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One of the proposed ways to reduce the climate impact of civil aviation is rerouting aircraft to minimise the formation of warming contrails. As this strategy may increase fuel consumption, it would only be beneficial if the climate impact reduction from the avoided contrails exceeds the negative impact of any additional carbon dioxide (CO2) emitted by the rerouted flight. In this study, we calculate the surface temperature response of almost half a million flights that crossed the North Atlantic sector in 2019 and compare it to the temperature response of hypothetical rerouted flights. The climate impacts of contrails and CO2 are assessed through the perspective of CO2-equivalence metrics, represented here as nine combinations of different definitions and time horizons. We estimate that the total emitted CO2 and the persistent contrails formed will have warmed the climate by 17.2 µK in 2039, 13.7 µK in 2069, and 14.1 µK in 2119. Under an idealised scenario where 1 % additional carbon dioxide is enough to reroute all contrail-forming flights and avoid contrail formation completely, total warming would decrease by 4.9 (−28 %), 2.6 (−19 %), and 1.9 (−13 %) µK in 2039, 2069, and 2119, respectively. In most rerouting cases, the results based on the nine different CO2-equivalence metrics agree that rerouting leads to a climate benefit, assuming that contrails are avoided as predicted. But the size of that benefit is very dependent on the choice of CO2-equivalence metrics, contrail efficacy and CO2 penalty. Sources of uncertainty not considered here could also heavily influence the perceived benefit. In about 10 % of rerouting cases, the climate damage resulting from contrail avoidance indicated by CO2-equivalence metrics integrated over a 100-year time horizon is not predicted by metrics integrated over a 20-year time horizon. This study highlights, using North Atlantic flights as a case study, the implications of the choice of CO2-equivalence metrics for contrail avoidance, but the choice of metric implies a focus on a specific climate objective, which is ultimately a political decision.

The current best-estimate of the global annual mean radiative forcing (RF) attributable to contrail cirrus is thought to be 3 times larger than the RF from aviation's cumulative CO2 emissions. Here, we simulate the global contrail RF for 2019–2021 using reanalysis weather data and improved engine emission estimates along actual flight trajectories derived from Automatic Dependent Surveillance–Broadcast telemetry. Our 2019 global annual mean contrail net RF (62.1 mW m−2) is 44 % lower than current best estimates for 2018 (111 [33, 189] mW m−2, 95 % confidence interval). Regionally, the contrail net RF is largest over Europe (876 mW m−2) and the USA (414 mW m−2), while the RF values over East Asia (64 mW m−2) and China (62 mW m−2) are close to the global average, because fewer flights in these regions form persistent contrails resulting from lower cruise altitudes and limited ice supersaturated regions in the subtropics due to the Hadley Circulation. Globally, COVID-19 reduced the flight distance flown and contrail net RF in 2020 (−43 % and −56 %, respectively, relative to 2019) and 2021 (−31 % and −49 %, respectively) with significant regional variations. Around 14 % of all flights in 2019 formed a contrail with a net warming effect, yet only 2 % of all flights caused 80 % of the annual contrail energy forcing. The spatiotemporal patterns of the most strongly warming and cooling contrail segments can be attributed to flight scheduling, engine particle number emissions, tropopause height, and background radiation fields. Our contrail RF estimates are most sensitive to corrections applied to the global humidity fields, followed by assumptions on the engine particle number emissions, and are least sensitive to radiative heating effects on the contrail plume and contrail–contrail overlapping. Using this sensitivity analysis, we estimate that the 2019 global contrail net RF could range between 34.8 and 74.8 mW m−2.

