While molar volume-based models for gas solubility in ionic liquids (ILs) have been proposed, free volume within the IL can be shown to be the underlying property driving gas solubility and ...selecitivity. Previously published observations as to the distinct differences in solubility trends for gases such as CH4 and N2 relative to CO2 in systematically varied ILs can be attributed to positive and negative effects arising from increasing free volume with increasing alkyl chain length. Through the use of COSMOtherm as a powerful and rapid tool to calculate free volumes in 165 existing and theoretical 1-n-alkyl-3-methylimidazolium (CnmimX) ILs, a previously unreported, yet speculated, critical underlying relationship between gas solubility in ILs is herein described. These results build upon previous assertions that Regular Solution Theory is applicable to imidazolium-based ILs, which appeared to indicate that a global maximum had already been observed for CO2 solubility in imidazolium-based ILs. However, the findings of this computational study suggest that the perceived maximum in CO2 solubility might be exceeded through rational design of ILs. We observe that although Henry’s constants in ILs are dependent on the inverse of molar volume and free volume, the volume-normalized solubility of CH4 and N2 are proportional to free volume, while CO2 is inversely proportional to the square root of free volume. Our free volume model is compared to experimental data for CO2/CH4 and CO2/N2 selectivity, and a nearly identical plot of selectivity relative to IL molar volume can be generated from the computational method alone. The overall implication is that large, highly delocalized anions paired with imidazolium cations that have minimally sized alkyl chains may hold the key to achieving greater CO2 solubility and selectivity in ILs.
Abstract Background Physical Activity Across the Curriculum (PAAC) was a three-year cluster randomized controlled trial to promote physical activity and diminish increases in overweight and obesity ...in elementary school children. Methods Twenty-four elementary schools were cluster randomized to the Physical Activity Across the Curriculum intervention or served as control. All children in grades two and three were followed to grades four and five. Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers. Body Mass Index was the primary outcome, daily Physical activity and academic achievement were secondary outcomes. Results The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0 ±1.9 and control 1.9 ± 1.9, respectively (NS). However, change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum. Schools with ≥ 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had < 75 min of Physical Activity Across the Curriculum (1.8 ± 1.8 vs. 2.4 ± 2.0, p = 0.02). Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores. Conclusions The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children. Additionally, 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index.
In 2023, the Keystone Symposia held the first international scientific conference convening research leaders investigating the pathology of post‐acute sequelae of COVID‐19 (PASC) or Long COVID, a ...growing and urgent public health priority. In this report, we present insights from the talks and workshops presented during this meeting and highlight key themes regarding what researchers have discovered regarding the underlying biology of PASC and directions toward future treatment. Several themes have emerged in the biology, with inflammation and other immune alterations being the most common focus, potentially related to viral persistence, latent virus reactivation, and/or tissue damage and dysfunction, especially of the endothelium, nervous system, and mitochondria. In order to develop safe and effective treatments for people with PASC, critical next steps should focus on the replication of major findings regarding potential mechanisms, disentangling pathogenic mechanisms from downstream effects, development of cellular and animal models, mechanism‐focused randomized, placebo‐controlled trials, and closer collaboration between people with lived experience, scientists, and other stakeholders. Ultimately, by learning from other post‐infectious syndromes, the knowledge gained may help not only those with PASC/Long COVID, but also those with other post‐infectious syndromes.
