered by extensive sequence diversity and low immunogenicity of envelope glycoprotein vaccine candidates, most notably soluble E2 (sE2). To overcome this, we employed two-component approaches using self-assembling virus-like particles (cVLPs; component 1), displaying monomeric or oligomeric forms of HCV sE2 (sE2mono or sE2oligo; component 2). Immunization studies were performed in BALB/c mice and the neutralizing capacity of vaccine-induced antibodies was tested in cultured-virus-neutralizations, using HCV of genotypes 1–6. sE2-cVLP vaccines induced significantly higher levels of NAbs (p = 0.0065) compared to corresponding sE2 vaccines. Additionally, sE2oligo-cVLP was superior to sE2mono-cVLP in inducing bNAbs. Interestingly, human monoclonal antibody AR2A had reduced binding in ELISA to sE2oligo-cVLP compared with sE2mono-cVLP and competition ELISA using mouse sera from vaccinated animals indicated that sE2oligo-cVLP induced significantly less non-bNAbs AR2A (p = 0.0043) and AR1B (p = 0.017). Thus, cVLP-displayed oligomeric sE2 shows promise as an HCV vaccine candidate.

ABSTRACT The autotransporter protein secretion system has been used previously to target the secretion of heterologous proteins to the bacterial cell surface and the extracellular milieu at the laboratory scale. The platform is of particular interest for the production of “difficult” recombinant proteins that might cause toxic effects when produced intracellularly. One such protein is IrmA. IrmA is a vaccine candidate that is produced in inclusion bodies requiring refolding. Here, we describe the use and scale-up of the autotransporter system for the secretion of an industrially relevant protein (IrmA). A plasmid expressing IrmA was constructed such that the autotransporter platform could secrete IrmA into the culture supernatant fraction. The autotransporter platform was suitable for the production and purification of IrmA with comparable physical properties to the protein produced in the cytoplasm. The production of IrmA was translated to scale-up protein production conditions resulting in a yield of 29.3 mg/L of IrmA from the culture supernatant, which is consistent with yields of current industrial processes. IMPORTANCE Recombinant protein production is an essential component of the biotechnology sector. Here, we show that the autotransporter platform is a viable method for the recombinant production, secretion, and purification of a “difficult” to produce protein on an industrially relevant scale. Use of the autotransporter platform could reduce the number of downstream processing operations required, thus accelerating the development time and reducing costs for recombinant protein production.

Introduction: Increased theta and delta power and decreased alpha and beta power, measured with quantitative electroencephalography (EEG), have been demonstrated to have utility for predicting the development of dementia in patients with Parkinson’s disease (PD). Noradrenaline modulates cortical activity and optimizes cognitive processes. We claim that the loss of noradrenaline may explain cognitive impairment and the pathological slowing of EEG waves. Here, we test the relationship between the number of noradrenergic α2 adrenoceptors and changes in the spectral EEG ratio in patients with PD. Methods: We included nineteen patients with PD and thirteen healthy control (HC) subjects in the study. We used positron emission tomography (PET) with [11C]yohimbine to quantify α2 adrenoceptor density. We used EEG power in the delta (δ, 1.5–3.9 Hz), theta (θ, 4–7.9 Hz), alpha (α, 8–12.9 Hz) and beta (β, 13–30 Hz) bands in regression analyses to test the relationships between α2 adrenoceptor density and EEG band power. Results: PD patients had higher power in the theta and delta bands compared to the HC volunteers. Patients’ theta band power was inversely correlated with α2 adrenoceptor density in the frontal cortex. In the HC subjects, age was correlated with, and occipital background rhythm frequency (BRF) was inversely correlated with, α2 adrenoceptor density in the frontal cortex, while occipital BRF was inversely correlated with α2 adrenoceptor density in the thalamus. Conclusions: The findings support the claim that the loss or dysfunction of noradrenergic neurotransmission may relate to the parallel processes of cognitive decline and EEG slowing.

Transiting giant exoplanets around M-dwarf stars (GEMS) are rare, owing to the low-mass host stars. However, the all-sky coverage of TESS has enabled the detection of an increasingly large number of them to enable statistical surveys like the Searching for GEMS survey. As part of this endeavor, we describe the observations of six transiting giant planets, which include precise mass measurements for two GEMS (K2-419Ab, TOI-6034b) and statistical validation for four systems, which includes validation and mass upper limits for three of them (TOI-5218b, TOI-5616b, TOI-5634Ab), while the fourth one—TOI-5414b is classified as a “likely planet.” Our observations include radial velocities from the Habitable-zone Planet Finder on the Hobby–Eberly Telescope, and MAROON-X on Gemini-North, along with photometry and high-contrast imaging from multiple ground-based facilities. In addition to TESS photometry, K2-419Ab was also observed and statistically validated as part of the K2 mission in Campaigns 5 and 18, which provide precise orbital and planetary constraints despite the faint host star and long orbital period of ∼20.4 days. With an equilibrium temperature of only 380 K, K2-419Ab is one of the coolest known well-characterized transiting planets. TOI-6034 has a late F-type companion about 40″ away, making it the first GEMS host star to have an earlier main-sequence binary companion. These confirmations add to the existing small sample of confirmed transiting GEMS.

