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We describe the development of Chempath : an open-source pathway analysis program for photochemical models. This algorithm can help understand the results of complex photochemical models by identifying the most important reaction chains (pathways) for the production and destruction of a species of interest in a reaction system. The algorithm can also quantify the contribution of the pathways to the production and destruction of a species. We demonstrate how to apply Chempath to a one-dimensional photochemical model, using an example of a reaction system for Earth's present-day atmosphere. We validate that Chempath can identify well-known chemical mechanisms for O3 production and destruction in this model, suggesting that this algorithm can be applied to understand photochemical models of less well-known atmospheres, like past and exoplanet atmospheres. [ABSTRACT FROM AUTHOR]

Excitation energy transfer (EET) is a key photoinduced process in biological chromophoric assemblies. Here we investigate the factors which can drive EET into efficient ultrafast sub-ps regimes. We demonstrate how a coherent transport of electronic population could facilitate this in water solvated NADH coenzyme and uncover the role of an intermediate dark charge-transfer state. High temporal resolution ultrafast optical spectroscopy gives a 54±11 fs time constant for the EET process. Nonadiabatic quantum dynamical simulations computed through the time-evolution of multidimensional wavepackets suggest that the population transfer is mediated by photoexcited molecular vibrations due to strong coupling between the electronic states. The polar aqueous solvent environment leads to the active participation of a dark charge transfer state, accelerating the vibronically coherent EET process in favorably stacked conformers and solvent cavities. Our work demonstrates how the interplay of structural and environmental factors leads to diverse pathways for the EET process in flexible heterodimers and provides general insights relevant for coherent EET processes in stacked multichromophoric aggregates like DNA strands. Excitation energy transfer is important for many photoinduced biological processes in systems with multiple chromophores. Here, the authors elucidate this process for the coenzyme NADH using ultrafast spectroscopy and quantum dynamics. [ABSTRACT FROM AUTHOR]

Ultra-lean hydrogen–air flames propagating in narrow gaps, under the influence of cold walls and high preferential diffusion, can form two distinct isolated structures. They exhibit either circular or double-cell shapes and propagate at different speeds, with the latter roughly doubling in size and traveling speed to the former. Hydrogen mass diffusivity, convective effects, and conductive heat losses are the physical mechanisms that explain the alterations in morphology and propagation speed. In previous experiments, Veiga-López et al. [Phys. Rev. Lett. 124, 174501 (2020)] found these clearly distinguished flame structures for different combinations of equivalence ratio, channel gap, and the effect of gravity on the dynamics of upward and downward propagating flames in a vertical chamber. Present observations in horizontal channels show the simultaneous appearance of these two stable structures, which arise under identical experimental conditions and conform the first evidence that multiplicity of stable solutions coexists in real devices. To explain the observations, we performed numerical simulations using the simplified model, which shows that symmetry-breaking details during the ignition transient explain the concurrent emergence of the two stable configurations. This discovery urges the need to implement additional engineering tools to account for the possibility of the formation and propagation of isolated flame kernels at different speeds in hydrogen-fueled systems. [ABSTRACT FROM AUTHOR]

In magnetized liner inertial fusion (MagLIF), a cylindrical liner filled with fusion fuel is imploded with the goal of producing a one-dimensional plasma column at thermonuclear conditions. However, structures attributed to three-dimensional effects are observed in self-emission x-ray images. Despite this, the impact of many experimental inputs on the column morphology has not been characterized. We demonstrate the use of a linear regression analysis to explore correlations between morphology and a wide variety of experimental inputs across 57 MagLIF experiments. Results indicate the possibility of several unexplored effects. For example, we demonstrate that increasing the initial magnetic field correlates with improved stability. Although intuitively expected, this has never been quantitatively assessed in integrated MagLIF experiments. We also demonstrate that azimuthal drive asymmetries resulting from the geometry of the "current return can" appear to measurably impact the morphology. In conjunction with several counterintuitive null results, we expect the observed correlations will encourage further experimental, theoretical, and simulation-based studies. Finally, we note that the method used in this work is general and may be applied to explore not only correlations between input conditions and morphology but also with other experimentally measured quantities. [ABSTRACT FROM AUTHOR]