Abstract
Transforming growth factor β (TGFβ) signaling has been recently shown to reduce antitumor response to PD-L1 blockade, leading to a renewed enthusiasm in developing anti-TGFβ therapies for ...potential combination with cancer immunotherapy agents. Inhibition of TGFβ signaling in nonclinical toxicology species is associated with serious adverse toxicities including cardiac valvulopathies and anemia. Previously, cardiovascular toxicities have been thought to be limited to small molecule inhibitors of TGFβ receptor and not considered to be a liability associated with pan-TGFβ neutralizing monoclonal antibodies (mAbs). Here, we report the toxicity findings associated with a potent pan-TGFβ neutralizing mAb (pan-TGFβ mAb; neutralizes TGFβ1, 2, and 3) after 5 weekly intravenous doses of 10, 30, and 100 mg/kg, followed by a 4-week recovery period, in mice and cynomolgus monkeys. Mortality was observed due to acute bleeding and cardiovascular toxicity in mice at ≥ 30 mg/kg and prolonged menstruation in female monkeys at 100 mg/kg. Additional findings considered to be on-target exaggerated pharmacology included generalized bleeding and cardiovascular toxicity in mice and monkeys; histopathologic changes in the teeth, tongue, and skin in mice; and abnormal wound healing and microscopic pathology in the bone in monkeys. Importantly, our data indicate that the cardiovascular toxicities associated with the inhibition of TGFβ signaling are not limited to small molecule inhibitors but are also observed following administration of a potent pan-TGFβ inhibiting mAb.
Sulfur dioxide (SO2) removal is a key component of many industrial processes, especially coal-fired power generation. Controlling SO2 emissions is vital to maintaining environmental quality, as SO2 ...is a contributor to acid rain, but has value as a chemical feedstock. Although a number of novel solvents/materials including ionic liquids (ILs) have recently been proposed for alternatives to limestone scrubbing for SO2 capture/removal from point sources, the imidazole architecture presents a convenient, inexpensive and efficient class of low volatility and low viscosity solvents to accomplish this goal. On the basis of our prior work with imidazoles for CO2 capture, we have extended our interests toward understanding the relationship between imidazole structure and SO2 absorption. Using a series of imidazole compounds with various substituents at the 1, 2 and/or 4(5) positions of the five-membered ring, SO2 absorption via both chemical and physical mechanisms was observed. The chemical absorption product is a relatively stable 1:1 SO2–imidazole complex, while physical absorption of SO2 is dependent on pressure and temperature. Because imidazoles are relatively small molecules, they are an efficient absorption medium for SO2 and can form adducts wherein the mass fraction of bound SO2 is >40 wt %. The SO2–imidazole complexes were also observed to produce distinct color and/or phase changes that are associated with the nature of the substituents present. The chemically bound SO2 can be released under vacuum at moderate temperature (∼100 °C) and vacuum, yielding the original neat solvent, while the physically dissolved SO2 can be readily removed at ambient temperature under vacuum. This behavior corresponds to a much smaller enthalpy of absorption for physical dissolution (−4 to −13 kJ/mol) as determined via thermodynamic relationships compared to the binding energies of chemical complexation (−35 to −42 kJ/mol) as determined via density functional theory calculations. Increasing chemical complexation energies are correlated with increased substitution on the imidazole ring. Simulations were also employed to gain insight into the structures of the SO2–imidazole complexes, illustrating changes in partial charge distribution before and after complexation as well as confirming a charge transfer complex is formed based on the N–S bond length.
Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral ...therapies only able to control, but not clear, these infections. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69-172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors.
Despite widespread use of the bacille Calmette-Guérin (BCG) vaccine, tuberculosis (TB) remains a leading cause of global mortality from a single infectious agent (Mycobacterium tuberculosis or Mtb). ...Here, over two independent Mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs) with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter referred to as RhCMV/TB)-which elicit and maintain highly effector-differentiated, circulating and tissue-resident Mtb-specific CD4
and CD8
memory T cell responses-can reduce the overall (pulmonary and extrapulmonary) extent of Mtb infection and disease by 68%, as compared to that in unvaccinated controls, after intrabronchial challenge with the Erdman strain of Mtb at ∼1 year after the first vaccination. Fourteen of 34 RhCMV/TB-vaccinated RMs (41%) across both studies showed no TB disease by computed tomography scans or at necropsy after challenge (as compared to 0 of 17 unvaccinated controls), and ten of these RMs were Mtb-culture-negative for all tissues, an exceptional long-term vaccine effect in the RM challenge model with the Erdman strain of Mtb. These results suggest that complete vaccine-mediated immune control of highly pathogenic Mtb is possible if immune effector responses can intercept Mtb infection at its earliest stages.