We present a comprehensive multiwavelength investigation into flares and activity in nearby M dwarf stars. We leverage the most extensive contemporaneous data set obtained through the Transiting Exoplanet Sky Survey, Kepler/K2, the Neil Gehrels Swift Observatory, and the Hubble Space Telescope, spanning the optical and near-ultraviolet (NUV) regimes. In total, we observed 213 NUV flares on 24 nearby M dwarfs, with ∼27% of them having detected optical counterparts, and found that all optical flares had NUV counterparts. We explore NUV/optical energy fractionation in M dwarf flares. Our findings reveal a slight decrease in the ratio of optical to NUV energies with increasing NUV energies, a trend in agreement with prior investigations on G–K stars’ flares at higher energies. Our analysis yields an average NUV fraction of flaring time for M0–M3 dwarfs of 2.1%, while for M4–M6 dwarfs it is 5%. We present an empirical relationship between NUV and optical flare energies and compare to predictions from radiative hydrodynamic and blackbody models. We conducted a comparison of the flare frequency distribution (FFDs) of NUV and optical flares, revealing that the FFDs of both NUV and optical flares exhibit comparable slopes across all spectral subtypes. NUV flares on stars affect the atmospheric chemistry, the radiation environment, and the overall potential to sustain life on any exoplanets they host. We find that early and mid-M dwarfs (M0–M5) have the potential to generate NUV flares capable of initiating abiogenesis.

Continued decreasing of the world’s average copper ore grades, coupled with a meteoric rise in the generation of consumer waste streams, has led to the processing of electronic scrap (e-scrap) and other secondaries assuming increasing importance within the global copper industry. Treatment of these secondary feeds has traditionally been carried out in the Blast furnace, Peirce-Smith converter and/or anode furnace. More recently however, bath smelting processes such as the Ausmelt TSL and Outotec Kaldo technologies have emerged as the preferred option for processing these materials due to their superior environmental performance and flexibility to operate under a wide range of conditions. Furthermore, the ability of these processes to handle a wide range of feed inputs make them ideally placed for the processing of not only e-scrap but also other waste streams from the clean energy transition such as end of life e-mobility batteries and photovoltaic systems. This paper focuses on the processing of electronic scrap and other copper secondaries with Ausmelt TSL technology and discusses specific issues facing secondary copper smelters in relation to impurity management and process offgas handling/cleaning.

Chromospheric condensations (CCs) are a prominent feature of flare footpoint heating in the solar flare standard model, yet their timescales and velocities are not well understood. Fisher derived several important analytical relationships, which have rarely been examined with modern spectral observations. The Interface Region Imaging Spectrograph (IRIS) provides a wealth of flare data with a high enough cadence to sufficiently capture CC evolution. We analyzed Doppler shifts in Mg ii 2791 and Fe ii 2814 from a sample of flare footpoint pixels observed by IRIS to compare with Fisher's analytics and recent flare models. We found a detection lifetime of 1 minute occurs in 50% of the sample, with Mg ii showing several pixels with longer values and Fe ii almost categorically shorter, and both growing with the maximum velocity, v _max . The shifts’ half-life is commonly

Optical flares have been observed from magnetically active stars for many decades; unsurprisingly, the spectra and temporal evolution are complicated. For example, the shortcomings of optically thin, static slab models have long been recognized when confronted with the observations. A less incorrect—but equally simple—phenomenological T ≈ 9000 K blackbody model has instead been widely adopted in the absence of realistic (i.e., observationally tested) time-dependent, atmospheric models that are readily available. We use the RADYN code to calculate a grid of 1D radiative-hydrodynamic stellar flare models that are driven by short pulses of electron-beam heating. The flare heating rates in the low atmosphere vary over many orders of magnitude in the grid, and we show that the models with high-energy electron beams compare well to the global trends in flux ratios from impulsive-phase stellar flare, optical spectra. The models also match detailed spectral line-shape properties. We find that the pressure broadening and optical depths account for the broad components of the hydrogen Balmer γ lines in a powerful flare with echelle spectra. The self-consistent formation of the wings and nearby continuum level provides insight into how high-energy electron-beam heating evolves from the impulsive to the gradual decay phase in white-light stellar flares. The grid is publicly available, and we discuss possible applications.