To assess the effects of the eFisioTrack monitoring system on clinical variables in patients with prescribed physiotherapy for shoulder injuries, twenty-four adult patients with shoulder orthopaedic injuries who underwent physical therapy treatment in a hospital setting participated in the study (twelve in the experimental group and twelve as controls). Clinical outcome measures were shoulder function and pain (Constant–Murley Score and Disabilities of the Arm, Shoulder, and Hand or DASH score). Each variable was measured by a blinded physiotherapist at baseline and at one month follow-up. Patients performed the prescribed exercises either supervised by the physiotherapist (control group) or in a separate room without therapist supervision (experimental group). There were no statistically significant differences between groups before treatment or at follow-up for any outcomes (p ≥ 0.05). There was a statistically significant decrease (p ≤ 0.05) of at least 10 points in both groups for the DASH score at follow-up. Differences in the total score and subjective components of the Constant–Murley were also evidenced within groups. The use of the eFisioTrack system showed similar results in clinical measures compared to those performed under the direct supervision of the physiotherapist. This approach might be suitable for providing an effective shoulder exercise program at home. [ABSTRACT FROM AUTHOR]

To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p =.002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p <.001). No serious adverse events were documented. Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population. Haematological patients face an increased risk for severe COVID-19. Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients. Persistent viral replication is increased in immunocompromised patients. Plitidepsin does not lead to new serious adverse events in immunocompromised patients. [ABSTRACT FROM AUTHOR]

Road structures undergo a series of chemical and physical processes once they are put into service. This phenomenon results from the action of the load and the influence of the environment, which causes their progressive deterioration. In order to mitigate the risk of progressive deterioration and guarantee their stability and durability, various maintenance tasks are required, including visual inspections. The Intelligent Bridge Management System of Colombia (SIGP) includes visual inspection as one of its modules. The system has been designed based on state-of-the-art criteria and national experience with relevant damages and bridge collapses. This paper presents the visual inspection methodology, which includes several stages such as a classification scale, condition index, evaluation areas, damage catalog, and evaluation criteria. In addition, a digital application has been developed to facilitate real-time data collection during field inspections using mobile devices, which can be uploaded directly to the system database hosted in the cloud. The results from the inspection of bridges of different typologies and years of construction are presented, as well as general inspection results from 150 bridges in Colombia. The relevance, comprehensiveness, and accuracy of the inspection are supported by a damage catalog, which allows the identification of intervention needs and reduces the bias of the collected data. [ABSTRACT FROM AUTHOR]

Existing mRNA COVID-19 vaccines have shown efficacy in reducing severe cases and fatalities. However, their effectiveness against infection caused by emerging SARS-CoV-2 variants has waned considerably, necessitating the development of variant vaccines. Ideally, next-generation vaccines will be capable of eliciting broader and more sustained immune responses to effectively counteract new variants. Additionally, in vitro assays that more closely represent virus neutralization in humans would greatly assist in the analysis of protective vaccine-induced antibody responses. Here, we present findings from a SARS-CoV-2 VLP vaccine encompassing three key structural proteins: Spike (S), Envelope (E), and Membrane (M). The VLP vaccine effectively produced neutralizing antibodies as determined by surrogate virus neutralization test, and induced virus-specific T-cell responses: predominantly CD4+, although CD8+ T cell responses were detected. T cell responses were more prominent with vaccine delivered with AddaVax compared to vaccine alone. The adjuvanted vaccine was completely protective against live virus challenge in mice. Furthermore, we utilized air–liquid-interface (ALI)-differentiated human nasal epithelium (HNE) as an in vitro system, which authentically models human SARS-CoV-2 infection and neutralization. We show that immune sera from VLP-vaccinated mice completely neutralized SARS-CoV-2 virus infection, demonstrating the potential of ALI-HNE to assess vaccine induced Nab. [ABSTRACT FROM AUTHOR]