Protein import and genome replication are essential processes for mitochondrial biogenesis and propagation. The J-domain proteins Pam16 and Pam18 regulate the presequence translocase of the mitochondrial inner membrane. In the protozoan Trypanosoma brucei, their counterparts are TbPam16 and TbPam18, which are essential for the procyclic form (PCF) of the parasite, though not involved in mitochondrial protein import. Here, we show that during evolution, the 2 proteins have been repurposed to regulate the replication of maxicircles within the intricate kDNA network, the most complex mitochondrial genome known. TbPam18 and TbPam16 have inactive J-domains suggesting a function independent of heat shock proteins. However, their single transmembrane domain is essential for function. Pulldown of TbPam16 identifies a putative client protein, termed MaRF11, the depletion of which causes the selective loss of maxicircles, akin to the effects observed for TbPam18 and TbPam16. Moreover, depletion of the mitochondrial proteasome results in increased levels of MaRF11. Thus, we have discovered a protein complex comprising TbPam18, TbPam16, and MaRF11, that controls maxicircle replication. We propose a working model in which the matrix protein MaRF11 functions downstream of the 2 integral inner membrane proteins TbPam18 and TbPam16. Moreover, we suggest that the levels of MaRF11 are controlled by the mitochondrial proteasome.

The radiative characteristics and lifetimes of contrails are dependent on the number concentration of ice-forming particles in the engine exhaust plume. Aircraft gas turbine engines produce a variety of particles, yet it is understood that non-volatile black carbon aggregates are the dominant source of ice-forming particles with typical, fossil-derived jet fuel. However, with cleaner combustion technologies and the adoption of alternative fuels (e.g. hydrogen or synthetic aviation fuel), non-volatile black carbon particle emissions are expected to decrease or even be eliminated. Under these conditions, contrail properties will depend upon the concentration and characteristics of particles other than black carbon. Ultrafine (< 100 nm) jet lubrication oil droplets constitute a significant fraction of the total organic particulate matter released by aircraft; however, their ability to form contrail ice crystals has hitherto been unexplored. In this work, we experimentally investigate the activation and freezing behaviour of lubrication oil droplets using an expansion chamber, assessing their potential as ice-forming particles. We generate lubrication oil droplets with a geometric mean mobility diameter of (100.9 ± 0.6) nm and show that these activate to form water droplets, which subsequently freeze when the temperature is below ∼ 235 K. We find that nucleation on lubrication oil droplets should be considered in future computational studies – particularly under soot-poor conditions – and that these studies would benefit from particle size distribution measurements at cruise altitude. Overall, taking steps to reduce lubrication oil number emissions would help reduce the climate impact of contrail cirrus.

Voice assistants (VAs) are increasingly integrated into everyday activities and tasks, raising novel challenges for users and researchers. One emergent research direction concerns proactive VAs, who can initiate interaction without direct user input, offering unique benefits including efficiency and natural interaction. Yet, there is a lack of review studies synthesizing the current knowledge on how proactive behavior has been implemented in VAs and under what conditions proactivity has been found more or less suitable. To this end, we conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We searched for articles in the ACM Digital Library, IEEExplore, and PubMed, and included primary research studies reporting user evaluations of proactive VAs, resulting in 21 studies included for analysis. First, to characterize proactive behavior in VAs we developed a novel conceptual model encompassing context, initiation, and action components: Activity/status emerged as the primary contextual element, direct initiation was more common than indirect initiation, and suggestions were the primary action observed. Second, proactive behavior in VAs was predominantly explored in domestic and in-vehicle contexts, with only safety-critical and emergency situations demonstrating clear benefits for proactivity, compared to mixed findings for other scenarios. The paper concludes with a summary of the prevailing knowledge gaps and potential research avenues.