Simple and easily integrated design of flexible and transparent electrode materials affixed to polymer-based substrates hold great promise to have a revolutionary impact on the functionality and ...performance of energy storage devices for many future consumer electronics. Among these applications are touch sensors, roll-up displays, photovoltaic cells, health monitors, wireless sensors, and wearable communication devices. Here, we report an environmentally friendly, simple, and versatile approach to produce optically transparent and mechanically flexible all-solid-state supercapacitor devices. These supercapacitors were constructed on tin-doped indium oxide coated polyethylene terephthalate substrates by intercalation of a polymer-based gel electrolyte between two reduced graphene oxide (rGO) thin-film electrodes. The rGO electrodes were fabricated simply by drop-casting of graphene oxide (GO) films, followed by a novel low-temperature (≤250 °C) vacuum-assisted annealing approach for the in situ reduction of GO to rGO. A trade-off between the optical transparency and electrochemical performance is determined by the concentration of the GO in the initial dispersion, whereby the highest capacitance (∼650 μF cm–2) occurs at a relatively lower optical transmittance (24%). Notably, the all-solid-state supercapacitors demonstrated excellent mechanical flexibility with a capacity retention rate above 90% under various bending angles and cycles. These attributes underscore the potential of the present approach to provide a path toward the realization of thin-film-based supercapacitors as flexible and transparent energy storage devices for a variety of practical applications.
Polyimides and ionic liquids (ILs) are two classes of materials that have been widely studied as gas separation membranes, each demonstrating respective advantages and limitations. Both polyimides ...and ILs are amenable to modification/functionalization based on selection of the requisite precursors. However, there have been but a handful of reports considering how polyimides and ILs could be integrated to obtain fundamentally new materials with synergistic properties. In this manuscript, we demonstrate a new and versatile way to synthesize polyimides with imidazolium cations directly located within the polymer backbone to form polyimide–ionene hybrids, or “ionic polyimides”. Our strategy for synthesizing ionic polyimides does not require the use of amino-functionalized ILs. Instead, the imidization reaction occurs prior to polymerization in the formation of an imidazole-functionalized diimide monomer. This monomer is then reacted via step-growth (condensation) polymerization with p-dichloroxylene via Menshutkin reactions, simultaneously linking the monomers and creating the ionic components. The resultant ionic polyimide is amenable to thermal processing (e.g., extrusion, melt-pressing) and capable of forming thin films. Upon soaking thin films of the ionic polyimide in a widely used IL, 1-butyl-3-methylimidazolium bistriflimide (C4mimTf2N), a stoichiometric absorption of the IL into the ionic polyimide was observed, forming an ionic polyimide + IL composite. The gas separation performances of ionic polyimide and ionic polyimide + IL composite membranes were studied with respect to CO2, N2, CH4, and H2. The neat ionic polyimide exhibits low permeability to CO2 and H2 (∼0.9 and ∼1.6 barrers, respectively) and very low permeability to N2 and CH4 (∼0.03 barrers for both). For the ionic polyimide + IL composite, the permeabilities of CO2, N2, and CH4 increase by 1800–2700%, while H2 permeability only increased by ∼200%. The large increases in permeability for CO2, N2, and CH4 are due to greatly increased gas diffusivity through the material, with gas solubility essentially unchanged with the IL present. The ionic polyimide and ionic polyimide + IL composite were characterized using a number of techniques. Most interestingly, X-ray diffractometry (XRD) of the films reveals that the ionic polyimide + IL composite displays a sharp peak, indicating that the ionic polyimide may experience supramolecular assembly around the IL. Although the performances of these first ionic polyimide and ionic polyimide + IL composite membranes fall short of Robeson’s Upper Bounds, this work provides a strong foundation on which ionic polyimide materials with more sophisticated structural elements can be developed to understand the structure–property relationships underlying the ionic polyimide platform and ultimately produce high-performance gas separation membranes.
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