We develop the impulsiveness index, a new classification system for solar flares using the Solar Dynamics Observatory/Extreme Ultraviolet Experiment 304 Å Sun-as-a-star light curves. Impulsiveness classifies events based on the duration and intensity of the initial high-energy deposition of energy into the chromosphere. In stellar flare U -band light curves, Kowalski et al. found that impulsiveness is related to quantities such as a proxy for the Balmer jump ratio. However, the lack of direct spatial resolution in stellar flares limits our ability to explain this phenomenon. We calculate impulsiveness for 1368 solar flares between 2010 April and 2014 May. We divide events into categories of low, mid, and high impulsiveness. We find, in a sample of 480 flares, that events with high maximum reconnection rate tend to also have high impulsiveness. For six case studies, we compare impulsiveness to magnetic shear, ribbon evolution, and energy release. We find that the end of the 304 Å light-curve rise phase in these case studies corresponds to the cessation of polarity inversion line (PIL)-parallel ribbon motion, while PIL-perpendicular motion persists afterward in most cases. The measured guide-field ratio for low- and mid-impulsiveness case-study flares decreases about an order of magnitude during the impulsive flare phase. Finally, we find that, in four of the six case studies, flares with higher, more persistent shear tend to have low impulsiveness. Our study suggests that impulsiveness may be related to other properties of the impulsive phase, though more work is needed to verify this relationship and apply our findings to stellar flare physics.

During solar flares, spectral lines formed in the photosphere have been shown to exhibit changes to their profiles despite the challenges of energy transfer to these depths. Recent work has shown that deep-forming spectral lines are subject to significant contributions from regions above the photosphere throughout the flaring period, resulting in a composite emergent intensity profile from multiple layers of the atmosphere. We employ radiative–hydrodynamic and radiative transfer calculations to simulate the response of the solar/stellar atmosphere to electron beam heating and synthesize spectral lines of Fe i to investigate the line-of-sight velocity fields information available from Doppler shifts of the emergent intensity profile. By utilizing the contribution function to deconstruct the line profile shape into its constituent sources, we show that variations in the line profiles are primarily caused by changes in the chromosphere. Up-flows in this region were found to create blueshifts or false redshifts in the line core dependent on the relative contribution of the chromosphere compared to the photosphere. In extreme solar and stellar flare scenarios featuring explosive chromospheric condensations, redshifted transient components can dominate the temporal evolution of the profile shape, requiring a tertiary component consideration to fully characterize. We conclude that deep-forming lines require a multicomponent understanding and treatment, with different regions of the spectral line being useful for probing individual regions of the atmosphere’s velocity flows.

We conducted the time-resolved simultaneous optical spectroscopic and photometric observations of mid-M-dwarf flare stars YZ CMi, EV Lac, and AD Leo. Spectroscopic observations were obtained using Apache Point Observatory 3.5 m and Small and Moderate Aperture Research Telescope System 1.5 m telescopes during 31 nights. Among the 41 detected flares, seven flares showed clear blue wing asymmetries in the H α line, with various correspondences in flare properties. The duration of the blue wing asymmetries range from 20 minutes to 2.5 hr, including a flare showing the shift from blue to red wing asymmetry. Blue wing asymmetries can be observed during both white-light and candidate non-white-light flares. All of the seven flares showed blue wing asymmetries also in the H β line, but there are large varieties on which other chromospheric lines showed blue wing asymmetries. One among the 7 flares was also observed with soft X-ray spectroscopy, which enabled us to estimate the flare magnetic field and length of the flare loop. The line-of-sight velocities of the blueshifted components range from –73 to –122 km s ^−1 . Assuming that the blueshifts were caused by prominence eruptions, the mass of upward-moving plasma was estimated to be 10 ^15 –10 ^19 g, which are roughly on the relation between flare energy and erupting mass expected from solar coronal mass ejections (CMEs). Although further investigations are necessary for understanding the observed various properties, these possible prominence eruptions on M-dwarfs could evolve into CMEs, assuming the similar acceleration mechanism with solar eruptions.

Mineral-organic associations play a key role in soil carbon preservation. Here, Georgiou et al. produce global estimates of mineral-associated soil carbon, providing insight into the world’s soils and their capacity to store carbon

The Gram-negative bacterium A. salmonicida is the causal agent of furunculosis and used to be one of the most loss-causing bacterial infections in the salmonid aquaculture industry with a mortality rate of about 90% until the 1990s, when an inactivated vaccine with mineral oil as adjuvant was successfully implemented to control the disease. However, the use of this vaccine is associated with inflammatory side effects in the peritoneal cavity as well as autoimmune reactions in Atlantic salmon, and incomplete protection has been reported in rainbow trout. We here aimed at developing and testing a recombinant alternative vaccine based on virus-like particles (VLPs) decorated with VapA, the key structural surface protein in the outer A-layer of A. salmonicida. The VLP carrier was based on either the capsid protein of a fish nodavirus, namely red grouper nervous necrotic virus (RGNNV) or the capsid protein of Acinetobacter phage AP205. The VapA and capsid proteins were expressed individually in E. coli and VapA was fused to auto-assembled VLPs using the SpyTag/SpyCatcher technology. Rainbow trout were vaccinated/immunized with the VapA-VLP vaccines by intraperitoneal injection and were challenged with A. salmonicida 7 weeks later. The VLP vaccines provided protection comparable to that of a bacterin-based vaccine and antibody response analysis demonstrated that vaccinated fish mounted a strong VapA-specific antibody response. To our knowledge, this is the first demonstration of the potential use of antigen-decorated VLPs for vaccination against a bacterial disease in salmonids.