Aviation emissions that are dispersed into the Earth's atmosphere affect the climate and air pollution, with significant spatiotemporal variation owing to heterogeneous aircraft activity. In this paper, we use historical flight trajectories derived from Automatic Dependent Surveillance–Broadcast (ADS-B) telemetry and reanalysis weather data for 2019–2021 to develop the Global Aviation emissions Inventory based on ADS-B (GAIA). In 2019, 40.2 million flights collectively travelled 61 billion kilometres using 283 Tg of fuel, leading to CO2, NOX and non-volatile particulate matter (nvPM) mass and number emissions of 893 Tg, 4.49 Tg, 21.4 Gg and 2.8 × 1026 respectively. Global responses to COVID-19 led to reductions in the annual flight distance flown and CO2 and NOX emissions in 2020 (−43 %, −48 % and −50 % respectively relative to 2019) and 2021 (−31 %, −41 % and −43 % respectively), with significant regional variability. Short-haul flights with durations < 3 h accounted for 83 % of all flights but only for 35 % of the 2019 CO2 emissions, while long-haul flights with durations > 6 h (5 % of all flights) were responsible for 43 % of CO2 and 49 % of NOX emissions. Globally, the actual flight trajectories flown are, on average, ∼ 5 % greater than the great circle path between the origin and destination airports, but this varies by region and flight distance. An evaluation of 8705 unique flights between London and Singapore showed large variabilities in the flight trajectory profile, fuel consumption and emission indices. GAIA captures the spatiotemporal distribution of aviation activity and emissions and is provided for use in future studies to evaluate the negative externalities arising from global aviation.

Abstract Schistosomiasis is a parasitic disease affecting more than 250 million people worldwide. The transcription factor c-Jun, which is induced in S. mansoni infection-associated liver disease, can promote hepatocyte survival but can also trigger hepatocellular carcinogenesis. We aimed to analyze the hepatic role of c-Jun following S. mansoni infection. We adopted a hepatocyte-specific c-Jun knockout mouse model (Alb-Cre/c-Jun loxP) and analyzed liver tissue and serum samples by quantitative real-time PCR array, western blotting, immunohistochemistry, hydroxyproline quantification, and functional analyses. Hepatocyte-specific c-Jun knockout (c-JunΔli) was confirmed by immunohistochemistry and western blotting. Infection with S. mansoni induced elevated aminotransferase-serum levels in c-JunΔli mice. Of note, hepatic Cyclin D1 expression was induced in infected c-Junf/f control mice but to a lower extent in c-JunΔli mice. S. mansoni soluble egg antigen-induced proliferation in a human hepatoma cell line was diminished by inhibition of c-Jun signaling. Markers for apoptosis, oxidative stress, ER stress, inflammation, autophagy, DNA-damage, and fibrosis were not altered in S. mansoni infected c-JunΔli mice compared to infected c-Junf/f controls. Enhanced liver damage in c-JunΔli mice suggested a protective role of c-Jun. A reduced Cyclin D1 expression and reduced hepatic regeneration could be the reason. In addition, it seems likely that the trends in pathological changes in c-JunΔli mice cumulatively led to a loss of the protective potential being responsible for the increased hepatocyte damage and loss of regenerative ability.

Schistosomiasis affects over 250 million people worldwide, with the highest prevalence at the age of 10–14 years. The influence of the host’s age on the severity of liver damage is unclear. We infected male 8, 14, and 20-week-old mice with S. mansoni. Hepatic damage, inflammation, fibrosis, and metabolism were analyzed by RT-qPCR, Western blotting, ELISA, immunohistochemistry, and mechanistic transwell chamber experiments using S. mansoni eggs and human hepatic stellate cells (HSCs) or primary mouse hepatocytes. Major results were validated in human biopsies. We found that hepatosplenomegaly, granuloma size, egg load, inflammation, fibrosis, and glycogen stores all improved with the increasing age of the host. However, serum alanine transaminase (ALT) levels were lowest in young mice infected with S. mansoni. Hepatic carbohydrate exploitation was characterized by a shift towards Warburg-like glycolysis in S. mansoni-infected animals. Notably, S. mansoni eggs stimulated hepatic stellate cells to an alternatively activated phenotype (GFAP+/desmin+/αSMA−) that secretes IL-6 and MCP-1. The reduction of fibrosis in older age likely depends on the fine-tuning of regulatory and inflammatory cytokines, alternative HSC activation, and the age-dependent preservation of hepatic energy stores. The current results emphasize the significance of investigations on the clinical relevance of host age-dependent liver damage in patients with schistosomiasis.