The temporal relationship between global glaciations and the Great Oxidation Event (GOE) suggests that climate change played an important role in Earth's oxygenation. The potential role of temperature is captured by the stratigraphic proximity between glacial deposits and sediments containing mass‐independent fractionation of sulfur isotopes (MIF‐S). We use a time‐dependent one‐dimensional photochemical model to investigate whether temperature changes associated with global glaciations can drive oscillations in atmospheric O2 levels and MIF‐S production across the GOE. We find that extreme climate change can cause atmospheric O2 to oscillate between pre (<10−6 times the present atmospheric level, PAL) and post‐GOE (>10−5 PAL) levels. Post‐glacial hot‐moist greenhouse climates lead to post‐GOE O2 levels because the abundant H2O vapor and oxidizing radicals drive the depletion of reduced species. This pattern is generally consistent with the MIF‐S signal observed in the sedimentary record, suggesting a link between global glaciations and O2 oscillations across the GOE. Plain Language Summary: The Great Oxidation Event was the most significant environmental and chemical transformation in Earth's history, marking the first time oxygen accumulated in the atmosphere around 2.4 billion years ago. Oxygen increased from below one millionth (low) to at least one‐thousandth of a percent (intermediate) of the present oxygen concentration during this event. However, measurements of geochemical oxygen proxies suggest that oxygen levels oscillated between low and intermediate levels before stabilizing after this event. The first rise of atmospheric oxygen occurred during a period of extreme climate variability indicated by the presence of glacial rock deposits around this time. In this study, we use a time‐dependent photochemical model to show that extreme temperature changes caused by global glaciations can drive oscillations in atmospheric oxygen levels across the Great Oxidation Event (GOE). Our results can help explain why atmospheric oxygen shows drastic changes across the GOE in a way that is consistent with the geochemical record. Key Points: Across the Great Oxidation Event (GOE), extreme climate change linked to global glaciations can drive oscillations in atmospheric O2 levels and mass‐independent fractionation of sulfur isotopes (MIF‐S) productionGlacial climates and hot‐moist greenhouse climates were likely characterized by pre‐GOE and post‐GOE O2 levels respectivelyTemperature changes associated with global glaciations can help explain the MIF‐S record across the GOE [ABSTRACT FROM AUTHOR]

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Copyright of Revista Catalana de Dret Ambiental is the property of Universitat Rovira I Virgili and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The role of the inflammasomes in aging and progeroid syndromes remain understudied. Recently, MCC950, a NLRP3 inhibitor, was used in Zmpste24−/− mice to ameliorate the phenotypes. However, the safety of MCC950 was questioned due to liver toxicity observed in humans. Nevertheless, inhibition of the inflammasomes would be a beneficial therapy for progeria. Here, we show that OLT1177 (dapansutrile), other NLRP3 inhibitor, improved cellular and animal phenotypes using progeroid fibroblasts and a LmnaG609G/G609G mouse model. In both cases dapansutrile reduced progerin accumulation, NLRP3‐inflammasome activation and secretory phenotype of senescence, extended the lifespan of progeroid animals, preserved bodyweight, and reduced kyphosis, inflammation, and senescence. Interestingly, dapansutrile further improved the effect of lonafarnib, the only FDA‐approved drug for the progeria. The combination of both drugs reduced the inflammation and senescence, extended survival and ameliorated various progeroid defects both in vitro and in vivo, compared with treatment using lonafarnib alone. These findings and the safety of dapansutrile demonstrated in several clinical trials proposes it as a possible co‐adjuvant treatment with lonafarnid in HGPS. [ABSTRACT FROM AUTHOR]

Developmental time is a fundamental life history trait that affects the reproductive success of animals. Developmental time is known to be regulated by many genes and environmental conditions, yet mechanistic understandings of how various cellular processes influence the developmental timing of an organism are lacking. The nervous system is known to control key processes that affect developmental time, including the release of hormones that signal transitions between developmental stages. Here we show that the excitability of neurons plays a crucial role in modulating developmental time. Genetic manipulation of neuronal excitability in Drosophila melanogaster alters developmental time, which is faster in animals with increased neuronal excitability. We find that selectively modulating the excitability of peptidergic neurons is sufficient to alter developmental time, suggesting the intriguing hypothesis that the impact of neuronal excitability on DT may be at least partially mediated by peptidergic regulation of hormone release. This effect of neuronal excitability on developmental time is seen during embryogenesis and later developmental stages. Observed phenotypic plasticity in the effect of genetically increasing neuronal excitability at different temperatures, a condition also known to modulate excitability, suggests there is an optimal level of neuronal excitability, in terms of shortening DT. Together, our data highlight a novel connection between neuronal excitability and developmental time, with broad implications related to organismal physiology and evolution. • Increasing neuronal excitability shortens developmental time. • Peptidergic neuron excitability regulates developmental time. • Genes and environments interact to affect development. [ABSTRACT FROM AUTHOR]