Schistosomiasis, a parasitic disease caused by Schistosoma spp., affects more than 250 million people worldwide. S. mansoni in particular affects the gastrointestinal tract and, through its eggs, induces a Th2 immune response leading to granuloma formation. The relationship between egg load and immune response is poorly understood. We investigated whether the quantity of parasitic eggs influences the immune response in S. mansoni-infected hamsters. The hepatic and intestinal egg load was assessed, and cytokine expression as well as the expression of three major egg-derived proteins were analyzed in monosex- and bisex-infected animals by qRT-PCR. Statistical correlations between egg load or egg-derived factors Ipse/alpha-1, kappa-5, and omega-1, and the immune response were analyzed in liver and colon tissue. Surprisingly, no correlation of the Th1 cytokines with the hepatic egg load was observed, while the Th2 cytokines Il4, Il5, and Il13 showed an inverse correlation in the liver but not in the colon. A longer embryogenesis of the parasitic eggs in the liver could explain this correlation. This conclusion is supported by the lack of any correlation with immune response in the colon, as the intestinal passage of the eggs is limited to a few days.

BackgroundHypoglycemia threatens cognitive function and driving safety. Previous research investigated in-vehicle voice assistants as hypoglycemia warnings. However, they could startle drivers. To address this, we combine voice warnings with ambient LEDs. ObjectiveThe study assesses the effect of in-vehicle multimodal warning on emotional reaction and technology acceptance among drivers with type 1 diabetes. MethodsTwo studies were conducted, one in simulated driving and the other in real-world driving. A quasi-experimental design included 2 independent variables (blood glucose phase and warning modality) and 1 main dependent variable (emotional reaction). Blood glucose was manipulated via intravenous catheters, and warning modality was manipulated by combining a tablet voice warning app and LEDs. Emotional reaction was measured physiologically via skin conductance response and subjectively with the Affective Slider and tested with a mixed-effect linear model. Secondary outcomes included self-reported technology acceptance. Participants were recruited from Bern University Hospital, Switzerland. ResultsThe simulated and real-world driving studies involved 9 and 10 participants with type 1 diabetes, respectively. Both studies showed significant results in self-reported emotional reactions (P

ABSTRACT The human colon hosts hundreds of commensal bacterial species, many of which ferment complex dietary carbohydrates. To transform these fibers into metabolically accessible compounds, microbes often express a series of dedicated enzymes homologous to the starch utilization system (Sus) encoded in polysaccharide utilization loci (PULs). The genome of Bacteroides thetaiotaomicron (Bt), a common member of the human gut microbiota, encodes nearly 100 PULs, conferring a strong metabolic versatility. While the structures and functions of individual enzymes within the PULs have been investigated, little is known about how polysaccharide complexity impacts the function of Sus-like systems. We here show that the activity of Sus-like systems depends on polysaccharide size, ultimately impacting bacterial growth. We demonstrate the effect of size-dependent metabolism in the context of dextran metabolism driven by the specific utilization system PUL48. We find that as the molecular weight of dextran increases, Bt growth rate decreases and lag time increases. At the enzymatic level, the dextranase BT3087, a glycoside hydrolase (GH) belonging to the GH family 66, is the main GH for dextran utilization, and BT3087 and BT3088 contribute to Bt dextran metabolism in a size-dependent manner. Finally, we show that the polysaccharide size-dependent metabolism of Bt impacts its metabolic output in a way that modulates the composition of a producer-consumer community it forms with Bacteroides fragilis. Altogether, our results expose an overlooked aspect of Bt metabolism that can impact the composition and diversity of microbiota.IMPORTANCEPolysaccharides are complex molecules that are commonly found in our diet. While humans lack the ability to degrade many polysaccharides, their intestinal microbiota contain bacterial commensals that are versatile polysaccharide utilizers. The gut commensal Bacteroides thetaiotaomicron dedicates roughly 20% of their genomes to the expression of polysaccharide utilization loci for the broad range utilization of polysaccharides. Although it is known that different polysaccharide utilization loci are dedicated to the degradation of specific polysaccharides with unique glycosidic linkages and monosaccharide compositions, it is often overlooked that specific polysaccharides may also exist in various molecular weights. These different physical attributes may impact their processability by starch utilization system-like systems, leading to differing growth rates and nutrient-sharing properties at the community level. Therefore, understanding how molecular weight impacts utilization by gut microbe may lead to the potential design of novel precision prebiotics.

IntroductionVarious methods have been described to create a functional neovagina with feminizing (male-to-female) gender affirming surgery. Intestinal vaginoplasty using ileal or colon segments confers natural mucus production and greater canal depth with primary vaginoplasty. In this work we describe an alternative approach to primary and salvage vaginoplasty using right colon. We focus on relative advantages compared to use of other bowel segments, and we review patient outcomes.MethodsTransgender women who had previously undergone primary vaginoplasty underwent laparoscopic right colon vaginoplasty at our center between 12/2017 and 7/2019. Demographic, medical, outcome, and satisfaction data was collected and retrospectively reviewed.ResultsTwenty-two consecutive transgender women patients underwent laparoscopic right colon vaginoplasty. Mean age was 39.3 years. There were two intraoperative complications:1 injury of the ileocolic pedicle, and 1 minor bladder injury. Four of 22 patients (18.2%) had short-term complications ( 30 days): 1 developed Crohn's (not involving the neovagina); 1 developed late small bowel obstruction (SBO) (managed conservatively); 5 developed neovagina prolapse; 4 developed stenosis (2 at the vaginal introitus, and 2 had extrinsic obstruction at the recto-vaginal junction (all underwent successful laparoscopic surgical correction); and 3 were diagnosed with diversion neovaginitis (all treated conservatively). All complications were successfully treated with conservative and/or surgical intervention. All (100%) patients reported satisfaction with neovagina function and appearance.ConclusionThis is the only outcomes series of transgender women patients who have undergone right colon vaginoplasty, to date. Our study finding suggests that laparoscopic right colon for primary or salvage vaginoplasty has several important advantages over use of Sigmoid colon or Ileum, and is a reliable technique whose complications can be managed successfully, with favorable, satisfactory long-term outcomes.

BackgroundHypoglycemia is a frequent and acute complication in type 1 diabetes mellitus (T1DM) and is associated with a higher risk of car mishaps. Currently, hypoglycemia can be detected and signaled through flash glucose monitoring or continuous glucose monitoring devices, which require manual and visual interaction, thereby removing the focus of attention from the driving task. Hypoglycemia causes a decrease in attention, thereby challenging the safety of using such devices behind the wheel. Here, we present an investigation of a hands-free technology—a voice warning that can potentially be delivered via an in-vehicle voice assistant. ObjectiveThis study aims to investigate the feasibility of an in-vehicle voice warning for hypoglycemia, evaluating both its effectiveness and user perception. MethodsWe designed a voice warning and evaluated it in 3 studies. In all studies, participants received a voice warning while driving. Study 0 (n=10) assessed the feasibility of using a voice warning with healthy participants driving in a simulator. Study 1 (n=18) assessed the voice warning in participants with T1DM. Study 2 (n=20) assessed the voice warning in participants with T1DM undergoing hypoglycemia while driving in a real car. We measured participants’ self-reported perception of the voice warning (with a user experience scale in study 0 and with acceptance, alliance, and trust scales in studies 1 and 2) and compliance behavior (whether they stopped the car and reaction time). In addition, we assessed technology affinity and collected the participants’ verbal feedback. ResultsTechnology affinity was similar across studies and approximately 70% of the maximal value. Perception measure of the voice warning was approximately 62% to 78% in the simulated driving and 34% to 56% in real-world driving. Perception correlated with technology affinity on specific constructs (eg, Affinity for Technology Interaction score and intention to use, optimism and performance expectancy, behavioral intention, Session Alliance Inventory score, innovativeness and hedonic motivation, and negative correlations between discomfort and behavioral intention and discomfort and competence trust; all P